54 results on '"Xiao-Jing Shi"'
Search Results
2. A comprehensive review of SHP2 and its role in cancer
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Moges Dessale Asmamaw, Xiao-Jing Shi, Li-Rong Zhang, and Hong-Min Liu
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Cancer Research ,Carcinogenesis ,Programmed Cell Death 1 Receptor ,Receptor Protein-Tyrosine Kinases ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,Antineoplastic Agents ,General Medicine ,Phosphatidylinositol 3-Kinases ,MicroRNAs ,Oncology ,Neoplasms ,Humans ,Cytokines ,Tyrosine ,Molecular Medicine ,Proto-Oncogene Proteins c-akt - Abstract
Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) is a non-receptor protein tyrosine phosphatase ubiquitously expressed mainly in the cytoplasm of several tissues. SHP2 modulates diverse cell signaling events that control metabolism, cell growth, differentiation, cell migration, transcription and oncogenic transformation. It interacts with diverse molecules in the cell, and regulates key signaling events including RAS/ERK, PI3K/AKT, JAK/STAT and PD-1 pathways downstream of several receptor tyrosine kinases (RTKs) upon stimulation by growth factors and cytokines. SHP2 acts as both a phosphatase and a scaffold, and plays prominently oncogenic functions but can be tumor suppressor in a context-dependent manner. It typically acts as a positive regulator of RTKs signaling with some inhibitory functions reported as well. SHP2 expression and activity is regulated by such factors as allosteric autoinhibition, microRNAs, ubiquitination and SUMOylation. Dysregulation of SHP2 expression or activity causes many developmental diseases, and hematological and solid tumors. Moreover, upregulated SHP2 expression or activity also decreases sensitivity of cancer cells to anticancer drugs. SHP2 is now considered as a compelling anticancer drug target and several classes of SHP2 inhibitors with different mode of action are developed with some already in clinical trial phases. Moreover, novel SHP2 substrates and functions are rapidly growing both in cell and cancer. In view of this, we comprehensively and thoroughly reviewed literatures about SHP2 regulatory mechanisms, substrates and binding partners, biological functions, roles in human cancers, and different classes of small molecule inhibitors target this oncoprotein in cancer.
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- 2022
3. Preclinical studies of the triazolo[1,5-a]pyrimidine derivative WS-716 as a highly potent, specific and orally active P-glycoprotein (P-gp) inhibitor
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Sai-Qi Wang, Qiu-Xu Teng, Shuai Wang, Zi-Ning Lei, Hui-Hui Hu, Hui-Fang Lv, Bei-Bei Chen, Jian-Zheng Wang, Xiao-Jing Shi, Wei-Feng Xu, Hong-Min Liu, Xiao-Bing Chen, Zhe-Sheng Chen, and Bin Yu
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General Pharmacology, Toxicology and Pharmaceutics - Published
- 2022
4. Discovery of Novel 1,3-Diphenylpyrazine Derivatives as Potent S-Phase Kinase-Associated Protein 2 (Skp2) Inhibitors for the Treatment of Cancer
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Kun Zhang, Kaizhao Hu, Qian Li, Min Li, Ke Gao, Kecheng Yang, Bing Zhao, Xiao-Jing Shi, Lirong Zhang, and Hong-Min Liu
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Drug Discovery ,Molecular Medicine - Published
- 2023
5. Skp2 is a novel regulator of LSD1 expression and function in gastric cancer
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Moges Dessale Asmamaw, Li-Rong Zhang, Hong-Min Liu, Xiao-Jing Shi, and Ying Liu
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Cell Biology ,Molecular Biology ,Biochemistry ,Genetics (clinical) - Published
- 2023
6. Microglia and astrocytes mediate synapse engulfment in a MER tyrosine kinase-dependent manner after traumatic brain injury
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Hui Shen, Xiao-Jing Shi, Lin Qi, Cheng Wang, Muyassar Mamtilahun, Zhi-Jun Zhang, Won-Suk Chung, Guo-Yuan Yang, and Yao-Hui Tang
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Developmental Neuroscience - Published
- 2023
7. Myofibroblast Deficiency of LSD1 Alleviates TAC-Induced Heart Failure
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Bingfei Wei, Le-Min Jiao, Wen Zhao, Erhe Gao, Hong-Min Liu, Yuruo Qi, Yi-Chao Zheng, Xiao-Jing Shi, Xiuying Chen, Dong Chen, Cong Wang, Qi An, and Jin-Ling Huo
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0301 basic medicine ,medicine.medical_specialty ,animal structures ,biology ,Physiology ,business.industry ,030204 cardiovascular system & hematology ,medicine.disease ,Muscle hypertrophy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Histone ,Fibrosis ,Heart failure ,Internal medicine ,biology.protein ,Cardiology ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Myofibroblast - Abstract
Rationale: Histone LSD1 (lysine-specific demethylase 1) is an important epigenetic antitumor drug target, whose inhibitors are currently in phase I/II clinical trials. However, the potential side effects of LSD1 inhibition in the progress of cardiac remodeling to heart failure remain to be investigated. Objective: To evaluate the roles of myofibroblast- or cardiomyocyte-specific LSD1 deficiency in pressure overload-induced cardiac remodeling. Methods and Results: Adult mouse cardiac fibroblasts, neonatal rat cardiac myocytes, and fibroblasts were isolated, respectively. The myofibroblast-specific and cardiomyocyte-specific LSD1 inducible knockout mice were then generated. We found that LSD1 was increased not only in human dilated cardiomyopathy hearts but also in wild-type mouse heart homogenates and isolated cardiac fibroblasts, following 20 weeks of transverse aortic constriction. The upregulation of LSD1 was also observed in Ang II-treated neonatal rat cardiac fibroblasts, which was reversed by LSD1 silence or its activity inhibition by ORY-1001. These findings suggested a potential involvement of LSD1 in cardiac remodeling. Importantly, myofibroblast-specific LSD1 inducible knockout in vivo significantly alleviated systolic dysfunction, cardiac hypertrophy, and fibrosis, following 6 and 20 weeks of transverse aortic constriction. Mechanistically, through RNA-sequencing and the following Western blot analysis, we found that loss of LSD1 in Ang II-induced myofibroblasts not only inhibited the intracellular upregulation of TGFβ1 (transforming growth factor β1), its downstream effectors Smad2/3 phosphorylation, as well as the phosphorylation of p38, ERK1/2 and JNK, but also reduced the supernatant TGFβ1 secretion, which then decreased myocyte hypertrophy in the indirect coculture model. On the other hand, cardiomyocyte-specific LSD1-inducible knockout in vivo triggered the reprogramming of fetal genes, mild cardiac hypertrophy, and dysfunction under both basal and stressed conditions. Conclusions: Our findings, for the first time, implicate that myofibroblast-specific LSD1 deletion attenuates transverse aortic constriction-induced cardiac remodeling and improves heart function, suggesting that LSD1 is a potential therapeutic target for late-stage heart failure.
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- 2021
8. Constructing carbon-coated Fe3O4 hierarchical microstructures with a porous structure and their excellent Cr(VI) ion removal properties
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Peng Wang, Xiao-Jing Shi, Cheng Lin, Lingbo Xu, Jin Li, Changsheng Song, Xiaoping Wu, Xiaoyun Li, Can Cui, Ping Lin, Shunli Wang, and Zhang Yizhe
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Materials science ,Aqueous solution ,Annealing (metallurgy) ,Magnetic separation ,chemistry.chemical_element ,Condensed Matter Physics ,Microstructure ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,Separation process ,Ion ,chemistry ,Chemical engineering ,Electrical and Electronic Engineering ,Porosity ,Carbon - Abstract
A facile solvothermal method coupled with an annealing strategy is developed to synthesize Fe3O4/carbon (Fe3O4@C) magnetic composite microstructures with different morphologies, including flower-like, hollow spheres and egg-like. The unique multiporous and hollow structure of the as-prepared hierarchical Fe3O4@C hollow microsphere results in an appealing performance as an absorber of Cr(VI) ions in aqueous solution, delivering a high capacity of ~ 197.2 mg/g. Meanwhile, the magnetic Fe3O4 ‘‘core’’ in the hierarchical microstructures can be easily separated from aqueous systems by magnetic separation. Furthermore, the carbon layers effectively prevent the aggregation of magnetic Fe3O4 nanoparticles. The excellent absorbing ability of Cr(VI) ions and easy separation process strongly suggest that the Fe3O4@C magnetic microstructures would have a great potential as adsorbing materials in the large-scale application in environmental purification.
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- 2021
9. Successful treatment of the Meige's syndrome with navigated repetitive transcranial magnetic stimulation: A case report
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Xiao-Jing Shi, Bin Jiang, Rui Shi, Li Li, Xin Guo, Chang-Geng Song, and Shun Qi
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,General Neuroscience ,medicine.medical_treatment ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Biophysics ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Meige's syndrome ,medicine.disease ,Transcranial magnetic stimulation ,Brain stimulation ,Anesthesia ,rTMS ,Medicine ,Neurology (clinical) ,business ,RC321-571 - Published
- 2022
10. All-fiber coherent lidar Doppler imaging based on phase correction with matching method
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Qiqi Wang, Xiao-Jing Shi, Jianfeng Sun, Peng Jiang, Qi Wang, and Wei Lu
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Heterodyne ,Physics ,Matching (statistics) ,Hardware_MEMORYSTRUCTURES ,business.industry ,Phase correction ,Physics::Optics ,01 natural sciences ,Doppler imaging ,Signal ,GeneralLiterature_MISCELLANEOUS ,Atomic and Molecular Physics, and Optics ,010309 optics ,symbols.namesake ,All fiber ,Lidar ,Optics ,0103 physical sciences ,symbols ,010306 general physics ,business ,Doppler effect - Abstract
For a coherent Doppler lidar system, it is extremely important to accurately extract the heterodyne signal while improving the system’s speed measurement accuracy. In this paper, All-fiber coherent...
