glyA Gene Knock-out in Escherichia coli Enhances L-serine Production without Glycine Addition

Ya Zhang,Pei Kang,Shuang Liu,Yujiao Zhao,Zhiwen Wang,Tao Chen 한국생물공학회 2017 Biotechnology and Bioprocess Engineering Vol.22 No.4

In E. coli, glyA encodes for serine hydroxymethyltransferase (SHMT), which converts L-serine to glycine. When engineering L-serine-producing strains, it is therefore favorable to inactivate glyA to prevent L-serine degradation. However, most glyA knockout strains exhibit slow cell growth because of the resulting lack of glycine and C1 units. To overcome this problem, we overexpressed the gcvTHP genes of the glycine cleavage system (GCV), to increase the C1 supply before glyA was knocked out. Subsequently, the kbl and tdh genes were overexpressed to provide additional glycine via the L-threonine degradation pathway, thus restoring normal cell growth independent of glycine addition. Finally, the plasmid pPK10 was introduced to overexpress pgk, serAΔ197, serC and serB, and the resulting strain E4G2 (pPK10) accumulated 266.3 mg/L of L-serine in a semi-defined medium without adding glycine, which was 3.18-fold higher than the production achieved by the control strain E3 (pPK10). This strategy can accordingly be applied to disrupt the L-serine degradation pathway in industrial production strains without causing negative side-effects, ultimately making L-serine production more efficient.

Value of Contrast-Enhanced Ultrasonography in the Differential Diagnosis of Enlarged Lymph Nodes: a Meta-Analysis of Diagnostic Accuracy Studies

Jin, Ya,He, Yu-Shuang,Zhang, Ming-Ming,Parajuly, Shyam Sundar,Chen, Shuang,Zhao, Hai-Na,Peng, Yu-Lan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Objective: To evaluate the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) in differentiating between benign and malignant enlarged lymph nodes using meta-analysis. Materials and Methods: Pubmed, Embase, SCI and Cochrane databases were searched for studies (up to September 1, 2014) reporting the diagnostic performance of CEUS in discriminating between benign and malignant lymph nodes. Inclusion criteria were: prospective study; histopathology as the reference standard; and sufficient data to construct $2{\times}2$ contingency tables. Methodological quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Patient clinical characteristics, sensitivity and specificity were extracted. The summary receiver operating characteristic curve was used to examine the accuracy of CEUS. A meta-analysis was performed to evaluate the clinical utility in identification of benign and malignant lymph nodes. Sensitivity analysis was performed after omitting outliers identified in a bivariate boxplot and publication bias was assessed with Egger testing. Results: The pooled sensitivity, specificity and AUROC were 0.92 (95%CI, 0.85-0.96), 0.91 (95%CI, 0.82-0.95) and 0.97 (95%CI, 0.95-0.98), respectively. After omitting 3 outlier studies, heterogeneity decreased. Sensitivity analysis demonstrated no disproportionate influences of individual studies. Publication bias was not significant. Conclusions: CEUS is a promising diagnostic modality in differentiating between benign and malignant lymph nodes and can potentially reduce unnecessary fine-needle aspiration biopsies of benign nodes.

Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas

Xiao, Li-Jun,Zhao, Shuang,Zhao, En-Hong,Zheng, Xin,Gou, Wen-Feng,Xing, Ya-Nan,Takano, Yasuo,Zheng, Hua-Chuan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background: The mucin components of the gastric gel layer function as a protective and lubricating factor against luminal acid and proteolytic enzymes. Alteration of mucin expression in gastric preneoplastic and neoplastic lesions has suggested potential roles in neoplastic processes. This study aimed to assess the clinicopathological and prognostic significance of MUC-2, MUC-4 and MUC-5AC in Japanese gastric cancer. Methods: Expression of MUC-2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas and adjacent non-cancerous mucosa specimens by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients. Results: The three mucins were found to be expressed to a lesser extent in gastric carcinomas in comparison with non-cancerous mucosa (p<0.05). MUC-2 expression was negatively correlated with tumor size, depth of invasion, and TNM staging of gastric cancer (p<0.05), while that of MUC-5AC was negatively associated with the depth of invasion, venous invasion, lymph node metastasis and TNM staging (p<0.05), but positively with MUC-4 and MUC-2 expression (p<0.05). There was higher MUC-2 expression in intestinal- than diffuse-type carcinomas (p<0.05). Kaplan-Meier analysis indicated no relationship between expression of the three mucins and the cumulative survival rate of patients, even stratified according to the depth of invasion (p>0.05). Conclusion: Down-regulated expression of MUC-2, -4 and -5AC may be involved in pathogenesis, invasion, metastasis or differentiation of gastric carcinoma. Their altered expression might therefore be employed as an indicator of pathobiological behavior.

