Single‐Cell RNA Sequencing Reveals the Temporal Diversity and Dynamics of Cardiac Immunity after Myocardial Infarction

Small Methods, Год журнала: 2022, Номер 6(3)

Опубликована: Янв. 13, 2022

Myocardial infarction (MI) is strongly associated with the temporal regulation of cardiac immunity. However, a variety current clinical trials have failed because lack post-MI immunomodulating/anti-inflammatory targets. Single-cell RNA sequencing analysis Cd45+ immune cell at 0, 3, 7, and 14 d after injury in mouse left anterior descending coronary artery ligation model performed. Major populations, distinct subsets, dynamic changes are identified. Macrophages (Mø) most abundant, peaking 3 infarction. Mø-5 Mø-6 predominant infiltrated subsets this time point, strong expression inflammatory factors. Further demonstrates that suppressing these sets attenuated pathological MI progression by preventing subsequent leukocyte extravasation adverse remodeling. Abundant apoptotic neutrophils profibrotic macrophage subset on days 7 14, respectively, also detected. These results provide basis for developing type- time-specific interventions MI.

Язык: Английский

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Bioactive components and molecular mechanisms of Salvia miltiorrhiza Bunge in promoting blood circulation to remove blood stasis

Journal of Ethnopharmacology, Год журнала: 2023, Номер 317, С. 116697 - 116697

Опубликована: Июнь 8, 2023

Язык: Английский

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Tanshinone IIA protects human coronary artery endothelial cells from ferroptosis by activating the NRF2 pathway

Biochemical and Biophysical Research Communications, Год журнала: 2021, Номер 575, С. 1 - 7

Опубликована: Авг. 24, 2021

The pathogenesis of atherosclerosis is closely related to endothelial cell injury caused by lipid peroxidation-induced ferroptosis. Tanshinone IIA (TSA) protects tissues from damage. In this study, we investigated whether TSA exerts its protective effect on cells inhibiting Ferroptosis was induced in human coronary artery (HCAECs), and were treated with TSA. Morphological examination indicated that exerted a significant the HCAECs. This further confirmed LDH release death detection assays. Flow cytometry revealed significantly reduced excessive accumulation total cellular ROS ferroptosis inducers. also restored reduction glutathione (GSH), potent abundant reductant cells. addition, found promoted expression NRF2, an essential player response oxidative stress, downstream genes. Immunofluorescent staining nuclear translocation NRF2. Increased NRF2 validated Western blot evaluation cytoplasmic protein extracts. Furthermore, inhibition abolished effects These data demonstrate represses via activation

Язык: Английский

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Tanshinone IIA inhibits cardiomyocyte pyroptosis through TLR4/NF-κB p65 pathway after acute myocardial infarction

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Сен. 12, 2023

Background: Tanshinone IIA, derived from Radix Salviae Miltiorrhizae (Salvia miltiorrhiza Bunge), constitutes a significant component of this traditional Chinese medicine. Numerous studies have reported positive outcomes regarding its influence on cardiac function. However, comprehensive comprehension the intricate mechanisms responsible for cardioprotective effects is still lacking. Methods: A rat model heart failure (HF) induced by acute myocardial infarction (AMI) was established via ligation left anterior descending coronary artery. Rats received oral administration tanshinone IIA (1.5 mg/kg) and captopril (10 8 weeks. Cardiac function assessed through various evaluations. Histological changes in tissue were observed using staining techniques, including Hematoxylin Eosin (HE), Masson, transmission electron microscopy. Tunel used to detect cell apoptosis. Serum levels NT-pro-BNP, IL-1β, IL-18 quantified enzyme-linked immunosorbent assay (ELISA). Expression TLR4, NF-κB p65, pyroptosis-related proteins determined western blotting (WB). H9C2 cardiomyocytes underwent hypoxia-reoxygenation (H/R) simulate ischemia-reperfusion (I/R) injury, viability apoptosis post treatment with different concentrations (0.05 μg/ml, 0.1 μg/ml). ELISA measured IL-18, LDH expression supernatant, while WB analysis evaluated protein levels. p65 nuclear translocation laser confocal Results: exhibited enhanced function, mitigated histological damage, lowered serum suppressed Moreover, downregulated pro-IL-1β, NLRP3, Caspase-1, GSDMD-N tissue. Additionally, it bolstered H/R cardiomyocyte viability, curbed apoptosis, reduced cells. Furthermore, hindered translocation. Conclusion: These findings indicate that enhances alleviates injury HF rats following AMI. demonstrates potential suppression pyroptosis. likely arise inhibition TLR4/NF-κB signaling pathway, presenting promising therapeutic target.

