Regulation of transforming growth factor beta 1 gene expression by dihydropteridine reductase in kidney 293T cells.

Quinoid dihydropteridine reductase (QDPR) is an enzyme involved in the metabolic pathway of tetrahydrobiopterin (BH4). BH4 is an essential cofactor of nitric oxide synthase (NOS) and can catalyze arginine to citrulline to release nitric oxide. Point mutations of QDPR have been found in the renal cortex of spontaneous Otsuka Long Evans Tokushima Fatty (OLETF) diabetic rats. However, the role of QDPR in DN is not clear. This study investigates the effects of QDPR overexpression and knockdown on gene expression in the kidney. Rat QDPR cDNA was cloned into pcDNA3.1 vector and transfected in human kidney cells (293T). The expression of NOS, transforming growth factor beta 1 (TGF-ß1), Smad3, and NADPH oxidase were examined by RT-PCR and Western blot analyses. BH4 was assayed by using ELISA. Expression of QDPR was significantly decreased and TGF-ß1 and Smad3 were increased in the renal cortex of diabetic rats. Transfection of QDPR into 293T cells increased the abundance of QDPR in cytoplasm and significantly reduced the expression of TGF-ß1, Smad3, and the NADPH oxidases NOX1 and NOX4. Moreover, abundance of neuronal NOS (nNOS) mRNA and BH4 content were significantly increased. Furthermore, inhibition of QDPR resulted in a significant increase in TGF-ß1 expression. In conclusion, QDPR might be an important factor mediating diabetic nephropathy through its regulation of TGF-ß1/Smad3 signaling and NADPH oxidase.

Soil Geochemical Properties Influencing the Diversity of Bacteria and Archaea in Soils of the Kitezh Lake Area, Antarctica.

It is believed that polar regions are influenced by global warming more significantly, and because polar regions are less affected by human activities, they have certain reference values for future predictions. This study aimed to investigate the effects of climate warming on soil microbial communities in lake areas, taking Kitezh Lake, Antarctica as the research area. Below-peak soil, intertidal soil, and sediment were taken at the sampling sites, and we hypothesized that the diversity and composition of the bacterial and archaeal communities were different among the three sampling sites. Through 16S rDNA sequencing and analysis, bacteria and archaea with high abundance were obtained. Based on canonical correspondence analysis and redundancy analysis, pH and phosphate had a great influence on the bacterial community whereas pH and nitrite had a great influence on the archaeal community. Weighted gene coexpression network analysis was used to find the hub bacteria and archaea related to geochemical factors. The results showed that in addition to pH, phosphate, and nitrite, moisture content, ammonium, nitrate, and total carbon content also play important roles in microbial diversity and structure at different sites by changing the abundance of some key microbiota.

The effects of ACEI/ARB, aldosterone receptor antagonists and statins on preventing recurrence of atrial fibrillation: A protocol for systematic review and network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmias, and is high relative to cardiovascular morbidity and mortality. AF-related complications and treatment costs bring about huge health burden, therefore the prevention recurrence of AF is imperative. "Upstream therapy" refers to the use of non-antiarrhythmic drugs (non-AADs) that modify the atrial substrate or target-specific mechanisms of AF to prevent the occurrence or recurrence of the arrhythmia. RAAS Blockers, aldosterone receptor antagonists and statins have an effect on preventing recurrence of atrial fibrillation. This protocol is designed for systematic review and network meta-analysis, which will assess comparative effects and safety of various non-antiarrhythmic drugs in preventing recurrence of atrial fibrillation. METHODS: The Cochrane Library, MEDLINE, EMBASE, ClinicalTrials.gov will be searched from inception to Aug 31, 2020 to identify relevant studies. The Cochrane "Risk of bias" tool will be used to assess the methodological quality of eligible studies. The pair-wise meta-analysis will be performed by STATA 14.0 software. The network meta-analysis will be implemented in a Bayesian framework using Win BUGS 1.4.3 and the package "gemtc" V.0.8.1 of R-3.6.2 software. The network plots will be drawn using STATA 14.0 software. A comparison-adjusted funnel plot will be used to assess the publication bias using STATA 14.0 software. Quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: The results of this network meta-analysis will determine the preventive effect and rank ordering of these interventions for recurrence of AF. The report will follow the PRISMA checklist for network meta-analysis. CONCLUSION: This network meta-analysis will provide comprehensive evidence-based information in clinical practice. INPLASY REGISTRATION NUMBER: INPLASY202090004.

The Effect of Nitrogen Content on Archaeal Diversity in an Arctic Lake Region.

The function of Arctic soil ecosystems is crucially important for the global climate, and nitrogen (N) is the major limiting nutrient in these environments. This study assessed the effects of changes in nitrogen content on archaeal community diversity and composition in the Arctic lake area (London Island, Svalbard). A total of 16S rRNA genes were sequenced to investigate archaeal community composition. First, the soil samples and sediment samples were significantly different for the geochemical properties and archaeal community composition. Thaumarchaeota was an abundant phylum in the nine soil samples. Moreover, Euryarchaeota, Woesearchaeota, and Bathyarchaeota were significantly abundant phyla in the three sediment samples. Second, it was found that the surface runoff caused by the thawing of frozen soil and snow changed the geochemical properties of soils. Then, changes in geochemical properties affected the archaeal community composition in the soils. Moreover, a distance-based redundancy analysis revealed that NH4+-N (p < 0.05) and water content were the most significant factors that correlated with the archaeal community composition. Our study suggests that nitrogen content plays an important role in soil archaeal communities. Moreover, archaea play an important role in the carbon and nitrogen cycle in the Arctic lake area.

