Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The ...Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.展开更多
Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on choli...Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease.Recent studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's disease.Alterations in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's disease.Glycolytic changes impact neuronal health and function,thus offering promising targets for therapeutic intervention.The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression.Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.展开更多
Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and mortality.Over the p...Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and mortality.Over the past decades,these infections have proven to be a significant challenge to health systems worldwide,particularly following the considerable geographic expansion of the dengue virus(DENV)and its most recent outbreak in Latin America as well as the difficult-tocontrol outbreaks of yellow fever virus(YFV),chikungunya virus(CHIKV),and Zika virus(ZIKV),leaving behind a substantial portion of the population with complications related to these infections.Currently,the world is experiencing a period of intense globalization,which,combined with global warming,directly contributes to wider dissemination of arbovirus vectors across the globe.Consequently,all continents remain on high alert for potential new outbreaks.Thus,this review aims to provide a comprehensive understanding of the pathogenesis of the four main arboviruses today(DENV,ZIKV,YFV,and CHIKV)discussing their viral characteristics,immune responses,and mechanisms of viral evasion,as well as important clinical aspects for patient management.This includes associated symptoms,laboratory tests,treatments,existing or developing vaccines and the main associated complications,thus integrating a broad historical,scientific and clinical approach.展开更多
Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immu...Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major determinants.The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans.The gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and urbanization.The majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the microbiome.We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.展开更多
Interleukins(ILs),a subset of cytokines,play a critical role in the pathogenesis of coronary heart disease(CHD)by mediating inflammation.This review article summarizes the role of ILs such as IL-1,IL-2,IL-3,IL-4,IL-5,...Interleukins(ILs),a subset of cytokines,play a critical role in the pathogenesis of coronary heart disease(CHD)by mediating inflammation.This review article summarizes the role of ILs such as IL-1,IL-2,IL-3,IL-4,IL-5,IL-6,IL-7,IL-8,IL-9,and IL-10 in the pathogenesis of CHD.Individuals with mild coronary artery disease(CAD)and angina who have ischemic heart disease have higher serum concentrations of IL-1b.Larger studies are needed to verify the safety and assess the effectiveness of low-dose IL-2 as an anti-inflammatory treatment.IL-3 is found more often in patients receiving coronary angioplasty compared to patients with asymptomatic CAD or without CAD.Serum levels of IL-4 are reliable indicators of CAD.An independent correlation between IL-5 and the incidence of CAD was demonstrated.IL-6 helps serve as a reliable biomarker for the degree of CAD,as determined by the Gensini score,and is a key factor in the development of atherosclerosis.Also,variants of IL-7/7R have been linked to the Han Chinese population's genetic susceptibility to CHD.IL-8 plays a role in the progression of CAD occurrences.By interacting with conventional risk factors for CAD,IL-9 may contribute to the development of CAD and offer an innovative approach to its prevention and management.There was a 34%increased risk of a CHD incident for every standard deviation rise in baseline IL-10 levels.展开更多
Adenosine triphosphate(ATP)-binding cassette(ABC)transporter systems are divided into importers and exporters that facilitate the movement of diverse substrate molecules across the lipid bilayer,against the concentrat...Adenosine triphosphate(ATP)-binding cassette(ABC)transporter systems are divided into importers and exporters that facilitate the movement of diverse substrate molecules across the lipid bilayer,against the concentration gradient.These transporters comprise two highly conserved nucleotide-binding domains(NBDs)and two transmembrane domains(TMDs).Unlike ABC exporters,prokaryotic ABC importers require an additional substrate-binding protein(SBP)as a recognition site for specific substrate translocation.The discovery of a large number of ABC systems in bacterial pathogens revealed that these transporters are crucial for the establishment of bacterial infections.The existing literature has highlighted the roles of ABC transporters in bacterial growth,pathogenesis,and virulence.These roles include importing essential nutrients required for a variety of cellular processes and exporting outer membrane-associated virulence factors and antimicrobial substances.This review outlines the general structures and classification of ABC systems to provide a comprehensive view of the activities and roles of ABC transporters associated with bacterial virulence and pathogenesis during infection.展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with diabetes.GDM is a unique among the four subtypes ...Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with diabetes.GDM is a unique among the four subtypes of diabetes classified by the international World Health Organization standards.Although GDM patients constitute a small proportion of the total number of diabetes cases,the incidence of GDM has risen significantly over the past decade,posing substantial risk to pregnant women and infants.Therefore,it warrants considerable attention.The pathogenesis of GDM is generally considered to resemble that of type II diabetes,though it may have distinct characteristics.Analyzing blood biochemical proteins in the context of GDM can help elucidate its pathogenesis,thereby facilitating more effective prevention and management strategies.This article reviews this critical clinical issue to enhance the medical community's sufficient understanding of GDM.展开更多
