Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
At the present,association of mitochondrial dysfunction and progression of neurological disorders has gained significant attention.Defects in mitochondrial network dynamics,point mutations,deletions,and interaction of...At the present,association of mitochondrial dysfunction and progression of neurological disorders has gained significant attention.Defects in mitochondrial network dynamics,point mutations,deletions,and interaction of pathogenomic proteins with mitochondria are some of the possible underlying mechanisms involved in these neurological disorders.Mitochondrial genetics,defects in mitochondrial oxidative phosphorylation machinery,and reactive oxygen species production might share common crosstalk in the progression of these neurological disorders.It is of significant interests to explore and develop therapeutic strategies aimed at correcting mitochondrial abnormalities.This review provided insights on mitochondrial dysfunction/mutations involved in the progression of Alzheimer’s disease,Huntington’s disease,and epilepsy with a special focus on Parkinson’s disease pathology.Along with the deleterious effects of mitochondrial mutations in aforesaid neurological disorders,this paper unraveled the available therapeutic strategy,specifically aiming to improve mitochondrial dysfunction,drugs targeting mitochondrial proteins,gene therapies aimed at correcting mutant mtDNA,peptide-based approaches,and lipophilic cations.展开更多
In 1945,Porter et al.published an electon microscopy study of cultured chick fibroblasts in which they observed：＇a granular background and details of a darker lacelike reticulum which in places appears to be made up...In 1945,Porter et al.published an electon microscopy study of cultured chick fibroblasts in which they observed：＇a granular background and details of a darker lacelike reticulum which in places appears to be made up of chains of＂vesicles＂＇（Porter et al.,1945）.This constituted the first published observation of the endoplasmic reticulum（ER）and,while it was not evident at that time,this cytoplasmic system of interconnecting membrane-lined channels, comprising vesicles, tubules and cisternae, has numerous important functions.展开更多
Wound healing is a complex and multistep biological process that involves the cooperation of various cell types.Programmed cell death,including apoptosis and necrotizing apoptosis,plays a crucial role in this process....Wound healing is a complex and multistep biological process that involves the cooperation of various cell types.Programmed cell death,including apoptosis and necrotizing apoptosis,plays a crucial role in this process.Apoptosis,a controlled and orderly programmed cell death regulated by genes,helps eliminate unnecessary or abnormal cells and maintain internal environmental stability.It also regulates various cell functions and contributes to the development of many diseases.In wound healing,programmed cell death is essential for removing inflammatory cells and forming scars.On the other hand,necroptosis,another form of programmed cell death,has not been thoroughly investigated regarding its role in wound healing.This review explores the changes and apoptosis of specific cell groups during wound healing after an injury and delves into the potential underlying mechanisms.Furthermore,it briefly discusses the possible mechanisms linking wound inflammation and fibrosis to apoptosis in wound healing.By understanding the relationship between apoptosis and wound healing and investigating the molecular mechanisms involved in apoptosis regulation,new strategies for the clinical treatment of wound healing may be discovered.展开更多
Multiple sclerosis is a chronic immune-mediated disorder of the central nervous system characterized by demyelination,axonal loss,and neuroinflammation,culminating in progressive neurological disability.Despite signif...Multiple sclerosis is a chronic immune-mediated disorder of the central nervous system characterized by demyelination,axonal loss,and neuroinflammation,culminating in progressive neurological disability.Despite significant advances in understanding its immunopathogenesis,current immunotherapies remain limited in their ability to halt disease progression,making multiple sclerosis incurable and highlighting the critical need for novel therapeutic strategies.Antigen-specific immunotherapy represents a groundbreaking approach that aims to restore immune tolerance to myelin-derived antigens while preserving the protective functions of the immune system.Unlike broad immunosuppressive strategies,antigen-specific immunotherapy offers the potential for highly targeted modulation of pathogenic immune responses,reducing off-target effects and enhancing safety profiles.Over the last two decades,preclinical studies and clinical trials have explored diverse antigen-specific immunotherapy modalities,ranging from peptide-based vaccines to nanoparticle platforms,each aimed at achieving durable tolerance in multiple sclerosis.This review provides a comprehensive overview of multiple sclerosis,covering its etiology,clinical features,pathogenesis,pathology,and current therapeutic approaches.Thus,it delves into the current state of antigen-specific immunotherapy research,critically examining its successes and limitations while addressing the translational challenges that must be overcome to realize its therapeutic potential.By integrating insights from immunology,biotechnology,and translational medicine,we propose directions for advancing antigen-specific approaches in the quest for transformative multiple sclerosis therapies.展开更多
Anxiety disorders,characterized by persistent apprehension,somatic symptoms and fatigue,are leading causes of disability worldwide.The burgeoning therapeutic potential of aerobic exercise has gained prominence as a le...Anxiety disorders,characterized by persistent apprehension,somatic symptoms and fatigue,are leading causes of disability worldwide.The burgeoning therapeutic potential of aerobic exercise has gained prominence as a leading non-pharmacological strategy,with evidence supporting its effectiveness in alleviating anxiety across diverse conditions.This review synthesizes current research to clarify the molecular mechanisms through which aerobic exercise ameliorates anxiety in terms of the effects of exercise on the hypothalamic–pituitary–adrenal(HPA)axis,the hepatic-brain axis and epigenetics;electroencephalographic alterations;inflammatory pathways;the balance between oxidative and nitrogenous stress;various substances,such as brain-derived neurotrophic factor(BDNF),atrial natriuretic peptide(ANP),and opioid peptides;and the 5-HT2C receptor and cannabinoid receptor type-1(CB1R),among others,reflecting the positive modulatory effects of aerobic exercise on anxiety.As a non-pharmacological intervention,aerobic exercise has been demonstrated to be useful in a variety of medical applications and has considerable potential for ameliorating symptoms of anxiety.展开更多
