Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.How...Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.展开更多
文摘Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.
文摘目的探讨基于肺超声滴定最佳呼气末正压(PEEP)和肺复张吸气峰压(Ppeak)指导个体化肺保护性通气策略对老年结肠癌根治术患者围术期肺功能的影响。方法选择择期全麻腹腔镜结肠癌根治术老年患者75例,男46例,女29例,年龄65~85岁,BMI 18.5~32.0 kg/m^(2),ASAⅡ或Ⅲ级,随机分为两组:个体化组(U组,n=37)和传统组(T组,n=38)。两组均以固定的小潮气量6 ml/kg通气。U组选择肺不张程度最重的肺窗作为肺超声滴定最佳PEEP和Ppeak的扫查点,采用压力滴定法获取最佳PEEP和Ppeak,实施个体化肺保护性通气策略,间断进行持续15 s肺复张。T组实施传统的肺保护性通气策略,设置PEEP 5 cmH_(2)O,Ppeak 30 cmH_(2)O,间断进行持续15 s肺复张。记录麻醉诱导前、气腹前即刻、气腹后10 min、1、2 h和拔管后30 min的氧合指数(OI)和呼吸指数(RI)。记录气腹前即刻、气腹后10 min、1、2 h的P ET CO_(2)、驱动压、PEEP、Ppeak和肺顺应性(Cdyn)。记录术前最后1次Hb、术前1 d屏气时间、手术时间、术中出血量、输液量、拔管时间、住院时间和术后7 d新增肺部并发症等情况。结果与麻醉诱导前比较,T组拔管后30 min OI明显降低,RI明显升高(P<0.05)。与T组比较,U组气腹后1、2 h、拔管后30 min OI明显升高,RI明显降低(P<0.05),气腹后10 min、1、2 h P ET CO_(2)明显降低,Cdyn明显升高(P<0.05),气腹前即刻、气腹后10 min、1 h PEEP明显降低(P<0.05),气腹前即刻、气腹后10 min、1、2 h驱动压、Ppeak明显降低(P<0.05),拔管时间、术后住院时间明显缩短(P<0.05),术后7 d内新增肺部并发症发生率明显降低(P<0.05)。结论以肺超声指导下的个体化肺保护性通气策略,更利于老年腹腔镜结肠癌根治术患者围术期肺功能保护,可有效缩短术后早期拔管时间和住院时间,降低术后肺部并发症的发生。
