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1.
Lactobacillus plantarum 24-7 improves postoperative bloating and hard stools by modulating intestinal microbiota in patients with congenital heart disease: a randomized controlled trial.
Yang, H, Lan, W, Luo, C, Huang, Q, Zhong, Z, Yang, J, Xiang, H, Chen, T, Tang, Y
Food & function. 2024;(4):2090-2102
Abstract
Gastrointestinal symptoms are a common postoperative complication in patients with congenital heart disease (CHD), affecting their postoperative recovery. Probiotic intervention may be a promising therapeutic approach to alleviate postoperative gastrointestinal symptoms. This study aimed to evaluate the potential of Lactobacillus plantarum 24-7 (L. plantarum 24-7) in mitigating postoperative gastrointestinal symptoms and promoting patient recovery. Adult CHD patients scheduled for surgical intervention were recruited. One hundred and twenty patients were randomized and received L. plantarum or placebo intervention twice daily for ten days. Gastrointestinal symptoms were assessed utilizing the Gastrointestinal Symptom Rating Scale (GSRS). Various postoperative variables were analyzed across both groups. Alterations in gut microbiota were evaluated through 16S rRNA sequencing. 112 patients completed the study, with 55 in the probiotic group and 57 in the placebo group. While the disparity in overall postoperative GSRS scores between the two groups did not reach statistical significance (P = 0.067), marked differences were observed in bloating (P = 0.004) and hard stool (P = 0.030) scores. Furthermore, individuals within the probiotic group exhibited lower postoperative neutrophil counts (P = 0.007) and concurrently higher lymphocyte counts (P = 0.001). Variations in the diversity and composition of postoperative gut microbiota were discerned between the probiotic and placebo groups. Remarkably, no probiotic-related adverse events were documented. Supplementation with L. plantarum was well-tolerated and demonstrated partial efficacy in ameliorating gastrointestinal symptoms in postoperative CHD patients. Modulating the gut microbiota may be a potential mechanism by which L. plantarum exerts clinical benefits.
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2.
BVES-AS1 suppresses the colorectal cancer progression via the miR-1269a/b-SVEP1-PI3K/AKT axis.
Yang, J, Deng, Q, Chen, Z, Chen, Y, Fu, Z
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2024
Abstract
BACKGROUND Numerous studies have indicated the engagement of long non-coding RNA (lncRNA) in various cancer types, including colorectal cancer (CRC). However, the functional and mechanistic roles of lncRNAs in CRC remain largely elusive. OBJECTIVES The aim of this study was to explore the function and mechanism of lncRNA BVES-AS1 in CRC. MATERIAL AND METHODS The expression levels of BVES-AS1 were validated in CRC tissues and paired normal samples using quantitative real-time polymerase chain reaction (qPCR) Subsequently, the biological functions of BVES-AS1 in CRC cells were investigated both in vitro and in vivo. Various experimental techniques such as western blot, fluorescence in situ hybridization, RNA-sequencing (RNA-seq), biotin-labeled miRNA pulldown assay, dual-luciferase reporter gene assay, and RNA-protein immunoprecipitation (RIP) assay were employed to elucidate the potential mechanism of BVES-AS1. RESULTS The findings of this study demonstrated that BVES-AS1 expression was downregulated in CRC tissues compared to normal tissues, and its expression level was associated with tumor infiltration and tumor-nodule-metastasis (TNM) stage. Furthermore, BVES-AS1 was found to suppress CRC cell proliferation, migration and metastasis both in vitro and in vivo. Mechanistically, BVES-AS1 acted as a sponge for miR-1269a and miR-1269b, thereby regulating SVEP1. Additionally, the silencing of SVEP1 activated the PI3K/AKT pathway. CONCLUSIONS These results suggest that BVES-AS1 plays a crucial role in the progression of CRC through the miR-1269a/b-SVEP1-PI3K/AKT axis, providing new insights into the therapeutic strategies for CRC.
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3.
Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials.
