Renal cell carcinoma (RCC) is the predominant form of kidney cancer. Despite the significant improvements in survival rates for advanced RCC patients due to targeted therapy and immunotherapy, challenges such as drug resistance and severe adverse reactions continue to hinder effective management. Therefore, there is an urgent need to identify new therapeutic agents for RCC. Natural products, derived from plants, animals, and microorganisms, are increasingly recognized for their potential in treating complex diseases such as cancer. Dendrobine, a natural product extracted from Dendrobium, holds significant anticancer potential. However, its role in anti-RCC therapy remains poorly understood. This study applied network pharmacology to explore the role of Dendrobine in RCC treatment, identifying STAT3 as a key target. Furthermore, a series of in vitro experiments confirmed that Dendrobine inhibits RCC cell growth. CCK-8 assays demonstrated that Dendrobine inhibits RCC cell viability in a concentration-dependent manner, with an IC50 of 142.5 μM for 786-O cells and 146.5 μM for A498 cells. Clonogenic formation assays and EdU staining confirmed that Dendrobine suppresses RCC cell proliferation. Wound healing and invasion assays showed that Dendrobine inhibits RCC cell migration and invasion. Hoechst 33342/PI co-staining demonstrated that Dendrobine induces apoptosis in RCC cells. Mechanistically, Western blot analysis revealed that Dendrobine targets the PI3K/Akt signaling pathway by inhibiting the expression of p-PI3K, p-Akt, and p-Erk. Overall, this study seeks to elucidate the underlying pharmacological mechanisms and provide new insights for potential therapeutic strategies in RCC.

Renal cell carcinoma (RCC) is the most lethal malignancy of the urinary system, with limited treatment options due to drug resistance and the adverse effects associated with current therapies. This review aims to systematically examine the therapeutic potential of flavonoids, which are natural polyphenolic compounds possessing anti-inflammatory, antioxidant, and anticancer properties, in the context of RCC treatment. We summarize the anticancer activities of 26 natural flavonoids, classified into six subclasses, and explore their mechanisms of action, including the inhibition of tumor cell proliferation, migration, and invasion, as well as the induction of apoptosis, autophagy, and ferroptosis. Particular attention is paid to their modulation of key signaling pathways such as the JAK/STAT3, PI3K/Akt/mTOR, and miRNA-related axes, including miR-21/YAP1 and miR-324-3p/GPX4, providing a molecular basis for their anti-RCC activity. We also address several pharmacological challenges that limit the clinical application of flavonoids, including poor bioavailability, metabolic instability, and potential toxicity. Emerging solutions such as novel flavonoid derivatives, advanced drug delivery systems, and rational combination therapy strategies are also discussed. Current clinical evidence, including a phase II trial of flavopiridol in advanced RCC, highlights the potential but also the need for further validation. In conclusion, flavonoids offer a promising approach to improving RCC treatment. Future research should focus on optimizing their therapeutic efficacy and ensuring their safe clinical translation, with the goal of achieving personalized and minimally invasive cancer therapies.

Sunitinib resistance presents a significant challenge in the treatment of clear cell renal cell carcinoma (ccRCC). The role of TRIB3, a newly identified oncogene, in tumor drug resistance has been widely studied. However, the mechanism by which TRIB3 contributes to sunitinib resistance in ccRCC has not been previously explored. This study aimed to investigate the mechanism through which TRIB3 regulates ferroptosis to increase the susceptibility of ccRCC to sunitinib treatment. Bioinformatics analysis and experimental validation revealed that TRIB3 is significantly upregulated in ccRCC tissues and is associated with poor prognosis. Knockdown of TRIB3 using siRNA transfection inhibited the proliferation and migration of ccRCC cells and induced ferroptosis. Following sunitinib treatment, TRIB3 knockdown increased cell sensitivity to sunitinib, enhanced the suppressive impact of sunitinib, and augmented sunitinib-induced ferroptosis. This study demonstrated that TRIB3 knockdown induces ferroptosis by targeting the SLC7A11/GPX4 pathway and enhances therapeutic efficacy of sunitinib for ccRCC, providing new insights and potential strategies to overcome the challenge of sunitinib resistance in ccRCC.

