Pharmacokinetics, withdrawal period and risk assessment of enrofloxacin in the northern snakehead (Channa argus) following bath administration.

Enrofloxacin (ENR) is widely used in aquaculture practice, but little is known about its pharmacokinetic, withdrawal period and dietary risk in fish via bath administration. The purpose of this study was to provide data support for the use of ENR bath therapy in the northern snakehead (Channa argus). The pilot study was carried out to evaluate the therapy concentrations of ENR in northern snakehead with immersion concentrations ranged from 5 to 40 mg/L for 6 h. Based on results of the pilot study, an ENR immersion concentration of 20 mg/L was used for the formal experiment. At this dose, the peak concentrations of ENR in plasma, muscle plus skin, liver and kidney were 4.85, 4.55, 3.87 and 7.42 µg/mL (or g), respectively. According to the AUC0-∞ values, the distribution of ENR in northern snakehead followed the order of kidney > plasma > liver > muscle + skin. The elimination of ENR in northern snakehead was very slow, the half-lives (T1/2λz ) were up to 90.31, 85.5, 104.56 and 120.9 h in plasma, muscle plus skin, liver and kidney, respectively. Ciprofloxacin (CIP) was not detected in any samples in the pilot study and was only occasionally detected in muscle plus skin and liver samples in formal experiment. Based on the calculated PK/PD index AUC/MIC and Cmax /MIC, the current bath treatment regimen will have a good therapeutic effect on infections caused by bacteria with MIC below 0.6 µg/mL. The dietary risk assessment suggested that there was a dietary risk (Hazard Quotients > 10%) until day 6 after bath treatment. It is mandatory for ENR to maintain a withdrawal period of at least 450°C-day in northern snakehead after bath treatment ceased.

The toxicokinetics and risk assessment of pyrethroids pesticide in tilapia (Oreochromis mossambicus) upon short-term water exposure.

Pyrethroids pesticides (PPs) are the widely adopted synthetic pesticides for agriculture and fishery. The frequent use of these pesticides leads to the accumulation of residues in the freshwater environments in China, subsequently affecting aquatic organisms and ecosystems. However, there are few reports on the toxicological and risk assessment of aquaculture aquatic products. In this study, the uptake, depuration kinetics and potential risk to human health and ecology of fenpropathrin, cypermethrin, fenvalerate, and deltamethrin were assessed using tilapia. The results indicated that four PPs were readily accumulated by tilapia. The bioconcentration factors (BCF) of the PPs in plasma and muscle were between 71.3 and 2112.1 L/kg and 23.9-295.3 L/kg, respectively. The half-lives (t1/2) of muscle and plasma were 2.90-9.20 d and 2.57-8.15 d. The risks of PPs residues in the muscle of tilapia and exposed water were evaluated by hazard quotient (HQ) and risk quotient (RQ). Although PPs residues in tilapia had a low dietary risk to human health, the residues in the exposed water had a high ecological risk to fish, daphnia, and green algae. Therefore, assessing the PPs content in freshwater aquaculture and monitoring their dosages and frequencies are highly necessitated to avoid their adverse effect on the aquaculture environment.

TRPC1/3/6 inhibition attenuates the TGF-ß1-induced epithelial-mesenchymal transition in gastric cancer via the Ras/Raf1/ERK signaling pathway.

