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Text : Herbal materials derived from Juniperus communis (JCo) possess anticancer activity. In this study, we evaluated the efficacy of a JCo berry extract in suppressing glioblastoma growth. The effects of JCo extract on the viability of normal and glioma cell lines was analyzed using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synergistic therapeutic effect of JCo extract and temozolomide (TMZ) on glioma cells was examined by MTT analysis. Flow cytometry analysis, the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) test, and western blotting were performed to identify the apoptotic pathway. To determine the in vivo efficacy of the JCo extract, rats were injected with 5 × 104 rat glioma RG2 cells in the back skin and brain hemisphere and then received a subcutaneous injection in the back skin that contained either JCo extract or vehicle. Finally, blood and histologic examinations were performed to evaluate JCo toxicity. The IC50 values of JCo extract were 57-69 µg/mL and 49-67 µg/mL in the glioblastoma cell lines after 24 and 48 h, respectively. However, in non-tumor cell lines, the respective IC50 values of JCo extract were 76-105 µg/mL and 77-108 µg/mL. The JCo extract had a stronger cytotoxicity and a larger range of IC50 values in glioma than in normal cells as compared to those effects caused by temozolomide (TMZ). In addition, the results of flow cytometry analysis, TUNEL test, and western blotting revealed that the JCo extract induced glioma cell cycle arrest through intrinsic and extrinsic apoptotic pathways. In the in vivo studies, a significant reduction of tumor size in JCo-treated rats, as measured by animal MRI, demonstrated that the JCo extract effectively inhibited glioma cell growth and successfully penetrated the blood-brain barrier. The immunohistochemical (IHC) staining detected positive signals of PCNA, VEGFR-1, and VEGFR -2 in 44.49%, 5.88%, and 5.85% of JCo-treated glioma cells, respectively. However, positive signals of PCNA, VEGFR-1, and VEGFR-2 were detected in 73.08%, 9.67%, and 11.70% of vehicle-treated glioma cells, respectively. The IHC examination of PCNA and VEGFR-1 and -2 indicated that JCo extract significantly decreased the degree of neovascularization. However, no significant differences in serum levels of blood cell count and hepatic enzymes, renal function index, and the histologic appearance of vital organs were detected between the JCo and vehicle-treated rats. The JCo extract penetrated the blood-brain barrier and significantly induced glioma cell apoptosis by reducing neovascularization via suppression of the PI3K/AKT/mTOR pathway. Furthermore, JCo extract was less cytotoxic to non-neoplastic vital organs than TMZ. | Authentic |
Text : This research aimed to study the associations between XPD (G751A, rs13181), hOGG1 (C326G, rs1052133) and XRCC4 (G1394T, rs6869366) gene polymorphisms and the risk of colorectal cancer (CRC) in a Chinese Han population. A total of 225 Chinese Han patients with CRC were selected as the study group, and 200 healthy subjects were recruited as the control group. The polymorphisms of XPD G751A, hOGG1 C326G and XRCC4 G1394T loci were detected by the RFLP-PCR technique in the peripheral blood of all subjects. Compared with individuals carrying the XPD751 GG allele, the A allele carriers (GA/AA) had a significantly increased risk of CRC (adjusted OR = 2.109, 95%CI = 1.352-3.287, P=0.003). Similarly, the G allele (CG/GG) of hOGG1 C326G locus conferred increased susceptibility to CRC (adjusted OR = 2.654, 95%CI = 1.915-3.685, P<0.001). In addition, the T allele carriers (GT/TT) of the XRCC4 G1394T locus have an increased risk of developing CRC (adjusted OR = 4.512, 95%CI = 2.785-7.402, P<0.001). The risk of CRC was significantly increased in individuals with both the XPD locus A allele and the hOGG1 locus G allele (adjusted OR = 1.543, 95%CI = 1.302-2.542, P=0.002). Furthermore, individuals with both the hOGG1 locus G allele and the XRCC4 locus T allele were predisposed to CRC development (adjusted OR = 3.854, 95%CI = 1.924-7.123, P<0.001). The risks of CRC in XPD gene A allele carriers (GA/AA) (adjusted OR = 1.570, 95%CI = 1.201-1.976, P=0.001), hOGG1 gene G allele carriers (CG/GG) (adjusted OR = 3.031, 95%CI = 2.184-4.225, P<0.001) and XRCC4 gene T allele carriers (GT/TT) (adjusted OR = 2.793, 95%CI = 2.235-3.222, P<0.001) were significantly higher in patients who smoked ≥16 packs/year. Our results suggest that XPD G751A, hOGG1 C326G and XRCC4 G1394T gene polymorphisms might play an important role in colorectal carcinogenesis and increase the risk of developing CRC in the Chinese Han population. The interaction between smoking and these gene polymorphisms would increase the risk of CRC. | Authentic |
Text : 2-O-methylmagnolol (MM1), a derivative of magnolol bearing one methoxy moiety, has been shown to display improved anti-tumor activity against skin cancers. In this study, we examined the anti-tumor effects of magnolol and MM1 on oral squamous cell carcinoma (OSCC). Trypane blue staining and clonogenic assays were performed to determine the cytotoxic effects of magnolol and MM1 in OSCC cells. Migration and matrigel invasion assays were carried out to examine the metastasis effects of magnolol and MM1 in OSCC cells. IL6-stimulation, Western blot, and immunohistochemistry were used to investigate the IL-6/STAT3 signaling and apoptosis. A bioluminescent mouse model of orthotopically implanted SAS cells was used to determine the anti-tumor activity of MM1 in vivo. MM1 displays greater activity than magnolol on affecting the cytotoxicity, migration, and invasion of OSCC cells cultured in vitro. The improved anti-tumor activity of MM1 was shown to associate with its greater activity to inhibit STAT3 signaling and to induce apoptosis in the OSCC. In addition, we presented evidence that MM1 is effective in inhibiting the growth of orthotopic implanted OSCC cells in vivo. Our data indicate that MM1 displays greater anti-tumor activity than magnolol in OSCC and is an attractive agent to be further explored for its potential clinical application. | Authentic |
Text : Let-7c-5p has been identified as a tumor suppressor in various malignancies; however, its function and mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we explored the role and potential molecular mechanism of let-7c-5p in ESCC. mRNA and protein expression levels were detected by quantitative real time-polymerase chain reaction (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK-8) assay was used to assess cell proliferation. Flow cytometry analysis was used to detect cell apoptosis, and cell migration was measured by wound healing assay and Transwell assays. The dual-luciferase reporter assay was used to verify the targeting relationship between let-7c-5p and CTHRC1. The tumor xenograft model was constructed to further verify the effect of let-7c-5p on the growth of ESCC in vivo. We found that let-7c-5p expression was downregulated in ESCC tissue and cell lines, and its reduced expression was correlated with TNM staging and lymph node metastasis. Next, we found that let-7c-5p can be used to discriminate ESCC patients from normal control subjects by receiver operating characteristic (ROC) curve analysis. Subsequently, we observed that let-7c-5p overexpression inhibited proliferation and migration and promoted apoptosis, while let-7c-5p down-regulation promoted proliferation and migration and inhibited apoptosis of TE-1 and KYSE150 cells. Furthermore, let-7c-5p overexpression inhibited tumor growth, while let-7c-5p inhibition promoted tumor growth in xenograft models. In addition, we confirmed that CTHRC1 was a direct target gene of let-7c-5p. Then, we found that let-7c-5p level was negatively correlated with CTHRC1 and negatively regulated expression of CTHRC1 in ESCC. Moreover, we confirmed that let-7c-5p upregulation significantly reduced the phosphorylation of AKT and ERK by directly inhibiting CTHRC1, while let-7c-5p downregulation showed the opposite effect. Our findings indicate that let-7c-5p is markedly downregulated in ESCC and suppresses proliferation and migration and promotes apoptosis of ESCC cells by inhibiting the AKT and ERK signaling pathways through negatively regulating CTHRC1. Therefore, these results suggest that let-7c-5p may represent a novel biomarker and therapeutic target for ESCC. | Authentic |
Text : Brusatol, a natural quassinoid isolated from a traditional Chinese herbal medicine known as Bruceae Fructus, has recently been reported to possess powerful cytotoxic effects against various cancer cell lines, highlighting its potential as an anti-cancer drug. However, the precise molecular mechanisms by which Brusatol exerts its anti-cancer effects remain poorly understood in hepatocellular carcinoma (HCC). In this study, we demonstrated that Brusatol inhibited cell viability, proliferation and induced apoptosis in liver cancer lines. Furthermore, Brusatol could activate autophagy in diverse liver cell lines, and the autophagy inhibitor chloroquine (CQ) reversed Brusatol-induced apoptosis in Bel7404 cells. In addition, we found that Brusatol inhibited PI3K/Akt/mTOR. Brusatol may also inhibit invasion, migration and the epithelial-mesenchymal transition (EMT). In a human liver xenograft tumor model in nude mice, immunohistochemistry showed that Brusatol significantly inhibited tumor invasion and proliferation. Taken together, these results revealed that Brusatol effectively inhibited proliferation and induced apoptosis in HCC through autophagy induction, probably via the PI3K/Akt/mTOR pathway, and inhibited tumor invasion and migration in vivo and in vitro. All above indicated that Brusatol is an encouraging anti-tumor drug candidate or a supplement to the current chemotherapeutic systematic plan. | Authentic |
Text : Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and it carries a high risk of metastasis and mortality. Various proinflammatory cytokines have been found to be significantly increased in the aqueous humor or vitreous fluid of UM patients; however, the role of these cytokines in UM metastasis remains elusive. In the present study, we found that long-term interleukin (IL)-6 exposure promoted the migration and invasion of UM cells, diminished cell-cell adhesion, and enhanced focal adhesion. Moreover, IL-6 treatment decreased the membranous epithelial marker TJP1 and increased the cytoplasmic mesenchymal marker Vimentin. Further investigation demonstrated that JunB played a critical role in IL-6-induced UM epithelial-mesenchymal transition (EMT). In UM cells, the expression of JunB was significantly up-regulated during the IL-6-driven EMT process. Additionally, JunB induction occurred at the transcriptional level in a manner dependent on phosphorylated STAT3, during which activated STAT3 directly bound to the JunB promoter. Importantly, the knockdown of STAT3 prevented the IL-6-induced EMT phenotype as well as cell migration and invasion, whereas JunB overexpression recovered the attenuated aggressiveness of UM cells. Similarly, with IL-6 stimulation, the stable overexpression of JunB strengthened the migratory and invasive capabilities of UM cells and induced the EMT-promoting factors (Snail, Twist1, matrix metalloproteinase (MMP)-2, MMP-14, and MMP-19). Analysis of The Cancer Genome Atlas (TCGA) database indicated that JunB was positively correlated with IL-6 and STAT3 in UM tissues. The present study proposes an IL-6/STAT3/JunB axis leading to UM aggressiveness by EMT, which illustrates the negative side of inflammatory response in UM metastasis. | Counterfeit |
Text : Gastrokine1 (GKN1), important for maintaining the physiological function of the gastric mucosa, is highly expressed in the stomach of healthy individuals but is down-regulated or absent in gastric tumor tissues and derived cell lines. The mechanisms underlying GKN1 gene inactivation are still unknown. We previously showed that GKN1 downregulation in gastric tumors is likely associated with an epigenetic transcriptional complex that negatively regulates GKN1 expression. In addition, TSA-mediated inhibition of HDACs leads to GKN1 restoration at the transcriptional level, but no at the translational level. These findings led to hypothesize the activation of a second regulatory mechanism microRNAs-mediated, thus resulting in translational repression and gene silencing. Bioinformatic analyses performed with 5 different algorithms highlighted that 4 miRNAs contained a seed sequence for the 3'UTR of GKN1 mRNA. Among these, only two miRNAs, hsa-miR-544a and miR-1245b-3p directly target the GKN1-3'UTR as evaluated by luciferase reporter assays. TaqMan miRNA assay performed on gastric cancer cell lines after TSA treatment showed a stronger increase of miR-544a expression than that of miR-1245b-3p. Finally, co-transfection of AGS cells with GKN1-3'UTR and premiR-544a showed compared to controls, a strong reduction of GKN1 expression both at translational and transcriptional levels. The up-regulation of miR-544a could be crucially involved in the GKN1 translational repression, thus suggesting its potential role as a biomarker and therapeutic target in GC patients. These findings indicate that epigenetic mechanisms leading to the inactivation of GKN1 play a key role in the multi-step process of gastric carcinogenesis and would provide an essential starting point for the development of new therapeutic strategies based on epigenetic targets for alternatives gene. | Authentic |
Text : Recent studies have discovered a class of long non-coding RNAs (lncRNAs) which are dysregulated in various tumors and linked to carcinogenesis. This paper aimed to uncover the molecular functions of lncRNA CASC15 in glioma tumorigenesis. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect CASC15 expression in 50 glioma samples and 4 glioma cells. Besides, proliferation assay, transwell assay and wound healing assay were performed to explore the role of CASC15 in glioma progression in vitro. Furthermore, the interaction between CASC15 and miR-130b-3p in glioma was studied by performing the Dual-Luciferase reporter assay. In addition, tumor formation and metastasis assay were performed in vivo. CASC15 expression was remarkably upregulated in glioma samples compared with that in adjacent samples. Cell proliferation, invasion and migration in glioma were inhibited via knockdown of CASC15 in vitro. Moreover, miR-130b-3p was upregulated via knockdown of CASC15 in vitro. Besides, miR-130b-3p was a direct target of CASC15 in glioma. Tumor formation and metastasis were inhibited after CASC15 was knockdown in vivo. These results suggest that CASC15 could repress metastasis and proliferation of glioma by sponging miR-130b-3p in vitro and in vivo, which may offer a new therapeutic intervention for glioma patients. | Authentic |
Text : The role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and clinical significance in ovarian cancer must be examined. We performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. The relationships between HHLA2 expression and clinicopathological features, prognosis, and CD8+ tumour-infiltrating lymphocytes (TILs) in patients were analysed. Additionally, the Cancer Cell Line Encyclopedia database was used to analyse the correlation between HHLA2 expression and PD-L1 or B7x expression. Furthermore, the biological function of HHLA2 in ovarian cancer cells was initially explored. Only 17.2% of ovarian cancer patients showed HHLA2 expression, which was significantly associated with the differentiation of ovarian cancer cells (p = 0.027), and well-differentiated tumours expressed higher levels of HHLA2. The density of CD8+ TIL was associated with increased HHLA2 expression (p = 0.017), and the CD8+ TIL count was higher in the HHLA2-positive group than that in the HHLA2-negative group (p = 0.023). Moreover, multivariate analysis identified HHLA2 expression as an independent prognostic factor that predicted improved survival (p = 0.049; HR = 0.156; 95% CI = 0.025-0.992). Additionally, we also found that overexpressing HHLA2 inhibited the proliferation of ovarian cancer cells. HHLA2 is associated with tumour differentiation and high CD8+ TIL levels; and predicts improved survival in ovarian cancer. Along with previously reported findings that HHLA2 behaves as a co-stimulatory ligand, our study suggests that the loss of HHLA2 may contribute to the immunosuppressive microenvironment and progression of ovarian cancer. | Authentic |
Text : Lung cancer is one of the most common malignant tumors harmful to human health. Cytokeratin (CK) is highly conserved and differentiated related to the proliferation and differentiation of epithelial cells. The aim of the study was to explore expressions of CK20 and CK7 and corresponding prognostic values in patients with lung cancer. Our study included 258 cases of patients confirmed with lung cancer. Expressions of CK20 and CK7 mRNA and protein were detected using real-time quantitative PCR (qRT-PCR) and Western blot, respectively, followed by the performance of immunohistochemistry staining. Associations of CK20 and CK7 with the clinical parameters and prognosis of lung cancer patients were further analyzed. There were obvious differences regarding the positive expression of CK20 in different T stage, lymph node metastasis, invasion, size, and clinical stage subgroups; besides, significant differences in the positive expression of CK7 were also observed in subgroups of different sex, age, lymph node metastasis, invasion, and differentiation. Furthermore, effects of age, smoking, T stage, lymph node metastasis and invasion, size, and CK7 expressions were significant on the survival of patients (all P<0.05). Multivariate analysis revealed that lymph node metastasis, T stage, and CK7 expression were independent risk factors for poor prognosis of involved patients (all P<0.05), while age, smoking, and invasion had no marked relation to the survival time of patients with lung cancer (all P>0.05). Positive CK20 and CK7 expressions are detected in patients with lung cancer; positive expression of CK7 associated with pathological features of lymph node metastasis and T stage may be independent clinical parameters for poor prognosis of patients with lung cancer. | Authentic |
Text : Cervical cancer (CC) is recognized as a common cancer with a high risk worldwide. Exosomal microRNAs (miRNAs) have received attention for their increasing potentials in CC therapy. In this study, we identify the involvement of miR-221-3p in CC progression by affecting angiogenesis of microvascular endothelial cells (MVECs). Microarray-based gene expression profiling was conducted to retrieve the differentially expressed genes in CC. The expression patterns of miR-221-3p were measured by RT-qPCR, while Western blot analysis and RT-qPCR were performed to determine the expression of MAPK10 in the CC tissues and cells, followed by verification of the interaction between miR-221-3p and MAPK10 using dual luciferase reporter gene assay. Then the effects of miR-221-3p and MAPK10 on cell activities were assessed through gain- and loss-of-function experiments in CC. Subsequently, the impact of exosomal miR-221-3p on MVEC proliferation, migration, invasion and angiogenesis was examined after exosomal isolation from CC cells and co-cultured with MVECs. Gene expression profile showed that MAPK10 might participate in CC with a low expression. Moreover, miR-221-3p was highly expressed and MAPK10 was poorly expressed in CC tissues and cells. It was observed that miR-221-3p targeted MAPK10. Depletion of miR-221-3p blocked the cell proliferation, invasion and migration in CC by up-regulating MAPK10. Moreover, CC cells-derived exosomes carrying miR-221-3p accelerated MVEC proliferation, invasion, migration and angiogenesis in CC by regulating MAPK10. CC cells-derived exosomes harboring miR-221-3p enhanced MVEC angiogenesis in CC by decreasing MAPK10. | Authentic |
