bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weighted gene co‐expression network analysis to explore the mechanism of heroin addiction in human nucleus accumbens
Authors: Shi Xugang , Li Yunxiao , Yan Peng , Shi Yuhui , Lai Jianghua 
Published: November 2019

AbstractHeroin dependence is a complex behavioral disease, and a chronic encephalopathy with the important feature of relapse. The purpose of the study was to identify the regulatory mechanism of the nucleus accumbens (NAc) in heroin dependence. We used weighted gene co‐expression network analysis to analyze the GSE87823 data package, which included 27 heroin users and 22 controls of human NAc tissue. Modules were correlated with basic information of samples and enrichment analyses used to identify biological function and transcription factors and online tools were used to perform the gene ontology of significant genes. We identified one gene module from the total data (blue) and the male data (turquoise), respectively. The overlap genes of top 10 hub genes in significant modules (PRR11, SLC35E1, LPP, ZNF721, ZNF611, LRRFIP1) were selected to identify as candidate genes in the regulation mechanism of NAc in heroin dependence. Then, we accorded the results to further explore that miRNA‐hsa‐miR‐155‐5p in male and total may be a potential marker. The candidate genes may serve as novel prognostic markers and treatment targets. Hsa‐miR‐155‐5p may be a promising regulatory point for the treatment of heroin addiction.
Combination of attenuated Salmonella carrying PD‐1 siRNA with nifuroxazide for colon cancer therapy
Authors: Zhao Tiesuo , Feng Yuchen , Guo Mengmeng , Zhang Chaohui , Wu Qiang , Chen Jian , Guo Sheng , Liu Shenzhen , Zhou Qingsa , Wang Zizhong , Fan Wenyan , Zhang Yongxi , Jia Huijie , Feng Zhiwei 
Published: November 2019

AbstractColon cancer is a member of malignant tumors in the digestive system. Traditional treatment strategies are ineffective and improving the treatment of colon cancer is an urgent need. Targeting programmed cell death‐1 (PD‐1) by monoclonal antibodies has shown some therapeutic effectiveness and has advantages. Additionally, the Stat3 inhibitor nifuroxazide was employed to promote the antitumor activity. Here, we hypothesized that combining nifuroxazide with PD‐1 small interfering RNA carried by attenuated Salmonella would exert a synergistic antitumor effect on colon cancer. Indeed, treatment with this combination effectively inhibited the development of colon cancer in mice and improved the survival rate. These two novel anticancer agents worked synergistically to elicit potent antitumor immunity and achieve improved therapeutic efficacy. The underlying mechanisms are mainly involved with immune regulation and cell apoptosis. This study provides a previous framework for combining this Stat3 inhibitor with RNAi designed to block immune checkpoint signaling for cancer therapy.
LINC00116 enhances cervical cancer tumorigenesis through miR‐106a/c‐Jun pathway
Authors: Lai Yiqing , Zhou Beibei , Tan Qingqing , Xu Juan , Wan Ting , Zhang Lina 
Published: November 2019

AbstractSome studies imply that LINC00116 is involved in cervical cancer progression; however, the molecular mechanism by which LINC00116 modulating tumorigenesis of cervical cancer remains not clear. Reverse transcription‐quantitative PCR (RT‐qPCR) and the Western blot approaches were employed to probe genes expression levels. To examine the tumorigenic abilities of cervical cancer cells, MTT assay, Transwell assay, and wound‐healing assay were used to investigate proliferation, invasion, and migration of HeLa or C‐33A cells. LINC00116 knockdown attenuates cell proliferation, invasion, and migration of cervical cancer cells. miR‐106a directly binds LINC00116 and regulate each other. Moreover, miR‐106a inhibitor remarkably enhanced tumorigenesis of shLINC00116 HeLa cells. Through bioinformatic and dual‐luciferase reporter assay, the results showed that miR‐106a mimic directly targeted and downregulated the c‐Jun. c‐Jun overexpression could greatly rescue miR‐106a mimic‐modulated cervical cancer tumorigenesis. LINC00116 knockdown and miR‐106a mimic‐modulated programmed cell death ligand 1 (PD‐L1) expression, which could be reverted by c‐Jun introduction. LINC00116, PD‐L1, and JUN were both upregulated in cervical cancer tumors compared to normal tissues. Lower expression levels of LINC00116 and JUN, as well as higher level of miR‐106a were closely associated with higher overall survival of cervical cancer patients. Here, we report a novel role for LINC00116 in tumorigenesis of cervical cancer by regulating miR‐106a/c‐Jun axis. Our findings provide a foundation for understanding cervical cancer and facilitate the development of therapeutical approaches by targeting LINC00116.
Coordinated expression of p300 and HDAC3 upregulates histone acetylation during dentinogenesis
Authors: Tao Huangheng , Li Qiuhui , Lin Yuxiu , Zuo Huanyan , Cui Yu , Chen Shuo , Chen Zhi , Liu Huan 
Published: November 2019