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- 2020
11. Discovery of [1,2,3]triazolo[4,5-d]pyrimidine derivatives as highly potent, selective, and cellularly active USP28 inhibitors
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Xiao-Jing Shi, Kai Sun, Zhong-Hua Li, Yun-Dong Fu, Bin Yu, Tao-Qian Zhao, Hong-Min Liu, Jimin Guo, Zhen-Zhen Liu, and Ting Cheng
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Pyrimidine ,BLI, biolayer interferometry technology ,IC50, half maximal inhibitory concentration ,USP7, ubiquitin specific peptidase 7 ,Deubiquitinating enzyme ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,CHX, cycloheximide ,Ubiquitin ,NSCLC, non-small cell lung cancer ,Potency ,General Pharmacology, Toxicology and Pharmaceutics ,Ub, ubiquitin ,MTT, 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazoliumbromide ,030304 developmental biology ,LSD1, lysine specific demethylase 1 ,0303 health sciences ,biology ,lcsh:RM1-950 ,EdU, 5-ethynyl-2′-deoxyuridine ,Ub-AMC, ubiquitin-7-amido-4-methylcoumarin ,Cell cycle ,Tris, 2-amino-2-(hydroxymethyl)-1,3-propanediol ,Dissociation constant ,MG132, proteasome inhibitor ,lcsh:Therapeutics. Pharmacology ,USP28 inhibitors ,chemistry ,Biochemistry ,GAPDH, glyceraldehyde-3-phosphate dehydrogenase ,Docking (molecular) ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,USP28, ubiquitin specific peptidase 28 ,Original Article ,Deubiquitination ,Gastric cancer ,DUBs, deubiquitinating enzymes ,EMT, epithelial-mesenchymal transition ,[1,2,3]Triazolo[4,5-d]pyrimidine derivatives ,Kd, dissociation constant - Abstract
Ubiquitin specific peptidase 28 (USP28) is closely associated to the occurrence and development of various malignancies, and thus has been validated as a promising therapeutic target for cancer therapy. To date, only few USP28 inhibitors with moderate inhibitory activity have been reported, highly potent and selective USP28 inhibitors with new chemotypes remain to be discovered for pathologically investigating the roles of deubiquitinase. In this current study, we reported the synthesis and biological evaluation of new [1,2,3]triazolo[4,5-d]pyrimidine derivatives as potent USP28 inhibitors. Especially, compound 19 potently inhibited USP28 (IC50 = 1.10 ± 0.02 μmol/L, Kd = 40 nmol/L), showing selectivity over USP7 and LSD1 (IC50 > 100 μmol/L). Compound 19 was cellularly engaged to USP28 in gastric cancer cells. Compound 19 reversibly bound to USP28 and directly affected its protein levels, thus inhibiting the proliferation, cell cycle at S phase, and epithelial-mesenchymal transition (EMT) progression in gastric cancer cell lines. Docking studies were performed to rationalize the potency of compound 19. Collectively, compound 19 could serve as a new tool compound for the development of new USP28 inhibitors for exploring the roles of deubiquitinase in cancers., Graphical abstract A new series of [1,2,3]triazolo[4,5-d]pyrimidine derivatives were identified to inhibit USP28. Compound 19 potently inhibited USP28 with the IC50 and Kd values of 1.1 μmol/L and 40 nmol/L, respectively.Image 1
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- 2020
12. Skp2 in the ubiquitin‐proteasome system: A comprehensive review
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Ying Liu, Yi-Chao Zheng, Hong-Min Liu, Xiao-Jing Shi, and Moges Dessale Asmamaw
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Proteasome Endopeptidase Complex ,Ubiquitin-Protein Ligases ,Biology ,medicine.disease_cause ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Ubiquitin ,law ,Neoplasms ,Drug Discovery ,SKP2 ,medicine ,Humans ,S-Phase Kinase-Associated Proteins ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Oncogene ,Cell growth ,Ubiquitination ,Cell biology ,Proteasome ,030220 oncology & carcinogenesis ,biology.protein ,Molecular Medicine ,Suppressor ,Signal transduction ,Carcinogenesis - Abstract
The ubiquitin-proteasome system (UPS) is a complex process that regulates protein stability and activity by the sequential actions of E1, E2 and E3 enzymes to influence diverse aspects of eukaryotic cells. However, due to the diversity of proteins in cells, substrate selection is a highly critical part of the process. As a key player in UPS, E3 ubiquitin ligases recruit substrates for ubiquitination specifically. Among them, RING E3 ubiquitin ligases which are the most abundant E3 ubiquitin ligases contribute to diverse cellular processes. The multisubunit cullin-RING ligases (CRLs) are the largest family of RING E3 ubiquitin ligases with tremendous plasticity in substrate specificity and regulate a vast array of cellular functions. The F-box protein Skp2 is a component of CRL1 (the prototype of CRLs) which is expressed in many tissues and participates in multiple cellular functions such as cell proliferation, metabolism, and tumorigenesis by contributing to the ubiquitination and subsequent degradation of several specific tumor suppressors. Most importantly, Skp2 plays a pivotal role in a plethora of cancer-associated signaling pathways. It enhances cell growth, accelerates cell cycle progression, promotes migration and invasion, and inhibits cell apoptosis among others. Hence, targeting Skp2 may represent a novel and attractive strategy for the treatment of different human cancers overexpressing this oncogene. In this review article, we summarized the known roles of Skp2 both in health and disease states in relation to the UPS.
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- 2020
13. Preclinical studies of the triazolo[1,5
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Sai-Qi, Wang, Qiu-Xu, Teng, Shuai, Wang, Zi-Ning, Lei, Hui-Hui, Hu, Hui-Fang, Lv, Bei-Bei, Chen, Jian-Zheng, Wang, Xiao-Jing, Shi, Wei-Feng, Xu, Hong-Min, Liu, Xiao-Bing, Chen, Zhe-Sheng, Chen, and Bin, Yu
- Abstract
Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5
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- 2022
14. Long-Term Outcomes among Patients with Prolonged Disorders of Consciousness
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Yan Liu, Xiao-Gang Kang, Qiong Gao, Yu Liu, Chang-Geng Song, Xiao-Jing Shi, Jia-Ning Wu, and Wen Jiang
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unresponsive wakefulness syndrome ,General Neuroscience ,mortality ,prognostic ,disorders of consciousness ,minimal consciousness state - Abstract
Purpose: To evaluate the long-term survival and functional outcomes of patients with prolonged disorders of consciousness (pDoC) 1–8 years after brain injuries. Methods: Retrospective study to assess the long-term survival and functional outcomes of patients with pDoC was conducted. We performed Cox regression and multivariate logistic regression to calculate hazard ratios (HRs) for the outcome of survival and to identify risk factors of the functional outcome. Results: We recruited 154 patients with pDoC. The duration of follow-up from disease onset was 1–8 years. The median age was 46 years (IQR, 32–59), and 65.6% (n = 101) of them were men. During the follow-up period, one hundred and ten patients (71.4%) survived; among them, 52 patients had a good outcome. From the overall survival curve, the 1-, 3-, and 8-year survival rates of patients were about 80.5%, 72.0%, and 69.7%, respectively. Cox regression analysis revealed a significant association between the lower APACHE II score (p = 0.005) (cut-off score ≥ 18) and the presence of sleep spindles (p = 0.001) with survival. Logistic regression analysis demonstrated a higher CRS-R score (cut-off score ≥ 7), and presence of sleep spindles were related to a favorable outcome among patients with pDoC. Conclusions: Sleep spindles are correlated with both long-term survival and long-term functional outcome in pDoC patients.
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- 2023
15. Establishment of High-throughput Screening HTRF Assay for Identification Small Molecule Inhibitors of Skp2-Cks1
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Xiao-Jing Li, Moges Dessale Asmamaw, Hong-Min Liu, Kaizhao Hu, and Xiao-Jing Shi
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Multidisciplinary ,biology ,Kinase ,High-throughput screening ,Protein subunit ,Science ,Small molecule ,Article ,Ubiquitylated proteins ,Ubiquitin ,Drug screening ,RNA interference ,Target identification ,Cell-cycle proteins ,Cancer research ,SKP2 ,biology.protein ,Screening ,Medicine ,Function (biology) - Abstract
S-phase kinase associated protein 2 (Skp2), a member of the F-box family that constitute the largest known class of ubiquitin E3 specificity components, is responsible for recognizing and recruiting cyclin-dependent kinase inhibitor p27 for its ubiquitination in the presence of the small accessory protein cyclin-dependent kinase regulatory subunit 1(Cks1). Skp2 is overexpressed in esophageal carcinoma tissues and closely related with tumor poor prognosis, and perturbation of the Skp2-Cks1 interaction by inhibitors or RNAi could inhibit the proliferation and metastasis of tumor cells. Therefore, inhibition of Skp2 function by small-molecule compounds targeting Skp2-Cks1 interaction is emerging as a promising and novel anti-cancer strategy. In this study, we establish an improved high-throughput screening platform to screen Skp2 inhibitors targeting Skp2-Cks1interaction, which may provide a new therapeutic approach for the clinic.
