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Article: Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice.

Ling, Chen / Liu, Su-Su / Wang, Yu-Ya / Huo, Gui-Tao / Yang, Yan-Wei / Xu, Nan / Wang, Hong / Wu, Yong / Miao, Yu-Fa / Fu, Rui / Zhao, Yu-Wei / Fan, Chang-Fa

Zoological research

2024 Volume 45, Issue 3, Page(s) 551–566

Abstract: Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic ... ...

Abstract	Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human
MeSH term(s)	Animals ; Non-alcoholic Fatty Liver Disease/pathology ; Non-alcoholic Fatty Liver Disease/genetics ; Carcinoma, Hepatocellular/pathology ; Mice ; Liver Neoplasms/pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Disease Models, Animal ; Mice, Transgenic ; Mice, Inbred C57BL ; Humans
Language	English
Publishing date	2024-05-16
Publishing country	China
Document type	Journal Article
ISSN	2095-8137
ISSN	2095-8137
DOI	10.24272/j.issn.2095-8137.2024.002
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Article: Evaluation of biomarkers for

Qiu, Xuan / Miao, Yufa / Geng, Xingchao / Zhou, Xiaobing / Li, Bo

Toxicology research

2020 Volume 9, Issue 2, Page(s) 91–100

Abstract: There have been intensive efforts to ... ...

Abstract	There have been intensive efforts to identify
Language	English
Publishing date	2020-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2684701-2
ISSN	2045-4538 ; 2045-452X
ISSN (online)	2045-4538
ISSN	2045-452X
DOI	10.1093/toxres/tfaa005
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Article: An

Qiu, Xuan / Zhou, Xiaobing / Miao, Yufa / Li, Bo

Toxicology research

2018 Volume 7, Issue 6, Page(s) 1205–1213

Abstract: The kidney is one of the major target organs for drug-induced toxicity. During drug development, the traditional markers of nephrotoxicity indicate only severe and late damage, which leads to high costs. The new biomarkers are needed for a more sensitive ...

Abstract	The kidney is one of the major target organs for drug-induced toxicity. During drug development, the traditional markers of nephrotoxicity indicate only severe and late damage, which leads to high costs. The new biomarkers are needed for a more sensitive and reliable evaluation of nephrotoxicity, especially for the regulatory accepted and validated
Language	English
Publishing date	2018-08-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2684701-2
ISSN	2045-4538 ; 2045-452X
ISSN (online)	2045-4538
ISSN	2045-452X
DOI	10.1039/c8tx00095f
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Article: Xian-Ling-Gu-Bao induced inflammatory stress rat liver injury: Inflammatory and oxidative stress playing important roles

Wu, Wenxiao / Wang, Ting / Sun, Bo / Liu, Dong / Lin, Zhi / Miao, Yufa / Wang, Chao / Geng, Xingchao / Li, Bo

Journal of ethnopharmacology. 2019 July 15, v. 239

2019

Abstract: Xian-Ling-Gu-Bao (XLGB) Fufang is an herbal formula that has been used in clinical settings to treat osteoporosis, osteoarthritis, aseptic bone necrosis, and climacteric syndrome. Despite its uses, XLGB treatment has been linked to potential liver injury. ...

