喜马拉雅土拨鼠非冬眠期乳酸脱氢酶同工酶基因表达特征

用聚丙烯酰胺凝胶电泳和紫外光谱法分析非冬眠期喜马拉雅土拨鼠4种组织的乳酸脱氢酶(LDH)同工酶的酶谱及其活力,该鼠骨骼肌酶带的多态分布,可能是潜在的调节基因调控所致。另外,本文还对构象异构体产生的亚带进行了研讨。     

GSTP1 Ile105Val Polymorphism and Prostate Cancer Risk: Evidence from a Meta-Analysis

Background

Glutathione S-transferase P1 (GSTP1) is thought to be involved in the detoxification of reactive carcinogen metabolites. Numerous epidemiological studies have evaluated the association of GSTP1 Ile105Val polymorphism with the risk of prostate cancer. However, the results remain inconclusive. To derive a more precise estimation, a meta-analysis was performed.

Methodology/Principal Findings

A comprehensive search was conducted to identify the eligible studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the relationship. The overall association was not significant (Val/Val vs. Ile/Ile OR = 1.06, 95% CI = 0.90–1.25, P = 0.50; Val/Val vs. Val/Ile+Ile/Ile: OR = 1.07, 95% CI = 0.91–1.25, P = 0.44). In subgroup analyses by ethnicity and prostate cancer grade, the similar results were observed. However, in stratified analysis by clinical stage, we found a significant association with low-stage prostate cancer (Val/Val vs. Ile/Ile: OR = 2.70, 95% CI = 1.73–4.22, P<0.001; Val/Val vs. Val/Ile+Ile/Ile: OR = 2.14, 95% CI = 1.38–3.33, P = 0.001). Moreover, there was no statistically significant evidence of multiplicative interactions neither between the GSTP1 Ile105Val polymorphism and GSTM1, nor between smoking status and GSTP1 on prostate cancer risk.

Conclusions

This meta-analysis showed that GSTP1 Ile105Val polymorphism might not be significantly associated with overall prostate cancer risk. Further stratified analyses showed a significant association with low-stage prostate cancer.     

P3 cap modified Phe*-Ala series BACE inhibitors

With the aim of reducing molecular weight and adjusting log D value of BACE inhibitors to more favorable range for BBB penetration and better bioavailability, we synthesized and evaluated several series of P3 cap modified BACE inhibitors obtained via replacement of the P3NHBoc moiety as seen in 3 with other polar functional groups such as amino, hydroxyl and fluorine. Several promising inhibitors emerging from this P3 cap SAR study (e.g., 15 and 19) demonstrated good enzyme inhibitory potencies (BACE-1 IC(50) <50 nM) and whole cell activities (IC(50) approximately 1 microM).     

CircFBXW8 Acts an Oncogenic Role in the Malignant Progression of Non-small Cell Lung Carcinoma by miR-370-3p-Dependent Regulation of TRIM44

Biochemical Genetics - Non-small cell lung carcinoma (NSCLC) is an aggressive malignant tumor. Growing evidences have revealed that circular RNA (circRNA) is involved in NSCLC progression. This...     

RNASEL Asp541Glu and Arg462Gln polymorphisms in prostate cancer risk: evidences from a meta-analysis

Epidemiological studies have evaluated the association between RNASEL Asp541Glu and Arg462Gln polymorphisms and prostate cancer (PCa) risk. However, the results remain inconclusive. To derive a more precise estimation of the association between RNASEL polymorphisms and PCa risk, we performed a meta-analysis based on nineteen case?Ccontrol studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both Asp541Glu and Arg462Gln polymorphisms were not associated with PCa risk (for Asp541Glu polymorphism: Glu/Glu vs. Asp/Asp: OR 1.17, 95% CI: 0.95?C1.45, P?=?0.13; Glu/Asp vs. Asp/Asp: OR 1.02, 95% CI: 0.92?C1.14, P?=?0.70; for Arg462Gln polymorphism: Gln/Gln vs. Arg/Arg: OR 0.98, 95% CI: 0.88?C1.08, P?=?0.62; Gln/Arg vs. Arg/Arg: OR 0.97, 95% CI: 0.91?C1.04, P?=?0.53). The insignificant association was maintained in the dominant and the recessive genetic models. In subgroup analyses, the significant association was not detected in Caucasian populations. However, we found the significant association of RNASEL Asp541Glu polymorphism with sporadic PCa (Glu/Glu vs. Asp/Asp: OR 1.29, 95% CI: 1.04?C1.59, P?=?0.02; Glu/Asp vs. Asp/Asp: OR 1.24, 95% CI: 1.03?C1.50, P?=?0.03). In conclusion, we found that these RNASEL polymorphisms were not related to overall PCa risk, especially in Caucasians. However, in subgroup analyses we found a suggestion that RNASEL 541Gln allele might be a low-penetrent risk factor for sporadic PCa.     

MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis

Epidemiological studies have evaluated the association between MTHFR 677C>T and 1298A>C polymorphisms and risk of male infertility. However, the results from the published studies on the association between these two MTHFR polymorphisms and male infertility risk are conflicting. To derive a more precise estimation of association between the MTHFR polymorphisms and risk of male infertility, we performed a meta-analysis. A comprehensive search was conducted to identify all case–control studies of MTHFR polymorphisms and male infertility risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both 677C>T and 1298A>C polymorphisms were not significantly associated with male infertility risk. However, in stratified analysis by ethnicity, we found that the 677C>T polymorphism was significantly associated with the risk of male infertility in Asian population (TT vs. CC: OR = 1.57, 95% CI: 1.05–2.37, P = 0.03; TT vs. TC + CC: OR = 1.40, 95% CI: 1.05–1.86, P = 0.02; TT + TC vs. CC: OR = 1.34, 95% CI: 1.01–1.77, P = 0.04). Although some modest bias could not be eliminated, this meta-analysis suggested that the MTHFR 677T allele might be a low-penetrant risk factor for male infertility, especially in Asian population.     

戊型肝炎病毒样颗粒在重组汉逊酵母中的发酵表达、纯化及其免疫原性分析

为了研制戊型肝炎新型基因工程疫苗,利用汉逊酵母表达系统表达重组戊型肝炎病毒样颗粒,成功构建了重组戊型肝炎疫苗工程菌株HP/HEV2.3,对该菌株的发酵条件和纯化工艺进行了研究。先将工作种子批进行发酵培养,收集发酵后的细胞培养物;对其先后进行细胞破碎、澄清和超滤、硅胶吸附和解吸附、超滤浓缩换液、色谱纯化及除菌过滤,制得重组汉逊酵母戊型肝炎病毒样颗粒,纯化收率为33%,纯度达99%;电镜观察显示该重组汉逊酵母戊型肝炎病毒样颗粒与天然戊型肝炎病毒颗粒理论大小一致,为32 nm;基因序列与理论一致;SDS-PAGE分析结果表明其表达的外源蛋白质分子量与预期的目的蛋白质分子量大小一致,均为56 k Da,表达量占细胞总蛋白的26%,表达水平为1.0 g/L发酵液;Western blotting、ELISA活性检测及小鼠免疫接种效力试验ED_(50)结果表明,此重组汉逊酵母戊型肝炎病毒样颗粒具有良好的抗原性和免疫原性,可用于制造戊型肝炎新型基因工程疫苗。     

A New Model for Predicting Non-Sentinel Lymph Node Status in Chinese Sentinel Lymph Node Positive Breast Cancer Patients

Background

Our goal is to validate the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Stanford Online Calculator (SOC) for predicting non-sentinel lymph node (NSLN) metastasis in Chinese patients, and develop a new model for better prediction of NSLN metastasis.

Methods

The MSKCC nomogram and SOC were used to calculate the probability of NSLN metastasis in 120 breast cancer patients. Univariate and multivariate analyses were performed to evaluate the relationship between NSLN metastasis and clinicopathologic factors, using the medical records of the first 80 breast cancer patients. A new model predicting NSLN metastasis was developed from the 80 patients.

Results

The MSKCC and SOC predicted NSLN metastasis in a series of 120 patients with an area under the receiver operating characteristic curve (AUC) of 0.688 and 0.734, respectively. For predicted probability cut-off points of 10%, the false-negative (FN) rates of MSKCC and SOC were both 4.4%, and the negative predictive value (NPV) 75.0% and 90.0%, respectively. Tumor size, Kiss-1 expression in positive SLN and size of SLN metastasis were independently associated with NSLN metastasis (p<0.05). A new model (Peking University People''s Hospital, PKUPH) was developed using these three variables. The MSKCC, SOC and PKUPH predicted NSLN metastasis in the second 40 patients from the 120 patients with an AUC of 0.624, 0.679 and 0.795, respectively.

Conclusion

MSKCC nomogram and SOC did not perform as well as their original researches in Chinese patients. As a new predictor, Kiss-1 expression in positive SLN correlated independently with NSLN metastasis strongly. PKUPH model achieved higher accuracy than MSKCC and SOC in predicting NSLN metastasis in Chinese patients.     

Amino acid conjugates as kappa opioid receptor agonists

A novel series of kappa (kappa) opioid receptor agonists were synthesized by incorporating the key structural features of known kappa opioid agonists while replacing the aryl acetamide portion with substituted amino acid conjugates. Compounds 3j (Ki = 6.7 nM), 3k (Ki = 3.6 nM), 3l (Ki = 4.6 nM), 3m (Ki = 0.83 nM) and 3o (Ki = 2 nM) possessed potent affinities for the kappa opioid receptor in vitro with reasonable selectivity over other opioid receptors.