Metformin Ameliorates Chronic Colitis-Related Intestinal Fibrosis via Inhibiting TGF-ß1/Smad3 Signaling.

Intestinal fibrosis is considered to be a chronic complication of inflammatory bowel disease (IBD) and seriously threatening human health. Effective medical therapies or preventive measures are desirable but currently unavailable. Metformin has been proved to have a satisfactory anti-inflammatory effects in ulcerative colitis (UC) patients. Whether metformin can ameliorate chronic colitis-related intestinal fibrosis and the possible mechanisms remain unclear. Here, we established colitis-related intestinal fibrosis in mice by repetitive administration of TNBS or DSS. Preventive and therapeutic administration of metformin to chronic TNBS or DSS colitis mice indicated that metformin significantly attenuated intestinal fibrosis by suppressing Smad3 phosphorylation. In vitro studies with human colon fibroblast cell line (CCD-18Co) and primary human intestinal fibroblast treated with TGF-ß1 confirmed the anti-fibrotic function of metformin for fibroblast activation, proliferation and collagen production. Mechanistically, metformin particularly inhibited phosphorylation and nuclear translocation of Smad3 by blocking the interaction of Smad3 with TßRI. These findings suggest that metformin will be an attractive anti-fibrotic drug for intestinal fibrosis in future therapies.

Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves' Disease.

Background: A growing number of studies have found dysbiosis of the intestinal microbiota in patients with Graves' disease (GD). The intestinal epithelial barrier serves as the first line of defense, protecting the immune system from excessive stimulation of microbiota and toxins. Most autoimmune diseases are associated with a gut barrier dysfunction (leaky gut) which allows bacterial translocation. However, to date, potential correlations between intestinal barrier dysfunction and GD have not been explored. Methods: Serum lipopolysaccharide (LPS), intestinal fatty acid-binding protein (I-FABP), zonulin, D-lactate, and diamine oxidase (DAO) were measured to assess barrier integrity in 91 patients with GD (61 initial GD and 30 euthyroid GD) and 44 healthy controls. The quality of life (QOL) of patients with GD was assessed using the thyroid-specific patient-reported outcome (ThyPRO-39) questionnaire. Results: The serum levels of LPS, I-FABP, zonulin, and D-lactate were significantly higher in patients with initial GD than in healthy controls. Logistic regression analysis revealed that zonulin and D-lactate were independently associated with risk for GD and circulating zonulin could effectively distinguish patients with initial GD from healthy controls. Correlation analyses showed that I-FABP, LPS, and D-lactate were positively associated with FT4 and negatively associated with TSH. In addition, circulating LPS, zonulin, and D-lactate levels were all independent predictors of TRAb levels. Moreover, higher circulating LPS levels in patients with GD were associated with more severe hyperthyroidism (higher concentrations of FT3, FT4, and TRAb and lower TSH concentrations) and worse scores of hyperthyroid and eye symptoms. Conclusion: Patients with initial GD show a disrupted intestinal barrier, characterized by elevated levels of leaky gut biomarkers. Increased intestinal permeability and bacterial translocation were associated with TRAb levels and hyperthyroidism in GD. Further research is required to elucidate the underlying mechanisms.

The enhancement of iron fuel cell on bio-cathode denitrification and its mechanism as well as the microbial community analysis of bio-cathode.

To address the issue of insufficient electrons during denitrification, an iron fuel cell (IFC) bioreactor using iron as abiotic anode was designed. The nitrogen removal efficiency (NRE) of IFC (2.54 ±â€¯0.016%) was significantly lower than microbial fuel cell (MFC) (32.58 ±â€¯0.033%) with same bio-cathode under autotrophic conditions, which was due to the permeation of acetate on proton exchange membrane (PEM) affected the process of enriching autotrophic denitrifying bacteria by MFC. When used in heterotrophic conditions, the NRE of the closed-circuits of IFC was 29.04%, 10.53%, 8.33% higher than open-circuits, respectively, when the COD/nitrogen (C/N) ratios was 1, 2 and 3. The enhancement of IFC was the iron anode could convert a portion of nitrate to nitrite according to the abiotic cathode control experiments. The mainly functional bacteria of bio-cathode was Paracoccus (53.04%). In conclusion, the IFC could be a theoretical model for using inorganic electron donor during denitrification.

Effect of air-exposed biocathode on the performance of a Thauera-dominated membraneless single-chamber microbial fuel cell (SCMFC).

To investigate the effect of air-exposed biocathode (AEB) on the performance of single-chamber microbial fuel cell (SCMFC), wastewater quality, bioelectrochemical characteristics and the electrode biofilms were researched. It was demonstrated that exposing the biocathode to air was beneficial to nitrogen removal and current generation. In Test 1 of 95% AEB, removal rates of ammonia, total nitrogen (TN) and chemical oxygen demand (COD) reached 99.34%±0.11%, 99.34%±0.10% and 90.79%±0.12%, respectively. The nitrogen removal loading rates were 36.38gN/m3/day. Meanwhile, current density and power density obtained at 0.7A/m3 and 104mW/m3 respectively. Further experiments on open-circuit (Test 2) and carbon source (Test 3) indicated that this high performance could be attributed to simultaneous biological nitrification/denitrification and aerobic denitrification, as well as bioelectrochemical denitrification. Results of community analysis demonstrated that both microbial community structures on the surface of the cathode and in the liquid of the chamber were different. The percentage of Thauera, identified as denitrifying bacteria, maintained at a high level of over 50% in water, but decreased gradually in the AEB. Moreover, the genus Nitrosomonas, Alishewanella, Arcobacter and Rheinheimera were significantly enriched in the AEB, which might contribute to both enhancement of nitrogen removal and electricity generation.

Simultaneous efficient removal of oxyfluorfen with electricity generation in a microbial fuel cell and its microbial community analysis.

The performance of a microbial fuel cell (MFC) to degrade oxyfluorfen was investigated. Approximately 77% of 50 mg/L oxyfluorfen was degraded within 24 h by anodic biofilm. The temperature, pH, and initial oxyfluorfen concentration had a significant effect on oxyfluorfen degrading, and a maximum degradation rate of 94.95% could theoretically be achieved at 31.96 °C, a pH of 7.65, and an initial oxyfluorfen concentration of 120.05 mg/L. Oxyfluorfen was further catabolized through various microbial metabolism pathways. Moreover, the anodic biofilm exhibited multiple catabolic capacities to 4-nitrophenol, chloramphenicol, pyraclostrobin, and sulfamethoxazole. Microbial community analysis indicated that functional bacteria Arcobacter, Acinetobacter, Azospirillum, Azonexus, and Comamonas were the predominant genera in the anodic biofilm. In terms of the efficient removal of various organic compounds and energy recovery, the MFC seemed to be a promising approach for the treatment of environmental contaminants.