Huntington’s disease is a genetic disease caused by expanded CAG repeats on exon 1 of the huntingtin gene located on chromosome 4.Compelling evidence implicates impaired mitochondrial energetics,altered mitochondrial...Huntington’s disease is a genetic disease caused by expanded CAG repeats on exon 1 of the huntingtin gene located on chromosome 4.Compelling evidence implicates impaired mitochondrial energetics,altered mitochondrial biogenesis and quality control,disturbed mitochondrial trafficking,oxidative stress and mitochondrial calcium dyshomeostasis in the pathogenesis of the disorder.Unfortunately,conventional mitochondrial-targeted molecules,such as cysteamine,creatine,coenzyme Q10,or triheptanoin,yielded negative or inconclusive results.However,future therapeutic strategies,aiming to restore mitochondrial biogenesis,improving the fission/fusion balance,and improving mitochondrial trafficking,could prove useful tools in improving the phenotype of Huntington’s disease and,used in combination with genome-editing methods,could lead to a cure for the disease.展开更多
The global healthcare landscape is increasingly challenged by the rising prevalence of chronic diseases and the demographic shift towards an aging population,necessitating the development of innovative and sustainable...The global healthcare landscape is increasingly challenged by the rising prevalence of chronic diseases and the demographic shift towards an aging population,necessitating the development of innovative and sustainable healthcare solutions.In this context,the emergence of triboelectric energy harvesters as a key technological breakthrough offers a viable pathway towards self-powered,efficient,and sustainable personal health management.This review critically examines the transformative potential of triboelectric nanogenerators(TENGs)in addressing the pressing challenges of modern healthcare,underscoring their unique benefits such as being battery-free,easy to fabricate,and cost-efficient.We begin by reviewing the fundamental mechanisms of triboelectrification at the atomic scale and presenting the contact electrification among various materials,such as metals,polymers,and semiconductors.The discussion subsequently extends to the commonly used materials for TENGs and explores advancements in their design and functionality,with an emphasis on structural and chemical innovations.Furthermore,the application spectrum of TENGs in personal health management is extensively reviewed,covering aspects including health monitoring,therapeutic intervention,health protection,and device powering,while highlighting their capacity for self-sustainability.The review concludes by addressing existing challenges while mapping out the latest significant contributions and prospective directions in TENG-based healthcare innovations.By facilitating a paradigm shift towards a more autonomous,cost-effective,and personalized healthcare model,independent of external power sources,TENGs are poised to markedly enhance the quality of care and overall well-being,marking the dawn of a new era in integrated personal health management.展开更多
The hematopoietic system stands as a cornerstone of organismal physiology,maintaining lifelong blood cell production while serving critical roles in immune defense and tissue homeostasis.With advancing age,this precis...The hematopoietic system stands as a cornerstone of organismal physiology,maintaining lifelong blood cell production while serving critical roles in immune defense and tissue homeostasis.With advancing age,this precisely regulated system undergoes progressive functional decline,driven by interconnected changes in hematopoietic stem cells(HSCs),their bone marrow(BM)niche,and systemic factors,all of which contribute to aging-related hematopoietic disorders.In this editorial,we synthesize these advances and explore how emerging insights into hematopoietic aging mechanisms present opportunities for developing targeted therapeutic interventions against age-related hematopoietic decline and its clinical consequences.展开更多
Increasing numbers of long noncoding RNAs(lncRNAs)are implicated in breast cancer oncogenicity.However,the contribution of LINC02568 toward breast cancer progression remains unclear and requires further investigation....Increasing numbers of long noncoding RNAs(lncRNAs)are implicated in breast cancer oncogenicity.However,the contribution of LINC02568 toward breast cancer progression remains unclear and requires further investigation.Herein,we evaluated LINC02568 expression in breast cancer and clarified its effect on disease malignancy.We also investigated the mechanisms underlying the pro-oncogenic role of LINC02568.Consequently,LINC02568 was upregulated in breast cancer samples,with a notable association with worse overall survival.Functionally,depleted LINC02568 suppressed cell proliferation,colony formation,and metastasis,whereas LINC02568 overexpression exerted the opposite effects.Our mechanistic investigations suggested that LINC02568 was physically bound to and sequestered microRNA-874-3p(miR-874-3p).Furthermore,miR-874-3p mediated suppressive effects in breast cancer cells by targeting cyclin E1(CCNE1).LINC02568 positively controlled CCNE1 expression by sequestering miR-874-3p.Rescue experiments revealed that increased miR-874-3p or decreased CCNE1 expression recovered cell growth and motility functions induced by LINC02568 in breast cancer cells.In conclusion,the tumor-promoting functions of LINC02568 in breast cancer cells were enhanced by sequestering miR-874-3p and consequently over-expressing CCNE1.Our data may facilitate the identification of novel therapeutic targets in clinical settings.展开更多
