AIM:To establish an appropriate primate model of fulminant hepatic failure (FHF).METHODS:We have,for the first time,established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and...AIM:To establish an appropriate primate model of fulminant hepatic failure (FHF).METHODS:We have,for the first time,established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin.Clinical features,biochemical indexes,histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model.RESULTS:Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration.Coagulation activity was significantly decreased.Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h.The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h,respectively.The autopsy showed typical yellow atrophy of the liver.Hepatic encephalopathy of the models was also confirmed by hepatic coma,MRI and pathological changes of cerebral edema.The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices,imaging and histopathology.CONCLUSION:We have established an appropriate large primate model of FHF,which is closely similar to clinic cases,and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies.展开更多
The aim of this study was to identify inflammation-associated markers during the early phase of sepsis in rhesus macaque. Four rhesus macaques were given an intravenous dose of 1010 CFU/kg of E. coli. Blood samples we...The aim of this study was to identify inflammation-associated markers during the early phase of sepsis in rhesus macaque. Four rhesus macaques were given an intravenous dose of 1010 CFU/kg of E. coli. Blood samples were collected before, or 30 minutes, 2, 4, 6 and 8 hours after E. coli infusion. Physiological parameters, bacteremia, endotoxemia, C-reactive protein(CRP), procalcitonin(PCT), and plasma cytokines/chemokines were determined for each animal. Bacteremia was present in all animals from 30 minutes to 3 hours after E. coli infusion whereas endotoxin was detected during the full-time course. CRP and PCT levels remained at detectable levels during the whole experimental window suggesting an ongoing inflammatory process. Signature cytokines and chemokines such as TNF-α, MIP-1α, and MIP-1β peaked about 2 hours after E. coli infusion and decreased thereafter. Plasma IL-6, IL-12 p40, IFN-γ, and IL-1 Ra, as well as I-TAC, MIG, IP-10 and MCP-1, remained at detectable levels after 4 hours of E. coli infusion. This nonhuman primate model could be useful for the assessment of new therapeutics aiming to suppress key inflammatory markers throughout sepsis early phases.展开更多
The recently discovered macaque fossils, including isolated teeth and mandible fragments, from Tianyuan Cave and the juvenile maxilla from Wanglaopu Cave near Zhoukoudian can be identified as Macaca mulatta; they repr...The recently discovered macaque fossils, including isolated teeth and mandible fragments, from Tianyuan Cave and the juvenile maxilla from Wanglaopu Cave near Zhoukoudian can be identified as Macaca mulatta; they represent the first recognized occurrence of fossil M. mulatta in the far north of China. Some previously unearthed but still unpublished Macaca specimens were also studied, including a cranium and the associated mandible from CKT Loc.13A, a maxilla and a mandible from Loc.1, a mandible from Loc.4, and a maxilla from Loc.20, as well as a mandible with complete toothrow from Zhoukoudian but without locality details, all of them can be referred to M. robusta. The study shows M. robusta is more closely related to M. mulatta than to M. anderssonL Zhoukoudian is the richest area of Macacina fossils in North China, totally 2 genera and 4 species were once recognized from 9 localities, namely, Procynocephalus wimani, M. cf. anderssoni, M. robusta and M. mulatta. The fossil records of Macacina in Zhoukoudian area were almost continuous through the Quaternary Period, and it＇s reasonable to assume that Zhoukoudian used to be an evolutionary center for macaques in North China. Therefore, the macaque population of M. mulatta once existed decades ago around Beijing probably originated from the Pleistocene ancestors in the local area, rather than being human-introduced as previously thought.展开更多
AIM: To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by observing replication and expression of the virus, as well as the serological and histological changes of Macaca mulatta infected with HG...AIM: To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by observing replication and expression of the virus, as well as the serological and histological changes of Macaca mulatta infected with HGV genomic RNA or HGV RNA-positive serum.METHODS: Full-length HGV cDNA clone (HGVqz) was constructed and proved to be infectious, from which HGV genomic RNA was transcribed in vitro. Macaca mulatta BY1 was intra-hepatically inoculated with HGV genomic RNA, HGV RNA-positive serum from BY1 was intravenously inoculated into Macaca mulatta BM1, and then BB1 was infected with serum from BM1. Serum and liver tissue were taken regularly, and checked with RT-PCR, in situ hybridization and other immunological, serological,histological assays.RESULTS: Serum