Abstract	Xian-Ling-Gu-Bao (XLGB) Fufang is an herbal formula that has been used in clinical settings to treat osteoporosis, osteoarthritis, aseptic bone necrosis, and climacteric syndrome. Despite its uses, XLGB treatment has been linked to potential liver injury. To date, there is a lack of clear demonstration of such toxicity in animal models.As animal models fail to reproduce the XLGB hepatotoxicity reported in humans, because human hepatocytes are clearly more sensitive to XLGB, this study was designed to investigate a more reliable animal model of such toxicity.We randomized rats into five groups, as follows: CON (control), XLGB, lipopolysaccharide (LPS), L-XLGB/LPS (XLGB, 0.125 g/kg; LPS, 0.1 mg/kg), and XLGB/LPS (XLGB, 1.25 g/kg; LPS, 0.1 mg/kg). These groups were treated with 0.5% sodium carboxymethyl cellulose (CMC-Na), XLGB suspension, normal saline, or LPS. The first administration of XLGB [0.125 g/kg or 1.25 g/kg, by mouth (PO)] or its solvent (0.5% CMC-Na) was delivered, and then food was removed. Twelve hours after the first administration of XLGB, rats received LPS [0.1 mg/kg, intravenously (IV)] or saline control. After 30 min, a second administration of XLGB (0.125 g/kg or 1.25 g/kg, PO) or solvent was administered. The rats were anesthetized at 12 h or 24 h following the second administration of XLGB. Liver function was evaluated by measuring liver weight, liver microscopy, serum biochemistry and plasma microRNA-122 (miR-122). The plasma levels of 27 cytokines were measured to evaluate inflammation. Moreover, the expression of cytochrome P450 2E1 (CYP2E1), nicotinic adenine dinucleotide phosphate (NADPH) oxidase and inducible nitric oxide synthase (iNOS) at protein levels were observed; immunofluorescence and immunohistochemistry were used to confirmed the hepatotoxicity of XLGB.Hepatotoxicity in male rats with moderate inflammation induced by XLGB was indicated by liver histopathology, serum biochemical analysis, serum miR-122 levels, and immunofluorescent assessments. We observed significant increases in liver weight and liver indexes in male rats with moderate inflammation in response to XLGB. Histopathological assessment further showed that extensive hepatocellular necrosis and inflammatory infiltration were evident in rats co-treated with XLGB/LPS. The levels of serum transaminases [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT)], total bilirubin (TBIL) and triglyceride (TG), which are markers of liver function, were also significantly increased by XLGB/LPS treatment. Similarly, miR-122 was significantly elevated in XLGB/LPS treated rats relative to other groups. An immunofluorescent assessment showed extensive apoptosis in hepatocytes from these co-treated rats. What is more, XLGB can dose-dependently induce liver injury in male rats with moderate inflammation.Hepatic CYP2E1, neutrophil chemotactic factor (NCF-1), iNOS, and NOX-2 (an NADPH oxidase subunit) levels were increased in response to XLGB treatment, and staining for DMPO nitrone adducts further showed elevated oxidative stress level in XLGB/LPS-treated rats relative to the other experimental groups.LPS and XLGB co-treatment in rats led to marked hepatotoxicity. This toxicity was associated with disrupted lipid metabolism, extensive liver necrosis and inflammatory infiltration, apoptosis, and expression of oxidative stress-related proteins. These results demonstrate a valuable model for the study of iDILI in the context of XLGB treatment, and further provide insights into the potential mechanisms by which XLGB may induce hepatotoxicity in humans.
Keywords	NAD(P)H oxidase (H2O2-forming) ; NADP (coenzyme) ; adenine ; alanine transaminase ; animal models ; apoptosis ; aspartate transaminase ; bilirubin ; blood chemistry ; blood serum ; carboxymethylcellulose ; chemoattractants ; climacteric fruits ; cytochrome P-450 ; cytokines ; fluorescent antibody technique ; gamma-glutamyltransferase ; hepatocytes ; hepatotoxicity ; histopathology ; immunohistochemistry ; inducible nitric oxide synthase ; inflammation ; intravenous injection ; lipid metabolism ; lipopolysaccharides ; liver ; liver function ; males ; microscopy ; neutrophils ; oral administration ; osteoarthritis ; osteonecrosis ; osteoporosis ; oxidative stress ; phosphates ; protein content ; rats ; solvents ; staining ; traditional medicine ; triacylglycerols
Language	English
Dates of publication	2019-0715
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2019.111910
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Article ; Online: Preclinical safety assessment of toxicity and biodistribution of oncolytic virus HSV-1 expressing human PD-1 antibody in mice.

Wang, Xin / Wang, Chao / Qu, Zhe / Tian, Chao / Wang, Tiantian / Miao, Yufa / Jiang, Hua / Li, Lulu / Liu, Jiajia / Zhao, Rui / Li, Xiaopeng / Geng, Xingchao

Regulatory toxicology and pharmacology : RTP

2022 Volume 132, Page(s) 105166

Abstract: HSV-1/hPD-1 is composed of engineered herpes simplex virus type-1 and two inserted copies of the human PD-1 antibody sequence. It is a novel oncolytic virus product designed to cure malignancies. The objective of this study was to estimate its toxicity ... ...

