Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes

GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood glucose. In this study, a series of novel GPR120 agonists were designed and synthesized to improve the stability and hydrophilicity of the phenylpropanoic acid GPR120 agonist TUG-891. Compound 11b showed excellent GPR120 agonistic activity and pharmacokinetic properties, and could reduce the blood glucose of normal mice in a dose-dependent manner. In addition, no hypoglycemic side effects were observed even at a dose of 100 mg/kg. Moreover, 11b showed good anti-hyperglycemic effects in diet-induced obese (DIO) mice. Molecular simulation illustrated that compound 11b could enter the active site of GPR120 and interact with ARG99. Taken together, the results indicate that compound 11b might be a promising drug candidate for the treatment of T2DM

Characterization of the <i>Liriodendron chinense</i> Pentatricopeptide Repeat (PPR) Gene Family and Its Role in Osmotic Stress Response

The Pentatricopeptide repeat (PPR) superfamily is a large gene family in plants that regulates organelle RNA metabolism, which is important for plant growth and development. However, a genome-wide analysis of the PPR gene family and its response to abiotic stress has not been reported for the relict woody plant Liriodendron chinense. In this paper, we identified 650 PPR genes from the L. chinense genome. A phylogenetic analysis showed that the LcPPR genes could roughly be divided into the P and PLS subfamilies. We found that 598 LcPPR genes were widely distributed across 19 chromosomes. An intraspecies synteny analysis indicated that duplicated genes from segmental duplication contributed to the expansion of the LcPPR gene family in the L. chinense genome. In addition, we verified the relative expression of Lchi03277, Lchi06624, Lchi18566, and Lchi23489 in the roots, stems, and leaves and found that all four genes had the highest expression in the leaves. By simulating a drought treatment and quantitative reverse transcription PCR (qRT-PCR) analysis, we confirmed the drought-responsive transcriptional changes in four LcPPR genes, two of which responded to drought stress independent of endogenous ABA biosynthesis. Thus, our study provides a comprehensive analysis of the L. chinense PPR gene family. It contributes to research into their roles in this valuable tree species’ growth, development, and stress resistance

Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes

GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood glucose. In this study, a series of novel GPR120 agonists were designed and synthesized to improve the stability and hydrophilicity of the phenylpropanoic acid GPR120 agonist TUG-891. Compound 11b showed excellent GPR120 agonistic activity and pharmacokinetic properties, and could reduce the blood glucose of normal mice in a dose-dependent manner. In addition, no hypoglycemic side effects were observed even at a dose of 100 mg/kg. Moreover, 11b showed good anti-hyperglycemic effects in diet-induced obese (DIO) mice. Molecular simulation illustrated that compound 11b could enter the active site of GPR120 and interact with ARG99. Taken together, the results indicate that compound 11b might be a promising drug candidate for the treatment of T2DM

Gibberellin Oxidase Gene Family in L. chinense: Genome-Wide Identification and Gene Expression Analysis

GAox is a key enzyme for the transformation of gibberellins, and belongs to the 2-ketoglutarate dependent dioxygenase gene family (2ODD). However, a systematic analysis of GAox in the angiosperm L. chinense has not yet been reported. Here, we identified all LcGAox gene family members in L. chinense, which were classified into the three subgroups of GA20ox, C19GA2ox, and C20GA2ox. Comparison of the gene structure, conserve motifs, phylogenetic relationships, and syntenic relationships of gibberellin oxidase gene families in different species indicated that the gene functional differences may be due to the partial deletion of their domains during evolution. Furthermore, evidence for purifying selection was detected between orthologous GAox genes in rice, grape, Arabidopsis, and L. chinense. Analysis of the codon usage patterns showed that mutation pressure and natural selection might have induced codon usage bias in angiosperms; however, the LcGAox genes in mosses, lycophytes, and ambarella plants exhibited no obvious codon usage preference. These results suggested that the gibberellin oxidase genes were more primitive. The gene expression pattern was analyzed in different organs subjected to multiple abiotic stresses, including GA, abscisic acid (ABA), and chlormequat (CCC) treatment, by RNA-seq and qRT-PCR, and the stress- and phytohormone-responsive cis-elements were counted. The results showed that the synthesis and decomposition of GA were regulated by different LcGAox genes in the vegetative and reproductive organs of L. chinense, and only LcGA2ox1,4, and 7 responded to the NaCl, polyethylene glycol, 4 °C, GA, ABA, and CCC treatment in the roots, stems, and leaves of seedlings at different time periods, revealing the potential role of LcGAox in stress resistance

