Preservation of TSPO by chronic intermittent hypobaric hypoxia confers antiarrhythmic activity

Abnormal activation of mitochondrial translocator protein (TSPO) contributes to arrhythmogenesis during cardiac metabolic compromise; however, its role in the antiarrhythmic activities of chronic hypoxia adaptation remains unclear. Our results demonstrated that 80% of normoxic rats developed ischaemic VF, whereas this condition was seldom observed in rats with 14 days of chronic intermittent hypobaric hypoxia (CIHH). TSPO stimulation or inhibition affected the arrhythmias incidence in normoxic rats, but did not change the CIHH‐mediated antiarrhythmic effects. Abrupt and excessive elevation of TSPO activity was positively linked to ischaemic VF, and CIHH preserved TSPO activity during ischaemia. The preservation of TSPO activity by CIHH also contributed to the maintenance of intracellular Ca homeostasis. These results suggest that the blunt sensitivity of TSPO to ischaemic stress may be responsible for the antiarrhythmic effects by CIHH.     

EV71灭活疫苗（人二倍体细胞）在恒河猴婴猴模型中的免疫保护性分析

肠道病毒71型作为引起儿童群体常见传染性手足口病（HFMD）的主要病原,具有导致少量感染个体出现脑炎等神经系统病变以及相关心肺功能衰竭的病理学特性．因此其预防性疫苗的研发具有重要的公共卫生意义．在前期工作的基础上,一种EV71灭活病毒疫苗（人二倍体细胞）在本研究中基于恒河猴婴猴模型进行了相应的免疫保护性分析．以160EU剂量对2～3月龄婴猴进行0,4周免疫后,动物在第4周接受了剂量为10。～CCID50的病毒经呼吸道的攻击．对病毒攻击后动物在14天内的临床症状、血液生物学、器官病原学分布以及病理学检测的动态观察表明,经疫苗免疫的动物未出现对照动物所具有的特征性临床表现,其血液生物学及病理学检测均无异常．同时,器官病原学分布亦呈阴性．结合动物中和抗体的明确增长及对照动物的综合表现分析,本文的工作证实了该EV71灭活病毒疫苗（人二倍体细胞）在恒河猴婴猴体内的免疫保护性．     

番茄钙依赖性蛋白激酶基因LeCPK2在热(光)胁迫中的功能鉴定

钙依赖性蛋白激酶(calcium-dependent protein kinases,CDPKs or CPKs)作为一类钙感知蛋白在植物的生长发育和胁迫应答中起着重要的作用.LeCPK2 (GenBank accession No.:GQ205414)是我们从番茄中分离的第3个CDPK基因,前期研究表明LeCPK2可能在植物热胁迫应答中发挥作用.为了进一步研究其在热胁迫中的功能,我们通过电子克隆的方法分离了LeCPK2的启动子序列,并通过LeCPK2过表达烟草分析其在高温胁迫中的潜在的功能.生物信息学分析显示,LeCPK2启动子中包含5个热响应元件,和前期试验结果一致.野生型植株在受到热胁迫后,对光更为敏感,强光照下植株叶片发生萎蔫,而强光本身不会对未受热胁迫的健康植株造成伤害.LeCPK2转基因植株热、光胁迫后不会出现受害表型.以上研究表明,LeCPK2在植物的热胁迫应答中发挥重要作用,能够有效保护植株免受高温胁迫的损害,是一个优秀的耐热(光)基因.本研究将为揭示番茄LeCPK2遗传功能及对其开发利用奠定基础.     

Internal heavy atom effect of Au(III) and Pt(IV) on hypocrellin A for enhanced in vitro photodynamic therapy of cancer

Hypocrellin A (HA), an a natural perylene quinine photosensitizers (PSs), can chelate with heavy metal ions, including Au(III) and Pt(IV), to form a 1:2 complex, which exhibits enhanced ¹O₂ generation quantum yield through the increased intersystem crossing efficiency mediated by internal heavy atom effect. Besides, the chelate process greatly improved the water solubility of HA. Comparative studies with HA and complexes have demonstrated that the heavy-atom effect on HA molecules enhances the efficiency of in vitro photodynamic (PDT) efficacy.     

