Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease...Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD.Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins.Bioinformatic analysis was applied to explore significantly enriched pathways.Results:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset.Different pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were identified.Moreover,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD patients.Conclusions:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.展开更多
Alzheimer’s disease(AD)is a neurodegenerative condition that disrupts nerve cell function due to the misfolding and buildup of proteins,resulting in cognitive loss and aberrant behavior.Microglia cellsare one of the ...Alzheimer’s disease(AD)is a neurodegenerative condition that disrupts nerve cell function due to the misfolding and buildup of proteins,resulting in cognitive loss and aberrant behavior.Microglia cellsare one of the crucial immune cells in the central nervous system.Depending on their activation levels,microglia cells in the degenerative phase of AD can serve either neuroprotective or neurotoxic roles.Microglia cells express several neurotransmitter receptors that play distinct functions in the degenerative progression of AD.These receptors facilitate bidirectional communication between microglia and nerve cells.The neurotransmitter receptors on microglia cells can mediate or affect the neuroprotective or toxic effects of microglia cells,thereby affecting AD pathology.This paper focuses on the gamma-aminobutyric acid,glutaminergic,cannabinoid,cholinergic,and adrenergic receptors on microglia cells and their relationship with AD.Understanding how neurotransmitter receptors on microglia function in AD will be crucial for identifying potential treatment targets.展开更多
In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regard...In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regarding“myocardial energy metabolism”and“aortic thrombosis”.Our goal is to elucidate the biological mechanism underlying the occurrence and development of coronary heart disease with blood stasis syndrome from the perspectives of“heart and vessels”and“Qi(in traditional Chinese medicine,it refers to the most fundamental and subtle substances that constitute the human body and maintain life activities.At the same time,it also has the meaning of physiological function.In terms of traditional Chinese medicine,Qi and different words are used together to express different meanings)and blood”.The research content is divided into four modules as follows:1.establishment of an animal model of coronary heart disease with blood stasis syndrome through fibrinogen overexpression.2.Investigation of the mitochondrial quality control system in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.3.Study of platelet autophagy in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.4.Examination of the relationship between the AMPK-mTOR pathway and metabolism in platelet autophagy of coronary heart disease with blood stasis syndrome under fibrinogen overexpression.Ninety-six Sprague Dawley rats will be randomly assigned to the following groups:control group,model group,fibrinogen group and adeno-associated virus group.All rats will undergo a 14-week model construction process,and modern molecular biology methods will be employed to evaluate the model and examine relevant research indicators.The obtained data will be analyzed according to a predefined statistical analysis plan.展开更多
Osteoporosis is a common bone disease in women worldwide, leading to decreased bone density and an accelerated risk of fractures. The causes of osteoporosis in women include age (senile osteoporosis), menopause-associ...Osteoporosis is a common bone disease in women worldwide, leading to decreased bone density and an accelerated risk of fractures. The causes of osteoporosis in women include age (senile osteoporosis), menopause-associated hormonal changes, deficiencies in calcium and vitamin D, genetics, lifestyle factors, medical conditions, and some type of medications. The consequences of osteoporosis are colossal, consisting of fractures, decreased quality of life, psychological impacts, and economic burden. To effectively control the menace of osteoporosis in women, numerous strategies are advocated. Adequate calcium and vitamin D consumption through diet or supplements is vital. Regular weight-bearing activities and strength training that promote bone density. Maintaining a healthy life-style through avoiding smoking, limiting alcohol in-take and maintaining a wholesome body weight is essential. Hormone replacement therapy and some medications may be recommended in certain cases. Early detection through regular bone density and blood tests is crucial to lowering its impact. Creating a supportive network through educational programs and resources fosters awareness and empowerment. By engaging these strategies, women can be empowered to combat osteoporosis, reduce fracture risk, and build stronger bones for their overall well-being.展开更多
Background:Alzheimer’s disease affects millions of people worldwide,and one of its major characteristics is the accumulation of extracellular Aβpeptides in the human brain,leading to neuronal death and resulting in ...Background:Alzheimer’s disease affects millions of people worldwide,and one of its major characteristics is the accumulation of extracellular Aβpeptides in the human brain,leading to neuronal death and resulting in memory deficits,disorientation,and inappropriate behaviour.Objective and Methodology:This review study aims to develop new molecular targets for major depression-associated cognitive dysfunction and determine the mechanisms of action of 1,3,4-oxadiazole-based drug candidates.It encourages scientists to develop and synthesize drugs with low side effects to treat Alzheimer’s disease.Furthermore,the drug has shown significant improvement in memory function among dementia patients,which is due to the increased production of acetylcholine in the brain.These derivatives show a high affinity to amyloid plaques,which are thought to cause cognitive damage in patients with Alzheimer’s disease.This review study emphasizes newly developed inhibitors of amyloid deposition using the enzymeα-secretase,which cleaves amyloid precursor protein into smaller fragments that are toxic to neurons.1,3,4-Oxadiazole compounds have demonstrated no significant toxicity to the central nervous system.The antioxidant properties of 1,3,4-oxadiazoles can reduce free radicals,which play an active role in cell damage and disease.Conclusion:This review aims to provide readers with an overview of the current state of knowledge about oxadiazole-related drugs,emphasizing their biological importance.Key aspects related to the discovery and development of these drug candidates are discussed in detail,including information on their structure,biological activity,chemistry,and pharmacological properties.In addition,different derivatives discovered for Alzheimer’s disease to enhance the therapeutic efficiency of oxadiazole drugs have been comprehensively discussed in this review.展开更多
