ABSTRACT
Ischemic stroke has been demonstrated to cause an imbalance of gut microbiota. However, the change in gut microbiota-mediated bile acids (BAs) metabolites remains unclear. Here, we observed a decrease in gut microbiota-mediated BAs, especially ursodeoxycholic acid (UDCA), in the serum of stroke patients as well as in the intestine, serum and brain of stroke mice. Restoration of UDCA could decrease the area of infarction and improve the neurological function and cognitive function in mice in association with inhibition of NLRP3-related pro-inflammatory cytokines through TGR5/PKA pathway. Furthermore, knocking out TGR5 and inhibiting PKA activity reduce the protective effect of UDCA. Taken together, our results suggest that microbiota-mediated UDCA plays an important role in alleviating inflammatory responses and might be a promising therapeutic target in ischemic stroke.
Subject(s)
Gastrointestinal Microbiome , Ischemic Stroke , Stroke , Animals , Humans , Mice , Bile Acids and Salts , Inflammation , Microglia/metabolism , Ursodeoxycholic Acid/metabolismABSTRACT
Obesity is a risk factor for the development of hyperuricemia, both of which were related to gut microbiota. However, whether alterations in the gut microbiota lie in the pathways mediating obesity's effects on hyperuricemia is less clear. Body mass index (BMI) and serum uric acid (SUA) were separately important indicators of obesity and hyperuricemia. Our study aims to investigate whether BMI-related gut microbiota characteristics would mediate the association between BMI and SUA levels. A total of 6,280 participants from Guangdong Gut Microbiome Project were included in this study. Stool samples were collected for 16S rRNA gene sequencing. The results revealed that BMI was significantly and positively associated with SUA. Meanwhile, BMI was significantly associated with the abundance of 102 gut microbial genera, 16 of which were also significantly associated with SUA. The mediation analysis revealed that the association between BMI and SUA was partially mediated by the abundance of Proteobacteria (proportion mediated: 0.94%, P < 0.05). At the genus level, 25 bacterial genera, including Ralstonia, Oscillospira, Faecalibacterium, etc., could also partially mediate the association of BMI with SUA (the highest proportion is mediated by Ralstonia, proportion mediated: 2.76%, P < 0.05). This study provided evidence for the associations among BMI, gut microbiota, and SUA, and the mediation analysis suggested that the association of BMI with SUA was partially mediated by the gut microbiota. IMPORTANCE Using 16S rRNA sequencing analysis, local interpretable machine learning technique analysis and mediation analysis were used to explore the association between BMI with SUA, and the mediating effects of gut microbial dysbiosis in the association were investigated.
ABSTRACT
Parabacteroides levels are reported to be low in obese individuals, and this genus has shown an anti-obesity capacity in animal studies. Nevertheless, the relationship between Parabacteroides and obesity in different subpopulations, e.g., with respect to age and sex, and its association with subsequent weight change have rarely been explored. The cross-sectional associations of Parabacteroides genus- and species-level OTU abundance with obesity were explored in the Guangdong Gut Microbiome Project (GGMP), which included 5843 adults, and replicated in the Guangzhou Nutrition and Health Study (GNSH), which included 1637 individuals. Furthermore, we assessed the prospective associations of Parabacteroides and its main OTUs' abundance with the subsequent changes in body mass index (BMI) in the GNSH. We found that Parabacteroides was inversely associated with obesity among females and participants aged 40-69 years in the GGMP and the replicated cohort in the GNSH. After a 3-year follow-up, there was no significant correlation between Parabacteroides and the subsequent changes in BMI. However, Seq4172 (P. johnsonii) showed a negative correlation with subsequent BMI changes in the female and middle-aged (40-69 years) subpopulations. Overall, our results indicate that Parabacteroides have an inverse relationship with obesity and that Seq4172 (P. johnsonii) have a negative association with subsequent changes in BMI among females and middle-aged populations in perspective analyses.
ABSTRACT
Background: To identify the 100 most-cited papers that have contributed to the understanding and treatment of nasopharyngeal carcinoma (NPC). Methods: We searched the NPC-related papers between 2000 and 2019 using the Web of Science database on October 12, 2022. Papers were identified in descending order according to the number of citations. The top 100 papers were analyzed. Results: These 100 most cited papers on NPC have been cited for a total of 35,273 times, with a median number of citations of 281 times. There were 84 research papers and 16 review papers. The Journal of Clinical Oncology (n=17), International Journal of Radiation Oncology Biology Physics (n=13), and Cancer Research (n=9) published the most papers. Cancer Epidemiology Biomarkers & Prevention, Lancet, Cancer Cell, Molecular Cancer, and the New England Journal of Medicine had the largest average citations per paper. China contributed the most papers (n=71), followed by USA (n=13), Singapore (n=4) and, France (n=4). There were 55 clinical research papers and 29 laboratory research papers. Intensity-modulated radiation therapy technology (n=13), concurrent chemoradiotherapy (n=9), and neoadjuvant chemoradiotherapy (n=5) were the top three research topics. Epstein-Barr virus-related genes (n=9) and noncoding RNA (n=8) were the research domains in laboratory research papers. The top three contributors were Jun Ma (n=9), Anthony T C Chan (n=8), and Anne Wing-Mui Lee (n=6). Conclusions: This study provides an overview of the major areas of interest in the field of NPC with bibliometric analyses. This analysis recognizes some important contributions in the field of NPC and stimulates future investigations in the scientific community.