The misfolding,aggregation,and deposition of alpha-synuclein into Lewy bodies are pivotal events that trigger pathological changes in Parkinson's disease.Extracellular vesicles are nanosized lipidbilayer vesicles ...The misfolding,aggregation,and deposition of alpha-synuclein into Lewy bodies are pivotal events that trigger pathological changes in Parkinson's disease.Extracellular vesicles are nanosized lipidbilayer vesicles secreted by cells that play a crucial role in intercellular communication due to their diverse cargo.Among these,brain-derived extracellular vesicles,which are secreted by various brain cells such as neurons,glial cells,and Schwann cells,have garnered increasing attention.They serve as a promising tool for elucidating Parkinson's disease pathogenesis and for advancing diagnostic and therapeutic strategies.This review highlights the recent advancements in our understanding of brain-derived extracellular vesicles released into the blood and their role in the pathogenesis of Parkinson's disease,with specific emphasis on their involvement in the aggregation and spread of alpha-synuclein.Brain-derived extracellular vesicles contribute to disease progression through multiple mechanisms,including autophagy-lysosome dysfunction,neuroinflammation,and oxidative stress,collectively driving neurodegeneration in Parkinson's disease.Their application in Parkinson's disease diagnosis is a primary focus of this review.Recent studies have demonstrated that brainderived extracellular vesicles can be isolated from peripheral blood samples,as they carryα-synuclein and other key biomarkers such as DJ-1 and various micro RNAs.These findings highlight the potential of brain-derived extracellular vesicles,not only for the early diagnosis of Parkinson's disease but also for disease progression monitoring and differential diagnosis.Additionally,an overview of explorations into the potential therapeutic applications of brain-derived extracellular vesicles for Parkinson's disease is provided.Therapeutic strategies targeting brain-derived extracellular vesicles involve modulating the release and uptake of pathological alpha-synuclein-containing brain-derived extracellular vesicles to inhibit the spread of the protein.Moreover,brain-derived extracellular vesicles show immense promise as therapeutic delivery vehicles capable of transporting drugs into the central nervous system.Importantly,brain-derived extracellular vesicles also play a crucial role in neural regeneration by promoting neuronal protection,supporting axonal regeneration,and facilitating myelin repair,further enhancing their therapeutic potential in Parkinson's disease and other neurological disorders.Further clarification is needed of the methods for identifying and extracting brain-derived extracellular vesicles,and large-scale cohort studies are necessary to validate the accuracy and specificity of these biomarkers.Future research should focus on systematically elucidating the unique mechanistic roles of brain-derived extracellular vesicles,as well as their distinct advantages in the clinical translation of methods for early detection and therapeutic development.展开更多
Hepatocellular carcinoma(HCC)represents a major global health burden,ranking third as the leading cause of cancer-related mortality worldwide.This compre-hensive review examines the substantial body of evidence linkin...Hepatocellular carcinoma(HCC)represents a major global health burden,ranking third as the leading cause of cancer-related mortality worldwide.This compre-hensive review examines the substantial body of evidence linking modifiable lifestyle factors to HCC pathogenesis and clinical outcomes.We systematically evaluate dietary components,alcohol consumption patterns,tobacco use,physical activity levels,and emerging factors including metabolic disorders,psychological stress,and sleep disturbances.These factors collectively influence hepatocarcino-genesis through diverse biological mechanisms,including genotoxic damage,metabolic dysregulation,chronic inflammatory responses,and gut microbiome-mediated pathways.The accumulated data underscore the urgent need to inte-grate lifestyle interventions into multidisciplinary HCC management.展开更多
Inflammatory bowel disease(IBD)is an incurable disease of the digestive system;however,the therapeutic methods for IBD remain limited.The pathogenesis of IBD was systematically discussed and compared in this paper,pri...Inflammatory bowel disease(IBD)is an incurable disease of the digestive system;however,the therapeutic methods for IBD remain limited.The pathogenesis of IBD was systematically discussed and compared in this paper,primarily comprising Crohn’s disease and ulcerative colitis.This paper focused on six common aspects:(1)Dysregulated immune responses;(2)Gene function changes;(3)Intestinal microbes disorder and imbalance;(4)Microbial infections;(5)Associations between IBD and other inflammatory diseases;and(6)Other factors.In addition,the pathogenesis differences between these two forms of IBD were unraveled and clearly distinguished.These unique aspects of pathogenesis provide crucial insights for the precise treatment of both Crohn’s disease and ulcerative colitis.This paper illustrates the root causes and beneficial factors of resistance to IBD,which provides novel insights on early prevention,development of new therapeutic agents,and treatment options of this disease.展开更多
