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Assessment of immune responses and intestinal flora in BALB/c mice model of wheat food allergy via different sensitization methods

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Food Science and Human Wellness 2023年第3期12卷 871-881页

作者： chenglong Liu chen chen Xingyu Yan Shimin Gu Xin Jia Wenhui Fu Xiao Meng Wentong Xue college of Food Science and Nutritional Engineering China Agricultural UniversityBeijing 100083China

Increasing incidences showed that food allergies have attracted more and more attention from researchers.BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal injection,transdermal sensitization,and oral gavage sensitization route.Results showed that all the three sensitization methods could induce allergic symptoms;increase the serum antibody(total immunoglobulin E(IgE),specific IgE,IgG,IgA)and histamine content;promote the secretion of Th2 cytokines(interleukin(IL)-4,IL-5,IL-13)and inflammatory factors(IL-6,IL-17 A,IL-10);and inhibit the production of Th1 cytokines(IFN-γ,IL-2).However,the allergic symptoms of mice sensitized by intraperitoneal injection were the most obvious among the three models.The level of serum antibodies in intraperitoneal injection group was significantly higher than control.Subsequently,16 S rRNA sequencing technology was used to analyze the intestinal flora of mice.The results showed that the abundance of Firmicutes in the wheat protein sensitized group was lower than that in the normal group,while the abundance of Bacteroidetes was higher,and Lactobacillus was the difference marker in normal group.Bacterial species diversity analysis showed that the species richness and diversity of intestinal flora in mice were decreased,the difference between mice induced by intraperitoneal injection and normal control group mice was the most significant.Taken together,these results show that among three sensitization methods used to build a mouse model with aluminum hydroxide as adjuvant,intraperitoneal injection is the comparably best way to build a mouse sensitization mode.

关键词： Allergy Wheat gluten BALB/c mice Sensitization methods Intestinal flora

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Salvianolic acid A alleviates renal injury in systemic lupus erythematosus induced by pristane in BALB/c mice

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Acta Pharmaceutica Sinica B 2017年第2期7卷 159-166页

作者： Yihuang Lin Yu Yan Huifang Zhang Yucai chen Yangyang He Shoubao Wang Lianhua Fang Yang Lv Guanhua Du State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College State Key Laboratory of cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular Diseases Beijing Key Laboratory of Drug Targets Identification and Drug Screening Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College Beijing Key Laboratory of Polymorphic Drugs Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

The purpose of this study was to investigate the effects of salvianolic acid A(SAA) in systemic lupus erythematosus(SLE) induced by pristane in BALB/c mice.Lupus mice were established by confirming elevated levels of autoantibodies and IL-6 after intraperitoneal injection of pristane.mice were then treated with daily oral doses of SAA for 5 months in parallel with mice treated with prednisone and aspirin as positive controls.The levels of autoantibodies were monitored at monthly intervals and nephritic symptoms observed by hematoxylin and eosin(H&E) and periodic acid-Schiff(PAS) staining.Western blot analysis of renal tissue was also employed.SAA treatment caused a significant reduction in the levels of anti-Sm autoantibodies and reduced renal histopathological changes and pathological effects.SAA treatment also significantly inhibited the phosphorylation of IKK,IκB and NFκB in renal tissues of lupus mice.In conclusion,the results suggest that SAA alleviates renal injury in pristane-induced SLE in BALB/c mice through inhibition of phosphorylation of IKK,IκB and NFκB.