Backgroud:Parkinson’s disease(PD)is a neurodegenerative disorder with an increasing global prevalence.However,the development of drugs for PD treatment has not kept pace with the continuously growing number of patien...Backgroud:Parkinson’s disease(PD)is a neurodegenerative disorder with an increasing global prevalence.However,the development of drugs for PD treatment has not kept pace with the continuously growing number of patients.Currently,the search for new effective substances from natural drugs is a major research direction.Two Chinese medicinal materials,Saposhnikoviae Radix(Fangfeng)and Chuanxiong Rhizoma(Chuanxiong),are commonly used in the treatment of PD in China.However,the mechanism of their combination is not clear,and further research is needed.Methods:Data were collected from publicly available databases:TCMSP,UnitProt,GeneCards OMIM,PharmGKB,Therapeutic Target Database and DrugBank.Network pharmacology and molecular docking methods was used to analyze the data to discover the possible pharmacological effects of the two drugs in the treatment of PD.Results:Beta-sitosterol,Mandenol and Wallichilide were the active components of Saposhnikoviae Radix and Chuanxiong Rhizoma(FC),and they stably bonded with PD targets,including PTGS2,CASP3,AKT1 and JUN.The target genes of FC were significantly enriched in PD-associated pathways,including calcium signaling and apoptosis pathways.Moreover,the study revealed that the active components of FC may affect cellular structures,such as membrane rafts,membrane microdomains,membrane regions,and postsynaptic membranes,which,in turn,affect a variety of molecular functions and biological processes.Conclusion:The results of this study indicate the direction for clarifying the pharmacodynamic substances of FC,the extraction method of pharmacodynamic substances,as well as the mechanism and efficacy of pharmacodynamic substances.Importantly,this study provides a strategy for developing new therapeutic drugs for PD.展开更多
Background:Dementia is a group of nervous system diseases characterized by progressive cognitive decline,leading to a loss of self-care ability and a decline in well-being.This places a significant burden on the globa...Background:Dementia is a group of nervous system diseases characterized by progressive cognitive decline,leading to a loss of self-care ability and a decline in well-being.This places a significant burden on the global healthcare system,with Chinese patients accounting for approximately one-quarter of the world’s dementia cases.Therefore,it is crucial to identify factors that impact the quality of life(QOL)among elderly Chinese individuals with dementia.Method:To achieve this,we conducted a comprehensive search of several databases,including PubMed,Embase,Web of Science,the Cochrane Library,China National Knowledge Infrastructure,Wanfang Data,China VIP Database and China Biomedical Literature Database.We reviewed cross-sectional studies from the inception of these databases until March 27,2022.QOL outcomes were assessed using standardized scales in the studies included in this review.Results:The search yielded a total of 1,235 relevant articles,from which we finally included 21 cross-sectional studies and one longitudinal study after rigorous quality assessment.Among these,10 studies were classified as high quality,while 12 were classified as fair quality.Through our analysis,we identified 28 patient-rated QOL factors and 14 caregiver-rated QOL factors.These factors were categorized into three groups:patient,disease-related and caregiver.Factors commonly found to influence patient-rated QOL included age,education,marital status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiver burden.Similarly,factors commonly influencing caregiver-rated QOL included economic status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiving time.Conclusion:This review clarifies the factors that influence the QOL of Chinese individuals with dementia.When implementing interventions,it is crucial to consider the differences between patient-rated QOL and caregiver-proxy-rated QOL,as well as their respective influencing factors.展开更多
Diabetic retinopathy is a predictable effect of diabetes mellitus and is classified as a microvascular disease.The treatment of diabetic retinopathy is complex and challenging.Vascular endothelial growth factor therap...Diabetic retinopathy is a predictable effect of diabetes mellitus and is classified as a microvascular disease.The treatment of diabetic retinopathy is complex and challenging.Vascular endothelial growth factor therapy has demonstrated significant clinical improvement in visual outcomes.However,many patients fail to achieve visual improvement,necessitating the development of modern treatment techniques.Some experiments suggest that inflammation and retinal neurodegeneration may contribute to retinal damage in the early stages of diabetic retinopathy.This review aims to explore the current and emerging treatment options and pathophysiology of diabetic retinopathy.展开更多
Parkinson’s disease(PD)is the second neurodegenerative disease in the world.The pathological characteristics of PD are degeneration,loss and death of dopaminergic neurons in the substantia nigra of the midbrain.At pr...Parkinson’s disease(PD)is the second neurodegenerative disease in the world.The pathological characteristics of PD are degeneration,loss and death of dopaminergic neurons in the substantia nigra of the midbrain.At present,most scholars believe that the main pathogenesis of PD is α-synuclein aggregation,oxidative stress,mitochondrial dysfunction and neuroinflammatory reaction.More and more studies have demonstrated that ferroptosis plays an important role in the occurrence and development of PD.Ferroptosis is a new type of cell death that is significantly different from traditional apoptosis,scorching and necrosis.Its main feature is iron-dependent lipid peroxidation.Some studies have found that the efficacy of acupuncture and moxibustion in the treatment of PD may be related to the regulation of ferroptosis.Therefore,this study mainly discusses the occurrence and development mechanism of ferroptosis and its role in PD,and the possible mechanism of acupuncture and moxibustion in the treatment of PD dopaminergic neurons,so as to provide theoretical basis for acupuncture and moxibustion in the treatment of PD.展开更多
Background and Objectives:Microneedling has been introduced as a new technique to address the growing concern of facial skin photoaging.Kangfuxin liquid has been found to promote the process of skin wound repair,inclu...Background and Objectives:Microneedling has been introduced as a new technique to address the growing concern of facial skin photoaging.Kangfuxin liquid has been found to promote the process of skin wound repair,including reducing inflammatory response,improving immunity and enhancing antioxidant levels.In this prospective randomized double-blinded study,we wanted to explore the clinical efficacy and safety of Kangfuxin liquid combined with microneedling in treating facial skin photoaging.Methods:57 patients with facial skin photoaging were randomly divided into two groups.The treatment group(28 cases)received microneedle therapy with Kangfuxin liquid,while the control group(29 cases)received microneedle therapy with physiological saline.The treatment interval was 4 weeks,and a total of 3 treatments were performed.Compare the VISIA scores of facial photoaging features such as wrinkles,texture,pores,spots and ultraviolet pigmentation between two groups of patients before and after treatment,Global Score for Photoaging,satisfaction evaluation,and record the occurrence of adverse reactions.Results:After treatment,the treatment group showed more significant improvement in wrinkles,texture,pores,spots and ultraviolet pigmentation,and the Global Score for Photoaging was better than the control group(P<0.05).The satisfaction rate with improving skin in the treatment group was 85.71%,which was higher than 75.86%in the control group(P<0.05).Both groups did not experience adverse reactions such as skin infection,pigmentation or hypopigmentation,scar formation,or worsening of melasma.Conclusion:Kangfuxin liquid combined with microneedling therapy has a good improvement effect on facial skin photoaging,with a low incidence of adverse reactions and high patient satisfaction.It is worthy of clinical promotion.展开更多