Abstract	HSV-1/hPD-1 is composed of engineered herpes simplex virus type-1 and two inserted copies of the human PD-1 antibody sequence. It is a novel oncolytic virus product designed to cure malignancies. The objective of this study was to estimate its toxicity in mice. In the single-dose toxicity study, no mortality and abnormal symptoms were observed in animals injected with 4.0 × 10
MeSH term(s)	Animals ; Antibodies, Viral ; Herpesvirus 1, Human ; Humans ; Mice ; Oncolytic Virotherapy/adverse effects ; Oncolytic Viruses/genetics ; Programmed Cell Death 1 Receptor ; Tissue Distribution
Chemical Substances	Antibodies, Viral ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2022-04-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604672-1
ISSN	1096-0295 ; 0273-2300
ISSN (online)	1096-0295
ISSN	0273-2300
DOI	10.1016/j.yrtph.2022.105166
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Zs.A 1711: Show issues

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Article ; Online: Xian-Ling-Gu-Bao induced inflammatory stress rat liver injury: Inflammatory and oxidative stress playing important roles.

Wu, Wenxiao / Wang, Ting / Sun, Bo / Liu, Dong / Lin, Zhi / Miao, Yufa / Wang, Chao / Geng, Xingchao / Li, Bo

Journal of ethnopharmacology

2019 Volume 239, Page(s) 111910

Abstract: Ethnopharmacological relevance: Xian-Ling-Gu-Bao (XLGB) Fufang is an herbal formula that has been used in clinical settings to treat osteoporosis, osteoarthritis, aseptic bone necrosis, and climacteric syndrome. Despite its uses, XLGB treatment has been ...

Abstract	Ethnopharmacological relevance: Xian-Ling-Gu-Bao (XLGB) Fufang is an herbal formula that has been used in clinical settings to treat osteoporosis, osteoarthritis, aseptic bone necrosis, and climacteric syndrome. Despite its uses, XLGB treatment has been linked to potential liver injury. To date, there is a lack of clear demonstration of such toxicity in animal models. Aim of the study: As animal models fail to reproduce the XLGB hepatotoxicity reported in humans, because human hepatocytes are clearly more sensitive to XLGB, this study was designed to investigate a more reliable animal model of such toxicity. Materials and methods: We randomized rats into five groups, as follows: CON (control), XLGB, lipopolysaccharide (LPS), L-XLGB/LPS (XLGB, 0.125 g/kg; LPS, 0.1 mg/kg), and XLGB/LPS (XLGB, 1.25 g/kg; LPS, 0.1 mg/kg). These groups were treated with 0.5% sodium carboxymethyl cellulose (CMC-Na), XLGB suspension, normal saline, or LPS. The first administration of XLGB [0.125 g/kg or 1.25 g/kg, by mouth (PO)] or its solvent (0.5% CMC-Na) was delivered, and then food was removed. Twelve hours after the first administration of XLGB, rats received LPS [0.1 mg/kg, intravenously (IV)] or saline control. After 30 min, a second administration of XLGB (0.125 g/kg or 1.25 g/kg, PO) or solvent was administered. The rats were anesthetized at 12 h or 24 h following the second administration of XLGB. Liver function was evaluated by measuring liver weight, liver microscopy, serum biochemistry and plasma microRNA-122 (miR-122). The plasma levels of 27 cytokines were measured to evaluate inflammation. Moreover, the expression of cytochrome P450 2E1 (CYP2E1), nicotinic adenine dinucleotide phosphate (NADPH) oxidase and inducible nitric oxide synthase (iNOS) at protein levels were observed; immunofluorescence and immunohistochemistry were used to confirmed the hepatotoxicity of XLGB. Results: Hepatotoxicity in male rats with moderate inflammation induced by XLGB was indicated by liver histopathology, serum biochemical analysis, serum miR-122 levels, and immunofluorescent assessments. We observed significant increases in liver weight and liver indexes in male rats with moderate inflammation in response to XLGB. Histopathological assessment further showed that extensive hepatocellular necrosis and inflammatory infiltration were evident in rats co-treated with XLGB/LPS. The levels of serum transaminases [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT)], total bilirubin (TBIL) and triglyceride (TG), which are markers of liver function, were also significantly increased by XLGB/LPS treatment. Similarly, miR-122 was significantly elevated in XLGB/LPS treated rats relative to other groups. An immunofluorescent assessment showed extensive apoptosis in hepatocytes from these co-treated rats. What is more, XLGB can dose-dependently induce liver injury in male rats with moderate inflammation. Hepatic CYP2E1, neutrophil chemotactic factor (NCF-1), iNOS, and NOX-2 (an NADPH oxidase subunit) levels were increased in response to XLGB treatment, and staining for DMPO nitrone adducts further showed elevated oxidative stress level in XLGB/LPS-treated rats relative to the other experimental groups. Conclusion: LPS and XLGB co-treatment in rats led to marked hepatotoxicity. This toxicity was associated with disrupted lipid metabolism, extensive liver necrosis and inflammatory infiltration, apoptosis, and expression of oxidative stress-related proteins. These results demonstrate a valuable model for the study of iDILI in the context of XLGB treatment, and further provide insights into the potential mechanisms by which XLGB may induce hepatotoxicity in humans.
MeSH term(s)	Animals ; Chemical and Drug Induced Liver Injury/blood ; Chemical and Drug Induced Liver Injury/pathology ; Cytokines/blood ; Drugs, Chinese Herbal/toxicity ; Lipopolysaccharides/pharmacology ; Liver/drug effects ; Liver/pathology ; Male ; MicroRNAs/blood ; Oxidative Stress/drug effects ; Rats, Sprague-Dawley
Chemical Substances	Cytokines ; Drugs, Chinese Herbal ; Lipopolysaccharides ; MIRN122 microRNA, rat ; MicroRNAs ; xian ling gu bao
Language	English
Publishing date	2019-04-23
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2019.111910
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Article ; Online: The HepaRG cell line, a superior in vitro model to L-02, HepG2 and hiHeps cell lines for assessing drug-induced liver injury.