Gastric cancer (GC) is one of the most common malignancies worldwide. TGF-ß1 induces the epithelial-mesenchymal transition (EMT) in GC, mainly through Smad-dependent pathways. Nevertheless, few studies have focused on the activation of non-canonical transduction pathways. TRPC, Ca2+ entry channels, are ubiquitously expressed in various cell types and are involved in many cellular functions. However, their roles in GC are not well elucidated. This study aimed to determine whether TRPC participates in the TGF-ß1-induced EMT of GC and to investigate the potential mechanisms. Immunofluorescence staining was performed to examine the distribution and expression of TRPCs and EMT-related proteins in SGC-7901 cells incubated with or without TGF-ß1. The expression of TRPC1/3/6 and EMT-related molecules, including E-cadherin, vimentin, and α-SMA, was detected by qRT-PCR and Western blotting. Additionally, the underlying mechanism was determined by treating cells with pharmacological inhibitors and examining the levels of proteins involved in the main signaling cascades using Western blotting. TRPC1/3/6 were expressed at high levels in SGC-7901 cells. Following TGF-ß1 stimulation, the expression of vimentin, α-SMA, and TRPC1/3/6 increased and E-cadherin expression decreased, accompanied by activation of the Ras/Raf1/ERK1/2 signaling pathway. Notably, activation of the Ras/Raf1/ERK1/2 signaling cascade was suppressed by SKF96365 and 2-APB. Both TRPC and ERK inhibitors mitigated EMT progression. Based on these results, TRPC1/3/6 inhibition attenuated the TGF-ß1-induced EMT in GC by suppressing Ras/Raf1/ERK signal transduction.

Rs1520220 and Rs2195239 Polymorphisms of IGF-1 Gene Associated with Histopathological Grades in IgA Nephropathy in Northwestern Chinese Han Population.

BACKGROUND/AIMS: Insulin-like growth factor-1 (IGF-1) plays important roles in cellular proliferation, differentiation, and growth. Previous studies showed that single-nucleotide polymorphisms (SNPs) of IGF-1 are associated with various diseases. This case-control study aimed to examine the relationship between IGF-1 polymorphisms and IgA nephropathy (IgAN) risk in a Chinese Han population. METHODS: We recruited 351 IgAN patients and 310 healthy controls from Northwestern China. Sequenom MassARRAY was utilized to examine the genotypes of two common IGF-1 SNPs (rs1520220 and rs2195239). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by the Chi square test to evaluate the associations between IGF-1 and IgAN. RESULTS: Our study demonstrated that IGF-1 gene rs1520220 and rs2195239 polymorphisms did not confer susceptibility to IgAN. We found no correlation between gender, blood pressure, proteinuria, eGFR, and IgAN in both SNPs. However, the rs1520220 and rs2195239 variants were correlated with M1 and E1 in patients with IgAN (M0/M1: CC vs. CG+GG: OR = 1.62, P = 0.04; E0/E1: CC vs. CG+GG: OR = 1.95, P = 0.004; GG vs. GC+CC: OR = 1.90, P = 0.004, respectively). CONCLUSION: These results indicate that IGF-1 gene polymorphisms play crucial roles in the histopathological progression of IgAN in the Chinese Han population.

Rosiglitazone Inhibits Angiotensin II-Induced Proliferation of Glomerular Mesangial Cells via the Gαq/Plcß4/TRPC Signaling Pathway.

BACKGROUND/AIMS: Mesangial cell proliferation and extracellular matrix accumulation (ECM) deposition play an important role in the pathogenesis of glomerulosclerosis. TRPC and PPAR-γ can regulate cell proliferation. Angiotensin II (AngII) can induce mesangial cell proliferation and affect TRPC expression. However, the mechanism has not been fully elucidated. This study was designed to investigate the role of TRPC and the effect of rosiglitazone (RSG) in the proliferation of rat glomerular mesangial cells (HBZY-1) that were stimulated by AngII and the underlying mechanisms. METHODS: Immunofluorescence staining and qRT-PCR were performed to examine the expression levels of TRPCs in HBZY-1. Gene expression levels of TRPC, PPAR-γ, RGS4 (regulators of G protein signaling), the GPCR/Gαq/PLCß4/TRPC signaling pathway and major downstream molecules (PCNA, SKP2, P21 and P27) were detected by qRT-PCR and western blotting. Additionally, changes in intracellular Ca2+ levels were determined through Fluo-4 Ca2+ imaging, and the cell cycle was analyzed by flow cytometry. RESULTS: Our results found that TRPC1 and 6 were at higher expression levels in HBZY-1 cells. Following AngII stimulation, there were increased levels of TRPC1 and 6, Ca2+ entry, PCNA and SKP2, decreased expression levels of P21 and P27 and a reduced G0/G1 percentage. Silencing TRPC1 and 6 by siRNAs led to decrease in Ca2+ influx, G0/G1 cell cycle arrest and cell proliferation. Notably, PPAR-γ activation by RSG upregulated RGS4 expression, which can interact with the Gαq family to inhibit the Gαq-mediated signaling cascade. The results were similar to silencing TRPC1 and 6 by siRNAs. CONCLUSION: All these results indicate that RSG could inhibit HBZY-1 cell proliferation via the Gαq/PLCß4/TRPC signaling pathway.