关键词： Salvianolic acid A SLE Renal injury Autoantibodies Pristane BALB/c mice NFκB

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Adjuvant activity of Pasteurella multocida A strain,Pasteurella multocida B strain and Salmonella typhimurium bacterial DNA on cellular and humoral immunity responses against Pasteurella multocida specific strain infections in BALB/c mice

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Asian Pacific Journal of Tropical Medicine 2018年第5期11卷 336-341页

作者： Maryam Homayoon Yahya Tahamtan Mohammad Kargar Seyed Mohammad Hossein Hosseini Abbas Akhavan Sepahy Department of Biology Science and Research BranchIslamic Azad University Department of Microbiology Shiraz BranchRazi Vaccine and Serum Research InstituteAgriculture ResearchEducation and Extension Organization Department of Microbiology Jahrom Branch Islamic Azad University Department of Microbiology Tehran North BranchIslamic Azad University

Objective: To evaluate the effects of Pasteurella multocida(P. multocida) vaccines on the expression and release of antibodies, interleukin(IL)-6 and IL-12 by serum. Methods: BALB/c mice were immunized with two formalin and iron inactivated vaccine doses within 2 weeks. The vaccines were adjuvant with P. multocida A strain, P. multocida B strain and Salmonella typhimurium bacterial DNA(AbDNA, BbDNA and SbDNA for short, respectively). The animals were challenged 4 weeks after immunization. Blood of mice was collected to detect the change of specific antibody, IL-6, and IL-12 using ELISA. Results: The specific antibody and interleukins in the immunized group increased significantly compared to the control mice after vaccination and challenge(Pcytokines was obtained by P.multocida inactivated with iron and adjuvant with AbDNA at a concentration of 25 μg/mL. The antibody titer peak was 0.447 in mice vaccinated with iron-killed whole-cell antigen adjunct with AbDNA. The time-courses of release showed that bacterial DNA was able to stimulate IL-6 and IL-12 production more than alum(Pconclusions: Our findings introduce that bacterial DNA is capable of releasing an immunological response with several cytokines.These indicate that bacterial DNA entrapped with killed P. multocida antigen is a new and effective adjuvant to enhance specific immunity and resistance of animal against the infectious pathogen, which could simplify the development of highly promising strong adjuvant.

关键词： Pasteurella multocida Bacterial DNA Adjuvant activity Vaccine Immunity BALB/c mice

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Immunotoxicological Evaluation of Wheat Genetically Modified with TaDREB4 Gene on BALB/c mice

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Biomedical and Environmental Sciences 2013年第8期26卷 663-670页

作者： LIANG chun Lai ZHANG Xiao Peng SONG Yan JIA Xu Dong Key Laboratory of Food Safety Risk Assessment Ministry of Health (China National Center for Food Safety Risk Assessment)

Objective To evaluate the immunotoxicological effects of genetically modified wheat with TaDREB4 gene in female BALB/c mice. Methods Female mice weighing 18-22 g were divided into five groups （10 mice/group）, which were set as negative control group, common wheat group, parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, respectively. mice in negative control group and positive control group were fed with AIN93G diet, mice in common wheat group, non-genetically modified parental wheat group and genetically modified wheat group were fed with feedstuffs added corresponding wheat （the proportion is 76%} for 30 days, then body weight, absolute and relative weight of spleen and thymus, white blood cell count, histological examination of immune organ, peripheral blood lymphocytes phenotyping, serum cytokine, serum immunoglobulin, antibody plaque-forming cell, serum half hemolysis value, mitogen-induced splenocyte proliferation, delayed-type hypersensitivity reaction and phagocytic activities of phagocytes were detected. Results No immunotoxicological effects related to the consumption of the genetically modified wheat were observed in BALB/c mice when compared with parental wheat group, common wheat group and negative control group. conclusion From the immunotoxicological point of view, results from this study demonstrate that genetically modified wheat with TaDREB4 gene is as safe as the parental wheat.

