Explore the vast range of titles available.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease which seriously affects public health. Gut microbiota remains a dynamic balance state in healthy individuals, and its disorder may affect health status and even results in metabolic diseases. Quercetin, a natural flavonoid, has been shown to have biological activities that can be used in the prevention and treatment of metabolic diseases. This study aimed to explore the mechanism of quercetin in alleviating T2DM based on gut microbiota. db/db mice were adopted as the model for T2DM in this study. After 10 weeks of administration, quercetin could significantly decrease the levels of body weight, fasting blood glucose (FBG), serum insulin (INS), the homeostasis model assessment of insulin resistance (HOMA-IR), monocyte chemoattractant protein-1 (MCP-1), D-lactic acid (D-LA), and lipopolysaccharide (LPS) in db/db mice. 16S rRNA gene sequencing and untargeted metabolomics analysis were performed to compare the differences of gut microbiota and metabolites among the groups. The results demonstrated that quercetin decreased the abundance of Proteobacteria, Bacteroides, Escherichia-Shigella and Escherichia_coli. Moreover, metabolomics analysis showed that the levels of L-Dopa and S-Adenosyl-L-methionine (SAM) were significantly increased, but 3-Methoxytyramine (3-MET), L-Aspartic acid, L-Glutamic acid, and Androstenedione were significantly decreased under quercetin intervention. Taken together, quercetin could exert its hypoglycemic effect, alleviate insulin resistance, repair the intestinal barrier, remodel the intestinal microbiota, and alter the metabolites of db/db mice.

Background Chimeric antigen receptor (CAR) engineered natural killer (NK) cells have shown their efficacy and superiority against cancer and possess the potential to become off-the-shelf immunotherapy products. Nonetheless, some challenges associated with CAR-NK cells still exist including inhibitory receptor engagement, antigen escape, and inadequate activation. Methods Given this, based on the concept of synthetic biology, we rationally designed a novel dual-targeted CAR (dtCAR), primarily comprising PD-L1 nanoantibody (PD-L1 Nb ) and NKG2D as the ectodomain, transmembrane and cytoplasmic domains (CP) of CD28, and the CP of 4-1BB and CD3ζ. NK92 cells were engineered to express this third-generation of dtCAR. We then elucidated the role of dtCAR-modified NK92 cells against cancer cells in vitro and in vivo. Results In vitro, the dtCAR-NK92 cells could still retain the characteristics of parental NK cells and exhibit improved NK cell cytotoxicity and produce more cytokines than NK92 cells when they were co-cultured with human lung cancer H1299 cells. Notably, the dtCAR-NK92 cell therapy might elicit clearance of H1299 cells by pyroptosis. Additionally, dtCAR-NK92 cells could considerably inhibit tumor growth in the human lung cancer H1299 cell tumor model. Conclusions We confirmed that expression of dtCAR enhanced NK92-cell activation and killing in vitro and in vivo, which provides a novel immunotherapeutic strategy for using NK-tailored CAR-engineered NK92 cells to treat human lung cancer.

Background As reported previously by our group, medium-chain triglycerides can ameliorate atherosclerosis. Given that TLR4 is closely related to atherosclerosis, we hypothesized herein that caprylic acid (C8:0) would suppress inflammation via TLR4/NF-κB signaling and further promote the amelioration of atherosclerosis in apoE- deficient (apoE −/− ) mice. Methods Fifty 6-week male apoE −/− mice were randomly allocated into five diet groups: a high-fat diet (HFD) without or with 2% caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0), or linolenic acid (C18:3). RAW246.7 cells were treated with caprylic acid (C8:0), docosahexenoic acid (DHA), palmitic acid (C16:0), and lipopolysaccharide (LPS) with or without TLR4 knock-down (TLR4-KD). The serum lipid profiles, inflammatory biomolecules, and mRNA and protein expression levels were measured. Atherosclerotic lesions that occurred in the aorta and aortic sinuses were evaluated and quantified. Results Our results indicated that C8:0 reduced body fat, improved the lipid profiles, suppressed inflammatory cytokine production, downregulated aortic TLR4, MyD88, NF-κB, TNF-α, IKKα, and IKKβ mRNA expression, and alleviated atherosclerosis in the apoE −/− mice ( P  < 0.05). In RAW 264.7 cells, C8:0 diminished the inflammatory response and both mRNA and protein expression of TLR4, MyD88, NF-κB, and TNF-α compared to those in the LPS and C16:0 groups ( P  < 0.05). However, in the TLR4-KD RAW 264.7 cells, C8:0 significantly upregulated NF-κB mRNA and protein expression compared to those in the C16:0 and DHA groups. Conclusions These results suggest that C8:0 functions via TLR4/NF-κB signaling to improve the outcomes of apoE −/− mice through suppressing inflammation and ameliorating atherosclerosis. Thus, C8:0 may represent as a promising nutrient against chronic inflammatory diseases.

