SIRT3 regulation of mitochondrial oxidative stress

Mitochondria play a central role in the production of reactive oxygen species as byproducts of metabolism and energy production. In order to protect cellular structures from oxidative stress-induced damage, cells have evolved elegant mechanisms for mitochondrial ROS detoxification. The mitochondrial sirtuin, SIRT3, is emerging as a pivotal regulator of oxidative stress by deacetylation of substrates involved in both ROS production and detoxification. This review will summarize recent findings on the regulation of mitochondrial ROS homeostasis by SIRT3.     

Treatment of hepatic amyloid light‐chain amyloidosis with bortezomib and dexamethasone in a liver transplant patient

Hepatic amyloid light‐chain (AL) amyloidosis is characterized by abnormal deposition of amyloid fibrils in the liver. As this precursor protein is produced by a proliferative plasma cell clone in the bone marrow, liver transplantation (LT) does not affect the disease's progression. Here, we describe the successful treatment using bortezomib‐ and dexamethasone‐based chemotherapy, following LT, of hepatic AL amyloidosis in a 65‐year‐old woman with progressive liver failure. The patient presented with progressive hepatic dysfunction accompanied by hepatorenal syndrome requiring hemodialysis, and living donor LT was successfully performed. Histology revealed amyloid deposits in the liver and stomach, and serum immunofixation revealed AL amyloidosis (κ‐type). The patient began chemotherapy on day 45 after the LT, and remission was achieved after one course. She was subsequently discharged 83 days after the LT, with normal liver and renal function, and no clinical evidence of recurrent disease was observed at the latest follow up (22 months post‐LT).     

微 RNA-21和微 RNA-146a 在结直肠肿瘤中的表达及临床意义

目的探讨结直肠肿瘤患者组织和血清中 miRNA-21和 miRNA-146a 的表达情况,并分析其临床意义。方法收集100例结直肠癌、80例结直肠腺瘤患者和65名健康对照者的内镜活检组织,同时收集其血清标本,应用实时荧光定量 PCR 检测 miRNA-21和 miRNA-146a 的表达水平,分析其表达与临床病理特征间的关系,并评估血清差异表达的 miRNA 在结直肠肿瘤诊断中的价值。组间比较采用 Mann-WhitneyU 检验和 Kruskal-Wallis 检验;Spearman 相关性检验用于分析组织和血清中 miRNA 表达的关联性。结果在结直肠癌和结直肠腺瘤患者病变组织中 miRNA-21的表达分别为8．573±0．898和7．746±1．183,显著高于健康对照者的6．160±0．835（U ＝120．129、33．230,P 均＜0．01）;在结直肠癌和结直肠腺瘤患者血清中的表达分别为1．829±0．303和1．624±0．226,也高于健康对照者的1．391±0．221（U ＝40．353、15．512,P 均＜0．01）;miRNA-21在结直肠癌患者组织中和血清中的表达均高于结直肠腺瘤患者（U＝11．384、10．189,P 均＜0．01）。miRNA-21在结直肠癌患者中的高表达与肿瘤临床分期、淋巴结转移有关;miRNA-21在结直肠腺瘤中的表达水平与病理类型有关。Spearman 分析结果示,miRNA-21在结直肠癌患者组织和血清中的表达呈正相关（r ＝0．459,P ＜0．01）。miRNA-146a 在结直肠癌患者组织中为2．556±0．351,血清中为0．249±0．038,低于健康对照者的3．428±0．328和0．279±0．053（U ＝102．134、30．111,P 均＜0．01）;其在结直肠腺瘤患者组织中为3．255±0．332,血清中为0．290±0．036,与健康对照者比较差异无统计学意义（U＝3．936、3．180,P 均＞0．05）。miRNA-146a 在结直肠癌患者组织中和血清中的表达均低于结直肠腺瘤患者（U＝73．809、21．123,P 均＜0．01）。结直肠癌患者miRNA-146a 的下降程度与肿瘤临床分期、肿瘤分化程度有关,而在结直肠腺瘤中的表达与临床特征间无明显关系。根据 ROC 曲线分析,鉴别结直肠癌与健康者,血清 miRNA-21、miRNA-146a 及二者联合检测 ROC 的 AUC 分别为0．889、0．791和0．863;鉴别结直肠腺瘤与健康者,其 AUC 分别为0．784、0．692和0．761;鉴别结直肠癌与结直肠腺瘤患者,其 AUC 分别为0．705、0．820和0．713。结论血清 miRNA-21和 miRNA-146a 的差异表达在结直肠癌的早期诊断中具有潜在的价值。     