关键词： Genetically modified wheat Immunotoxicological effects BALB/c mice

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Response of BALB/c mice to a monovalent influenza A （H1N1） 2009 split vaccine

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cellular & Molecular Immunology 2010年第2期7卷 116-122页

作者： Penghui Yang Li Xing chong Tang Weihong Jia Zhongpeng Zhao Kun Liu Xiao Gao Xiliang Wang Beijing Institute of Microbiology and Epidemiology State Key Laboratory of Pathogen and Biosecurity Beijing China

The novel influenza A （H1N1） 2009 virus has emerged to cause the first pandemic of the twenty-first century. Disease outbreaks caused by the influenza A （H 1N 1） virus have prompted concerns about the potential for a pandemic and have driven the development of vaccines against this subtype of influenza A. In this study, we developed a monovalent influenza A （H 1N 1） split vaccine and evaluated its effects in BALB/c mice. mice were immunized subcutaneously with 2 doses of the vaccine containing hemagglutinin （HA） alone or HA plus an aluminum hydroxide （AI（OH）3） adjuvant. Immunization with varying doses of HA （3.75, 7.5, 15, 30, 45 or 60μg） was performed to induce the production of neutralizing antibodies. The vaccine elicited strong hemagglutination inhibition （HI） and microneutralization, and addition of the adjuvant augmented the antibody response. A preliminary safety evaluation showed that the vaccine was not toxic at large doses （0.5 ml containing 60 μg HA＋600 μg AI（OH）3 or 60 μg HA）. Moreover, the vaccine was found to be safe at a dose of 120 μg HA＋ 1200 μg AI（OH）3 or 120 μg HA in 1.0 ml in rats. In conclusion; the present study provides support for the clinical evaluation of influenza A （H1N1） vaccination as a public health intervention to mitigate a possible pandemic. Additionally, our findings support the further evaluation of the vaccine used in this study in primates or humans.

关键词： BALB/c mice influenza influenza A （H1N1） split vaccine

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Short-lived AIM2 Inflammasome Activation Relates to chronic McMV Infection in BALB/c mice

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current Medical Science 2019年第6期39卷 899-905页

作者： Yuan-yuan LU Xing-lou LIU Yuan HUANG Yi LIAO Ting XI Ya-nan ZHANG Lin-lin ZHANG Sai-nan SHU Feng FANG Department of Pediatrics Tongji Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Absent in melanoma 2(AIM2)inflammasome is a crucial link bridging the innate host defense and the subsequent adaptive immunity when activated by exogenous double stranded DNA(dsDNA).Through establishing models of disseminated murine cytomegalovirus(McMV)infection in balb/c and c57BL/6 mice,we evaluated dynamic expression of AIM2 inflammasome components and its relationship with pathological damage and viral replication,trying tofigure out whether AIM2 inflammasome is related to the chronic mechanism of McMV.balb/c and c57BL/6 mice were sacrificed on day 0,1,3,7,14 and 28 post infection.Expression levels of AIM2,pro-caspase-1,caspase-1 p20,pro-IL1β and mature IL1β in primary peritoneal macrophages(PMs)and spleens were detected by Western blotting.contents of IL18 in the serum were detected by ELISA.Pathological examinations of livers were performed,and mRNA levels of McMV glycoprotein B(gB)in salivary glands also assessed.Results showed that expression levels of AIM2 in PMs and spleens of c57BL/6 mice increased on day 3,even continued to day 28;caspase-1 p20 and mature IL1β increased on day 7,14 and 28;the persistently high expression of IL1β in the serum started on day 1,showing a double peak curve.As for BALB/c mice,expression of AIM2 in PMs increased on day 1 and day 7,while contents of AIM2 in spleens increased on day 1 and day 3;caspase-1 p20 and mature ILip merely increased 7 days fter infection.Thereafter,expression levels of AIM2,caspase-1 p20,mature IL1β and IL18 were limited;the duration of AIM2 inflammasome activation in BALB/c mice was much shorter than that in c57BL/6 mice.The severer pathological damage and more viral replications in BALB/c mice further proved the deficient antiviral immunity to McMV.In conclusion,the activation of AIM2 inflammasome in BALB/c mice was short-lived,which is quite possibly related to the chronicity of McMV infection.

