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Effect of Fuzheng Jiedu granule on immunological function and level of immune-related cytokines in immune-suppressed mice

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Journal of Integrative Agriculture 2016年第3期15卷 650-657页

作者： YU Zhan-mei HUANG Xian-hui YAN Chao-qun GAO Jin LIANG Zi-sen guangdong Provincial key laboratory of veterinary Pharmaceutics development and safety evaluation College of Veterinary Medicine South China Agricultural University

Fuzheng Jiedu granule exhibits a number of health benefits and it is thought that the mechanisms involved in these effects are due to the modulation of immunity. In this article, we studied the effect of Fuzheng Jiedu granule on immunological function and the expression of immune-related cytokines in immune-suppressed mice. 72 mice were randomly divided into six groups, with 12 in each group. The control groups included an untreated group, a negative control group（Cyclophosphamide） and a positive control group（Astragalus polysaccharide）. There were three treated groups, which were given different doses of Fuzheng Jiedu granule： a low dose（100 mg kg^（–1））, a medium dose（400 mg kg^（–1）） and a high dose（600 mg kg^（–1））. With the exception of the untreated control animals, each group received an intraperitoneal injection of Cyclophosphamide（100 mg kg^（–1）） for 3 days to establish the immune-suppressed model. Mice were then treated for 19 consecutive days and, 24 h after the last treatment, blood was taken for the eyeballs and serum separation was performed. Analysis was made of the levels of related cytokines（IgA, IgG, IgM, IL-6, IFN-γ, C3, C4 and TNF-α）, the transformation of lymphocytes and the immune organ indexes. The results showed that Fuzheng Jiedu granule can improve the levels of cytokines, the rate of proliferation of lymphocytes and the immune organ indexes of immune-suppressed mice.

关键词： Fuzheng Jiedu granule immune suppression cytokines lymphocytes immune organ index

A Rigid Nanoplatform for Precise and Responsive Treatment of Intracellular Multidrug-Resistant Bacteria

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Engineering 2022年第8期8卷 57-66页

作者： Shaoqi Qu Xiaoyong Huang Xiangbin Song Yifan Wu Xiaowei Ma Jianzhong Shen Kui Zhu National Center for veterinary drug safety evaluation College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China guangdong laboratory for Lingnan Modern Agricultur

Antibiotic treatment failure against life-threatening bacterial pathogens is typically caused by the rapid emergence and dissemination of antibiotic *** current lack of antibiotic discovery and development urgently calls for new strategies to combat multidrug-resistant(MDR)bacteria,especially those that survive in host *** nanoparticles are promising intracellular drug delivery systems whose advantages include their high biocompatibility and tunable surface *** by the fact that the rigidity of nanoparticles potentiates their cellular uptake,rigidity-functionalized nanoparticles(RFNs)coated with bacteria-responsive phospholipids were fabricated to boost endocytosis,resulting in the increased accumulation of intracellular *** delivery and high antibacterial efficacy were demonstrated by the clearing of 99%of MDR bacteria in 4 h using methicillin-resistant Staphylococcus aureus(MRSA)and pathogenic Bacillus cereus as *** addition,the subcellular distribution of the RFNs was modulated by altering the phospholipid composition on the surface,thereby adjusting the electrostatic effects and reprograming the intracellular behavior of the RFNs by causing them to accurately target ***,the RFNs showed high efficacy against MRSA-associated infections in animal models of wound healing and *** findings provide a controllable rigidity-regulated delivery platform with responsive properties for precisely reprograming the accumulation of cytosolic antibiotics,shedding light on precision antimicrobial therapeutics against intracellular bacterial pathogens in the future.

关键词： Antibiotic Bacteria Mesoporous silica Phospholipid Rigidity

Identification of blaIMI-mediated carbapenem-resistant Enterobacter from a duck farm in China

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Journal of Integrative Agriculture 2023年第8期22卷 2500-2508页

作者： HUANG Hong-hao LU Yi-xing WU Su-juan MA Zhen-bao ZENG Dong-ping ZENG Zhen-ling National laboratory of safety evaluation(Environmental Assessment)of veterinary drugs College of Veterinary Medicine/China National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria/Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety EvaluationCollege of Veterinary MedicineSouth China Agricultural University guangdong Haid Group Co. Ltd.Guangzhou 511400P.R.China

