bluuebunny/crossref_metadata_2025 huggingface dataset:
The expression of ubiquitin‐specific peptidase 8 and its prognostic role in patients with breast cancer
Authors: Qiu Han , Kong Jun , Cheng Yunfei , Li Gang
Published: August 2018

Objectives

To clarify the clinical relevance of ubiquitin‐specific protease 8 (USP8) for patients with breast cancer (BC).

Methods

Previous BC microarray studies GSE37751, GSE7390, and GSE21653 were reanalyzed to determine the USP8 levels between BC patients and the corresponding normal breast tissues and the correlation between USP8 expression and clinical features and clinical outcomes of patients with BC. Gene set enrichment analysis (GSEA) was conducted to investigate the potential mechanisms.

Results

USP8 was downregulated in BC cells compared with that in normal breast tissues (P < 0.0001). The Χ2 test and logistic regression analysis demonstrated that patients in USP8 high‐expression group were correlated with better clinical features (including histopathological grading, estrogen receptors, clinical risk group according to Nottingham prognostic index [NPI] criteria and clinical risk group according to Veridex signature) compared with patients in USP8 low‐expression group. Kaplan‐Meier survival and Cox proportional regression analysis suggested that USP8 predicted better survivals of BC patients in terms of distant metastasis‐free survival, time to distant metastasis, disease‐free survival, and overall survival. GSEA suggested that USP8 might impact the proliferation of BC cells through several biological processes associated tumorigenesis of BC. USP8 was significantly downregulated in BC patients (P < 0.0001).

Conclusions

Our results demonstrated that USP8 might predict better clinical characteristics and might be a protective factor for patients with BC.
Identification of therapeutic effect of glucagon‐like peptide 1 in the treatment of STZ‐induced diabetes mellitus in rats by restoring the balance of intestinal flora
Authors: Yuan Xiao , Ni Haixiang , Chen Xialiang , Feng Xiaohong , Wu Qiaomin , Chen Jie
Published: August 2018

Objective

The objective of this study was to identify the therapeutic effect and the underlying mechanism of glucagon‐like peptide 1 (GLP‐1) in the treatment of STZ‐induced diabetes mellitus (DM).

Methods

Mice were treated with STZ to establish an animal model of DM, which was further treated with a GLP‐1 receptor agonist. Subsequently, the status of glucose, insulin, nitric oxide, inflammatory and oxidative factors was evaluated and compared among Sham, STZ, and STZ + GLP‐1 groups. In addition, the intestinal flora spectrum in each group was also evaluated.

Results

In this study, it was found that the administration of STZ increased the level of glucose and glycosylated hemoglobin but reduced the level of insulin. It was also found that the levels of inflammation and oxidative stress in STZ‐induced DM were both enhanced, as evidenced by a decreased level of catalase, superoxide dismutase, glutathione peroxidase, as well as increased levels of malonyldialdehyde, interleukin‐1β (IL‐1β), and IL‐6. Meanwhile, the expression of nitric oxide, a factor associated with both oxidative stress and inflammation, was also suppressed in STZ‐induced DM. More importantly, the imbalance of intestinal flora was observed in STZ‐induced DM, as shown by a decreased level of both total bacteria and that of some strains including Clostridium, Bacteroides, Lactobacilli, and Bifidobacteria.

Conclusion

In summary, the findings of this study confirmed the antihyperglycemic effect of GLP‐1 and demonstrated that the therapeutic effect of GLP‐1 in the treatment of STZ‐induced DM was mediated, at least partially, by its ability to restore the balance of intestinal flora.
The expression levels of long noncoding RNAs lnc0640 and lnc5150 and its gene single‐nucleotide polymorphisms in rheumatoid arthritis patients
Authors: Zhang Tian‐Ping , Zhang Qin , Wu Jun , Zhao Yu‐Lan , Wang Jie‐Bing , Leng Rui‐Xue , Fan Yin‐Guang , Li Xiao‐Mei , Pan Hai‐Feng , Ye Dong‐Qing
Published: August 2018

Objectives

The aim of our study was to evaluate two lncRNAs (lnc0640 and lnc5150) expressions and gene single‐nucleotide polymorphisms (SNPs) in rheumatoid arthritis (RA) patients.

Methods

The expressions of lncRNAs in peripheral blood mononuclear cells (PBMCs) were examined by quantitative real‐time reverse transcription polymerase chain reaction from 65 RA patients and 54 controls. Simultaneously, three SNPs (rs13039216, rs6085189, and rs6085190) of lnc0640, three SNPs (rs1590666, rs141561256, and rs144047453) of lnc5150 were genotyped using TaqMan SNP‐genotyping assays in 627 RA patients and 590 controls.

Results

The lnc0640 level in PBMCs from RA patients was significantly increased (P = 0.001), whereas the lnc5150 level was significantly reduced (P < 0.001) compared to controls. There were significant associations of lnc0640 and lnc5150 levels with C‐reactive protein in RA patients (P = 0.011 and P = 0.014, respectively), while lnc5150 level was associated with erythrocyte sedimentation rate (P = 0.022). TT genotype of rs13039216 in lnc0640 gene was statistically associated with a reduced risk of RA (TT vs CC; P = 0.046), and a decreased risk of rs13039216 variant was observed under the recessive model (P = 0.038). In addition, the G allele of rs141561256 polymorphism in lnc5150 gene was significantly associated with rheumatoid factor in RA patients (P = 0.034). There were no associations between lnc0640 and lnc5150 levels and their respective genotype in RA patients.