关键词： AIM2 murine cytomegalovirus BALB/c mice c57BL/6 mice macrophages

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Molecular cloning of a Novel cDNA From Mus Muscular BALB/c mice Encoding Glycosyl Hydrolase Family 1: A Homolog of Human Lactase-Phlorizin Hydrolase

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Biomedical and Environmental Sciences 2006年第5期19卷 340-345页

作者： WEI HE ZHEN-YU JI cHENG-YU HUANG Department of Nutrition and Food Hygiene Huaxi School of Public Health Sichuan University Chengdu 610041 Sichuan China Henan Institute of Medical Sciences Zhengzhou 450052 Henan China

Objective To study the mechanism of lactose intolerance （LI） by cloning the mouse lactase cDNA and recombining a vector. Methods Total murine RNA was isolated from the small intestine of a 4-week-old balb/c mouse （δ）. crene-specific primers were designed and synthesized according to the cDNA sequences of lactase-phlorizin hydrolase （LPH） in human, rat, and rabbit. A coding sequence （cDS） fragment was obtained using RT-PcR, and inserted into a clone vector pNEB-193, then the cDNA was sequenced and analyzed using bioinformatics. Results The cDNA from the balb/c mouse with 912 bp encoding 303 amino acid residues. Analysis of the deduced amino acid sequence using bioinforrnatics revealed that this cDNA shared extensive sequence homology with human LPH containing a conserved glycosyl hydrolase family 1 motif important for regulating lactase intolerance. conclusion balb/c mouse LPH cDNA （GenBank accession No： AY751548） provides a necessary foundation for study of the biological function and regulatory mechanism of the lactose intolerance in mice.

关键词： BALB/c mice LPH cDNA pNEB 193 cloning Sequence

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Humoral immune responses induced by anti-idiotypic antibody fusion protein of 6B11scFv/hGM-cSF in BALB/c mice

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chinese Medical Journal 2006年第2期119卷 131-139页

作者： cHANG Xiao-hong YE Xue cUI Heng FENG Jie LI Yi ZHU Hong-lan YANG Wen-lan FU Tian-yun cHENG Hong-yan GUO Hui-fang Gynecologic Oncology center Peking University People＇s Hospital Beijing 100044 China

Background We have previously developed and characterized a monoclonal anti-idiotype antibody, designated 6B 11, which mimics an ovarian carcinoma associated antigen Oc166-9 and whose corresponding monoclonal antibody is cOc166-9 （Abl）. In this study, we evaluate the humoral immune responses induced by the fusion protein 6B11 single-chain variable fragment （scFv）/human granulocyte macrophage colony-stimulating factor （hGM-cSF） and 6B 1 lscFv in BALB/c mice. Methods The fusion protein 6B 11 scFv/hGM-cSF was constructed by fusing a recombinant single-chain variable fragment of 6B11scFv to GM-cSE BALB/c mice were administrated by 6B11scFv/hGM-cSF and 6B11scFv, respectively. Results The fusion protein 6B11scFv/hGM-cSF retained binding to the anti-mouse F（ab）2＇ and was also biologically active as measured by proliferation of human GM-cSF dependent cell TF1 in vitro. After immunization with the 6B11scFv/hGM-cSF and 6BllScFv, BALB/c mice showed significantly enhanced Ab3 antibody responses to 6B11 scFv/hGM-cSF compared with the 6B11 scFv alone. The level of Ab3 was the highest after the first week and maintained for five weeks after the last immunization. Another booster was given when the Ab3 titer descended, and it would reach to the high level in a week. conclusion The fusion protein 6B11scFv/hGM-cSF can induce humoral immunity against ovarian carcinoma in vivo. We also provide the theoretical foundation for the application of the fusion protein 6B11 scFv/hGM-cSF for active immunotherapy of ovarian cancer.

