Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia （T-ALL） cells and potential molecular mechanisms. Methods The anti-proliferation effect of resve...Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia （T-ALL） cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTI- test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and dose and time-dependent manner. It also induced cyclin-dependent kinase （CDK） inhibitors p21 and induced apoptosis and autophagy in T-ALL cells in a cell cycle arrest at G0/G1 phase via up regulating p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins （Mcl-1 and Bcl-2） and increased the expression of proapoptotic proteins （Bax, Bim, and Bad）, and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-11/LC3-1 and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. Conclusion Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p7OS6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.展开更多
The accurate and automatic segmentation of retinal vessels fromfundus images is critical for the early diagnosis and prevention ofmany eye diseases,such as diabetic retinopathy(DR).Existing retinal vessel segmentation...The accurate and automatic segmentation of retinal vessels fromfundus images is critical for the early diagnosis and prevention ofmany eye diseases,such as diabetic retinopathy(DR).Existing retinal vessel segmentation approaches based on convolutional neural networks(CNNs)have achieved remarkable effectiveness.Here,we extend a retinal vessel segmentation model with low complexity and high performance based on U-Net,which is one of the most popular architectures.In view of the excellent work of depth-wise separable convolution,we introduce it to replace the standard convolutional layer.The complexity of the proposed model is reduced by decreasing the number of parameters and calculations required for themodel.To ensure performance while lowering redundant parameters,we integrate the pre-trained MobileNet V2 into the encoder.Then,a feature fusion residual module(FFRM)is designed to facilitate complementary strengths by enhancing the effective fusion between adjacent levels,which alleviates extraneous clutter introduced by direct fusion.Finally,we provide detailed comparisons between the proposed SepFE and U-Net in three retinal image mainstream datasets(DRIVE,STARE,and CHASEDB1).The results show that the number of SepFE parameters is only 3%of U-Net,the Flops are only 8%of U-Net,and better segmentation performance is obtained.The superiority of SepFE is further demonstrated through comparisons with other advanced methods.展开更多
Objective We observed and compared the differences in immune reconstruction between single-infusion anti-B-cell maturation antigen(BCMA),chimeric antigen receptor T cells(CAR-T),and combined infusion of anti-CD19 CAR-...Objective We observed and compared the differences in immune reconstruction between single-infusion anti-B-cell maturation antigen(BCMA),chimeric antigen receptor T cells(CAR-T),and combined infusion of anti-CD19 CAR-T cells in the treatment of recurrent/refractory multiple myeloma(RRMM).Methods Sixty-one patients with RRMM who underwent CAR-T cell therapy in our hospital from June 2017 to December 2020 were selected.Among them,26 patients received anti-BCMA target,and 35 patients received anti-BCMA combined with anti-CD19 target.展开更多
基金supported by grants from the Department of Science and Technology of Sichuan Province,China (No.2008JY0029-1 and No.07FG002-024)research funds from the Program for Changjiang Scholars and Innovative-Research Team in University (No.IRT0935)
文摘Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia （T-ALL） cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTI- test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and dose and time-dependent manner. It also induced cyclin-dependent kinase （CDK） inhibitors p21 and induced apoptosis and autophagy in T-ALL cells in a cell cycle arrest at G0/G1 phase via up regulating p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins （Mcl-1 and Bcl-2） and increased the expression of proapoptotic proteins （Bax, Bim, and Bad）, and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-11/LC3-1 and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. Conclusion Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p7OS6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.
基金supported by the Hunan Provincial Natural Science Foundation of China(2021JJ50074)the Scientific Research Fund of Hunan Provincial Education Department(19B082)+6 种基金the Science and Technology Development Center of the Ministry of Education-New Generation Information Technology Innovation Project(2018A02020)the Science Foundation of Hengyang Normal University(19QD12)the Science and Technology Plan Project of Hunan Province(2016TP1020)the Subject Group Construction Project of Hengyang Normal University(18XKQ02)theApplication Oriented SpecialDisciplines,Double First ClassUniversity Project of Hunan Province(Xiangjiaotong[2018]469)the Hunan Province Special Funds of Central Government for Guiding Local Science and Technology Development(2018CT5001)the First Class Undergraduate Major in Hunan Province Internet of Things Major(Xiangjiaotong[2020]248,No.288).
文摘The accurate and automatic segmentation of retinal vessels fromfundus images is critical for the early diagnosis and prevention ofmany eye diseases,such as diabetic retinopathy(DR).Existing retinal vessel segmentation approaches based on convolutional neural networks(CNNs)have achieved remarkable effectiveness.Here,we extend a retinal vessel segmentation model with low complexity and high performance based on U-Net,which is one of the most popular architectures.In view of the excellent work of depth-wise separable convolution,we introduce it to replace the standard convolutional layer.The complexity of the proposed model is reduced by decreasing the number of parameters and calculations required for themodel.To ensure performance while lowering redundant parameters,we integrate the pre-trained MobileNet V2 into the encoder.Then,a feature fusion residual module(FFRM)is designed to facilitate complementary strengths by enhancing the effective fusion between adjacent levels,which alleviates extraneous clutter introduced by direct fusion.Finally,we provide detailed comparisons between the proposed SepFE and U-Net in three retinal image mainstream datasets(DRIVE,STARE,and CHASEDB1).The results show that the number of SepFE parameters is only 3%of U-Net,the Flops are only 8%of U-Net,and better segmentation performance is obtained.The superiority of SepFE is further demonstrated through comparisons with other advanced methods.
文摘Objective We observed and compared the differences in immune reconstruction between single-infusion anti-B-cell maturation antigen(BCMA),chimeric antigen receptor T cells(CAR-T),and combined infusion of anti-CD19 CAR-T cells in the treatment of recurrent/refractory multiple myeloma(RRMM).Methods Sixty-one patients with RRMM who underwent CAR-T cell therapy in our hospital from June 2017 to December 2020 were selected.Among them,26 patients received anti-BCMA target,and 35 patients received anti-BCMA combined with anti-CD19 target.
