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To explore a new approach for the treatment of renal interstitial fibrosis (RIF), we detected the expression of matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor (VEGF). Twenty-four male Sprague Dawley (SD) rats were randomly divided into 2-week normal control (2NC) group, 4-week NC (4NC) group, 2- week unilateral ureteral obstruction (2UUO) group, and 4-week UUO (4UUO) group. We performed left ureteral ligation on UUO groups. Then, we sacrificed the rats of the 2NC group and 2UUO group at 2 weeks and the other groups at 4 weeks after the surgery. Immunohistochemistry and western blot were applied to detect the expression of MMP9, VEGF, fibronectin (FN), type IV collagen (Col-IV), and transforming growth factor-β1 (TGF-β1). MMP9 levels reduced after UUO surgery. Its expression was less in the 4UUO group than in the 2UUO group (P<0.05). The expression of VEGF, TGF- β1, FN, and Col-IV was higher in UUO groups than in NC groups (P<0.05). The expression of these indicators was higher in the 4UUO group than in the 2UUO group (P<0.05). In the correlation analysis, MMP9 levels in UUO groups had a negative correlation with the expression of TGF-β1, VEGF, Col-IV, FN, and RIF index (all P<0.05). In UUO groups, VEGF levels had a positive correlation with the expression of TGF-β1, Col-IV, FN, and RIF index (all P<0.05). In conclusion, with the aggravation of RIF lesions, MMP9 levels decreased, and VEGF levels increased. Whether there is a mutual inhibition relationship between them remains to be confirmed by further experiments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Kidney stones constitute a disease of the urinary system of high incidence that has only a few available stone dissolving drugs as treatment options. The mechanism of calcium oxalate stone formation is still largely unclear. Various aspects and theories for initiation and formation of the renal stones have been suggested, and the complex multistep formation process of the kidney stones includes supersaturation, nucleation, growth and aggregation of a crystal, and crystal retention in cells after adhesion. During the initial stage of crystal formation, high concentrations of oxalate exposure may damage the renal tubular cells and cause oxidative stress after which the cells may be attached to the crystal thus supporting the oxalate-induced injury as the driving factor of crystal precipitation and cellular adhesion. However, at present, although various drugs targeting kidney stones have been proposed and evaluated both in vitro and in vivo, clinical drugs for stone dissolution have rarely been explored. Moreover, numerous advances in renal calcium oxalate stone associated target and drugs warrant their summarization until now, which could be further discussed and may provide potential ideas or options for exploration of renal calcium oxalate stone treatment targets and drugs., Competing Interests: Declaration of competing interest The authors declare no competing interests related to this work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

All-trans retinoic acid (ATRA) is one of essentially active metabolite of vitamin A, and plays an important role in diverse physiological processes, such as cellular growth and function. Renal interstitial fibrosis (RIF) is a common pathological characteristic of chronic renal disease causing end-stage renal disease currently lacking effective treatment. Low level of Angiopoietins-1 (Angpt-1) is associated with extracellular matrix accumulation and fibrosis diseases. This study was performed to assess the association of ATRA with Angpt-1 in RIF disease. Rats were divided into three groups: group of sham (SHO group), group of unilateral ureteral obstruction group (UUO group), UUO mice administrated daily at the dose of ATRA (ATRA group). Masson-staining was used to detect the histologic lesion. Immunohistochemistry and Western-blot were applied to determine the targeted proteins. RIF score was significantly increased in UUO rats when compared with that of SHO group, and the fibrosis score was notably reduced in ATRA group. Transforming growth factor-β1 (TGF-β1), collagen IV (Col-IV) and fibronectin (FN) expressions in UUO group were significantly up-regulated, whereas Angpt-1 expression was significantly down-regulated compared with the SHO group. ATRA treatment reduced TGF-β1, Col-IV and FN expressions and improved Angpt-1 expression compared with the UUO group. The protein expression of Angpt-1 in kidney tissue of UUO group was negatively correlated with RIF index and protein expressions of Col-IV, FN and TGF-β1. In conclusion, low expression of Angpt-1 was associated with the RIF disease and ATRA treatment can increase the Angpt-1 and alleviate the RIF lesion in UUO rats.

