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
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
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
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
BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-assoc...BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-associated steatotic liver disease(MASLD)have not been fully understood.AIMTo investigate the therapeutic effects and mechanisms of BSP on MASLD by centering on the hepatocyte nuclearfactor kappa B p65(RelA)/hepatocyte nuclear factor-1 alpha(HNF1α)signaling.METHODSA mouse model of MASLD was induced by feeding with a high-fat-diet(HFD)and a hepatocyte model of steatosiswas induced by treatment with sodium oleate(SO)and sodium palmitate(SP).The therapeutic effects of BSP onMASLD were examined in vivo and in vitro.The mechanisms underlying the action of BSP were analyzed for theireffect on lipid metabolism disorder,endoplasmic reticulum(ER)stress,and the RelA/HNF1αsignaling.RESULTSHFD feeding reduced hepatocyte RelA and HNF1αexpression,induced ER stress,lipid metabolism disorder,andnecroptosis in mice,which were significantly mitigated by treatment with BSP.Furthermore,treatment with BSP orBSP-containing conditional rat serum significantly attenuated the sodium oleate/sodium palmitate(SO/SP)-induced hepatocyte steatosis by decreasing lipid accumulation,and lipid peroxidation,and enhancing theexpression of RelA,and HNF1α.The therapeutic effects of BSP on MASLD were partially abrogated by RELAsilencing in mice and RELA knockout in hepatocytes.RELA silencing or knockout significantly down-regulatedHNF1αexpression,and remodeled ER stress and oxidative stress responses during hepatic steatosis.CONCLUSIONTreatment with BSP ameliorates MASLD,associated with enhancing the RelA/HNF1αsignaling,remodeling ERstress and oxidative stress responses in hepatocytes.展开更多
Objective To investigate the mechanisms of catgut implantation at acupoints on ulcerative colitis. Methods Eighteen SD rats were randomly divided into a normal control group （NC）, a model group （MO） and a catgut i...Objective To investigate the mechanisms of catgut implantation at acupoints on ulcerative colitis. Methods Eighteen SD rats were randomly divided into a normal control group （NC）, a model group （MO） and a catgut implantation group （CI） with 6 rats in each group. Animals in group MO and group CI were treated by trinitro-benzene-sulfonic acid （TNBS） to establish model with colitis. No other treatment was given to the rats in group MO, but catgut was implanted at ＂Shàngjùxū＂ （上 巨虚 ST 37）, ＂Tiānshū＂ （天枢 ST 25） and ＂Dàchángshū＂ （大肠俞 BL 25） in the rats in group CI. The symptoms of diarrhea and bloody stool, and changes in histopathology were detected 15 days after the treatment. Expressions of splenic lymphocyte nuclear factor κB p65（NF-κB p65）and correlated signaling molecules（β2AR）were detected by the western blot method. Results Diarrhea and mucus bloody purulent stool were soon controlled, and mucous injures were obviously improved in group CI. The NF-κB p65 value of splenic lymphocytes was signifi cantly increased （P0.01） and expression of β2AR remarkably reduced in group MO （P0.01）, compared with group NC. But, the NF-κB p65 value was significantly decreased （P0.01） and expression of β2AR remarkably increased in group CI （P 0.01） , compared with group MO. Conclusion Catgut implantation at acupoints is obviously effective in treating experimental colitis. Modulation of NF-κB p65 and the correlated signaling molecules β2AR may be involved in the mechanisms.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.
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.
基金National Natural Science Foundation of China,No.32260089Science and Technology Research Foundation of Guizhou Province,No.QKHJC-ZK(2022)YB642+3 种基金Science and Technology Research Foundation of Hubei Province,No.2022BCE030Science and Technology Research Foundation of Changzhou City,No.CE20225040Science and Technology Research Foundation of Zunyi City,No.ZSKHHZ(2022)344 and No.ZSKHHZ(2022)360WBE Liver Fibrosis Foundation,No.CFHPC2025028.
文摘BACKGROUND Bletilla striata polysaccharides(BSP)have antioxidant,immune regulation,and anti-fibrotic activities.However,the therapeutic effect and mechanisms underlying the action of BSP in metabolic dysfunction-associated steatotic liver disease(MASLD)have not been fully understood.AIMTo investigate the therapeutic effects and mechanisms of BSP on MASLD by centering on the hepatocyte nuclearfactor kappa B p65(RelA)/hepatocyte nuclear factor-1 alpha(HNF1α)signaling.METHODSA mouse model of MASLD was induced by feeding with a high-fat-diet(HFD)and a hepatocyte model of steatosiswas induced by treatment with sodium oleate(SO)and sodium palmitate(SP).The therapeutic effects of BSP onMASLD were examined in vivo and in vitro.The mechanisms underlying the action of BSP were analyzed for theireffect on lipid metabolism disorder,endoplasmic reticulum(ER)stress,and the RelA/HNF1αsignaling.RESULTSHFD feeding reduced hepatocyte RelA and HNF1αexpression,induced ER stress,lipid metabolism disorder,andnecroptosis in mice,which were significantly mitigated by treatment with BSP.Furthermore,treatment with BSP orBSP-containing conditional rat serum significantly attenuated the sodium oleate/sodium palmitate(SO/SP)-induced hepatocyte steatosis by decreasing lipid accumulation,and lipid peroxidation,and enhancing theexpression of RelA,and HNF1α.The therapeutic effects of BSP on MASLD were partially abrogated by RELAsilencing in mice and RELA knockout in hepatocytes.RELA silencing or knockout significantly down-regulatedHNF1αexpression,and remodeled ER stress and oxidative stress responses during hepatic steatosis.CONCLUSIONTreatment with BSP ameliorates MASLD,associated with enhancing the RelA/HNF1αsignaling,remodeling ERstress and oxidative stress responses in hepatocytes.
基金Supported by the National Scientific Foundation:30772878
文摘Objective To investigate the mechanisms of catgut implantation at acupoints on ulcerative colitis. Methods Eighteen SD rats were randomly divided into a normal control group （NC）, a model group （MO） and a catgut implantation group （CI） with 6 rats in each group. Animals in group MO and group CI were treated by trinitro-benzene-sulfonic acid （TNBS） to establish model with colitis. No other treatment was given to the rats in group MO, but catgut was implanted at ＂Shàngjùxū＂ （上 巨虚 ST 37）, ＂Tiānshū＂ （天枢 ST 25） and ＂Dàchángshū＂ （大肠俞 BL 25） in the rats in group CI. The symptoms of diarrhea and bloody stool, and changes in histopathology were detected 15 days after the treatment. Expressions of splenic lymphocyte nuclear factor κB p65（NF-κB p65）and correlated signaling molecules（β2AR）were detected by the western blot method. Results Diarrhea and mucus bloody purulent stool were soon controlled, and mucous injures were obviously improved in group CI. The NF-κB p65 value of splenic lymphocytes was signifi cantly increased （P0.01） and expression of β2AR remarkably reduced in group MO （P0.01）, compared with group NC. But, the NF-κB p65 value was significantly decreased （P0.01） and expression of β2AR remarkably increased in group CI （P 0.01） , compared with group MO. Conclusion Catgut implantation at acupoints is obviously effective in treating experimental colitis. Modulation of NF-κB p65 and the correlated signaling molecules β2AR may be involved in the mechanisms.
