Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach

Acute coronary syndrome (ACS) results from inadequate supply of blood flow from the coronary arteries to the heart or ischemia. ACS has an extremely high morbidity and mortality. The levels of biomarkers currently used for detection of ACS also increase in response to myocardial necrosis and other diseases and are not elevated immediately after symptoms appear, thus limiting their diagnostic capacity. Therefore, we aimed to discover new ACS diagnostic biomarkers with high sensitivity and specificity that are specifically related to ACS pathogenesis. Sera from 50 patients with ACS and healthy controls (discovery cohort) each were analyzed using mass spectrometry (MS) to identify differentially expressed proteins, and protein candidates were evaluated as ACS biomarkers in 120 people in each group (validation cohort). α-1-acid glycoprotein 1 (AGP1), complement C5 (C5), leucine-rich α-2-glycoprotein (LRG), and vitronectin (VN) were identified as biomarkers whose levels increase and gelsolin (GSN) as a biomarker whose levels decrease in patients with ACS. We concluded that these biomarkers are associated with the pathogenesis of ACS and can predict the onset of ACS prior to the appearance of necrotic biomarkers.     

LncRNA UCA1 elevates the resistance of human leukemia cells to daunorubicin by the PI3K/AKT pathway via sponging miR-613

Acute leukemia is a hematological malignant tumor. Long non-coding RNA urothelial cancer-associated 1 (UCA1) is involved in the chemo-resistance of diverse cancers, but it is unclear whether UCA1 is associated with the sensitivity of acute leukemia cells to daunorubicin (DNR). DNR (100 nM) was selected for functional analysis. The viability, cell cycle progression, apoptosis, and invasion of treated acute leukemia cells (HL-60 and U-937) were evaluated by cell counting kit-8 (CCK-8) assay, flow cytometry assay, or transwell assay. Protein levels were detected with Western blot analysis. Expression patterns of UCA1 and miR-613 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between UCA1 and microRNA-613 (miR-613) was verified by dual-luciferase reporter assay. We observed that UCA1 expression was elevated in HL-60 and U-937cells. DNR constrained viability, cell cycle progression, invasion, and facilitated apoptosis of HL-60 and U-937 cells in a dose-dependent manner, but these impacts mediated by DNR were reverted after UCA1 overexpression. MiR-613 was down-regulated in HL-60 and U-937 cells, and UCA1 was verified as a miR-613 sponge. MiR-613 inhibitor reversed DNR treatment-mediated effects on viability, cell cycle progression, apoptosis, and invasion of HL-60 and U-937 cells, but these impacts mediated by miR-613 inhibitor were counteracted after UCA1 inhibition. Notably, the inactivation of the PI3K/AKT pathway caused by DNR treatment was reversed after miR-613 inhibitor introduction, but this influence mediated by miR-613 inhibitor was offset after UCA1 knockdown. In conclusion, UCA1 up-regulation facilitated the resistance of acute leukemia cells to DNR via the PI3K/AKT pathway by sponging miR-613.     

