Regulatory T Cells Accelerate the Repair Process of Renal Fibrosis by Regulating Mononuclear Macrophages.

BACKGROUND: We aimed to investigate the mechanisms of renal fibrosis and explore the effect of CD4+CD25+Foxp3+ regulatory T cells (Treg) on renal fibrosis after the obstruction was removed. METHODS: Fifty-five C57BL/6 mice were randomly divided into three groups: the unilateral ureteral obstruction (UUO) group, the relief for unilateral ureteral obstruction (RUUO) group, and the RUUO+Treg group. Renal fibrosis indexes of RUUO mice were evaluated using hematoxylin and eosin (HE) and, Masson staining and immunohistochemistry after CD4+CD25+Treg cells were injected into the tail vein at the moment of recanalization. We detected the levels of Treg, M1, and M2 markers by flow cytometry, and the levels of transforming growth factor (TGF)-ß1, interleukin (IL)-1ß, IL-6 and IL-10 using ELISA. RESULTS: The tubular necrosis score, AO value of α-SMA (smooth muscle actin), and collagen area on the 3rd and 14th days post RUUO were up-regulated compared with the 7th day post RUUO (P<0.05). After injection of Treg via tail vein, the tubular necrosis score, AO value of α-SMA, TGF-ß1 level, and collagen area in the RUUO+Treg group on the 14th day were down-regulated compared with the RUUO group (P<0.05). Moreover, Treg could transform M1 macrophages into M2 macrophages, manifesting as up-regulated expression of CD206 compared with the RUUO group (P<0.05). Treg could also down-regulate the secretion of IL-6 and IL-1ß while up-regulating the secretion of IL-10 in vitro compared with the M1 group (P<0.05). CONCLUSIONS: The kidney could deteriorate into a state of injury and fibrosis after the obstruction was removed, and Treg could effectively protect the kidney function.

Role of GPR40 in pathogenesis and treatment of Alzheimer's disease and type 2 diabetic dementia.

G-protein coupled receptor 40 (GPR40) is also known as free fatty acid receptor 1. It is a typical 7 transmembrane receptor and currently the natural receptor of the saturated or unsaturated long-chain fatty acids. It could trigger the intracellular signalling pathway when combined with the free long-chain fatty acids, thereby controlling cells physiological function. In this review, we summarised the relationships and the potential mechanisms between the promising target GPR40, and pathogenesis and treatment of Alzheimer's disease and type 2 diabetic dementia. It may provide a theoretical reference for the development of clinical drug targeting GPR40.

Melatonin ameliorates Aß1-42 -induced Alzheimer's cognitive deficits in mouse model.

OBJECTIVES: The objective of this study was to evaluate whether melatonin could ameliorate cognitive function in Aß1-42 -induced mouse model and its underlying mechanisms. METHODS: Series behaviour tests were performed to demonstrate the amelioration of cognitive function of the Alzheimer's disease (AD) mice induced by Aß1-42 . Additionally, enzyme-linked immunosorbent assay was applied to detect the expression of Aß1-42 , BACE1 and p-tau protein in the brain of the AD mice. JC-1 was performed to investigate the role in alleviating mitochondrial damage by melatonin in vitro. Western blot was used to detect the expression of melatonin on apoptosis-related factors caspase-3 and Bcl-2, as well as the expressions of GSK-3ß and PP2A to further determine the mechanisms of melatonin on the expression of p-tau protein. KEY FINDINGS: Melatonin significantly ameliorated the cognitive function and mitochondrial damage in AD mice, reduced the expression levels of GSK-3ß, caspase-3, Aß1-42 , BACE1, p-tau protein and increased the expressions of PP2A and Bcl-2. CONCLUSION: From the overall results, we concluded that melatonin alleviated the mitochondrial damage effectively and decreased the expressions of the p-tau and some key proteins of apoptosis, leading to the improvement of cognitive function of the mice induced by Aß1-42 .