HGV RNA was detectable in all the 3Macaca mulattas, serological and histological examinations showed the experimental animals had slightly elevated alanine transaminase (ALT) and developed HGV viremia during the infectious period. The histology, immunohistochemistry, and in situ hybridization in liver tissues of the inoculated animals demonstrated a very mild hepatitis with HGV antigen expression in cytoplasm of hepatocytes.RT-PCR and quantitative PCR results showed that HGV could replicate in liver.CONCLUSION: The genomic RNA from full-length HGV cDNA is infectious to the Macaca mulatta and can cause mild hepatitis. HGV RNA-positive serum, from HGV RNA inoculated Macaca mulatta, is infectious to other Macaca mulattas. Macaca mulatta is susceptible to the inoculated HGV, and therefore can be used as an experimental animal model for the studies of HGV infection and pathogenesis.展开更多
Background: Anesthetic agents are commonly utilized in the handling of non‐human primates for prevent the stress caused in physical exploration or physical restrain. For this reason, the objective of this work was to...Background: Anesthetic agents are commonly utilized in the handling of non‐human primates for prevent the stress caused in physical exploration or physical restrain. For this reason, the objective of this work was to describe the effect of age and dissociative anesthetics (ketamine and tiletamine), and their combinations with acepromazine, xylazine and zolazepam, on the physiological and blood biochemical parameters in Macaca mulatta. Methods: Eighty male Macaca mulatta were divided into four experimental groups depending on the anesthetic mixture applied. Each group of 20 males was divided into five sub‐groups according to age. Physiological parameters were recorded every five minutes during a 30‐minute period. A blood sample was drawn to analyze blood biochemistry. Results: Statistical analyses revealed significant differences in the physiological parameters between the ketamine‐acepromazine and ketamine‐xylazine groups compared to the control group. The analysis of blood biochemistry found significant differences by age and by anesthetic mixture among all groups. Conclusion: These findings contribute to standardizing this animal model in biological research.展开更多
Massive actions have been and are being taken into protecting the world’s primates from extinction,while the study of the properties of genetic diversity,demographic history,and ecological relationships will benefit t...Massive actions have been and are being taken into protecting the world’s primates from extinction,while the study of the properties of genetic diversity,demographic history,and ecological relationships will benefit the understand-ing of the long-term survival of a species.The Taihangshan macaque(Macaca mulatta tcheliensis),a subspecies of rhesus macaque(Macaca mulatta),is endemic to China and currently restricted to southern Mt.Taihangshan area.Herein,we evaluated the genetic diversity,population structure,and demographic history of this subspecies using mitochondrial(Cytb and high variable region I:HVR I)and nuclear markers(microsatellite loci)of 131 in-dividuals collected from 9 localities covering the distribution range of this subspecies.Both phylogenetic analyses and genetic assignment revealed that the wild populations of Taihangshan macaques could be divided into 2 major highly divergent clades,THS-east and THS-west.Low genetic diversity(π:0.00266±0.00016)but high haplotype diversity(Hd:0.80352±0.015)were detected in the Taihangshan macaques,particularly in THS-east.Analyses of demographic history suggested that the Taihangshan macaques experiencedfirst a stable historical population size from Holocene to early 19th century but a subtle decline and then slight growth in the recent 200 years.We suggest that bridging the neighbor populations(i.e.setting corridors)would facilitate the male-mediated geneflow and subsequently increase the genetic diversity of the Taihangshan macaque populations.展开更多
基金Supported by National Basic Research Program of China,No.2009CB522401grand from Natural Science Foundation ofChina,No. 30870983 and 30971118
文摘AIM:To establish an appropriate primate model of fulminant hepatic failure (FHF).METHODS:We have,for the first time,established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin.Clinical features,biochemical indexes,histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model.RESULTS:Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration.Coagulation activity was significantly decreased.Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h.The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h,respectively.The autopsy showed typical yellow atrophy of the liver.Hepatic encephalopathy of the models was also confirmed by hepatic coma,MRI and pathological changes of cerebral edema.The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices,imaging and histopathology.CONCLUSION:We have established an appropriate large primate model of FHF,which is closely similar to clinic cases,and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies.
