High mobility group box 1(HMGB1),when released extracellularly,plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system.In experimental auto...High mobility group box 1(HMGB1),when released extracellularly,plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system.In experimental autoimmune encephalomyelitis(EAE),a condition that models multiple sclerosis,the levels of extracellular HMGB1 and interleukin-33(IL-33)have been found to be inversely correlated.However,the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive.Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes,upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice.Conversely,the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes.These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.展开更多
Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed ...Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.展开更多
The problem of ulcerative colitis(UC)is becoming increasingly relevant due to its prevalence and combination with psychological disorders.UC is associated with alterations in the intestinal microbiocenosis as one of t...The problem of ulcerative colitis(UC)is becoming increasingly relevant due to its prevalence and combination with psychological disorders.UC is associated with alterations in the intestinal microbiocenosis as one of the factors reducing tolerance to self-antigens.In addition,patients with UC often experience anxiety,depression and other negative emotional and psychological factors aggravating the course of the underlying disease.The study presented by Wang et al shows that the traditional Chinese medicine Wuling can exert its therapeutic effect by reversing the aberrant precursor of brain-derived neurotrophic factor(BDNF)/BDNF signaling in mice with UC and depression.The combination of Wuling powder with mesalazine can exhibit an antidepressant effect and reduce intestinal inflammation.Undoubtedly,the study by Chinese authors deserves attention,and changes in the balance of precursor of BDNF/p75 neurotrophin receptor/sortilin and BDNF/tropomyosin receptor kinase B signaling may become a novel therapeutic target for clinical treatment and further development of research.展开更多
目的探讨心电图P波参数与脑白质病变(white matter lesions,WMLs)严重程度之间的关联,为WMLs的预防和治疗提供科学依据。方法选取289例符合入组标准的WMLs住院患者作为研究对象,其均接受常规12导联心电图和头颅磁共振成像检查。根据Faze...目的探讨心电图P波参数与脑白质病变(white matter lesions,WMLs)严重程度之间的关联,为WMLs的预防和治疗提供科学依据。方法选取289例符合入组标准的WMLs住院患者作为研究对象,其均接受常规12导联心电图和头颅磁共振成像检查。根据Fazekas量表评分将这些患者分为无-轻度组(158例)和中-重度组(131例)。收集两组患者的临床资料、既往病史、心电图P波参数[包括P波时限、P波电轴、V_(1)导联P波终末电势(terminal force of P-wave in lead V_(1),PTFV_(1))],以及血脂等数据,并进行比较分析。采用Logistic回归模型分析影响WMLs的独立危险因素。结果中-重度组患者的年龄、有高血压或糖尿病病史者占比及PTFV_(1)>4000μV·ms者占比均明显高于无-轻度组,且差异均有统计学意义(均P<0.01)。多变量Logistic回归分析表明,年龄增长、高血压、糖尿病以及PTFV_(1)>4000μV·ms均为WMLs的独立危险因素。结论无创心电图指标PTFV_(1)经济便捷、易于获取,可用于评估心房异常,对WMLs的防治具有一定的应用价值。展开更多
Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve deve...Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.展开更多
OBJECTIVE:To investigate the effect of Neferine(Nef)on diabetic nephropathy(DN)and to explore the mechanism of Nef in DN based on miRNA regulation theory.METHODS:A DN mouse model was constructed and treated with Nef.S...OBJECTIVE:To investigate the effect of Neferine(Nef)on diabetic nephropathy(DN)and to explore the mechanism of Nef in DN based on miRNA regulation theory.METHODS:A DN mouse model was constructed and treated with Nef.Serum creatinine(Crea),blood urea(UREA)and urinary albumin were measured in mice by kits,and renal histopathological changes and fibrosis were observed by hematoxylin-eosin staining and Masson staining.Renal tissue superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)activities were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)signaling pathway-related proteins in kidney tissues.Quantitative reverse transcription-polymerase chain reaction(q RT-PCR)was used to detect the expression of miR-17-5p in kidney tissues.Subsequently,a DN in vitro model was constructed by high glucose culture of human mesangial cells(HMCs),cells were transfected with miR-17-5p mimic and/or treated with Nef,and we used q RTPCR to detect cellular miR-17 expression,flow cytometry to detect apoptosis,ELISAs to detect cellular SOD,MDA,and GSH-Px activities,Western blots to detect Nrf2/HO-1 signaling pathway-related protein expression,and dual luciferase reporter gene assays to verify the targeting relationship between Nrf2 and miR-17-5p.RESULTS:Administration