Introduction About 72%of human genome is transcribed to non-coding RNAs,which have captivated researchers a lot for shedding light on their pivotal roles in regulating the initiation and progression of various disease...Introduction About 72%of human genome is transcribed to non-coding RNAs,which have captivated researchers a lot for shedding light on their pivotal roles in regulating the initiation and progression of various diseases,including cancers[1].Among these,long non-coding RNAs(lncRNAs)have emerged as key players in the complex landscape of gene regulation.LncRNAs perform a variety of roles,including scaffolding to encourage the interaction of related proteins,decoys to thwart transcriptional factors from the target gene’s promoter,sponges of linked miRNA to prevent target gene destruction,and guide molecules to recruit components for chromatin remodeling[1].Many cancers are closely related to age[2-5]and such patients are expected be increased gradually as almost 20%of the world’s population will be 65 or older by 2030[6]and those over the age of 65 have an 11-fold higher incidence of cancer than people under that age[7].As one of the typical hallmarks of aging[8],cellular senescence is Cellular senescence is induced by stressful insults and certain physiological processes and is characterized by a prolonged and essentially irreversible cell-cycle arrest with secretory features,macromolecular damage,and altered metabolism[9].Here,we aim to provide insights of the intersection between lncRNAs,cellular senescence,and urinary tumors,unraveling the potential implications and therapeutic avenues within this multifaceted network.展开更多
Parkinson’s disease(PD)is characterized by motor symptoms and non-motor symptoms chiefly attributed to the loss of dopaminergic neurons in the substantia nigra pars compacta[1].Approximately 3 million PD patients suf...Parkinson’s disease(PD)is characterized by motor symptoms and non-motor symptoms chiefly attributed to the loss of dopaminergic neurons in the substantia nigra pars compacta[1].Approximately 3 million PD patients suffer from motor deficits including tremors,muscle rigidity,bradykinesia and psychological abnormality[2].The main pathological change of PD is the degeneration and death of dopaminergic neurons in the substantia nigra pars compacta,which leads to a significant decrease in dopamine content in the striatum.The pathogenesis of PD is fairly complex.Genetic factors,environmental factors,aging,oxidative stress,and inflammation may be related to the degeneration and death of PD dopaminergic neurons[3].展开更多
Parkinson’s disease(PD)is a prevalent neurological disorder around the globe,currently affecting over 6 million people globally[1].It is estimated that by 2040,this number may double to more than 12 million[2].Aging ...Parkinson’s disease(PD)is a prevalent neurological disorder around the globe,currently affecting over 6 million people globally[1].It is estimated that by 2040,this number may double to more than 12 million[2].Aging is strongly associated with PD,as it is a significant risk factor for its development[3].Clinically,PD presents with various motor and non-motor signs.Movement-related issues mainly consist of slowed motion,involuntary shaking at rest,stiff muscles,and balance difficulties.At the same time,non-movement-related issues include impaired sense of smell,sleep disturbances,bowel irregularities,feelings of sadness,and problems with the body’s automatic functions[4].The typical pathological features of PD patients include the gradual loss of dopaminergic neurons within the substantia nigra pars compacta,coupled with the buildup ofα-synuclein(α-Syn)in neurons,the aggregates of which form inclusions known as Lewy bodies[5].The A53T mutant of humanα-Syn has a propensity to aggregate,a characteristic closely associated with the neurotoxicity seen in familial PD[6].A synthesis of both in vitro and in vivo research indicates that the misfolding and aggregation ofα-Syn are key pathogenic mechanisms in the development of PD[7-9].展开更多
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, characterized by a progressive decline in cognitive ability. Around 50 million people worldwide are reportedly affected, with annual los...Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, characterized by a progressive decline in cognitive ability. Around 50 million people worldwide are reportedly affected, with annual losses estimated at about $1 trillion [1]. Nevertheless, there remains unknown about the exact pathological mechanisms of AD and currently available treatments have a lack of efficacy. Thus, experts have reached a consensus that interventions in the preclinical stage of AD should be prioritized [2], especially when the amount of patients is set to reach 78 million by the end of this decade [3]. Recently, the proposition “integrating food and nutrition into healthcare” has been promoted [4]. Prevention from dietary eating and drinking may be an effective and age-friendly method. Nowadays, many beverages have been proven to offer great preventative benefits to AD like coffee, soy milk, tea, and wine. Coffee, consumed by tens of thousands of people every day, has been proven in several epidemiological studies to have a protective effect against AD [5-7]. A study including 411 individuals shows that significant negative correlation between stratified lifetime coffee intake and β-amyloid positivity [8]. In other words, higher coffee intake (≥ 2 cups/day) is associated with lower risk of AD. However, a Mendelian randomization (MR) analysis came to the opposite conclusion, with an additional 1 cup of coffee per day being associated with a 1.16-fold increased risk of developing AD [9]. In meta-analyses of cohort studies, it was proposed that there was a non-linear “U-shaped” link between coffee consumption and AD, with 3-4 cups per day being optimal [10]. In addition to the possibility that different conclusions are due to inconsistent estimations of coffee intake and populations in these studies, research recently proposed a hypothesis that the cytochrome P450 1A2 played an essential role in the metabolism of coffee in the human body [11]. Rs762551 is its most representative and commonly studied single nucleotide polymorphism. In detail, carriers of the rs762551 gene metabolize caffeine more rapidly and are at greater risk of developing AD when they consume large amounts of coffee. Conversely, people with slow caffeine metabolism who consume more coffee would have a preventive effect on AD, which might be a result of being exposed to coffee for a longer duration of time to the point of absorbing more potential beneficial effects of caffeine.展开更多
Cardiovascular diseases(CVDs),encompassing diverse pathologies such as atherosclerosis,hypertension,cardiomyopathy,arrhythmia,and valvular diseases,represent a significant public health challenge,severely undermining ...Cardiovascular diseases(CVDs),encompassing diverse pathologies such as atherosclerosis,hypertension,cardiomyopathy,arrhythmia,and valvular diseases,represent a significant public health challenge,severely undermining human health[1].According to the World Health Organization,CVDs claimed approximately 17.9 million deaths in 2019,representing 32%of all global deaths[2,3].The risk of CVDs morbidity and mortality increases with age,with the majority of CVDs and deaths occurring in elderly aged 75 years and older[4,5].In developed nations,CVDs are the principal cause of mortality,while in developing countries,they are a leading cause of death as well.展开更多
