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 d...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.展开更多
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...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.展开更多
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 preval...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.展开更多
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 us...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.展开更多
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 ...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.展开更多
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 nam...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.展开更多
The hidden world of amyloid biology has suddenly snapped into atomic-level focus,revealing over 80 amyloid protein fibrils,both pathogenic and functional.Unlike globular proteins,amyloid proteins flatten and stack int...The hidden world of amyloid biology has suddenly snapped into atomic-level focus,revealing over 80 amyloid protein fibrils,both pathogenic and functional.Unlike globular proteins,amyloid proteins flatten and stack into unbranched fibrils.Stranger still,a single protein sequence can adopt wildly different two-dimensional conformations,yielding distinct fibril polymorphs.展开更多
Multiple sclerosis(MS) is a chronic inflammatory demyelinating disease of the central nervous system.A certain population of patients with MS present with a relapse-remitting disease course(RRMS) during the early phas...Multiple sclerosis(MS) is a chronic inflammatory demyelinating disease of the central nervous system.A certain population of patients with MS present with a relapse-remitting disease course(RRMS) during the early phase and eventually advance to a progressive course(PMS).While immune modulation therapies have recently seen tremendous success in RRMS,our limited knowledge of pathogenesis hampers the development of effective treatments for PMS.展开更多
In recent years,there has been a steady growth of interest in non-alcoholic fatty liver disease(NAFLD),which is associated with negative epidemiological data on the prevalence of the disease and its clinical significa...In recent years,there has been a steady growth of interest in non-alcoholic fatty liver disease(NAFLD),which is associated with negative epidemiological data on the prevalence of the disease and its clinical significance.NAFLD is closely related to the metabolic syndrome and these relationships are the subject of active research.A growing body of evidence shows cross-linkages between metabolic abnormalities and the innate immune system in the development and progression of NAFLD.These links are bidirectional and largely still unclear,but a better understanding of them will improve the quality of diagnosis and management of patients.In addition,lipid metabolic disorders and the innate immune system link NAFLD with other diseases,such as atherosclerosis,which is of great clinical importance.展开更多
Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic p...Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.展开更多
The amyloid cascade hypothesis of Alzheimer’s pathogenesis:The amyloid cascade hypothesis of Alzheimer’s disease(AD)pathogenesis will shortly celebrate its thirtieth birthday(Hardy and Higgins,1992).Based on abundan...The amyloid cascade hypothesis of Alzheimer’s pathogenesis:The amyloid cascade hypothesis of Alzheimer’s disease(AD)pathogenesis will shortly celebrate its thirtieth birthday(Hardy and Higgins,1992).Based on abundant genetic and biochemical evidence,it proposes that deposition of the amyloid-β(Aβ)peptide in brain parenchyma is an essential upstream trigger in AD pathogenesis that drives a cascade of events,specifically including the recruitment and pathological hyper-phosphorylation of the micro-tubule-associated protein tau,that culminate in derangement of synaptic function and,eventually,neuronal death.展开更多
The novel coronavirus pneumonia(COVID-19)is spreading worldwide and threatening people greatly.The routes by which SARS-CoV-2 causes lung injury have grown to be a major concern in the scientific community since patie...The novel coronavirus pneumonia(COVID-19)is spreading worldwide and threatening people greatly.The routes by which SARS-CoV-2 causes lung injury have grown to be a major concern in the scientific community since patients with new Coronavirus,severe acute respiratory syndrome coronavirus(SARS-CoV-2)have a high likelihood of developing acute respiratory distress syndrome(ARDS)in severe cases.The mortality rate of COVID-19 has increased over the period due to rapid spread,and it becomes crucial to understand the disease epidemiology,pathogenic mechanisms,and suitable treatment strategies.ARDS is a respiratory disorder and is one of the clinical manifestations observed in patients with severe COVID-19.In this scenario,it is important to address this problem to develop suitable treatment strategies.This review attempts to present the prevalence of ARDS in COVID-19 patients and their predictive causes and risk factors,highlighting the contrasting features of COVID-19-induced ARDS with typical ARDS.This review also presents insights into the association between SARS-CoV-2 and lung damage while exploring the potential COVID-19 mechanisms in ARDS from the perspective of the angiotensin-converting enzyme 2 protein,cytokine storm,immune responses,and other signaling pathways.The review also discusses the diagnosis strategies,pathogenesis,risk factors,and treatment options of COVID-19-related ARDS.展开更多
