AIM: to establish a new animal model for the research of human rotavirus(HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines.METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou an...AIM: to establish a new animal model for the research of human rotavirus(HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines.METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and bamma, were inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and PbS(control), respectively, and fecal samples of pigs from 0 to 7 d post infection(DPI) were collected individually. Enzyme linked immunosorbent assay was used to detect HRV antigen in feces. the HRV was tested by real-time PCR(Rt-PCR). the sections of the intestinal tissue were stained with hematoxylin and eosin to observe the morphologic variation by microscopy. Immunofluorescence was used to determine the HRV in intestinal tissue. HRV particles in cells of the ileum were observed by electron micrography.RESULTS: When inoculated with HRV, mini-pigs younger than 30 d developed diarrhea in an agedependent manner and shed HRV antigen of the sameinoculum, as demonstrated by Rt- PCR.Histopathological changes were observed in HRV inoculated mini-pigs including small intestinal cell tumefaction and necrosis. HRV that was distributed in the small intestine was restricted to the top part of the villi on the internal wall of the ileum, which was observed by immunofluorescence and transmission electron microscopy. Virus particles were observed in Golgi like follicles in HRV-infected neonatal minipigs. Guizhou mini-pigs were more sensitive to HRV than bamma with respect to RV antigen shedding and clinical diarrhea.CONCLUSION: these results indicate that we have established a mini-pig model of HRV induced diarrhea. Our findings are useful for the understanding of the pathogenic mechanisms of HRV infection.展开更多
Various epidemics have occurred throughout history,which has led to the investigation and understanding of their transmission dynamics.As a result,non-local operators are used for mathematical modeling in this study.T...Various epidemics have occurred throughout history,which has led to the investigation and understanding of their transmission dynamics.As a result,non-local operators are used for mathematical modeling in this study.Therefore,this research focuses on developing a dysentery diarrhea model with the use of a fractional operator using a one-parameter Mittag–Leffler kernel.The model consists of three classes of the human population,whereas the fourth one belongs to the pathogen population.The model carefully deals with the dimensional homogeneity among the parameters and the fractional operator.In addition,the model was validated by fitting the actual number of dysentery diarrhea infected cases covering 52 weeks in 2017,which occurred in Ethiopia.The biological parameters were fitted,and fractional orderνwas optimized.The basic reproduction numbers R0 were 1.7031 and 1.9581,which correspond to the fractional and integer-order models,respectively.The fractional model showed smaller discrepancies compared to the integer-order model when the models were fitted and validated with the actual cases of infected humans.Qualitative theory for the existence and uniqueness of the solutions was extensively explored,and the stability of equilibria was investigated.The most influential parameters were found via forward sensitivity indices.This multidisciplinary research shows and explains the results of numerical simulations applied to a biological issue.展开更多
This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 ...This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 Tibetan veterinary drugs, Veronica ciliate Fisch, Usnea diffracta Vain, Sophoraflavescens var. flavescens, Lamiophlomis rotata （ Benth. ） Kudo on 14 common diarrheagenic bacteria were detected by K-B diffusion method and micro-broth dilution method. Optimization was performed on prescriptions of the 4 Tibetan veterinary drugs using orthogonal design software, and a mouse bacterial diarrhea model was established with a clinical isolate, Salmonella blegdam. According to the LD50 value of the optimal prescription of the 4 Tibetan veterinary drugs, the established mouse bacterial diarrhea model was treated in 3 dose groups, i. e. , the high, middle and low dose groups （0. 060, 0. 030 and 0. 020 g/ml, respectively）. The results showed that the 4 Tibetan veterinary drugs had very good inhibitory effects on most of the tested diarrheagenic bacteria, and among them, U. diffracta had better inhibitory effects on all the tested bacteria. The optimal prescription of the d Tibetan veterinary drugs （high dose, 0.06 g/ml） exhibited very good inhibitory effect on mouse diarrhea, indicating that the prescription has very good anti-diarrhea effect, which is beneficial to the clinical treatment of such disease and the development of Tibetan veterinary drugs.展开更多
AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neona...AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neonatal rhesus monkeys with an average age of 15-20 d and an average weight of 500 g ± 150 g received intragastric administration of varying doses of SA11 RV( 107 PFUs/mL, 106 PFUs/mL, or 105 PFUs/mL, 10 mL/animal) to determine whether the SA11 strain can effectively infect these animals by observing their clinical symptoms, fecal shedding of virus antigen by ELISA, distribution of RV antigen in the organs by immunofluorescence, variations of viral RNA load in the organs by qRT-PCR, histopathological changes in the small intestine by HE staining, and apoptosis of small intestinal epithelial cells by TUNEL assay.RESULTS The RV monkey model showed typical clinical diarrhea symptoms in the 108 PFUs SA11 group, where we observed diarrhea 1-4 d post infection(dpi) and viral antigen shed in the feces from 1-7 dpi. RV was found in jejunal epithelial cells. We observed a viral load of approximately 5.85 × 103 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 105 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in mesenteric lymph nodes at 2 dpi and 3 dpi. The following histopathological changes were observed in the small intestine following intragastric administration of SA11 RV: vacuolization, edema, and atrophy. Apoptosis in the jejunal villus epithelium was also detectable at 3 dpi.CONCLUSION Our results indicate that we have successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys. Future studies will elucidate the mechanisms underlying the pathogenesis of RV infection, and we will use the model to evaluate the protective effect of candidate vaccines.展开更多
基金Supported by National Natural Science Foundation of China,No.30400402 and No.30571708
文摘AIM: to establish a new animal model for the research of human rotavirus(HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines.METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and bamma, were inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and PbS(control), respectively, and fecal samples of pigs from 0 to 7 d post infection(DPI) were collected individually. Enzyme linked immunosorbent assay was used to detect HRV antigen in feces. the HRV was tested by real-time PCR(Rt-PCR). the sections of the intestinal tissue were stained with hematoxylin and eosin to observe the morphologic variation by microscopy. Immunofluorescence was used to determine the HRV in intestinal tissue. HRV particles in cells of the ileum were observed by electron micrography.RESULTS: When inoculated with HRV, mini-pigs younger than 30 d developed diarrhea in an agedependent manner and shed HRV antigen of the sameinoculum, as demonstrated by Rt- PCR.Histopathological changes were observed in HRV inoculated mini-pigs including small intestinal cell tumefaction and necrosis. HRV that was distributed in the small intestine was restricted to the top part of the villi on the internal wall of the ileum, which was observed by immunofluorescence and transmission electron microscopy. Virus particles were observed in Golgi like follicles in HRV-infected neonatal minipigs. Guizhou mini-pigs were more sensitive to HRV than bamma with respect to RV antigen shedding and clinical diarrhea.CONCLUSION: these results indicate that we have established a mini-pig model of HRV induced diarrhea. Our findings are useful for the understanding of the pathogenic mechanisms of HRV infection.
基金This project was funded by the Deanship of Scientific Research(DSR)at King Abdulaziz University,Jeddah,under Grant No.RG-6-135-40.The authors,therefore,gratefully acknowledge DSR technical and financial support.
文摘Various epidemics have occurred throughout history,which has led to the investigation and understanding of their transmission dynamics.As a result,non-local operators are used for mathematical modeling in this study.Therefore,this research focuses on developing a dysentery diarrhea model with the use of a fractional operator using a one-parameter Mittag–Leffler kernel.The model consists of three classes of the human population,whereas the fourth one belongs to the pathogen population.The model carefully deals with the dimensional homogeneity among the parameters and the fractional operator.In addition,the model was validated by fitting the actual number of dysentery diarrhea infected cases covering 52 weeks in 2017,which occurred in Ethiopia.The biological parameters were fitted,and fractional orderνwas optimized.The basic reproduction numbers R0 were 1.7031 and 1.9581,which correspond to the fractional and integer-order models,respectively.The fractional model showed smaller discrepancies compared to the integer-order model when the models were fitted and validated with the actual cases of infected humans.Qualitative theory for the existence and uniqueness of the solutions was extensively explored,and the stability of equilibria was investigated.The most influential parameters were found via forward sensitivity indices.This multidisciplinary research shows and explains the results of numerical simulations applied to a biological issue.
