With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer’s disease(AD) is the most common form of dementia ...With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer’s disease(AD) is the most common form of dementia observed in the elderly, but its pathogenetic mechanism has still not been fully elucidated. Furthermore, no effective treatment strategy has been developed to date, despite considerable efforts. This can be mainly attributed to the paucity of animal models of AD that are sufficiently similar to humans. Among the presently established animal models, non-human primates share the closest relationship with humans, and their neural anatomy and neurobiology share highly similar characteristics with those of humans. Thus, there is no doubt that these play an irreplaceable role in AD research. Considering this, the present literature on non-human primate models of AD was reviewed to provide a theoretical basis for future research.展开更多
Alzheimer's disease(AD)is a neurodegenerative disorder.The pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,syn...Alzheimer's disease(AD)is a neurodegenerative disorder.The pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,synapse loss,and brain atrophy.Many therapies have been tested to improve or at least effectively modify the course of AD.Meaningful data indicate that the transplantation of stem cells can alleviate neuropathology and significantly ameliorate cognitive deficits in animal models with Alzheimer's disease.Transplanted stem cells have shown their inherent advantages in improving cognitive impairment and memory dysfunction,although certain weak-nesses or limitations need to be overcome.This review recapitulates rodent models for AD,the therapeutic efficacy of stem cells,influencing factors,and the underlying mechanisms behind these changes.Stem cell therapy provides perspective and chal-lenges for its clinical application in the future.展开更多
Background: With the aim of establishing the most comprehensive database of laboratory animal strains, the "laboratory animal strain resources database"(LasDB)was constructed as a searchable online database ...Background: With the aim of establishing the most comprehensive database of laboratory animal strains, the "laboratory animal strain resources database"(LasDB)was constructed as a searchable online database of all laboratory animal strains,stocks and mutant embryonic stem-cell lines available worldwide, including inbred,outbred, mutant and genetically engineered strains.Methods: MySQL database software was used to construct the LasDB, offering an easy-to-use interface.Results: To date, LasDB has a collection covering data for 21 596 mouse strains,2062 rat strains, 13 monkey strains, 2 hamster strains, 5 dog strains, 5 rabbit strains and more than 50 other laboratory animal strains. LasDB will be continually improved with regular updates of new laboratory animal strains from all over the world.Conclusion: To the best of our knowledge, this is the first database that attempts to systematically integrate all available laboratory animal strain data with the aim of supporting open usage and full resource sharing.展开更多
Autophagy is one of the degradation pathways to remove proteins or damaged or-ganelles in cells that plays an important role in neuroprotection.Different stages of autophagy are regulated by autophagy-related genes,an...Autophagy is one of the degradation pathways to remove proteins or damaged or-ganelles in cells that plays an important role in neuroprotection.Different stages of autophagy are regulated by autophagy-related genes,and many molecules such as transcription factor EB(TFEB)are involved.The complete autophagy process plays an important role in maintaining the dynamic balance of autophagy and is crucial to the homeostasis of intracellular substance and energy metabolism.Autophagy balance is disrupted in neurodegenerative diseases,accounting for a variety of degeneration dis-orders.These impairments can be alleviated or treated by the regulation of autophagy through molecules such as TFEB.展开更多
Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created...Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created three groups of K/BxN female mice that were positive for the anti‐glucose‐6‐phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), anti‐ GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing. Results: Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL‐C, TCHO, and TG, decreased serum levels of HDL‐C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL‐C, TCHO, and TG, increased serum levels of HDL‐C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA‐associated atherosclerosis and dyslipidemia. Conclusion: Our mouse model of RA indicated that HFD increased ankle width and aggravated a therosclerosis a nd d yslipidemia, a nd t hat H CQ a lleviated t he d yslipidemia and atherosclerosis, but had no effect on ankle width.展开更多
Objective Airborne microbial communities include a significant number of uncultured and poorly characterized bacteria.No effective method currently exists to evaluate the health risks of such complex bacterial populat...Objective Airborne microbial communities include a significant number of uncultured and poorly characterized bacteria.No effective method currently exists to evaluate the health risks of such complex bacterial populations,particularly for pneumonia.Methods We developed a method to evaluate risks from airborne microorganisms,guided by the principle that closer evolutionary relationships reflect similar biological characteristics,and thus used16 S rDNA sequences of 10 common pneumonia-related bacterial pathogens.We calculated a risk of breath-related(Rbr)index of airborne bacterial communities and verified effectiveness with artificial flora and a clinical project.Results We suggested applying Rbr80 to evaluate the health risks of airborne bacterial communities that comprise 80% of dominant operational taxonomic units(OTUs).The feasibility of Rbr80 was confirmed by artificial flora and by pneumonia data from a hospital.A high Rbr80 value indicated a high risk of pneumonia from airborne bacterial communities.Conclusion Rbr80 is an effective index to evaluate the pneumonia-associated risk from airborne bacteria.Values of Rbr80 greater than 15.40 are considered high risk.展开更多