of Nef significantly reduced the levels of blood glucose,Crea,and UREA and the expression of miR-17-5p,improved renal histopathology and fibrosis,significantly reduced MDA levels,elevated SOD and GSH-Px activities,and activated Nrf2 expression in kidney tissues from mice with DN.Nrf2 is a post-transcriptional target of miR-17-5p.In HMCs transfected with miR-17-5p mimics,the m RNA and protein levels of Nrf2 were significantly suppressed.Furthermore,miR-17-5p overexpression and Nef intervention resulted in a significant increase in high glucose-induced apoptosis and MDA levels in HMCs and a significant decrease in the protein expression of HO-1 and Nrf2.CONCLUSION:Collectively,these results indicate that Nef has an ameliorative effect on DN,and the mechanism may be through the miR-17-5p/Nrf2 pathway.展开更多
Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019)...Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.展开更多
This study demonstrated that brain areas surrounding the site of hematoma following intracerebral hemorrhage are characterized by significantly increased apoptosis and expression of neurotrophin receptor p75 and sorti...This study demonstrated that brain areas surrounding the site of hematoma following intracerebral hemorrhage are characterized by significantly increased apoptosis and expression of neurotrophin receptor p75 and sortilin. However, as detected by terminal deoxynucleotidyl transferase dUTP nick end labeling and immunohistochemical staining, there was no significant change in nerve growth factor precursor expression levels. The appearance of neurotrophin receptor p75 expressing cells was positively correlated with cells that were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. These findings confirm that the nerve growth factor precursor-neurotrophin receptor p75-sortilin heterotrimeric complex-mediated apoptosis pathway may play an important role in cellular apoptosis following intracerebral hemorrhage.展开更多
The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becomi...The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becoming a significant threat to human health. More and more studies have found that Toll-like receptor 4 (TLR4), as a member of the Toll-like receptor family, can promote the generation of inflammatory factors and is closely related to the body’s immune response and inflammatory response. Nuclear factor-κB p65 (NF-κB p65) is a nuclear transcription factor that can interact with various cytokines, growth factors, and apoptotic factors, participating in processes such as oxidative stress, apoptosis, and inflammation in the body [1]. This article elaborates on the structure, function, and signaling pathways of TLR4 and NF-κB p65 proteins in the pathogenesis of otitis media, aiming to provide more precise targets and better therapeutic efficacy for the diagnosis and treatment of otitis media. The role of inflammation in disease.展开更多
Background:Growth differentiation factor 11(GDF11),a transforming growth factor-beta superfamily member,is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis,and it has bee...Background:Growth differentiation factor 11(GDF11),a transforming growth factor-beta superfamily member,is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis,and it has been extensively characterized due to its capacity to target poorly differentiated cells,including transformed or cancer cells.Aim:In the present work,we aimed to describe the effects on migration,proliferation,and metabolism in the T-cell acute lymphoblastic leukemia-derived cell line Jurkat.Methods:Based on previous evidence,we analyzed metabolic changes exerted by GDF11 and its relationship with the aggressive phenotype.Results:We found a profound impact on mitochondrial metabolism and reactive oxygen species content;these were related to a decrement in the expression of the transcription factor forkhead-box-protein P3(FOXP3),which is highly involved in aggressiveness in leukemia cells;this was verified by a decrement in invasion capacity exhibited by the Jurkat cells under the GDF11 treatment.Conclusion:The results position the GDF11 response as a good alternative in the search for new therapeutic options for these diseases.展开更多
基金supported by the National Natural Science Foundation of China(82001281 and 82371195)Hubei Provincial Natural Science Foundation of China for Distinguished Young Scholars(2022CFA104)the Research Fund of Jianghan University(2022XKZX28).