Modified McKeown Minimally Invasive Esophagectomy for Esophageal Cancer: A 5-Year Retrospective Study of 142 Patients in a Single Institution

Background

To achieve decreased invasiveness and lower morbidity, minimally invasive esophagectomy (MIE) was introduced in 1997 for localized esophageal cancer. The combined thoracoscopic-laparoscopic esophagectomy (left neck anastomosis, defined as the McKeown MIE procedure) has been performed since 2007 at our institution. From 2007 to 2011, our institution subsequently evolved as a high-volume MIE center in China. We aim to share our experience with MIE, and have evaluated the outcomes of 142 patients.

Methods

We retrospectively reviewed 142 consecutive patients who had presented with esophageal cancer undergoing McKeown MIE from July 2007 to December 2011. The procedure, surgical outcomes, disease-free and overall survival of these cases were assessed.

Results

The average total procedure time was 270.5±28.1 min. The median operation time for thoracoscopy was 81.5±14.6 min and for laparoscopy was 63.8±9.1 min. The average blood loss associated with thoracoscopy was 123.8±39.2 ml, and for laparoscopic procedures was 49.9±14.3 ml. The median number of lymph nodes retrieved was 22.8. The 30 day mortality rate was 0.7%. Major surgical complications occurred in 24.6% and major non-surgical complications occurred in 18.3% of these patients. The median DFS and OS were 36.0±2.6 months and 43.0±3.4 months respectively.

Conclusions

Surgical and oncological outcomes following McKeown MIE for esophageal cancer were acceptable and comparable with those of open-McKeown esophagectomy. The procedure was both feasible and safe – properties that can be consolidated by experience.     

Mechanism of neoagarotetraose protects against intense exercise-induced liver injury based on molecular ecological network analysis

Here we have explored the effect of neoagarotetraose (NAT) on liver injury caused by intense exercise. Our results showed that NAT treatment obviously decreased liver weight (p < 0.01), improved the liver morphological structure, decreased ALT level (p < 0.05) and endotoxin (LPS) (p < 0.01). In addition, NAT could regulate bile acid profiles in feces and serum of mice, which indicated the potential of liver function, suggesting that NAT was effective to relieve intense exercise-induced liver injury. NAT could regulate the expression of colon genes. NAT tended to alter the microbial composition of mice under intense exercise. We uncovered the network interactions between liver traits and microbial communities in NAT treatment mice. Interestingly, our data indicated that intense exercise-induced liver injury may be related to Clostridiales. In summary, these results demonstrated that NAT relieved liver injury induced by intense exercise may be related to gut microbiota.     

Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer

Gastric cancer (GC) is a heavy health burden around the world, which is the fifth most frequent tumor and leads to the third most common cancer-related deaths. It is urgent to identify prognostic markers as the guideline for personalized treatment and follow-up. We accessed the prognostic value of Early B-cell factors (EBFs) in GC. A total of 415 GC tissues and 34 normal tissues from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, 616 external patients from {"type":"entrez-geo","attrs":{"text":"GSE15459","term_id":"15459"}}GSE15459, {"type":"entrez-geo","attrs":{"text":"GSE22377","term_id":"22377"}}GSE22377, {"type":"entrez-geo","attrs":{"text":"GSE51105","term_id":"51105"}}GSE51105, {"type":"entrez-geo","attrs":{"text":"GSE62245","term_id":"62245"}}GSE62245 were enrolled for analysis. Univariate and multivariate Cox regression analyses were employed to evaluate the sole and integrative prognostic value of EBFs, respectively. Genetic alterations, DNA methylation of EBFs were also evaluated, as well as the involved signaling pathways. We revealed that increased EBFs associated with the poor prognosis of GC patients, the prognostic model was established in TCGA-STAD cohort, and validated in Gene Expression Omnibus (GEO) cohorts, with effectiveness in both HER2 positive and negative patients. DNA methylation was involved in the impact on prognosis. Cell cycle, immune-associated, and MAPK pathways were influenced by EBFs. Anti-CTLA4 immunotherapy is more suitable for EBFs determining high-risk groups, but not anti-PD-1/PD-L1 therapy. 5-Fluorouracil, methotrexate, vorinostat are suitable to inhibit the function of EBFs. Our new findings provide novel insight into the prediction of prognosis and clinical treatment of GC patients based on EBFs.     