Cervical cancer, often driven by high-risk human papillomavirus (HPV) infections such as HPV16 or HPV18, remains a leading cause of cancer-related deaths. HPV16, found in about 90% of cervical cancer patients, harbors key oncogenic related genes (E6, E7, E2, E5) and an upstream regulatory region (URR) that contribute to cancer progression. This study introduces a novel approach using a recombinant oncolytic herpes simplex virus type 1 (HSV-1) named SONC103, armed with a CRISPR/Cas9 gene editing system. The aim was to target and disrupt integrated HPV16 genes in cervical cancer cells. Results demonstrated SONC103's capability to specifically and effectively knock down HPV16 oncogenes, thereby reducing cell proliferation and promoting apoptosis. Analyses further revealed loss of HPV16 DNA probes in infected cells' chromosomes, significant regulation of cellular processes related to tumor apoptosis, and downregulation of E6/E7 oncoproteins while increasing tumor suppressor proteins P53 and pRB. Notably, SONC103 exhibited substantial inhibition of tumor growth in a murine xenograft cervical cancer model. This study showcases the potential of the recombinant oncolytic HSV-1 virus (SONC103) in combating HPV16-positive cervical cancer by targeting oncogenes and facilitating oncolysis.

Syringin, a natural bioactive compound extracted from Acanthopanax senticosus, has demonstrated potential therapeutic value in cancer treatment. However, its efficacy in treating renal cell carcinoma (RCC) remains unexplored. This study aims to investigate the therapeutic effects and underlying mechanisms of Syringin in RCC. In this study, network pharmacology, molecular docking validation, and bioinformatics were employed to predict the mechanisms by which Syringin affects RCC. In vitro experiments showed that Syringin inhibited RCC cell viability and reduced the IC50 of Sunitinib, enhancing its therapeutic effect. Syringin also inhibited RCC cell proliferation and migration and promoted apoptosis. The combination of Syringin and Sunitinib demonstrated an enhanced inhibitory effect. Western blot analysis confirmed that Syringin’s anti-RCC effects are mediated through the EGFR/PI3K/Akt pathway. In conclusion, our findings indicate that Syringin exhibits inhibitory effects on RCC cells and enhances their sensitivity to Sunitinib, offering a novel approach to exploring treatment strategies for Sunitinib-resistant RCC.

Renal cell carcinoma (RCC) originates from the epithelial cells of renal tubules and is the most common type of renal cancer, as well as the urological tumor with the highest mortality rate. Over the past half-century, the morbidity and mortality of RCC have been increasing, posing a significant threat to human health. Although surgical treatment offers the possibility of a cure for most RCC patients, tumor recurrence or metastasis leads to the failure of traditional treatment options to achieve the desired results. The advent of targeted drugs, such as receptor tyrosine kinase inhibitors and immune checkpoint inhibitors, has brought new hope for the treatment of RCC. Targeted therapy has become the mainstay of treatment for advanced RCC. Sunitinib is a receptor tyrosine kinase inhibitor that plays a pivotal role in the treatment of RCC. It inhibits the activity of various receptor tyrosine kinases, including epidermal growth factor receptor, platelet-derived growth factor receptor, and vascular endothelial growth factor receptor. This, in turn, inhibits tumor angiogenesis and cellular proliferation, effectively controlling tumor progression. However, a considerable number of RCC patients develop resistance to sunitinib within 15 months of initiating treatment, presenting new challenges for the treatment of RCC. Therefore, this paper summarizes the mechanism of sunitinib resistance in RCC and reviews the treatment of sunitinib resistance in RCC, in order to provide ideas for overcoming the resistance of RCC to sunitinib, and developing a more effective treatment plan for patients with advanced RCC.

