Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheime...Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.展开更多
The dynamics of animal social structures are heavily influenced by environmental patterns of competition and cooperation.In folivorous colobine primates,prevailing theories suggest that larger group sizes should be fa...The dynamics of animal social structures are heavily influenced by environmental patterns of competition and cooperation.In folivorous colobine primates,prevailing theories suggest that larger group sizes should be favored in rainforests with a year-round abundance of food,thereby reducing feeding competition.Yet,paradoxically,larger groups are frequently found in high-altitude or high-latitude montane ecosystems characterized by a seasonal scarcity of leaves.This contradiction is posited to arise from cooperative benefits in heterogeneous environments.To investigate this hypothesis,we carried out a six-year field study on two neighboring groups of golden snub-nosed monkey(Rhinopithecus roxellana),a species representing the northernmost distribution of colobine primates.Results showed that the groups adjusted their movement and habitat selection in response to fluctuating climates and spatiotemporal variability of resources,indicative of a dynamic foraging strategy.Notably,during the cold,resource-scarce conditions in winter,the large group occupied food-rich habitats but did not exhibit significantly longer daily travel distances than the smaller neighboring group.Subsequently,we compiled an eco-behavioral dataset of 52 colobine species to explore their evolutionary trajectories.Analysis of this dataset suggested that the increase in group size may have evolved via home range expansion in response to the cold and heterogeneous climates found at higher altitudes or latitudes.Hence,we developed a multi-benefits framework to interpret the formation of larger groups by integrating environmental heterogeneity.In cold and diverse environments,even smaller groups require larger home ranges to meet their dynamic survival needs.The spatiotemporal distribution of high-quality resources within these expanded home ranges facilitates more frequent interactions between groups,thereby encouraging social aggregation into larger groups.This process enhances the benefits of collaborative actions and reproductive opportunities,while simultaneously optimizing travel costs through a dynamic foraging strategy.展开更多
Biliary dyskinesia is a relatively common gastrointestinal disease that is increas-ing in incidence as living standards improve.However,its underlying pathogenesis remains unclear,hindering the development of therapeu...Biliary dyskinesia is a relatively common gastrointestinal disease that is increas-ing in incidence as living standards improve.However,its underlying pathogenesis remains unclear,hindering the development of therapeutic drugs.Recently,“Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct”demonstrated that cholecystokinin(CCK)regulates the contractile function of the common bile duct through interaction with the CCK-A receptor in interstitial Cajal-like cells,contributing to improving the academic understanding of biliary tract dynamics and providing emerging directions for the pathogenesis and clinical management of biliary dyskinesia.This letter provides a brief overview of the role of CCK and CCK-A receptors in biliary dyskinesia from the perspective of animal experiments and clinical studies,and discusses prospects and challenges for the clinical application of CCK and CCK-A receptors as potential therapeutic targets.展开更多
BACKGROUND Synaptophysin plays a key role in synaptic development and plasticity of neurons and is closely related to the cognitive process of Alzheimer’s disease(AD)patients.Exogenous neural stem cells(NSCs)improve ...BACKGROUND Synaptophysin plays a key role in synaptic development and plasticity of neurons and is closely related to the cognitive process of Alzheimer’s disease(AD)patients.Exogenous neural stem cells(NSCs)improve the damaged nerve function.The effects of Sanjiao acupuncture on cognitive impairment may be related to the regulation of the NSC microenvironment.AIM To explore the anti-dementia mechanism of acupuncture by regulating the NSC microenvironment.METHODS NSCs were isolated from pregnant senescence-accelerated mouse resistant 1(SAMR1)mice,labeled with BrdU,and injected into the hippocampus of senescence-accelerated mouse prone 8(SAMP8)mice.Eight-month-old senescence-accelerated mice(SAM)were randomly divided into six groups:SAMR1(RC),SAMP8(PC),sham transplantation(PS),NSC transplantation(PT),NSC transplantation with acupuncture(PTA),and NSC transplantation with nonacupoint acupuncture(PTN).Morris water maze test was used to study the learning and memory ability of mice after NSC transplantation.Hematoxylin-eosin staining and immunofluorescence were used to observe the histopathological changes and NSC proliferation in mice.A co-culture model of hippocampal slices and NSCs was established in vitro,and the synaptophysin expression in the hippocampal microenvironment of mice was observed by flow cytometry after acupuncture treatment.RESULTS Morris water maze test showed significant cognitive impairment of learning and memory in 8-mo-old SAMP8,which