2nd International Conference on Agricultural and Biological Sciences (ABS 2016), Shanghai, China, July 23-26, 2016 Abstracts

Table of contents 01 The influence of soil salt content on the photosynthetic characteristics of spring wheat with trickle irrigation Lei Pei, Zhenhua Wang, Jinzhu Zhang, Wenhao Li 02 Comparing growth of fast-growing and slow-growing endophytes in plants via ergosterol quantification Adeline SY Ting, Yiing Y Chow, Sadequr Rahman 03 Transcriptome and digital gene expression analysis identifies putative triterpene saponin-biosynthetic genes of Panax notoginseng Rongchang Wei 04 Chitosan-assisted isolation and antioxidant evaluation of flavonoids from Sophora japonica L. Zhang Hu, Sidong Li, Chuyan Li, Zijuan Li 05 Two kinds of new characteristics of the ektexine ornamentation of ginkgo pollen Guoxia Wang, Yuzhen Yang, Gang Chen, Qing Luo 06 Analysis of nutrient and medicinal ingredients of Ginkgo pollen in different regions Guoxia Wang, Ruixia Liu, Yuzhen Yang, Lipei Chen 07 Photosynthetic performance of greening seedlings of seven species to drought stress Zhiyang Lie, Tongtong Zhou, Weilong Huang, Li Xue 08 Changes of fluorescence parameters of greening seedlings of seven species under drought stress Jie Li, Zhuomin Wang, Li Xue 09 Mammalian sex hormone affects regeneration capacity and enzymes activity of Triticale L in vitro culture Ismail Bezirganoglu, Pınar Uysal 10 Fractional Fourier entropy increases the recognition rate of fruit type detection Shuihua Wang, Zhihai Lu, Jiquan Yang, Yudong Zhang, John Liu, Ling Wei, Shufang Chen, Preetha Phillips, Zhengchao Dong 11 Banana-peanut intercropping reduces Fusarium wilt disease in banana from enhancing soil bacterial microorganisms and leaf nutrition Hong Li, Xutong Wang, Fengliang Zhao, Guisheng Yang 12 Manganese stress impairs stem ureide nitrogen fixation in yardlong-bean plants in the acidic environment Hong Li 13 A new pest control method for Rhytidodera bowringii Larvae Haijie Huang, Li Zhao, Weijian Huang, Jinhui Wang, Zhongrun Zhang 14 Research on the seed-like Fruits of Subg. Sclarea of Salvia of Labiatae in China Xiaojuan Li, Ning Xu, Guofu Zhou, Ming Wan, Qi Lin, Fanyun Meng, Jianxiu Li 15 Three pulling resistance models of pioneer plant in landslide area Yichang Chen, Koayung Yu, Chunpin Chang 16 The comparison of physiological and biochemical mechanisms of Reaumuria soongorica and Salsola passerine in different growth pattern Zijuan Zhou, Peixi Su, Rui Shi, Tingting Xie 17 Resources use efficiency of the cosmopolitan plant Potentilla anserina L. in different alpine habitats in China Rui Shi, Peixi Su, Zijuan Zhou 18 Cloning of PPDK gene from Red Amaranand transformation of Alfalfa Xuelan Liu, Yan Zhang, Xiangfa Wei 19 Variation and cluster analysis of morphological characters and nutrient content of Chucrasia tabularis seed Chong Wu, Yanlei Yin, Lijuan Feng, Xuemei Yang, Fei Wang 20 Effect of the planting density of the areca nut on the growth of intercropped Vanilla Hua Wang, Huifa Zhuang, Zihui Zhu, Hui Wan