Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathologica...Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.展开更多
Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at th...Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at the molecular,cellular,and neural circuit levels.Abnormal molecular signaling pathways or dysfunction of specific cell types can lead to epilepsy by disrupting the normal functioning of neural circuits.The continuous emergence of new technologies and the rapid advancement of existing ones have facilitated the discovery and comprehensive understanding of the neural circuit mechanisms underlying epilepsy.Therefore,this review aims to investigate the current understanding of the neural circuit mechanisms in epilepsy based on various technologies,including electroencephalography,magnetic resonance imaging,optogenetics,chemogenetics,deep brain stimulation,and brain-computer interfaces.Additionally,this review discusses these mechanisms from three perspectives:structural,synaptic,and transmitter circuits.The findings reveal that the neural circuit mechanisms of epilepsy encompass information transmission among different structures,interactions within the same structure,and the maintenance of homeostasis at the cellular,synaptic,and neurotransmitter levels.These findings offer new insights for investigating the pathophysiological mechanisms of epilepsy and enhancing its clinical diagnosis and treatment.展开更多
Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal micro...Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.展开更多
Varicocele(VC)is widely recognized as a prevalent and clinically significant cause of male infertility.However,the comprehensive pathogenic mechanisms underlying VC development and progression remain incompletely unde...Varicocele(VC)is widely recognized as a prevalent and clinically significant cause of male infertility.However,the comprehensive pathogenic mechanisms underlying VC development and progression remain incompletely understood,creating an important knowledge gap in the field of andrology.This review establishes that VC pathogenesis centers on abnormal vascular remodeling and integrates multiple contributing elements,including anatomical abnormalities,biochemical disturbances,genetic factors,low body mass index(BMI),age,and specific sports habits,while secondary varicoceles are primarily induced by compressive pathologies.Through a systematic synthesis of current evidence and recent advances,this review aims to elucidate the complex pathogenic network of VC and provide valuable insights to guide future research directions and inform the development of targeted clinical applications.展开更多
The plant pathogenic fungus Sclerotinia sclerotiorum is the causative agent of Sclerotinia stem rot(SSR)disease in most dicotyledons.Among the various proteins involved in drug efflux or substance transport,ATP-bindin...The plant pathogenic fungus Sclerotinia sclerotiorum is the causative agent of Sclerotinia stem rot(SSR)disease in most dicotyledons.Among the various proteins involved in drug efflux or substance transport,ATP-binding cassette(ABC)transporters constitute a superfamily of membrane-bound proteins that may play a crucial role in the survival of S.sclerotiorum.However,the expression patterns and functions of ABC transporter genes in S.sclerotiorum remain largely uncharacterized.This study characterized a highly expressed S.sclerotiorum ABC transporter gene during inoculation on host plants,Ss BMR1.Silencing Ss BMR1 resulted in a significant reduction in hyphal growth,infection cushion development,sclerotia formation,and virulence.Moreover,host-induced gene silencing(HIGS)of Ss BMR1 significantly enhanced plant resistance.Transcriptome and metabolomics analyses suggested that Ss BMR1 is involved in antioxidant and toxin transport,thereby influencing fungal defense and cell rescue mechanisms.In comparison to the wild-type strain,Ss BMR1 gene-silenced transformants exhibited a diminished response to extracellar oxidative stress and a decreased exporting of antioxidant glutathione.Tolerance assays further demonstrated the crucial role of Ss BMR1 in conferring resistance to the plant antifungal substances,camalexin and brassinin,as well as certain fungicides.Furthermore,Ss BMR1 gene-silenced transformants showed enhanced repression on virulence when sprayed with camalexin and brassinin on the leaves.Thus,Ss BMR1 likely contributes to virulence by facilitating the export of antioxidant and providing resistance against antifungal agents.The findings of this study provide valuable insights that could contribute to the development of novel management techniques for SSR.展开更多
Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory condition affecting the gastrointestinal tract.The global incidence and prevalence of IBD continu...Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory condition affecting the gastrointestinal tract.The global incidence and prevalence of IBD continue to increase.While multiple clinical treatments exist,conventional therapies frequently present limitations and adverse effects.Natural polysaccharides(PSs)have emerged as a significant focus of research interest due to their therapeutic potential and applications in functional foods and health products.This review synthesizes current understanding of IBD pathophysiology and the mechanisms by which natural PSs counter IBD,including their capacity to restore immune homeostasis and intestinal barrier function,modulate gut microbiota and metabolites,reduce oxidative stress,and address irregularities in autophagy and endoplasmic reticulum stress(ERS).The review examines the structure-activity relationships of PSs demonstrating anti-IBD effects and identifies promising therapeutic products.The discussion encompasses pharmacokinetics,safety evaluations,and clinical applications of these compounds.This comprehensive review establishes a theoretical foundation for developing natural PS-based therapeutic approaches for IBD management.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