The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function,...The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.展开更多
Vestibular Migraine (VM) is a common neurological disorder characterized by recurrent episodes of vertigo and migraine symptoms. The pathogenesis of VM is complex and involves multiple genetic and environmental factor...Vestibular Migraine (VM) is a common neurological disorder characterized by recurrent episodes of vertigo and migraine symptoms. The pathogenesis of VM is complex and involves multiple genetic and environmental factors. Recent studies have suggested that the pathogenesis of vestibular migraine may be associated with variations in the CACNA1A gene, which is an important gene target for controlling calcium ion channels. Such variations may further affect the functions of the vestibular nervous system, thereby causing a series of vestibular nervous system-related symptoms. This article will summarize the genetic association studies of vestibular migraine, vestibular function studies, and research on how to establish relevant animal models to illustrate the possible association between CACNA1A variations and the pathogenesis of VM, providing new ideas for clarifying the pathogenesis of VM.展开更多
Helicobacter pylori(H.pylori)infection is one of the most prevalent bacterial infections affecting mankind.About half of the world’s population is infected with it.It causes several upper gastrointestinal diseases,in...Helicobacter pylori(H.pylori)infection is one of the most prevalent bacterial infections affecting mankind.About half of the world’s population is infected with it.It causes several upper gastrointestinal diseases,including gastric cancer(GC).It has been identified as a major risk factor for GC.GC is one of the most common cancers affecting humans and the third leading cause of cancer-related deaths worldwide.H.pylori infection causes an inflammatory response that progresses through a series of intermediary stages of precancerous lesions(gastritis,atrophy,intestinal metaplasia,and dysplasia)to the final development of GC.Among infected individuals,approximately 10%develop severe gastric lesions such as peptic ulcer disease,1%-3%progress to GC,and 0.1%develop mucosa-associated lymphoid tissue followed by the development of lymphoma.The bacterium has many virulence factors,including cytotoxin-associated gene A,vacuolating cytotoxin A,and the different outer membrane proteins that cause cancer by different mechanisms.These virulence factors activate cell signaling pathways such as PI3-kinase/Akt,JAK/STAT,Ras,Raf,and ERK signaling that control cell proliferation.Uncontrolled proliferation can lead to cancer.In addition,the repair of DNA damage may also be impaired by H.pylori infection.Reduced DNA repair in combination with increased DNA damage can result in carcinogenic mutations.The accurate identification of pathogenetic pathways is imperative for the development of targeted diagnostic markers and personalized treatments.This scoping review aims to update the readers on the role of H.pylori in the development of GC.It will focus on the molecular mechanisms underpinning gastric carcinogenesis in H.pylori infection.It will highlight the interaction between bacterial virulence factors and host cellular pathways,providing insights into potential therapeutic targets and preventive strategies.展开更多
This article summarized the role of interleukins(ILs)in the pathogenesis of cholangiocarcinoma(CCA).It discovered a negative feedback mechanism wherein alternative splicing led to the upregulation of the IL 1 receptor...This article summarized the role of interleukins(ILs)in the pathogenesis of cholangiocarcinoma(CCA).It discovered a negative feedback mechanism wherein alternative splicing led to the upregulation of the IL 1 receptor antagonist(IL1RN)isoforms IL1RN-201 and IL1RN-203,which play a crucial anti-inflammatory role in KRAS-mutant intrahepatic CCA(iCCA).Higher levels of IL-4 receptor were associated with a worse survival rate in patients with CCA.In addition,elevated levels of serum IL-6 have been associated with the start and progression of CCA,a common cancer generated by inflammation.IL-8 was a useful predictor of human hilar CCA.Mechanistically,signal transducer and activator of transcription 3 signaling was used by IL-10 produced from M2-polarized tumor-associated macrophages to enhance the malignant characteristics of iCCA cells.It was suggested that IL-17A and IL-22 have an impact on the development of CCA associated with hepatic fluke infection.The most significant finding was the decreased expression of the IL-23 receptor,a prognostic gene,in iCCA.IL-25 may be a useful prognostic biomarker as aberrant expression of the protein in CCA tissue was linked to tumor spread and a poor prognosis.Tumor cell migration and proliferation were both accelerated by homogenized liver tissue that expressed IL-33 significantly.The correlation between high IL-35 expression and aggressiveness in iCCA highlights it as a useful biomarker for assessing the course and prognosis of iCCA in clinical settings.This article concluded that IL-1,IL-4,IL-6,IL-8,IL-10,IL-17,IL-23,IL-25,IL-33,and IL-35 play significant roles in the pathogenesis of CCA.Further research is required to find the association of other ILs such as IL-2,IL-3,IL-5,IL-7,IL-11,and more in the pathogenesis of CCA.展开更多