Purpose: This study aims to explore the potential mechanisms of esculin in the treatment of renal cell carcinoma (RCC). Methods: We employed network pharmacology to predict the potential mechanisms and targets of esculin in RCC. Molecular docking techniques were then employed to validate the predicted targets. Additionally, a series of in vitro experiments were conducted to verify the anticancer effects of esculin on RCC cells, including the CCK-8 assay, EdU assay, wound healing assay, apoptosis assay, and Western blot. Results: Network pharmacology and molecular docking results identified GAPDH, TNF, GSK3B, CCND1, MCL1, IL2, and CDK2 as core targets. GO and KEGG analyses suggested that esculin may influence apoptotic processes and target the PI3K/Akt pathway in RCC. Furthermore, the CCK-8 assay demonstrated that esculin inhibited RCC cell viability. Microscopic observations revealed that following esculin treatment, there was an increase in cell crumpling, a reduction in cell density, and an accumulation of floating dead cells. Additionally, with increasing esculin concentrations, the proportion of EdU-positive cells decreased, the wound closure ratio decreased, the proportion of PI-positive cells increased, the expression levels of BAX and cleaved-caspase-3 proteins increased, and the expression level of Bcl2 protein decreased. These findings suggested that esculin inhibits the proliferation and migration of RCC cells while promoting apoptosis. Moreover, esculin was found to target GAPDH and inhibit the PI3K/Akt pathway. Conclusions: This study is the first to elucidate the therapeutic effects of esculin on RCC cells. The results provide evidence supporting the clinical application of esculin and introduce a promising new candidate for RCC treatment.

Kidney clear cell carcinoma (KIRC) commonly presents with metastases upon diagnosis, highlighting the critical need to identify more precise biomarkers for early detection, intervention, and personalized treatment. Although The REEP family has been investigated in cancer development, the specific relationship between REEP4 and cancer remains unclear. In our study, we employed bioinformatics analysis and conducted fundamental experiments to evaluate the potential of REEP4 as a biomarker for predicting the prognosis and therapeutic efficacy of KIRC. Comparing KIRC tumor tissues to normal tissues, we observed a significant upregulation in REEP4 expression, with higher levels of REEP4 correlating positively with tumor malignancy. Further COX regression analysis, as well as single and multifactorial analyses, confirmed that high REEP4 expression indicated lower survival rates in KIRC. Gene function analysis also identified associations between REEP4 and critical pathways such as the cell cycle, along with its involvement in protein binding. Furthermore, our investigation of the immune response suggests that a favorable immunotherapeutic response is linked to a reduction in REEP4 expression. Subsequently, we conducted in vitro experiments to confirm the overexpression of REEP4 in KIRC tumor tissues and renal cancer cells. In summary, our study revealed a close association between REEP4 expression and KIRC, emphasizing its correlation with prognosis and the immune response. These findings suggest that REEP4 is a potential biomarker for KIRC.

Objective:To investigate the correlation between endothelial dysfunction and cardiomyocyte apoptosis during myocardial ischemia-reperfusion.Methods:A total of 63 male rats were selected to establish the rat model of myocardial ischemia-reperfusion by the ligation of the left anterior descending(LAD)coronary artery to simulate myocardial ischemia.Rats were divided into the control group and group Ⅰb, group Ⅰa, group Ⅱb, group Ⅱa, group Ⅲb and group Ⅲa.Control rats were treated only with LAD threading without ligation.In observation group, at 30, 90, 120 min after LAD ligation(marked as Ⅰ, Ⅱ, Ⅲ group respectively), loosen the ligation to simulate ischemia-reperfusion.In the observation group, captopril sublingual injection of 0.25 mg/kg before ligation were marked as group b, and as group a with no captopril injection.The circulating endothelial cells(CEC), endothelin(ET), nitric oxide(NO)and the apoptosis rate of cardiomyocytes in each group were measured.Results:The CEC and ET levels showed a continuous upward trend, and a NO level showed a continuous downward trend from group Ⅰa to Ⅱa to Ⅲa as compared with the control group( P<0.05). After using preventive intervention of captopril, the CEC and ET levels were lower and NO levels were higher in group Ⅱb and Ⅲb than in group Ⅱa and Ⅲa, respectively( P<0.05). The apoptotic rate of cardiomyocytes was higher in group Ⅰa than in the control group, and the apoptotic rate from high to low were from group Ⅲa[(235.71±40.25)%]to group Ⅱa[(197.28±43.56)%]to group Ⅰa[(138.55±32.87)%]and to the control group[(5.81±2.02)%]( P<0.05). The apoptotic rate of cardiomyocytes was lower in group Ⅱb[(125.67±26.51)%]and Ⅲb[(124.91±33.28)%]than in group Ⅱa and Ⅲa, respectively( P<0.05). Conclusions:The ischemia-reperfusion can cause endothelial dysfunction and the apoptosis of cardiomyocytes, and there is a close relationship between the degree of this lesions and the duration of ischemia-reperfusion.While, the appropriate application of angiotensin converting enzyme inhibitor can inhibit the damage of cardiomyocytes to a some extent.

