bluuebunny/crossref_metadata_2025_split huggingface dataset:
CASTOR1 suppresses the progression of lung adenocarcinoma and predicts poor prognosis
Authors: Zhou Xuefeng , Cheng Zhenshun , Chen Hao , Shi Shenqi , Wang Xianguo , Orang Matthew , Zhao Jinping 
Published: August 2018

AbstractAs a naturally occurring inhibitor of mammalian target of rapamycin (mTOR), accumulated evidence has confirmed that CASTOR1 plays a pivotal role in regulating the progression of human malignancies. However, the function of CASTOR1 in the development of lung adenocarcinoma is still unclear. Here we report that the expression of CASTOR1 is significantly reduced in lung adenocarcinoma cell lines as compared with that in normal lung epithelial cells. Cellular studies further revealed that ectopic CASTOR1 expression led to a significant suppression of the cellular proliferation, migration, and invasion of PC‐9 cells. To further test the role of CASTOR1 in human patients with lung cancers, tumor tissues derived from lung cancer patients and paired adjacent normal lung tissues were collected for immunohistochemical​​​​​​, biochemical, and molecular biology analysis. Immunoblotting and real‐time quantitative reverse transcription polymerase chain reaction analysis is revealed that CASTOR1 was significantly reduced in tumor tissues as compared with that in paired normal lung tissues. With immunostaining and retrospective analysis of pathological samples from lung cancer patients further revealed that expression of CASTOR1 was negatively correlated with smoking history, TNM stage, lymphnode metastasis, and distant metastasis. Furthermore, Kaplan‐Meier survival analysis indicated that patients with low CASTOR1 expression levels had a significantly worse 5‐year survival rate than those with high CASTOR1 expression. To further explore the molecular actions of CASTOR1 in lung cancer development, biochemical assays were performed and the results suggested that ectopic CASTOR1 expression resulted significant suppression of mTOR and downstream S6K phosphorylation, indicating that CASTOR1 might regulate the progression of lung adenocarcinoma by controlling mTOR activation. Thus, these findings demonstrated that CASTOR1 inhibits the tumorigenesis of lung adenocarcinoma cells and might serve as a potential therapeutic target or prognostic marker for human patients with lung adenocarcinoma.
Targeting axonal degeneration and demyelination using combination administration of 17β‐estradiol and Schwann cells in the rat model of spinal cord injury
Authors: Namjoo Zeinab , Mortezaee Keywan , Joghataei Mohammad T. , Moradi Fateme , Piryaei Abbas , Abbasi Yusef , Hosseini Amir , Majidpoor Jamal 
Published: August 2018

AbstractSchwann cells (SCs) are known to be responsible for axonal ensheathing and myelination, and their transplantation is used commonly for treatment of spinal cord injury (SCI). 17β‐estradiol (E2) has also reported for its protective roles in neurons in the transplanted SCs to the SCI model. In the current study, we evaluated the roles of E2 administration before SCs transplantation in targeting SCI‐induced axonal degeneration and demyelination. E2 (25 µg/kg, IP) was administered to the male Wistar rats underwent contusive SCI at T10 segment. At 7 days after injury, 1 × 106 SCs were transplanted to the injury epicenter of the spinal cord. The groups were laminectomy, SCI, SCI+E2, and SCI+E2+SCs. Functional recovery was evaluated using the Basso‐Bresnahan‐Beattie locomotor test. Sections from spinal cord were also assessed for histoloical staining, including Luxol fast blue, Bielschowsky's silver and immunofluorescence evaluation of myelin basic protein (MBP). The SCI group showed impaired locomotion in the hind limb, increased number of cavities within spinal cord, low observable numbers of regenerating fibers, and a significant decrease in the rate of expression for MBP. These changes were counteracted in the treatment groups (
P < 0.05 vs SCI) with no significant changes among them. From the results, it may be concluded that application of E2 and SCs could be effective when axons undergo demyelination and degenerative processes, and their combination could partly provide cumulative outcomes.
Chrysophanol induces cell death and inhibits invasiveness via mitochondrial calcium overload in ovarian cancer cells
Authors: Lim Whasun , An Yikyung , Yang Changwon , Bazer Fuller W. , Song Gwonhwa 
Published: August 2018

