BACKGROUND Necroptosis has emerged as a novel molecular pathway that can be targeted by chemotherapy agents in the treatment of cancer.OSW-1,which is derived from the bulbs of Ornithogalum saundersiae Baker,exerts a w...BACKGROUND Necroptosis has emerged as a novel molecular pathway that can be targeted by chemotherapy agents in the treatment of cancer.OSW-1,which is derived from the bulbs of Ornithogalum saundersiae Baker,exerts a wide range of pharmaco-logical effects.AIM To explore whether OSW-1 can induce necroptosis in colorectal cancer(CRC)cells,thereby expanding its range of clinical applications.METHODS We performed a sequence of functional experiments,including Cell Counting Kit-8 assays and flow cytometry analysis,to assess the inhibitory effect of OSW-1 on CRC cells.We utilized quantitative proteomics,employing tandem mass tag label-ing combined with liquid chromatography-tandem mass spectrometry,to analyze changes in protein expression.Subsequent bioinformatic analysis was conducted to elucidate the biological processes associated with the identified proteins.Transmission electron microscopy(TEM)and immunofluorescence studies were also performed to examine the effects of OSW-1 on necroptosis.Finally,western blotting,siRNA experiments,and immunoprecipitation were employed to evaluate protein interactions within CRC cells.RESULTS The results revealed that OSW-1 exerted a strong inhibitory effect on CRC cells,and this effect was accompanied by a necroptosis-like morphology that was observable via TEM.OSW-1 was shown to trigger necroptosis via activation of the RIPK1/RIPK3/MLKL pathway.Furthermore,the accumulation of p62/SQSTM1 was shown to mediate OSW-1-induced necroptosis through its interaction with RIPK1.CONCLUSION We propose that OSW-1 can induce necroptosis through the RIPK1/RIPK3/MLKL signaling pathway,and that this effect is mediated by the RIPK1-p62/SQSTM1 complex,in CRC cells.These results provide a theoretical foundation for the use of OSW-1 in the clinical treatment of CRC.展开更多
研究发现细胞死亡与骨关节炎(osteoarthritis,OA)的发病机制密切相关,除了凋亡、铁死亡、焦亡以外,目前又发现了一种全新的由受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)和受体相互作用蛋白激酶3(receptor-int...研究发现细胞死亡与骨关节炎(osteoarthritis,OA)的发病机制密切相关,除了凋亡、铁死亡、焦亡以外,目前又发现了一种全新的由受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)和受体相互作用蛋白激酶3(receptor-interacting protein kinase 3,RIPK3)介导的细胞死亡方式——程序性坏死。作为一种新型的受调控的细胞死亡方式,细胞的程序性坏死已被证实在部分炎症性疾病中扮演着重要的角色,但其与OA的关系还不够明晰。本文通过对PubMed、Web of Science、中国知网数据库的检索结果进行分析,总结了程序性坏死的特征、分子机制及其与软骨细胞炎症的关系等,期望对阐明软骨细胞程序性坏死在OA疾病进程中的作用有所帮助。展开更多
Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary disease typically caused bymicrobial infections, trauma, inhalation of harmful gases, and other factors. It is characterized by an inflammatio...Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary disease typically caused bymicrobial infections, trauma, inhalation of harmful gases, and other factors. It is characterized by an inflammation inthe lungs and increased alveolar permeability, leading to pulmonary edema and consequently, a low oxygen supply orhypoxemia. ARDS is responsible for 1 in 10 admissions to intensive care units, and the mortality rate for patientswith severe ARDS is as high as 46%. Extensive efforts have been devoted to investigating the pathological mechanismsof ARDS to develop new effective clinical strategies. Recent studies have reported that receptor-interacting serine/threonine kinase 1 (RIPK1) is involved in the pathogenesis of ARDS. RIPK1 is a critical mediator of programmed celldeath and inflammation. Growing evidence suggests that RIPK1 plays a role in the pathogenesis of differentinflammatory diseases and serves as a promising pharmaceutical target. This review summarizes and sheds some lighton the recent findings regarding the role of RIPK1 and related molecules in the pathogenesis of ARDS.展开更多
基金Supported by the Natural Science Foundation of Liaoning Province,No.2022-MS-330and Key Projects in Liaoning Province,No.2020JH2/10300046.
