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Ulcerative colitis (UC) is a relapsing inflammatory disease with an unknown precise etiology. The purpose of this study is to investigate the protective effects of Gardenia jasminoides Ellis fruit extracts (GFE) on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. GFE (50 mg/kg, 100 mg/kg) were administered orally for 7 days after induction. Meanwhile, the chemical components of GFE were performed by UPLC-QTOF-MS/MS. GFE significantly decreased DAI scores and ameliorated macroscopic and histologic damage. It also reduced the levels of MPO, NO, MDA, IL-1β, TNF-α, and IL-6, while increasing the level of SOD. Moreover, 56 components were identified in GFE using a UPLC-QTOF-MS/MS method, which can be categorized into six structural groups. Our results indicated that GFE has an ameliorative effect on TNBS-induced colitis in rats, which may further verify its anti-inflammatory and antioxidative properties. Therefore, GFE can be a promising protective agent of colitis that deserves further investigation. [ABSTRACT FROM AUTHOR]

Val‐Val‐Tyr‐Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride‐induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non‐alcoholic steatohepatitis (NASH) have not been discovered. Our present study was designed to investigate the preventive effect of VVYP on NASH and its underlying specific mechanisms. We found that VVYP inhibited the cytotoxicity and lipid accumulation in L‐02 cells that were exposed to a mixture of free fatty acid (FFA). VVYP effectively alleviated the liver injury induced by methionine‐choline‐deficient (MCD) diet, demonstrated by reducing the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/triglycerides (TG)/non‐esterified fatty acids (NEFA) and improving liver histology. VVYP decreased expression levels of lipid synthesis‐related genes and reduced levels of the proinflammation cytokines in the liver of mice fed by MCD diet. Moreover, VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction induced by MCD diet. Meanwhile, VVYP significantly increased the abundance of beneficial bacteria such as Eubacteriaceae, coriobacteriacease, Desulfovibrionaceae, S24‐7 and Bacteroidia in high‐fat diet (HFD)‐fed mice, however, VVYP reduced the abundance of Lactobacillus. Moreover, VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)‐associated genes and inhibited subsequent liver inflammatory responses. These results indicated that the protective role of VVYP on NASH is mediated by modulating gut microbiota imbalance and related gut‐liver axis activation. VVYP might be a promising drug candidate for NASH. [ABSTRACT FROM AUTHOR]

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC0–2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction). [ABSTRACT FROM AUTHOR]

A trimeric tri-Tb3+-including antimonotungstate (AMT) hybrid Na17{(WO4)[Tb(H2O)(Ac)(B-α-SbW9O31(OH)2)]3}·50H2O (Tb3W28) was successfully synthesized, in which the capped tetrahedral {WO4} group plays a significant template role in directing the aggregation of three [B-α-SbW9O33]9− fragments and three Tb3+ ions. Eu3+/Tb3+/Dy3+/Gd3+-codoped AMT materials based on Tb3W28 were firstly prepared and their luminescence properties were investigated. The red emitter Eu3+, yellow emitter Dy3+, and nonluminous Gd3+ ions were codoped into Tb3W28 to substitute Tb3+ ions for investigating the energy transfer (ET) mechanism among Eu3+, Tb3+, and Dy3+ ions. Upon the 6H15/2 → 4I13/2 excitation at 389 nm of the Dy3+ ion, the ET1 mechanism (Dy3+ → Tb3+) was confirmed as a non-radiative dipole–dipole interaction. Under the 7F6 → 5L10 excitation at 370 nm of the Tb3+ ion, the ET2 mechanism (Tb3+ → Eu3+) was identified as a non-radiative quadrupole–quadrupole interaction. Under excitation at 389 nm, the two-step successive Dy3+ → Tb3+ → Eu3+ ET3 process was proved in Dy1.2Tb3zEu0.03Gd1.77−3zW28. Through changing the excitation wavelengths, the emission color of Dy1.2Tb1.2Eu0.03Gd0.57W28 can vary from blue to yellow, in which a near-white-light emission case was observed upon excitation at 378 nm. This work not only provides a systematic ET mechanism study of hetero-Ln-codoped AMTs, but also offers some useful guidance for designing novel performance-oriented Ln-codoped polyoxometalate-based materials. [ABSTRACT FROM AUTHOR]

