The oncogenic impact of RNF2 on cell proliferation,invasion and migration through EMT on mammary carcinoma

Mammary carcinoma (MC) is one of most common malignancy in women, and ring finger protein 2 (RNF2) possesses various roles in vast human tumors. In MC tissues as well as in cell lines RNF2 exhibited high expression, had significant association with tumor size, lymph node status, TNM stage, patients’ poor survival, and promoted cell proliferation, colony formation, cell migration and invasion of MC cell lines which was mediated by downregulation of E-cadherin protein. These data reveal that RNF2 protein plays a vital role in the development of MC and may be a potential therapy target of MC.     

Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

Moderate protection is induced by a chimeric protein composed of leucine aminopeptidase and cathepsin L1 against Fasciola hepatica challenge in sheep

Leucine aminopeptidase (FhLAP) and cathepsin L1 (FhCL1) of Fasciola hepatica play a critical role in parasite feeding, migration through host tissue, and immune evasion. These antigens have been tested for immune protection as single components with variable degrees of success. The chimeric-protein approach could improve protection levels against fasciolosis. Previously, we reported the design and construction of a chimeric protein composed of antigenic sequences of FhLAP and FhCL1 of F. hepatica. The goal of the present study was to express and evaluate the immune-protective capacity of this chimeric protein (rFhLAP-CL1) in sheep. Animals were randomly allocated into five groups with five animals in each group. Groups 1, 2 and 3 were immunized twice with 100 μg, 200 μg and 400 μg of rFhLAP-CL1 emulsified with Quil A adjuvant, whereas groups 4 and 5 were the adjuvant control and infection control groups, respectively. The animals were then challenged with 200 metacercariae two weeks after the rFhLAP-CL1 booster. The fluke burden was reduced by 25.5%, 30.7% (p < 0.05) and 46.5% (p < 0.01) in sheep immunized with 100 μg, 200 μg and 400 μg of chimeric protein, respectively, in comparison to the infection control group. There was a reduction of 22.7% (p < 0.05) and 24.4% (p < 0.01) in fecal egg count in groups 2 and 3, respectively, compared to the infection control group. Sheep immunized with chimeric protein produced F. hepatica excretion-secretion product-specific total IgG antibody, which were increased after challenge. Moreover, the levels of rFhLAP-CL1-specific IgG1 and IgG2 isotypes in immunized sheep increased rapidly two weeks after the first immunization and were significantly more elevated than those of the control groups, indicating a mixed Th1/Th2 response. This is a preliminary evaluation of the chimeric protein rFhLAP-CL1 as a possible immunogen against F. hepatica infection in sheep.     

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

2型糖尿病患者不同脂质参数与糖尿病肾病的关系

目的:探讨2型糖尿病(T2DM)患者不同脂质参数与糖尿病肾病(DKD)发生的相关性。方法:检测226例T2DM患者血清TC、TG、LDL-C、HDL-C水平及相关生化指标,计算血浆致动脉硬化指数(AIP)以及脂质三角相关指标(TC/HDL-C、TG/HDL-C、LDL-C/HDL-C)。根据DKD临床诊断标准和Mogensen分期标准分为:Ⅰ~Ⅱ期组136例,Ⅲ期组55例,Ⅳ~Ⅴ期组35例。应用多因素logistic回归分析不同脂质参数与DKD发生的关系。结果:与Ⅰ~Ⅱ期组相比,随着DKD分期加重,TC、TG、LDL-C、LDL-C/HDL-C、AIP水平明显增高(P<0.01)。LDL-C/HDL-C和AIP与24 h尿蛋白水平呈正相关(r=0.724;r=0.769,均P<0.05)。LDL-C/HDL-C和AIP是T2DM合并DKD患者的独立预测因子(P=0.002;P=0.004)。结论:LDL-C/HDL-C和AIP对T2DM合并DKD病情进展有较高的预测价值,可为临床诊治提供参考。     

Magnesium lithospermate B acts against dextran sodiumsulfate-induced ulcerative colitis by inhibiting activation of the NRLP3/ASC/Caspase-1 pathway

This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.     

IFI 30、PD-L1在人脑胶质瘤中的表达及与病人预后的关系

目的 探讨γ干扰素诱导蛋白30（IFI 30）、程序性死亡因子配体1（PD-L1）在人脑胶质瘤中的表达及与病人预后的关系。方法 选择2015年5月~2019年5月手术切除的103例人脑胶质瘤组织和瘤旁组织，采用免疫组织化学染色检测IFI 30、PD-L1表达情况。随访24个月，记录无进展生存期和总生存期。结果 胶质瘤组织IFI 30、PD-L1高表达率[分别为70.87%（73/103）、68.93%（71/103）]明显高于瘤旁组织[分别为19.42%（20/103）、21.36%（22/103）；P<0.001]。胶质瘤组织IFI 30表达水平与PD-L1表达水平呈明显正相关（r=0.583，P<0.05）。随访24个月，生存75例，死亡28例；多因素logistic回归分析显示，IFI 30高表达、PD-L1高表达是增加病人死亡风险的独立危险因素（P<0.05）。生存曲线分析显示，IFI 30高表达组2年累积生存率（64.52%）和2年累积无进展生存率（65.56%）均明显低于低表达组（分别为82.25%、89.45%；P<0.05）。PD-L1高表达组2年累积生存率（61.78%）和2年累积无进展生存率（60.14%）均明显低于低表达组（分别为88.52%、79.86%；P<0.05）。结论 人脑胶质瘤组织IFI 30、PD-L1呈高表达，与病人不良预后密切相关。