The rapid spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social,economic,and health burdens worldwide.Despite considera...The rapid spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social,economic,and health burdens worldwide.Despite considerable efforts to combat coronavirus disease 2019(COVID-19),various SARS-CoV-2 variants have emerged,and their underlying mechanisms of pathogenicity remain largely unknown.Furthermore,effective therapeutic drugs are still under development.Thus,an ideal animal model is crucial for studying the pathogenesis of COVID-19 and for the preclinical evaluation of vaccines and antivirals against SARS-CoV-2 and variant infections.Currently,several animal models,including mice,hamsters,ferrets,and nonhuman primates(NHPs),have been established to study COVID-19.Among them,ferrets are naturally susceptible to SARS-CoV-2 infection and are considered suitable for COVID-19 study.Here,we summarize recent developments and application of SARS-CoV-2 ferret models in studies on pathogenesis,therapeutic agents,and vaccines,and provide a perspective on the role of these models in preventing COVID-19 spread.展开更多
The pandemic of coronavirus disease 2019(COVID-19),caused by a newly identifiedβ-coronavirus(SARS-CoV-2)has emerged as a dire health problem,causing a massive crisis for global health.Primary method of transmission w...The pandemic of coronavirus disease 2019(COVID-19),caused by a newly identifiedβ-coronavirus(SARS-CoV-2)has emerged as a dire health problem,causing a massive crisis for global health.Primary method of transmission was firstly thought to be animal to human transmission.However,it has been observed that the virus is transmitted from human to human via respiratory droplets.Interestingly,SARS-CoV-2 ribonucleic acid(RNA)has been isolated from patient stools,suggesting a possible gastrointestinal(GI)involvement.Most commonly reported clinical manifestations are fever,fatigue and dry cough.Interestingly,a small percentage of patients experience GI symptoms with the most common being anorexia,diarrhea,nausea and vomiting.The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples.The exact incidence of digestive symptoms is a matter of debate.The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms’mechanism.Cases with solely GI symptoms have been reported in both adults and children.Viral RNA has also been detected in stool and blood samples,indicating the possibility of liver damage,which has been reported in COVID-19 patients.The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis,however data from these cases is lacking.The aim of this review is firstly,to briefly update what is known about the origin and the transmission of SARS-CoV-2,but mainly to focus on the manifestations of the GI tract and their pathophysiological background,so that physicians on the one hand,not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other,to have SARS-CoV-2 on their mind when the“gastroenteritis”type symptoms predominate.展开更多
基金supported by the S&T Program of Hebei(20277705D and 20372601D)Natural Science Foundation of Hebei Province,China (H2020206352)+2 种基金Science and Technology Project of Hebei Education Department (QN2018150)Hebei Medical Science Research Project (20220973)Chinese Medicine Research Program of Hebei Province (2021119)。
文摘The rapid spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social,economic,and health burdens worldwide.Despite considerable efforts to combat coronavirus disease 2019(COVID-19),various SARS-CoV-2 variants have emerged,and their underlying mechanisms of pathogenicity remain largely unknown.Furthermore,effective therapeutic drugs are still under development.Thus,an ideal animal model is crucial for studying the pathogenesis of COVID-19 and for the preclinical evaluation of vaccines and antivirals against SARS-CoV-2 and variant infections.Currently,several animal models,including mice,hamsters,ferrets,and nonhuman primates(NHPs),have been established to study COVID-19.Among them,ferrets are naturally susceptible to SARS-CoV-2 infection and are considered suitable for COVID-19 study.Here,we summarize recent developments and application of SARS-CoV-2 ferret models in studies on pathogenesis,therapeutic agents,and vaccines,and provide a perspective on the role of these models in preventing COVID-19 spread.
文摘本研究旨在观察血管紧张素转换酶Ⅱ(Angiotensin Converting EnzymeⅡ,ACE2)在CCl4中毒大鼠肝脏中的表达,并探讨其参与抗损伤的作用机制。16只120 g左右雄性SD大鼠随机分成对照组和试验组(n=8)。对照组大鼠腹腔注射生理盐水,试验组大鼠腹腔注射40%CCl4,首次剂量为5 mL.kg-1,以后每3 d 1次(剂量为3mL.kg-1),每周称重1次,4周后宰杀。测定平均日增体质量、血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、白蛋白(Alb)、总蛋白(TP)、总胆红素(TBIL)、血浆血管紧张素Ⅱ(AngⅡ)含量、肝组织中ACE2含量和Mas受体mR-NA的表达及ACE2 mRNA的分布。结果表明:与对照组相比,试验组大鼠平均日增体质量、血清Alb和TP含量均显著下降(P<0.05),血清ALT和AST活性显著升高(P<0.05),血清TBIL和血浆AngⅡ含量没有显著性变化,Real-time PCR结果提示肝脏中ACE2和Mas受体的mRNA表达均显著上升(3.21±0.52 vs 1.03±0.11,P<0.01;1.64±0.22 vs 1.02±0.10,P<0.05),原位杂交结果显示对照组大鼠ACE2 mRNA着色较少,主要集中在中央静脉周围细胞,试验组大鼠ACE2大量出现在病变区域、胆管周围细胞、血管及微管内皮细胞当中。本研究表明CCl4诱导的肝损伤大鼠肝脏中ACE2和Mas受体的mRNA表达均增加,提示ACE2参与了肝脏的抗损伤过程,其机制可能是通过激活ACE2-Ang 1-7-Mas轴,减少AngⅡ的产生,从而减轻肝损伤。
文摘The pandemic of coronavirus disease 2019(COVID-19),caused by a newly identifiedβ-coronavirus(SARS-CoV-2)has emerged as a dire health problem,causing a massive crisis for global health.Primary method of transmission was firstly thought to be animal to human transmission.However,it has been observed that the virus is transmitted from human to human via respiratory droplets.Interestingly,SARS-CoV-2 ribonucleic acid(RNA)has been isolated from patient stools,suggesting a possible gastrointestinal(GI)involvement.Most commonly reported clinical manifestations are fever,fatigue and dry cough.Interestingly,a small percentage of patients experience GI symptoms with the most common being anorexia,diarrhea,nausea and vomiting.The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples.The exact incidence of digestive symptoms is a matter of debate.The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms’mechanism.Cases with solely GI symptoms have been reported in both adults and children.Viral RNA has also been detected in stool and blood samples,indicating the possibility of liver damage,which has been reported in COVID-19 patients.The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis,however data from these cases is lacking.The aim of this review is firstly,to briefly update what is known about the origin and the transmission of SARS-CoV-2,but mainly to focus on the manifestations of the GI tract and their pathophysiological background,so that physicians on the one hand,not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other,to have SARS-CoV-2 on their mind when the“gastroenteritis”type symptoms predominate.
基金the funding support from the National Natural Science Foundation of China(No.81774126,No.81973670)the Natural Science Foundation of Hunan Province(No.2016JJ2095,No.2017JJ3232)+2 种基金Scientific Research Project of Traditional Chinese Medicine for the Prevention and Treatment of New Pneumonia in Hunan Province(No.GYGG007)the Construction Project of Specialty of Traditional Chinese Medicine in Guangdong Provincethe Construction Project of Specialty of Traditional Chinese Medicine in Shenzhen。