improved in all the NSC transplantation groups.The behavioral change in the PTA group was stronger than those in the other two groups(P<0.05).Histopathologically,the hippocampal structure was clear,the cell arrangement was dense and orderly,and the necrosis of cells in CA1 and CA3 areas was significantly reduced in the PTA group when compared with the PC group.The BrdU-positive proliferating cells were found in NSC hippocampal transplantation groups,and the number increased significantly in the PTA group than in the PT and PTN groups(P<0.05).Flow cytometry showed that after co-culture of NSCs with hippocampal slices in vitro,the synaptophysin expression in the PC group decreased in comparison to the RC group,that in PT,PTA,and PTN groups increased as compared to the PC group,and that in the PTA group increased significantly as compared to the PTN group with acupointrelated specificity(P<0.05).CONCLUSION Acupuncture may promote nerve regeneration and synaptogenesis in SAMP8 mice by regulating the microenvironment of NSC transplantation to improve the nerve activity and promote the recovery of AD-damaged cells.展开更多
Sanjiao acupuncture and Huang Di San can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8(SAMP8) mice and can improve learning and memory ...Sanjiao acupuncture and Huang Di San can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8(SAMP8) mice and can improve learning and memory impairment and behavioral function in dementia-model mice. Thus, we sought to determine whether Sanjiao acupuncture and Huang Di San can elevate the effect of neural stem cell transplantation in Alzheimer's disease model mice. Sanjiao acupuncture was used to stimulate Danzhong(CV17), Zhongwan(CV12), Qihai(CV6), bilateral Xuehai(SP10) and bilateral Zusanli(ST36) 15 days before and after implantation of neural stem cells(5 × 105) into the hippocampal dentate gyrus of SAMP8 mice. Simultaneously, 0.2 m L Huang Di San, containing Rehmannia Root and Chinese Angelica, was intragastrically administered. Our results demonstrated that compared with mice undergoing neural stem cell transplantation alone, learning ability was significantly improved and synaptophysin m RNA and protein levels were greatly increased in the hippocampus of mice undergoing both Sanjiao acupuncture and intragastric administration of Huang Di San. We conclude that the combination of Sanjiao acupuncture and Huang Di San can effectively improve dementia symptoms in mice, and the mechanism of this action might be related to the regulation of synaptophysin expression.展开更多
Island ecosystems,serving as natural laboratories,facilitate geographical isolation,ecological specialization,and species divergence.The Sichuan Basin,surrounded by mountain ranges,represents a typical continental isl...Island ecosystems,serving as natural laboratories,facilitate geographical isolation,ecological specialization,and species divergence.The Sichuan Basin,surrounded by mountain ranges,represents a typical continental island due to its marked environmental spatial heterogeneity.This heterogeneity may contribute to geographical isolation and habitat heterogeneity,resulting in genetic divergence within populations.Therefore,we used the White-browed Laughingthrush(Garrulax sannio)as a model specimen to investigate the genetic divergence in the Sichuan Basin and its surrounding mountain ranges,given its presence in various habitats within and beyond this basin.Employing a RAD-seq dataset of 140 G.sannio individuals from 17 distinct ecological zones in the Sichuan Basin and its surrounding mountain ranges,we conducted PCA,population structure analysis,phylogenetic tree construction,and gene flow analysis to comprehensively analyze G.sannio groups.Additionally,in conjunction with geographical and ecological data,we performed isolation by distance,isolation by environment,PCA,and latent factor mixed model analysis to identify factors influencing the genetic divergence among these G.sannio groups.In summary,the 17 G.sannio groups were categorized into high-elevation,medium-elevation,and lowelevation groups.Genetic divergence in G.sannio may be attributed to both geographical distance and key ecological factors,particularly elevation and key climatic variables.Notably,the high-elevation group exhibited a greater number of SNPs and selected genes associated with the key ecological factors compared to the lowelevation group.The ADCY9 gene and several associated key pathways were identified as crucial elements driving ecological adaptation(elevation and key climatic variables)in the high-elevation group.Furthermore,climate changes during the glacial cycles may have facilitated gene flow among these groups residing in the Sichuan Basin and its surrounding mountain ranges.Our findings provide evidence of genetic divergence in G.sannio influenced by the geographical distance and key ecological factors between the Sichuan Basin and its surrounding mountain ranges.These results lay the groundwork for future research on the molecular systematics of continental islands.展开更多