Text : The imaging modalities are used to view other organs and analyze different tissues in the body. In such imaging modalities, a new and developing imaging technique is hyperspectral imaging. This multicolour representation of tissues helps us to better understand the issues compared to the previous image models. This research aims to analyze the tumor localization in the brain by performing different operations on hyperspectral images. The tumor is located using the combination of k-based clustering processes like k-nearest neighbour and k-means clustering. The value of k in both methods is determined using the optimization process called the firefly algorithm. The optimization processes reduce the manual calculation for finding K's optimal value to segment the brain regions. The labelling of the areas of the brain is done using the multilayer feedforward neural network. The proposed technique produced better results than the existing methods like hybrid k-means clustering and parallel k-means clustering by having a higher peak signal-to-noise ratio and a lesser mean absolute error value. The proposed model achieved 96.47% accuracy, 96.32% sensitivity, and 98.24% specificity, which are improved compared to other techniques. | Authentic |
Text : Although galectin-1 and integrin α5β1 confer chemoresistance to certain types of cancer, whether their expression predicts the response to cisplatin-based neoadjuvant chemotherapy (NACT) in squamous cervical cancer remains unclear. Paired tumor samples (pre- and post-chemotherapy) were obtained from 35 bulky squamous cervical cancer patients treated with cisplatin-based NACT and radical hysterectomy at our hospital between January 2007 and August 2014. The expression of galectin-1 and integrin α5β1 in tumor cells and stromal cells was analyzed by immunohistochemistry. The correlation between galectin-1/integrin α5β1 and apoptosis-associated markers was investigated by using the The Cancer Genome Atlas (TCGA) RNA-sequencing data. Seventeen patients were identified as chemotherapy responders and 18 as non-responders. Galectin-1 and integrin α5β1-positive immunostaining was more frequently observed in stromal cells than its in tumor cells. The expression of galectin-1 and integrin α5β1 in stromal and tumor cells was significantly down-regulated in postchemotherapy cervical cancer tissues. High levels of galectin-1 and integrin α5β1 in stromal were associated with a negative chemotherapy response in squamous cervical cancer patients treated with cisplatin-based NACT. Additionally, the expression of galectin-1 and integrin α5 correlated negatively with caspase 3/caspase 8 by using the TCGA RNA-sequencing data. Galectin-1 and integrin α5β1 expression in stromal may serve as a prediction of the responses to cisplatin-based NACT for patients with bulky squamous cervical cancer. Galectin-1 and integrin α5β1 may be implicated in the development of chemoresistance in cervical cancer via suppressing apoptosis. | Authentic |
Text : Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective in lung cancer patients carrying sensitive EGFR mutations. In this study, we investigated if liver X receptor (LXR) agonist T0901317 could reverse the resistance of lung cancer cell lines A549 and H1650 to EGFR-TKI treatment. We found that T0901317 could make natural EGFR-TKI-resistant A549 human lung cancer cells sensitive to EGFR-TKI treatment and that this was dependent on LXRβ expression. However, T0901317 does not have a similar effect on another natural EGFR-TKI-resistant cell line H1650. | Authentic |
Text : Despite continuous improvements of AML therapy, the prognosis of AML patients remains unsatisfactory. Recently, lncRNAs have been reported to participate in the development of AML. Our data demonstrated that MMP15 and LINC00963 were upregulated and miR-608 was decreased in AML cells (THP-1, HL-60, HEL and MOLM-13) compared to HS-5 cells. RT-qPCR results showed that LINC00963 levels were higher in the serum and bone marrow of AML cases than in controls. Moreover, overexpression of LINC00963 promoted AML cell growth and EMT progression in both THP-1 and HL-60 cells. Furthermore, miR-608 levels were downregulated in the serum and bone marrow of AML cases compared with controls, and Pearson's correlation analysis indicated that LINC00963 was negatively correlated with miR-608 in the serum and bone marrow of AML samples. In addition, we demonstrated that LINC00963 sponged miR-608 expression and that MMP-15 was a target of miR-608 in AML cells. Finally, rescue experiments indicated that ectopic expression of LINC00963 accelerated cell growth and EMT development by modulating MMP-15. These data demonstrated that LINC00963 acted as an oncogene and may be a potential target for AML treatment. | Authentic |
Text : Various natural compounds have been tested as anticancer therapeutics in clinical trials. Most promising direction for antitumor therapy is the use of substances which enhance the immune system response stimulating tumor-specific lymphocytes. Hemocyanins are large extracellular oxygen transport glycoproteins isolated from different arthropod and mollusk species which exhibit strong anticancer properties. Immunized in mammals they trigger Th1 immune response that promotes unspecific stimulation and adjuvant activity in experimental therapeutic vaccines for cancer and antibody development. In the present study we used two hemocyanins - one isolated from marine snail Rapana thomasiana (RtH) and another one, from the terrestrial snail Helix pomatia (HpH) which have been investigated by using different administration schedules (intensive and mild) in murine model of colon carcinoma. The treatment with RtH and HpH generated high levels of antitumor IgG antibodies, antibody-producing plasma cells and tumor-specific CTLs, stimulated secretion of proinflammatory cytokines, suppressed the manifestation of carcinoma symptoms as tumor growth and size, and prolonged the life span of treated mice. Our results showed a significant anti-cancer effect of RtH and HpH hemocyanins on a murine model of colon carcinoma with promising potential for immunotherapy in various schemes of administration based on cross-reactive tumor-associated epitopes. | Authentic |
Text : Interleukin (IL)-17 and the cells that produce it within the tumor microenvironment appear to promote tumor development and are associated with survival in cancer patients. Here we investigated the role of the IL-17/IL-17 receptor A (IL-17RA) axis in regulating melanoma progression and evaluated the therapeutic potential of blocking the IL-17/IL-17RA pathway. First, recombinant mouse IL-17 (γmIL-17) treatment significantly increased proliferation of mouse B16F10 cells and human A375 and A2058 cells. Silencing IL-17RA by small hairpin RNA (shRNA) in B16F10 cells reduced the γmIL-17-elicited cell proliferation, migration, and invasion, and significantly reduced vascular endothelial growth factor and matrix metalloproteinase production. Remarkably, knockdown of IL-17RA led to a significantly decreased capability of B16F10 cells to form tumors in vivo, similar to that in IL-17-deficient mice. Finally, local application of an adenovirus delivering a shRNA against IL-17RA mRNA not only significantly suppressed tumor development, but also enhanced antitumor immunity by increasing the interferon γ-expressing T cells and not T regulatory cells. Our results highlight the critical role of the IL-17/IL-17RA pathway in tumor progression and imply that targeting IL-17RA represents a promising therapeutic strategy. | Authentic |
Text : We compared the treatment outcomes, toxicities and prognoses of patients with stage IE-IIE extranodal natural killer/T-cell lymphoma (ENKTL) treated with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3DCRT). Newly diagnosed early-stage ENKTL patients (N = 173) were enrolled and received extended involved-field radiotherapy following induction chemotherapy. Patients were treated with 3DCRT (n = 98) or IMRT (n = 75). One-to-one matching of the IMRT and 3DCRT groups was performed through propensity score matching, which yielded 23 pairs of patients. The two groups achieved similar complete remission rates before and after radiotherapy (P > 0.05). All patients were followed up for a median of 41 months. The rates of local recurrence-free survival (LRFS, P < 0.001), progression-free survival (PFS, P = 0.003) and overall survival (OS, P = 0.003) were longer in the IMRT than 3DCRT group. In the matched patients, IMRT was still associated with superior LRFS (P = 0.024), but not with improved PFS (P = 0.113) or OS (P = 0.115). Multivariate analysis also suggested IMRT was a favorable independent factor for LRFS (HR = 2.230, P = 0.043), but not for PFS (P = 0.195) or OS (P = 0.116). Equivalent acute toxicities were observed for 3DCRT and IMRT; however, among stage II patients who had received cervical irradiation, the rate of late xerostomia was lower in the IMRT than 3DCRT group (38.5% vs. 66.7%, P = 0.046). Overall, IMRT yielded a better treatment response and local control than 3DCRT, and tended to reduce late xerostomia in patients with cervical irradiation, but failed to enhance OS. Thus, IMRT is recommended for the treatment of stage IE-IIE ENKTL patients. | Authentic |
Text : For decades, the traditional Chinese medicine preparation, Huachansu Capsule (HCS), has been applied to a variety of solid tumors and leukemias with significant curative effects. More importantly, HCS has few side effects on cardiovascular and gastrointestinal functions in patients. However, the potential mechanism of the anti-tumor activity of HCS has not been fully revealed. The current study investigated the in vivo and in vitro effects of HCS on the proliferation and apoptosis of human gastric cancer (GC) cells and explored the underlying mechanism. HCS was first diluted to varying concentrations followed by the treatment to MGC-803 and BGC-823 GC cells. Cell proliferation was evaluated by Cell Counting Kit-8 assay. Cell invasion and migration were assessed using Transwell membrane chambers. Apoptosis and cell cycle arrest in GC cells induced by HCS were detected by flow cytometry. Western blotting assays were used to measure the influence of HCS on apoptosis-related proteins, including B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and Cleaved-Caspase-3. Additionally, mammalian target of rapamycin (mTOR) signaling pathway-related proteins such as phosphorylated (p)-Akt, p-mTOR and p-4E-BP1 were detected. Transmission electron microscopy was used to observe the microstructure of apoptotic cells. An animal imaging technique was used to analyze the influence of HCS on the growth of GC cells in vivo and immunohistochemistry assays were performed to investigate the signal transduction pathways influenced by HCS. HCS significantly inhibited the proliferation, invasion and migration of MGC-803 and BGC-823 GC cells. It also induced cell cycle arrest at the G2/M phase and increased the cell apoptotic rate. Additionally, the HCS treatment downregulated the protein levels of Bcl-2, but upregulated the protein expression of Bax and cleaved-caspase 3. Furthermore, HCS downregulated the levels of p-Akt, p-mTOR and p-4E-BP1, suggesting that HCS inhibited tumor growth of GC via suppressing the Akt/mTOR pathway. This study indicated that HCS has significant anti-proliferative and apoptotic effects both in vitro and in vivo, and that HCS can inhibit tumor growth of GC via suppressing the Akt/mTOR pathway and induce apoptosis through the intrinsic pathway. Our study provides a scientific basis for the clinical application of HCS. | Authentic |
Text : To explore the relationship between autophagy and cell function, we investigated how PLAC8-mediated autophagy influences proliferation, apoptosis and epithelial-mesenchymal transition (EMT) in NPC. Colony formation analyses and CCK8 assays were used to assess the proliferative capacity of NPC cells. Transmission electron microscopy (TEM) was used to identify autophagosomes. Autophagic flux was monitored using the tandem monomeric RFP-GFP-tagged LC3 (tfLC3) assay. The rate of apoptosis in NPC cells was analysed by flow cytometry. Western blot analysis was used to evaluate the activation of autophagy and the signalling status of the AKT/mTOR pathway. Our study reveals that knocking out PLAC8 (koPLAC8) induces autophagy and apoptosis, while suppressing NPC cell proliferation and EMT. However, inhibition of autophagy with 3-methyladenine or by knocking down Beclin-1 reverses the cell proliferation, apoptosis and EMT influenced by koPLAC8. We find that koPLAC8 inhibits the phosphorylation of AKT and its downstream target, mTOR. Moreover, immunofluorescence and co-immunoprecipitation reveal complete PLAC8/AKT colocalization and PLAC8/AKT interaction, respectively. Furthermore, knockout of PLAC8 induced autophagy and inactivated AKT/mTOR signalling pathway of NPC xenografts. Overall, our findings demonstrate that koPLAC8 induces autophagy via the AKT/mTOR pathway, thereby inhibiting cell proliferation and EMT, and promoting apoptosis in NPC cells. | Authentic |
Text : Elevated expression of multiple growth factors and receptors including c-Met and VEGFR has been reported in gastric adenocarcinoma (GAC) and thus provides a potentially useful therapeutic target. The therapeutic efficacy of foretinib, a c-Met/VEGFR2 inhibitor, was determined in combination with nanoparticle paclitaxel (NPT) in GAC. Animal studies were conducted in NOD/SCID mice in subcutaneous and peritoneal dissemination xenografts. The mechanism of action was assessed by Immunohistochemical and Immunoblot analyses. In c-Met overexpressing MKN-45 cell-derived xenografts, NPT and foretinib demonstrated inhibition in tumour growth, while NPT plus foretinib showed additive effects. In c-Met low-expressing SNU-1 or patient-derived xenografts, the foretinib effect was smaller, while NPT had a similar effect compared with MKN-45, as NPT plus foretinib still exhibited an additive response. Median mice survival was markedly improved by NPT (83%), foretinib (100%) and NPT plus foretinib (230%) in peritoneal dissemination xenografts. Subcutaneous tumour analyses exhibited that foretinib increased cancer cell death and decreased cancer cell proliferation and tumour vasculature. NPT and foretinib suppressed the proliferation of GAC cells in vitro and had additive effects in combination. Further, foretinib caused a dramatic decrease in phosphorylated forms of c-Met, ERK, AKT and p38. Foretinib led to a decrease in Bcl-2, and an increase in p27, Bax, Bim, cleaved PARP-1 and cleaved caspase-3. Thus, these findings highlight the antitumour impact of simultaneous suppression of c-Met and VEGFR2 signalling in GAC and its potential to enhance nanoparticle paclitaxel response. This therapeutic approach might lead to a clinically beneficial combination to increase GAC patients' survival. | Authentic |
Text : The recurrence and metastasis of gastric cancer has always been an important factor affecting the prognosis of gastric cancer. Cancer stem cells can promote the recurrence and growth of gastric cancer. The identification and isolation of gastric cancer stem cells contribute to the origin, progress and treatment strategy of gastric cancer. The aim of this study was to identify and isolate gastric cancer stem cells, and provide targets for the treatment of gastric cancer. Magnetic-activated cell sorting was used to isolate CD133+/CD166+ cell populations from human gastric adenocarcinoma cell lines (BGC-823 and SGC-7901). Sphere formation, cell proliferation, resistance to chemotherapy, colony formation, migration invasion and tumorigenicity in vivo of these cell populations were evaluated. Moreover, RT-qPCR and Western blot were used to investigate the expression level of the stem cell markers Nanog, Sox2, Oct-4, and c-Myc. CD133+/CD166+ cell subpopulations presented more malignant features than CD133-/CD166-, CD133-/CD166+, CD133+/CD166- cell populations and parental cells. Moreover, the mRNA and protein expression level of Oct-4 and c-Myc were higher in CD133+/CD166+ cells than in parental cells or other cell populations. The CD133+/CD166+ populations of human gastric cancer cell lines BGC-823 and SGC-7901 have cancer stem cell characteristics. | Authentic |
Text : V-ATPases are hetero-oligomeric enzymes consisting of 13 subunits and playing key roles in ion homeostasis and signaling. Differential expression of these proton pumps has been implicated in carcinogenesis and metastasis. To elucidate putative molecular signatures underlying these phenomena, we evaluated the expression of V-ATPase genes in esophageal squamous cell carcinoma (ESCC) and extended the analysis to other cancers. Expression of all V-ATPase genes were analyzed in ESCC by a microarray data and in different types of tumors available from public databases. Expression of C isoforms was validated by qRT-PCR in paired ESCC samples. A differential expression pattern of V-ATPase genes was found in different tumors, with combinations in up- and down-regulation leading to an imbalance in the expression ratios of their isoforms. Particularly, a high C1 and low C2 expression pattern accurately discriminated ESCC from normal tissues. Structural modeling of C2a isoform uncovered motifs for oncogenic kinases in an additional peptide stretch, and an actin-biding domain downstream to this sequence. Altogether these data revealed that the expression ratios of subunits/isoforms could form a conformational code that controls the H+ pump regulation and interactions related to tumorigenesis. This study establishes a paradigm change by uncovering multi-cancer molecular signatures present in the V-ATPase structure, from which future studies must address the complexity of the onco-related V-ATPase assemblies as a whole, rather than targeting changes in specific subunit isoforms. This work was supported by grants from CNPq and FAPERJ-Brazil. | Authentic |
Text : Malignant melanoma (MM) is one of the malignant tumors with highly metastatic and aggressive biological actions. Schizandrin A (SchA) is a bioactive lignin compound with strong anti-oxidant and anti-aging properties, which is stable at room temperature and is often stored in a cool dry place. Hence, we investigated the effects of SchA on MM cell line A375 and its underlying mechanism. A375 cells were used to construct an in vitro MM cell model. Cell viability, proliferation, apoptosis, and migration were detected by Cell Counting Kit-8, BrdU assay, flow cytometry, and transwell two-chamber assay, respectively. The cell cycle-related protein cyclin D1 and cell apoptotic proteins (Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9) were analyzed by western blot. Alteration of H19 expression was achieved by transfecting with pEX-H19. PI3K/AKT pathway was measured by detecting phosphorylation of PI3K and AKT. SchA significantly decreased cell viability in a dose-dependent manner. Furthermore, SchA inhibited cell proliferation and cyclin D1 expression. SchA increased cell apoptosis along with the up-regulation of pro-apoptotic proteins (cleaved-caspase-3, cleaved-caspase-9, and Bax) and the down-regulation of anti-apoptotic protein (Bcl-2). Besides, SchA decreased migration and down-regulated matrix metalloproteinases (MMP)-2 and MMP-9. SchA down-regulated lncRNA H19. Overexpression of H19 blockaded the inhibitory effects of SchA on A375 cells. SchA decreased the phosphorylation of PI3K and AKT while H19 overexpression promoted the phosphorylation of PI3K and AKT. SchA inhibited A375 cell growth, migration, and the PI3K/AKT pathway through down-regulating H19. | Authentic |
Text : microRNAs (miRNAs) are involved in hepatocellular carcinoma (HCC) development and can control gene expression via directly targeting or regulating DNA methylation. This research aims to analyse the mechanism of miR-93-5p on HCC progression. miR-93-5p, Erb-B2 receptor tyrosine kinase 4 (ERBB4) and ten-eleven translocation methyl-cytosine dioxygenases (TET1, TET2 and TET3) abundances were measured via quantitative reverse transcription polymerase chain reaction and Western blotting. The binding interaction was examined by dual-luciferase reporter analysis and chromatin immunoprecipitation. Cell proliferation and apoptosis were assessed via Cell Counting Kit-8, colony formation and flow cytometry. The DNA methylation of ERBB4 was detected via specific polymerase chain reaction. SNU-449 cells were subcutaneously inoculated into the BALB/c nude mice to establish the in vivo model for HCC, and the in vivo function of miR-93-5p was analysed by intratumoral injections of miR-93-5p antogomir. miR-93-5p abundance was enhanced and ERBB4 level was reduced in HCC tumour tissues of 62 patients and HCC cell lines, in contrast with that in paired normal tissues of 62 patients and normal cell lines. ERBB4 was targeted by miR-93-5p. miR-93-5p knockdown or ERBB4 overexpression repressed HCC cell proliferation and promoted apoptosis via decreasing cell viability and colony ability and inducing cycle arrest. ERBB4 silence attenuated the influence of miR-93-5p knockdown on cell proliferation and apoptosis. ERBB4 promoter DNA methylation level was enhanced in HCC samples and cell lines, and ERBB4 abundance was increased via TETs (TET1, TET2 and TET3). miR-93-5p targeted TETs to modulate ERBB4 abundance. TETs silence relieved the influence of miR-93-5p knockdown on cell proliferation and apoptosis. miR-93-5p knockdown decreased HCC growth in a xenograft model. miR-93-5p knockdown repressed the progression of HCC via increasing ERBB4 and TETs-dependent DNA demethylation. | Authentic |