Improving the reliability of electronic devices requires effective heat management, and the key is the relationship between the thermal transport and temperature. Inspired by synthesized T-carbon and H-boron, the 3- X structural models are proposed to unify the two-dimensional (2D) multitriangle materials. Employing structural searches, we identify the stability of the 3- X configuration in 2D boron carbides as 3-9 BC 3 monolayer, which, unexpectedly, exhibits a linear thermal conductivity versus temperature, not the traditional ∼1/ T trend. We summarize the common characteristics and explore why this behavior is absent in 3-9 AlC 3 and graphene via investigating the optical modes. We show that the linear behavior is a direct consequence of the special oscillation modes by the 3- X model associated with the largest group velocity. We find that 2D materials with such behavior usually share a relatively low thermal conductivity. Our work paves the way to deeply understand the lattice thermal transport and to widen nanoelectronic applications.

Introduction: Membranous nephropathy (MN) is an organ-specific autoimmune disease, and its prevalence is increasing. B lymphocytes activated by T cells produce antibodies. CD19+/CD20+ plasma cells may contribute to autoantibody and alloantibody production. Rituximab has been effective in treating MN in many clinical trials. Thus, we conducted a meta-analysis to explore the clinical efficacy and safety of rituximab with MN., Material and Methods: We searched Embase, PubMed, Cochrane Library and ClinicalTrials.gov without language or publication date limitations. Studies were classified in high-risk, medium-risk and low-risk groups based on baseline proteinuria. Follow-up periods and different administrations of rituximab were also compared. Complete remission (CR) and partial remission (PR) were assessed to measure the efficacy of rituximab, and adverse effects were also extracted. Dichotomous data were expressed by the odds ratio (OR), and the 95% confidence intervals (95% CI) were used for the recruited studies., Results: Fourteen articles, including 17 studies, were included in this meta-analysis. The pooled OR of overall PR and CR remission rate was 0.58 (95% CI: 0.53-0.63; p = 0.003). No studies belonged to the low-risk group. The overall PR and CR remission rate in the medium-risk group was 0.56 (95% CI: 0.36-0.73; p = 0.57). The pooled OR of overall PR and CR remission rate in the high-risk group was 0.59 (95% CI: 0.53-0.65; p = 0.03). At the 12-month follow-up, the pooled OR of overall PR and CR remission rate was 0.51 (95% CI: 0.43-0.59; p = 0.72). At the 24-month follow-up, the pooled OR of overall PR and CR remission rate was 0.71 (95% CI: 0.48-0.86; p = 0.07). The pooled OR of efficacy of rituximab at 375 mg/m 2 × 4 was 0.63 (95% CI: 0.55-0.70; p = 0.001). Rituximab was tolerated in MN, and most adverse effects were mild. The pooled OR of infusion reaction rate of rituximab was 0.25 (95% CI: 0.13-0.44; p = 0.01) in MN. The pooled OR of cardiovascular-related event rate of rituximab in MN was 0.04 (95% CI: 0.02-0.11). The pooled OR of infection rate of rituximab in MN was 0.06 (95% CI: 0.03-0.12; p < 0.00001)., Conclusions: Rituximab is safe and effective in MN and a promising alternative treatment. More randomized control trials and studies on the role of MN are expected., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

Background and Objectives: Apolipoprotein E (apoE) plays a central role in the metabolism and homeostasis of lipids. ApoE gene encodes three major isoforms: ε2, ε3 a nd ε4 forming six phenotypes: E2E2, E2E3, E2E4, E3E3, E3E3 and E4E4. Disorders of the lipid metabolism and the homeostasis are frequently coexist in renal diseases. The association between gene polymorphisms of apoE and lipid metabolism were not consistent. This meta-analysis was performed to assess the association between gene polymorphisms of apoE and lipid metabolism in renal diseases., Methods: A pre-defined literatures search and selection of eligible relevant investigations were performed to extract and collect data from electronic databases., Results: Sixteen articles were enrolled for the analysis of association between apoE gene polymorphisms and lipid metabolism. Subjects with E3E4 had a higher total cholesterol (TC) than those with E3E3, and subjects with E2E3 had a lower TC than those with E3E3. Subjects with ε2, had a lower TC than those with ε3 or ε4, and subjects with ε4 had a higher TC than those with, ε3. Subjects with E2E2, E2E3 or E4E4 had a higher triglyceride (TG) than those with E3E3. Subjects with ε4 had a higher TG than those with ε3. Subjects with ε2, had a higher level of TG than those with non-ε2. Subjects with E3E4 had a slightly lower high-density lipoprotein (HDL) than those with E3E3. E3E4 appeared to be associated with lower levels of HDL. Subjects with E2E2, E2E3 had a notably lower low-density lipoprotein (LDL) than those with E3E3. Subjects with ε2, had a lower LDL than those with ε3 or ε4 ApoE gene polymorphisms were not associated with very low-density lipoprotein, and lipoprotein (a) [Lp(a)]. Subjects with E2E3 or E2E4 had higher apoE levels than those with E3E3, and subjects with E4E4 had lower apoE levels than those with E3E3., Conclusion: ApoE gene polymorphisms are associated with the expression of TC, TG HDL, LDL, Lp(a) or apoE., (© 2020 Zhou T et al.)

