Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabo...Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabolism.In the context of galactose metabolism,intracellular glucose levels are heightened.Galactose mutarotase(GALM)plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion ofβ-D-galactose intoα-D-galactose(α-D-G).The latter is then converted into glucose-6-phosphate,improving glucose metabolism levels.However,the involvement of GALM in AD progression is still unclear.In the present study,we found that the expression of GALM was significantly increased in AD patients and model mice.Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein(APP)and APP-cleaving enzymes including a disintegrin and metalloprotease 10(ADAM10),β-site APP-cleaving enzyme 1(BACE1),and presenilin-1(PS1).Interestingly,genetic overexpression of GALM reduced APP and Aβdeposition by increasing the maturation of ADAM10,although it did not alter the expression of BACE1 and PS1.Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation(LTP)and spatial learning and memory in AD model mice.Importantly,directα-D-G(20 mg/kg,i.p.)also inhibited Aβdeposition by increasing the maturation of ADAM10,thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice.Taken together,our results indicate that GALM shifts APP processing towardsα-cleavage,preventing Aβgeneration by increasing the level of mature ADAM10.These findings indicate that GALM may be a potential therapeutic target for AD,andα-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.展开更多
Magnetic stimulation has made significant strides in the treatment of psychiatric disorders.Nonetheless,current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot real...Magnetic stimulation has made significant strides in the treatment of psychiatric disorders.Nonetheless,current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation.To address this,we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration.We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system(pMSS)with repetitive transcranial magnetic stimulation in mice.Oxytocin levels,dendritic morphology and density,and mouse behavior were measured before and after pMSS intervention.Our findings suggest that pMSS can activate oxytocinergic neurons,leading to upregulation of oxytocin secretion and neurite outgrowth.As a result,sociability was rapidly improved after a one-week pMSS treatment regimen.These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.展开更多
Antibiotics in poultry feed to boost growth performance are becoming increasingly contentious due to concerns over antimicrobial resistance development.Essential oils(EOs),as natural,plant-derived compounds,have demon...Antibiotics in poultry feed to boost growth performance are becoming increasingly contentious due to concerns over antimicrobial resistance development.Essential oils(EOs),as natural,plant-derived compounds,have demonstrated antimicrobial and antioxidant properties.EOs may potentially improve poultry health and growth performance when included in poultry feed.Nevertheless,the incorporation of EOs as nutritional additives is hindered by their high volatility,low water solubility,poor intestinal absorption,and sensitivity to environmental conditions.Recently,nanoencapsulation strategies using nanoformulations have emerged as a potential solution to these challenges,improving the stability and bioavailability of EOs,and enabling targeted delivery in poultry feed.This review provides an overview of the antioxidant and antibacterial properties of EOs,the current limitations of their applications in poultry feed,and the recent advancements in nano-engineering to overcome these limitations.Furthermore,we outline the potential future research direction on EO nanoformulations,emphasizing their promising role in advancing sustainable poultry nutrition.展开更多
Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian cysts.This study aimed to assess the association between NAD^(+)levels and nabothian c...Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian cysts.This study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese women.Methods Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian cysts.Results The mean age was 43.0±11.5 years,and the mean level of NAD^(+)was 31.3±5.3μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from37.4%to 21.6%from Q1 to Q4 of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)quartiles.As compared with the highest NAD^(+)quartile(≥34.4μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14–3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 28.0 to35.0μmol/L.Conclusion:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.展开更多
Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangle...Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.展开更多
The proteasome,an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles,performs both shared and distinct functions across various tissues and organs.Spermatogenesi...The proteasome,an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles,performs both shared and distinct functions across various tissues and organs.Spermatogenesis,a highly complex developmental process,relies on proteasome activity at multiple stages to regulate protein turnover.In this study,we selected the 20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis.Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models,we confirmed the expression of both subunits in all spermatogenic cell types,with pronounced presence in early germ cell development.To further clarify their functional significance,we specifically knocked out Psma1 and Psmd2 in germ cells.Deletion of either PSMA1 or PSMD2 led to disrupted spermatogenesis,characterized by the complete absence of sperm in the epididymis.Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation.Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1,a key regulator of mitosis-to-meiosis transition,leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation.This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.展开更多