Conclusions

The expressions of lnc0640 and lnc5150 were alternated in the RA patients, suggesting that these lncRNAs may involve in the development of RA.
Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway
Authors: Wang Yan , Li Guoce , Zhao Li , Lv Jianping
Published: August 2018

HOXA transcript at the distal tip (HOTTIP), which is a long noncoding RNA, plays an important role in multiple cancers and in coronary artery disease. Elevated microRNA‐143 (miR‐143) expression causes impaired glucose uptake that is responsible for the ischemic cerebral injury. However, the role and mechanism of HOTTIP in ischemic stroke are still unknown. The expression of HOTTIP and miR‐143 was first detected in mouse models of transient middle cerebral artery occlusion and in primary neurons exposed to oxygen‐glucose deprivation (OGD). We used gain‐of function and loss‐of function approaches in vitro to investigate the effect and mechanism of HOTTIP on ischemic stroke by evaluating cell viability, apoptosis, and glycolytic metabolism of neurons exposed to OGD. The HOTTIP expression was decreased, whereas miR‐143 increased in experimental ischemic stroke models. Overexpression of HOTTIP by the pcDNA3.1‐HOTTIP plasmid significantly increased cell viability, glucose uptake, and the expression of hexokinase 2 (HK‐2) and pyruvate kinase M2 that were reduced by OGD insult. The HOTTIP overexpression also diminished OGD induced the apoptosis and the caspase‐3 activity of neurons. The miR‐143 mimic reversed these effects, and anti‐miR‐143 enhanced them. In addition, we found that HOTTIP could function as a competing endogenous RNA for miR‐143 to modulate HK‐2 expression. In conclusion, the HOTTIP expression was reduced in ischemic stroke. The HOTTIP overexpression attenuated OGD‐induced neuronal injury and imbalanced glycolytic metabolism by sponging miR‐143, resulting in the de‐repression of its endogenous target HK‐2. Taken together, these findings improve understanding of the pathogenesis of ischemic stroke.
Crocin synergistically enhances the antiproliferative activity of 5‐flurouracil through Wnt/PI3K pathway in a mouse model of colitis‐associated colorectal cancer
Authors: Amerizadeh Forouzan , Rezaei Nastaran , Rahmani Farzad , Hassanian Seyed Mahdi , Moradi‐Marjaneh Reyhaneh , Fiuji Hamid , Boroumand Nadia , Nosrati‐Tirkani Abolfazl , Ghayour‐Mobarhan Majid , Ferns Gordon A. , Khazaei Majid , Avan Amir
Published: August 2018

Colorectal cancer (CRC) is the third most common cause of cancer‐related death, and hence there is a need for the identification of novel‐agents to improve the efficacy of existing therapies. There is growing evidence for the antitumor activity of crocin, although its activity and molecular mechanisms in CRC remains to be elucidated. Here we explored the therapeutic application of crocin or its combination with 5‐flurouracil in a mouse model of colitis‐associated colon cancer. The antiproliferative activity of crocin was assessed in two‐dimensional and three‐dimensional cell‐culture models. The migratory behaviors were determined, while the expression levels of several genes were assessed by quantitative reverse transcriptase polymerase chain reaction/Western blot analysis. We examined the anti‐inflammatory properties of crocin by pathological evaluation and disease‐activity index as well as oxidative or antioxidant markers: malondialdehyde (MDA) and total‐thiols (T‐SH) levels and superoxide dismutase (SOD) and catalase (CAT) activity. Crocin suppressed cell‐growth and the invasive behavior of CRC cells through modulation of the Wnt‐pathway and E‐cadherin. Moreover, administration of crocin alone, or in combination with 5‐FU dramatically reduced the tumor number and tumor size in both distal/mid‐colon followed by reduction in disease‐activity index. Crocin also suppressed the colonic inflammation induced by dextran‐sulfate‐sodium and notably recovered the increased levels of MDA, decreased thiol levels and activity of CAT levels. Crocin was able to ameliorate the severe inflammation with mucosal ulcers and high‐grade dysplastic crypts as detected by inflammation score, crypt loss, pathological changes and histology scores. We demonstrated an antitumor activity of crocin in CRC and its potential role in improvement of inflammation with mucosal ulcers and high‐grade dysplastic crypts, supporting the desireability of further investigations on the therapeutic potential of this approach in CRC.
β‐Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats
Authors: Ames‐Sibin Ana P. , Barizão Camila L. , Castro‐Ghizoni Cristiane V. , Silva Francielli M. S. , Sá‐Nakanishi Anacharis B. , Bracht Lívia , Bersani‐Amado Ciomar A. , Marçal‐Natali Maria R. , Bracht Adelar , Comar Jurandir F.
Published: August 2018

The current study investigated the action of β‐caryophyllene, the major constituent of copaiba oil, on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant‐induced arthritis, a model for rheumatoid arthritis. This study also compared the actions of β‐caryophyllene with those previously reported for copaiba oil on arthritic rats. For this purpose, Holtzman healthy and arthritic rats received 215 and 430 mg·kg−1 β‐caryophyllene orally once a day during 18 days. Both doses of β‐caryophyllene reduced the adjuvant‐induced paw edema, swollen of lymph nodes, and number of circulating and articular leukocytes. β‐Caryophyllene, at the dose of 430 mg·kg
−1, abolished the increases of protein carbonyl groups and myeloperoxidase activity in the liver and plasma of arthritic rats and, at both doses, it restored the increased levels of reactive oxygen species and reduced glutathione in the arthritic liver. These beneficial actions were of the same extension as those of copaiba oil (
Copaifera reticulata) and, therefore, β‐caryophyllene is possibly responsible for the anti‐inflammatory and antioxidant actions of the oil. Hepatic gluconeogenesis was 40% lower in arthritic rats, which also presented a reduced number of hepatocytes per liver area (−23%) associated with increased hepatocyte area (+18%) and liver weight (+50%). None of these hepatic alterations were improved by β‐caryophyllene, but not even by ibuprofen. However, unlike copaiba oil, β‐caryophyllene did not modify the hepatic morphology and metabolism of healthy rats. These results reveal that β‐caryophyllene improves the systemic inflammation and oxidative status of arthritic rats and, in addition, it was not associated with hepatotoxicity.
MicroRNA‐224 inhibition prevents progression of cervical carcinoma by targeting PTX3
Authors: Yu Li‐Mei , Wang Wei‐Wei , Qi Rong , Leng Tian‐Gang , Zhang Xiao‐Lu
Published: August 2018