脂多糖致急性肺血管内皮屏障功能失调小鼠FLI-1蛋白表达的变化及其意义

目的: 观察感染性急性肺损伤(ALI)肺血管内皮屏障功能失调小鼠肺组织中弗里德白血病病毒插入位点1(FLI-1)蛋白表达的变化,以探讨FLI-1在感染性ALI肺血管内皮屏障功能失调发生发展中的意义。方法: SPF级雄性ICR小鼠60只,腹腔注射脂多糖(LPS,7.5 mg/kg)复制ALI模型,在给予LPS 0 h、12 h、24 h、48 h后,检测小鼠肺血管内皮屏障通透性和肺湿干重比,ELISA法检测肺泡灌洗液中TNF-α和IL-6含量,Western blot法检测肺组织FLI-1和Src酪氨酸激酶(SRC)蛋白的表达。结果: 与0 h组比较,12 h组、24 h组肺血管内皮屏障通透性分别升高74.3%和162.4%,而48 h组较24 h组降低27.0%(P均＜0.05);与0 h组比较,12 h组、24 h组肺湿干重比分别升高50.1%和122.9%,而48 h组较24 h组降低10.7%(P均＜0.05);与0 h组比较,12 h、24 h肺泡灌洗液IL-6和TNF-α含量均显著升高,而48 h肺泡灌洗液IL-6和TNF-α含量较24 h分别下降28.3%和21.6%(P均＜ 0.05);与0 h组比较,12 h组、24 h组肺组织FLI-1蛋白表达水平分别下调20.4%和56.9%,而48 h组较24 h组上调18.2%(P均＜0.05);与0 h组比较,12 h组、24 h组肺组织SRC蛋白表达水平分别上调76.8%和176.7%,而48 h组较24 h组下调33.4%(P均＜0.05);肺血管内皮屏障通透性与FLI-1蛋白表达水平呈显著负相关(r= -0.8992,P＜0.01),而与SRC蛋白表达水平呈显著正相关(r=0.8918,P＜0.01),肺组织FLI-1与SRC蛋白表达呈显著负相关(r=-0.8087,P=0.0014)。结论: FLI-1可能参与LPS诱导的急性肺损伤肺血管内皮屏障功能失常过程。     

金银花提取物对重症急性胰腺炎肺损伤大鼠的保护作用及机制研究

摘要 目的：探讨金银花提取物对重症急性胰腺炎肺损伤大鼠的保护作用及其分子机制。方法：选择60只大鼠并将其分为假手术组、模型组、金银花低剂量组、金银花中剂量组和金银花高剂量组。比较各组的肺组织和胰腺组织病理评分。采用全自动血气分析仪检测各组大鼠血氧分压、二氧化碳分压和氧合指数。采用酶联免疫吸附法检测各组炎症因子[白细胞介素（IL）-1、IL-6和肿瘤坏死因子-α（TNF-α）]水平。免疫印迹法检测各组肺组织中NF-κB通路相关蛋白（p-p65、p-IκBα、p65和IκBα蛋白）水平。结果：与假手术组相比,模型组肺组织和胰腺组织病理评分以及二氧化碳分压明显升高（P<0.05）。与模型组相比,金银花各剂量组肺组织和胰腺组织病理评分以及二氧化碳分压明显下降,并且呈剂量依赖性（P<0.05）。与假手术组相比,模型组血氧分压和氧合指数明显下降（P<0.05）。与模型组相比,金银花各剂量组血氧分压和氧合指数明显升高,并且呈剂量依赖性（P<0.05）。与假手术组相比,模型组IL-1、IL-6和TNF-α水平以及p-p65和p-IκBα蛋白水平明显升高（P<0.05）。与模型组相比,金银花各剂量组IL-1、IL-6和TNF-α水平以及p-p65和p-IκBα蛋白水平明显下降,并且呈剂量依赖性（P<0.05）。结论：金银花提取物对大鼠重症急性胰腺炎肺损伤具有一定保护作用,能够升高血氧分压和氧合指数并降低二氧化碳分压,并且其保护作用可能是通过抑制NF-κB通路介导的促炎症因子IL-1、IL-6和TNF-α的产生,缓解炎症性肺损伤。     

Structure and Function of N-Terminal Zinc Finger Domain of SARS-CoV-2 NSP2

Virologica Sinica - SARS-CoV-2 has become a global pandemic threatening human health and safety. It is urgent to find effective therapeutic agents and targets with the continuous emergence of novel...     

Generation and Characterization of a Nanobody Against SARS-CoV

Virologica Sinica - The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) has caused global panic in 2003, and the risk of SARS-CoV outbreak still exists. However, no...     

