The Effect of Microbiome-Modulating Agents (MMAs) on Type 1 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Gut microbiome-modulating agents (MMAs), including probiotics, prebiotics, postbiotics, and synbiotics, are shown to ameliorate type 1 diabetes (T1D) by restoring the microbiome from dysbiosis. The objective of this systematic review and meta-analysis was to assess the impact of MMAs on hemoglobin A1c (HbA1c) and biomarkers associated with (T1D). A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, National Knowledge Infrastructure, WeiPu, and WanFang Data up to 30 November 2023. Ten randomized controlled trials (n = 630) were included, with study quality evaluated using the Cochrane risk-of-bias tool. Random-effect models with standardized mean differences (SMDs) were utilized. MMA supplementation was associated with improvements in HbA1c (SMD = -0.52, 95% CI [-0.83, -0.20]), daily insulin usage (SMD = -0.41, 95% confidence interval (CI) [-0.76, -0.07]), and fasting C-peptide (SMD = 0.99, 95% CI [0.17, 1.81]) but had no effects on FBG, CRP, TNF-α, IL-10, LDL, HDL, and the Shannon index. Subgroup analysis of HbA1c indicated that a long-term intervention (>3 months) might exert a more substantial effect. These findings suggest an association between MMAs and glycemic control in T1D. Further large-scale clinical trials are necessary to confirm these findings with investigations on inflammation and gut microbiota composition while adjusting confounding factors such as diet, physical activity, and the dose and form of MMA intervention.

Sesquiterpene lactones from Carpesium abrotanoides L. and their activity in inducing protective autophagy.

Fourteen sesquiterpene lactones were isolated from the whole plant of Carpesium abrotanoides L. Their structures were determined on the basis of comprehensive spectroscopic data analysis. All compounds were screened for their cytotoxic activity, and compound 6 showed the strongest activity (IC50 2.73 - 7.21 µM) against five human cancer cell lines, including A549, HepG2, HCT116, MDA-MB-231, and CNE2. Compound 6 was further investigated. Compound 6 effectively induced G2/M cell cycle arrest and ROS accumulation in a dose-dependent manner, which further led to apoptosis in cancer cells. Interestingly, compounds 1 and 6 could also activate protective autophagy, which was reported for the first time in sesquiterpene isolated from Carpesium abrotanoides. In addition, compounds 1 and 6 could induce lysosomal biogenesis by 173.2% and 163.7%, respectively. In sum, sesquiterpene lactones from Carpesium abrotanoides could induce apoptosis and protective autophagy in cancer cells, which provide a serial of compounds with potential clinical applications.

Linking annual N2O emission in organic soils to mineral nitrogen input as estimated by heterotrophic respiration and soil C/N ratio.

Organic soils are an important source of N2O, but global estimates of these fluxes remain uncertain because measurements are sparse. We tested the hypothesis that N2O fluxes can be predicted from estimates of mineral nitrogen input, calculated from readily-available measurements of CO2 flux and soil C/N ratio. From studies of organic soils throughout the world, we compiled a data set of annual CO2 and N2O fluxes which were measured concurrently. The input of soil mineral nitrogen in these studies was estimated from applied fertilizer nitrogen and organic nitrogen mineralization. The latter was calculated by dividing the rate of soil heterotrophic respiration by soil C/N ratio. This index of mineral nitrogen input explained up to 69% of the overall variability of N2O fluxes, whereas CO2 flux or soil C/N ratio alone explained only 49% and 36% of the variability, respectively. Including water table level in the model, along with mineral nitrogen input, further improved the model with the explanatory proportion of variability in N2O flux increasing to 75%. Unlike grassland or cropland soils, forest soils were evidently nitrogen-limited, so water table level had no significant effect on N2O flux. Our proposed approach, which uses the product of soil-derived CO2 flux and the inverse of soil C/N ratio as a proxy for nitrogen mineralization, shows promise for estimating regional or global N2O fluxes from organic soils, although some further enhancements may be warranted.