Lei, L, Hui, S, Chen, Y, Yan, H, Yang, J, Tong, S
Nutrition journal. 2024;(1):32
Abstract
BACKGROUND Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting outcomes concerning the correlation between soy isoflavone consumption and blood pressure levels. Consequently, a comprehensive meta-analysis of all eligible randomized controlled trials (RCTs) was conducted to explore the influence of soy isoflavones on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. METHODS A thorough search of PubMed, Embase, and the Cochrane Library for relevant literature up to April 30, 2023 was conducted. RCTs involving adults that compared soy isoflavone supplementation with a placebo (the same matrix devoid of soy isoflavone) were included. The combined effect size was presented as the weighted mean difference (WMD) along with 95% confidence interval (CI), employing a fixed-effects model. RESULTS Our meta-analysis included a total of 24 studies involving 1945 participants. The results revealed a significant reduction in both SBP and DBP with soy isoflavone supplementation. Subgroup analyses suggested more pronounced reductions in SBP and DBP for interventions lasting ≥6 months, in individuals receiving mixed-type soy isoflavone, and among patients with metabolic syndrome or prehypertension. However, we did not detect significant nonlinear associations between supplementation dosage and intervention duration concerning both SBP and DBP. The overall quality of evidence was deemed moderate. CONCLUSIONS The current meta-analysis revealed that supplementation with soy isoflavones alone effectively reduces blood pressure. Additional high-quality studies are required to investigate the efficacy of blood pressure reduction through supplementation with an optimal quantity and proportion of soy isoflavone.
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4.
Quantitative assessment of retinal vasculature changes in systemic lupus erythematosus using wide-field OCTA and the correlation with disease activity.
Meng, L, Chen, L, Zhang, C, Chen, H, Yang, J, Wang, Y, Zhang, W, Cheng, S, Zhao, Q, Zhao, X, et al
Frontiers in immunology. 2024;:1340224
Abstract
PURPOSE To assess the retinal vasculature changes quantitatively using wide-field optical coherence tomography angiography (OCTA) in systemic lupus erythematosus (SLE), and explore its correlation with systemic clinical features. DESIGN Prospective, cross-sectional, observational study. PARTICIPANTS AND CONTROLS Patients with SLE who presented to the Ophthalmology Department of Peking Union Medical College Hospital from November 2022 to April 2023 were collected. The subjects were divided into retinopathy and without retinopathy groups. Age and gender-matched healthy subjects were selected as controls. METHODS Patients with SLE and control subjects were imaged with 24×20 mm OCTA scans centered on the fovea and 6×6 mm OCTA scans centered on the optic disc. The sub-layers of OCTA images were stratified by the built-in software of the device and then the retinal thickness and vessel density were measured automatically. The characteristics of retinal OCTA parameters of SLE and its correlation with systemic clinical indicators of patients without retinopathy were analyzed. MAIN OUTCOME MEASURES OCTA parameters, visual acuity, intraocular pressure, and systemic clinical indicators of patients such as disease activity index, autoimmune antibodies, and inflammatory marker levels were collected. RESULTS A total of 102 SLE patients were included, 24 of which had retinopathy, and 78 had unaffected retina. Wide-field OCTA could effectively detect retinal vascular obstruction, non-perfusion area, and morphological abnormalities in patients with lupus retinopathy. SLE patients without retinopathy had significantly higher retinal superficial vessel density (SVD) in foveal (P=0.02), para-foveal temporal (P=0.01), nasal (P=0.01), peripheral foveal temporal (P=0.02), and inferior areas (P=0.02), as well as subregion temporal (P=0.01) and inferior areas (P=0.03) when compared with healthy controls (n=65 eyes from 65 participants). The area under curve (AUC) value of subregion inferior SVD combined parafoveal temporal SVD was up to 0.70. There was a significantly positive correlation between SVD and disease activity in SLE without retinopathy group. Patients with severe activity had the most significant increase in SVD. CONCLUSION Wide-field OCTA can provide a relatively comprehensive assessment of the retinal vasculature in SLE. In the absence of pathological changes of the retina, the SVD was significantly increased and was positively correlated with the disease activity of SLE.
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5.
Joint Exposure to Ambient Air Pollutants, Genetic Risk, and Ischemic Stroke: A Prospective Analysis in UK Biobank.
Li, P, Wang, Y, Tian, D, Liu, M, Zhu, X, Wang, Y, Huang, C, Bai, Y, Wu, Y, Wei, W, et al
Stroke. 2024;(3):660-669
Abstract
BACKGROUND Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility. METHODS This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS. RESULTS Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m3 increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33-2.14), 1.24 (0.88-1.70), 1.13 (0.89-1.33), 1.03 (0.98-1.08), and 1.04 (1.02-1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%-189%) greater risk of IS than participants with low polygenic risk score and air pollution score. CONCLUSIONS Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.
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6.