AbstractCellular differentiation is caused by highly controlled modifications in the gene expression but rarely involves a change in the DNA sequence itself. Histone acetylation is a major epigenetic factor that adds an acetyl group to histone proteins, thus altering their interaction with DNA and nuclear proteins. Illumination of the histone acetylation during dentinogenesis is important for odontoblast differentiation and dentinogenesis. In the current study, we aimed to discover the roles and regulation of acetylation at histone 3 lysine 9 (H3K9ac) and H3K27ac during dentinogenesis. We first found that both of these modifications were enhanced during odontoblast differentiation and dentinogenesis. These modifications are dynamically catalyzed by histone acetyltransferases (HATs) and deacetylases (HDACs), among which HDAC3 was decreased while p300 increased during odontoblast differentiation. Moreover, overexpression of HDAC3 or knockdown p300 inhibited odontoblast differentiation in vitro, and inhibition of HDAC3 and p300 with trichostatin A or C646 regulated odontoblast differentiation. Taken together, the results of our present study suggest that histone acetylation is involved in dentinogenesis and coordinated expression of p300‐ and HDAC3‐regulated odontoblast differentiation through upregulating histone acetylation.
Retracted: Long noncoding RNA ZFPM2‐AS1 is involved in lung adenocarcinoma via miR‐511‐3p/AFF4 pathway
Authors: Li Juan , Ge Jun , Yang Ye , Liu Bin , Zheng Min , Shi Rui 
Published: November 2019

AbstractLung cancer is the dominating cause of cancer‐induced death and can be classified into small cell lung cancer and non–small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the most common histological subtype of NSCLC and its pathology remains unclear. Mounting reports have revealed that lncRNAs could regulate cellular activities in cancers. Yet the role of ZFPM2 antisense RNA 1 (ZFPM2‐AS1) in LUAD has not been elucidated. Using GEPIA online dataset, we identified the amplification of ZFPM2‐AS1 in LUAD tissues. Through quantitative real‐time reverse transcription‐polymerase chain reaction analysis, we observed an upregulation of ZFPM2‐AS1 in LUAD cell lines. Conducting loss‐of‐function assays, we found that ZFPM2‐AS1 depletion impaired cell viability, suppressed cell migration, and reversed epithelial‐mesenchymal transition progress in LUAD cells. Mechanism investigation manifested that ZFPM2‐AS1 was distributed in the cytoplasm of LUAD cells. Moreover, ZFPM2‐AS1 functioned as a molecular sponge of miR‐511‐3p, which was a suppressor in LUAD. Moreover, ZFPM2‐AS1 sponged miR‐511‐3p and thereby deregulated AF4/FMR2 family member 4 (AFF4), a target of miR‐511‐3p. At length, rescue assays indicated that AFF4 overexpression revived the inhibiting effects of ZFPM2‐AS1 knockdown on the biological processes in LUAD. All in all, this study uncovered the function and the mechanism of ZFPM2‐AS1 in LUAD.
Genome‐wide screening diagnostic biomarkers and the construction of prognostic model of hepatocellular carcinoma
Authors: Liu Furong , Liao Zhibin , Song Jia , Yuan Chaoyi , Liu Yachong , Zhang Hongwei , Pan Yonglong , Zhang Zhanguo , Zhang Bixiang 
Published: November 2019