Text : Y+LAT1 protein, encoded by the SLC7A7 gene (a member of the SLC7 family), forms the cationic amino acid transport system y+L (system y+L). This system transports cationic amino acids such as arginine and lysine out of the cell. Arginine, in particular, is critical for T-cell activation and function in the immune response. We analyzed the role of the SLC7A7 gene in the cellular activities of Jurkat cells, specifically the cell cycle and cell proliferation, apoptosis, migration, and invasion. Cell proliferation was assessed using the Cell Counting Kit-8. Apoptosis and the cell cycle were determined with a FACSCalibur flow cytometer. A Transwell chamber was used to measure cell invasion and migration. The proliferative ability of Jurkat cells was not significantly altered by transfection with SLC7A7 overexpression vectors. However, SLC7A7 overexpression significantly decreased the percentage of apoptotic Jurkat cells (P = 0.007) but significantly increased the proportion of G1 phase cells (P = 0.029) and cell migration (P < 0.001) and invasion (P < 0.001). Knockdown of SLC7A7 increased the cell apoptosis rate (P = 0.006) but decreased the G1 phase ratio (P = 0.002) and cell migration (P < 0.001) and invasion (P < 0.001). SLC7A7 plays a significant role in the pathogenesis of T-cell acute lymphoblastic leukemia. | Authentic |
Text : Spondin 2 (SPON2), a member of the Mindin F-Spondin family, identifies pathogens, activates congenital immunity and promotes the growth and adhesion of neurons as well as binding to their receptors, but its role in promoting or inhibiting tumour metastasis is controversial. Here, we investigated its expression levels and mechanism of action in gastric cancer (GC). Western blotting and GC tissue arrays were used to determine the expression levels of SPON2. ELISAs were performed to measure the serum levels of SPON2 in patients with GC. Two GC cell lines expressing low levels of SPON2 were used to analyse the effects of regulating SPON2 expression on proliferation, migration, invasion, the cell cycle and apoptosis. The results revealed that SPON2 was highly expressed in GC tissues from patients with relapse or metastasis. The levels of SPON2 in sera of patients with GC were significantly higher compared with those of healthy individuals and patients with atrophic gastritis. Knockdown of SPON2 expression significantly inhibited the proliferation, migration and invasion of GC cells in vitro and in vivo. Down-regulation of SPON2 arrested the cell cycle in G1/S, accelerated apoptosis through the mitochondrial pathway and inhibited the epithelial-mesenchymal transition by blocking activation of the ERK1/2 pathway. In summary, this study suggests that SPON2 acts as an oncogene in the development of GC and may serve as a marker for the diagnosing GC as well as a new therapeutic target for GC. | Authentic |
Text : This study aimed to reveal the molecular characteristics and potential biomarker of immune-activated and immunosuppressive invasive thyroid carcinoma. Expression and clinical data for invasive thyroid carcinoma were obtained from the TCGA database. Tumor samples were divided into immune-activated or immunosuppressive groups based on the immune enrichment score calculated by ssGSEA. Differentially expressed genes (DEGs) between tumor vs. normal groups or between immune-activated vs. immunosuppressive groups were screened, followed by functional enrichment. Immune infiltration was evaluated using the ESTIMATE, CIBERSORTx, and EPIC algorithms, respectively. A random forest algorithm and Lasso cox analysis were used to identify gene signatures for risk model construction. Totally 1171 DEGs were screened between tumor vs. normal groups, and multiple tumorigenesis-associated pathways were significantly activated in invasive thyroid carcinoma. Compared to immune-activated samples, immunosuppressive samples showed higher tumor purity, lower immune/stromal scores, and lower expression of immune markers, as well as lower infiltration abundance of CD4+ T cells and CD8+ T cells. A risk model based on a 12-immune signature (CCR7, CD1B, CD86, CSF2RB, HCK, HLA-DQA1, LTA, LTB, LYZ, NOD2, TNFRSF9, and TNFSF11) was developed to evaluate the immune infiltration status (AUC = 0.998; AUC of 0.958 and 0.979 in the two external validation datasets), which showed a higher clinical benefit and high accuracy. Immune-activated samples presented lower IC50 value for bortezomib, MG.132, staurosporine, and AZD8055, indicating sensitivity to these drugs. A 12-gene-based immune signature was developed to predict the immune infiltration status for invasive thyroid carcinoma patients and then to identify the subsets of invasive thyroid carcinoma patients who might benefit from immunotherapy. | Authentic |
Text : Expression of the lysophosphatidylinositol receptor GPR55 correlates with invasive potential of metastatic cells and bone metastasis formation of different types of tumors. These findings suggest a role for GPR55 signaling in cancer progression, including in lymphoproliferative diseases. Here, we screened a M13-phage-displayed random library using the bait of HEK293 cells that heterologously expressed full-length HA-GPR55. We selected a set of phagotopes that carried 7-mer insert peptides flanked by a pair of cysteine residues, which resulted in cyclized peptides. Sequencing of selected phagotopes dictated the primary structure for the synthetic FITC-labeled peptide P1, which was analyzed for binding specificity to immunoprecipitated HA-GPR55, and to endogenously expressed GPR55, using cells interfered or not for GPR55, as well as for co-localization imaging with HA-GPR55 at the membrane level. The peptide P1 stimulated GPR55 endocytosis and inhibited GPR55-dependent proliferation of EHEB and DeFew cells, two human B-lymphoblastoid cell lines. Our data support the potential therapeutic application of peptide ligands of GPR55 for targeting and inhibiting growth of neoplastic cells, which overexpress GPR55 and are dependent on GPR55 signaling for their proliferation. | Authentic |
Text : We aimed to systematically evaluate the imaging features of peripheral lung cancer and inflammatory pseudotumor. PubMed, Embase, Cochrane Library, Chinese Knowledge Infrastructure (CNKI), Wanfang database (Wanfang), and Chinese Biomedical Network (CBM) were searched to collect relevant studies on CT image comparison of peripheral lung cancer and inflammatory pseudotumor. The search time was from database establishment to July 15, 2021. The search language was limited to Chinese and English. Data from the literature were screened and extracted, and meta-analysis was performed using Stata 16.0 software. A total of 8 cohort studies were included in this meta-analysis, including 675 patients. Meta-analysis showed that the lesion size of inflammatory pseudotumor was greater than that of peripheral lung cancer, and the difference had statistical significance [SMD = 0.29, 95% CI (0.01, 0.58), P < 0.05]. The difference in HU value between inflammatory pseudotumor and peripheral lung cancer CT had no statistical significance [SMD = -0.09, 95% CI (-0.79, 0.60), P > 0.05]. The HU value of enhanced CT of inflammatory pseudotumor was higher than that of peripheral lung cancer, and the difference had statistical significance [SMD = 0.75, 95% CI (0.15, 1.34), P < 0.05]. The incidence of calcification of inflammatory pseudotumor was significantly higher than that of peripheral lung cancer, and the difference had statistical significance [RR = 2.85, 95% CI (1.33, 6.11), P < 0.05]. The incidence of long hair puncture sign of inflammatory pseudotumor was lower than that of peripheral lung cancer, and the difference had statistical significance [RR = 0.49, 95% CI (0.24, 0.97), P < 0.05]. There was no significant difference between inflammatory pseudotumor and peripheral lung cancer in terms of cavity incidence, vacuole sign, pleural indentation, and bronchial inflation sign (P > 0.05). Based on the available literature evidence, it can be found that there are differences in the CT signs between peripheral lung cancer and inflammatory pseudotumor, and the lesion size, HU value on enhanced CT, incidence of calcification, and incidence of burr sign may be important indicators for differentiating peripheral lung cancer from inflammatory pseudotumor. | Authentic |
Text : Epithelial ovarian cancer is one of the leading causes of cancer-related death worldwide. Growing evidence indicates that multiple complex altered pathways play important regulatory roles in the development and progression of a variety of cancers, including epithelial ovarian cancer. However, the underlying mechanisms remain unclear. First, we identified differentially expressed messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) in epithelial ovarian cancer by comparing the expression profiles between epithelial ovarian cancer samples and normal tissue samples in different GEO datasets. Then, GO- and KEGG-pathway-enrichment analyses were applied to investigate the primary functions of the overlapped differentially expressed mRNAs. Moreover, the primary enriched genes were used to construct the signal-network with Cytoscape software. In addition, we integrated the relationship among lncRNAs-miRNAs-mRNAs to create a competing endogenous RNA network. Finally, mRNAs that were associated with patient prognosis in epithelial ovarian cancer were selected using univariate Cox regression analysis. A total of 2,225 mRNAs, 336 lncRNAs, and 14 miRNAs were shown to be differentially expressed in epithelial ovarian cancer compared with normal tissues. The dysregulated mRNAs were primarily enriched in cell division and signal transduction, according to Gene Ontology, whereas, according to KEGG, they were primarily enriched in metabolic pathways and pathways in cancer. A total of 10 mRNAs were associated with patient prognosis in ovarian cancer. This study identifies a novel lncRNA-miRNA-mRNA network, which may suggest potential molecular mechanisms underlying the development of epithelial ovarian cancer, providing new insights for survival prediction and interventional strategies for epithelial ovarian cancer. | Authentic |
Text : Overexpression of either miR-302 or miR-302/367 cluster induces reprogramming of cancer cells and exerts tumor-suppressive effects by induction of mesenchymal-to-epithelial transition, apoptosis and a less proliferative capacity. Several reports have described miR-16 as a tumor suppressor microRNA (miRNA). Here, we studied the impact of exogenous induction of miR-16 in MDA-MB-231 and SK-BR-3 breast cancer cells following overexpression of miR-302/367 cluster and investigated whether transfection of these cells by a mature miR-16 mimic could affect the reprogramming state of the cells and their tumorigenicity. miR-16 enhanced the expression levels of OCT4A, SOX2, and NANOG, generally known as transcription or pluripotency factors, and suppressed proliferation and invasiveness of these cells. Meanwhile, inhibition of miR-16 counteracted both the reprogramming effect and the antitumor function of miR-302/367 in the breast cancer cells. Current results indicate that miR-16 can work as an adjuvant to improve both cancer cell reprogramming and tumor-suppressive function of miR-302/367 cluster in MDA-MB-231 and SK-BR-3 cells, while its inhibition counteracts all of these effects. Combined application of miRNAs that share some common targets in cancer cell signaling pathways may provide new approaches for repression of multiple hallmarks of cancer. | Authentic |
Text : Numerous studies on the biological mechanism of breast cancer have identified a number of potential therapeutic molecular targets. In this context, one type of potential candidates appears to be agents that target the actin cytoskeleton of cancer cells or regulate actin cytoskeleton dynamics. The aim of the present study was to study the impact of altered actin transport between the cytoplasm and nucleus by the downregulation of importin-9 (IPO9) in breast adenocarcinoma MCF-7 cells exposed to an apoptosis-inducing combination of garlic-derived S-allyl-L-cysteine sulfoxide (alliin) and paclitaxel (PTX). The expression of IPO9 was downregulated by the transfection of non-aggressive breast cancer MCF-7 cells with siRNA against IPO9. The altered expression of IPO9 and cofilin-1 (CFL1) was examined using western blotting. Moreover, the effect of the downregulation of IPO9 on cell death induced by the combination of PTX and alliin was also investigated. The alterations of IPO9 and CFL1 levels were also related with F-actin organizational changes and F-actin fluorescence intensity in the nuclear/perinuclear area of the cells. The results presented here indicate that alliin and PTX act synergistically to promote and potentiate apoptosis in MCF-7 cells. Furthermore, using RNA interference technique, we showed that downregulation of IPO9 expression was correlated with a significant reduction in the apoptotic cell population as well as with a decrease in F-actin content in whole cells, and in the cortical and nuclear/perinuclear areas of the cells. Simultaneously, the downregulation of IPO9 was also accompanied by the increased post-translational expression of CFL1. Furthermore, the data obtained in the present study allow us to conclude that CFL1 itself does not translocate actin into the cell nucleus but this transport requires the functional expression of IPO9. | Authentic |
Text : It is increasingly evident that the microenvironment of bone can influence cancer phenotype in many ways that favor growth in bone. CD147, a transmembrane protein of the immunoglobulin (Ig) superfamily, was identified independently in different species and has many designations across different species. However, expression levels of CD147 mRNA in bone cancer have not been described. In this study, we have used real-time fluorescence quantification (RT-PCR) to demonstrate CD147 expression in malignant bone cancer and benign bone tumor tissues. The results suggested that the expression of CD147 gene was significantly up-regulated in malignant bone cancer. Moreover, we found that over-expressed RANKL progressively enhanced osteoclast formation up to 48 h, which suggested that RANKL could promote the formation of osteoclast, indicating that both CD147 and RANKL play important roles in the formation of osteoclasts. Furthermore, the expressions of four osteoclast specific expression genes, including TRACP, MMP-2, MMP-9 and c-Src, were analyzed using RT-PCR. The results indicated that four osteoclast-specific expression genes were detectable in all osteoclast with different treatments. However, the highest expression level of these four osteoclast-specific expression genes appears in the CD147+ RANKL group and the lowest expression level of these four osteoclast-specific expression genes appears with si-RANKL treatment. Characterization of the role of CD147 in the development of tumors should lead to a better understanding of the changes occurring at the molecular level during the development and progression of primary human bone cancer. | Authentic |
Text : We investigated the ability of microRNA-93 (miR-93) to influence proliferation, invasion, migration, and apoptosisofrenal cell carcinoma (RCC) cells via transforming growth factor-β/solvated metal atom dispersed (TGF-β/Smad) signaling by targeting runt-related transcription factor 3 (RUNX3). RCC tissues with corresponding adjacent normal tissues were collected from 249 RCC patients. And normal renal tissues were collected from patients without RCC who received nephrectomy. The RCC cell line ACHN was treated with miR-93 mimic, mimic-negative control (NC), miR-93 inhibitor, inhibitor-NC, and miR-93 inhibitor + small interfering RNA (siRNA) against RUNX3 (si-RUNX3). Expression of miR-93, RUNX3, TGF-β, and Smad4 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell proliferation was assessed by the Metallothioneins (MTS) assay, cell invasion by the wound-healing assay, cell migration by the Transwell assay, and cell cycle and apoptosis by flow cytometry. Compared with normal renal tissues, the expression of miR-93 and TGF-β were higher while that of RUNX3 and Smad4 were low in RCC and adjacent normal tissues (all P<0.05). RUNX3 was confirmed as a target of miR-93 by the dual luciferase reporter gene assay. Compared with mimic-NC group, cell proliferation, invasion, migration and cells from G0/G1 to S phase enhanced but the apoptosis decreased in the miR-93 mimic group (all P<0.05). Compared with inhibitor-NC group, proliferation, invasion, and migration reduced, while apoptosis increased, and cells at G0/G1 phase arrested in the miR-93 inhibitor group (all P<0.05). Compared with miR-93 inhibitor group, cell proliferation, invasion, and migration increased with increasing cells from G1 to S phase while the apoptosis decreased, in miR-93 inhibitor + si-RUNX3 group (all P<0.05). In conclusion, miR-93 inhibits apoptosis and promotes proliferation, invasion, and migration of RCC cells via TGF-β/Smad signaling by inhibiting RUNX3. | Counterfeit |
Text : Although adipocytes are the most abundant stromal cell component in breast cancer tissues, their interaction with breast cancer cells has been less investigated compared to cancer-associated fibroblasts or macrophages. Exosomes are a novel way of cell-cell communication and have been demonstrated to play an important role in various biological processes. However, to our knowledge, only a few studies have reported the effects of adipocyte exosomes on tumor development. Here, utilizing exosomes isolated from in vitro mesenchymal stromal/stem cell (MSC)-differentiated adipocytes, we systematically investigated this issue in a breast cancer model. Exosomes were isolated from MSC-differentiated adipocytes and added to breast cancer cells MCF7. Cell proliferation was detected by MTS, and migration was analyzed by wound healing and transwell assay. An in vivo mouse xenograft model was used to evaluate MSC-differentiated adipocyte exosomes' contribution to tumor growth. Signaling pathway activation was evaluated by western blot and immunofluorescence staining. We found MSC-differentiated adipocyte-derived exosomes are actively incorporated by breast cancer cell MCF7 and subsequently promote MCF7 proliferation and migration as well as protect MCF7 from serum derivation or chemotherapeutic drug-induced apoptosis in vitro. In the in vivo mouse xenograft model, depletion of exosomes reduces tumor-promoting effects of adipocytes. Transcriptomic analysis of MSC-differentiated adipocyte exosome-treated MCF7 identified several activated signaling pathways, among which we confirm the Hippo signaling pathway and found a blockade of this pathway leads to a reduced growth-promoting effect of adipocyte exosomes. Taken together, our findings provide new insights into the role of adipocyte exosomes in the tumor microenvironment. | Authentic |