巴西橡胶树HbHEV3基因的克隆和表达分析

根据EST序列信息,通过RT-PCR获得了一个编码橡胶素前体的基因,命名为HbHEV3。HbHEV3编码区cDNA长度为630bp,编码209个氨基酸。预测的HbHEV3蛋白包含1个信号肽,1个具有几丁质结合特性的Hevein结构域和1个Barwinn结构域,HbHEV3与橡胶树及其他植物中类似蛋白具有很高的同源性。分离获得了HbHEV3起始密码子上游1 050bp的启动子序列,该序列含有众多应答激素和胁迫信号元件。实时荧光定量PCR分析结果表明,HbHEV3在所检测的组织中均有表达,其中在胶乳中的表达量最高,乙烯诱导能显著上调胶乳中HbHEV3的表达。研究表明,HbHEV3可能参与了橡胶树乙烯介导的防御反应,并在橡胶凝集过程中具有重要功能。     

Precise Reconstruction of Veins and Bile Ducts in Rat Liver Transplantation

Rat orthotopic liver transplantation (ROLT) remains a technically demanding procedure, especially regarding the reconstruction of the suprahepatic vena cava (SHVC). In this study, a new microsuture technique was developed for anastomosis of the SHVC, and a special single-groove cuff and blade-cut stent were introduced. With these modified techniques, we aimed to make a precise anastomosis of the SHVC and to provide optimal cuffs and stents for the reconstruction of the veins and bile ducts. According to different microsuture techniques for the SHVC and different types of cuffs and stents, three ROLT groups were created to compare the operation times and prognoses. Sham operations were performed as controls in the fourth group. The time expenditures with each step were compared among the transplantation groups. Biochemical parameters were tested at the end of a 1-month observation period. The short- and long-term survival rates of the transplantation groups were recorded and compared. Our new microsuture technique was faster than the conventional continuous suture technique for SHVC anastomosis (P < 0.05). The use of a single-groove cuff for reconstruction of the portal vein and the infrahepatic vena cava shortened the anastomotic time (P < 0.05). The use of blade-cut stents resulted in fewer biliary complications and better survival over the short and long terms (P < 0.05). Our new microsuture technique and the single-groove cuffs proved to be a precise method for venous reconstruction which shortened the anhepatic time and the anastomotic time significantly. The blade-cut stents apparently reduced the incidence of biliary complications. In summary, with this precise microsuture technique and delicate cuffs and stents, excellent long-term survival can be achieved easily and stably for ROLT.     

Trichloroethylene-Induced Gene Expression and DNA Methylation Changes in B6C3F1 Mouse Liver

Trichloroethylene (TCE), widely used as an organic solvent in the industry, is a common contaminant in air, soil, and water. Chronic TCE exposure induced hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s) for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE (0, 100, 500 and 1000 mg/kg b.w. per day) for 5 days. After 5 days TCE treatment at a dose level of 1000 mg/kg b.w., a total of 431 differentially expressed genes were identified in mouse liver by microarray, of which 291 were up-regulated and 140 down-regulated. The expression changed genes were involved in key signal pathways including PPAR, proliferation, apoptosis and homologous recombination. Notably, the expression level of a number of vital genes involved in the regulation of DNA methylation, such as Utrf1, Tet2, DNMT1, DNMT3a and DNMT3b, were dysregulated. Although global DNA methylation change was not detected in the liver of mice exposed to TCE, the promoter regions of Cdkn1a and Ihh were found to be hypo- and hypermethylated respectively, which correlated negatively with their mRNA expression changes. Furthermore, the gene expression and DNA methylation changes induced by TCE were dose dependent. The overall data indicate that TCE exposure leads to aberrant DNA methylation changes, which might alter the expression of genes involved in the TCE-induced liver tumorgenesis.