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 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
Nuclear factor kappa B(NF-κB) is one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli,including inflammatory cytokines, phorbol esters, ...Nuclear factor kappa B(NF-κB) is one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli,including inflammatory cytokines, phorbol esters, growth factors, and bacterial and viral products. The aim of this study is to demonstrate NF-κB expression in the mouse cochlea and its enhancement in response to lipopolysaccharides(LPS) and kanamycin(KA) treatment. Methods KA treatment consisted of subcutaneous KA injections at 700 mg/kg twice a day with an eight-hour interval between the two injections for 3 or 7 days. For animals in the LPS treatment group, a single dose of 0.3 mg LPS dissolved in 0.2 ml sterile saline were injected into both bullae through the tympanic membrane and kept there for 3 hours. Animals in the control group received subcutaneous saline injection for 7 days. Following immmunohistochemichal processing with rabbit polyclonal anti-NF-κB p65 antibodies, cryosections of the cochlea were examined for expression of NF-κB p65 in various structures in the cochlea. Results NF-κB p65 expression, identified by presence of brown reaction products characteristic of DAB immunohistochemistry, was visible in the spiral ligament, spiral prominence, tectorial membrane(TM), spiral ganglion and nerve fibers. Relatively weak NF-κB p65 expression was also visualized in the organ of Corti. Within the organ of Corti, the inner hair cells(IHC), outer hair cells(OHC), inner pillar cells(IP), outer pillar cells (OP), Deiter’s cells(DC), and Boettcher’s cells exhibited stronger staining than the inner sulcus cells, Hensen’s cells(HC) and Claudius’cells. No NF-κB p65 expression was seen in the nucleus of the IHC and OHC. NF-κB p65 expression was increased in animals exposed to LPS or KA, demonstrating significant differences in the staining between control animals and LPS/KA-treated animals. NF-κB p65 expression was not significantly different between LPS treated and KA treated animals or between 3 and 7 days in KA-treated animals. Conclusion LPS and KA exposure increases expression of NF-κB p65 in the mouse cochlea.展开更多
目的研究姜黄素对高脂诱导的非酒精性脂肪性肝病(NAFLD)中肝过氧化物酶体增殖物激活受体γ(PPAR-γ)和核因子κB(NF-κB)p65 m RNA及蛋白表达的影响。方法建立大鼠NAFLD模型,按照随机化原则分为5组:正常组、模型组、低剂量治疗组、中剂...目的研究姜黄素对高脂诱导的非酒精性脂肪性肝病(NAFLD)中肝过氧化物酶体增殖物激活受体γ(PPAR-γ)和核因子κB(NF-κB)p65 m RNA及蛋白表达的影响。方法建立大鼠NAFLD模型,按照随机化原则分为5组:正常组、模型组、低剂量治疗组、中剂量治疗组、高剂量治疗组。正常组给予普通饮食,其余4组给予高脂饮食,同时分别用羧甲基纤维素钠(CMC)和低、中、高剂量姜黄素进行治疗。持续治疗12周后,处死各组大鼠并进行处理分析。血清生物化学方法检测大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)和总胆固醇(TC)的含量;HE染色对大鼠肝组织进行病理学观察;免疫组织化学检测大鼠肝组织PPAR-γ和NF-κB p65蛋白的表达情况;RT-PCR检测PPAR-γ和NF-κB p65 m RNA的表达情况。结果治疗组(低、中、高剂量)大鼠血清中ALT、AST、TG、TC含量较模型组明显降低(P<0.05)。治疗组(低、中、高剂量)大鼠肝组织的脂肪变性程度较模型组明显减轻。与正常组比较,模型组肝组织PPAR-γm RNA及蛋白的表达水平均明显降低(P<0.05),而NF-κB p65 m RNA及蛋白的表达水平均明显升高(P<0.05)。与模型组比较,治疗组(低、中、高剂量)大鼠肝组织PPAR-γ的表达明显增加(P<0.05),PPAR-γ的表达水平以高剂量治疗组升高更加明显(P<0.01);与模型组相比,治疗组(低、中、高剂量)大鼠肝组织NF-κB p65的表达显著减少(P<0.05),NF-κB p65的表达水平以高剂量治疗组降低更加明显(P<0.01)。结论姜黄素可明显减轻高脂诱导的大鼠NAFLD肝组织的脂肪变性和炎性反应,其抗脂肪变性和抗炎的机制可能与姜黄素激活PPAR-γ的表达,从而抑制NF-κB p65的活性有关。PPAR-γ和NF-κB p65的表达参与了NAFLD的发生发展,控制这些信号分子的表达可能是姜黄素治疗NAFLD的重要机制之一。展开更多
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.