Cervical carcinoma is known as one of the most lethal and common conditions in women worldwide. Increasing evidence shows that microRNAs (miRs) may be involved in the pathogenesis of cervical carcinoma. This study investigates the correlation between expression of miR‐224 in peripheral blood mononuclear cells and both diagnosis and prognosis of cervical carcinoma to clarify the effect miR‐224 has on the biological behaviors of the subjected cervical carcinoma cells. Initially, 132 patients diagnosed with cervical carcinoma and 120 healthy subjects were recruited. Peripheral blood expression of miR‐224 and PTX3 was detected. A telephone follow‐up was performed every 3 months after treatment. The diagnostic value of miR‐224 in cervical carcinoma was analyzed using the Receiver Operating Characteristic curve. The effects of both miR‐224 and PTX3 on cell proliferation, migration, and invasion were evaluated with an intervention of miR‐224 ectopic expression or depletion and PTX3 silencing. The bioinformatics prediction website and dual‐luciferase reporter assay revealed PTX3 to be a target gene for miR‐224. Moreover, miR‐224 was detected as over‐expressed, but PTX3 was under‐expressed in cervical carcinoma. Additionally, as a diagnostic biomarker, a high miR‐224 expression was closely linked with the progression of cervical carcinoma. Both miR‐224 overexpression and PTX3 silencing promoted cell proliferation, migration, and invasion, whereas, the aforementioned properties were depressed when miR‐224 was inhibited. Altogether, the miR‐224 overexpression may be a biological indicator in predicting the progression of cervical carcinoma. Thus, miR‐224 inhibition may significantly prevent cervical carcinoma progression by targeting the PTX3 gene.
Graphene oxide–nano‐titania composites for efficient photocatalytic degradation of indigo carmine
Authors: Ryali Somasekhar , Sanasi Paul Douglas
Published: August 2018

Nano‐titania composites assembled with variable weight percentages (wt%) of graphene oxide (GO) were synthesized, and their effectiveness as photocatalysts was investigated for the degradation of indigo carmine under visible light irradiation. Controlled hydrolysis of titanium tetrachloride (TiCl4) was performed in aqueous medium, and 1% aqueous solution of GO was added under ultrasonication. Depending on the wt% of GO, the materials were designated as 1, 2, 5, 10, 15 wt%GO–nano‐titania (GO–NT) composites. Their morphology and structural properties were characterized using X‐ray diffraction (XRD), UV–vis diffuse reflectance spectroscopy (UV–vis DRS), high‐resolution transmission electron microscopy (HRTEM), and field‐emission scanning electron microscopy (FE‐SEM). Excellent photocatalytic activity was demonstrated by the NT composite containing 10%GO in 60 min, and the required optimum conditions were established.
Naked eye detection of the Mycobacterium tuberculosis complex by recombinase polymerase amplification—SYBR green I assays
Authors: Singpanomchai Nuntita , Akeda Yukihiro , Tomono Kazunori , Tamaru Aki , Santanirand Pitak , Ratthawongjirakul Panan
Published: August 2018

Background

Rapid diagnosis of Mycobacterium tuberculosis (Mtb) is key to controlling the spread of tuberculosis, which is a global health concern. In this study, isothermal recombinase polymerase amplification (RPA) was developed to detect specific targets of Mtb, IS6110 and IS1081. Additionally, SYBR Green I was used for endpoint detection of the RPA products by the naked eye.

Method

A total of 146 genomic Mtb DNA samples and 24 genomic nontuberculous mycobacteria (NTM) DNA samples were amplified at IS6110 and IS1081 by RPA. After a complete amplification, the RPA amplicons were examined by agarose gel electrophoresis (RPA‐AGE) and SYBR Green I (RPA‐S) assays. The performance of the RPA assays was evaluated by comparing them to a conventional PCR.

Results

The RPA assay demonstrated to have a good capability to differentiate Mtb from NTM with a very short turnaround time at a constant temperature. Compared to conventional PCR, the sensitivities and specificities of RPA‐AGE for IS6110 and IS1081 were 100%. The specificity of RPA‐S was 100% for both targets; however, its sensitivities for IS6110 and IS1081 were 97.95% and 99.32%, respectively. The limits of detection of IS6110 RPA‐AGE and RPA‐S were 0.05 and 0.5 ng, respectively, while the LODs of IS1081 RPA‐AGE and RPA‐S were 0.00005 and 0.05 ng, respectively. Both RPA assays showed a satisfying diagnostic specificity, with no cross‐reaction with other bacteria.