Mesenchymal stem cells (MSCs), discovered and isolated from the bone marrow in the 1960s and with self-renewal capacity and multilineage differentiation potential, have valuable immunomodulatory abilities. Acute kidney injury (AKI) refers to rapid renal failure, which exhibits as quickly progressive decreasing excretion in few hours or days. This study was performed to assess the efficacy of MSCs in the treatment of AKI induced by ischemia-reperfusion using a meta-analysis method. A literature search using corresponding terms was performed in the following databases: Embase, Cochrane Library, PubMed, and ISI Web of Science databases up to Dec 31, 2019. Data for outcomes were identified, and the efficacy of MSCs for AKI was assessed using Cochrane Review Manager Version 5.3. Nineteen studies were eligible and recruited for this meta-analysis. MSC treatment can reduce the Scr levels at 1 day, 2 days, 3 days, 5 days, and >7 days (1 day: WMD = -0.56, 95% CI: -0.78, -0.34, P < 0.00001; 2 days: WMD = -0.58, 95% CI: -0.89, -0.28, P = 0.0002; 3 days: WMD = -0.65, 95% CI: -0.84, -0.45, P < 0.00001; 5 days: WMD = -0.35, 95% CI: -0.54, -0.16, P = 0.0003; and >7 days: WMD = -0.22, 95% CI: -0.36, -0.08, P = 0.002) and can reduce the levels of BUN at 1 day, 2 days, 3 days, and 5 days (1 day: WMD = -11.72, 95% CI: -18.80, -4.64, P = 0.001; 2 days: WMD = -33.60, 95% CI: -40.15, -27.05, P < 0.00001; 3 days: WMD = -21.14, 95% CI: -26.15, -16.14, P < 0.00001; and 5 days: WMD = -8.88, 95% CI: -11.06, -6.69, P < 0.00001), and it also can reduce the levels of proteinuria at 3 days and >7 days and alleviate the renal damage in animal models of AKI. In conclusion, MSCs might be a promising therapeutic agent for AKI induced by ischemia-reperfusion., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Tianbiao Zhou et al.)

Background: Lupus nephritis is usually manifested by proteinuria, active urinary sediment, hypertension, and renal failure and is a serious complication with more than 50% occurrence in systemic lupus erythematosus patients. Mesenchymal stem cells (MSC) present remarkable immunomodulatory ability, and these cells are potential therapeutic agents for autoimmune disorders. In clinical trials, the effectiveness of MSC in the treatment of lupus nephritis is still controversial. A meta-analysis was performed to assess whether MSC can achieve good efficacy in the treatment of lupus nephritis in mice., Methods: A comprehensive literature search was performed in Cochrane Library, ISI Web of Science, PubMed, and EMBASE from inception to Oct 1, 2019. Two authors independently extracted the data, which were pooled and calculated using RevMan 5.3., Results: A total of 28 studies met the inclusion criteria. MSC treatment resulted in lower levels of ds-DNA (OR = - 29.58, 95% CI - 29.58, - 17.99; P < 0.00001), ANA (OR = - 70.93, 95% CI - 104.55, - 37.32; P < 0.0001), Scr (OR = - 8.20, 95% CI - 12.71, - 3.69; P = 0.0004), BUN (OR = - 14.57, 95% CI - 20.50, - 8.64; P < 0.00001), proteinuria (OR = - 4.26, 95% CI - 5.15 to - 3.37; P < 0.00001), and renal sclerosis score (OR = - 1.92, 95% CI - 2.66 to - 1.18; P < 0.00001), and MSC treatment could get higher levels of albumin. To detect the potential, the cytokines were also assessed, and the MSC treatment group had lower levels of IL-2, IL-12, IL-17, and IFN-γ when compared with the control group. However, the difference was not notable for IL-4, IL-6, IL-10, TGF-β, MCP-1, TNF-α, Th1, Th17, Foxp3, or Tregs., Conclusion: Our study confirmed that MSC treatment in an animal model for lupus nephritis in the studies included in the meta-analysis resulted in lower levels of ds-DNA, ANA, Scr, BUN, proteinuria, and renal sclerosis score, and MSC treatment could get higher levels of albumin.