Therapeutic Effects of FK506 on IgA Nephropathy Rat.

BACKGROUND/AIMS: FK506 is an immunosuppressive drug and a calcineurin inhibitor that has been widely used in kidney disease in recent years. FK506 shows a wide range of biological and pharmaceutical effects; however, the mechanism of its anti- proliferative effect has not been well elucidated. An IgA nephropathy (IgAN) model was used to generate a mesangial cell proliferation model. This study aims to examine the effect of FK506 on IgAN rats and the underlying mechanisms. METHODS: Hematuria, proteinuria and renal function were measured. To observe the pathological conditions, we performed HE (hematoxylin - eosin) and PAS (periodic acid - schiff) staining. Transcription and protein expression levels were detected by qRT - PCR (quantitative real-time polymerase chain reaction) and Wb (western blotting). The location and semi-quantitative expression levels of TRPCs, CaN (Calcineurin) and α-SMA were examined by IHC (Immunohistochemical staining). RESULTS: We found that FK506 could improve hematuria, proteinuria and renal function, especially in the HF (high-dose FK506) groups. Renal pathological changes were ameliorated in the treatment groups. FK506 could significantly decrease TRPCs, CaN, phosphorylation of ERK1/2 and α-SMA expression. CONCLUSION: Taken together, these results suggest that the therapeutic effect of FK506 on IgAN might be partially associated with the down-regulated expression of TRPC channels, CaN and phosphorylation of ERK1/2.

The Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with the Susceptibility to Immunoglobulin a Nephropathy in Chinese Population.

BACKGROUND/AIMS: Endothelial nitric oxide synthase (eNOS) is one of the most important enzymes for producting nitric oxide (NO), which regulate the function of many organs and cells. The single nucleotide polymorphisms (SNPs) of eNOS were found to be associated with many kidney diseases. However, it is lack of relevant studies to evaluate the associations between eNOS polymorphisms and immunoglobulin A nephropathy (IgAN). This case-control study aimed to evaluate the relationship between eNOS polymorphisms and IgAN. METHODS: We recruited 351 IgAN patients and 310 age- and sex-matched healthy controls from Northwest China. Sequenom MassARRAY was used to detect the genotypes of two common eNOS SNPs (rs1799983 and rs2070744). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by the Chi square test to evaluate the associations between eNOS and IgAN. Phase 2.1 was used to conduct haplotype analysis. RESULTS: In the overall analysis, we found that the rs1799983 polymorphism was associated with a decreased risk of IgAN (G/T vs. G/G: OR=0.57, 95%CI=0.34-0.96; G/T+T/T vs. G/G: OR=0.52, 95%CI=0.31-0.86; G/T vs. G/G-T/T: OR=0.60, 95%CI=0.36-0.99; Log-additive model: OR=0.48, 95%CI=0.30-0.78). Haplotype analysis indicated that Trs1799983Crs2070744 is a protective factor against IgAN (OR=0.62, 95%CI=0.42--0.92). However, no significant differences were found between the two SNPs (rs1799983 and rs2070744) and clinical features (age, sex, blood pressure, and Lee's grade) of IgAN. CONCLUSION: The eNOS gene rs1799983 polymorphism and Trs1799983Crs2070744 haplotype may reduce the risk of IgAN in Chinese populations.

Association of Interleukin-10 Polymorphisms (rs1800872, rs1800871, and rs1800896) with Predisposition to IgA Nephropathy in a Chinese Han Population: A Case-Control Study.

