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A Sophisticated Network of Signaling Pathways Regulates Stomatal Defenses to Bacterial Pathogens

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Molecular Plant 2015年第4期8卷 566-581页

作者： Dominique Arnaud Ildoo Hwang department of Life sciences POSTECH Biotech Center Pohang University of Science and Technology Pohang /90-/84 Korea

Guard cells are specialized cells forming stomatal pores at the leaf surface for gas exchanges between the plant and the atmosphere. Stomata have been shown to playan important role in plant defense as a part of the innate immune response. Plants actively close their stomata upon contact with microbes, thereby preventing pathogen entry into the leaves and the subsequent colonization of host tissues. In this review, we present current knowledge of molecular mechanisms and signaling pathways implicated in stomatal defenses, with particular emphasis on plant-bacteria interactions. Stomatal defense responses begin from the perception of pathogen-associated molecular patterns （PAMPs） and activate a signaling cascade involving the production of secondary messengers such as reactive oxygen species, nitric oxide, and calcium for the regulation of plasma membrane ion channels. The analyses on downstream molecular mechanisms implicated in PAMP-triggered stomatal closure have revealed extensive interplays among the components regulating hormonal signaling pathways. We also discuss the strategies deployed by pathogenic bacteria to counteract stomatal immunity through the example of the phytotoxin coronatine.

关键词： stomata immunity hydrogen peroxide nitric oxide calcium hormones

Mechanism of cancer: Oncohistones in action

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Journal of Genetics and Genomics 2018年第5期45卷 227-236页

作者： Lei Qiu Xiaoyan Hu Qian Jing Xinyi Zeng Kui-Ming Chan Junhong Han department of Abdominal Oncology State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center department of Biomedical sciences City University of Hong Kong

Oncohistones are histones with high-frequency point mutations that are associated with tumorigenesis. Although each histone variant is encoded by multiple genes, a single mutation in one allele of one gene seems to have a dominant effect over global histone H3 methylation level at the relevant amino acid residue. These oncohistones are highly tumor type specific. For example, H3K27M and H3G34V/R mutations occur only in pediatric brain cancers, whereas H3K36M and H3G34W/L have only been found in pediatric bone tumors. H1 mutations also seem to be exclusively linked to lymphomas. In this review, we discuss the occurrence, frequency and potential functional mechanisms of each oncohistone in tumorigenesis of its relevant cancer. We believe that further investigation into the mechanism regarding their tumor type specificity and cancer-related functions will shed new light on their application in cancer diagnosis and targeted therapy development.

关键词： Oncohistone Histone modification Tumorigenesis Pediatric cancer

Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

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World Journal of Gastroenterology 2008年第39期14卷 5945-5961页

作者： Mamta Kalra Jary Mayes Senait Assefa Anil K Kaul Rashmi Kaul department of Biochemistry and Microbiology Oklahoma State University Center for Health SciencesTulsaOklahoma 74107United States

The striking gender disparity observed in the incidence of hepatocellutar carcinoma （HCC） suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor （ER） and androgen receptor （AR） in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.

关键词： Sex hormones Estrogen receptor Androgen receptor Hepatocellular carcinoma Hepatocarcinogenesis

Medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors

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Acta Pharmaceutica Sinica B 2022年第2期12卷 581-599页

作者： Shenghua Gao Tianguang Huang Letian Song Shujing Xu Yusen Cheng Srinivasulu Cherukupalli Dongwei Kang Tong Zhao Lin Sun Jian Zhang Peng Zhan Xinyong Liu department of Medicinal Chemistry Key Laboratory of Chemical BiologyMinistry of EducationSchool of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJi’nan 250012China China-Belgium Collaborative Research center for Innovative Antiviral Drugs of Shandong Province Ji’nan 250012China

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 ***,we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors wi... 详细信息

关键词： SARS-CoV-2 COVID-19 Antiviral drugs Drug design Medicinal chemistry strategies

Preparation and pharmacokinetic study of fenofibrate cubic liquid crystalline

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Asian Journal of pharmaceutical sciences 2017年第6期12卷 580-585页