AbstractAlthough methods in diagnosis and therapy of hepatocellular carcinoma (HCC) have made significant progress in decades, the overall survival (OS) of HCC remains dissatisfactory, so it is particularly important to find better diagnostic and prognostic biomarkers. In this study, we found a more reliable potential diagnostic biomarkers and constructed a more accurate prognostic evaluation model based on integrated transcriptome sequencing analysis of multiple independent data sets. First, we performed quality evaluation and differential analysis on seven Gene Expression Omnibus (GEO) data sets, and then comprehensively analyzed the differentially expressed genes with a robust rank aggregation algorithm. Next, Least absolute shrinkage and selection operator (LASSO) regression was used to establish an 8‐gene prognostic risk score (RS) model. Finally, the prognostic model was further validated in the GEO data set. Also, RS has independence on other clinicopathological characteristics but has similarities in prognostic assessment compared with the T stage. Moreover, the combination of T stage and prognostic RS model based on the 8‐gene had a better prognostic evaluation effect. In brief, our research suggest that the prognostic risk model of 8 genes has important clinical significance in HCC patients, and can further enrich the prognostic guidance value of the traditional T stage.
Chrm3 protects against acinar cell necrosis by stabilizing caspase‐8 expression in severe acute pancreatitis mice model
Authors: Huang Ning , Murtaza Ghulam , Wang Lujing , Luan Jing , Wang Xinlei , Sun Yumiao , Wu Xing , Tao Yuxi , Shi Shuoxi , Cao Peihua , Qiao Yu , Han Dong , Kou Jiayuan , Ma Ning , Gao Xu 
Published: November 2019

AbstractAcinar cells in acute pancreatitis (AP) die through apoptosis and necrosis, the impacts of which are quite different. Early clinical interference strategies on preventing the progress of AP to severe acute pancreatitis (SAP) are the elimination of inflammation response and inhibition of necrosis. Muscarinic acetylcholine receptor M3 was encoded by Chrm3 gene. It is one of the best‐characterized receptors of pancreatic β cells and regulates insulin secretion, but its function in AP remains unclear. In this study, we explored the function of Chrm3 gene in the regulation of cell death in l‐arginine‐induced SAP animal models. We found that Chrm3 was upregulated in pancreatitis, and we further confirmed the localization of Chrm3 resided in both pancreatic islets and acinar cell membranes. The reduction of Chrm3 decreased the pathological lesion of SAP and reduced amylase activities in serum. Consistently, Chrm3 can suppress acinar cells necrosis markedly, but has no effect on regulating apoptosis after l‐arginine treatment. It was shown that Chrm3 attenuated acinar cells necrosis at least in part by stabilizing caspase‐8. Thus, this study indicates that Chrm3 is critical participants in SAP, and regulation of Chrm3 expression might be a useful therapeutic strategy for preventing pathologic necrosis.
Retracted: Silencing circular RNA circANKRD36 remits lipopolysaccharide‐induced inflammatory damage by regulating microRNA‐15/MyD88
Authors: Wang Qiaoyan , Tao Shujun , Zhu Nan , Li Tingting , Yu Lingling 
Published: November 2019

AbstractBedsore 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.
Diagnostic and mechanistic values of microRNA‐130a and microRNA‐203 in patients with papillary thyroid carcinoma
Authors: Zhu Jie , Zheng Xiaoyu , Yang Xi 
Published: November 2019

AbstractThis research was determined to unearth the diagnostic values and the effects of microRNA (miR)‐130a and miR‐203 on cell proliferation and apoptosis of papillary thyroid carcinoma (PTC). Expression of miR‐130a and miR‐203 were evaluated and were subjected to correlation analysis. The diagnostic values of miR‐130a and miR‐203 and their associations with clinicopathological characteristics of patients with PTC were measured. The expression levels of miR‐130a and miR‐203 in K1, IHH4, TPC‐1, and BCPAP cells together with Nthy‐ori 3‐1 cells were measured. Cells were transfected with miR‐130a mimics, miR‐203 mimics, and coordinate of miR‐130a mimics and miR‐203 mimics. Cell growth, colony formation, and apoptosis were detected by cell counting kit‐8 (CCK‐8) assay, colony formation assay, and flow cytometry. PTC tissues had decreased miR‐130a and miR‐203 relative to adjacent normal tissues and normal thyroid tissue (both P < .05). miR‐130a was in positive correlation with miR‐203 (r = 0.754, P < .01). miR‐130a was related with tumor infiltration and tumor stage while miR‐203 was implicated in tumor stage and lymph‐node metastasis. The area under the curve (AUC), sensitivity, as well as specificity for miR‐130 in predicting PTC was 0.839, 74.5%, and 85.0% and those for miR‐203 were 0.818, 73.7%, and 84.0%, respectively. PTC cells had lower expression of miR‐130a and miR‐203 than that in Nthy‐ori 3‐1 cells. After transfected miR‐130a and miR‐203 mimics in BCPAP and TPC‐1 cells, both cells had increased miR‐130a and miR‐203, promoted cell apoptosis rate and decreased cell growth rate, and colony formation ability. After coordinately transfected with miR‐130a mimics and miR‐203 mimics, the cell growth and colony formation ability of PTC cells were restrained, and apoptosis of PTC cells was elevated (all P < .05). This study highlights that miR‐130a and miR‐203 have satisfactory diagnostic value in PTC and upregulated miR‐130a and miR‐203 can inhibit PTC cell growth and promote cell apoptosis.
Antioxidant, hepatoprotective, genoprotective, and cytoprotective effects of quercetin in a murine model of arthritis
Authors: Saccol Renata da Silva Pereira , da Silveira Karine Lanes , Manzoni Alessandra Guedes , Abdalla Fátima Husein , de Oliveira Juliana Sorraila , Dornelles Guilherme Lopes , Barbisan Fernanda , Passos Daniela Ferreira , Casali Emerson André , de Andrade Cinthia Melazzo , da Cruz Ivana Beatrice Mânica , Leal Daniela Bitencourt Rosa 
Published: November 2019