Anemia is a common complication of chronic kidney disease (CKD), and its prevalence has shown a tendency to increase in many countries. Anemia is associated with incident heart failure and increases mortality in CKD patients, garnering public attention. Here, we reviewed recent studies about CKD with anemia, and tried to summarize the risks and causes and new progress in the treatment of renal anemia. Among the risks and causes, calcium and phosphorus metabolism disorders should be pointed out along with common causes such as iron and erythropoietin deficiencies, hypoxia, inflammation and uremic toxins, and so on. The new anti-anemia treatments mainly include hematopoietic materials supplementation, erythropoietin-stimulating agents, calcium and phosphorus regulators and hypoxia-inducible factor prolyl hydroxylase inhibitors.

Background: The purpose of this study was to determine efficacy and safety of cyclosporine A (CsA) for patients with steroid-resistant nephrotic syndrome (SRNS)., Methods: The Cochrane Library and PubMed were searched to extract the associated studies on Oct 10, 2018, and the meta-analysis method was used to pool and analyze the applicable investigations included in this study. The P(opulation) I(ntervention) C(omparison) O(utcome) of the study were defined as follows: P: Patients with SRNS; I: treated with CsA, cyclophosphamide (CYC), tacrolimus (TAC) or placebo/not treatment (P/NT); C: CsA vs. placebo/nontreatment (P/NT), CsA vs. CYC, CsA vs. TAC; O: complete remission (CR), total remission (TR; complete or partial remission (PR)), urine erythrocyte number, proteinuria levels, albumin, proteinuria, serum creatinine, and plasma cholesterol, etc. Data were extracted and pooled using RevMan 5.3., Results: In the therapeutic regimen of CsA vs. placebo/nontreatment (P/NT), the results indicated that the CsA group had high values of CR, TR, and low values of proteinuria, serum creatinine, and plasma cholesterol when compared with those in the placebo group. In comparing CsA vs. cyclophosphamide (CYC), the results indicated that the CsA group had higher TR than the CYC group. In comparing CsA vs. tacrolimus (TAC), the results revealed insignificant differences in CR, and TR between the CsA and TAC groups. The safety of CsA was also assessed. The incidence of gum hyperplasia in CsA group was higher than that in the P/NT group, with no differences in incidence of infections or hypertension between CsA and P/NT groups. There was no difference in the incidence of hypertension between the CsA and TAC groups., Conclusions: CsA is an effective and safe agent in the therapy of patients with SRNS.

Introduction: Patients with steroid-dependent nephrotic syndrome (SDNS) suffer frequent relapse with adverse effects caused by long-term prednisolone treatment. Recently, the chimeric monoclonal antibody against the protein CD20 (rituximab - RTX) was observed to be efficacious and safe in the treatment of patients with SDNS. We summarized the scientific literature to evaluate RTX therapy in the clinical management of SDNS., Material and Methods: PubMed, EMBASE, and Cochrane Library databases were investigated from interception to 2019-6-6, without language limitation. The analysis was restricted to adults ≥ 19 years of age. Data were administered and analyzed through the Review manager 5.3 software., Results: After RTX treatment, relapse times, prednisolone dose, and proteinuria decreased, whereas serum albumin was increased. The clinical parameters blood pressure and total cholesterol diminished also, whereas bone mineral density was improved. Overall, RTX ameliorated the adverse effects of prednisolone. Moreover, the Th1/Th2 ratio was changed except for the CD19 and CD20 cell counts. Additionally, most of the adverse effects of RTX were mild and well tolerated., Conclusions: In the studies that we considered, we concluded that RTX treatment was effective and safe in the therapy of patients with SDNS. Nevertheless, more randomized controlled trials are required to explore the mechanism of RTX action and verify its efficacy., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

All-trans retinoic acid (ATRA) is a critical component in cell processes such as cell growth, differentiation and apoptosis, and it is also crucial in the regulation of extracellular matrix (ECM) deposition. Prohibitin (PHB) can regulate cell proliferation, apoptosis and differentiation. The current study investigated whether ATRA regulated PHB is induced by hypoxia/reoxygenation injury in renal tubular epithelial cells (RTEC), using gene interference treatments (knockdown or overexpression of RARα). Our results indicate that ATRA can augment the expression of RARα and PHB proteins and reduce the expression of TGF-β1, FN and Col-IV proteins. PHB expression was reduced in an ATRA treated RARα- group, and TGF-β1, FN and Col-IV were up-regulated compared to the ATRA treated RARα+ group. We postulate that ATRA can induce the PHB expression by RARα in hypoxia/reperfusion related RTEC injury.