Background:Adolescent depression and school refusal(SR)are prevalent and important global concerns that need to be understood and addressed.Cross-sectional associations have been reported but prospective relationships...Background:Adolescent depression and school refusal(SR)are prevalent and important global concerns that need to be understood and addressed.Cross-sectional associations have been reported but prospective relationships between them remain unclear.This longitudinal study investigated the bidirectional relationships between these two problems among Chinese adolescents.Methods:A longitudinal study was conducted in Taizhou,China,surveying students of three junior high schools,three senior high schools,and one vocational high school.A total of 3882 students completed the questionnaire at baseline(T1);3167 of them completed an identical follow-up questionnaire after 6 months(T2).Depression was assessed via the Patient Health Questionnaire(PHQ-9)and SR via the modified Chinese version of The School Refusal Assessment Scale-Revised(SRAS-R).Cross-lagged panel modeling(CLPM)analysis was conducted to test the reciprocal relationships,adjusting for socio-demographic factors.Multiple group analysis was conducted to test whether the CLPM differed by gender and grade.Results:Statistically significant bidirectional relationships were found.A higher level of SR assessed at T1 is prospectively associated with a higher level of depression at T2(β=0.07,p=0.006);a higher level of depression at T1 also is prospectively associated with a higher level of SR at T2(β=0.14,p<0.001).Such models differed significantly by neither gender nor grade.Conclusion:SR and depression should be seen as each other’s mutually reinforcing association.The bidirectional relationships potentially result in a vicious cycle.Early interventions may target both problems concurrently.Future studies may involve more time points and test some mediators.展开更多
Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the ...Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein （BiP） interacts with the three sensors （protein kinase RNA-like ER kinase （PERK）, activating transcription factor 6 （ATF6）, and inositol-requiring enzyme la （IREla）） Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor （VEGF）-VEGF receptor （VEGFR）-phospholipase C-~ （PLCy）-mammalian target of rapamycin complex 1 （mTORC1） pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IREla also can be activated by activated RAC-alpha serine/threonine-protein kinase （AKT）. A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species （ROS）, Ca2＋ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase （JNK）, signal transducer and activator of transcription 3 （STAT3）, and P38, when cellular damage exceeds the capacity of this adaptive response.展开更多
With over 50 million people currently living with dementia and numbers expected to double every twenty years,the world is currently facing a dementia epidemic.Nevertheless,a poor understanding of the etiology of demen...With over 50 million people currently living with dementia and numbers expected to double every twenty years,the world is currently facing a dementia epidemic.Nevertheless,a poor understanding of the etiology of dementia has resulted in the inability to develop any successful disease-modifying treatment.Over the past year,several researchers have highlighted the role of systemic infections in increasing the risk of developing dementia.These findings are particularly troubling given the ongoing coronavirus 19(COVID-19)pandemic,adding yet another cause for concern over the long-term impact of COVID-19 on the public’s mental health.展开更多
The melanoma differentiation-associated gene-7（mda-7）,IL-24,has the specific functions that induce cancer cell apoptosis without doing harm to normal cells. We systematically review the apoptotic signal pathways and...The melanoma differentiation-associated gene-7（mda-7）,IL-24,has the specific functions that induce cancer cell apoptosis without doing harm to normal cells. We systematically review the apoptotic signal pathways and their regulatory mechanisms induced by Ad.IL-24 and IL-24 in diverse cancer cells. IL-24 can participate in varied signal transduction pathways,including JAK,p38 MAPK,Wnt/β-catenin,JNK,ER stress and mitochondria-associated signal pathways. And we review five proteins interacting with IL-24,including Bip/GRP78,S1 R,PKR,Beclin1 and soluble clusterin,which are relative to the tumor-specific effect of IL-24. It is speculated that ER stress,G-protein pathways and MAPK signal pathways may be the primary upstream effectors which activate the sequential downstream mediators resulting in apoptosis induced by IL-24 in tumor cells. Experimental results also show that IL-24 sensitizes cancer cells and indirectly promotes apoptosis rather than functions as a direct apoptosis inducer itself.展开更多