基金Office of Research Infrastructure Program of NIH(ORIP-NIH)2016-2021,Grant/Award Number:P40OD012217National Institute on Minority Health and Health Disparities,Grant/Award Number:5R25GM061151,G12MD007600 and R25GM061838Southwest National Primate Research Centre,Grant/Award Number:P51 OD011133
文摘The aim of this study was to identify inflammation-associated markers during the early phase of sepsis in rhesus macaque. Four rhesus macaques were given an intravenous dose of 1010 CFU/kg of E. coli. Blood samples were collected before, or 30 minutes, 2, 4, 6 and 8 hours after E. coli infusion. Physiological parameters, bacteremia, endotoxemia, C-reactive protein(CRP), procalcitonin(PCT), and plasma cytokines/chemokines were determined for each animal. Bacteremia was present in all animals from 30 minutes to 3 hours after E. coli infusion whereas endotoxin was detected during the full-time course. CRP and PCT levels remained at detectable levels during the whole experimental window suggesting an ongoing inflammatory process. Signature cytokines and chemokines such as TNF-α, MIP-1α, and MIP-1β peaked about 2 hours after E. coli infusion and decreased thereafter. Plasma IL-6, IL-12 p40, IFN-γ, and IL-1 Ra, as well as I-TAC, MIG, IP-10 and MCP-1, remained at detectable levels after 4 hours of E. coli infusion. This nonhuman primate model could be useful for the assessment of new therapeutics aiming to suppress key inflammatory markers throughout sepsis early phases.
基金supported by the Key Research Program of the Chinese Academy of Sciences (Grants No.KZZD-EW-15 and No.KZZD-EW-03)the Project from the P.R.C. Ministry of Land and Resources (Grant No. 201211005-3)
文摘The recently discovered macaque fossils, including isolated teeth and mandible fragments, from Tianyuan Cave and the juvenile maxilla from Wanglaopu Cave near Zhoukoudian can be identified as Macaca mulatta; they represent the first recognized occurrence of fossil M. mulatta in the far north of China. Some previously unearthed but still unpublished Macaca specimens were also studied, including a cranium and the associated mandible from CKT Loc.13A, a maxilla and a mandible from Loc.1, a mandible from Loc.4, and a maxilla from Loc.20, as well as a mandible with complete toothrow from Zhoukoudian but without locality details, all of them can be referred to M. robusta. The study shows M. robusta is more closely related to M. mulatta than to M. anderssonL Zhoukoudian is the richest area of Macacina fossils in North China, totally 2 genera and 4 species were once recognized from 9 localities, namely, Procynocephalus wimani, M. cf. anderssoni, M. robusta and M. mulatta. The fossil records of Macacina in Zhoukoudian area were almost continuous through the Quaternary Period, and it＇s reasonable to assume that Zhoukoudian used to be an evolutionary center for macaques in North China. Therefore, the macaque population of M. mulatta once existed decades ago around Beijing probably originated from the Pleistocene ancestors in the local area, rather than being human-introduced as previously thought.