The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does...The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does not adequately account for all clinical characteristics and heterogeneity of OA.Genetics has emerged as a nascent and crucial area of research in OA.The epigenetic module presents a potential link between genetic and environmental risk factors and the susceptibility and pathogenesis of OA.As a critical epigenetic alteration,DNA methylation has been shown to have an important role in the etiology of OA and is a viable biomarker for predicting disease progression and medication response,as shown in this research.This review aims to update knowledge in the field of DNA methylation associated with OA to better identify the essential features of OA subtypes and pathological conditions,hence accelerating individualized treatment and precision medicine.展开更多
Polyglutamine(polyQ) diseases are a group of different neurodegenerative disorders characterized by an abnormal expansion of the trinucleotide cytosine-adenine-guanine(CAG)within coding regions of each disease-associa...Polyglutamine(polyQ) diseases are a group of different neurodegenerative disorders characterized by an abnormal expansion of the trinucleotide cytosine-adenine-guanine(CAG)within coding regions of each disease-associated gene.The abnormal expansion translates into a protein bearing an abnormally long tract of glutamines.展开更多
Alzheimer’s disease (AD) is the leading neurodegenerative disorder globally.Despite this,there is minimal effective therapeutics proven to reduce or prevent the progression of this disease.Glutamate is the main excit...Alzheimer’s disease (AD) is the leading neurodegenerative disorder globally.Despite this,there is minimal effective therapeutics proven to reduce or prevent the progression of this disease.Glutamate is the main excitatory neurotransmitter within the central nervous system and plays a crucial role in neuronal and synaptic functions.展开更多
Multiple sclerosis(MS)is a chronic immune-mediated disorder of the central nervous system(CNS)that causes focal demyelinating lesions,followed by axonal and neuronal degeneration.Several genetic and environmental fact...Multiple sclerosis(MS)is a chronic immune-mediated disorder of the central nervous system(CNS)that causes focal demyelinating lesions,followed by axonal and neuronal degeneration.Several genetic and environmental factors are found to be associated with MS incidence.While MS etiology seems to be multifactorial and needs further elucidation,it is understood that the response of an immune system to specific myelin antigens triggers the onset of MS(Dendrou et al.,2015).However,how the autoimmune response initiates against myelin,and the cellular and molecular mechanisms underpinning the development and progression of MS are not fully understood.Thus,deconstructing MS pathogenesis is of paramount importance for identifying novel diagnostic and therapeutic targets for this complex disease.展开更多
The specific pathogenesis of steroid-induced osteonecrosis of the femoral head(SONFH)is still not fully understood,and there is currently no effective early cure.Understanding the role and mechanism of long noncoding ...The specific pathogenesis of steroid-induced osteonecrosis of the femoral head(SONFH)is still not fully understood,and there is currently no effective early cure.Understanding the role and mechanism of long noncoding RNAs(lnc RNAs)in the pathogenesis of SONFH will help reveal the pathogenesis of SONFH and provide new targets for its early prevention and treatment.In this study,we first confirmed that glucocorticoid(GC)-induced apoptosis of bone microvascular endothelial cells(BMECs)is a pre-event in the pathogenesis and progression of SONFH.Then,we identified a new lnc RNA in BMECs via lnc RNA/m RNA microarray,termed Fosassociated linc RNA ENSRNOT00000088059.1(FAR591).FAR591 is highly expressed during GC-induced BMEC apoptosis and femoral head necrosis.Knockout of FAR591 effectively blocked the GC-induced apoptosis of BMECs,which then alleviated the damage of GCs to the femoral head microcirculation and inhibited the pathogenesis and progression of SONFH.In contrast,overexpression of FAR591 significantly promoted the GC-induced apoptosis of BMECs,which then aggravated the damage of GCs to the femoral head microcirculation and promoted the pathogenesis and progression of SONFH.Mechanistically,GCs activate the glucocorticoid receptor,which translocates to the nucleus and directly acts on the FAR591 gene promoter to induce FAR591 gene overexpression.Subsequently,FAR591 binds to the Fos gene promoter(–245–51)to form a stable RNA:DNA triplet structure and then recruits TATA-box binding protein associated factor 15 and RNA polymerase II to promote Fos expression through transcriptional activation.Fos activates the mitochondrial apoptotic pathway by regulating the expression of Bcl-2 interacting mediator of cell death(Bim)and P53 upregulated modulator of apoptosis(Puma)to mediate GC-induced apoptosis of BMECs,which leads to femoral head microcirculation dysfunction and femoral head necrosis.In conclusion,these results confirm the mechanistic link between lnc RNAs and the pathogenesis of SONFH,which helps reveal the pathogenesis of SONFH and provides a new target for the early prevention and treatment of SONFH.展开更多