Carbapenem-and colistin-resistant Enterobacter has been a clinical and therapy problem in recent ***,we report the carbapenem-and colistin-resistant Enterobacter harboring bla_(IMI) isolated from intestinal samples and the environment of a duck farm in *** bla_(IMI)-positive Enterobacter isolates were resistant to carbapenem and *** bla_(IMI) subtypes were detected in different molecular categories of *** detection of the various IMI producers highlights the diversity of carbapenemases in a duck ***-genome sequencing demonstrated the bla_(IMI) genes were present in chromosomes or plasmids in these *** conjugation experiment demonstrated the ability of bla_(IMI)-carrying plasmid to transmit *** molecular evolution characteristics were examined through comparative genetic *** study demonstrated the presence of chromosomal and plasmid bla_(IMI) and the bla_(IMI)-carrying plasmid exhibits a horizontal transmission between Enterobacter and Escherichia coli *** similar genetic content was discovered between two bla_(IMI-16)-positive Enterobacter *** addition,a bla_(IMI-16)-carrying plasmid is an IncFII(Yp)plasmid,and a substantial amount of mobile genetic elements were identified around bla_(IMI-16).The IS-like elements and IncFII(Yp)plasmid are significant in the propagation of bla_(IMI).Our study provides evidence for the transmission of diverse bla_(IMI) genes in China and supplies additional reference data for bla_(IMI)-positive antimicrobialresistant *** surveys of bla_(IMI)-positive Enterobacter from animal-raising environments must be given more focus.

关键词： Enterobacter antimicrobial resistance carbapenemases colistin

Characterization of NDM-5-producing Enterobacteriaceae isolates from retail grass carp(Ctenopharyngodon idella) and evidence of blaNDM-5-bearing IncHI2 plasmid transfer between ducks and fish

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Zoological Research 2022年第2期43卷 255-264页

作者： Lu-Chao Lv Yao-Yao Lu Xun Gao Wan-Yun He Ming-Yi Gao Kai-Bin Mo Jian-Hua Liu College of veterinary Medicine Key Laboratory of Zoonosis of Ministry of Agricultural and Rural AffairsNational Risk Assessment Laboratory for Antimicrobial Resistant of Microorganisms in AnimalsGuangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety EvaluationSouth China Agricultural UniversityGuangzhouGuangdong 510642China guangdong laboratory for Lingnan Modern Agriculture GuangzhouGuangdong 510642China

We aimed to characterize NDM-5-producing Enterobacteriaceae from aquatic products in Guangzhou,China.A total of 196 intestinal samples of grass carp collected in 2019 were screened for carbapenemase *** of bla_(NDM-5) positive isolates and plasmids was determined by antimicrobial susceptibility testing,conjugation experiments,Illumina HiSeq,and Nanopore *** Citrobacter freundii and six Escherichia coli strains recovered from seven intestinal samples were verified as bla_(NDM-5) carriers(3.57%,7/196).The bla_(NDM-5) genes were located on the lncX3(n=5),lncHI2(n=1),or lncHI2-lncF(n=1)*** bla_(NDM-5)-bearing plasmids were transferred by conjugation at frequencies of~10^(-4)-10^(-6).Based on sequence analysis,the lncHI2 plasmid pHNBYF33-1 was similar to other bla_(NDM-5)-carrying lncHI2 plasmids deposited in GenBank from guangdong *** all lncHI2 plasmids,bla_(NDM-5)was embedded in a novel transposon,Tn7057(IS3000-△ISAba125-IS5-△ISAba125-bla_(NDM-5)-bleMBL-trpF-tat-△dct-IS26-△umuD-△ISKox3-IS3000),which was identical to the genetic structure surrounding bla_(NDM-5)found in some IncX3 *** lncHI2-lncF hybrid plasmid pHNTH9F11-1 was formed by homologous recombination of the bla_(NDM-5)-carrying lncHI2 plasmid and a heavy-metal-resistant IncF plasmid through△Tn1721 To the best of our knowledge,this is the first report on the characterization of bla_(NDM-5)-bearing plasmids in fish in *** lncHI2 plasmid pHNBYF33-1 may be transmitted from ducks,considering the common duck-fish freshwater aquaculture system in ***7051 is likely responsible for the transfer of bla_(NDM-5) from lncX3 to lncHI2 plasmids in Enterobacteriaceae,resulting in the expansion of transmission vectors of bla_(NDM-5).

