ATGL and CGI-58 are lipid droplet proteins of the hepatic stellate cell line HSC-T6

Lipid droplets (LDs) of hepatic stellate cells (HSCs) contain large amounts of vitamin A [in the form of retinyl esters (REs)] as well as other neutral lipids such as TGs. During times of insufficient vitamin A availability, RE stores are mobilized to ensure a constant supply to the body. To date, little is known about the enzymes responsible for the hydrolysis of neutral lipid esters, in particular of REs, in HSCs. In this study, we aimed to identify LD-associated neutral lipid hydrolases by a proteomic approach using the rat stellate cell line HSC-T6. First, we loaded cells with retinol and FAs to promote lipid synthesis and deposition within LDs. Then, LDs were isolated and lipid composition and the LD proteome were analyzed. Among other proteins, we found perilipin 2, adipose TG lipase (ATGL), and comparative gene identification-58 (CGI-58), known and established LD proteins. Bioinformatic search of the LD proteome for α/β-hydrolase fold-containing proteins revealed no yet uncharacterized neutral lipid hydrolases. In in vitro activity assays, we show that rat (r)ATGL, coactivated by rat (r)CGI-58, efficiently hydrolyzes TGs and REs. These findings suggest that rATGL and rCGI-58 are LD-resident proteins in HSCs and participate in the mobilization of both REs and TGs.     

Testosterone levels and cognitive functioning in women with polycystic ovary syndrome and in healthy young women

We investigated the possible influence of testosterone (T) on cognitive functioning in women with polycystic ovary syndrome (PCOS), an endocrine disorder associated with elevated levels of free testosterone (free T). Performance on a battery of neuropsychological tests in 29 women with elevated free T levels due to PCOS was compared to the performance of 22 age- and education-matched, healthy control women with free T levels in the normal female range. Women with PCOS had significantly higher levels of free T (estimated by the free androgen index) and demonstrated significantly worse performance on tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory than the healthy control women. No differences between the groups were found on tests of mental rotation, spatial visualization, spatial perception, or perceptual speed. These results suggest that, in women, elevations in free T may be associated with poorer performance on cognitive tasks that tend to show a female advantage.     

心理应激对小鼠脂肪组织黄嘌呤氧化酶表达、活性及相关指标的影响*

目的:探讨心理应激对小鼠脂肪组织黄嘌呤氧化酶表达、活性及相关指标的作用。方法:雄性无特定病原体(SPF)级20只昆明小鼠随机分2组(每组10只),即慢性束缚应激(Stress)组和正常对照(Control)组。Stress组小鼠每天在自制式束缚器中限制活动2 h,其余时间两组小鼠在相同环境中自由饮水摄食,实验持续14 d,取血和白色脂肪组织(WAT);观察脂肪组织病理学改变,检测WAT中黄嘌呤氧化酶(XO)和烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(Nox-4)的蛋白水平,检测WAT组织中XO、Nox-4、超氧化物歧化酶(Mn SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、脂联素(ADPN)、单核细胞趋化蛋白1(MCP-1)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)、胰岛素受体底物1(IRS-1)、葡萄糖转运蛋白4(GLUT-4)、组织因子(TF)、纤溶酶原激活物抑制物1(PAI-1)的mRNA表达,检测血清和WAT组织中XO酶活性以及血清甘油三酯(TG)、总胆固醇(T-Cho)、游离脂肪酸(FFA)、尿酸(UA)的含量。结果:与control组比较,stress小鼠腹股沟WAT组织中XO免疫染色阳性着色细胞黄褐色沉淀深且丰富,WAT中出现大量的单核细胞、中性粒细胞、嗜酸性粒细胞及浆细胞浸润反应和炎症性的改变;血清XO浓度、WAT组织中XO mRNA水平和XO的酶活性显著升高(P＜0.01),血清游离脂肪酸(FFA)和尿酸(UA)的含量显著增高(P＜0.01),WAT组织中Nox-4蛋白、MCP-1、IL-6、TNF-α、TF、PAI-1mRNA的表达水平显著增高(P＜0.01),而Mn-SOD、GSH-Px、CAT、ADPN、IRS-1和GLUT-4的mRNA水平则显著降低(P＜0.01)。结论:心理应激可诱发脂肪XO过量表达及其活性增高,进而引起脂肪炎症、糖代谢及凝血酶原异常等反应。     

The prognostic value of the neutrophil/lymphocyte ratio in patients with snake bites for clinical outcomes and complications

