Resistant Dextrin Protects Rats Against Streptozotocin Induced Gestational Diabetes Mellitus via Alteration of TLR4/MyD88/NF-κB Signaling Pathway.

Objective: Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs in 3-5% of pregnancies. The inflammatory response is essential to the development of GDM. Resistant dextrin is a natural fiber and exhibits an antidiabetic effect against diabetes. We investigate resistant dextrin's preventive role and underlying mechanism against STZ-induced GDM. Material and method: Female Wistar rats were utilized, and GDM was induced in pregnant rats using STZ. The levels of glycated hemoglobin (HbA1c), resistin, serum-c-peptide, free fatty acid, antioxidant, hepatic glycogen, lipid, inflammatory cytokines, apoptosis, and inflammatory parameters were estimated. mRNA expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) was estimated. We also estimated the histopathology of pancreatic and liver tissue. Result: Body weight, plasma insulin, fetal body weight, and blood glucose levels were all considerably (P < .001) improved by resistant dextrin, while placental weight and blood sugar levels were also decreased. Resistant dextrin significantly (P < .001) suppressed the levels of HbA1c, resistin, serum-c-peptide, and hepatic glycogen and improved the free fatty acid (FFA) level. Resistant dextrin significantly (P < .001) altered the level of adiponectin, leptin, intercellular Adhesion Molecule 1 (ICAM-1), and visfatin; antioxidant parameters such as malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase GST, inflammatory cytokines like tumor necrosis factor- α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-2 (IL-2), interferon- γ (INF-γ), interleukin-10 (IL-10); apoptosis parameters include Bcl-2, caspase-3, and Bax, respectively. Resistant dextrin significantly (P < .001) suppressed the mRNA expression of NF-κB, MyD88, NLRP3, and TLR4. Resistant dextrin altered the histopathological changes in the pancreas and hepatic tissue. Discussion and Conclusion: In short, resistant dextrin demonstrated a protective effect against STZ-induced GDM by modulating the TLR4/MyD88/NF-κB signaling pathway.

Viral community distribution, assembly mechanism, and associated hosts in an industrial park wastewater treatment plant.

Viruses manipulate bacterial community composition and impact wastewater treatment efficiency. Some viruses pose threats to the environment and human populations through infection. Improving the efficiency of wastewater treatment and ensuring the health of the effluent and receptor pools requires an understanding of how viral communities assemble and interact with hosts in wastewater treatment plants (WWTPs). We used metagenomic analysis to study the distribution, assembly mechanism, and sensitive hosts for the viral communities in raw water, anaerobic tanks, and returned activated sludge units of a large-scale industrial park WWTP. Uroviricota (53.42% ± 0.14%) and Nucleocytoviricota (26.1% ± 0.19%) were dominant in all units. Viral community composition significantly differed between units, as measured by ß diversity (P = 0.005). Compared to raw water, the relative viral abundance decreased by 29.8% in the anaerobic tank but increased by 9.9% in the activated sludge. Viral community assembly in raw water and anaerobic tanks was predominantly driven by deterministic processes (MST <0.5) versus stochastic processes (MST >0.5) in the activated sludge, indicating that differences in diffusion limits may fundamentally alter the assembly mechanisms of viral communities between the solid and liquid-phase environments. Acidobacteria was identified as the sensitive host contributing to viral abundance, exhibiting strong interactions and a mutual dependence (degree = 59). These results demonstrate the occurrence and prevalence of viruses in WWTPs, their different assembly mechanism, and sensitive hosts. These observations require further study of the mechanisms of viral community succession, ecological function, and roles in the successive wastewater treatment units.