Human papillomavirus (HPV)16 gene mutation is usually associated with persistent HPV infection and cervical intraepithelial neoplasia (CIN). However, the functional implications of HPV16 mutations remain poorly understood.145 LCR/E6/E7 of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the LCR, 13 in E6, 8 in E7) were discovered, 11 of which were nonsynonymous mutations (8 in E6, 3 in E7). The H85Y and E120D variants in E6 were significantly reduced in the high-grade squamous intraepithelial lesion (HSIL) group compared to the T," a potential binding site for TATA-binding protein, is the most common in LCR variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1-3(P = .009). The H85/E120 in E6 and N29 in HPV16 E7 might play a critical role in carcinogenesis by disrupting p53 and Rb degradation due to affecting their interaction, respectively. In a word, the findings in this study provide preventative and therapeutic interventions of HPV16 -related cervical lesions/cancer.

PURPOSE:The primary aim of this study was to evaluate the diagnostic accuracy of colposcopy in identifying high-grade squamous intraepithelial lesion or worse (HSIL+) and the characteristic performance of colposcopic images with various severity levels of cervical lesions.METHODS:The medical records from 1828 women who underwent colposcopy at Affiliated Hospital of Tongji University from February 2016 to March 2019 were reviewed. Human papilloma virus (HPV) GenoArray test kit (HybriBio Ltd) and Thinprep cytologic test (TCT, Hologic, USA) were used to perform HPV genotyping and cytology. All colposcopic images were collected from the standard-of-care colposcope (Leisegang 3ML LED) and evaluated based on the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) Colposcopy Standards. The linear by linear association, Pearson χ2 test, χ2 test, Kappa test, McNemar test and risk test were used to perform statistical analyses.RESULTS:The consistency between colposcopy and biopsy pathology was 59.35% with the moderate strength of kappa coefficient of 0.464. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy and cytology for HSIL+ were 56.29%, 93.82%, 77.47%, 85.04% and 37.13%, 98.49%, 90.29%, 80.58%, respectively. The colposcopic features of HSIL+ were as follows: (1) thick or bulgy acetowhite epithelium with sharp border; (2) completely nonstained of Lugol's iodine; (3) type III/IV/V of gland openings; (4) punctation or atypical vessels.CONCLUSION:The data and findings herein provide the resource for evaluating the diagnostic value of colposcopy, and suggested that the accuracy of colposcopy is required to be further improved.