Background: Chondrogenic progenitor cells (CPCs) have high self-renewal capacity and chondrogenic potential. Intra-articular delivery of purified mesenchymal stem cells (MSCs) from MRL/MpJ "superhealer" mice increased bone volume during repair and prevents post-traumatic arthritis. Recently, although extracellular vesicles released from MSCs have been used widely for treating OA, the application of extracellular vesicles secreted by CPCs from MRL/MpJ mice in OA therapy has never been reported. In this study, we evaluated the effects of extracellular vesicles secreted by CPCs from control CBA (CBA-EVs) and MRL/MpJ mice (MRL-EVs) on proliferation and migration of murine chondrocytes. We also determined here if weekly intra-articular injections of CBA-EVs and MRL-EVs would repair and regenerate surgically induced model in mice. Methods: CPC surface markers were detected by flow cytometry. CBA-EVs and MRL-EVs were isolated using an ultrafiltration method. Nanoparticle tracking analysis, transmission electron microscopy, and western blots were used to identify extracellular vesicles. CBA-EVs and MRL-EVs were injected intra-articularly in a mouse model of surgical destabilization of the medial meniscus (DMM)-induced OA, and histological and immunohistochemistry analyses were used to assess the efficacy of exosome injections. We used miRNA-seq analysis to analyze the expression profiles of exosomal miRNAs derived from CBA-EVs as well as MRL-EVs. Cell-counting and scratch assays were used to evaluate the effects of CBA-EVs and MRL-EVs on proliferation and migration of murine chondrocytes, respectively. Meanwhile, a specific RNA inhibitor assesses the roles of the candidate miRNAs in CPC-EV-induced regulation of function of chondrocytes. Results: Both CBA-EVs and MRL-EVs stimulated chondrocyte proliferation and migration, but MRL-EVs exerted a stronger effect than CBA-EVs. The similar result was also observed in in vivo study, which indicated that injecting either CBA-EVs or MRL-EVs attenuated OA, but MRL-EVs showed a superior therapeutic effect in comparison with CBA-EVs. The results of bioinformatics analyses revealed that the differentially expressed exosomal miRNAs participated in multiple biological processes. We identified 80 significantly upregulated and 100 downregulated miRNAs. Moreover, we found that the top 20 differentially expressed exosomal miRNAs connected OA repair to processes such as AMPK signaling, regulation of autophagy, and insulin signaling. Notably, miRNA 221-3p were highly enriched in MRL-Exos and treatment with miR 221-3p inhibitor markedly decreased chondrocyte proliferation and migration induced by CBA-EVs or MRL-EVs in vitro. Conclusions: This is the first study to demonstrate MRL-EVs had a greater therapeutic effect on the treatment of OA than CBA-EVs. This study will hopefully provide new insight into the pathogenesis, prevention, and treatment of OA. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) has a high mortality rate due to liver metastasis. The insulin‐like growth factor‐1 receptor (IGF‐1R) is highly expressed in UM and has been shown to be associated with hepatic metastases. Targeting IGF signalling may be considered as a promising approach to inhibit the process of metastatic UM cells. Pristimerin (PRI) has been demonstrated to inhibit the growth of several cancer cells, but its role and underlying mechanisms in the IGF‐1‐induced UM cell proliferation are largely unknown. The present study examined the anti‐proliferative effect of PRI on UM cells and its possible role in IGF‐1R signalling transduction. MTT and clonogenic assays were used to determine the role of PRI in the proliferation of UM cells. Flow cytometry was performed to detect the effect of PRI on the cell cycle distribution of UM cells. Western blotting was carried out to assess the effects of PRI and IGF‐1 on the IGF‐1R phosphorylation and its downstream targets. The results indicated that IGF‐1 promoted the UM cell proliferation and improved the level of IGF‐1R phosphorylation, whereas PRI attenuated the effect of IGF‐1. Interestingly, PRI could not only induce the G1 phase accumulation and reduce the G2 phase induced by IGF‐1, but also could stimulate the expression of p21 and inhibit the expression of cyclin D1. Besides, PRI could attenuate the phosphorylations of Akt, mTOR and ERK1/2 induced by IGF‐1. Furthermore, the molecular docking study also demonstrated that PRI had potential inhibitory effects on IGF‐1R. Taken together, these results indicated that PRI could inhibit the proliferation of UM cells through down‐regulation of phosphorylated IGF‐1R and its downstream signalling. [ABSTRACT FROM AUTHOR]