Osteomyelitis is a common musculoskeletal infection in children,and the acute and chronic osteomyelitis are the two most common type.Acute osteomyelitis affects about 1 in every 5,000 to 10,000 people and is more comm...Osteomyelitis is a common musculoskeletal infection in children,and the acute and chronic osteomyelitis are the two most common type.Acute osteomyelitis affects about 1 in every 5,000 to 10,000 people and is more common in developing countries and economically disadvantaged areas.展开更多
BACKGROUND The molecular mechanisms of heart failure(HF) are still poorly understood. Circular RNA(circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more...BACKGROUND The molecular mechanisms of heart failure(HF) are still poorly understood. Circular RNA(circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF.METHODS & RESULTS We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs(DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-mi RNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10m RNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively.CONCLUSION These findings demonstrated circRNAs have species and tissue specific expression patterns;while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.展开更多
Achalasia cardia,type of esophageal dynamic disorder,is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sph...Achalasia cardia,type of esophageal dynamic disorder,is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter.Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia,and is more likely to occur in the elderly.Histological changes in the esophageal mucosa are considered pathogenic;however,studies have found that inflammation and genetic changes at the molecular level may also cause achalasia cardia,resulting in dysphagia,reflux,aspiration,retrosternal pain,and weight loss.Currently,the treatment options for achalasia focus on reducing the resting pressure of the lower esophageal sphincter,helping to empty the esophagus and relieve symptoms.Treatment measures include botulinum toxin injection,inflatable dilation,stent insertion,and surgical myotomy(open or laparoscopic).Surgical procedures are often subject to controversy owing to concerns about safety and effectiveness,particularly in older patients.Herein,we review clinical epidemiological and experimental data to determine the prevalence,pathogenesis,clinical presentation,diagnostic criteria,and treatment options for achalasia to support its clinical management.展开更多
文摘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.
基金supported by a Neurological Foundation First Postdoctoral Research Fellowship(2001 FFE)an Auckland Medical Research Foundation Grant (1121013)(to OOM)。
文摘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.
文摘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.
文摘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.
文摘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.
基金This work was supported by China Academy of Chinese Medical Sciences’Science and technology innovation project(CI2021B001)-Innovation team of Basic Theories of Chinese MedicineChina Academy of Chinese Medical Sciences’Youth Science and Technology Talent Project(Inheritance)(ZZ13-YQ-112)+2 种基金Shanxi Province Traditional Chinese Medicine Research Project(2022ZYYC280)Shanxi province Basic Research Program(202303021212235)Fundamental Research Funds for the Central public welfare research institutes(YZ-202034).
文摘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.
文摘The hidden world of amyloid biology has suddenly snapped into atomic-level focus,revealing over 80 amyloid protein fibrils,both pathogenic and functional.Unlike globular proteins,amyloid proteins flatten and stack into unbranched fibrils.Stranger still,a single protein sequence can adopt wildly different two-dimensional conformations,yielding distinct fibril polymorphs.
文摘Multiple sclerosis(MS) is a chronic inflammatory demyelinating disease of the central nervous system.A certain population of patients with MS present with a relapse-remitting disease course(RRMS) during the early phase and eventually advance to a progressive course(PMS).While immune modulation therapies have recently seen tremendous success in RRMS,our limited knowledge of pathogenesis hampers the development of effective treatments for PMS.
文摘In recent years,there has been a steady growth of interest in non-alcoholic fatty liver disease(NAFLD),which is associated with negative epidemiological data on the prevalence of the disease and its clinical significance.NAFLD is closely related to the metabolic syndrome and these relationships are the subject of active research.A growing body of evidence shows cross-linkages between metabolic abnormalities and the innate immune system in the development and progression of NAFLD.These links are bidirectional and largely still unclear,but a better understanding of them will improve the quality of diagnosis and management of patients.In addition,lipid metabolic disorders and the innate immune system link NAFLD with other diseases,such as atherosclerosis,which is of great clinical importance.
基金Ningxia Natural Science Foundation,No.2020AAC03329the Key Research and Development Projects of Ningxia,No.2022BEG03128.
文摘Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.