Currently,the number of patients with myopia is increasing rapidly across the globe.Traditional Chinese medicine(TCM),with its long history and rich experience,has shown promise in effectively managing and treating th...Currently,the number of patients with myopia is increasing rapidly across the globe.Traditional Chinese medicine(TCM),with its long history and rich experience,has shown promise in effectively managing and treating this condition.Nevertheless,considering the vast amount of research that is currently being conducted,focusing on the utilization of TCM in the management of myopia,there is an urgent requirement for a thorough and comprehensive review.The review would serve to clarify the practical applications of TCM within this specific field,and it would also aim to elucidate the underlying mechanisms that are at play,providing a deeper understanding of how TCM principles can be effectively integrated into modern medical practices.Here,some modern medical pathogenesis of myopia and appropriate TCM techniques studies are summarized in the prevention and treatment of myopia.Further,we discussed the potential mechanisms and the future research directions of TCM against myopia.Identifying these mechanisms is crucial for understanding how TCM can be effectively utilized in this context.The combination of various TCM methods or the combination of traditional Chinese and Western medicine is of great significance for the prevention and control of myopia in the future.展开更多
Human cardiac organoids have revolutionized the study of cardiac development,disease modeling, drug discovery, and regenerative therapies. This review systematically discusses strategies and progress in the constructi...Human cardiac organoids have revolutionized the study of cardiac development,disease modeling, drug discovery, and regenerative therapies. This review systematically discusses strategies and progress in the construction of cardiac organoids, categorizing them into three main types:cardiac spheroids, self-organizing/assembloid organoids, and organoid-on-a-chip systems. This review uniquely integrates the advances in vascularization, organ-on-chip design, and environmental cardiotoxicity modeling within cardiac organoid platforms, offering a critical synthesis that is absent in the literature. In the context of escalating environmental threats to cardiovascular health, there is an urgent need for physiologically relevant models to accurately identify cardiac toxicants and elucidate their underlying mechanisms of action. This review highlights advances in cardiac organoid applications for disease modeling-including congenital heart defects and acquired cardiovascular diseases-drug development, toxicity screening, and the study of environmentally induced cardiovascular pathogenesis. In addition, it critically examines ongoing challenges and underscores opportunities brought by bioengineering approaches. Finally, we propose future directions for developing standardized cardiac organoid platforms with clinical predictability, aiming to expand the utility of this technology across broader research applications.展开更多
It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing a...It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.展开更多
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
Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This...Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.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
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
Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mu...Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mucosal samples from patients with ulcers and healthy controls,revealing significant changes in microbial diversity and composition.This article reviews their findings,emphasizing H.pylori’s role in gastric ulcers and the need for further research on its impact on duodenal ulcers.We evaluate the study’s strengths and limitations,suggesting future research directions to enhance our understanding of H.pylori’s contribution to ulcerative diseases.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
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
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
文摘Alzheimer's disease,a progressively degenerative neurological disorder,is the most common cause of dementia in the elderly.While its precise etiology remains unclear,researchers have identified diverse pathological characteristics and molecular pathways associated with its progression.Advances in scientific research have increasingly highlighted the crucial role of non-coding RNAs in the progression of Alzheimer's disease.These non-coding RNAs regulate several biological processes critical to the advancement of the disease,offering promising potential as therapeutic targets and diagnostic biomarkers.Therefore,this review aims to investigate the underlying mechanisms of Alzheimer's disease onset,with a particular focus on microRNAs,long non-coding RNAs,and circular RNAs associated with the disease.The review elucidates the potential pathogenic processes of Alzheimer's disease and provides a detailed description of the synthesis mechanisms of the three aforementioned non-coding RNAs.It comprehensively summarizes the various non-coding RNAs that have been identified to play key regulatory roles in Alzheimer's disease,as well as how these noncoding RNAs influence the disease's progression by regulating gene expression and protein functions.For example,miR-9 targets the UBE4B gene,promoting autophagy-mediated degradation of Tau protein,thereby reducing Tau accumulation and delaying Alzheimer's disease progression.Conversely,the long non-coding RNA BACE1-AS stabilizes BACE1 mRNA,promoting the generation of amyloid-βand accelerating Alzheimer's disease development.Additionally,circular RNAs play significant roles in regulating neuroinflammatory responses.By integrating insights from these regulatory mechanisms,there is potential to discover new therapeutic targets and potential biomarkers for early detection and management of Alzheimer's disease.This review aims to enhance the understanding of the relationship between Alzheimer's disease and non-coding RNAs,potentially paving the way for early detection and novel treatment strategies.