Rheumatoid arthritis(RA),an autoimmune disease characterized by chronic inflammation of synovial tissue,is divided into two subtypes-anti-citrullinated protein antibody(ACPA)-positive and ACPA-negative RA.While the pa...Rheumatoid arthritis(RA),an autoimmune disease characterized by chronic inflammation of synovial tissue,is divided into two subtypes-anti-citrullinated protein antibody(ACPA)-positive and ACPA-negative RA.While the pathogenic mechanisms of ACPA-positive RA are well-understood,the etiology of ACPA-negative RA remains largely unknown.The association between RA and periodontitis(PD)has been observed since the early 190os,with the two diseases sharing common genetic and environmental risk factors that lead to the progressive destruction of bone and connective tissue.However,the associations between PD and the two subtypes of RA differ.This comprehensive review aims to provide an updated understanding of the epidemiological association between RA and PD,explore potential pathogenic mechanisms linking the two diseases,and highlight the key distinctions between the subtypes of RA and their respective associations with PD.We also discuss the possibility of early intervention or the treatment of the two diseases.Ultimately,this review aims to provide valuable insights for future research in this field.展开更多
This letter addresses Pravda's innovative review,which proposes hydrogen pe-roxide as the primary pathogenic factor in ulcerative colitis(UC).Although the author presents intriguing mechanistic insights and report...This letter addresses Pravda's innovative review,which proposes hydrogen pe-roxide as the primary pathogenic factor in ulcerative colitis(UC).Although the author presents intriguing mechanistic insights and reports encouraging clinical outcomes with reducing agents,several methodological and clinical considera-tions require discussion.We examine three key aspects:The selective evidence synthesis approach;the need for rigorous clinical validation of proposed thera-pies;and the integration of this novel hypothesis with established inflammatory bowel disease pathogenesis.Given the complexity of UC,future therapeutic ad-vances may require collaborative approaches that integrate redox-based mecha-nisms into existing evidence-based frameworks rather than replacing current paradigms.展开更多
Inflammatory bowel disease(IBD),consisting primarily of ulcerative colitis and Crohn’s disease,is a chronic,relapsing inflammatory disorder of the gastrointestinal tract.The pathogenesis of IBD has been thoroughly st...Inflammatory bowel disease(IBD),consisting primarily of ulcerative colitis and Crohn’s disease,is a chronic,relapsing inflammatory disorder of the gastrointestinal tract.The pathogenesis of IBD has been thoroughly studied throughout the past few decades,such as defective gut epithelial barrier,immune responses,genetic predisposition,infections,and dysbiosis.Recent studies have revealed the unexpected importance of intestinal stem cells(ISCs)in the pathophysiology of IBD.The rapid recovery and continuous self-renewal of intestinal epithelial cells depend on ISCs within the crypts.Proliferation and differentiation of ISCs is an important cytological basis for repairing damaged intestinal mucosa.Unfortunately,as a new therapeutic goal in IBD,mucosal healing is difficult to achieve with current treatments.Stem cell therapy is an emerging treatment for IBD that allows mucosal healing by rebuilding the mucosal barrier.In this review,we present the current research progress on the role of ISCs in IBD and discuss stem cell-based therapies that have been specifically designed for its treatment.展开更多
Background:Pulmonary blastoma(PB)is a rare subtype of lung cancer.Currently,the underlying pathogenesis mechanisms of PB have not been fully illustrated,and the therapeutic approach for this entity is limited.Methods:...Background:Pulmonary blastoma(PB)is a rare subtype of lung cancer.Currently,the underlying pathogenesis mechanisms of PB have not been fully illustrated,and the therapeutic approach for this entity is limited.Methods:Whole-exome sequencing(WES),RNA sequencing,and DNA methylation profiling are applied to seven PB patients.Multi-omics data of pulmonary sarcomatoid carcinoma(PSC)and pituitary blastoma(PitB)from previous studies are invoked to illuminate the associations among PB and these malignacies.Results:We portray the genomic alteration spectrum of PB and find that DICER1 is with the highest alteration rate(86%).We uncover that DICER1 alterations,Wnt signaling pathway dysregulation and IGF2 imprinting dysregulation are the potential pathogenesis mechanisms of PB.Moreover,we reveal that the integrated molecular features of PB are distinct from PSC,and the molecular characteristics of PB are more similar to PitB than to PSC.Pancancer analysis show that the tumor mutation burden(TMB)and leukocyte fraction(LF)of PB are low,while some cases are positive for PD-L1 or have CD8-positive focal areas,implying the potential applicability of immunotherapy in selected PB patients.Conclusion:This study depicts the integrated molecular characteristics of PB and offers novel insights into the pathogenesis and therapeutic strategies of PB.展开更多
Oral submucous fibrosis(OSF),characterized by excessive deposition of extracellular matrix(ECM)that causes oral mucosal tissue sclerosis,and even cancer transformation,is a chronic,progressive fibrosis disease.However...Oral submucous fibrosis(OSF),characterized by excessive deposition of extracellular matrix(ECM)that causes oral mucosal tissue sclerosis,and even cancer transformation,is a chronic,progressive fibrosis disease.However,despite some advancements in recent years,no targeted antifibrotic strategies for OSF have been approved;likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined.In this review,we briefly introduce the epidemiology and etiology of OSF.Then,we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors,secretion function,and activation of ECM-producing myofibroblasts.In addition,we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF.Finally,we summarize strategies to interrupt key mechanisms that cause OSF,including modulation of the ECM,inhibition of inflammation,improvement of vascular disturbance.This review will provide potential routes for developing novel anti-OSF therapeutics.展开更多
基金supported by the National Natural Science Foundation of China,No.32130060(to XG).