This article explores the intricate relationship between attachment styles formed during early childhood and the subsequent responses to traumatic events, particularly the death of a parent. Drawing on the theoretical...This article explores the intricate relationship between attachment styles formed during early childhood and the subsequent responses to traumatic events, particularly the death of a parent. Drawing on the theoretical framework of attachment theory and incorporating contemporary research, the paper discusses how parental interactions shape the neural circuitry of infants and children, influencing their ability to form secure or insecure attachments. These attachment styles, in turn, play a critical role in determining the child’s coping mechanisms when faced with trauma. This paper focuses on trying to understand how attachment theory is connected to the reaction to trauma with a highlight on the four major styles of attachments which are secure, anxious, avoidant, and disorganized to mention but a few, and how they influence stress and adversity in children. Attachment theory holds that human beings’ ability to form affectional bonds in infancy determines their patterns of relatedness across the life cycle. The type of attachment that is secure usually supports healthy adaptation and good coping mechanisms regardless of the trauma in the childhood of the child. While secure attachment mostly facilitates favorable trauma-related outcomes, anxious or avoidant attachment can exacerbate or alter the responses. The caregiving system that is avoidant attachment has implications of autonomous self-functioning which has features of suppression of the emotional response and poor search for emotional support during stress. From the principles of developmental psychology and trauma theory, the paper also focuses on the major significance of the child’s early caregivers’ interactions that define the resilience and vulnerability factor. This knowledge is therefore critical in designing specific interventions based on the improvement of coping behaviors and emotional regulatory systems of children who have been exposed to trauma. Finally, we have the synthesis of new knowledge about the role of secure attachment relationships as its fundamental element in shaping adaptive traumatization and psychological development. The article also delves into the physiological processes involved in emotional regulation and the role of cortisol in disrupting attachment. Finally, the implications of these findings for therapeutic interventions and the challenges of addressing prolonged grief and traumatic responses in clinical settings are considered.展开更多
Cancer is a complex disease influenced by various factors,including DNA damage,growth signals,and inflammation.Although inflammation has commonly not been considered carcinogenic,increasing evidence indicates its subs...Cancer is a complex disease influenced by various factors,including DNA damage,growth signals,and inflammation.Although inflammation has commonly not been considered carcinogenic,increasing evidence indicates its substantial involvement in the onset and progression of cancer,especially in the presence of chronic microbial infections.This review thoroughly analyzes the complex relationship between cancer,health,and inflammation by introducing pathological and physiological features of inflammation.The study explores the various factors that might enhance inflammation,including infections and para-inflammation caused by tissue stress.It will also explore the changing comprehension of microorganisms about health and illness,clarifying their possible influence on the development of several malignancies,including colon,pancreatic,gastric,and prostate cancers.In addition,the study emphasizes the development of new therapy approaches that specifically target chronic inflammations and their associated cancers.This review seeks to enhance the comprehension of the intricate correlation between cancer,inflammation,and human health by combining existing research.展开更多
Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels resulting from im-paired insulin secretion or insulin resistance.Diabetes poses a major global health concern,because of...Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels resulting from im-paired insulin secretion or insulin resistance.Diabetes poses a major global health concern,because of its increasing prevalence and substantial morbidity and mortality.This review explores the relationships between altered fatty acid metabolism and microcirculatory impairments in diabetes.Dysregulation of fatty acid metabolism in diabetes leads to changes in fatty acid profiles,abnormal lipid accumulation,and increased oxidative stress.These changes contribute to microvascular dysfunction through mechanisms such as endothelial dysfunction,impaired nitric oxide availability,inflammation,and oxidative damage.Understanding this intricate interplay is essential for identifying novel thera-peutic strategies to alleviate vascular complications in diabetes.By targeting specific pathways involved in fatty acid metabolism and microvascular dysfunction,interventions can be developed to improve patient outcomes.This review is aimed at contributing to future research and the development of effective strategies for preventing and managing dia-betes-associated microcirculatory impairments,to ultimately enhance the quality of life for people living with diabetes.展开更多
Obesity,a global health concern,is associated with severe health issues like type 2 diabetes,heart disease,and respiratory complications.It also increases the risk of various cancers,including melanoma,endometrial,pro...Obesity,a global health concern,is associated with severe health issues like type 2 diabetes,heart disease,and respiratory complications.It also increases the risk of various cancers,including melanoma,endometrial,prostate,pancreatic,esophageal adenocarcinoma,colorectal carcinoma,renal adenocarcinoma,and pre-and post-menopausal breast cancer.Obesity-induced cellular changes,such as impaired CD8^(+)T cell function,dyslipi-demia,hypercholesterolemia,insulin resistance,mild hyperglycemia,and fluctuating levels of leptin,resistin,adiponectin,and IL-6,contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes.Adipocytes release leptin,a pro-inflammatory substance that stimulates cancer cell proliferation,inflammation,and invasion,altering the tumor cell metabolic pathway.Adiponectin,an insulin-sensitizing adipokine,is typically downregulated in obese individuals.It has antipro-liferative,proapoptotic,and antiangiogenic properties,making it a potential cancer treatment.This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer,draw-ing on an extensive,though non-systematic,survey of the recent literature.This approach allows us to integrate and synthesize findings from various studies,offering a cohesive perspective on emerging themes and potential therapeutic targets.The review explores the metabolic disturbances,cellular alterations,inflammatory responses,and shifts in the tumor microenvironment that contribute to the obesity-cancer link.Finally,it discusses poten-tial therapeutic strategies aimed at disrupting these connections,offering valuable insights into future research directions and the development of targeted interventions.展开更多
