Design of potent, non-toxic anticancer peptides based on the structure of the antimicrobial peptide, temporin-1CEa

Qing-Zhu Yang,Che Wang,Lei Lang,Yang Zhou,He Wang,De-Jing Shang 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.11

Recent advances in the search for novel anticanceragents have indicated that the positively chargedantimicrobial peptides have emerged as promising agentsoffering several advantages over the conventional anticancerdrugs. As a naturally occurring, cationic, a-helicalantimicrobial peptide, temproin-1CEa has been proved toexhibit a potent anticancer effect and a moderate hemolyticactivity. In order to reduce the hemolytic activity of temporin-1CEa and improve its anticancer potency towards arange of human breast cancer cells, in the present study, sixanalogs of temporin-1CEa were rationally designed andsynthesized. The amphipathicity levels and a-helicalstructural patterns of peptides were reserved, while theircationic property and hydrophobicity were changed. Theresults of MTT and hemolysis assay indicated that theanalog peptides displayed an improved anticancer activityand showed an overall optimized therapeutic index. Thehydrophobicity of peptides was positively correlated withtheir hemolytic and antitumor activities. Moreover, the datasuggest a strategy of increasing the cationicity whilemaintaining the moderate hydrophobicity of naturallyoccurring amphipathic a-helical peptides to generate analogswith improved cytotoxicity against tumor cells butdecreased activity against non-neoplastic cells such ashuman erythrocytes. This work highlights the potential forrational design and synthesis of improved antimicrobialpeptides that have the capability to be used therapeuticallyfor treatment of cancers.

Synthesis, Characterization and Biological Activities of Novel (E)-3-(1-(Alkyloxyamino)ethylidene)-1-alkylpyrrolidine-2,4-dione Derivatives

Zhu, Zhao-Yong,Shi, Qing-Ming,Han, Bao-Feng,Wang, Xian-Feng,Qiang, Sheng,Yang, Chun-Long Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.9

Twenty novel tetramic acid derivatives (E)-3-(1-(alkyloxyamino)ethylidene)-1-alkylpyrrolidine-2,4-diones were synthesized by the reaction of 3-(1-hydroxyethylidene)pyrrolidine-2,4-diones with O-alkyl hydroxylamines. The title compounds were confirmed by IR, $^1H$ NMR, MS and elemental analysis. The structure of compound 6r was further verified by X-ray diffraction crystallography. The bioassays showed that most of the title compounds exhibited noticeable herbicidal and fungicidal activities.

Comparative Phylogenetic Relationships and Genetic Structure of the Caterpillar Fungus Ophiocordyceps sinensis and Its Host Insects Inferred from Multiple Gene Sequences

Qing-Mei Quan,Qing-Xia Wang,Xue-Li Zhou,Shan Li,Xiao-Ling Yang,Yun-Guo Zhu,Zhou Cheng 한국미생물학회 2014 The journal of microbiology Vol.52 No.2

Ophiocordyceps sinensis (Ascomycota: Ophiocordycipitaceae)is a native fungal parasite of Hepialidae caterpillars and oneof the most economically important medicinal caterpillarfungi in China. However, little is known about the phylogeneticand evolutionary relationships between O. sinensis andits host insects. In this study, nuclear ITS and β-tubulin sequencesfrom O. sinensis and mitochondrial COI, COII, andCytb sequences from its hosts were analyzed across 33 populationssampled from five regions in China. Phylogenetically,both O. sinensis and its hosts were divided into three geographicallycorrelated clades, and their phylogenies were congruent. Analysis of molecular variance and calculated coefficientsof genetic differentiation revealed significant geneticdivergence among the clades within both O. sinensis (FST=0.878, NST=0.842) and its hosts (FST=0.861, NST=0.816). Estimatedgene flow was very low for O. sinensis (Nm=0.04) andthe host insects (Nm=0.04) among these three clades. Manteltests demonstrated a significant correlation (P<0.01) betweenthe genetic distances for O. sinensis and its hosts, as well as asignificant association (P<0.05) between geographic and geneticdistances in both. The similar phylogenetic relationships,geographic distributions, and genetic structure and differentiationbetween O. sinensis and its hosts imply that they have coevolved.

Genetic Effects of Polymorphisms in Myogenic Regulatory Factors on Chicken Muscle Fiber Traits

Yang, Zhi-Qin,Qing, Ying,Zhu, Qing,Zhao, Xiao-Ling,Wang, Yan,Li, Di-Yan,Liu, Yi-Ping,Yin, Hua-Dong Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.6

The myogenic regulatory factors is a family of transcription factors that play a key role in the development of skeletal muscle fibers, which are the main factors to affect the meat taste and texture. In the present study, we performed candidate gene analysis to identify single-nucleotide polymorphisms in the MyoD, Myf5, MyoG, and Mrf4 genes using polymerase chain reaction-single strand conformation polymorphism in 360 Erlang Mountain Chickens from three different housing systems (cage, pen, and free-range). The general linear model procedure was used to estimate the statistical significance of association between combined genotypes and muscle fiber traits of chickens. Two polymorphisms (g.39928301T>G and g.11579368C>T) were detected in the Mrf4 and MyoD gene, respectively. The diameters of thigh and pectoralis muscle fibers were higher in birds with the combined genotypes of GG-TT and TTCT (p<0.05). Moreover, the interaction between housing system and combined genotypes has no significant effect on the traits of muscle fiber (p>0.05). Our findings suggest that the combined genotypes of TT-CT and GG-TT might be advantageous for muscle fiber traits, and could be the potential genetic markers for breeding program in Erlang Mountain Chickens.