文摘Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.
基金supported by the National Natural Science Foundation of China,No.82271214(to ZY)the Natural Science Foundation of Hubei Province of China,No.2022CFB109(to ZY)。
文摘Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease.Recent studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's disease.Alterations in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's disease.Glycolytic changes impact neuronal health and function,thus offering promising targets for therapeutic intervention.The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression.Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.
基金Supported by the Permanecer Program(part of the actions of the Office of Affirmative Actions)Education and Diversity of the Dean of Student Assistance at the Federal University of Bahia(UFBA)and CNPq Research Productivity Fellow.
文摘Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and mortality.Over the past decades,these infections have proven to be a significant challenge to health systems worldwide,particularly following the considerable geographic expansion of the dengue virus(DENV)and its most recent outbreak in Latin America as well as the difficult-tocontrol outbreaks of yellow fever virus(YFV),chikungunya virus(CHIKV),and Zika virus(ZIKV),leaving behind a substantial portion of the population with complications related to these infections.Currently,the world is experiencing a period of intense globalization,which,combined with global warming,directly contributes to wider dissemination of arbovirus vectors across the globe.Consequently,all continents remain on high alert for potential new outbreaks.Thus,this review aims to provide a comprehensive understanding of the pathogenesis of the four main arboviruses today(DENV,ZIKV,YFV,and CHIKV)discussing their viral characteristics,immune responses,and mechanisms of viral evasion,as well as important clinical aspects for patient management.This includes associated symptoms,laboratory tests,treatments,existing or developing vaccines and the main associated complications,thus integrating a broad historical,scientific and clinical approach.
文摘Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the intes-tine.While the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major determinants.The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans.The gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and urbanization.The majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the microbiome.We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.
文摘Interleukins(ILs),a subset of cytokines,play a critical role in the pathogenesis of coronary heart disease(CHD)by mediating inflammation.This review article summarizes the role of ILs such as IL-1,IL-2,IL-3,IL-4,IL-5,IL-6,IL-7,IL-8,IL-9,and IL-10 in the pathogenesis of CHD.Individuals with mild coronary artery disease(CAD)and angina who have ischemic heart disease have higher serum concentrations of IL-1b.Larger studies are needed to verify the safety and assess the effectiveness of low-dose IL-2 as an anti-inflammatory treatment.IL-3 is found more often in patients receiving coronary angioplasty compared to patients with asymptomatic CAD or without CAD.Serum levels of IL-4 are reliable indicators of CAD.An independent correlation between IL-5 and the incidence of CAD was demonstrated.IL-6 helps serve as a reliable biomarker for the degree of CAD,as determined by the Gensini score,and is a key factor in the development of atherosclerosis.Also,variants of IL-7/7R have been linked to the Han Chinese population's genetic susceptibility to CHD.IL-8 plays a role in the progression of CAD occurrences.By interacting with conventional risk factors for CAD,IL-9 may contribute to the development of CAD and offer an innovative approach to its prevention and management.There was a 34%increased risk of a CHD incident for every standard deviation rise in baseline IL-10 levels.
基金supported by the Universiti Kebangsaan Malaysia under the Research University Grant(No.GUP-2020-030)awarded to Sylvia CHIENG.
文摘Adenosine triphosphate(ATP)-binding cassette(ABC)transporter systems are divided into importers and exporters that facilitate the movement of diverse substrate molecules across the lipid bilayer,against the concentration gradient.These transporters comprise two highly conserved nucleotide-binding domains(NBDs)and two transmembrane domains(TMDs).Unlike ABC exporters,prokaryotic ABC importers require an additional substrate-binding protein(SBP)as a recognition site for specific substrate translocation.The discovery of a large number of ABC systems in bacterial pathogens revealed that these transporters are crucial for the establishment of bacterial infections.The existing literature has highlighted the roles of ABC transporters in bacterial growth,pathogenesis,and virulence.These roles include importing essential nutrients required for a variety of cellular processes and exporting outer membrane-associated virulence factors and antimicrobial substances.This review outlines the general structures and classification of ABC systems to provide a comprehensive view of the activities and roles of ABC transporters associated with bacterial virulence and pathogenesis during infection.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
基金Supported by National Natural Science Foundation of China,No.32060182Qiannan Prefecture Science and Technology Plan Project in China:Qiannan Kehe She Zi[2022]No.1.
文摘Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with diabetes.GDM is a unique among the four subtypes of diabetes classified by the international World Health Organization standards.Although GDM patients constitute a small proportion of the total number of diabetes cases,the incidence of GDM has risen significantly over the past decade,posing substantial risk to pregnant women and infants.Therefore,it warrants considerable attention.The pathogenesis of GDM is generally considered to resemble that of type II diabetes,though it may have distinct characteristics.Analyzing blood biochemical proteins in the context of GDM can help elucidate its pathogenesis,thereby facilitating more effective prevention and management strategies.This article reviews this critical clinical issue to enhance the medical community's sufficient understanding of GDM.
