BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory...BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination degradation.CONCLUSION The regulatory mechanism of TQ on HIF-1αprotein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90;Secondly,TQ reduced the initial expression of HIF-1αprotein by inhibiting the PI3K/AKT/mTOR pathway.展开更多
Plant height(PH)is associated with lodging resistance and planting density,which is regulated by a complicated gene network.In this study,we identified a spontaneous dwarfing mutation in maize,m30,with decreased inter...Plant height(PH)is associated with lodging resistance and planting density,which is regulated by a complicated gene network.In this study,we identified a spontaneous dwarfing mutation in maize,m30,with decreased internode number and length but increased internode diameter.A candidate gene,ZmCYP90D1,which encodes a member of the cytochrome P450 family,was isolated by map-based cloning.ZmCYP90D1 was constitutively expressed and showed highest expression in basal internodes,and its protein was targeted to the nucleus.A G-to-A substitution was identified to be the causal mutation,which resulted in a truncated protein in m30.Loss of function of ZmCYP90D1 changed expression of hormoneresponsive genes,in particular brassinosteroid(BR)-responsive genes which is mainly involved in cell cycle regulation and cell wall extension and modification in plants.The concentration of typhasterol(TY),a downstream intermediate of ZmCYP90D1 in the BR pathway,was reduced.A haplotype conferring dwarfing without reducing yield was identified.ZmCYP90D1 was inferred to influence plant height and stalk diameter via hormone-mediated cell division and cell growth via the BR pathway.展开更多
As the third leading cause of cancer-related deaths worldwide,hepatocellular carcinoma(HCC)represents a significant global health challenge.This paper provides an introduction and comprehensive review of transarterial...As the third leading cause of cancer-related deaths worldwide,hepatocellular carcinoma(HCC)represents a significant global health challenge.This paper provides an introduction and comprehensive review of transarterial radioembolization(TARE)with Yttrium-90(Y90),a widely performed transcatheter procedure for HCC patients who are not suitable candidates for surgery.TARE involves the targeted delivery of radioactive microspheres to liver tumors,offering a promising treatment option for managing HCC across various stages of the disease.By evaluating Y90 TARE outcomes across early,intermediate,and advanced stages of HCC,the review aims to present a thorough understanding of its efficacy and safety.Additionally,this paper highlights future research directions focusing on the potential of combination therapies with systemic and immunotherapies,as well as personalized treatments.The exploration of these innovative approaches aims to improve treatment outcomes,reduce adverse events,and provide new therapeutic opportunities for HCC patients.The review underscores the importance of ongoing research and clinical trials to optimize TARE further and integrate it into comprehensive HCC treatment paradigms.展开更多
目的通过门静脉部分结扎建立门静脉高压症大鼠模型,检测大鼠肠系膜动脉内皮一氧化氮合酶(e NOS)、热休克蛋白90(Hsp90)的表达,探讨二者在门静脉高压大鼠内脏高动力循环中的作用。方法检测假手术组(SHAM组)和门静脉高压症组(PHG组)大鼠...目的通过门静脉部分结扎建立门静脉高压症大鼠模型,检测大鼠肠系膜动脉内皮一氧化氮合酶(e NOS)、热休克蛋白90(Hsp90)的表达,探讨二者在门静脉高压大鼠内脏高动力循环中的作用。方法检测假手术组(SHAM组)和门静脉高压症组(PHG组)大鼠肠系膜动脉中e NOS、Hs P90的表达。结果 e NOS、Hs P90在门静脉高压症组(PHG组)的表达比假手术组(SHAM组)显著升高。结论 e NOS和Hsp90S在门静脉高压症高动力循环中发挥重要作用。展开更多
目的探讨热休克蛋白90α(heat shock protein 90α,Hsp90α)在结肠癌中的表达及潜在的临床价值。方法采用生物信息学和免疫组化法分析结肠癌中Hsp90α的表达水平,及其与临床病理学特征、预后和免疫细胞浸润水平的关系;采用CCK-8细胞增...目的探讨热休克蛋白90α(heat shock protein 90α,Hsp90α)在结肠癌中的表达及潜在的临床价值。方法采用生物信息学和免疫组化法分析结肠癌中Hsp90α的表达水平,及其与临床病理学特征、预后和免疫细胞浸润水平的关系;采用CCK-8细胞增殖实验和平板克隆实验检测敲除Hsp90AA1前后结肠癌细胞的增殖能力。结果生物信息学分析结果显示,Hsp90AA1在结肠癌组织中异常高表达,其表达水平越高,患者预后越差;Hsp90AA1表达与CD4^(+)T细胞(Th2)、CD8^(+)T细胞、髓样抑制细胞、Tregs细胞、中性粒细胞、巨噬细胞、M1巨噬细胞、M2巨噬细胞的浸润水平呈正相关;免疫组化结果显示结肠癌组织中Hsp90α表达明显高于癌旁正常组织,Hsp90α表达与患者性别、肿瘤大小、位置、分化程度、TNM分期、淋巴结转移、脉管癌栓、神经侵犯、远处转移等无关(P>0.05),与结肠癌患者年龄具有相关性(P<0.05)。Hsp90α高表达是影响结肠癌患者预后的独立危险因素。细胞实验结果显示,敲除Hsp90AA1可抑制结肠癌细胞的生长及增殖能力。结论Hsp90α在结肠癌中高表达,可能是结肠癌预后不良的潜在分子学标志物。展开更多
基金Supported by Health Commission of Qinghai Province,No.2021-wjzdx-18.