基金Supported by the Science and Technology Training Plan Project of Sichuan Province(2016KZ0007)the Fundamental Research Funds for the Central Universitiesof Southwest University for Nationalities(2017NZYQN38)
文摘This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 Tibetan veterinary drugs, Veronica ciliate Fisch, Usnea diffracta Vain, Sophoraflavescens var. flavescens, Lamiophlomis rotata （ Benth. ） Kudo on 14 common diarrheagenic bacteria were detected by K-B diffusion method and micro-broth dilution method. Optimization was performed on prescriptions of the 4 Tibetan veterinary drugs using orthogonal design software, and a mouse bacterial diarrhea model was established with a clinical isolate, Salmonella blegdam. According to the LD50 value of the optimal prescription of the 4 Tibetan veterinary drugs, the established mouse bacterial diarrhea model was treated in 3 dose groups, i. e. , the high, middle and low dose groups （0. 060, 0. 030 and 0. 020 g/ml, respectively）. The results showed that the 4 Tibetan veterinary drugs had very good inhibitory effects on most of the tested diarrheagenic bacteria, and among them, U. diffracta had better inhibitory effects on all the tested bacteria. The optimal prescription of the d Tibetan veterinary drugs （high dose, 0.06 g/ml） exhibited very good inhibitory effect on mouse diarrhea, indicating that the prescription has very good anti-diarrhea effect, which is beneficial to the clinical treatment of such disease and the development of Tibetan veterinary drugs.
基金the CAMS Initiative for Innovative Medicine,No.2016-I2M-1-019National Natural Science Foundation of China,No.31700154+4 种基金Major Science and Technology Special Project of Yunnan Province(Biomedicine),No.2018ZF006Science and Technology Project of Yunnan Province-general program,No.2016FB034Science and Technology Innovation Team Project of Kunming,No.2016-2-R-07674the Project of National Nonprofit Scientific Institutes Basic Scientific Service Fee,No.2016ZX310179-4Science and Technology Project of Yunnan Province,Key New Product Development,No.2014BC008
文摘AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neonatal rhesus monkeys with an average age of 15-20 d and an average weight of 500 g ± 150 g received intragastric administration of varying doses of SA11 RV( 107 PFUs/mL, 106 PFUs/mL, or 105 PFUs/mL, 10 mL/animal) to determine whether the SA11 strain can effectively infect these animals by observing their clinical symptoms, fecal shedding of virus antigen by ELISA, distribution of RV antigen in the organs by immunofluorescence, variations of viral RNA load in the organs by qRT-PCR, histopathological changes in the small intestine by HE staining, and apoptosis of small intestinal epithelial cells by TUNEL assay.RESULTS The RV monkey model showed typical clinical diarrhea symptoms in the 108 PFUs SA11 group, where we observed diarrhea 1-4 d post infection(dpi) and viral antigen shed in the feces from 1-7 dpi. RV was found in jejunal epithelial cells. We observed a viral load of approximately 5.85 × 103 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 105 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in mesenteric lymph nodes at 2 dpi and 3 dpi. The following histopathological changes were observed in the small intestine following intragastric administration of SA11 RV: vacuolization, edema, and atrophy. Apoptosis in the jejunal villus epithelium was also detectable at 3 dpi.CONCLUSION Our results indicate that we have successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys. Future studies will elucidate the mechanisms underlying the pathogenesis of RV infection, and we will use the model to evaluate the protective effect of candidate vaccines.