Ischemic stroke(IS)is the most prevalent form of brain disease,characterized by high morbidity,disability,and mortality.However,there is still a lack of ideal prevention and treatment measures in clinical practice.Not...Ischemic stroke(IS)is the most prevalent form of brain disease,characterized by high morbidity,disability,and mortality.However,there is still a lack of ideal prevention and treatment measures in clinical practice.Notably,the trans-plantation therapy of mesenchymal stem cells(MSCs)has been a hot research topic in stroke.Nevertheless,there are risks associated with this cell therapy,including tumor formation,coagulation dysfunction,and vascular occlusion.Also,a growing number of studies suggest that the therapeutic effect after transplantation of MSCs is mainly attributed to MSC-derived exosomes(MSC-Exos).And this cell-free mediated therapy appears to circumvent many risks and difficulties when compared to cell therapy,and it may be the most promising new strategy for treating stroke as stem cell replacement therapy.Studies suggest that suppressing inflammation via modulation of the immune response is an additional treatment option for IS.Intriguingly,MSC-Exos mediates the inflam-matory immune response following IS by modulating the central nervous system,the peripheral immune system,and immunomodulatory molecules,thereby promoting neurofunctional recovery after stroke.Thus,this paper reviews the role,potential mechanisms,and therapeutic potential of MSC-Exos in post-IS inflammation in order to identify new research targets.展开更多
Acupuncture can improve the cognitive state of Alzheimer's disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer's disease brain are positively correlated with cognitive dam...Acupuncture can improve the cognitive state of Alzheimer's disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer's disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on improving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai(CV6), Zhongwan(CV12), Danzhong(CV17), bilateral Zusanli(ST36), and bilateral Xuehai(SP10) acupoints was performed once a day(1-day rest after 6-day treatment) for 14 consecutive days. Senescence-accelerated mouse prone 8(SAMP8) mice without acupuncture and senescence-accelerated mouse resistant 1(SAMR1) mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.展开更多
β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis(OA) development in temporomandibular joint(TMJ), we have generated β-catenin con...β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis(OA) development in temporomandibular joint(TMJ), we have generated β-catenin conditional activation mice(β-cat(ex3)^(Agc1CreER))by breeding Agc1-CreER mice with β-catenin^(flox(ex3)/+)mice. Results of histologic analysis showed the progressive TMJ defects in 3-and 6-month-old β-cat(ex3)^(Agc1CreER)mice(tamoxifen induction was performed at 2 weeks of age), including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat(ex3)^(Col2CreER)mice, β-cat(ex3)^(Agc1CreER)mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4,and Adamts5 in TMJ of β-cat(ex3)^(Agc1CreER)mice. Results of proliferating cell nuclear antigen(PCNA), Ki67, and terminal deoxinucleotidyl transferase-mediated d UTP-fluorescein nick end labeling(TUNEL) staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat(ex3)^(Agc1CreER)mice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.展开更多
Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment.It is caused by synaptic failure and excessive accumulation of misfolded proteins.To date,alm...Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment.It is caused by synaptic failure and excessive accumulation of misfolded proteins.To date,almost all advanced clinical trials on specific AD-related pathways have failed mostly due to a large number of neurons lost in the brain of patients with AD.Also,currently available drug candidates intervene too late.Stem cells have improved characteristics of self-renewal,proliferation,differentiation,and recombination with the advent of stem cell technology and the transformation of these cells into different types of central nervous system neurons and glial cells.Stem cell treatment has been successful in AD animal models.Recent preclinical studies on stem cell therapy for AD have proved to be promising.Cell replacement therapies,such as human embryonic stem cells or induced pluripotent stem cell–derived neural cells,have the potential to treat patients with AD,and human clinical trials are ongoing in this regard.However,many steps still need to be taken before stem cell therapy becomes a clinically feasible treatment for human AD and related diseases.This paper reviews the pathophysiology of AD and the application prospects of related stem cells based on cell type.展开更多
Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovasculardiseases, and traumatic brain injuries, are among the major disordersinfluencing human health, currently with no effective therapy. D...Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovasculardiseases, and traumatic brain injuries, are among the major disordersinfluencing human health, currently with no effective therapy. Due to the lowregeneration capacity of neurons, insufficient secretion of neurotrophic factors,and the aggravation of ischemia and hypoxia after nerve injury, irreversible lossof functional neurons and nerve tissue damage occurs. This damage is difficult torepair and regenerate the central nervous system after injury. Neural stem cells(NSCs) are pluripotent stem cells that only exist in the central nervous system.They have good self-renewal potential and ability to differentiate into neurons,astrocytes, and oligodendrocytes and improve the cellular microenvironment.NSC transplantation approaches have been made for various neurodegenerativedisorders based on their regenerative potential. This review summarizes anddiscusses the characteristics of NSCs, and the advantages and effects of NSCs inthe treatment of brain diseases and limitations of NSC transplantation that need tobe addressed for the treatment of brain diseases in the future.展开更多
BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulatio...BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.AIM To investigate the effects of BMSCs on gut microbiota after ischemic stroke.METHODS A total of 30 Sprague-Dawley rats were randomly divided into three groups,including sham operation control group,transient middle cerebral artery occlusion(MCAO)group,and MCAO with BMSC treatment group.The modified Neurological Severity Score(mNSS),beam walking test,and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation.Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus.Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.RESULTS BMSC transplantation significantly reduced mNSS(P<0.01).Rats performed better in the beam walking test in the BMSC group than in the MCAO group(P<0.01).The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory.Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group,cells were orderly arranged with significantly reduced necrosis.Moreover,BMSCs regulated microbial structure composition.In rats treated with BMSCs,the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.CONCLUSION BMSC transplantation is a potential therapeutic option for ischemic stroke,and it promotes neurological functions by regulating gut microbiota dysbiosis.展开更多
Oviparous female reptiles select nesting sites with optimal ecological factors that contribute to egg development. Chinese alligator(Alligator sinensis), an oviparous reptile, is a critically endangered crocodilian wi...Oviparous female reptiles select nesting sites with optimal ecological factors that contribute to egg development. Chinese alligator(Alligator sinensis), an oviparous reptile, is a critically endangered crocodilian with temperature-dependent sex determination. Research on its nesting behavior may facilitate the protection of this species. In this study, we monitored nesting behavior over eight years. We compared selected frequency of nest sites, distance from nest site to water, height from nest site top to the water surface, distance from nest site to human activity region, and canopy density between nest sites on the island and bank. The results showed that 45 nest sites were used by female alligators over eight years and each site was selected from one to 10 times. The selected frequency of nest site occurrence on the island was higher than that on the bank(P < 0.001). We observed that 88% of the individual alligators(15/17) showed different degrees of nest site fidelity. However, Chinese alligators might not always be loyal to only one nest site because of environmental changes or interspecific competition at nest sites. Our findings suggest that female alligators prefer to nest at island, which might be because of the nests on the island had a higher canopy density(P = 0.010) and were further from the human activity region(P < 0.001) than those on the bank did. It would be beneficial to reduce human activities during the breeding season and protect the vegetation of Chinese alligator habitats in the future. of the beach(Ali et al., 2005; Kamel and Mrosovsky, 2005; Turkozan et al., 2012). Other species such as snakes and lizards select nest sites with more moist substrates, which significantly increases their body size at hatching(Brown and Shine, 2004; Reedy et al., 2013). Nest site preference may be maintained for one or more breeding seasons(Janzen and Morjan, 2001; Kamel et al., 2006). When female chose the same site or area during different years, it is called nest site fidelity(Switzer, 1993). This nest choice behavior may influence offspring survival(Lindeman, 1992) and nest site fidelity has been documented in numerous species such as birds(Lindberg and Sedinger, 1997), turtles(Mitrus, 2006; Walde et al., 2007), tuatara(Refsnider et al., 2010), and crocodilians(Elsey et al., 2008).Chinese alligator(Alligator sinensis) is a critically endangered freshwater crocodilian endemic to China(Thorbjarnarson and Wang, 1999). Recent investigations show that there are no more than 130 Chinese展开更多
Since the nineteenth century, the chlor-alkali process entails the electrochemical oxidation of sodium chloride solutions to Cl_(2) by the chlorine evolution reaction(CER) and the simultaneous production of sodium hyd...Since the nineteenth century, the chlor-alkali process entails the electrochemical oxidation of sodium chloride solutions to Cl_(2) by the chlorine evolution reaction(CER) and the simultaneous production of sodium hydroxide and H_(2) at the cathode, of which sodium hydroxide and Cl_(2) are widely used as important chemicals [1].展开更多
基金supported by the National Natural Science Foundation of China,No.82074533(to LZ).
文摘Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.