Conclusion

A rapid, sensitive, naked eye RPA assay can be integrated into point‐of‐care diagnosis for Mtb detection, especially in remote areas where laboratory instrument resources are limited.
Functions and regulatory mechanisms of metastasis‐associated lung adenocarcinoma transcript 1
Authors: Lei Li , Chen Jing , Huang Jinhua , Lu Jianyun , Pei Shiyao , Ding Shu , Kang Liyang , Xiao Rong , Zeng Qinghai
Published: August 2018

Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA whose transcript is around 8 kb in length. As an important stress response molecule, MALAT1 can be expressed differently under stress conditions, such as hypoxia, high glucose, hydrogen peroxide, ultraviolet irradiation, infection, and chemical stimulation. MALAT1 is involved in regulating multiple cell behaviors, such as proliferation, apoptosis, differentiation, migration, epithelial–mesenchymal transition, autophagy, and morphological maintenance. Extensive evidence show that MALAT1 plays critical roles in the physiopathological process of embryo implantation, angiogenesis, tissue inflammation, tumor progression, liver fibrosis, cardiovascular remodeling, and diabetes progression by regulating gene transcription, forming RNA–protein complexes with proteins as a structural component, regulating protein activity, assisting protein localization, mediating epigenetic changes, or by acting as a competing endogenous RNA. Furthermore, MALAT1 can affect the sensitivity of chemotherapy and radiotherapy; therefore, it could be used as a potential drug target for chemotherapy and radiotherapy sensitization. The levels of MALAT1 are reported to be overexpressed in most tumor tissues or sera, and the expression levels of MALAT1 often affect the tumor size, stage, lymph node metastasis, and distant invasion. Therefore, MALAT1 can be used as a biomarker for early diagnosis, severity assessment, or prognostic assessment. This review outlines the current understanding of the biological role and function of MALAT1. In the meantime, we have summarized the mechanisms involved in the reulation of MALAT1 expression and the mechanisms by which MALAT1 regulates the physiological and pathological processes.
Regulation by Hsp27/P53 in testis development and sperm apoptosis of male cattle (cattle‐yak and yak)
Authors: Liu Penggang , Yu Sijiu , Cui Yan , He Junfeng , Zhang Qian , Sun Juan , Huang Yufeng , Yang Xiaoqing , Cao Mixia , Liao Bo , Ma Junxing
Published: August 2018

Heat shock protein 27 (Hsp27)/protein 53 (P53) plays an important role in testis development and spermatozoa regulation, but the relationship between Hsp27/P53 and infertility in cattle is unclear. Here, we focus on male cattle‐yak and yak to investigate the expression and localization of Hsp27/P53 in testis tissues and to explore the influence of Hsp27/P53 on infertility. In our study, a total of 54 cattle (24 cattle‐yak and 30 yak) were examined. The Hsp27 and P53 messenger RNA (mRNA) of cattle‐yak were cloned, and amino acid variations in Hsp27 and P53 were found; the variations led to differences in the protein spatial structure compared with yak. We used real‐time quantitative polymerase chain reaction and western blot to investigate whether the expression of Hsp27/P53 mRNA and protein was different in cattle‐yak and yak. We found that the expression levels of Hsp27/P53 mRNA and protein were different in the testis developmental stages and the highest expression was observed in testicles during adulthood. Moreover, the Hsp27 expression was significantly higher in yak, whereas P53 expression was higher in cattle‐yak (p < 0.01). On this basis, we detected the location of Hsp27/P53 in the testis by immunohistochemistry and immunofluorescence. The results demonstrated that Hsp27 was located in spermatogenic cells at different developmental stages and mesenchymal cells of the yak testicles. However, P53 was located in the primary spermatocyte and interstitial cells of the cattle‐yak testicles. In summary, our study proved that the expression of Hsp27/P53 differed across the testis developmental stages and the expression of P53 was higher in the testis of cattle‐yak, which suggested that the infertility of cattle‐yak may be caused by the upregulation of P53.
Activation of peroxisome proliferation–activated receptor‐γ inhibits transforming growth factor‐β1‐induced airway smooth muscle cell proliferation by suppressing Smad–miR‐21 signaling
Authors: Liu Lu , Pan Yilin , Zhai Cui , Zhu Yanting , Ke Rui , Shi Wenhua , Wang Jian , Yan Xin , Su Xiaofan , Song Yang , Gao Li , Li Manxiang
Published: August 2018

The aims of the current study were to examine the signaling mechanisms for transforming growth factor‐β1 (TGF‐β1)‐induced rat airway smooth muscle cell (ASMC) proliferation and to determine the effect of activation of peroxisome proliferation–activated receptor‐γ (PPAR‐γ) on TGF‐β1‐induced rat ASMC proliferation and its underlying mechanisms. TGF‐β1 upregulated microRNA 21 (miR‐21) expression by activating Smad2/3, and this in turn downregulated forkhead box O1 (FOXO1) mRNA expression. In addition, TGF‐β1–Smad–miR‐21 signaling also downregulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression and thus de‐repressed the PI3K–Akt pathway. Depletion of PTEN reduced the nuclear FOXO1 protein level without affecting its mRNA level. Inhibition of the PI3K–Akt pathway or proteasome function reversed PTEN knockdown‐induced nuclear FOXO1 protein reduction. Our study further showed that loss of FOXO1 increased cyclin D1 expression, leading to rat ASMC proliferation. Preincubation of rat ASMCs with pioglitazone, a PPAR‐γ activator, blocked TGF‐β1‐induced activation of Smad2/3 and its downstream targets changes of miR‐21, PTEN, Akt, FOXO1, and cyclin D1, resulting in the inhibition of rat ASMC proliferation. Our study suggests that the activation of PPAR‐γ inhibits rat ASMC proliferation by suppressing Smad–miR‐21 signaling and therefore has a potential value in the prevention and treatment of asthma by negatively modulating airway remodeling.
Molecular characterization of autophagic and apoptotic signaling induced by sorafenib in liver cancer cells
Authors: Rodríguez‐Hernández María A. , González Raúl , de la Rosa Ángel J. , Gallego Paloma , Ordóñez Raquel , Navarro‐Villarán Elena , Contreras Laura , Rodríguez‐Arribas Mario , González‐Gallego Javier , Álamo‐Martínez José M. , Marín‐Gómez Luís M. , Del Campo José A. , Quiles José L. , Fuentes José M. , de la Cruz Jesús , Mauriz José L. , Padillo Francisco J. , Muntané Jordi
Published: August 2018

Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of endoplasmic reticulum (ER) stress, c‐Jun‐N‐terminal kinase (JNK), Akt, and 5′AMP‐activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3–12 hr) ER stress characterized by an increase of Ser51P‐eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185P‐JNK1/2/JNK1/2, Thr172P‐AMPKα, Ser413P‐Foxo3a, Thr308P‐AKt/AKt and Thr32P‐Foxo3a/Foxo3a ratios, and reduction of Ser2481P‐mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim
EL, Beclin‐1, Bcl‐xL, Bcl‐2, autophagy markers, and reduction of myeloid cell leukemia‐1 (Mcl‐1) expression. The progressive increase of CHOP expression, and reduction of Thr308P‐AKt/AKt and Ser473P‐AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim
EL expression and caspase‐3 activity (24 hr). Small interfering‐RNA (si‐RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase‐3 in sorafenib‐treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor‐derived xenograft model. In conclusion, the early sorafenib‐induced ER stress and regulation of JNK and AMPK‐dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK‐CHOP‐dependent rise of Bim
EL, which was associated with the shift from autophagy to apoptosis. The kinetic of Bim
EL expression profile might also be related to the tight balance between AKt‐ and AMPK‐related signaling leading to Foxo3a‐dependent BIM
EL upregulation.
Methylation‐independent ITGA2 overexpression is associated with poor prognosis in de novo acute myeloid leukemia
Authors: Lian Xin‐Yue , Zhang Wei , Wu De‐Hong , Ma Ji‐Chun , Zhou Jing‐Dong , Zhang Zhi‐Hui , Wen Xiang‐Mei , Xu Zi‐Jun , Lin Jiang , Qian Jun
Published: August 2018

Previous studies have been indicated that integrin α2 (ITGA2) may be important in cell migration, invasion, survival, and angiogenesis. However, the correlation between ITGA2 expression and acute myeloid leukemia (AML) is still unclear. Real‐time quantitative polymerase chain reaction was carried out to analyze ITGA2 messenger RNA level. Methylation‐specific polymerase chain reaction (PCR) and bisulfite sequencing PCR were performed to detect the methylation of ITGA2 promoter. ITGA2 expression was significantly upregulated in 134 de novo AML patients compared with 33 controls (p = 0.007). ITGA2high group had markedly lower complete remission (CR) rate than ITGA2low group (p = 0.011). Furthermore, the overall survival in ITGA2high patients was significantly shorter than ITGA2low patients throughout AML cohort, non–acute promyelocytic leukemia (APL) and cytogenetic normal‐AML (p = 0.001, 0.002, and 0.044, respectively). Multivariate analysis confirmed that ITGA2 overexpression served as an independent prognostic factor in both whole‐cohort AML patients (p = 0.018) and non‐APL AML patients (p = 0.021). Besides, ITGA2 expression level was significantly decreased in AML patients after CR (p = 0.011), and was returned at the time of relapse phase (p = 0.021). Moreover, unmethylated ITGA2 promoter was identified in normal controls, leukemia cell lines, and primary leukemia cells with low or high ITGA2 expression. In conclusions, methylation‐independent ITGA2 overexpression is associated with poor prognosis in AML.
Peroxidase expression is decreased by palmitate in cultured podocytes but increased in podocytes of advanced diabetic nephropathy
Authors: Lee Eugene , Lee Hyun Soon
Published: August 2018

High levels of serum free fatty acids (FFAs) are associated with lipotoxicity and type 2 diabetes. Palmitic acid (PA) is the predominant circulating saturated FFA. PA induces mitochondrial superoxide and hydrogen peroxide (H2O
2) generation in cultured podocytes. To elucidate the role of PA in antioxidant defense systems in diabetic nephropathy (DN), cultured podocytes were exposed to 250 μM PA for 1–24 hr, and protein expressions of catalase, peroxiredoxins (Prxs), and glutathione peroxidase (GPx) were examined by western blot analysis. PA induced an early transient increase in the Prx1, Prx2, and GPx1 levels in podocytes, but not catalase. Long‐term exposure of PA to podocytes significantly decreased the protein levels of Prx1, Prx2, GPx1, and catalase. Coincubation of PA‐treated cells with oleic acid, however, restored the expression of these proteins. In advanced human diabetic glomeruli, H2O2 generation was elevated as shown by increased fluorescence of dichlorofluorescein. Strong immunostaining for Prx1, Prx2, GPx1, and catalase was observed in the podocytes of advanced human DN, wherein transforming growth factor‐β1 staining was also positive. These results suggest that podocytes are susceptible to PA‐induced oxidative damage with impaired peroxidase activity and that peroxidases have futile antioxidant effects in the podocytes in the late stages of DN. Given this, PA‐induced podocyte injury via inadequate peroxidase response to H2O2 appears to play an important role in the pathogenesis of DN.
Inhibition of smoothened in breast cancer cells reduces CAXII expression and cell migration
Authors: Guerrini Giuditta , Criscuoli Mattia , Filippi Irene , Naldini Antonella , Carraro Fabio
Published: August 2018