Since its inauguration in 2003, China Interventional Therapeutics （CIT） congress has witnessed the growth of percutaneous cardiovascular intervention in China. In 2003 the total number ofpercutaneous coronary interv...Since its inauguration in 2003, China Interventional Therapeutics （CIT） congress has witnessed the growth of percutaneous cardiovascular intervention in China. In 2003 the total number ofpercutaneous coronary intervention （PCI） in China was about 40 000 cases,1 while by CIT＇s 10th anniversary in 2012, the annual number of PCI in China had reached 340 000 cases. CIT has grown along with PCI practice in the country; last year the CIT congress hosted 6000 attendees, including 180 international faculty members and over 750 foreign participants from 42 countries or regions.展开更多
Objective To explore the efficacy of transcatheter closure of patent ductus arteriosus (PDA) with detachable coil and Amplatzer duct occluder (ADO). Methods Transcatheter colsure of PDA was performed in 160 case...Objective To explore the efficacy of transcatheter closure of patent ductus arteriosus (PDA) with detachable coil and Amplatzer duct occluder (ADO). Methods Transcatheter colsure of PDA was performed in 160 cases, aged 4.56±2.67 years, of whom 3 had residual shunt after surgical ligation, 2 had pulmomary stenosis (PS), 1 had coarctation of aorta (COA), 1 had right aortic arch, and 2 had atrial septal defect (ASD). Results Detachable coils (Duct Occlude pfm or Cook Inc) were successfully used in 51 patients with a smallest PDA diameter of 1.86±0.78mm. Amplatzer duct occluders were also successfully performed in other 109 with a moderate to large PDA diameter of 3.89±1.32mm, of whom 3 with PS or COA were performed balloon dilation firstly, and 2 with ASD were performed PDA occlusion firstly; 1 month to 4.8 years follow-up coil or Amplatzer device closure of PDA showed that neither residual shunt nor any complication. Conclusion It is suggested that the detachable coil and Amplatzer duct occluder are simple and safe for the catheter closure from small to large sized PDA.展开更多
The recent outbreak of the human Zaire ebolavirus(EBOV)epidemic is spiraling out of control in West Africa.Human EBOV hemorrhagic fever has a case fatality rate of up to 90%.The EBOV is classified as a biosafety level...The recent outbreak of the human Zaire ebolavirus(EBOV)epidemic is spiraling out of control in West Africa.Human EBOV hemorrhagic fever has a case fatality rate of up to 90%.The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention,with no approved therapies and vaccines available for its treatment apart from supportive care.Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial,the current epidemic might be outpacing the speed at which drugs and vaccines can be produced.Like all viruses,the EBOV largely relies on host cell factors and physiological processes for its entry,replication,and egress.We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies.Most of the therapeutic agents in this review are directed against non-mutable targets of the host,which is independent of viral mutation.These medications are approved by the Food and Drug Administration(FDA)for the treatment of other diseases.They are available and stockpileable for immediate use.They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.展开更多
Molecular chaperones,a class of complex client regulatory systems,play significant roles in the prevention of protein misfolding and abnormal aggregation,the modulation of protein homeostasis,and the protection of cel...Molecular chaperones,a class of complex client regulatory systems,play significant roles in the prevention of protein misfolding and abnormal aggregation,the modulation of protein homeostasis,and the protection of cells from damage under constantly changing environmental conditions.As the understanding of the biological mechanisms of molecular chaperones has increased,their link with the occurrence and progression of disease has suggested that these proteins are promising targets for therapeutic intervention,drawing intensive interest.Here,we review recent advances in determining the structures of molecular chaperones and heat shock protein 90(HSP90)chaperone system complexes.We also describe the features of molecular chaperones and shed light on the complicated regulatory mechanism that operates through interactions with various co-chaperones in molecular chaperone cycles.In addition,how molecular chaperones affect diseases by regulating pathogenic proteins has been thoroughly analyzed.Furthermore,we focus on molecular chaperones to systematically discuss recent clinical advances and various drug design strategies in the preclinical stage.Recent studies have identified a variety of novel regulatory strategies targeting molecular chaperone systems with compounds that act through different mechanisms from those of traditional inhibitors.Therefore,as more novel design strategies are developed,targeting molecular chaperones will significantly contribute to the discovery of new potential drugs.展开更多
China’s newborn screening(NBS)system,initiated over four decades ago with dual-disease detection[phenylketonuria(PKU)and congenital hypothyroidism(CH)],has progressively expanded to encompass congenital adrenocortica...China’s newborn screening(NBS)system,initiated over four decades ago with dual-disease detection[phenylketonuria(PKU)and congenital hypothyroidism(CH)],has progressively expanded to encompass congenital adrenocortical hyperplasia(CAH)and glucose-6-phosphate dehydrogenase(G6PD)deficiency,achieving nationwide universal coverage.This systematic progression has substantially elevated diagnostic rates for these disorders,enabling timely therapeutic interventions[1].Over the past two decades,technological innovations—notably the integration of tandem mass spectrometry(MS/MS)platforms in pioneering regions such as Shanghai and Zhejiang—have extended NBS to over 40 inherited metabolic diseases(IMDs).展开更多
