ABSTRACT
Lupus nephritis (LN) is a kidney disorder that is a critical cause of mortality in patients with systemic lupus erythematosus. The present study aimed to explore the protective role of complement component 1q (C1q) on LN and the underlying mechanism involving the nuclear factor (NF)κB singling pathway. MRL/lpr mice served as the LN mouse model, and pcDNAC1q was injected into LN mice to determine the role of C1q. C1q mRNA expression was detected using reverse transcriptionquantitative PCR. Urine protein and blood urea nitrogen (BUN) levels were measured, and the histological damage index was determined using H&E staining. ELISA was used to measure the levels of tumor necrosis factorα (TNFα), interleukin (IL)1ß, IL6, antiC1q and antidouble stranded DNA (dsDNA). CD68 and Ki67positivity were detected using immunofluorescence, and NFκBrelated protein expression was examined using western blotting. C1q mRNA expression was downregulated in renal tissues of LN mice. Overexpression of C1q decreased urine protein, BUN levels and the histological damage index in LN mice. The levels of TNFα, IL1ß, IL6, antiC1q and antidsDNA in renal tissues of LN mice were also reduced after pcDNAC1q treatment. Additionally, overexpression of C1q decreased the CD68 and Ki67positivity in glomeruli and attenuated the expression of NFκBrelated proteins. Phorbol 12myristate 13acetate, an NFκB pathway activator, reversed the inhibitory effect of C1q on inflammation, macrophage infiltration and mesangial cell (MC) proliferation in renal tissues of LN mice. Thus, it was demonstrated that C1q ameliorated inflammation and macrophage infiltration and decreased MC proliferation in renal tissues of LN mice by inhibiting the NF-κB pathway.
Subject(s)
Complement C1q/pharmacology , Lupus Nephritis/metabolism , NF-kappa B/metabolism , Animals , Antibodies, Antinuclear/blood , China , Disease Models, Animal , Inflammation/pathology , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Kidney/pathology , Kidney Diseases/pathology , Lupus Erythematosus, Systemic/pathology , Lupus Nephritis/immunology , Lupus Nephritis/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Inbred MRL lpr , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Signal Transduction/physiology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Flame-retardant bio-based cellulose aerogels, with abundant renewable sources, are considered as promising sustainable heat-insulation alternatives to conventional petroleum-based foams. An environmentally friendly method was employed to fabricate phosphorylated microcrystalline cellulose (PMCC) aerogel through the gelation of PMCC/H2O dispersion and freeze-drying of PMCC hydrogel. The dispersion stability of PMCC and its readiness to undergo gelation in the aqueous phase were enhanced by increasing the phosphorous content via phosphorylation, thereby effectively weakening the strong intra- and intermolecular hydrogen-bond interactions of the cellulose chains. The morphology of the PMCC aerogel changed from a short rod-shaped and sheet-like aggregation of a three-dimensional skeleton structure to a mostly sheet-like aggregation of a three-dimensional structure with increased phosphate esterification. Remarkably, PMCC aerogels exhibited improved flame retardancy and superior suppression of toxic gas, compared to MCC. This is attributable to the synergic effect of phosphate dehydration, catalytic carbonization, and protection of the aerogel network structure.
Subject(s)
Cellulose/chemistry , Hydrogels/chemistry , Molecular Structure , Particle Size , Phosphorylation , Surface PropertiesABSTRACT
A highly efficient flame-retardant and ultra-low-smoke-toxicity biodegradable material, poly(vinyl alcohol) (PVA)/alginate/montmorillonite (MMT) composite aerogel, was fabricated by a new environment-friendly two-step crosslinking strategy using borate and calcium ions. Compressive and specific moduli of the crosslinked PVA/alginate/MMT (P4A4M4/BA/Ca) aerogel increased to 7.2- and 1.9-folds those of the non-crosslinked aerogel, respectively, and the limited oxygen index value increased to 40.0%. Cone calorimeter tests revealed that the total heat release and peak heat release rate values of the P4A4M4/BA/Ca composite aerogel distinctly decreased. Remarkably, the total smoke release value of the P4A4M4/BA/Ca aerogel was considerably lower than those of non-crosslinked PVA composite aerogels, indicating its superior smoke suppression ability and high fire hazardous safety. The flame-retardancy mechanism of the crosslinked P4A4M4/BA/Ca composite aerogels involved a combination of the gaseous phase and condensed phase flame retardancy. The high-performance PVA/alginate/MMT biodegradable composite aerogels with good sustainability is a promising alternative to conventional flame-retardant foams.