Aging is related to physiological decline and the development of chronic diseases,yet molecular changes and mechanisms underlying the aging process remain unclear.Could certain“dark matter”,such as transposable elem...Aging is related to physiological decline and the development of chronic diseases,yet molecular changes and mechanisms underlying the aging process remain unclear.Could certain“dark matter”,such as transposable elements with viral origins in the genome,be activated and participate in the aging process?Excitingly,a study by Liu and colleagues revealed that the reactivation of endogenous retroviruses(ERVs)during aging enhances senescence[1].By using cross-species models and multiple techniques,the team uncovered the unusual role of ERV reactivation as a hallmark and driver of aging.The authors identified that ERV expression is associated with cellular and tissue aging(Fig.1).They found that the accumulation of human ERV group K(HERVK)retrovirus-like particles(RVLPs)mediates aging-promoting effects in recipient cells.展开更多
SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study...SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.展开更多
The population aged 60 and over in China reached approximately 297 million in 2023 according to the National Bureau of Statistics,accounting for 21.1%of the national population.The population aged 65 and over was abou...The population aged 60 and over in China reached approximately 297 million in 2023 according to the National Bureau of Statistics,accounting for 21.1%of the national population.The population aged 65 and over was about 217 million,accounting for 15.4%[1].It is estimated that by 2035,China will have an elderly population of over 400 million,accounting for more than 30%of the total population,thereby entering a stage of severe aging.Aging brings many challenges to the society,especially in terms of medical care for elderly patients.The continuous advancement of science and technology,especially the breakthrough in basic research as well as new technologies and interdisciplinary integration,has brought new opportunities for the development of various professional fields.To better address the challenges of anesthesia and perioperative medicine in the aging era and to accelerate the rehabilitation of patients while maintaining life and health services,it is crucial to promote interdisciplinary integration.展开更多
Inflammation is a driving force of hematopoietic stem cells(HSCs)aging,causing irreversible exhaustion of functional HSCs.However,the underlying mechanism of HSCs erosion by inflammatory insult remains poorly understo...Inflammation is a driving force of hematopoietic stem cells(HSCs)aging,causing irreversible exhaustion of functional HSCs.However,the underlying mechanism of HSCs erosion by inflammatory insult remains poorly understood.Here,we find that transient LPS exposure primes aged HSCs to undergo accelerated differentiation at the expense of self-renewal,leading to depletion of HSCs.Meanwhile,the central regulator nuclear factor kappa B(NF-κB)mediating functional impairment by inflammation insult induces differential transcriptional response in aged HSCs compared with young HSCs,with precocious activation of myeloid lineage genes.Altered compartmentalization and chromatin loop formation are associated with aging-related differential transcriptional response in HSCs upon lipopolysaccharide(LPS)stimulation.Mechanistically,enhancer and promoter regions of myeloid lineage genes in aged HSCs are more accessible and display more rapid and prominent CTCF occupancy upon LPS stimulation.Our study provides comprehensive resources for the three-dimensional(3D)genome structure of HSCs and sheds light into the ordered genome organization and the associated transcriptome signature underlying HSCs aging.展开更多
Perioperative neurocognitive disorder(PND) is a significant neurological complication in aging perioperative patients that impacts postoperative cognition.PND is currently diagnosed through cognitive function testing,...Perioperative neurocognitive disorder(PND) is a significant neurological complication in aging perioperative patients that impacts postoperative cognition.PND is currently diagnosed through cognitive function testing,which is limited by its subjectivity and time requirements.Thus,the identification of biomarkers to assess PND onset is a priority to identify at-risk individuals and enable interventions and treatments to patient outcomes.This article synthesizes expert perspectives on brain aging and PND,presents the latest clinical evidence on PND biomarkers(imaging,electroencephalography,and molecular biomarkers),and delves into the relationship between PND and other age-related cognitive disorders.Thorough review of PND research identified several biomarkers with high sensitivity and specificity,offering a solid scientific foundation to predict and diagnose PND.These biomarkers not only enhance diagnostic accuracy for clinicians but also provide opportunities for earlier intervention and more effective treatment,potentially enhancing patient outcomes and quality of life.展开更多
Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for ge...Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.展开更多