BACKGROUND/AIMS: IgA nephropathy (IgAN) is a common form of primary glomerulonephritis worldwide. Previous studies indicated that IL-10 single nucleotide polymorphisms (SNP) play an important role in IgAN pathogenesis, but the results were controversy. This study aimed to investigate the association between IL-10 SNPs (rs1800872, rs1800871, and rs1800896) with IgAN in a Chinese Han population. METHODS: We conducted a case-control study that included 351 patients with IgAN and 310 age-, gender- and ethnicity-matched healthy controls. Three promoter SNPs (rs1800872, rs1800871, and rs1800896) of IL-10 were genotyped by Sequenom MassARRAY. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. RESULTS: We found that the rs1800896 did not correlate with IgAN risk, whereas rs1800872 and rs1800871 were significantly associated with increased IgAN risk in all genetic models. The haplotype analysis indicated that the CCA haplotype was associated with increased IgAN risk (OR = 1.36; 95% CI = 1.05-1.75). Moreover, there were no associations between these SNPs and blood pressure or gender, whereas the rs1800896 variant was correlated with higher 24-hour urine protein in patients with IgAN. CONCLUSION: Taken together, these results suggest that IL-10 is a susceptibility gene in patients with IgAN.

Association Between IFN-γ Gene Polymorphisms and IgA Nephropathy in a Chinese Han Population.

BACKGROUND/AIMS: IFN-γ was reported to be involved in the development and progression of Immunoglobulin A nephropathy (IgAN), however, few studies have investigated the association between IFN-γ polymorphisms and IgAN. Therefore, we performed a case-control study to assess the association between IFN-γ polymorphisms and the risk of IgAN. METHODS: Sequenom MassARRAY was used to genotype two SNPs (rs1861494 and rs2430561) in 351 patients with IgAN and 310 healthy controls. Associations were evaluated as odd ratios (OR) with 95% confidence intervals (CI). RESULTS: No association was found between IFN-γ rs1861494 and IgAN risk or clinical parameters. For rs2430561, the AA genotype was more common in patients with IgAN, compared with controls (AT vs. AA: OR = 0.57, P = 0.035). IFN-γ-rs2430561 T allele may be a protective factor for IgAN susceptibility (T vs. A: OR = 0.59, P = 0.04). Subgroup analysis based on clinical features revealed no significant association between rs2430561 polymorphism and clinical data such as gender, 24-h urine protein, blood pressure, Oxford classifcation and estimated glomerular fltration rate. IgAN patients had a higher IFN-γ serum level than healthy controls and patients with rs1861494 AA genotype had a higher IFN-γ serum level compared with those with AG/GG genotypes. CONCLUSIONS: IFN-γ polymorphisms may be involved in the development and progression of IgAN.

WIP1-mediated regulation of p38 MAPK signaling attenuates pyroptosis in sepsis-associated acute kidney injury.

Wild-Type p53-Induced Phosphatase 1 (WIP1/PPM1D) is a serine/threonine phosphatase that plays a significant role in various physiological processes. However, the involvement of WIP1 in kidney remains unclear. Lipopolysaccharide (LPS) was administered to induce acute injury in mice and human kidney 2 (HK2) cells in the study. The WIP1 inhibitor, CCT007093, was administered both in vitro and in vivo to assess its effect on kidney. The single-cell sequencing (scRNA-seq) data revealed that Ppm1d mRNA reached peak on day 2 following unilateral ischemia-reperfusion injury (uni-IRI) in mice, especially in the proximal renal tubules during repair phase. Compared to the control group, WIP1 protein exhibited a significant increase in renal tubules of patients with acute tubular injury (ATI) and mice with LPS-induced acute kidney injury (AKI), as well as in LPS-injured HK2 cells. In vitro experiments showed that CCT007093 increased the protein levels of NLRP3, cleaved-Caspase1, GSDMD-N and IL-1ß in HK2 cells and further reduced the viability of LPS-stimulated HK2 cells. In vivo experiments showed that inhibition of WIP1 activity with CCT007093 further increased cleaved-Caspase1, GSDMD-N protein levels in kidney tissue from mice with LPS-induced AKI. In addition, LPS induces phosphorylation of p38 MAPK, a key regulator of pyroptosis, which is further activated by CCT007093. In conclusion, inhibition of WIP1 activity acts as a positive regulator of renal tubular pyroptosis mainly through the mediation of phospho-p38 MAPK.