Protective effect of soy isolate protein against streptozotocin induced gestational diabetes mellitus via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Gestational diabetes mellitus (GDM) is a serious complication of pregnancy that is characterized by high blood sugar levels that occur due to insulin resistance and dysfunction in glucose metabolism during pregnancy. It usually develops in the second or third trimester of pregnancy and affects about 7 % of all pregnancies worldwide. In this experimental study, we scrutinized the GDM protective effect of soy isolate protein against streptozotocin (STZ) induced GDM in rats and explore the underlying mechanism. MATERIAL AND METHODS: Sprague-Dawley (SD) rats were used in this experimental study. A 55 mg/kg intraperitoneal injection of streptozotocin (STZ) was administered to induce diabetes in female rats, followed by oral administration of soy isolate protein for 18 days. Body weight, glucose levels, and insulin were measured at different time intervals (0, 9, and 18 days). Lipid profiles, antioxidant levels, inflammatory cytokines, apoptosis parameters, and mRNA expression were also assessed. Pancreatic and liver tissues were collected for histopathological examination during the experimental study. RESULTS: Soy isolate protein significantly (P < 0.001) reduced the glucose level and enhanced the insulin level and body weight. Soy isolate protein remarkably decreased the placental weight and increased the fetal weight. Soy isolate protein significantly (P < 0.001) decreased the HbA1c, hepatic glycogen, serum C-peptide and increased the level of free fatty acid. Soy isolate protein significantly (P < 0.001) altered the level of lipid, antioxidant and inflammatory cytokines. Soy isolate protein significantly (P < 0.001) improved the level of adiponectin, visfatin and suppressed the level of leptin and ICAM-1. Soy isolate protein significantly (P < 0.001) altered the mRNA expression and also restored the alteration of histopathology. CONCLUSION: Based on the result, soy isolate protein exhibited the GDM protective effect against the STZ induced GDM in rats via alteration of TLR4/MyD88/NF-κB signaling pathway.

Antibiotics inhibit methanogenesis during municipal solid waste decomposition.

Municipal solid waste (MSW) landfills are significant sources of antibiotics. However, the effects of antibiotics on MSW decomposition process and methanogenesis during solid waste decomposition remain insufficiently characterized. This study investigated the effects of environmentally relevant concentrations (ERCs) of antibiotics (200 µg/kg for each antibiotic) on MSW decomposition and methanogenesis in bioreactors treated with and without eight antibiotics (three tetracyclines, three sulfonamides, and two macrolides). The key phases of MSW decomposition, namely the aerobic, anaerobic acid, and methanogenic phases, were determined by analyzing the key physiochemical parameters of the leachate, including pH, chemical oxygen demand, and biochemical oxygen demand. We assessed the bacterial and archaeal compositions, along with the abundance of the gene encoding the alpha subunit of methyl-coenzyme M reductase (mcrA), during MSW decomposition using high throughput 16S ribosomal RNA (rRNA) gene sequencing and quantitative polymerase chain reactions, respectively. Our results revealed that antibiotics significantly altered the compositions of bacteria and methanogens, leading to decreased mcrA abundance and methanogenesis. Specifically, antibiotics inhibited cellulose-degrading bacteria (Firmicutes) and archaea (E2) in the anaerobic acid phase and hydrolytic bacteria (Proteobacteria) in the methanogenic phase, resulting in lower degradation of biodegradable matter than that of the biodegradation without antibiotics treatment. However, the typical MSW decomposition process indicated by the key decomposition phases was successfully separated in both bioreactors, suggesting that antibiotics did not affect overall MSW decomposition process development or the associated individual decomposition phases establishment. These findings suggest that antibiotics at ERCs may inhibit methanogenesis during MSW decomposition, thereby providing fundamental information for methane management and climate change studies.

A Phase III Clinical Trial Evaluating the Efficacy of Yinghua Tablet in the Treatment of Sequelae of Pelvic Inflammatory Disease.

Objective: To evaluate the efficacy and safety of the Yinghua tablet in treating sequelae of pelvic inflammatory diseases (PID) that manifest as the syndrome of dampness-heat stasis. Methods: The experimental group enrolled 360 cases, while the control group enrolled 120 cases. The experimental group took Yinghua tablets three times a day, three tablets each time, and the control group took Fuyankang tablets three times a day, three tablets each time. The treatment course was six weeks. Before treatment, at three weeks and six weeks of treatment, the patients were scored for TCM syndrome, clinical symptoms and, signs, and adverse events during treatment were recorded. Results: The experimental group included 340 cases, and the control group finally included 114 cases. After six weeks of treatment, statistically significant differences were observed between the two groups in the treatment effect, recovery rate, markedly effective rate, and total effective rate (P < .05). The two groups had no significant difference in the effective rate of local signs (P > .05). However, the two groups had a significant difference in the total effective rate (P < .05). Before and after treatment, traditional Chinese medicine (TCM) symptoms score, symptom sign score, and local sign score were statistically significant (P < .05). The incidence of adverse events (AEs) after taking Yinghua Tablets was 3.61% (13 times), of which the incidence of adverse events related to study drugs was 0.28% (1 case). The AEs of Fuyankang Tablets were 1.67% (2 times), of which the incidence of adverse events related to study drugs was 1.67% (2 cases). There was no significant difference in the incidence of AEs between the two groups as compared to Fisher (P = .3767), indicating that no serious AEs occurred in either group. Conclusions: Yinghua tablet was effective and safe in treating sequelae of pelvic inflammatory diseases.

