Relationships among gut microbes, the interleukin family, and hypertension: a mediation Mendelian randomization study

PurposeObservational studies have increasingly recognized the influence of gut microbes on blood pressure modulation. Despite these findings, a direct causal link between gut flora and hypertension remains unestablished due to inherent confounders and the challenges of reverse causality in observational research. In this study, we sought to elucidate the causal relationship between specific gut flora and hypertension and its intermediary mediators.MethodsWe employed a two-sample Mendelian randomization (MR) and mediation MR analysis, analyzing 211 species of gut bacteria, with a focus on the interleukin family as potential mediators and hypertension as the primary outcome. The central methodological technique was inverse variance-weighted estimation, supplemented by various other estimators.ResultsOur findings revealed that two bacterial species positively correlated with hypertension risk, while five exhibited a negative association. Further validation was conducted using sensitivity analyses. Notably, our mediation MR results suggest interleukin-1 receptor type 2 (IL-1R2) as a mediator for the effect of the genus Clostridium innocuum group on hypertension, accounting for a mediation proportion of 14.07% [mediation effect: (b = 0.0007, 95%CI: 0.0002–0.0011); proportion mediation = 14.07% (4.26–23.40%)].ConclusionOur research confirms a genetic causal relationship between specific gut microbes and hypertension, emphasizing the potential mediating role of interleukin-1 receptor type 2 (IL-1R2) and offering insights for clinical hypertension interventions

Ephedra sinica polysaccharide regulate the anti-inflammatory immunity of intestinal microecology and bacterial metabolites in rheumatoid arthritis

IntroductionEphedra sinica polysaccharide (ESP) exerts substantial therapeutic effects on rheumatoid arthritis (RA). However, the mechanism through which ESP intervenes in RA remains unclear. A close correlation has been observed between enzymes and derivatives in the gut microbiota and the inflammatory immune response in RA.MethodsA type II collagen-induced arthritis (CIA) mice model was treated with Ephedra sinica polysaccharide. The therapeutic effect of ESP on collagen-induced arthritis mice was evaluated. The anti-inflammatory and cartilage-protective effects of ESP were also evaluated. Additionally, metagenomic sequencing was performed to identify changes in carbohydrate-active enzymes and resistance genes in the gut microbiota of the ESP-treated CIA mice. Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry were performed to observe the levels of serum metabolites and short-chain fatty acids in the gut. Spearman’s correlational analysis revealed a correlation among the gut microbiota, antibiotic-resistance genes, and microbiota-derived metabolites.ResultsESP treatment significantly reduced inflammation levels and cartilage damage in the CIA mice. It also decreased the levels of pro-inflammatory cytokines interleukin (IL)-6, and IL-1-β and protected the intestinal mucosal epithelial barrier, inhibiting inflammatory cell infiltration and mucosal damage. Here, ESP reduced the TLR4, MyD88, and TRAF6 levels in the synovium, inhibited the p65 expression and pp65 phosphorylation in the NF-κB signaling pathway, and blocked histone deacetylase (HDAC1 and HDAC2) signals. ESP influenced the gut microbiota structure, microbial carbohydrate-active enzymes, and microbial resistance related to resistance genes. ESP increased the serum levels of L-tyrosine, sn-glycero-3-phosphocholine, octadecanoic acid, N-oleoyl taurine, and decreased N-palmitoyl taurine in the CIA mice.ConclusionESP exhibited an inhibitory effect on RA. Its action mechanism may be related to the ability of ESP to effectively reduce pro-inflammatory cytokines levels, protect the intestinal barrier, and regulate the interaction between mucosal immune systems and abnormal local microbiota. Accordingly, immune homeostasis was maintained and the inhibition of fibroblast-like synoviocyte (FLS) proliferation through the HDAC/TLR4/NF-κB pathway was mediated, thereby contributing to its anti-inflammatory and immune-modulating effects

Gestational hypoxia and epigenetic programming of brain development disorders

Adverse environmental conditions faced by an individual early during its life, such as gestational hypoxia, can have a profound influence on the risk of diseases, such as neurological disorders, in later life. Clinical and preclinical studies suggest that epigenetic programming of gene expression patterns in response to maternal stress have a crucial role in the fetal origins of neurological diseases. Herein, we summarize recent studies regarding the role of epigenetic mechanisms in the developmental programming of neurological diseases in offspring, primarily focusing on DNA methylation/demethylation and miRNAs. Such information could increase our understanding of the fetal origins of adult diseases and help develop effective prevention and intervention against neurological diseases

