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Xin Xie,Wanzhi Tu,Chenwen Huang,Ziyang Chen,Xinyue Ren,Bingqing He,Xiaoyan Ding,Yuelei Chen,Xin Xie 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.12
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have great potential in applications such as regenerative medicine, cardiac disease modeling, and in vitro drug evaluation. However, hPSC-CMs are immature, which limits their applications. During development, the maturation of CMs is accompanied by a decline in their proliferative capacity. This phenomenon suggests that regulating the cell cycle may facilitate the maturation of hPSC-CMs. Aurora kinases are essential kinases that regulate the cell cycle, the role of which is not well studied in hPSC-CM maturation. Here, we demonstrate that CYC116, an inhibitor of Aurora kinases, significantly promotes the maturation of CMs derived from both human embryonic stem cells (H1 and H9) and iPSCs (induced PSCs) (UC013), resulting in increased expression of genes related to cardiomyocyte function, better organization of the sarcomere, increased sarcomere length, increased number of mitochondria, and enhanced physiological function of the cells. In addition, a number of other Aurora kinase inhibitors have also been found to promote the maturation of hPSC-CMs. Our data suggest that blocking aurora kinase activity and regulating cell cycle progression may promote the maturation of hPSC-CMs.
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Xin Xie,Wanzhi Tu,Chenwen Huang,Ziyang Chen,Xinyue Ren,Bingqing He,Xiaoyan Ding,Yuelei Chen,Xin Xie 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.12
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have great potential in applications such as regenerative medicine, cardiac disease modeling, and in vitro drug evaluation. However, hPSC-CMs are immature, which limits their applications. During development, the maturation of CMs is accompanied by a decline in their proliferative capacity. This phenomenon suggests that regulating the cell cycle may facilitate the maturation of hPSC-CMs. Aurora kinases are essential kinases that regulate the cell cycle, the role of which is not well studied in hPSC-CM maturation. Here, we demonstrate that CYC116, an inhibitor of Aurora kinases, significantly promotes the maturation of CMs derived from both human embryonic stem cells (H1 and H9) and iPSCs (induced PSCs) (UC013), resulting in increased expression of genes related to cardiomyocyte function, better organization of the sarcomere, increased sarcomere length, increased number of mitochondria, and enhanced physiological function of the cells. In addition, a number of other Aurora kinase inhibitors have also been found to promote the maturation of hPSC-CMs. Our data suggest that blocking aurora kinase activity and regulating cell cycle progression may promote the maturation of hPSC-CMs.
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Podophyllotoxin Induces CREB Phosphorylation and CRE-Driven Gene Expression via PKA but Not MAPKs
Xin Xie,Ya Qiong Chen 한국분자세포생물학회 2010 Molecules and cells Vol.29 No.1
CRE-driven luciferase reporter is commonly used in drug screening systems involving G protein-coupled receptors (GPCRs). In a screen campaign designed to search for melanocortin-4 receptor (MC4R) agonists, podophyllotoxin, a microtubules disruptor, was found to induce cAMP-responsive element (CRE)-driven reporter expression. MC4R was not involved because podophyllotoxin induced CREB activation and CRE-driven transcription in cells not express-ing MC4R. Previous studies indicated that intracellular cal-cium, PKA, and MAPKs are involved in CREB phosphoryla-tion and activation. Our studies revealed that podophyl-lotoxin did not affect intracellular calcium level and the phosphorylation state of p38. Podophyllotoxin induced JNK and ERK activation, but blockade of JNK and ERK activation with specific inhibitors had no effect on podophyllotoxin-induced CREB activation and CRE-regulated gene expression. Further experiments revealed that H89, a specific inhibitor of PKA, significantly inhibited podophyllotoxin-induced CREB activation. Podophyllotoxin itself did not alter intracellular cAMP level. Taken together, podophyllotoxin induces CREB activation and CRE-driven gene expression via PKA activa-tion by a cAMP-independent mechanism.
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Guo Xin,Xie Yong-Xin,Guo Chen,Wei Jing-Lin,Yang Hui-Fang 대한독성 유전단백체 학회 2021 Molecular & cellular toxicology Vol.17 No.2
Background In recent years, studies have shown that cyfluthrin is harmful to the reproductive system. Lycium barbarum polysaccharide may be a protective agent. Objective To investigate the effect of cyfluthrin (Cy) on testosterone B (inhibin B, INHB) in male rats and the intervention of Lycium barbarum polysaccharide (LBP). Results Compared with the control group, the mRNA and protein expression levels of INH α and INH βB in the testis tissue decreased, and the difference was statistically significant (P < 0.05). The LBP intervention group can significantly increase the expression level, and the difference is statistically significant (P < 0.05). Conclusion The decrease of INHα and INHβB expression caused by Cy exposure indicates that Cy has a toxic effect on the testis of rats, and the addition of LBP has a certain protective effect on the testis of rats. Background In recent years, studies have shown that cyfluthrin is harmful to the reproductive system. Lycium barbarum polysaccharide may be a protective agent. Objective To investigate the effect of cyfluthrin (Cy) on testosterone B (inhibin B, INHB) in male rats and the intervention of Lycium barbarum polysaccharide (LBP). Results Compared with the control group, the mRNA and protein expression levels of INH α and INH βB in the testis tissue decreased, and the difference was statistically significant (P < 0.05). The LBP intervention group can significantly increase the expression level, and the difference is statistically significant (P < 0.05). Conclusion The decrease of INHα and INHβB expression caused by Cy exposure indicates that Cy has a toxic effect on the testis of rats, and the addition of LBP has a certain protective effect on the testis of rats.