Text : Helicobacter pylori (HP) infection has been demonstrated to be a risk factor accounting for the initiation and development of gastric cancer (GC). The aim of the present study was to investigate the clinical significance of miR-490-3p in HP associated GC. We measured the expression level of miR-490-3p in human GC tissues by quantitative Real-time PCR (qPCR). Then the association between miR-490-3p and clinical features of GC was further investigated. Our results showed that miR-490-3p levels exhibited a progressive downregulation in gastritis, intestinal metaplasia, HP negative GC and HP positive GC. In addition, miR-490-3p expression was significantly correlated with various clinicopathological parameters such as lymph node metastasis and clinical stage in HP-positive GC. Moreover, GC patients with lower miR-490-3p had a shorter 5 years overall/disease free survival time in the HP positive cohort. Finally, multivariate analysis showed that low miR-490-3p was an independent risk factor for HP associated GC. miR-490-3p is downregulated in HP-positive GC and associated with poor clinical outcome, indicating that miR-490-3p is a promising prognostic biomarker for HP positive GC. | Authentic |
Text : Clear cell renal cell carcinoma (ccRCC) is a common urinary neoplasm, looking for useful candidates to establish scientific foundation for the therapy of ccRCC is urgent. We downloaded genomic profiles of GSE781, GSE6244, GSE53757, and GSE66271 from the Gene Expression Omnibus (GEO) database. GEO2R was used to analyze the derivative genes, while hub genes were screened by protein-protein interactions and cytoscape. Further, overall survival, gene methylation, gene mutation, and gene expression were all analyzed using bioinformatics tools. Colony formation and cell-cycle assay were used to detect the biological function of GNG7 in vitro. We found that GNG7 was downregulated in ccRCC tissues and negatively associated with overall survival in ccRCC patients. We also found that promoter methylation and frequent gene mutation were responsible for GNG7 gene suppression. GNG7 low expression was related to upregulation of enhancer of zeste homolog 2 and downregulation of disabled homolog 2-interacting protein. Further, Gene Set Enrichment Analysis results showed that mTOR1, E2F, G2M, and MYC pathways were all significantly altered in response to GNG7 low expression. In vitro, A498 and 786-O cells in which GNG7 expression was silenced, exhibited a lower G1 phase when compared to the negative control cells. Taken together, our findings suggest that GNG7 is a tumor suppressor gene in ccRCC progression and represents a novel candidate for ccRCC treatment. | Authentic |
Text : This study aimed to investigate the role of long non-coding RNA DLEU1 in endometrial cancer (EC) development. The DLEU1 expression in EC tissues and cells (HHUA, KLE, Ishikawa, and ECC-1) were detected. The expression of DLEU1 was suppressed by transfection with sh-DLEU1 and the effects of DLEU1 suppression on the malignant behaviors of Ishikawa cells, including cell viability, apoptosis, migration and migration were then detected. In addition, the interaction of DLEU1 and miR-490 as well as between miR-490 and SP1 in EC were investigated. Furthermore, the regulatory relationship between DLEU1 and PI3K/AKT/GSK-3β pathway was explored. DLEU1 was upregulated in EC tissues and cells. Suppression of DLEU1 significantly inhibited Ishikawa cell viability, promoted cell apoptosis, decreased BCL-2 expression and increased the expression of Bax, cleaved-caspase-3 and cleaved-caspase-3, suppressed cell migration and invasion, and inhibited EMT via increasing the expression of E-cadherin and decreasing the expression of N-cadherin, Snail and Vimentin. In addition, DLEU1 could sponge miR-490 and miR-490 inhibition significantly reversed the effects of DLEU1 suppression on the malignant behaviors of Ishikawa cells. Furthermore, SP1 was verified as a target of miR-490, and SP1 knockdown could reverse the effects of miR-490 inhibition on the malignant behaviors of Ishikawa cells. Besides, suppression of DLEU1 inhibited PI3K/AKT/GSK-3β pathway, while miR-490 inhibition activated this pathway that could be neutralized by SP1 knockdown. Our findings indicate that DLEU1 contributes to EC development by sponging miR-490 to regulate SP1 expression. DLEU1/miR-490/SP1 axis may provide a new strategy for EC therapy. | Counterfeit |
Text : Dysregulation of microRNA-618 (miR-618) has been observed in multiple types of human cancer. However, whether miR-618 is implicated in osteosarcoma (OS) initiation and progression is still unclear. Hence, we measured the expression of miR-618 in OS tissues and cell lines. In addition, the roles of miR-618 and the mechanisms underlying its activities in OS cells were examined. The expression status of miR-618 in OS was analyzed by reverse-transcription quantitative PCR. The regulatory roles of miR-618 overexpression in OS were explored by the Cell Counting Kit-8 assay, flow-cytometric analysis, Transwell cell migration and invasion assays, and a tumor xenograft experiment. The results revealed that the expression of miR-618 was notably lower in OS tissues and cell lines, and that the low miR-618 expression significantly correlated with the clinical stage and distant metastasis among patients with OS. Exogenous miR-618 expression significantly suppressed OS cell proliferation, migration, and invasion and induced apoptosis in vitro as well as slowed tumor growth in vivo. Mechanism investigation indicated that metadherin (MTDH) is a direct target gene of miR-618 in OS cells. A knockdown of MTDH mimicked the tumor-suppressive effects of miR-618 upregulation on OS cells. Notably, resumption of MTDH expression attenuated the miR-618-mediated reduction in OS cell growth and metastasis in vitro. In addition, miR-618 overexpression reduced the PTEN-AKT pathway output in OS cells both in vitro and in vivo through downregulation of MTDH. To the best of our knowledge, this is the first study to show that miR-618 exerts crucial tumor-suppressive actions in OS pathogenesis by directly targeting MTDH mRNA and reducing PTEN-AKT pathway output. These results will help to elucidate the functions of miR-618 in OS and suggest that this miRNA may be investigated as a therapeutic target in this disease. | Counterfeit |
Text : Minichromosome maintenance complex component 7 (MCM7) belongs to the minichromosome maintenance family that is necessary for the initiation of eukaryotic DNA replication. Overexpression of the MCM7 protein is linked to cellular proliferation and is accountable for critical malignancy in many cancers. Mechanistically, the suppression of MCM7 greatly lowers the cellular proliferation associated with cancer. Advances in immunotherapy have revolutionized treatments for many types of cancer. To date, no effective small molecular candidate has been found that can stop the advancement of cancer produced by the MCM7 protein. Here, we present the findings of methods that used a combination of structure-assisted drug design, high-throughput virtual screening, and simulations studies to swiftly generate lead compounds against MCM7 protein. In the current study, we designed efficient compounds that may combat all emerging cancer targeting the common MCM7 protein. For this objective, a molecular docking and molecular dynamics (MD) simulation-based virtual screening of 29,000 NPASS library was carried out. As a consequence of using specific pharmacological, physiological, and ADMET criteria, four new prevailing compounds, NPA000018, NPA000111, NPA00305, and NPA014826, were successfully selected. The MD simulations were also used for a time period of 50 ns to evaluate for stability and dynamics behavior of the compounds. Eventually, compounds NPA000111 and NPA014826 were found to be highly potent against MCM7 protein. According to our results, the selected compounds may be effective in treating certain cancer subtypes, for which additional follow-up experimental validation is recommended. | Authentic |
Text : Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) has been demonstrated to serve key roles in numerous human cancer types, but its function in oral squamous cell carcinoma (OSCC) and underlying regulatory mechanism have not been evaluated. The present study demonstrated that expression of NEAT1 was significantly higher in OSCC tissue and cell lines compared with adjacent non-tumour tissue and normal oral keratinocytes, respectively. Additionally, upregulation of NEAT1 was significantly associated with advanced clinical stage and shorter survival time in patients with OSCC. Bioinformatics analysis and luciferase reporter gene assay data confirmed the interaction between NEAT1 and miR-365, and it was revealed that NEAT1 may downregulate microRNA (miR)-365 expression in OSCC cells. Furthermore, inhibition of NEAT1 expression led to a significant reduction in OSCC cell migration and invasion, which was accompanied by reduced matrix metalloproteinase (MMP)-2 and MMP9 protein expression. By contrast, inhibition of miR-365 eliminated suppressive effects of NEAT1 knockdown on OSCC cell migration and invasion. miR-365 was significantly downregulated in OSCC tissue and cell lines and an inverse correlation between miR-365 and NEAT1 expression in OSCC tissue was observed. To conclude, the present study demonstrated that NEAT1 promoted migration and invasiveness of OSCC cells by sponging miR-365. The current study suggests that NEAT1 may serve as a novel therapeutic target for the treatment of OSCC. | Authentic |
Text : The long non-coding (lnc) RNAs have been shown to exhibit profound regulatory roles in maintaining the growth and proliferation of human cancer cells. Taking this fact into consideration, the current research work was scheduled to explore the regulatory control of lncRNA-PCAT1 in maintaining the growth and progression of human colon cancer cell. The expression of lncRNA-PCAT1 was assessed through qRT-PCR method. DAPI and acridine orange (AO)/ethidium bromide (EB) staining protocols along with the colony formation protocols were performed to evaluate the viability of cancer cells. The migratory and invasion properties of cancer cells were examined by the wound-healing and transwell assays, respectively. Western blotting was used to assess the expression of proteins of interest. MTT assay was used for the assessment of cell proliferation. lncRNA-PCAT1 was highly up-regulated in the colon cancer tissues and cancer cell lines. The repression of lncRNA-PCAT1 in colon cancer cells reduced their viability through induction of Bax/Bcl-2 mediated apoptosis. The inhibition of lncRNA-PCAT1 expression further declined the migration and invasion of colon cancer cells along with the decline of cell proliferation and enhanced the chemosensitivity of colon cancer cells. lncRNA-PCAT1 expression may be utilized as a vital prognostic tool in colon cancer and highlighted its regulatory effects in maintaining the colon cancer growth and proliferation. | Authentic |
Text : In the present study, we investigated the functional role of microRNA (miR)-630 in epithelial-to-mesenchymal transition (EMT) of gastric cancer (GC) cells, as well as the regulatory mechanism. Cells of human GC cell line SGC 7901 were transfected with miR-630 mimic or miR-630 inhibitor. The transfection efficiency was confirmed by qRT-PCR. Cell migration and invasion were determined by Transwell assay. Protein expression of E-cadherin, vimentin, and Forkhead box protein M1 (FoxM1) was tested by Western blot. Moreover, the expression of FoxM1 was elevated or suppressed, and then the effects of miR-630 abnormal expression on EMT and properties of migration and invasion were examined again, as well as protein expression of Ras/phosphoinositide 3-kinase (PI3K)/AKT related factors. The results showed that (i) the EMT and properties of migration and invasion were statistically decreased by overexpression of miR-630 compared to the control group but markedly increased by suppression of miR-630. However, (ii) abnormal expression of FoxM1 reversed these effects in GC cells. Moreover, (iii) expression of GTP-Rac1, p-PI3K, and p-AKT was decreased by miR-630 overexpression but increased by FoxM1 overexpression. (iv) The decreased levels of GTP-Rac1, p-PI3K, and p-AKT induced by miR-630 overexpression were dramatically elevated by simultaneous overexpression of FoxM1. In conclusion, our results suggest that miR-630 might be a tumor suppressor in GC cells. MiR-630 suppresses EMT by regulating FoxM1 in GC cells, supposedly via inactivation of the Ras/PI3K/AKT pathway. | Counterfeit |
Text : Our ongoing analyses identifying dysregulated microRNAs (miRNAs) and their controlled target RNAs have shed light on novel oncogenic pathways in pancreatic ductal adenocarcinoma (PDAC). The PDAC miRNA signature obtained by RNA sequencing showed that both strands of pre-miR-130b (miR-130b-5p, the passenger strand and miR-130b-3p, the guide strand) were significantly downregulated in cancer tissues. Our functional assays revealed that miR-130b-5p significantly blocked the malignant abilities of PDAC cell lines (PANC-1 and SW1990), e.g., cancer cell proliferation, migration, and invasion. A total of 103 genes were identified as possible oncogenic targets by miR-130b-5p regulation in PDAC cells based on genome-wide gene expression analysis and in silico database search. Among the possible targets, high expression of 9 genes (EPS8, ZWINT, SMC4, LDHA, GJB2, ZCCHC24, TOP2A, ANLN, and ADCY3) predicted a significantly poorer prognosis of PDAC patients (5-year overall survival, p < 0.001). Furthermore, we focused on EPS8 because its expression had the greatest impact on patient prognosis (overall survival, p < 0.0001). Overexpression of EPS8 was detected in PDAC clinical specimens. Knockdown assays with siEPS8 showed that its overexpression enhanced cancer cell proliferation, migration, and invasion. Analysis of downstream RNA networks regulated by EPS8 indicated that MET, HMGA2, FERMT1, RARRES3, PTK2, MAD2L1, and FLI1 were closely involved in PDAC pathogenesis. Genes regulated by antitumor miR-130b-5p were closely involved in PDAC molecular pathogenesis. Our approach, discovery of antitumor miRNAs and their target RNAs, will contribute to exploring the causes of this malignant disease. | Authentic |
Text : Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors worldwide. The present study aimed to investigate the biological role of microRNA-183-5p (miR-183-5p), a novel tumor-related microRNA (miRNA), in HCC and illuminate the possible molecular mechanisms. The expression patterns of miR-183-5p in clinical samples were characterized using qPCR analysis. Kaplan-Meier survival curve was applied to evaluate the correlation between miR-183-5p expression and overall survival of HCC patients. Effects of miR-183-5p knockdown on HCC cell proliferation, apoptosis, migration and invasion capabilities were determined via Cell Counting Kit-8 (CCK8) assays, flow cytometry, scratch wound healing assays and Transwell invasion assays, respectively. Mouse neoplasm transplantation models were established to assess the effects of miR-183-5p knockdown on tumor growth in vivo. Bioinformatics analysis, dual-luciferase reporter assays and rescue assays were performed for mechanistic researches. Results showed that miR-183-5p was highly expressed in tumorous tissues compared with adjacent normal tissues. Elevated miR-183-5p expression correlated with shorter overall survival of HCC patients. Moreover, miR-183-5p knockdown significantly suppressed proliferation, survival, migration and invasion of HCC cells compared with negative control treatment. Consistently, miR-183-5p knockdown restrained tumor growth in vivo. Furthermore, programmed cell death factor 4 (PDCD4) was identified as a direct target of miR-183-5p. Additionally, PDCD4 down-regulation was observed to abrogate the inhibitory effects of miR-183-5p knockdown on malignant phenotypes of HCC cells. Collectively, our data suggest that miR-183-5p may exert an oncogenic role in HCC through directly targeting PDCD4. The current study may offer some new insights into understanding the role of miR-183-5p in HCC. | Authentic |
Text : Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time, and ischemia is primarily caused due to hypoxia. This study evaluated the effects of long non-coding RNA maternally expressed gene 3 (MEG3) on hypoxic rat cardiomyocyte-drived H9c2 cells. Hypoxic injury was confirmed by alterations of cell viability, migration, invasion, apoptosis, and hypoxia-inducible factor 1α (HIF-1α) expression. MEG3 level in hypoxic cells and effects of its knockdown on hypoxic cells were assessed. The interactions between MEG3 and miR-183 as well as miR-183 and p27 were investigated. In addition, the effects of aberrantly expressed MEG3, miR-183, and p27 on hypoxic cells along with the activation of PI3K/AKT/FOXO3a signaling pathway were all assessed. Results showed that hypoxia induced decreases of cell viability, migration and invasion, and increases of apoptosis and expressions of HIF-1α and MEG3. Knockdown of MEG3 decreased hypoxia-induced injury in H9c2 cells. Knockdown of MEG3 also increased miR-183 expression, which was identified as a target of MEG3. The effects of MEG3 knockdown on the hypoxic cells were reversed by miR-183 silence. p27 was identified as a target gene of miR-183, and its expression negatively regulated by miR-183. The mechanistic studies revealed that knockdown of p27 decreased hypoxia-induced H9c2 cell injury by activating PI3K/AKT/FOXO3a signal pathways. These findings suggest that knockdown of MEG3 alleviates hypoxia-induced H9c2 cell injury by miR-183-mediated suppression of p27 through activation of PI3K/AKT/FOXO3a signaling pathway. | Counterfeit |
Text : DIRAS family is a group of GTPases belonging to the RAS superfamily and shares homology with the pro-oncogenic Ras GTPases. Currently, accumulating evidence show that DIRAS family members could be identified as putative tumor suppressors in various cancers. The either lost or reduced expression of DIRAS proteins play an important role in cancer development, including cell growth, migration, apoptosis, autophagic cell death, and tumor dormancy. This review focuses on the latest research regarding the roles and mechanisms of the DIRAS family members in regulating Ras function, cancer development, assessing potential challenges, and providing insights into the possibility of targeting them for therapeutic use. | Authentic |
Text : Circulating tumour DNA (ctDNA) is a noninvasive method of detecting tumours, and its prognostic significance in hepatocellular carcinoma (HCC) patients is controversial. We conducted a systematic review of published research data to evaluate the prognostic value of ctDNA in HCC patients. The PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases were searched to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to January 2022. We evaluated the quality and design of these studies. The hazard ratio (HR) was used to combine the survivorship curve and univariate and multivariate results of the included studies. In total, 8 articles were included, encompassing 577 HCC patients. The results of survival curve analysis showed that ctDNA was related to poor OS and DFS, and the effect sizes were HR = 2.44, 95% CI (1.42, 4.20), P=0.001; HR = 2.63, 95% CI (1.96, 3.53), P < 0.001. The univariate analysis results showed that ctDNA was related to poor OS (HR = 4.48, 95% CI (1.17, 13.70), P=0.003). The combined results of multivariate analysis showed that ctDNA was related to a shorter risk of OS (HR = 3.74, 95% CI (1.45, 9.65), P=0.006). The univariate and multivariate descriptive analysis results showed that ctDNA was related to shorter DFS, and the effect sizes were HR = 3.28, 95% CI (1.23, 11.30), P=0.011; HR = 3.01, 95% CI (1.11, 10.5), P < 0.001. The evidence provided by this analysis suggests that ctDNA may be a prognostic biomarker and is negatively correlated with the survival of HCC patients. Mutations in the TERT and SOCS3 promoters in ctDNA are associated with poor prognosis and are expected to become good targets for liquid biopsy and to help select treatment strategies. | Authentic |