基金supported by the Biodiversity Survey and Assessment Project of the Ministry of Ecology and Environment,China(2019HJ2096001006)National Natural Science Foundation of China(32001099,32170512,32370524)China Postdoctoral Science Foundation(2020M683539)。
文摘The dynamics of animal social structures are heavily influenced by environmental patterns of competition and cooperation.In folivorous colobine primates,prevailing theories suggest that larger group sizes should be favored in rainforests with a year-round abundance of food,thereby reducing feeding competition.Yet,paradoxically,larger groups are frequently found in high-altitude or high-latitude montane ecosystems characterized by a seasonal scarcity of leaves.This contradiction is posited to arise from cooperative benefits in heterogeneous environments.To investigate this hypothesis,we carried out a six-year field study on two neighboring groups of golden snub-nosed monkey(Rhinopithecus roxellana),a species representing the northernmost distribution of colobine primates.Results showed that the groups adjusted their movement and habitat selection in response to fluctuating climates and spatiotemporal variability of resources,indicative of a dynamic foraging strategy.Notably,during the cold,resource-scarce conditions in winter,the large group occupied food-rich habitats but did not exhibit significantly longer daily travel distances than the smaller neighboring group.Subsequently,we compiled an eco-behavioral dataset of 52 colobine species to explore their evolutionary trajectories.Analysis of this dataset suggested that the increase in group size may have evolved via home range expansion in response to the cold and heterogeneous climates found at higher altitudes or latitudes.Hence,we developed a multi-benefits framework to interpret the formation of larger groups by integrating environmental heterogeneity.In cold and diverse environments,even smaller groups require larger home ranges to meet their dynamic survival needs.The spatiotemporal distribution of high-quality resources within these expanded home ranges facilitates more frequent interactions between groups,thereby encouraging social aggregation into larger groups.This process enhances the benefits of collaborative actions and reproductive opportunities,while simultaneously optimizing travel costs through a dynamic foraging strategy.
文摘Biliary dyskinesia is a relatively common gastrointestinal disease that is increas-ing in incidence as living standards improve.However,its underlying pathogenesis remains unclear,hindering the development of therapeutic drugs.Recently,“Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct”demonstrated that cholecystokinin(CCK)regulates the contractile function of the common bile duct through interaction with the CCK-A receptor in interstitial Cajal-like cells,contributing to improving the academic understanding of biliary tract dynamics and providing emerging directions for the pathogenesis and clinical management of biliary dyskinesia.This letter provides a brief overview of the role of CCK and CCK-A receptors in biliary dyskinesia from the perspective of animal experiments and clinical studies,and discusses prospects and challenges for the clinical application of CCK and CCK-A receptors as potential therapeutic targets.
基金Supported by National Natural Science Foundation of China,No.81202740and Tianjin Natural Science Fund,No.17JCYBJC26200。
文摘BACKGROUND Synaptophysin plays a key role in synaptic development and plasticity of neurons and is closely related to the cognitive process of Alzheimer’s disease(AD)patients.Exogenous neural stem cells(NSCs)improve the damaged nerve function.The effects of Sanjiao acupuncture on cognitive impairment may be related to the regulation of the NSC microenvironment.AIM To explore the anti-dementia mechanism of acupuncture by regulating the NSC microenvironment.METHODS NSCs were isolated from pregnant senescence-accelerated mouse resistant 1(SAMR1)mice,labeled with BrdU,and injected into the hippocampus of senescence-accelerated mouse prone 8(SAMP8)mice.Eight-month-old senescence-accelerated mice(SAM)were randomly divided into six groups:SAMR1(RC),SAMP8(PC),sham transplantation(PS),NSC transplantation(PT),NSC transplantation with acupuncture(PTA),and NSC transplantation with nonacupoint acupuncture(PTN).Morris water maze test was used to study the learning and memory ability of mice after NSC transplantation.Hematoxylin-eosin staining and immunofluorescence were used to observe the histopathological changes and NSC proliferation in mice.A co-culture model of hippocampal slices and NSCs was established in vitro,and the synaptophysin expression in the hippocampal microenvironment of mice was observed by flow cytometry after acupuncture treatment.RESULTS Morris water maze test showed significant cognitive impairment of learning and memory in 8-mo-old SAMP8,which improved in all the NSC transplantation groups.The behavioral change in the PTA group was stronger than those in the other two groups(P<0.05).Histopathologically,the hippocampal structure was clear,the cell arrangement was dense and orderly,and the necrosis of cells in CA1 and CA3 areas was significantly reduced in the PTA group when compared with the PC group.The BrdU-positive proliferating cells were found in NSC hippocampal transplantation groups,and the number increased significantly in the PTA group than in the PT and PTN groups(P<0.05).Flow cytometry showed that after co-culture of NSCs with hippocampal slices in vitro,the synaptophysin expression in the PC group decreased in comparison to the RC group,that in PT,PTA,and PTN groups increased as compared to the PC group,and that in the PTA group increased significantly as compared to the PTN group with acupointrelated specificity(P<0.05).CONCLUSION Acupuncture may promote nerve regeneration and synaptogenesis in SAMP8 mice by regulating the microenvironment of NSC transplantation to improve the nerve activity and promote the recovery of AD-damaged cells.