OBJECTIVE:Bladder cancer (BLCA) is the most common genitourinary malignancy in the world. Recent studies have revealed that circular RNAs (circRNAs) are dysregulated in malignant tumors and participate in carcinogenesis. The purpose of our work is to uncover how hsa_circ_0017247 functions in BLCA.PATIENTS AND METHODS:In this research, Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was conducted to monitor hsa_circ_0017247 expression in BLCA samples. Besides, proliferation assay, colony formation assay, and flow cytometry assay were performed in BLCA cells after hsa_circ_0017247 was knocked down. Meanwhile, the Western blot assay was conducted to explore the target signaling pathway of hsa_circ_0017247. Furthermore, tumor formation and metastasis assays were also conducted in vivo.RESULTS:Compared with the adjacent tissues, a significant upregulation in hsa_circ_0017247 expression was observed in BLCA samples. Functional assays showed that the inhibition of cell proliferation was induced via downregulating hsa_circ_0017247 in BLCA in vitro, while the promotion of cell proliferation was induced via downregulating hsa_circ_0017247 in BLCA in vitro. Moreover, the results of further experiments revealed that the targeted proteins in the Wnt/β-catenin signaling pathway were downregulated via knockdown of hsa_circ_0017247 in BLCA. In addition, tumor formation and metastasis of BLCA were inhibited via knockdown of hsa_circ_0017247 in nude mice.CONCLUSIONS:We discovered a vital regulatory mechanism of hsa_circ_0017247 in BLCA which might serve as a new therapeutic intervention for BLCA patients.

OBJECTIVE:To elucidate the correlation between microRNA-1266 (miR-1266) and prostate cancer (PCa) progression, and to investigate the possible underlying mechanism.PATIENTS AND METHODS:The expression level of miR-1266 and protein arginine methyltransferase 5 (PRMT5) in PCa tissues and cell lines was first detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After up-regulating or down-regulating miR-1266 expression in cells, cell proliferation, migration and invasion abilities were detected. Possible target genes of miR-1266 were predicted and validated by bioinformatics analysis and dual-luciferase reporter gene assay, respectively. Finally, abnormal expression of PRMT5 was ascertained after transfection.RESULTS:MiR-1266 was lowly expressed in PCa tissues and cell lines, whereas PRMT5 exhibited the opposite results. Up-regulated expression of miR-1266 significantly inhibited the proliferation, migration and invasion abilities of PC-3 cells. However, the growth and migration of DU145 cells with low miR-1266 expression were significantly accelerated. Meanwhile, the number of invading cells was significantly increased. PRMT5 was verified as a potential target gene of miR-1266. Furthermore, results found that miR-1266 was negatively correlated with PRMT5. In addition, the expression of PRMT5 was remarkably decreased after miR-1266 overexpression, which could be restored after knockdown of miR-1266.CONCLUSIONS:MiR-1266 inhibits the growth and metastasis of PCa by targeting PRMT5. We may provide a potential and prospective therapeutic target for PCa.

BACKGROUND:This study aims to investigate the clinical characterization and causative genetic defect of a four-generation Chinese family with autosomal dominant aniridia.METHODS:The recruited family members underwent comprehensive routine and ophthalmic examinations, and Sanger sequencing was performed to screen the mutation in PAX6.RESULTS:A novel heterozygous PAX6 deletion c.435_445delTAGCGAAAAGC (p.Ser146ThrfsX9) in exon 7 was identified in all affected individuals, but this was absent in any of the unaffected family members and in the 200 unrelated controls.CONCLUSION:A novel deletion in the PAX6 gene was identified in a Chinese family associated with aniridia, which expands the spectrum of the PAX6 mutation and its associated phenotype.

Attachment of monocytes to endothelial cells is a major event in the pathogenesis of atherosclerosis and cardiovascular disease. As atherosclerosis is considered to be an inflammatory disease, increased expression of proinflammatory cytokines greatly contributes to endothelial dysfunction and atherogenesis. Additionally, attachment of monocytes to endothelial cells triggered by cellular adhesion molecules such as vascular cellular adhesion molecule 1 (VCAM-1) and E-selectin plays a vital role in the development of atherosclerotic plaques. Zinc therapy has been suggested as a potential strategy for countering atherosclerosis. In the present study, for the first time to our knowledge, we investigated the potential role of the GPR39 zinc-sensing receptor in mediating the adhesion of monocytes to endothelial cells, oxidative stress and inflammation in human aortic endothelial cells induced by oxidized low-density lipoprotein (ox-LDL). Our findings show that agonism of GPR39 by the selective agonist TC-G 1008 potently reversed the effects of ox-LDL including increased expression of proinflammatory cytokines and chemokines, markers of oxidative stress, and enhanced expression of cellular adhesion molecules. Importantly, we also show that this protective effect is mediated through the nuclear factor-κB (NF-κB) pathway. Taken together, our findings suggest a potential role of GPR39 as a novel therapeutic target for the treatment and prevention of atherosclerosis induced by ox-LDL.

