Effects of galactooligosaccharides on maternal gut microbiota, glucose metabolism, lipid metabolism and inflammation in pregnancy: A randomized controlled pilot study

BackgroundGut microbiota of pregnant women change with the gestational week. On the one hand, they participate in the metabolic adaptation of pregnant women. On the other hand, the abnormal composition of gut microbiota of pregnant women is more likely to suffer from gestational diabetes mellitus (GDM). Therefore, gut microbiota targeted treatment through dietary supplements is particularly important for prevention or treatment. Prebiotic supplements containing galactooligosaccharides (GOS) may be an intervention method, but the effect is still unclear.ObjectiveThis study aims to evaluate the feasibility and acceptability of prebiotic intervention in healthy pregnant women during pregnancy, and to explore the possible effects of intervention on pregnant women and the influence on gut microbiota as preliminaries.MethodsAfter recruitment in first trimester, 52 pregnant women were randomly assigned to receive GOS intervention or placebo containing fructooligosaccharides. 16S rRNA sequencing technology was used to detect the composition, diversity and differential flora of gut microbiota. Lipid metabolism, glucose metabolism and inflammatory factors during pregnancy were also analyzed.ResultsThe adverse symptoms of GOS intervention are mild and relatively safe. For pregnant women, there was no significant difference in the GDM incidence rates and gestational weight gain (GWG) in the GOS group compared with placebo (P > 0.05). Compared with the placebo group, the levels of FPG, TG, TC, HDL-C LDL-C, and IL-6 had no significant difference in GOS group (P > 0.05). For newborns, there was no significant difference between GOS group and placebo group in the following variables including gestational week, birth weight, birth length, head circumference, chest circumference, sex, and delivery mode (P > 0.05). And compared with the placebo group, the GOS group had a higher abundance of Paraprevotella and Dorea, but lower abundance of LachnospiraceaeUCG_001.ConclusionsGOS prebiotics appear to be safe and acceptable for the enrolled pregnancies. Although GOS intervention did not show the robust benefits on glucose and lipid metabolism. However, the intervention had a certain impact on the compostion of gut microbiota. GOS can be considered as a dietary supplement during pregnancy, and further clinical studies are needed to explore this in the future

Nuclear Factor Erythroid 2-Related Factor 2 Deficiency Results in Amplification of the Liver Fat-Lowering Effect of Estrogen

Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates multiple biologic processes, including hepatic lipid metabolism. Estrogen exerts actions affecting energy homeostasis, including a liver fat-lowering effect. Increasing evidence indicates the crosstalk between these two molecules. The aim of this study was to evaluate whether Nrf2 modulates estrogen signaling in hepatic lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) was induced in wild-type and Nrf2-null mice fed a high-fat diet and the liver fat-lowering effect of exogenous estrogen was subsequently assessed. We found that exogenous estrogen eliminated 49% and 90% of hepatic triglycerides in wild-type and Nrf2-null mice with NAFLD, respectively. This observation demonstrates that Nrf2 signaling is antagonistic to estrogen signaling in hepatic fat metabolism; thus, Nrf2 absence results in striking amplification of the liver fat-lowering effect of estrogen. In addition, we found the association of trefoil factor 3 and fatty acid binding protein 5 with the liver fat-lowering effect of estrogen. In summary, we identified Nrf2 as a novel and potent inhibitor of estrogen signaling in hepatic lipid metabolism. Our finding may provide a potential strategy to treat NAFLD by dually targeting Nrf2 and estrogen signaling

Topic evolution and sentiment comparison of user reviews on an online medical platform in response to COVID-19: taking review data of Haodf.com as an example

IntroductionThroughout the COVID-19 pandemic, many patients have sought medical advice on online medical platforms. Review data have become an essential reference point for supporting users in selecting doctors. As the research object, this study considered Haodf.com, a well-known e-consultation website in China.MethodsThis study examines the topics and sentimental change rules of user review texts from a temporal perspective. We also compared the topics and sentimental change characteristics of user review texts before and after the COVID-19 pandemic. First, 323,519 review data points about 2,122 doctors on Haodf.com were crawled using Python from 2017 to 2022. Subsequently, we employed the latent Dirichlet allocation method to cluster topics and the ROST content mining software to analyze user sentiments. Second, according to the results of the perplexity calculation, we divided text data into five topics: diagnosis and treatment attitude, medical skills and ethics, treatment effect, treatment scheme, and treatment process. Finally, we identified the most important topics and their trends over time.ResultsUsers primarily focused on diagnosis and treatment attitude, with medical skills and ethics being the second-most important topic among users. As time progressed, the attention paid by users to diagnosis and treatment attitude increased—especially during the COVID-19 outbreak in 2020, when attention to diagnosis and treatment attitude increased significantly. User attention to the topic of medical skills and ethics began to decline during the COVID-19 outbreak, while attention to treatment effect and scheme generally showed a downward trend from 2017 to 2022. User attention to the treatment process exhibited a declining tendency before the COVID-19 outbreak, but increased after. Regarding sentiment analysis, most users exhibited a high degree of satisfaction for online medical services. However, positive user sentiments showed a downward trend over time, especially after the COVID-19 outbreak.DiscussionThis study has reference value for assisting user choice regarding medical treatment, decision-making by doctors, and online medical platform design