Background: This meta-analysis was performed to evaluate the relationship between hypoxia-inducible factor-1α (HIF1α) 1790G/A gene polymorphism and the susceptibility to renal cell carcinoma (RCC) and prostate cancer (PCa)., Methods: Association investigations were identified and included from the Embase, Cochrane Library and PubMed databases on March 1, 2018, and eligible investigations were analyzed by meta-analysis. Odds ratios (OR) were used to express the dichotomous data, and the 95% confidence intervals (CI) were also calculated., Results: In this meta-analysis, we found that the AA genotype of HIF1α 1790G/A was positively associated with the risk of RCC in overall populations, Caucasians, but not for Asians. G allele and GG genotype were not associated with the susceptibility of RCC in overall populations, Caucasians, and Asians. The G allele was negatively associated with PCa susceptibility in overall populations, Asians, but not for Caucasians. GG genotype was negatively associated with PCa susceptibility in Asians, but not for overall populations and Caucasians. HIF1α 1790G/A AA genotype was not associated with PCa susceptibility in overall populations of Caucasians or Asians., Conclusion: AA genotype of HIF1α 1790G/A was positively associated with RCC risk in overall populations and Caucasians. Furthermore, the G allele was negatively associated with prostate cancer susceptibility in overall populations, Asians, and GG genotype was negatively associated with PCa susceptibility in Asians.

Background: The purpose of this study was to detect the effects of vascular endothelial growth factor (VEGF) on systemic lupus erythematosus (SLE) risk., Methods: Associated studies were extracted from the China Biological Medicine Database (CBM), and PubMed on June 10, 2018, and applicable investigations were pooled and analyzed by meta-analysis using RevMan 5.3., Results: VEGF levels was associated with SLE risk (mean differences (MD) =196.02, 95% CI: 135.29-256.75, P < 0.00001), and VEGF levels was associated with active SLE risk (MD =77.51, 95% CI: 10.98-144.05, P = 0.02). We also found that VEGF levels was associated with SLE developing into lupus nephritis (LN) risk (MD =223.16, 95% CI: 144.38-301.93, P < 0.00001). However, VEGF -634G/C gene polymorphism (rs2010963) was not associated with SLE risk., Conclusions: VEGF levels was associated with SLE risk, active SLE risk and SLE developing into LN risk. However, there was no an association between VEGF -634G/C gene polymorphism and SLE risk.

Background: Long-term treatment programs with low toxicity represent a therapeutic challenge in lupus nephritis (LN). Although a therapeutic benefit of rituximab (RTX) has been reported in LN patients who have failed conventional treatment, the results are controversial. We aimed to assess the clinical efficacy and safety of RTX as a new immunosuppressive medicine in the treatment of LN with a meta-analysis., Methods: Based on predetermined criteria, PubMed, Embase, and Cochrane Library were used to identify the eligible studies. Cochrane Review Manager version 5.3 was applied to pool the data extracted from individual investigations and provide summary effect estimates., Results: Twenty-four studies with 940 patients were analyzed. In case series trials with specific LN assessment, the complete remission (CR) rate at 12 months was 35.9% (95% CI: 24.2%-49.5%), and total remission (TR: CR plus partial remission) was 73.4% (95% CI: 66.0%-79.7%). In controlled trials, RTX was associated with a higher probability of TR (OR =2.02, 95% CI: 1.23-3.32, P <0.01). The CR in the RTX group was higher than that in the control group, although there was no significant difference between the two groups (OR =1.98, 95% CI: 0.90-4.39, P >0.05). Additionally, RTX treatment significantly decreased proteinuria (mean difference: -2.79, 95% CI: -3.95 to -1.62, P <0.01) as well as the renal activity index in patients with LN (mean difference: -3.46, 95% CI: -4.43 to -2.50, P <0.01). In controlled trials, the relative risks of the adverse events of infection and infusion reaction were not notably different between the two groups., Conclusion: RTX is a promising therapy for the treatment of LN due to significant clinical efficacy and a favorable safety profile. In future studies, larger study populations and longer-term time points may identify additional important patient-centered outcomes., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

In this meta-analysis, we investigated the association of methylenetetrahydrofolate reductase, vitamin D receptor, and interleukin-16 gene polymorphisms with the risk of renal cell carcinoma. We searched the PubMed and Cochrane Library databases up to July 1, 2017, and included 12 eligible case-control studies in our analysis. The vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype were all associated with the risk of renal cell carcinoma in Asian populations. However, methylenetetrahydrofolate reductase (rs1801133 and rs1801131), vitamin D receptor (TaqI and Fok1), and interleukin-16 (rs4778889 and rs11556218) gene polymorphisms were not associated with the risk of renal cell carcinoma. Our study indicates that the vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype are associated with renal cell carcinoma risk.

