Hepatocellular carcinoma(HCC)is a major global health challenge,particularly in regions with high aflatoxin B1(AFB1)exposure.This editorial explores the mechanistic interplay between AFB1 and tissue inhibitor of metal...Hepatocellular carcinoma(HCC)is a major global health challenge,particularly in regions with high aflatoxin B1(AFB1)exposure.This editorial explores the mechanistic interplay between AFB1 and tissue inhibitor of metalloproteinase-3(TIMP-3)in AFB1-related HCC.TIMP-3,frequently downregulated in HCC due to promoter methylation,is linked to increased tumor aggressiveness and poor prognosis.We propose that AFB1 induces epigenetic silencing of TIMP-3,potentially via DNA adducts and oxidative stress,exacerbating AFB1-related HCC progression.This AFB1-TIMP-3 axis highlights TIMP-3’s potential as a prognostic biomarker and therapeutic target.Future research should focus on elucidating these molecular pathways and integrating TIMP-3 into clinical practice for early detection and targeted therapies in AFB1-prevalent regions.展开更多
A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANC...A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission. Four of these 5 patients were steroid-dependence, and immunosuppressants, such as azathioprine and cyclophosphamide, were in effective. In 3 patients, only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates thatulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients, with additional advantages of having no noticeable side-effects and less financial burden.展开更多
BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associa...BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.展开更多
Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix remodeling during embryonic develop- ment and disease. TIMP-3 expression was examined during Xenopus laevis embryogenesis: TIMP-3 transcrip...Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix remodeling during embryonic develop- ment and disease. TIMP-3 expression was examined during Xenopus laevis embryogenesis: TIMP-3 transcripts detected in the maternal pool of RNA increased at the mid-blastula transition, decreased dramatically during gastrulation and increased again during neurulation and axis elongation. Interestingly, the decrease during gastrulation was not seen in LiCl treated (dorsalized) embryos. Whole mount in situ hybridization of TIMP-3 using DIG-labeled RNA probes demonstrated that the transcripts were present in all dorsal tissues during embryogenesis, but were prominent only in head structures starting at stage 35. Overexpression of TIMP-3 through transgenesis and RNA injections led to devel- opmental abnormalities and death. Both overexpression strategies resulted in post-gastrulation perturbation including those to neural and head structures, as well as truncated axes. However, RNA injections resulted in more severe early defects such as failure of neural tube closure, and transgenesis caused truncated axes and head abnormalities. No transgenic embryo expressing TIMP-3 survived past stage 40.展开更多
背景:骨代谢紊乱会引起骨相关疾病的发生,而叉头框转录因子O3可以通过调节氧化应激、自噬水平等来影响骨组织细胞增殖、分化与凋亡,调控骨代谢过程。目的:系统性分析叉头框转录因子O3调控骨代谢及其在骨科疾病中作用机制的相关研究文献...背景:骨代谢紊乱会引起骨相关疾病的发生,而叉头框转录因子O3可以通过调节氧化应激、自噬水平等来影响骨组织细胞增殖、分化与凋亡,调控骨代谢过程。目的:系统性分析叉头框转录因子O3调控骨代谢及其在骨科疾病中作用机制的相关研究文献,为后续以叉头框转录因子O3为靶点治疗骨疾病的研究提供参考。方法:以“(SU=FoxO3a OR SU=Foxo3 OR SU=Forkhead box O3 OR SU=叉头框转录因子O3)AND SU=骨”为检索句在中国知网进行检索,以“主题:(“FoxO3a”)OR主题:(“Foxo3”)OR主题:(“Forkhead box O3”)OR主题:(“叉头框转录因子O3”)AND主题:(“骨”)”为检索句在万方医学数据库进行检索;以“((FoxO3a)OR(Foxo3)OR(Forkhead box O3))AND((bone)OR(Skeleton))”为检索句在PubMed数据库进行检索,排除陈旧、重复、质量较差以及不相关的文献,最终纳入56篇文献进行综述分析。结果与结论:①叉头框转录因子O3与骨髓间充质干细胞:叉头框转录因子O3能够促进成骨谱系的形成,还可通过激活自噬促进早期成骨分化。同时,叉头框转录因子O3在骨髓间充质干细胞中体现抗氧化特性,保护细胞免受氧化应激诱导的衰老。②叉头框转录因子O3与成骨细胞:叉头框转录因子O3在成骨细胞中能通过干扰Wnt/β-连环蛋白通路抑制成骨,同时能激活抗氧化酶保护成熟成骨细胞。叉头框转录因子O3能促进成骨祖细胞的增殖,并通过激活自噬促进成骨分化。③叉头框转录因子O3与破骨细胞:叉头框转录因子O3表达可抵抗氧化应激和激活自噬抑制破骨细胞生成。④叉头框转录因子O3与骨细胞:叉头框转录因子O3可通过抗氧化作用保护骨细胞,还可通过抑制p16和p53信号通路和抑制衰老相关分泌表型来减少骨流失。⑤叉头框转录因子O3与软骨细胞:叉头框转录因子O3在骨关节炎中对软骨细胞起到保护作用,抑制软骨细胞分解或凋亡,促进软骨细胞外基质合成,可抑制软骨细胞肥大;然而,叉头框转录因子O3与Runt相关转录因子1在软骨细胞中高度共表达却会促进软骨祖细胞的早期软骨形成和终末肥大。⑥叉头框转录因子O3通过参与氧化应激抵抗与调控自噬等过程影响骨代谢,参与多类骨相关疾病的病理进程。展开更多
