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Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice 被引量:1
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作者 Rui-Xue Jiang Nan Hu +5 位作者 Yu-Wei Deng Long-Wei Hu Hao Gu Nan Luo Jin Wen Xin-Quan Jiang 《Zoological Research》 SCIE CSCD 2024年第2期367-380,共14页
Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the devel... Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents. 展开更多
关键词 OSTEOPOROSIS SPERMINE RAC1 ZEBRAFISH mice
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Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice 被引量:1
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作者 Dechang Xu Jielun Hu +4 位作者 Yadong Zhong Yanli Zhang Wenting Liu Shaoping Nie Mingyong Xie 《Food Science and Human Wellness》 SCIE CSCD 2024年第1期154-165,共12页
With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune func... With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice. 展开更多
关键词 Fermented foods Immunosuppressed mice Immune response Gut microbiota Short-chain fatty acids
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Application of transgenic mice to the molecular pathogenesis of cataract
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作者 Yue Zhang Xiao-Ya Chen +3 位作者 Yu-Zhu Hu Xiao Zhang Shun-Fei Zheng Shan-Shan Hu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第10期1929-1948,共20页
One of the most prevalent disorders that cause blindness worldwide is cataract,and its essence is the visual disorder caused by the opacity of the lens.The significant degree of variation in cataracts and the fact tha... One of the most prevalent disorders that cause blindness worldwide is cataract,and its essence is the visual disorder caused by the opacity of the lens.The significant degree of variation in cataracts and the fact that a variety of factors can impact a patient’s lens transparency make it especially crucial to investigate the pathogenesis of cataracts at the molecular level.It has been found that more than 60 genes are linked to the formation of cataracts,and the construction of a transgenic mouse model of cataract similar to the selection of human lens clouding due to a variety of causes has become an important means of studying the pathogenesis of cataract.Therefore,the research on the application of transgenic mice to the molecular pathogenesis of cataracts will be the main topic of this review of the literature. 展开更多
关键词 transgenic mice CATARACT LENS
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Skeletal phenotypes and molecular mechanisms in aging mice
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作者 Qiao Guan Yuan Zhang +3 位作者 Zhi-Kun Wang Xiao-Hua Liu Jun Zou Ling-Li Zhang 《Zoological Research》 SCIE CSCD 2024年第4期724-746,共23页
Aging is an inevitable physiological process,often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health risks.Research on skeletal diseases caused by aging in humans is ch... Aging is an inevitable physiological process,often accompanied by age-related bone loss and subsequent bone-related diseases that pose serious health risks.Research on skeletal diseases caused by aging in humans is challenging due to lengthy study durations,difficulties in sampling,regional variability,and substantial investment.Consequently,mice are preferred for such studies due to their similar motor system structure and function to humans,ease of handling and care,low cost,and short generation time.In this review,we present a comprehensive overview of the characteristics,limitations,applicability,bone phenotypes,and treatment methods in naturally aging mice and prematurely aging mouse models(including SAMP6,POLG mutant,LMNA,SIRT6,ZMPSTE24,TFAM,ERCC1,WERNER,and KL/KL-deficient mice).We also summarize the molecular mechanisms of these aging mouse models,including cellular DNA damage response,senescence-related secretory phenotype,telomere shortening,oxidative stress,bone marrow mesenchymal stem cell(BMSC)abnormalities,and mitochondrial dysfunction.Overall,this review aims to enhance our understanding of the pathogenesis of aging-related bone diseases. 展开更多
关键词 AGING Premature aging mice BONE Gene knockout
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Textile dyeing wastewater negatively influences the hematological profile and reproductive health of male Swiss albino mice