Background: Diabetes mellitus (DM) is divided into four different etiological categories: type 1 DM (T1DM), type 2 DM (T2DM), other specific types, and gestational DM. One severe complication of T2DM is type 2 diabetic nephropathy (T2DN). The possible association of serum transforming growth factor-β1 (TGF-β1) levels and the TGF-β1 T869C gene polymorphism with patient susceptibility to T2DN in Chinese population is unclear at present. This study was conducted to assess these relationships in Chinese population by a meta-analysis., Methods: Association reports were searched and pulled from the Cochrane Library, the China Biological Medicine Database (CBM), and PubMed on March 1, 2018, and eligible studies were selected and used for calculations. The results were expressed as weighted mean differences (MD) for continuous data. Odds ratios (OR) were used to express the results for dichotomous data. Additionally, 95% confidence intervals (CI) were calculated., Results: Forty-eight reports for the relationship between serum TGF-β1 levels and the risk of T2DN and 13 studies on the association of the TGF-β1 T869C gene polymorphism with susceptibility to T2DN in Chinese population were retrieved from this study. Serum TGF-β1 levels in the T2DM group were higher than those in the normal control group (MD = 17.30, 95% CI: 12.69-21.92, P < 0.00001). The serum TGF-β1 level in the T2DN group was significantly higher than that in the normal control group (MD = 70.03, 95% CI: 60.81-79.26, P < 0.00001;). The serum TGF-β1 level in the T2DN group was significantly higher than that in the T2DM group (MD = 56.18, 95% CI: 46.96-65.39, P < 0.00001). Serum TGF-β1 levels in T2DM patients with microalbuminuria were increased when compared with those in T2DM patients with normoalbuminuria. Furthermore, serum TGF-β1 levels in T2DM patients with macroalbuminuria were increased when compared with those in T2DM patients with microalbuminuria. The TGF-β1 T allele, TT allele and CC genotype were associated with T2DN susceptibility in Chinese population (T: OR = 0.74, 95% CI: 0.59-0.92, P = 0.007; TT: OR = 0.55, 95% CI: 0.31-0.96, P = 0.04; CC: OR = 1.38, 95% CI: 1.14-1.67, P = 0.001)., Conclusions: High levels of TGF-β1 are associated with susceptibility to T2DM, T2DN and the progression of proteinuria in T2DN patients in Chinese population. Further, the TGF-β1 T allele, and TT genotype were protective factors against the onset of T2DN and CC genotype was a risk factor for the susceptibility of T2DN in Chinese populations.

Background: We conducted a meta-analysis to evaluate the relationship between the glutathione S-transferase μ1 (GSTM1)- and glutathione S-transferase θ1 (GSTT1)- null genotypes and susceptibility to bladder cancer., Methods: We identified association reports from the databases of PubMed, Embase, the Cochrane Library and the China Biological Medicine Database (CBM disc) on July 1, 2017 and synthesized eligible investigations. Results were expressed using odds ratios (ORs) for dichotomous data, and we also calculated 95% confidence intervals (CIs)., Results: In this meta-analysis, we found that the GSTM1-null genotype was associated with bladder cancer risk in the overall population, and individually in whites, Africans and Asians (overall population: OR = 1.40, 95% CI: 1.31-1.48, P<0.00001; whites: OR = 1.39, 95% CI: 1.26-1.54, P<0.00001; Africans: OR = 1.54, 95% CI: 1.16-2.05, P = 0.003; Asians: OR = 1.45, 95% CI: 1.33-1.59, P<0.00001). The GSTT1-null genotype was associated with bladder cancer risk in the overall population, but not in whites, in Africans or Asians (overall population: OR = 1.11, 95% CI: 1.01-1.22, P = 0.03; whites: OR = 1.16, 95% CI: 0.99-1.36, P = 0.07; Africans: OR = 1.07, 95% CI: 0.65-1.76, P = 0.79; Asians: OR = 1.05, 95% CI: 0.91-1.22, P = 0.51). Interestingly, a dual-null GSTM1-GSTT1 genotype was associated with bladder cancer risk in the overall population and in Asians (overall population: OR = 1.48, 95% CI: 1.15-1.92, P = 0.002; Asians: OR = 1.62, 95% CI: 1.15-2.28, P = 0.006). In conclusion, the GSTM1-null, GSTT1-null and dual-null GSTM1-GSTT1 genotypes might be associated with the onset of bladder cancer, but additional genetic-epidemiological studies should be conducted to explore this association further.