PURPOSE:Clear-cell renal cell carcinoma (ccRCC) is characterized by genetic abnormalities, while the role of Guanine Nucleotide-Binding Protein Beta 1 (GNB1) in ccRCC has not been studied. We thus aimed to evaluate the expression and prognostic value of GNB1 in ccRCC.METHODS:A two-stage study (exploration and validation) was conducted using in silico and immunohistochemical (IHC) scoring of ccRCC samples from our institute, to evaluate the association between GNB1 expression and clinicopathological parameters of ccRCC patients. Pathway analyses were performed for genes coexpressed with GNB1 using the KOBAS platform to profile the function of GNB1 and IHC validation.RESULTS:In the exploration stage, data from TCGA ccRCC dataset were reproduced, which contained 537 patients with ccRCC and found that downregulation of GNB1 was significantly associated with worse prognosis. IHC staining from the Human Protein Atlas showed significantly downregulation of GNB1 in ccRCC tissue compared with normal kidney. Pathway analysis showed significantly altered vascular endothelial growth factor (VEGF) signaling pathways among which expressions of 3 genes (WASF2, NRP1, and HIP1) were significantly associated with GNB1 expression, respectively. In the validation stage, included were 80 ccRCC samples and GNB1 expression was scored using IHC positivity. GNB1 expression was negatively associated with tumor stage, lymph node invasion, metastasis, older age, and increased tumor grade. Female gender and receiving neoadjuvant therapy were also associated with decreased GNB1 expression. The expressions of WASF2, NRP1 and HIP1 were also studied and found that they were significantly associated with GNB1.CONCLUSION:GNB1 was downregulated in ccRCC. Decreased GNB1 expression was associated with worsened disease characteristics and prognosis. GNB1 was related with VEGF signaling in ccRCC, implying a therapeutic potential of this factor.

Fast growing social networks have been integrated into people's daily lives and play an important role,which makes more and more academics study the social networks from different perspectives.The research of information diffusion over online social networks can help users to obtain information,enterprises to promote product,politicians to regulate public opinion,and is with the significant value in theory and application.In the recent years,although there have been a number of significant advancements on information diffusion,most of them have been mainly focusing on optimization algorithm for user extraction,or evolution equations for behavior law.No attempts have been made to quantify user susceptibility through the forwarding action,and dynamically extract susceptible users.In fact,at different times,the influence of users on information diffusion cannot be exactly the same due to the uncertainty and complexity of social networks.In this sense,dynamic analysis and study of user forwarding action is of great importance,and is precisely what we do in this paper.To address dynamically the business information diffusion problem over online social networks,the randomness and uncertainties of user forwarding action are first analyzed,and then a novel dynamic extraction model for the susceptible users is presented,which is based on Universal Generating Function(UGF) method and Discrete StressStrength Interference (DSSI) theory.In the model,the random forwarding action of the user is firstly quantified as Node Susceptibility (NS),and NS is relevant to two random variables of information receiving Xnmt and forwarding Ynmt.Then,according to UGF method and DSSI theory,the values of NS in regard to different kinds of information at different periods are obtained by deriving the probability distributions of Xnmt and Y and UGFs of Xnmt and Ynmt Finally,the susceptible users are extracted based on dynamic order of the values of NS.The decision results of the model can effectively address the following three issues:(1) the most susceptible users;(2) the kinds of information that they are most susceptible to;and (3) the period when they are most susceptible.The answers to these three questions can provide theoretical basis for making effective strategy of information diffusion,and the decision results can be updated dynamically with the observation parameters.A case study of online group buying website illustrates the feasibility and practicality of the proposed model.Further,based on the same experimental data set,the proposed model is compared with Influence-Susceptibility-Cynical (ISC) model in literature,and different susceptible users are extracted based on ISC model and our model.The results show that the susceptible users extracted in these two models are roughly the same,and the consistency is more than 70 percent.The consistency also illustrates the validity of our model to some extent.On the other hand,the difference between user extractions in different models is analyzed from both theoretical and practical perspectives.Since the quantification of user susceptibility in our model is based on the statistics characteristics of observation parameters,it is concluded that our model is more scientific and reasonable in quantifying user susceptibility.