DNA double-strand break(DSB) is the most severe form of DNA damage,which is repaired mainly through high-fidelity homologous recombination(HR) or error-prone non-homologous end joining(NHEJ).Defects in the DNA damage ...DNA double-strand break(DSB) is the most severe form of DNA damage,which is repaired mainly through high-fidelity homologous recombination(HR) or error-prone non-homologous end joining(NHEJ).Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer.Nicotinamide phosphoribosyltransferase(Nampt),which is involved in nicotinamide adenine dinucleotide metabolism,is overexpressed in a variety of tumors.In this report,we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80,which are key factors in HR and NHEJ,respectively.Depletion of Nampt by small interfering RNA(siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair.Furthermore,the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining,indicating a delay in the onset of cellular senescence in normal human fibroblasts.Taken together,our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair,contributing to the acceleration of cellular senescence.展开更多
Aging-induced alternations of vasculature structures,phenotypes,and functions are key in the occurrence and development of vascular aging-related diseases.Multiple molecular and cellular events,such as oxidative stres...Aging-induced alternations of vasculature structures,phenotypes,and functions are key in the occurrence and development of vascular aging-related diseases.Multiple molecular and cellular events,such as oxidative stress,mitochondrial dysfunction,vascular inflammation,cellular senescence,and epigenetic alterations are highly associated with vascular aging physiopathology.Advances in nanoparticles and nanotechnology,which can realize sensitive diagnostic modalities,efficient medical treatment,and better prognosis as well as less adverse effects on non-target tissues,provide an amazing window in the field of vascular aging and related diseases.Throughout this review,we presented current knowledge on classification of nanoparticles and the relationship between vascular aging and related diseases.Importantly,we comprehensively summarized the potential of nanoparticles-based diagnostic and therapeutic techniques in vascular aging and related diseases,including cardiovascular diseases,cerebrovascular diseases,as well as chronic kidney diseases,and discussed the advantages and limitations of their clinical applications.展开更多
Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the in...Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca2+ overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation(CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.展开更多
The process of aging is mitigated by the maintenance and repair of chromosome ends(telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the e...The process of aging is mitigated by the maintenance and repair of chromosome ends(telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase(TERT),which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy.Underpinning increased cell proliferation,telomerase is also a key factor in facilitating cancer cell immortalization.The review focuses on aspects of hormonal regulations of telomerase,and the intracellular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels.In addition,the basic structure and function of two key telomerase enzyme components—the catalytic subunit TERTand the template RNA(TERC)are discussed briefly.展开更多
基金supported by grants from the National Natural Science Foundation of China(32371030,82371194,and 82071395)the Natural Science Foundation of Chongqing(CSTB2022NSCQ-LZX0010 and CSTB2024NSCQ-MSX0269)the CQMU Program for Youth Innovation in Future Medicine(W0044).
文摘Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabolism.In the context of galactose metabolism,intracellular glucose levels are heightened.Galactose mutarotase(GALM)plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion ofβ-D-galactose intoα-D-galactose(α-D-G).The latter is then converted into glucose-6-phosphate,improving glucose metabolism levels.However,the involvement of GALM in AD progression is still unclear.In the present study,we found that the expression of GALM was significantly increased in AD patients and model mice.Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein(APP)and APP-cleaving enzymes including a disintegrin and metalloprotease 10(ADAM10),β-site APP-cleaving enzyme 1(BACE1),and presenilin-1(PS1).Interestingly,genetic overexpression of GALM reduced APP and Aβdeposition by increasing the maturation of ADAM10,although it did not alter the expression of BACE1 and PS1.Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation(LTP)and spatial learning and memory in AD model mice.Importantly,directα-D-G(20 mg/kg,i.p.)also inhibited Aβdeposition by increasing the maturation of ADAM10,thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice.Taken together,our results indicate that GALM shifts APP processing towardsα-cleavage,preventing Aβgeneration by increasing the level of mature ADAM10.These findings indicate that GALM may be a potential therapeutic target for AD,andα-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
基金supported by the China Science and Technology Innovation 2030-Major Project(2022ZD0211700)the Major Program of the National Natural Science Foundation of China(62394312)+2 种基金the National Natural Science Foundation of China(82471536)the Wenzhou Science and Technology Projects(ZY2023006,2024R2002)Oujiang Laboratory(OJQD2022002).