Wu, Yu / Geng, Xing-chao / Wang, Ju-feng / Miao, Yu-fa / Lu, Yan-li / Li, Bo

Cell biology and toxicology

2016 Volume 32, Issue 1, Page(s) 37–59

Abstract: Drug-induced liver injury (DILI) is a leading cause of discontinuation of new drug approval or withdrawal of marketed medicine based on safety due to organ vulnerability. The aim of this research is to investigate the potential abilities of four ... ...

Abstract	Drug-induced liver injury (DILI) is a leading cause of discontinuation of new drug approval or withdrawal of marketed medicine based on safety due to organ vulnerability. The aim of this research is to investigate the potential abilities of four different in vitro cell models (L-02, HepG2, HepaRG, and hiHeps cell lines) in assessing marketed drugs labeled with apparently different types of liver injury. A total of 17 drugs with versatile pharmacological profiles were chosen, of which, 14 drugs are recognized as DILI agents and 3 drugs are DILI irrelevant. Preliminary cellular screening assays indicated that the HepaRG cell line had an advantage over other cell lines in predicting drugs associated with DILI in vitro as it had the highest Youden's index (71.4%). A multi-parametric screening assay showed that oxidative stress, mitochondrial damage, and disorders of neutral lipid metabolism were changed notably in the HepaRG cell line after DILI-related drugs exposure, accounting for its high sensitivity in comparison with other three cell lines. In addition, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) all correlated with the cytotoxic effects of diclofenac sodium (p < 0.05), buspirone hydrochloride (p < 0.01), and danazol (p < 0.01) in the HepaRG cell line. We conclude that the HepaRG cell line is a superior in vitro cell model to other three cell lines for evaluating drugs with DILI potential.
MeSH term(s)	Aspartate Aminotransferases/metabolism ; Cell Line, Tumor ; Chemical and Drug Induced Liver Injury/enzymology ; Chemical and Drug Induced Liver Injury/etiology ; Chemical and Drug Induced Liver Injury/metabolism ; Chemical and Drug Induced Liver Injury/pathology ; Hep G2 Cells/metabolism ; Hepatocytes/cytology ; Hepatocytes/drug effects ; Hepatocytes/enzymology ; Humans ; L-Lactate Dehydrogenase/metabolism ; Lipid Metabolism ; Liver/cytology ; Liver/drug effects ; Liver/enzymology ; Malate Dehydrogenase/metabolism
Chemical Substances	L-Lactate Dehydrogenase (EC 1.1.1.27) ; Malate Dehydrogenase (EC 1.1.1.37) ; Aspartate Aminotransferases (EC 2.6.1.1)
Language	English
Publishing date	2016-02
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	48824-0
ISSN	1573-6822 ; 0742-2091
ISSN (online)	1573-6822
ISSN	0742-2091
DOI	10.1007/s10565-016-9316-2
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Article ; Online: Urinary biomarker evaluation for early detection of gentamycin-induced acute kidney injury.

