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Ammonia is a major aquatic environmental pollutants. However, the underlying molecular mechanism of ammonia-induced toxicity is not fully understood. In this study, we investigated the physiological response and molecular mechanism in mud crab (Scylla paramamosain) exposed to the acute total ammonia (30 mg L−1) for 48 h. The results shown that ammonia exposure induced oxidative stress, and subsequently led to cytological damage and DNA damage. Transcriptome analysis was applied to investigate the key genes and pathways involved in the responses to ammonia exposure. A total of 722 differentially expressed genes (DEGs) (526 up-regulated and 196 down-regulated) were identified. DEGs mainly involved in pathways including metabolism, cellular processes, signal transduction and immune functions. Additionally, transcriptome analysis revealed that ATM/p53-Caspase3 pathway involved in apoptosis induced by ammonia stress. These results provided a new insight into the mechanism of the potential toxic effects of ammonia on crustaceans. • Ammonia exposure induced oxidative stress, and led to cytological damage and DNA damage. • Some genes involved in response to environmental stress were found. • ATM/p53-Caspase3 pathway could be involved in response to ammonia exposure. [ABSTRACT FROM AUTHOR]

Background The association between vitamin D receptor (VDR) gene polymorphisms and multiple sclerosis (MS) has been extensively studied, but results were controversial. Methods This meta-analysis aimed to confirm whether VDR gene polymorphisms were associated with MS. Meta-analysis on the association between MS and VDR Apa I, Bsm I, Taq I and Fok I polymorphisms were conducted using allelic contrast, recessive, homozygotes and dominant models. Data were extracted by standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated using the random effects model if the results were heterogeneous. Stratification analysis by the selected study characteristics were performed to detect potential source of heterogeneity. Results A total of 21 relevant studies involving 3593 MS patients and 3917 controls were included in the analysis. The association between Taq I polymorphism and MS risk was significant in the homozygous model (p = 0.006) indicated a significant protective effect of TT Taq I genotype. High latitude (40.1–50°N) was also found markedly influenced Taq I polymorphism and MS risk in the recessive and homozygous models (p = 0.045 and p = 0.015, respectively). Additionally, Asian or low latitude (20.1–30°N) people with Apa I homozygous genotype, ‘> 2013’ publication year people in the allele contrast and dominant models of Fok I, ‘> 40 years’ age people with Bsm I recessive model also indirectly significantly affected the association between VDR gene polymorphisms and MS risk. Conclusion Taq I polymorphism is a significant protective factor for MS. However, the associations between Apa I, Fok I and Bsm I polymorphisms and MS were found only by study characteristics. [ABSTRACT FROM AUTHOR]

Abstract Diabetic retinopathy (DR) is a progressive microvascular complication associated with diabetes, and remains the leading cause of preventable blindness worldwide. Recent studies have revealed that microRNAs (miRNAs) were involving in the physiological and pathophysiological processes of diabetes and its microvascular and macrovascular complications. The purpose of the current investigation is to identify the candidate miR-211 as a novel biomarker for occurrence and progression of DR in clinical study and experimental research. Firstly, miR-211 was considered as a candidate miRNA identifying by miRNA microarray analysis, Venn diagram analysis, real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and receiver operating characteristic curve in clinical study. Then, the predicted Sirtuin 1 (SIRT1) may be the target gene of miR-211 searching by TargetScan 7.2. Moreover, miR-211 was significantly up-regulated, while SIRT1 mRNA significantly down-regulated measuring by qRT-PCR, meanwhile, SIRT1 protein was significantly down-regulated in coincidence with SIRT1 mRNA detecting by western blot, and even aggravated associated with diabetes duration in diabetic retinal tissues of vivo experiment. Additionally, miR-211 was directly targeted SIRT1 confirming by dual-luciferase reporter assay. Furthermore, with transfection of antagomiR-211, the apoptosis of HUVECs was significantly suppressed employing by flow cytometry analysis, nevertheless the viability of HUVECs was significantly promoted exploiting by Cell Counting Kit-8 assay. Finally, SIRT1 mRNA and SIRT1 protein were significantly up-regulated testing by qRT-PCR and western blot respectively in hyperglycemic HUVECs transfected with antagomiR-211 of vitro experiment. Consequently, the current clinical study and experimental research imply that serum miR-211 as a novel biomarker with high sensitivity and specificity could be associated with occurrence and progression of DR via targeting SIRT1. Highlights • Serum miR-211 was significantly up-regulated in patients with diabetic retinopathy. • miR-211 was significantly up-regulated associated with diabetes duration. • miR-211 could directly target SIRT1 and may regulate the expression of SIRT1. • Serum miR-211 as a biomarker for diabetic retinopathy via modulating Sirtuin 1. [ABSTRACT FROM AUTHOR]