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Article ; Online: Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance.

Ashrafizadeh, Milad / Dai, Jingyuan / Torabian, Pedram / Nabavi, Noushin / Aref, Amir Reza / Aljabali, Alaa A A / Tambuwala, Murtaza / Zhu, Minglin

Cellular and molecular life sciences : CMLS

2024 Volume 81, Issue 1, Page(s) 214

Abstract: The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially ... ...

Abstract	The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors.
MeSH term(s)	Humans ; RNA, Circular/genetics ; RNA, Circular/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/metabolism ; Neoplasm Metastasis ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Drug Resistance, Neoplasm/genetics ; Cell Plasticity/genetics ; Animals ; Gene Expression Regulation, Neoplastic
Chemical Substances	RNA, Circular
Language	English
Publishing date	2024-05-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-024-05236-w
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Article ; Online: TNFα blockade reverses vascular and uteroplacental matrix metalloproteinases imbalance and collagen accumulation in hypertensive pregnant rats.

Ren, Zongli / Cui, Ning / Zhu, Minglin / Khalil, Raouf A

Biochemical pharmacology

2021 Volume 193, Page(s) 114790

Abstract: Preeclampsia is a pregnancy-related disorder of maternal hypertension-in-pregnancy (HTN-Preg) and often fetal growth restriction (FGR). Placental ischemia could be an initiating event leading to inadequate vascular and uteroplacental remodeling and HTN- ... ...

Abstract	Preeclampsia is a pregnancy-related disorder of maternal hypertension-in-pregnancy (HTN-Preg) and often fetal growth restriction (FGR). Placental ischemia could be an initiating event leading to inadequate vascular and uteroplacental remodeling and HTN-Preg; however, the molecular targets are unclear. To test the hypothesis that placental ischemia-induced release of proinflammatory cytokines target vascular and uteroplacental matrix metalloproteinases (MMPs), we tested if infusing TNFα (200 ng/kg/day) in day-14 pregnant (Preg) rats causes MMP imbalance and collagen accumulation, and if infusing TNFα decoy receptor Etanercept (0.4 mg/kg/day) in HTN-Preg rats with reduced uteroplacental perfusion pressure (RUPP) reverses MMP imbalance and collagen accumulation. On gestational day-19, blood pressure (BP) was higher in Preg + TNFα and RUPP vs Preg rats, and restored in RUPP + Etanercept rats. Gelatin zymography and Western blots revealed decreases in MMP-2 and MMP-9 and increases in MMP-1 and MMP-7 in aorta, uterus and placenta of Preg + TNFα and RUPP, that were reversed in RUPP + Etanercept rats. Collagen-I and IV were abundant in Preg + TNFα and RUPP, and were decreased in RUPP + Etanercept rats. The litter size, uterine, placenta, and pup weight were markedly reduced in RUPP, insignificantly reduced in Preg + TNFα, and slightly improved in RUPP + Etanercept rats. Thus TNFα blockade reverses the decreases in vascular and uteroplacental MMP-2 and MMP-9, and the increases in MMP-1, MMP-7 and accumulation of collagen-I and IV induced by placental ischemia and TNFα in HTN-Preg rats. Targeting TNFα using cytokine antagonists, or MMPs using MMP modulators could rectify MMP imbalance and collagen accumulation, restore vascular and uteroplacental remodeling, and improve BP in HTN-Preg and preeclampsia.
MeSH term(s)	Animals ; Etanercept/pharmacology ; Female ; Gene Expression Regulation, Enzymologic/drug effects ; Hypertension ; Litter Size ; Matrix Metalloproteinases/genetics ; Matrix Metalloproteinases/metabolism ; Placenta/enzymology ; Placental Circulation ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/pharmacology ; Uterus/enzymology
Chemical Substances	Tumor Necrosis Factor-alpha ; Matrix Metalloproteinases (EC 3.4.24.-) ; Etanercept (OP401G7OJC)
Language	English
Publishing date	2021-10-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2021.114790
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Article: Quercetin prevents alcohol-induced liver injury through targeting of PI3K/Akt/nuclear factor-κB and STAT3 signaling pathway.

Zhu, Minglin / Zhou, Xuefeng / Zhao, Jinping

Experimental and therapeutic medicine

2017 Volume 14, Issue 6, Page(s) 6169–6175

Abstract: Quercetin is a type of flavonoid compound, which has potent antioxidant and anti-inflammatory activities, capable of treating a variety of diseases including neurodegenerative diseases, tumors, diabetes and obesity. The present study selected alcohol- ... ...

Abstract	Quercetin is a type of flavonoid compound, which has potent antioxidant and anti-inflammatory activities, capable of treating a variety of diseases including neurodegenerative diseases, tumors, diabetes and obesity. The present study selected alcohol-induced liver injury model mice and aimed at studying the protective role of quercetin in preventing alcohol-induced liver injury. In alcohol-induced liver injury mice treated with quercetin, it was demonstrated that levels of aspartate transaminase, alanine transaminase, total bilirubin and triglyceride were reduced. In addition to this, the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were increased, malondialdehyde was inhibited, and interleukin (IL)-1β, IL-6, IL-10 and inducible nitric oxide synthase were suppressed. Quercetin additionally suppressed the protein expression levels of B-cell lymphoma (Bcl)-2, Bcl-2 associated X apoptosis regulator, Caspase-3, poly ADP-ribose polymerase, and signal transducer and activator of transcription (STAT) 3 phosphorylation, nuclear factor (NF)-κB and protein kinase B (Akt) phosphorylation levels in alcohol-induced liver injured mice. These results suggested that the protective role of quercetin prevents alcohol-induced liver injury through the phosphoinositide 3-kinase/Akt/NF-κB and STAT3 pathway.
Language	English
Publishing date	2017-10-18
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2683844-8
ISSN	1792-1015 ; 1792-0981
ISSN (online)	1792-1015
ISSN	1792-0981
DOI	10.3892/etm.2017.5329
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Article ; Online: Placental growth factor reverses decreased vascular and uteroplacental MMP-2 and MMP-9 and increased MMP-1 and MMP-7 and collagen types I and IV in hypertensive pregnancy.

Ren, Zongli / Cui, Ning / Zhu, Minglin / Khalil, Raouf A

American journal of physiology. Heart and circulatory physiology

2018 Volume 315, Issue 1, Page(s) H33–H47

Abstract: Preeclampsia is a complication of pregnancy manifested as maternal hypertension (HTN) and fetal intrauterine growth restriction, with unclear mechanisms. Placental ischemia increases antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) relative to ... ...

Abstract	Preeclampsia is a complication of pregnancy manifested as maternal hypertension (HTN) and fetal intrauterine growth restriction, with unclear mechanisms. Placental ischemia increases antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) relative to angiogenic placental growth factor (PlGF); however, the molecular targets are unclear. To test the hypothesis that placental ischemia-induced changes in sFlt-1 and PlGF target vascular and uteroplacental matrix metalloproteinases (MMPs), we tested whether raising the sFlt-1-to-PlGF ratio by infusing sFlt-1 (10 µg·kg
MeSH term(s)	Angiogenesis Inducing Agents/pharmacology ; Angiogenesis Inducing Agents/therapeutic use ; Animals ; Blood Pressure ; Collagen/genetics ; Collagen/metabolism ; Female ; Fetal Growth Retardation/prevention & control ; Matrix Metalloproteinases/genetics ; Matrix Metalloproteinases/metabolism ; Placenta/blood supply ; Placenta/drug effects ; Placenta/metabolism ; Placenta Growth Factor/pharmacology ; Placenta Growth Factor/therapeutic use ; Pre-Eclampsia/drug therapy ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Uterus/blood supply ; Uterus/drug effects ; Uterus/metabolism ; Vascular Endothelial Growth Factor Receptor-1/pharmacology ; Vascular Endothelial Growth Factor Receptor-1/therapeutic use ; Vascular Remodeling
Chemical Substances	Angiogenesis Inducing Agents ; Placenta Growth Factor (144589-93-5) ; Collagen (9007-34-5) ; Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1) ; Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2018-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00045.2018
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Article ; Online: Decreased uterine vascularization and uterine arterial expansive remodeling with reduced matrix metalloproteinase-2 and -9 in hypertensive pregnancy.

Lin, Chen / He, Hong / Cui, Ning / Ren, Zongli / Zhu, Minglin / Khalil, Raouf A

American journal of physiology. Heart and circulatory physiology

2019 Volume 318, Issue 1, Page(s) H165–H180

Abstract: Normal pregnancy involves extensive remodeling of uterine and spiral arteries and matrix metalloproteinases (MMPs)-mediated proteolysis of extracellular matrix (ECM). Preeclampsia is characterized by hypertension in pregnancy (HTN-Preg) and intrauterine ... ...

Abstract	Normal pregnancy involves extensive remodeling of uterine and spiral arteries and matrix metalloproteinases (MMPs)-mediated proteolysis of extracellular matrix (ECM). Preeclampsia is characterized by hypertension in pregnancy (HTN-Preg) and intrauterine growth restriction (IUGR) with unclear mechanisms. Initial faulty placentation and reduced uterine perfusion pressure (RUPP) could release cytoactive factors and trigger an incessant cycle of suppressed trophoblast invasion of spiral arteries, further RUPP, and progressive placental ischemia leading to HTN-Preg and IUGR; however, the extent and depth of uterine vascularization and the proteolytic enzymes and ECM proteins involved are unclear. We hypothesized that HTN-Preg involves decreased uterine vascularization and arterial remodeling by MMPs and accumulation of ECM collagen. Blood pressure (BP) and fetal parameters were measured in normal Preg rats and RUPP rat model, and the uteri were assessed for vascularity, MMP levels, and collagen deposition. On
MeSH term(s)	Animals ; Animals, Newborn ; Birth Weight ; Blood Pressure ; Collagen Type IV/metabolism ; Disease Models, Animal ; Down-Regulation ; Female ; Ischemia/complications ; Ischemia/physiopathology ; Litter Size ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/metabolism ; Neovascularization, Physiologic ; Placenta/blood supply ; Pre-Eclampsia/enzymology ; Pre-Eclampsia/etiology ; Pre-Eclampsia/pathology ; Pre-Eclampsia/physiopathology ; Pregnancy ; Rats, Sprague-Dawley ; Regional Blood Flow ; Signal Transduction ; Trophoblasts/metabolism ; Trophoblasts/pathology ; Uterine Artery/enzymology ; Uterine Artery/pathology ; Uterine Artery/physiopathology ; Uterus/blood supply ; Vascular Remodeling
Chemical Substances	Collagen Type IV ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Mmp2 protein, rat (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Mmp9 protein, rat (EC 3.4.24.35)
Language	English
Publishing date	2019-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00602.2019
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Article ; Online: Co-expression network analysis identified KIF2C in association with progression and prognosis in lung adenocarcinoma.

Bai, Yuquan / Xiong, Lecai / Zhu, Minglin / Yang, Zetian / Zhao, Jinping / Tang, Hexiao

Cancer biomarkers : section A of Disease markers

2019 Volume 24, Issue 3, Page(s) 371–382

Abstract: Lung cancer is a malignant tumor with high morbidity and mortality, of which 80% is non-small cell lung cancer (NSCLC). And lung adenocarcinoma (LUAD) is the most important and common subtype in the NSCLC. In current study, the microarray data GSE31210 ... ...

Abstract	Lung cancer is a malignant tumor with high morbidity and mortality, of which 80% is non-small cell lung cancer (NSCLC). And lung adenocarcinoma (LUAD) is the most important and common subtype in the NSCLC. In current study, the microarray data GSE31210 containing LUAD (n= 226) and normal lung tissue (n= 20) was analyzed to identify 965 differentially expressed genes, on which weighted gene co-expression network analysis was performed. Finally, it was confirmed that there was a significant correlation between brown module and LUAD stage. In the significant module, a total of 54 network hub genes were identified, and six of them were also identified as hub genes of the protein-protein interaction network. In validation, KIF2C showed a higher correlation with disease stage than other hub genes (p< 0.001, R2 = 0.955). Functional enrichment suggests that KIF2C is associated with cell mitosis and cell cycle. Combined with clinicopathological parameters, we found that the high expression of KIF2C is closely related to the relapse and tumor stage of LUAD. Survival analysis showed a significant reduction in overall survival in LUAD patients with high expression of KIF2C. Gene set enrichment analysis (GSEA) also showed that the "cell cycle signaling pathway" and "P53 related pathway" were significantly enriched in LUAD samples with high expression of KIF2C (FDR < 0.05). In conclusion, based on the co-expression analysis, KIF2C was identified in the association with progression and prognosis of LUAD, which might refer a poor prognosis probably by regulating cell cycle signaling pathway.
MeSH term(s)	Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/metabolism ; Adenocarcinoma of Lung/mortality ; Adenocarcinoma of Lung/pathology ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Computational Biology ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Ontology ; Gene Regulatory Networks ; Humans ; Kinesin/genetics ; Kinesin/metabolism ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein Interaction Mapping ; Protein Interaction Maps ; Transcriptome
Chemical Substances	Biomarkers, Tumor ; KIF2C protein, human ; Kinesin (EC 3.6.4.4)
Language	English
Publishing date	2019-03-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2203517-5
ISSN	1875-8592 ; 1574-0153 ; 1875-8592
ISSN (online)	1875-8592 ; 1574-0153
ISSN	1875-8592
DOI	10.3233/CBM-181512
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Article ; Online: Decreased homodimerization and increased TIMP-1 complexation of uteroplacental and uterine arterial matrix metalloproteinase-9 during hypertension-in-pregnancy.

Chen, Juanjuan / Ren, Zongli / Zhu, Minglin / Khalil, Raouf A

Biochemical pharmacology

2017 Volume 138, Page(s) 81–95

Abstract: Preeclampsia is a complication of pregnancy manifested as hypertension-in-pregnancy (HTN-Preg) and often intrauterine growth restriction (IUGR). Placental ischemia could be an initiating event, but the molecular mechanisms are unclear. To test the ... ...

Abstract	Preeclampsia is a complication of pregnancy manifested as hypertension-in-pregnancy (HTN-Preg) and often intrauterine growth restriction (IUGR). Placental ischemia could be an initiating event, but the molecular mechanisms are unclear. To test the hypothesis that dimerization of matrix metalloproteinases (MMPs) plays a role in HTN-Preg and IUGR, the levels/activity of MMP-9, tissue inhibitor of metalloproteinase (TIMP-1), and their dimerization forms were measured in the placenta, uterus, and uterine artery of normal pregnant (Preg) rats and a rat model of reduced uteroplacental perfusion pressure (RUPP). Consistent with our previous report, blood pressure (BP) was higher, pup weight was lower, and gelatin zymography showed different gelatinolytic activity for pro-MMP-9, MMP-9, pro-MMP-2 and MMP-2 in RUPP vs Preg rats. Careful examination of the zymograms showed additional bands at 200 and 135kDa. Western blots with MMP-9 antibody suggested that the 200kDa band was a MMP-9 homodimer. Western blots with TIMP-1 antibody as well as reverse zymography suggested that the 135kDa band was a MMP-9/TIMP-1 complex. The protein levels and gelatinase activity of MMP-9 homodimer were decreased while MMP-9/TIMP-1 complex was increased in placenta, uterus and uterine artery of RUPP vs Preg rats. The epidermal growth factor (EGF) receptor blocker erlotinib and protein kinase C (PKC) inhibitor bisindolylmaleimide decreased MMP-9 homodimer and increased MMP-9/TIMP-1 complex in placenta, uterus and uterine artery of Preg rats. EGF and the PKC activator phorbol-12,13-dibutyrate (PDBu) reversed the decreases in MMP-9 homodimer and the increases in MMP-9/TIMP-1 complex in tissues of RUPP rats. Thus, the increased BP and decreased pup weight in placental ischemia model of HTN-Preg are associated with a decrease in MMP-9 homodimer and an increase in MMP-9/TIMP-1 complex in placenta, uterus, and uterine artery, which together would cause a net decrease in MMP-9 activity and reduce uteroplacental and vascular remodeling in the setting of HTN-Preg and IUGR. Enhancing EGFR/PKC signaling may reverse the MMP-9 unfavorable dimerization patterns and thereby promote uteroplacental and vascular remodeling in preeclampsia.
MeSH term(s)	Animals ; Dimerization ; Disease Models, Animal ; Enzyme Activators/pharmacology ; Enzyme Precursors/chemistry ; Enzyme Precursors/metabolism ; Female ; Fetal Growth Retardation/etiology ; Gelatinases/chemistry ; Gelatinases/metabolism ; Hypertension, Pregnancy-Induced/metabolism ; Hypertension, Pregnancy-Induced/physiopathology ; Matrix Metalloproteinase 2/chemistry ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/chemistry ; Matrix Metalloproteinase 9/metabolism ; Placenta/blood supply ; Placenta/drug effects ; Placenta/metabolism ; Pre-Eclampsia/etiology ; Pregnancy ; Protein Kinase Inhibitors/pharmacology ; Protein Multimerization/drug effects ; Rats, Sprague-Dawley ; Tissue Culture Techniques ; Tissue Inhibitor of Metalloproteinase-1/chemistry ; Tissue Inhibitor of Metalloproteinase-1/metabolism ; Uterine Artery/drug effects ; Uterine Artery/metabolism ; Uterus/blood supply ; Uterus/drug effects ; Uterus/metabolism ; Vascular Remodeling
Chemical Substances	Enzyme Activators ; Enzyme Precursors ; Protein Kinase Inhibitors ; TIMP1 protein, rat ; Tissue Inhibitor of Metalloproteinase-1 ; Gelatinases (EC 3.4.24.-) ; pro-matrix metalloproteinase 9 (EC 3.4.24.-) ; progelatinase (EC 3.4.24.-) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Mmp2 protein, rat (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Mmp9 protein, rat (EC 3.4.24.35)
Language	English
Publishing date	2017-05-12
Publishing country	England
Document type	Journal Article
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2017.05.005
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Article ; Online: Associations of Various Physical Activities with Mortality and Life Expectancy are Mediated by Telomere Length.

Zhou, Huan-Huan / Jin, Biyu / Liao, Yuxiao / Hu, Yaling / Li, Pengwan / YangLha, Tesring / Liu, Yiran / Xu, Jingwen / Wang, Biyao / Zhu, Minglin / Xiao, Jie / Liu, Jinping / Nüssler, Andreas K / Liu, Liegang / Hao, Xingjie / Chen, Jiuling / Peng, Zhao / Yang, Wei

Journal of the American Medical Directors Association

2023 Volume 25, Issue 3, Page(s) 431–438.e15

Abstract: Objectives: Physical activity (PA) and telomeres both contribute to healthy aging and longevity. To investigate the optimal dosage of various PA for longevity and the role of telomere length in PA and mortality.: Design: Prospective cohort study.: ... ...

Abstract	Objectives: Physical activity (PA) and telomeres both contribute to healthy aging and longevity. To investigate the optimal dosage of various PA for longevity and the role of telomere length in PA and mortality. Design: Prospective cohort study. Setting and participants: A total of 333,865 adults (mean age of 56 years) from the UK Biobank were analyzed. Methods: Walking, moderate PA (MPA), and vigorous PA (VPA) were self-reported via questionnaire, and leukocyte telomere length (LTL) was measured. Cox proportional hazards regression was used to predict all-cause mortality risk. A flexible parametric Royston-Parmar survival model was used to estimate life expectancy. Results: During a median follow-up of 13.8 years, 19,789 deaths were recorded. Compared with the no-walking group, 90 to 720 minutes/week of walking was similarly associated with 27% to 31% of lower mortality and about 6 years of additional life expectancy. We observed nearly major benefits for mortality and life expectancy among those meeting the PA guidelines [151-300 minutes/wk for MPA: hazard ratio (HR) 0.80, 95% CI 0.75-0.85, 3.40-3.42 additional life years; 76-150 minutes/wk for VPA: HR 0.78, 95% CI 0.75-0.82, 2.61 years (2.33-2.89)] vs the no-PA group. Similar benefits were also observed at 76-150 and 301-375 minutes/wk of MPA (18%-19% lower mortality, 3.20-3.42 gained years) or 151-300 minutes/wk of VPA (20%-26% lower mortality, 2.41-2.61 gained years). The associations between MPA, VPA, and mortality risk were slightly mediated by LTL (≈1% mediation proportion, both P < .001). Conclusions and implications: Our study suggests a more flexible range of PA than the current PA guidelines, which could gain similar benefits and is easier to achieve: 90 to 720 minutes/wk of walking, 75 to 375 minutes/wk of MPA, and 75 to 300 minutes/wk of VPA. Telomeres might be a potential mechanism by which PA promotes longevity.
MeSH term(s)	Adult ; Humans ; Middle Aged ; Prospective Studies ; Exercise ; Life Expectancy ; Longevity ; Telomere
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2171030-2
ISSN	1538-9375 ; 1525-8610
ISSN (online)	1538-9375
ISSN	1525-8610
DOI	10.1016/j.jamda.2023.08.002
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Zs.A 5971: Show issues

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Article ; Online: Resveratrol Attenuates Aortic Dissection by Increasing Endothelial Barrier Function Through the SIRT1 Pathway.

Wang, Kaijie / Zhao, Jinping / Zhang, Wenwen / Zhu, Minglin / Xu, Ming / Li, Dan / Shi, Hongjie / Zhang, Ming / Shi, Jiajun / Dong, Zhe

Journal of cardiovascular pharmacology

2020 Volume 76, Issue 1, Page(s) 86–93

Abstract: Aortic dissection (AD) is a serious condition and a health issue on a global scale. β-Aminopropionitrile-induced AD in mice is similar to the pathogenesis of AD in humans. Resveratrol (RSV) is a natural polyphenolic substance that provides anti- ... ...

Abstract	Aortic dissection (AD) is a serious condition and a health issue on a global scale. β-Aminopropionitrile-induced AD in mice is similar to the pathogenesis of AD in humans. Resveratrol (RSV) is a natural polyphenolic substance that provides anti-inflammatory and cardiovascular effects, but the role of RSV in AD is unclear. In this study, we investigated the effects and mechanisms of RSV on β-aminopropionitrile-induced AD in mice. Our results indicate that RSV can prevent the occurrence of AD. More meaningfully, we found that the protective effect comprises an increase in sirtuin 1 (SIRT1) expression in endothelial cells for the reconstruction of their structure, reducing the recruitment of inflammatory cells by endothelial cells and inhibiting the inflammation response, thereby suppressing the occurrence of AD.
MeSH term(s)	Aminopropionitrile ; Aneurysm, Dissecting/chemically induced ; Aneurysm, Dissecting/enzymology ; Aneurysm, Dissecting/pathology ; Aneurysm, Dissecting/prevention & control ; Animals ; Anti-Inflammatory Agents/pharmacology ; Aorta/drug effects ; Aorta/enzymology ; Aorta/pathology ; Aortic Aneurysm/chemically induced ; Aortic Aneurysm/enzymology ; Aortic Aneurysm/pathology ; Aortic Aneurysm/prevention & control ; Cell Adhesion/drug effects ; Cytoskeleton/drug effects ; Cytoskeleton/enzymology ; Cytoskeleton/pathology ; Disease Models, Animal ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/enzymology ; Human Umbilical Vein Endothelial Cells/pathology ; Humans ; Male ; Mice, Inbred C57BL ; Resveratrol/pharmacology ; Signal Transduction ; Sirtuin 1/metabolism ; THP-1 Cells
Chemical Substances	Anti-Inflammatory Agents ; Aminopropionitrile (151-18-8) ; SIRT1 protein, human (EC 3.5.1.-) ; Sirt1 protein, mouse (EC 3.5.1.-) ; Sirtuin 1 (EC 3.5.1.-) ; Resveratrol (Q369O8926L)
Language	English
Publishing date	2020-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391970-5
ISSN	1533-4023 ; 0160-2446
ISSN (online)	1533-4023
ISSN	0160-2446
DOI	10.1097/FJC.0000000000000837
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Article ; Online: Structure guided design of potent indole-based ATX inhibitors bearing hydrazone moiety with tumor suppression effects.

Lei, Hongrui / Li, Changtao / Yang, Yu / Jia, Fang / Guo, Ming / Zhu, Minglin / Jiang, Nan / Zhai, Xin

European journal of medicinal chemistry

2020 Volume 201, Page(s) 112456

Abstract: ATX was capable of catalyzing the hydrolysis of LPC to the lipid mediator LPA which attracted considerable attention on the development of potent ATX inhibitors. Herein, driven by the HTS product indole-based lead 1, a hybridization strategy was utilized ...

Abstract	ATX was capable of catalyzing the hydrolysis of LPC to the lipid mediator LPA which attracted considerable attention on the development of potent ATX inhibitors. Herein, driven by the HTS product indole-based lead 1, a hybridization strategy was utilized to construct the trifluoroacetyl hydrazone moiety through assembling the phenyl thiazole fragment to the indole skeleton of lead 1. After a systematic structure guided optimization, by cycling the phenyl thiazole to the compacted benzothiazole or decreasing the lipophilicity, two promising ATX inhibitors (9j and 25a) were identified with IC
MeSH term(s)	Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacology ; Catalytic Domain ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Humans ; Hydrazones/chemical synthesis ; Hydrazones/metabolism ; Hydrazones/pharmacology ; Indoles/chemical synthesis ; Indoles/metabolism ; Indoles/pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Phosphodiesterase Inhibitors/chemical synthesis ; Phosphodiesterase Inhibitors/metabolism ; Phosphodiesterase Inhibitors/pharmacology ; Phosphoric Diester Hydrolases/chemistry ; Phosphoric Diester Hydrolases/metabolism ; Protein Binding ; Structure-Activity Relationship ; Thermodynamics
Chemical Substances	Antineoplastic Agents ; Hydrazones ; Indoles ; Phosphodiesterase Inhibitors ; Phosphoric Diester Hydrolases (EC 3.1.4.-) ; alkylglycerophosphoethanolamine phosphodiesterase (EC 3.1.4.39)
Language	English
Publishing date	2020-06-01
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2020.112456
Database	MEDical Literature Analysis and Retrieval System OnLINE

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