AbstractRheumatoid arthritis is a highly debilitating inflammatory autoimmune disease which is characterized by joint destruction. The present study sought to investigate the effect of quercetin in rats with complete Freund's adjuvant‐induced arthritis. Animals were divided into control/saline, control/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg) arthritis/saline, and arthritis/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg); the treatments were administered for 45 days. Biochemical, oxidative stress, genotoxicity, and cytotoxicity parameters were evaluated. All doses of quercetin reduced the levels of aspartate aminotransferase, thiobarbituric acid‐reactive substances, and reactive oxygen species; however, only treatment with 25 or 50 mg/kg increased catalase activity. Total thiol and reduced glutathione levels were not significantly affected by the induction nor by the treatments. Genotoxicity assessed by DNA damage, and cytotoxicity through picogreen assay, decreased after treatments with quercetin. Our results present evidence of the antioxidant, cytoprotective, genoprotective and hepatoprotective, and effects of quercetin, demonstrating its potential as a candidate for coadjuvant therapy.
Formin mDia1 contributes to migration and epithelial‐mesenchymal transition of tubular epithelial cells exposed to TGF‐β1
Authors: Li Yu‐Ying , Jiang Guo‐Tao , Chen Li‐Jie , Jiang Yan‐Hong , Jiao Jun‐Dong 
Published: November 2019

AbstractRenal tubular epithelial cells may undergo epithelial‐mesenchymal transition (EMT) in response to stimuli, such as transforming growth factor (TGF)‐β1, leading to myofibroblast activation and renal fibrosis. The formin mDia1 is required for nucleation and polymerization of actin and the microtubule cytoskeleton. The present study sought to explore the role of mDia1 in EMT of tubular epithelial cells. A rat model of unilateral ureteral obstruction (UUO) was established. The expression of TGF‐β1, collagen I, collagen III, and mDia1 in the kidneys was examined at day 7 after surgery. The effect of mDia1 on EMT was explored in NRK‐52E cells by exposing them to TGF‐β1. Increased expression of TGF‐β1, collagen I, collagen III, and mDia1 was found in obstructive kidneys of UUO model rats. Exposing rat tubular epithelial cells to TGF‐β1 promoted collagen I and collagen III expression but had no effect on mDia1 expression. Silencing mDia1 expression impeded epithelial cell migration as well as reduced TGF‐β1, collagen, and Profilin1 expression, whereas mDia1 overexpression exerted an opposite effect. Furthermore, mDia1 regulated the expression of vimentin, α‐smooth muscle actin, and E‐cadherin and focal adhesion‐kinase (FAK)/Src activation through Profilin1. Inhibition of the mDia1 activator RhoA by fasudil reversed EMT, and FAK/Src activation induced by mDia1. In conclusion, mDia1 regulated tubular epithelial cell migration, collagen expression, and EMT in NRK‐52E cells exposed to TGF‐β1. Thus, suppression of mDia1 activation might be a strategy to counteract renal fibrosis.
MicroRNA‐7 promotes neural differentiation of trabecular meshwork mesenchymal stem cell on nanofibrous scaffold
Authors: Jedari Behrouz , Rahmani Ali , Naderi Mahmood , Nadri Samad 
Published: November 2019