基金supported by the National Natural Science Foundation of China,No.822712782019 Wuhan Huanghe Talents Program+3 种基金2020 Wuhan Medical Research Project,No.20200206010123032021 Hubei Youth Top-notch Talent Training Program2022 Outstanding Youth Project of Natural Science Foundation of Hubei Province,No.2022CFA106Medical Research Program of Huatongguokang,No.2023HT036(all to NX)。
文摘The misfolding,aggregation,and deposition of alpha-synuclein into Lewy bodies are pivotal events that trigger pathological changes in Parkinson's disease.Extracellular vesicles are nanosized lipidbilayer vesicles secreted by cells that play a crucial role in intercellular communication due to their diverse cargo.Among these,brain-derived extracellular vesicles,which are secreted by various brain cells such as neurons,glial cells,and Schwann cells,have garnered increasing attention.They serve as a promising tool for elucidating Parkinson's disease pathogenesis and for advancing diagnostic and therapeutic strategies.This review highlights the recent advancements in our understanding of brain-derived extracellular vesicles released into the blood and their role in the pathogenesis of Parkinson's disease,with specific emphasis on their involvement in the aggregation and spread of alpha-synuclein.Brain-derived extracellular vesicles contribute to disease progression through multiple mechanisms,including autophagy-lysosome dysfunction,neuroinflammation,and oxidative stress,collectively driving neurodegeneration in Parkinson's disease.Their application in Parkinson's disease diagnosis is a primary focus of this review.Recent studies have demonstrated that brainderived extracellular vesicles can be isolated from peripheral blood samples,as they carryα-synuclein and other key biomarkers such as DJ-1 and various micro RNAs.These findings highlight the potential of brain-derived extracellular vesicles,not only for the early diagnosis of Parkinson's disease but also for disease progression monitoring and differential diagnosis.Additionally,an overview of explorations into the potential therapeutic applications of brain-derived extracellular vesicles for Parkinson's disease is provided.Therapeutic strategies targeting brain-derived extracellular vesicles involve modulating the release and uptake of pathological alpha-synuclein-containing brain-derived extracellular vesicles to inhibit the spread of the protein.Moreover,brain-derived extracellular vesicles show immense promise as therapeutic delivery vehicles capable of transporting drugs into the central nervous system.Importantly,brain-derived extracellular vesicles also play a crucial role in neural regeneration by promoting neuronal protection,supporting axonal regeneration,and facilitating myelin repair,further enhancing their therapeutic potential in Parkinson's disease and other neurological disorders.Further clarification is needed of the methods for identifying and extracting brain-derived extracellular vesicles,and large-scale cohort studies are necessary to validate the accuracy and specificity of these biomarkers.Future research should focus on systematically elucidating the unique mechanistic roles of brain-derived extracellular vesicles,as well as their distinct advantages in the clinical translation of methods for early detection and therapeutic development.
基金Supported by Chinese Academy of Medical Sciences Initiative for Innovative Medicine,No.2021-I2M-1-015the National Natural Science Foundation of China,No.82330061 and No.82001937+1 种基金the Peking Union Medical College Graduate Curriculum Informatization Development Special Fund Project,No.2024YXX004the Science and Education Cultivation Fund of the National Cancer and Regional Medical Center of Shanxi Provincial Cancer Hospital,No.TD2023003.
文摘Hepatocellular carcinoma(HCC)represents a major global health burden,ranking third as the leading cause of cancer-related mortality worldwide.This compre-hensive review examines the substantial body of evidence linking modifiable lifestyle factors to HCC pathogenesis and clinical outcomes.We systematically evaluate dietary components,alcohol consumption patterns,tobacco use,physical activity levels,and emerging factors including metabolic disorders,psychological stress,and sleep disturbances.These factors collectively influence hepatocarcino-genesis through diverse biological mechanisms,including genotoxic damage,metabolic dysregulation,chronic inflammatory responses,and gut microbiome-mediated pathways.The accumulated data underscore the urgent need to inte-grate lifestyle interventions into multidisciplinary HCC management.
基金Supported by Tianjin Municipal Science and Technology Commission Grant,No.24ZXRKSY00010Program for Innovative Research Team in Peking Union Medical College,CAMS Initiative for Innovative Medicine,No.2023-I2M-2-008.
文摘Inflammatory bowel disease(IBD)is an incurable disease of the digestive system;however,the therapeutic methods for IBD remain limited.The pathogenesis of IBD was systematically discussed and compared in this paper,primarily comprising Crohn’s disease and ulcerative colitis.This paper focused on six common aspects:(1)Dysregulated immune responses;(2)Gene function changes;(3)Intestinal microbes disorder and imbalance;(4)Microbial infections;(5)Associations between IBD and other inflammatory diseases;and(6)Other factors.In addition,the pathogenesis differences between these two forms of IBD were unraveled and clearly distinguished.These unique aspects of pathogenesis provide crucial insights for the precise treatment of both Crohn’s disease and ulcerative colitis.This paper illustrates the root causes and beneficial factors of resistance to IBD,which provides novel insights on early prevention,development of new therapeutic agents,and treatment options of this disease.