The low success rates in the treatment of multidrug-resistant tuberculosis(MDR-TB)and extensively drug-resistant TB(XDR-TB),which account for 55%and 34%respectively,led the WHO to conclude that MDR/XDR-TB is a serious...The low success rates in the treatment of multidrug-resistant tuberculosis(MDR-TB)and extensively drug-resistant TB(XDR-TB),which account for 55%and 34%respectively,led the WHO to conclude that MDR/XDR-TB is a serious public health crisis.However,the virulence of MDR/XDR-Mycobacterium Tuberculosis(Mtb)has not been analyzed in details,which could provide a specific guidance for the control and prevention.In this review,we discuss different aspects of MDR/XDR-Mtb virulence and its relationship to fitness cost by probing the following questions:(1)what mediates the virulence of MDR/XDR-Mtb?(What is the relationship between fitness and virulence of Mtb?(2)Is it possible that drug-resistant Mtb(DR Mtb)can show higher fitness?(3)What is the definite effect on fitness of each drug-resistant mutant?(4)What other important factors affecting fitness in the mutant strain?(5)How to study the virulence of a large number of DR Mtb?And what prevention and control measures will be taken in the future,especially for the high virulent DR Mtb?We therefore summarized the congruent relationship between drug resistance and fitness from the global response-related genes to antibiotic resistance-contributing mutation,provided methods to explore the virulence of DR Mtb.This review may offer some critical information and concise guide to creating strategies for the prevention and control of drug-resistant Mtb.展开更多
基金The CAMS Innovation Fund for Medical Science(2016-12M-2-006 and 2016-12M-1-10)the PUMC Innovation Fund for Graduate Students(Grant/Award number:2017-1001-07)
文摘With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer’s disease(AD) is the most common form of dementia observed in the elderly, but its pathogenetic mechanism has still not been fully elucidated. Furthermore, no effective treatment strategy has been developed to date, despite considerable efforts. This can be mainly attributed to the paucity of animal models of AD that are sufficiently similar to humans. Among the presently established animal models, non-human primates share the closest relationship with humans, and their neural anatomy and neurobiology share highly similar characteristics with those of humans. Thus, there is no doubt that these play an irreplaceable role in AD research. Considering this, the present literature on non-human primate models of AD was reviewed to provide a theoretical basis for future research.
基金National Natural Science Foundation of China Grant(81941012)CAMS initiative for Innovative Medicine of China(2021-I2 M-1-034)National Key Research and Development Project(2017YFA0105200).
文摘Alzheimer's disease(AD)is a neurodegenerative disorder.The pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,synapse loss,and brain atrophy.Many therapies have been tested to improve or at least effectively modify the course of AD.Meaningful data indicate that the transplantation of stem cells can alleviate neuropathology and significantly ameliorate cognitive deficits in animal models with Alzheimer's disease.Transplanted stem cells have shown their inherent advantages in improving cognitive impairment and memory dysfunction,although certain weak-nesses or limitations need to be overcome.This review recapitulates rodent models for AD,the therapeutic efficacy of stem cells,influencing factors,and the underlying mechanisms behind these changes.Stem cell therapy provides perspective and chal-lenges for its clinical application in the future.
基金the Central Research Institutes Basic Operating Grants,Grant/Award Number:DWS201512CAMS Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2016-I2M-2-006-03National Major Scientific and Technological Special Project for Key Infectious Diseases,Grant/Award Number:2017ZX10304402-001
文摘Background: With the aim of establishing the most comprehensive database of laboratory animal strains, the "laboratory animal strain resources database"(LasDB)was constructed as a searchable online database of all laboratory animal strains,stocks and mutant embryonic stem-cell lines available worldwide, including inbred,outbred, mutant and genetically engineered strains.Methods: MySQL database software was used to construct the LasDB, offering an easy-to-use interface.Results: To date, LasDB has a collection covering data for 21 596 mouse strains,2062 rat strains, 13 monkey strains, 2 hamster strains, 5 dog strains, 5 rabbit strains and more than 50 other laboratory animal strains. LasDB will be continually improved with regular updates of new laboratory animal strains from all over the world.Conclusion: To the best of our knowledge, this is the first database that attempts to systematically integrate all available laboratory animal strain data with the aim of supporting open usage and full resource sharing.