Breast cancer (BC) relapse and metastasis are the leading cause of death and, together with drug resistance, keep mortality still high. The Hedgehog (Hh) pathway is expressed during embryogenesis, organogenesis and in adult tissue homeostasis and its aberrant activation is often associated with cancer. Carbonic anhydrase (CA) enzymes are important during development; they play a key role in controlling several cellular mechanisms, such as pH regulation, survival, and migration, and they are aberrantly expressed in cancer. The goal of this study was to investigate the interplay between the Hh pathway and CAXII in terms of BC cell migration. We here demonstrated that smoothened (SMO) silencing resulted in a reduction of CAXII expression at mRNA and protein level. This led to a decrease in cell migration, which was restored when cells were treated with an SMO agonist, Sag dihydrochloride (SAG), but not when cells were cotreated with SAG and the CAs inhibitor Acetazolamide. This suggested that the ability of SAG to promote cell migration was impaired when CAXII was inhibited. The reduction was also confirmed within hypoxic and inflammatory microenvironment, typical of BC, indicating a key role of the Hh pathway in controlling CAXII expression. Our results may contribute to further understand the physiology of BC cells and indicate that the Hh pathway controls BC cell migration and cell invasion also through CAXII, with important implications in identifying novel therapeutic targets.
Retracted: Downregulated microRNA‐488 enhances odontoblast differentiation of human dental pulp stem cells via activation of the p38 MAPK signaling pathway
Authors: Yu Dan , Zhao Xue , Cheng Jin‐Zhang , Wang Di , Zhang Hui‐Hui , Han Guang‐Hong
Published: August 2018

Human dental pulp stem cells (hDPSCs) are primarily derived from the pulp tissues of permanent third molar teeth. They were widely used in human bone tissue engineering. It was previously indicated that microRNA (miR) expressions are closely associated with hDPSCs development. However, the specific effect of miR‐488 on hDPSCs still remains unclear. In this study, we aimed to investigate effects of miR‐488 on the differentiation of hDPSCs into odontoblast cells through the p38 mitogen‐activated protein kinases (MAPK) signaling pathway by binding to MAPK1. The hDPSCs were isolated and cultured in vitro. Dual‐luciferase reporter gene assay was performed to test the relationship between MAPK1 (p38) and miR‐488. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to detect the mRNA and protein expressions of p38 MAPK signaling pathway‐related genes (MAPK1, Ras, and Mitogen‐activated protein kinase kinase 3/6 [MKK3/6]), along with expressions of dentin Sialophosphoprotein (DSPP), alkaline phosphatase (ALP), and osteonectin (OCN). ALP staining and alizarin red staining were conducted to detect ALP activity and degree of mineralization. Initially, we found that MAPK1 was the target gene of miR‐488. Besides, downregulation of miR‐488 was observed to stimulate the p38 MAPK signaling pathway and to increase the messenger RNA and protein expressions of DSPP, ALP, and OCN. Furthermore, ALP activity and formation of a mineralized nodule in hDPSCs were enhanced upon downregulation of miR‐488. The aforementioned findings provided evidence supporting that downregulation of miR‐488 promotes odontoblastic differentiation of hDPSCs through the p38 MAPK signaling pathway by targeting MAPK1, paving the basis for further study about hDPSCs.
LncRNA AK077216 promotes RANKL‐induced osteoclastogenesis and bone resorption via NFATc1 by inhibition of NIP45
Authors: Liu Chuan , Cao Zhen , Bai Yun , Dou Ce , Gong Xiaoshan , Liang Mengmeng , Dong Rui , Quan Hongyu , Li Jianmei , Dai Jingjin , Kang Fei , Zhao Chunrong , Dong Shiwu
Published: August 2018

Osteoclasts derived from the monocyte/macrophage hematopoietic lineage regulate bone resorption, a process balanced by bone formation in the continual renewal of the skeletal system. As dysfunctions of these cells result in bone metabolic diseases such as osteoporosis and osteopetrosis, the exploration of the mechanisms regulating their differentiation is a priority. A potential mechanism may involve long noncoding RNAs (lncRNAs), which are known to regulate various cell biology activities, including proliferation, differentiation, and apoptosis. The expression of the lncRNA AK077216 (Lnc‐AK077216) is significantly upregulated during osteoclastogenesis identified by microarray and verified by qPCR. Up‐ and downregulation of Lnc‐AK077216, respectively promotes and inhibits osteoclast differentiation, bone resorption, and the expression of related genes on the basis of tartrate‐resistant acid phosphatase staining, qPCR, and western blot results. In addition, Lnc‐AK077216 suppresses NIP45 expression and promotes the expression of NFATc1, an essential transcription factor during osteoclastogenesis. Besides, it was found that the expression of Lnc‐AK077216 and Nfatc1 is upregulated, whereas Nip45 expression is downregulated in bone marrow and spleen tissues of ovariectomized mice. The results suggest that Lnc‐AK077216 regulates NFATc1 expression and promotes osteoclast formation and function, providing a novel mechanism of osteoclastogenesis and a potential biomarker or a new drug target for osteoporosis.
mTOR inhibitor INK128 attenuates dextran sodium sulfate‐induced colitis by promotion of MDSCs on Treg cell expansion
Authors: Shi Guoping , Li Dan , Ren Jing , Li Xiaojing , Wang Tingting , Dou Huan , Hou Yayi
Published: August 2018