基金supported by the National Natural Science Foundation of China(grant no.82370015).
文摘The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.
文摘Vestibular Migraine (VM) is a common neurological disorder characterized by recurrent episodes of vertigo and migraine symptoms. The pathogenesis of VM is complex and involves multiple genetic and environmental factors. Recent studies have suggested that the pathogenesis of vestibular migraine may be associated with variations in the CACNA1A gene, which is an important gene target for controlling calcium ion channels. Such variations may further affect the functions of the vestibular nervous system, thereby causing a series of vestibular nervous system-related symptoms. This article will summarize the genetic association studies of vestibular migraine, vestibular function studies, and research on how to establish relevant animal models to illustrate the possible association between CACNA1A variations and the pathogenesis of VM, providing new ideas for clarifying the pathogenesis of VM.
文摘Helicobacter pylori(H.pylori)infection is one of the most prevalent bacterial infections affecting mankind.About half of the world’s population is infected with it.It causes several upper gastrointestinal diseases,including gastric cancer(GC).It has been identified as a major risk factor for GC.GC is one of the most common cancers affecting humans and the third leading cause of cancer-related deaths worldwide.H.pylori infection causes an inflammatory response that progresses through a series of intermediary stages of precancerous lesions(gastritis,atrophy,intestinal metaplasia,and dysplasia)to the final development of GC.Among infected individuals,approximately 10%develop severe gastric lesions such as peptic ulcer disease,1%-3%progress to GC,and 0.1%develop mucosa-associated lymphoid tissue followed by the development of lymphoma.The bacterium has many virulence factors,including cytotoxin-associated gene A,vacuolating cytotoxin A,and the different outer membrane proteins that cause cancer by different mechanisms.These virulence factors activate cell signaling pathways such as PI3-kinase/Akt,JAK/STAT,Ras,Raf,and ERK signaling that control cell proliferation.Uncontrolled proliferation can lead to cancer.In addition,the repair of DNA damage may also be impaired by H.pylori infection.Reduced DNA repair in combination with increased DNA damage can result in carcinogenic mutations.The accurate identification of pathogenetic pathways is imperative for the development of targeted diagnostic markers and personalized treatments.This scoping review aims to update the readers on the role of H.pylori in the development of GC.It will focus on the molecular mechanisms underpinning gastric carcinogenesis in H.pylori infection.It will highlight the interaction between bacterial virulence factors and host cellular pathways,providing insights into potential therapeutic targets and preventive strategies.
文摘This article summarized the role of interleukins(ILs)in the pathogenesis of cholangiocarcinoma(CCA).It discovered a negative feedback mechanism wherein alternative splicing led to the upregulation of the IL 1 receptor antagonist(IL1RN)isoforms IL1RN-201 and IL1RN-203,which play a crucial anti-inflammatory role in KRAS-mutant intrahepatic CCA(iCCA).Higher levels of IL-4 receptor were associated with a worse survival rate in patients with CCA.In addition,elevated levels of serum IL-6 have been associated with the start and progression of CCA,a common cancer generated by inflammation.IL-8 was a useful predictor of human hilar CCA.Mechanistically,signal transducer and activator of transcription 3 signaling was used by IL-10 produced from M2-polarized tumor-associated macrophages to enhance the malignant characteristics of iCCA cells.It was suggested that IL-17A and IL-22 have an impact on the development of CCA associated with hepatic fluke infection.The most significant finding was the decreased expression of the IL-23 receptor,a prognostic gene,in iCCA.IL-25 may be a useful prognostic biomarker as aberrant expression of the protein in CCA tissue was linked to tumor spread and a poor prognosis.Tumor cell migration and proliferation were both accelerated by homogenized liver tissue that expressed IL-33 significantly.The correlation between high IL-35 expression and aggressiveness in iCCA highlights it as a useful biomarker for assessing the course and prognosis of iCCA in clinical settings.This article concluded that IL-1,IL-4,IL-6,IL-8,IL-10,IL-17,IL-23,IL-25,IL-33,and IL-35 play significant roles in the pathogenesis of CCA.Further research is required to find the association of other ILs such as IL-2,IL-3,IL-5,IL-7,IL-11,and more in the pathogenesis of CCA.
基金supported by the National Natural Science Foundation of China(Nos.82171768,81701600,and 82001048)the National Key Research and Development Program of China(No.2022YFC3602000)the Young Elite Scientist Support Program by CSA(Chinese Stomatological Association)(No.2020PYRC001).