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作者 Taimur Islam Nusrat Binte Rafique +7 位作者 Mohosina Mou Dipu Roy Robius Sani Sadi Ziban Chandra Das Anup Kumar Talukder Minhaz Ahmed Mizanur Rahman Golam Haider 《Asian pacific Journal of Reproduction》 CAS 2024年第4期169-177,共9页
Objective:To determine the effects of textile dyeing industrial wastewater on the hematological parameters and reproductive health including histoarchitecture of male gonad(testes)of mice.Methods:Twenty-four Swiss alb... Objective:To determine the effects of textile dyeing industrial wastewater on the hematological parameters and reproductive health including histoarchitecture of male gonad(testes)of mice.Methods:Twenty-four Swiss albino mice at 4-weeks old were divided into four groups(n=6 per group).Mice of group 1 supplied with normal drinking water were served as the control group.Mice of group 2,3 and 4 were supplied normal drinking water mixed with textile dyeing wastewater at 5%,10% and 20% concentration,respectively.After completing 24 weeks of treatment,different hematological profile,weight of testes,gonadosomatic index(GSI),sperm concentration and morphology were measured.Moreover,histopathological changes in testes were examined.Results:Hematocrit value and hemoglobin concentrations were decreased in all groups of wastewater-treated mice compared to the control group.Likewise,weight of testes,GSI and sperm concentration were decreased significantly in wastewater-treated mice in comparison to the control group.The percentage of morphologically healthy epididymal sperm was significantly reduced in wastewater-treated mice.Histopathological examination revealed degenerative changes in seminiferous tubules,a smaller number of spermatogenic cells,elongation of seminiferous tubules and degenerative changes of seminiferous tubules in wastewater-treated mice.Conclusions:Textile dyeing wastewater has harmful effects on hematological profile and reproductive health of male mice. 展开更多
关键词 Textile dyeing wastewater Gonads HEMATOLOGY HISTOPATHOLOGY mice
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Apolipoprotein E4 interferes with lipid metabolism to exacerbate depression-like behaviors in 5xFAD mice
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作者 Yanju Gong Mingfeng Li +4 位作者 Min Liu Xinghan Wu Yanhong Li Chuan Qin Ling Zhang 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第3期347-361,共15页
Background:Apolipoprotein E4(ApoE4)allele is the strongest genetic risk factor for late-onset Alzheimer's disease,and it can aggravate depressive symptoms in non-AD patients.However,the impact of ApoE4 on AD-assoc... Background:Apolipoprotein E4(ApoE4)allele is the strongest genetic risk factor for late-onset Alzheimer's disease,and it can aggravate depressive symptoms in non-AD patients.However,the impact of ApoE4 on AD-associated depression-l ike behaviors and its underlying pathogenic mechanisms remain unclear.Methods:This study developed a 5xFAD mouse model overexpressing human ApoE4(E4FAD).Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD mice.Changes in peripheral and central lipid metabolism,as well as the levels of serotonin(5-HT)andγ-aminobutyric acid(GABA)neurotransmitters in the prefrontal cortex,were examined.In addition,the protein levels of 24-dehydrocholesterol reductase/glycogen synthase kinase-3 beta/mammalian target of rapamycin(DHCR24/GSK3β/m TOR)and postsynaptic density protein 95/calmodulin-dependent protein kinase II/brain-derived neurotrophic factor(PSD95/CaMK-II/BDNF)were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD mice.Results:Compared with 5xFAD mice,E4FAD mice exhibited more severe depressionlike behaviors and cognitive impairments.These mice also exhibited increased amyloid-beta deposition in the hippocampus,increased astrocyte numbers,and decreased expression of depression-related neurotransmitters 5-HT and GABA in the prefrontal cortex.Furthermore,lipid metabolism disorders were observed in E4FAD,manifesting as elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol in peripheral blood,decreased cholesterol level in the prefrontal cortex,and reduced expression of key enzymes and proteins related to cholesterol synthesis and homeostasis.Abnormal expression of proteins related to the DHCR24/GSK3β/m TOR and PSD95/CaMK-II/BDNF pathways was also observed.Conclusion:This study found that ApoE4 overexpression exacerbates depressionlike behaviors in 5xFAD mice and confirmed that ApoE4 reduces cognitive function in these mice.The mechanism may involve the induction of central and peripheral lipid metabolism disorders.Therefore,modulating ApoE expression or function to restore cellular lipid homeostasis may be a promising therapeutic target for AD comorbid with depression.This study also provided a better animal model for studying AD comorbid with depression. 展开更多
