314 results on '"Zeng, Qingyu"'
Search Results
102. Adjudin synergizes with paclitaxel and inhibits cell growth and metastasis by regulating the sirtuin 3–Forkhead box O3a axis in human small‐cell lung cancer
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Wang, Xue, primary, Zeng, Qingyu, additional, Li, Ziming, additional, Yang, Xiao, additional, Xia, Weiliang, additional, and Chen, Zhiwei, additional
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- 2019
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103. BAFF inhibits autophagy promoting cell proliferation and survival by activating Ca2+-CaMKII-dependent Akt/mTOR signaling pathway in normal and neoplastic B-lymphoid cells
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Dong, Xiaoqing, primary, Qin, Jiamin, additional, Ma, Jing, additional, Zeng, Qingyu, additional, Zhang, Hai, additional, Zhang, Ruijie, additional, Liu, Chunxiao, additional, Xu, Chong, additional, Zhang, Shuangquan, additional, Huang, Shile, additional, and Chen, Long, additional
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- 2019
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104. Single-cell transcriptomic analysis reveals the critical molecular pattern of UV-induced cutaneous squamous cell carcinoma.
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Yan, Guorong, Li, Liang, Zhu, Sibo, Wu, Yuhao, Liu, Yeqiang, Zhu, Lude, Zhao, Zijun, Wu, Fei, Jia, Ning, Liao, Caihe, Jiang, Long, Zeng, Qingyu, Wang, Peiru, Shi, Lei, Zheng, Zhe, Fang, Shan, Zhang, Guolong, Tang, Yichen, and Wang, Xiuli
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- 2020
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105. Corrigendum to “The Hippo/YAP1 pathway interacts with FGFR1 signaling to maintain stemness in lung cancer” [Canc. Lett. 423 (2018) 36–46]
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Lu, Tingting, primary, Li, Ziming, additional, Yang, Ying, additional, Ji, Wenxiang, additional, Yu, Yongfeng, additional, Niu, Xiaomin, additional, Zeng, Qingyu, additional, Xia, Weiliang, additional, and Lu, Shun, additional
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- 2018
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106. The Hippo/YAP1 pathway interacts with FGFR1 signaling to maintain stemness in lung cancer
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Lu, Tingting, primary, Li, Ziming, additional, Yang, Ying, additional, Ji, Wenxiang, additional, Yu, Yongfeng, additional, Niu, Xiaomin, additional, Zeng, Qingyu, additional, Xia, Weiliang, additional, and Lu, Shun, additional
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- 2018
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107. Effect of pH, temperature and freezing-thawing on quantity changes and cellular uptake of exosomes
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Cheng, Yirui, primary, Zeng, Qingyu, additional, Han, Qing, additional, and Xia, Weiliang, additional
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- 2018
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108. Comparison of Multidirectional Myocardial Deformation Result From Pressure and Volume Overload in Compensatory Stage
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Zeng, Qingyu, primary, Wang, Lei, additional, Yang, Yali, additional, Kong, Shuangshuang, additional, Li, Yuman, additional, Xie, Mingxing, additional, and Zhang, Li, additional
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- 2018
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109. Time-Dependent Testing Evaluation and Modeling for Rubber Stopper Seal Performance
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Zeng, Qingyu, primary and Zhao, Xia, additional
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- 2017
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110. GW28-e0235 Assessment of left ventricular function in patients with chronic aortic regurgitation by three dimensional strain imaging: Comparison with cardiac magnetic resonance imaging
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Zeng, Qingyu, primary, Zhang, Li, additional, and Xie, Mingxing, additional
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- 2017
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111. Effects of Simulated Annealing Strategy on Swarm Intelligence Algorithm
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Zhuanzhou Zhang, Chengqi Li, Yanmin Liu, Rui Liu, Zeng Qingyu, and Tao Huang
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Computer science ,Computer Science::Neural and Evolutionary Computation ,MathematicsofComputing_NUMERICALANALYSIS ,Evolutionary algorithm ,Swarm behaviour ,010103 numerical & computational mathematics ,02 engineering and technology ,Adaptive simulated annealing ,01 natural sciences ,Swarm intelligence ,Search algorithm ,Simulated annealing ,Mutation (genetic algorithm) ,0202 electrical engineering, electronic engineering, information engineering ,020201 artificial intelligence & image processing ,0101 mathematics ,Algorithm ,Premature convergence - Abstract
Swarm intelligence algorithm (SI) is a kind of stochastic search algorithm based on swarm. Similar to other evolutionary algorithm, when solving the complicated multimodal problem using SI, it is easy to have premature convergence. So, to promote the optimization of swarm intelligence algorithm, the typical algorithm (Particle swarm optimizer) of swarm intelligence algorithm is selected to explore some strategies how to improve the performance. In this paper, we explore the follow research: firstly, the mutation operation is introduced to produce new learn example for each individual in itself evolution process; secondly, in the view of the idea of simulated annealing, the range strategy of fitness of each individual is proposed; finally, to make best use of each individual information, the comprehensive learning strategy is adopted to improve each individual evolution mechanism.
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- 2016
112. Particle Swarm Optimizer with Full Information
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Rui Liu, Yanmin Liu, Chengqi Li, Zeng Qingyu, Tao Huang, and Xiangbiao Wu
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Mathematical optimization ,Mutation operator ,Computer science ,MathematicsofComputing_NUMERICALANALYSIS ,Swarm behaviour ,Particle swarm optimization ,020206 networking & telecommunications ,02 engineering and technology ,Function (mathematics) ,ComputingMethodologies_ARTIFICIALINTELLIGENCE ,Dimension (vector space) ,Position (vector) ,Mutation (genetic algorithm) ,0202 electrical engineering, electronic engineering, information engineering ,Benchmark (computing) ,020201 artificial intelligence & image processing ,Multi-swarm optimization - Abstract
In order to improve the particle swarm optimizer (PSO) for solving complex multimodal problems, an improved PSO with full information and mutation operator (PSOFIM) is proposed base basic PSO and mutation thought. In PSOFIM, a novel mutation is adopted to improve the history optimal position of particle (pbest) by disturbance in operation of each dimension. Additionally, a full information strategy for each particle is introduced to make best use of each dimension of each particle to ensure the information utility for swarm topology where each particle learns from its neighborhood information for his optimal position to improve itself study ability, whose strategies improve the swarm fly to the probability of the optimal solution. The simulation experiment results of benchmark function tests show PSOFIM has better performance than the basic PSO algorithm.
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- 2016
113. Rapamycin attenuates BAFF‐extended proliferation and survival via disruption of mTORC1/2 signaling in normal and neoplastic B‐lymphoid cells
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Zeng, Qingyu, primary, Qin, Shanshan, additional, Zhang, Hai, additional, Liu, Beibei, additional, Qin, Jiamin, additional, Wang, Xiaoxue, additional, Zhang, Ruijie, additional, Liu, Chunxiao, additional, Dong, Xiaoqing, additional, Zhang, Shuangquan, additional, Huang, Shile, additional, and Chen, Long, additional
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- 2017
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114. IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability and survival by activating Erk1/2 and S6K1 pathways in neoplastic B-lymphoid cells
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Gui, Lin, primary, Zeng, Qingyu, additional, Xu, Zhigang, additional, Zhang, Hai, additional, Qin, Shanshan, additional, Liu, Chunxiao, additional, Xu, Chong, additional, Qian, Zhou, additional, Zhang, Shuangquan, additional, Huang, Shile, additional, and Chen, Long, additional
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- 2016
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115. Assessment of left ventricular performance in heart transplant recipients by three-dimensional speckle tracking imaging.
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Dan Wang, Li Zhang, Qingyu Zeng, Mingxing Xie, Wang, Dan, Zhang, Li, Zeng, Qingyu, and Xie, Mingxing
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- 2017
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116. Bone Mineral Density in Patients With Rheumatoid Arthritis and 4-Year Follow-up Results.
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Jianhua Peng, Yao Gong, Yuping Zhang, Zhengyu Xiao, Qingyu Zeng, Subiao Chen, Peng, Jianhua, Gong, Yao, Zhang, Yuping, Xiao, Zhengyu, Zeng, Qingyu, and Chen, Subiao
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- 2016
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117. ketogenic diet alters the expression of chromatin modifying enzymes in GBM to potentiate the effects of chemotherapy and radiotherapy.
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Zeng, Qingyu, Stylianou, Tzouliana, Preston, Jessica, O'Neill, Kevin, Scheck, Adrienne C, and Syed, Nelofer
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- 2021
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118. fMRI study in posterior cingulate and adjacent precuneus cortex in healthy elderly adults using problem solving task
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Jin, Guangwei, primary, Li, Kuncheng, additional, Qin, Yulin, additional, Zhong, Ning, additional, Zhou, Haiyan, additional, Wang, Zhiqun, additional, Xiang, Jie, additional, Hu, Yingying, additional, Wang, Mingxiao, additional, and Zeng, Qingyu, additional
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- 2012
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119. Method for the determination of blood methotrexate by high performance liquid chromatography with online post-column electrochemical oxidation and fluorescence detection
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Li, Hui, Luo, Wenhong, Zeng, Qingyu, Lin, Zhexuan, Luo, Hongjun, and Zhang, Yuan
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- 2007
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120. Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry VI: Effect of Cigarette Smoking on the Clinical Phenotype of Chinese Patients with Systemic Lupus Erythematosus.
