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Repurposing Loperamide as an Anti-Infection drug for the Treatment of Intracellular Bacterial Pathogens

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Engineering 2024年第8期39卷 180-193页

作者： Hongtao Liu Siqi Li Le Deng Zhenxu Shi Chenxiao Jiang Jingyan Shu Yuan Liu Xuming Deng Jianfeng Wang Zhimin Guo Jiazhang Qiu State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases&Key Laboratory of Zoonosis Research Ministry of EducationInstitute of ZoonosisCollege of Veterinary Medicine&Jilin UniversityChangchun 130062China center for Pathogen Biology and Infectious Diseases The First Hospital of Jilin UniversityChangchun 130031China Jiangsu Co-Innovation center for Prevention and control of Important Animal Infectious Diseases and Zoonoses Institute of Comparative MedicineCollege of Veterinary MedicineYangzhou UniversityYangzhou 225009China

Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within *** rapid development and dissemination of antimicrobial–resistant strains have exacerbated this *** the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular ***,we applied a cell-based screening approach to a US food and drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(***).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of *** intracellular *** treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by *** addition,LPD treatment effectively protected against *** infection in Galleria mellonella and mouse ***,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial ***,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.

关键词： Intracellular bacteria US food and drug Administration(FDA)-approved drugs drug repurposing Loperamide Autophagy Glycoprotein nonmetastatic melanoma protein B

In silico and in vitro genotoxicity evaluation of descarboxyl levofloxacin,an impurity in levofloxacin

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中国药理学与毒理学杂志 2013年第3期 470-471页

作者： ZHU Qing-fen WEI Xi QU Jian-song LI Jun WANG Wei-jian Shandong Institute for food and drug control

OBJECTIVE To evaluate the genotoxicity of Descarboxyl Levofloxacin by In silico and In vitro *** Assessment of genotoxicity using Derek for Windows We used DEREK for Windows(DfW,Lhasa Ltd.,Leeds,UK) version 11.0 for toxicity *** structures are entered into the program in *** *** program applies structure-activity relationships 〔(Q) SARs〕and other expert knowledge rules to derive a reasoned prediction about the potential toxicity of the query *** reverse mutation assay(Ames test) The Salmonella histidine point mutation assay proposed by Maron and Ameswas *** *** histidine autotrophic strains(TA97,TA98,TA100 and TA102) used in this test were obtained from Shandong center for disease *** saline(NS) was used as a vehicle control.2-Aminofluorene(2-AF,10 μg /plate),1,8-dihydroxyanthraquinone(50 μg /plate),Sodium azide(NaN3,1.5 μg /plate),and Dexon(50 μg /plate) were used as positive *** levofloxacin was assayed at concentrations of 31.25,62.5,125,250,and 500 μg /***,0.1 ml of test substance(or control solution),0.1 ml of bacterial culture 〔(1-2) × 1012 L-1 〕and 0.5 ml of S9 mix(NS for treatment without activation) were mixed and poured onto the agar plates after addition of 1.8 ml of top agar(0.6% agar Difco,0.5% NaCl,50 μmol·L-1 L-histidine,50 μmol·L-1 biotin,45℃) at 45℃.Plates were inverted and incubated for 48h at 37℃ in the *** colonies were counted and the background lawn was inspected for signs of toxicity or compound *** assay was performed two times in triple and included negative and positive *** al aberrations in Chinese ham ster lung cells Chinese Hamster Lung(CHL) cells were obtained from Shandong center for disease *** cells were grown in DMEM medium supplemented with 10% heat-inactivated calf serum at 37℃ in an atmosphere containing 5% of *** test for Chromosomal aberrations in CHL cells was con

关键词： genotoxicity impurity descarboxyl levofloxacin SARs CHL chromosomal aberration

Chemotherapy-based control of Ascariasis and Hookworm in Highly Endemic Areas of China:Field Observations and a Modeling Analysis

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Biomedical and Environmental Sciences 2012年第3期25卷 272-281页