Creating cell-specific computational models of stem cell-derived cardiomyocytes using optical experiments.
Yang, J, Daily, N, Pullinger, TK, Wakatsuki, T, Sobie, EA
bioRxiv : the preprint server for biology. 2024
Abstract
Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have gained traction as a powerful model in cardiac disease and therapeutics research, since iPSCs are self-renewing and can be derived from healthy and diseased patients without invasive surgery. However, current iPSC-CM differentiation methods produce cardiomyocytes with immature, fetal-like electrophysiological phenotypes, and the variety of maturation protocols in the literature results in phenotypic differences between labs. Heterogeneity of iPSC donor genetic backgrounds contributes to additional phenotypic variability. Several mathematical models of iPSC-CM electrophysiology have been developed to help understand the ionic underpinnings of, and to simulate, various cell responses, but these models individually do not capture the phenotypic variability observed in iPSC-CMs. Here, we tackle these limitations by developing a computational pipeline to calibrate cell preparation-specific iPSC-CM electrophysiological parameters. We used the genetic algorithm (GA), a heuristic parameter calibration method, to tune ion channel parameters in a mathematical model of iPSC-CM physiology. To systematically optimize an experimental protocol that generates sufficient data for parameter calibration, we created simulated datasets by applying various protocols to a population of in silico cells with known conductance variations, and we fitted to those datasets. We found that calibrating models to voltage and calcium transient data under 3 varied experimental conditions, including electrical pacing combined with ion channel blockade and changing buffer ion concentrations, improved model parameter estimates and model predictions of unseen channel block responses. This observation held regardless of whether the fitted data were normalized, suggesting that normalized fluorescence recordings, which are more accessible and higher throughput than patch clamp recordings, could sufficiently inform conductance parameters. Therefore, this computational pipeline can be applied to different iPSC-CM preparations to determine cell line-specific ion channel properties and understand the mechanisms behind variability in perturbation responses.
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7.
Effects of chronic low-level lead (Pb) exposure on cognitive function and hippocampal neuronal ferroptosis: An integrative approach using bioinformatics analysis, machine learning, and experimental validation.
Cao, Y, Zhao, W, Zhong, Y, Jiang, X, Mei, H, Chang, Y, Wu, D, Dou, J, Vasquez, E, Shi, X, et al
The Science of the total environment. 2024;:170317
Abstract
Lead (Pb), a pervasive and ancient toxic heavy metal, continues to pose significant neurological health risks, particularly in regions such as Southeast Asia. While previous research has primarily focused on the adverse effects of acute, high-level lead exposure on neurological systems, studies on the impacts of chronic, low-level exposure are less extensive, especially regarding the precise mechanisms linking ferroptosis - a novel type of neuron cell death - with cognitive impairment. This study aims to explore the potential effects of chronic low-level lead exposure on cognitive function and hippocampal neuronal ferroptosis. This research represents the first comprehensive investigation into the impact of chronic low-level lead exposure on hippocampal neuronal ferroptosis, spanning clinical settings, bioinformatic analyses, and experimental validation. Our findings reveal significant alterations in the expression of genes associated with iron metabolism and Nrf2-dependent ferroptosis following lead exposure, as evidenced by comparing gene expression in the peripheral blood of lead-acid battery workers and workers without lead exposure. Furthermore, our in vitro and in vivo experimental results strongly suggest that lead exposure may precipitate cognitive dysfunction and induce hippocampal neuronal ferroptosis. In conclusion, our study indicates that chronic low-level lead exposure may activate microglia, leading to the promotion of ferroptosis in hippocampal neurons.
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8.
Xylo-oligosaccharides improve functional constipation by targeted enrichment of Bifidobacterium.
Yi, W, Wang, Q, Xue, Y, Cao, H, Zhuang, R, Li, D, Yan, J, Yang, J, Xia, Y, Zhang, F
Food science & nutrition. 2024;(2):1119-1132
Abstract
Functional constipation (FC) has a negative impact on patients' quality of life. We hypothesized that dietary supplementation with xylo-oligosaccharides (XOS) or fructo-oligosaccharides (FOS) would improve constipation symptoms by influencing the gut microbiota. A randomized double-blind controlled trial was conducted in FC patients. Patients were randomly divided into 6 groups and given a dietary supplement containing XOS at doses of 3, 5, or 10 g/day, FOS at doses of 10 and 20 g/day, or placebo at 5 g/day for one month. We compared improvements in gastrointestinal function after the intervention using the Bristol Stool Form Scale (BSFS), Cleveland Clinic Constipation Score (CCCS), and Quality of Life Scale for Patients with Constipation (PAC-QoL). 16S rRNA sequencing was used to assess changes in the structure of the gut microbiota. Changes in individual bacteria had significant effects in reducing gastrointestinal symptoms during the intervention, even though the flora structure remained unchanged from baseline. Compared to FOS, XOS enriched Bifidobacterium at a lower dose, and patients receiving XOS supplementation showed significant improvements in constipation symptoms without side effects such as diarrhea and flatulence.