基金Supported by National Natural Science Foundation of China (No.30471596)Shanghai Science and Technology Research Project(04DZ19221)
文摘AIM: To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by observing replication and expression of the virus, as well as the serological and histological changes of Macaca mulatta infected with HGV genomic RNA or HGV RNA-positive serum.METHODS: Full-length HGV cDNA clone (HGVqz) was constructed and proved to be infectious, from which HGV genomic RNA was transcribed in vitro. Macaca mulatta BY1 was intra-hepatically inoculated with HGV genomic RNA, HGV RNA-positive serum from BY1 was intravenously inoculated into Macaca mulatta BM1, and then BB1 was infected with serum from BM1. Serum and liver tissue were taken regularly, and checked with RT-PCR, in situ hybridization and other immunological, serological,histological assays.RESULTS: Serum HGV RNA was detectable in all the 3Macaca mulattas, serological and histological examinations showed the experimental animals had slightly elevated alanine transaminase (ALT) and developed HGV viremia during the infectious period. The histology, immunohistochemistry, and in situ hybridization in liver tissues of the inoculated animals demonstrated a very mild hepatitis with HGV antigen expression in cytoplasm of hepatocytes.RT-PCR and quantitative PCR results showed that HGV could replicate in liver.CONCLUSION: The genomic RNA from full-length HGV cDNA is infectious to the Macaca mulatta and can cause mild hepatitis. HGV RNA-positive serum, from HGV RNA inoculated Macaca mulatta, is infectious to other Macaca mulattas. Macaca mulatta is susceptible to the inoculated HGV, and therefore can be used as an experimental animal model for the studies of HGV infection and pathogenesis.
文摘Background: Anesthetic agents are commonly utilized in the handling of non‐human primates for prevent the stress caused in physical exploration or physical restrain. For this reason, the objective of this work was to describe the effect of age and dissociative anesthetics (ketamine and tiletamine), and their combinations with acepromazine, xylazine and zolazepam, on the physiological and blood biochemical parameters in Macaca mulatta. Methods: Eighty male Macaca mulatta were divided into four experimental groups depending on the anesthetic mixture applied. Each group of 20 males was divided into five sub‐groups according to age. Physiological parameters were recorded every five minutes during a 30‐minute period. A blood sample was drawn to analyze blood biochemistry. Results: Statistical analyses revealed significant differences in the physiological parameters between the ketamine‐acepromazine and ketamine‐xylazine groups compared to the control group. The analysis of blood biochemistry found significant differences by age and by anesthetic mixture among all groups. Conclusion: These findings contribute to standardizing this animal model in biological research.
基金financially supported by the Cultivation Fund for Young Teachers in Natural Science Basic Research of Zhengzhou University(JC2020043029)the National Natural Science Foundation of China(Nos.31672302 and 32070446).
文摘Massive actions have been and are being taken into protecting the world’s primates from extinction,while the study of the properties of genetic diversity,demographic history,and ecological relationships will benefit the understand-ing of the long-term survival of a species.The Taihangshan macaque(Macaca mulatta tcheliensis),a subspecies of rhesus macaque(Macaca mulatta),is endemic to China and currently restricted to southern Mt.Taihangshan area.Herein,we evaluated the genetic diversity,population structure,and demographic history of this subspecies using mitochondrial(Cytb and high variable region I:HVR I)and nuclear markers(microsatellite loci)of 131 in-dividuals collected from 9 localities covering the distribution range of this subspecies.Both phylogenetic analyses and genetic assignment revealed that the wild populations of Taihangshan macaques could be divided into 2 major highly divergent clades,THS-east and THS-west.Low genetic diversity(π:0.00266±0.00016)but high haplotype diversity(Hd:0.80352±0.015)were detected in the Taihangshan macaques,particularly in THS-east.Analyses of demographic history suggested that the Taihangshan macaques experiencedfirst a stable historical population size from Holocene to early 19th century but a subtle decline and then slight growth in the recent 200 years.We suggest that bridging the neighbor populations(i.e.setting corridors)would facilitate the male-mediated geneflow and subsequently increase the genetic diversity of the Taihangshan macaque populations.