Exposure to airborne hazards during deployment is associated with persistent respiratory symptoms among military veterans even years after deployment. Circulating monocytes, key components of the innate immune response, are implicated in inflammatory processes that may be sustained long after such exposures and contribute to related health issues. This cross-sectional study, conducted years after deployment, aimed to characterize monocyte activation profiles in veterans with deployment-related respiratory symptoms and investigate associations with physiological markers of pulmonary and vascular function. Circulating monocyte immunophenotype, pulmonary function, and brachial artery flow-mediated dilation (FMD) were assessed in 82 previously deployed veterans. Using principal component and hierarchical clustering analyses, we identified two distinct monocyte activation phenotypes: Cluster 1, characterized by elevated CD87, CD11b, and CD163, and cluster 2 which expressed markers of non-classical monocytes and CD195, indicative of a chronic inflammatory phenotype. Veterans in cluster 2 exhibited impaired endothelial-dependent vasodilation (FMD/NMD ratio; p = 0.02) and elevated airway resistance (R5; p = 0.01), despite normal pulmonary function. These findings suggest an association between distinct monocyte activation profiles and measures of microvascular and airway dysfunction in this cohort, potentially reflecting sustained inflammation secondary to environmental exposure. These observed associations underscore the need for further research into the role of monocytes in these long-term physiological changes. Elucidating the mechanistic pathways by which these monocyte phenotypes may contribute to persistent physiological alterations is critical and could inform future strategies for identifying at-risk veterans or exploring novel immunomodulatory approaches if such links are further substantiated.

Background Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Riboflavin, one of water soluble vitamins, plays a role in lipid metabolism and antioxidant function. However, the effects of riboflavin deficiency on NAFLD development have not yet to be fully explored. Methods In the present study, an animal model of NAFLD was induced by high fat diet feeding in mice and a cellular model of NAFLD was developed in HepG2 cells by palmitic acid (PA) exposure. The effects of riboflavin deficiency on lipid metabolism and antioxidant function were investigated both in vivo and in vitro. In addition, the possible role of peroxisome proliferator-activated receptor gamma (PPARγ) was studied in HepG2 cells using gene silencing technique. Results The results showed that riboflavin deficiency led to hepatic lipid accumulation in mice fed high fat diet. The expressions of fatty acid synthase (FAS) and carnitine palmitoyltransferase 1 (CPT1) were up-regulated, whereas that of adipose triglyceride lipase (ATGL) down-regulated. Similar changes in response to riboflavin deficiency were demonstrated in HepG2 cells treated with PA. Factorial analysis revealed a significant interaction between riboflavin deficiency and high dietary fat or PA load in the development of NAFLD. Hepatic PPARγ expression was significantly upregulated in mice fed riboflavin deficient and high fat diet or in HepG2 cells treated with riboflavin deficiency and PA load. Knockdown of PPARγ gene resulted in a significant reduction of lipid accumulation in HepG2 cells exposed to riboflavin deficiency and PA load. Conclusions There is a synergetic action between riboflavin deficiency and high dietary fat on the development of NAFLD, in which PPARγ may play an important role.

In mammals, a constant body temperature is maintained for survival in cold environments, primarily through the activation of thermogenic mechanisms. In this review, we discussed the advances in research on cold-adaptive thermogenic substances and their regulation. First, we outlined the primary thermogenic responses to cold exposure, including shivering thermogenesis (ST) and non-shivering thermogenesis (NST), and emerging thermogenic pathways. Next, we discussed the mechanism of action of various thermogenic substances, including nutrients, traditional Chinese medicine (TCM), TCM extracts, and dietary functional factors. This review provides a theoretical foundation for developing cold-resistance preparations with minimal side effects.