关键词 5xFAD mice Alzheimer's disease ApoE4 allele depression like
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Insights into sensitizing and eliciting capacity of gastric and gastrointestinal digestion products of shrimp(Penaeus vannamei)proteins in BALB/c mice
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作者 Yao Liu Songyi Lin +3 位作者 Kexin Liu Shan Wang Wang Li Na Sun 《Food Science and Human Wellness》 SCIE CSCD 2024年第1期339-348,共10页
Shrimp(Penaeus vannamei)proteins have been shown an allergenic potential;however,little information is available on the sensitizing and eliciting capacity of shrimp protein digestion products.In this study,a BALB/c mi... Shrimp(Penaeus vannamei)proteins have been shown an allergenic potential;however,little information is available on the sensitizing and eliciting capacity of shrimp protein digestion products.In this study,a BALB/c mice model was used to explore the allergenicity of shrimp protein sample(SPS)and their gastric and gastrointestinal digestion products(GDS/GIDS).As compared with the SPS groups,the GDS/GIDS groups caused lower specific immunoglobulins(Ig E/Ig G1)levels(P<0.05),but higher than the control groups,indicating that the digestion products sensitized the mice.Meanwhile,spleen index,mouse mast cell protease-1(m MCP-1)concentration and proportion of degranulated mast cells were significantly reduced in the GDS/GIDS groups(P<0.05);simultaneously,allergic symptoms,vascular permeability and histopathological changes of tissues were alleviated.Nevertheless,the allergenicity of digestion products cannot be eliminated and still cause systemic allergic reactions in mice.The study showed that the digestion products of shrimp still had high sensitizing and eliciting capacity. 展开更多
关键词 Penaeus vannamei ALLERGENICITY DIGESTION BALB/c mice model
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Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement
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作者 Hanwei Yue Lin Bai 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第1期3-11,共9页
In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking ... In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development. 展开更多
关键词 ANTITUMOR ANTIVIRAL CAR-T humanized immune system model humanized mice preclinical research
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Prevelance of Bovine Cysticercosis in Egypt and the Cysticidal Effect of Two Extracts Obtained from Balanites aegyptiaca and Moringa oleifera on Mice Model Affected with T. saginata Cysticerci
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作者 Omnia M. Kandil Noha M. F. Hassan +7 位作者 Doaa Sedky Hatem A. Shalaby Heba M. Ashry Nadia M. T. Abu El Ezz Sahar M. Kandeel Mohamed S. Abdelfattah L. Ying Ebtesam M. Al-Olayan 《Open Journal of Animal Sciences》 2024年第2期39-55,共17页
The aim of the present study was to determine the prevalence of bovine cysticercosis in both cattle and buffloas, in Egypt and to assess the cysticidal efficacy of Balanites aegyptiaca fruits (B. aegyptiaca) and Morin... The aim of the present study was to determine the prevalence of bovine cysticercosis in both cattle and buffloas, in Egypt and to assess the cysticidal efficacy of Balanites aegyptiaca fruits (B. aegyptiaca) and Moringa oleifera seeds (M. oleifera) extracts in experimentally infected mice. The study detected the level of tumor necrosis factor (TNF-α) to monitor the immune and inflammatory responses of experimentally infected mice. Through meat inspection, a total number of 2125 male bovine, 2 to 5 years old, (1125 cattle and 1000 buffloes) were examined under the authority of Albsatine and Alwaraq official abattoirs in Cairo Governorate, Egypt covering the period extended from March 2022 to April 2023. The overall prevalence of the disease among bovine was 7.8% (6.31% of cattle and 9.5% of