AbstractChrysophanol is a phytochemical typically extracted from rhubarb. Similar to other extracts from rhubarb, chrysophanol possesses anticancer activity against diverse cancerous cells. However, the apoptotic effects of chrysophanol in ovarian cancer remain unknown. In the current study, we examined the antitumorigenic activity of chrysophanol in human epithelial ovarian cancer cells, such as ES2 and OVCAR3. Chrysophanol decreased cell viability and increased cell death in a dose‐dependent manner. In addition, chrysophanol markedly increased the intracellular reactive oxygen species production in ES2 cells, but only increased it slightly in OVCAR3 cells. Consistent with increased reactive oxygen species production, extensive lipid peroxidation was detected in chrysophanol‐treated ES2 cells compared with that in untreated cells, whereas lipid peroxidation was unchanged in OVCAR3 cells in response to chrysophanol. Although there were no significant changes in calcium ions in the of ES2 and OVCAR3 cells, the concentration of calcium in the mitochondria increased dose dependent through disruption of the mitochondrial membrane potential in both ES2 and OVCAR3 cells compared with nontreated control cells. Moreover, chrysophanol activated the MAPK signaling pathways in the ovarian cancer cells. In addition, ovarian cancer cell invasiveness was suppressed, which implied that chrysophanol plays a role in preventing ovarian cancer metastasis. In conclusion, chrysophanol exhibits an anticancer effect via mitochondrial calcium overload and MAPK activation, suggesting its potential as a novel anticancer agent for human epithelial ovarian cancer.
EGFL7 promotes hepatocellular carcinoma cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/β‐catenin signaling
Authors: Li Zhi , Xue Tong‐Qing , Yang Chao , Wang Yun‐Liang , Zhu Xiao‐Li , Ni Cai‐Fang 
Published: August 2018

AbstractEpidermal growth factor‐like domain multiple 7 (EGFL7) is an important sport stimulating factor and motility related factors significantly enhanced the tumor cell metastasis and overexpressed in many cancers, including hepatocellular carcinoma (HCC), associated with tumorigenesis. However, the molecular mechanism by which EGFL7 regulates HCC cell proliferation and apoptosis and the correlation between EGFL7 and cyclin‐dependent kinases regulatory subunit 2 (CKS2), which is essential for biological function, have not fully explained. In this study, EGFL7 and CKS2 expression in patients with HCC was measured by real‐time polymerase chain reaction and immunohistochemistry. After HCC cells respectively transfected with pLKO.1‐EGFL7‐shRNA, pLVX‐Puro‐EGFL7 recombined vector or CKS2 small interfering RNA, cell counting kit‐8 and flow cytometry was performed to examine the cell proliferation and apoptosis, respectively, and the expression of β‐catenin, CKS2, CDK2, and cleaved caspase‐3 was measured by Western blot analysis. We found that EGFL7 and CKS2 were overexpressed in HCC tissues and a positive correlation was found between them. EGFL7 knockdown markedly inhibited proliferation and promoted apoptosis of HCC cells, along with decreased expression of CKS2 and CDK2, but increased cleaved caspase‐3 expression, while EGFL7 overexpression showed an opposite effect. EGFL7 silencing in nude mice also showed decreased tumor growth and altered protein expression similar to its effect in HCC cells in vitro. Importantly, CKS2 silencing significantly inhibited EGFL7‐induced HCC cell proliferation and protein expression, and Wnt/β‐catenin signaling pathway inhibitor IWR‐1‐endo significantly inhibited CKS2 expression in HCC cells. Taken together, EGFL7 promotes HCC cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/β‐catenin signaling.
TGF‐β/SMAD signaling inhibits intermittent cyclic mechanical tension‐induced degeneration of endplate chondrocytes by regulating the miR‐455‐5p/RUNX2 axis
Authors: Xiao Liang , Xu Shujuan , Xu Yongming , Liu Chen , Yang Bijing , Wang Jing , Xu Hongguang 
Published: August 2018

AbstractA mechanical stimulation plays a pivotal role in maintaining normal cartilage function. Our objective was to reveal the mechanism of action of the tension‐sensitive molecule miR‐455‐5p in the degeneration of endplate chondrocytes and to identify whether the transforming growth factor beta (TGF‐β)/SMAD signaling pathway has a regulatory effect on it. The expression profiles of members of the TGF‐β/SMAD pathway, miR‐455‐5p, and RUNX2 were determined by microRNA microarray analysis, reverse transcription quantitative polymerase chain reaction, luciferase reporter assay, and Western blot analysis. Intermittent cyclic mechanical tension (ICMT) induced the degeneration of endplate chondrocytes without affecting their viability. The tension‐sensitive molecule miR‐455‐5p specifically bound to RUNX2, a gene involved in the degeneration of endplate chondrocytes. Activation of the TGF‐β/SMAD signaling pathway upregulated miR‐455‐5p expression and thus inhibited RUNX2 levels. Therefore, the TGF‐β/SMAD signaling pathway inhibits the ICMT‐induced degeneration of endplate chondrocytes by regulating the miR‐455‐5p/RUNX2 axis.
Effect of a functional variant of tumor necrosis factor‐β gene in temporomandibular disorders: A pilot study
Authors: Yerliyurt Kaan , Nursal Ayse Feyda , Tekcan Akin , Karakus Nevin , Tumer Mehmet K. , Yigit Serbulent 
Published: August 2018