文摘The amyloid cascade hypothesis of Alzheimer’s pathogenesis:The amyloid cascade hypothesis of Alzheimer’s disease(AD)pathogenesis will shortly celebrate its thirtieth birthday(Hardy and Higgins,1992).Based on abundant genetic and biochemical evidence,it proposes that deposition of the amyloid-β(Aβ)peptide in brain parenchyma is an essential upstream trigger in AD pathogenesis that drives a cascade of events,specifically including the recruitment and pathological hyper-phosphorylation of the micro-tubule-associated protein tau,that culminate in derangement of synaptic function and,eventually,neuronal death.
文摘The novel coronavirus pneumonia(COVID-19)is spreading worldwide and threatening people greatly.The routes by which SARS-CoV-2 causes lung injury have grown to be a major concern in the scientific community since patients with new Coronavirus,severe acute respiratory syndrome coronavirus(SARS-CoV-2)have a high likelihood of developing acute respiratory distress syndrome(ARDS)in severe cases.The mortality rate of COVID-19 has increased over the period due to rapid spread,and it becomes crucial to understand the disease epidemiology,pathogenic mechanisms,and suitable treatment strategies.ARDS is a respiratory disorder and is one of the clinical manifestations observed in patients with severe COVID-19.In this scenario,it is important to address this problem to develop suitable treatment strategies.This review attempts to present the prevalence of ARDS in COVID-19 patients and their predictive causes and risk factors,highlighting the contrasting features of COVID-19-induced ARDS with typical ARDS.This review also presents insights into the association between SARS-CoV-2 and lung damage while exploring the potential COVID-19 mechanisms in ARDS from the perspective of the angiotensin-converting enzyme 2 protein,cytokine storm,immune responses,and other signaling pathways.The review also discusses the diagnosis strategies,pathogenesis,risk factors,and treatment options of COVID-19-related ARDS.
基金supported by the Anhui Famous Traditional Chinese Medicine Liu Jian Studio Construction Project(Traditional Chinese Medicine Development Secret[2018]No.11)the Ministry of Science and Technology National Key Research and Development Program Chinese Medicine Modernization Research Key Project(No.2018YFC1705204)+1 种基金Anhui Province Traditional Chinese Medicine Leading Talent Project(Traditional Chinese Medicine Development Secret[2018]No.23)the Anhui Key Research and Development Program Foreign Science and Technology Cooperation Project(No.201904b11020011).
文摘The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does not adequately account for all clinical characteristics and heterogeneity of OA.Genetics has emerged as a nascent and crucial area of research in OA.The epigenetic module presents a potential link between genetic and environmental risk factors and the susceptibility and pathogenesis of OA.As a critical epigenetic alteration,DNA methylation has been shown to have an important role in the etiology of OA and is a viable biomarker for predicting disease progression and medication response,as shown in this research.This review aims to update knowledge in the field of DNA methylation associated with OA to better identify the essential features of OA subtypes and pathological conditions,hence accelerating individualized treatment and precision medicine.
基金funded by the Portuguese Science and Technology Foundation (FCT) projectby the French Muscular Dystrophy Association(AFM-Téléthon).by the Ataxia UK+1 种基金by the CureCSB project.AndréConceicao and Rebekah Koppenol are supported by Ph.D.fellowships from FCT (DFA/BD/7892/2020SFRH/BD/148533/2019,respectively)
文摘Polyglutamine(polyQ) diseases are a group of different neurodegenerative disorders characterized by an abnormal expansion of the trinucleotide cytosine-adenine-guanine(CAG)within coding regions of each disease-associated gene.The abnormal expansion translates into a protein bearing an abnormally long tract of glutamines.
文摘Alzheimer’s disease (AD) is the leading neurodegenerative disorder globally.Despite this,there is minimal effective therapeutics proven to reduce or prevent the progression of this disease.Glutamate is the main excitatory neurotransmitter within the central nervous system and plays a crucial role in neuronal and synaptic functions.