buffloes). Besides, B. aegyptiaca and M. oleifera extracts showed cysticidal activity in experimentally infected mice. A decrease in the numbers of cysticerci was found in all treated mice groups, and up to 88% reduction was achieved in the B. aegyptiaca-treated group;higher than that was recorded in both M. oleifera (72.23%) and albendazole-treated ones (80.56%). Postmortem findings proved that M. oleifera and B. aegyptiaca reduced cysticerci numbers comparable to a commercial anthelmintic. The study showed a significant decrease (P 0.001) in TNF-α levels after treatment with Balanites and Moringa extracts, compared with the untreated control and the albendazole-treated groups. 展开更多
关键词 PREVALENCE Balanites aegyptiaca Moringa oleifera mice T. saginata Cysticerci
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Impacts of angiotensin II on retinal artery changes in apolipoprotein E deficient mice
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作者 Li-Hui Meng Shi-Yu Cheng +5 位作者 He Chen Yue-Lin Wang Wen-Fei Zhang Huan Chen Xin-Yu Zhao You-Xin Chen 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第1期16-24,共9页
AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(... AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane. 展开更多
关键词 angiotensin II retinal artery ANEURYSM apoE^(-/-)mice
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Against all odds:The road to success in the development of human immune reconstitution mice
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作者 Yixiao Bin Jing Ren +7 位作者 Haowei Zhang Tianjiao Zhang Peijuan Liu Zhiqian Xin Haijiao Yang Zhuan Feng Zhinan Chen Hai Zhang 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第4期460-470,共11页
The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimen... The mouse genome has a high degree of homology with the human genome,and its physiological,biochemical,and developmental regulation mechanisms are similar to those of humans;therefore,mice are widely used as experimental animals.However,it is undeniable that interspecies differences between humans and mice can lead to experimental errors.The differences in the immune system have become an impor-tant factor limiting current immunological research.The application of immunodefi-cient mice provides a possible solution to these problems.By transplanting human immune cells or tissues,such as peripheral blood mononuclear cells or hematopoietic stem cells,into immunodeficient mice,a human immune system can be reconstituted in the mouse body,and the engrafted immune cells can elicit human-specific immune responses.Researchers have been actively exploring the development and differen-tiation conditions of host recipient animals and grafts in order to achieve better im-mune reconstitution.Through genetic engineering methods,immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts.From initially only being able to reconstruct single T lymphocyte lineages,it is now possible to reconstruct lymphoid and myeloid cells,providing important research tools for immunology-related studies.In this review,we compare the differences in immune systems of humans and mice,describe the devel-opment history of human immune reconstitution from the perspectives of immuno-deficient mice and grafts,and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution,aiming to provide important references for im-munological related researches. 展开更多
关键词 hematopoietic stem cell human immune reconstitution immune response immunodeficient mice peripheral blood mononuclear cell TRANSPLANTATION
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Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice
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作者 Han Duan Ning Tao +8 位作者 Lin Lv Kai-Xin Yan Yong-Gang You Zhuang Mao Chang-Yao Wang Xue Li Jia-Yan Jin Chu-Tse Wu Hua Wang 《World Journal of Stem Cells》 SCIE 2024年第5期575-590,共16页
BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammato... BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS. 展开更多
关键词 ATHEROSCLEROSIS Apolipoprotein E-knockout mice Cell therapy Dental pulp stem cells Hepatocyte growth factor
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Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice
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作者 Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel 《Neural Regeneration Research》 SCIE CAS 2025年第8期2348-2360,共13页
TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal... TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies. 展开更多
关键词 human induced pluripotent stem cell MICROTUBULES P301L pR5 mice TAU TAUOPATHY tubulin code
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Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future
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作者 Zhiyuan Yin Jiahui Kang +3 位作者 Xuan Cheng Hui Gao Shujia Huo Haiwei Xu 《Neural Regeneration Research》 SCIE CAS 2025年第4期946-959,共14页
Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume respon... Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice. 展开更多
关键词 cell fusion chemical small-molecules EPIGENETIC extracellular matrix immune metabolic mice Müller glia neurodegenerative diseases REPROGRAMMING retina regeneration
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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice
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作者 Zhengwei Hu Jing Yang +7 位作者 Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe Shi Yuming Xu 《Neural Regeneration Research》 SCIE CAS 2025年第1期253-264,共12页
The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed... The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease. 展开更多
关键词 adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy
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Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach
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作者 Roa'a H.S.Yosief Iqbal M.Lone +3 位作者 Aharon Nachshon Heinz Himmelbauer Irit Gat-Viks Fuad A.Iraqi 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第1期36-47,共12页
Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidat... Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis. 展开更多
关键词 aspergillus fumigatus infection collaborative cross(CC)mice gene expression profile gene-network host susceptibility quantitative trait loci(QTL)mapping RNA-SEQ
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Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice
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作者 Yanli Zhang Tian Li +8 位作者 Jie Miao Zhina Zhang Mingxuan Yang Zhuoran Wang Bo Yang Jiawei Zhang Haiting Li Qiang Su Junhong Guo 《Neural Regeneration Research》 SCIE CAS 2025年第2期533-547,共15页
In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A... In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease. 展开更多
关键词 Alzheimer’s disease amyloid-β APP/PS1 mice cerebrovascular endothelial cells cognitive deficits gamma-glutamyl transferase 5 neurovascular unit nuclear factor‐kappa B synaptic plasticity β-site APP cleaving enzyme 1
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2024年泰国MICE路演在中国举行——中国赴泰会展商旅人数再创新高
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《中国会展》 2024年第16期75-76,共2页
泰国会议展览局(TCEB)于2024年8月20日在上海举办2024年泰国MICE中国路演活动,以吸引中国的会展业者,挖掘泰国新的发展和潜在商业机会。此次路演举行之时,暨泰国会展局2024财年的前三个季度(2023年10月-2024年6月),前往泰国的中国会展... 泰国会议展览局(TCEB)于2024年8月20日在上海举办2024年泰国MICE中国路演活动,以吸引中国的会展业者,挖掘泰国新的发展和潜在商业机会。此次路演举行之时,暨泰国会展局2024财年的前三个季度(2023年10月-2024年6月),前往泰国的中国会展商旅游客数量达到了历史性的新高,达312,909人次,超过了2019年全年247,660人次的记录。在中泰建交50周年前夕出现这样的积极趋势,也为未来进一步深化合作奠定了更坚实的基础。 展开更多
关键词 路演 会议展览 深化合作 会展业 mice 游客数量 商业机会
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MICE的着力点——产业赋能下MICE行业的发展前景
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作者 裴超 《中国会展》 2024年第12期20-25,共6页
当前,全球MICE市场随经济形势发展,逐步恢复活力,并呈现联通性、创新性和可持续性三大属性。MICE行业的市场价值、消费环境、投资发展和技术潜力得到了充分释放。半年来,随着产业供应链、价值链和创新链正在加速恢复,促进了旅游业发展,... 当前,全球MICE市场随经济形势发展,逐步恢复活力,并呈现联通性、创新性和可持续性三大属性。MICE行业的市场价值、消费环境、投资发展和技术潜力得到了充分释放。半年来,随着产业供应链、价值链和创新链正在加速恢复,促进了旅游业发展,也成就了MICE市场的良好运行,并进入了“品质需求引导供给创新,创新供给推动需求升级”的良性循环阶段,与其他产业跨界融合、协同发展,新产品、新业态和新商业模式不断涌现。 展开更多
关键词 经济形势发展 技术潜力 良性循环 创新链 供给创新 价值链 协同发展 mice
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突破与变革——突破瓶颈,MICE行业发展迎来新机变
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作者 裴超 《中国会展》 2024年第6期22-27,共6页
2024年,随着全球经济的发展与技术的创新,产业迎来新一轮变革。新业态的不断涌现,也促使MICE行业步入新发展格局,并进一步加剧全球会议市场的竞争。这其中,作为会议领域重要组成部分的MICE行业,已处于新的“风口浪尖”。不论是会议企业... 2024年,随着全球经济的发展与技术的创新,产业迎来新一轮变革。新业态的不断涌现,也促使MICE行业步入新发展格局,并进一步加剧全球会议市场的竞争。这其中,作为会议领域重要组成部分的MICE行业,已处于新的“风口浪尖”。不论是会议企业、策划公司,还是技术企业与目的地服务商都在为争夺新的市场机会不断改善服务模式。虽然传统意义上的服务方式与运营理念依然具有一定市场,但影响力正不断减弱。 展开更多
关键词 策划公司 新业态 突破瓶颈 mice 改善服务 服务商 技术的创新 运营理念
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