基金Supported by the Chongqing Health Commission and Science and Technology Bureau,No.2023MSXM060.
文摘Hepatocellular carcinoma(HCC)is a major global health challenge,particularly in regions with high aflatoxin B1(AFB1)exposure.This editorial explores the mechanistic interplay between AFB1 and tissue inhibitor of metalloproteinase-3(TIMP-3)in AFB1-related HCC.TIMP-3,frequently downregulated in HCC due to promoter methylation,is linked to increased tumor aggressiveness and poor prognosis.We propose that AFB1 induces epigenetic silencing of TIMP-3,potentially via DNA adducts and oxidative stress,exacerbating AFB1-related HCC progression.This AFB1-TIMP-3 axis highlights TIMP-3’s potential as a prognostic biomarker and therapeutic target.Future research should focus on elucidating these molecular pathways and integrating TIMP-3 into clinical practice for early detection and targeted therapies in AFB1-prevalent regions.
基金Supported by National Natural Science Foundation of China, No. 30570829
文摘A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission. Four of these 5 patients were steroid-dependence, and immunosuppressants, such as azathioprine and cyclophosphamide, were in effective. In 3 patients, only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates thatulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients, with additional advantages of having no noticeable side-effects and less financial burden.
基金the Science-Technology Planning Project of Guangxi,No.Guike-AD19245174Guangxi Training Program for Medical High-level Academic Leaders,No.6 of Guiweikejiaofa[2020]-15+3 种基金Bose Talent Highland,No.2020-3-2Building Projects from the Key Laboratory of Molecular Pathology(Hepatobiliary Diseases)of Guangxi,No.Guiweikejiaofa[2020]-17the Key Laboratory of Tumor Molecular Pathology of Guangxi Colleges and Universities,No.Guijiaokeyan[2022]-10Clinical Key Specialty Building Project(For Pathology)of Guangxi,No.Guiweiyifa[2022]-21.
文摘BACKGROUND The dysregulation of tissue inhibitor of metalloproteinase-3(TIMP3)was positively correlated with the progression of hepatocellular carcinoma(HCC).However,it is not clear whether TIMP3 expression is associated with the clinico-pathological features and prognosis of aflatoxin B1(AFB1)-related HCC(AHCC).A retrospective study,including 182 patients with AHCC,was conducted to explore the link between TIMP3 expression in cancerous tissues and the clinico-pathological characteristics and prognosis of AHCC.TIMP3 expression was detected by immunohistochemistry and its effects on the clinicopathological features and prognosis of AHCC were evaluated by Kaplan-Meier survival analysis and Cox regression survival analysis.Odds ratio,hazard ratio(HR),median overall survival time(MST),median tumor recurrence-free survival time(MRT),and corresponding 95%confidential interval(CI)was calculated to RESULTS Kaplan-Meier survival analysis showed that compared with high TIMP3 expression,low TIMP3 expression in tumor tissues significantly decreased the MST(36.00 mo vs 18.00 mo)and MRT(32.00 mo vs 16 mo)of patients with AHCC.Multivariate Cox regression survival analysis further proved that decreased expression of TIMP3 increased the risk of death(HR=2.85,95%CI:2.04-4.00)and tumor recurrence(HR=2.26,95%CI:1.57-3.26).Furthermore,decreased expression of TIMP3 protein in tissues with AHCC was significantly correlated with tumor clinicopatho-logical features,such as tumor size,tumor grade and stage,tumor microvessel density,and tumor blood invasion.Additionally,TIMP3 protein expression was also negatively associated with amount of AFB1-DNA adducts in tumor tissues.CONCLUSION These findings indicate that the dysregulation of TIMP3 expression is related to AHCC biological behaviors and affects tumor outcome,suggesting that TIMP3 may act as a prognostic biomarker for AHCC.