醒脑静联合纳洛酮对急性脑出血伴意识障碍患者神经功能、炎性因子和氧化应激的影响

摘要 目的：探讨纳洛酮联合醒脑静对急性脑出血（ACH）伴意识障碍患者炎性因子、神经功能和氧化应激的影响。方法：选取2017年2月~2019年12月期间我院收治的95例ACH伴意识障碍患者,按照随机数字表法将上述患者分为对照组（n=47）和研究组（n=48）,对照组患者予以纳洛酮治疗,研究组则在对照组的基础上联合醒脑静治疗,比较两组患者疗效、神经功能、炎性因子和氧化应激指标,记录两组不良反应发生情况。结果：研究组治疗10 d后的临床总有效率为91.67%（44/48）,高于对照组的74.47%（35/47）（P<0.05）。两组治疗10 d后美国国立卫生研究院卒中量表（NIHSS）评分,白介素-6（IL-6）、C反应蛋白（CRP）以及肿瘤坏死因子-α（TNF-α）、丙二醛（MDA）水平均较治疗前下降,且研究组低于对照组（P<0.05）。两组治疗10 d后超氧歧化酶 (SOD)水平均较治疗前升高,且研究组高于对照组（P<0.05）。两组不良反应发生率对比未见统计学差异（P>0.05）。结论：醒脑静联合纳洛酮治疗ACH伴意识障碍患者,疗效显著,可有效改善患者神经功能、炎性因子和氧化应激,且安全性较好。     

入院时血清钙水平与高血压性脑出血血肿体积、神经功能及预后的关系研究

摘要 目的：探讨入院时血清钙水平与高血压性脑出血血肿体积、神经功能及预后的关系。方法：选择2018年9月-2020年4月我院收治的高血压性脑出血患者102例,根据患者入院时血清钙水平将其分为低血钙组（血清钙<2.1 mmol/L, n=34）、正常血钙组（2.1 mol/L≤血清钙≤2.7 mmol/L, n=39）和高血钙组（血清钙>2.7 mmol/L, n=29）,比较各组性别、血肿体积、入院美国国立卫生研究院卒中量表（NIHSS）评分等临床资料。所有患者随访1年,观察患者格拉斯哥预后量表（GOS）评分,根据患者预后情况将患者分为预后良好组（n=84）和预后不良组（n=18）,比较两组血清钙、血肿体积、入院NIHSS评分、GOS评分。应用受试者工作特征（ROC）曲线分析血清钙水平对患者预后的预测价值。结果：三组血肿体积、入院NIHSS评分、GOS评分、1年病死率、1年再出血率、总预后不良率比较有统计学差异（P<0.05）。预后不良组血清钙水平、GOS评分显著低于预后良好组,血肿体积、入院NIHSS评分显著高于预后良好组（P<0.05）。Pearson相关性分析显示：高血压性脑出血患者入院时血清钙水平与脑出血血肿体积、入院NIHSS评分呈负相关,与GOS评分呈正相关（P＜0.05）。ROC曲线分析显示入院时血清钙预测高血压脑出血不良预后的曲线下面积为0.129（95%CI：0.073~0.179）。结论：高血压性脑出血患者入院时血清钙水平与血肿体积、神经功能及预后存在一定关联,且入院时血清钙对高血压性脑出血不良预后具有一定预测价值。     

转录因子PU.1的最新研究进展

PU.1是ETS转录因子家族(E26 transformation-specific family)的成员,在机体多种组织发育中发挥重要作用。近年来的研究发现,PU.1不仅在造血谱系的确定和分化中起作用,而且还在机体免疫、脂肪形成、组织纤维化、神经发育中发挥功能。在造血及免疫等系统中,PU.1与多个靶基因形成复杂的调节网络,并且PU.1受组蛋白修饰和非编码RNA等表观遗传的调控,参与细胞增殖、分化等多个过程,对维持细胞稳态具有一定意义。PU.1与红细胞白血病、前B细胞急性淋巴细胞白血病、急性髓细胞白血病、过敏性疾病、类风湿性关节炎、肥胖相关疾病、骨硬病、神经胶质瘤等疾病的发生相关。该文从功能方面阐述PU.1的最新研究进展,为该基因和ETS家族的后续研究提供新思路。