A comparison of chemiluminescent immunoassay and enzyme-linked immunosorbent assay for detecting phospholipase A2 receptor antibody in primary membranous nephropathy.

Objective: The accurate detection of phospholipase A2 receptor (PLA2R) autoantibody is crucial in the diagnosis and monitoring of primary membranous nephropathy (pMN). While enzyme-linked immunosorbent assay (ELISA) is the commonly used detection method, its complexity and time-consuming nature pose challenges, especially for small sample sizes. Chemiluminescence immunoassay (CLIA) has emerged as a rapid alternative for clinical immunoassays. This study aims to compare the sensitivity, specificity, and precision of CLIA and ELISA in detecting PLA2R autoantibody. Method: A total of 145 patients with biopsy-confirmed primary membranous nephropathy and 85 patients with non-membranous nephropathy were enrolled in this comparative study. CLIA and ELISA were employed to test all samples for the presence of PLA2R autoantibodies. Statistical analysis of sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) was performed using SPSS 26.0. The diagnostic value of ELISA and CLIA for pMN was analyzed using the ROC curve, and Correlation analysis was performed using Spearman. Results: Serum levels of anti-PLA2R antibody in pMN group were significantly higher than those in nMN group(P < 0.05). The accuracy of CLIA for detecting anti-PLA2R antibody was 76.96%, while ELISA showed an accuracy of 74.78%. The sensitivity for CLIA was 64.83%, compared to 60% for ELISA. However, no statistically significant difference was observed between the two methods (P > 0.05). The overall qualitative agreement of anti-PLA2R detection was 93.35% (95% confidence interval[CI] 89.47-96.3). ROC curve analysis showed that AUC of anti-PLA2R antibody detected by ELISA and CLIA were 0.8737 (95% confidence interval [CI] 0.8270-0.9204), 0.8914 (95% confidence interval [CI]0.8495-0.9332), respectively. The Spearman correlation analysis revealed a significant correlation between them(P < 0.05). Notably, CLIA demonstrated a significant time-saving advantage, particularly when the sample size was less than 200, and especially when it was less than 20. Conclusion: CLIA and ELISA showed similar accuracy and consistency in detecting anti-PLA2R antibody for primary membranous nephropathy. However, CLIA exhibited a significant advantage in terms of automation and time-saving compared to ELISA, particularly for smaller sample sizes. This finding suggests that CLIA has the potential to become a preferred and widely adopted test in the future.

DPP8/9 inhibition attenuates the TGF-ß1-induced excessive deposition of extracellular matrix (ECM) in human mesangial cells via Smad and Akt signaling pathways.

The pathogenesis of glomerular diseases is strongly influenced by abnormal extracellular matrix (ECM) deposition in mesangial cells. Dipeptidyl peptidase IV (DPPIV) enzyme family contains DPP8 and DPP9, which are involved in multiple diseases. However, the pathogenic roles of DPP8 and DPP9 in mesangial cells ECM deposition remain unclear. In this study, we observed that DPP8 and DPP9 were significantly increased in glomerular mesangial cells and podocytes in CKD patients compared with healthy individuals, and DPP9 levels were higher in the urine of IgA nephropathy (IgAN) patients than in control urine. Therefore, we further explored the mechanism of DPP8 and DPP9 in mesangial cells and revealed a significant increase in the expression of DPP8 and DPP9 in human mesangial cells (HMCs) following TGF-ß1 stimulation. Silencing DPP8 and DPP9 by siRNAs alleviated the expression of ECM-related proteins including collagen Ⅲ, collagen Ⅳ, fibronectin, MMP2, in TGF-ß1-treated HMCs. Furthermore, DPP8 siRNA and DPP9 siRNA inhibited TGF-ß1-induced phosphorylation of Smad2 and Smad3, as well as the phosphorylation of Akt in HMCs. The findings suggested the inhibition of DPP8/9 may alleviate HMCs ECM deposition induced by TGF-ß1 via suppressing TGF-ß1/Smad and AKT signaling pathways.