作者： Shijie Wei Jingbo Ren Ning Li Wuzhen Huo Chongkai Gao Guangdong Provincial Engineering center of topical precise drug delivery system Guangdong Pharmaceutical UniversityGuangzhouGuangdongChina department of Pharmaceutics School of PharmacyGuangdong Pharmaceutical UniversityGuangzhouGuangdongChina Research&Development Institute of Chinese Materia Medica Guangdong Pharmaceutical UniversityGuangzhouGuangdongChina

An LCC delivery system for Fenofibrate (Fen) was developed to improve its poorly oral bioavailability. Fen-LCC preparation methods were screened, and the prepared Fen-LCC was then characterized by a polarizing microscope and transmission electron microscopy (TEM).The spray drying technique was selected to dry and solidify particles into powder. The in vitro release of Fen-LCC was measured and in vivo pharmacokinetic experiments were carried out on rats after oral administration. Particles prepared through the high-temperature input method exhibited structural characteristics of LCC, and re-dissolved particles maintained the same features. The LCC delivery system can significantly improve in vitro release outcomes. After oral administration, AUCs of the suspension and LCC systems were measured at 131.6853 μg·h/ml and 1435.72893 μg·h/ml, respectively. The spray drying process presented here better maintains cubic structures, and the LCC system significantly improves bioavailability levels.

关键词： Lipid cubic liquid crystalline Fenofibrate Spray drying Bioavailability

Distinct functions of Trio GEF domains in axon outgrowth of cerebellar granule neurons

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Journal of Genetics and Genomics 2019年第2期46卷 87-96页

作者： Tao Tao Jie Sun Yajing Peng Pei Wang Xin Chen Wei Zhao Yeqiong Li Lisha Wei Wei Wang Yanyan Zheng Ye Wang Xuena Zhang Min-Sheng Zhu Model Animal Research center State Key Laboratory of Pharmaceutical Biotechnology Department of Neurology of the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School Nanjing University

As a critical guanine nucleotide exchange factor(GEF) regulating neurite outgrowth, Trio coordinates multiple processes of cytoskeletal dynamics through activating Rac1, Cdc42 and RhoA small GTPases by two GEF domains, but the in vivo roles of these GEF domains and corresponding downstream effectors have not been determined yet. We established multiple lines of knockout mice and assessed the respective roles of Trio GEF domains and Rac1 in axon outgrowth. Knockout of total Trio in cerebellar granule neurons(CGNs) led to an impaired F-actin rearrangement of growth cone and hence a retarded neurite outgrowth. Such a retardation was reproduced by inhibition of GEF1 domain or knockdown of Cdc42 and restored apparently by introduction of active Cdc42. As Rac1 deficiency did not affect the neurite outgrowth of CGNs, we suggested that Trio GEF1-mediated Cdc42 activation was required for neurite outgrowth. We established a GEF2-knockout line with deletion of all Trio isoforms except a cerebella-specific Trio8, a short isoform of Trio without GEF2 domain, and used this line as a GEF2-deficient animal model. The GEF2-deficient CGNs had a normal neurite outgrowth but abolished Netrin-1-promoted growth, without affecting Netrin-1 induced Rac1 activation. We thus suggested that Trio GEF1-mediated Cdc42 activation rather than Rac1 activation drives the F-actin dynamics necessary for neurite outgrowth, while GEF2 functions in Netrin-1-promoted neurite elongation. Our results delineated the distinct roles of Trio GEF domains in neurite outgrowth, which is instructive to understand the pathogenesis of clinical Trio-related neurodevelopmental disorders.

关键词： Trio GEF Rho GTPases Axon outgrowth Cerebellar granule neuron

Simplification of vacuole structure during plant cell death triggered by culture filtrates of Erwinia carotovora

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Journal of Integrative Plant Biology 2015年第1期57卷 127-135页

作者： Yumi Hirakawa Toshihisa Nomura Seiichiro Hasezawa Takumi Higaki department of Integrated Biosciences Graduate School of Frontier Sciences The University of Tokyo RIKEN Center for Sustainable Resource Science

Vacuoles are suggested to play crucial roles in plant defense-related cell death. During programmed cell death, previous live cell imaging studies have observed vacuoles to become simpler in structure and have implicated this simplification as a prelude to the vacuole＇s rupture and consequent lysis of the plasma membrane. Here, we examined dynamics of the vacuole in cell cycle-synchronized tobacco BY-2 （Nicotiana tabacum L. cv. Bright Yellow 2） cells during ceil death induced by application of culture filtrates of Erwinia carotovora. The filtrate induced death in about 90% of the cells by 24 h. Prior to cell death, vacuole shape simplified and endoplasmic actin filaments disassembled; however, the vacuoles did not rupture until after plasma membrane integrity was lost. Instead of facilitating rupture, the simplification of vacuole structure might play a role in the retrieval of membrane components needed for defense-related cell death.