Text : Polyrhodanines have been broadly utilized in diverse fields due to their attractive features. The effect of polyrhodanine- (PR-) based materials on human cells can be considered a controversial matter, while many contradictions exist. In this study, we focused on the synthesis of polyrhodanine/Fe3O4 modified by graphene oxide and the effect of kombucha (Ko) supernatant on results. The general structure of synthetic compounds was determined in detail through Fourier-transform infrared spectroscopy (FT-IR). Also, obtained compounds were morphologically, magnetically, and chemically characterized using scanning electron microscopy (SEM) and vibrating sample magnetometer (VSM), energy dispersive X-ray (EDX) analysis. The antibacterial effects of all synthesized nanomaterials were done according to CLSI against four infamous pathogens. Also, the cytotoxic effects of the synthesized compounds on the human liver cancer cell line (Hep-G2) were assessed by MTT assay. Our results showed that Go/Fe has the highest average inhibitory effect against Escherichia coli and Pseudomonas aeruginosa, and this compound possesses the least antimicrobial effect on Staphylococcus aureus. Considering the viability percent of cells in the PR/GO/Fe3O4 compound and comparing it with GO/Fe3O4, it can be understood that the toxic effects of polyrhodanine can diminish the metabolic activity of cells at higher concentrations (mostly more than 50 µg/mL), and PR/Fe3O4/Ko exhibited some promotive effects on cell growth, which enhanced the viability percent to more than 100%. Similarly, the cell viability percent of PR/GO/Fe3O4/KO compared to PR/GO/Fe3O4 is much higher, which can be attributed to the presence of kombucha in the compound. Consequently, based on the results, it can be concluded that this novel polyrhodanine-based nanocompound can act as drug carriers due to their low toxic effects and may open a new window on the antibacterial agents. | Authentic |
Text : Extremism has an antilegal nature, that is, it denies consensus ways of solving social problems, giving preference to violent methods and methods of achieving various goals, in particular political ones. The spread of radical, intolerant leadership among young people and attempts to involve young people in extremist activities are especially dangerous. The novelty of the research is determined by the fact that the socio-psychological characteristics inherent in a young person, his superficial and uncritical perception of social life, determine his appeal to protest-activist methods of increasing his social status and role in public life, which are mostly spontaneous, spontaneous. The authors show that the affective, heightened emotional reactions of young people to social events are based not only on the intrapersonal but also on the irrational element. The propensity for extremist forms of political participation is determined both by the individual psychological characteristics of a young person and by the social conditions of his existence. The latter is based on a complex set of interrelated socioeconomic problems, socio-political contradictions, socio-cultural, and spiritual-ideological factors. The practical significance of the study is determined by the possibility of preventing unlawful acts by young people and reducing the manifestation of extremist sentiments in society as a whole. | Counterfeit |
Text : Colorectal cancer (CRC) is one of the most common malignancies worldwide. However, therapies against CRC have not been completely effective. Astragaloside IV (AS-IV) has shown anti-tumorigenic properties in certain cancers, but its role in CRC remains unclear. In this study, we investigated the therapeutic effect of AS-IV in CRC and explored its underlying mechanism. The results showed that AS-IV dose-dependently inhibited the proliferation of CRC cells and suppressed tumor growth in CRC xenograft mouse models. In addition, AS-IV promoted cell cycle arrest in the G0 phase, associated with increased expression of p21. Furthermore, flow cytometry demonstrated that AS-IV promoted apoptosis of CRC cells in a dose-dependent manner. AS-IV induced caspase-dependent apoptosis, which involved the increased release of cytochrome c and Omi from the mitochondria into the cytoplasm and the up-regulation of Bax/Bcl-2 ratio, as well as the activation of PARP and caspase cascade (caspase-3 and -9). Taken together, our study has identified a novel function of AS-IV and provided a molecular basis for AS-IV's potential applications in the treatment of CRC and other cancers. | Counterfeit |
Text : To study the relationship between the expression of TRβ1 and the molecular typing and clinicopathological features of breast cancer. The expression of TRβ1, ER, PR and HER-2 proteins in 208 cases of invasive breast cancer, 52 intraductal carcinoma and 22 normal breast tissue was detected by immunohistochemistry in order to analyze the relationship between the expression of TRβ1 protein and clinicopathological parameters of breast cancer. Western blot was performed to detect the effect of TRβ1 silencing on the expression of Notch signaling pathway proteins and Epithelial-mesenchymal transition (EMT)-related proteins in MCF-7 cells. In the 208 cases of invasive breast cancer tissues, over expression of TRβ1 protein was found in 88 cases while low expression in 120 cases, and the immunohistochemical score was (3.9±3.1). TRβ1 protein was found over expressed in all the 52 cases of intraductal carcinoma and 22 cases of normal breast tissue, with the immunohistochemical score of (9.7±2.1) and 12.0, respectively, and there was no significant difference between the two groups (P>0.05) while both of them were significantly lower than the invasive breast cancer group (P<0.05). The expression of TRβ1 protein in the invasive breast cancer tissues was significantly correlated with lymph node metastasis (P=0.041), molecular typing (P=0.037) and histological grade (P<0.001) while it was negatively correlated with HER-2 expression (r=0.926; P<0.001) and irrelevant with age (P=1.024), ER expression (P=0.834), PR expression (P=0.351) or TNM staging (P=1.032). Compared to normal MCF-7 cells, the expression of Notch1, Dell 1, Jagged-1 and vimentin proteins increased by 1.44 times, 1.53 times, 1.50 times and 1.45 times respectively in the TRβ1 expression silenced MCF-7 cell. The expression of TRβ1 protein in breast cancer tissues decreased with the increase of HER-2 expression and histological grade. The depletion of TRβ1 protein may activate the Notch signaling pathway and enhance the EMT ability of breast cancer cells thus promoting the cancer cell migration. | Authentic |
Text : Totally implantable intravenous ports (TIVAPs) are mostly used for long-term intravenous infusion therapy in cancer patients and can be left in the body for long periods of time for easy management, making them a simple and safe infusion device. Although the risks associated with long-term retention of fully implantable IV ports are less than those associated with other intravenous catheters, various complications may still occur at the time of implantation or during long-term use. To provide a scientific basis for clinical reduction of implantable intravenous port-associated infection complications by studying the risk factors for catheter-associated infection complications in patients applying implantable intravenous ports. A retrospective study was conducted on oncology patients treated with TIVAP at our hospital between January 2017 and November 2021, with a review of patients who were unplanned for extubation. Their demographic data, underlying disease status, and surgery-related data were counted to summarize and analyze the complications and related influencing factors of implantation and postimplantation. A total of 70 individuals with a mean age of 56.49 ± 12.19 years were included in the study. Among them, 39 were male and 64 had the highest percentage of epithelial tumors, followed by tumors of the lymphopoiesis system and mesenchymal tumors with 4 and 2 cases, respectively. Forty-eight of these patients did not have their ports removed as planned due to the occurrence of catheter-related hematogenous infections. In univariate analysis, BMI and neutropenia were risk factors for catheter-associated infections. In the multivariate analysis, BMI (OR = 1.38, 95% CI: 1.07-1.78, p=0.013) was an independent risk factor for catheter-associated infections. The overall complication rate of fully implanted intravenous ports was high, but most complications improved with symptomatic management, and no deaths due to port complications were identified. Infection was the most common complication, with catheter-associated bloodstream infection being the most common cause of unplanned port extraction. Patients with a higher BMI were at high risk of developing implantable IV port-associated infections, which may be an independent risk factor for implantable IV port-associated infections. | Authentic |
Text : In the treatment of hemoglobinopathies, amending altered hemoglobins and/or globins produced in excess is an important part of therapeutic strategies and the selective inhibition of globin production may be clinically beneficial. Therefore the development of drug-based methods for the selective inhibition of globin accumulation is required. In this study, we employed peptide nucleic acids (PNAs) to alter globin gene expression. The main conclusion of the present study was that PNAs designed to target adult murine β-globin mRNA inhibit hemoglobin accumulation and erythroid differentiation of murine erythroleukemia (MEL) cells with high efficiency and fair selectivity. No major effects were observed on cell proliferation. Our study supports the concept that PNAs may be used to target mRNAs that, similar to globin mRNAs, are expressed at very high levels in differentiating erythroid cells. Our data suggest that PNAs inhibit the excess production of globins involved in the pathophysiology of hemoglobinopathies. | Authentic |
Text : MIR143 is pathologically downregulated and may function as a tumor suppressor in prostate cancer. Likewise, the urokinase plasminogen activator receptor (UPAR) is overexpressed in prostate carcinoma, representing a negative prognostic marker and putative therapeutic target gene. In this paper, we establish UPAR as a new direct target of MIR143. Luciferase reporter gene constructs identify one of the two in silico-predicted binding sites as functionally relevant for direct MIR143 binding to the 3' UTR, and, concomitantly, transfection of MIR143 reduces UPAR protein levels in prostate carcinoma cells in vitro. Inhibitory effects on cell proliferation and colony formation, spheroid growth and integrity, and cell viability are extensively analyzed, and they are compared to direct small interfering RNA (siRNA)-mediated uPAR knockdown or combined microRNA (miRNA)-siRNA treatment. Switching to a therapeutically more relevant in vivo model, we demonstrate tumor-inhibitory effects of MIR143 replacement therapy by systemic treatment of mice bearing subcutaneous PC-3 tumor xenografts with MIR143 formulated in polymeric nanoparticles. This efficient, nanoparticle-mediated delivery of intact MIR143 mediates the marked downregulation of uPAR protein, but not mRNA levels, thus indicating translational inhibition rather than mRNA degradation. In summary, we identify UPAR as a direct target gene of MIR143, and we establish the therapeutic anti-tumor potential of nanoparticle-based MIR143 replacement in prostate cancer. | Authentic |
Text : Epidemiological evidence suggests that obesity can significantly increase the risk of various cancers, although the mechanisms underlying this link are completely unknown. Here, we analyzed the effect of adipocytes on melanoma and colon cancer cells proliferation, migration, and invasion. The potential effects of conditioned media (CM) obtained from differentiated mouse 3T3-L1 cells and human adipose tissue-derived mesenchymal stem cells (hAMSC) on the proliferation, migration, and invasion of B16BL6 melanoma and colon 26-L5 cancer cells were investigated. The 3T3-L1 and hAMSC CM increased cell proliferation, migration, and invasion in both the cell lines. In addition, adipocytes CM increased matrix metalloproteinase 9 (MMP-9) and MMP-2 activity in both B16BL6 and colon 26-L5 cells. These effects were found to be associated with an increased expression of various oncogenic proteins in B16BL6 and colon 26-L5 cells. Also, adipocyte CM induced Akt and mTOR activation in both tumor cell lines, and the pharmacological inhibition of Akt and mTOR blocked the CM induced Akt as well as mTOR activation and CM-stimulated melanoma and colon cancer cell proliferation, migration, and invasion. These data suggest that adipocyte promotes melanoma and colon cancer progression through modulating the expression of diverse proteins associated with cancer growth and metastasis as well as modulation of the Akt/mTOR signaling. | Authentic |
Text : Recent studies have shown that distal-less homeobox 6 antisense 1 (DLX6-AS1) is aberrantly expressed in various cancers and is associated with poor prognosis. This meta-analysis is designed to investigate the effects of DLX6-AS1 expression on clinicopathological features and survival outcomes. All eligible studies were searched from Pubmed, Web of Science, Embase, the Cochrane Library, and Wanfang database, up to August 2019. The literature was selected according to the inclusion and exclusion criteria listed in this work, and the quality of each eligible study was assessed. Each patient's clinicopathological features and survival data were analyzed using Stata12.0 software. Begg's test and sensitivity analysis were also conducted. A total of 12 articles were included, covering 841 patients. Results showed that high expression of DLX6-AS1 was significantly closely associated with poor overall survival in tumor patients (hazard ratio (HR) = 2.30, confidence interval (95% CI): 1.70-3.09, P<0.01). This meta-analysis also showed that overexpression of DLX6-AS1 was significantly associated with tumor stage (P<0.01), tumor size (P<0.01), lymph node metastasis (P<0.01), and distant metastasis (P<0.01). Begg's test suggested no publication bias. This meta-analysis revealed that high expression of DLX6-AS1 was related to the advanced clinicopathological characteristics of human digestive system cancers (gastric cancer, esophageal cancer, colon cancer, pancreatic cancer, and hepatocellular carcinoma) and other cancers such as ovarian cancer, osteosarcoma and non-small cell lung cancer, and DLX6-AS1 has important predictive value for poor prognosis. However, more studies are needed to further corroborate these findings. | Authentic |
Text : Whether Neo-adjuvant chemotherapy can affect patients' postoperative brain function is not clear. In this study, we investigated the effect of preoperative cisplatin treatment on postoperative cognitive function and its possible mechanism in rats. Moreover, we also tested whether the NMDAR inhibitor memantine could attenuate cisplatin-induced alterations. 12-month-oldSprague-Dawley rats randomly received an intraperitoneal injection of either cisplatin once a week at a dose of 3mg/kg for three consecutive weeks or an equivalent volume of normal saline. After the injections, the normal saline injection group was divided into 3 groups (n=5 each): a normal saline group (group S), normal saline+pentobarbital group (group SP), and normal saline+pentobarbital+operation group (group SPO).The cisplatin injection group was divided into 3 groups: a cisplatin group (group C), cisplatin+pentobarbital group (group CP), and cisplatin+pentobarbital+operation group (group CPO).Rats in the group SP, SPO,CP and CPO were anaesthetized with sodium pentobarbital and then the SPO and CPO groups underwent a simple laparotomy operation. The effects of memantine were tested through two additional groups of rats (cisplatin+memantine group (group CM) and cisplatin+pentobarbital+operation+memantine group (group CPOM)). A Morris water maze test was performed to evaluate the spatial learning and memory ability five days after anesthesia or operation. After the test, the hippocampi were removed for detection of the expression of NMDAR by western bloting. The relevant protein expression levels of PSD95 and ERK1/2 were detected by western blot analysis. Rats treated with cisplatin had a longer mean escape latency and spent a shorter amount of time in the target quadrant than did the normal saline injection rats. Furthermore, the protein expression levels of NMDA receptors, PSD95 and ERK1/2 were decreased in cisplatin group and memantine could up-regulate their expression. These results suggest that neo-adjuvant chemotherapy with cisplatin exacerbate the postoperative cognitive dysfunction in rats, and this may be caused by a lower expression of NMDA receptors in the hippocampus. Memantine could attenuate these alterations. | Authentic |
Text : The present study aimed to investigate the effects of miR-338 on morphine tolerance through the targeting of CXC chemokine receptor-4 (CXCR4) in a rat model of bone cancer pain (BCP). Sprague-Dawley (SD) rats were obtained and divided into model saline (n=10), model morphine (n=50), normal saline (n=10) and normal morphine (healthy rats, n=10) groups. After BCP rat model establishment, the remaining SD rats (n=40) in the model saline group were assigned into pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA, blank and PBS groups. Luciferase reporter gene assay was used for luciferase activity. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to detect the miR-338 and CXCR4 mRNA and protein expression. The model saline group showed increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group, and the model morphine group had increased mRNA and protein expressions of CXCR4 but decreased miR-338 compared with the model saline group. The mRNA and protein expressions of miR-338 in the pLV-THM-miR-338 group increased remarkably while those of the pLV-THM-anti-miR-338 group decreased significantly compared with the CXCR4 shRNA, blank and PBS groups. The pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA and CXCR4 mRNA groups all had lower mRNA and protein expressions of CXCR4 than those in the blank and PBS groups. miR-338 exerts significant influence in the inhibition of morphine tolerance by suppressing CXCR4 in BCP. | Authentic |
Text : It has been suggested that modestly elevated circulating D-dimer values may be associated with acute ischemic stroke (AIS). Thus, the purpose of this study was to investigate the association between plasma D-dimer level at admission and AIS in Chinese population. In a prospective observational study, plasma D-dimer levels were measured using a particle-enhanced, immunoturbidimetric assay on admission in 240 Chinese patients with AIS. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to D-dimer levels. Plasma median D-dimer levels were significantly (P = 0.000) higher in AIS patients as compared to healthy controls (0.88; interquartiler range [IQR], 0.28-2.11 mg/L and 0.31; IQR, 0.17-0.74 mg/L). D-dimer levels increased with increasing severity of stroke as defined by the NIHSS score(r = 0.179, p = 0.005) and infarct volume(r = 0.425, p = 0.000). Those positive trends still existed even after correcting for possible confounding factors (P = 0.012, 0.000; respectively). Based on the Receiver operating characteristic (ROC) curve, the optimal cut-off value of plasma D-dimer levels as an indicator for diagnosis of cardioembolic strokes was projected to be 0.91 mg/L, which yielded a sensitivity of 83.7% and a specificity of 81.5%, the area under the curve was 0.862(95% confidence interval [CI], 0.811-0.912). We had shown that plasma D-dimer levels increased with increasing severity of stroke as defined by the NIHSS score and infarct volume. These associations were independent other possible variables. In addition, cardioembolic strokes can be distinguished from other stroke etiologies by measuring plasma D-dimer levels very early (0-48 hours from stroke symptom onset). | Counterfeit |