Accumulating evidence has shown that mammalian target of rapamycin (mTOR) pathway and myeloid‐derived suppressor cells (MDSCs) are involved in pathogenesis of inflammatory bowel diseases (IBDs). INK128 is a novel mTOR kinase inhibitor in clinical development. However, the exact roles of MDSCs and INK128 in IBD are unclear. Here, we showed that the INK128 treatment enhanced the resistance of mice to dextran sodium sulfate (DSS)–induced colitis and inhibited the differentiation of MDSCs into macrophages. Moreover, interferon (IFN)‐α level was elevated in INK128‐treated colitis mice. When stimulated with IFN‐α in vitro, MDSCs showed a superior immunosuppression activity. Of note, the regulatory T cells (Tregs) increased but Th1 cells decreased in INK128‐treated colitis mice. These results indicate that mTOR inhibitor INK128 attenuates DSS‐induced colitis via Treg expansion promoted by MDSCs. Our work provides a new evidence that INK128 is potential to be a therapeutic drug on DSS‐induced colitis via regulating MDSCs as well as maintaining Treg expansion.
Antioxidant effect of human placenta hydrolysate against oxidative stress on muscle atrophy
Authors: Bak Dong‐ho , Na Jungtae , Im Song I , Oh Chang Taek , Kim Jeom‐Yong , Park Sun‐Kyu , Han Hae Jung , Seok Joon , Choi Sun Young , Ko Eun Jung , Mun Seog‐Kyun , Ahn Suk‐Won , Kim Beom Joon
Published: August 2018

Sarcopenia, which refers to the muscle loss that accompanies aging, is a complex neuromuscular disorder with a clinically high prevalence and mortality. Despite many efforts to protect against muscle weakness and muscle atrophy, the incidence of sarcopenia and its related permanent disabilities continue to increase. In this study, we found that treatment with human placental hydrolysate (hPH) significantly increased the viability (approximately 15%) of H2O2‐stimulated C2C12 cells. Additionally, while H2O2‐stimulated cells showed irregular morphology, hPH treatment restored their morphology to that of cells cultured under normal conditions. We further showed that hPH treatment effectively inhibited H2O2‐induced cell death. Reactive oxygen species (ROS) generation and Mstn expression induced by oxidative stress are closely associated with muscular dysfunction followed by atrophy. Exposure of C2C12 cells to H2O2 induced abundant production of intracellular ROS, mitochondrial superoxide, and mitochondrial dysfunction as well as myostatin expression via nuclear factor‐κB (NF‐κB) signaling; these effects were attenuated by hPH. Additionally, hPH decreased mitochondria fission–related gene expression (Drp1 and BNIP3) and increased mitochondria biogenesis via the Sirt1/AMPK/PGC‐1α pathway and autophagy regulation. In vivo studies revealed that hPH‐mediated prevention of atrophy was achieved predominantly through regulation of myostatin and PGC‐1α expression and autophagy. Taken together, our findings indicate that hPH is potentially protective against muscle atrophy and oxidative cell death.
Noncoding RNAs within the HOX gene network in tumor pathogenesis and progression
Authors: Botti Gerardo , De Chiara Anna , Di Bonito Maurizio , Cerrone Margherita , Malzone Maria Gabriella , Collina Francesca , Cantile Monica
Published: August 2018

HOX genes are involved with normal development, cell identity, cell differentiation, cell metabolism, apoptosis, autophagy as well as with diseases such as tumor pathogenesis and progression. In particular, the genes belonging to HOX paralogous 13 seem to carry out a relevant role in both tumor development and disease progression. In recent years, several noncoding RNAs (ncRNA) sequences have been identified in HOX loci, including long noncoding RNA (lncRNA) and microRNA (miRNA), highly conserved during evolution. Many studies have shown that specific intergenic ncRNAs in HOX loci could directly modulate HOX genes expression in normal and pathological conditions. In the present review we attempt to describe the role of these ncRNAs, through the regulation of the HOX gene network, in normal cell biology, and, with particular emphasis, in diseases such as in cancer pathogenesis and progression.
FOXO3a is essential for murine endometrial decidualization through cell apoptosis during early pregnancy
Authors: Long Jing , Yang Cheng‐Shun , He Jun‐Lin , Liu Xue‐Qing , Ding Yu‐Bin , Chen Xue‐Mei , Tong Chao , Peng Chuan , Wang Ying‐Xiong , Gao Ru‐Fei
Published: August 2018

Embryo implantation is essential for normal pregnancy, and the process of decidualization is critical for embryo implantation. However, the mechanism of decidualization during early pregnancy is still unknown. Forkhead box O3a (FOXO3a) is the most important functional transcription factor of the forkhead box family and is a highly conserved transcription factor of apoptosis‐related genes. In the mouse uterus, FOXO3a was found to be expressed regularly from Days 1–7 of early pregnancy. Upon further exploration, it was found that FOXO3a was expressed at significantly higher levels at the implantation site than at the interimplantation site on Days 5–7 of pregnancy. Under artificial decidualization, FOXO3a was highly expressed in the first and second decidual zones. After decidualization, the expression of FOXO3a was significantly increased both in vivo and vitro. In primary stromal cells, apoptosis was reduced by decreased expression of FOXO3a after inducing decidualization. Moreover, when FOXO3a‐small interfering RNA was transfected into the uteri of mice, the expression of decidualization‐ and apoptosis‐related factors was impaired. Thus, FOXO3a might play an important role in decidualization during early pregnancy, and cell apoptosis might be one of pathways for FOXO3a‐regulated decidualization.
Epigenetic alterations of CYLD promoter modulate its expression in gastric adenocarcinoma: A footprint of infections
Authors: Ghadami Elham , Nikbakhsh Novin , Fattahi Sadegh , Kosari‐Monfared Mohadeseh , Ranaee Mohammad , Taheri Hassan , Amjadi‐Moheb Fatemeh , Godazandeh Gholamali , Shafaei Shahryar , Nosrati Anahita , Pilehchian Langroudi Maryam , Samadani Ali Akbar , Amirbozorgi Galia , Mirnia Vahideh , Akhavan‐Niaki Haleh
Published: August 2018