New insights on municipal solid waste (MSW) landfill plastisphere structure and function.

Plastisphere plays crucial role in global carbon and nitrogen cycles and microplastics formation. Global Municipal Solid Waste (MSW) landfills contain 42 % plastic waste, therefore representing one of the most significant plastispheres. MSW landfills are also the third largest anthropogenic methane sources and the important anthropogenic N2O source. Surprisingly, knowledge of microbiota and the associated microbial carbon and nitrogen cycles of landfill plastispheres is very limited. In this study, we characterized and compared the organic chemicals profile, bacterial community structure and metabolic pathway on plastisphere and the surrounding refuse in a large-scale landfill using GC/MS and 16S rRNA genes high-throughput sequencing, respectively. Landfill plastisphere and the surrounding refuse differed in organic chemicals composition. However, abundant phthalate-like chemicals were determined in both environments, implying the plastics additives leaching. Bacterial colonizing on the plastics surface had significantly higher richness than that in the surrounding refuse. Plastic surface and the surrounding refuse had distinct bacterial community composition. Genera of Sporosarcina, Oceanobacillus and Pelagibacterium were detected on the plastic surface with high abundance, while Ignatzschineria, Paenalcaligenes and Oblitimonas were rich in the surrounding refuse. Typical plastics biodegradation genus Bacillus, Pseudomonas and Paenibacillus were detected in both environments. However, Pseudomonas was dominant in plastic surface (up to 88.73 %), whereas Bacillus was rich in the surrounding refuse (up to 45.19 %). For the carbon and nitrogen cycle, plastisphere was predicted to had significant (P < 0.05) higher functional genes involved in carbon metabolism and nitrification, indicating more activated carbon and nitrogen microbial activity on the plastics surface. Additionally, pH was the main driver in shaping the bacterial community composition on plastic surface. These results indicate that landfill plastispheres serve as unique niches for microbial community habitation and function on microbial carbon and nitrogen cycles. These observations invite further study of the landfill plastispheres ecological effect.

Occurrence and prevalence of antibiotic resistance genes and pathogens in an industrial park wastewater treatment plant.

Antibiotic resistance genes (ARGs) and pathogens are emerging environmental pollutants that pose a threat to human health and ecosystem. Industrial park wastewater treatment plants (WWTPs) treat large amounts of comprehensive wastewater derived from industrial production and park human activity, which is possible a source of ARGs and pathogens. Therefore, this study investigated the occurrence and prevalence of ARGs, ARGs hosts and pathogens and assesses the ARGs health risk in the biological treatment process in a large-sale industrial park WWTP using metagenomic analysis and omics-based framework, respectively. Results show that the major ARG subtypes are multidrug resistance genes (MDRGs), macB, tetA(58), evgS, novA, msbA and bcrA and the ARGs main hosts were genus Acidovorax, Pseudomonas, Mesorhizobium. In particular, all determined ARGs genus level hosts are pathogens. The total removal percentage of ARGs, MDRGs and pathogens were 12.77 %, 12.96 % and 25.71 % respectively, suggesting that the present treatment could not efficiently remove these pollutants. The relative abundance of ARGs, MDRGs and pathogens varied along biological treatment process that ARGs and MDRGs were enriched in activated sludge and pathogens were enriched in both secondary sedimentation tank and activated sludge. Among 980 known ARGs, 23 ARGs (e.g., ermB, gadX and tetM) were assigned into risk Rank I with characters of enrichment in the human-associated environment, gene mobility and pathogenicity. The results indicate that industrial park WWTPs might serve as an important source of ARGs, MDRGs, and pathogens. These observations invite further study of the origination, development, dissemination and risk assessment of industrial park WWTPs ARGs and pathogens.