Risk Factors for Early Recurrence of HBV-related Hepatocellular Carcinoma Meeting Milan Criteria after Curative Resection

Zhu, Wen-Jiang,Huang, Chu-Ying,Li, Chuan,Peng, Wei,Wen, Tian-Fu,Yan, Lv-Nan,Li, Bo,Wang, Wen-Tao,Xu, Ming-Qing,Yang, Jia-Yin,Jiang, Li Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: The prognosis of patients with hepatocellular carcinoma (HCC) after curative resection varies greatly. Few studies had investigated the risk factors for early recurrence (recurrence-free time ${\leq}$ 1 year) of hepatitis B virus (HBV)-related HCCs meeting Milan criteria. Methods: A retrospective analysis was performed on the 224 patients with HCC meeting Milan criteria who underwent curative liver resection in our center between February 2007 and March 2012. The overall survival (OS) rate, recurrence-free survival (RFS) rate and risk factors for early recurrence were analyzed. Results: After a median follow-up of 33.3 months, HCC reoccurred in 105 of 224 patients and 32 died during the period. The 1-, 3- and 5-year OS rates were 97.3%, 81.6% and 75.6% respectively, and the 1-, 3- and 5-year RFS rates were 73.2%, 53.7% and 41.6%. Cox regression showed alpha-fetoprotein (AFP) > 800 ng/ml (HR 2.538, 95% CI 1.464-4.401, P=0.001), multiple tumors (HR 2.286, 95% CI 1.123-4.246, P=0.009) and microvascular invasion (HR 2.518, 95% CI 1.475-4.298, P=0.001) to be associated with early recurrence (recurrence-free time ${\leq}$ 1-year) of HCC meeting Milan criteria. Conclusions: AFP > 800 ng/ml, multiple tumors and microvascular invasion are independent risk factors affecting early postoperative recurrence of HCC. In addition resection appears capable of replacing liver transplantation in some situations with safety and a better outcome.

Genetic Effects of Polymorphisms in Myogenic Regulatory Factors on Chicken Muscle Fiber Traits

Zhiqin Yang,Ying Qing,Qing Zhu,Xiao-Ling Zhao,Yan Wang,Diyan Li,Yi-Ping Liu,Huadong Yin 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.6

The myogenic regulatory factors is a family of transcription factors that play a key role in the development of skeletal muscle fibers, which are the main factors to affect the meat taste and texture. In the present study, we performed candidate gene analysis to identify single-nucleotide polymorphisms in the MyoD, Myf5, MyoG, and Mrf4 genes using polymerase chain reaction-single strand conformation polymorphism in 360 Erlang Mountain Chickens from three different housing systems (cage, pen, and free-range). The general linear model procedure was used to estimate the statistical significance of association between combined genotypes and muscle fiber traits of chickens. Two polymorphisms (g.39928301T>G and g.11579368C>T) were detected in the Mrf4 and MyoD gene, respectively. The diameters of thigh and pectoralis muscle fibers were higher in birds with the combined genotypes of GG-TT and TT-CT (p<0.05). Moreover, the interaction between housing system and combined genotypes has no significant effect on the traits of muscle fiber (p>0.05). Our findings suggest that the combined genotypes of TT-CT and GG-TT might be advantageous for muscle fiber traits, and could be the potential genetic markers for breeding program in Erlang Mountain Chickens.

Cloning and expression of a wild eggplant cytochrome P450 gene, StoCYP77A2, involved in plant resistance to Verticillium dahliae

Liu Yang,Ce Shi,Xiaoying Mu,Chao Liu,Ke Shi,Wen-jiao Zhu,Qing Yang 한국식물생명공학회 2015 Plant biotechnology reports Vol.9 No.4

Plant P450s play an important role in plant response to environmental stimuli, especially to pathogen challenge, besides leading to the biosynthesis of secondary metabolites. In this work, a Verticillium dahliae-induced cDNA sequence was cloned from wild eggplant Solanum torvum and designated StoCYP77A2. StoCYP77A2 encodes a 511-amino acid peptide that shows sequence homology to the plant CYP77 family. StoCYP77A2 is expressed in a tissue-specific manner with the highest expression level in stem. The expression level of StoCYP77A2 was increased in wild eggplants which were infected with Verticillium dahlia. We expressed StoCYP77A2 in V. dahliae-sensitive tobacco, and the transgenic tobacco plants were more resistant to V. dahliae infection than the wild type. Protein extraction of transgenic tobacco showed strong antifungal activity against V. dahliae, indicating that StoCYP77A2 may be involved in the synthesis of some antimicrobial compounds. These results suggest that StoCYP77A2 plays a role in plant defense to V. dahliae infection.