Geochemical-Compositional-Functional Changes in Arctic Soil Microbiomes Post Land Submergence Revealed by Metagenomics.

Lakes of meltwater in the Artic have become one of the transforming landscape changes under global warming. We herein compared microbial communities between sediments and bank soils at an arctic lake post land submergence using geochemistry, 16S rRNA amplicons, and metagenomes. The results obtained showed that each sample had approximately 2,609 OTUs on average and shared 1,716 OTUs based on the 16S rRNA gene V3-V4 region. Dominant phyla in sediments and soils included Proteobacteria, Acidobacteria, Actinobacteria, Gemmatimonadetes, and Nitrospirae; sediments contained a unique phylum, Euryarchaeota, with the phylum Thaumarchaeota being primarily present in bank soils. Among the top 35 genera across all sites, 17 were more abundant in sediments, while the remaining 18 were more abundant in bank soils; seven out of the top ten genera across all sites were only from sediments. A redundancy analysis separated sediment samples from soil samples based on the components of nitrite and ammonium. Metagenome results supported the role of nitrite because most of the genes for denitrification and methane metabolic genes were more abundant in sediments than in soils, while the abundance of phosphorus-utilizing genes was similar and, thus, was not a significant explanatory factor. We identified several modules from the global networks of OTUs that were closely related to some geochemical factors, such as pH and nitrite. Collectively, the present results showing consistent changes in geochemistry, microbiome compositions, and functional genes suggest an ecological mechanism across molecular and community levels that structures microbiomes post land submergence.

Direct and Indirect Effects of Penguin Feces on Microbiomes in Antarctic Ornithogenic Soils.

Expansion of penguin activity in maritime Antarctica, under ice thaw, increases the chances of penguin feces affecting soil microbiomes. The detail of such effects begins to be revealed. By comparing soil geochemistry and microbiome composition inside (one site) and outside (three sites) of the rookery, we found significant effects of penguin feces on both. First, penguin feces change soil geochemistry, causing increased moisture content (MC) of ornithogenic soils and nutrients C, N, P, and Si in the rookery compared to non-rookery sites, but not pH. Second, penguin feces directly affect microbiome composition in the rookery, not those outside. Specifically, we found 4,364 operational taxonomical units (OTUs) in 404 genera in six main phyla: Proteobacteria, Actinobacteria, Gemmatimonadetes, Acidobacteria, Chloroflexi, and Bacteroidetes. Although the diversity is similar among the four sites, the composition is different. For example, penguin rookery has a lower abundance of Acidobacteria, Chloroflexi, and Nitrospirae but a higher abundance of Bacteroidetes, Firmicutes, and Thermomicrobia. Strikingly, the family Clostridiaceae of Firmicutes of penguin-feces origin is most abundant in the rookery than non-rookery sites with two most abundant genera, Tissierella and Proteiniclasticum. Redundancy analysis showed all measured geochemical factors are significant in structuring microbiomes, with MC showing the highest correlation. We further extracted 21 subnetworks of microbes which contain 4,318 of the 4,364 OTUs using network analysis and are closely correlated with all geochemical factors except pH. Our finding f penguin feces, directly and indirectly, affects soil microbiome suggests an important role of penguins in soil geochemistry and microbiome structure of maritime Antarctica.

Yi qi qing re gao attenuates podocyte injury and inhibits vascular endothelial growth factor overexpression in puromycin aminonucleoside rat model.

Proteinuria is the hallmark of chronic kidney disease. Podocyte damage underlies the formation of proteinuria, and vascular endothelial growth factor (VEGF) functions as an autocrine/paracrine regulator. Yi Qi Qing Re Gao (YQQRG) has been used to treat proteinuria for more than two decades. The objective of this study was to investigate the protective effect and possible mechanisms of YQQRG on puromycin aminonucleoside (PAN) rat model. Eighty male Sprague-Dawley rats were randomized into sham group, PAN group, PAN + YQQRG group, and PAN + fosinopril group. Treatments were started 7 days before induction of nephrosis (a single intravenous injection of 40 mg/kg PAN) until day 15. 24 h urinary samples were collected on days 5, 9, and 14. The animals were sacrificed on days 3, 10, and 15, respectively. Blood samples and renal tissues were obtained for detection of biochemical and molecular biological parameters. YQQRG significantly reduced proteinuria, elevated serum albumin, and alleviated renal pathological lesions. YQQRG inhibited VEGF-A, nephrin, podocin, and CD2AP mRNA expression and elevated nephrin, podocin, and CD2AP protein levels starting on day 3. In conclusion, YQQRG attenuates podocyte injury in the rat PAN model through downregulation of VEGF-A and restoration of nephrin, podocin, and CD2AP protein expression.