Background: Colchicine is a natural alkaloid that is mainly used for the treatment of inflammatory diseases. Effective and toxic doses are very similar, but case reports of higher colchicine doses inducing acute toxicosis is rare., Case Presentation: A 19-year-old woman was sent to the emergency room for taking 80 colchicine tablets (0.5 mg per tablet) 44 h previously. The main physical symptom was abdominal pain. Following ingestion, the patient suffered multi-system failure including renal, respiratory, circulatory, and digestive. Continuous renal replacement therapy (CRRT) and other treatment measures were used to remove metabolic wastes and poisons, and to treat other complications. Renal function was restored after a series of treatments., Conclusion: We report a case of an acute kidney injury induced by an overdose of colchicine. CRRT and a series of related treatments were beneficial for the treatment of colchicine poisoning.

Introduction: The purpose of this study was to analyze the effects of hypoxia-inducible factor (HIF) stabilizers on anemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) chronic kidney disease (CKD) patients., Methods: Published studies were extracted from PubMed, China Biological Medicine Database (CBM), Wanfang database, and Cochrane Library on March 10, 2018, and relevant studies were pooled and included in a meta-analysis. Data on hemoglobin (Hb), ferritin, and hepcidin levels, total iron-binding capacity (TIBC), and incidence of adverse events (AEs) were extracted and pooled using Review Manager Version 5.3., Results: Data from nine selected studies were extracted. Meta-analysis of the included studies showed that HIF stabilizers reduced ferritin and hepcidin levels and increased Hb level and TIBC in NDD-CKD patients. However, HIF stabilizers only increased TIBC, and did not affect ferritin, hepcidin, and Hb levels in DD-CKD patients. Furthermore, no notable differences in AEs and severe AEs between NDD-CKD and DD-CKD patients were detected., Conclusion: HIF stabilizers are effective for the treatment of anemia in NDD-CKD patients and safe for short-term use., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Association of GSTM1- and GSTT1-null genotypes, GSTP1 A/G gene polymorphism with renal cell carcinoma (RCC) susceptibility was detected, and the relationship between the GSTM1/GSTT1-null genotype and clinical TNM stages of RCC was assessed, using meta-analysis method., Methods: Association investigations according to eligibility criteria were searched and identified from the databases of Cochrane Library, PubMed, and Embase from establishment time of databases to July 1, 2017, and eligible reports were analyzed by meta-analysis. 95% confidence intervals (CI) were also detected, and odds ratios (OR) was used to express the results for dichotomous data., Results: This meta-analysis indicated that there was no an association between GSTM1-null genotype, GSTT1-null genotype, GSTP1 A/G gene polymorphism and RCC risk in the overall population of Caucasians or Asians. The dual GSTM1-GSTT1-null genotype was also not associated with RCC in the overall population of Caucasians. Interestingly, there was an association between the dual GSTM1-GSTT1-null genotype and the susceptibility of RCC in Asians. Relationship of the GSTM1-null genotype with clinical TNM stage of RCC was not observed in the overall population of Asians or Caucasians. In this meta-analysis, no association between the GSTT1-null genotype and clinical TNM stage of RCC was observed in Caucasians or Asians. Interestingly, GSTT1-null genotype was detected to be associated with the clinical TNM stages in patients with RCC in the overall population., Conclusion: The dual GSTM1-GSTT1-null genotype is detected to be associated with the onset of RCC in Asians, and there is an association between the GSTT1-null genotype and the clinical TNM stages in patients with RCC in the overall population.

