Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

NLRP3 inflammasome plays a vital role in the pathogenesis of age-related diseases in the eye and brain

Key points:With aging,there is increased nucleotide-binding oligomerization domain-(NOD-)like receptor(NLR) protein-3(NLRP3) activation in neural and ocular tissues.Activation of the NLRP3 inflammasome appears to be a common denominator in the pathogenesis of age-related diseases of the eye and brain.Pharmacological inhibition of the NLRP3 inflammasome may be a potent therapy for preventing the development and progression of age-related eye and brain diseases.

Exploring the autophagy-related pathogenesis of active ulcerative colitis

BACKGROUND The pathogenesis of ulcerative colitis(UC)is complex,and recent therapeutic advances remain unable to fully alleviate the condition.AIM To inform the development of novel UC treatments,bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC.METHODS The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria.Differential analysis was conducted to obtain differentially expressed genes(DEGs).Au-tophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes(DEARGs)associated with active UC.DEARGs were then subjected to KEGG,GO,and DisGeNET disease enrichment analyses using R software.Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm.The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs,and the top five targets in the Dgree ranking were designated as core targets.RESULTS A total of 4822 DEGs were obtained,of which 58 were classified as DEARGs.SERPINA1,BAG3,HSPA5,CASP1,and CX3CL1 were identified as core targets.GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy.KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways.Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion.Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls.CONCLUSION Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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.

Disruption of non-classically secreted protein(MoMtp)compromised conidiation,stress homeostasis,and pathogenesis of Magnaporthe oryzae

Blast disease,caused by the hemibiotrophic ascomycete fungus,Magnaporthe oryzae,is a significant threat to sustainable rice production worldwide.Studies have shown that the blast fungus secretes vast arrays of functionally diverse proteins into the host cell for a successful disease progression.However,the final destinations of these effector proteins inside the host cell and their role in advancing fungal pathogenesis remain a mystery.Here,we reported that a putative mitochondrial targeting non-classically secreted protein(MoMtp)positively regulates conidiogenesis and appressorium maturation in M.oryzae.Moreover,MoM TP gene deletion mutant strains triggered a hypersensitive response when inoculated on rice leaves displaying that MoMtp is essential for the virulence of M.oryzae.In addition,cell wall and oxidative stress results indicated that MoMtp is likely involved in the maintenance of the structural integrity of the fungus cell.Our study also demonstrates an upregulation in the expression pattern of the MoMTP gene at all stages of infection,indicating its possible regulatory role in host invasion and the infectious development of M.oryzae.Furthermore,Agrobacterium infiltration and sheath inoculation confirmed that MoMtpGFP protein is predominantly localized in the host mitochondria of tobacco leaf and rice cells.Taken together,we conclude that MoMtp protein likely promotes the normal conidiation and pathogenesis of M.oryzae and might have a role in disturbing the proper functioning of the host mitochondria during pathogen invasion.

Glycolytic dysregulation in Alzheimer's disease:unveiling new avenues for understanding pathogenesis and improving therapy

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.