Background:The occurrence of early neurological deterioration following intravenous thrombolysis(IVT)is considered a particularly ominous clinical event and is strongly correlated with poor outcomes.Initiating tirofib...Background:The occurrence of early neurological deterioration following intravenous thrombolysis(IVT)is considered a particularly ominous clinical event and is strongly correlated with poor outcomes.Initiating tirofiban within 24 h after IVT has been suggested as a better treatment option to achieve long-term functional outcomes.However,the rationality of this remedy is a controversial.The purpose of the study was to evaluate the safety and efficacy of early intravenous tirofiban administration after IVT in patients with acute ischemic stroke(AIS).Methods:Databases including PubMed,EMBASE,Cochrane Library,and Web of Science were searched for clinical trials on early tirofiban implementation after IVT in patients with AIS from inception to September 2022.Odds ratios(ORs)were generated for dichotomous variants via meta-analysis using STATA 17.0 MP.Results:Five clinical trials with 725 patients were eligible.The study outcomes demonstrated that early tirofiban administration after IVT was not associated with symptomatic intracranial hemorrhage(OR,0.78;95%confidence interval(CI),0.22–2.74;P=0.70),asymptomatic intracranial hemorrhage(OR,1.11;95%CI,0.52–2.37;P=0.80),systemic bleeding(OR,0.97;95%CI,0.42–2.23;P=0.94),and death(OR,1.05;95%CI,0.47–2.31;P=0.91),but may reduce the incidence of early neurological deterioration(OR,0.09;95%CI,0.02–0.50;P=0.01),and was significantly associated with 90-day excellent(modified Rankin scale score 0–1)(OR,2.01;95%CI,1.35–3.02;P=0.00)and favorable(modified Rankin scale score 0–2)(OR,2.30;95%CI,1.63–3.23;P=0.00)functional outcomes.Conclusion:The early intravenous administration of tirofiban after IVT in patients with AIS may be a safe and effective treatment strategy that improves long-term neurological functional outcomes without increasing the risk of adverse events.展开更多
Tremendous research efforts have been made regarding the pathogenesis of Parkinson’s disease(PD).However,there are still no effective strategies to restore midbrain dopaminergic(mDA)innervation and prevent disease pr...Tremendous research efforts have been made regarding the pathogenesis of Parkinson’s disease(PD).However,there are still no effective strategies to restore midbrain dopaminergic(mDA)innervation and prevent disease progression.One possibility is that we may have been neglecting the role of axons in mDA neuronal degeneration.This review first summarizes mDA axon development during the early stage of PD and discusses how axon guidance defects contribute to PD vulnerability.Furthermore,we review axonal transport dysregulation in the numerous PD-related genetic mutations,including Parkin,PINK1,DJ1,LRRK2 and SNCA.The evidence suggests that proper axonal transport is crucial for neuronal function and survival.Finally,advanced tools for axonal studies were evaluated,including light-sheet and super-resolution microscopy.These adapted microscopes have been used to help solve questions unanswered before.Overall,the role of axon terminals in the initiation of the degeneration cascade remains undeciphered,and more research in the related area may be conducted further to restore dopamine levels in the striatum to alleviate the motor complications of PD.展开更多
Traditional Chinese medicine(TCM)has rich theories and techniques for health maintenance.Its cultural tradition of emphasizing health maintenance is not only related to its medical function of treating injuries and di...Traditional Chinese medicine(TCM)has rich theories and techniques for health maintenance.Its cultural tradition of emphasizing health maintenance is not only related to its medical function of treating injuries and diseases and prolonging life span but also closely related to Daoism,which is the fundamental religious tenet of pursuing immortality in Chinese culture.As this paper reviews,the fanatical Daoist religious culture of pursuing immortality has influenced the formation of a medical culture in TCM that cares about longevity and values health and wellness.However,this health and wellness culture is more practical–it replaces immortality with longevity as the goal.The Daoist religious concept of longevity is preserved in the basic principles and ethical values of health care:it emphasizes the harmony and consistency of the spirit and the body.It turns a lifestyle of maintaining physical and spiritual health into the pursuit of an ideal state of life.As for the specific Daoist health techniques,there are various cases of inheritance,change or abandonment:TCM inherited most of the drugs and prescriptions from the Daoist longevity techniques based on natural medicines taking and formed a popular health culture of medicinal and dietary supplements;TCM also developed internal health techniques such as internal elixir and breathing practice from Daoist internal health maintenance techniques for physical health care and disease treatment;TCM did not completely accept recipe techniques such as inedia and sex manual from Daoism because they contradicted with its secularization concept,but their general value orientation of lightness and low desire also influenced its concept of health care.展开更多
Background:The liver is fundamental for keeping up the entire body’s homeostasis.The liver hepatocytes have been shown to undergo genomic instability with aging.The stability of the hepatocytes depends on its nuclear...Background:The liver is fundamental for keeping up the entire body’s homeostasis.The liver hepatocytes have been shown to undergo genomic instability with aging.The stability of the hepatocytes depends on its nuclear architecture.Calorie restriction has been shown to extend life-span favorably and this may be through the reorganization of the nuclear structure.Objective:To study the effect of cyclic feeding regime on the chromatin assembly anchored to the nuclear membrane scaffold of rat models hepatocytes nuclei.Method:Rats models underwent cyclic feeding regime,after which nuclei were isolated;then,we investigated the chromatin decondensation and nuclear membrane disintegration of the hepatocytes using fluorescence imaging methods.Results:In 60 seconds,protease decondensed the chromatin and disintegrated the nuclear membrane structure of controls.After the first fasting,the time increased to 145 seconds in 3-month-old rats.The first refeeding increased the time to 156 seconds with a further rise to 340 seconds following the second fasting,then dropped to 116 seconds by the second refeeding.20 months old rats showed 186 seconds increase in the time of chromatin decondensation and nuclear membrane disintegration after the first fasting,with a decrease to 140 seconds observed after first refeeding.The second fasting increased the time to 165 seconds,which then slightly decreased to 163 seconds after the second refeeding.Conclusion:These results show that intermittent fasting may have acted on chromatin histone interactions and the structural lamin networks of the nuclear membranes in bringing about nuclear stability,which is essential for normal cellular function.展开更多
Parkinson’s disease(PD)is the second most common degenerative neurological disorder after Alzheimer’s disease.As one of fastest growing neurological conditions,PD affects millions of elderly people worldwide.PD pati...Parkinson’s disease(PD)is the second most common degenerative neurological disorder after Alzheimer’s disease.As one of fastest growing neurological conditions,PD affects millions of elderly people worldwide.PD patients display progressive motor symptoms,including resting tremor,slowed movement,impaired posture and balance,and rigid muscles[1].Additionally,they also often suffer from chronic pain,depression,dementia,and other non-motor symptoms[2].Medications and surgery can improve patient’s motor performance to some degree,while the treatment for non-motor conditions is limited.Moreover,long-term medication can cause severe side effects,such as dyskinesia and impulse control disorders[3,4].Therefore,new mechanistic insights and therapeutic agents/procedures are still needed to improve the treatment of increasing number of PD patients.展开更多
基金University of Massachusetts Lowell-Bedford VA Healthcare System Pilot Award(NM,WX,EG),I01 BX004730 and I01 BX003527 Merit Awards from the Biomedical Laboratory Research and Development of the Veterans Affairs Office of Research and Development(WX)RF1AG063913 from the NIH(WX).