Genetic Loci Associated With Fluoride Resistance in Streptococcus mutans

The prolonged exposure of the cariogenic bacterial species Streptococcus mutans to high concentrations of fluoride leads to the development of fluoride resistance in this species. Previous studies confirmed the involvement of a mutation in a single chromosomal region in the occurrence of fluoride resistance. The involvement of multiple genomic mutations has not been verified. The aim of this study is to identify multiple genetic loci associated with fluoride resistance in S. mutans. The previously published whole genome sequences of two fluoride-resistant S. mutans strains (UA159-FR and C180-2FR) and their corresponding wild-type strains (UA159 and C180-2) were analyzed to locate shared chromosomal mutations in fluoride-resistant strains. Both fluoride-resistant strains were isolated in laboratory by culturing their mother strains in media with high concentrations of fluoride. The corresponding gene expression and enzyme activities were accordingly validated. Mutations were identified in two glycolytic enzymes, namely pyruvate kinase and enolase. Pyruvate kinase was deactivated in fluoride-resistant strain C180-2FR. Enolase was less inhibited by fluoride in fluoride-resistant strain UA159-FR than in its wild-type strain. Mutations in the promoter mutp constitutively increased the promoter activity and up-regulated the expression of the downstream fluoride antiporters in fluoride-resistant strains. Mutations in the intergenic region glpFp led to lower expression of glpF, encoding a glycerol uptake facilitator protein, in fluoride-resistant strains than in wild-type strains. Our results revealed that there is overlap of chromosomal regions with mutations among different fluoride-resistant S. mutans strains. They provide novel candidates for the study of the mechanisms of fluoride resistance

The Perturbation of Infant Gut Microbiota Caused by Cesarean Delivery Is Partially Restored by Exclusive Breastfeeding

Early establishment of the infant gut microbiome has been attributed to various environmental factors that may influence long-term health. The aim of this study was to determine the single and combined impacts of the delivery mode, feeding pattern and postnatal antibiotic exposure on the initial establishment of infant gut microbiome at 6 weeks postpartum. A cross-sectional study was conducted at a single center in China. Fecal samples were collected from 120 infants at 6 weeks postpartum. The V3-V4 regions of 16S rRNA gene were analyzed by Illumina sequencing, and clinical information was obtained from medical records and questionnaire survey. Compared with vaginally delivered infants, the gut microbial community structure of cesarean delivered infants were significantly different (P = 0.044), in parallel with the decreased relative abundance of Bifidobacterium (P = 0.028), which contrasts with the normal gut microbial establishment. Using the vaginally delivered and exclusively breastfed (VB) infants as a reference, the comparative analysis of cesarean delivered and exclusively breastfed (CB) infants with cesarean delivered and mixed-fed (CM) infants showed that both within- and between-group UniFrac distance were significantly smaller in CB infants (P < 0.001, P < 0.001). LEfSe analysis showed that the relative abundances of Enterococcus, Veillonella, and Faecalibacterium were significantly different between CB and CM infants, whereas the relative abundances of those genera in VB infants were close to those of CB infants, and distinct from those of CM infants. Additionally, no significant difference of microbial composition, alpha diversity, or community structure was observed between postnatal antibiotics exposed infants and unexposed infants. In summary, delivery mode had a significant impact on the infant gut microbial community structure and composition, and the gut microbiota was disturbed in infants delivered by cesarean section. However, our study showed that this disturbance of gut microbiota in cesarean delivered infants was partially restored by exclusive breastfeeding in comparison with mixed feeding. No distinct impact of postnatal antibiotic exposure on infant gut microbiome was found at 6 weeks of age

Assessment of Cardiovascular Health of Children Ages 6 to 10 Years Conceived by Assisted Reproductive Technology