基金National Natural Science Foundation of China grant(31970510,81941012)CAMS Innovation Fund for Medical Sciences(CIFMS)grant(2016-I2M-2-006,2016-I2M-1-010).
文摘Autophagy is one of the degradation pathways to remove proteins or damaged or-ganelles in cells that plays an important role in neuroprotection.Different stages of autophagy are regulated by autophagy-related genes,and many molecules such as transcription factor EB(TFEB)are involved.The complete autophagy process plays an important role in maintaining the dynamic balance of autophagy and is crucial to the homeostasis of intracellular substance and energy metabolism.Autophagy balance is disrupted in neurodegenerative diseases,accounting for a variety of degeneration dis-orders.These impairments can be alleviated or treated by the regulation of autophagy through molecules such as TFEB.
基金supported by CAMS Initiative for Innovative Medicine of China,Grant/Award Number:No.2016-12M-1-006National Key R&D Program of China,Grant/Award Number:No.2017YFC1103603
文摘Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created three groups of K/BxN female mice that were positive for the anti‐glucose‐6‐phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), anti‐ GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing. Results: Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL‐C, TCHO, and TG, decreased serum levels of HDL‐C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL‐C, TCHO, and TG, increased serum levels of HDL‐C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA‐associated atherosclerosis and dyslipidemia. Conclusion: Our mouse model of RA indicated that HFD increased ankle width and aggravated a therosclerosis a nd d yslipidemia, a nd t hat H CQ a lleviated t he d yslipidemia and atherosclerosis, but had no effect on ankle width.
基金supported by the CAMS Innovation Fund for Medical Science[CIFMS,2018-I2M-1-001]the National Key R&D Program of China[2017YFC0702800]+1 种基金the National Natural Science Foundation of China[82070103]the Central Public-interest Scientific Institution Basal Research Fund[2016ZX310037]。
文摘Objective Airborne microbial communities include a significant number of uncultured and poorly characterized bacteria.No effective method currently exists to evaluate the health risks of such complex bacterial populations,particularly for pneumonia.Methods We developed a method to evaluate risks from airborne microorganisms,guided by the principle that closer evolutionary relationships reflect similar biological characteristics,and thus used16 S rDNA sequences of 10 common pneumonia-related bacterial pathogens.We calculated a risk of breath-related(Rbr)index of airborne bacterial communities and verified effectiveness with artificial flora and a clinical project.Results We suggested applying Rbr80 to evaluate the health risks of airborne bacterial communities that comprise 80% of dominant operational taxonomic units(OTUs).The feasibility of Rbr80 was confirmed by artificial flora and by pneumonia data from a hospital.A high Rbr80 value indicated a high risk of pneumonia from airborne bacterial communities.Conclusion Rbr80 is an effective index to evaluate the pneumonia-associated risk from airborne bacteria.Values of Rbr80 greater than 15.40 are considered high risk.
基金This research was supported by multiple grants:Major innovation engineering project of Chinese Academy of Medical Sciences(2016-I2M-2-006 and 2016-I2M-1-013)the National Natural Science Foundation of China(81801986).
文摘The low success rates in the treatment of multidrug-resistant tuberculosis(MDR-TB)and extensively drug-resistant TB(XDR-TB),which account for 55%and 34%respectively,led the WHO to conclude that MDR/XDR-TB is a serious public health crisis.However,the virulence of MDR/XDR-Mycobacterium Tuberculosis(Mtb)has not been analyzed in details,which could provide a specific guidance for the control and prevention.In this review,we discuss different aspects of MDR/XDR-Mtb virulence and its relationship to fitness cost by probing the following questions:(1)what mediates the virulence of MDR/XDR-Mtb?(What is the relationship between fitness and virulence of Mtb?(2)Is it possible that drug-resistant Mtb(DR Mtb)can show higher fitness?(3)What is the definite effect on fitness of each drug-resistant mutant?(4)What other important factors affecting fitness in the mutant strain?(5)How to study the virulence of a large number of DR Mtb?And what prevention and control measures will be taken in the future,especially for the high virulent DR Mtb?We therefore summarized the congruent relationship between drug resistance and fitness from the global response-related genes to antibiotic resistance-contributing mutation,provided methods to explore the virulence of DR Mtb.This review may offer some critical information and concise guide to creating strategies for the prevention and control of drug-resistant Mtb.