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Arjun Sinkemani,Xin Hong,Zeng-Xin Gao,Su-Yang Zhuang,Zan-Li Jiang,Shao-Dong Zhang,Jun-Ping Bao,Lei Zhu,Pei Zhang,Xin-Hui Xie,Feng Wang,Xiao-Tao Wu 대한척추외과학회 2015 Asian Spine Journal Vol.9 No.6
Study Design: Retrospective, case control evaluation of 86 patients who underwent microendoscopic discectomy (MED) and percutaneous transforaminal endoscopic discectomy (PTED) for the treatment of lumbar disc herniation (LDH). Purpose: To evaluate the safety and the outcomes of MED and PTED for the treatment of LDH. Overview of Literature: MED and PTED are minimally invasive surgical techniques for lower back pain. Studies to date have shown that MED and PTED are safe and effective treatment modalities for LDH. Methods: A retrospective study was performed in patients with LDH treated with MED (n=50) and transforaminal endoscopic discectomy (PTED; n=36) in our hospital. All patients were followed-up with self-evaluation questionnaires, Oswestry disability index (ODI), medical outcomes study 36-item short form health survey and MacNab criteria. All the patients in both groups were followed up to 12 months after the operation. Results: ODI questionnaire responses were not statistically different between the MED and PTED groups (53.00 vs. 48.72) before treatment. Average scores and minimal disability after 5 days to 12 months of follow-up were 4.96 in the MED group and 3.61 in the PTED group. According to MacNab criteria, 92.0% of the MED group and 94.4% of the PTED group had excellent or good results with no significant difference. Conclusions: There was no significant difference between MED and PTED outcomes. Further large-scale, randomized studies with long-term follow-up are needed.
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Xiaoyan Feng,Xin Wen,Ling Li,Zhenchang Sun,Xin Li,Lei Zhang,Jingjing Wu,Xiaorui Fu,Xinhua Wang,Hui Yu,Xinran Ma,Xudong Zhang,Xinli Xie,Xingmin Han,Mingzhi Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.3
Purpose There is no optimal prognostic model for T-cell lymphoblastic lymphoma (T-LBL). Here, we discussed the predictive value of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) in T-LBL.Materials and Methods Thirty-seven treatment naïve T-LBL patients with PET-CT scans were enrolled. TMTV was obtained using the 41% maximum standardized uptake value (SUVmax) threshold method, and TLG was measured as metabolic tumor volume multiplied by the mean SUV. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier curves and compared by the log-rank test.Results The optimal cutoff values for SUVmax, TMTV, and TLG were 12.7, 302 cm3, and 890, respectively. A high SUVmax, TMTV, and TLG indicated a shorten PFS and OS. On multivariable analysis, TMTV ≥ 302 cm3, and central nervous system (CNS) involvement predicted inferior PFS, while high SUVmax, TLG and CNS involvement were associated with worse OS. Subsequently, we generated a risk model comprising high SUVmax, TMTV or TLG and CNS involvement, which stratified the population into three risk groups, which had significantly different median PFS of not reached, 14 months, and 7 months for low-risk group, mediate-risk group, and high-risk group, respectively (p < 0.001). Median OS were not reached, 27 months, and 13 months, respectively (p < 0.001).Conclusion Baseline SUVmax, TMTV, and TLG measured on PET-CT are strong predictors of worse outcome in T-LBL. A risk model integrating these three parameters with CNS involvement identifies patients at high risk of disease progression.
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( Xin Ran Li ),( Hui Xu ),( Jie Xie ),( Qiao Fu Yi ),( Wei Li ),( Dai Rong Qiao ),( Yi Cao ),( Yu Cao ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.4
In order to improve the expression of heat-resistant xylanase XYNB from Aspergillus niger SCTCC 400264, XynB has been cloned into Pichia pastoris secretary vector pPIC9K. The XynB production of recombinant P. pastoris was four times that of E. coli, and the Vmax and specific activity of XynB reached 2,547.7 umol/mg and 4,757 U/mg, respectively. XynB still had 74% residual enzyme activity after 30 min of heat treatment at 80°C. From the van der Waals force analysis of XYNB (ACN89393 and AAS67299), there is one more oxygen radical in AAS67299 in their catalytic site, indicating that the local cavity is much more free, and it is more optimal for substrate binding, affinity reaction, and proton transfer, etc, and e ventually i ncreasing enzyme activity. The H-bonds analysis of XYNB indicated that there are two more H-bonds in the 33rd Ser of XYNB (AAS67299) than in the 33rd Ala(ACN89393 ), and two H-bonds between Ser70 and Asp67.
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Xie, Qin-Jian,Cao, Xin-Li,Bai, Lu,Wu, Zheng-Rong,Ma, Ying-Ping,Li, Hong-Yu Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6
Background: Realgar which contains arsenic components has been used in traditional Chinese medicine (TCM) as an anticancer drug. However, neither Realgar nor its formula are soluble in water. As a result, high dose of Realgar has to be administered to achieve an effective blood medicine concentration, and this is associated with adverse side effects. The objective of the present study was to increase the solubility of a formula using hydrometallurgy technology as well as investigating its effects on in vitro and in vivo cell proliferation and apoptosis in Sarcoma-180 cell line. Materials and Methods: Antiproliferative activity of Realgar Bioleaching Solution (RBS) was evaluated by MTT assay. Further, effects of RBS on cell proliferation and apoptosis were studied using flow cytometry and transmission electron microscopy. Kunming mice were administered RBS in vivo, where arsenic specifically targeted solid tumors. Results: The results indicated that RBS extract potently inhibited the tumor growth of Sarcoma-180 cell line in a dose-dependent manner. Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner. Further, on RBS administration to mice, arsenic was specifically targeted to solid tumor.s Conclusions: RBS could substitute for traditional Realgar or its formula to work as a potent tool in cancer treatment.
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