The Gastrointestinal Tract Is an Alternative Route for SARS-CoV-2 Infection in a Nonhuman Primate Model

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Axin2+ Peribiliary Glands in the Periampullary Region Generate Biliary Epithelial Stem Cells That Give Rise to Ampullary Carcinoma

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突变富集型PCR-RFLP粪检对大肠癌的诊断价值

[目的]探讨突变富集型聚合酶链反应-限制性片段长度多态性(mutant-enriched PCR-RFLP)方法粪检对大肠癌的诊断价值.[方法]提取25例大肠癌患者粪便、相应肿瘤组织DNA和17例正常对照者粪便DNA,结合限制性内切酶Mva I,运用突变富集型PCR-RFLP,分析c-ki-ras2基因点突变;随机取10例患者、10例正常对照作PCR片段测序以分析特异性,用已知含突变的A549肺腺癌细胞株(12GGT→AGT)与正常人结肠黏膜上皮细胞按不同比例混合反应分析敏感性.[结果]突变富集型PCR-RFLP特异性达100%,敏感度0.1%即能分辨混杂在1 000个正常细胞中的1个含突变的肿瘤细胞.[结论]突变富集型PCR-RFLP粪检大肠癌致癌基因点突变特异性强,敏感性高,对诊断大肠癌有一定的应用前景,但如何选取敏感的肿瘤检测指标是一个有待解决的重要问题.     

FAK regulates cardiomyocyte survival following ischemia/reperfusion

Myocyte apoptosis is central to myocardial dysfunction following ischemia/reperfusion (I/R) and during the transition from hypertrophy to heart failure. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase regulates adhesion-dependent survival signals and unopposed FAK activation has been linked to tumor development. We previously showed that conditional myocyte-specific deletion of FAK (MFKO) in the adult heart did not affect basal cardiomyocyte survival or cardiac function but led to dilated cardiomyopathy and heart failure following pressure overload. In the present study, we sought to determine if FAK functions to limit stress-induced cardiomyocyte apoptosis. We reasoned that (I/R), which stimulates robust apoptotic cell death, might uncover an important cardioprotective function for FAK. We found that depletion of FAK markedly exacerbates hypoxia/re-oxygenation-induced cardiomyocyte cell death in vitro. Moreover, deletion of FAK in the adult myocardium resulted in significant increases in I/R-induced infarct size and cardiomyocyte apoptosis with a concomitant reduction in left ventricular function. Finally, our results suggest that NF-κB signaling may play a key role in modulating FAK-dependent cardioprotection, since FAK inactivation blunted activation of the NF-κB survival signaling pathway and reduced levels of the NF-κB target genes, Bcl2 and Bcl-xl. Since the toggling between pro-survival and pro-apoptotic signals remains central to preventing irreversible damage to the heart, we conclude that targeted FAK activation may be beneficial for protecting stress-dependent cardiac remodeling.     

组织学三联征和聚合酶链反应在弓形虫淋巴结炎病理诊断中的应用

目的 经典的组织学三联征诊断法和荧光原位杂交(PCR)法在提高石蜡包埋组织弓形虫淋巴结炎确诊率中的价值.方法 收集本院1999年4月至2009年9月诊断的46例符合组织学三联征形态改变的石蜡包埋淋巴结组织,采用半嵌套式PCR方法 对提取DNA进行弓形虫基因组的片段扩增;另选取30例组织中可见三联征中的二个或一个特征的病例作为对照.结果 组织学三联征组PCR阳性率为76.1%(35/46),对照组阳性率仅为10.0%(3/30,P<0.01);组织学三联征诊断弓形虫淋巴结炎的灵敏度为92.1%(35/38),特异度为71.1%(27/38);PCR法的阳性预测值为76.1%(35/46),阴性预测值为90.0%(27/30).结论 经典的组织学三联征对于诊断弓形虫淋巴结炎的特异性很强,但敏感性较低,且易漏诊部分非典型病例.在组织形态改变的基础上结合半嵌套式PCR对刚地弓形虫基因片段的检测可大大提高检出敏感性和准确性.