Premature senescence and cellular phenotype transformation of mesangial cells induced by TGF-B1.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a polypeptide member of the transforming growth factor ß superfamily of cytokines and performs many cellular functions. Its overexpression may lead to renal fibrosis. AIM: This study planed to investigate the effects of TGF-ß1 on the cell cycle and phenotype of mesangial cells. METHODS: Rat mesangial cells were cultured together with different concentrations (0, 1, 2, 5, and 10 ng/mL) of TGF-ß1 for specified times from 0 min to 72 h. 0 ng/mL TGF-ß1 and 0 min served as controls. Cell cycles were assessed by flow cytometry and α-smooth muscle actin expression (α-SMA) protein expression by western blot analysis. All data were presented as Mean ± SD. Statistical analysis was performed by using one-way analysis of variance and correlation analysis. Results were considered significant at p < 0.05. RESULTS: After 15 min of co-culture with different concentrations of TGF-ß1, the percentage of mesangial cells in G0/G1 phase was significantly elevated compared to the control (p < 0.05). 12 h co-culture induced cell hyperplasia, 24 h co-culture obvious up-regulation of α-SMA (p < 0.01) and one or two cells' myofibroblast phenotype transition, and 36 h co-culture several cells' phenotype transition. Correlation analysis prompted that the TGF-ß1-induced premature aging was time-dependent (p < 0.01). CONCLUSION: TGF-ß1 may induce mesangial cells' premature senescence and myofibroblast-like phenotype transformation time-dependently, which may contribute to the development of early stage of glomerulosclerosis.

New insights into the role of dipeptidyl peptidase 8 and dipeptidyl peptidase 9 and their inhibitors.

Dipeptidyl peptidase 8 (DPP8) and 9 (DPP9) are widely expressed in mammals including humans, mainly locate in the cytoplasm. The DPP8 and DPP9 (DPP8/9) belong to serine proteolytic enzymes, they can recognize and cleave N-terminal dipeptides of specific substrates if proline is at the penultimate position. Because the localization of DPP8/9 is different from that of DPP4 and the substrates for DPP8/9 are not yet completely clear, their physiological and pathological roles are still being further explored. In this article, we will review the recent research advances focusing on the expression, regulation, and functions of DPP8/9 in physiology and pathology status. Emerging research results have shown that DPP8/9 is involved in various biological processes such as cell behavior, energy metabolism, and immune regulation, which plays an essential role in maintaining normal development and physiological functions of the body. DPP8/9 is also involved in pathological processes such as tumorigenesis, inflammation, and organ fibrosis. In recent years, related research on immune cell pyroptosis has made DPP8/9 a new potential target for the treatment of hematological diseases. In addition, DPP8/9 inhibitors also have great potential in the treatment of tumors and chronic kidney disease.

Chromium ion removal from raw water by magnetic iron composites and Shewanella oneidensis MR-1.

In this study, nanoiron active carbon composites (NZVI/GAC) were used to remove chromium ions from raw water. The composites were synthesized from a novel formula of biological activated carbon and characterized by various techniques. The adsorption test data were fit by a pseudo-second-order kinetic model and Langmuir model. The qe and R2 values were 187 mg Cr/g and 0.9960, respectively, with 0.2 g/L NZVI/GAC at an initial concentration of 118 mg/L Cr according to the Langmuir isotherm model. Moreover, a Cr6+ detoxification reactor was constructed with the magnetic iron composite. The results indicated that the synthesized magnetic iron composite was a significant adsorbent for Cr6+ removal from aqueous solutions. The detoxification reactor was able to remove Cr6+ from raw water at an initial concentration of 26.5 mg/L within a short time period (3-5 min), with a removal efficiency of up to 99.90% and a treatment capacity of 45.0 mg Cr6+/g of adsorbent; the Cr6+ concentrations in the outflow met the GB5749-2006 requirements for drinking water. A synergistic effect between NZVI/GAC and a suspension of the bacterium Shewanella oneidensis MR-1 was found, showing that this bacterium can be used as a regeneration agent for iron-depleted activated carbon materials.