Role of Vickers Ligament in the Pathogenesis of Madelung Deformity

Objective The Vickers ligament is thought to hinder the growth of palmar ulnar radius by tethering the lunate to the radius,leading to Madelung deformity.The purpose of this study was to clarify the nature of the Vickers ligament and investigate its pathogenesis in Madelung deformities based on our observation of the Vickers ligament.Methods All 22 patients(33 wrists)with Madelung deformities treated surgically between 2018 and 2022 were included.The diagnosis was confirmed radiographically in all patients.The three-dimensional computed tomography(3D-CT)data of 16 patients(19 wrists)were available.Magnetic resonance imaging(MRI)data were available for 9 patients(14 wrists).Wrist arthroscopy was used in 4 patients.The Vickers ligament was resected and submitted for histopathological examination in 8 patients.Radiographic outcomes,3D-CT,MRI,arthroscopy,surgical findings,and histopathology of the Vickers ligament were evaluated.Results The 3D-CT revealed that the Vickers ligament originated in the metaphysis and formed a metaphyseal defect at the palmar ulnar radius.In the sequential MR coronal images,the Vickers ligament could be divided into 3 branches,extending to the lunate,triquetrum and ulnar styloid.Arthroscopy and surgical findings revealed that the nature of the Vickers ligament was the stretched palmar ligament of the wrist.The histopathology results revealed ligamentous tissue and fibrocartilaginous metaplasia with a structure similar to that of the triangular fibrocartilage complex(TFCC).Conclusions The Vickers ligament is not a separate aberrant ligament.The nature of the Vickers ligament is a combination of the stretched TFCC ligament(palmar radioulnar ligament,ulnotriquetral ligament and ulnolunate ligament)and radiolunate ligament.The possible pathogenesis of Madelung deformity might be focal early epiphyseal closure at the middle part of the sigmoid notch,which leads to focal growth retardation of the radius and pulls palmar ligaments proximally to form the Vickers ligament.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

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.

Urolithiasis: From pathogenesis to management (part two)

Embarking on a scholarly exploration of the intricate landscape of urolithiasis,the second part of the special section in the Asian Journal of Urology serves as a continuum to the scholarly discourse initiated in its predecessor.Urolithiasis is a common condition affecting 5%-10%of the global population[1].Despite significant progress in understanding the pathogenesis and management of urolithiasis,it remains a substantial public health concern.The objective of the special section in the Asian Journal of Urology is to provide an updated knowledge on the pathogenesis,diagnosis,and management of urolithiasis.In this part two of the special section,we stillfocus on the aspects of stone pathogenesis,treatment,complications prevention,and the application of new technologies.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.

Unraveling autophagy-related pathogenesis in active ulcerative colitis:A bioinformatics approach

In this editorial,we provide commentary on the study by Gong et al.In this original research article,Gong et al employed a bioinformatics approach to investigate the involvement of autophagy in active ulcerative colitis(UC).Through differential gene expression analysis,they identified 58 differentially expressed autophagy-related genes in UC patients compared to healthy controls.Notably,HSPA5,CASP1,SERPINA1,CX3CL1,and BAG3,were found to be upregulated in active UC patients,suggesting their significance as core autophagyrelated targets.Enrichment analysis unveiled associations with crucial signaling pathways and diseases such as middle cerebral artery occlusion and glomerulonephritis.Moreover,immune cell infiltration analysis revealed notable differences in immune cell composition between UC patients and healthy controls.These findings offer valuable insights into the role of autophagy in UC pathogenesis and potential therapeutic targets.

New exploration on pathogenesis and early diagnosis of gestational diabetes

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.

The role of glycoproteins in nasopharyngeal carcinoma pathogenesis

Nasopharyngeal carcinoma(NPC)is a malignant tumor arising from the nasopharyngeal epithelium.It consists of undifferentiated squamous cells in the nasopharynx.This type of epithelial cell neoplasm is globally distributed,with the highest prevalence observed in certain regions of the world.It has been known since ancient times.The incidence of NPC is steadily decreasing as data on the molecular factors involved in the pathogenesis of NPC accumulate.Glycoproteins are characterized by polymers of saccharides attached to the amino acid sequences of proteins during the process of glycosylation.They are present in all animal cells and are especially abundant on the surface of tumor cells.Alterations in expression of cellular glycoproteins have recently attracted attention as a key component of neoplastic progression.Tumor-associated glycoproteins may serve as a hallmark of cancer cells and thus represent novel diagnostic and even therapeutic targets.Interest in the role of glycoproteins in cancer in general and specifically in NPC pathology has steadily increased over the past fifty years,reaching over thousands and two hundred publications in the last five years,respectively.Here,data on a specific class of proteins,glycoproteins,involved in tumorigenesis of NPCs are summarized,with a focus on a few of the best-studied ones.Relevant studies performed mainly in the last five years were retrieved and collected through the PubMed system.