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Xu, Dong, You, Xin, Wang, Zhengang, Zeng, Qingyu, Xu, Jianhua, Jiang, Lindi, Gong, Lu, Wu, Fengqi, Gu, Jieruo, Tao, Yi, Chen, Jinwei, Zhao, Jiuliang, Li, Mengtao, Zhao, Yan, Zeng, Xiaofeng, and null, null
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SYSTEMIC lupus erythematosus ,HEALTH ,SMOKING ,PHENOTYPES ,CHINESE people ,KIDNEY diseases ,HEMATURIA ,DISEASES - Abstract
Objectives: Our study aimed to investigate the effect of cigarette smoking on the clinical phenotype of patients registered in the Chinese Systemic Lupus Erythematosus (SLE) Treatment and Research (CSTAR) group registry database, the first online registry of Chinese patients with SLE. Methods: A prospective cross-sectional study of Chinese SLE patients was conducted using the CSTAR. Our case-control analysis was performed on age- and gender-matched subjects to explore the potential effect of cigarette smoking on the clinical manifestation of SLE. Results: Smokers comprised 8.9% (65/730) of patients, and the ratio of females/males was 19/46. Thirty-nine patients were current smokers, and 26 were ex-smokers. Data showed significant differences between smokers and nonsmokers in the following areas: nephropathy (58.5% vs. 39.2%; p = 0.003), microscopic hematuria (30.8% vs. 19.1%; p = 0.025), proteinuria (53.8% vs. 34.4%; p = 0.002), and SLE Disease Activity Index(DAI) scores (12.38±8.95 vs. 9.83±6.81; p = 0.028). After adjusting for age and gender, significant differences between smokers and nonsmokers were found with photosensitivity (35.9% vs. 18%; p = 0.006), nephropathy (59.4% vs. 39.8%; p = 0.011), and proteinuria (54.7% vs. 35.2%). Although smokers tended to have greater disease severity compared with nonsmokers (SLEDAI scores: 12.58±8.89 vs.10.5±7.09), the difference was not significant (p = 0.081). Conclusions: Cigarette smoking triggers the development and exacerbation of SLE, especially with respect to renal involvement. Chinese smokers with SLE should be advised to discontinue cigarette use. [ABSTRACT FROM AUTHOR]
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- 2015
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121. BAFF activates Erk1/2 promoting cell proliferation and survival by Ca2+-CaMKII-dependent inhibition of PP2A in normal and neoplastic B-lymphoid cells.
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Liang, Dingfang, Zeng, Qingyu, Xu, Zhigang, Zhang, Hai, Gui, Lin, Xu, Chong, Chen, Sujuan, Zhang, Shuangquan, Huang, Shile, and Chen, Long
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TALL-1 (Protein) , *CELL proliferation , *CALCIUM-dependent protein kinase , *AUTOIMMUNE diseases , *EXTRACELLULAR signal-regulated kinases , *B cells , *PATHOLOGICAL physiology , *PHYSIOLOGY - Abstract
Abstract: B-cell activating factor (BAFF) is involved in not only the physiology of normal B cells, but also the pathophysiology of aggressive B cells related to malignant and autoimmune diseases. However, how excessive BAFF promotes aggressive B-cell proliferation and survival is not well understood. Here we show that excessive human soluble BAFF (hsBAFF) enhanced cell proliferation and survival in normal and B-lymphoid (Raji) cells, which was associated with suppression of PP2A, resulting in activation of Erk1/2. This is supported by the findings that pretreatment with U0126 or PD98059, expression of dominant negative MKK1, or overexpression of PP2A prevented hsBAFF-induced activation of Erk1/2 and cell proliferation/viability in the cells. It appears that hsBAFF-mediated PP2A-Erk1/2 pathway and B-cell proliferation/viability was Ca2+-dependent, as pretreatment with BAPTA/AM, EGTA or 2-APB significantly attenuated these events. Furthermore, we found that inhibiting CaMKII with KN93 or silencing CaMKII also attenuated hsBAFF-mediated PP2A-Erk1/2 signaling and B-cell proliferation/viability. The results indicate that BAFF activates Erk1/2, in part through Ca2+-CaMKII-dependent inhibition of PP2A, increasing cell proliferation/viability in normal and neoplastic B-lymphoid cells. Our data suggest that inhibitors of CaMKII and Erk1/2, activator of PP2A or manipulation of intracellular Ca2+ may be exploited for prevention of excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases. [Copyright &y& Elsevier]
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- 2014
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122. Excellent Endpoints from Step-Down Bridge Combination Therapy of 5 Immunosuppressants in NSAID-Refractory Ankylosing Spondylitis: 6 Year International Study in Asia — WHO-ILAR COPCORD Stage II Treatment of the Autoimmune Diseases
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DARMAWAN, JOHN, NASUTION, A., CHEN, SHUN-LE, HAQ, SYED, ZHAO, DONGBAO, ZENG, QINGYU, and DAVATCHI, FEREYDOUN
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OBJECTIVE:. To achieve induction and maintenance of remission in ankylosing spondylitis (AS) refractory to nonsteroidal antiinflammatory drugs with "step-down bridge combination" of 5 immunosuppressants, as an alternative to costly biologic DMARD. Primary endpoints were the percentage of patients achieving ASAS 20 at the end of Year 6; secondary endpoints were patients achieving ASAS 50 and ASAS 70, induction and maintenance of clinical and radiological remission, and the side effects of this combination of immunosuppressive drugs. METHODS: In a 6-year uncontrolled international open-label prospective study, 54 men and 25 women with AS were enrolled after exclusion criteria were applied. Included patients were treated with individualized combinations of low-dose intravenous methylprednisolone + cyclophosphamide + methotrexate (for the first 6 mo). When erythrocyte sedimentation rate dropped to ≤ 20 mm (men ≤ 10 mm), low-dose oral mycophenolate mofetil and cyclosporine were prescribed for at least 2 years. Assessments were executed at baseline, Weeks 1 and 2; Months 1, 2, 4, and 6; and Years 1, 2, 4, and 6. RESULTS: After 15/79 dropouts were accounted for, 64/79 patients achieved ASAS 20, ASAS 50, and ASAS 70. Disease remission occurred in 60/79 at 6 months when IV drugs were tapered. Gastrointestinal side effects were observed in 20/79 patients; no liver, renal, cardiovascular, and hematologic adverse effects were observed. CONCLUSION: Step-down bridge combination of 5 immunosuppressants achieved ASAS 20, ASAS 50, and ASAS 70 in 64/79 patients, and remission in 60/79 patients with NSAID-refractory AS. Controlled studies are needed to confirm this method, and to study the role of these different drugs in developing countries in Asia, where the majority of patients with NSAID-refractory AS are unable to obtain treatment with tumor necrosis factor-a blockers.
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- 2006
123. THE FIELD TESTS ON POWER SYSTEM STABILIZERS FOR DAMPING LOW FREQUENCY OSCILLATION
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Zeng Qingyu and Yan Zhonghen
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- 1987
124. The Msegram: A useful multichannel feature synchronous extraction tool for detecting rolling bearing faults.
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Yuan, Jing, Song, Zhitian, Jiang, Huiming, Zhao, Qian, Zeng, Qingyu, and Wei, Ying
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ROLLER bearings , *FEATURE extraction , *SINGULAR value decomposition , *ENTROPY , *PHASE space , *FAULT diagnosis , *NOISE control , *BRIDGE bearings - Abstract
• A multichannel feature synchronous extraction tool i.e. Msegram is proposed for detecting rolling bearing faults. • Tensor synchronous denoising by HOSVD is studied for multichannel signal preprocessing. • Multi-layer K -value MVMD is designed for multichannel synchronous adaptive decomposition. • A tower-shaped EC map is proposed to visualize the feature output of multichannel bearing faults. • Simulations and experimental cases of compound faults are used to testify Msegram with comparisons. Multichannel signals collected by multiple sensors contain richer condition information of equipment than single-channel signals. However, such issues as simultaneous denoising, adaptive decomposition and synchronous extraction are still challenging for multichannel signals, which are beneficial to accurate fault diagnosis. Thus, a useful multichannel feature synchronous extraction tool is proposed for detecting rolling bearing faults, named as Msegram. First, a tensor synchronization denoising method based on high order singular value decomposition (HOSVD) is proposed for multichannel signal preprocessing. Original multichannel signals of testing bearings are constructed to be a third-order tensor by phase space reconstruction. Hereinto, a singular entropy increment is adopted to determine a reasonable singular order for each unfolding, and an optimal core tensor is obtained for local reconstruction analysis. Second, multi-layer K -value multivariate variational mode decomposition (MVMD) is designed after the multichannel noise reduction to realize synchronous adaptive filtering and decomposition for the multichannel signals. Third, inspired by the idea of the spectral kurtosis, a tower-shaped crest factor of envelope spectrum (EC) diagram similar to Fast Kurtogram (FK) is proposed to visualize the output of multichannel bearing fault feature results. According to the tower-shaped EC diagram with the maximum fault crest factor, the optimal analytic results of multichannel signals are selected and output to synchronously extract bearing fault features. Finally, repeatable simulations and two experimental fault cases of rolling bearings are implemented to demonstrate the practicability and effectiveness of the proposed method. The results show that the proposed method can successfully reveal the compound faults from experimental bearing and effectively identify the compound faults from locomotive wheelset bearing. [ABSTRACT FROM AUTHOR]
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- 2023
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125. Dietary supplementation of n-3 PUFAs ameliorates LL37-induced rosacea-like skin inflammation via inhibition of TLR2/MyD88/NF-κB pathway.
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Shen, Shuzhan, Yan, Guorong, Cao, Yajing, Zeng, Qingyu, Zhao, Jingjun, Wang, Xiuli, and Wang, Peiru
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ROSACEA , *DIETARY supplements , *SKIN inflammation , *ESSENTIAL fatty acids , *OMEGA-3 fatty acids , *UNSATURATED fatty acids , *THYMIC stromal lymphopoietin , *ALPHA-linolenic acid - Abstract
Rosacea is a facial chronic inflammatory skin disease with dysfunction of immune and neurovascular system and treatments for rosacea are challenging. N-3 polyunsaturated fatty acids (PUFAs), one of essential fatty acids, are needed for health maintenance and exert anti-inflammation and immunomodulatory effects in a series of cutaneous diseases such as atopic dermatitis and photoaging through dietary supplementation. However, the role of n-3 PUFAs on rosacea remains to be elucidated. In this study, KEGG enrichment analysis and GO analysis indicated that the biological process and signaling pathways, including chemokine signaling pathway, regulated by n-3 PUFAs highly overlapped with those in the pathogenic biological process of rosacea, especially the erythema telangiectasia type. Next, mice were randomized to fed with a customized n-3 PUFAs diet. We showed that n-3 PUFAs ameliorated skin erythema, inhibited dermal inflammatory cell infiltration (mast cells, neutrophils, and CD4 +T cells) and suppressed elevated pro-inflammatory cytokines in LL37-induced rosacea-like mice. Besides, n-3 PUFAs were also verified to repress angiogenesis in LL37-induced mice skin. Further investigation revealed that n-3 PUFAs attenuated LL37-induced inflammation via TLR2/ MyD88/ NF-κB pathway both in mice and in keratinocytes. In conclusion, our findings underscore that dietary supplementation of n-3 PUFAs have the potential to become an efficient and safe clinical therapeutic candidate for rosacea. • Dietary supplementation of n-3 PUFAs ameliorates rosacea-like features in LL37-induced mice. • N-3 PUFAs reduce the infiltration of mast cells, neutrophils and CD4 + T cells, and repress angiogenesis in rosacea lesions. • N-3 PUFAs downregulated LL37-induced inflammation via TLR2/ MyD88/ NF-κB pathway. • Dietary supplementation of n-3 PUFAs could be a potential therapeutic strategy for rosacea. [ABSTRACT FROM AUTHOR]
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- 2023
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126. High value-added utilization of artificial marble wastes and potential applications in biodegradable sustainable packaging.
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Zhu, Yan, Wang, Zhongmin, Chen, Zhenming, Lin, Cheng, Li, Peng, Huang, Zhimin, Cai, Ping, Wu, Chenxi, and Zeng, Qingyu
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WASTE recycling , *POLLUTION , *SOLID waste , *PLASTICS in packaging , *MARBLE , *PACKAGING recycling , *ENVIRONMENTAL degradation - Abstract
Approximately up to 2 billion tons of solid waste are generated globally each year. The resource recovery utilization of solid waste has become an urgent need, which can not only greatly improve environmental pollution but also alleviate the problem of resource shortage. In this work, artificial marble waste (AMW) was introduced into polylactic acid/polyvinyl alcohol/polyethylene glycol (PLA/PVA/PEG) composites to develop AMWs-reinforced biodegradable sustainable composites (BSC). AMWs-reinforced BSC exhibited excellent strength, toughness, processability, and can withstand more than 8000 times its weight. Notably, AMWs significantly accelerated the degradation rate of the composite. Compared with the BSC without AMWs, the weight loss of 8%AMWs-reinforced BSC was increased by nearly 20% after 28 days of degradation. The promising application of AMWs-reinforced BSC in next-generation biodegradable sustainable packaging (BSP) was demonstrated. This not only enabled high value-added utilization of AMWs but also greatly accelerated the degradation rate of plastic packaging and reduced white pollution. The work effectively promotes resource utilization and environmental improvement through resource recovery and accelerated degradation of solid wastes, providing new ideas to solve resource shortages and environmental problems. [Display omitted] • The interaction mechanism of PLA, PVA, PEG, and AMWs was analyzed. • AMWs significantly accelerated the degradation rate of the PLA-based composites. • AMWs recovery utilization was beneficial to effectively alleviate environmental pollution. [ABSTRACT FROM AUTHOR]
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- 2022
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127. Ruyi Jinhuang Powder accelerated diabetic ulcer wound healing by regulating Wnt/β-catenin signaling pathway of fibroblasts In Vivo and In Vitro.
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Wu, Minfeng, Huang, Jianhua, Shi, Jingjuan, Shi, Lei, Zeng, Qingyu, and Wang, Hongwei
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RNA analysis , *INFLAMMATION prevention , *WOUND healing , *IN vitro studies , *INTERLEUKINS , *HERBAL medicine , *FIBROBLASTS , *IN vivo studies , *HIGH performance liquid chromatography , *SEQUENCE analysis , *DIABETIC foot , *ANIMAL experimentation , *WESTERN immunoblotting , *ANTI-inflammatory agents , *AMINOGLYCOSIDES , *WNT proteins , *CYTOSKELETAL proteins , *CELLULAR signal transduction , *POLYMERASE chain reaction , *CHINESE medicine , *DRUG administration , *DRUG dosage - Abstract
Diabetic ulcer is a common complication of diabetes. Therapies of diabetic ulcer are still challenging due to the complicated aetiology. Ruyi Jinhuang Powder (RJP) is gradually adopted to treat diabetic ulcer and has a significant therapeutic effect. Aim of the study : To investigate the therapeutic potential for diabetic ulcer in vivo and in vitro , we explored whether and how RJP influences wound healing in mice and fibroblasts at the tissular, cellular and molecular levels. The chemical composition of RJP was identified by HPLC. Streptozotocin (STZ) induced diabetic mice were used to confirm the curative effect of RJP in vivo. Besides, the impact of RJP in stimulating fibroblasts proliferation, migration and reducing inflammation was studied through CCK-8 assay, cell scratch assay, PCR, WB, etc. A total of 17 compounds were identified in RJP by HPLC. Our data indicated that RJP promoted fibroblasts proliferation and migration via activating Wnt/β-catenin signaling pathway. Consistently, RNA-seq analysis of mice skin samples also showed that the shared differentially expressed genes (DEGs) between RJP group and control group were most enriched in wnt signaling pathway. These DEGs were closely related with wound repair. In addition, the anti-inflammation effect of RJP was also confirmed through downregulation of IL-1α, IL-1β, IL-6 and IL-10 expression levels. These biological effects were reduced when the Wnt/β-catenin signaling was blocked. The in vivo study also demonstrated the effect of RJP in improving epidermal wound closure, which was consistent with the in vitro results. Topical application of RJP was effective in treating diabetic ulcer. This research is helpful to provide new insights and evidence into the role of RJP in accelerating unhealing wound and reducing wound inflammation. [Display omitted] • RJP accelerated diabetic wound healing through Wnt signaling. • RJP could stimulate angiogenesis and collagen synthesis. • RJP could reduce inflammation. [ABSTRACT FROM AUTHOR]
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- 2022
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128. Sodium Selenite Induces Autophagy and Apoptosis in Cervical Cancer Cells via Mitochondrial ROS-Activated AMPK/mTOR/FOXO3a Pathway.
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Lv C, Zeng Q, Qi L, Wang Y, Li J, Sun H, Du L, Hao S, Li G, Feng C, Zhang Y, Wang C, Wang X, Ma R, Wang T, and Li Q
- Abstract
Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS's anti-CC effects, and SS's inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca
2+ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC.- Published
- 2024
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129. Echinatin suppresses cutaneous squamous cell carcinoma by targeting GSTM3-mediated ferroptosis.
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Kang Z, Wang P, Wang B, Yan Y, Zhao Z, Li C, Wen L, Wu M, Yan G, Wang X, Zhang G, and Zeng Q
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- Animals, Humans, Cell Line, Tumor, Mice, Peroxiredoxins metabolism, Antineoplastic Agents, Phytogenic pharmacology, Mice, Inbred BALB C, Cell Proliferation drug effects, Molecular Docking Simulation, Mice, Nude, Cell Movement drug effects, Xenograft Model Antitumor Assays, Keratinocytes drug effects, Chalcones, Ferroptosis drug effects, Skin Neoplasms drug therapy, Carcinoma, Squamous Cell drug therapy, Glutathione Transferase metabolism
- Abstract
Background: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers for which effective drugs are urgently needed. Echinatin, a natural compound extracted from Glycyrrhiza plants, has shown promising antitumour effects. However, the efficacy and the direct target of echinatin in cSCC remain unclear., Purpose: This study conducted a systematic investigation of the antitumour effects of echinatin on cSCC and the underlying mechanisms involved., Study Design and Methods: Three cSCC cell lines, a xenograft model, and a UV-induced cSCC mouse model were used to investigate the potential protective effects of echinatin. The interactions between echinatin and glutathione S-transferase mu3 (GSTM3) and between echinatin and peroxiredoxin-2 (PRDX2) were evaluated by a proteome microarray assay, pull-down LC‒MS/MS analysis, surface plasmon resonance, and molecular docking. The potential mechanisms of GSTM3-mediated echinatin activity were analysed by using western blotting, lentivirus infection and small interfering RNA (siRNA) transfection., Results: In this study, we found that echinatin inhibited the proliferation and migration of cSCC cells but had no cytotoxic effect on primary human keratinocytes. Furthermore, echinatin significantly inhibited tumour growth in vivo. Mechanistically, our data showed that echinatin could directly bind to GSTM3 and PRDX2. Notably, echinatin inhibited GSTM3 and PRDX2 levels by promoting their proteasomal degradation, which led to the disruption of ROS production. We then revealed that echinatin increased mitochondrial ROS production by inhibiting GSTM3. Moreover, echinatin triggered ferroptosis by inhibiting GSTM3-mediated ferroptosis negative regulation (FNR) proteins. In addition, echinatin regulated GSTM3-mediated ROS/MAPK signalling., Conclusion: Echinatin has good antitumour effects both in vitro and in vivo. Moreover, our findings indicate that GSTM3 and PRDX2 could function as viable targets of echinatin in cSCC. Consequently, echinatin represents a novel treatment for cSCC through the targeting of GSTM3-mediated ferroptosis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)
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- 2024
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130. A novel H‑tert immortalized human sebaceous gland cell line (XL-i-20) for the investigation of photodynamic therapy.
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Liu J, Xu D, Yan J, Wang B, Zhang L, Liu X, Zhang H, Yan G, Yang J, Zeng Q, and Wang X
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- Humans, Cell Line, Telomerase, Acne Vulgaris drug therapy, Sebum metabolism, Photochemotherapy methods, Sebaceous Glands drug effects, Sebaceous Glands cytology, Aminolevulinic Acid pharmacology, Photosensitizing Agents pharmacology, Cell Proliferation drug effects
- Abstract
Background: Acne vulgaris is a species-specific human disease. To date, there has been no established human sebocyte cell line of Asian origin. Our previous study has demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of acne vulgaris, primarily attributed to its cytotoxic properties; however, its regulatory mechanism remains largely unknown., Objectives: To establish an immortalized human sebocyte cell line derived from Chinese population and investigate the underlying mechanism of ALA-PDT., Methods: Human primary sebocytes were transfected with the human tert gene (h‑tert). The biological characteristics, including cell proliferation, cell markers, and sebum secretion function, were compared between primary sebocytes and the immortalized sebocytes (XL-i-20). Stimulations such as ALA-PDT, were applied respectively to both primary sebocytes and XL-i-20 cells to assess changes in their cellular functions. The transcriptome differences between primary sebocytes and XL-i-20 sebocytes were investigated using RNA-seq analysis. The XL-i-20 cell line was used to establish a sebaceous gland (SG) organoid culture, serving as a representative model of SG for the investigation of ALA-PDT., Results: The h‑tert immortalized sebocyte cell line exhibited the ability to be consecutively cultured for more than fifty passages. Both primary and immortalized cells expressed sebocyte markers such as epithelial membrane antigens (EMA, or MUC-1), Cytokeratin 7 (CK7) and adipose differentiation-related protein associated antigens (ADRP), and maintained sebum secretion function. The proliferative capacity of XL-i-20 was found to be significantly higher than that of primary sebocytes. The responses of XL-i-20 to ALA-PDT were indistinguishable from those elicited by primary sebocytes. Cell viability and sebum secretion were decreased after ALA-PDT in both two cell lines, and lipid-related proteins (SREBP-1/PPARγ) were down-regulated. The transcriptome data consistently demonstrated upregulation of genes related to inflammatory responses and downregulation of genes involved in lipid metabolism in both cell types following PDT. The analysis of common differential genes of primary sebocytes and XL-i-20 sebocytes post ALA-PDT showed that TNF signaling pathways, MAPK signaling pathways and JAK-STAT signaling pathways were activated. The SG organoids were spherical, which expressed markers of FANS and PLET1. Ki-67 was down-regulated after ALA-PDT., Conclusions: We have developed an h‑tert immortalized sebocyte cell line from an Asian population. The cell line, XL-i-20, maintains the essential characteristics of its parent primary sebocytes. Moreover, XL-i-20 sebocyte exhibited a significant respond to ALA-PDT, demonstrating comparable phenotypic and molecular changes to primary sebocytes. Therefore, XL-i-20 and its derived SG organoid serve as appropriate in vitro models for investigating the efficacy and mechanisms of ALA-PDT in SG-related diseases., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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131. Photothermal therapy improves the efficacy of topical immunotherapy against melanoma.
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Shi L, Zhang F, Yan J, Luo M, Liu K, Liu P, Yan G, Li C, Yang Y, Zeng Q, Zhang G, Chen WR, and Wang X
- Abstract
Background: Melanoma is an aggressive cancer with poor response to traditional therapies. A combination of photothermal therapy and topical immunotherapy is expected to eliminate melanoma effectively., Materials and Methods: C57BL/6 mice with early stage and metastatic melanoma were treated with laser immunotherapy (LIT), combining near-infrared laser-based photothermal therapy (PTT) and topical imiquimod (IMQ)-based immunotherapy. The volume of primary and abscopal melanoma, animal survival, tissue temperature, transcriptome, and immune cell response were investigated to evaluate the effect of LIT., Results: LIT could eliminate primary tumors, inhibited abscopal tumors, and prolonged animal survival. The tumor tissues were selectively destroyed under a photothermal gradient between 38.2 ± 3.7°C and 73.0 ± 2.3°C. Gene expression analysis showed a significant increase in the expression of damage associated molecular patterns. Additionally, the expression of mature dendritic cells, CD4
+ T cells, and CD8+ T cells were increased, while myeloid-derived suppressor cells were downregulated after LIT., Conclusion: The study showed that LIT inhibited the growth of both primary and abscopal melanoma by activating systemic antitumor immune responses and reversing the immunosuppressive tumor microenvironment, making LIT a potential method for advanced melanoma treatment., Competing Interests: Declaration of competing interest The authors declare no financial or commercial conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
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132. Compared with other methods, cyanoacrylate and lauromacrogol in treating esophagogastric varices did not increase the risk of postoperative infection.
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Zeng Q, Lan C, He B, Tao Z, Liu J, Kong T, and Xu S
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- Humans, Male, Female, Retrospective Studies, Middle Aged, Risk Factors, Ligation, Aged, Treatment Outcome, Polyethylene Glycols administration & dosage, Polyethylene Glycols therapeutic use, Polyethylene Glycols adverse effects, Adult, Surgical Wound Infection etiology, Liver Cirrhosis complications, Esophageal and Gastric Varices etiology, Esophageal and Gastric Varices therapy, Cyanoacrylates adverse effects, Cyanoacrylates administration & dosage, Cyanoacrylates therapeutic use, Gastrointestinal Hemorrhage etiology, Gastrointestinal Hemorrhage therapy, Recurrence
- Abstract
Background: Patients with cirrhosis commonly undergo endoscopic cyanoacrylate injection for gastric and esophageal variceal bleeding. However, postoperative infections can increase the risk of rebleeding and mortality., Aim: This study aimed to determine the risk of postoperative infections and its associated factors following cyanoacrylate injection treatment in these patients., Methods: A retrospective analysis was conducted on 57 patients treated with ligation (ligation group), 66 patients treated with cyanoacrylate injection (injection group), and 91 patients treated with conservative treatment (control group) at the Nanchong Central Hospital., Results: The rate of postoperative infection was similar among the cyanoacrylate, ligation, and conservative treatment groups, with no significant statistical difference observed ( P = 0.97). Multivariate analysis identified postoperative Child-Pugh score and renal insufficiency as two independent risk factors for postoperative infection. The rebleeding rate in the injection group was significantly lower than in the other groups ( P = 0.01). Mortality was significantly higher in the control group compared with the ligation and injection groups ( P = 0.01)., Conclusion: Cyanoacrylate combined with lauromacrogol injection did not significantly increase the risk of infection compared with ligation and conservative treatments, and it was more effective in reducing the risk of rebleeding. This method is safe, effective, and holds clinical value for broader application., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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133. Prenatal sonographic evidence of hypohidrotic ectodermal dysplasia and postnatal genetic testing of a family line of child.