基金supported by a University of Manitoba Graduate FellowshipGraduate Enhancement of Tricouncil Supplement (GETS)+2 种基金Hillary Kaufman Lerner Memorial Fundssupported by the grants from Multiple Sclerosis Society of Canada (EGDI-2936, EGDI-3742)the Canadian Institute of Health Research (133721 and 156218)
文摘Multiple sclerosis(MS)is a chronic immune-mediated disorder of the central nervous system(CNS)that causes focal demyelinating lesions,followed by axonal and neuronal degeneration.Several genetic and environmental factors are found to be associated with MS incidence.While MS etiology seems to be multifactorial and needs further elucidation,it is understood that the response of an immune system to specific myelin antigens triggers the onset of MS(Dendrou et al.,2015).However,how the autoimmune response initiates against myelin,and the cellular and molecular mechanisms underpinning the development and progression of MS are not fully understood.Thus,deconstructing MS pathogenesis is of paramount importance for identifying novel diagnostic and therapeutic targets for this complex disease.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82260429,82060397,82260434)the Guizhou Provincial Natural Science Foundation(Grant Nos.:Qiankehebasis[2020]1Y311,Qiankehebasis-ZK[2022]general 399,Qiankehebasis-ZK[2022]general 447)+3 种基金the Science and Technology Foundation of Guizhou Provincial Health Committee(Grant Nos.:gzwkj2021-232,gzwjkj2020-1-130,and gzwkj2021-234)the Start-up Fund for Doctoral Research at the Affiliated Hospital of Guizhou Medical University(gyfybsky-2022-14)the NSFC Cultivation Project of Guizhou Medical University(21NSFCP08)the Discipline Outstanding Reserve Talent Program of Affiliated Hospital of Guizhou Medical University。
文摘The specific pathogenesis of steroid-induced osteonecrosis of the femoral head(SONFH)is still not fully understood,and there is currently no effective early cure.Understanding the role and mechanism of long noncoding RNAs(lnc RNAs)in the pathogenesis of SONFH will help reveal the pathogenesis of SONFH and provide new targets for its early prevention and treatment.In this study,we first confirmed that glucocorticoid(GC)-induced apoptosis of bone microvascular endothelial cells(BMECs)is a pre-event in the pathogenesis and progression of SONFH.Then,we identified a new lnc RNA in BMECs via lnc RNA/m RNA microarray,termed Fosassociated linc RNA ENSRNOT00000088059.1(FAR591).FAR591 is highly expressed during GC-induced BMEC apoptosis and femoral head necrosis.Knockout of FAR591 effectively blocked the GC-induced apoptosis of BMECs,which then alleviated the damage of GCs to the femoral head microcirculation and inhibited the pathogenesis and progression of SONFH.In contrast,overexpression of FAR591 significantly promoted the GC-induced apoptosis of BMECs,which then aggravated the damage of GCs to the femoral head microcirculation and promoted the pathogenesis and progression of SONFH.Mechanistically,GCs activate the glucocorticoid receptor,which translocates to the nucleus and directly acts on the FAR591 gene promoter to induce FAR591 gene overexpression.Subsequently,FAR591 binds to the Fos gene promoter(–245–51)to form a stable RNA:DNA triplet structure and then recruits TATA-box binding protein associated factor 15 and RNA polymerase II to promote Fos expression through transcriptional activation.Fos activates the mitochondrial apoptotic pathway by regulating the expression of Bcl-2 interacting mediator of cell death(Bim)and P53 upregulated modulator of apoptosis(Puma)to mediate GC-induced apoptosis of BMECs,which leads to femoral head microcirculation dysfunction and femoral head necrosis.In conclusion,these results confirm the mechanistic link between lnc RNAs and the pathogenesis of SONFH,which helps reveal the pathogenesis of SONFH and provides a new target for the early prevention and treatment of SONFH.
文摘Osteomyelitis is a common musculoskeletal infection in children,and the acute and chronic osteomyelitis are the two most common type.Acute osteomyelitis affects about 1 in every 5,000 to 10,000 people and is more common in developing countries and economically disadvantaged areas.
基金funded by the National Natural Science Foundation of China(81900245,81730009,81941002 and 81700256).
文摘BACKGROUND The molecular mechanisms of heart failure(HF) are still poorly understood. Circular RNA(circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF.METHODS & RESULTS We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs(DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-mi RNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10m RNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively.CONCLUSION These findings demonstrated circRNAs have species and tissue specific expression patterns;while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.
文摘Achalasia cardia,type of esophageal dynamic disorder,is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter.Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia,and is more likely to occur in the elderly.Histological changes in the esophageal mucosa are considered pathogenic;however,studies have found that inflammation and genetic changes at the molecular level may also cause achalasia cardia,resulting in dysphagia,reflux,aspiration,retrosternal pain,and weight loss.Currently,the treatment options for achalasia focus on reducing the resting pressure of the lower esophageal sphincter,helping to empty the esophagus and relieve symptoms.Treatment measures include botulinum toxin injection,inflatable dilation,stent insertion,and surgical myotomy(open or laparoscopic).Surgical procedures are often subject to controversy owing to concerns about safety and effectiveness,particularly in older patients.Herein,we review clinical epidemiological and experimental data to determine the prevalence,pathogenesis,clinical presentation,diagnostic criteria,and treatment options for achalasia to support its clinical management.