基金supported by the National Natural Science Foundation of China,No.81202740 and 81603686the Natural Science Foundation of Tianjin of China,No.17JCYBJC26200 and 12JCQNJC07400+1 种基金the Public Health Bureau Science and Technology Foundation of Tianjin of China,No.2014KY15the Specialized Research Foundation for the Doctoral Program of Higher Education,No.20121210120002
文摘Sanjiao acupuncture and Huang Di San can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8(SAMP8) mice and can improve learning and memory impairment and behavioral function in dementia-model mice. Thus, we sought to determine whether Sanjiao acupuncture and Huang Di San can elevate the effect of neural stem cell transplantation in Alzheimer's disease model mice. Sanjiao acupuncture was used to stimulate Danzhong(CV17), Zhongwan(CV12), Qihai(CV6), bilateral Xuehai(SP10) and bilateral Zusanli(ST36) 15 days before and after implantation of neural stem cells(5 × 105) into the hippocampal dentate gyrus of SAMP8 mice. Simultaneously, 0.2 m L Huang Di San, containing Rehmannia Root and Chinese Angelica, was intragastrically administered. Our results demonstrated that compared with mice undergoing neural stem cell transplantation alone, learning ability was significantly improved and synaptophysin m RNA and protein levels were greatly increased in the hippocampus of mice undergoing both Sanjiao acupuncture and intragastric administration of Huang Di San. We conclude that the combination of Sanjiao acupuncture and Huang Di San can effectively improve dementia symptoms in mice, and the mechanism of this action might be related to the regulation of synaptophysin expression.
基金supported by the National Science Foundation of China(31372171)Leshan Normal University research grants(205210094,ZZ201805,CGZZ202002,205220114,DGZZ202006).
文摘Island ecosystems,serving as natural laboratories,facilitate geographical isolation,ecological specialization,and species divergence.The Sichuan Basin,surrounded by mountain ranges,represents a typical continental island due to its marked environmental spatial heterogeneity.This heterogeneity may contribute to geographical isolation and habitat heterogeneity,resulting in genetic divergence within populations.Therefore,we used the White-browed Laughingthrush(Garrulax sannio)as a model specimen to investigate the genetic divergence in the Sichuan Basin and its surrounding mountain ranges,given its presence in various habitats within and beyond this basin.Employing a RAD-seq dataset of 140 G.sannio individuals from 17 distinct ecological zones in the Sichuan Basin and its surrounding mountain ranges,we conducted PCA,population structure analysis,phylogenetic tree construction,and gene flow analysis to comprehensively analyze G.sannio groups.Additionally,in conjunction with geographical and ecological data,we performed isolation by distance,isolation by environment,PCA,and latent factor mixed model analysis to identify factors influencing the genetic divergence among these G.sannio groups.In summary,the 17 G.sannio groups were categorized into high-elevation,medium-elevation,and lowelevation groups.Genetic divergence in G.sannio may be attributed to both geographical distance and key ecological factors,particularly elevation and key climatic variables.Notably,the high-elevation group exhibited a greater number of SNPs and selected genes associated with the key ecological factors compared to the lowelevation group.The ADCY9 gene and several associated key pathways were identified as crucial elements driving ecological adaptation(elevation and key climatic variables)in the high-elevation group.Furthermore,climate changes during the glacial cycles may have facilitated gene flow among these groups residing in the Sichuan Basin and its surrounding mountain ranges.Our findings provide evidence of genetic divergence in G.sannio influenced by the geographical distance and key ecological factors between the Sichuan Basin and its surrounding mountain ranges.These results lay the groundwork for future research on the molecular systematics of continental islands.
基金Supported by National Natural Science Foundation of China,No.82074533.