Importance: Assisted reproductive technology (ART) has been widely used for treatment of infertility and has brought millions of births worldwide. The health of offspring conceived by ART has been of much concern, and adverse cardiovascular health outcomes have been reported by previous studies.Objective: To assess the cardiovascular health of children conceived by ART.Design, setting, and participants: This cohort study was conducted among participants recruited from November 2017 to February 2019. Participants were 382 children conceived by ART who were selected from a single reproductive center and 382 children who were naturally conceived, randomly selected from a primary school, and matched by sex, age, and maternal age at the child's birth (2 years older or younger). Data were analyzed from March 2019 through December 2019.Exposures: Conception by ART.Main outcomes and measures: Blood pressure was measured, and echocardiography was performed to determine left ventricular structural and functional parameters. Adjusted relative wall thickness (aRWT) was found for age, with high RWT defined as an aRWT of 0.375 or more.Results: Among 764 children aged 6 to 10 years, 382 children were conceived by ART (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys) and 382 children were naturally conceived (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys). Children conceived by ART had statistically significantly increased mean (SD) height (130.2 [9.5] cm vs 128.5 [8.1] cm; P = .007) and body mass index (17.6 [3.6] vs 17.1 [2.7]; P = .03). Those conceived by ART, compared with children in the matched control group, had statistically significantly increased blood pressure (mean [SD] systolic blood pressure, 105.5 [6.9] mm Hg vs 103.5 [8.4] mm Hg; adjusted P P P P 2.7 vs 28.28 [3.54] g/m2.7; adjusted P P P = .03), high RWT (61 children [16.0%] vs 0 children; P P for left ventricle remodeling Conclusions and relevance: This study found that children conceived by ART had increased blood pressure and unfavorable changes in left ventricular structure and function compared with children who were naturally conceived. These findings suggest that further studies are needed to investigate the potential mechanisms and long-term outcomes associated with these differences.</p

Three Generic Nevirapine-Based Antiretroviral Treatments in Chinese HIV/AIDS Patients: Multicentric Observation Cohort

The purpose of this study was to evaluate the efficacy and safety of three nevirapine-based antiretroviral treatments for adult antiretroviral-naïve Chinese patients with HIV-1 infection.This was a prospective, multicenter study. 198 antiretroviral-naïve HIV-1 positive subjects with CD4 lymphocyte counts between 100/ul and 350/ul and plasma HIV-1 RNA levels more than 500 copies/ml were randomized to start three NVP-based antiretroviral treatments: group A, NVP+AZT+ddI; group B, NVP+3TC+d4T; group C, NVP+AZT+3TC. Viral responses, immunologic responses, adverse events and drug resistance were monitored at baseline and the end of week 4, 12, 24, 36, 52. Viralogical response and immunological response were also compared in different strata of baseline CD4 T lymphocyte counts and plasma HIV-1 RNA concentrations. At baseline, the plasma HIV-1 RNA was 4.44+/-0.68, 4.52+/-0.71 and 4.41+/-0.63 lg copies/ml in group A, B and C respectively (p = 0.628). At the end of the study, the plasma viral load reached 2.54+/-1.11, 1.89+/-0.46 and 1.92+/-0.58 lg copies/ml in group A, B and C respectively (p<0.001). At week 52, suppression of plasma HIV-1 RNA to less than 50 copies/ml was achieved in more patients in group B and C than in group A (68.2%, 69% vs. 39.7%; p<0.001). In planned subgroup analyses, the decrease of viral response rate was seen in group A when CD4 cell count >200/ul (subgroup H). But in subgroup L, viral response rate of three groups has no significant statistic difference. There were no statistically significant differences among three groups in immunological response within any of the CD4 or pVL strata. 3 out of 193 patients with available genotype at baseline showed primary drug resistant. Of 26 patients with virologic failure, 17 patients showed secondary drug resistant, 16 subjects in group A and 1 subject in group B. Logistic regression analysis indicated that presence of hepatotoxicity was associated with HCV-Ab positive (OR = 2.096, 95%CI: 1.106-3.973, P = 0.023) and higher CD4 baseline (CD4 count >250/ul) (OR = 2.096, 95%CI: 1.07-4.107, P = 0.031).Our findings strongly support the use of 3TC+d4T and 3TC+AZT as the nucleoside analogue combination in NVP-based antiretroviral therapy. The regimen of AZT+ddI+NVP produced poor virological response especially in the stratum of CD4 count more than 200/ul. More patients showed secondary drug resistant in this arm too. Patients with HCV-Ab+ and CD4 count >250/ul appear to have significantly high risk of hepatoxicity.ClinicalTrials.gov NCT00618176

CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation.

Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.Bloodwise, CRUK, MRC, Wellcome Trust, NIH, Leukemia and Lymphoma Societ