The role of glucose transporters in the transport of flavonoids remains ambiguous. In this study, we examined whether quercitrin would be absorbed intactly in modeled Caco-2 cells, as well as determined the involvement of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in its transmembrane transport. The first experiment was conducted to examine the uptake of quercitrin into Caco-2 cells 24 h after they were seeded and the second experiment was conducted to determine the transport across the apical and basolateral membrane of Caco-2 cells after they were cultured for 21 days in a Millicell system. Quercitrin was administered at 3, 9, or 18 μg/mL; and the time points of sampling were 30, 60, 90, 120, and 150 min. In the uptake experiment, the highest intracellular quercitrin concentration was observed in the cells treated with 18 μg/mL quercitrin at 60 min, with a bell-shaped kinetic curve. Quercetin, isorhamnetin, and tamarixetin were detected inside the cells, particularly when treated with a high dose. In the transport experiment, quercitrin was transported from the apical to basolateral side and vice versa; its concentrations depended on dose, time, and transport direction ( < 0.0001). Only trace amounts of isorhamnetin and tamarixetin were detected in the apical chamber when quercitrin was added to the basolateral chamber. Phloridzin and phloretin, potent inhibitors of SGLT1 and GLUT2, respectively, significantly diminished quercitrin transport from the apical to basolateral side; and phloretin had a greater inhibitory effect compared to phloridzin. Our results demonstrate that quercitrin is absorbed intactly and then effluxed out of Caco-2 cells through both apical and basolateral membranes probably via SGLT1 and GLUT2.

The dynamic characteristics of pipe piles are of considerable importance for the dynamic foundation design of offshore wind turbines. In this study, we develop an analytical model for the lateral vibration of offshore pipe piles with consideration of the inertia effect and axial loading from the superstructure. A coupled dynamic saturated soil–pile interaction model is established based on Biot’s poroelastic theory and Euler–Bernoulli theory. The potential function, operator decomposition method, variable separation method and matrix transfer method are introduced herein to obtain the lateral force of the inner and outer soil acting on the pile shaft. Then, the analytical solution of the pile dynamic impedance in the frequency domain is derived by employing the soil–pile continuous deformation conditions and the boundary conditions of the pile. The rationality and accuracy of the presented solution have were by comparing its results with those predicted by existing solutions. The influence of superstructure, pile geometry and soil plug height on the lateral dynamic impedance and natural frequency of pipe piles was thoroughly investigated based on the theoretical model. The main findings can be summarized as: (1) The dynamic stiffness of piles will be remarkably underestimated if the inertia effect of the superstructure is not accounted for. (2) The vertical load of the superstructure is main factor affecting the natural frequency, whereas the inertia effect of the superstructure will enlarge the resonance amplitude. (3) The overall lateral dynamic impedance and first-order natural frequency of the pile increase significantly with the soil plug height.

The aim of this study was to determine the effects of quercetin on homocysteine (Hcy) metabolism and hepatic antioxidant status in high methionine (Met)-fed rats. Rats were fed for 6 wk the following diets: control, 1.0% Met, 1.0% Met and 0.1% quercetin, 1.0% Met and 0.5% quercetin, 1.0% Met and 2.5% quercetin-supplemented diets. Serum Hcy, Met, cysteine, serine, taurine, glutathione (GSH), quercetin and its metabolites, and activities of alanine transaminase (ALT) and aspartate transaminase (AST) were assayed. Hepatic malondialdehyde, GSH and carbonyls, and activity of superoxide dismutase and ferric-reducing antioxidant power also were measured. Serum Hcy was increased significantly after Met treatment and decreased after quercetin supplementation. Meanwhile, serum taurine was increased and serine decreased. However, the content of GSH in serum and liver was decreased in the quercetin-supplemented groups and activities of serum ALT and AST were enhanced in the 1.0% Met and 2.5% quercetin-supplemented groups. Quercetin is effective in decreasing serum Hcy level in high Met-fed rats and one of possible mechanisms is associated with increased transsulfuration of Hcy. Quercetin can acts as a prooxidant at high intake levels.