Gastric cancer (GC) is one of the most common causes of cancer‐related death in the world, with multiple genetic and epigenetic alterations involved in disease development. CYLD tumor suppressor gene encodes a multifunctional deubiquitinase which negatively regulates various signaling pathways. Deregulation of this gene has been found in different types of cancer. This study aimed to evaluate for the first time the CpG island methylation pattern of CYLD gene promoter, and its expression level in gastric adenocarcinoma. CYLD messenger RNA expression and promoter methylation in 53 tumoral and their non‐neoplastic counterpart tissues were assessed using quantitative polymerase chain reaction and bisulfite sequencing. Also, we investigated the impacts of the infectious agents including Helicobacter pylori (H. pylori), EBV, and CMV on CYLD expression and promoter methylation in GC. Results showed that the expression level of CYLD was downregulated in GC, and was significantly associated with gender (female), patient’s age (<60), high grade, and no lymph‐node metastasis (p = 0.001, 0.002, 0.03, and 0.003, respectively). Among the 31 analyzed CpG sites located in about 600 bp region within the promoter, two CpG sites were hypermethylated in GC tissues. We also found a significant inverse association between DNA promoter methylation and CYLD expression (p = 0.02). Furthermore, a direct association between H. pylori, EBV, and CMV infections with hypermethylation and reduced CYLD expression was observed (p = 0.04, 0.03, and 0.03, respectively). Our findings indicate that CYLD is downregulated in GC. Infectious agents may influence CYLD expression.
Different Effects of Atorvastatin on Cardiometabolic Risk Factors in Young Women With and Without Hyperprolactinemia
Authors: Krysiak Robert , Szkróbka Witold , Okopień Bogusław
Published: August 2018

Long‐term prolactin excess is often accompanied by numerous metabolic complications. No previous study has compared the effect of statin therapy on circulating levels of cardiometabolic risk factors in patients with elevated and normal prolactin levels. The study population consisted of 3 age‐, weight‐, and lipid‐matched groups of young women: 19 women with untreated hyperprolactinemia (group A), 20 normoprolactinemic women receiving bromocriptine treatment (because of previous hyperprolactinemia) (group B), and 20 untreated women with prolactin levels within the reference range (group C). Because of elevated total and low‐density lipoprotein cholesterol levels, all women were then treated with atorvastatin (40 mg daily). Apart from measuring plasma lipids, glucose homeostasis markers, and hormone levels at the beginning of the study and 12 weeks later, we measured circulating levels of uric acid, high‐sensitivity C‐reactive protein, homocysteine, and fibrinogen. Despite similar baseline levels of plasma lipids, levels of uric acid, high‐sensitivity C‐reactive protein, homocysteine, and fibrinogen as well as the degree of insulin resistance were higher in group A than in the remaining 2 groups. Atorvastatin reduced total and low‐density lipoprotein cholesterol levels in all study groups. However, only in normoprolactinemic women (groups B and C) did atorvastatin reduce circulating levels of nonlipid cardiometabolic risk factors, whereas only in group A did the drug slightly impair insulin sensitivity. The results of the study suggest that cardiometabolic effects of atorvastatin depend on the prolactin status of patients.
Investigation of fluorapatite crystallization in a fluidized bed reactor for the removal of fluoride from groundwater
Authors: Deng Linyu , Zhang Xiao , Huang Tinglin , Zhou Jianqi
Published: August 2018

BACKGROUND

This work further investigates fluoride removal from groundwater by induced crystallization in batch experiments and in a fluidized bed reactor (FBR). Phosphate rock (PR), which is an abundant ore and represents the basic raw material for the phosphatic fertilizer industry, was used as seed crystal in the induced crystallization process.

RESULTS

Induced crystallization in FBR reduced the concentration of F− in synthetic groundwater from 9.5 mg L‐1 to <1.0 mg L‐1. Phases with the potential for precipitation were calculated through thermodynamic equilibrium modeling. The formed precipitates were identified by powder x‐ray diffraction (XRD) and scanning electron microscopy, coupled with energy dispersive spectroscopy (SEM–EDS). Finally, fluorapatite crystallization mechanisms were confirmed by the induced crystallization of Ca5(PO4)3F on the surface of PR.

CONCLUSION

The fluorapatite crystallization process in FBR removed F− from groundwater, and the used seed crystal PR was rich in phosphorus and that could be recovered as raw material for the phosphatic fertilizer industry. © 2018 Society of Chemical Industry
Amino‐functionalized material from a bio‐template for silver adsorption: process evaluation in batch and fixed bed
Authors: Romero‐Cano Luis A , García‐Rosero Helena , del Olmo‐Iruela Monsalud , Carrasco‐Marín Francisco , González‐Gutiérrez Linda V
Published: August 2018

BACKGROUND

The modification of an organic matrix as a bio‐template (grapefruit peel) using urea and melamine was carried out to introduce amino groups on its surface and favor Ag(I) adsorption in aqueous solution for metal recovery.

RESULTS

Adsorption capacity in batch mode was proportional to the nitrogen content within the adsorbents, the maximum being the one obtained with the adsorbent functionalized with urea, 72.33 mg g−1, which was tested as a fixed bed in a column to evaluate the metal adsorption in a continuous flow model. The adsorption capacity of the fixed bed was 15.14 mg g−1, and its use was proved over three adsorption–desorption cycles.

CONCLUSION

Amino‐functionalized adsorbent achieved a high Ag+ uptake capacity; from the characterization it is proposed that the adsorption mechanism consists in the formation of the complex R‐NH2Ag+ and R‐COOAg. © 2018 Society of Chemical Industry