Subject(s)
Alginates/chemistry , Bentonite/chemistry , Flame Retardants/chemical synthesis , Hydrogels/chemistry , Polyvinyl Alcohol/chemistry , Alginates/chemical synthesis , Alginates/toxicity , Bentonite/chemical synthesis , Bentonite/toxicity , Borates/chemistry , Cross-Linking Reagents/chemistry , Flame Retardants/toxicity , Hydrogels/chemical synthesis , Hydrogels/toxicity , Polyvinyl Alcohol/chemical synthesis , Polyvinyl Alcohol/toxicity , SmokeABSTRACT
BACKGROUND: Diabetic nephropathy (DN) is a common complication in patients with diabetic mellitus (DM). Growing evidences have demonstrated that the polymorphisms of angiotensin II receptor type 1 (AGTR1) showed significant association with DN onset, but no consensus has been achieved yet. Therefore, we performed this meta-analysis to combine the findings of previous researches for a more comprehensive conclusion. METHODS: Eligible publications were identified through electronic databases. The intensity of the correlation between AGTR1 A1166C polymorphism and DN susceptibility was evaluated through calculating pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs). Heterogeneity among included studies was examined with Q test. When P-value less than .05, significant heterogeneity presented, random-effects model was used to calculate the pooled ORs, otherwise, the fixed-effects model was used. Stratification analyses were also performed based on ethnicity and the type of DM. RESULTS: Seventeen eligible articles were finally included in the present meta-analysis. The analysis results showed that AGTR1 A1166C polymorphism was significantly related to increased risk of DN under CC versus AA (ORâ=â1.723, 95% CIâ=â1.123-2.644), CCâ+âAC versus AA (ORâ=â1.179, 95% CIâ=â1.004-1.383), CC versus AAâ+âAC (ORâ=â1.662, 95% CIâ=â1.112-2.486), and C versus A (ORâ=â1.208, 95% CIâ=â1.044-1.397) genetic models. Additionally, a similar result was also found in Asian and T2DM (type 2 diabetic mellitus) groups after subgroup analyses of ethnicity and DM type. CONCLUSION: AGTR1 A1166C polymorphism may increase the susceptibility to DN, especially in Asians and T2DM population.
Subject(s)
Diabetic Nephropathies/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Receptor, Angiotensin, Type 1/genetics , Genetic Association Studies , Genetic Markers , Humans , Models, Statistical , Odds RatioABSTRACT
The aim of the study was to explore the correlation between rs7903146 and rs290487 polymorphisms in transcription factor 7-like 2 (TCF7L2) gene and diabetic nephropathy (DN) in Chinese Han population.Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of TCF7L2 polymorphisms in 90 patients with DN and 96 diabetes patients without DN. The linkage disequilibrium (LD) and haplotype analysis were performed with haploview software. Hardy-Weinberg equilibrium was assessed in the control group based on the genotype distributions of TCF7L2 polymorphisms. The genotype, allele, and haplotype distribution differences between the case and control groups were analyzed by chi-squared test, and odds ratio (OR) and 95% confidence interval (CI) were used to indicate the relative risk of DN.People carrying TT genotype of rs7903146 were more easily to be attacked by DN than CC genotype carriers (Pâ=â.02, ORâ=â4.26, 95% CIâ=â1.12-16.24). Meanwhile, T allele also showed 1.85 times risk to suffer from DN compared with C allele (ORâ=â1.85, 95% CIâ=â1.02-3.10). However, there was no significant difference in genotypes and alleles frequencies of rs290487 between 2 groups. The strong LD existed between the 2 single nucleotide polymorphisms and haplotype T-T (rs7903146-rs290487) increased the susceptibility to DN (ORâ=â2.63, 95% CIâ=â1.31-5.25).TCF7L2 rs7903146 polymorphism may be associated with the susceptibility to DN in Chinese Han population, but rs290487 is not. Additionally, haplotype is also a risk factor for DN.
Subject(s)
Diabetic Nephropathies/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Transcription Factor 7-Like 2 Protein/genetics , Adult , Aged , Alleles , Case-Control Studies , Chi-Square Distribution , China , Female , Gene Frequency , Genotype , Haplotypes , Humans , Linkage Disequilibrium/genetics , Male , Middle Aged , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk FactorsABSTRACT
AIMS: To investigate the prospective association between changes in the urinary albumin-creatinine ratio (ACR) and abnormal ankle-brachial index (ABI) in a community-based Chinese population. METHODS: This prospective cohort study included 799 residents aged 58.3±9.2 years and without a history of cardiovascular disease from an urban district of Beijing, China. Urinary ACR was measured at baseline, and at 4 and 6 years of follow-up. The 75th percentile of the baseline urinary ACR (5.82 mg/g) was used to define "high" ACR. The changes in urinary ACR were categorized as consistently low urinary ACR, intermittent high urinary ACR, and consistently high urinary ACR. ABI was measured at 6 years of follow-up. Multinomial logistic regression was used to evaluate the associations of changes in urinary ACR categories with the ABI categories. RESULTS: During 6 years of follow-up, 16.1% of participants (n= 128) had low ABI and 13.9% of participants (n= 111) had high ABI. After adjusting for potential confounders including baseline albuminuria, individuals who had consistently high urinary ACR or intermittent high urinary ACR had a significantly higher risk for low ABI than individuals who had consistently low urinary ACR, with odds ratios (OR) of 2.75 (95%CI, 1.37-5.52) and 2.06 (95%CI, 1.18-3.57), respectively. No independent association was observed between changes in urinary ACR and high ABI among participants. CONCLUSION: Changes in urinary ACR below the definition for albuminuria predict low ABI among this community-based population without a history of cardiovascular disease.