基金supported by Basic Research Programs of Science and Technology Commission Foundation of Shanxi Province,No.20210302123486(to WJ).
文摘Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at the molecular,cellular,and neural circuit levels.Abnormal molecular signaling pathways or dysfunction of specific cell types can lead to epilepsy by disrupting the normal functioning of neural circuits.The continuous emergence of new technologies and the rapid advancement of existing ones have facilitated the discovery and comprehensive understanding of the neural circuit mechanisms underlying epilepsy.Therefore,this review aims to investigate the current understanding of the neural circuit mechanisms in epilepsy based on various technologies,including electroencephalography,magnetic resonance imaging,optogenetics,chemogenetics,deep brain stimulation,and brain-computer interfaces.Additionally,this review discusses these mechanisms from three perspectives:structural,synaptic,and transmitter circuits.The findings reveal that the neural circuit mechanisms of epilepsy encompass information transmission among different structures,interactions within the same structure,and the maintenance of homeostasis at the cellular,synaptic,and neurotransmitter levels.These findings offer new insights for investigating the pathophysiological mechanisms of epilepsy and enhancing its clinical diagnosis and treatment.
基金supported by the National Key R&D Program of China(2023YFD1801100)China National Postdoctoral Program for Innovative Talents(BX20230140)China Postdoctoral Science Foundation(2023M741348)。
文摘Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.
基金funded by China Postdoctoral Science Foundation(Grant Number:2025M773939)NationalNatural Science Foundation of China(Grant Number:82205131)Sichuan Science and Technology Program(Grant Number:2025ZNSFSC1798).
文摘Varicocele(VC)is widely recognized as a prevalent and clinically significant cause of male infertility.However,the comprehensive pathogenic mechanisms underlying VC development and progression remain incompletely understood,creating an important knowledge gap in the field of andrology.This review establishes that VC pathogenesis centers on abnormal vascular remodeling and integrates multiple contributing elements,including anatomical abnormalities,biochemical disturbances,genetic factors,low body mass index(BMI),age,and specific sports habits,while secondary varicoceles are primarily induced by compressive pathologies.Through a systematic synthesis of current evidence and recent advances,this review aims to elucidate the complex pathogenic network of VC and provide valuable insights to guide future research directions and inform the development of targeted clinical applications.
基金received financial support from the Natural Science Foundation of Chongqing,China(CSTB2023NSCQMSX0355)the Fundamental Research Funds for the Central Universities,China(SWU120075)the National Natural Science Foundation of China(32372077)。
文摘The plant pathogenic fungus Sclerotinia sclerotiorum is the causative agent of Sclerotinia stem rot(SSR)disease in most dicotyledons.Among the various proteins involved in drug efflux or substance transport,ATP-binding cassette(ABC)transporters constitute a superfamily of membrane-bound proteins that may play a crucial role in the survival of S.sclerotiorum.However,the expression patterns and functions of ABC transporter genes in S.sclerotiorum remain largely uncharacterized.This study characterized a highly expressed S.sclerotiorum ABC transporter gene during inoculation on host plants,Ss BMR1.Silencing Ss BMR1 resulted in a significant reduction in hyphal growth,infection cushion development,sclerotia formation,and virulence.Moreover,host-induced gene silencing(HIGS)of Ss BMR1 significantly enhanced plant resistance.Transcriptome and metabolomics analyses suggested that Ss BMR1 is involved in antioxidant and toxin transport,thereby influencing fungal defense and cell rescue mechanisms.In comparison to the wild-type strain,Ss BMR1 gene-silenced transformants exhibited a diminished response to extracellar oxidative stress and a decreased exporting of antioxidant glutathione.Tolerance assays further demonstrated the crucial role of Ss BMR1 in conferring resistance to the plant antifungal substances,camalexin and brassinin,as well as certain fungicides.Furthermore,Ss BMR1 gene-silenced transformants showed enhanced repression on virulence when sprayed with camalexin and brassinin on the leaves.Thus,Ss BMR1 likely contributes to virulence by facilitating the export of antioxidant and providing resistance against antifungal agents.The findings of this study provide valuable insights that could contribute to the development of novel management techniques for SSR.