文摘Nuclear factor kappa B(NF-κB) is one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli,including inflammatory cytokines, phorbol esters, growth factors, and bacterial and viral products. The aim of this study is to demonstrate NF-κB expression in the mouse cochlea and its enhancement in response to lipopolysaccharides(LPS) and kanamycin(KA) treatment. Methods KA treatment consisted of subcutaneous KA injections at 700 mg/kg twice a day with an eight-hour interval between the two injections for 3 or 7 days. For animals in the LPS treatment group, a single dose of 0.3 mg LPS dissolved in 0.2 ml sterile saline were injected into both bullae through the tympanic membrane and kept there for 3 hours. Animals in the control group received subcutaneous saline injection for 7 days. Following immmunohistochemichal processing with rabbit polyclonal anti-NF-κB p65 antibodies, cryosections of the cochlea were examined for expression of NF-κB p65 in various structures in the cochlea. Results NF-κB p65 expression, identified by presence of brown reaction products characteristic of DAB immunohistochemistry, was visible in the spiral ligament, spiral prominence, tectorial membrane(TM), spiral ganglion and nerve fibers. Relatively weak NF-κB p65 expression was also visualized in the organ of Corti. Within the organ of Corti, the inner hair cells(IHC), outer hair cells(OHC), inner pillar cells(IP), outer pillar cells (OP), Deiter’s cells(DC), and Boettcher’s cells exhibited stronger staining than the inner sulcus cells, Hensen’s cells(HC) and Claudius’cells. No NF-κB p65 expression was seen in the nucleus of the IHC and OHC. NF-κB p65 expression was increased in animals exposed to LPS or KA, demonstrating significant differences in the staining between control animals and LPS/KA-treated animals. NF-κB p65 expression was not significantly different between LPS treated and KA treated animals or between 3 and 7 days in KA-treated animals. Conclusion LPS and KA exposure increases expression of NF-κB p65 in the mouse cochlea.
文摘目的研究姜黄素对高脂诱导的非酒精性脂肪性肝病(NAFLD)中肝过氧化物酶体增殖物激活受体γ(PPAR-γ)和核因子κB(NF-κB)p65 m RNA及蛋白表达的影响。方法建立大鼠NAFLD模型,按照随机化原则分为5组:正常组、模型组、低剂量治疗组、中剂量治疗组、高剂量治疗组。正常组给予普通饮食,其余4组给予高脂饮食,同时分别用羧甲基纤维素钠(CMC)和低、中、高剂量姜黄素进行治疗。持续治疗12周后,处死各组大鼠并进行处理分析。血清生物化学方法检测大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)和总胆固醇(TC)的含量;HE染色对大鼠肝组织进行病理学观察;免疫组织化学检测大鼠肝组织PPAR-γ和NF-κB p65蛋白的表达情况;RT-PCR检测PPAR-γ和NF-κB p65 m RNA的表达情况。结果治疗组(低、中、高剂量)大鼠血清中ALT、AST、TG、TC含量较模型组明显降低(P<0.05)。治疗组(低、中、高剂量)大鼠肝组织的脂肪变性程度较模型组明显减轻。与正常组比较,模型组肝组织PPAR-γm RNA及蛋白的表达水平均明显降低(P<0.05),而NF-κB p65 m RNA及蛋白的表达水平均明显升高(P<0.05)。与模型组比较,治疗组(低、中、高剂量)大鼠肝组织PPAR-γ的表达明显增加(P<0.05),PPAR-γ的表达水平以高剂量治疗组升高更加明显(P<0.01);与模型组相比,治疗组(低、中、高剂量)大鼠肝组织NF-κB p65的表达显著减少(P<0.05),NF-κB p65的表达水平以高剂量治疗组降低更加明显(P<0.01)。结论姜黄素可明显减轻高脂诱导的大鼠NAFLD肝组织的脂肪变性和炎性反应,其抗脂肪变性和抗炎的机制可能与姜黄素激活PPAR-γ的表达,从而抑制NF-κB p65的活性有关。PPAR-γ和NF-κB p65的表达参与了NAFLD的发生发展,控制这些信号分子的表达可能是姜黄素治疗NAFLD的重要机制之一。
