中药治疗肝纤维化大鼠对ALR基因表达的影响

目的：从分子水平探测中药治疗肝纤维化的作用及机制。方法：利用CCL4复合因素建立SD大鼠肝纤雏化模型。实验动物分成正常对照、模型、中药治疗三组，分别检测各组生化、肝纤维化指标和肝组织中ALR mRNA表达变业。结果：1．ALT、AST、A／G、HA、PCⅢ、LN、PLD各指标：模型组均高于对照组（P〈0．01），中药治疗组低于模型组（P〈0．01），并且，HA、PCⅢ、LN、PLD的降低与病理组织反应肝纤维化的好转程度一致；2．肝组织中ALR mRNA的相对表达量：中药治疗组、模型组明显高于对照组（P〈0．01），中药治疗组高于模型组（P〈0．01）。结论：联联合检测生化、肝纤维化指标可提高肝纤维化早期诊断；肝纤维化时肝组织ALR mRNA的高表达可逆转肝纤维化。     

脐血干细胞移植与肝再生增强因子联合治疗急性肝衰竭的实验研究

目的：观察脐血干细胞移植与肝再生增强因子联合治疗急性肝衰竭大鼠的疗效,以期为肝脏组织工程修复提供依据。方法建立肝衰竭大鼠模型40只,按照随机数表法将大鼠随机分为对照组(采用腹腔注射生理盐水)、脐血干细胞移植组(移植组,采用腹腔移植2×107脐血干细胞)、脐血干细胞移植联合肝再生增强因子组(联合组,采用腹腔移植2×107脐血干细胞联合注射肝再生增强因子50μg·kg-1·d-1)和肝再生增强因子组(增强因子组,采用腹腔注射肝再生增强因子50μg·kg-1·d-1),每组各10只。用DAPI标记肝细胞。大鼠肝衰竭造模成功后,经治疗一个月后分别取四组大鼠的肝组织制作冰冻切片,并于荧光显微镜下观察肝组织中DAPI标记的细胞计数。结果移植组肝脏归巢及定植的干细胞为(12.6±2.0)个细胞/100倍视野,多于增强因子组的(8.1±3.4)个细胞/100倍视野,差异有统计学意义(P<0.05),增强因子组到肝脏归巢及定植的干细胞又多于对照组的(3.1±3.4)个细胞/100倍视野,差异有统计学意义(P<0.05),而联合组肝脏归巢及定植的干细胞为(18.1±3.4)个细胞/100倍视野,多于以上各组,差异有统计学意义(P<0.05)。结论不同干预手段对脐血干细胞归巢、定植于肝脏有一定影响,联合组的干细胞归巢率优于单行移植组和增强因子组。因此脐血干细胞移植联合肝再生增强因子是一种较为理想的急性肝衰竭治疗手段。     

Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development

Magnesium (Mg²⁺) is the second most abundant cation in cells, yet relatively few mechanisms have been identified that regulate cellular levels of this ion. The most clearly identified Mg²⁺ transporters are in bacteria and yeast. Here, we use a yeast complementary screen to identify two mammalian genes, MagT1 and TUSC3, as major mechanisms of Mg²⁺ influx. MagT1 is universally expressed in all human tissues and its expression level is up-regulated in low extracellular Mg²⁺. Knockdown of either MagT1 or TUSC3 protein significantly lowers the total and free intracellular Mg²⁺ concentrations in mammalian cell lines. Morpholino knockdown of MagT1 and TUSC3 protein expression in zebrafish embryos results in early developmental arrest; excess Mg²⁺ or supplementation with mammalian mRNAs can rescue the effects. We conclude that MagT1 and TUSC3 are indispensable members of the vertebrate plasma membrane Mg²⁺ transport system.     

Augmenter of liver regeneration: A key protein in liver regeneration and pathophysiology

Liver is constantly exposed to pathogens, viruses, chemicals, and toxins, and several of them cause injury, leading to the loss of liver mass and sometimes resulting in cirrhosis and cancer. Under physiological conditions, liver can regenerate if the loss of cells is less than the proliferation of hepatocytes. If the loss is more than the proliferation, the radical treatment available is liver transplantation. Due to this reason, the search for an alternative therapeutic agent has been the focus of liver research. Liver regeneration is regulated by several growth factors; one of the key factors is augmenter of liver regeneration (ALR). Involvement of ALR has been reported in crucial processes such as oxidative phosphorylation, maintenance of mitochondria and mitochondrial biogenesis, and regulation of autophagy and cell proliferation. Augmenter of liver regeneration has been observed to be involved in liver regeneration by not only overcoming cell cycle inhibition but by maintaining the stem cell pool as well. These observations have created curiosity regarding the possible role of ALR in maintenance of liver health. Thus, this review brings a concise presentation of the work done in areas exploring the role of ALR in normal liver physiology and in liver health maintenance by fighting liver diseases, such as liver failure, non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis, viral infections, cirrhosis, and hepatocellular carcinoma.     