Text : Dysfunction of vascular smooth muscle cells (VSMCs) may be linked to intracranial aneurysm (IA) formation. VSMCs possess a phenotypic plasticity, capable of changing from a mature, contractile to a less differentiated, synthetic phenotype. In this study, we identify a microRNA candidate miR-331-3p that participates in regulating differentiation properties of VSMCs. The expression of TNF-α and CD14 was quantified in IA wall tissues obtained from 96 IA patients and their associations with clinicopathological features of IA were assessed. Then the interactions between miR-331-3p, TNF-α and CD14 were evaluated by determination of luciferase activity. Differentiated properties of VSMCs were assessed from phenotypic markers of contractile VSMCs, a-SMA and E-cadherin, and of synthetic VSMCs, ICAM-1, MCP-1, IL-6, MMP-2 and MMP-9. Rat IA models by ligation of left carotid artery and left renal artery and histological analysis of induced IAs were performed. The TNF-α and CD14 was highly expressed in IA wall tissues and associated with the type and diameter of aneurysm. Depletion of TNF-α or CD14 retarded VSMC apoptosis and transformation to the synthetic type but facilitated cell proliferation. Elevations in miR-331-3p, a direct negative regulator of both TNF-α and CD14, also reduced VSMC apoptosis and prevented VSMCs from synthetic type and increase their proliferation. Furthermore, miR-331-3p was demonstrated to inhibit the formation of IA by down-regulating TNF-α and CD14 in vivo. In conclusion, miR-331-3p maintains the contractile type of VSMCs, thus possibly inhibiting the progression of IA. These findings provide potential new strategies for the clinical treatment of IA. | Counterfeit |
Text : Cisplatin-based treatment is first-line chemotherapy for several cancers including ovarian cancer. The development of cisplatin resistance results in treatment failure, but the underlying mechanisms are not fully understood. Histone deacetylases (HDACs) are a large family of enzymes that deacetylate lysine residues on histones and non-histone proteins. High expression of HDAC1 is associated with poor outcomes in ovarian cancer. Furthermore, resistance to chemotherapeutic agents is associated with HDAC1 overexpression in ovarian cancer cells. The goals of this study were to determine whether targeting HDAC1 can sensitize ovarian cancer cells to cisplatin and to explore the underlying mechanisms. Small interfering RNA (siRNA)-targeting HDAC1 was designed to silence HDAC1 in the cisplatin-resistant ovarian cancer cell line A2780CDDP and its cisplatin-sensitive cell line A2780. The effects of targeting HDAC1 on cell viability assay, colony formation, and apoptosis were detected. c-Myc re-expression or miR-34a inhibitors were used to examine the relationship among HDAC1, c-Myc, and miR-34a expression, which was assessed by western blot analysis and quantitative reverse transcription PCR. We established stable transfectants of A2780CDDP/HDAC1 short hairpin RNA (shRNA) and A2780/HDAC1 shRNA. The therapeutic effectiveness of cisplatin in murine xenograft models was assessed following shRNA-mediated HDAC1 silencing in A2780CDDP and A2780 cells. The mechanism of cell death was studied in tumor sections obtained from different mouse tumors. In cisplatin-resistant A2780CDDP cells, HDAC1 knockdown by siRNA suppressed cell proliferation, and increased apoptosis and chemosensitivity by downregulating c-Myc and upregulating miR-34a. In cisplatin-sensitive A2780 cells, HDAC1 knockdown did not affect cell proliferation and apoptosis. Cisplatin treatment activated HDAC1 and c-Myc and inactivated miR-34a. Inhibition of HDAC1 with siRNA reduced c-Myc expression, increased miR-34a expression, and sensitized A2780 cells to cisplatin-induced apoptosis. c-Myc re-expression or miR-34a targeting by miR-34a inhibitors protected cells from apoptosis or reversed cisplatin resistance following HDAC1 knockdown or/and cisplatin exposure. Finally, in vivo studies showed that targeting HDAC1 inhibited A2780CDDP-induced xenograft tumor growth but not A2780-induced xenograft tumor growth. Targeting HDAC1 sensitized both A2780- and A2780CDDP-induced xenograft tumors to cisplatin treatment. Upregulation of HDAC1 is a crucial event in the development of drug resistance to current treatments in ovarian cancer. Thus, targeting HDAC1 by enhancing c-Myc-dependent miR-34a expression might be an effective strategy for increasing the efficacy of cisplatin treatment. | Authentic |
Text : Excessive generation of oxidants by immune cells results in acute tissue damage. One mechanism by which oxidant exposure could have long-term effects is modulation of epigenetic pathways. We hypothesized that methylation of newly synthesized DNA in proliferating cells can be altered by oxidants that target DNA methyltransferase activity or deplete its substrate, the methyl donor SAM. To this end, we investigated the effect of two oxidants produced by neutrophils, H2O2 and glycine chloramine, on maintenance DNA methylation in Jurkat T lymphoma cells. Using cell synchronization and MS-based analysis, we measured heavy deoxycytidine isotope incorporation into newly synthesized DNA and observed that a sublethal bolus of glycine chloramine, but not H2O2, significantly inhibited DNA methylation. Both oxidants inhibited DNA methyltransferase 1 activity, but only chloramine depleted SAM, suggesting that removal of substrate was the most effective means of inhibiting DNA methylation. These results indicate that immune cell-derived oxidants generated during inflammation have the potential to affect the epigenome of neighboring cells. | Authentic |
Text : Glioma is the most common and lethal malignant intracranial tumor. Long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in the tumorigenesis of glioma. However, the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in glioma genesis is still unknown. The purpose of this study was to investigate the underlying function of UCA1 on glioma genesis. The results demonstrated that UCA1 was upregulated in glioma tissue and indicated a poor prognosis. UCA1 knockdown induced by si-UCA1 significantly suppressed the proliferative, migrative, and invasive activities of glioma cell lines (U87 and U251). Bioinformatics analysis and luciferase reporter assay verified the complementary binding within UCA1 and miR-122 at the 3'-UTR. Functional experiments revealed that UCA1 acted as an miR-122 "sponge" to modulate glioma cell proliferation, migration, and invasion via downregulation of miR-122. Overall, the present study demonstrated that lncRNA UCA1 acts as an endogenous sponge of miR-122 to promote glioma cell proliferation, migration, and invasion, which provides a novel insight and therapeutic target in the tumorigenesis of glioma. | Authentic |
Text : The capacity of the immune system to influence tumor progression has been a long-standing notion that first generated clinical traction over a 100 years ago when Dr. William Coley injected disaggregated bacterial components into sarcomas and noted that the ensuing inflammation commonly associated with tumor regression.1 Since then, our understanding of the individual components and the overall interaction of the immune system has expanded exponentially. This has led to the development of a robust understanding of how components of innate and adaptive immunity recognize and respond to tumors and leveraging this information for the development of tumor immunotherapies. However, clinical failures have also deepened our knowledge of how tumors might adapt/be selected to avoid or inhibit immune responses, which, in turn, has led to the further iteration of immunotherapies. In this tutorial, the established elements of tumor immunity are explained, and areas where our knowledge base is too thin is highlighted. The principles of tumor immunity that guide the development of cancer vaccines are further illustrated, and potential considerations of how to integrate cancer vaccines with conventional therapies and other immunotherapies are proposed. | Authentic |
Text : Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with a high incidence and high mortality in East Asia. Identifying biomarkers and clarifying the regulatory mechanisms of HCC are of great importance. Herein, we report the role and mechanism of activating transcription factor 3 (ATF3), a member of the ATF/cAMP-responsive element-binding protein family of transcription factors in HCC. ATF3 overexpression vector and shRNAs were transfected into HCC cancer cells to upregulate or downregulate ATF3 expression. In vitro and in vivo assays were performed to investigate the functional role of ATF3 in hepatocellular carcinoma. RNA-Seq was performed to screen the differentially expressed genes downstream of ATF3. The dual-luciferase reporter assay, chromatin immunoprecipitation (Ch-IP) analysis and functional rescue experiments were used to confirm the target gene regulated by ATF3. Tissue microarrays (TMAs) comprising 236 human primary HCC tissues were obtained and immunohistochemical staining were carried out to analyze the clinical significance of ATF3. The results indicate that ATF3 significantly inhibited the proliferation and mobility of HCC cells both in vitro and in vivo. Cysteine-rich angiogenic inducer 61 (CYR61) is a key target for transcriptional regulation by ATF3. Both ATF3 and CYR61 were consistently downregulated in human HCC tissues, and their expression levels were significantly and positively correlated with each other. Our findings indicate that ATF3 functions as a tumor suppressor in HCC through targeting and regulating CYR61. | Authentic |
Text : Previous studies have demonstrated that zinc (Zn) is an essential trace element which is involved in male reproduction. The zinc transporter (ZnT) family, SLC30a, is involved in the maintenance of Zn homeostasis and in mediating intracellular signaling events; however, relatively little is known regarding the effect of ZnTs on testosterone synthesis. Thus, in the present study, we aimed to determine the effect of Zn transporter 7 (ZnT7) on testosterone synthesis in male CD-1 mice and mouse Leydig cells. The findings of the present study revealed that the concentrations of Zn in the testes and Leydig cells were significantly lower in mice fed a Zn-deficient diet compared with the control mice fed a Zn-adequate diet. In addition, ZnT7 was principally expressed and colocalized with steroidogenic acute regulatory protein (StAR) in the Leydig cells of male CD-1 mice. ZnT7 expression was downregulated in the mice fed a Zn-deficient diet, which led to decreases in the expression of the enzymes involved in testosterone synthesis namely cholesterol side‑chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase/D5-D4 isomerase (3β-HSD) as well as decreased serum testosterone levels. These results suggested that Znt7 may be involved in testosterone synthesis in the mouse testes. To examine this hypothesis, we used the mouse Leydig tumor cell line (MLTC-1 cell line) in which the ZnT7 gene had been silenced, in order to gauge the impact of changes in ZnT7 expression on testosterone secretion and the enzymes involved in testosterone synthesis. The results demonstrated that ZnT7 gene silencing downregulated the expression of StAR, P450scc and 3β-HSD as well as progesterone concentrations in the human chorionic gonadotrophin (hCG)-stimulated MLTC-1 cells. Taken together, these findings reveal that ZnT7 may play an important role in the regulation of testosterone synthesis by modulating steroidogenic enzymes, and may represent a therapeutic target in testosterone deficiency. | Authentic |
Text : To investigate the effect of different body mass indexes (BMIs) on patients' puncture pain, puncture success rate, and image quality in coronary angiography (CAG) performed with an intravenous indwelling needle, and to provide a basis for selecting the appropriate intravenous indwelling needle for CAG in patients with different BMIs in an outpatient clinic. In this study, 300 patients undergoing CTA at the department of radiology in the First Affiliated Hospital of Wenzhou Medical University from January to May 2021 were divided into group 1 (BMI 1 ≤ 18.5), group 2 (18.5 < BMI ≤ 24), and group 3 (BMI > 24) according to their BMI, with 100 cases in each group, and a 20 G intravenous indwelling needle was used in each group. The age, sex, height, and weight of each patient were recorded, and the primary puncture success rate, contrast leakage rate, injection success rate, pain perception, and subjective ratings of image quality and objective indicators were compared in patients with different BMI values. There was no statistically significant difference between the age, gender, and heart rate of the patients in the three groups (P > 0.05). There was no statistically significant difference between the primary puncture success rate, injection success rate, and contrast leakage rate of the three groups of patients (P > 0.05). The pain scores of group 3 during contrast injection were significantly higher than those of the remaining two groups (P < 0.05), while the differences between the pain scores of group 2 and group 1 during contrast injection were not statistically significant (P > 0.05); the comparison of the pain scores of the three groups during puncture and during retention was not statistically significant (P > 0.05). The differences between the subjective ratings of image quality and the objective indicators of the three groups were not statistically significant (P > 0.05). The 20 G indwelling needle can basically meet the coronary angiography examination of patients with different body mass indexes, but patients with a BMI greater than 24 are recommended to use a larger diameter indwelling needle to reduce contrast leakage as well as to reduce patient pain and improve patient comfort. | Counterfeit |
Text : Interleukin (IL)-7 enhances cytokines secretion by CD14+ monocytes, and induces recruitment of monocytes to endothelium. As an important regulator to different types of immune cells, the role of IL-7 in modulation of CD14+ monocytes is still not fully elucidated. Thus, the aim of current study was to investigate the immunoregulatory activity of IL-7 to peripheral and lung-resident CD14+ monocytes in lung squamous carcinoma patients. Thirty-seven lung squamous carcinoma patients and eighteen healthy individuals were enrolled. CD14+ monocytes and CD4+ T cells were purified from both peripheral bloods and bronchoalveolar lavage fluids (BALF). IL-7 expression in plasma and BALF was measured by ELISA, and CD127 expression in peripheral and lung-resident CD14+ monocytes was investigated by real-time PCR and flow cytometry, respectively. Cellular proliferation, cytokine production, and molecules in IL-7 signaling pathway was assessed in CD14+ monocytes in response to IL-7 stimulation. IL-7-induced CD14+ monocytes activity to CD4+ T cells was also assessed in direct and indirect contact co-culture system. There were no remarkable differences of plasma IL-7 concentration or CD127 level between healthy individuals and lung squamous carcinoma patients. However, IL-7 expression was significantly reduced in BALF from tumor site in squamous carcinoma patients, especially in stage III and IV. IL-7 stimulation not only promoted proliferation, cytokines secretion, and STAT-5 phosphorylation in lung-resident CD14+ monocytes, but also enhanced CD14+ monocytes-induced Th1 and T follicular helper cells activation, which presented as elevated interferon-γ and IL-21 secretion by CD4+ T cells. This process required direct cell-to-cell contact, and was dependent on IL-6 secretion. The current data revealed a potential immunopromotive property of IL-7 to lung-resident CD14+ monocytes in lung squamous carcinoma. | Authentic |
Text : Cancer progression involves a variety of pro-tumorigenic biological processes including cell proliferation, migration, invasion, and survival. A cellular pathway implicated in these pro-tumorigenic processes is autophagy, a catabolic route used for recycling of cytoplasmic components to generate macromolecular building blocks and energy, under stress conditions, to remove damaged cellular constituents to adapt to changing nutrient conditions and to maintain cellular homeostasis. During autophagy, cells form a double-membrane sequestering a compartment termed the phagophore, which matures into an autophagosome. Following fusion with the lysosome, the cargo is degraded inside the autolysosomes and the resulting macromolecules released back into the cytosol for reuse. Cancer cells use this recycling system during cancer progression, however the key autophagy players involved in this disease is unclear. Accumulative evidences show that autophagy receptors, crucial players for selective autophagy, are overexpressed during cancer progression, yet the mechanisms whereby pro-tumorigenic biological processes are modulated by these receptors remains unknown. In this review, we summarized the most important findings related with the pro-tumorigenic role of autophagy receptors p62/SQSTM1, NBR1, NDP52, and OPTN in cancer progression. In addition, we showed the most relevant cargos degraded by these receptors that have been shown to function as critical regulators of pro-tumorigenic processes. Finally, we discussed the role of autophagy receptors in the context of the cellular pathways implicated in this disease, such as growth factors signaling, oxidative stress response and apoptosis. In summary, we highlight that autophagy receptors should be considered important players of cancer progression, which could offer a niche for the development of novel diagnosis and cancer treatment strategies. | Authentic |
Text : Gastric carcinoma (GC) remains the second leading cause of cancer-related deaths worldwide. Good biomarkers are of paramount importance for GC therapy. This study aimed to assess the role of long noncoding RNA (lncRNA) CAT104 in GC. We found that CAT104 was highly expressed in human GC NCI-N87, SGC7901, BGC823, BGC803, and AGS cells. Suppression of CAT104 decreased NCI-N87 cell viability, migration, and invasion, but promoted apoptosis. CAT104 knockdown enhanced the expression of microRNA-381 (miR-381) expression in NCI-N87 cells. miR-381 participated in the regulatory effects of CAT104 on NCI-N87 cell viability, migration, invasion, and apoptosis. Zinc finger E-box-binding homeobox 1 (ZEB1) was identified as a direct target of miR-381. Overexpression of ZEB1 reversed the miR-381 mimic-induced cell viability, migration, and invasion inhibition. Suppression of ZEB1 reversed the miR-381 inhibitor-induced activation of the c-Jun N-terminal kinase (JNK) pathway and Wnt/β-catenin signaling pathways in NCI-N87 cells. In conclusion, CAT104 might function as an oncogenic factor in GC cells via regulating the expression of miR-381 and ZEB1. | Authentic |
Text : Using proteomics analysis, we previously compared MCF7 breast cancer cells grown as 3D tumor spheres, with the same cell line grown as monolayers. Our results indicated that during 3D anchorage-independent growth, the cellular machinery associated with i) mitochondrial biogenesis and ii) ribosomal biogenesis, were both significantly increased. Here, for simplicity, we refer to these two new oncogenic hallmarks as "mito-stemness" and "ribo-stemness" features. We have now applied this same type of strategy to begin to understand how fibroblasts and MCF7 breast cancer cells change their molecular phenotype, when they are co-cultured together. We have previously shown that MCF7-fibroblast co-cultures are a valuable model of resistance to apoptosis induced by hormonal therapies, such as Tamoxifen and Fulvestrant. Here, we directly show that these mixed co-cultures demonstrate the induction of mito-stemness and ribo-stemness features, likely reflecting a mechanism for cancer cells to increase their capacity for accumulating biomass. In accordance with the onset of a stem-like phenotype, KRT19 (keratin 19) was induced by ~6-fold during co-culture. KRT19 is a well-established epithelial CSC marker that is used clinically to identify metastatic breast cancer cells in sentinel lymph node biopsies. The potential molecular therapeutic targets that we identified by label-free proteomics of MCF7-fibroblast co-cultures were then independently validated using a bioinformatics approach. More specifically, we employed publically-available transcriptional profiling data derived from primary tumor samples from breast cancer patients, which were previously subjected to laser-capture micro-dissection, to physically separate breast cancer cells from adjacent tumor stroma. This allowed us to directly validate that the proteins up-regulated in this co-culture model were also transcriptionally elevated in patient-derived breast cancer cells in vivo. This powerful approach for target identification and translational validation, including the use of patient outcome data, can now be applied to other tumor types as well, to validate new therapeutic targets that are more clinically relevant, for patient benefit. Moreover, we discuss the therapeutic implications of these findings for new drug development, drug repurposing and Tamoxifen-resistance, to effectively target mito-stemness and ribo-stemness features in breast cancer patients. We also discuss the broad implications of this "organelle biogenesis" approach to cancer therapy. | Authentic |