关键词： bla_(NDM-5) Enterobacteriaceae Plasmid Fish Carbapenemase

Core and variable antimicrobial resistance genes in the gut microbiomes of Chinese and European pigs

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Zoological Research 2024年第1期45卷 189-200页

作者： Cui-Hong Tong Zhi-Peng Huo Lu Diao Dan-Yu Xiao Ruo-Nan Zhao Zhen-Ling Zeng Wen-Guang Xiong guangdong Provincial key laboratory of veterinary Pharmaceutics development and safety evaluation South China Agricultural UniversityGuangzhouGuangdong 510642China National Risk Assessment laboratory for Antimicrobial Resistance of Animal Original Bacteria College of Veterinary MedicineSouth China Agricultural UniversityGuangzhouGuangdong 510642China National laboratory of safety evaluation(Environmental Assessment)of veterinary drugs South China Agricultural UniversityGuangzhouGuangdong 510642China National Reference laboratory of veterinary drug Residues South China Agricultural UniversityGuangzhouGuangdong 510642China

Monitoring the prevalence of antimicrobial resistance genes(ARGs)is vital for addressing the global crisis of antibiotic-resistant bacterial *** its importance,the characterization of ARGs and microbiome structures,as well as the identification of indicators for routine ARG monitoring in pig farms,are still lacking,particularly concerning variations in antimicrobial exposure in different countries or ***,metagenomics and random forest machine learning were used to elucidate the ARG profiles,microbiome structures,and ARG contamination indicators in pig manure under different antimicrobial pressures between China and *** showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs(P<0.05).ANT(6)-Ib,APH(3')-IIIa,and tet(40)were identified as shared core ARGs between the two pig ***,the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical *** and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs,*** ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100%and 98.7%,*** for assessing ARG contamination in Chinese and European pigs also achieved high accuracy(r=0.72-0.88).Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 *** results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.

关键词： Metagenomic Pig manure Antimicrobial pressure Antimicrobial resistance genes Microbiome

Insights into the effects of pulsed antimicrobials on the chicken resistome and microbiota from fecal metagenomes

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Journal of Integrative Agriculture 2023年第6期22卷 1857-1869页

作者： ZHAO Ruo-nan CHEN Si-yuan TONG Cui-hong HAO Jie LI Pei-si XIE Long-fei XIAO Dan-yu ZENG Zhen-ling XIONG Wen-guang guangdong Provincial key laboratory of veterinary Pharmaceutics development and safety evaluation College of Veterinary MedicineSouth China Agricultural UniversityGuangzhou 510642P.R.China guangdong laboratory for Lingnan Modern Agriculture Guangzhou 510642P.R.China National laboratory of safety evaluation(Environmental Assessment)of veterinary drugs College of Veterinary MedicineSouth China Agricultural UniversityGuangzhou 510642P.R.China

Antimicrobial resistance has become a global problem that poses great threats to human health. Antimicrobials are widely used in broiler chicken production and consequently affect their gut microbiota and resistome. To better understand how continuous antimicrobial use in farm animals alters their microbial ecology, we used a metagenomic approach to investigate the effects of pulsed antimicrobial administration on the bacterial community, antibiotic resistance genes(ARGs) and ARG bacterial hosts in the feces of broiler chickens. Chickens received three 5-day courses of individual or combined antimicrobials, including amoxicillin, chlortetracycline and florfenicol. The florfenicol administration significantly increased the abundance of mcr-1 gene accompanied by floR gene, while amoxicillin significantly increased the abundance of genes encoding the AcrAB-tolC multidrug efflux pump(marA, soxS, sdiA, rob, evgS and phoP).These three antimicrobials all led to an increase in Proteobacteria. The increase in ARG host, Escherichia, was mainly attributed to the β-lactam, chloramphenicol and tetracycline resistance genes harbored by Escherichia under the pulsed antimicrobial treatments. These results indicated that pulsed antimicrobial administration with amoxicillin,chlortetracycline, florfenicol or their combinations significantly increased the abundance of Proteobacteria and enhanced the abundance of particular ARGs. The ARG types were occupied by the multidrug resistance genes and had significant correlations with the total ARGs in the antimicrobial-treated groups. The results of this study provide comprehensive insight into pulsed antimicrobial-mediated alteration of chicken fecal microbiota and resistome.