人肝再生增强因子的分子克隆及生物学活性研究

在众多参与肝细胞再生调控的细胞因子中,如TGF、EGF及大分子HGF等都缺乏器官特异性,而     

大鼠肝再生增强因子的基因克隆

目的克隆大鼠肝再生增强因子 (ALR)编码序列 ,并在原核细胞表达。方法按文献报道大鼠肝再生增强因子核苷酸序列合成引物 ,从2周龄大鼠肝组织提取RNA ,利用RT_PCR扩增大鼠肝再生增强因子基因编码区 ;将PCR扩增片断亚克隆到pBV221质粒 ,构建原核表达重组载体 ,导入到大肠杆菌后热诱导表达目的蛋白。结果从大鼠肝脏的RNA中扩增到长约400bp的ALRcDNA编码区基因 ,序列分析表明与文献报道一致 ;重组克隆经热诱导表达出分子量约15kD大小的蛋白质 ,与预期值一致。结论从2周龄大鼠肝组织中成功克隆肝再生增强因子基因 ,并获得了原核细胞高效表达     

Novel aldose reductase inhibitors: a patent survey (2006 – present)

Introduction: Initially studied for its central role in the pathogenesis of chronic diabetic complications, aldose reductase (ALR2) gains more attention over the years as its implication in inflammatory diseases is being established, along with the therapeutic potential of its inhibitors.

Areas covered: Reviewing the patents that were published since 2006, it is getting clear that the search for new chemical entities has subsided, giving rise to natural products and plant extracts with ALR2 inhibitory activity. Other aspects that were prominent were the search for proper forms of known inhibitors, in a way to improve their impaired physicochemical profile, as well as potential combination therapies with other compounds of pharmaceutical interest. On the spotlight were patents enhancing the therapeutic usage of aldose reductase inhibitors (ARIs) to various pathological conditions including cancer and inflammation-mediated diseases such as sepsis, asthma, and cancer.

Expert opinion: Although new chemical entities are scarcely registered and patented after many years of inconclusive clinical trials, the involvement of ALR2 to inflammatory pathologies might renew the interest in the field of ARIs.     

Implication of a novel postoperative recovery protocol to increase day 1 discharge rate after anatomic lung resection

BackgroundChest-tube drainage and prolonged air leak after anatomic lung resection (ALR) continue to drive admission days for most programs employing minimal access techniques. The aim of the study was to evaluate the impact of a novel postoperative recovery protocol with revised chest tube management strategies to target discharge on post-operative day 1 (POD1) after ALR.MethodsThis is a pilot study investigating a novel enhanced recovery protocol which either allowed chest tube removal on POD1 or ambulatory management with indwelling chest tube using a portable closed drainage system. We included all patients undergoing video-assisted thoracoscopic surgery (VATS)-ALR; exclusion criteria were open surgery, non-anatomic or extended resections.ResultsA total of 139 patients were included in the study [N=29 portable drainage (PD), N=110 standard pathway (SP)]. POD1 discharge rate was 72% in PD vs. 15% in SP cohort (P<0.001). Median length of stay (LOS) was 1 day [interquartile range (IQR), 1–2 days] in PD cohort, while it was 3 days (IQR, 2–5 days) in SP cohort (P<0.001). There were no significant differences in length of indwelling chest-tube, rate of discharge with chest-tube, post-operative complications, or readmissions. On multivariate analysis, PD pathway as well as short surgical time were significant predictors of discharge on POD1.ConclusionsOur results indicate that POD1 discharge rates of 72% after VATS-ALR can be safely achieved by a well-developed perioperative care pathway and simple chest tube drainage interventions. Based on these findings we are currently drafting a follow-up study to investigate the possibility of performing ALRs as day surgery.     

中药对大鼠中毒性肝纤维化ALR表达丰度的影响

目的;从分子水平检测中药预防肝纤维化的作用及机理。方法：利用CCl4复合因素对SD大鼠制造肝纤维化模型,然后用中药灌胃进行预防,检测其生化指标、肝纤维化指标、病理情况以及肝组织中ALRmRNA表达量。结果：HA,PCⅢ,LN,PLD的升降与病理组织切片反映的肝纤维化程度相一致,在肝纤维化形成的同时给予中药预防,ALRmRNA的表达增强。结论：联合检测生化、肝纤维化指标,可提高肝纤维化早期诊断;通过促进ALR的表达可延缓或减轻肝硬化的发生。