Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasio...Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasionally,chronic liver disease.We report an incidental finding of a novel null AAT allele,Q0Milano,consisting of a 17 nucleotides deletion in exon 3 of SERPINA1 gene,in an Italian child with persistently increased liver enzymes,a mild decrease in circulating AAT levels and without any pulmonary disease.Q0Milano variant results in an unfunctional protein lacking of AAT active site,as the resultant protein is truncated near PiS locus involved in AAT protein stability.展开更多
Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has no...Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.展开更多
OBJECTIVE:To evaluate the effect of Fuzi Lizhong decoction(附子理中汤)on intestinal flora,serum inflammatory factors,and hypoxia inducible factor-1α(HIF-1α)in patients with colorectal cancer associated with spleen a...OBJECTIVE:To evaluate the effect of Fuzi Lizhong decoction(附子理中汤)on intestinal flora,serum inflammatory factors,and hypoxia inducible factor-1α(HIF-1α)in patients with colorectal cancer associated with spleen and kidney Yang deficiency.METHODS:A total of 100 patients diagnosed with advanced colorectal cancer were randomly divided into two groups:a control group(CON,50)and a Traditional Chinese Medicine(TCM)group(n=50).The control group received treatment with the Capecitabine+Oxaliplatin(CAPEOX)regimen,while the TCM group received the same regimen along with Fuzi Lizhong decoction for six weeks.Changes in intestinal flora were assessed before and after six weeks in both groups.Serum markers,including HIF-1α,vascular endothelial growth factor(VEGF),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α),were measured using enzyme-linked immunosorbent assay.Adverse reactions,clinical efficacy,and TCM syndrome efficacy were also monitored.RESULTS:After six weeks,the levels of Lactobacillus and Bifidobacterium were significantly higher,while the levels of Enterobacter and Enterococcus were significantly lower in the TCM group compared to the control group(P<0.05).Serum levels of HIF-1α,VEGF,IL-6,and TNF-αwere also significantly reduced in the TCM group compared to the control group(P<0.05).Additionally,the incidence of adverse reactions was lower,and the clinical efficacy was higher in the TCM group compared to the control group(P<0.05).CONCLUSION:Fuzi Lizhong decoction effectively improves intestinal microbiota composition,reduces inflammatory factors and HIF-1αexpression,alleviates chemotherapy-related adverse reactions,enhances clinical efficacy,and may inhibit tumor growth in patients with colorectal cancer.展开更多
A hair tonic containing 1.0%Arctium lappa root extract(ALRE)was evaluated for its efficacy and tolerability in Chinese consumers.ALRE was selected based on its ability to promote Collagen Type XVII Alpha 1(COL17A1)syn...A hair tonic containing 1.0%Arctium lappa root extract(ALRE)was evaluated for its efficacy and tolerability in Chinese consumers.ALRE was selected based on its ability to promote Collagen Type XVII Alpha 1(COL17A1)synthesis,along with other active ingredients targeting scalp health and follicular regeneration.In vitro assays confirmed that ALRE significantly enhanced COL17A1 expression.A 28-day clinical trial involving Chinese participants demonstrated that the tonic reduced hair loss by 37.61%and increased local hair density by 26.63%,with no reported adverse effects.These findings validate the product’s effectiveness in a distinct consumer population and highlight the importance of integrating mechanistic insights with clinical validation.Further research should explore long-term efficacy and demographic-specific responses to optimize its application.展开更多
BACKGROUND The upregulation of serpin family B member 5(SERPINB5)has been linked to the progression of rectal cancer.However,the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully unde...BACKGROUND The upregulation of serpin family B member 5(SERPINB5)has been linked to the progression of rectal cancer.However,the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully understood.AIM To investigate the roles and mechanisms of SERPINB5 in rectal cancer.METHODS SERPINB5 protein level in rectal cancer tissues and cell lines was measured through western blot analysis.SW480 cells were transfected with pcDNASERPINB5 or short-hairpin RNA targeting SERPINB5(sh-SERPINB5).Cell proliferation,invasion,and apoptosis were then evaluated.The interaction between SERPINB5 and heat shock protein 90 alpha class A member 1(HSP90AA1)was confirmed through a co-immunoprecipitation assay.Subsequently,pcDNAHSP90AA1 or sh-HSP90AA1 was transfected into SW480 cells,and cell progression was then detected.Moreover,rescue experiments were used to investigate the effect of the SERPINB5/HSP90AA1 