The Beneficial Effects of Electroacupuncture at PC6 Acupoints (Neiguan) on Myocardial Ischemia in ASIC3 / mice

Ying-Wang,Yi-guo Chen,Wan-shuang Zhao,Di Li,Ya-han Xu,Meng-di Li,Jin Chen,Zhi-jun Kou,Qi-ge Wang,Nsoa dimitri Joseph 사단법인약침학회 2018 Journal of Acupuncture & Meridian Studies Vol.11 No.3

This study aims to investigate the possible mechanisms of electroacupuncture (EA) at PC6to improve myocardial ischemia (MI) by regulating the cardiac transient outward potassiumcurrent channel (Ito). According to the random number table, the mice were dividedinto six groups of six mice each: control group, MI group, PC6, LU7 (Lieque-point), ST36(Zusanli-point), and nonacupoint group. Mice in the control group were injected with saline(20 mg/kg, 24 hours interval), and the other ASIC3 / mice were injected subcutaneouslytwice with isoproterenol (ISO) (20 mg/kg, 24 hours interval). In thepreexperiment, 5 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg of ISO were used, andthe results showed that 5 mg/kg and 10 mg/kg of ISO both could induce acute MI, butshorter duration of sustained MI. On the other hand, an injection of 30 mg/kg can makethe mice experience arrhythmia or die immediately, and EA was operated at PC6, LU7,ST36 acupoints, and nonacupoint in the mice of PC6, LU7, ST36, and nonacupoint groups,respectively, after injecting twice. Then Western blotting techniques (Western Blot) wereused to analyze the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KchIP2. The results ofthis experiment showed that the protein expressions of Kv1.4, Kv4.2, Kv4.3, and KChIP2 inMI group were significantly lower than those in the control group (p < 0.01). Comparedwith MI group, the results of PC6, LU7, and ST36 groups obviously increased (p < 0.05). Furthermore, the expressions of PC6 group were higher than LU7 group and ST36 group(p < 0.05). And electrocardiogram’s T-waves showed obvious pathological changes inthe MI group compared to the control group (p < 0.01). After EA, the abnormal T-waves voltage of ECG in PC6, LU7, and ST36 groups was improved (p < 0.05). In addition, therate change of PC6 group was larger than that of both LU7 and ST36 groups (p < 0.05). But the T-waves voltage of the nonacupoint group was not significantly different than thatof the MI group (p > 0.05).

Methylation Status of Transcriptional Modulatory Genes Associated with Colorectal Cancer in Northeast China

Han-Lu Gao,Xuan Wang,Hong-Ru Sun,Jun-De Zhou,Shang-Qun Lin,Yu-Hang Xing,Lin Zhu,Hai-Bo Zhou,Ya-Shuang Zhao,Qiang Chi,Yu-Peng Liu 거트앤리버 소화기연관학회협의회 2018 Gut and Liver Vol.12 No.2

Background/Aims: Methylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear. Methods: We performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting. Results: Total heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [ORadjusted], 5.445; 95% confidence interval [CI], 3.075 to 9.643; ORadjusted, 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (ORadjusted, 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant. Conclusions: The gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.

Breastfeeding and Ovarian Cancer Risk: a Systematic Review and Meta-analysis of 40 Epidemiological Studies

Li, Da-Peng,Du, Chen,Zhang, Zuo-Ming,Li, Guang-Xiao,Yu, Zhi-Fu,Wang, Xin,Li, Peng-Fei,Cheng, Cheng,Liu, Yu-Peng,Zhao, Ya-Shuang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

The present systematic review and meta-analysis was conducted to assess any association between breastfeeding and the risk of ovarian cancer. A systematic search of published studies was performed in PUBMED and EMBASE and by reviewing reference lists from retrieved articles through March 2013. Data extraction was conducted independently by two authors. Pooled relative risk ratios were calculated using random-effect models. Totals of 5 cohort studies and 35 case-control studies including 17,139 women with ovarian cancer showed a 30% reduced risk of ovarian cancer when comparing the women who had breastfed with those who had never breastfed (pooled RR = 0.70, 95% CI: 0.64-0.76; p = 0.00), with significant heterogeneity in the studies (p = 0.00; I2 = 76.29%). A significant decreasd in risk of epithelial ovarian cancer was also observed (pooled RR = 0.68, 95% CI: 0.61-0.76). When the participants were restricted to only parous women, there was a slightly attenuated but still significant risk reduction of ovarian cancer (pooled RR = 0.76, 95% CI: 0.69-0.83). For total breastfeeding duration, the pooled RRs in the < 6 months, 6-12 months and > 12 months of breastfeeding subgroups were 0.85 (95% CI: 0.77-0.93), 0.73 (95% CI: 0.65-0.82) and 0.64 (95%CI: 0.56-0.73), respectively. Meta-regression of total breastfeeding duration indicated an increasing linear trend of risk reduction of ovarian cancer with the increasing total breastfeeding duration (p = 0.00). Breastfeeding was inversely associated with the risk of ovarian cancer, especially long-term breastfeeding duration that demonstrated a stronger protective effect.