文摘BACKGROUND Necroptosis has emerged as a novel molecular pathway that can be targeted by chemotherapy agents in the treatment of cancer.OSW-1,which is derived from the bulbs of Ornithogalum saundersiae Baker,exerts a wide range of pharmaco-logical effects.AIM To explore whether OSW-1 can induce necroptosis in colorectal cancer(CRC)cells,thereby expanding its range of clinical applications.METHODS We performed a sequence of functional experiments,including Cell Counting Kit-8 assays and flow cytometry analysis,to assess the inhibitory effect of OSW-1 on CRC cells.We utilized quantitative proteomics,employing tandem mass tag label-ing combined with liquid chromatography-tandem mass spectrometry,to analyze changes in protein expression.Subsequent bioinformatic analysis was conducted to elucidate the biological processes associated with the identified proteins.Transmission electron microscopy(TEM)and immunofluorescence studies were also performed to examine the effects of OSW-1 on necroptosis.Finally,western blotting,siRNA experiments,and immunoprecipitation were employed to evaluate protein interactions within CRC cells.RESULTS The results revealed that OSW-1 exerted a strong inhibitory effect on CRC cells,and this effect was accompanied by a necroptosis-like morphology that was observable via TEM.OSW-1 was shown to trigger necroptosis via activation of the RIPK1/RIPK3/MLKL pathway.Furthermore,the accumulation of p62/SQSTM1 was shown to mediate OSW-1-induced necroptosis through its interaction with RIPK1.CONCLUSION We propose that OSW-1 can induce necroptosis through the RIPK1/RIPK3/MLKL signaling pathway,and that this effect is mediated by the RIPK1-p62/SQSTM1 complex,in CRC cells.These results provide a theoretical foundation for the use of OSW-1 in the clinical treatment of CRC.
文摘研究发现细胞死亡与骨关节炎(osteoarthritis,OA)的发病机制密切相关,除了凋亡、铁死亡、焦亡以外,目前又发现了一种全新的由受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)和受体相互作用蛋白激酶3(receptor-interacting protein kinase 3,RIPK3)介导的细胞死亡方式——程序性坏死。作为一种新型的受调控的细胞死亡方式,细胞的程序性坏死已被证实在部分炎症性疾病中扮演着重要的角色,但其与OA的关系还不够明晰。本文通过对PubMed、Web of Science、中国知网数据库的检索结果进行分析,总结了程序性坏死的特征、分子机制及其与软骨细胞炎症的关系等,期望对阐明软骨细胞程序性坏死在OA疾病进程中的作用有所帮助。
基金supported by the National Natural Science Foundation of China under Grant 31970897Outstanding Youth Foundation of Jiangsu Province(BK20190069,China)+1 种基金the Fundamental Research Funds for the Central Universities No.30919011102(China)Qing Lan Project of Jiangsu Province,China.
文摘Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary disease typically caused bymicrobial infections, trauma, inhalation of harmful gases, and other factors. It is characterized by an inflammation inthe lungs and increased alveolar permeability, leading to pulmonary edema and consequently, a low oxygen supply orhypoxemia. ARDS is responsible for 1 in 10 admissions to intensive care units, and the mortality rate for patientswith severe ARDS is as high as 46%. Extensive efforts have been devoted to investigating the pathological mechanismsof ARDS to develop new effective clinical strategies. Recent studies have reported that receptor-interacting serine/threonine kinase 1 (RIPK1) is involved in the pathogenesis of ARDS. RIPK1 is a critical mediator of programmed celldeath and inflammation. Growing evidence suggests that RIPK1 plays a role in the pathogenesis of differentinflammatory diseases and serves as a promising pharmaceutical target. This review summarizes and sheds some lighton the recent findings regarding the role of RIPK1 and related molecules in the pathogenesis of ARDS.