Protein citrullination involves the deimination of arginine or methylarginine resi-dues in peptide chains to form citrulline by peptidyl arginine deiminases.This process is an important protein post-translational modi...Protein citrullination involves the deimination of arginine or methylarginine resi-dues in peptide chains to form citrulline by peptidyl arginine deiminases.This process is an important protein post-translational modification that affects molecular structure and func-tion of various proteins,including histones.In recent years,protein citrullination has attracted widespread attention for its influence on gene transcription.Studies on the impact of protein citrullination modification on chromatin structure remodeling and the establishment of gene regulatory networks have made rapid progress.In this review,we briefly summarize the phys-iological functions of protein citrullination modification.Specifically,we comprehensively outline the latest progress in the study of the role of protein citrullination modification in gene transcription regulation,focusing on the interaction of protein citrullination with other post-translational modifications.展开更多
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
文摘At the present,association of mitochondrial dysfunction and progression of neurological disorders has gained significant attention.Defects in mitochondrial network dynamics,point mutations,deletions,and interaction of pathogenomic proteins with mitochondria are some of the possible underlying mechanisms involved in these neurological disorders.Mitochondrial genetics,defects in mitochondrial oxidative phosphorylation machinery,and reactive oxygen species production might share common crosstalk in the progression of these neurological disorders.It is of significant interests to explore and develop therapeutic strategies aimed at correcting mitochondrial abnormalities.This review provided insights on mitochondrial dysfunction/mutations involved in the progression of Alzheimer’s disease,Huntington’s disease,and epilepsy with a special focus on Parkinson’s disease pathology.Along with the deleterious effects of mitochondrial mutations in aforesaid neurological disorders,this paper unraveled the available therapeutic strategy,specifically aiming to improve mitochondrial dysfunction,drugs targeting mitochondrial proteins,gene therapies aimed at correcting mutant mtDNA,peptide-based approaches,and lipophilic cations.
文摘In 1945,Porter et al.published an electon microscopy study of cultured chick fibroblasts in which they observed：＇a granular background and details of a darker lacelike reticulum which in places appears to be made up of chains of＂vesicles＂＇（Porter et al.,1945）.This constituted the first published observation of the endoplasmic reticulum（ER）and,while it was not evident at that time,this cytoplasmic system of interconnecting membrane-lined channels, comprising vesicles, tubules and cisternae, has numerous important functions.
基金supported by grants from the National Natural Science Foundation of China(82160770,81960741)the Guizhou Provincial Natural Science Foundation(QKH-J-2020-1Z070)+2 种基金Outstanding Young Scientific and Technological Talents Project of Guizhou Province(20215639)Zunyi Science and Technology Talent Platform Carrier Construction Project(ZSKRPT20231)Scientific and Technological Innovation Talent Team of Guizhou Province(CXTD[2023]024).
文摘Wound healing is a complex and multistep biological process that involves the cooperation of various cell types.Programmed cell death,including apoptosis and necrotizing apoptosis,plays a crucial role in this process.Apoptosis,a controlled and orderly programmed cell death regulated by genes,helps eliminate unnecessary or abnormal cells and maintain internal environmental stability.It also regulates various cell functions and contributes to the development of many diseases.In wound healing,programmed cell death is essential for removing inflammatory cells and forming scars.On the other hand,necroptosis,another form of programmed cell death,has not been thoroughly investigated regarding its role in wound healing.This review explores the changes and apoptosis of specific cell groups during wound healing after an injury and delves into the potential underlying mechanisms.Furthermore,it briefly discusses the possible mechanisms linking wound inflammation and fibrosis to apoptosis in wound healing.By understanding the relationship between apoptosis and wound healing and investigating the molecular mechanisms involved in apoptosis regulation,new strategies for the clinical treatment of wound healing may be discovered.
基金funding from the MCIN/AEI/10.13039/501100011033the European Union-NextGenerationEU/PRTR through the CPP2021-008475 project+1 种基金supported by the“Agència de Gestiód’Ajuts Universitaris i de Recerca”(AGAURGeneralitat de Catalunya)through Consolidated Research Groups 2021SGR00782.
文摘Multiple sclerosis is a chronic immune-mediated disorder of the central nervous system characterized by demyelination,axonal loss,and neuroinflammation,culminating in progressive neurological disability.Despite significant advances in understanding its immunopathogenesis,current immunotherapies remain limited in their ability to halt disease progression,making multiple sclerosis incurable and highlighting the critical need for novel therapeutic strategies.Antigen-specific immunotherapy represents a groundbreaking approach that aims to restore immune tolerance to myelin-derived antigens while preserving the protective functions of the immune system.Unlike broad immunosuppressive strategies,antigen-specific immunotherapy offers the potential for highly targeted modulation of pathogenic immune responses,reducing off-target effects and enhancing safety profiles.Over the last two decades,preclinical studies and clinical trials have explored diverse antigen-specific immunotherapy modalities,ranging from peptide-based vaccines to nanoparticle platforms,each aimed at achieving durable tolerance in multiple sclerosis.This review provides a comprehensive overview of multiple sclerosis,covering its etiology,clinical features,pathogenesis,pathology,and current therapeutic approaches.Thus,it delves into the current state of antigen-specific immunotherapy research,critically examining its successes and limitations while addressing the translational challenges that must be overcome to realize its therapeutic potential.By integrating insights from immunology,biotechnology,and translational medicine,we propose directions for advancing antigen-specific approaches in the quest for transformative multiple sclerosis therapies.