Text : Long non-coding RNAs (lncRNAs) have recently been found to be important in gene regulation. lncRNA H19 has been reported to play an oncogenic role in many human cancers. Its specific regulatory role is still elusive. In this study, we developed a novel analytic approach by integrating the synergistic regulation among lncRNAs (e.g., H19), transcription factors (TFs), target genes, and microRNAs (miRNAs) and then applied it to the pan-cancer expression datasets from The Cancer Genome Atlas (TCGA). Using linear regression models, we identified 88 H19-TF-gene co-regulatory triplets, in which 93% of the TF-gene pairs were related to cancer, indicating that our approach was effective to identify disease-related lncRNA-TF-gene co-regulation mechanisms. lncRNAs can function as miRNA sponges. Our further experiments found that H19 might regulate SP1-TGFBR2 through let-7b and miR-200b, ETS1-TGFBR2 through miR-29a and miR-200b, and STAT3-KLF11 through miR-17 in breast cancer cell lines. Our work suggests that miRNA-mediated lncRNA-TF-gene co-regulation is complicated yet important in cancer. | Authentic |
Text : Ionic channel activity is involved in fundamental cellular behaviour and participates in cancerous features such as proliferation, migration and invasion which in turn contribute to the metastatic process. In this study, we investigated the expression and role of voltage-gated sodium channels in non-small-cell lung cancer cell lines. Functional voltage-gated sodium channels expression was investigated in normal and non-small-cell lung cancer cell lines. The measurement, in patch-clamp conditions, of tetrodotoxin-inhibitable sodium currents indicated that the strongly metastatic cancerous cell lines H23, H460 and Calu-1 possess functional sodium channels while normal and weakly metastatic cell lines do not. While all the cell lines expressed mRNA for numerous sodium channel isoforms, only H23, H460 and Calu-1 cells had a 250 kDa protein corresponding to the functional channel. The other cell lines also had another protein of 230 kDa which is not addressed to the membrane and might act as a dominant negative isoform to prevent channel activation. At the membrane potential of these cells, channels are partially open. This leads to a continuous entry of sodium, disrupting sodium homeostasis and down-stream signaling pathways. Inhibition of the channels by tetrodotoxin was responsible for a 40-50% reduction of in vitro invasion. These experiments suggest that the functional expression of voltage-gated sodium channels might be an integral component of the metastatic process in non-small-cell lung cancer cells probably through its involvement in the regulation of intracellular sodium homeostasis. These channels could serve both as novel markers of the metastatic phenotype and as potential new therapeutic targets. | Authentic |
Text : Triple-negative breast cancer (TNBC) is a subtype of cancer with aggressive behaviors (high recurrence and metastasis rate) and poor prognosis. Therefore, studying the determining factors that lead to malignant TNBCs is necessary to develop personalized therapy and improve survival rates. In this study, we first analyzed levels of chromodomain helicase DNA binding protein 4 (CHD4) in 60 TNBC patients by immunohistochemical staining. We then clarified the role of CHD4 in TNBC and non-TNBC cell lines. Our clinical data indicated that higher CHD4 expression is positively correlated with metastatic stage, tumor recurrence, and survival status. Consistent with the clinical analytical data, our in vitro data also indicated that high level of CHD4 is positively correlated with malignant behaviors in TNBC cells, such as cell motility and mortality. For further analyses, we found that E-cadherin, N-cadherin and fibronetin are involved in CHD4-mediated epithelial-mesenchymal transition (EMT). Silencing of CHD4 also increased drug sensitivity to cisplatin and PARP1 inhibitor, especially in TNBC cells. Altogether, our findings showed that CHD4 is not only a potential prognostic biomarker for TNBC patient survival, but is also a powerful candidate in the development of new anti-cancer agents in TNBC. | Authentic |
Text : Bedsore is a familiar disease, which fearfully harms the health of the patients. We investigated the efficacy and mechanism of circular RNA circANKRD36 on HaCaT cell in inflammatory damage. CCK-8 and flow cytometry were respectively used to investigate the efficacies of lipopolysaccharide (LPS), circANKRD36, and microRNA (miR)-15 on cell viability and apoptosis. Moreover, circANKRD36 and miR-15 expression were changed by cell transfection and investigated by reverse transcription-quantitative polymerase chain reaction. Furthermore, the levels of Bax, pro caspase-3, cleaved caspase-3, interleukin (IL)-1β, IL-6, and proteins of the pathway were investigated by Western blot. Otherwise, the levels of IL-1β and IL-6 were investigated by enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) was investigated by ROS assay. The relation between myeloid differentiation factor 88 (MyD88) and miR-15 was investigated by luciferase assay. LPS caused inflammatory damage and upregulated circANKRD36. circANKRD36 was silenced in cells and si-circANKRD36 remitted inflammatory damage. Furthermore, si-circANKRD36 negatively regulated miR-15 and miR-15 inhibitor could reverse the efficacies of si-circANKRD36. Besides, si-circANKRD36 restrained the NF-κB pathway by upregulating miR-15. Finally, MyD88 was authenticated as a target of miR-15. circANKRD36 remitted cell inflammatory damage upregulating miR-15/MyD88 via the NF-κB pathway in HaCaT cells. | Counterfeit |
Text : The tumor microenvironment (TME) contributes to the initiation and progression of many neoplasms. However, the impact of low-grade glioma (LGG) purity on carcinogenesis remains to be elucidated. We selected 509 LGG patients with available genomic and clinical information from the TCGA database. The percentage of tumor infiltrating immune cells and the tumor purity of LGG were evaluated using the ESTIMATE and CIBERSORT algorithms. Stromal-related genes were screened through Cox regression, and protein-protein interaction analyses and survival-related genes were selected in 487 LGG patients from GEO database. Hub genes involved in LGG purity were then identified and functionally annotated using bioinformatics analyses. Prognostic implications were validated in 100 patients from an Asian real-world cohort. Elevated tumor purity burden, immune scores, and stromal scores were significantly associated with poor outcomes and increased grade in LGG patients from the TCGA cohort. In addition, CD3E was selected with the most significant prognostic value (Hazard Ratio=1.552, P<0.001). Differentially expressed genes screened according to CD3E expression were mainly involved in stromal related activities. Additionally, significantly increased CD3E expression was found in 100 LGG samples from the validation cohort compared with adjacent normal brain tissues. High CD3E expression could serve as an independent prognostic indicator for survival of LGG patients and promotes malignant cellular biological behaviors of LGG. In conclusion, tumor purity has a considerable impact on the clinical, genomic, and biological status of LGG. CD3E, the gene for novel membrane immune biomarker deeply affecting tumor purity, may help to evaluate the prognosis and develop individual immunotherapy strategies for LGG patients. Evaluating the ratio of differential tumor purity and CD3E expression levels may provide novel insights into the complex structure of the LGG microenvironment and targeted drug development. | Authentic |
Text : MicroRNAs (miRNAs) have been validated as critical regulators in the development of melanoma. miR-140 was abnormally downregulated in uveal melanoma samples. However, the expression level and roles of miR-140-5p remain unclear in melanoma for now. We speculate that miR-140-5p is abnormally expressed and may play an important role in melanoma. The expressions of miR-140-5p and SOX4 messenger RNA were determined by quantitative real-time polymerase chain reaction assays. Western blot assays were employed to detect the expression levels of SOX4, Ki67, MMP-2, MMP-7, p-β-catenin, c-Myc, cyclin D1, p65, and IκBα. Luciferase reporter assays were employed to elucidate the interaction between SOX4 and miR-140-5p. MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) and transwell invasion assays were applied to evaluate capabilities of cell proliferation and invasion, respectively. Xenograft models of melanoma were established to verify the role and molecular basis of miR-140-5p. Immunohistochemical (IHC) assays were employed to measure the Ki67 and SOX4 at the protein level in xenografted melanoma tissues. Herein, these observations showed that, miR-140-5p was abnormally downregulated in melanoma tissues and cells, while SOX4 was upregulated. miR-140-5p directly targeted SOX4 and inhibited its expression in melanoma cells. miR-140-5p overexpression repressed melanoma cell proliferation and invasion and its effects were partially restored SOX4 overexpression. Moreover, miR-140-5p hindered melanoma growth in vivo by downregulating SOX4. Mechanistically, miR-140-5p suppressed activation of the Wnt/β-catenin and NF-κB pathways by targeting SOX4. Our study concluded that miR-140-5p hindered cell proliferation, invasion, and tumorigenesis by targeting SOX4 via inactivation of the Wnt/β-catenin and NF-κB signaling pathways in malignant melanoma, which provides an underlying molecular mechanism for the treatment for melanoma with miRNAs. | Authentic |
Text : Our research aimed to illuminate the role of miR-100-5p in chordoma and potential mechanism. We used microRNA array analysis to explore differentially expressed miRNAs in chordoma tissue and then verified by qRT-PCR. Cell proliferation and transwell assay were used to evaluate the function of miR-100-5p. Cell apoptosis was analyzed by flow cytometry, and using biological software, we predicted that the insulin-like growth factor 1 receptor (IGF1R) could be the target gene of miR-100-5p, which was then validated by dual luciferase assays and Western blot. miR-100-5p was downregulated in chordoma tissues. Overexpression of miR-100-5p could suppress the growth of chordoma both in vitro and in vivo, and miR-100-5p could inhibit the migration and invasion of chordoma cells partially by suppressing epithelial-mesenchymal transition (EMT). Furthermore, IGF1R was validated as the target gene of miR-100-5p and expressed in most chordoma tissues. In conclusion, our results showed that miR-100-5p was lowly expressed in chordoma and inhibited tumor malignant progression by targeting IGF1R. | Authentic |
Text : Altered or aberrant glycosylation is a common phenomenon in cancer cells and it originates from changes in the expression of the enzymes, glycosyltransferase, and glycosidase which up-regulate in response to some oncogenes in the glycan synthesis pathway. In this present study, it has been aimed to determine the alteration of sialic acid and fucose expressions in the cell surface of human thyroid carcinoma cells and investigate the changes in tumorigenic and malignant characters after treating them with specific plant lectins. Our study showed that the cell surface glycan chains of anaplastic 8305C, follicular FTC-133, and papillary K1 thyroid carcinoma cells were rich in α-2,6, α-2,3, sialic acid, and α-1,6 fucose residues. When the cells were treated with specific doses of Maackia amurensis lectin II (MAL), Sambucus nigra agglutinin (SNA), and Aleuria aurantia lectin (AAL) which have specific binding capacity for the detected glycan residues, respectively their cancerous traits changed dramatically. Remarkable findings obtained from MAL treatment leading to necrosis in 8505C cells without any toxicity for normal thyroid epithelial cells but it had proliferative effect on K1 and FCT-133 cells. Besides, MAL and SNA treatment decreased the mobility of 8505C and K1 cells. MAL and SNA lectins dramatically reduced the endothelial affinity of the cells and AAL significantly attenuated that of 8050C and K1 cells but not FTC-133. These results suggest that altered cell surface glycosylation in thyroid cancer seems to be a strong candidate for developing new therapeutic strategies. | Authentic |
Text : Skin cancer, particularly melanoma, is a leading cause of death worldwide. The therapeutic methods for this malignancy are not effective, and due to the side effects of these treatments, applying an appropriate alternative or complementary treatment is important. According to available data, melatonin as the main product of the pineal gland has oncostatic and antitumoral properties. Also, melatonin acts as an anti-inflammatory and reactive oxygen species inducer agent which suppresses the growth of tumors. It also has apoptosis induction characteristics through regulating signaling pathways, including heat shock protein 70, nuclear factor-erythroid 2 p45-related factor 2 and others. Thus, adding melatonin to chemo- and radiotherapy may have synergistic therapeutic effects and increase the survival time in patients with skin cancer. Few clinical studies have evaluated the efficacy of melatonin in skin cancer. Based on the related mechanisms, this review discusses about how melatonin may improve outcomes in skin cancer patients. | Authentic |
Text : Pirfenidone (PFD), which is an antifibrotic agent used for treatment of idiopathic pulmonary fibrosis, induces G0/G1 cell cycle arrest in fibroblasts. We hypothesized that PFD-induced G0/G1 cell cycle arrest might be achieved in other types of cells, including cancer cells. Here we investigated the effects of PFD on the proliferation of pancreatic cancer cells (PCCs) in vitro. Human skin fibroblasts ASF-4-1 cells and human prostate stromal cells (PrSC) were used as fibroblasts. PANC-1, MIA PaCa-2, and BxPC-3 cells were used as human PCCs. Cell cycle and apoptosis were analyzed using flow cytometer. First, we confirmed that PFD suppressed cell proliferation of ASF-4-1 cells and PrSC and induced G0/G1 cell cycle arrest. Under these experimental conditions, PFD also suppressed cell proliferation and induced G0/G1 cell cycle arrest in all PCCs. In PFD-treated PCCs, expression of p21 was increased but that of CDK2 was not clearly decreased. Of note, PFD did not induce significant apoptosis among PCCs. These results demonstrated that the antifibrotic agent PFD might have antiproliferative effects on PCCs by inducing G0/G1 cell cycle arrest. This suggests that PFD may target not only fibroblasts but also PCCs in the tumor microenvironment of pancreatic cancer. | Authentic |
Text : We present a case of a 55-year-old female who suffered from a mass in the right upper abdomen, which had been present for over six months. Pre-operative blood examinations, including tumor markers, were normal. Initially, the admitting diagnosis was a giant celiac cyst, due to its liquid cystic appearance and large size (approximately 30.0×18.0 cm), visible in the hepatic region under ultrasound. Following the discovery of a cystic duct during surgery, the diagnosis was corrected to be a giant gallbladder. As no obstructive matter was observed, the giant gallbladder was considered to be congenital. | Authentic |
Text : Ganoderma lucidum polysaccharides (GLPs), which were purified from the medicinal herb G. lucidum followed by ethanol precipitation, protein depletion using the Sevage assay, purification using DEAE‑cellulose (DE-52), dialysis and the use of ultrafiltration membranes, are used as an ingredient in traditional anticancer treatments in China. The aim of the current study was to evaluate the anticancer effects and investigate the underlying molecular mechanisms of GLPs on LoVo human colon cancer cells. The results demonstrated that the GLP‑mediated anticancer effect in LoVo cells was characterized by cytotoxicity, migration inhibition, enhanced DNA fragmentation, morphological alterations and increased lactate dehydrogenase release. Furthermore, the activation of caspases‑3, ‑8 and ‑9 was involved in GLP‑stimulated apoptosis. Additionally, treatment with GLPs promoted the expression of Fas and caspase‑3 proteins, whilst reducing the expression of cleaved poly(ADP‑ribose) polymerase. These data indicate that GLPs demonstrate potential antitumor activity in human colon cancer cells, predominantly through the inhibition of migration and induction of apoptosis. Furthermore, activation of the Fas/caspase-dependent apoptosis pathway is involved in the cytotoxicity of GLPs. | Authentic |
Text : Our study is aim to investigate the influence of miR-892a on proliferative and invasive activities of human hepatocellular carcinoma (HCC) cells through regulating CD226 expression. QRT-PCR was used to detect the expression levels of miR-892a and CD226 mRNA in HCC tissues and adjacent tissues or HCC cells and normal cells whereas Western Blot was used to detect the CD226 protein expression in tissue and cell samples. Then HuH-7 cell line was selected for following assays and respectively transfected with miR-892a mimics, miR-NC, Plenti-GIII-Ubc-CD226, and Plenti-GIII-Ubc followed by qRT-PCR assay to detect the miR-892a and CD226 expression. The luciferase reporter assay was conducted to determine if miR-892a directly targeted CD226 and then CCK-8 assay, wound healing assay, Transwell assay, and flow cytometry were used to detect cell proliferation, migration, invasion ability, cell cycle, and cell apoptosis. What's more, relationships between expression levels of miR-892a or CD226 and overall survival (OS) or disease-free survival (DFS) of HCC patients were investigated based on TCGA database. MiR-892a was high-expressed in HCC tissues or cells while CD226 was low-expressed. MiR-892a directly targeted CD226 and up-regulating miR-892a expression could promote proliferative, migrating, and invasive activities of HCC cells. Different expression levels of miR-892a and CD226 both related to the prognosis of HCC. MiR-892a promotes hepatocellular carcinoma cells proliferation and invasion through regulating CD226 expression. J. Cell. Biochem. 118: 1489-1496, 2017. © 2016 Wiley Periodicals, Inc. | Counterfeit |
Text : A large number of studies have shown that stem cells from human exfoliated deciduous teeth (SHED) has a protective effect on brain damage, but its specific mechanism is unclear. This research focused on the effect of microRNA (miR)-26a that transmitted by SHED in intracerebral hemorrhage (ICH). SHED were extracted from deciduous teeth of healthy children and miR-26a expression in SHED was altered through transfection, and then the SHED were conducted with neuron differentiated induction, expression of β3 tubulin, MAP-2 and glial fibrillary acidic protein (GFAP), number of dendritic spines and cell proliferation were detected. ICH rat models were established by stereotactic injection of collagenase VII into the left striatum and the modeled rats were injected with miR-26a mimic or inhibitor-transfected SHED suspension. Then, the brain water content, blood-brain barrier permeability, pathological changes, and injury and apoptosis in the nervous cells in brain were assessed. The expression of miR-26a and CTGF in SHED and rats' brain tissues was evaluated and the target relation between miR-26a and CTGF was detected. In SHED after induction, upregulated miR-26a could increase number of dendritic spines, cell proliferation, and expression of β3 tubulin, MAP-2 and GFAP, and restrain CTGF expression. In rat models, SHED engineered to overexpress miR-26a could attenuate brain water content, Evans blue content, apoptosis, pathological injury and expression of CTGF and Bax, while promoted number of Nissl bodies and expression of Bcl-2 in the nervous cells in brain in ICH rats. Furthermore, miR-26a competitively bound to CTGF. Our findings provided the evidence that SHED could transmit miR-26a to protect ICH rats from cerebral injury by repressing CTGF, which may contribute to ICH therapy. | Counterfeit |