文摘Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD.Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins.Bioinformatic analysis was applied to explore significantly enriched pathways.Results:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset.Different pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were identified.Moreover,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD patients.Conclusions:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.
文摘Alzheimer’s disease(AD)is a neurodegenerative condition that disrupts nerve cell function due to the misfolding and buildup of proteins,resulting in cognitive loss and aberrant behavior.Microglia cellsare one of the crucial immune cells in the central nervous system.Depending on their activation levels,microglia cells in the degenerative phase of AD can serve either neuroprotective or neurotoxic roles.Microglia cells express several neurotransmitter receptors that play distinct functions in the degenerative progression of AD.These receptors facilitate bidirectional communication between microglia and nerve cells.The neurotransmitter receptors on microglia cells can mediate or affect the neuroprotective or toxic effects of microglia cells,thereby affecting AD pathology.This paper focuses on the gamma-aminobutyric acid,glutaminergic,cannabinoid,cholinergic,and adrenergic receptors on microglia cells and their relationship with AD.Understanding how neurotransmitter receptors on microglia function in AD will be crucial for identifying potential treatment targets.
基金This work was supported by the National Natural Science Foundation of China(No.81973753 to Jian WX)Hunan Postgraduate Scientific Research Innovation Project(CX 20220781)Hunan University Students’Innovation and Entrepreneurship Training Program(S202210541116).
文摘In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regarding“myocardial energy metabolism”and“aortic thrombosis”.Our goal is to elucidate the biological mechanism underlying the occurrence and development of coronary heart disease with blood stasis syndrome from the perspectives of“heart and vessels”and“Qi(in traditional Chinese medicine,it refers to the most fundamental and subtle substances that constitute the human body and maintain life activities.At the same time,it also has the meaning of physiological function.In terms of traditional Chinese medicine,Qi and different words are used together to express different meanings)and blood”.The research content is divided into four modules as follows:1.establishment of an animal model of coronary heart disease with blood stasis syndrome through fibrinogen overexpression.2.Investigation of the mitochondrial quality control system in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.3.Study of platelet autophagy in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.4.Examination of the relationship between the AMPK-mTOR pathway and metabolism in platelet autophagy of coronary heart disease with blood stasis syndrome under fibrinogen overexpression.Ninety-six Sprague Dawley rats will be randomly assigned to the following groups:control group,model group,fibrinogen group and adeno-associated virus group.All rats will undergo a 14-week model construction process,and modern molecular biology methods will be employed to evaluate the model and examine relevant research indicators.The obtained data will be analyzed according to a predefined statistical analysis plan.
文摘Osteoporosis is a common bone disease in women worldwide, leading to decreased bone density and an accelerated risk of fractures. The causes of osteoporosis in women include age (senile osteoporosis), menopause-associated hormonal changes, deficiencies in calcium and vitamin D, genetics, lifestyle factors, medical conditions, and some type of medications. The consequences of osteoporosis are colossal, consisting of fractures, decreased quality of life, psychological impacts, and economic burden. To effectively control the menace of osteoporosis in women, numerous strategies are advocated. Adequate calcium and vitamin D consumption through diet or supplements is vital. Regular weight-bearing activities and strength training that promote bone density. Maintaining a healthy life-style through avoiding smoking, limiting alcohol in-take and maintaining a wholesome body weight is essential. Hormone replacement therapy and some medications may be recommended in certain cases. Early detection through regular bone density and blood tests is crucial to lowering its impact. Creating a supportive network through educational programs and resources fosters awareness and empowerment. By engaging these strategies, women can be empowered to combat osteoporosis, reduce fracture risk, and build stronger bones for their overall well-being.
文摘Background:Alzheimer’s disease affects millions of people worldwide,and one of its major characteristics is the accumulation of extracellular Aβpeptides in the human brain,leading to neuronal death and resulting in memory deficits,disorientation,and inappropriate behaviour.Objective and Methodology:This review study aims to develop new molecular targets for major depression-associated cognitive dysfunction and determine the mechanisms of action of 1,3,4-oxadiazole-based drug candidates.It encourages scientists to develop and synthesize drugs with low side effects to treat Alzheimer’s disease.Furthermore,the drug has shown significant improvement in memory function among dementia patients,which is due to the increased production of acetylcholine in the brain.These derivatives show a high affinity to amyloid plaques,which are thought to cause cognitive damage in patients with Alzheimer’s disease.This review study emphasizes newly developed inhibitors of amyloid deposition using the enzymeα-secretase,which cleaves amyloid precursor protein into smaller fragments that are toxic to neurons.1,3,4-Oxadiazole compounds have demonstrated no significant toxicity to the central nervous system.The antioxidant properties of 1,3,4-oxadiazoles can reduce free radicals,which play an active role in cell damage and disease.Conclusion:This review aims to provide readers with an overview of the current state of knowledge about oxadiazole-related drugs,emphasizing their biological importance.Key aspects related to the discovery and development of these drug candidates are discussed in detail,including information on their structure,biological activity,chemistry,and pharmacological properties.In addition,different derivatives discovered for Alzheimer’s disease to enhance the therapeutic efficiency of oxadiazole drugs have been comprehensively discussed in this review.