文摘High mobility group box 1(HMGB1),when released extracellularly,plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system.In experimental autoimmune encephalomyelitis(EAE),a condition that models multiple sclerosis,the levels of extracellular HMGB1 and interleukin-33(IL-33)have been found to be inversely correlated.However,the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive.Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes,upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice.Conversely,the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes.These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
文摘Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.
文摘The problem of ulcerative colitis(UC)is becoming increasingly relevant due to its prevalence and combination with psychological disorders.UC is associated with alterations in the intestinal microbiocenosis as one of the factors reducing tolerance to self-antigens.In addition,patients with UC often experience anxiety,depression and other negative emotional and psychological factors aggravating the course of the underlying disease.The study presented by Wang et al shows that the traditional Chinese medicine Wuling can exert its therapeutic effect by reversing the aberrant precursor of brain-derived neurotrophic factor(BDNF)/BDNF signaling in mice with UC and depression.The combination of Wuling powder with mesalazine can exhibit an antidepressant effect and reduce intestinal inflammation.Undoubtedly,the study by Chinese authors deserves attention,and changes in the balance of precursor of BDNF/p75 neurotrophin receptor/sortilin and BDNF/tropomyosin receptor kinase B signaling may become a novel therapeutic target for clinical treatment and further development of research.
文摘目的探讨心电图P波参数与脑白质病变(white matter lesions,WMLs)严重程度之间的关联,为WMLs的预防和治疗提供科学依据。方法选取289例符合入组标准的WMLs住院患者作为研究对象,其均接受常规12导联心电图和头颅磁共振成像检查。根据Fazekas量表评分将这些患者分为无-轻度组(158例)和中-重度组(131例)。收集两组患者的临床资料、既往病史、心电图P波参数[包括P波时限、P波电轴、V_(1)导联P波终末电势(terminal force of P-wave in lead V_(1),PTFV_(1))],以及血脂等数据,并进行比较分析。采用Logistic回归模型分析影响WMLs的独立危险因素。结果中-重度组患者的年龄、有高血压或糖尿病病史者占比及PTFV_(1)>4000μV·ms者占比均明显高于无-轻度组,且差异均有统计学意义(均P<0.01)。多变量Logistic回归分析表明,年龄增长、高血压、糖尿病以及PTFV_(1)>4000μV·ms均为WMLs的独立危险因素。结论无创心电图指标PTFV_(1)经济便捷、易于获取,可用于评估心房异常,对WMLs的防治具有一定的应用价值。
文摘Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.