Glutamic Acid Decarboxylase Autoantibody Detection by Electrochemiluminescence Assay Identifies Latent Autoimmune Diabetes in Adults with Poor Islet Function

Yuxiao Zhu,Li Qian,Qing Liu,Jing Zou,Ying Zhou,Tao Yang,Gan Huang,Zhiguang Zhou,Yu Liu 대한당뇨병학회 2020 Diabetes and Metabolism Journal Vol.44 No.2

Background: The detection of glutamic acid decarboxylase 65 (GAD65) autoantibodies is essential for the prediction and diagnosis of latent autoimmune diabetes in adults (LADA). The aim of the current study was to compare a newly developed electrochemiluminescence (ECL)-GAD65 antibody assay with the established radiobinding assay, and to explore whether the new assay could be used to define LADA more precisely. Methods: Serum samples were harvested from 141 patients with LADA, 95 with type 1 diabetes mellitus, and 99 with type 2 diabetes mellitus, and tested for GAD65 autoantibodies using both the radiobinding assay and ECL assay. A glutamic acid decarboxylase antibodies (GADA) competition assay was also performed to assess antibody affinity. Furthermore, the clinical features of these patients were compared. Results: Eighty-eight out of 141 serum samples (62.4%) from LADA patients were GAD65 antibody-positive by ECL assay. Compared with ECL-GAD65 antibody-negative patients, ECL-GAD65 antibody-positive patients were leaner (P<0.0001), had poorer β-cell function (P<0.05), and were more likely to have other diabetes-associated autoantibodies. The β-cell function of ECLGAD65 antibody-positive patients was similar to that of type 1 diabetes mellitus patients, whereas ECL-GAD65 antibody-negative patients were more similar to type 2 diabetes mellitus patients. Conclusion: Patients with ECL-GAD65 antibody-negative share a similar phenotype with type 2 diabetes mellitus patients, whereas patients with ECL-GAD65 antibody-positive resemble those with type 1 diabetes mellitus. Thus, the detection of GADA using ECL may help to identify the subtype of LADA.

Polymorphisms in the Perilipin Gene May Affect Carcass Traits of Chinese Meat-type Chickens

Zhang, Lu,Zhu, Qing,Liu, Yiping,Gilbert, Elizabeth R.,Li, Diyan,Yin, Huadong,Wang, Yan,Yang, Zhiqin,Wang, Zhen,Yuan, Yuncong,Zhao, Xiaoling Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.6

Improved meat quality and greater muscle yield are highly sought after in high-quality chicken breeding programs. Past studies indicated that polymorphisms of the Perilipin gene (PLIN1) are highly associated with adiposity in mammals and are potential molecular markers for improving meat quality and carcass traits in chickens. In the present study, we screened single nucleotide polymorphisms (SNPs) in all exons of the PLIN1 gene with a direct sequencing method in six populations with different genetic backgrounds (total 240 individuals). We evaluated the association between the polymorphisms and carcass and meat quality traits. We identified three SNPs, located on the 5' flanking region and exon 1 of PLIN1 on chromosome 10 (rs315831750, rs313726543, and rs80724063, respectively). Eight main haplotypes were constructed based on these SNPs. We calculated the allelic and genotypic frequencies, and genetic diversity parameters of the three SNPs. The polymorphism information content (PIC) ranged from 0.2768 to 0.3750, which reflected an intermediate genetic diversity for all chickens. The CC, CT, and TT genotypes influenced the percentage of breast muscle (PBM), percentage of leg muscle (PLM) and percentage of abdominal fat at rs315831750 (p<0.05). Diplotypes (haplotype pairs) affected the percentage of eviscerated weight (PEW) and PBM (p<0.05). Compared with chickens carrying other diplotypes, H3H7 had the greatest PEW and H2H2 had the greatest PBM, and those with diplotype H7H7 had the smallest PEW and PBM. We conclude that PLIN1 gene polymorphisms may affect broiler carcass and breast muscle yields, and diplotypes H3H7 and H2H2 could be positive molecular markers to enhance PEW and PBM in chickens.

Synthesis, Characterization and Biological Activities of Novel (E)-3-(1-(Alkyloxyamino)ethylidene)-1-alkylpyrrolidine-2,4-dione Derivatives

Zhao-Yong Zhu,Qing-Ming Shi,Bao-Feng Han,Xian-Feng Wang,Sheng Qiang,Chun-Long Yang 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.9

Twenty novel tetramic acid derivatives (E)-3-(1-(alkyloxyamino)ethylidene)-1-alkylpyrrolidine-2,4-diones were synthesized by the reaction of 3-(1-hydroxyethylidene)pyrrolidine-2,4-diones with O-alkyl hydroxylamines. The title compounds were confirmed by IR, 1H NMR, MS and elemental analysis. The structure of compound 6r was further verified by X-ray diffraction crystallography. The bioassays showed that most of the title compounds exhibited noticeable herbicidal and fungicidal activities.