IntroductionSnake bites have cardiotoxicity, neurotoxic, myotoxic, nephrotoxic, and hemotoxic features. The neutrophil/lymphocyte ratio (NLR) provides valuable information for the determination of the diagnosis and prognosis of various diseases. In this study, we aimed to investigate the relationship between NLR with the development of complications and duration of hospital stay in snakebite cases.MethodIn this study, 107 patients with snakebite complaints that applied to a tertiary care university hospital between 2011 and 2014 were retrospectively reviewed. The control group compromised of 107 age-and gender-matched healthy subjects. These patients were examined using their previous laboratory results, bite areas pictures, geographic location, and analysis of complications that developed during the hospitalization.ResultsPatients in our snake bites group (n = 107), included males (64%) and females (36%). When NLR1–NLR2, NLR1–NLR3, and NLR2–NLR3 were compared, a statistically significant difference was found (p < 0.001). No mortality was observed in our patients. In cases of snakebites, 4.67% of the patients underwent finger amputation. Compartment syndrome occurred in 3.73% of patients. In one case that developed compartment syndrome, a finger amputation was made. When 8 patients with a complication were compared with patients having snakebite but no complication, the initial NLR was found to be higher and statistically significant (p = 0.042). The average length of stay of patients in the hospital was 9 days. In the analysis of the correlation between the duration of hospitalization and NLR, the patients with a high level of NLR were found to have a longer hospital stay compared to lower NLR levels (p = 0.012).ConclusionNLR was significantly increased in patients that developed complications and needed a longer stay in the hospital.     

A phase II randomized clinical trial for the treatment of recalcitrant chronic leg ulcers using centrifuged adipose tissue containing progenitor cells

Background aims

Preclinical and observational reports indicate that adipose tissue (AT) is a safe and promising tool to treat non-healing venous leg ulcers (VLUs).

Proteasome Inhibitor PS-341 Effectively Blocks Infection by the Severe Fever with Thrombocytopenia Syndrome Virus

Severe fever with thrombocytopenia syndrome(SFTS) is an emerging hemorrhagic fever disease caused by SFTSV, a newly discovered phlebovirus that is named after the disease. Currently, no effective vaccines or drugs are available for use against SFTSV infection, as our understanding of the viral pathogenesis is limited. Bortezomib(PS-341), a dipeptideboronic acid analog, is the first clinically approved proteasome inhibitor for use in humans. In this study, the antiviral efficacy of PS-341 against SFTSV infection was tested in human embryonic kidney HEK293 T(293 T) cells. We employed four different assays to analyze the antiviral ability of PS-341 and determined that PS-341 inhibited the proliferation of SFTSV in 293 T cells under various treatment conditions. Although PS-341 did not affect the virus absorption, PS-341 treatment within a non-toxic concentration range resulted in a significant reduction of progeny viral titers in infected cells.Dual-luciferase reporter assays and Western blot analysis revealed that PS-341 could reverse the SFTSV-encoded nonstructural protein(NS) mediated degradation of retinoic acid-inducible gene-1(RIG-I), thereby antagonizing the inhibitory effect of NSs on interferons and blocking virus replication. In addition, we observed that inhibition of apoptosis promotes virus replication. These results indicate that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections.     

多囊卵巢综合征肥胖患者血清维生素D、铁蛋白水平、sICAM-1与胰岛素抵抗、糖脂代谢指标的相关性

摘要 目的：探讨多囊卵巢综合征（PCOS）肥胖患者血清维生素D、铁蛋白、可溶性细胞间粘附分子-1（sICAM-1）水平与胰岛素抵抗、糖脂代谢指标的相关性。方法：2018年8月到2021年11月,选择在本院妇科诊治的PCOS患者65例作为研究对象,分为PCOS肥胖组（n=30,体重指数＜28 kg/m²）和PCOS非肥胖组（n=35,体重指数<28 kg/m²）。检测与计算两组清维生素D、铁蛋白、sICAM-1、胰岛素抵抗、糖脂代谢指标并进行相关性分析。结果：两组的血清甲状腺素（T4）、促甲状腺激素（TSH）与泌乳素（PRL）对比差异无统计学意义（P>0.05）,肥胖组的血清促黄体生成素（LH）、促卵泡生成素（FSH）、睾酮（T）水平高于非肥胖组（P<0.05）。肥胖组的血清铁蛋白、sICAM-1水平高于非肥胖组,血清维生素D水平低于非肥胖组（P<0.05）。肥胖组的胰岛素抵抗指数（HOMA-IR）、胰岛素水平（FINS）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）较非肥胖组,高密度脂蛋白胆固醇（HDL-C）低于非肥胖组（P<0.05）。在PCOS肥胖患者中,Pearson分析显示血清维生素D、铁蛋白、sICAM-1与胰岛素抵抗、糖脂代谢指标都存在相关性（P<0.05）。结论：PCOS肥胖患者与非肥胖患者的血清维生素D、铁蛋白、sICAM-1、胰岛素抵抗、糖脂代谢指标水平存在差异,血清维生素D、铁蛋白、sICAM-1水平与胰岛素抵抗、糖脂代谢指标存在相关性。