基金supported by the National Natural Science Foundation of China(No.82405550 and No.82374584).
文摘Anxiety disorders,characterized by persistent apprehension,somatic symptoms and fatigue,are leading causes of disability worldwide.The burgeoning therapeutic potential of aerobic exercise has gained prominence as a leading non-pharmacological strategy,with evidence supporting its effectiveness in alleviating anxiety across diverse conditions.This review synthesizes current research to clarify the molecular mechanisms through which aerobic exercise ameliorates anxiety in terms of the effects of exercise on the hypothalamic–pituitary–adrenal(HPA)axis,the hepatic-brain axis and epigenetics;electroencephalographic alterations;inflammatory pathways;the balance between oxidative and nitrogenous stress;various substances,such as brain-derived neurotrophic factor(BDNF),atrial natriuretic peptide(ANP),and opioid peptides;and the 5-HT2C receptor and cannabinoid receptor type-1(CB1R),among others,reflecting the positive modulatory effects of aerobic exercise on anxiety.As a non-pharmacological intervention,aerobic exercise has been demonstrated to be useful in a variety of medical applications and has considerable potential for ameliorating symptoms of anxiety.
文摘Huntington’s disease is a genetic disease caused by expanded CAG repeats on exon 1 of the huntingtin gene located on chromosome 4.Compelling evidence implicates impaired mitochondrial energetics,altered mitochondrial biogenesis and quality control,disturbed mitochondrial trafficking,oxidative stress and mitochondrial calcium dyshomeostasis in the pathogenesis of the disorder.Unfortunately,conventional mitochondrial-targeted molecules,such as cysteamine,creatine,coenzyme Q10,or triheptanoin,yielded negative or inconclusive results.However,future therapeutic strategies,aiming to restore mitochondrial biogenesis,improving the fission/fusion balance,and improving mitochondrial trafficking,could prove useful tools in improving the phenotype of Huntington’s disease and,used in combination with genome-editing methods,could lead to a cure for the disease.
基金supported by the National Research Foundation of Korea(NRF)Grant funded by the Korea government(MSIT)(Nos.2020R1A5A1019131 and 2022M3D1A2054488)。
文摘The global healthcare landscape is increasingly challenged by the rising prevalence of chronic diseases and the demographic shift towards an aging population,necessitating the development of innovative and sustainable healthcare solutions.In this context,the emergence of triboelectric energy harvesters as a key technological breakthrough offers a viable pathway towards self-powered,efficient,and sustainable personal health management.This review critically examines the transformative potential of triboelectric nanogenerators(TENGs)in addressing the pressing challenges of modern healthcare,underscoring their unique benefits such as being battery-free,easy to fabricate,and cost-efficient.We begin by reviewing the fundamental mechanisms of triboelectrification at the atomic scale and presenting the contact electrification among various materials,such as metals,polymers,and semiconductors.The discussion subsequently extends to the commonly used materials for TENGs and explores advancements in their design and functionality,with an emphasis on structural and chemical innovations.Furthermore,the application spectrum of TENGs in personal health management is extensively reviewed,covering aspects including health monitoring,therapeutic intervention,health protection,and device powering,while highlighting their capacity for self-sustainability.The review concludes by addressing existing challenges while mapping out the latest significant contributions and prospective directions in TENG-based healthcare innovations.By facilitating a paradigm shift towards a more autonomous,cost-effective,and personalized healthcare model,independent of external power sources,TENGs are poised to markedly enhance the quality of care and overall well-being,marking the dawn of a new era in integrated personal health management.
文摘The hematopoietic system stands as a cornerstone of organismal physiology,maintaining lifelong blood cell production while serving critical roles in immune defense and tissue homeostasis.With advancing age,this precisely regulated system undergoes progressive functional decline,driven by interconnected changes in hematopoietic stem cells(HSCs),their bone marrow(BM)niche,and systemic factors,all of which contribute to aging-related hematopoietic disorders.In this editorial,we synthesize these advances and explore how emerging insights into hematopoietic aging mechanisms present opportunities for developing targeted therapeutic interventions against age-related hematopoietic decline and its clinical consequences.
文摘Increasing numbers of long noncoding RNAs(lncRNAs)are implicated in breast cancer oncogenicity.However,the contribution of LINC02568 toward breast cancer progression remains unclear and requires further investigation.Herein,we evaluated LINC02568 expression in breast cancer and clarified its effect on disease malignancy.We also investigated the mechanisms underlying the pro-oncogenic role of LINC02568.Consequently,LINC02568 was upregulated in breast cancer samples,with a notable association with worse overall survival.Functionally,depleted LINC02568 suppressed cell proliferation,colony formation,and metastasis,whereas LINC02568 overexpression exerted the opposite effects.Our mechanistic investigations suggested that LINC02568 was physically bound to and sequestered microRNA-874-3p(miR-874-3p).Furthermore,miR-874-3p mediated suppressive effects in breast cancer cells by targeting cyclin E1(CCNE1).LINC02568 positively controlled CCNE1 expression by sequestering miR-874-3p.Rescue experiments revealed that increased miR-874-3p or decreased CCNE1 expression recovered cell growth and motility functions induced by LINC02568 in breast cancer cells.In conclusion,the tumor-promoting functions of LINC02568 in breast cancer cells were enhanced by sequestering miR-874-3p and consequently over-expressing CCNE1.Our data may facilitate the identification of novel therapeutic targets in clinical settings.
