The tragic fate of group 3 innate lymphoid cells during HIV-1 infection

HIV-1 infection usually leads to systemic chronic inflammation that is associated with gut microbial translocation. The recently defined group 3 innate lymphoid cells (ILC3s) are critical for maintenance of intestinal barrier function; however, it is not clear whether and how HIV-1 infection influences the function of these cells. In this issue of the JCI, Zhang and colleagues present compelling evidence that the survival and function of ILC3s are dramatically impaired by HIV-1 infection. The authors provide evidence that HIV-1 infection induces persistent activation of plasmacytoid dendritic cells (pDCs) and production of type I IFNs, which together increase expression of death receptor CD95 on ILC3s and thereby promote subsequent ILC3 apoptosis. Together, these results identify a mechanism that explains the impaired intestinal barrier function that results from chronic HIV-1 infection and shed light on the role of pDCs in HIV-1 immunopathogenesis and therapy.     

Targeting USP1‐dependent KDM4A protein stability as a potential prostate cancer therapy

The histone demethylase lysine‐specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48‐linked deubiquitin and stability. Interestingly, we found c‐Myc was a key downstream effector of the USP1‐KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC.     

Urinary Cyclophilin A as a New Marker for Diabetic Nephropathy: A Cross-Sectional Analysis of Diabetes Mellitus

Type 2 diabetes mellitus (DM) is the most common single cause of end-stage renal disease. Albuminuria is the most commonly used marker to predict onset of diabetic nephropathy (DN) without enough sensitivity and specificity to detect early DN. This is the first study to identify urinary cyclophilin A (CypA) as a new biomarker for early DN.We recruited DM outpatients and healthy control subjects from January 2014 to December 2014. In this cross-sectional study, patients’ urine samples were collected to determine the expression of urinary CypA. We also treated mesangial (MES-13) and tubular (HK-2) cells with glucose or free radicals to observe the expression of secreted CypA in Western blot analysis.A total of 100 DN patients and 20 healthy control subjects were enrolled. All variables were matched. In univariate analysis, the concentration of urinary CypA correlated well with the progression of renal function. A significant increase in urinary CypA was noted in stage 2 DN and persisted in later stages. We could diagnose stage 2 DN using urinary CypA with a sensitivity of 90.0% and specificity of 72.7%. The area under curve was up to 0.85, indicating a good discriminatory power. In cellular models, MES-13 and HK-2 cells can both release CypA.Urinary CypA is a good biomarker for early DN detection in humans and it can be released from either mesangial or tubular cells. The underlying molecular mechanisms still need further clarification in cellular and animal studies.     

Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies

The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC₆₀) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity.     

以格林模式为指导的健康宣教对尖锐湿疣患者情绪及自我效能的影响

目的探讨以格林模式为指导的健康宣教对尖锐湿疣患者情绪及自我效能的干预作用。方法将220例尖锐湿疣患者按就诊时间分为两组,各110例。对照组予以常规护理干预,观察组在此基础上实施以格林模式为指导的健康宣教,观察6个月,治疗后随访6个月统计复发率。干预前后采用医院自制尖锐湿疣患者健康知识调查问卷调查健康知识掌握情况,采用焦虑自评量表、抑郁自评量表评定焦虑、抑郁情绪,采用医学应对问卷评定应对方式,采用一般自我效能感量表评定自我效能。干预后采用纽卡斯尔护理满意度量表评定护理满意度。结果干预后观察组尖锐湿疣患者健康知识调查问卷总分及尖锐湿疣疾病知识、自我保健知识评分显著高于对照组(P<0.01),焦虑自评量表、抑郁自评量表评分显著低于对照组(P<0.01)。干预后观察组一般自我效能感量表评分及医学应对问卷的面对、自我效能评分显著高于对照组(P<0.01),回避、屈服评分显著低于对照组(P<0.01)。观察组复发率显著低于对照组(P<0.05),总满意率显著高于对照组(P<0.01)。结论以格林模式为指导的健康宣教能提高尖锐湿疣患者健康知识掌握度及自我效能水平,有效缓解其不良情绪,改变其应对方式,降低复发率,提高患者满意度。