文摘Magnetic stimulation has made significant strides in the treatment of psychiatric disorders.Nonetheless,current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation.To address this,we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration.We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system(pMSS)with repetitive transcranial magnetic stimulation in mice.Oxytocin levels,dendritic morphology and density,and mouse behavior were measured before and after pMSS intervention.Our findings suggest that pMSS can activate oxytocinergic neurons,leading to upregulation of oxytocin secretion and neurite outgrowth.As a result,sociability was rapidly improved after a one-week pMSS treatment regimen.These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
基金supported by the Queensland-Chinese Academy of Sciences Collaborative Science Fund(QCSA-0001)。
文摘Antibiotics in poultry feed to boost growth performance are becoming increasingly contentious due to concerns over antimicrobial resistance development.Essential oils(EOs),as natural,plant-derived compounds,have demonstrated antimicrobial and antioxidant properties.EOs may potentially improve poultry health and growth performance when included in poultry feed.Nevertheless,the incorporation of EOs as nutritional additives is hindered by their high volatility,low water solubility,poor intestinal absorption,and sensitivity to environmental conditions.Recently,nanoencapsulation strategies using nanoformulations have emerged as a potential solution to these challenges,improving the stability and bioavailability of EOs,and enabling targeted delivery in poultry feed.This review provides an overview of the antioxidant and antibacterial properties of EOs,the current limitations of their applications in poultry feed,and the recent advancements in nano-engineering to overcome these limitations.Furthermore,we outline the potential future research direction on EO nanoformulations,emphasizing their promising role in advancing sustainable poultry nutrition.
基金supported by grants from the NSFC-Regional Innovation and Development Joint Fund(No.U22A20364)the National Key R&D Program of China(No.2021YFC2500500)the National Natural Science Foundation of China(No.81973112,No.92049302)。
文摘Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian cysts.This study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese women.Methods Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian cysts.Results The mean age was 43.0±11.5 years,and the mean level of NAD^(+)was 31.3±5.3μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from37.4%to 21.6%from Q1 to Q4 of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)quartiles.As compared with the highest NAD^(+)quartile(≥34.4μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14–3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 28.0 to35.0μmol/L.Conclusion:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.
基金supported by a grant from Key Laboratory of Alzheimer's Disease of Zhejiang Province,Institute of Aging,Wenzhou Medical University,No.ZJAD-2021002(to ZW)。
文摘Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.
基金supported by the National Science Fund for Distinguished Young Scholars (81925015)Science and Technology Project of Guangzhou (2023A03J0886,2023A03J0871)National Natural Science Foundation of China (82030039,32400709)。
文摘The proteasome,an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles,performs both shared and distinct functions across various tissues and organs.Spermatogenesis,a highly complex developmental process,relies on proteasome activity at multiple stages to regulate protein turnover.In this study,we selected the 20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis.Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models,we confirmed the expression of both subunits in all spermatogenic cell types,with pronounced presence in early germ cell development.To further clarify their functional significance,we specifically knocked out Psma1 and Psmd2 in germ cells.Deletion of either PSMA1 or PSMD2 led to disrupted spermatogenesis,characterized by the complete absence of sperm in the epididymis.Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation.Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1,a key regulator of mitosis-to-meiosis transition,leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation.This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.
基金funded by Science and Technology Program of Wenzhou(Y20220843).