Effect of Aeration and External Carbon Source on Nitrogen Removal and Distribution Patterns of Related-Microorganisms in Horizontal Subsurface Flow Constructed Wetlands

Nitrogen pollution of surface water is still a critical issue worldwide. In this study, a total of four treatments were conducted in horizontal subsurface flow constructed wetlands (HSSFCWs) to explore the removal rate of nitrogen in the carbon-deficient wastewater, including combination of aeration and external carbon source (CW_CA), external carbon source (CW_C), aeration (CW_A), and control group without aeration and carbon source (CW_CK). Results showed that the removal rates of total nitrogen (TN) in the enhanced treatments were increased compared with CW_CK. The highest removal rates of COD (66.56%), NH4+-N (73.51%), NO3−-N (79.31%), and TN (76.19%) were observed in the CW_CA treatment. The bacterial community structure at the fore and rear ends of HSSFCWs was simultaneously changed in the CW_CA and CW_C treatments, respectively. The highest richness index at both the fore and rear ends of HSSFCWs was found in the CW_CA treatment. The richness and diversity indices of CW_C declined at the fore ends of HSSFCWs, but increased at the rear ends of HSSFCWs. Furthermore, the functional bacteria and genes significantly changed among different treatments. At the fore ends of HSSFCWs, the highest relative abundance of nitrifiers and absolute abundance of amoA and nxrA were obtained in CW_A, and the highest relative abundance of denitrifying bacteria and absolute abundance of nirS, nirK, nosZ were found in CW_C. However, at the rear ends of HSSFCWs, the highest relative abundance of nitrifiers and denitrifying bacteria as well as the absolute abundance of related genes were also observed in the CW_CA treatment. Overall, CW_CA improved the nitrogen removal rate by increasing the abundance of nitrogen-converting functional microbes and the genes associated with nitrification and denitrification

Quantitative analysis of the MRI features in the differentiation of benign, borderline, and malignant epithelial ovarian tumors

Abstract Objective This study aims to investigate the value of the quantitative indicators of MRI in the differential diagnoses of benign, borderline, and malignant epithelial ovarian tumors (EOTs). Materials and methods The study population comprised 477 women with 513 masses who underwent MRI and operation, including benign EOTs (BeEOTs), borderline EOTs (BEOTs), and malignant EOTs (MEOTs). The clinical information and MRI findings of the three groups were compared. Then, multivariate logistic regression analysis was performed to find the independent diagnostic factors. The receiver operating characteristic (ROC) curves were also used to evaluate the diagnostic performance of the quantitative indicators of MRI and clinical information in differentiating BeEOTs from BEOTs or differentiating BEOTs from MEOTs. Results The MEOTs likely involved postmenopausal women and showed higher CA-125, HE4 levels, ROMA indices, peritoneal carcinomatosis and bilateral involvement than BeEOTs and BEOTs. Compared with BEOTs, BeEOTs and MEOTs appeared to be more frequently oligocystic (P < 0.001). BeEOTs were more likely to show mild enhancement (P < 0.001) and less ascites (P = 0.003) than BEOTs and MEOTs. In the quantitative indicators of MRI, BeEOTs usually showed thin-walled cysts and no solid component. BEOTs displayed irregular thickened wall and less solid portion. MEOTs were more frequently characterized as solid or predominantly solid mass (P < 0.001) than BeEOTs and BEOTs. The multivariate logistic regression analysis showed that volume of the solid portion (P = 0.006), maximum diameter of the solid portion (P = 0.038), enhancement degrees (P < 0.001), and peritoneal carcinomatosis (P = 0.011) were significant indicators for the differential diagnosis of the three groups. The area under the curves (AUCs) of above indicators and combination of four image features except peritoneal carcinomatosis for the differential diagnosis of BeEOTs and BEOTs, BEOTs and MEOTs ranged from 0.74 to 0.85, 0.58 to 0.79, respectively. Conclusion In this study, the characteristics of MRI can provide objective quantitative indicators for the accurate imaging diagnosis of three categories of EOTs and are helpful for clinical decision-making. Among these MRI characteristics, the volume, diameter, and enhancement degrees of the solid portion showed good diagnostic performance

Dexamethasone Treatment of Newborn Rats Decreases Cardiomyocyte Endowment in the Developing Heart through Epigenetic Modifications.

The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1), 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2'-deoxycytidine (5-AZA) blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner