International Heart Journal
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2022
·Vol. 63
·期 3
·578-590
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IF 1.823
Haibo Du,Lianqin Ding,Tian Zeng,Di Li,Li Liu
Myocardial ischemia-reperfusion (I/R) injury is a serious complication of acute myocardial infarction. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) can regulate I/R-induced cardiomyocyte apoptosis. Here, we investigated the mechanism of SNHG15 activity in I/R-induced cardiomyocyte injury.SNHG15, microRNA (miR)-335-3p, and toll-like receptor 4 (TLR4) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2´-deoxyuridine (EDU) assay, and flow cytometry, respectively. The direct relationship between miR-335-3p and SNHG15 or TLR4 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays.SNHG15 was overexpressed in the infarcted area tissues of I/R mice and I/R-stimulated AC16 cells. SNHG15 knockdown alleviated I/R injury in AC16 cells. Mechanistically, SNHG15 directly targeted miR-335-3p, and miR-335-3p was a functional mediator of SNHG15. MiR-335-3p inhibited TLR4 expression by targeting TLR4, and miR-335-3p-mediated inhibition of TLR4 alleviated I/R-induced injury in AC16 cells. Moreover, SNHG15 regulated the TLR4/nuclear factor-κB (NF-κB) signaling pathway through miR-335-3p.Our findings identify a novel mechanism, the miR-335-3p/TLR4/NF-κB pathway, for the regulation of SNHG15 in myocardial I/R injury.
研究领域:
分子生物学
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心脏病学
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细胞生物学
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DOI
高影响因子
Future Medicinal Chemistry
·
2023
·
IF 4.2
Li Zhu,Xiujin Chang,Shengpeng Zhang,Xiumei Bai,Alexander V Finko,Xi Xu,Jinlei Bian,Xiaoping Liu,Huidan Huang
Aim: A series of novel GLS1 irreversible allosteric inhibitors targeting Lys320 might have robust enzyme inhibitory activity and potent antitumor activity. Materials & methods: Novel GLS1 allosteric inhibitors targeting Lys320 were synthesized and their anticancer activity was assessed. Moreover, GLS1 protein was used as a model system to analyze the reactivity of these electrophilic groups in GLS1 irreversible allosteric inhibitors with other amino acids, including tyrosine, histidine, serine and threonine, using biochemical and biophysical assays. Results: AC16 exhibited robust GLS1 inhibitory activity, antiproliferative effect in vitro, good plasma stability and potential covalent addition with GLS1 K320. Conclusion: This study opens a novel avenue for the design of robust irreversible GLS1 inhibitors targeting the allosteric site K320.Graphical abstract
研究领域:
癌症研究
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分子生物学
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药理学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Demin Li,Yachen Hou,Yang Lu,Pengchong Du,Ge Zhang,Yan Lv,Ke Hu,Rilige Su,Bolin Jiao,Yangyang Wu,Yujia Wang,Jinying Zhang,Junnan Tang
ZFP36 was selected as an MI-associated candidate for donor-cell engineering. • ZFP36 OE -EV attenuated RSL3-induced ferroptosis-related endothelial injury. • ZFP36 OE -EV showed beneficial biological activity in a mouse MI model. • EV-functionalized NiTi interfaces improved vascular healing after implantation. Myocardial infarction (MI) is associated with persistent myocardial injury and vascular dysfunction despite advances in reperfusion therapy. Delayed endothelial recovery, inflammation, and vascular remodeling remain important challenges during post-MI repair and vascular intervention. Here, we investigated whether extracellular vesicles (EVs) derived from ZFP36-overexpressing AC16 cells could attenuate ferroptosis-related endothelial injury, improve cardiac function after MI, and be integrated into a bioactive NiTi surface for vascular repair. Bioinformatic screening identified ZFP36 as an MI-associated candidate linked to ferroptosis-related processes; increased expression was subsequently observed in the mouse MI model. ZFP36-overexpressing AC16 cells were generated, and the released EVs were designated ZFP36 OE -EV. In RSL3-treated HUVECs, ZFP36 OE -EV improved cell viability, reduced oxidative stress, preserved mitochondrial membrane potential, and partially restored ferroptosis-related molecular changes. In a mouse MI model, intramyocardial delivery of ZFP36 OE -EV improved cardiac function and reduced myocardial fibrosis. To explore the use of the same engineered EV preparation for vascular interface functionalization, ZFP36 OE -EV was immobilized onto a polydopamine/hyaluronic acid (PDA/HA)-modified NiTi surface to generate the NPH@Z-EV coating. The coating supported EV loading and gradual particle release in vitro. Under direct cell–material contact conditions, the NPH@Z-EV coating exhibited endothelial protective activity under ferroptosis-related stress. In a rat femoral artery injury model, the NPH@Z-EV coating supported vascular repair, with improved endothelial recovery, reduced local inflammatory activation, attenuated lipid peroxidation-associated vascular injury, and a VSMC marker pattern consistent with reduced phenotypic switching. These findings support further evaluation of engineered EVs as a strategy for functionalizing NiTi vascular interfaces to improve vascular healing after implantation.
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高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
·
2026
·Vol. 1870
·期 11
·130988
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IF 2.9
Jingxian Han,Lei Hua,Siqi Zhang,Bin Yang,Zhiying Li,Xiangguang Meng
Background Heart failure (HF) remains a leading cause of death worldwide. Stem cells represent a promising strategy for myocardial regeneration due to their differentiation potential and paracrine effects. This study investigated the effect of human pericardial fluid Sca-1 + /Nanog + cells Conditioned Medium (hPFCs-CM) on doxorubicin (DOX)-induced damage to AC16 cardiomyocytes using transcriptomic analysis. Methods Human AC16 cardiomyocytes were divided into Control (CON), DOX, DOXh, and hPFCs groups. Cell viability, cytotoxicity (LDH release), reactive oxygen species (ROS) levels, and apoptosis were assessed. Transcriptomic sequencing was performed on CON, DOX, and DOXh groups. MYH3 and IFI16 genes were knocked down using siRNA, followed by Western blot analysis of apoptosis. Results DOX significantly increased ROS and apoptosis compared with CON group ( P < 0.05), while hPFCs-CM attenuated these effects ( P < 0.05). RNA-seq identified 52 differentially expressed genes between DOX and DOXh groups (adj P < 0.05). Three target genes ( MYH3 , IFI16 , and KCTD14 ) were selected for RT-qPCR validation. Further functional assays revealed that MYH3 knockdown significantly potentiated the anti-apoptotic activity of hPFCs-CM ( P < 0.05), whereas IFI16 knockdown showed no significant effect. Conclusion hPFCs-CM effectively attenuated DOX-induced AC16 cardiomyocyte damage through MYH3, providing potential molecular targets for future mechanistic studies in myocardial injury treatment.
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高影响因子
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