// Min Liu 1 , Guang-Chun Wang 1 , Yuan Feng 2 , Jian-Ping Che 1 , Hai-Min Zhang 1 , Yang Yan 1 , Jian-Hua Huang 1 , Xu-Dong Yao 1 and Jun-Hua Zheng 1 1 Department of Urology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, 200072, China 2 Department of Nephrology, Nanjing University Affiliated Drum Tower Hospital, Nanjing, Jiangsu, 210093, China Correspondence to: Xu-Dong Yao, email: fibrosis744@126.com Jun-Hua Zheng, email: junhuazheng006@163.com Keywords: renal fibrosis, GAS5, rs145204276, miR-21, SMAD/TGFB1 Received: January 02, 2017 Accepted: April 19, 2017 Published: January 11, 2018 ABSTRACT Background: Growth arrest-specific 5 (GAS5), a long non-coding RNA (lncRNA), has been identified as a key gene expression regulator in multiple cancers. The polymorphism of the promoter region of GAS5 promotes the transcription level of GAS5, and then supervises its downstream signal pathway. This study was designed to investigate the mechanism between GAS5 and renal fibrosis. Results: rs145204276 polymorphism (INS or DEL allele) located in promoter of GAS5. The DEL/DEL of GAS5 promotes the transcription of GAS5 and lower Histological score of kidneys disease samples. QRTPCR of clinical sample show that the DEL/DEL genotype group displayed higher levels of GAS5 and SMAD7 mRNA, and lower levels of miR-21 and TGFB1 protein than INS/INS group. Further mechanism study show that GAS5 inhibits the expression level of miR-21 and then the miR-21/SMAD7/SMAD3 feedback loop. Our further study confirmed that the expression of GAS5 supervised the expression of miR21, SMAD7 and TGFB1. Meanwhile, SMAD7 is a directly target gene of miR-21. Materials and Methods: Bioinformatics analysis and luciferase assay were employed to investigate the role of rs145204276 polymorphism in gene expression regulation. Quantitative real-time Polymerase Chain Reaction (qRT-PCR) and western-blot were employed to study the expression level. Hematoxylin-eosin staining was performed to explore role of rs145204276 polymorphism of GAS5 in renal fibrosis. Conclusions: our study shows that GAS5 (lncRNAs) supervises SMAD/TGF- β 1 -mediated renal fibrosis via miR-21. In addition, rs145204276 polymorphism (INS or DEL allele) of GAS5 contributes to renal fibrosis via transcription of the GAS5, and then serves as a potential therapeutic target for renal fibrosis.

《2014年国民体质监测公报》显示,大学生除了肥胖检出率仍在不断攀升之外,他们的速度、力量、耐力、柔韧和爆发力等重要身体素质依然处于下滑趋势.T大学作为中国大学的一个缩影也十分典型,虽然在竞技体育方面,游泳、健美操和足球等人才辈出,位居2016年中国高校体育竞赛榜Top100前列,但大学生的体质健康并不乐观.尽管总体及格率达到了95％,但随着年级的增长,及格率从1年级的97％降到4年级的93％.这说明尽管学校的体育运动设施已大为改善,在校大学生对运动参与依然缺乏足够的热情.这不符合国家《中长期教育改革和发展规划纲要(2010—2020年)》中提出的学生要"天天锻炼、健康成长、终身受益",从单纯地学习和掌握运动技能,向增进健康、提高心理健康水平和社会适应能力、提升运动技能等综合性素质的转变要求.因此,如何提高大学生的体质健康水平,已成为我国高校管理层和体育教学部门的一大目标,而公体课作为实现这个重要目标的主要载体,左右着大学生的体质健康的走向和归宿.