Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19

Liver damage in severe acute respiratory coronavirus 2 infection occurs in patients with or without preexisting liver disorders, posing a significant complication and mortality risk. During coronavirus disease 2019 (COVID-19), abnormal liver function is typically observed. However, liver injury may occur because of the treatment as well. Ischemia, cytokine storm, and hypoxia were identified as the three major factors contributing to liver damage during COVID-19. Indeed, raised liver enzymes during hospitalizations may be attributed to medications used, as well as sepsis and shock. As a result, the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14% to 53%. Aminotransferases and bilirubin are found most often elevated. Usually, increased gamma-glutamyltransferase, alkaline phosphatase, and decreased serum albumin levels are demonstrated. Additionally, although there is no specific treatment for COVID-19, many of the drugs used to treat the infection are hepatotoxic. In this mini-review, we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm. Furthermore, data show that liver injury can be an independent predictor of severe COVID-19, the need for hospitalization, and death.     

耐力运动对关节炎大鼠氧化应激与软骨炎性表达及CHRNA7信号的影响

目的 探讨耐力运动对关节炎大鼠氧化应激、软骨炎性表达及CHRNA7信号表达的影响。方法 将50只SD大鼠随机分为健康组、关节炎组、低耐力组、中耐力组、高耐力组，每组10只。检测各组大鼠行为学及氧化应激水平差异性；采用热板致痛阈值（PWTL）及机械性撤足阈值（PWT）；酶联免疫法检测各组大鼠炎性因子水平；采用Western Blot法检测滑膜组织中a7nAChR、STAT3表达情况；HE染色观察大鼠膝关节软骨组织的形态。结果 HE染色结果显示，健康组大鼠膝关节软骨表面平整光滑，无裂缝或缺损；关节炎组大鼠膝关节软骨的表面不平整，有缺损；低耐力组大鼠膝关节软骨的表面比较光滑、平整；中、高耐力组大鼠膝关节软骨的表面平整，软骨细胞排列较为整齐。 与健康组相比，关节炎组TNF-α、IL-1水平升高（P＜0.05）；与关节炎组相比，低耐力组、中耐力组和高耐力组TNF-α、IL-1水平降低明显（P＜0.05）；与低耐力相比，中耐力组TNF-α、IL-1降低明显（P＜0.05）；与中耐力组相比，高耐力组TNF-α、IL-1水平升高（P＜0.05）。与健康组相比，关节炎组大鼠PWTL、PWT、SOD、GSH-Px、α7nAChR、STAT3表达水平明显降低，MDA水平升高(P＜0.05)；与关节炎组大鼠相比，低、中和高耐力组大鼠PWTL、PWT、SOD、GSH-Px、α7nAChR、STAT3水平升高，MDA水平降低(P＜0.05)；与低耐力组相比，中耐力组PWTL、PWT、SOD、GSH-Px、α7nAChR、STAT3水平升高，MDA水平降低(P＜0.05)；与中耐力组相比，高耐力组PWTL、PWT、SOD、GSH-Px、α7nAChR、STAT3水平下降，MDA水平升高(P＜0.05)。结论 中强度耐力运动可抑制TNF-α、IL-1炎性水平，改善疼痛水平及氧化应激反应，对关节起到保护作用，其机制可能与调控α7nAChR/STAT3蛋白表达有关。     

DNA损伤在衰老相关疾病中的研究进展

DNA损伤是衰老相关疾病领域的研究热点, 可引起细胞周期停滞、凋亡, 加快个体衰老速度、增加衰老相关疾病的患病风险。本文将从细胞衰老和个体衰老两个层面阐述其与衰老之间的研究进展, 并综述其与衰老常见相关疾病(肿瘤、心血管疾病、阿尔茨海默病)及早衰综合征的关系, 为抗衰老研究和临床干预衰老相关疾病提供理论依据。     

