The mechanism of the NFAT transcription factor family involved in oxidative stress response.

As a transcriptional activator widely expressed in various tissues, nuclear factor of activated T cells (NFAT) is involved in the regulation of the immune system, the development of the heart and brain systems, and classically mediating pathological processes such as cardiac hypertrophy. Oxidative stress is an imbalance of intracellular redox status, characterized by excessive generation of reactive oxygen species, accompanied by mitochondrial dysfunction, calcium overload, and subsequent lipid peroxidation, inflammation, and apoptosis. Oxidative stress occurs during various pathological processes, such as chronic hypoxia, vascular smooth muscle cell phenotype switching, ischemia-reperfusion, and cardiac remodeling. Calcium overload leads to an increase in intracellular calcium concentration, while NFAT can be activated through calcium-calcineurin, which is also the main regulatory mode of NFAT factors. This review focuses on the effects of NFAT transcription factors on reactive oxygen species production, calcium overload, mitochondrial dysfunction, redox reactions, lipid peroxidation, inflammation, and apoptosis in response to oxidative stress. We hope to provide a reference for the functions and characteristics of NFAT involved in various stages of oxidative stress as well as related potential targets.

Molecular regulatory mechanism of LILRB4 in the immune response.

Immune diseases are caused by the imbalance of immune regulation. This imbalance is regulated by many factors, both negative and positive. Leukocyte immunoglobulin-like receptor B4 (LILRB4) is a member of leukocyte immunoglobulin-like receptors (LILRs). LILRs are expressed constitutively on the surface of multiple immune cells which associate with membrane adaptors to signal through multi- ple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or immunoreceptor tyro-sine-based activation motifs (ITAMs). Through ITIM, LILRB4 could recruit the src homology domain type-2-containing tyrosine phosphatase 1 or 2 (SHP-1 or SHP-2) into the cell membrane. In addition, many factors can induce the expression of LILRB4, such as vitamin D, interferon and so on. Studies have demonstrated that LILRB4 had a negative regulatory role in various of immune diseases. The present review intends to expound the structure and function of LILRB4, as well as its regulators and receptors in the immune cells, so as to provide a theoretical basis for immune disease therapy.

Research progress of B subfamily of leucocyte immunoglobulin-like receptors in inflammation.

Leucocyte immunoglobulin-like receptors subfamily B (LILRB) belongs to the type I transmembrane glycoproteins, which is the immunosuppressive receptor. LILRBs are widely expressed in bone marrow cells, hematopoietic stem cells, nerve cells and other body cells. Studies have found that LILRBs receptor can bind to a variety of ligands and has a variety of biological functions such as regulating inflammatory response, immune tolerance and cell differentiation. Inflammatory reaction plays a vital role in resisting microorganisms. The function of inhibitory immune receptors can recognize the signs of infection and promote the function of anti-microbial effect. The inflammatory response must be strictly regulated to prevent excessive inflammation and tissue damage. Therefore, it is of general interest to understand the role of LILRBs in the inflammatory response. Because they can inhibit the anti-microbial response of neutrophils, some human pathogens use these receptors to escape immunity. This article reviews the biological role of LILRBs in the inflammatory response. We focus on the known ligands of LILRBs, their different roles after binding with ligands, and how these receptors help to form neutrophil responses during infection. Recent studies have shown that LILRBs recruit phosphatases through intracellular tyrosine-based immunoreceptor inhibitory motifs to negatively regulate immune activation, thereby transmitting inflammation-related signals, suggesting that LILRBs may be an ideal target for the treatment of inflammatory diseases. Here, we describe in detail the regulation of LILRBs on the inflammatory response, its signal transduction mode in inflammation, and the progress in the treatment of inflammatory diseases, providing a reference for further research.

Mesenchymal stem cells ameliorate renal fibrosis by galectin-3/Akt/GSK3ß/Snail signaling pathway in adenine-induced nephropathy rat.

BACKGROUND: Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics. METHODS: TIF model was induced by adenine gavage. Bone marrow-derived MSCs was injected by tail vein after modeling. Renal function and fibrosis related parameters were assessed by Masson, Sirius red, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry. Further possible mechanism was explored by transfected galectin-3 gene for knockdown (Gal-3 KD) and overexpression (Gal-3 OE) in HK-2 cells with lentiviral vector. RESULTS: MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-ß1, Kim-1, p-Smad2/3, IL-6, IL-1ß, and TNFα compared with model rats, while p38 MAPK increased. Proteomics showed that only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared MSCs group with the model group. Galectin-3 was downregulated significantly in renal tissues and TGF-ß1-induced rat tubular epithelial cells and interstitial fibroblasts, consistent with the iTRAQ results. Gal-3 KD notably inhibited the expression of p-Akt, p-GSK3ß and snail in TGF-ß1-induced HK-2 cells fibrosis. On the contrary, Gal-3 OE obviously increased the expression of p-Akt, p-GSK3ß and snail. CONCLUSION: The mechanism of MSCs anti-renal fibrosis was probably mediated by galectin-3/Akt/GSK3ß/Snail signaling pathway. Galectin-3 may be a valuable target for treating renal fibrosis.

The effects of low-carbohydrate diets on cardiovascular risk factors: A meta-analysis.

BACKGROUND: Low-carbohydrate diets are associated with cardiovascular risk factors; however, the results of different studies are inconsistent. PURPOSE: The aim of this meta-analysis was to assess the relationship between low-carbohydrate diets and cardiovascular risk factors. METHOD: Four electronic databases (PubMed, Embase, Medline, and the Cochrane Library) were searched from their inception to November 2018. We collected data from 12 randomized trials on low-carbohydrate diets including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, and blood pressure levels, as well as weight as the endpoints. The average difference (MD) was used as the index to measure the effect of a low-carbohydrate diet on cardiovascular risk factors with a fixed-effects model or random-effects model. The analysis was further stratified by factors that might affect the results of the intervention. RESULTS: From 1292 studies identified in the initial search results, 12 randomized studies were included in the final analysis, which showed that a low-carbohydrate diet was associated with a decrease in triglyceride levels of -0.15mmol/l (95% confidence interval -0.23 to -0.07). Low-carbohydrate diet interventions lasting less than 6 months were associated with a decrease of -0.23mmol/l (95% confidence interval -0.32 to -0.15), while those lasting 12-23 months were associated with a decrease of -0.17mmol/l (95% confidence interval -0.32 to -0.01). The change in the body weight in the observation groups was -1.58kg (95% confidence interval -1.58 to -0.75); with for less than 6 months of intervention,this change was -1.14 kg (95% confidence interval -1.65 to -0.63),and with for 6-11 months of intervention, this change was -1.73kg (95% confidence interval -2.7 to -0.76). The change in the systolic blood pressure of the observation group was -1.41mmHg (95% confidence interval-2.26 to -0.56); the change in diastolic blood pressure was -1.71mmHg (95% confidence interval-2.36 to -1.06); the change in plasma HDL-C levels was 0.1mmHg (95% confidence interval 0.08 to 0.12); and the change in serum total cholesterol was 0.13mmol/l (95% confidence interval 0.08 to 0.19). The plasma LDL-C level increased by 0.11mmol/l (95% confidence interval 0.02 to 0.19), and the fasting blood glucose level changed 0.03mmol/l (95% confidence interval -0.05 to 0.12),which was not significant. CONCLUSIONS: This meta-analysis confirms that low-carbohydrate diets have a beneficial effect on cardiovascular risk factors but that the long-term effects on cardiovascular risk factors require further research.