作者： WANG Jun LI Hua Zhong CHEN Ying Dan LIU Chang Hua TANG Lin Hua National Institute of Parasitic Disease Chinese Center for Disease Control and Prevention Shanghai 200025 China center for drug Evaluation SFDA Beijing 100038 China Office for Disease control and Emergency Response Chinese Center for Disease Control and Prevention Beijing 102206 China Sichuan center for Disease control and Prevention Chengdu 610041 Sichuan China

Objective Our objective was to systematically evaluate chemotherapy-based control of ascariasis and hookworm infection and make predictions of the effectiveness of repeated mass treatment at different levels of coverage in highly endemic areas of China. Methods Field surveys were carried out to acquire the ascariasis and hookworm prevalence and intensity （mean worm burden） at baseline, one month and one year later. We calculated model parameters based on the survey data, then incorporated them into a quantitative framework to predict the prevalence and intensity one year later. Sensitivity analyses were performed to assess the influence of the chemotherapy measures on prevalence and intensity, and model simulations were performed to evaluate the feasibility of achieving the proposed transmission control criteria under different chemotherapy measures. Results The predicted prevalence and intensity one year from baseline were within the 95% confidence interval of actual values. As treatment frequency or coverage increased, the prevalence and intensity decreased. Model simulations show that many rounds of treatment are needed to maintain the prevalence at a low level in highly endemic areas of China. Conclusion We should select different combinations of treatment frequency, coverage and drug efficacy according to available resources and practical attainable conditions. Mathematical modeling could be used to help optimize the chemotherapeutic scheme aiming at specific parasitic species and areas, and to direct the establishment of soil-transmitted helminthiasis control criteria in China.

关键词： Ascariasis Hookworm Chemotherapy Field survey Mathematical modeling

Texosome-based drug delivery system for cancer therapy: from past to present

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Cancer Biology & Medicine 2015年第3期12卷 150-162页

作者： Hamideh Mahmoodzadeh Hosseini Raheleh Halabian Mohsen Amin Abbas Ali Imani Fooladi Applied Microbiology Research center Baqiyatallah University of Medical Sciences Department of drug and food control Faculty of Pharmacy Tehran University of Medical Sciences

Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Malfunction of the immune system, particularly in the tumor microenvironment, causes tumor growth and enhances tumor progression. Thus, cancer immunotherapy can be an appropriate approach to provoke the systemic immune system to combat tumor expansion. Texosomesj which are endogenous nanovesicles released by all tumor cells, contribute to cell-cell communication and modify the phenotypic features of recipient cells due to the texosomes＇ ability to transport biological components. For this reason, texosome-based delivery system can be a valuable strategy for therapeutic purposes. To improve the pharmaceutical behavior of this system and to facilitate its use in medical applications, biotechnology approaches and mimetic techniques have been utilized. In this review, we present the development history oftexosome-based delivery systems and discuss the advantages and disadvantages of each system.

关键词： Cancer therapy texosome mimetic tumor microenvironment immunotherapy

Study on screening potential allergenic proteins from infant milk powders based on human mast cell membrane chromatography and histamine release assays

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Journal of Pharmaceutical Analysis 2019年第1期9卷 55-61页

作者： Ping Zhang Yingdi Shi Xiaoshuang He Wei Sun Yanni Lv Xiaofang Hou School of Pharmacy Xi'an Jiaotong University Linyi Institute for food and drug control Shaanxi Engineering Research center of Cardiovascular drugs Screening & Analysis