文摘This article explores the intricate relationship between attachment styles formed during early childhood and the subsequent responses to traumatic events, particularly the death of a parent. Drawing on the theoretical framework of attachment theory and incorporating contemporary research, the paper discusses how parental interactions shape the neural circuitry of infants and children, influencing their ability to form secure or insecure attachments. These attachment styles, in turn, play a critical role in determining the child’s coping mechanisms when faced with trauma. This paper focuses on trying to understand how attachment theory is connected to the reaction to trauma with a highlight on the four major styles of attachments which are secure, anxious, avoidant, and disorganized to mention but a few, and how they influence stress and adversity in children. Attachment theory holds that human beings’ ability to form affectional bonds in infancy determines their patterns of relatedness across the life cycle. The type of attachment that is secure usually supports healthy adaptation and good coping mechanisms regardless of the trauma in the childhood of the child. While secure attachment mostly facilitates favorable trauma-related outcomes, anxious or avoidant attachment can exacerbate or alter the responses. The caregiving system that is avoidant attachment has implications of autonomous self-functioning which has features of suppression of the emotional response and poor search for emotional support during stress. From the principles of developmental psychology and trauma theory, the paper also focuses on the major significance of the child’s early caregivers’ interactions that define the resilience and vulnerability factor. This knowledge is therefore critical in designing specific interventions based on the improvement of coping behaviors and emotional regulatory systems of children who have been exposed to trauma. Finally, we have the synthesis of new knowledge about the role of secure attachment relationships as its fundamental element in shaping adaptive traumatization and psychological development. The article also delves into the physiological processes involved in emotional regulation and the role of cortisol in disrupting attachment. Finally, the implications of these findings for therapeutic interventions and the challenges of addressing prolonged grief and traumatic responses in clinical settings are considered.
文摘Cancer is a complex disease influenced by various factors,including DNA damage,growth signals,and inflammation.Although inflammation has commonly not been considered carcinogenic,increasing evidence indicates its substantial involvement in the onset and progression of cancer,especially in the presence of chronic microbial infections.This review thoroughly analyzes the complex relationship between cancer,health,and inflammation by introducing pathological and physiological features of inflammation.The study explores the various factors that might enhance inflammation,including infections and para-inflammation caused by tissue stress.It will also explore the changing comprehension of microorganisms about health and illness,clarifying their possible influence on the development of several malignancies,including colon,pancreatic,gastric,and prostate cancers.In addition,the study emphasizes the development of new therapy approaches that specifically target chronic inflammations and their associated cancers.This review seeks to enhance the comprehension of the intricate correlation between cancer,inflammation,and human health by combining existing research.
基金This study was funded by grants from National Natural Science Foundation of China(No.81901853)to FYAdditional support was supported by Specially Funded scientific research project of the Fourth Affiliated Hospital of Harbin Medical University(No.HYDSYTB202126)to DWY.
文摘Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels resulting from im-paired insulin secretion or insulin resistance.Diabetes poses a major global health concern,because of its increasing prevalence and substantial morbidity and mortality.This review explores the relationships between altered fatty acid metabolism and microcirculatory impairments in diabetes.Dysregulation of fatty acid metabolism in diabetes leads to changes in fatty acid profiles,abnormal lipid accumulation,and increased oxidative stress.These changes contribute to microvascular dysfunction through mechanisms such as endothelial dysfunction,impaired nitric oxide availability,inflammation,and oxidative damage.Understanding this intricate interplay is essential for identifying novel thera-peutic strategies to alleviate vascular complications in diabetes.By targeting specific pathways involved in fatty acid metabolism and microvascular dysfunction,interventions can be developed to improve patient outcomes.This review is aimed at contributing to future research and the development of effective strategies for preventing and managing dia-betes-associated microcirculatory impairments,to ultimately enhance the quality of life for people living with diabetes.
基金supported by Sidra Medicine Research Fund to Ajaz A.Bhat(grant number:SDR400190)Ammira S.Al-Shabeeb Akil(grant number:SDR400175).
文摘Obesity,a global health concern,is associated with severe health issues like type 2 diabetes,heart disease,and respiratory complications.It also increases the risk of various cancers,including melanoma,endometrial,prostate,pancreatic,esophageal adenocarcinoma,colorectal carcinoma,renal adenocarcinoma,and pre-and post-menopausal breast cancer.Obesity-induced cellular changes,such as impaired CD8^(+)T cell function,dyslipi-demia,hypercholesterolemia,insulin resistance,mild hyperglycemia,and fluctuating levels of leptin,resistin,adiponectin,and IL-6,contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes.Adipocytes release leptin,a pro-inflammatory substance that stimulates cancer cell proliferation,inflammation,and invasion,altering the tumor cell metabolic pathway.Adiponectin,an insulin-sensitizing adipokine,is typically downregulated in obese individuals.It has antipro-liferative,proapoptotic,and antiangiogenic properties,making it a potential cancer treatment.This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer,draw-ing on an extensive,though non-systematic,survey of the recent literature.This approach allows us to integrate and synthesize findings from various studies,offering a cohesive perspective on emerging themes and potential therapeutic targets.The review explores the metabolic disturbances,cellular alterations,inflammatory responses,and shifts in the tumor microenvironment that contribute to the obesity-cancer link.Finally,it discusses poten-tial therapeutic strategies aimed at disrupting these connections,offering valuable insights into future research directions and the development of targeted interventions.