Sun, Bo / Zhou, Xiaobing / Qu, Zhe / Sun, Li / Cheng, Guilin / Yang, Yanwei / Miao, Yufa / Chen, Xiaoguang / Li, Bo

Toxicology letters

2018 Volume 300, Page(s) 73–80

Abstract: Drug-induced acute kidney injury is a serious problem in drug development and clinical treatment. Thus, highly efficient and non-invasive urinary biomarkers are required to control and prevent drug-induced acute kidney injury. Expanding on a previous ... ...

Abstract	Drug-induced acute kidney injury is a serious problem in drug development and clinical treatment. Thus, highly efficient and non-invasive urinary biomarkers are required to control and prevent drug-induced acute kidney injury. Expanding on a previous study, we evaluated 9 novel urinary biomarkers in beagles, which were treated with gentamycin at a dose of 40 mg/kg for 12 consecutive days. N-acetyl-β-D-glucosaminidase was detected with high sensitivity and specificity at the early stage of renal injury (Area under the ROC cure (AUC) = 0.929, 95%CI: 0.722-0.995, P < 0.05 vs. serum creatinine and blood urea nitrogen). More importantly, the results indicated that albumin and trefoil factor-3 were significantly increased 6 days after gentamycin injection (compared with the control group, both P < 0.05). Receiver operator characteristics analysis showed that the diagnostic value of these two biomarkers were both high (both AUCs=1.000; both 95% CI: 0.832-1.000; albumin or trefoil factor-3 vs. serum creatinine or blood urea nitrogen, both P < 0.05). Moreover, albumin and trefoil factor-3 levels were highly correlated to the degree of kidney injury (both Pearson's r > 0.8, P < 0.05). Our data indicate that albumin and trefoil factor-3 may have value in the early diagnosis of kidney injury in non-rodent species and may thus inspire the preclinical use of urinary biomarkers in drug-induced acute kidney injury.
MeSH term(s)	Acute Kidney Injury/chemically induced ; Animals ; Biomarkers/blood ; Biomarkers/urine ; Blood Urea Nitrogen ; Creatinine/blood ; Dogs ; Early Diagnosis ; Gentamicins/adverse effects ; Humans ; Male
Chemical Substances	Biomarkers ; Gentamicins ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2018-10-28
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2018.10.027
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Article ; Online: Quality, bioactivity study, and preclinical acute toxicity, safety pharmacology evaluation of PEGylated recombinant human endostatin (M

Guo, Lifang / Geng, Xingchao / Liu, Li / Miao, Yufa / Lin, Zhi / Yu, Min / Fu, Yan / Liu, Lihong / Li, Bo / Luo, Yongzhang

Journal of biochemical and molecular toxicology

2018 Volume 33, Issue 3, Page(s) e22257

Abstract: Endostar, a potent endogenous antiangiogenic factor, is wildly used in clinics. However, it was easily degraded by enzymes and rapidly cleared by the kidneys. To overcome these shortcomings, PEGylated recombinant human endostatin was developed. In this ... ...

Abstract	Endostar, a potent endogenous antiangiogenic factor, is wildly used in clinics. However, it was easily degraded by enzymes and rapidly cleared by the kidneys. To overcome these shortcomings, PEGylated recombinant human endostatin was developed. In this study, the purity of M
MeSH term(s)	Animals ; Cells, Cultured ; Endostatins/adverse effects ; Endostatins/pharmacology ; Endostatins/therapeutic use ; Endostatins/toxicity ; Endothelial Cells/drug effects ; Female ; Humans ; Macaca mulatta ; Male ; Mice ; Mice, Nude ; Neoplasms/drug therapy ; Recombinant Proteins/adverse effects ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use ; Recombinant Proteins/toxicity ; Xenograft Model Antitumor Assays
Chemical Substances	Endostatins ; Recombinant Proteins
Language	English
Publishing date	2018-12-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1410020-4
ISSN	1099-0461 ; 1095-6670
ISSN (online)	1099-0461
ISSN	1095-6670
DOI	10.1002/jbt.22257
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Article ; Online: A safety and immunogenicity study of a novel subunit plague vaccine in cynomolgus macaques.

