Increased expression of GAB1 promotes inflammation and fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2‐associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)‐induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6‐fold higher in peripheral blood mononuclear cells (PBMC), 2.5‐fold higher in CD4 + T cells, and 2‐fold higher in skin from of SSc patients (P < .01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8‐fold higher) in SSc skin. Additionally, BLM‐induced SSc mice showed mRNA levels of Gab1 2‐fold higher than saline‐treated controls, and Gab1 expression correlated positively with collagen content. A further in vitro study showed silencing of GAB1 suppressed inflammatory gene expression in TNF‐α induced fibroblasts. Additionally, GAB1 deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF‐β induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes.     

Modulating effects of preconditioning exercise in the expression of ET-1 and BNP via HIF-1α in ischemically injured brain

It is well-known that in ischemia-induced hypoxia, hypoxia-inducible factor -1α (HIF-1α) is critical in triggering expression of its downstream target genes to produce several products, such as erythropoietin (EPO), vascular endothelial growth factor (VEGF), nitric oxide synthesis (NOS), glucose transportor-1 (GLUT-1), insulin-like growth factor (IGF), which further promote erythropoiesis, angiogenesis, vasodilation and capitalization of glucose to overcome hypoxia. Meanwhile, as the factors with opposite effects on blood vessels, endothelin-1 (ET-1) and brain natriuretic peptide (BNP) also stand out strikingly in ischemic pathophysiology. To this day, several preconditioning manners have been used to induce tolerance to ischemia. During our research, exercise preconditioning was applied and it was demonstrated that HIF-1α triggered expression of ET-1 and BNP, which confirmed their downstream target genes for HIF-1α. And ET-1 may influcence expression of BNP to some degree but not the only factor which regulates BNP expression. Therefore, our findings suggest exercise preconditioning may provide protection to the ischemic brain tissue via HIF-1α which in turn increases expression of BNP to cause vasodilation in cooperation with some other factors, such as VEGF and EPO, to increase the blood flow in the ischemic area and then relieve the injuries induced by ischemia.

     

Relationship between rosacea and dietary factors: A multicenter retrospective case–control survey

Although patients with rosacea often consult dermatologists for dietary factors that might be related to their skin disorders, few studies have been conducted to research the relationship between rosacea and dietary factors. The purpose of this study was to evaluate the potential relationship between rosacea and diet among the large Chinese population with rosacea, which would provide dietary guidelines for patients with rosacea. A multicenter case–control study was conducted. The feeding frequency 2 years before the occurrence of rosacea was collected by standardized questionnaires. Multiple logistic regression analysis was used to calculate risks related to the diet. One thousand three hundred and forty‐seven patients with rosacea and 1290 controls were enrolled in our study. We found that high‐frequency intake of fatty food and tea presented a positive correlation with rosacea, while high‐frequency dairy product intake showed significant negative correlation with rosacea. Sweet food, coffee and spicy food appeared to be independent of any subset of rosacea in our study. However, high‐frequency dairy product intake showed a borderline beneficial effect on rosacea severity. We further analyzed the correlation between diet and the subtype of rosacea. We found that high‐frequency fatty intake was associated with erythematotelangiectatic rosacea (ETR) and phymatous rosacea, while high‐frequency tea intake was only associated with ETR. In addition, high‐frequency dairy product intake showed negative correlations with ETR and papulopustular rosacea. Rosacea is associated with some dietary factors, and our study is valuable in establishing dietary guidelines to prevent and improve rosacea.     

左、右半结肠癌骨转移病理特征及预后分析

目的:比较左半结肠癌（LSCC）和右半结肠癌（RSCC）骨转移的病理特征和临床预后差异。方法:对漯河市中心医院2007年1月至2015年12月收治的103例结肠癌骨转移病例资料进行回顾性分析，据解剖位置将64例纳入LSCC组，39例纳入RSCC组，对比分析其病理学特征,绘制并分析生存曲线,筛选预后因素。结果:RSCC骨转移相对LSCC表现为:CA199 阳性率高、年龄大、分化程度更差、分期更晚、预后更差。单因素分析结果示原发肿瘤位置、TNM分期、LDH水平、ALP水平是影响结肠癌骨转移3年生存的相关因素。Logistic多因素回归分析显示原发肿瘤位置、TNM分期、ALP水平是结肠癌骨转移的独立危险因素。结论:左、右半结肠癌在病理特点、临床表现、生物学行为、生存预后等方面存在差异，本文为区分左、右半结肠癌骨转移的不同病理特征及预后评价提供了依据。     

Profilin 1, negatively regulated by microRNA-19a-3p,serves as a tumor suppressor in human hepatocellular carcinoma

Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients.     

miR-34c-3p与M2型肿瘤相关巨噬细胞在三阴性乳腺癌中的表达及意义

目的:检测miR-34c-3p与M2型肿瘤相关巨噬细胞（tumor-associated macrophage,TAM)在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达，并探讨其在乳腺癌发病中的意义。方法:选择2017年2月至2018年1月于西京医院就诊的68例TNBC患者作为实验组(A组)，以同期就诊的70例乳腺纤维腺瘤患者作为对照组(B组)。采用Real-time RT-PCR 检测组织标本中miR-34c-3p的表达；流式细胞检测M2型TAM的表达；ELISA法检测血清中IL-10的表达。并进一步分析miR-34c-3p的表达与乳腺癌M2型TAM及血清IL-10水平的相关性。结果:A、B组miR-34c-3p的相对表达量分别为0.84±0.08、1.29±0.71，A组明显低于B组，差异有统计学意义(P<0.05)。与B组比较，A组M2型TAM(CD68+CD163+)细胞比例显著升高(P<0.05)。A组血清IL-10的表达［(19.69±4.93) pg/ml］较B组［(17.26±3.51) pg/ml］显著升高，差异有统计学意义(P<0.05)。TNBC组织中miR-34c-3p的表达与M2型TAM比例及血清IL-10表达均呈显著负相关(r=-0.508，r=-0.656，P<0.05)。结论:TNBC组织中miR-34c-3p的表达下调，M2型TAM比例及血清IL-10表达均显著升高，促进TNBC进展。