Tang (2020) Phlorizin ameliorates obesity-associated endotoxemia and insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity,

No abstract

No abstract

Objective Prevalence of vitamin D-deficiency and its association with the risk of cardiovascular disease prompted us to evaluate the effect of vitamin D status on lipid metabolism and atherosclerosis in hypercholesterolemic microswine. Approach and Results Yucatan microswine were fed with vitamin D-deficient (0IU/d), vitamin D-sufficient (1,000IU/d) or vitamin D-supplemented (3,000IU/d) high cholesterol diet for 48 weeks. Serum lipids and 25(OH)-cholecalciferol levels were measured biweekly. Histology and biochemical parameters of liver and arteries were analyzed. Effect of 1,25(OH)2D3 on cholesterol metabolism was examined in human HepG2 and THP-1 macrophage-derived foam cells. Vitamin D-deficiency decreased plasma HDL levels, expression of liver-X-receptors (LXRs), ATP binding cassette transporter A1 (ABCA1) and ABCG1, and promoted cholesterol accumulation and atherosclerosis in hypercholesterolemic microswine. Vitamin D promoted nascent HDL formation in HepG2 cells via ABCA1-mediated cholesterol efflux. CYP27B1 and VDR were predominantly present in the CD206 + M2 macrophage foam cell-accumulated cores in coronary artery plaques. 1,25(OH)2D3 increased the expression of LXRs, ABCA1, ABCG1, and promoted cholesterol efflux in THP-1 macrophage-derived foam cells. 1,25(OH)2D3 decreased intracellular free cholesterol and polarized macrophages to M2-phenotype with decreased expression of TNF-α, IL-1β, IL-6 under LPS-stimulation. 1,25(OH)2D3 markedly induced CYP27A1 expression via a VDR-dependent JNK1/2 signaling pathway and increased 27-hydroxycholesterol levels, which induced LXRs, ABCA1 and ABCG1 expression, stimulated cholesterol efflux that was inhibited by VDR antagonist and JNK1/2 signaling inhibitor in THP-1 macrophage-derived foam cell. Conclusion Vitamin D protects against atherosclerosis in hypercholesterolemic swine via controlling cholesterol efflux and macrophage polarization via increased CYP27A1 activation.

No abstract

Bone morphogenetic protein (BMP) is a bone-derived growth factor capable of promoting the differentiation of mesenchymal cells into osteogenic lineage pathways. Recently, immunosuppressants were reported to cause a moderate increase in osteoblastic differentiation in a rat osteoblast-like osteosarcoma cell line. If immunosuppressants can induce osteoblastic differentiation, it will be useful for bone tissue transplantation. We assessed the effect of immunosuppressants with or without BMP-4 on inducing osteoblastic differentiation in osteoblast-like and other mesenchymal cells. FK506, an immunosuppressant often used clinically, induced a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, one of the markers of osteoblast differentiation, in cells derived from mesenchyma. In the presence of BMP-4, ALP activity, mRNA levels of ALP and osteocalcin increased. FK506 was found to not only stimulate osteoblastic differentiation, but also to enhance BMP-4 induced osteoblastic differentiation. These results suggest that FK506 promotes differentiation of osteoblastic cells.

No abstract

BackgroundThis study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats.MethodsExpression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were tested by QT-PCR and Western blot, and levels of 5-hydroxytryptamine (5-HT), KYN, TRY, 3-hydroxykynurenine (3-HK), and kynurenic acid (KA) in different brain regions were estimated using HPLC. Effects of the IDO direct inhibitor 1-methyl-l-tryptophan (1-MT) on cognitive, anxiety, and depressive-like behavior were evaluated in bile duct ligation (BDL) rats.ResultsIncreased serum TNF-α, IL-1β, and IL-6 levels were shown in rats 7 days after BDL, and these increases were observed earlier than those in the brain, indicating peripheral immune activation may result in central upregulation of proinflammatory cytokines. Moreover, BDL rats showed a progressive decline in memory formation, as well as anxiety and depressive-like behavior. Further study revealed that IDO expression increased after BDL, accompanied by a decrease of 5-HT and an increase of KYN, as well as abnormal expression of 3-HK and KA. The above results affected by BDL surgery were reversed by IDO inhibitor 1-MT treatment.ConclusionTaken together, these findings indicate that (1) behavioral impairment in BDL rats is correlated with proinflammatory cytokines; (2) TRY pathway of KYN metabolism, activated by inflammation, may play an important role in HE development; and (3) 1-MT may serve as a therapeutic agent for HE.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1037-9) contains supplementary material, which is available to authorized users.