文摘Backgroud:Parkinson’s disease(PD)is a neurodegenerative disorder with an increasing global prevalence.However,the development of drugs for PD treatment has not kept pace with the continuously growing number of patients.Currently,the search for new effective substances from natural drugs is a major research direction.Two Chinese medicinal materials,Saposhnikoviae Radix(Fangfeng)and Chuanxiong Rhizoma(Chuanxiong),are commonly used in the treatment of PD in China.However,the mechanism of their combination is not clear,and further research is needed.Methods:Data were collected from publicly available databases:TCMSP,UnitProt,GeneCards OMIM,PharmGKB,Therapeutic Target Database and DrugBank.Network pharmacology and molecular docking methods was used to analyze the data to discover the possible pharmacological effects of the two drugs in the treatment of PD.Results:Beta-sitosterol,Mandenol and Wallichilide were the active components of Saposhnikoviae Radix and Chuanxiong Rhizoma(FC),and they stably bonded with PD targets,including PTGS2,CASP3,AKT1 and JUN.The target genes of FC were significantly enriched in PD-associated pathways,including calcium signaling and apoptosis pathways.Moreover,the study revealed that the active components of FC may affect cellular structures,such as membrane rafts,membrane microdomains,membrane regions,and postsynaptic membranes,which,in turn,affect a variety of molecular functions and biological processes.Conclusion:The results of this study indicate the direction for clarifying the pharmacodynamic substances of FC,the extraction method of pharmacodynamic substances,as well as the mechanism and efficacy of pharmacodynamic substances.Importantly,this study provides a strategy for developing new therapeutic drugs for PD.
文摘Background:Dementia is a group of nervous system diseases characterized by progressive cognitive decline,leading to a loss of self-care ability and a decline in well-being.This places a significant burden on the global healthcare system,with Chinese patients accounting for approximately one-quarter of the world’s dementia cases.Therefore,it is crucial to identify factors that impact the quality of life(QOL)among elderly Chinese individuals with dementia.Method:To achieve this,we conducted a comprehensive search of several databases,including PubMed,Embase,Web of Science,the Cochrane Library,China National Knowledge Infrastructure,Wanfang Data,China VIP Database and China Biomedical Literature Database.We reviewed cross-sectional studies from the inception of these databases until March 27,2022.QOL outcomes were assessed using standardized scales in the studies included in this review.Results:The search yielded a total of 1,235 relevant articles,from which we finally included 21 cross-sectional studies and one longitudinal study after rigorous quality assessment.Among these,10 studies were classified as high quality,while 12 were classified as fair quality.Through our analysis,we identified 28 patient-rated QOL factors and 14 caregiver-rated QOL factors.These factors were categorized into three groups:patient,disease-related and caregiver.Factors commonly found to influence patient-rated QOL included age,education,marital status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiver burden.Similarly,factors commonly influencing caregiver-rated QOL included economic status,depression,self-care ability,dementia severity,cognitive function,behavioral and psychological symptoms of dementia and caregiving time.Conclusion:This review clarifies the factors that influence the QOL of Chinese individuals with dementia.When implementing interventions,it is crucial to consider the differences between patient-rated QOL and caregiver-proxy-rated QOL,as well as their respective influencing factors.
文摘Diabetic retinopathy is a predictable effect of diabetes mellitus and is classified as a microvascular disease.The treatment of diabetic retinopathy is complex and challenging.Vascular endothelial growth factor therapy has demonstrated significant clinical improvement in visual outcomes.However,many patients fail to achieve visual improvement,necessitating the development of modern treatment techniques.Some experiments suggest that inflammation and retinal neurodegeneration may contribute to retinal damage in the early stages of diabetic retinopathy.This review aims to explore the current and emerging treatment options and pathophysiology of diabetic retinopathy.
基金This work was supported by,the Shenzhen Science and Technology Program(JCYJ20210324123614040)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2022A151510450)+3 种基金the Medical Scientific Research Foundation of Guangdong Province(No.B2023087)the Sanming Project of Medicine in Shenzhen(Grant No.SZZYSM202106009)the Bao’an TCM Development Foundation(Grant No.2022KJCX-ZJZL-7)National Administration of Traditional Chinese Medicine(GZY-FJS-2022-59).
文摘Parkinson’s disease(PD)is the second neurodegenerative disease in the world.The pathological characteristics of PD are degeneration,loss and death of dopaminergic neurons in the substantia nigra of the midbrain.At present,most scholars believe that the main pathogenesis of PD is α-synuclein aggregation,oxidative stress,mitochondrial dysfunction and neuroinflammatory reaction.More and more studies have demonstrated that ferroptosis plays an important role in the occurrence and development of PD.Ferroptosis is a new type of cell death that is significantly different from traditional apoptosis,scorching and necrosis.Its main feature is iron-dependent lipid peroxidation.Some studies have found that the efficacy of acupuncture and moxibustion in the treatment of PD may be related to the regulation of ferroptosis.Therefore,this study mainly discusses the occurrence and development mechanism of ferroptosis and its role in PD,and the possible mechanism of acupuncture and moxibustion in the treatment of PD dopaminergic neurons,so as to provide theoretical basis for acupuncture and moxibustion in the treatment of PD.
文摘Background and Objectives:Microneedling has been introduced as a new technique to address the growing concern of facial skin photoaging.Kangfuxin liquid has been found to promote the process of skin wound repair,including reducing inflammatory response,improving immunity and enhancing antioxidant levels.In this prospective randomized double-blinded study,we wanted to explore the clinical efficacy and safety of Kangfuxin liquid combined with microneedling in treating facial skin photoaging.Methods:57 patients with facial skin photoaging were randomly divided into two groups.The treatment group(28 cases)received microneedle therapy with Kangfuxin liquid,while the control group(29 cases)received microneedle therapy with physiological saline.The treatment interval was 4 weeks,and a total of 3 treatments were performed.Compare the VISIA scores of facial photoaging features such as wrinkles,texture,pores,spots and ultraviolet pigmentation between two groups of patients before and after treatment,Global Score for Photoaging,satisfaction evaluation,and record the occurrence of adverse reactions.Results:After treatment,the treatment group showed more significant improvement in wrinkles,texture,pores,spots and ultraviolet pigmentation,and the Global Score for Photoaging was better than the control group(P<0.05).The satisfaction rate with improving skin in the treatment group was 85.71%,which was higher than 75.86%in the control group(P<0.05).Both groups did not experience adverse reactions such as skin infection,pigmentation or hypopigmentation,scar formation,or worsening of melasma.Conclusion:Kangfuxin liquid combined with microneedling therapy has a good improvement effect on facial skin photoaging,with a low incidence of adverse reactions and high patient satisfaction.It is worthy of clinical promotion.
