Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),wh...Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2)to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2)redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2)signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2)reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2)signaling.GBM cells were used to verify the role of H_(2)O_(2)signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2)via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2)levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.展开更多
[目的]评价SH3结构域谷氨酸富集样蛋白3(SH3BGRL3)在非小细胞肺癌中的表达及其与临床病理特征的相关性。[方法]选取2014年10月至2017年12月确诊并接受手术治疗的46例非小细胞肺癌患者的癌组织标本以及距离癌组织5cm以上的癌旁组织,免疫...[目的]评价SH3结构域谷氨酸富集样蛋白3(SH3BGRL3)在非小细胞肺癌中的表达及其与临床病理特征的相关性。[方法]选取2014年10月至2017年12月确诊并接受手术治疗的46例非小细胞肺癌患者的癌组织标本以及距离癌组织5cm以上的癌旁组织,免疫组化染色检测SH3BGRL3相对表达量,荧光定量RT-PCR检测SH3BGRL3 m RNA表达。[结果]癌组织中SH3BGRL3相对表达量、SH3BGRL3 mRNA表达高于癌旁组织(P<0.05)。肿瘤体积≥5cm3、侵及浆膜、病理分期Ⅲ~Ⅳ期、有淋巴结转移患者SH3BGRL3、SH3BGRL3 m RNA相对表达量高于肿瘤体积<5cm3、未及浆膜、病理分期Ⅰ~Ⅱ期、无淋巴结转移患者(P<0.05)。病理分期、SH3BGRL3、SH3BGRL3 mRNA表达是影响非小细胞肺癌患者预后的主要危险因素。[结论]SH3BGRL3在非小细胞肺癌中呈现异常高表达,且与肿瘤体积、浸润程度、病理分期、淋巴结转移等临床病理参数具有一定相关性。SH3BGRL3、SH3BGRL3 m RNA表达是影响非小细胞肺癌患者预后的危险因素。展开更多
Sour liquid fermentation is a traditional and unique method used in China to produce starch that has favorable sensory evaluation,especially a pleasant mouthfeel.However,the complexity of the natural microbial flora u...Sour liquid fermentation is a traditional and unique method used in China to produce starch that has favorable sensory evaluation,especially a pleasant mouthfeel.However,the complexity of the natural microbial flora used in the method often caused severe fluctuations in production efficiency and product quality.Hence,it is important to explore the performance and impact of each starch-flocculating bacteria on starch structure.In this study,five previously isolated starch-flocculating bacterial strains were used to ferment sweet potato starch individually.Through analyzing fermentation parameters,Leuconostoc citreum SJ-48 was identified as the strain with the highest starch flocculation ability.A more dispersed particle size distribution of starch after fermentation was observed,possibly due to the clumping of starch granules by the bacteria.It was found that the amylose content of fermented starch increased by 27.57%-42.28%,and the relative crystallinity of starch increased significantly after fermentation.Finally,the starch-binding proteins of the bacterial cell were characterized using LC-ESI-MS/MS,and it was revealed that the strong starch flocculation ability of L.citreum SJ-48 was linked to the glycoside hydrolase family 70 on its surface.This study demonstrated that the discrepancies in the flocculation ability of the different bacterial strains and subsequent changes in the fermented starch properties were mainly influenced by the different proteins on their surfaces.展开更多
基金supported by research grants from the Ministry of Science and Technology(MOST 108-2314-B-400-026 and 109-2013-B-400-036)National Science and Technology Council(NSTC 112-2320-B-214-010 and 113-2320-B-214-002)I-Shou University(ISU-112-01-12A,ISU112-S-02 and ISU114-S-04).
文摘Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2)to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2)redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2)signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2)reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2)signaling.GBM cells were used to verify the role of H_(2)O_(2)signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2)via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2)levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.
文摘[目的]评价SH3结构域谷氨酸富集样蛋白3(SH3BGRL3)在非小细胞肺癌中的表达及其与临床病理特征的相关性。[方法]选取2014年10月至2017年12月确诊并接受手术治疗的46例非小细胞肺癌患者的癌组织标本以及距离癌组织5cm以上的癌旁组织,免疫组化染色检测SH3BGRL3相对表达量,荧光定量RT-PCR检测SH3BGRL3 m RNA表达。[结果]癌组织中SH3BGRL3相对表达量、SH3BGRL3 mRNA表达高于癌旁组织(P<0.05)。肿瘤体积≥5cm3、侵及浆膜、病理分期Ⅲ~Ⅳ期、有淋巴结转移患者SH3BGRL3、SH3BGRL3 m RNA相对表达量高于肿瘤体积<5cm3、未及浆膜、病理分期Ⅰ~Ⅱ期、无淋巴结转移患者(P<0.05)。病理分期、SH3BGRL3、SH3BGRL3 mRNA表达是影响非小细胞肺癌患者预后的主要危险因素。[结论]SH3BGRL3在非小细胞肺癌中呈现异常高表达,且与肿瘤体积、浸润程度、病理分期、淋巴结转移等临床病理参数具有一定相关性。SH3BGRL3、SH3BGRL3 m RNA表达是影响非小细胞肺癌患者预后的危险因素。
基金supported by the Natural Science Foundation of Sichuan Province 2023NSFSC0181the 2115 Talent Development Program of China Agricultural University.
文摘Sour liquid fermentation is a traditional and unique method used in China to produce starch that has favorable sensory evaluation,especially a pleasant mouthfeel.However,the complexity of the natural microbial flora used in the method often caused severe fluctuations in production efficiency and product quality.Hence,it is important to explore the performance and impact of each starch-flocculating bacteria on starch structure.In this study,five previously isolated starch-flocculating bacterial strains were used to ferment sweet potato starch individually.Through analyzing fermentation parameters,Leuconostoc citreum SJ-48 was identified as the strain with the highest starch flocculation ability.A more dispersed particle size distribution of starch after fermentation was observed,possibly due to the clumping of starch granules by the bacteria.It was found that the amylose content of fermented starch increased by 27.57%-42.28%,and the relative crystallinity of starch increased significantly after fermentation.Finally,the starch-binding proteins of the bacterial cell were characterized using LC-ESI-MS/MS,and it was revealed that the strong starch flocculation ability of L.citreum SJ-48 was linked to the glycoside hydrolase family 70 on its surface.This study demonstrated that the discrepancies in the flocculation ability of the different bacterial strains and subsequent changes in the fermented starch properties were mainly influenced by the different proteins on their surfaces.