我国弓形虫Chinese 1优势基因型感染对小鼠脑组织铁代谢影响

目的　探讨我国弓形虫Chinese 1优势基因型感染对宿主脑组织铁代谢及脑损伤的影响。方法　将20只C57BL/6（体质量15～17 g）小鼠随机分为对照组和感染组，每组10只。感染组每只小鼠腹腔注射4 000个弓形虫Chinese 1优势基因型TgCtwh3虫株速殖子，对照组小鼠注射等量无菌PBS，饲养6 d后处死小鼠并取其脑组织。采用电感耦合等离子体质谱法（inductively coupled plasma mass spectrometry, ICP⁃MS）检测小鼠脑组织铁元素水平；采用RNA芯片检测两组小鼠脑组织差异基因数目并对功能基因表达情况进行基因本体论（Gene Ontology, GO）功能富集；采用实时荧光定量PCR（fluorescent quantitative real⁃time PCR, qPCR）技术检测小鼠脑组织中弓形虫表面抗原1（Toxoplasma gondii surface antigen 1，TgSAG1）基因及部分锌铁调控蛋白（Zrt⁃ and Irt⁃like protein, ZIP）家族mRNA表达水平；采用光镜和电镜观察小鼠脑组织海马齿轮回（dentate gyrus, DG）超微结构；采用Western blotting检测谷胱甘肽过氧化物酶4（glutathione peroxidase 4, GPx4）蛋白表达水平；采用硫代巴比妥酸（TBA）法检测丙二醛（malondialdehyde, MDA）水平；采用免疫组化检测血管内皮生长因子（vascular endothelial growth factor, VEGF）蛋白表达光密度（optical density, OD）值。结果　光镜下可见感染组小鼠脑组织海马DG区细胞坏死，电镜下见感染组小鼠脑组织海马区出现胞质空泡化、核皱缩坏死、线粒体嵴断裂消融、自噬小体增加等超微结构变化。与对照组相比，感染组小鼠脑组织中铁元素水平上调[（32.92 ± 0.90） µg/g vs.（37.72 ± 1.10） µg/g；t = 3.397, P < 0.01]；RNA芯片检测感染组小鼠脑组织发现721个基因上调、276个基因下调，差异表达基因在金属离子结合能力上有明显富集。与对照组相比，感染组小鼠脑组织金属元素转运体ZIP2 mRNA表达水平上调（t = 8.659，P < 0.05）、GPx4表达下降[（1.046 ± 0.025） vs. （0.720 ± 0.101）；t = 3.129，P < 0.01]）、MDA水平升高[（4.37 ± 0.33） nmol/mgprot vs.（5.93 ± 0.54） nmol/mgprot；t = 2.451，P < 0.05）]、VEGF蛋白平均OD值上调[（0.348 3 ± 0.017 8） vs. （0.490 6 ± 0.010 5）；t = 6.641，P < 0.01]。结论　Chinese 1优势基因型弓形虫感染后，小鼠脑组织中铁元素蓄积、抗氧化能力下调、氧化应激水平升高，提示弓形虫感染可影响宿主脑组织铁代谢而导致脑损伤。     

Personal and family history of cancer and the risk of Barrett's esophagus in men

The association between Barrett's esophagus (BE) and a personal or family history of cancer other than gastroesophageal remains unknown. To evaluate the effect of personal and family history of certain cancers and cancer treatments on the risk of BE, we analyzed data from a Veterans Affairs case‐control study that included 264 men with definitive BE (cases) and 1486 men without BE (controls). Patients with history of esophageal or gastric cancer were excluded. Patients underwent elective esophagogastroduodenoscopy or a study esophagogastroduodenoscopy concurrently with screening colonoscopy to determine BE status. Personal and family history of several types of cancer was obtained from self‐reported questionnaires, supplemented and verified by electronic medical‐record reviews. We estimated the association between personal and family history of cancer or radiation/chemotherapy, and BE. Personal history of oropharyngeal cancer (1.5% vs. 0.4%) or prostate cancer (7.2% vs. 4.4%) was more frequently present in cases than controls. The association between BE and prostate cancer persisted in multivariable analyses (adjusted odds ratio 1.90; 95% confidence interval 1.07–3.38, P = 0.028) while that with oropharyngeal cancer (adjusted odds ratio 3.63; 95% confidence interval 0.92–14.29, P = 0.066) was attenuated after adjusting for retained covariates of age, race, gastroesophageal reflux disease, hiatal hernia, and proton pump inhibitor use. Within the subset of patients with cancer, prior treatment with radiation or chemotherapy was not associated with BE. There were no significant differences between cases and controls in the proportions of subjects with several specific malignancies in first‐ or second‐degree relatives. In conclusion, the risk of BE in men may be elevated with prior personal history of oropharyngeal or prostate cancer. However, prior cancer treatments and family history of cancer were not associated with increased risk of BE. Further studies are needed to elucidate if there is a causative relationship or shared risk factors between prostate cancer and BE.     

Heart-type fatty acid binding protein and cardiac troponin I may have a diagnostic value in electrocution: A rat model

Although cardiac injury is known to be the leading cause of death in electrocution, the differential diagnosis can be challenging in forensic practice since the exact mechanism is poorly understood and there is lack of reliable markers. Thus, death due to electrocution may be classified as a negative autopsy. The serum levels of and myocardial immunostaining loss for cardiac troponins and heart-type fatty acid binding protein (H-FABP) are highly sensitive and specific biomarkers of ischemic myocardial damage and may have a diagnostic value in determining the myocardial injury or the cause of death due to electrocution. Due to this reason, a rat model is prepared to investigate these issues. Thirty-two Wistar albino female rats were included and randomly divided into four groups of eight subjects. Group A was the control group, and Group B, C, and D were exposed to electrical current of 110 volt (V), 220 V, and 600 V, respectively. Blood samples and the hearts were collected from the rats for biochemical and immunostaining analyses.It is found that increased serum H-FABP levels were significantly associated with the higher voltage immediately after electrocution. However, serum cardiac troponin I (cTnI) levels did not show significant changes associated with the higher voltage in the early period of electrocution. As for histopathological examinations, the only significant difference in myocardial immunostaining loss was for H-FABP in Group B.Serum H-FABP levels may have a diagnostic value in the early postmortem period immediately after electrocution. Besides, it seems that serum H-FABP levels may be a better indicator than those of cTnI to reflect the myocardial damage in the early period of the electrocution.