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Lin D, Li H, Tian L, Liu L, Zhang J, Wang Y, Zhang J, Su L, Zeng Q, and Wu Q
- Abstract
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1429/coif). J.Z. is an employee of Shanghai Lianying Medical Technology Co., Ltd., and reports that he had no financial or other conflicts with respect to this study. The other authors have no conflicts of interest to declare to this study.
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- 2024
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134. A review on ferroptosis and photodynamic therapy synergism: Enhancing anticancer treatment.
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Chang Q, Wang P, Zeng Q, and Wang X
- Abstract
Ferroptosis is an iron-dependent programmed cell death modality, which has showed great potential in anticancer treatment. Photodynamic therapy (PDT) is widely used in clinic as an anticancer therapy. PDT combined with ferroptosis-promoting therapy has been found to be a promising strategy to improve anti-cancer therapy efficacy. Fenton reaction in ferroptosis can provide oxygen for PDT, and PDT can produce reactive oxygen species for Fenton reaction to enhance ferroptosis. In this review, we briefly present the importance of ferroptosis in anticancer treatment, mechanism of ferroptosis, researches on PDT induced ferroptosis, and the mechanism of the synergistic effect of PDT and ferroptosis on cancer killing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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135. Oroxylin A suppress LL-37 generated rosacea-like skin inflammation through the modulation of SIRT3-SOD2-NF-κB signaling pathway.
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Feng C, Zhang H, Wang P, Zhang L, Liu X, Yan G, Yan Y, Yang J, Liu J, Tan F, Wang X, and Zeng Q
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- Humans, NF-kappa B metabolism, Reactive Oxygen Species metabolism, Signal Transduction, Inflammation drug therapy, Sirtuin 3 metabolism, Rosacea drug therapy, Dermatitis, Flavonoids
- Abstract
Rosacea is a long-term inflammatory skin disease associated with the dysfunction of vascular and immunological systems. Treatment options for rosacea are difficult to implement. Oroxylin A(OA), a traditional Chinese medicine, has anti-inflammation effects in a variety of inflammatory diseases. However, it is not known that whether OA exerts protective effects against LL-37-induced rosacea. In this study, bioinformatics analyses showed that the mechanisms of rosacea and the pharmacological targets of OA were highly overlapped. Subsequently, it was shown that the administration of OA resulted in a notable amelioration of rosacea-like skin lesions, as evidenced by a reduction in immune cell infiltration, modulation of cytokine production, and inhibition of angiogenesis. Plus, it was shown that OA effectively suppressed the generation of ROS generated by LL-37, as well as the subsequent activation of NF-κB signaling pathway. To explore further, we found that OA inhibited LL-37-induced ROS production via SIRT3-SOD2 signaling pathway in keratinocytes. Based on the aforementioned evidence, it can be inferred that OA exhibits a mitigating effect on the inflammatory response in rosacea by modulating the SIRT3-SOD2-NF-κB signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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136. Modified 5-aminolevulinic acid photodynamic therapy induces cutaneous squamous cell carcinoma cell pyroptosis via the JNK signaling pathway.
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Chen D, Wang B, Zhao Z, Zhang G, Wang P, Zhang L, Liu X, Zhang H, Zeng Q, and Wang X
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- Humans, Inflammasomes metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Reactive Oxygen Species metabolism, MAP Kinase Signaling System, Aminolevulinic Acid pharmacology, Aminolevulinic Acid metabolism, Pyroptosis, Carcinoma, Squamous Cell drug therapy, Skin Neoplasms drug therapy, Photochemotherapy
- Abstract
Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) is a novel therapeutic modality for cutaneous squamous cell carcinoma (cSCC) that is reported to be effective and well tolerated. However, the mechanisms underlying its antitumor effects are not fully understood. In this research, we investigated the effects of M-PDT on pyroptosis, a form of programmed cell death characterized by cell swelling, ruptures of cell membrane, and inflammatory cytokine release, in two human cSCC cell lines, SCL-1 and HSC-5. We found that M-PDT triggered pyroptosis in a dose-dependent manner, as evidenced by increased lactate dehydrogenase release, propidium iodide staining, and expression of pyroptosis-related proteins, such as NLR family pyrin domain containing 3 (NLRP3), N-terminal of gasdermin D (N-GSDMD), cleaved caspase-1, and mature interleukin 1 beta (IL-1B) in both cell lines. This process was inhibited by treatment with MCC950, an NLRP3-specific inhibitor, suggesting the involvement of the NLRP3 inflammasome in M-PDT-induced pyroptosis. We also demonstrated that M-PDT activated c-Jun N-terminal kinase (JNK) signaling, which is required for pyroptosis induction, as treatment with SP600125, a JNK inhibitor, suppressed the expression of pyroptosis-related proteins after M-PDT. JNK activation enhanced M-PDT-induced pyroptosis, highlighting the significance of the JNK pathway in M-PDT. Moreover, M-PDT increased intracellular reactive oxygen species (ROS) levels, which are responsible for JNK activation and pyroptosis induction. In summary, our results revealed that M-PDT triggers pyroptosis through ROS-mediated JNK activation and subsequent NLRP3 inflammasome activation in cSCC cells, providing a better understanding of the molecular mechanism of M-PDT and promoting its clinical application., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2024
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137. 5-aminolevulinic acid sonodynamic therapy for cutaneous squamous cell carcinoma.
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Li C, Yan J, Wang P, Zhang H, Zeng Q, Zhang G, and Wang X
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- Mice, Animals, Aminolevulinic Acid pharmacology, Aminolevulinic Acid therapeutic use, Photosensitizing Agents pharmacology, Photosensitizing Agents therapeutic use, Reactive Oxygen Species, Body Weight, Cell Line, Tumor, Ultrasonic Therapy, Carcinoma, Squamous Cell drug therapy, Photochemotherapy methods, Skin Neoplasms drug therapy
- Abstract
Background: The treatment of deep-invasive cutaneous squamous cell carcinoma (cSCC) is difficult. Sonodynamic therapy (SDT) has showed advantages in large penetration depth, small trauma, good repeatability, high targeting selectivity and effective protection for intact structure and function of tissues and organs., Objective: To study the efficacy and safety of 5-aminolevulinic acid SDT (ALA-SDT) in the treatment of cSCC., Methods: The absorption and transformation of ALA after co-incubation with cSCC were detected by UV-Vis and fluorescence absorption. The production of reactive oxygen species (ROS) when protoporphyrin IX (PpIX) excited with ultrasound was detected by ROS detection probe. Cytotoxicity of ALA-SDT to cSCC was detected with cytotoxicity indicators. The tumor volume changes and tumor weight of mice after ALA-SDT were detected. The effects of ALA-SDT on the growth of mice were evaluated through the changes in body weight of mice. Biosafety of treatment was further evaluated by histopathology to determine whether the tissues and organs of mice were affected after ALA-SDT., Results: ALA can be absorbed and converted into PpIX when incubated with cSCC cells and produces ROS with ultrasound irradiation. ALA-SDT showed a significant cytotoxicity on cSCC cells. With one session of ALA-SDT in vivo, tumor growth was slowed but not stopped and would proceed once treatment was ended. ALA-SDT had no significant effect on body weight changes and major tissues and organs of the mice., Conclusion: ALA-SDT could safely and reduce cSCC cells growth both in vitro and in vivo., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2023
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138. Non-Surgical Therapeutic Strategies for Non-Melanoma Skin Cancers.