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9.
Efficacy and safety of short-term edaravone or nerve growth factor add-on therapy for alcohol-related brain damage: A multi-centre randomised control trial.
Wang, H, Liu, L, Zhou, X, Guan, Y, Li, Y, Chen, P, Duan, R, Yang, W, Rong, X, Wu, C, et al
Addiction (Abingdon, England). 2024;(4):717-729
Abstract
AIMS: To measure the therapeutic effect of an anti-oxidant, edaravone (EDV), or neurotrophic treatment with nerve growth factor (NGF) as an add-on treatment for alcohol-related brain damage (ARBD). DESIGN Multi-centre, randomised, single-blinded, comparative clinical trial. SETTING AND PARTICIPANTS One hundred and twenty-two inpatients recruited from seven hospitals in different regions of China, all diagnosed with ARBD and aged 18 to 65 years old; among them, only two were female. INTERVENTION AND COMPARATOR Patients were randomly assigned to receive one of three treatments for 2 weeks: 40 patients, treatment as usual (TAU: a combination of intramuscular injections of thiamine, intravenous infusions of other B vitamins with vitamin C and oral medication with vitamin E per day); 40, EDV add-on treatment to TAU (intravenous infusion with 30 mg of EDV twice per day); and 42, NGF add-on treatment to TAU (intramuscular injection of 20 μg of NGF per day). The patients underwent follow-up for 24 weeks. MEASUREMENTS The primary outcome was the composite score of executive cognitive function in the 2nd week after treatment, which was measured as the mean of the Z scores of the assessments, including the digit symbol substitute test (DSST), digit span memory test-forward (DST-F), digit span memory test-reverse (DST-R) and space span memory test (SSMT). The secondary outcomes were the composite scores at later follow-ups, the score for each component of cognitive function, global cognitive function measured by the Montreal Cognitive Assessment (MoCA), craving for alcohol and the safety of the therapies. FINDINGS EDV add-on treatment improved the composite score of executive cognitive function better than TAU in the 2nd week (adjusted mean difference: 0.24, 95% confidence interval 0.06 to 0.41; P = 0.008), but NGF add-on treatment did not (adjusted mean difference: 0.07, 95% confidence interval -0.09 to 0.24; P = 0.502). During the follow-up to 24 weeks, EDV add-on treatment improved the composite score of executive cognitive function and DST-R score better than TAU (both P < 0.01). Craving for alcohol was relieved in all three groups. No severe adverse events were observed. CONCLUSION The short-term addition of edaravone to supplementary therapy treatment for alcohol-related brain damage (ARBD) improved executive cognitive function in patients with ARBD.
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10.
Recent Progress on Copper-Based Bimetallic Heterojunction Catalysts for CO2 Electrocatalysis: Unlocking the Mystery of Product Selectivity.
Huang, J, Zhang, X, Yang, J, Yu, J, Chen, Q, Peng, L
Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2024;:e2309865
Abstract
Copper-based bimetallic heterojunction catalysts facilitate the deep electrochemical reduction of CO2 (eCO2RR) to produce high-value-added organic compounds, which hold significant promise. Understanding the influence of copper interactions with other metals on the adsorption strength of various intermediates is crucial as it directly impacts the reaction selectivity. In this review, an overview of the formation mechanism of various catalytic products in eCO2RR is provided and highlight the uniqueness of copper-based catalysts. By considering the different metals' adsorption tendencies toward various reaction intermediates, metals are classified, including copper, into four categories. The significance and advantages of constructing bimetallic heterojunction catalysts are then discussed and delve into the research findings and current development status of different types of copper-based bimetallic heterojunction catalysts. Finally, insights are offered into the design strategies for future high-performance electrocatalysts, aiming to contribute to the development of eCO2RR to multi-carbon fuels with high selectivity.