Impact of the gut microbiota on angiotensin â ¡-related disorders and its mechanisms.

The renin-angiotensin system (RAS) consists of multiple angiotensin peptides and performs various biological functions mediated by distinct receptors. Angiotensin II (Ang II) is the major effector of the RAS and affects the occurrence and development of inflammation, diabetes mellitus and its complications, hypertension, and end-organ damage via the Ang II type 1 receptor. Recently, considerable interest has been given to the association and interaction between the gut microbiota and host. Increasing evidence suggests that the gut microbiota may contribute to cardiovascular diseases, obesity, type 2 diabetes mellitus, chronic inflammatory diseases, and chronic kidney disease. Recent data have confirmed that Ang II can induce an imbalance in the intestinal flora and further aggravate disease progression. Furthermore, angiotensin converting enzyme 2 is another player in RAS, alleviates the deleterious effects of Ang II, modulates gut microbial dysbiosis, local and systemic immune responses associated with coronavirus disease 19. Due to the complicated etiology of pathologies, the precise mechanisms that link disease processes with specific characteristics of the gut microbiota remain obscure. This review aims to highlight the complex interactions between the gut microbiota and its metabolites in Ang II-related disease progression, and summarize the possible mechanisms. Deciphering these mechanisms will provide a theoretical basis for novel therapeutic strategies for disease prevention and treatment. Finally, we discuss therapies targeting the gut microbiota to treat Ang II-related disorders.

Impact of Sub-MIC Eugenol on Klebsiella pneumoniae Biofilm Formation via Upregulation of rcsB.

The Rcs phosphorelay system is present in many members of the Enterobacteriaceae. The aim of this study was to illustrate the possible mechanisms of eugenol on ultimate targets of Klebsiella pneumoniae (K. pneumoniae) Rcs phosphorelay, rcsB, and impact on biofilm formation. The minimum inhibitory concentration (MIC) of eugenol against K. pneumoniae KP1 and KP1 ΔrcsB strain was determined using the 2-fold micro-dilution method. Biofilm was measured by crystal violet staining. Transcriptome sequencing was performed to investigate sub-MIC eugenol on K. pneumoniae, and gene expression at mRNA level was analyzed by RT-qPCR. In vitro biofilm formation test and molecular docking were used to evaluate the effect of eugenol and to predict potential interactions with RcsB. MicroScale Thermophoresis (MST) was conducted for further validation. MIC of eugenol against K. pneumoniae KP1 and KP1 ΔrcsB strain was both 200 µg/ml. Transcriptome sequencing and RT-qPCR results indicated that rpmg, degP, rnpA, and dapD were downregulated, while rcsB, rcsD, rcsA, yiaG, and yiaD were upregulated in the eugenol-treated group. ΔrcsB exhibited a weakened biofilm formation capacity. Additional isopropyl-ß-d-thiogalactoside (IPTG) hinders biofilm formation, while sub-MIC eugenol could promote biofilm formation greatly. Docking analysis revealed that eugenol forms more hydrophobic bonds than hydrogen bonds. MST assay also showed a weak binding affinity between eugenol and RcsB. These results provide significant evidence that rcsB plays a key role in K. pneumoniae biofilm formation. Sub-MIC eugenol facilitates biofilm formation to a large extent instead of inhibiting it. Our findings reveal the potential risk of natural anti-biofilm ingredients at sub-MIC to treat drug-resistance bacteria.

Nitrogen-doped graphene-chitosan matrix based efficient chemiluminescent immunosensor for detection of chicken interleukin-4.

Chicken interleukin-4 (ChIL-4), which is released by activated type 2 helper (Th2) cells following their stimulation in vitro, is an important indicator for the study of cell-mediated immunity in chickens after infection or vaccination. In this work, the first ChIL-4 chemiluminescent (CL) immunosensor was developed via the immobilization of monoclonal ChIL-4 antibodies on a nitrogen-doped graphene (NG)-chitosan nanocomposite matrix. NG nanosheets were used for the first time in the CL immunoassay to provide a biocompatible microenvironment for the immobilized capture antibody. The ChIL-4 immunosensor was characterized systematically. The proposed immunosensor displayed a wide linear range from 0.05 to 70ngmL-1 and a low detection limit of 0.02ngmL-1 at a signal-to-noise ratio of 3. Compared to traditional assay methods, this system was more flexible, simple, rapid, and sensitive. Moreover, this CL immunoassay system had an excellent detection and fabrication reproducibility, a high specificity, an acceptable accuracy, and a high stability. This work enables the specific detection of ChIL-4 and the further study of its role in the immune responses of poultry.