文摘Background:Adolescent depression and school refusal(SR)are prevalent and important global concerns that need to be understood and addressed.Cross-sectional associations have been reported but prospective relationships between them remain unclear.This longitudinal study investigated the bidirectional relationships between these two problems among Chinese adolescents.Methods:A longitudinal study was conducted in Taizhou,China,surveying students of three junior high schools,three senior high schools,and one vocational high school.A total of 3882 students completed the questionnaire at baseline(T1);3167 of them completed an identical follow-up questionnaire after 6 months(T2).Depression was assessed via the Patient Health Questionnaire(PHQ-9)and SR via the modified Chinese version of The School Refusal Assessment Scale-Revised(SRAS-R).Cross-lagged panel modeling(CLPM)analysis was conducted to test the reciprocal relationships,adjusting for socio-demographic factors.Multiple group analysis was conducted to test whether the CLPM differed by gender and grade.Results:Statistically significant bidirectional relationships were found.A higher level of SR assessed at T1 is prospectively associated with a higher level of depression at T2(β=0.07,p=0.006);a higher level of depression at T1 also is prospectively associated with a higher level of SR at T2(β=0.14,p<0.001).Such models differed significantly by neither gender nor grade.Conclusion:SR and depression should be seen as each other’s mutually reinforcing association.The bidirectional relationships potentially result in a vicious cycle.Early interventions may target both problems concurrently.Future studies may involve more time points and test some mediators.
基金Project supported by the National Basic Research Program(973)of China(No.2012CB518900)the National Natural Science Foundation of China(Nos.31160240 and 31260621)+2 种基金the National Major Scientific and Technological Special Project during the Twelfth Five-year Plan Period of China(No.2012ZX10002006)the Hangzhou Normal University Supporting Project(No.PE13002004042)the Natural Science Foundation of Jiangxi Province(No.20114BAB204016),China
文摘Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein （BiP） interacts with the three sensors （protein kinase RNA-like ER kinase （PERK）, activating transcription factor 6 （ATF6）, and inositol-requiring enzyme la （IREla）） Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor （VEGF）-VEGF receptor （VEGFR）-phospholipase C-~ （PLCy）-mammalian target of rapamycin complex 1 （mTORC1） pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IREla also can be activated by activated RAC-alpha serine/threonine-protein kinase （AKT）. A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species （ROS）, Ca2＋ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase （JNK）, signal transducer and activator of transcription 3 （STAT3）, and P38, when cellular damage exceeds the capacity of this adaptive response.
文摘With over 50 million people currently living with dementia and numbers expected to double every twenty years,the world is currently facing a dementia epidemic.Nevertheless,a poor understanding of the etiology of dementia has resulted in the inability to develop any successful disease-modifying treatment.Over the past year,several researchers have highlighted the role of systemic infections in increasing the risk of developing dementia.These findings are particularly troubling given the ongoing coronavirus 19(COVID-19)pandemic,adding yet another cause for concern over the long-term impact of COVID-19 on the public’s mental health.
基金Supported by the National Program on Key Basic Research Project(973 Program)(2012CB518900)the National Natural Science Foundation of China(31160240,31260621)+2 种基金the 12th Five Years Key Programs for Science and Technology Development of China(2012ZX10002006)the Hangzhou Normal University Supporting Project(PE13002004042)the Natural Science Foundation of China of Jiangxi(20114BAB204016)
文摘The melanoma differentiation-associated gene-7（mda-7）,IL-24,has the specific functions that induce cancer cell apoptosis without doing harm to normal cells. We systematically review the apoptotic signal pathways and their regulatory mechanisms induced by Ad.IL-24 and IL-24 in diverse cancer cells. IL-24 can participate in varied signal transduction pathways,including JAK,p38 MAPK,Wnt/β-catenin,JNK,ER stress and mitochondria-associated signal pathways. And we review five proteins interacting with IL-24,including Bip/GRP78,S1 R,PKR,Beclin1 and soluble clusterin,which are relative to the tumor-specific effect of IL-24. It is speculated that ER stress,G-protein pathways and MAPK signal pathways may be the primary upstream effectors which activate the sequential downstream mediators resulting in apoptosis induced by IL-24 in tumor cells. Experimental results also show that IL-24 sensitizes cancer cells and indirectly promotes apoptosis rather than functions as a direct apoptosis inducer itself.
