Dose-Response Relationship between Alanine Aminotransferase Levels within the Reference Interval and Metabolic Syndrome in Chinese Adults

Peipei Wu,Shumei Wang,Qicai Chen,Lili Chen,Pengpeng Zhang,Juan Xiao,Xiaoxiao Chen,Meng Liu 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.1

Purpose: Elevation in serum alanine aminotransferase (ALT) levels is a biomarker for metabolic syndrome (MS); however, the relationshiphas not been fully investigated within the reference interval of ALT levels. Our objective was to explore the relationship between serum ALT levels within the reference interval and MS in Chinese adults. Materials and Methods: This cross-sectional study included 16028 adults, who attended routine health check-ups at Shengli OilfieldCentral Hospital from January 2006 to March 2012. The reference interval of serum ALT level was defined as less than 40 U/L. Logistic regression models and restricted cubic spline were used to evaluate the association of ALT with MS. Results: The prevalence of MS in the total population was 13.7% (6.4% for females and 18.4% for males). Multiple logistic regressionshowed that ALT levels were positively associated with MS after adjustment for potential confounding factors. The odds ratio of MS in the top quartile was 4.830 [95% confidence interval (CI): 2.980–7.829] in females and 3.168 (95% CI: 2.649–3.790) in males, compared with the ALT levels in the bottom quartile. The restricted cubic spline models revealed a positive non-linear dose-response relationship between ALT levels and the risk of MS in women (p for nonlinearity was 0.0327), but a positive linear dose-response relationship in men (p for nonlinearity was 0.0659). Conclusion: Serum ALT levels within the reference interval are positively associated with MS in a dose-response manner. ElevatedALT levels, even within the reference interval, may reflect early dysmetabolic changes.

Detection of genome-wide structural variations in the Shanghai Holstein cattle population using next-generation sequencing

Dengying Liu,Zhenliang Chen,Zhe Zhang,Hao Sun,Peipei Ma,Kai Zhu,Guanglei Liu,Qishan Wang,Yuchun Pan 아세아·태평양축산학회 2019 Animal Bioscience Vol.32 No.3

Objective: The Shanghai Holstein cattle breed is susceptible to severe mastitis and other diseases due to the hot weather and long-term humidity in Shanghai, which is the main distribution centre for providing Holstein semen to various farms throughout China. Our objective was to determine the genetic mechanisms influencing economically important traits, especially diseases that have huge impact on the yield and quality of milk as well as reproduction. Methods: In our study, we detected the structural variations of 1,092 Shanghai Holstein cows by using next-generation sequencing. We used the DELLY software to identify deletions and insertions, cn.MOPS to identify copy-number variants (CNVs). Furthermore, we annotated these structural variations using different bioinformatics tools, such as gene ontology, cattle quantitative trait locus (QTL) database and ingenuity pathway analysis (IPA). Results: The average number of high-quality reads was 3,046,279. After filtering, a total of 16,831 deletions, 12,735 insertions and 490 CNVs were identified. The annotation results showed that these mapped genes were significantly enriched for specific biological functions, such as disease and reproduction. In addition, the enrichment results based on the cattle QTL database showed that the number of variants related to milk and reproduction was higher than the number of variants related to other traits. IPA core analysis found that the structural variations were related to reproduction, lipid metabolism, and inflammation. According to the functional analysis, structural variations were important factors affecting the variation of different traits in Shanghai Holstein cattle. Our results provide meaningful information about structural variations, which may be useful in future assessments of the associations between variations and important phenotypes in Shanghai Holstein cattle. Conclusion: Structural variations identified in this study were extremely different from those of previous studies. Many structural variations were found to be associated with mastitis and reproductive system diseases; these results are in accordance with the characteristics of the environment that Shanghai Holstein cattle experience.

Centromere protein N promotes lung adenocarcinoma progression by activating PI3K/AKT signaling pathway

Zheng Yi,You Hui,Duan Jingzhu,Chen Biyu,Wu Chenlin,Chen Peipei,Wang Meifang 한국유전학회 2022 Genes & Genomics Vol.44 No.9

Background: As an important member of centromere family, centromere associated protein N (CENPN) was abnormally expressed in varied malignant tumors. Objective: This paper aimed to analyze the expression and related mechanism of CENPN in lung adenocarcinoma (LUAD). Methods: The expression of CENPN in LUAD was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) database. The mRNA expression, protein expression, cell viability, cell invasion, cell apoptosis, cell stem like characteristics were detected by RT-PCR, western blot, CCK8 assay, transwell assay, flow cytometry and spheroidization assay, respectively. Finally, the pathological changes of xenograft were estimated by H&E staining, and the expression of proteins was detected by immunohistochemistry. Results: GEPIA analysis showed that the CENPN expression in LUAD was significantly higher than that in normal lung tissue, which was negatively correlated with the prognosis. These results were consistent with our clinical data. Besides, CENPN was highly expressed in LUAD cell lines. In addition, the upregulation of CENPN amplified the cell viability, stemness and invasive ability in PC9 cells. However, the knockdown of CENPN inhibited the cell activity, stemness, invasive ability with increased cell apoptosis in A549. Furthermore, CENPN could positively regulate the phosphorylation of PI3K and AKT. The PI3K inhibitor, 740Y-P, could reverse the effect of CENPN silencing on the expression of Ki-67, cleaved caspase 3, OCT4, and snail 1. Finally, the downregulation of CENPN restrained the growth of xenograft and inactivated the PI3K/AKT pathway. Conclusion: CENPN was abnormally overexpressed in LUAD, and promoted tumor progression of LUAD by affecting PI3K/AKT pathway.