文摘Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix remodeling during embryonic develop- ment and disease. TIMP-3 expression was examined during Xenopus laevis embryogenesis: TIMP-3 transcripts detected in the maternal pool of RNA increased at the mid-blastula transition, decreased dramatically during gastrulation and increased again during neurulation and axis elongation. Interestingly, the decrease during gastrulation was not seen in LiCl treated (dorsalized) embryos. Whole mount in situ hybridization of TIMP-3 using DIG-labeled RNA probes demonstrated that the transcripts were present in all dorsal tissues during embryogenesis, but were prominent only in head structures starting at stage 35. Overexpression of TIMP-3 through transgenesis and RNA injections led to devel- opmental abnormalities and death. Both overexpression strategies resulted in post-gastrulation perturbation including those to neural and head structures, as well as truncated axes. However, RNA injections resulted in more severe early defects such as failure of neural tube closure, and transgenesis caused truncated axes and head abnormalities. No transgenic embryo expressing TIMP-3 survived past stage 40.
文摘背景:骨代谢紊乱会引起骨相关疾病的发生,而叉头框转录因子O3可以通过调节氧化应激、自噬水平等来影响骨组织细胞增殖、分化与凋亡,调控骨代谢过程。目的:系统性分析叉头框转录因子O3调控骨代谢及其在骨科疾病中作用机制的相关研究文献,为后续以叉头框转录因子O3为靶点治疗骨疾病的研究提供参考。方法:以“(SU=FoxO3a OR SU=Foxo3 OR SU=Forkhead box O3 OR SU=叉头框转录因子O3)AND SU=骨”为检索句在中国知网进行检索,以“主题:(“FoxO3a”)OR主题:(“Foxo3”)OR主题:(“Forkhead box O3”)OR主题:(“叉头框转录因子O3”)AND主题:(“骨”)”为检索句在万方医学数据库进行检索;以“((FoxO3a)OR(Foxo3)OR(Forkhead box O3))AND((bone)OR(Skeleton))”为检索句在PubMed数据库进行检索,排除陈旧、重复、质量较差以及不相关的文献,最终纳入56篇文献进行综述分析。结果与结论:①叉头框转录因子O3与骨髓间充质干细胞:叉头框转录因子O3能够促进成骨谱系的形成,还可通过激活自噬促进早期成骨分化。同时,叉头框转录因子O3在骨髓间充质干细胞中体现抗氧化特性,保护细胞免受氧化应激诱导的衰老。②叉头框转录因子O3与成骨细胞:叉头框转录因子O3在成骨细胞中能通过干扰Wnt/β-连环蛋白通路抑制成骨,同时能激活抗氧化酶保护成熟成骨细胞。叉头框转录因子O3能促进成骨祖细胞的增殖,并通过激活自噬促进成骨分化。③叉头框转录因子O3与破骨细胞:叉头框转录因子O3表达可抵抗氧化应激和激活自噬抑制破骨细胞生成。④叉头框转录因子O3与骨细胞:叉头框转录因子O3可通过抗氧化作用保护骨细胞,还可通过抑制p16和p53信号通路和抑制衰老相关分泌表型来减少骨流失。⑤叉头框转录因子O3与软骨细胞:叉头框转录因子O3在骨关节炎中对软骨细胞起到保护作用,抑制软骨细胞分解或凋亡,促进软骨细胞外基质合成,可抑制软骨细胞肥大;然而,叉头框转录因子O3与Runt相关转录因子1在软骨细胞中高度共表达却会促进软骨祖细胞的早期软骨形成和终末肥大。⑥叉头框转录因子O3通过参与氧化应激抵抗与调控自噬等过程影响骨代谢,参与多类骨相关疾病的病理进程。
