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Elicitation of strong immune responses by a DNA vaccine expressing a secreted form of hepatitis C virus envelope protein E2 in murine and porcine animal models

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World Journal of Gastroenterology 2006年第44期12卷 7126-7135页

作者： Yi-Ping Li Hye Na Kang Lorne A Babiuk Qiang Liu Vaccine and Infectious Disease Organization University of Saskatchewan Saskatoon Saskatchewan Canada danish Institute for food and veterinary Research Arhus N Denmark Korea food and Drug administration Seoul Republic of Korea

AIM： To characterize the immunogenicity of a hepatitis C virus （HCV） E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models. METHODS： A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without boosting with a recombinant E2 protein vaccine formulated with CpG ODN and 10% Emulsigen. The immunogenicity of HCV E2 vaccines was analyzed by ELISA for antibody responses, MTT assay for lymphocyte proliferation, ELISPOT for the number of interferon-γ secreting cells, and cytotoxic T lymphocyte assays. RESULTS： Intradermal injection of E2 DNA vaccine induced strong Th1-1ike immune responses in mice. In piglets, E2 DNA vaccine elicited moderate and more balanced immune responses. A DNA vaccine prime and protein boost vaccination strategy induced significantly higher E2-specific antibody levels and shifted the immune response towards Th2-1ike ones in piglets. CONCLUSION： A DNA vaccine expressing a secreted form of HCV E2 protein elicited E2-specific immune responses in mice and piglets. Recombinant E2 protein vaccination following DNA immunization significantly increased the antibody response in piglets. These HCV E2 vaccines may represent promising hepatitis C vaccine candidates for further investigations.

关键词： Hepatitis C virus E2, DNA vaccine DNA vaccine prime-protein boost

Mori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway

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Journal of Animal Science and Biotechnology 2023年第4期14卷 1418-1437页

作者： Yuanyuan Wei Chen Gao Huiru Wang Yannan Zhang Jinhua Gu Xiuying Zhang Xuhao Gong Zhihui Hao Innovation Centre of Chinese veterinary medicine College of Veterinary MedicineChina Agricultural UniversityNo.2 Yuanmingyuan West RoadBeijing 100193China Key Biology Laboratory of Chinese veterinary Medicine Ministry of Agriculture and Rural AffairsBeijing 100193P.R.China National Center of Technology Innovation for Medicinal function of food National Food and Strategic Reserves AdministrationBeijingChina China Institute of veterinary Drug Control Beijing 100081China

Background Liver fibrosis and hepatocellular carcinogenesis secondary to liver fibrosis are serious liver diseases with no effective *** fructus aqueous extracts(MFAEs)have served as successful treatments for many types of liver injury including fibrosis although the molecular mechanisms are unknown at *** To investigate the effect of MFAEs in alleviating acute and chronic liver injury and tried to decipher the underlying *** and results Mice were divided into 5 groups(n ps:contro=8)for acute(groups:control,0.3%CCl_(4),bifendate(BD),100 and 200 mg/kg MFAEs,7 d)and chronic(groul,10%CCl_(4),BD,100 and 200 mg/kg MFAEs,4 weeks)liver injury *** mouse was injected intraperitoneally with 10μL/g corn oil containing CCl_(4)expect the control ***2 cells were used in vitro *** communal components were identified by *** utilized a mouse model for acute and chronic liver injury using CCl_(4)and MFAEs administration effectively blocked fibrosis and significantly inhibited inflammation in the *** activated the nuclear factor erythroid derived 2 like 2/heme oxygenase 1(Nrf2/HO-1)pathway and promoted the synthesis of the antioxidants glutathione(GSH),superoxidedismutase(SOD)and glutathione peroxidase(GSH-Px)that resulted in reduced levels of CCl_(4)-induced oxidative stress molecules including reactive oxygen *** extracts administered to mice also inhibited ferroptosis in the liver by regulating the expression of Acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),thus reducing the occurrence of liver *** in vivo and in vitro tests indicated that the mechanism of MFAEs protection against liver fibrosis was linked to activation of Nrf2 *** effects were blocked in vitro by the addition of a specific Nrf2 *** MFAEs inhibited oxidative stress,ferroptosis and inflammation o

关键词： Acute and chronic liver injury Ferroptosis Mori fructus aqueous extracts Nrf2 Oxidative stress

Comparing invasive effects of five foodborne bacterial pathogens in human embryonic intestine 407 cells and human ileocecum HCT-8 cells

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Asian Pacific Journal of Tropical Biomedicine 2017年第10期7卷 937-944页

作者： Lan Hu Tint T. Wai Center for food Safety and Applied Nutrition Food and Drug AdministrationLaurelMD 20708USA

