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Abstract

Aim
Fish oil (FO) and mesalazine have well-known anti-inflammatory and antioxidant effects; on the other hand, information related to combined intrarectal administration of FO and mesalazine is limited.

The present study was conducted to make comparison on therapeutic effectiveness of rectally administered FO and mesalazine in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis.

Methods
Wistar rats were randomly assigned to 5 groups as (1) Control, (2) Colitis, (3) Colitis + Mesalazine (Colitis + M), (4) Colitis + Fish Oil (Colitis + F), and (5) Colitis + Mesalazine + Fish Oil (Colitis + M + F). Intrarectally administered TNBS induced colitis. At the end of the trial, the rats’ macroscopic and histopathologic lesions were rated and tumour necrosis factor (TNF)-α, Interleukin 6 (IL6), glutathione reductase (GR), glutathione peroxidase (GP), myeloperoxidase (MPO), malondialdehyde (MDA), Superoxide dismutase (SOD), Total nitrate and nitrite, and catalase (CAT) in serum and tissue were detected.

Results

As a result of macroscopic and microscopic examination, although separate administrations of FO and mesalazine partly decreased the damage, their combined administration decreased the damage scores significantly (p < 0.01). It was observed that separate and combined administrations of FO and mesalazine decreased the increase in the serum and tissue TNF-α and IL-6 levels caused by colitis (p < 0.05). It was observed that the serum MPO, serum GR, tissue SOD, tissue nitrite/nitrate values of both Colitis + M and Colitis + F groups were close to the control in terms of all the parameter values in Colitis + M + F group (p > 0.05).Also based on the histological results, the inflammation damage in the tissue caused by colitis in the Colitis + M + F group recovered significantly.


Conclusions
We found that microscopic and macroscopic damage, serum IL-6 level decreased and increased serum and tissue GP and tissue GR values in Colitis + M + F group compared to Colitis + M and Colitis + F groups. Combined intrarectal administration of FO and mesalazine may bring a new insight concerning the treatment of ulcerative colitis.

Abstract

The total accumulative stockpiles of gangue from long-term coal mining exceed 1 billion tons and occupy 182 square kilometers, and 50 million tons of additional gangue are generated per year in Shanxi, a major energy province in China. The objective of this study was to examine whether exposure to village soils affected by gangue stacking would disrupt thyroid hormone system homeostasis and eventually affect endocrine system and development, using zebrafish (Danio rerio) as a model organism. The zebrafish embryos were exposed to village soil leachates at 0, 1:9, 1:3 and 1:1 from 1 to 120 h postfertilization (hpf), and the sample caused a dose-dependent increase in the mortality and malformation rate, and decrease in the heart rate, hatching rate and body length of zebrafish larvae. Importantly, the soil leachate alleviated the whole-body triiodothyronine (T3) and thyroxine (T4) levels at higher concentrations, and altered the expression of the hypothalamic-pituitary-thyroid (HPT) axis-regulating genes crh, trh, tshβ, nis, tg, nkx2.1, pax8, hhex, ttr, dio1, dio2, ugt1ab, trα, and trβ and the PAH exposure-related genes ahr2 and cyp1a. These findings highlight the potential risk of thyroid hormone disruption and developmental toxicity from soil samples around coal gangue stacking areas.

Abstract

Albumin absorbed by renal tubular epithelial cells induces inflammation and plays a key role in promoting diabetic kidney disease (DKD) progression. Macrophages are prominent inflammatory cells in the kidney, and their role there is dependent on their phenotypes. However, whether albuminuria influences macrophage phenotypes and underlying mechanisms during the development of DKD is still unclear. We found that M1 macrophage-related markers were increased in diabetes mellitus (DM) mouse renal tissues with the development of DKD, and coculture of extracellular vesicles (EVs) from human serum albumin (HSA)-induced HK-2 cells with macrophages induced macrophage M1 polarization in the presence of lipopolysaccharide (LPS). Through a bioinformatic analysis, miR-199a-5p was selected and found to be increased in EVs from HSA-induced HK-2 cells and in urinary EVs from DM patients with macroalbuminuria. Tail-vein injection of DM mice with EVs from HSA-induced HK-2 cells induced kidney macrophage M1 polarization and accelerated the progression of DKD through miR-199a-5p. miR-199a-5p exerted its effect by targeting Klotho, and Klotho induced macrophage M2 polarization through the Toll-like receptor 4 (TLR4) pathway both in vivo and in vitro. In summary, miR-199a-5p from HSA-stimulated HK-2 cell-derived EVs induces M1 polarization by targeting the Klotho/TLR4 pathway and further accelerates the progression of DKD.

Abstract

This study aims to investigate the impact of ACE (rs4343) and AT1R (rs 5182) genetic polymorphisms on the outcome of acute coronary syndrome (ACS) in patients on captopril. Two hundred and fifty participants with ACS were included in this study (Group 1 (120) participants on captopril 25?mg twice daily and Group 2 (130) participants received no captopril (control study)). Participants were genotyped for ACE (rs4343) and AT1R (rs5182) polymorphisms and the phenotype was determined. ACE polymorphism (rs 4343) GG and GA genotypes are more related to STEMI (OR?=?1.7, 1.5 respectively) and NSTEMI (OR?=?3, 3.8 respectively), and they were more prone to have Percutaneous Coronary Intervention after ACS attack (OR?=?11.6, 14.1 respectively).

AT1R (rs 5182) CT genotype is mildly associated with STEMI (OR?=?1.1), but also prone to have PCI after ACS attack (OR?=?1.6) while TT genotype has a risk to get less improvement (OR?=?1.8).

Abstract

Macrophages infiltrated in adipose tissue play a key role in obesity. Some traditional pharmaceutical compounds may shift the polarization of recruited macrophages to improve metabolic homeostasis. TanshinoneⅡA (TAN2A) is a major active component of Salvia miltiorrhiza, a traditional anti-inflammatory cardiovascular medicine. In our study, we firstly constructed a phenanthroimidazole derivative of TAN2A named TAN20 by chemical synthesis, then identified its structure by chromatography and hydrogen spectroscopy, and finally examined its effects on immunometabolic responses. We found that TAN20 significantly induced the alternatively-activated (M2) rather than the classically-activated macrophages (M1), mainly through releasing the type II cytokines. Such effects were more pronounced than that from TAN2A. Compared to TAN2A, TAN20 substantially reduced body weight, decreased serum free fatty acid and HOMA-IR, and increased insulin sensitivity in obesity-induced diabetic mice. These effects of TAN20 were further validated on diabetic cynomolgus monkeys, which are closer to human physiological conditions. Taken together, our findings explicitly showed that TAN20 significantly polarized the macrophage and improved metabolic homeostasis in obesity-induced diabetic models, suggesting that TAN20 may be a potential drug against diabetes and obesity.

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