文摘Introduction About 72%of human genome is transcribed to non-coding RNAs,which have captivated researchers a lot for shedding light on their pivotal roles in regulating the initiation and progression of various diseases,including cancers[1].Among these,long non-coding RNAs(lncRNAs)have emerged as key players in the complex landscape of gene regulation.LncRNAs perform a variety of roles,including scaffolding to encourage the interaction of related proteins,decoys to thwart transcriptional factors from the target gene’s promoter,sponges of linked miRNA to prevent target gene destruction,and guide molecules to recruit components for chromatin remodeling[1].Many cancers are closely related to age[2-5]and such patients are expected be increased gradually as almost 20%of the world’s population will be 65 or older by 2030[6]and those over the age of 65 have an 11-fold higher incidence of cancer than people under that age[7].As one of the typical hallmarks of aging[8],cellular senescence is Cellular senescence is induced by stressful insults and certain physiological processes and is characterized by a prolonged and essentially irreversible cell-cycle arrest with secretory features,macromolecular damage,and altered metabolism[9].Here,we aim to provide insights of the intersection between lncRNAs,cellular senescence,and urinary tumors,unraveling the potential implications and therapeutic avenues within this multifaceted network.
基金This study was financially supported by Henan Youth Science Foundation of Henan Province(No.232300421310)Postdoctoral Foundation of China(No.2022M711080)+4 种基金The National Natural Science Foundation of China(No.82274612)Program for Science&Technology Innovation Talents in Universities of Henan Province(No.23HASTIT044)Innovative Research Team(in Science and Technology)in University of Henan Province(21IRTSTHN026)Henan Province Traditional Chinese Medicine Scientific Research Special Project(No.2022ZYZD21)Joint Research Fund of Science and Technology R&D Plan of Henan Province(NO.222301420068).
文摘Parkinson’s disease(PD)is characterized by motor symptoms and non-motor symptoms chiefly attributed to the loss of dopaminergic neurons in the substantia nigra pars compacta[1].Approximately 3 million PD patients suffer from motor deficits including tremors,muscle rigidity,bradykinesia and psychological abnormality[2].The main pathological change of PD is the degeneration and death of dopaminergic neurons in the substantia nigra pars compacta,which leads to a significant decrease in dopamine content in the striatum.The pathogenesis of PD is fairly complex.Genetic factors,environmental factors,aging,oxidative stress,and inflammation may be related to the degeneration and death of PD dopaminergic neurons[3].
基金This study was financially supported by the National Natural Science Foundation of China(No.82271563 and No.82204786)The Natural Science Foundation of Guangdong Province of China(No.2022A1515012512)The Academic Promotion Program of Shandong First Medical University.
文摘Parkinson’s disease(PD)is a prevalent neurological disorder around the globe,currently affecting over 6 million people globally[1].It is estimated that by 2040,this number may double to more than 12 million[2].Aging is strongly associated with PD,as it is a significant risk factor for its development[3].Clinically,PD presents with various motor and non-motor signs.Movement-related issues mainly consist of slowed motion,involuntary shaking at rest,stiff muscles,and balance difficulties.At the same time,non-movement-related issues include impaired sense of smell,sleep disturbances,bowel irregularities,feelings of sadness,and problems with the body’s automatic functions[4].The typical pathological features of PD patients include the gradual loss of dopaminergic neurons within the substantia nigra pars compacta,coupled with the buildup ofα-synuclein(α-Syn)in neurons,the aggregates of which form inclusions known as Lewy bodies[5].The A53T mutant of humanα-Syn has a propensity to aggregate,a characteristic closely associated with the neurotoxicity seen in familial PD[6].A synthesis of both in vitro and in vivo research indicates that the misfolding and aggregation ofα-Syn are key pathogenic mechanisms in the development of PD[7-9].
文摘Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, characterized by a progressive decline in cognitive ability. Around 50 million people worldwide are reportedly affected, with annual losses estimated at about $1 trillion [1]. Nevertheless, there remains unknown about the exact pathological mechanisms of AD and currently available treatments have a lack of efficacy. Thus, experts have reached a consensus that interventions in the preclinical stage of AD should be prioritized [2], especially when the amount of patients is set to reach 78 million by the end of this decade [3]. Recently, the proposition “integrating food and nutrition into healthcare” has been promoted [4]. Prevention from dietary eating and drinking may be an effective and age-friendly method. Nowadays, many beverages have been proven to offer great preventative benefits to AD like coffee, soy milk, tea, and wine. Coffee, consumed by tens of thousands of people every day, has been proven in several epidemiological studies to have a protective effect against AD [5-7]. A study including 411 individuals shows that significant negative correlation between stratified lifetime coffee intake and β-amyloid positivity [8]. In other words, higher coffee intake (≥ 2 cups/day) is associated with lower risk of AD. However, a Mendelian randomization (MR) analysis came to the opposite conclusion, with an additional 1 cup of coffee per day being associated with a 1.16-fold increased risk of developing AD [9]. In meta-analyses of cohort studies, it was proposed that there was a non-linear “U-shaped” link between coffee consumption and AD, with 3-4 cups per day being optimal [10]. In addition to the possibility that different conclusions are due to inconsistent estimations of coffee intake and populations in these studies, research recently proposed a hypothesis that the cytochrome P450 1A2 played an essential role in the metabolism of coffee in the human body [11]. Rs762551 is its most representative and commonly studied single nucleotide polymorphism. In detail, carriers of the rs762551 gene metabolize caffeine more rapidly and are at greater risk of developing AD when they consume large amounts of coffee. Conversely, people with slow caffeine metabolism who consume more coffee would have a preventive effect on AD, which might be a result of being exposed to coffee for a longer duration of time to the point of absorbing more potential beneficial effects of caffeine.
文摘Cardiovascular diseases(CVDs),encompassing diverse pathologies such as atherosclerosis,hypertension,cardiomyopathy,arrhythmia,and valvular diseases,represent a significant public health challenge,severely undermining human health[1].According to the World Health Organization,CVDs claimed approximately 17.9 million deaths in 2019,representing 32%of all global deaths[2,3].The risk of CVDs morbidity and mortality increases with age,with the majority of CVDs and deaths occurring in elderly aged 75 years and older[4,5].In developed nations,CVDs are the principal cause of mortality,while in developing countries,they are a leading cause of death as well.
基金supported by the Natural Science Foundation of Inner Mongolia(No.2021MS08169)the Medical and health Science and Technology Project of Inner Mongolia(No.202201571).