AbstractBackgroundTemporomandibular disorders (TMD) are a group of conditions that cause chronic orofacial pain. The tumor necrosis factor β (TNF‐β) is a proinflammatory cytokine that is involved in the various aspects of the inflammatory process including organization and maintenance, and in the arrangement of cells at the inflammation site. The purpose of this study was to evaluate the correlation between TNF‐β +252A/G (rs909253) variant and susceptibility to TMD in a Turkish cohort.MethodsThe study included 104 patients (26 males, 78 females) with TMD and 126 healthy controls (44 males, 82 females). The TNF‐β +252A/G variant analysis was based on Polymerase Chain Reaction‐Restriction Fragment Length Polymorphism (PCR‐RFLP).ResultsThere was no deviation from HWA for TNF‐β +252A/G variant in patient and control groups. There was significant difference in genotype and allele frequencies between patient group and control group in terms of TNF‐β +252A/G variant, respectively (P = 0.010, 0.015). A significant increase in the TNF‐β +252 AG genotype and G allele frequencies were observed in TMD patients compared to healthy controls. The individuals with GG genotype and G allele had an increased risk of developing TMD. A statistically significant association was observed when the patients were compared with the controls according to AA genotype vs AG+GG genotypes (P = 0.002, OR: 2.23, 95% CI:1.31‐3.82). TNF‐β +252A/G genotype distribution was associated with chewing problems (P = 0.046).ConclusionsIn conclusion, our results provided evidence that TNF‐β +252A/G variant may contribute to TMD development in a Turkish cohort. Further studies are needed to confirm this observation.
Comparative evaluation of in‐house Carba NP test with other phenotypic tests for rapid detection of carbapenem‐resistant Enterobacteriaceae
Authors: Bir Raunak , Mohapatra Sarita , Kumar Amarjeet , Tyagi Sonu , Sood Seema , Das Bimal Ku , Kapil Arti 
Published: August 2018

AbstractBackgroundThe prevalence of carbapenem‐resistant Enterobacteriaceae (CRE) is alarming worldwide causing serious infections. Rapid and accurate identification of CRE is crucial to reduce the mortality and morbidity. In this study, we tried to develop an in‐house Carba NP test for detection of CRE and evaluate its performance with others.MethodsA prospective study was conducted with 40 nonrepeating Enterobacteriaceae isolates over a period of 3 months. All the isolates were screened for carbapenem resistance as per CLSI 2016 guidelines followed by PCR for blaNDM‐1, blaOXA‐48, blaKPC, blaVIM, and blaIMP genes. All the isolates were subjected to five phenotypic tests, that is, in‐house Carba NP (iCarba NP), commercial Carba NP (cCarba NP), Blue‐Carba, modified Hodge test (MHT), and CHROMagar.ResultsAmong the 40 isolates, 87.5% were identified as Escherichia coli, 7.5% were Klebsiella pneumoniae, 2.5% were Enterobacter cloacae, and 2.5% were Citrobacter freundii. Thirty‐three of 40 (82.5%) isolates were found to harbor one or more resistant genes. Considering PCR to be the gold standard test, sensitivity of the phenotypic methods for CRE detection ranged from 63.6% (MHT) to 96.9% (CHROMagar). Both cCarba NP and iCarba NP observed to have highest specificity. The performance of iCarba NP was found comparable with cCarba NP by kappa score 1 and found approximately 10 times less expensive than cCarba NP.ConclusionCHROMagar was observed most sensitive assay for detection of CRE followed by both Carba NP tests. iCarba NP was proved cheaper and equally good as cCarba NP for detection of CRE.
Trust, sense of community, and civic engagement: Lessons from Australia
Authors: Miranti Riyana , Evans Mark 
Published: August 2018

AbstractThis article examines the association between trust, sense of community, and civic engagement, with a particular focus on the socioeconomic characteristics of individuals, using data from the Household, Income, and Labor Dynamics in Australia Survey. Through the use of panel logit and binary panel data models, we draw three core observations. First, there is evidence that trust is associated with civic engagement in Australia, particularly in the case of volunteering. Trust is a prerequisite for women to participate in volunteering but not for men, where a sense of community matters more. Second, a high sense of community matters for both types of participation, political and volunteering. Third, the relationships between trust, sense of community, and civic engagement are present among the Baby Boomer and Generation X generations but not the Generation Y generation, which participates differently. The study makes an important contribution to the literature by unmasking the gender and generation stories and debunking popular myths about the unwillingness of new Australians to engage in associative behavior.
Cytosolic sodium regulation in mouse cortical astrocytes and its dependence on potassium and bicarbonate
Authors: Noor Zinnia N. , Deitmer Joachim W. , Theparambil Shefeeq M. 
Published: August 2018