To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography

BACKGROUND Over 90%of rectal cancer patients develop low anterior resection syndrome(LARS)after sphincter-preserving resection.The current globally recognized evaluation method has many drawbacks and its subjectivity is too strong,which hinders the research and treatment of LARS.AIM To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging(MRI)defecography,and pathogenesis of LARS.METHODS We evaluated 34 patients using the standard LARS score,and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS score.RESULTS In the LARS score model,there were 10(29.41%)mild and 24(70.58%)severe cases of LARS.The comparison of defecation rate between the two groups was 29.36±14.17%versus 46.83±18.62%(P=0.004);and MRI-rectal compliance(MRI-RC)score was 3.63±1.96 versus 7.0±3.21(P=0.001).Severe and mild LARS had significant differences using the two evaluation methods.There was a significant negative correlation between LARS and MRI-RC score(P<0.001),and they had a negative correlation with defecation rate(P=0.028).CONCLUSION MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.

Research Progress on the Pathogenesis of Acute Lung Injury(ALI)

In this review,the databases searched were PubMed and Web of Science.It is believed that the main causes of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are inflammatory response disorders,excessive oxidative stress,cell death,endoplasmic reticulum stress,coagulation dysfunction,and weakened aquaporin function.

Role of Immune Cells and Non-immune Cells with Immune Functions in the Pathogenesis of ALI/ARDS

This review outlines the effects of different types of cells with immune function on acute lung injury(ALI)inflammation and the regulation of inflammatory responses between these cells via cell-cell interactions.It is expected to provide some possible strategies for the research and treatment of ALI and acute respiratory distress syndrome(ARDS).

The Pathogenesis and Treatment Progress of Androgenic Alopecia

Androgenic alopecia, also known as seborrheic alopecia, is the most common hair loss disorder in dermatology clinics, mainly characterized by hair follicle miniaturization and progressive hair loss. The etiology and pathogenesis of androgenic alopecia are not clear, but may be related to heredity and androgen metabolism. Currently, minoxidil and finasteride are the only two drugs approved by the U.S. Food and Drug Administration (FDA) for AGA treatment, other treatments include oral minoxidil, hair transplantation, low energy laser therapy (LLLT), platelet-rich plasma (PRP), Chinese medicine microneedles, and combination therapy. With the development of medicine and science, we have ushered in the era of biologics and targeted therapy. In recent years, a variety of signaling pathways for androgenic alopecia have been found, which may provide a basis for targeted therapy for androgenic alopecia.

Advances in the pathogenesis of postherpetic neurosymptoms of herpes zoster

Herpes zoster(HZ)is an acute infectious disease caused by varicella-zoster virus.The neurological sequelae of HZ include postherpetic neuralgia(PHN)and postherpetic itch(PHI).Severe pain and recurrent itching seriously affect the quality of life of patients.The pathogenesis of PHN is related to the mediation of immune-inflammatory response,activation of neuroglial cells,structural and functional alterations of the brain,aberrant expression of ion channels,and gene mediation.Overall,the immune-inflammatory response is a key factor mediating the pathogenesis of PHN.By reviewing the literature,the authors found that there are few studies on PHN both at home and abroad,so its pathogenesis is still unclear.No new progress has been made in recent years either,resulting in the understanding of PHI remaining in a state of confusion.The pathogenesis of PHI may be related to the loss of epidermal nerves,excitation of itch-specific neurons,absence of itch-inhibitory neurons,the action of itch-causing factors,and the vicious circle of itch and mood disorders.In general,most of them are conjectures,not supported by relevant experimental data.The treatments for PHN are varied and effective,while the pathogenesis of PHI is still unclear,so the treatment is often passive.This paper reviews the pathogenesis of PHN and PHI,expecting to provide new ideas for clinical treatment.