Background: There is mounting evidence that microRNAs play an important role in nasopharyngeal carcinoma, which is widely prevalent in South China and is the most prevalent metastatic cancer among head and neck cancers. Recently, it has been shown that miR-494 is involved in the progression and prognosis of nasopharyngeal carcinoma. However, little is known about the function and mechanism of miR-494-3p in nasopharyngeal carcinoma. In the present study, we aimed to investigate the effects of miR-494-3p on the migration and invasion of nasopharyngeal carcinoma and to further explore the underlying mechanisms of these processes., Methods: The expression levels of miR-494-3p and Sox7 in nasopharyngeal carcinoma specimens and nasopharyngeal carcinoma cell lines were measured using quantitative reverse transcription polymerase chain reaction. Luciferase reporter assay, quantitative reverse transcription polymerase chain reaction, and Western blotting were used to confirm whether Sox7 was a direct target of miR-494-3p. Additionally, the roles of miR-494-3p and Sox7 on cell proliferation, migration, and invasion of nasopharyngeal carcinoma were analyzed by Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and Boyden chamber assay, respectively., Results: Our study demonstrated that miR-494-3p was commonly upregulated in nasopharyngeal carcinoma specimens and nasopharyngeal carcinoma cell lines compared with nontumor nasopharyngeal epithelial tissue or nasopharyngeal cells (NP69). Moreover, miR-494-3p negatively regulated Sox7 at the posttranscriptional level by binding to a specific site in the Sox7 3'-untranslated region. In addition, synthetic miR-494-3p mimics significantly promoted proliferation, migration, and invasion of S18 and S26 nasopharyngeal carcinoma cells, while a synthetic miR-494-3p inhibitor resulted in suppressed nasopharyngeal carcinoma cell migration and invasion., Conclusion: miR-494-3p promotes nasopharyngeal carcinoma cell growth, migration, and invasion by directly targeting Sox7. Our results suggest that miR-494-3p might be a potential therapeutic target for nasopharyngeal carcinoma.

Non-small cell lung cancer (NSCLC) is the major cause of deaths among all the cancer types worldwide. Most of the NSCLC is diagnosed at an advanced stage and the 5-year overall survival rate is low. The reason for the low survival rate of patients with NSCLC is mainly due to distant metastasis. Matrine, a traditional Chinese medicine, has been shown a significant anti-proliferation and anti-invasive effect in tumors. However, little is known on the anti-invasive mechanism of matrine in lung cancer. Therefore, we tried to investigate the molecular mechanism of matrine on the invasive ability of NSCLC cells in vitro. Cell Counting Kit-8 assay was used to evaluate the cell viability. Transwell assay was used to detect the migration and invasion abilities. Microarray assay was used to analyze the differentiated expression genes with or without matrine treatment. Western blotting and real-time polymerase chain reaction were applied to detect the expressions of PAX2 , E-cadherin and N-cadherin. Our study showed that matrine could suppress the proliferative activity of NSCLC cells in a dose- and time-dependent manner. Further investigation discovered that the migration and invasion of NSCLC cells were significantly inhibited by treatment with different concentrations of matrine. Microarray assay, real-time polymerase chain reaction and western blotting showed that matrine could significantly decrease the expression of PAX2. In addition, epithelial-mesenchymal transition and related proteins were decreased. In conclusion, matrine may block PAX2 expression to interfere with epithelial-mesenchymal transition signaling pathway that ultimately inhibit the migration and invasion of NSCLC cells in vitro. Matrine might serve as a potential agent for NSCLC treatment., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Amorphigenin, a rotenoid compouns, from seeds of Amorpha fruticosa, has been shown to possess anti-proliferation activities in several cancer cells. To explore the antitumor effects of amorphigenin on cisplatin-resistant human lung adenocarcinoma A549/DDP cells and explore the underlying mechanisms., Methods: CCK-8 assay was used to measure the proliferation of A549/DDP cells; Colony formation assay was used to measure the colony formation of A549/DDP cells; Flow cytometry assay was used to detect the apoptosis rates; Western blot analysis was used to explore the expression of apoptosis-related proteins (caspase-3 protein, PARP protein) and lung resistance protein (LRP)., Results: Our results demonstrated that amorphigenin could inhibit the proliferation of A549/DDP cells with a inhibition concentration of 50% cell growth (IC50) at 48 h of (2.19±0.92) μmol/L. Amorphigenin could inhibit the colony formation ability and induce apoptosis of A549/DDP cells; Furthermore, amorphigenin combined with cisplatin showed synergistic proliferation-inhibitory effect and apoptosis-promoting effect in A549/DDP cells; reduced the expression of LRP of A549/DDP cells., Conclusions: Amorphigenin remarkably inhibits the proliferation and induces apoptosis in A549/DDP cells. Combination of amorphigenin with cisplatin had the synergistic inhibitory effect on A549/DDP cells by downregulating the expression of LRP.
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