文摘Background:The occurrence of early neurological deterioration following intravenous thrombolysis(IVT)is considered a particularly ominous clinical event and is strongly correlated with poor outcomes.Initiating tirofiban within 24 h after IVT has been suggested as a better treatment option to achieve long-term functional outcomes.However,the rationality of this remedy is a controversial.The purpose of the study was to evaluate the safety and efficacy of early intravenous tirofiban administration after IVT in patients with acute ischemic stroke(AIS).Methods:Databases including PubMed,EMBASE,Cochrane Library,and Web of Science were searched for clinical trials on early tirofiban implementation after IVT in patients with AIS from inception to September 2022.Odds ratios(ORs)were generated for dichotomous variants via meta-analysis using STATA 17.0 MP.Results:Five clinical trials with 725 patients were eligible.The study outcomes demonstrated that early tirofiban administration after IVT was not associated with symptomatic intracranial hemorrhage(OR,0.78;95%confidence interval(CI),0.22–2.74;P=0.70),asymptomatic intracranial hemorrhage(OR,1.11;95%CI,0.52–2.37;P=0.80),systemic bleeding(OR,0.97;95%CI,0.42–2.23;P=0.94),and death(OR,1.05;95%CI,0.47–2.31;P=0.91),but may reduce the incidence of early neurological deterioration(OR,0.09;95%CI,0.02–0.50;P=0.01),and was significantly associated with 90-day excellent(modified Rankin scale score 0–1)(OR,2.01;95%CI,1.35–3.02;P=0.00)and favorable(modified Rankin scale score 0–2)(OR,2.30;95%CI,1.63–3.23;P=0.00)functional outcomes.Conclusion:The early intravenous administration of tirofiban after IVT in patients with AIS may be a safe and effective treatment strategy that improves long-term neurological functional outcomes without increasing the risk of adverse events.
基金supported by funding from the Key Research and Development Program of Sichuan(2021YFS0382 to CX)the Medical Research Project of Jiangsu Commission of Health(M2022004 to CWL)+2 种基金Huai'an Natural Science Research Program(HAB202239 to CWL)the National Natural Science Foundation of China(General Program)(82271524 to LWD)the National Natural Science Foundation of China(Key Program)(32220103006 to LWD).
文摘Tremendous research efforts have been made regarding the pathogenesis of Parkinson’s disease(PD).However,there are still no effective strategies to restore midbrain dopaminergic(mDA)innervation and prevent disease progression.One possibility is that we may have been neglecting the role of axons in mDA neuronal degeneration.This review first summarizes mDA axon development during the early stage of PD and discusses how axon guidance defects contribute to PD vulnerability.Furthermore,we review axonal transport dysregulation in the numerous PD-related genetic mutations,including Parkin,PINK1,DJ1,LRRK2 and SNCA.The evidence suggests that proper axonal transport is crucial for neuronal function and survival.Finally,advanced tools for axonal studies were evaluated,including light-sheet and super-resolution microscopy.These adapted microscopes have been used to help solve questions unanswered before.Overall,the role of axon terminals in the initiation of the degeneration cascade remains undeciphered,and more research in the related area may be conducted further to restore dopamine levels in the striatum to alleviate the motor complications of PD.
基金supported by the Fundamental Research Funds for the Central Universities(No.21lzujbkydx036).
文摘Traditional Chinese medicine(TCM)has rich theories and techniques for health maintenance.Its cultural tradition of emphasizing health maintenance is not only related to its medical function of treating injuries and diseases and prolonging life span but also closely related to Daoism,which is the fundamental religious tenet of pursuing immortality in Chinese culture.As this paper reviews,the fanatical Daoist religious culture of pursuing immortality has influenced the formation of a medical culture in TCM that cares about longevity and values health and wellness.However,this health and wellness culture is more practical–it replaces immortality with longevity as the goal.The Daoist religious concept of longevity is preserved in the basic principles and ethical values of health care:it emphasizes the harmony and consistency of the spirit and the body.It turns a lifestyle of maintaining physical and spiritual health into the pursuit of an ideal state of life.As for the specific Daoist health techniques,there are various cases of inheritance,change or abandonment:TCM inherited most of the drugs and prescriptions from the Daoist longevity techniques based on natural medicines taking and formed a popular health culture of medicinal and dietary supplements;TCM also developed internal health techniques such as internal elixir and breathing practice from Daoist internal health maintenance techniques for physical health care and disease treatment;TCM did not completely accept recipe techniques such as inedia and sex manual from Daoism because they contradicted with its secularization concept,but their general value orientation of lightness and low desire also influenced its concept of health care.
基金funding agency in the public,commercial,or not-for-profit sectors.
文摘Background:The liver is fundamental for keeping up the entire body’s homeostasis.The liver hepatocytes have been shown to undergo genomic instability with aging.The stability of the hepatocytes depends on its nuclear architecture.Calorie restriction has been shown to extend life-span favorably and this may be through the reorganization of the nuclear structure.Objective:To study the effect of cyclic feeding regime on the chromatin assembly anchored to the nuclear membrane scaffold of rat models hepatocytes nuclei.Method:Rats models underwent cyclic feeding regime,after which nuclei were isolated;then,we investigated the chromatin decondensation and nuclear membrane disintegration of the hepatocytes using fluorescence imaging methods.Results:In 60 seconds,protease decondensed the chromatin and disintegrated the nuclear membrane structure of controls.After the first fasting,the time increased to 145 seconds in 3-month-old rats.The first refeeding increased the time to 156 seconds with a further rise to 340 seconds following the second fasting,then dropped to 116 seconds by the second refeeding.20 months old rats showed 186 seconds increase in the time of chromatin decondensation and nuclear membrane disintegration after the first fasting,with a decrease to 140 seconds observed after first refeeding.The second fasting increased the time to 165 seconds,which then slightly decreased to 163 seconds after the second refeeding.Conclusion:These results show that intermittent fasting may have acted on chromatin histone interactions and the structural lamin networks of the nuclear membranes in bringing about nuclear stability,which is essential for normal cellular function.
基金supported by the Intramural Research Programs of National Institute on Aging,NIH(HC,ZIA AG000944,AG000928).
文摘Parkinson’s disease(PD)is the second most common degenerative neurological disorder after Alzheimer’s disease.As one of fastest growing neurological conditions,PD affects millions of elderly people worldwide.PD patients display progressive motor symptoms,including resting tremor,slowed movement,impaired posture and balance,and rigid muscles[1].Additionally,they also often suffer from chronic pain,depression,dementia,and other non-motor symptoms[2].Medications and surgery can improve patient’s motor performance to some degree,while the treatment for non-motor conditions is limited.Moreover,long-term medication can cause severe side effects,such as dyskinesia and impulse control disorders[3,4].Therefore,new mechanistic insights and therapeutic agents/procedures are still needed to improve the treatment of increasing number of PD patients.