Sodium plays a major role in different astrocytic functions, including maintenance of ion homeostasis and uptake of neurotransmitters and metabolites, which are mediated by different Na+‐coupled transporters. In the current study, the role of an electrogenic sodium‐bicarbonate cotransporter (NBCe1), a sodium‐potassium‐chloride transporter 1 (NKCC1) and sodium‐potassium ATPase (Na+‐K+‐ATPase) for the maintenance of [Na+]i was investigated in cultured astrocytes of wild‐type (WT) and of NBCe1‐deficient (NBCe1‐KO) mice using the Na+‐sensitive dye, asante sodium green‐2. Our results suggest that cytosolic Na+ was higher in the presence of CO2/HCO3− (15 mM) than CO2/HCO3−‐free, HEPES‐buffered solution in WT, but not in NBCe1‐KO astrocytes (12 mM). Surprisingly, there was a strong dependence of cytosolic [Na+] on the extracellular [HCO3−] attributable to NBCe1 activity. Pharmacological blockage of NKCC1 with bumetanide led to a robust drop in cytosolic Na+ in both WT and NBCe1‐KO astrocytes by up to 6 mM. There was a strong dependence of the cytosolic [Na+] on the extracellular [K+]. Inhibition of the Na+‐K+‐ATPase led to larger increase in cytosolic Na+, both in the absence of K+ as compared with the presence of ouabain and in NBCe1‐KO astrocytes as compared with WT astrocytes. Our results show that cytosolic Na+ in mouse cortical astrocytes can vary considerably and depends greatly on the concentrations of HCO3− and K+, attributable to the activity of the Na+‐K+‐ATPase, of NBCe1 and NKCC1.
Thrombospondin‐4 critically controls transforming growth factor β1 induced hypertrophic scar formation
Authors: Qian Wei , Li Ning , Cao Qian , Fan Jufeng 
Published: August 2018

Transforming growth factor β (TGF‐β) is a growth factor presenting important functions during tissue remodeling and hypertrophic scar (HS) formation. However, the underlying molecular mechanisms are largely unknown. In this study, we identified thrombospondin‐4 (TSP‐4) as a TGF‐β1 target that essentially mediates TGF‐β1‐induced scar formation both in vitro and in vivo. The expression of TSP‐4 was compared on both mRNA and protein levels between hypertrophic scar fibroblasts (HSFs) and normal skin fibroblast (NFs) in response to TGF‐β1 treatment. Two signaling molecules, Smad3 and p38, were assessed for their importance in regulating TGF‐β1‐mediated TSP‐4 expression. The significance of TSP‐4 in controlling TGF‐β1‐induced proliferation, invasion, migration, and fibrosis in HSFs was analyzed by knocking down endogenous TSP‐4 using small hairpin RNA (shRNA) (TSP‐4 shRNA). Finally, a skin HS model was established in rats and the scar formation was compared between rats treated with vehicle (saline), TGF‐β1, and TGF‐β1 + TSP‐4 shRNA. The TSP‐4 level was significantly higher in HSFs than in NFs and TGF‐β1 more potently boosted TSP‐4 expression in the former than in the latter. Both Smad3 and p38 essentially mediated TGF‐β1‐induced TSP‐4 expression. TSP‐4 shRNA significantly suppressed TGF‐β1‐stimulated proliferation, invasion, migration, or fibrosis of HSFs in vitro and drastically improved wound healing in vivo. TGF‐β1, by activating both Smad3 and p38, induces TSP‐4, which in turn not only presents a positive feedback regulation on the activation of Smad3 and p38, but also essentially mediates TGF‐β1‐induced HS formation. Targeting TSP‐4 thus may benefit HS treatment.
Exosome‐encapsulated miR‐6089 regulates inflammatory response via targeting TLR4
Authors: Xu Donghua , Song Meiyan , Chai Chunxiang , Wang Jinghua , Jin Chengwen , Wang Xiaodong , Cheng Min , Yan Shushan 
Published: August 2018