axis on rectal cancer progression.Additionally,sh-SERPINB5-transfected SW480 cells were implanted into nude mice,and xenograft tumor growth was then evaluated.RESULTS SERPINB5 was prominently upregulated in rectal cancer tissues and cells.SERPINB5 overexpression increased SW480 cell proliferation and invasion while reducing apoptosis.In contrast,SERPINB5 knockdown had the opposite effects.Moreover,SERPINB5 could interact with HSP90AA1 and promote HSP90AA1 expression in SW480 cells.HSP90AA1 overexpression facilitated SW480 cell proliferation and invasion and restrained apoptosis.By contrast,HSP90AA1 knockdown suppressed cell progression.The upregulation of HSP90AA1 reversed the SERPINB5 silencing-mediated inhibition of SW480 cell progression.Additionally,SERPINB5 knockdown retarded the growth of rectal cancer tumors in vivo.CONCLUSION SERPINB5 knockdown inhibited rectal cancer cell proliferation and invasion and retarded xenograft tumor growth by inhibiting HSP90AA1 expression.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
目的探讨苦参素联合胸腺肽α1治疗失代偿期肝硬化的抗病毒疗效。方法将42例失代偿期丙型肝炎肝硬化患者按照随机数字表分成2组,对照组(n=21)给予保肝、白蛋白基础治疗,观察组(n=21)在基础治疗之上加用苦参素、胸腺肽α1治疗,疗程48周。...目的探讨苦参素联合胸腺肽α1治疗失代偿期肝硬化的抗病毒疗效。方法将42例失代偿期丙型肝炎肝硬化患者按照随机数字表分成2组,对照组(n=21)给予保肝、白蛋白基础治疗,观察组(n=21)在基础治疗之上加用苦参素、胸腺肽α1治疗,疗程48周。比较2组患者治疗前后临床症状改善、Child-Pugh评分、血生化指标、HCV-RNA(hepatitis C virus-RNA)变化情况。结果对照组65.0%患者乏力消失,62.5%患者腹胀消失,50%患者腹水消失Child-Pugh评分由治疗前的(9.7±1.4)分降至治疗后的(8.3±0.7)分,观察组85.7%患者乏力消失,87.5%患者腹胀消失,88.3%患者腹水消失Child-Pugh评分由治疗前的(9.8±1.6)分降至治疗后的(5.7±0.6)分,2组临床症状改善、Child-Pugh评分差异均具有统计学意义(P<0.05);观察组患者血生化指标改善与对照组相比有统计学意义(P<0.05);对照组治疗前后HCV-RNA无显著变化,观察组治疗前后HCV-RNA有显著性差异(P<0.05)。结论苦参素联合胸腺肽α1治疗失代偿期丙型肝炎肝硬化有效降低HCV-RNA水平,延缓肝硬化进展。展开更多
基金Supported by The Borsa M.Coppo AISF,Italian Association for the Study of the Liver to Rametta R
文摘Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasionally,chronic liver disease.We report an incidental finding of a novel null AAT allele,Q0Milano,consisting of a 17 nucleotides deletion in exon 3 of SERPINA1 gene,in an Italian child with persistently increased liver enzymes,a mild decrease in circulating AAT levels and without any pulmonary disease.Q0Milano variant results in an unfunctional protein lacking of AAT active site,as the resultant protein is truncated near PiS locus involved in AAT protein stability.
基金supported by the National Natural Science Foundation of China(82270479,82070460)the Beijing Natural Science Foundation(7242084 to Xun-De Xian)the National Key Research and Development Program of China from the Ministry of Science and Technology(2021YFF0702802 to Yu-Hui Wang).
文摘Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.
基金Supported by the Guangxi Natural Science Foundation“Controllable Synthesis of Ordered Mesoporous Seafoam-Loaded g-C3N4 Gomposites and Their Mechanism of Adsorption-Photocatalytic Degradation of Antidepressants in Water Bodies”(2017GXNSFBA198216)the Open Fund for the Director of Guangxi Key Laboratory of Spatial Information and Geographic Information“Geographic Spatial Analysis of Regional Urinary Tract Stone Disease”(19-185-10-04)。
文摘OBJECTIVE:To evaluate the effect of Fuzi Lizhong decoction(附子理中汤)on intestinal flora,serum inflammatory factors,and hypoxia inducible factor-1α(HIF-1α)in patients with colorectal cancer associated with spleen and kidney Yang deficiency.METHODS:A total of 100 patients diagnosed with advanced colorectal cancer were randomly divided into two groups:a control group(CON,50)and a Traditional Chinese Medicine(TCM)group(n=50).The control group received treatment with the Capecitabine+Oxaliplatin(CAPEOX)regimen,while the TCM group received the same regimen along with Fuzi Lizhong decoction for six weeks.Changes in intestinal flora were assessed before and after six weeks in both groups.Serum markers,including HIF-1α,vascular endothelial growth factor(VEGF),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α),were measured using enzyme-linked immunosorbent assay.Adverse reactions,clinical efficacy,and TCM syndrome efficacy were also monitored.RESULTS:After six weeks,the levels of Lactobacillus and Bifidobacterium were significantly higher,while the levels of Enterobacter and Enterococcus were significantly lower in the TCM group compared to the control group(P<0.05).Serum levels of HIF-1α,VEGF,IL-6,and TNF-αwere also significantly reduced in the TCM group compared to the control group(P<0.05).Additionally,the incidence of adverse reactions was lower,and the clinical efficacy was higher in the TCM group compared to the control group(P<0.05).CONCLUSION:Fuzi Lizhong decoction effectively improves intestinal microbiota composition,reduces inflammatory factors and HIF-1αexpression,alleviates chemotherapy-related adverse reactions,enhances clinical efficacy,and may inhibit tumor growth in patients with colorectal cancer.