Resveratrol down-regulates endothelin type B receptors in vascular smooth muscle cells via Sirt1/ERK1/2/NF-кB signaling pathways.

Silent information regulator family protein 1 (Sirt1) has gained attention for protective effects against cardiovasc diseases. Vascular smooth muscle endothelin type B (ETB) receptors are related to the pathogenesis of cardiovascular diseases. Elevated oxidized low-density lipoprotein (ox-LDL) is associated with atherosclerosis. This study will investigate whether resveratrol (a Sirt1 activator, Res) is involved in oxidized low density lipoprotein (ox-LDL)-mediated- regulation of ETB receptors in rat superior mesenteric arteries (SMA). The rat SMA segments were cultured in the presence and absence of ox-LDL with or without Res and specific inhibitor (U0126) for the extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) for 24 h. After organ culture, the contractile responses to sarafotoxin 6c (S6c) were studied using a sensitive myograph, and the ETB receptor protein expression was detected using Western blotting. The results showed that Res concentration-dependently suppressed the ox-LDL -induced up-regulation of ETB receptors expression and receptor-mediated vasoconstriction. In addition, these effects could be inhibited by U0126. Furthermore, activity of ERK1/2 phosphorylation and P65 acetylation induced by ox-LDL were blocked by Res. In conclusion, Res down-regulated ETB receptors through up-regulating Sirt1 and followed by ERK1/2/NF-кB signaling pathways in the organ culture SMA.

Polarized M2c macrophages have a promoting effect on the epithelial-to-mesenchymal transition of human renal tubular epithelial cells.

This study planned to explore the effects of M2c macrophages on epithelial-to-mesenchymal transition (EMT) of human renal proximal tubular epithelial cells (HK-2). Human monocytic leukaemia cells were induced by TPA and IL-10 to differentiate M2c macrophages. Subsequently HK-2 cells were co-cultured with the M2c macrophages in Transwell chamber. After 48 h of co-culturing the HK-2 cells were detected in the mRNA and protein expression of E-cadherin, α-SMA and vimentin with RT-PCR, immunofluorescence and Western blot respectively. Besides, the migration ability of the HK-2 cells was estimated with Transwell migration assay. ANOVA was used to compare the difference between groups and Student's t-test to conduct multiple comparisons of two groups. P < 0.05 was considered statistically significant. The results showed that the mRNA and protein expression of α-SMA and vimentin of the HK-2 cells were increased but the E-cadherin decreased significantly after 48 h co-culturing with the M2c macrophages (P < 0.05 or P < 0.01). And the migration ability of HK-2 cells were also increased significantly (P < 0.05). It may be concluded that polarized M2c macrophages may have a promoting effect on the EMT of HK-2 cells.

Meta-analysis of programmed cell death 1 polymorphisms with systemic lupus erythematosus risk.

The association of polymorphisms in programmed cell death 1 (PDCD1) gene with systemic lupus erythematosus (SLE) risk is inconsistent across different studies. This meta-analysis is aimed to provide reliable evidence to the association of five common PDCD1 polymorphisms (PD1.1, PD1.2, PD1.3, PD1.5 and PD1.6) with SLE risk. A total of 28 studies with 4,344 SLE cases and 5,474 healthy controls were included in this meta-analysis. PD1.3 polymorphism was significantly associated with SLE in the overall population (A vs. G: OR = 1.35, 95% CI = 1.12-1.63; GA vs.GG: OR = 1.41, 95% CI = 1.12-1.76; AA+GA vs. GG: OR = 1.41, 95% CI = 1.13-1.7). In the stratified analyses based on ethnicity, we found a significant association in Caucasians and in Mexicans. In the subgroup analyses by gender, a significant association was found between PD1.3 polymorphism and SLE risk in males. The results also suggested an association between the PD1.6 polymorphism and decreased SLE risk (A vs. G: OR = 0.84, 95% CI = 0.73-0.96). Our meta-analysis revealed that PD1.3 polymorphism may increase the susceptibility to SLE, particularly in Caucasians, while PD1.6 may be a protective factor to SLE.