文摘Aging is related to physiological decline and the development of chronic diseases,yet molecular changes and mechanisms underlying the aging process remain unclear.Could certain“dark matter”,such as transposable elements with viral origins in the genome,be activated and participate in the aging process?Excitingly,a study by Liu and colleagues revealed that the reactivation of endogenous retroviruses(ERVs)during aging enhances senescence[1].By using cross-species models and multiple techniques,the team uncovered the unusual role of ERV reactivation as a hallmark and driver of aging.The authors identified that ERV expression is associated with cellular and tissue aging(Fig.1).They found that the accumulation of human ERV group K(HERVK)retrovirus-like particles(RVLPs)mediates aging-promoting effects in recipient cells.
基金National Natural Science Foundation of China(82230043,82293642)。
文摘SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.
文摘The population aged 60 and over in China reached approximately 297 million in 2023 according to the National Bureau of Statistics,accounting for 21.1%of the national population.The population aged 65 and over was about 217 million,accounting for 15.4%[1].It is estimated that by 2035,China will have an elderly population of over 400 million,accounting for more than 30%of the total population,thereby entering a stage of severe aging.Aging brings many challenges to the society,especially in terms of medical care for elderly patients.The continuous advancement of science and technology,especially the breakthrough in basic research as well as new technologies and interdisciplinary integration,has brought new opportunities for the development of various professional fields.To better address the challenges of anesthesia and perioperative medicine in the aging era and to accelerate the rehabilitation of patients while maintaining life and health services,it is crucial to promote interdisciplinary integration.
基金supported by the National Natural Science Foundation of China (32122030, 32470845, 32330030, 92168205, 92049304, 82030039, 32341004, 82230047, 32122030, 31721003, 32000562, 32170589, 31970758, 31972882, and 92049112)the Ministry of Science and Technology of China (2024YFA1107000, 2022YFC2702200, 2021YFC2700301, 2021YFA1100103, 2021YFA1100302, 2024YFA098701)+5 种基金the Science and Technology Innovation Action Plan of the Science and Technology Commission of Shanghai Municipality (21JC1405500)the innovation team project of universities in Guangdong province (2023KCXTD004)Shanghai Rising-Star Program (A type) of the Science, Technology Commission of Shanghai Municipality (21QA1409500)the Fundamental Research Funds for the Central Universities (22120240435)the Peak Disciplines (Type Ⅳ) of Institutions of Higher Learning in Shanghaithe Guangdong Basic and Applied Basic Research Foundation (2022A1515011204)
文摘Inflammation is a driving force of hematopoietic stem cells(HSCs)aging,causing irreversible exhaustion of functional HSCs.However,the underlying mechanism of HSCs erosion by inflammatory insult remains poorly understood.Here,we find that transient LPS exposure primes aged HSCs to undergo accelerated differentiation at the expense of self-renewal,leading to depletion of HSCs.Meanwhile,the central regulator nuclear factor kappa B(NF-κB)mediating functional impairment by inflammation insult induces differential transcriptional response in aged HSCs compared with young HSCs,with precocious activation of myeloid lineage genes.Altered compartmentalization and chromatin loop formation are associated with aging-related differential transcriptional response in HSCs upon lipopolysaccharide(LPS)stimulation.Mechanistically,enhancer and promoter regions of myeloid lineage genes in aged HSCs are more accessible and display more rapid and prominent CTCF occupancy upon LPS stimulation.Our study provides comprehensive resources for the three-dimensional(3D)genome structure of HSCs and sheds light into the ordered genome organization and the associated transcriptome signature underlying HSCs aging.
基金supported by the National Natural Science Foundation of China (82171194,82371204,82171183,82293642)the Shanghai Municipal Science and Technology Commission Biomedical Science and Technology Project (22S31902600)。
文摘Perioperative neurocognitive disorder(PND) is a significant neurological complication in aging perioperative patients that impacts postoperative cognition.PND is currently diagnosed through cognitive function testing,which is limited by its subjectivity and time requirements.Thus,the identification of biomarkers to assess PND onset is a priority to identify at-risk individuals and enable interventions and treatments to patient outcomes.This article synthesizes expert perspectives on brain aging and PND,presents the latest clinical evidence on PND biomarkers(imaging,electroencephalography,and molecular biomarkers),and delves into the relationship between PND and other age-related cognitive disorders.Thorough review of PND research identified several biomarkers with high sensitivity and specificity,offering a solid scientific foundation to predict and diagnose PND.These biomarkers not only enhance diagnostic accuracy for clinicians but also provide opportunities for earlier intervention and more effective treatment,potentially enhancing patient outcomes and quality of life.
