Shizukaol C alleviates trimethylamine oxide-induced inflammation through activating Keap1-Nrf2-GSTpi pathway in vascular smooth muscle cell.

BACKGROUND: Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. PURPOSE: The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. METHODS: The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo, TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. RESULTS: Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. CONCLUSION: Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB/p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo, suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.

Study on uranium ion adsorption property of porous glass modified with amidoxime group.

In this paper, we prepared three types of porous glasses (PGs) with specific surface areas of 311.60 m2/g, 277.60 m2/g, and 231.38 m2/g, respectively, via borosilicate glass phase separation. These glasses were further modified with amidoxime groups (AO) using the hydroxylamine method, yielding adsorbents named 1.5-PG-AO, 2-PG-AO, and 3-PG-AO. The adsorption performance of these adsorbents under various conditions was investigated, including sorption kinetics and adsorption mechanisms. The results reveal that the number of micropores and specific surface area of PG are significantly reduced after AO modification. All three adsorbents exhibit similar adsorption capabilities. Particularly, pH has a pronounced effect on U (VI) adsorption of PG-AO, with a maximum value at pH = 4.5. Equilibrium adsorption is achieved within 2 h, with a maximum adsorption capacity of 129 mg/g. Notably, a uranium removal rate of 99.94% is attained. Furthermore, the adsorbents show high selectivity in uranium solutions containing Na+ or K+. Moreover, the adsorbents demonstrate exceptional regeneration ability, with the removal rate remaining above 80% even after undergoing five adsorption-desorption cycles. The adsorption reaction of uranium on PG-AO involves a combination of multiple processes, with monolayer chemisorption being the dominant mechanism. Both the complex adsorption of AO and the ion exchange and physical adsorption of PG contribute to the adsorption of uranyl ions on the PG-AO adsorbents.

Dietary supplementation with pseudostellaria heterophylla polysaccharide enhanced immunity and changed mRNA expression of spleen in chicks.

In recent years, increasing interest has focused on natural components extracted from plants, among which plant polysaccharides as natural immunomodulators that can promote animal immunity. The present study was performed to investigate the effect of feed supplement Pseudostellaria Heterophylla Polysaccharide (PHP) on serum Immunoglobulins, T lymphocyte subpopulations, Cytokines and Lysozyme (LZM) activity in chicks. In addition, the influence of PHP on splenic gene expression was investigated by transcriptome sequencing. Four hundred 7-day-old Gushi cocks were randomly divided into four groups in a completely randomized design. The chicks were fed with a basal diet supplemented with 0 (CON-A), 100 (PHP-L), 200 (PHP-M) and 400 (PHP-H) mg/kg PHP. Blood and spleen samples were collected from 6 randomly selected chicks in each group at 14, 21, 28, and 35 days of age. The results showed that compared to the CON-A group, the PHP-M group exhibited significant increases in the levels of IgA, IgG, IgM, CD3, and LZM in the serum at 14, 21, 28, and 35 days (P < 0.05), and at 28 d, there was a significant quadratic relationship between the levels of dietary PHP and the levels of IgG, IgM, IFN-γ, IL-2, CD3, and LZM. Furthermore, a total of 470 differentially expressed genes (DEGs) were identified in spleen from PHP-M and CON-A at 28 d. These DEGs were significantly enriched in the Phagosome, Intestinal immune network for IgA production and Cytokine-cytokine receptor interaction pathways. The present investigation highlights the ameliorating effect of dietary PHP on immunological variables and spleen of chicks, the study suggests that PHP supplementation can enhance immunity and positively impact spleen mRNA expression in chicks.

The transcribed centromeric gene OsMRPL15 is essential for pollen development in rice.

Centromeres consist of highly repetitive sequences that are challenging to map, clone, and sequence. Active genes exist in centromeric regions, but their biological functions are difficult to explore owing to extreme suppression of recombination in these regions. In this study, we used the CRISPR/Cas9 system to knock out the transcribed gene Mitochondrial Ribosomal Protein L15 (OsMRPL15), located in the centromeric region of rice (Oryza sativa) chromosome 8, resulting in gametophyte sterility. Osmrpl15 pollen was completely sterile, with abnormalities appearing at the tricellular stage including the absence of starch granules and disrupted mitochondrial structure. Loss of OsMRPL15 caused abnormal accumulation of mitoribosomal proteins and large subunit rRNA in pollen mitochondria. Moreover, the biosynthesis of several proteins in mitochondria was defective, and expression of mitochondrial genes was upregulated at the mRNA level. Osmrpl15 pollen contained smaller amounts of intermediates related to starch metabolism than wild-type pollen, while biosynthesis of several amino acids was upregulated, possibly to compensate for defective mitochondrial protein biosynthesis and initiate consumption of carbohydrates necessary for starch biosynthesis. These results provide further insight into how defects in mitoribosome development cause gametophyte male sterility.

Vitexin prevents colitis-associated carcinogenesis in mice through regulating macrophage polarization.

BACKGROUND: Patients with inflammatory bowel disease are at increased risks of developing ulcerative colitis-associated colorectal cancer (CAC). Vitexin can suppress the proliferation of colorectal carcinoma cells in vitro orin vivo. However, different from colorectal carcinoma, CAC is more consistent with the transformation from inflammation to cancer in clinical chronic IBD patients. Therefore, we aim to investigated that vitexin whether possess benefic effects on CAC mice. PURPOSE: We aimed to determine the beneficial effects of vitexin on CAC mice and reveal its underlying mechanism. METHODS: The mouse CAC model was induced by Azoxymethane and dextran sodium sulfate (AOM/DSS) and CAC mice were treated with vitexin. At the end of this study, inflammatory cytokines of IL-1ß, IL-6, TNF-α, IL-10 as well as nitric oxide (NO) were detected by kits after long-term treatment of vitexin. Pathological changes and macrophage polarization were determined by H&E and immunofluorescence in adjacent noncancerous tissue and carcinomatous tissue respectively of CAC mice. RESULTS: Our results showed that oral administration of vitexin could significantly improve the clinical signs and symptoms of chronic colitis, relieve colon damage, regulate colonic inflammatory cytokines, as well as suppress tumor incidence and tumor burden. Interesting, vitexin caused a significant increase in serum level of NO and a higher content of NO in tumor tissue. In addition, vitexin significantly decreased M1 phenotype macrophages in the adjacent noncancerous tissue, while markedly up-regulated M1 macrophage polarization in the tumor tissue in the colon of CAC mice. CONCLUSION: Vitexin can attenuate chronic colitis-associated carcinogenesis induced by AOM/DSS in mice and its protective effects are partly associated with its alternations in macrophage polarization in the inflammatory and tumor microenvironment .