Etiology and pathogenesis of corona virus disease 2019 on the view of Chinese medicine

Traditional Chinese Medicine has played an important role in the prevention and treatment of the Corona Virus Disease 2019 epidemic.But in views of different TCM scholars there are different opinions about disease name,characteristic of etiology,law of pathogenesis about this epidemic.Based on related literatures,this article overviews of the characteristics of TCM etiology,law of pathogenesis and methods of syndrome differentiation,hoping to find research method that fit in with TCM clinical practice.Prerequisite of treatment is identifying the cause.The clinical manifestations of patients are important to TCM,and the etiological attributes can be inferred from the clinical manifestations.SARS-CoV-2 belongs to exogenous etiological factors,but there are different opinions about its characteristics of six pathogenic factors.Cold,Dampness,Warm,Dry,Toxin,Summer-heat,Wind,are all involved.Thus,different understanding of the pathogenesis and the law of transmission is caused.Such as cold and dampness hurt Yang,furthermore,consumed of Qi;dampness and toxin infected from external environment,turbid dampness produced inside the body;dryness affecting lungs and consume of Yin;warm-heat-turbid-toxin affected lungs,stomach and intestine;and then produced phlegm stagnation or blood stasis,furthermore consumed Qi and Yin.Based on those differences,methods of syndrome differentiation in treatment of COVID-19 are diverse,which contain pattern differentiation of zang-fu organs,pattern differentiation of Wei-defence,Qi,Ying nutrients and blood;pattern differentiation by the eight principles,and pattern differentiation of six meridians.Because of SARS-CoV-2 can spread to the whole country or even the whole world in a short period of time,its pathogenic nature should be roughly the same.So studying the treatment of COVID-19 based on clinical cases,refining the similarities and differences in the clinical presentation of patients with different subtypes during the epidemic,clarification of the etiologic attribution and evolutionary patterns of disease mechanisms,developing a comprehensive understanding of COVID-19 in Chinese medicine is needed.Furthermore,getting a full understanding of COVID-19,and providing reference for the prevention and treatment of unknown infectious diseases.

Team players in the pathogenesis of metabolic dysfunctionsassociated steatotic liver disease:The basis of development of pharmacotherapy

Nutrient metabolism is regulated by several factors.Social determinants of health with or without genetics are the primary regulator of metabolism,and an unhealthy lifestyle affects all modulators and mediators,leading to the adaptation and finally to the exhaustion of cellular functions.Hepatic steatosis is defined by presence of fat in more than 5%of hepatocytes.In hepatocytes,fat is stored as triglycerides in lipid droplet.Hepatic steatosis results from a combination of multiple intracellular processes.In a healthy individual nutrient metabolism is regulated at several steps.It ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural component.Several hormones,peptides,and genes have been described that participate in nutrient metabolism.Several enzymes participate in each nutrient metabolism as described above from ingestion to generation of ATP.As of now several publications have revealed very intricate regulation of nutrient metabolism,where most of the regulatory factors are tied to each other bidirectionally,making it difficult to comprehend chronological sequence of events.Insulin hormone is the primary regulator of all nutrients’metabolism both in prandial and fasting states.Insulin exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes;metabolic,inflammation and repair,and cell growth and regeneration.Final regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands,adiponectin,leptin,and adiponutrin.Insulin hormone has direct effect on these final modulators.Whereas blood glucose level,serum lipids,incretin hormones,bile acids in conjunction with microbiota are intermediary modulators which are controlled by lifestyle.The purpose of this review is to overview the key players in the pathogenesis of metabolic dysfunction-associated steatotic liver disease(MASLD)that help us understand the disease natural course,risk stratification,role of lifestyle and pharmacotherapy in each individual patient with MASLD to achieve personalized care and target the practice of precision medicine.PubMed and Google Scholar databases were used to identify publication related to metabolism of carbohydrate and fat in states of health and disease states;MASLD,cardiovascular disease and cancer.More than 1000 publications including original research and review papers were reviewed.