关键词： Actin filaments defense-related cell death Erwiniacarotovora tobacco BY-2 cells vacuoles

Characterization and performance of Pt/SBA-15 for low-temperature SCR of NO by C_3H_6

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Journal of Environmental sciences 2013年第5期25卷 1023-1033页

作者： Xinyong Liu Zhi Jiang Mingxia Chen Jianwei Shi Wenfeng Shangguan Yasutake Teraoka Research center for Combustion and Environmental Technology Shanghai Jiao Tong University department of Energy and Material sciences Faculty of Engineering SciencesKyushu UniversityKasugaFukuoka 816-8580Japan

Pt supported on mesoporous silica SBA-15 was investigated as a catalyst for low temperature selective catalytic reduction（SCR） of NO by C 3 H 6 in the presence of excess *** prepared catalysts were characterized by means of XRD,BET surface area,TEM,NO-TPD,NO/C 3 H 6-TPO,NH 3-TPD,XPS and 27 Al MAS *** effects of Pt loading amount,O 2 /C 3 H 6 concentration,and incorporation of Al into SBA-15 have been *** was found that the removal efficiency increased significantly after Pt loading,but an optimal loading amount was *** particular,under an atmosphere of 150 ppm NO,150 ppm C 3 H 6,and 18 vol.% O 2,0.5% Pt/SBA-15 showed remarkably high catalytic performance giving 80.1% NOx reduction and 87.04% C 3 H 6 conversion simultaneously at 140°*** enhanced SCR activity of Pt/SBA-15 is associated with its outstanding oxidation activities of NO to NO 2 and C 3 H 6 to CO 2 in low temperature *** research results also suggested that higher concentration of O 2 and higher concentration of C 3 H 6 favored NO *** incorporation of Al into SBA-15 improved catalytic performance,which could be ascribed to the enhancement of catalyst surface acidity caused by tetrahedrally coordinated AlO ***,the catalysts could be easily reused and possessed good stability.

关键词： low-temperature selective catalytic reduction C 3 H 6 Pt/SBA-15

Purification and characterization of a novel anti-coagulant from the leech Hirudinaria manillensis

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Zoological Research 2019年第3期40卷 205-210页

作者： Ruo-Mei Cheng Xiao-Peng Tang Ai-Lin Long James Mwangi Ren Lai Rui-Pu Sun Cheng-Bo Long Zhen-Qing Zhang department of pharmaceutical sciences College of Pharmaceutical SciencesSoocbow UniversitySuzhou Jiangsu 215123China Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyKunming Yunnan 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming Yunnan 650204China Jiangxi Medical College Nanchang UniversityNanchang Jiangxi 330006China

Protease inhibitors have been reported rarely from the leech Hirudinaria *** this study,we purified a novel protease inhibitor(bdellin-HM-2)with anticoagulant properties from *** a molecular weight of 1.4x104,bdellin-HM-2 was also characterized with three intra?molecular disulfide bridges at the N-terminus and multiple HHXDD and HXDD motifs at *** revealed that the putative nucleotide-encoding protein of bdellin-HM-2 contained 132 ami no acids and was encoded by a 399 bp open reading frame(ORF).Sequence alignment showed that bdellin-HM-2 shared similarity with the“non-classical"Kazal-type serine protease inhibitors,but had no inhibitory effect on trypsin,elastase,chymotrypsin,kallikrein,factor Xlla(FXIIa),factor Xia(FXIa),factor Xa(FXa),thrombin,or ***-HM-2 showed anticoagulant effects by proIonging the activated partial thromboplastin time(aPTT),indicating a role in enabling *** to obtain a blood meal from its *** results suggest that bdellin-HM丒2 may play a crucial role in blood-sucking in this leech species and may be a pote ntial can didate for the development of clinical anti-thrombotic drugs.

关键词： Hirudinaria manillensis Bdellin-HM-2 "Non-classical"Kazal inhibitors Blood sucking Anticoagulant Anti-thrombotic drugs