文摘Rheumatoid arthritis(RA),an autoimmune disease characterized by chronic inflammation of synovial tissue,is divided into two subtypes-anti-citrullinated protein antibody(ACPA)-positive and ACPA-negative RA.While the pathogenic mechanisms of ACPA-positive RA are well-understood,the etiology of ACPA-negative RA remains largely unknown.The association between RA and periodontitis(PD)has been observed since the early 190os,with the two diseases sharing common genetic and environmental risk factors that lead to the progressive destruction of bone and connective tissue.However,the associations between PD and the two subtypes of RA differ.This comprehensive review aims to provide an updated understanding of the epidemiological association between RA and PD,explore potential pathogenic mechanisms linking the two diseases,and highlight the key distinctions between the subtypes of RA and their respective associations with PD.We also discuss the possibility of early intervention or the treatment of the two diseases.Ultimately,this review aims to provide valuable insights for future research in this field.
文摘This letter addresses Pravda's innovative review,which proposes hydrogen pe-roxide as the primary pathogenic factor in ulcerative colitis(UC).Although the author presents intriguing mechanistic insights and reports encouraging clinical outcomes with reducing agents,several methodological and clinical considera-tions require discussion.We examine three key aspects:The selective evidence synthesis approach;the need for rigorous clinical validation of proposed thera-pies;and the integration of this novel hypothesis with established inflammatory bowel disease pathogenesis.Given the complexity of UC,future therapeutic ad-vances may require collaborative approaches that integrate redox-based mecha-nisms into existing evidence-based frameworks rather than replacing current paradigms.
文摘Inflammatory bowel disease(IBD),consisting primarily of ulcerative colitis and Crohn’s disease,is a chronic,relapsing inflammatory disorder of the gastrointestinal tract.The pathogenesis of IBD has been thoroughly studied throughout the past few decades,such as defective gut epithelial barrier,immune responses,genetic predisposition,infections,and dysbiosis.Recent studies have revealed the unexpected importance of intestinal stem cells(ISCs)in the pathophysiology of IBD.The rapid recovery and continuous self-renewal of intestinal epithelial cells depend on ISCs within the crypts.Proliferation and differentiation of ISCs is an important cytological basis for repairing damaged intestinal mucosa.Unfortunately,as a new therapeutic goal in IBD,mucosal healing is difficult to achieve with current treatments.Stem cell therapy is an emerging treatment for IBD that allows mucosal healing by rebuilding the mucosal barrier.In this review,we present the current research progress on the role of ISCs in IBD and discuss stem cell-based therapies that have been specifically designed for its treatment.
基金supported by National Natural Sciences Foundation(grant number:82203827).
文摘Background:Pulmonary blastoma(PB)is a rare subtype of lung cancer.Currently,the underlying pathogenesis mechanisms of PB have not been fully illustrated,and the therapeutic approach for this entity is limited.Methods:Whole-exome sequencing(WES),RNA sequencing,and DNA methylation profiling are applied to seven PB patients.Multi-omics data of pulmonary sarcomatoid carcinoma(PSC)and pituitary blastoma(PitB)from previous studies are invoked to illuminate the associations among PB and these malignacies.Results:We portray the genomic alteration spectrum of PB and find that DICER1 is with the highest alteration rate(86%).We uncover that DICER1 alterations,Wnt signaling pathway dysregulation and IGF2 imprinting dysregulation are the potential pathogenesis mechanisms of PB.Moreover,we reveal that the integrated molecular features of PB are distinct from PSC,and the molecular characteristics of PB are more similar to PitB than to PSC.Pancancer analysis show that the tumor mutation burden(TMB)and leukocyte fraction(LF)of PB are low,while some cases are positive for PD-L1 or have CD8-positive focal areas,implying the potential applicability of immunotherapy in selected PB patients.Conclusion:This study depicts the integrated molecular characteristics of PB and offers novel insights into the pathogenesis and therapeutic strategies of PB.
基金study was supported by the National Key Research and Development Program of China(2022YFC2402900)National Natural Science Foundation of China(82470989,52103327)+3 种基金The Joint Funds of the Hunan Provincial Natural Science Foundation(2023JJ60509)The Science and Technology Talent Support Project of the Hunan Provincial Science Popularization Special Project(2023TJ-Z08)Hunan Provincial Innovation Foundation for Postgraduate(2023ZZTS0218)The Postgraduate Inde-pendent Exploration Innovation Fund of the Central South University(2023ZZTS0987)。
文摘Oral submucous fibrosis(OSF),characterized by excessive deposition of extracellular matrix(ECM)that causes oral mucosal tissue sclerosis,and even cancer transformation,is a chronic,progressive fibrosis disease.However,despite some advancements in recent years,no targeted antifibrotic strategies for OSF have been approved;likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined.In this review,we briefly introduce the epidemiology and etiology of OSF.Then,we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors,secretion function,and activation of ECM-producing myofibroblasts.In addition,we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF.Finally,we summarize strategies to interrupt key mechanisms that cause OSF,including modulation of the ECM,inhibition of inflammation,improvement of vascular disturbance.This review will provide potential routes for developing novel anti-OSF therapeutics.