关键词： anti-idiotypic antibody ovarian carcinoma recombinant fusion protein humoral immune responses BALB/c mice

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Evaluation of the adjuvanticity of artemisinin with soluble Leishmania major antigens in BALB/c mice

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Journal of Nanjing Medical University 2009年第6期23卷 359-372页

作者： Albert Kimutai Willy K. Tonui Michael M. Gicheru Peter Kamau Ngure Johnstone Ingonga Stella Kepha Laban Ireri Njeru Dorcas Wachira Robert Karanja Muhia Milkah Mwangi Lydia B. Nyamwamu Department of Zoological Sciences Kenyatta University centre for Biotechnology Research and Development Kenya Medical Research Institute Science Department Daystar University School of Biological Sciences University of Nairobi

Objective： To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice. Methods： Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble Leishmania antigens （SLA） alone, artemisinin co-administered with SLA, SLA and Bacille calmette Gu fin （BcG） vaccine, and artemisinin and BcG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin （IL）-4, IL-5 and gamma interferon （IFN-γ） determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad. Results： mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 （P 〈 0.05） and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA ＋ artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice （P 〉 0.05）, resulting in exacerbated disease. conclusion： These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.

关键词： Artemisinin Leishmania Soluble Leishmania antigens BALB/c mice immunity cytokine adjuvant interleukin-4 （IL-4） IL-5 IFN-γ lesion size footpad lesion vaccine parasite burden proliferation stimulation index

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In Vivo Animal Model Evaluation of a Powerful Oral Nanomedicine for Treating Breast cancer in BALB/c mice Using 4T1 cell Lines without chemotherapy

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Advances in Nanoparticles 2022年第3期11卷 73-109页

作者： Zahra Fakhroueian Alireza Massiha Pegah Esmaeilzadeh Mehdi Assmar Afshin Zahedi Pouriya Esmaeilzadeh Sara Rezaei Shahab Rabiei Lalehdasht School of chemical Engineering (Nanomedicine) College of Engineering University of Tehran Tehran Iran Department of Biotechnology Lahijan Branch Islamic Azad University Lahijan Iran Institute of Pharmacy Martin Luther University Halle Wittenberg Halle (Saale) Germany Department of Microbiology Lahijan Branch Islamic Azad University Lahijan Iran Department of Veterinary Pathology Islamic Azad University Rasht Branch Rasht Iran Department of chemical Engineering Sharif University of Technology Tehran Iran Research Department Production and Laboratory Company ZFP Rasht Iran Department of Biology Faculty of Science Rasht Branch Islamic Azad University Guilan Iran

Nanopharmaceuticals containing quantum dot nanoparticles (Q-Dot NPs) for treating serious cancers such as breast cancer have made fantastic proposals. In this study, ZnO quantum dot NPs are formulated via ZnO@PVP nanopolymer as co-assistants coordinating with efficacious suitable wetting agents, PEG-binding compound, and W/O emulsifier for producing eco-friendly water-based nanodrug. Several characterization techniques containing SEM, TEM, FTIR, photoluminescence, zeta potential, and UV-Vis absorption were employed for ZnO Q-Dot NPs in nanodrug. This work aims to investigate the anti-tumor effects of such nanomedicine on the 4T1 breast cancer cell line in BALB/c mice, being elaborated through intraperitoneal, injection (IVP) and oral therapy. The impressive findings showed that ZnO nanodrug caused changes in blood factors, having the most effectiveness at 40 μg/ml concentration after two weeks of oral treatments. The significant increase in white blood cells (WBc) neutrophils and meaningful decreases in lymphocytes and especially cholesterol were powerful simultaneous impacts, successfully treating malignant breast cancer masses. In this significant animal model research for breast cancer, the sick mice recovered entirely and even had a safe space to mate. Histopathological results showed no evidence of breast tumor formation or metastasis in the group treated with nanodrug and their children. This nanomedicine has a therapeutic effect, and is ready to be applied for treating volunteer breast cancer patients. However, its prevention (inhibitory) effect can also be analyzed and added to current data in future studies.

关键词： Nanomedicine Nanodrug ZnO Q-Dot NPs In Vivo Breast cancer BALB/c mice 4T1 cell Lines Metastasis Oral Treatment

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