文摘A hair tonic containing 1.0%Arctium lappa root extract(ALRE)was evaluated for its efficacy and tolerability in Chinese consumers.ALRE was selected based on its ability to promote Collagen Type XVII Alpha 1(COL17A1)synthesis,along with other active ingredients targeting scalp health and follicular regeneration.In vitro assays confirmed that ALRE significantly enhanced COL17A1 expression.A 28-day clinical trial involving Chinese participants demonstrated that the tonic reduced hair loss by 37.61%and increased local hair density by 26.63%,with no reported adverse effects.These findings validate the product’s effectiveness in a distinct consumer population and highlight the importance of integrating mechanistic insights with clinical validation.Further research should explore long-term efficacy and demographic-specific responses to optimize its application.
基金Supported by the Medical Science Research Project Plan of the Hebei Provincial Health Commission,No.20210027.
文摘BACKGROUND The upregulation of serpin family B member 5(SERPINB5)has been linked to the progression of rectal cancer.However,the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully understood.AIM To investigate the roles and mechanisms of SERPINB5 in rectal cancer.METHODS SERPINB5 protein level in rectal cancer tissues and cell lines was measured through western blot analysis.SW480 cells were transfected with pcDNASERPINB5 or short-hairpin RNA targeting SERPINB5(sh-SERPINB5).Cell proliferation,invasion,and apoptosis were then evaluated.The interaction between SERPINB5 and heat shock protein 90 alpha class A member 1(HSP90AA1)was confirmed through a co-immunoprecipitation assay.Subsequently,pcDNAHSP90AA1 or sh-HSP90AA1 was transfected into SW480 cells,and cell progression was then detected.Moreover,rescue experiments were used to investigate the effect of the SERPINB5/HSP90AA1 axis on rectal cancer progression.Additionally,sh-SERPINB5-transfected SW480 cells were implanted into nude mice,and xenograft tumor growth was then evaluated.RESULTS SERPINB5 was prominently upregulated in rectal cancer tissues and cells.SERPINB5 overexpression increased SW480 cell proliferation and invasion while reducing apoptosis.In contrast,SERPINB5 knockdown had the opposite effects.Moreover,SERPINB5 could interact with HSP90AA1 and promote HSP90AA1 expression in SW480 cells.HSP90AA1 overexpression facilitated SW480 cell proliferation and invasion and restrained apoptosis.By contrast,HSP90AA1 knockdown suppressed cell progression.The upregulation of HSP90AA1 reversed the SERPINB5 silencing-mediated inhibition of SW480 cell progression.Additionally,SERPINB5 knockdown retarded the growth of rectal cancer tumors in vivo.CONCLUSION SERPINB5 knockdown inhibited rectal cancer cell proliferation and invasion and retarded xenograft tumor growth by inhibiting HSP90AA1 expression.
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.
文摘目的探讨苦参素联合胸腺肽α1治疗失代偿期肝硬化的抗病毒疗效。方法将42例失代偿期丙型肝炎肝硬化患者按照随机数字表分成2组,对照组(n=21)给予保肝、白蛋白基础治疗,观察组(n=21)在基础治疗之上加用苦参素、胸腺肽α1治疗,疗程48周。比较2组患者治疗前后临床症状改善、Child-Pugh评分、血生化指标、HCV-RNA(hepatitis C virus-RNA)变化情况。结果对照组65.0%患者乏力消失,62.5%患者腹胀消失,50%患者腹水消失Child-Pugh评分由治疗前的(9.7±1.4)分降至治疗后的(8.3±0.7)分,观察组85.7%患者乏力消失,87.5%患者腹胀消失,88.3%患者腹水消失Child-Pugh评分由治疗前的(9.8±1.6)分降至治疗后的(5.7±0.6)分,2组临床症状改善、Child-Pugh评分差异均具有统计学意义(P<0.05);观察组患者血生化指标改善与对照组相比有统计学意义(P<0.05);对照组治疗前后HCV-RNA无显著变化,观察组治疗前后HCV-RNA有显著性差异(P<0.05)。结论苦参素联合胸腺肽α1治疗失代偿期丙型肝炎肝硬化有效降低HCV-RNA水平,延缓肝硬化进展。