Objective: To refine the infectious doses of enteric bacterial pathogens in animal assays and vaccine clinical trials by studying the invasion kinetics of five bacterial pathogens with human intestinal ***: Utilizing in vitro cultured cell invasion assays with gentamicin-killing step,the invasive effects were analyzed in foodborne pathogens including Salmonella,Shigella, Yersinia, Escherichia coli(E. coli) O157 and opportunistic pathogens Citrobacter in human embryonic intestine 407 cells and ileocecum HCT-8 cells at multiplicities of infection(MOIs) of 0.04–4 000.00 E. coli HS served as a noninvasive ***: The study results showed that the bacterial invasive efficiency and the average number of internalized bacteria per host cell changed with different starting MOIs. Higher starting MOIs did not always produce more bacterial internalization. The bacterial invasion effects varied with different bacterial strains and host cell lines. E. coli O157:H7 did invade human ileocecum HCT-8 ***: This study shows that these bacteria possess different invasive patterns at various starting MOIs and also in different cell lines. The results could help to figure out the appropriate infectious doses of the bacteria in animal assays and in vaccine clinical trials. The bacterial invasion kinetics is also valuable in evaluating the safety and efficacy of live attenuated bacterial vaccines.

关键词： Invasion Infectious dose foodborne bacterial pathogens Salmonella Shigella Vaccine

Probiotic bacteria attenuates cisplatin-induced nephrotoxicity through modulation of oxidative stress, inflammation and apoptosis in rats

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Asian Pacific Journal of Tropical Biomedicine 2019年第3期9卷 116-122页

作者： Emin Sengul Sevda Ur?ar Gelen Serkan Y?ld?r?m Fikret ?elebi Ali ??nar Department of Physiology Faculty of Veterinary Ataturk University Department of food Hygiene and Technology Faculty of Veterinary Ataturk University Department of Pathology Faculty of Veterinary Ataturk University

Objective: To investigate the effects of probiotic bacteria on cisplatin(CP)-induced nephrotoxicity. Methods: In the present study, 50 Sprague-Dawley rats were used and randomly divided into five groups including control, CP, probiotic bacteria treatment groups with different doses(0.5 and 1 mL) and only probiotic bacteria group. After CP and probiotic administration on seven days, rats sacrificed under anesthesia on the eighth day. The serum urea, creatinine, and blood urea nitrogen levels were analyzed. In renal tissue, malondialdehyde levels, superoxide dismutase and glutathione activity, interleukin-8, interleukin-1β and tumor necrosis factor-alpha levels were determined and histopathological and immunohistochemical changes were also examined. Results: According to results, urea, creatinine and blood urea nitrogen levels as well as kidney weights increased in CP group. Also, CP induced inflammation, oxidative stress, DNA damage and apoptosis in kidney tissue and caused histopathological changes. administration of the high dose of probiotic bacteria could prevent these changes and damages. Conclusions: This study reveals that probiotic bacteria has protective effects on CP-induced renal damage in rats.

关键词： Apoptosis Cisplatin Nephrotoxicity Probiotic Rat

Studies on abacavir-induced hypersensitivity reaction:a successful example of translation of pharmacogenetics to personalized medicine

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Science China(Life Sciences) 2013年第2期56卷 119-124页

作者： GUO YongLi SHI LeMing HONG HuiXiao SU ZhenQiang FUSCOE James NING BaiTang Division of Systems Biology National Center for Toxicological Researchthe US Food and Drug Administration Division of Bioinformatics and Biostatistics National Center for Toxicological Researchthe US Food and Drug Administration

Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected *** main side effect is hypersensitivity reaction(HSR).The incidence of the HSR is associated with ethnicity among patients exposed to abacavir,and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen(HLA)-B*57:01-carrying *** studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire,leading to a systemic autoimmune ***-B*57:01 screening,combined with patch testing,had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the ***,the US food and Drug administration(FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced *** studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.

关键词： personalized medicine pharmacogenetics drug safety abacavir hypersensitivity reaction (HSR) HLA-B*57:01 HLA-B*57-01 screening

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

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food Science and Human Wellness 2024年第4期13卷 2266-2276页

作者： Yu Ga Yuanyuan Wei Qingyu Zhao Yimeng Fan Yannan Zhang Zhifang Zhang Sijia Hao Lixia Wang Zhifen Wang Jinlong Han Shuang Wu Zhihui Hao Innovation Centre of Chinese veterinary Medicine College of Veterinary MedicineChina Agricultural UniversityBeijing 100086China National Center of Technology Innovation for Medicinal Function of food National Food and Strategic Reserves AdministrationBeijing 100193China Inner Mongolia Medical University Hohhot 010059China China Agricultural University Yantai Institute Yantai 264670China Shandong Academy of Agricultural Sciences Jinan 250100China

Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal *** Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal *** aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR *** chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other *** results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC *** also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin *** treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression *** addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of *** results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.