文摘Since its inauguration in 2003, China Interventional Therapeutics （CIT） congress has witnessed the growth of percutaneous cardiovascular intervention in China. In 2003 the total number ofpercutaneous coronary intervention （PCI） in China was about 40 000 cases,1 while by CIT＇s 10th anniversary in 2012, the annual number of PCI in China had reached 340 000 cases. CIT has grown along with PCI practice in the country; last year the CIT congress hosted 6000 attendees, including 180 international faculty members and over 750 foreign participants from 42 countries or regions.
文摘Objective To explore the efficacy of transcatheter closure of patent ductus arteriosus (PDA) with detachable coil and Amplatzer duct occluder (ADO). Methods Transcatheter colsure of PDA was performed in 160 cases, aged 4.56±2.67 years, of whom 3 had residual shunt after surgical ligation, 2 had pulmomary stenosis (PS), 1 had coarctation of aorta (COA), 1 had right aortic arch, and 2 had atrial septal defect (ASD). Results Detachable coils (Duct Occlude pfm or Cook Inc) were successfully used in 51 patients with a smallest PDA diameter of 1.86±0.78mm. Amplatzer duct occluders were also successfully performed in other 109 with a moderate to large PDA diameter of 3.89±1.32mm, of whom 3 with PS or COA were performed balloon dilation firstly, and 2 with ASD were performed PDA occlusion firstly; 1 month to 4.8 years follow-up coil or Amplatzer device closure of PDA showed that neither residual shunt nor any complication. Conclusion It is suggested that the detachable coil and Amplatzer duct occluder are simple and safe for the catheter closure from small to large sized PDA.
文摘The recent outbreak of the human Zaire ebolavirus(EBOV)epidemic is spiraling out of control in West Africa.Human EBOV hemorrhagic fever has a case fatality rate of up to 90%.The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention,with no approved therapies and vaccines available for its treatment apart from supportive care.Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial,the current epidemic might be outpacing the speed at which drugs and vaccines can be produced.Like all viruses,the EBOV largely relies on host cell factors and physiological processes for its entry,replication,and egress.We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies.Most of the therapeutic agents in this review are directed against non-mutable targets of the host,which is independent of viral mutation.These medications are approved by the Food and Drug Administration(FDA)for the treatment of other diseases.They are available and stockpileable for immediate use.They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.
基金supported by the National Natural Science Foundation of China(82173741,82003582 and 81930100)Youth Fund of the National Natural Science Foundation of China(82304309)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20230103,BK20231014)China Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)。
文摘Molecular chaperones,a class of complex client regulatory systems,play significant roles in the prevention of protein misfolding and abnormal aggregation,the modulation of protein homeostasis,and the protection of cells from damage under constantly changing environmental conditions.As the understanding of the biological mechanisms of molecular chaperones has increased,their link with the occurrence and progression of disease has suggested that these proteins are promising targets for therapeutic intervention,drawing intensive interest.Here,we review recent advances in determining the structures of molecular chaperones and heat shock protein 90(HSP90)chaperone system complexes.We also describe the features of molecular chaperones and shed light on the complicated regulatory mechanism that operates through interactions with various co-chaperones in molecular chaperone cycles.In addition,how molecular chaperones affect diseases by regulating pathogenic proteins has been thoroughly analyzed.Furthermore,we focus on molecular chaperones to systematically discuss recent clinical advances and various drug design strategies in the preclinical stage.Recent studies have identified a variety of novel regulatory strategies targeting molecular chaperone systems with compounds that act through different mechanisms from those of traditional inhibitors.Therefore,as more novel design strategies are developed,targeting molecular chaperones will significantly contribute to the discovery of new potential drugs.
基金funded by Innovation Foundation of Jinan Clinical Medicine Science and Technology(202225012).
文摘China’s newborn screening(NBS)system,initiated over four decades ago with dual-disease detection[phenylketonuria(PKU)and congenital hypothyroidism(CH)],has progressively expanded to encompass congenital adrenocortical hyperplasia(CAH)and glucose-6-phosphate dehydrogenase(G6PD)deficiency,achieving nationwide universal coverage.This systematic progression has substantially elevated diagnostic rates for these disorders,enabling timely therapeutic interventions[1].Over the past two decades,technological innovations—notably the integration of tandem mass spectrometry(MS/MS)platforms in pioneering regions such as Shanghai and Zhejiang—have extended NBS to over 40 inherited metabolic diseases(IMDs).
基金supported by the Tianjin Synthetic Biotech-nology Innovation Capacity Improvement Project(Grant No.TSBICIP-CXRC-048).
文摘Protein citrullination involves the deimination of arginine or methylarginine resi-dues in peptide chains to form citrulline by peptidyl arginine deiminases.This process is an important protein post-translational modification that affects molecular structure and func-tion of various proteins,including histones.In recent years,protein citrullination has attracted widespread attention for its influence on gene transcription.Studies on the impact of protein citrullination modification on chromatin structure remodeling and the establishment of gene regulatory networks have made rapid progress.In this review,we briefly summarize the phys-iological functions of protein citrullination modification.Specifically,we comprehensively outline the latest progress in the study of the role of protein citrullination modification in gene transcription regulation,focusing on the interaction of protein citrullination with other post-translational modifications.
