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        Molecular and Cellular Microbiology / Biomedical Sciences : Alteration of the Metabolome Profile in Endothelial Cells by Overexpression of miR-143/145

        ( Wenshuo Wang ),( Ye Yang ),( Yiqing Wang ),( Liewen Pang ),( Jiechun Huang ),( Hongyue Tao ),( Xiaotian Sun ),( Chen Liu ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.3

        Communication between endothelial cells (ECs) and smooth muscle cells (SMCs) via miR-143/145 clusters is vital to vascular stability. Previous research demonstrates that miR-143/145 released from ECs can regulate SMC proliferation and migration. In addition, a recent study has found that SMCs also have the capability of manipulating EC function via miR-143/145. In the present study, we artificially increased the expression of miR-143/145 in ECs, to mimic a similar change caused by miR-143/145 released by SMCs, and applied untargeted metabolomics analysis, aimed at investigating the consequential effect of miR-143/145 overexpression. Our results showed that miR-143/145 overexpression alters the levels of metabolites involved in energy production, DNA methylation, and oxidative stress. These changed metabolites indicate that metabolic pathways, such as the SAM cycle and TCA cycle, exhibit significant differences from the norm with miR-143/145 overexpression.

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        Small Molecule-Based Strategy Promotes Nucleus Pulposus Specific Differentiation of Adipose-Derived Mesenchymal Stem Cells

        Hua, Jianming,Shen, Ning,Wang, Jingkai,Tao, Yiqing,Li, Fangcai,Chen, Qixin,Zhou, Xiaopeng Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.9

        Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising for regenerating degenerated intervertebral discs (IVDs), but the low efficiency of nucleus pulposus (NP)-specific differentiation limits their clinical applications. The Sonic hedgehog (Shh) signaling pathway is important in NP-specific differentiation of ADSCs, and Smoothened Agonist (SAG) is a highly specific and effective agonist of Shh signaling. In this study, we proposed a new differentiation strategy with the use of the small molecule SAG. The NP-specific differentiation and extracellular matrix (ECM) synthesis of ADSCs were measured in vitro, and the regenerative effects of SAG pretreated ADSCs in degenerated IVDs were verified in vivo. The results showed that the combination of SAG and transforming growth factor-${\beta}3$ ($TGF-{\beta}3$) is able to increase the ECM synthesis of ADSCs. In addition, the gene and protein expression levels of NP-specific markers were increased by treatment with SAG and $TGF-{\beta}3$. Furthermore, SAG pretreated ADSCs can also improve the disc height, water content, ECM content, and structure of degenerated IVDs in vivo. Our new differentiation scheme has high efficiency in inducing NP-specific differentiation of ADSCs and is promising for stem cell-based treatment of degenerated IVDs.

      • KCI등재

        Small Molecule-Based Strategy Promotes Nucleus Pulposus Specific Differentiation of Adipose-Derived Mesenchymal Stem Cells

        Jianming Hua,Ning Shen,Jingkai Wang,Yiqing Tao,Fangcai Li,Qixin Chen,Xiaopeng Zhou 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.9

        Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising for regenerating degenerated intervertebral discs (IVDs), but the low efficiency of nucleus pulposus (NP)-specific differentiation limits their clinical applications. The Sonic hedgehog (Shh) signaling pathway is important in NP-specific differentiation of ADSCs, and Smoothened Agonist (SAG) is a highly specific and effective agonist of Shh signaling. In this study, we proposed a new differentiation strategy with the use of the small molecule SAG. The NP-specific differentiation and extracellular matrix (ECM) synthesis of ADSCs were measured in vitro, and the regenerative effects of SAG pretreated ADSCs in degenerated IVDs were verified in vivo. The results showed that the combination of SAG and transforming growth factor-β3 (TGF-β3) is able to increase the ECM synthesis of ADSCs. In addition, the gene and protein expression levels of NP-specific markers were increased by treatment with SAG and TGF-β3. Furthermore, SAG pretreated ADSCs can also improve the disc height, water content, ECM content, and structure of degenerated IVDs in vivo. Our new differentiation scheme has high efficiency in inducing NP-specific differentiation of ADSCs and is promising for stem cell-based treatment of degenerated IVDs.

      • KCI등재

        Risk of Death in Colorectal Cancer Patients with Multi-morbidities of Metabolic Syndrome: A Retrospective Multicohort Analysis

        Qingting Feng,Lingkai Xu,Lin Li,Junlan Qiu,Ziwei Huang,Yiqing Jiang,Tao Wen,Shun Lu,Fang Meng,Xiaochen Shu 대한암학회 2021 Cancer Research and Treatment Vol.53 No.3

        Purpose The prevalence of multi-morbidities with colorectal cancer (CRC) is known to be increasing. Particularly prognosis of CRC patients co-diagnosed with metabolic syndrome (MetSyn) was largely unknown. We aimed to examine the death risk of CRC patients according to the multiple MetSyn morbidities.Materials and Methods We identified CRC patients with MetSyn from the electronic medical records (EMR) systems in five independent hospitals during 2006-2011. Information on deaths was jointly retrieved from EMR, cause of death registry and chronic disease surveillance as well as study-specific questionnaire. Cox proportional hazards regression was used to calculate the overall and CRC-specific hazards ratios (HR) comparing MetSyn CRC cohort with reference CRC cohort.Results A total of 682 CRC patients in MetSyn CRC cohort were identified from 24 months before CRC diagnosis to 1 month after. During a median follow-up of 92 months, we totally observed 584 deaths from CRC, 245 being in MetSyn cohort and 339 in reference cohort. Overall, MetSyn CRC cohort had an elevated risk of CRC-specific mortality (HR, 1.49; 95% confidence interval [CI], 1.07 to 1.90) and overall mortality (HR, 1.43; 95% CI, 1.09 to 1.84) compared to reference cohort after multiple adjustment. Stratified analyses showed higher mortality risk among women (HR, 1.87; 95% CI, 1.04 to 2.27) and specific components of MetSyn. Notably, the number of MetSyn components was observed to be significantly related to CRC prognosis.Conclusion Our findings supported that multi-morbidities of MetSyn associated with elevated death risk after CRC. MetSyn should be considered as an integrated medical condition more than its components in CRC prognostic management.

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