Cow's milk allergy is mainly observed in infants and young children. Most allergic reactions affect the skin, followed by the gastrointestinal and respiratory systems. Conventional diagnosis is based on positive allergy studies and evaluation of parameters including IgE and IgG1 levels, acute allergic skin response and anaphylactic shock reactions. We developed a cell membrane chromatographic(CMC)method based on human mast cells(HMC-1) for screening potential allergens in infant formula milk powders(IFMP). HMC-1 cell membranes were extracted and mixed with silica to prepare cell membrane chromatography columns(10 mm ? 2 mm i.d., 5 mm). Under the conditions of 0.2 mL/min flow rate and214 nm detection wavelength, human breast milk showed no retention. However, IFMP showed clear retention. The retained fractions were collected and analyzed through matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS). Four major milk proteins, i.e., α-casein, β-casein, α-lactalbumin, and β-lactoglobulin A, were identified. Furthermore, these proteins and β-lactoglobulin B showed clear retention on HMC-1/CMC columns. To test the degranulation effects of the five proteins, histamine and β-hexosaminidase release assays were carried out. All five proteins induced HMC-1 cells to release histamine and β-hexosaminidase. Also, we established a reversed phase liquid chromatographic(RPLC) method for the determination of the five proteins in IFMP and the results showed that 90% proteins in IFMP were α-casein and β-casein. We concluded that cow's milk proteins may be potential allergens and caseins cause more β-casein allergic risk than other proteins. This conclusion was consistent with other studies.

关键词： Allergenic proteins Cell membrane chromatography Milk powders

Simultaneous determination mercury species of Su-He-Xiang-Wan in rat tissues by HPLC-CVG-AFS

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Journal of Central South University 2013年第4期20卷 894-901页

作者：王伟萍张明玥艾则孜葛婧梁逸曾 Research center of Modernization of Chinese Medicines College of Chemistry and Chemical Engineering Central South University Xinjiang Uygur Autonomous Region Institute for food and drug control

A simple and sensitive high performance liquid chromatography-chemical vapour generation-atom fluorescent spectrometry （HPLC-CVG-AFS） method was developed and validated for simultaneous determination mercury species in Su-He-Xiang-Wan （SHXW） and in tissues of rats, respectively. The species of mercury were separated by a Venusil MP-C 18 （5μm, 150 mm×4.6 ram） column with the optimized mobile phase containing 5% （w/v） acetonitrile, 0.01 mol/L L-cysteine and 0.06 moL/L ammonium acetate. The tissues of rats were freeze-dried after giving the medicine for 10 d, and then added into the solution containing 10% （w/v） HC1, 1% （w/v） sulfocarbamide and 0.15% （w/v） KC1 for increasing extraction rate. The resolutions of Hg2＋, MeHg and EtHg were 1.5 and 2.9, respectively. The detection limits of Hg2＋, MeHg and EtHg were 2.0, 1.0 and 0.9 ng/mL, respectively. The relative standard deviation （RSD） of inter- and intra-day precisions ranged from 1.56% to 2.86%. The recovery rates of three different adding level were 87%-101% （n=6）, and the RSDs were smaller than 8.2%. The results show that no MeHg and EtHg were detected in rat tissues. Only soluble mercury （Hg2＋） was determined for the mercury species of SHXW in rat tissues.

关键词： HPLC-CV-AFS mercury species rat tissue traditional Chinese medicine Su-He-Xiang-Wan (SHXW)

Recent advances in metal-free CDs/g-C_(3)N_(4) photocatalysts:Synthetic strategies,mechanism insight,and applications

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Journal of Materials Science & Technology 2023年第19期150卷 11-26页

作者： Xingxing Yang Lina Sheng Yongli Ye Jiadi Sun Zaijun Li Xiao Ning Jin Cao Xiulan Sun State Key Laboratory of food Science and Technology School of Food Science and TechnologyCollaborative Innovation Center of Food Safety and Quality ControlJiangnan UniversityWuxi 214122China Yixing Institute of food and Biotechnology Co. LtdYixing 214200China School of Chemical and Material Engineering Jiangnan UniversityWuxi 214122China National Institutes for food and drug control Beijing 100050China