文摘BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination degradation.CONCLUSION The regulatory mechanism of TQ on HIF-1αprotein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90;Secondly,TQ reduced the initial expression of HIF-1αprotein by inhibiting the PI3K/AKT/mTOR pathway.
基金This work was supported by the National Natural Science Foundation of China(U2004144,31971893,32101743)the Key Technologies R&D Program of Henan Province(232102111080)Yunnan Academician Expert Workstation(202305AF150082).
文摘Plant height(PH)is associated with lodging resistance and planting density,which is regulated by a complicated gene network.In this study,we identified a spontaneous dwarfing mutation in maize,m30,with decreased internode number and length but increased internode diameter.A candidate gene,ZmCYP90D1,which encodes a member of the cytochrome P450 family,was isolated by map-based cloning.ZmCYP90D1 was constitutively expressed and showed highest expression in basal internodes,and its protein was targeted to the nucleus.A G-to-A substitution was identified to be the causal mutation,which resulted in a truncated protein in m30.Loss of function of ZmCYP90D1 changed expression of hormoneresponsive genes,in particular brassinosteroid(BR)-responsive genes which is mainly involved in cell cycle regulation and cell wall extension and modification in plants.The concentration of typhasterol(TY),a downstream intermediate of ZmCYP90D1 in the BR pathway,was reduced.A haplotype conferring dwarfing without reducing yield was identified.ZmCYP90D1 was inferred to influence plant height and stalk diameter via hormone-mediated cell division and cell growth via the BR pathway.
文摘As the third leading cause of cancer-related deaths worldwide,hepatocellular carcinoma(HCC)represents a significant global health challenge.This paper provides an introduction and comprehensive review of transarterial radioembolization(TARE)with Yttrium-90(Y90),a widely performed transcatheter procedure for HCC patients who are not suitable candidates for surgery.TARE involves the targeted delivery of radioactive microspheres to liver tumors,offering a promising treatment option for managing HCC across various stages of the disease.By evaluating Y90 TARE outcomes across early,intermediate,and advanced stages of HCC,the review aims to present a thorough understanding of its efficacy and safety.Additionally,this paper highlights future research directions focusing on the potential of combination therapies with systemic and immunotherapies,as well as personalized treatments.The exploration of these innovative approaches aims to improve treatment outcomes,reduce adverse events,and provide new therapeutic opportunities for HCC patients.The review underscores the importance of ongoing research and clinical trials to optimize TARE further and integrate it into comprehensive HCC treatment paradigms.
文摘目的通过门静脉部分结扎建立门静脉高压症大鼠模型,检测大鼠肠系膜动脉内皮一氧化氮合酶(e NOS)、热休克蛋白90(Hsp90)的表达,探讨二者在门静脉高压大鼠内脏高动力循环中的作用。方法检测假手术组(SHAM组)和门静脉高压症组(PHG组)大鼠肠系膜动脉中e NOS、Hs P90的表达。结果 e NOS、Hs P90在门静脉高压症组(PHG组)的表达比假手术组(SHAM组)显著升高。结论 e NOS和Hsp90S在门静脉高压症高动力循环中发挥重要作用。
文摘目的探讨热休克蛋白90α(heat shock protein 90α,Hsp90α)在结肠癌中的表达及潜在的临床价值。方法采用生物信息学和免疫组化法分析结肠癌中Hsp90α的表达水平,及其与临床病理学特征、预后和免疫细胞浸润水平的关系;采用CCK-8细胞增殖实验和平板克隆实验检测敲除Hsp90AA1前后结肠癌细胞的增殖能力。结果生物信息学分析结果显示,Hsp90AA1在结肠癌组织中异常高表达,其表达水平越高,患者预后越差;Hsp90AA1表达与CD4^(+)T细胞(Th2)、CD8^(+)T细胞、髓样抑制细胞、Tregs细胞、中性粒细胞、巨噬细胞、M1巨噬细胞、M2巨噬细胞的浸润水平呈正相关;免疫组化结果显示结肠癌组织中Hsp90α表达明显高于癌旁正常组织,Hsp90α表达与患者性别、肿瘤大小、位置、分化程度、TNM分期、淋巴结转移、脉管癌栓、神经侵犯、远处转移等无关(P>0.05),与结肠癌患者年龄具有相关性(P<0.05)。Hsp90α高表达是影响结肠癌患者预后的独立危险因素。细胞实验结果显示,敲除Hsp90AA1可抑制结肠癌细胞的生长及增殖能力。结论Hsp90α在结肠癌中高表达,可能是结肠癌预后不良的潜在分子学标志物。