文摘Ischemic stroke(IS)is the most prevalent form of brain disease,characterized by high morbidity,disability,and mortality.However,there is still a lack of ideal prevention and treatment measures in clinical practice.Notably,the trans-plantation therapy of mesenchymal stem cells(MSCs)has been a hot research topic in stroke.Nevertheless,there are risks associated with this cell therapy,including tumor formation,coagulation dysfunction,and vascular occlusion.Also,a growing number of studies suggest that the therapeutic effect after transplantation of MSCs is mainly attributed to MSC-derived exosomes(MSC-Exos).And this cell-free mediated therapy appears to circumvent many risks and difficulties when compared to cell therapy,and it may be the most promising new strategy for treating stroke as stem cell replacement therapy.Studies suggest that suppressing inflammation via modulation of the immune response is an additional treatment option for IS.Intriguingly,MSC-Exos mediates the inflam-matory immune response following IS by modulating the central nervous system,the peripheral immune system,and immunomodulatory molecules,thereby promoting neurofunctional recovery after stroke.Thus,this paper reviews the role,potential mechanisms,and therapeutic potential of MSC-Exos in post-IS inflammation in order to identify new research targets.
基金supported by the National Natural Science Foundation of China,No.81603686,81603684the High School Science and Technology Fund Planning Project of Tianjin of China,No.20120211+1 种基金the Natural Science Foundation of Tianjin of China(Key Program),No.15JCZDJC36700,16JCZDJC37500the Natural Science Foundation of Tianjin of China,No.17JCYBJC26200
文摘Acupuncture can improve the cognitive state of Alzheimer's disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer's disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on improving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai(CV6), Zhongwan(CV12), Danzhong(CV17), bilateral Zusanli(ST36), and bilateral Xuehai(SP10) acupoints was performed once a day(1-day rest after 6-day treatment) for 14 consecutive days. Senescence-accelerated mouse prone 8(SAMP8) mice without acupuncture and senescence-accelerated mouse resistant 1(SAMR1) mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.
基金supported by the National Institutes of Health Grants R01 AR054465 and R01 AR070222 to D.Cpartially supported by the Natural Science Foundation of China(NSFC)(grant#81371999)to D.C+2 种基金partially supported by the State Scholarship Fund(No.201406240061)partially sponsored by a grant from Shenzhen Science and Technology Innovation Committee(JCYJ20160331114205502 and JCYJ20150626090344603)partially supported by NSFC grants(grant#81301531 and 81572104),China
文摘β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis(OA) development in temporomandibular joint(TMJ), we have generated β-catenin conditional activation mice(β-cat(ex3)^(Agc1CreER))by breeding Agc1-CreER mice with β-catenin^(flox(ex3)/+)mice. Results of histologic analysis showed the progressive TMJ defects in 3-and 6-month-old β-cat(ex3)^(Agc1CreER)mice(tamoxifen induction was performed at 2 weeks of age), including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat(ex3)^(Col2CreER)mice, β-cat(ex3)^(Agc1CreER)mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4,and Adamts5 in TMJ of β-cat(ex3)^(Agc1CreER)mice. Results of proliferating cell nuclear antigen(PCNA), Ki67, and terminal deoxinucleotidyl transferase-mediated d UTP-fluorescein nick end labeling(TUNEL) staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat(ex3)^(Agc1CreER)mice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.
文摘Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment.It is caused by synaptic failure and excessive accumulation of misfolded proteins.To date,almost all advanced clinical trials on specific AD-related pathways have failed mostly due to a large number of neurons lost in the brain of patients with AD.Also,currently available drug candidates intervene too late.Stem cells have improved characteristics of self-renewal,proliferation,differentiation,and recombination with the advent of stem cell technology and the transformation of these cells into different types of central nervous system neurons and glial cells.Stem cell treatment has been successful in AD animal models.Recent preclinical studies on stem cell therapy for AD have proved to be promising.Cell replacement therapies,such as human embryonic stem cells or induced pluripotent stem cell–derived neural cells,have the potential to treat patients with AD,and human clinical trials are ongoing in this regard.However,many steps still need to be taken before stem cell therapy becomes a clinically feasible treatment for human AD and related diseases.This paper reviews the pathophysiology of AD and the application prospects of related stem cells based on cell type.