Carbon dots/graphite carbon nitride(CDs/g-C_(3)N_(4)),a novel composite photocatalyst,has shown great po-tential for applications in energy regeneration and environmental remediation owing to its following advantages:metal-free,low cost,easily tunable,and excellent photocatalytic ***,we reviewed the development of synthetic strategies,photocatalytic enhancement mechanisms,and pho-tocatalytic applications of CDs/g-C_(3)N_(4) in this ***,the three composite strategies of CDs and g-C_(3)N_(4)-self-assembly,solvothermal,and calcination polymerization are outlined,and their advantages and disadvantages are described in ***,the photocatalytic enhancement mechanism of the com-posite strategies was elucidated according to the variation trends of CDs/g-C_(3)N_(4) band structure,electronic properties,light absorption range,and interfacial charge ***,the applications of CDs/g-C_(3)N_(4) in hydrogen evolution,pollutant degradation,CO_(2) reduction,and bacterial disinfection in recent years are reviewed ***,the current obstacles and future research directions of CDs/g-C_(3)N_(4) are discussed from the perspective of preparation technology and practical applications,respectively.

关键词： Photocatalysis Graphite carbon nitride Carbon dots Synthetic strategy Photocatalytic application

Modification and Evaluation of Brucella Broth Based Campylobacter jejuni Transport Medium

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Biomedical and Environmental Sciences 2014年第6期27卷 466-470页

作者： BAI Yao CUI Sheng Hui XU Xiao LI Feng Qin Key Laboratory of food Safety Risk Assessment National Health and Family Planning Commission China NationalCenter for Food Safety Risk Assessment National Institute for Nutrition and food Safety Chinese Center for Disease Control and Prevention National Institutes for food and drug control

Reliable transport of Campylobocter jejuni isolates is critical to microbial epidemiology research, especially in developing countries without a good temperature control mailing system. Various factors, including oxygen, temperature, transport medium composition, could affect the survival of C jejunL In this study, the protective effects of different ingredients in C. jejuni transport media at 4 ℃ and 25 ℃ and under aerobic condition were quantitatively evaluated respectively. The results showed that enriched medium, supplementation with 5% blood and being kept at 4 ℃ could improve the viability of different C. jejuni strains during transport. In addition, supplementation with 25 mmol/L L-fucose in Wang＇s transport medium could significantly improve the survival of C.

关键词： Modification and Evaluation of Brucella Broth Based Campylobacter jejuni Transport Medium

Trends of foodborne diseases in China： lessons from laboratory- based surveillance since 2011

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Frontiers of Medicine 2018年第1期12卷 48-57页

作者： Jikai Liu Li Bai Weiwei Li Haihong Han Ping Fu Xiaochen Ma Zhenwang Bi Xiaorong Yang Xiuli Zhang Shiqi Zhen Xiaoling Deng Xiumei Liu Yunchang Guo Key Laboratory of food Safety Risk Assessment Ministry of Health and China National Center for Food Safety Risk Assessment Beijing 100022 China center for Disease control and Prevention of Beijing Beijing 100013 China Shandong center for Disease control and Prevention Jinan 250014 China center for Disease control and Prevention of Sichuan Province Chengdu 610041 China center forDisease control and Prevention of Henan Province Zhengzhou 450016 China center for Disease control and Prevention of Jiangsu Province Nanjing 210009 China Guangdong Provincial center for Disease control and Prevention Guangzhou 511430 China

Abstract foodborne disease is one of the most important public health issues worldwide. China faces various and unprecedented challenges in all aspects of the food chain. Data from laboratory-based foodborne disease surveillance systems from 2013 to 2016, as well as different regions and ages, can be found along with differences in the patterns of pathogens detected with diverse characteristics. Vibrioparahaemolyticus has been the leading cause of infectious diarrhea in China, especially among adults in coastal regions. Salmonella has been a serious and widely distributed pathogen responsible for substantial socioeconomic burden. Shigella was mostly identified in Northwest China and the inland province （Henan） with less-developed regions among children under 5 years. Data from foodborne disease outbreak reporting system from 2011 to 2016 showed that poisonous animals and plant factors responsible for most deaths were poisonous mushrooms （54.7%） in remote districts in southwest regions. The biological hazard that caused most cases reported （42.3%） was attributed to V. parahaemolyticus, the leading cause of foodborne outbreaks. In this review, we summarize the recent monitoring approach to foodborne diseases in China and compare the results with those in developed countries.

关键词： foodbome diseases surveillance TraNet China