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- 2021
16. Discovery of the antitumor activities of a potent DCN1 inhibitor compound 383 targeting LSD1 in gastric cancer
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Zan Song, Ke Gao, Moges Dessale Asmamaw, Yue-Jiao Liu, Yi-Chao Zheng, Xiao-Jing Shi, and Hong-Min Liu
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Pharmacology ,Histone Demethylases ,Structure-Activity Relationship ,Stomach Neoplasms ,Cell Line, Tumor ,Drug Discovery ,Intracellular Signaling Peptides and Proteins ,Humans ,Enzyme Inhibitors - Abstract
Dual target compounds have become a hot spot in the treatment of cancer in recent years. Histone lysine specific demethylase 1 (LSD1) is identified as histone demethylase and acts as a key regulator involved in many other cellular activities through its demethylation function. We have reported a triazolo [1,5-α] pyrimidine-based DCN1(defective in cullin neddylation protein 1) inhibitor compound 383 (IC
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- 2021
17. IL33 attenuates ventricular remodeling after myocardial infarction through inducing alternatively activated macrophages ethical standards statement
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Deliang Shen, Yue Xiao, Jing Li, Yunzhe Wang, Wen Zhao, Junnan Tang, Hong-Min Liu, Chang Cao, Bo Wang, Jin-Ying Zhang, and Xiao-Jing Shi
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Male ,0301 basic medicine ,medicine.medical_treatment ,Myocardial Infarction ,Macrophage polarization ,Apoptosis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,medicine ,Animals ,Macrophage ,Myocardial infarction ,Ventricular remodeling ,Janus Kinases ,Pharmacology ,Ventricular Remodeling ,business.industry ,Macrophages ,Myocardium ,JAK-STAT signaling pathway ,Macrophage Activation ,Interleukin-33 ,medicine.disease ,M2 Macrophage ,Mice, Inbred C57BL ,STAT Transcription Factors ,RAW 264.7 Cells ,030104 developmental biology ,Cytokine ,Cancer research ,business ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Interleukin 33 (IL33) has been found to be cardioprotective on various cardiovascular pathologies. However, it is not clear whether IL33 may inhibit myocardial infarction-related ventricular remodeling through inducing macrophage polarization. The objective of present study is to assess whether IL33 can improve ventricular remodeling after myocardial infarction by inducing macrophage polarization. In this study, the direct influence of IL33 on the polarization of macrophages and its mechanism in vitro were investigated. The potential protective effects of IL33 on acute and chronic myocardial infarction (MI) in vivo as well as its underlying mechanism through macrophage polarization were also determined. We found that IL33 significantly enhanced M2 macrophage and decreased the proportion of M1 macrophage. Importantly, IL33 induced M2 macrophage polarization by activating the JAK/STAT signaling pathway. In vivo, IL33 weaken the inflammatory level and myocardial apoptosis after MI and improved the systolic and diastolic function of the heart. Furthermore, IL33 significantly reduced infarct area and prevented the progression of fibrosis by inducing M2 macrophage polarization. The protective effects of IL33 were suppressed by JAK/STAT signaling pathway inhibitor. Our findings highlighted that IL33 not only reduced the early inflammatory response and inhibited myocardial apoptosis, but also increased the number of M2 macrophage in the infarcted area, significantly reduced infarct area and prevented the progression of fibrosis by activating JAK/STAT pathway. Therefore, IL33 may be a novel cardiac protective cytokine for myocardial infarction.
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- 2019
18. Research of detecting the laser’s secondary reflected echo from target by using Geiger-mode avalanche photodiode
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Xiao-Jing Shi, Peng Jiang, Jianfeng Sun, Qi Wang, Liu Di, and Xin Zhou
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Physics ,Pixel ,business.industry ,Echo (computing) ,Near and far field ,Ranging ,Field of view ,Laser ,Avalanche photodiode ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,law.invention ,Optics ,law ,Reflection (physics) ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,business - Abstract
When the Geiger-mode avalanche photodiode (Gm-APD) laser detection and ranging (LADAR) carries out the air-to-ground detection, it can detect the echo that is successively reflected by targets and the ground, which causes the false target in the image obtained by the LADAR. In this paper, the echo which is successively reflected by two surfaces is called the secondary reflected echo, and the echo which is just reflected once is called the single reflected echo. Considering the Gm-APD’s superior ability to detect photon, we investigate and analyze the triggering characteristics of the Gm-APD for detecting the secondary reflected laser echo from the targets, also, we carry out the experiments on detecting the secondary reflected echo in near field and far field by using array Gm-APD to verify that the array Gm-APD can effectively detect the secondary reflected echo, and this paper lays the foundation for the research of the secondary reflection’s influence on the images obtained by Gm-APD. In this paper, firstly, we use the echo triggering model, which contains LADAR ranging equation and Poisson probability model, and the Monte Carlo simulating method to completely verify the possibility of detecting the secondary reflected echo by using Gm-APD, in theory. The theoretical results show that Gm-APD can detect the secondary reflected echo, and the wider the field of view(FOV) is, the longer the detecting range is, besides, the higher the LADAR is located at, the lower the target’s secondary reflected echo’s intensity is and the higher the ground’s single reflected echo’s intensity is; then, using the Gm-APD with an array of 64 × 64 and 32 × 32 to detect the indoor scene and the moving van in far field, respectively, the results show that the indoor experiment obtains the complete first and second reflected image and the single pixel can detect the secondary reflected echo from multiple targets, also, for the far-field experiment, the single reflected echo and second reflected echo can be obtained in a single frame image, and under this experimental conditions, two pixels which are studied, realize the range extension of 25.6 m and 41.9 m respectively, which shows that the Gm-APD can likely detect the false target in the far field; finally, the methods that finding the secondary reflected surface by using the multiple-frame statistics for static targets and the image of triggering position in chronological order for moving targets, respectively, are proposed to eliminate the secondary reflected image. This article can provide some theoretical references for eliminating the secondary reflection before target recognition.
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- 2019
19. Constructing Carbon-Coated Fe3O4 Hierarchical Microstructures with a Porous Structure and their Excellent Cr(VI) Ion Removal Properties
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xiaoping wu, Lin Cheng, Chang-Sheng Song, Yi-Zhe Zhang, Xiao-Jing Shi, Xiao-Yun Li, Ping Lin, Shun-Li Wang, Peng Wang, Ling-Bo Xu, Li Jin, and Can Cui
- Abstract
Here, a facile solvothermal method coupled with an annealing strategy is developed to synthesize Fe3O4/carbon (Fe3O4@C) magnetic composite microstructures with different morphologies, including flower-like, hollow spheres and egg-like. Owing to the unique multi-porous and hollow structure, the as-prepared hierarchical Fe3O4@C hollow microspheres composite exhibit appealing performance as an absorbent of Cr(VI) ions in aqueous solution, delivering a high capacity of ca.197.2mg/g. Furthermore, the magnetic Fe3O4 ‘‘core’’ in composite hierarchical microstructures makes them easy to separate from aqueous systems by magnetic separation, the layer of carbon effectively prevents agglomerations of magnetic nanoparticles and expands their range of applications. The excellent Cr(VI) ions adsorbent activities of the Fe3O4@C magnetic composite microstructures would have a potential adsorbing material application in environmental purification.
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- 2021
20. Research progress of dual inhibitors targeting crosstalk between histone epigenetic modulators for cancer therapy
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Lin-Feng Jin, Tong Yu, Ying-Chao Duan, Xiao-Jing Shi, Yu Song, Yuan-Yuan Guan, and Shao-Jie Zhang
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Cancer therapy ,Antineoplastic Agents ,Safety margin ,Computational biology ,01 natural sciences ,Epigenesis, Genetic ,Histones ,03 medical and health sciences ,Neoplasms ,Drug Discovery ,Epigenetic Profile ,Humans ,Epigenetics ,Cell Proliferation ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Molecular Structure ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Dual inhibitor ,General Medicine ,Anticancer drug ,0104 chemical sciences ,Crosstalk (biology) ,Histone ,biology.protein ,Drug Screening Assays, Antitumor - Abstract
Abnormal epigenetics is a critical hallmark of human cancers. Anticancer drug discovery directed at histone epigenetic modulators has gained impressive advances with six drugs available for cancer therapy and numerous other candidates undergoing clinical trials. However, limited therapeutic profile, drug resistance, narrow safety margin, and dose-limiting toxicities pose intractable challenges for their clinical utility. Because histone epigenetic modulators undergo intricate crosstalk and act cooperatively to shape an aberrant epigenetic profile, co-targeting histone epigenetic modulators with a different mechanism of action has rapidly emerged as an attractive strategy to overcome the limitations faced by the single-target epigenetic inhibitors. In this review, we summarize in detail the crosstalk of histone epigenetic modulators in regulating gene transcription and the progress of dual epigenetic inhibitors targeting this crosstalk.
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- 2021
21. Pyrimethanil sensitivity and fitness in Botrytis cinerea populations from Shanxi Province, China
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Ping-yi Guo, Xiao-jing Shi, Xiao-jun Zhao, Lu Ren, and Ju-cai Han
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0106 biological sciences ,0301 basic medicine ,Population ,Plant Science ,Horticulture ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Botany ,Spore germination ,education ,Mycelium ,Botrytis cinerea ,education.field_of_study ,biology ,fungi ,biology.organism_classification ,Spore ,Fungicide ,030104 developmental biology ,chemistry ,Potato dextrose agar ,Pyrimethanil ,Agronomy and Crop Science ,010606 plant biology & botany - Abstract
Pyrimethanil is a fungicide that is highly active against the plant pathogen Botrytis cinerea. The sensitivity of B. cinerea to pyrimethanil and the risk of resistance were investigated in Shanxi, China. A total of 169 B. cinerea isolates from decayed cucumber leaves were collected and tested for their sensitivity to pyrimethanil based on mycelial growth inhibition. The EC50 values ranged from 0.09 to 12.26 μg/ml (average = 3.19 μg/ml, SD = 0.95) for pyrimethanil. Sensitive isolates (54.4%) had EC50 values of
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- 2017
22. RICTOR/mTORC2 affects tumorigenesis and therapeutic efficacy of mTOR inhibitors in esophageal squamous cell carcinoma
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Shenglei Li, Yandan Ren, Fanghua Gong, Mengyin Zhang, Wen Zhao, Xiao-Jing Shi, Guiqin Hou, Zhaoming Lu, Yang Wang, Bin Yu, Jianying Zhang, and Yan Li
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Original article ,Cell cycle checkpoint ,AKT, protein kinase B (PKB) ,IC50, half maximal inhibitory concentration ,mTORC1 ,mTOR, mammalian target of rapamycin ,pp242 ,medicine.disease_cause ,mTORC2 ,TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling ,4EBP-1, E binding protein-1 ,03 medical and health sciences ,0302 clinical medicine ,PI3K, phosphatidylinositol 3 kinase ,In vivo ,Esophageal squamous cell carcinoma ,Medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Protein kinase B ,RAD001 ,030304 developmental biology ,0303 health sciences ,business.industry ,H&E staining, hematoxylin and eosin staining ,AKT ,lcsh:RM1-950 ,mTORC2, mTOR complex 2 ,rapalogs, rapamycin and its analogs ,TNM, tumor-node-metastasis ,FDA, U.S. Food and Drug Administration ,lcsh:Therapeutics. Pharmacology ,RICTOR, rapamycin-insensitive companion of mTOR ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,Phosphorylation ,p70S6K, p70 ribosomal S6 kinase-1 ,ESCC, esophageal squamous cell carcinoma ,mTORC1, mTOR complex 1 ,business ,Carcinogenesis ,RICTOR - Abstract
Dysregulation of mTORC1/mTORC2 pathway is observed in many cancers and mTORC1 inhibitors have been used clinically in many tumor types; however, the mechanism of mTORC2 in tumorigenesis is still obscure. Here, we mainly explored the potential role of mTORC2 in esophageal squamous cell carcinoma (ESCC) and its effects on the sensitivity of cells to mTOR inhibitors. We demonstrated that RICTOR, the key factor of mTORC2, and p-AKT (Ser473) were excessively activated in ESCC and their overexpression is related to lymph node metastasis and the tumor-node-metastasis (TNM) phase of ESCC patients. Furthermore, we found that mTORC1/ mTORC2 inhibitor PP242 exhibited more efficacious anti-proliferative effect on ESCC cells than mTORC1 inhibitor RAD001 due to RAD001-triggered feedback activation of AKT signal. Another, we demonstrated that down-regulating expression of RICTOR in ECa109 and EC9706 cells inhibited proliferation and migration as well as induced cell cycle arrest and apoptosis. Noteworthy, knocking-down stably RICTOR significantly suppresses RAD001-induced feedback activation of AKT/PRAS40 signaling, and enhances inhibition efficacy of PP242 on the phosphorylation of AKT and PRAS40, thus potentiates the antitumor effect of RAD001 and PP242 both in vitro and in vivo. Our findings highlight that selective targeting mTORC2 could be a promising therapeutic strategy for future treatment of ESCC., Graphical abstract This study demonstrated that mTORC2 subunit, RICTOR, and p-AKT (Ser473) have hyperactivity in esophageal squamous cell carcinoma (ESCC) and promotes its development. Moreover, down-regulation of RICTOR can improve the sensitivity of ESCC cells to the pan-mTOR inhibitor PP242 as well as mTORC1 inhibitor RAD001.Image 1
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- 2019
23. Development of Highly Potent, Selective, and Cellular Active Triazolo[1,5- a]pyrimidine-Based Inhibitors Targeting the DCN1-UBC12 Protein-Protein Interaction
- Author
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Xiao-Jing Li, Shaomeng Wang, Linlin Yang, Huiju Li, Hong-Min Liu, Bin Yu, Shuai Wang, Xiao-Jing Shi, Kai Tang, Zhi-Zheng Wang, Maa Mamun, Yi-Chao Zheng, Li-Jie Zhao, Dan-Dan Shen, and Lina Ding
- Subjects
Pyrimidine ,Plasma protein binding ,01 natural sciences ,Protein–protein interaction ,03 medical and health sciences ,chemistry.chemical_compound ,Ubiquitin ,Drug Discovery ,Humans ,IC50 ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,biology ,Molecular Structure ,Kinase ,Target engagement ,Intracellular Signaling Peptides and Proteins ,Triazoles ,0104 chemical sciences ,Cell biology ,010404 medicinal & biomolecular chemistry ,Pyrimidines ,chemistry ,Ubiquitin-Conjugating Enzymes ,biology.protein ,Molecular Medicine ,Neddylation ,Protein Binding - Abstract
The cullin-RING ubiquitin ligases (CRLs) are responsible for about 20% of cellular protein degradation and regulate diverse cellular processes, and the dysfunction of CRLs is implicated in human diseases. Targeting the CRLs has become an emerging strategy for the treatment of human diseases. Herein, we describe the discovery of a hit compound from our in-house library and further structure-based optimizations, which have enabled the identification of new triazolo[1,5-a]pyrimidine-based inhibitors targeting the DCN1–UBC12 interaction. Compound WS-383 blocks the DCN1–UBC12 interaction (IC50 = 11 nM) reversibly and shows selectivity over selected kinases. WS-383 exhibits cellular target engagement to DCN1 in MGC-803 cells. WS-383 inhibits Cul3/1 neddylation selectively over other cullins and also induces accumulation of p21, p27, and NRF2. Collectively, targeting the DCN1–UBC12 interaction would be a viable strategy for selective neddylation inhibition of Cul3/1 and may be of therapeutic potential for diseas...
- Published
- 2019
24. A novel ent-kaurane diterpenoid analog, DN3, selectively kills human gastric cancer cells via acting directly on mitochondria
- Author
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Nan Su, Xiao-Jing Shi, Ai-Feng Wang, Yong-Cheng Ma, Hong-Min Liu, Xia-Xia Fan, Ying-Li Zhu, and Yu Ke
- Subjects
0301 basic medicine ,Male ,Voltage-dependent anion channel ,Cell Survival ,Mice, Nude ,Mitochondrion ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Stomach Neoplasms ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cell Line, Transformed ,Pharmacology ,Mice, Inbred BALB C ,biology ,Dose-Response Relationship, Drug ,Chemistry ,Cytochrome c ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,Cell biology ,Mitochondria ,Tumor Burden ,030104 developmental biology ,Mitochondrial permeability transition pore ,Apoptosis ,Cancer cell ,biology.protein ,Diterpenes ,Diterpenes, Kaurane ,VDAC1 ,030217 neurology & neurosurgery - Abstract
Targeting mitochondria using proper pharmacological agents is considered an attractive strategy for cancer control and management. Herein, we report a newly synthetic triazole analog of Jaridonin, DN3, which exhibits more potent antitumor activity via acting directly on mitochondria. DN3 potently reduced viabilities of gastric cancer cell lines HGC-27 and MGC-803 through inducing apoptosis and cell cycle arrest. But, normal human gastric epithelial cell line GES-1 is more resistant to the growth inhibition by DN3 compared with gastric cancer cells. DN3 induced mitochondrial membrane potential (MMP) decrease and cytochrome c release in intact gastric cancer cell lines. Meanwhile, the DN3 treatment also caused the release of cytochrome c from mitochondria isolated from cancer cell lines in a mitochondrial permeability transition pore complex (PTPC) mediated manner, but not from mitochondria isolated from normal gastric epithelial cell. The induction of mitochondrial PTPC proteins voltage-dependent anion channel (VDAC) and cyclophilin D (CypD) were also observed in DN3-treated cells. More interestingly, DN3 mediated MMP decrease, release of cytochrome c, the expression of VDAC and CypD and apoptosis were blocked by the pretreatment of VDAC1 inhibitor (4, 4′-diisothiocyanatostilbene-2,2′-disulfonic acid, DIDS) and CypD inhibitor (cyclosporine A, CsA). In a mouse xenograft model of human gastric cancer, the treatment of 5 mg/kg DN3 led to significant tumor regression without affecting body weight. In conclusion, our findings indicate that DN3 is a potential agent for the treatment of gastric cancer through acting directly on mitochondria, and would be useful for us to design more and better anti-cancer compounds.
- Published
- 2018
25. Design, synthesis, and preliminary evaluation of the biological activity of dithiocarbamate-3-epi-jaspine B hybrids
- Author
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Hong-Min Liu, Xiao-Jing Shi, Yan-Chao Wang, Jin-Mei Xu, Wang Yana, Wei-Wei Jiao, Wang Shang, and En Zhang
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Biological activity ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,In vitro ,0104 chemical sciences ,Design synthesis ,Ic50 values ,Cytotoxic T cell ,General Pharmacology, Toxicology and Pharmaceutics ,Dithiocarbamate ,Alkyl ,Hybrid - Abstract
A series of dithiocarbamate-3-epi-jaspine B hybrids have been designed and synthesized from D-xylose based on the introduction of long lipophilic alkyl dithiocarbamate moieties at the C4 position of 3-epi-jaspine B. The anticancer activities of these compounds have been evaluated against two selected tumor cell lines (MGC-803 and B16-F10 cells), with most of the synthesized compounds exhibiting moderate activity. Among them, compounds 20d and 20f showed the highest levels of inhibitory activity of all the compounds tested against MGC-803 and B16-F10 cells with IC50 values of 16.39 and 14.83 µM, respectively. This work therefore represents the first reported account of the synthesis and in vitro cytotoxic evaluation of dithiocarbamate-3-epi-jaspine B hybrids.
- Published
- 2016
26. Discovery of tofacitinib derivatives as orally active antitumor agents based on the scaffold hybridization strategy
- Author
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Xiao-Jing Li, Hong-Min Liu, Shuai Wang, Xiao-Han Yuan, Xiao-Jing Shi, Li-Juan Cao, and Bin Yu
- Subjects
p38 mitogen-activated protein kinases ,Administration, Oral ,Antineoplastic Agents ,Apoptosis ,01 natural sciences ,Mice ,03 medical and health sciences ,Piperidines ,Cell Movement ,Cell Line, Tumor ,Drug Discovery ,medicine ,Animals ,Humans ,IC50 ,Cell Proliferation ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Tofacitinib ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,food and beverages ,Cancer ,Cell migration ,General Medicine ,Cell cycle ,medicine.disease ,Xenograft Model Antitumor Assays ,Mitochondria ,0104 chemical sciences ,Pyrimidines ,Drug Design ,Cancer research ,lipids (amino acids, peptides, and proteins) ,Signal transduction - Abstract
In this work, a novel series of tofacitinib analogs were designed and synthesized based on the scaffold hybridization strategy and then evaluated for their antiproliferative activity toward three gastric cancer cell lines, leading to the identification of compound C18 which exhibited potent inhibitory activity against MGC-803 cell lines with an IC50 value of 2.68 μM. Compound C18 could effectively inhibit the colony formation, suppress the cell migration and induce apoptosis of MGC-803 cells through activating the p38 and JNK signaling pathways, while C18 showed no obvious effect on the cell cycle distribution in MGC-803 cells. In addition, C18 could initiate mitochondrial dysfunction of MGC-803 cells. Besides, in vivo antitumor studies indicated that C18 could inhibit gastric cancer tumor growth in vivo without obvious global toxicity.
- Published
- 2020
27. Down-regulation of Rictor enhances cell sensitivity to PI3K inhibitor LY294002 by blocking mTORC2-medicated phosphorylation of Akt/PRAS40 in esophageal squamous cell carcinoma
- Author
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Xiao-Jing Shi, Qi Zhao, Jiaxu Zhou, Yang Wang, Zhaoming Lu, Guiqin Hou, Yandan Ren, Tianli Fan, Mingyue Liu, and Mengying Zhang
- Subjects
0301 basic medicine ,Cell cycle checkpoint ,Time Factors ,Morpholines ,Cell ,Down-Regulation ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,Mechanistic Target of Rapamycin Complex 2 ,mTORC2 ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Phosphorylation ,Protein kinase B ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Phosphoinositide-3 Kinase Inhibitors ,Pharmacology ,Dose-Response Relationship, Drug ,Cell growth ,Chemistry ,digestive, oral, and skin physiology ,General Medicine ,Xenograft Model Antitumor Assays ,Tumor Burden ,G2 Phase Cell Cycle Checkpoints ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,Rapamycin-Insensitive Companion of mTOR Protein ,Chromones ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Esophageal Squamous Cell Carcinoma ,Signal transduction ,Phosphatidylinositol 3-Kinase ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
PI3K/Akt/mTOR signaling pathway plays a vital role in regulating cell survival, differentiation, metabolism and migration, which is frequently hyperactive in a number of cancers, including esophageal squamous cell carcinoma (ESCC). As the core subunit of mTORC2, Rictor is shown to be amplified in ESCC patients' tissues and plays an important role in regulation of Akt. The objective of this study is to evaluate the effects of Rictor knockdown on cell sensitivity to PI3K inhibitor LY294002 in ESCC cells and ESCC xenografts as well as its mechanisms. We found LY294002 obviously restrained cell proliferation in dose-dependent and time-dependent manners by inhibiting PI3K/Akt/mTOR/p70S6K signaling pathway, whereas triggered mTORC2-medicated phosphorylation of Akt (Ser473)/PRAS40 (Thr246) in ECa109 and EC9706 cells. Stable knockdown of Rictor by shRNA enhanced the inhibitory effects of LY294002 on cell proliferative, migration and colony formation, as well as promoted its effects on cell cycle arrest and cell apoptosis in vitro. Furthermore, stable knockdown of Rictor enhanced the antitumor effects of LY294002 by inhibiting tumor growth and promoting cell apoptosis in vivo. Mechanistic assay revealed that knockdown of Rictor could attenuate LY294002-induced phosphorylation of Akt (Ser473)/PRAS40 (Thr246). Our results provide rationale that combined inhibition of Rictor/mTORC2 and PI3K for the treatment of ESCC.
- Published
- 2018
28. A Systematic Review of Histone Lysine-Specific Demethylase 1 and Its Inhibitors
- Author
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Jinfeng Li, Wen Zhao, Wenjuan Zhou, Wang Xixin, Xiao-Jing Shi, Yi-Chao Zheng, Hong-Min Liu, Bai-Ling Jiang, Jin-Lian Ma, and Zhi-Ru Wang
- Subjects
Pharmacology ,Histone H3 Lysine 4 ,animal structures ,Histone deacetylase 2 ,EZH2 ,Biology ,Biochemistry ,Histone methyltransferase ,Drug Discovery ,Histone H2A ,Histone methylation ,biology.protein ,Molecular Medicine ,Demethylase ,JARID1B - Abstract
Histone lysine-specific demethylase 1 (LSD1) is the first discovered and reported histone demethylase by Dr. Shi Yang's group in 2004. It is classified as a member of amine oxidase superfamily, the common feature of which is using the flavin adenine dinucleotide (FAD) as its cofactor. Since it is located in cell nucleus and acts as a histone methylation eraser, LSD1 specifically removes mono- or dimethylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through formaldehyde-generating oxidation. It has been indicated that LSD1 and its downstream targets are involved in a wide range of biological courses, including embryonic development and tumor-cell growth and metastasis. LSD1 has been reported to be overexpressed in variety of tumors. Inactivating LSD1 or downregulating its expression inhibits cancer-cell development. LSD1 targeting inhibitors may represent a new insight in anticancer drug discovery. This review summarizes recent studies about LSD1 and mainly focuses on the basic physiological function of LSD1 and its involved mechanisms in pathophysiologic conditions, as well as the development of LSD1 inhibitors as potential anticancer therapeutic agents.
- Published
- 2015
29. Gene expression profiling and pathway network analysis of anti-tumor activity by Jaridon 6 in esophageal cancer
- Author
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Fen Yin, Jun-Wei Wang, Xiao-Jing Shi, Hong-Min Liu, Zhao Peirong, Yu Ke, Xiao-Rui Li, Ling Fu, Bing-Kai Han, and Yu-Qing Wang
- Subjects
0301 basic medicine ,Pharmacology ,Esophageal Neoplasms ,Microarray analysis techniques ,Wnt signaling pathway ,LRP5 ,Antineoplastic Agents ,Apoptosis ,Biology ,Molecular biology ,Gene expression profiling ,Reverse transcription polymerase chain reaction ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Cell Line, Tumor ,Survivin ,Gene chip analysis ,AXIN2 ,Humans ,Diterpenes, Kaurane ,Transcriptome ,Wnt Signaling Pathway - Abstract
Jaridon 6, a novel ent-kaurene diterpenoid derived from Rabdosia rubescens (Hemsl.) Hara, possesses strong anti-tumor activity in esophageal cancer cells. In this study, we explored the underlying molecular events of the anti-tumor activity of Jaridon 6. Cell viability and apoptosis results obtained by flow cytometry confirmed the tumor inhibitory effect of Jaridon 6 in esophageal cancer cells. A cDNA microarray was performed and the observations were validated using quantitative reverse transcription polymerase chain reaction. The microarray data showed that 151 genes were differentially expressed between the untreated group and the Jaridon 6-treated group, among these were 57 upregulated genes, and 94 downregulated genes (P < 0.01, fold change threshold: 2). These included genes such as Wnt, peroxisome, and genes involved in chemokine signaling pathways. In addition, Western blot analysis demonstrated that Jaridon 6 regulated the expression of Wnt pathway proteins, including reduced levels of Dvl 2, survivin and cyclin D1, and increased levels of p-β-catenin, and AXIN2 in EC109 and EC9706 esophageal cancer cells. In addition, recombinant murine Wnt3a could change the regulation of Jaridon 6 on Wnt pathway proteins. Immunohistochemical analysis indicated that the anti-tumor activity of Jaridon 6 was closely related to the Wnt signaling pathway in esophageal cancer cells.
- Published
- 2017
30. Pro-Apoptotic Effects of JDA-202, a Novel Natural Diterpenoid, on Esophageal Cancer Through Targeting Peroxiredoxin I
- Author
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Hong-Min Liu, Yu Ke, Guozhong Jiang, Wenjuan Zhou, Lina Ding, Wen Zhao, Kai Tang, Ya-Ge Ji, Yong-Cheng Ma, Huimin Wang, Xiao-Jing Shi, and Jun-Wei Wang
- Subjects
0301 basic medicine ,Programmed cell death ,Small interfering RNA ,Esophageal Neoplasms ,Physiology ,Cell Survival ,Clinical Biochemistry ,Cell ,Biology ,Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Phosphorylation ,Molecular Biology ,General Environmental Science ,Cell Proliferation ,Gene knockdown ,Cell Biology ,Hydrogen Peroxide ,Peroxiredoxins ,Xenograft Model Antitumor Assays ,In vitro ,Gene Expression Regulation, Neoplastic ,Original Research Communications ,030104 developmental biology ,medicine.anatomical_structure ,Cell culture ,Apoptosis ,030220 oncology & carcinogenesis ,Isodon ,Cancer research ,General Earth and Planetary Sciences ,Mitogen-Activated Protein Kinases ,Diterpenes, Kaurane ,Drugs, Chinese Herbal - Abstract
Aims: Esophageal cancer (EC) is an aggressive malignancy and the most common solid tumor of gastrointestinal tract all over the world, with high incidence in Asia. The current study was designed to investigate the anticancer efficacy and mechanism that is involved in the action of a natural ent-kaurene diterpenoid, JDA-202, targeting EC. Results: We found that an antioxidant protein peroxiredoxin I (Prx I) was upregulated in human EC tissues as well as in EC cell lines. JDA-202, a novel natural compound isolated from Isodon rubescens (Labiatae), was proved to possess strong anti-proliferative activities on those cell lines. Importantly, JDA-202 does not only bind to Prx I directly and markedly inhibit the activity of Prx I in vitro, but it also significantly induces hydrogen peroxide (H2O2)-related cell death. Furthermore, overexpression of Prx I significantly reversed EC109 cell apoptosis caused by JDA-202, whereas short interfering RNA (siRNA)-induced Prx I knockdown resulted in marked cell dea...
- Published
- 2016
31. All-fiber coherent laser image Lidar based on phase correction
- Author
-
Qi Wang, Wei Lu, Xiao-Jing Shi, Jianfeng Sun, Peng Jang, and Qiqi Wang
- Subjects
Physics ,Heterodyne ,business.industry ,Noise (signal processing) ,Local oscillator ,Physics::Optics ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Signal ,Atomic and Molecular Physics, and Optics ,010309 optics ,Speckle pattern ,Optics ,Lidar ,0103 physical sciences ,Heterodyne detection ,Time domain ,0210 nano-technology ,business - Abstract
Owing to the weak signals produced by all-fiber coherent lidar systems, when the instability of the local oscillator laser power is greater than the target echo signal, it is difficult to extract a target's intensity image. In this study, an intensity imaging method for weak signal all-fiber lidars is proposed. First, a phase compensation method is used to correct the position of the heterodyne signal in the time domain to reduce the impact of noise on the positioning heterodyne signal. In addition, an algorithm is proposed to extract the weak echo signal from the corrected heterodyne signal in the time domain to obtain the relative intensity of the echo signal of a single pixel point. Finally, we analyze and verify the proposed imaging method by using false alarm rates, range, intensity accuracy, and the speckle characteristics of the target. The method proposed in this study only requires that the phase of the heterodyne signal be corrected by the proposed numerical method without the need for other optical equipment, thus simplifying the entire system. It is very important to improve the detection sensitivity of coherent lidar remote imaging system.
- Published
- 2019
32. A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer: Synthesis and its cytotoxic activity
- Author
-
De Quan Yu, Yong-Fei Zheng, Hong-Min Liu, En Zhang, Bin Yu, Yuan Fang, and Xiao-Jing Shi
- Subjects
Pyrimidine ,Dimer ,medicine.medical_treatment ,Antineoplastic Agents ,Apoptosis ,Cell Line ,Steroid ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Humans ,Cytotoxic T cell ,Cytotoxicity ,Cell Proliferation ,Pharmacology ,Molecular Structure ,Chemistry ,Liver cell ,Cell Cycle ,Organic Chemistry ,General Medicine ,Triazoles ,Pyrimidines ,Biochemistry ,Cell culture ,MCF-7 Cells ,Steroids ,Drug Screening Assays, Antitumor ,Dimerization - Abstract
A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer was designed, synthesized and evaluated for its cytotoxic activity against five human cancer cell lines and the cytotoxicity against human normal liver cell L-02. Compound 3 showed excellent cytotoxic activity and good selectivity between cancer and normal cells. Further mechanistic studies revealed that treatment of EC109 cells with compound 3 caused an obvious G2/M arrest in a concentration- and time-dependent manner and induced apoptosis probably through the mitochondrial pathway accompanied with the decrease of mitochondrial membrane potential, activations of caspase-9/-3, cleavage of MDM2 as well as up-regulation of the expressions of p53 and Bax.
- Published
- 2013
33. Stereoselective synthesis of novel antiproliferative steroidal (E, E) dienamides through a cascade aldol/cyclization process
- Author
-
Ping-Ping Qi, Xiao-Nan Sun, Xiao-Jing Shi, En Zhang, Bin Yu, Yuan Fang, De-Quan Yu, and Hong-Min Liu
- Subjects
medicine.drug_class ,Stereochemistry ,Clinical Biochemistry ,Antineoplastic Agents ,Carboxamide ,Chemistry Techniques, Synthetic ,Biochemistry ,Substrate Specificity ,Endocrinology ,Aldol reaction ,Cell Line, Tumor ,medicine ,Humans ,Molecular Biology ,Inhibitory effect ,Cell Proliferation ,Biological evaluation ,Pharmacology ,Aldehydes ,Chemistry ,Organic Chemistry ,Stereoisomerism ,Amides ,Cyclization ,Steroids ,Stereoselectivity ,Cancer cell lines - Abstract
The stereoselective and metal-free protocol involving a cascade aldol/cyclization process for the synthesis of steroidal (E, E) dienamides from steroidal α, α-dicyanoalkene was reported. This protocol efficiently achieved the construction of C C bond and selective conversion of cyano group into carboxamide in one-pot procedure under mild condition. Further biological evaluation showed that some of these compounds had moderate to excellent cytotoxic activities against all the tested cancer cell lines and were more potent than well-known drug 5-fluorouracil. Particularly, compound 3c represented excellent inhibitory effect against MCF-7 (IC50 = 0.76 μM), which was about 10-fold more potent than 5-fluorouracil.
- Published
- 2013
34. Study on Construction of Long Span and Soft Rock Tunnel with Numerical Simulation
- Author
-
Xiao Jing Shi and Bin Zhu
- Subjects
Long span ,Heading (navigation) ,Engineering ,Computer simulation ,business.industry ,Excavation ,General Medicine ,Structural engineering ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,Stress field ,Condensed Matter::Superconductivity ,Displacement field ,Geotechnical engineering ,Rock tunnel ,Finite element program ,business - Abstract
With characteristics of the long span and soft rock tunnel, this paper analyzes the main factors affecting tunnel stable on the basis of the way of tunnel excavation method. The large finite element program is used in research of a tunnel, with a numerical simulation of two different way, top heading and bench method and double side drift method. From the result of stress field and displacement field of the tunnel , some useful conclusion are obtained, that double side drift method is appropriate for this kind of soft rock tunnel.
- Published
- 2013
35. A Digital Readout Approach for Differential Capacitive Pressure Sensor
- Author
-
Han Li, Chong Wei Zheng, Xiao Jing Shi, and Xiao Luo Jiang
- Subjects
Engineering ,business.industry ,Capacitive sensing ,Electrical engineering ,Electronic engineering ,General Medicine ,Differential (infinitesimal) ,Capacitive pressure sensor ,business ,Capacitance ,Realization (systems) - Abstract
An approach providing a digital output linearly proportional to capacitance difference for capacitive pressure sensor is presented. Based on sigma-delta (ΣΔ) technique, the structure is insensitive to circuit imperfections and component mismatch, permitting the realization of digitized capacitive sensor readout with good accuracy. Analysis shows that a resolution as high as 20 bits is achievable. Simulation results are given to confirm the effectiveness.
- Published
- 2013
36. Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents
- Author
-
Yong-Cheng Ma, Ying-Chao Duan, Hong-Min Liu, Xian-Wei Ye, Meng-Meng Wang, En Zhang, and Xiao-Jing Shi
- Subjects
Cell cycle checkpoint ,1,2,3-Triazole ,Stereochemistry ,Antineoplastic Agents ,Apoptosis ,Flow cytometry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Thiocarbamates ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Structure–activity relationship ,Dithiocarbamate ,Cell Proliferation ,Pharmacology ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,medicine.diagnostic_test ,Cell Cycle ,Organic Chemistry ,General Medicine ,Triazoles ,Dose–response relationship ,chemistry ,Biochemistry ,Cell culture ,Drug Design ,MCF-7 Cells ,Drug Screening Assays, Antitumor - Abstract
A series of novel 1,2,3-triazole-dithiocarbamate hybrids were designed, synthesized and evaluated for anticancer activity against four selected human tumor cell lines (MGC-803, MCF-7, PC-3, EC-109). Majority of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 3a and 3c showed excellent broad spectrum anticancer activity with IC50 values ranging from 0.73 to 11.61 μM and 0.49-12.45 μM, respectively. Particularly, compound 3a was more potent than 5-fluorouracil against all tested human cancer cell lines. Flow cytometry analysis demonstrated that treatment of MGC-803 with 3c led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death after 12 h.
- Published
- 2013
37. Structurally novel steroidal spirooxindole by241 potently inhibits tumor growth mainly through ROS-mediated mechanisms
- Author
-
Bin Yu, Kai Tang, Xin Huang, Jun-Wei Wang, Xiao-Jing Shi, Ping-Ping Qi, and Hong-Min Liu
- Subjects
0301 basic medicine ,Indoles ,Administration, Oral ,Antineoplastic Agents ,Apoptosis ,Article ,03 medical and health sciences ,Mice ,Cell Line, Tumor ,Animals ,Humans ,Spiro Compounds ,Viability assay ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Multidisciplinary ,Molecular Structure ,Cell growth ,Chemistry ,Cell biology ,030104 developmental biology ,Biochemistry ,Cell culture ,Cancer cell ,Signal transduction ,Reactive Oxygen Species - Abstract
Cancer cells always have increased ROS levels, thus making them more vulnerable to persistent endogenous oxidative stress. The biochemical difference between cancer and normal cells could be exploited to achieve selective cancer cell killing by exogenous ROS-producing agents. Herein we described a structurally novel steroidal spirooxindole by241 and its anticancer efficacy. By241 exhibited potent inhibition against human cancer cells and less toxic to normal cells. By241 concentration-dependently induced apoptosis of MGC-803 and EC9706 cells, accompanied with the mitochondrial dysfunction and increased ROS levels. NAC can completely restore the decreased cell viability of MGC-803 cells caused by by241, suggesting ROS-mediated mechanisms. The expression levels of proteins involved in the mitochondrion-related pathways were detected, showing increased expression of proapoptotic proteins and decreased expression of anti-apoptotic proteins and activation of caspases-9/-3, but without activating caspase-8 expression. Pretreatment with Z-VAD-FMK partially rescued by241-induced apoptosis of MGC-803 cells. Additionally, by241 inhibited mTOR, activated p53 and its downstream proteins, cleaved MDM2 and PI3K/AKT as well as NF-κB signaling pathway. In vivo experiments showed that by241 did not have significant acute oral toxicity and exerted good anticancer efficacy against MGC-803 bearing mice models. Therefore, by241 may serve as a lead for further development for cancer therapy.
- Published
- 2016
38. A New Coumarin and Carbazole Alkaloid from Clausena vestita D. D. Tao
- Author
-
Guan Ye, Wei-Min Zhao, Xiao-Jing Shi, and Wen-Jie Tang
- Subjects
Stereochemistry ,Carbazole ,Alkaloid ,Chemical structure ,Plant composition ,Organic Chemistry ,Clausena vestita ,Coumarin ,Biochemistry ,Catalysis ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Phytochemical ,Drug Discovery ,Organic chemistry ,Physical and Theoretical Chemistry ,Chemical composition - Abstract
Phytochemical investigation of the EtOH extract of Clausena vestita D. D. Tao led to the isolation of one new coumarin, clauslactone U (1), and one new carbazole alkaloid, clauszoline N (2), together with 28 known compounds. The structures of these compounds were established by using MS and 1D- and 2D-NMR techniques, and by comparison with known analogues.
- Published
- 2010
39. Natural Product-Derived Spirooxindole Fragments Serve as Privileged Substructures for Discovery of New Anticancer Agents
- Author
-
Bin Yu, Xiao-Jing Shi, Ping-Ping Qi, Hong-Min Liu, and Yi-Chao Zheng
- Subjects
Drug ,Cancer Research ,Indazoles ,Indoles ,media_common.quotation_subject ,Cancer therapy ,Antineoplastic Agents ,Computational biology ,010402 general chemistry ,01 natural sciences ,chemistry.chemical_compound ,Drug Discovery ,Humans ,Spiro Compounds ,media_common ,Pharmacology ,Biological Products ,Clinical Trials as Topic ,Natural product ,010405 organic chemistry ,Chemistry ,Drug discovery ,Anticancer drug ,Preclinical data ,Combinatorial chemistry ,Chemical space ,0104 chemical sciences ,Molecular Medicine ,Identification (biology) - Abstract
The utility of natural products for identifying anticancer agents has been highly pursued in the last decades and over 100 drug molecules in clinic are natural products or natural product-derived compounds. Natural products are believed to be able to cover unexplored chemical space that is normally not occupied by commercially available molecule libraries. However, the low abundance and synthetic intractability of natural products have limited their applications in drug discovery. Recently, the identification of biologically relevant fragments derived from biologically validated natural products has been recognized as a powerful strategy in searching new biological probes and drugs. The spirocyclic oxindoles, as privileged structural scaffolds, have shown their potential in designing new drugs. Several anticancer drug candidates such as SAR405838, RO8994, CFI-400945 and their bioisosteres are undergoing clinical trials or preclinical studies. To highlight the significant progress, we focus on illustrating the discovery of SAR405838, RO8994, CFI-400945 and their bioisosteres for cancer therapy using substructure-based strategies and discussing modes of action, binding models and preclinical data.
- Published
- 2015
40. Efficient synthesis of novel antiproliferative steroidal spirooxindoles via the [3+2] cycloaddition reactions of azomethine ylides
- Author
-
Xiao-Nan Sun, Yi-Chao Zheng, Xiao-Jing Shi, Bin Yu, Hong-Min Liu, De-Quan Yu, and Ping-Ping Qi
- Subjects
G2 Phase ,Thiosemicarbazones ,Cell cycle checkpoint ,Stereochemistry ,Clinical Biochemistry ,Antineoplastic Agents ,Biochemistry ,Pyrrolidine ,Stereocenter ,chemistry.chemical_compound ,Endocrinology ,Catalytic Domain ,medicine ,Humans ,Molecular Biology ,Pharmacology ,biology ,Dose-Response Relationship, Drug ,Organic Chemistry ,Regioselectivity ,Active site ,Proto-Oncogene Proteins c-mdm2 ,Cycloaddition ,Molecular Docking Simulation ,chemistry ,Docking (molecular) ,Pregnenolone ,biology.protein ,MCF-7 Cells ,Female ,Azo Compounds ,Cell Division ,medicine.drug - Abstract
A series of novel steroidal spirooxindoles 3a-h were synthesized from pregnenolone in a high regioselective manner using the 1,3-dipolar cycloaddition as the key step. This protocol resulted in the formation of two C-C bonds, one C-N bond and the creation of one pyrrolidine ring and three contiguous stereocenters in a single operation. Biological evaluation showed that these synthesized steroidal spirooxindoles exhibited moderate to good antiproliferative activity against the tested cell lines and some of them were more potent than 5-FU. Among them, compounds 3e and 3f displayed the best antiproliferative activity against MCF-7 cells with the IC50 values of 4.0 and 3.9μM, respectively. Flow cytometry analysis demonstrated that compound 3d caused the cellular apoptosis and cell cycle arrest at G2/M phase in a concentration-dependent manner. Docking results indicated that compound 3d fitted well into the MDM2 active site 1RV1 by interacting with Lys94 and Thr101 residues.
- Published
- 2015
41. GW27-e0404 The protective effects of Peroxiredoxin II on cardiac ischemia-reperfusion injury in prxII transgenic mice
- Author
-
Wenjuan Zhou, Ke Yang, Xiao-Jing Shi, Yue Xiao, Wen Zhao, Kai Tang, Xue-Peng Geng, Hong-Min Liu, and Huimin Wang
- Subjects
Genetically modified mouse ,business.industry ,Cardiac ischemia ,Peroxiredoxin II ,Medicine ,Pharmacology ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Reperfusion injury - Published
- 2016
42. Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM-Chk1/2-Cdc25C pathway
- Author
-
Yong-Cheng Ma, Yu-Hua Qin, Xiaolin Zi, Wen Zhao, Ning-Min Zhao, Hong-Min Liu, Hong-Wei Zhao, Nan Su, Yu Ke, and Xiao-Jing Shi
- Subjects
G2 Phase ,Cell cycle checkpoint ,Cell division ,Esophageal Neoplasms ,DNA damage ,Antineoplastic Agents ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,Biology ,Toxicology ,Article ,Cell Line, Tumor ,CDC2 Protein Kinase ,Humans ,Phosphorylation ,Checkpoint Kinase 2 ,Pharmacology ,Cyclin-dependent kinase 1 ,Kinase ,Cell Cycle ,Cell cycle ,Glutathione ,enzymes and coenzymes (carbohydrates) ,Biochemistry ,Checkpoint Kinase 1 ,Cancer research ,Diterpenes, Kaurane ,Reactive Oxygen Species ,Protein Kinases ,Cell Division - Abstract
Jaridonin, a novel diterpenoid from Isodon rubescens, has been shown previously to inhibit proliferation of esophageal squamous cancer cells (ESCC) through G2/M phase cell cycle arrest. However, the involved mechanism is not fully understood. In this study, we found that the cell cycle arrest by Jaridonin was associated with the increased expression of phosphorylation of ATM at Ser1981 and Cdc2 at Tyr15. Jaridonin also resulted in enhanced phosphorylation of Cdc25C via the activation of checkpoint kinases Chk1 and Chk2, as well as in increased phospho-H2A.X (Ser139), which is known to be phosphorylated by ATM in response to DNA damage. Furthermore, Jaridonin-mediated alterations in cell cycle arrest were significantly attenuated in the presence of NAC, implicating the involvement of ROS in Jaridonin's effects. On the other hand, addition of ATM inhibitors reversed Jaridonin-related activation of ATM and Chk1/2 as well as phosphorylation of Cdc25C, Cdc2 and H2A.X and G2/M phase arrest. In conclusion, these findings identified that Jaridonin-induced cell cycle arrest in human esophageal cancer cells is associated with ROS-mediated activation of ATM–Chk1/2–Cdc25C pathway.
- Published
- 2014
43. ChemInform Abstract: A Novel [1,2,4]Triazolo[1,5-a]pyrimidine-Based Phenyl-Linked Steroid Dimer: Synthesis and Its Cytotoxic Activity
- Author
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Yong-Fei Zheng, En Zhang, De Quan Yu, Bin Yu, Hong-Min Liu, Yuan Fang, and Xiao-Jing Shi
- Subjects
Pyrimidine ,Stereochemistry ,Dimer ,medicine.medical_treatment ,education ,Cancer ,General Medicine ,medicine.disease ,humanities ,Steroid ,chemistry.chemical_compound ,chemistry ,medicine ,Cytotoxic T cell ,Selectivity - Abstract
Title compound (I) shows excellent cytotoxic activity and good selectivity between cancer and normal cells.
- Published
- 2014
44. Discovery of novel steroidal pyran-oxindole hybrids as cytotoxic agents
- Author
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Bin Yu, Hong-Min Liu, De-Quan Yu, Xiao-Jing Shi, Ping-Ping Qi, and Lihong Shan
- Subjects
Indoles ,Time Factors ,Stereochemistry ,Clinical Biochemistry ,Antineoplastic Agents ,Apoptosis ,Biochemistry ,chemistry.chemical_compound ,Endocrinology ,Aldol reaction ,Cell Line, Tumor ,Ic50 values ,Humans ,Oxindole ,Cytotoxicity ,Molecular Biology ,Malononitrile ,Pyrans ,Pharmacology ,Dose-Response Relationship, Drug ,Organic Chemistry ,Cell Cycle ,Oxindoles ,chemistry ,Pyran ,Drug Design ,Steroids - Abstract
A series of novel steroidal pyran–oxindole hybrids were efficiently synthesized in a single operation through the vinylogous aldol reaction of vinyl malononitrile 3 with substituted isatins involving the construction of C–C and C–O bonds. Some compounds displayed moderate to good cytotoxicity against T24, SMMC-7721, MCF-7 and MGC-803 cells. Compounds 4f and 4i were more potent than 5-Fu against T24 and MGC-803 cells with the IC50 values of 4.43 and 8.45 μM, respectively. Further mechanism studies indicated that compound 4i induced G2/M arrest and early apoptosis in a concentration- and time-dependent manner.
- Published
- 2014
45. Design, synthesis and biological evaluation of novel steroidal spiro-oxindoles as potent antiproliferative agents
- Author
-
Hong-Min Liu, De-Quan Yu, Ping-Ping Qi, Xiao-Jing Shi, and Bin Yu
- Subjects
Cell cycle checkpoint ,Indoles ,Pyrrolidines ,Stereochemistry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Dimer ,Clinical Biochemistry ,Antineoplastic Agents ,Apoptosis ,Biochemistry ,Pyrrolidine ,Steroid ,chemistry.chemical_compound ,Endocrinology ,Cell Line, Tumor ,medicine ,Humans ,Spiro Compounds ,Molecular Biology ,IC50 ,Cell Proliferation ,Cycloaddition Reaction ,Cell growth ,Cell Biology ,Cell Cycle Checkpoints ,Ketosteroids ,Cycloaddition ,chemistry ,Drug Design ,1,3-Dipolar cycloaddition ,Molecular Medicine ,Drug Screening Assays, Antitumor - Abstract
Two series of novel steroidal spiro-pyrrolidinyl oxindoles 3a-t and 6a-c were designed and synthesized from dehydroepiandrosterone using the 1,3-dipolar cycloaddition as the key step and further evaluated for their antiproliferative activities for four human cancer cell lines (MGC-803, EC109, SMMC-7721 and MCF-7). This protocol achieved the formation of two CC bonds, one CN bond and the creation of one new five-membered pyrrolidine ring and three contiguous stereocenters in a single operation. Biological evaluation showed that these synthesized steroidal spiro-pyrrolidinyl oxindoles possessed moderate to good antiproliferative activities against the tested cell lines and some of them were more potent than 5-Fu. Particularly, compound 3g showed good antiproliferative activity against SMMC-7721 (IC50=0.71μM). Steroid dimer 6b showed improved antiproliferative activities against SMMC-7721 and MCF-7 with the IC50 values of 4.30 and 2.06μM, respectively. Flow cytometry analysis demonstrated that compound 3n caused the cellular early apoptosis and cell cycle arrest at G2/M phase in a concentration- and time-dependent manner. [Corrected]
- Published
- 2013
46. Synthesis and preliminary biological evaluation of 1,2,3-triazole-Jaspine B hybrids as potential cytotoxic agents
- Author
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Bin Yu, Ya-Zhuo Guo, Xiao-Jing Shi, Jin-Mei Xu, En Zhang, Yan-Chao Wang, Wei-Wei Jiao, and Hong-Min Liu
- Subjects
Cell cycle checkpoint ,1,2,3-Triazole ,Stereochemistry ,Antineoplastic Agents ,Apoptosis ,Chemistry Techniques, Synthetic ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Sphingosine ,Cell Line, Tumor ,Drug Discovery ,Cytotoxic T cell ,Humans ,Cytotoxicity ,Cell Proliferation ,Pharmacology ,Chemistry ,Organic Chemistry ,Cell Cycle ,General Medicine ,Cell cycle ,Triazoles ,Biochemistry ,Cell culture ,Click chemistry ,Hydrophobic and Hydrophilic Interactions - Abstract
Two series of more available novel 1,2,3-triazole-Jaspine B hybrids were efficiently synthesized employing click chemistry approach and evaluated for their cytotoxic activities against three human cancer cell lines (EC-9706, MGC-803 and MCF-7). Among them, compound 14h showed excellent inhibition against MCF-7 (IC 50 = 1.93 μM) and was more potent than 5-Fu and Jaspine B against all three cancer cell lines. Further investigation of apoptosis assay and cell cycle analysis demonstrated that compound 14h caused cellular early and late apoptosis and arrested the cell cycle at G2/M phase in a concentration- and time-independent manner. This was the first report about the synthesis and in vitro cytotoxic evaluation of 1,2,3-triazole-Jaspine B hybrids.
- Published
- 2013
47. Efficient construction of novel D-ring modified steroidal dienamides and their cytotoxic activities
- Author
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Yuan Fang, Xiao Jing Shi, Jing-Li Ren, De Quan Yu, Xiao Nan Sun, Jun-Wei Wang, Bin Yu, Hong-Min Liu, Xian Wei Ye, Meng Meng Wang, Ping Ping Qi, and En Zhang
- Subjects
Cell cycle checkpoint ,Nitrile ,Double bond ,medicine.drug_class ,Stereochemistry ,Carboxamide ,Antineoplastic Agents ,Flow cytometry ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Cell Line, Tumor ,Drug Discovery ,medicine ,Cytotoxic T cell ,Humans ,Cytotoxicity ,Pharmacology ,chemistry.chemical_classification ,medicine.diagnostic_test ,Organic Chemistry ,Cell Cycle ,General Medicine ,chemistry ,Drug Design ,Steroids ,Selectivity - Abstract
Two series of steroidal dienamides 4aeq and 5aef were designed, synthesized and evaluated for cytotoxic activities against five human cancer cell lines (MGC-803, EC109, PC-3, SMMC-7721 and MCF-7). The protocol developed efficiently achieved the construction of carbonecarbon double bond and selective conversion of nitrile group into carboxamide in one-pot procedure. Besides, compounds 4aeq and 5aef showed moderate to excellent cytotoxic activities with the IC50 values ranging from 0.1 to 40 mM and most of them were more potent than 5-fluorouracil. Particularly, four compounds 4d, 4e, 4q and 5a showed excellent selectivity against MGC-803 with the IC50 values less than 1 mM. Flow cytometry analysis demonstrated that compound 4c caused the cellular early apoptosis and cell cycle arrest in G2/M phase in a concentration-independent manner.
- Published
- 2013
48. GW27-e0400 Cardioprotection of Peroxiredoxin II on doxorubicin-induced cardiotoxicity
- Author
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Renfeng Zhang, Wen Zhao, Huimin Wang, Xiao-Jing Shi, Xin Huang, Yue Xiao, and Kai Tang
- Subjects
Cardioprotection ,Drug ,Cardiotoxicity ,Side effect ,business.industry ,media_common.quotation_subject ,Peroxiredoxin II ,Oxidative phosphorylation ,Pharmacology ,polycyclic compounds ,Medicine ,Doxorubicin ,Cardiology and Cardiovascular Medicine ,business ,media_common ,medicine.drug - Abstract
The application of doxorubicin (DOX), a well-known antitumor drug, is limited due to its cumulative cardiotoxicity. Up to now, no effective prevention is available for its side effect. It has been shown that peroxiredoxin II (Prx II) protects cardiomyocytes from oxidative stress-induced injury and
- Published
- 2016
49. [Clinical significance of absolute lymphocyte count in de novo patients with multiple myeloma]
- Author
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Xiao-Cheng, Cheng, Xiao-Li, Zhang, Xian, Ye, and Xiao-Jing, Shi
- Subjects
Adult ,Aged, 80 and over ,Male ,T-Lymphocyte Subsets ,Humans ,Female ,Lymphocyte Count ,Middle Aged ,Multiple Myeloma ,Prognosis ,Aged ,Retrospective Studies - Abstract
This study was purposed to investigate the correlation of absolute lymphocyte count (ALC) in peripheral blood of de novo multiple myeloma (MM) patients with clinical characteristics, therapeutic efficacy and prognosis. The clinical data of 34 de novo patients with MM in our hospital from January 2002 to August 2011 were analysed retrospectively. According to ALC, patients were divided into ALC1.3×10(9)/L (n = 15) group and ALC ≥ 1.3×10(9)/L (n = 19) group. The correlation of incipient ALC levels of de novo MM patients with clinical data such as sex, age, type of MM, bone destruction, clinical staging and grouping, levels of LDH, β(2)-MG, creatinine and albumin, as well as therapeutic efficacy was analysed. The results showed that ALC was (0.4 - 2.9)×10(9)/L (median ALC was 1.3×10(9)/L) in untreated patients. The effective rate of therapy was 20% in ALC1.3×10(9)/L group while it was 57.9% in ALC ≥ 1.3×10(9)/L group. There was statistical difference in effective rate between two groups (χ(2) = 4.9696, P0.05). Compared with the ALC ≥ 1.3×10(9)/L group, the percentage of the CD4 and CD4/CD8 ratio were reduced and the percentage of the CD8 increased (P0.05). But no significant differences were found in sex, age, type of MM, bone destruction, clinical staging and grouping, levels of LDH, β(2)-MG, creatinine and albumin in those patients (P0.05). It is concluded that ALC in de novo patients with MM may be used as the important indication for analysing therapy effect and prognosis.
- Published
- 2012
50. Jaridonin, a novel ent-kaurene diterpenoid from Isodon rubescens, inducing apoptosis via production of reactive oxygen species in esophageal cancer cells
- Author
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Yong-Cheng Ma, Wen Zhao, Hong-Min Liu, Xiao-Jing Shi, Xiaolin Zi, and Yu Ke
- Subjects
G2 Phase ,Cancer Research ,China ,Esophageal Neoplasms ,DNA damage ,Cell Survival ,Cell ,Apoptosis ,Biology ,Article ,Inhibitory Concentration 50 ,Annexin ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Cells, Cultured ,Cell Proliferation ,Pharmacology ,chemistry.chemical_classification ,Membrane Potential, Mitochondrial ,Reactive oxygen species ,Cytochrome c ,Molecular biology ,Antineoplastic Agents, Phytogenic ,Plant Leaves ,Cytosol ,medicine.anatomical_structure ,Oncology ,Biochemistry ,chemistry ,Cell culture ,Ethnopharmacology ,Isodon ,biology.protein ,Hepatocytes ,Diterpenes, Kaurane ,Reactive Oxygen Species ,DNA Damage ,Drugs, Chinese Herbal - Abstract
Isodon rubescens, a Chinese herb, has been used as a folk, botanical medicine in China for inflammatory diseases and cancer treatment for many years. Recently, we isolated a new ent-kaurene diterpenoid, named Jaridonin, from Isodon rubescens. The chemical structure of Jaridonin was verified by infrared (IR), nuclear magnetic resonance (NMR), and mass spectrum (MS) data as well as X-ray spectra. Jaridonin potently reduced viabilities of several esophageal cancer cell lines, including EC109, EC9706 and EC1. Jaridonin treatment resulted in typical apoptotic morphological characteristics, increased the number of annexin V-positive staining cells, as well as caused a G2/M arrest in cell cycle progression. Furthermore, Jaridonin resulted in a significant loss of mitochondrial membrane potential, release of cytochrome c into the cytosol, and then activation of Caspase-9 and -3, leading to activation of the mitochondria mediated apoptosis. Furthermore, these effects of Jaridonin were accompanied by marked reactive oxygen species (ROS) production and increased expression of p53, p21(waf1/Cip1) and Bax, whereas two ROS scavengers, N-acetyl-L-cysteine (LNAC) and Vitamin C, significantly attenuated the effects of Jaridonin on the mitochondrial membrane potential, DNA damage, expression of p53 and p21(waf1/Cip1) and reduction of cell viabilities. Taken together, our results suggest that a natural ent-kaurenoid diterpenoid, Jaridonin, is a novel apoptosis inducer and deserves further investigation as a new chemotherapeutic strategy for patients with esophageal cancer.
- Published
- 2012
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