基金supported by the National Natural Science Foundation of China(Nos.82003977,82274134 and 82274139)the National Key Research and Development Plan(No.2017YFC1702200)+1 种基金the Key Research and Development Program of Zhejiang Province(No.2020C04020)the Science and Technology Program of Zhejiang Province(No.2025C02183).
文摘Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory condition affecting the gastrointestinal tract.The global incidence and prevalence of IBD continue to increase.While multiple clinical treatments exist,conventional therapies frequently present limitations and adverse effects.Natural polysaccharides(PSs)have emerged as a significant focus of research interest due to their therapeutic potential and applications in functional foods and health products.This review synthesizes current understanding of IBD pathophysiology and the mechanisms by which natural PSs counter IBD,including their capacity to restore immune homeostasis and intestinal barrier function,modulate gut microbiota and metabolites,reduce oxidative stress,and address irregularities in autophagy and endoplasmic reticulum stress(ERS).The review examines the structure-activity relationships of PSs demonstrating anti-IBD effects and identifies promising therapeutic products.The discussion encompasses pharmacokinetics,safety evaluations,and clinical applications of these compounds.This comprehensive review establishes a theoretical foundation for developing natural PS-based therapeutic approaches for IBD management.
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 Healthy China initiative of Traditional Chinese Medicine(No.889042).
文摘Currently,the number of patients with myopia is increasing rapidly across the globe.Traditional Chinese medicine(TCM),with its long history and rich experience,has shown promise in effectively managing and treating this condition.Nevertheless,considering the vast amount of research that is currently being conducted,focusing on the utilization of TCM in the management of myopia,there is an urgent requirement for a thorough and comprehensive review.The review would serve to clarify the practical applications of TCM within this specific field,and it would also aim to elucidate the underlying mechanisms that are at play,providing a deeper understanding of how TCM principles can be effectively integrated into modern medical practices.Here,some modern medical pathogenesis of myopia and appropriate TCM techniques studies are summarized in the prevention and treatment of myopia.Further,we discussed the potential mechanisms and the future research directions of TCM against myopia.Identifying these mechanisms is crucial for understanding how TCM can be effectively utilized in this context.The combination of various TCM methods or the combination of traditional Chinese and Western medicine is of great significance for the prevention and control of myopia in the future.
基金supported by the Innovation Promotion Program of NHC and Shanghai Key Labs,SIBPT(grant number PT2025-01)。
文摘Human cardiac organoids have revolutionized the study of cardiac development,disease modeling, drug discovery, and regenerative therapies. This review systematically discusses strategies and progress in the construction of cardiac organoids, categorizing them into three main types:cardiac spheroids, self-organizing/assembloid organoids, and organoid-on-a-chip systems. This review uniquely integrates the advances in vascularization, organ-on-chip design, and environmental cardiotoxicity modeling within cardiac organoid platforms, offering a critical synthesis that is absent in the literature. In the context of escalating environmental threats to cardiovascular health, there is an urgent need for physiologically relevant models to accurately identify cardiac toxicants and elucidate their underlying mechanisms of action. This review highlights advances in cardiac organoid applications for disease modeling-including congenital heart defects and acquired cardiovascular diseases-drug development, toxicity screening, and the study of environmentally induced cardiovascular pathogenesis. In addition, it critically examines ongoing challenges and underscores opportunities brought by bioengineering approaches. Finally, we propose future directions for developing standardized cardiac organoid platforms with clinical predictability, aiming to expand the utility of this technology across broader research applications.
基金supported by the National Natural Science Foundation of China,Nos.82274313(to YD),82204746(to ML),82003982(to TL).
文摘It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic stroke.As a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers.This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling pathway.The key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke.Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.
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 National Health Institute(NIH)grant NS099596(to LW and SPY),NS114221(to LW and SPY)Veterans Affair(VA)SPiRE grant RX003865(to SPY)+1 种基金supported by the O.Wayne Rollins Endowment Fund(to SPY)John E.Steinhaus Endowment Fund(to LW)。
文摘Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.
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.
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Helicobacter pylori(H.pylori)infection plays a critical role in gastric diseases,impacting the microbiota structure in gastric and duodenal ulcers.In their study,Jin et al utilized metagenomic sequencing to analyze mucosal samples from patients with ulcers and healthy controls,revealing significant changes in microbial diversity and composition.This article reviews their findings,emphasizing H.pylori’s role in gastric ulcers and the need for further research on its impact on duodenal ulcers.We evaluate the study’s strengths and limitations,suggesting future research directions to enhance our understanding of H.pylori’s contribution to ulcerative diseases.
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.
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.