Exosome‐encapsulated microRNAs (miRNAs) have been identified as potential biomarkers in autoimmune diseases. However, little is known about the role of exosome‐delivered miRNAs in rheumatoid arthritis (RA). In this study, we investigated the profile of specific exosomal miRNAs by microarray analysis of serum exosomes from three patients with RA and three healthy controls. Quantitative real‐time PCR (qRT‐PCR) was performed to validate the aberrantly expressed exosomal miRNAs. A total of 20 exosome‐encapsulated miRNAs were identified to be differently expressed in the serum of patients with RA compared with controls. Interestingly, we found that exosome‐encapsulated miR‐6089 was significantly decreased after validation by qRT‐PCR in serum exosomes from 76 patients with RA and 20 controls. Besides, miR‐6089 could inhibit lipopolysaccharide (LPS)‐induced cell proliferation and activation of macrophage‐like THP‐1 cells. TLR4 was a direct target for miR‐6089. MiR‐6089 regulated the generation of IL‐6, IL‐29, and TNF‐α by targetedly controlling TLR4 signaling. In conclusion, exosome‐encapsulated miR‐6089 regulates LPS/TLR4‐mediated inflammatory response, which may serve as a novel, promising biomarker in RA.
Combination therapy with KRAS siRNA and EGFR inhibitor AZD8931 suppresses lung cancer cell growth in vitro
Authors: Zarredar Habib , Pashapour Shadi , Ansarin Khalil , Khalili Majid , Baghban Roghayyeh , Farajnia Safar 
Published: August 2018

Lung cancer is a leading cause of cancer‐related deaths worldwide, with less than a 5‐year survival rate for both men and women. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma oncogene (KRAS) signaling pathways play a critical role in the proliferation and progression of various cancers, including lung cancer. Genetic studies have shown that amplification, over‐expression, or mutation of EGFR is an early and major molecular event in many human tumors. KRAS mutation is a negative factor in various cancer, including non‐small‐cell lung cancer, and complicates therapeutic approaches with adjuvant chemotherapy and anti‐EGFR directed therapies. This article is dedicated to evaluating the synergistic effect of a novel EGFR inhibitor AZD8931 and KRAS small interfering RNA (siRNA) on the proliferation and apoptosis of lung adenocarcinoma cancer cells. A549 lung cancer cells were treated with KRAS siRNA and the EGFR inhibitor alone or in combination. The cytotoxic effects of KRAS siRNA and te EGFR inhibitor were determined usingMTT assay, and induction of apoptosis was determined by FACS analysis. Suppression of KRAS, Her‐2, and EGFR expression by treatments was measured by qRT‐PCR and western blotting. KRAS siRNA and the EGFR inhibitor significantly reduced the proliferation of A549 cells as well as KRAS and EGFR mRNA levels 24 hr after treatment. The results also indicated that the silencing of KRAS and EGFR has synergistic effects on the induction of apoptosis on the A549 cells. These results indicated that KRAS and EGFR might play important roles in the progression of lung cancer and could be potential therapeutic targets for treatment of lung cancer.
HPV16 E7‐induced upregulation of KDM2A promotes cervical cancer progression by regulating miR‐132–radixin pathway
Authors: Ou Rongying , Zhu Linyu , Zhao Liang , Li Wenfeng , Tao Fengxing , Lu Yiyi , He Qin , Li Jianrong , Ren Yi , Xu Yunsheng 
Published: August 2018

BackgroundHuman papillomavirus (HPV) infection and viral proteins expression cause a number of epigenetic alterations leading to cervical carcinogenesis. The recent discovery of a large amount of histone methylation modifiers reveals important roles of these enzymes in regulating tumor progression.MethodsThe changes in expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E7 in CaSki cells. Lysine‐specific demethylase 2A (KDM2A)‐regulated microRNAs (miRNAs) in cervical cancer pathogenesis were disclosed using quantitative real‐time polymerase chain reaction. The function of KDM2A–miRNAs on cervical cancer was investigated in vitro and in vivo.ResultsUpregulation of KDM2A induced by HPV16 E7 promotes cervical cancer cell proliferation and invasion and is correlated with poor prognosis in patients with cervical cancer. KDM2A physically interacts with the promoter of miR‐132 and suppresses its expression by removing the mono or dimethyl group from H3K36 at the miR‐132 locus. Functionally, miR‐132 represses cancer cell proliferation and invasion by inhibiting radixin (RDX). Upregulated KDM2A promotes cervical cancer progression by repressing miR‐132, which results in a derepression of RDX. Therefore, KDM2A functions as a tumor activator in cervical cancer pathogenesis by binding miR‐132 promoter and abrogating its tumor suppressive function.ConclusionOur results suggest a function for KDM2A in cervical cancer progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of cervical cancer.