Cd-Resistant Strains of B. cereus S5 with Endurance Capacity and Their Capacities for Cadmium Removal from Cadmium-Polluted Water.

The goal of this study was to identify Cd-resistant bacterial strains with endurance capacity and to evaluate their ability to remove cadmium ions from cadmium-polluted water. The Bacillus cereusS5 strain identified in this study had the closest genetic relationship with B. cereus sp. Cp1 and performed well in the removal of Cd2+ions from solution. The results showed that both the live and dead biomasses of the Cd2+-tolerant B. cereus S5 strain could absorb Cd2+ ions in solution but that the live biomass of the B. cereus S5 strain outperformed the dead biomass at lower Cd2+concentrations. An analysis of the cadmium tolerance genes of B. cereus S5 identified ATPase genes that were associated with cadmium tolerance and involved in the ATP pumping mechanism. The FTIR spectra revealed the presence of amino, carboxyl and hydroxyl groups on the pristine biomass and indicated that the cadmium ion removal ability was related to the structure of the strain. The maximum absorption capacity of the B. cereus S5 strain in viable spore biomass was 70.16 mg/g (dry weight) based on a pseudo-second-order kinetic model fit to the experimental data. The Langmuir and Langmuir-Freundlich isotherm adsorption models fit the cadmium ion adsorption data well, and the kinetic curves indicated that the adsorption rate was second-order. For Cd2+ concentrations (mg/L) of 1-109 mg/L, good removal efficiency (>80%) was achieved using approximately 3.48-10.3 g/L of active spore biomass of the B. cereus S5 strain. A cadmium-tolerant bacteria-activated carbon-immobilized column could be used for a longer duration and exhibited greater treatment efficacy than the control column in the treatment of cadmium-polluted water. In addition, a toxicity assessment using mice demonstrated that the biomass of the B. cereus S5 strain and its fermentation products were non-toxic. Thus, the isolated B. cereus S5 strain can be considered an alternative biological adsorbent for use in emergency responses to severe cadmium pollution and in the routine treatment of trace cadmium pollution.

Association of Megsin Gene Variants With IgA Nephropathy in Northwest Chinese Population: A STROBE-Compliant Observational Study.

Megsin is a mesangial cell-predominant gene that encodes a serpin family protein which is expressed in the renal mesangium. Overexpression of megsin has been observed in the glomeruli of patients with IgA nephropathy (IgAN). The aim of this study was to evaluate the association of megsin polymorphisms (rs1055901 and rs1055902) with IgAN in a Chinese population.We examined 351 patients with histologically proven IgAN and compared them with 310 age, sex, and ethnicity-matched healthy subjects. Two single nucleotide polymorphisms (SNPs) in megsin were genotyped by Sequenom MassARRAY. SPSS 18.0 was used for statistical analyses, and SNP Stats to test for associations between these polymorphisms and IgAN risk. Odds ratios with 95% confidence intervals were used to assess the relationships.We found that rs1055901 and rs1055902 SNPs were not correlated with susceptibility to IgAN in Northwest Chinese population. Analyses of the relationship between genotypes and clinical variables indicated that in patients with IgAN, rs1055901 was associated with 24-hour proteinuria, an increase in blood pressure, and Lee's grade (P = 0.04, 0.02, and 0.04, respectively), and rs1055902 was associated with 24-hour proteinuria and Lee's grade (P = 0.03 and 0.01, respectively). However, the results showed no association between these gene variants and sex of the patients.These results indicate that megsin gene variants may play a role in the severity, development, and/or progression of IgAN in Northwest Chinese population.