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Zeng Q, Chen C, Chen D, Zhang G, and Wang X
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- Humans, Aged, Hedgehog Proteins, Skin Neoplasms therapy, Skin Neoplasms drug therapy, Carcinoma, Basal Cell therapy, Carcinoma, Basal Cell drug therapy, Carcinoma, Squamous Cell therapy, Carcinoma, Squamous Cell drug therapy, Antineoplastic Agents therapeutic use
- Abstract
Opinion Statement: Non-melanoma skin cancer (NMSC) is a globally prevalent skin disease, with basal cell carcinoma and squamous cell carcinoma accounting for 99% of NMSC cases. While surgical excision is the most common approach, numerous non-surgical therapies have rapidly advanced in recent years. In cases of low-risk NMSC, alongside surgical excision, priority should be given to physical therapy and photodynamic therapy. Physical therapy modalities, exemplified by electrodessication and curettage, emerge as safe and efficacious alternatives. In juxtaposition, photodynamic therapy, albeit relatively more costly, assumes preference for patients exhibiting heightened cosmetic concerns owing to the scarring risks inherent to physical therapy and surgical excision. Notably, the combination of curettage and photodynamic therapy has exhibited remarkable efficacy in the treatment of nodular basal cell carcinoma. Additionally, for elderly patients who may be intolerant to stimulation, modified photodynamic therapy offers an almost painless option. When surgery is unavoidable, photodynamic therapy can be a valuable adjunct, allowing for a more conservative surgical approach, either before or after the procedure. Radiotherapy holds a prominent role in comprehensive treatment strategies, especially for patients ineligible for surgical intervention or those with lesions precluding further surgical measures. In cases of NMSC exhibiting perineural invasion or lymphovascular involvement, adjunctive radiotherapy is advised; however, potential adverse effects necessitate careful consideration. For advanced NMSC cases where surgery and physical therapy fall short, immunotherapy provide viable solutions. Systemic therapy employing Hedgehog pathway inhibitors can be considered for patients with distant metastatic basal cell carcinoma, despite its low incidence, or individuals with locally advanced lesions who are not surgical candidates, or those encountering recurrences after resection and radiotherapy. However, close monitoring of disease progression and adverse reactions is crucial. In this evolving landscape of NMSC treatment, personalized and multidisciplinary approaches are key, ensuring optimal outcomes while prioritizing patient safety and satisfaction., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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139. Successful appendiceal incision by endoscopic submucosal dissection to allow endoscopic removal of an encapsulated fecalith.
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Zeng Q, Tao Z, Liu J, Tao K, Shan X, and Chen YL
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- Humans, Endoscopy, Endoscopic Mucosal Resection, Fecal Impaction, Appendix
- Abstract
Competing Interests: The authors declare that they have no conflict of interest.
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- 2023
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140. 5-Aminolevulinic acid photodynamic therapy versus minocycline for moderate-to-severe rosacea: A single-center, randomized, evaluator-blind controlled study.
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Yang J, Liu X, Cao Y, Wang P, Zhang H, Chen Q, Yang Y, Zeng Q, Zhang L, and Wang X
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- Humans, Aminolevulinic Acid adverse effects, Minocycline adverse effects, Quality of Life, Treatment Outcome, Photosensitizing Agents adverse effects, Photochemotherapy adverse effects, Rosacea drug therapy
- Abstract
Background: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) showed potential to treat rosacea according to recent studies; however, a lack of clinical evidence and unclear adverse effects limit its use., Objective: To compare the effect of ALA-PDT vs minocycline on rosacea., Methods: In this single-center, randomized, evaluator-blind, controlled study, patients with moderate-to-severe rosacea were allocated to receive 3 to 5 sessions of ALA-PDT or 8 weeks of 100 mg daily minocycline treatment, followed by a 24-week follow-up., Results: Of all the 44 randomized patients, 41 received complete treatment (ALA-PDT: 20 and minocycline: 21 patients). At the end of treatment, ALA-PDT showed noninferior improvement of papulopustular lesions and Rosacea-specific Quality of Life compared with minocycline (median reduction of lesion count: 19 vs 22, median change of Rosacea-specific Quality of Life score: 0.48 vs 0.53). The Clinician's Erythema Assessment success of ALA-PDT was lower than that of minocycline's (35% vs 67%). Demodex density and relapse rate were comparable in both groups. Erythema, mild pain, and exudation were the most common adverse reactions of ALA-PDT., Limitations: Limited sample size restricted us from drawing further conclusions., Conclusion: As minocycline does, ALA-PDT can improve rosacea mainly in papulopustular lesions and patients' quality of life, indicating a new option for rosacea., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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141. A chlorin e6 derivative-mediated photodynamic therapy inhibits cutaneous squamous cell carcinoma cell proliferation via Akt/mTOR signaling pathway.
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Tao H, Zhang H, Xu D, Yan G, Wu Y, Zhang G, Zeng Q, and Wang X
- Subjects
- Animals, Photosensitizing Agents therapeutic use, Proto-Oncogene Proteins c-akt, Signal Transduction, TOR Serine-Threonine Kinases metabolism, Cell Proliferation, Cell Line, Tumor, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell metabolism, Photochemotherapy methods, Skin Neoplasms drug therapy, Skin Neoplasms metabolism, Porphyrins
- Abstract
Background and Objectives: Although most cutaneous squamous cell carcinoma (cSCC) cases are generally nonlethal and manageable with surgical excision, there ares till significant hazards for patients who are ineligible for surgical resection. We sought to find a suitable and effective treatment for cSCC., Methods: We modified chlorin e6 by adding a hydrogen chain with a six-carbon ring to the benzene ring and named this new photosensitizer as STBF. We first investigated the fluorescence characteristics, cellular uptake of STBF and subcellular localization. Next, cell viability was detected by CCK-8 assay and the TUNEL staining was performed. Akt/mTOR-related proteins were examined by western blot., Results: STBF-photodynamic therapy (PDT) inhibits cSCC cells viability in a light dose dependent manner. The antitumor mechanism of STBF-PDT might be due to the suppression of the Akt/mTOR signaling pathway. Further animal investigation determined that STBF-PDT led to a marked reduction in tumor growth., Conclusions: Our results suggest that STBF-PDT exerts significant therapeutic effects in cSCC. Thus, STBF-PDT is expected to be a promising method for the treatment of cSCC and the photosensitizer STBF may be destined for a wider range of applications in photodynamic therapy., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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142. Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth.
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Schaf J, Shinhmar S, Zeng Q, Pardo OE, Beesley P, Syed N, and Williams RSB
- Abstract
Glioblastomas are a highly aggressive cancer type which respond poorly to current pharmaceutical treatments, thus novel therapeutic approaches need to be investigated. One such approach involves the use of the bioactive natural product Tanshinone IIA (T2A) derived from the Chinese herb Danshen, where mechanistic insight for this anti-cancer agent is needed to validate its use. Here, we employ a tractable model system, Dictyostelium discoideum, to provide this insight. T2A potently inhibits cellular proliferation of Dictyostelium, suggesting molecular targets in this model. We show that T2A rapidly reduces phosphoinositide 3 kinase (PI3K) and protein kinase B (PKB) activity, but surprisingly, the downstream complex mechanistic target of rapamycin complex 1 (mTORC1) is only inhibited following chronic treatment. Investigating regulators of mTORC1, including PKB, tuberous sclerosis complex (TSC), and AMP-activated protein kinase (AMPK), suggests these enzymes were not responsible for this effect, implicating an additional molecular mechanism of T2A. We identify this mechanism as the increased expression of sestrin, a negative regulator of mTORC1. We further show that combinatory treatment using a PI3K inhibitor and T2A gives rise to a synergistic inhibition of cell proliferation. We then translate our findings to human and mouse-derived glioblastoma cell lines, where both a PI3K inhibitor (Paxalisib) and T2A reduces glioblastoma proliferation in monolayer cultures and in spheroid expansion, with combinatory treatment significantly enhancing this effect. Thus, we propose a new approach for cancer treatment, including glioblastomas, through combinatory treatment with PI3K inhibitors and T2A., (© 2023. The Author(s).)
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- 2023
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143. Molecular characterization of gene expression changes in murine cutaneous squamous cell carcinoma after 5-aminolevulinic acid photodynamic therapy.
- Author
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Fang S, Wu Y, Zhang H, Zeng Q, Wang P, Zhang L, Yan G, Zhang G, and Wang X
- Subjects
- Aminolevulinic Acid pharmacology, Aminolevulinic Acid therapeutic use, Animals, Cell Line, Tumor, Gene Expression, Mice, Phosphatidylinositol 3-Kinases, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Photochemotherapy methods, RNA, Long Noncoding, Skin Neoplasms pathology
- Abstract
5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) is an effective therapy in treating inoperable cutaneous squamous cell carcinoma (cSCC) in China. However, its exact mechanism in treating cSCC is still unclear. Here, we analyzed expression profiles of lncRNAs and mRNAs of cSCC after ALA-PDT in a mouse model using Mouse Transcriptome Assay 1.0 chip. A total of 592 and 828 differentially expressed genes were identified in comparisons of ALA-PDT after 3 h vs. control, ALA-PDT after 6 h vs. control respectively. Regarding the lncRNAs analysis, a total of 185 and 410 differentially expressed lncRNAs were sought out. Bioinformatics analyses including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, pathway relation network, and gene set enrichment analysis revealed that the pathways of ALA-PDT in treating cSCC were mainly associated with immune regulation, NF-κB signaling pathway, TLR signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, and MAPK signaling pathway, which was validated by western blot analysis. Furthermore, a lncRNA-mRNA co-expression network revealed 118 network pairs comprising 36 lncRNAs and 68 mRNAs. These findings provide a basis for investigations into the treatment mechanisms of ALA-PDT in treating cSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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144. Celastrol inhibits LL37-induced rosacea by inhibiting Ca 2+ /CaMKII-mTOR-NF-κB activation.