Liu, Li / Wei, Dong / Qu, Zhe / Sun, Li / Miao, Yufa / Yang, Yanwei / Lu, Jinbiao / Du, Weixin / Wang, Bingxiang / Li, Bo

Journal of applied toxicology : JAT

2017 Volume 38, Issue 3, Page(s) 408–417

Abstract: Plague has led to millions of deaths in history and outbreaks continue to the present day. The efficacy limitations and safety concerns of the existing killed whole cell and live-attenuated vaccines call for the development of new vaccines. In this study, ...

Abstract	Plague has led to millions of deaths in history and outbreaks continue to the present day. The efficacy limitations and safety concerns of the existing killed whole cell and live-attenuated vaccines call for the development of new vaccines. In this study, we evaluated the immunogenicity and safety of a novel subunit plague vaccine, comprising native F1 antigen and recombinant V antigen. The cynomolgus macaques in low- and high-dose vaccine groups were vaccinated at weeks 0, 2, 4 and 6, at dose levels of 15 μg F1 + 15 μg rV and 30 μg F1 + 30 μg rV respectively. Specific antibodies and interferon-γ and interleukin-2 expression in lymphocytes were measured. For safety, except for the general toxicity and local irritation, we made a systematic immunotoxicity study on the vaccine including immunostimulation, autoimmunity and anaphylactic reaction. The vaccine induced high levels of serum anti-F1 and anti-rV antibodies, and caused small increases of interferon-γ and interleukin-2 in monkeys. The vaccination led to a reversible increase in the number of peripheral blood eosinophils, the increases in serum IgE level in a few animals and histopathological change of granulomas at injection sites. The vaccine had no impact on general conditions, most clinical pathology parameters, percentages of T-cell subsets, organ weights and gross pathology of treated monkeys and had passable local tolerance. The F1 + rV subunit plague vaccine can induce very strong humoral immunity and low level of cellular immunity in cynomolgus macaques and has a good safety profile.
MeSH term(s)	Animals ; Antibodies, Bacterial/blood ; Antigens, Bacterial/administration & dosage ; Antigens, Bacterial/immunology ; Antigens, Bacterial/toxicity ; Bacterial Proteins/administration & dosage ; Bacterial Proteins/immunology ; Bacterial Proteins/toxicity ; Eosinophils/drug effects ; Eosinophils/immunology ; Female ; Granuloma/chemically induced ; Granuloma/immunology ; Granuloma/pathology ; Immunity, Cellular/drug effects ; Immunity, Humoral/drug effects ; Immunogenicity, Vaccine ; Immunoglobulin E/blood ; Injection Site Reaction/immunology ; Injection Site Reaction/pathology ; Injections, Intramuscular ; Interferon-gamma/blood ; Interleukin-2/blood ; Macaca fascicularis ; Male ; Plague Vaccine/administration & dosage ; Plague Vaccine/immunology ; Plague Vaccine/toxicity ; Pore Forming Cytotoxic Proteins/administration & dosage ; Pore Forming Cytotoxic Proteins/immunology ; Pore Forming Cytotoxic Proteins/toxicity ; Vaccines, Subunit/immunology ; Vaccines, Synthetic/immunology
Chemical Substances	Antibodies, Bacterial ; Antigens, Bacterial ; Bacterial Proteins ; Interleukin-2 ; LcrV protein, Yersinia ; Plague Vaccine ; Pore Forming Cytotoxic Proteins ; Vaccines, Subunit ; Vaccines, Synthetic ; caf1 protein, Yersinia pestis ; Immunoglobulin E (37341-29-0) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2017-11-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604625-3
ISSN	1099-1263 ; 0260-437X
ISSN (online)	1099-1263
ISSN	0260-437X
DOI	10.1002/jat.3550
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Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito