Simple Synthesis of Multi-Halogen Pyrazino[1,2-a]indole-1,8(2H,5aH)-diones

Rui-Xia Yang,Yu-Cheng Zhao,Ling-Bin Kong,Sheng-jiao Yan,Jun Lin 대한화학회 2016 Bulletin of the Korean Chemical Society Vol.37 No.10

A concise and efficient one-pot synthesis of multi-halogen pyrazino[1,2-a]indole-1,8(2H,5aH)-dione (MHPID) derivatives by the reaction of an enamino ester with multi-halogen benzoquinone derivatives is described. MHPIDs 3a–3d were obtained with good yields (78–83%) by refluxing enamino esters 1a and 1b and tetrahalogen-1,4-benzoquinones 2a and 2b for 24 h without the use of catalysts. Compounds 3e–3p were also obtained with excellent yields (69–92%) via the reaction of the phenyl-substituted enamino esters 1c–1h with tetrahalogen-1,4-benzoquinones 2a and 2b in CH3CN catalyzed by Cs2CO3. These two protocols are efficient and effective for the synthesis of MHPIDs.

Deciphering the Biodiversity of Listeria monocytogenes Lineage III Strains by Polyphasic Approaches

Hanxin Zhao,Jianshun Chen,Chun Fang,Ye Xia,Changyong Cheng,Lingli Jiang,Weihuan Fang 한국미생물학회 2011 The journal of microbiology Vol.49 No.5

Listeria monocytogenes is a foodborne pathogen of humans and animals. The majority of human listeriosis cases are caused by strains of lineages I and II, while lineage III strains are rare and seldom implicated in human listeriosis. We revealed by 16S rRNA sequencing the special evolutionary status of L. monocytogenes lineage III, which falls between lineages I and II strains of L. monocytogenes and the non-pathogenic species L. innocua and L. marthii in the dendrogram. Thirteen lineage III strains were then characterized by polyphasic approaches. Biochemical reactions demonstrated 8 biotypes, internalin profiling identified 10 internalin types clustered in 4 groups, and multilocus sequence typing differentiated 12 sequence types. These typing schemes show that lineage III strains represent the most diverse population of L. monocytogenes, and comprise at least four subpopulations IIIA-1, IIIA-2, IIIB, and IIIC. The in vitro and in vivo virulence assessments showed that two lineage IIIA-2 strains had reduced pathogenicity, while the other lineage III strains had comparable virulence to lineages I and II. The IIIB strains are phylogenetically distinct from other subpopulations, providing additional evidence that this sublineage represents a novel lineage. The two biochemical reactions L-rhamnose and L-lactate alkalinization, and 10 internalins were identified as potential markers for lineage III subpopulations. This study provides new insights into the biodiversity and population structure of lineage III strains, which are important for understanding the evolution of the L. monocytogenes-L. innocua clade.

Moderate tetrabasic zinc chloride supplementation improves growth performance and reduces diarrhea incidence in weaned pigs

Zhang, Gang,Xia, Tian,Zhao, Jinbiao,Liu, Ling,He, Pingli,Zhang, Shuai,Zhang, Liying Asian Australasian Association of Animal Productio 2020 Animal Bioscience Vol.33 No.2