基金supported by the National Key Research and Development Program of China(2017YFA0103304)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010100)+5 种基金the National Key Research and Development Program of China(2015CB964800,2017YFA0102802,2014CB910503 and 2018YFA0107203)the National High Tech no logy Research and Development Program of China(2015AA020307)the National Natural Science Foundation of China(Grant Nos.31671429,91749202,91749123,81625009,81330008,81371342,81471414,81422017,81601233,81671377,31601109,31601158,81771515 and 81701388)Program of Beijing Municipal Science and Technology Commission(Z151100003 915072)Key Research Program of the Chinese Academy of Sciences(KJZDEW-TZ-L05),Beijing Municipal Commission of Health and Family Planning(PXM2018_026283_000002)Advanced Innovation Center for Human Brain Protection(117212).
文摘Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.
基金was supported by the National Natural Science Foundation of China (No.31130017, 31071190, and 30711120570)the 973 project 2010CB911904+1 种基金Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality (No. PHR20110508) to XXthe 973 project 2012CB911203 to YSC
文摘DNA double-strand break(DSB) is the most severe form of DNA damage,which is repaired mainly through high-fidelity homologous recombination(HR) or error-prone non-homologous end joining(NHEJ).Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer.Nicotinamide phosphoribosyltransferase(Nampt),which is involved in nicotinamide adenine dinucleotide metabolism,is overexpressed in a variety of tumors.In this report,we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80,which are key factors in HR and NHEJ,respectively.Depletion of Nampt by small interfering RNA(siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair.Furthermore,the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining,indicating a delay in the onset of cellular senescence in normal human fibroblasts.Taken together,our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair,contributing to the acceleration of cellular senescence.
基金supported by the National Natural Science Foundation of China(Nos.82071593,82101663,81974223,and 81770833)National Key R&D(or Research and Development)Program of China(Nos.2020YFC2009000 and 2020YFC2009001).
文摘Aging-induced alternations of vasculature structures,phenotypes,and functions are key in the occurrence and development of vascular aging-related diseases.Multiple molecular and cellular events,such as oxidative stress,mitochondrial dysfunction,vascular inflammation,cellular senescence,and epigenetic alterations are highly associated with vascular aging physiopathology.Advances in nanoparticles and nanotechnology,which can realize sensitive diagnostic modalities,efficient medical treatment,and better prognosis as well as less adverse effects on non-target tissues,provide an amazing window in the field of vascular aging and related diseases.Throughout this review,we presented current knowledge on classification of nanoparticles and the relationship between vascular aging and related diseases.Importantly,we comprehensively summarized the potential of nanoparticles-based diagnostic and therapeutic techniques in vascular aging and related diseases,including cardiovascular diseases,cerebrovascular diseases,as well as chronic kidney diseases,and discussed the advantages and limitations of their clinical applications.
基金Supported by Grants from The United States National Institute of Neurological Disorders and Stroke,No.R01 NS076975-03a predoctoral fellowship from the United States National Institute of Aging,Training in the Neurobiology of Aging,No.T31 AG020494a predoctoral fellowship from the University of North Texas Health Science Center’s Physician Scientist Program
文摘Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca2+ overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation(CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.
基金supported by grants from the National Health and Medical Research Council of Australia,Cancer Council of Victoria,Australiathe National Basic Research Program of China(Grant No.2012CB911200)a recipient of Monash Postgraduate Scholarship.
文摘The process of aging is mitigated by the maintenance and repair of chromosome ends(telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase(TERT),which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy.Underpinning increased cell proliferation,telomerase is also a key factor in facilitating cancer cell immortalization.The review focuses on aspects of hormonal regulations of telomerase,and the intracellular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels.In addition,the basic structure and function of two key telomerase enzyme components—the catalytic subunit TERTand the template RNA(TERC)are discussed briefly.