关键词： metagenomic chicken antimicrobials resistome microbial community

Small molecule-based immunomodulators for cancer therapy

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4287-4308页

作者： Yinrong Wu Zichao Yang Kui Cheng Huichang Bi Jianjun Chen guangdong Provincial key laboratory of New drug Screening NMPA Key Laboratory for Research and Evaluation of Drug MetabolismSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Immunotherapy has led to a paradigm shift in the treatment of *** cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral *** addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse ***,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with ***,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic *** years have witnessed the rapid development of small molecule-based cancer *** this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),*** tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.

关键词： Cancer immunotherapy Small molecules Immunomodulators Inhibitors Agonists

Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib

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Acta Pharmaceutica Sinica B 2024年第2期14卷 517-532页

作者： Shuang Xiang Xiaoyun Lu International Cooperative laboratory of Traditional Chinese Medicine Modernization and Innovative drug Discovery of Chinese Ministry of Education(MOE) Guangdong Provincial Key Laboratory of New Drug Design and EvaluationGuangzhou City Key Laboratory of Precision Chemical Drug DevelopmentSchool of PharmacyJinan UniversityGuangzhou 510632China

Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these ***,two generations TRK inhibitors have been *** representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target ***,xDFG(TRKAG667C/A/S,homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical *** this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated ***,we concluded our perspectives on new challenges and future directions in this field.

关键词： NTRK fusions TRK kinase Clinical resistance xDFG mutations Selective type II inhibitors

Andrographolide and Its Derivative Potassium Dehydrographolide Succinate Suppress PRRSV Replication in Primary and Established Cells via Differential Mechanisms of Action

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Virologica Sinica 2021年第6期36卷 1626-1643页

作者： Lizhan Su Yarou Gao Mingxin Zhang Zexin Liu Qisheng Lin Lang Gong Jianying Guo Lixia Chen Tongqing An Jianxin Chen guangdong Provincial key laboratory of veterinary Pharmaceutics development and safety evaluation College of Veterinary MedicineSouth China Agricultural UniversityGuangzhou 510642China guangdong laboratory for Lingnan Modern Agriculture College of Veterinary MedicineSouth China Agricultural UniversityGuangzhou 510642China Department of Natural Products Chemistry School of Traditional Chinese Materia MedicaKey Laboratory of Structure-Based Drug Design&DiscoveryMinistry of EducationShenyang Pharmaceutical UniversityShenyang 110016China State key laboratory of veterinary Biotechnology Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150001China

Porcine reproductive and respiratory syndrome virus(PRRSV) continues to cause significant economic loss worldwide and remains a serious threat to the pork industry. Currently, vaccination strategies provide limited protection against PRRSV infection, and consequently, new antiviral strategies are urgently required. Andrographolide(Andro) and its derivative potassium dehydrographolide succinate(PDS) have been used clinically in China and other Asian countries as therapies for inflammation-related diseases, including bacterial and viral infections, for decades. Here, we demonstrate that Andro and PDS exhibit robust activity against PRRSV replication in Marc-145 cells and primary porcine alveolar macrophages(PAMs). The two compounds exhibited broad-spectrum inhibitory activities in vitro against clinically circulating type 2 PRRSV GD-HD, XH-GD, and NADC30-like HNhx strains in China. The EC_(50)values of Andro against three tested PRRSV strain infections in Marc-145 cells ranged from 11.7 to 15.3 lmol/L, with selectivity indexes ranging from 8.3 to10.8, while the EC_(50)values of PDS ranged from 57.1 to 85.4 lmol/L, with selectivity indexes ranging from 344 to ***, the anti-PRRSV activity of the two compounds is closely associated with their potent suppression on NFj B activation and enhanced oxidative stress induced by PRRSV infection. Further mechanistic investigations revealed that PDS, but not Andro, is able to directly interact with PRRSV particles. Taken together, our findings suggest that Andro and PDS are promising PRRSV inhibitors in vitro and deserves further in vivo studies in swine.

关键词： Porcine reproductive and respiratory syndrome virus(PRRSV) Andrographolide(Andro) Potassium dehydrographolide succinate(PDS) Inhibit NF-kB signaling pathway Oxidative stress