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Zeng Q, Yang J, Yan G, Zhang L, Wang P, Zhang H, Chen Q, Cao Y, Liu X, and Wang X
- Subjects
- Animals, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Humans, Inflammation drug therapy, Mice, NF-kappa B metabolism, Neovascularization, Pathologic drug therapy, Pentacyclic Triterpenes therapeutic use, TOR Serine-Threonine Kinases metabolism, Rosacea chemically induced, Rosacea drug therapy, Triterpenes pharmacology, Triterpenes therapeutic use
- Abstract
Rosacea is a common chronic facial inflammatory disease that affects millions of people worldwide. Due to the unclear etiology of rosacea, effective treatments are limited. Celastrol, a plant-derived triterpene, has been reported to alleviate inflammation in various diseases. However, whether celastrol exerts protective effects in rosacea remains to be elucidated. In this study, weighted gene co-expression network analyses (WGCNA) were performed. Hub modules closely related to rosacea clinical characteristics were identified and found to be involved in inflammation- and angiogenesis-related signaling pathways. Then, the pharmacological targets of celastrol were predicted using the TargetNet and Swiss Target Prediction databases. A GO analysis indicated that the biological process regulated by celastrol highly overlapped with the pathogenic biological processes in rosacea. Next, we showed that celastrol ameliorated erythema, skin thickness and inflammatory cell infiltration in the dermis of LL37-treated mice. Celastrol suppressed the expression of rosacea-related inflammatory cytokines and inhibited the Th17 immune response and cutaneous angiogenesis in LL37-induced rosacea-like mice. We further demonstrated that celastrol attenuated LL37-induced inflammation by inhibiting intracellular-free calcium ([Ca
2+ ]i )-mediated mTOR signaling in keratinocytes. Chelating intracellular Ca2+ with BAPTA/AM potentiated celastrol-induced repression of LL37-induced p-S6 elevation. The mTOR agonist MHY1485 dramatically reinforced LL37-induced rosacea-like characteristics, while celastrol attenuated these outcomes. Moreover, celastrol inhibited LL37-activated NF-κB in a mTOR signaling-dependent manner. In conclusion, our findings underscore that celastrol may be a rosacea protective agent by inhibiting the LL37-activated Ca2+ /CaMKII-mTOR-NF-κB pathway associated with skin inflammation disorders., Competing Interests: Conflict of interest statement The authors have declared no conflicting interests., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)- Published
- 2022
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145. Halofuginone enhances the anti-tumor effect of ALA-PDT by suppressing NRF2 signaling in cSCC.
- Author
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Lv T, Huang J, Wu M, Wang H, Zeng Q, and Wang X
- Subjects
- Aminolevulinic Acid pharmacology, Aminolevulinic Acid therapeutic use, Animals, Apoptosis, Cell Line, Tumor, Mice, NF-E2-Related Factor 2 pharmacology, NF-E2-Related Factor 2 therapeutic use, Photosensitizing Agents pharmacology, Photosensitizing Agents therapeutic use, Piperidines, Quinazolinones, Carcinoma, Squamous Cell drug therapy, Photochemotherapy methods, Skin Neoplasms pathology
- Abstract
Background: 5-aminolevulinic acid-mediated PDT (ALA-PDT) has been used in a variety of skin diseases including cSCC (cutaneous squamous cell carcinoma). Halofuginone (HL) is a less-toxic febrifugine derivative and has inhibitory effects on a variety of cancer cells. For now, there are no published study focusing on the combination use of ALA-PDT with HL to improve clinical efficacy of cSCC., Objective: In this study, we will examine the effectiveness of combined treatment of ALA-PDT and HL in cSCC as well as its underlying mechanism., Methods: The human epidermoid carcinoma cell line SCL-1 was treated with ALA-PDT or/ and HL, and cell viability, cell migration, ROS production, apoptosis were evaluated by CCK-8, colony formation, scratch assay, DCFH-DA probe, flow cytometry, respectively. The protein expression of NRF2 signaling was examined by western blot., Results: HL strengthened ALA-PDT's inhibition of SCL-1 cell viability, migration, as well as NRF2 related β-catenin, p-Erk1/2, p-Akt and p-S6K1 expression. Overexpression of NRF2 conferred resistance to co-treatment's effects on c-Myc, Cyclin D1, Bcl-2, as well as cell proliferation. HL also strengthened ALA-PDT's inhibition of tumor volume in cSCC mouse model and elevated ROS generation of ALA-PDT., Conclusion: HL enhances the anti-tumor effect of ALA-PDT in vitro and in vivo. HL has the potential to enhance the anti-tumor effect of ALA-PDT in cSCC via inhibiting NRF2 signaling., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2022
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146. 5-Aminolaevulinic acid photodynamic therapy suppresses lipid secretion of primary sebocytes through AMPK/SREBP-1 pathway.
- Author
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Yang J, Shi L, Xu D, Liu J, Zhang L, Liu X, Zeng Q, and Wang X
- Subjects
- AMP-Activated Protein Kinases, Aminolevulinic Acid pharmacology, Aminolevulinic Acid therapeutic use, Animals, Cricetinae, Humans, Lipids therapeutic use, Photosensitizing Agents pharmacology, Photosensitizing Agents therapeutic use, Sterol Regulatory Element Binding Protein 1, Acne Vulgaris drug therapy, Photochemotherapy methods
- Abstract
Background: Acne vulgaris is a chronic inflammatory skin disease around pilosebaceous unit. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for severe acne vulgaris. However, its specific treatment mechanism remains unclear. In the present study, we investigated the potential mechanism of how ALA-PDT induced lipid secretion inhibition in acne vulgaris., Methods: Primary human sebocytes and sebaceous gland of golden hamster were treated with/without ALA-PDT. Cell viability was evaluated by Live/Dead Cell assay. Fluorescence microscope was used to observe lipids secretion in sebocytes after Nile red staining. The expression of SREBP-1 after ALA-PDT was evaluated by qRT-PCR. Regulation of ALA-PDT on AMPK/SREBP-1 was evaluated by western blot., Results: The results showed that ALA-PDT suppressed lipid secretion of primary human sebocytes. In addition, ALA-PDT could inhibit the expression of SREBP-1 in vitro. We also found that ALA-PDT activated AMPK pathway, down-regulating the expression of SREBP-1 in sebocytes after ALA-PDT., Conclusions: These findings elucidate that ALA-PDT suppresses lipid secretion through AMPK/SREBP-1 pathway in treatment of acne vulgaris., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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147. Rapamycin inhibits B-cell activating factor (BAFF)-stimulated cell proliferation and survival by suppressing Ca 2+ -CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway in normal and neoplastic B-lymphoid cells.
- Author
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Zeng Q, Zhou Z, Qin S, Yao Y, Qin J, Zhang H, Zhang R, Xu C, Zhang S, Huang S, and Chen L
- Subjects
- Animals, Apoptosis drug effects, B-Lymphocytes drug effects, B-Lymphocytes pathology, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Cyclin-Dependent Kinases metabolism, Down-Regulation drug effects, Humans, Lymphoma, B-Cell metabolism, MAP Kinase Signaling System, Mice, Models, Biological, B-Cell Activating Factor metabolism, B-Lymphocytes metabolism, Calcium metabolism, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Lymphoma, B-Cell pathology, PTEN Phosphohydrolase metabolism, Proto-Oncogene Proteins c-akt metabolism, Sirolimus pharmacology
- Abstract
B-cell activating factor (BAFF) is a crucial survival factor for B cells, and excess BAFF contributes to development of autoimmune diseases. Recent studies have shown that rapamycin can prevent BAFF-induced B-cell proliferation and survival, but the underlying mechanism remains to be elucidated. Here we found that rapamycin inhibited human soluble BAFF (hsBAFF)-stimulated cell proliferation by inducing G
1 -cell cycle arrest, which was through downregulating the protein levels of CDK2, CDK4, CDK6, cyclin A, cyclin D1, and cyclin E. Rapamycin reduced hsBAFF-stimulated cell survival by downregulating the levels of anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xL and survivin) and meanwhile upregulating the levels of pro-apoptotic proteins (BAK and BAX). The cytostatic and cytotoxic effects of rapamycin linked to its attenuation of hsBAFF-elevated intracellular free Ca2+ ([Ca2+ ]i ). In addition, rapamycin blocked hsBAFF-stimulated B-cell proliferation and survival by preventing hsBAFF from inactivating PTEN and activating the Akt-Erk1/2 pathway. Overexpression of wild type PTEN or ectopic expression of dominant negative Akt potentiated rapamycin's suppression of hsBAFF-induced Erk1/2 activation and proliferation/viability in Raji cells. Interestingly, PP242 (mTORC1/2 inhibitor) or Akt inhibitor X, like rapamycin (mTORC1 inhibitor), reduced the basal or hsBAFF-induced [Ca2+ ]i elevations. Chelating [Ca2+ ]i with BAPTA/AM, preventing [Ca2+ ]i elevation using EGTA, 2-APB or verapamil, inhibiting CaMKII with KN93, or silencing CaMKII strengthened rapamycin's inhibitory effects. The results indicate that rapamycin inhibits BAFF-stimulated B-cell proliferation and survival by blunting mTORC1/2-mediated [Ca2+ ]i elevations and suppressing Ca2+ -CaMKII-dependent PTEN/Akt-Erk1/2 signaling pathway. Our finding underscores that rapamycin may be exploited for prevention of excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
148. Time Temperature Superposition Evaluation and Modeling for Container Closure System's Seal Performance at Low Temperatures.