Objective: Two experiments were conducted to evaluate tetrabasic zinc chloride (TBZC) on the health of weaned pigs, and to determine the optimal supplemental concentrations and whether dietary TBZC could replace the pharmacological concentrations of dietary zinc oxide (ZnO) to improve growth performance and decrease Zn excretion in weaned pigs. Methods: In Exp. 1, 180 weaned pigs (8.92±1.05 kg body weight [BW]) were randomly assigned to 1 of 5 treatments, including the basal diet containing 125 mg/kg zinc sulfate (ZnSO₄), and the basal diet with 1,200, 1,800, 2,400, or 3,000 mg/kg TBZC supplementation. In Exp. 2, 240 weaned pigs (7.66±1.09 kg BW) were randomly assigned to 1 of 5 treatments, including a negative control diet without Zn supplementation, a positive control diet (2,250 mg/kg ZnO), and 3 experimental diets with different concentrations of TBZC supplementation (1,000, 1,250, and 1,500 mg/kg). Results: In Exp. 1, the average daily gain (ADG), feed efficiency (G:F) and diarrhea incidence responded quadratically (p<0.01) as the TBZC supplemental concentrations increased, and pigs fed 1,200 and 1,800 mg/kg TBZC showed the best growth performance. Moreover, 1,800 mg/kg TBZC supplementation showed the greatest (p<0.01) total antioxidant capacity and glutathione peroxidase activities in liver of pigs. Histopathological examination revealed lesions in heart, liver, lung and kidney, and mild or severe histological lesions mainly occurred with the supplementation of 2,400 and 3,000 mg/kg TBZC. In Exp. 2, 1,000 and 1,250 mg/kg TBZC supplementation in diets significantly (p<0.01) increased ADG and G:F of weaned pigs, reduced Zn excretion in feces, and had no effect on diarrhea-reducing compared to 2,250 mg/kg ZnO supplementation. Conclusion: The TBZC is a potential alternative to ZnO. The recommended concentration of TBZC in weaned pig diets is 1,000 to 1,250 mg/kg.

Simple and Sensitive Electrochemical Sandwich-type Immunosensing of Human Chorionic Gonadotropin based on b-cyclodextrin Functionalized Graphene

Linfen Xu,Ling liu,Xiaoyan Zhao,Jinyu Lin,Shaohan Xu,Jinlian He,Debin Jiang,Yong Xia The Korean Electrochemical Society 2023 Journal of electrochemical science and technology Vol.14 No.1

The effective detection of human chorionic gonadotropin (HCG) is considerably important for the clinical diagnosis of both of early pregnancy and nonpregnancy-related diseases. In this work, a simple and sensitive electrochemical sandwich-type immunosensing platform was designed by synthesizing b-cyclodextrin (CD) functionalized graphene (CD/GN) hybrid as simultaneously sensing platform and signal transducer coupled with rhodamine b (RhB) as probe. In brief, GN offers large surface area and high conductivity, while CD exhibits superior host-guest recognition capability, thus the primary antibody (Ab1) of HCG can be bound into the cavities of CD/GN to form stable Ab1/CD/GN inclusion complex; meanwhile, the secondary antibody (Ab2) and RhB can also enter into the cavities, producing RhB/Ab2/CD/GN complex. Then, by using Ab1/CD/GN as sensing platform and RhB/Ab2/CD/GN as signal transducer (in which RhB was signal probe), a simple sandwich-type immunosensor was constructed. Under the optimum parameters, the designed immunosensor exhibited a considerable low analytical detection of 1.0 pg mL^-1 and a wide linearity of 0.002 to 10.0 ng mL^-1 for HCG, revealing the developed sandwich-type electrochemical immunosensing platform offered potential real applications for the determination of HCG.

Cell surface vimentin-targeted monoclonal antibody 86C increases sensitivity to temozolomide in glioma stem cells

Noh, Hyangsoon,Zhao, Qingnan,Yan, Jun,Kong, Ling-Yuan,Gabrusiewicz, Konrad,Hong, Sungguan,Xia, Xueqing,Heimberger, Amy B.,Li, Shulin Elsevier 2018 Cancer letters Vol.433 No.-