文摘Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovasculardiseases, and traumatic brain injuries, are among the major disordersinfluencing human health, currently with no effective therapy. Due to the lowregeneration capacity of neurons, insufficient secretion of neurotrophic factors,and the aggravation of ischemia and hypoxia after nerve injury, irreversible lossof functional neurons and nerve tissue damage occurs. This damage is difficult torepair and regenerate the central nervous system after injury. Neural stem cells(NSCs) are pluripotent stem cells that only exist in the central nervous system.They have good self-renewal potential and ability to differentiate into neurons,astrocytes, and oligodendrocytes and improve the cellular microenvironment.NSC transplantation approaches have been made for various neurodegenerativedisorders based on their regenerative potential. This review summarizes anddiscusses the characteristics of NSCs, and the advantages and effects of NSCs inthe treatment of brain diseases and limitations of NSC transplantation that need tobe addressed for the treatment of brain diseases in the future.
基金National Natural Science Foundation of China,No.81774059 and No.82074533Tianjin Natural Science Foundation,No.19JCZDJC37100.
文摘BACKGROUND As a cellular mode of therapy,bone marrow mesenchymal stem cells(BMSCs)are used to treat stroke.However,their mechanisms in stroke treatment have not been established.Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.AIM To investigate the effects of BMSCs on gut microbiota after ischemic stroke.METHODS A total of 30 Sprague-Dawley rats were randomly divided into three groups,including sham operation control group,transient middle cerebral artery occlusion(MCAO)group,and MCAO with BMSC treatment group.The modified Neurological Severity Score(mNSS),beam walking test,and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation.Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus.Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.RESULTS BMSC transplantation significantly reduced mNSS(P<0.01).Rats performed better in the beam walking test in the BMSC group than in the MCAO group(P<0.01).The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory.Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group,cells were orderly arranged with significantly reduced necrosis.Moreover,BMSCs regulated microbial structure composition.In rats treated with BMSCs,the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.CONCLUSION BMSC transplantation is a potential therapeutic option for ischemic stroke,and it promotes neurological functions by regulating gut microbiota dysbiosis.
基金supported by the Major Research Plan of the National Natural Science Foundation of China (Nos. 31230010 and 31530087)the National Key Program (2016YFC0503200) from Ministry of Science and Technology of China+1 种基金a special grant from the State Forestry Administrationthe Fundamental Research Funds for the Central Universities of China
文摘Oviparous female reptiles select nesting sites with optimal ecological factors that contribute to egg development. Chinese alligator(Alligator sinensis), an oviparous reptile, is a critically endangered crocodilian with temperature-dependent sex determination. Research on its nesting behavior may facilitate the protection of this species. In this study, we monitored nesting behavior over eight years. We compared selected frequency of nest sites, distance from nest site to water, height from nest site top to the water surface, distance from nest site to human activity region, and canopy density between nest sites on the island and bank. The results showed that 45 nest sites were used by female alligators over eight years and each site was selected from one to 10 times. The selected frequency of nest site occurrence on the island was higher than that on the bank(P < 0.001). We observed that 88% of the individual alligators(15/17) showed different degrees of nest site fidelity. However, Chinese alligators might not always be loyal to only one nest site because of environmental changes or interspecific competition at nest sites. Our findings suggest that female alligators prefer to nest at island, which might be because of the nests on the island had a higher canopy density(P = 0.010) and were further from the human activity region(P < 0.001) than those on the bank did. It would be beneficial to reduce human activities during the breeding season and protect the vegetation of Chinese alligator habitats in the future. of the beach(Ali et al., 2005; Kamel and Mrosovsky, 2005; Turkozan et al., 2012). Other species such as snakes and lizards select nest sites with more moist substrates, which significantly increases their body size at hatching(Brown and Shine, 2004; Reedy et al., 2013). Nest site preference may be maintained for one or more breeding seasons(Janzen and Morjan, 2001; Kamel et al., 2006). When female chose the same site or area during different years, it is called nest site fidelity(Switzer, 1993). This nest choice behavior may influence offspring survival(Lindeman, 1992) and nest site fidelity has been documented in numerous species such as birds(Lindberg and Sedinger, 1997), turtles(Mitrus, 2006; Walde et al., 2007), tuatara(Refsnider et al., 2010), and crocodilians(Elsey et al., 2008).Chinese alligator(Alligator sinensis) is a critically endangered freshwater crocodilian endemic to China(Thorbjarnarson and Wang, 1999). Recent investigations show that there are no more than 130 Chinese
文摘Since the nineteenth century, the chlor-alkali process entails the electrochemical oxidation of sodium chloride solutions to Cl_(2) by the chlorine evolution reaction(CER) and the simultaneous production of sodium hydroxide and H_(2) at the cathode, of which sodium hydroxide and Cl_(2) are widely used as important chemicals [1].