Text : Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The pathogenesis of NSCLC has not yet been fully understood, and the therapeutic efficacy of current anti-NSCLC medication remains unsatisfactory. Previous studies indicated that miR-296-3p was down-regulated in NSCLC, suggesting that miR-296-3p may participate in the pathogenesis of NSCLC; however, the specific mechanisms still need to be further explored. The aim of this work is to investigate the roles of miR-296-3p in NSCLC and the related mechanism. Thirty NSCLC tissue and paired adjacent tissue were collected, and Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to examine the expression of miR-296-3p in cancer tissue and the adjacent tissue. Next, A549 cells were cultured and transfected with miR-296-3p mimics, and cell migration and invasion were determined using scratch wound-healing and transwell assays. Moreover, Western blot assay was performed to determine the effect of miR-296-3p on the expression of Rab-like 3 (RABL3), Matrix metallopeptidase (MMP)-2, Janus kinase (JAK) and Signal transducer and activator of transcription 3 (STAT3); next, Dual-Luciferase reporter assay has been conducted to prove the direct targeting relationship between miR-296-3p and RABL3. Finally, the cells of different treatments were subcutaneously implanted into nude mice to investigate the effect of miR-296-3p mimics in the xenograft mice tumor models. Our data indicated that miR-296-3p was significantly down-regulated and RABL3 was markedly up-regulated in NSCLC tissue compared with the adjacent tissue. Moreover, transient over-expression of miR-296-3p in A549 cells induced a significant decrease in the proliferation and invasion ability of A549 cells, as well as decreased expression of RABL3, MMP-2, JAK and STAT3. Furthermore, the Dual-Luciferase reporter assay confirmed that RABL3 is a direct target of miR-296-3p. Finally, the results of animal studies indicated that miR-296-3p can regulate the tumorigenesis of A549 cells in vivo. Our findings proved that miR-296-3p may play a role as a tumor suppressor in NSCLC both in vitro and in vivo, and we first reported that miR-296-3p can regulate the migration and invasion of A549 cells via targeting RABL3. Our data suggested that miR-296-3p may serve as a potential therapeutic target for treating NSCLC. | Authentic |
Text : Head and neck squamous cell carcinoma (HNSCC) is an highly aggressive tumor with heterogeneous prognosis. We here report that immune-related genes (IRGs) could effectively distinguish prognostically different HNSCC patients. MRNA levels of 1333 IRGs that from ImmPort database in HNSCC samples were acquired from the Cancer Genome Atlas (TCGA). H2o, a machine learning-based R package, was used for screening the top most representative genes from the IRGs. Univariate Cox-regression analysis was performed to identify prognostically-related genes based on the randomly generated training samples from TCGA set. LASSO Cox-regression analysis was applied for the construction of prognostic model for HNSCC. A total of six IRGs were finally retained for their prognostic significance and used for LASSO Cox-regression analysis. Samples from exclusive training and testing set that randomly generated from TCGA, and another independent validation set from the Gene Expression Omnibus (GEO) were divided into high- and low-risk groups according to the prognostic model. HNSCC samples within high-risk groups have significantly inferior overall survival (OS) compared with those within low-risk groups. Differences in genomic mutation landscape and tumor infiltration immune cells also exist between the two sample groups. What's more, risk score was proved to be an independent prognostic factor for HNSCC by stratification analysis. IRGs are pivotal HNSCC prognostic signatures and should be helpful for its clinical decision-making. | Authentic |
Text : Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide due to its asymptomatic onset and poor survival rate. This highlights the urgent need for developing novel diagnostic markers for early HCC detection. The circadian clock is important for maintaining cellular homeostasis and is tightly associated with key tumorigenesis-associated molecular events, suggesting the so-called chronotherapy. An analysis of these core circadian genes may lead to the discovery of biological markers signaling the onset of the disease. In this study, the possible functions of 13 core circadian clock genes (CCGs) in HCC were systematically analyzed with the aim of identifying ideal biomarkers and therapeutic targets. Profiles of HCC patients with clinical and gene expression data were downloaded from The Cancer Genome Atlas and International Cancer Genome Consortium. Various bioinformatics methods were used to investigate the roles of circadian clock genes in HCC tumorigenesis. We found that patients with high TIMELESS expression or low CRY2, PER1, and RORA expressions have poor survival. Besides, a prediction model consisting of these four CCGs, the tumor-node-metastasis (TNM) stage, and sex was constructed, demonstrating higher predictive accuracy than the traditional TNM-based model. In addition, pathway analysis showed that these four CCGs are involved in the cell cycle, PI3K/AKT pathway, and fatty acid metabolism. Furthermore, the network of these four CCGs-related coexpressed genes and immune infiltration was analyzed, which revealed the close association with B cells and nTreg cells. Notably, TIMELESS exhibited contrasting effects against CRY2, PER1, and RORA in most situations. In sum, our works revealed that these circadian clock genes TIMELESS, CRY2, PER1, and RORA can serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets, for HCC patients, which may promote HCC chronotherapy by rhythmically regulating drug sensitivity and key cellular signaling pathways. | Authentic |
Text : Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, which threats peoples' health. Unfortunately, the pathogenesis of PDAC remains unclear. Recent studies have indicated that long non-coding RNAs (lncRNAs) can regulate the development and progression of malignant tumors through varying mechanisms. LncRNA H19 has a unique expression profile and can act as a sponger of specific miRNAs to regulate the pathogenic process of many diseases, including PDAC and several other types of cancers. Here, we review the research approaches to understanding the regulatory role of H19 and potential mechanisms in the progression of PDAC and other types of cancers and diseases. These studies suggest that H19 may be a novel therapeutic target for PDAC and our findings may open new revenues for scientific researches and development of valuable therapies for these diseases in the future. | Authentic |
Text : Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. Critical roles for long non-coding RNAs (lncRNAs) have recently been demonstrated for a variety of cancers, including hepatocellular carcinoma. However, the effect and mechanism of lncRNAs in HCC tumorigenesis and chemoresistance have not been extensively characterized. In the current study, we have identified a HCC-expressed lncRNA termed as HANR (HCC associated long non-coding RNA). We identified HANR by microarray analysis and validated its up-regulated expression by quantitative PCR. RNA pull-down and pathway analyses were conducted to evaluate physical and functional interactions with HANR. In vivo experiments were performed to assess tumorigenesis and increase of chemoresistance. In addition, the HANR expression in HCC specimens was detected by FISH. Xenograft and orthotopic mice model was constructed to observe the effect of HANR on tumorigenesis and chemoresistance in vivo. HANR was demonstrated to be up-regulated in HCC patients and HCC cell lines. Increased HANR expression in HCC predicted short survival of patients. Knock-down of HANR markedly retarded cell proliferation, suppressed HCC xenograft/orthotopic tumor growth, induced apoptosis and enhanced chemosensitivity to doxorubicin, while over-expression of HANR showed the opposite effects. It was found that HANR bind to GSKIP for regulating the phosphorylation of GSK3β in HCC. Our results demonstrate that HANR contributes to the development of HCC and is a promising therapeutic target for chemosensitization of HCC cells to doxorubicin, which may represent a promising therapeutic target in the future. | Authentic |
Text : Prostate cancer is the second most commonly occurring cancer in men. Regardless of statistics, screening for prostate cancer is an individual decision and most male patients come for their first examination with an already developed disease, as they are not adequately informed. The study aimed to emphasize the importance of preventive tests for urological diseases in the Republic of Serbia, raise awareness about urinary problems, and present social marketing strategies for prevention. The results confirm the generally lower awareness of respondents under the age of 30, followed by those who finished university, go to the doctor two or three times a year, and receive information other than by watching TV. Implemented research indicates the influence of the marketing principles and social marketing strategies on possible target groups of the male population over 50, which is aimed at raising awareness of the importance of prevention of urological diseases and the expected changes in the health behavior of the target population. | Authentic |
Text : Epirubicin (EPI) is one of the standard anticancer drugs that apply for various cancers treatment. However, the accumulation of EPI in the human body can be highly toxic, and it causes inevitable harm to organs. As a result, the evaluation of low concentrations of this drug in body samples requires sensitive, rapid, and accurate analysis methods. The fluorescence method is an efficient way in comparison of the traditional methods such as liquid chromatography, capillary electrophoresis, and electrochemical methods. Herein, we synthesized a novel fluorescence nanosensor named CMC-CdTe/ZnS based on using quantum dots (QDs). The structure of the prepared nanosensor is confirmed by different analysis methods such as FT-IR, TGA, and TEM. Besides that, the fluorescence intensity response of CMC-CdTe/ZnS QDs in the presence of Epirubicin drug is investigated. Based on obtained results, not only this nanosensor developed, but also the fluorescence quenching was explained by the typical Stern-Volmer equation. The best linear quenching equation for entitled nanosensor in the presence of Epirubicin is F0/F = 0.0346Q + 1.08 (R2 = 0.99), and the detection limit of Epirubicin is around 0.04 × 10-6 mol/L at 25 °C. All of the results display that this method could be reliable and suitable approach for determination of Epirubicin in commercial samples as well. | Authentic |
Text : Ovarian cancer is the major cause of death in gynecologic diseases worldwide. Ferroptosis, a nonapoptotic form of cell death, is featured by accumulation of iron-based lipid peroxidation. The elevated iron level and malondialdehyde (MDA) in ovarian cancer cells suggest more vulnerable to ferroptosis, nevertheless, ferroptosis is not observed in ovarian cancer cells. Glutathione peroxidase 4 (GPX4) is a critical regulator of ferroptosis. We determined whether GPX4 knockdown could induce ferroptosis to prevent cell proliferation in ovarian cancer. Human ovarian cancer cells and normal human ovarian epithelial cell line IOSE-80 were cultured and administrated with deferoxamine (DFO) or ferric ammonium citrate (FAC). GPX4 knockdown was established for investigating the functions of GPX4 in ovarian cancer cells and in tumor xenograft mice. A positively correlation was showed among the levels of GPX4, iron and cell proliferation. Chelation of intracellular iron by DFO disrupted intracellular iron level and was detrimental to ovarian cancer cell survival. FAC-induced elevation of intracellular iron inhibited proliferation, aggravated apoptosis, boosted inflammation and suppressed lipid peroxide reducibility in ovarian cancer cells. Knockdown of GPX4 had similar effects with FAC in ovarian cancer cells. Inhibition of GPX4 suppressed tumor growth, induced ferroptosis, accelerated cell apoptosis, reduced Fe3+ accumulation and suppressed lipid peroxide reducibility in tumor bearing mice. We demonstrate the significance of GPX4 and intracellular iron level in ovarian cancer cells. Importantly, inhibition of GPX4 interferes with both intracellular iron homeostasis and lipid peroxide reducibility, inducing ferroptosis and exerting anti-cancer effect, which can be a potential effective strategy for ovarian cancer therapy. | Authentic |
Text : Emerging studies indicate that long noncoding RNAs (lncRNAs) play crucial roles in ovarian cancer (OC). By analyzing high-throughput data, we found that SNHG17 was highly expressed in multiple OC cohorts. However, its functions in OC were not explored. In this study, lncRNA expression in OC was analyzed by a series of microarray data. The functions of SNHG17 were investigated by various in vitro and in vivo assays. Fluorescence in situ hybridization (FISH), RNA pull-down, chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were used to reveal the potential mechanisms involved in the effects of SNHG17. We found that SNHG17 was overexpressed in OC and that the oncogenic transcription factor STAT3 was involved in promoting its expression. In addition, high SNHG17 expression was associated with a poor prognosis in OC. Functional analysis revealed that SNHG17 could promote OC cell growth. Mechanistically, SNHG17 was found to be located predominantly in the cytoplasm. It could regulate expression of CDK6, an important cell-cycle regulator, by acting as a molecular sponge for miR-214-3p. In summary, our study suggested that SNHG17 acted as an oncogene in OC, which might serve as a novel target for OC diagnosis and therapy. | Authentic |
Text : Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment that can be polarized into different phenotypes, including tumor-inhibiting M1 macrophages and tumor-promoting M2 macrophages. To elucidate the biological and clinical significance of M2 TAMs in non-small-cell lung cancer (NSCLC), a comprehensive clinical assessment of the tissue distribution of M2 TAMs was performed. The tissue distribution of M2 TAMs was retrospectively analyzed using CD163 immunohistochemistry in 160 consecutive patients who underwent NSCLC resection. Tumor proliferation was evaluated via the Ki-67 proliferation index. The results revealed that the stromal density of M2 TAMs was significantly associated with the C-reactive protein (CRP) level (P=0.0250), the Ki-67 proliferation index (P=0.0090) and invasive size (P=0.0285). Furthermore, the stromal M2 TAM density was significantly associated with tumor differentiation (P=0.0018), lymph node metastasis (P=0.0347) and pathological stage (P=0.0412). The alveolar M2 TAM density was also significantly associated with the CRP level (P=0.0309), invasive size (P<0.0001), tumor differentiation (P=0.0192), tumor status (P=0.0108) and pathological stage (P=0.0110). By contrast, no association was observed between islet M2 TAM density and the aforementioned biological and clinical factors. In regards to prognosis, disease-free survival rate was significantly lower in patients with stromal M2 TAM-high tumors (P=0.0270) and in those with alveolar M2 TAM-high tumors (P=0.0283). Furthermore, the overall survival rate was also significantly lower in patients with stromal M2 TAM-high tumors (P=0.0162) and in those with alveolar M2 TAM-high tumors (P=0.0225). Therefore, during NSCLC progression, M2 TAMs may induce tumor cell aggressiveness and proliferation and increase metastatic potential, resulting in a poor prognosis in patients with NSCLC. | Authentic |
Text : Emerging evidences has demonstrated that dysregulation of long non-coding RNAs (lncRNAs) is critically involved in esophageal squamous cell carcinoma (ESCC) progression. However, the function of lncRNA PSMA3-AS1 in ESCC is unclear. Therefore, we aimed to explore the functions and potential mechanisms of PSMA3-AS1 in ESCC cells progression. Here, we found that PSMA3-AS1 expression was significantly up-regulated in ESCC tissues. Forced PSMA3-AS1 expression was correlated with tumor size, distant metastasis, and poor prognosis in ESCC patients. Functionally, PSMA3-AS1-overexpression promoted ESCC cells proliferation, invasion, and migration in vitro. Mechanistically, PSMA3-AS1 up-regulated EZH2 expression by competitively binding to miR-101. PSMA3-AS1 is significantly up-regulated in ESCC tissues, and the PSMA3-AS1/miR-101/EZH2 axis plays a critical role in ESCC progression. Taken together, our results may provide promising targets for ESCC therapy. PSMA3-AS1 and miR-101 expression were explored using qRT-PCR in ESCC tissues and cell lines. Immunohistochemistry assays were carried out to analyze EZH2 (enhancer of zeste homolog) protein expression. RIP, dual-luciferase reporter, fluorescence in situ hybridization, and biotin pull-down assays were used to detect the interactions of PSMA3-AS1, miR-101 and EZH2. The biological functions of PSMA3-AS1 in PSMA3-AS1-altered cells were explored using CCK-8, colony formation, wound healing, and transwell assays in vitro. | Authentic |
Text : Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Inflammatory cells in the EOC microenvironment play a key role in tumor progression. In the present study, we investigated the mechanism of the accumulation of regulatory T cells (Tregs) induced by interleukin-10 (IL-10) derived from tumor-associated macrophages (TAMs) in the EOC microenvironment. The frequency of Tregs and TAMs was detected by immunofluorescence in 40 EOC tissues and 20 benign ovarian tumors, as well as the expression of IL-10 which was assessed by immunohistochemistry. It was found that the frequency of Treg cells and TAMs was significantly higher in the EOC than those in the benign ovarian tumors. The expression of IL-10 was also found to be higher in the EOC than that in the benign tumors. EOC patients with a high frequency of Tregs exhibited a significantly shorter overall survival time compared to those with a low frequency of Tregs. In addition, the expression of IL-10 in ascites and blood serum and the IL-10 released in the co-cultured system supernatants were detected by ELISA. Following CD4+ T-cell co-culturing with macrophages and IL-10, it was observed by flow cytometric analysis that the frequency of Treg cells was increased in the presence of IL-10. It was also established that IL-10 released in the co-cultured supernatants was increased. We also detected the mechanism of Treg cells induced by IL-10 in vivo. The SKOV3 cell tumor volume and weight were much higher in the presence of IL-10 in a mouse subcutaneous model. These data suggest that IL-10 secreted by TAMs increase the frequency of Treg cells through the activation of Foxp3 during T-cell differentiation and promotes tumor progression. | Authentic |
Text : RLIP76 is a stress-responsive membrane protein regulating multiple cellular signaling pathways and is overexpressed in a number of malignant tumor cells. The aim of this study is to test whether the RLIP76 plays a critical role in cellular growth, apoptosis, cell cycle distribution and chemoresistance in melanoma. In this study, human melanoma cell line A375 was stably transfected with an RLIP76-targeted shRNA-containing vector to investigate the role of RLIP76 in cellular function. Quantitative RT-PCR and Western blot revealed significant suppression of RLIP76 in A375 cells after transfection with shRNA-containing vector. Cell proliferation was determined by MTT assay. Wound scratch ad transwell assays were used for cell migration and invasion. The results showed that shRNA decreased the expression of RLIP76 in human melanoma cell line A375, and the knockdown of RLIP76 gene significantly inhibited A375 cell growth, resulted in G1 phase arrest and apoptosis increase of A375. Moreover, by testing the cell migratory and invasive abilities by wound scratch and transwell assays, it determined that the RLIP76 also suppressed cell migration and invasion in A375 cells and P13K/Akt signalling CONCLUSIONS: Overall, this study suggests that RLIP76 is a potential therapeutic target against melanoma. | Authentic |