<P><B>Abstract</B></P> <P>Glioblastoma multiforme (GBM) is the most prevalent and aggressive brain tumor. The current standard therapy, which includes radiation and chemotherapy, is frequently ineffective partially because of drug resistance and poor penetration of the blood-brain barrier. Reducing resistance and increasing sensitivity to chemotherapy may improve outcomes. Glioma stem cells (GSCs) are a source of relapse and chemoresistance in GBM; sensitization of GSCs to temozoliomide (TMZ), the primary chemotherapeutic agent used to treat GBM, is therefore integral for therapeutic efficacy. We previously discovered a unique tumor-specific target, cell surface vimentin (CSV), on patient-derived GSCs. In this study, we found that the anti-CSV monoclonal antibody 86C efficiently increased GSC sensitivity to TMZ. The combination TMZ+86C induced significantly greater antitumor effects than TMZ alone in eight of 12 GSC lines. TMZ+86C–sensitive GSCs had higher CSV expression overall and faster CSV resurfacing among CSV<SUP>−</SUP> GSCs compared with TMZ+86C–resistant GSCs. Finally, TMZ+86C increased apoptosis of tumor cells and prolonged survival compared with either drug alone in GBM mouse models. The combination of TMZ+86C represents a promising strategy to reverse GSC chemoresistance.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Anti-CSV monoclonal antibody 86C sensitize GSCs to TMZ treatment. </LI> <LI> GSCs with higher CSV expression are more sensitive to TMZ+86C. </LI> <LI> GSCs with higher CSV resurfacing rate among CSV<SUP>−</SUP> cells are more sensitive to TMZ+86C. </LI> <LI> TMZ+86C increased apoptosis and prolonged survival in GBM models. </LI> <LI> Tumor-specific CSV antibody 86C can efficiently target human GSCs to increase their sensitivity to TMZ. </LI> </UL> </P>

Association of Reduced Immunohistochemical Expression of E-cadherin with a Poor Ovarian Cancer Prognosis - Results of a Meta-analysis

Peng, Hong-Ling,He, Lei,Zhao, Xia Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Purpose: E-cadherin is a transmemberane protein which is responsible for adhesion of endothelial cells. The aim of our study was to assess existing evidence of associations between reduced expression of E-cadherin and prognosis of ovarian cancer with a discussion of potential approaches to exploiting any prognostic value for improved clinical management. Methods: We conducted a meta-analysis of 9 studies (n=915 patients) focusing on the correlation of reduced expression of E-cadherin with overall survival. Data were synthesized with random or fixed effect hazard ratios. Results: The studies were categorized by author/year, number of patients, FIGO stage, histology, cutoff value for E-cadherin positivity, and methods of hazard rations (HR) estimation, HR and its 95% confidence interval (CI). Combined hazard ratios suggested that reduced expression of E-cadherin positivity was associated with poor overall survival (OS), HR= 2.10, 95% CI:1.13-3.06. Conclusion: The overall survival of the E-cadherin negative group with ovarian cancer was significant poorer than the E-cadherin positive group. Upregulation of E-cadherin is an attractive therapeutic approach that could exert significant effects on clinical outcome of ovarian cancer.

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

Xu, Jia-Li,Hu, Ling-Min,Huang, Ming-De,Zhao, Wan,Yin, Yong-Mei,Hu, Zhi-Bin,Ma, Hong-Xia,Shen, Hong-Bing,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.

Characterization and Expression Profile Analysis of a New cDNA Encoding Taxadiene Synthase from Taxus media

Guo Yin Kai,Ling Xia Zhao,Lei Zhang,Zhu Gang Li,Bin Hui Guo,Dong Li Zhao,Xiao Fen Sun,Zhi Qi Miao,Ke Xuan Tang 한국생활환경학회 2005 BMB Reports Vol.38 No.6

Alkylglyceronephosphate Synthase (AGPS) Alters Lipid Signaling Pathways and Supports Chemotherapy Resistance of Glioma and Hepatic Carcinoma Cell Lines

Zhu, Yu,Liu, Xing-Jun,Yang, Ping,Zhao, Meng,Lv, Li-Xia,Zhang, Guo-Dong,Wang, Qin,Zhang, Ling Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2. ${\beta}$-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells.

Causes, Features, and Outcomes of Drug-Induced Liver Injury in 69 Children from China

( Yun Zhu ),( Yong Gang Li ),( Jia Bo Wang ),( Shu Hong Liu ),( Li Fu Wang ),( Yan Ling Zhao ),( Yun Feng Bai ),( Zhong Xia Wang ),( Jian Yu Li ),( Xiao He Xiao ) 대한소화기학회 2015 Gut and Liver Vol.9 No.4

Background/Aims: Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited. Methods: All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied. Results: A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows: hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs 18/39, p=0.031). Conclusions: Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable. (Gut Liver 2015;9:525-533)