关键词： Puerariae Radix Ulcerative colitis Molecular mechanisms Pyroptosis NOD-like receptor protein 3 inflammasome

Phenolic compounds and hepatoprotective potential of Anastatica hierochuntica ethanolic and aqueous extracts against CCl4-induced hepatotoxicity in rats

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Journal of Traditional Chinese Medicine 2020年第6期40卷 947-955页

作者： Hassan Barakat Tariq I.Almundarij Department of food Science and Human Nutrition College of Agriculture and Veterinary MedicineQassim UniversityBuraydah 51452Saudi Arabia food Technology Department Faculty of AgricultureBenha University13736 MoshtohorQaliuobiaEgypt Department of veterinary Medicine College of Agriculture and Veterinary MedicineQassim UniversityBuraydah 51452Saudi Arabia

OBJECTIVE:To investigate the effect of Anastatica hierochuntica ethanolic(KEE),aqueous(KAE)extracts,and their combination against CCl4-induced hepatotoxicity in ***:The HPLC analysis for KEE and KAE was quantitatively carried *** liver markers,antioxidant enzymes,and histopathological alterations were examined then total hepatoprotection potential was ***:Among 9 identified phenolic compounds(PC)in KEA,sinapic acid was the highest while syringic acid was the highest among 21 identified PC in *** flavonoids were identified in KEE and two in KAE using HPLC,*** administration of KEE,KAE,and KEE+KAE at 250 mg/kg body weight significantly reduced aspartate aminotransferase(AST),alanine aminotransferase(ALT)levels,alkaline phosphatase(ALP),total bilirubin(TBILI),and also attenuated histopathological ***,they reduced malondialdehyde(MOD),restored reduced-glutathione(GSH),and enhanced superoxide dismutase(SOD)***,KAE,and KEE+KAE protected the liver from CCl4-hepatotoxicity as they mainly attenuating oxidative *** hepatoprotection was about 128.3%,114.5%,and 103.8%for KEE,KAE,and KEE+KAE,***:Biochemical observations,supplemented by histopathological examination revealed that AH affords extract-depending protection against CCl4-hepatotoxicity.

关键词： Phenolic compounds Anastatica hierochuntica Liver markers Antioxidant enzymes Hepatoprotection

Early-phase clinical trials of anti-HIV Drugs——understanding and discussion

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Science China(Life Sciences) 2009年第6期52卷 521-527页

作者： LI YaJie,ZHAO Ming & ZHAO DeHeng Center for Drug Evaluation,State food and Drug administration,Beijing 100038,China Center for Drug Evaluation State Food and Drug Administration Beijing 100038 China

Innovative anti-HIV drugs developed by local sponsors in China have come into the stage of early-phase clinical *** to systemically design the clinical trials of innovative anti-HIV drugs still remains a challenge for *** article references the literature and the experience of reviewers,to introduce general considerations concerning early-phase clinical trials of innovative anti-HIV drugs.

关键词： HIV tolerance dose exploration drug-drug interaction drug resistance

Lablab purpureus(L.) Sweet alleviated rhubarb induced diarrhea in a gut microbiota-dependent manner

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food Science and Human Wellness 2024年

作者： Yi-meng Fan Qing-yu Zhao Yuan-yuan Wei Hui-ru Wang Yan-nan Zhang Jian-yu Lü Zhi-hui Hao National Key Laboratory of veterinary Public Health Security.College of veterinary Medicine.China Agricultura University Key Biology Laboratory of Chinese veterinary Medicine， Ministry of Agriculture and Rural Affairs National Center of Technology Innovation for Medicinal function of food， National food and Strategic Reserves administration

Lablab purpureus (L.) Sweet (L. purpureus) has been reported to alleviate diarrhea， although the precise mechanism remains unclear. This study identified the primary active components of L. purpureus utilizing UPLC-MS/MS. A rhubarb-induced diarrhea model in rats was utilized to assess the therapeutic efficacy of L. purpureus. Alterations in gut microbiota and fecal metabolism were analyzed via 16S rDNA analysis and targeted metabolomics. Flora elimination and fecal transplantation techniques were employed to deepen understanding of the role of intestinal flora in L. purpureus treatment. The study findings indicated that the main constituents of L. purpureus included trigonelline， piperidinic acid， and L-(-)-malic acid， among others. L. purpureus treatment significantly alleviated all diarrhea symptoms in rats， encompassing reduced fecal water content， weight loss， shortened colon length， diminished histological damage， and decreased inflammatory factors. Furthermore， L. purpureus significantly enhanced the expression of tight junction markers and restored the dysregulated intestinal flora in diarrheic rats by increasing Prevotella and reducing Lactobacillus. Additionally， the production of propionic acid and other short-chain fatty acids (SCFAs) increased in diarrheic rats treated with L. purpureus， suggesting a substantial alteration in the intestinal environment. Crucially， the protective efficacy of L. purpureus diminishes in the absence of gut flora. Subsequent fecal transplantation tests demonstrated that feces from the L. purpureus-treated group alleviated rhubarb-induced diarrhea， emphasizing the pivotal role of gut microbiota in the antidiarrheal efficacy of L. purpureus. In conclusion， our findings elucidate the underlying mechanisms of L. purpureus' antidiarrheal action and its beneficial impact on intestinal microflora. Moreover， these results provide compelling evidence supporting the therapeutic use of L. purpureus for the treatment of diarrhea and its

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