Anaerobic Digestion of Food Waste and Its Microbial Consortia: A Historical Review and Future Perspectives.

Renewable energy source, such as food waste (FW), has drawn great attention globally due to the energy crisis and the environmental problem. Anaerobic digestion (AD) mediated by novel microbial consortia is widely used to convert FW to clean energy. Despite of the considerable progress on food waste and FWAD optimization condition in recent years, a comprehensive and predictive understanding of FWAD microbial consortia is absent and therefore represents a major research challenge in FWAD. The review begins with a global view on the FWAD status and is followed by an overview of the role of AD key conditions' association with microbial community variation during the three main energy substances (hydrogen, organic acids, and methane) production by FWAD. The following topic is the historical understanding of the FWAD microorganism through the development of molecular biotechnology, from classic strain isolation to low-throughput sequencing technologies, to high-throughput sequencing technologies, and to the combination of high-throughput sequencing and isotope tracing. Finally, the integration of multi-omics for better understanding of the microbial community activity and the synthetic biology for the manipulation of the functioning microbial consortia during the FWAD process are proposed. Understanding microbial consortia in FWAD helps us to better manage the global renewable energy source.

Association of aspirin therapy with risk of hepatocellular carcinoma: A systematic review and dose-response analysis of cohort studies with 2.5 million participants.

Although aspirin is commonly used for the prevention of cardiovascular disease, evidence from research has shown that these beneficial effects might extend to hepatocellular carcinoma (HCC). This dose-response analysis was performed to investigate the association between aspirin use and risk of HCC. A systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception up to 29th October 2019. DerSimonian and Laird Random-effects model was used to estimate pooled hazard ratios (HRs) from included studies. Overall, eight studies containing 2,604,319 participants evaluating the association between aspirin use and risk of HCC were uncovered and included in the present meta-analysis. Pooled results of included studies showed a significant reduction in risk of HCC in participants who used aspirin (HR 0.59, 95 % CI 0.47-0.75, Pheterogeneity = 0.001, I2 = 90 %). In total, 13,636 cases of HCC detected during the follow-up period of these studies. Furthermore, linear dose-response model showed an significant inverse association between aspirin dose and risk of HCC (exp (b) = 0.994, p < 0.001), while non-linear dose-response analysis revealed an even more robust association (Coef1=-0.008, p1 = 0.04, Coef2 = 0.033, p2 = 0.13). This systematic review and dose-response analysis identified significant inverse relation between aspirin and risk of HCC using both linear and non-linear models.

Vascular endothelial growth factor stimulates endothelial differentiation from mesenchymal stem cells via Rho/myocardin-related transcription factor--a signaling pathway.

Mesenchymal stem cells (MSCs) are pluripotent progenitors that can differentiate into a variety of cell types. Vascular endothelial growth factor (VEGF) is one of the major factors of initiating and regulating angiogenesis. It has been reported that VEGF can induce MSCs differentiated into endothelial cells (ECs). However, the mechanism that VEGF-induced MSC differentiation is not completely understood. Here, we showed that VEGF induced human and rat bone marrow-derived MSCs differentiation to ECs. Rho family plays an important role in VEGF-induced endothelial cell migration and angiogenesis. Our results indicated that in MSCs, VEGF activated Rho/ROCK signaling pathway and promoted nuclear translocation of myocardin-related transcription factor-A (MRTF-A), which is controlled by Rho/ROCK signaling. In addition, Rho inhibitor C3 transferase, ROCK inhibitor Y27632 or depletion of endogenous MRTF-A abolished the VEGF-induced differentiation of MSCs into ECs. Furthermore, VEGF also enhanced the expression levels of CYR61/CCN1, as a regulator of vascular development and angiogenesis, and knockdown of endogenous MRTF-A reduced VEGF-induced the upregulation of CYR61/CCN1. Report assays with site-direct mutation analysis of CYR61/CCN1 promoter demonstrated that MRTF-A transactivated CYR61/CCN1 promoter mainly depending on CArG box. In this study, we identify the Rho/MRTF-A signaling pathway as a main actor in controlling VEGF-induced differentiation of human and rat bone marrow-derived MSCs into endothelial cells.