Establishment and Application of Target Gene Disruption System in Saccharomyces boulardii

Longjiang Wang,Hui Sun,Jie Zhang,Qing Liu,Tiantian Wang,Peipei Chen,Hongmei Li,Yihong Xiao,Fangkun Wang,Xiaomin Zhao 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.1

Saccharomyces boulardii is the best knownprobiotic yeast, widely used as a therapeutic agent for thetreatment or prevention of diarrhea and intestine disorders. In the present work, we established a target gene disruptionsystem for S. boulardii based on the Cre-loxP system usedfor S. cerevisiae and other fungi by screening out selectionmarkers, working out the transformation method, andconstructing essential plasmids for S. boulardii. Theestablished system was successfully applied to the URA3gene disruption and created an ura3 null mutant strain ofS. boulardii. The system can be used for PCR mediatedgene disruption, cloning mediated gene disruption, andreintroduction of the deleted gene back to the mutant. Allthe introduced exogenous DNAs in the gene disruptionprocedures were removed from the final mutant strainexcept the two 34 bp loxP pieces left in deleted gene loci.

Anti-Tumor Effect of a Novel DOX/GA-CdTe QD was Mediated by Apoptotic and Autophagic Cell Death

Huaqin Zuo,Fan Wang,Di Zhou,Yi Zhou,Bing Chen,Jian Ouyang,Peipei Xu 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2017 NANO Vol.12 No.1

Burkitt's lymphoma is a highly proliferative B-cell malignancy characterized by MYC oncogene translocation. Intensive short-cycle chemotherapy could effectively improve the outcome of this disease. However, drug resistance limits the treatment of refractory/relapsed disease. Thus, we constructed and investigated a novel cadmium–tellurium quantum dot conjugated with doxorubicin and gambogic acid (DOX/GA-CdTe QDs) for cancer cell combined treatment in Raji, a Burkitt's lymphoma cell line. Results showed that DOX/GA-CdTe QDs could significantly improve anti-tumor effects compared with drugs alone in the Raji cell line. Flow cytometry, transmission electron micrographs and overexpression of Beclin1 and LC3 II/I showed that apoptosis and autophagy were involved in the process. However, DOX/GA-CdTe QDs did not cause cell cycle arrest, whereas DOX alone or combined with GA could cause apparent G2/M phase arrest. Hence, the novel DOX/GA-CdTe QDs offer a promising approach of drug delivery into cancer cells.

Bone Morphogenetic Protein 9 Overexpression Reduces Osteosarcoma Cell Migration and Invasion

Zilan Lv,Ya-guang Weng,Dandan Yang,Jie Li,Min Hu,Min Luo,Xiaoqin Zhan,Peipei Song,Chen Liu,Huili Bai,Baolin Li,Yang Yang,Yingying Chen,Qiong Shi 한국분자세포생물학회 2013 Molecules and cells Vol.36 No.2

Transforming growth factor- (TGF-) is known to pro-mote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF- family expressed in a variety of human carcinoma cell lines. The role of bone morphogenetic protein 9 (BMP9), the most powerful osteogenic factor, in osteosarcoma (OS) progression has not been fully clarified. The expression of BMP9 and its receptors in OS cell lines was analyzed by RT-PCR. We found that BMP9 and its receptors were expressed in OS cell lines. We further investigated the influence of BMP9 on the biological behaviors of OS cells. BMP9 overexpression in the OS cell lines 143B and MG63 inhibited in vitro cell migration and invasion. We further investigated the ex-pression of a panel of cancer-related genes and found that BMP9 overexpression increased the phosphorylation of Smad1/5/8 proteins, increased the expression of ID1, and reduced the expression and activity of matrix metalloproteinase 9 (MMP9) in OS cells. BMP9 silencing induced the opposite effects. We also found that BMP9 may not affect the chemokine (C-X-C motif) ligand 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis to regulate the invasiveness and metastatic capacity of OS cells. Interestingly, CXCR4 was expressed in both 143B and MG63 cells, while CXCL12 was only detected in MG63 cells. Taken together, we hypothesize that BMP9 inhibits the migration and invasiveness of OS cells through a Smad-dependent pathway by downregulating the expression and activity of MMP9.

Phase II trial of VEGFR2 inhibitor apatinib for metastatic sarcoma: focus on efficacy and safety

Zhichao Liao,Feng Li,Chao Zhang,Lei Zhu,Yehui Shi,Gang Zhao,Xu Bai,Shafat Hassan,Xinyue Liu,Ting Li,Peipei Xing,Jun Zhao,Jin Zhang,Ruwei Xing,Sheng Teng,Yun Yang,Kexin Chen,Jilong Yang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Apatinib (YN968D1) is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR- 2). We conducted a single-arm, nonrandomized phase II study (NCT03121846) to assess the efficacy and safety of apatinib in patients with stage IV sarcoma. We recruited 64 patients with stage IV sarcoma who had failed chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were progression-free survival rate (PFR), objective response rate (ORR), and disease control rate (DCR) at week 12. Treatment-related adverse effects (AEs) were evaluated. Fifty-nine patients were assessed for efficacy and 64 patients for AEs. The median PFS was 7.93 months. At 12 weeks, the PFR was 74%, the ORR was 16.95% (10/59), and the DCR was 86.44% (51/59). The final ORR was 15.25% (9/59) and the DCR was 57.63% (34/59). Notably, 22 patients (34.38%) who developed hypertension, hand-foot-skin reaction, or proteinuria had significantly longer OS than those without these AEs (18.20 vs. 10.73 months; P = 0.002). We conclude that apatinib is effective and well tolerated in patients with advanced sarcoma. The development of hypertension, hand-foot-skin reaction, or proteinuria may indicate a favorable prognosis, representing a novel finding in sarcoma patients.