- Author
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Zeng Q, Bucci A, and Ho L
- Subjects
- Drug Packaging methods, Materials Testing methods, Rubber standards, Stainless Steel standards, Cold Temperature, Drug Packaging standards, Glass standards, Materials Testing standards
- Abstract
There has been a growing interest in the assessment of container closure systems (CCS) for cold storage and shipment. Prior publications have lacked systematic considerations for the impact of dynamic time temperature transition on sealing performance associated with the viscoelastic characteristics of rubber stoppers used in container closure systems (CCSs). This paper demonstrates that sealing performance changes inherently and is fundamentally both time- and temperature-dependent. Our research results display this critical time temperature transition impact on CCS sealing performance by applying compression stress relaxation (CSR) on a rubber stopper for experimental data collection and modeling evaluation. The experimental results agree with modeling evaluation following Maxwell-Wiechert theory and the time temperature superposition based on the Arrhenius and Williams-Landel-Ferry methods. Both testing and modeling data show good consistency, demonstrating that the sealing force inevitably changes over time together with temperature transition because of the viscoelastic nature of the rubber stoppers. Our results show that compression seal force decreases quickly as temperature decreases. The significant loss of rubber stopper sealing force at lower temperature transitions could contribute significant risk to CCI at low storage and transport temperatures. Modeling evaluation, with a powerful capability to handle actual testing data, can be employed as a predictive tool to evaluate the time- and temperature-dependent sealing force throughout the entire sealed drug product life span. The present study is only applicable before reaching the rubber glass transition temperature Tg - a critical transition phase that can not be skipped/separated from real time temperature transition, and it will further determine the CCS sealing performance while approaching cryogenic temperature. The present work provides a new, integrated methodology framework and some fresh insights to the parenteral packaging industry for practically and proactively considering, designing, setting up, controlling, and managing stopper sealing performance throughout the entire sealed drug product life span., (© PDA, Inc. 2020.)
- Published
- 2020
- Full Text
- View/download PDF
149. Time-Dependent Testing Evaluation and Modeling for Rubber Stopper Seal Performance.
- Author
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Zeng Q and Zhao X
- Subjects
- Drug Compounding, Elasticity, Equipment Design, Materials Testing, Models, Statistical, Technology, Pharmaceutical methods, Temperature, Time Factors, Viscosity, Drug Packaging, Rubber chemistry
- Abstract
Sufficient rubber stopper sealing performance throughout the entire sealed product life cycle is essential for maintaining container closure integrity in the parenteral packaging industry. However, prior publications have lacked systematic considerations for the time-dependent influence on sealing performance that results from the viscoelastic characteristics of the rubber stoppers. In this paper, we report results of an effort to study these effects by applying both compression stress relaxation testing and residual seal force testing for time-dependent experimental data collection. These experiments were followed by modeling fit calculations based on the Maxwell-Wiechert theory modified with the Kohlrausch-Williams-Watts stretched exponential function, resulting in a nonlinear, time-dependent sealing force model. By employing both testing evaluations and modeling calculations, an in-depth understanding of the time-dependent effects on rubber stopper sealing force was developed. Both testing and modeling data show good consistency, demonstrating that the sealing force decays exponentially over time and eventually levels off because of the viscoelastic nature of the rubber stoppers. The nonlinearity of stress relaxation derives from the viscoelastic characteristics of the rubber stoppers coupled with the large stopper compression deformation into restrained geometry conditions. The modeling fit with capability to handle actual testing data can be employed as a tool to calculate the compression stress relaxation and residual seal force throughout the entire sealed product life cycle. In addition to being time-dependent, stress relaxation is also experimentally shown to be temperature-dependent. The present work provides a new, integrated methodology framework and some fresh insights to the parenteral packaging industry for practically and proactively considering, designing, setting up, controlling, and managing stopper sealing performance throughout the entire sealed product life cycle. LAY ABSTRACT: Historical publications in the parenteral packaging industry have lacked systematic considerations for the time-dependent influence on the sealing performance that results from effects of viscoelastic characteristic of the rubber stoppers. This study applied compression stress relaxation testing and residual seal force testing for time-dependent experimental data collection. These experiments were followed by modeling fit calculations based on the Maxwell-Wiechert theory modified with the Kohlrausch-Williams-Watts stretched exponential function, resulting in a nonlinear, time-dependent sealing force model. Experimental and modeling data show good consistency, demonstrating that sealing force decays exponentially over time and eventually levels off. The nonlinearity of stress relaxation derives from the viscoelastic characteristics of the rubber stoppers coupled with the large stopper compression deformation into restrained geometry conditions. In addition to being time-dependent stress relaxation, it is also experimentally shown to be temperature-dependent. The present work provides a new, integrated methodology framework and some fresh insights to the industry for practically and proactively considering, designing, setting up, controlling, and managing of the stopper sealing performance throughout the entire sealed product life cycle., (© PDA, Inc. 2018.)
- Published
- 2018
- Full Text
- View/download PDF
150. Rapamycin attenuates BAFF-extended proliferation and survival via disruption of mTORC1/2 signaling in normal and neoplastic B-lymphoid cells.
- Author
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Zeng Q, Qin S, Zhang H, Liu B, Qin J, Wang X, Zhang R, Liu C, Dong X, Zhang S, Huang S, and Chen L
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, B-Lymphocytes enzymology, B-Lymphocytes pathology, Cell Cycle Proteins, Cell Line, Tumor, Cell Survival drug effects, Dose-Response Relationship, Drug, Gene Expression Regulation, Neoplastic, Humans, Lymphoma, B-Cell genetics, Lymphoma, B-Cell pathology, Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Phosphoproteins genetics, Phosphoproteins metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, RNA Interference, Ribosomal Protein S6 Kinases, 70-kDa genetics, Ribosomal Protein S6 Kinases, 70-kDa metabolism, Transfection, Antineoplastic Agents pharmacology, B-Cell Activating Factor metabolism, B-Lymphocytes drug effects, Cell Proliferation drug effects, Lymphoma, B-Cell drug therapy, Multiprotein Complexes metabolism, Signal Transduction drug effects, Sirolimus pharmacology, TOR Serine-Threonine Kinases metabolism
- Abstract
B cell activating factor from the TNF family (BAFF) stimulates B-cell proliferation and survival, but excessive BAFF promotes the development of aggressive B cells leading to malignant and autoimmune diseases. Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)-stimulated B-cell proliferation/survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway. Here, we show that the inhibitory effect of rapamycin on hsBAFF-promoted B cell proliferation/survival is also related to blocking hsBAFF-stimulated phosphorylation of Akt, S6K1, and 4E-BP1, as well as expression of survivin in normal and B-lymphoid (Raji and Daudi) cells. It appeared that both mTORC1 and mTORC2 were involved in the inhibitory activity of rapamycin, as silencing raptor or rictor enhanced rapamycin's suppression of hsBAFF-induced survivin expression and proliferation/viability in B cells. Also, PP242, an mTORC1/2 kinase inhibitor, repressed survivin expression, and cell proliferation/viability more potently than rapamycin (mTORC1 inhibitor) in B cells in response to hsBAFF. Of interest, ectopic expression of constitutively active Akt (myr-Akt) or constitutively active S6K1 (S6K1-ca), or downregulation of 4E-BP1 conferred resistance to rapamycin's attenuation of hsBAFF-induced survivin expression and B-cell proliferation/viability, whereas overexpression of dominant negative Akt (dn-Akt) or constitutively hypophosphorylated 4E-BP1 (4EBP1-5A), or downregulation of S6K1, or co-treatment with Akt inhibitor potentiated the inhibitory effects of rapamycin. The findings indicate that rapamycin attenuates excessive hsBAFF-induced cell proliferation/survival via blocking mTORC1/2 signaling in normal and neoplastic B-lymphoid cells. Our data underscore that rapamycin may be a potential agent for preventing excessive BAFF-evoked aggressive B-cell malignancies and autoimmune diseases., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2018
- Full Text
- View/download PDF
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