基金the Chengdu Health and Wellness Commission:Exploring the Mechanism of Neferine on Diabetic Nephropathy Based on mi R-17/Nrf2 Axis(No.2021127)。
文摘OBJECTIVE:To investigate the effect of Neferine(Nef)on diabetic nephropathy(DN)and to explore the mechanism of Nef in DN based on miRNA regulation theory.METHODS:A DN mouse model was constructed and treated with Nef.Serum creatinine(Crea),blood urea(UREA)and urinary albumin were measured in mice by kits,and renal histopathological changes and fibrosis were observed by hematoxylin-eosin staining and Masson staining.Renal tissue superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)activities were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)signaling pathway-related proteins in kidney tissues.Quantitative reverse transcription-polymerase chain reaction(q RT-PCR)was used to detect the expression of miR-17-5p in kidney tissues.Subsequently,a DN in vitro model was constructed by high glucose culture of human mesangial cells(HMCs),cells were transfected with miR-17-5p mimic and/or treated with Nef,and we used q RTPCR to detect cellular miR-17 expression,flow cytometry to detect apoptosis,ELISAs to detect cellular SOD,MDA,and GSH-Px activities,Western blots to detect Nrf2/HO-1 signaling pathway-related protein expression,and dual luciferase reporter gene assays to verify the targeting relationship between Nrf2 and miR-17-5p.RESULTS:Administration of Nef significantly reduced the levels of blood glucose,Crea,and UREA and the expression of miR-17-5p,improved renal histopathology and fibrosis,significantly reduced MDA levels,elevated SOD and GSH-Px activities,and activated Nrf2 expression in kidney tissues from mice with DN.Nrf2 is a post-transcriptional target of miR-17-5p.In HMCs transfected with miR-17-5p mimics,the m RNA and protein levels of Nrf2 were significantly suppressed.Furthermore,miR-17-5p overexpression and Nef intervention resulted in a significant increase in high glucose-induced apoptosis and MDA levels in HMCs and a significant decrease in the protein expression of HO-1 and Nrf2.CONCLUSION:Collectively,these results indicate that Nef has an ameliorative effect on DN,and the mechanism may be through the miR-17-5p/Nrf2 pathway.
基金supported by the UTHSC Bridge funding award (E073005058 Bridge Support-2022)the National Institute of Health (R01-NS09 7800 and R56 NS127924-01) to TI。
文摘Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.
基金the Science and Technology Research and Development Program of Shaanxi Province, No. 2007K15-01
文摘This study demonstrated that brain areas surrounding the site of hematoma following intracerebral hemorrhage are characterized by significantly increased apoptosis and expression of neurotrophin receptor p75 and sortilin. However, as detected by terminal deoxynucleotidyl transferase dUTP nick end labeling and immunohistochemical staining, there was no significant change in nerve growth factor precursor expression levels. The appearance of neurotrophin receptor p75 expressing cells was positively correlated with cells that were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. These findings confirm that the nerve growth factor precursor-neurotrophin receptor p75-sortilin heterotrimeric complex-mediated apoptosis pathway may play an important role in cellular apoptosis following intracerebral hemorrhage.
文摘The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becoming a significant threat to human health. More and more studies have found that Toll-like receptor 4 (TLR4), as a member of the Toll-like receptor family, can promote the generation of inflammatory factors and is closely related to the body’s immune response and inflammatory response. Nuclear factor-κB p65 (NF-κB p65) is a nuclear transcription factor that can interact with various cytokines, growth factors, and apoptotic factors, participating in processes such as oxidative stress, apoptosis, and inflammation in the body [1]. This article elaborates on the structure, function, and signaling pathways of TLR4 and NF-κB p65 proteins in the pathogenesis of otitis media, aiming to provide more precise targets and better therapeutic efficacy for the diagnosis and treatment of otitis media. The role of inflammation in disease.
基金funded by a grant from the Consejo Nacional de humanidades Ciencia y Tecnología(Conahcyt).Fronteras de la Ciencia 1320,Infra-2017280788Universidad Autónoma Metropolitana-Iztapalapa.
文摘Background:Growth differentiation factor 11(GDF11),a transforming growth factor-beta superfamily member,is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis,and it has been extensively characterized due to its capacity to target poorly differentiated cells,including transformed or cancer cells.Aim:In the present work,we aimed to describe the effects on migration,proliferation,and metabolism in the T-cell acute lymphoblastic leukemia-derived cell line Jurkat.Methods:Based on previous evidence,we analyzed metabolic changes exerted by GDF11 and its relationship with the aggressive phenotype.Results:We found a profound impact on mitochondrial metabolism and reactive oxygen species content;these were related to a decrement in the expression of the transcription factor forkhead-box-protein P3(FOXP3),which is highly involved in aggressiveness in leukemia cells;this was verified by a decrement in invasion capacity exhibited by the Jurkat cells under the GDF11 treatment.Conclusion:The results position the GDF11 response as a good alternative in the search for new therapeutic options for these diseases.