AbstractThe purpose of this study was to investigate miR‐7 overexpression effects on neural differentiation of mesenchymal stem cells (MSCs) on both two‐dimensional (2D) and three‐dimensional (3D) culture systems. We upregulated miR‐7 through lentiviral vector in trabecular meshwork MSCs (TMMSCs) and polymers of poly l‐lactic acid/polycaprolactone fibrous scaffold were fabricated by electrospinning and characterized using scanning electron microscopy (SEM) and Fourier transform infrared (FTIR). Neural markers expression was evaluated through quantitative‐polymerase chain reaction (q‐PCR) and immunostaining. The results showed that the high percentage of cell transduction (84.9%) and miR‐7 expression (folds: 677.93 and 556.4) was detected in TMMSCs‐miR‐7(+). SEM and FTIR established the fabrication of the hybrid scaffold. q‐PCR analysis showed that on days 14 and 21 of transduction, the expression level of Nestin and glial fibrillary acidic protein (GFAP) genes were significantly higher in the scaffold (3D) compared with tissue culture polystyrene (2D) culture. The expression of microtubule‐associated protein‐2 (MAP‐2) and GFAP genes in TMMSCs‐miR‐7(+) cells were significantly higher than those miR‐7(−) cells after 21 days of cell culture. Also, MAP‐2 and Nestin proteins were detected in TMMSCs‐miR‐7(+) cells. Our results demonstrate that miR‐7 is involved in neural differentiation of TMMSCs and scaffold can improve differentiate into glial and neural progenitor cells. These findings provided some information for future use of microRNAs and scaffold in tissue engineering and cell therapy for neurological diseases.
CDK2 destabilizes tumor suppressor C/EBPα expression through ubiquitin‐mediated proteasome degradation in acute myeloid leukemia
Authors: Thacker Gatha , Mishra Mukul , Sharma Akshay , Singh Anil Kumar , Sanyal Sabyasachi , Trivedi Arun Kumar 
Published: November 2019

AbstractDeregulation and functional inhibition of CCAAT‐enhancer‐binding protein α (C/EBPα), a key transcription factor of myeloid lineage leads to development of myeloid leukemia. In this study, we show that cyclin‐dependent kinase 2 (CDK2) negatively regulates C/EBPα protein levels in myeloid leukemia cells. The overexpression of CDK2 inhibited C/EBPα both in a heterologous HEK293T and U937 myeloid leukemia cells. On the contrary, CDK2 depletion enhanced endogenous C/EBPα protein levels. CDK2 mitigated C/EBPα levels by promoting its ubiquitin‐mediated proteasome degradation. We further showed that although CDK2 interacted with C/EBPα, direct interaction of CDK2 with C/EBPα is not involved in C/EBPα downregulation. CDK2‐dependent phosphorylation of C/EBPα on its widely reported phosphorylatable amino acid residues is apparently not required for C/EBPα degradation by CDK2. Furthermore, our data demonstrate that CDK2‐driven C/EBPα inhibition mitigates its transactivation potential and cellular functions such as ability to promote myeloid differentiation and growth arrest.
MicroRNA‐326 attenuates hepatic stellate cell activation and liver fibrosis by inhibiting TLR4 signaling
Authors: Liao Xin , Zhan Wei , Tian Tian , Yu Lei , Li Rui , Yang Qin 
Published: November 2019

AbstractHepatic fibrosis is a chronic inflammatory and reversible repair reaction of the liver under the continuous action of virus or various injuries. In this study, we aimed at identifying the role of miR‐326 in the hepatic stellate cell (HSC) activation and liver fibrosis and its potential mechanism. In this study, the liver fibrosis mouse model was developed by injecting CCl4. Liver tissue morphology was observed and the expression level of α‐smooth muscle actin, collagen1α1 and miR‐326 was measured. Target gene identification was performed by loss‐of‐function and gain‐of‐function. The effect of miR‐326 on the expression level of the cytokines associated with the TLR4/MyD88/nuclear factor‐κB (NF‐κB) pathway was assessed in vitro and in vivo. We show that miR‐326 was downregulated in CCl4‐induced fibrotic mice and activated HSCs. The target gene of miR‐326 is TLR4. Moreover, miR‐326 inhibited the activation of HSCs in vitro through TLR4/MyD88/NF‐κB signaling. miR‐326 attenuated hepatic fibrosis and inflammation of CCl4‐induced mice in vivo. Our results demonstrate for the first time that miR‐326 inhibits HSC activation through TLR4/MyD88/NF‐κB signaling. Furthermore, miR‐326 plays critical roles in attenuating liver fibrosis and inflammation, suggesting the therapeutic potential of miRNAs.