Язык: Английский

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Anti-Inflammatory Effect of Ebractenoid F, a Major Active Compound of Euphorbia ebracteolata Hayata, through Inhibition of Nuclear Factor-κB Activation

Plants, Год журнала: 2023, Номер 12(15), С. 2845 - 2845

Опубликована: Авг. 1, 2023

Euphorbia ebracteolata Hayata (Euphorbiaceae family) is a perennial plant that widely distributed in Korea, Japan, and China. Its roots contain bioactive diterpenes have anti-inflammatory properties. However, the mechanisms are not yet fully understood. This study aimed to identify most active compound from of E. Hayata, using bioassay-guided fractionation combinative method high-speed countercurrent chromatography (HSCCC) preparative high-performance liquid (HPLC). Then, we investigated its mechanism lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Ebractenoid F was identified as potent Hayata. significantly decreased nitric oxide (NO) production nuclear factor-κB (NF-κB) activation induced by LPS Moreover, ebractenoid degradation inhibitory κB-α, translocation p65 p50 subunits NF-κB, expression NF-κB downstream genes. Furthermore, inhibited phosphorylation Akt mitogen-activated protein kinases (MAPKs), such extracellular signal-regulated kinase (ERK) c-Jun NH2 terminal (JNK), LPS-stimulated cells. In conclusion, exerts effect suppressing NF-κB-mediated NO may be useful therapeutic for prevention or treatment inflammation-associated diseases.

Язык: Английский

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Prussian Blue Nanozyme Featuring Enhanced Superoxide Dismutase-like Activity for Myocardial Ischemia Reperfusion Injury Treatment

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

The blood flow, when restored clinically following a myocardial infarction (MI), disrupts the physiological and metabolic equilibrium of ischemic area, resulting in secondary damage termed ischemia-reperfusion injury (MIRI). Reactive oxygen species (ROS) generation inflammatory reactions stand as primary culprits behind MIRI. Current strategies focusing on ROS-scavenging anti-inflammatory actions have limited remission Prussian blue nanozyme (PBNz) exhibits multiple enzyme-like activities including catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), which are beneficial for ROS clearance fighting inflammation. Herein, formulation PBNz coated with polydextrose-sorbitol carboxymethyl ether (PBNz@PSC) was developed to enhance its efficacy, biocompatibility, safety treatment PBNz@PSC not only showed enhanced SOD-like activity due polysaccharide attributes but also could passively target damaged myocardium through permeability retention (EPR) effect. Both vitro vivo studies validated their excellent safety, ability, capacity drive macrophage polarization from M1 toward M2, thereby diminishing levels IL-1β, IL-6, TNF-α combat Consequently, can reverse ischemia reperfusion-induced injury, reduce coronary microvascular obstruction (MVO), improve remodeling cardiac function. Moreover, more pronounced therapeutic effects MIRI than clinical drug, sulfotanshinone IIA sodium. Notably, our findings revealed possible mechanism treating MIRI, mediated AMPK activation. In conclusion, this study presents pioneering strategy addressing promising improved outcomes.

Язык: Английский

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Tanshinone IIA mitigates postoperative cognitive dysfunction in aged rats by inhibiting hippocampal inflammation and ferroptosis: role of Nrf2/SLC7A11/GPX4 axis activation

NeuroToxicology, Год журнала: 2025, Номер 107, С. 62 - 73

Опубликована: Фев. 16, 2025

Язык: Английский

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The plasticity of pancreatic cancer stem cells: implications in therapeutic resistance

Cancer and Metastasis Reviews, Год журнала: 2021, Номер 40(3), С. 691 - 720

Опубликована: Авг. 28, 2021

The ever-growing perception of cancer stem cells (CSCs) as a plastic state rather than hardwired defined entity has evolved our understanding the functional and biological plasticity these elusive components in malignancies. Pancreatic (PC), based on its features clinical evolution, is prototypical example CSC-driven disease. Since discovery pancreatic CSCs (PCSCs) 2007, evidence unraveled their control over many facets natural history PC, including primary tumor growth, metastatic progression, disease recurrence, acquired drug resistance. Consequently, current near-ubiquitous treatment regimens for PC using aggressive cytotoxic agents, aimed at ''tumor debulking'' eradication CSCs, have proven ineffective providing clinically convincing improvements patients with this dreadful Herein, we review key hallmarks well intrinsic extrinsic resistance mechanisms that mediate failure enlist potential CSC-targeting 'natural agents' are gaining popularity recent years. A better molecular landscape PCSC-intrinsic evasion chemotherapeutic drugs offers facile opportunity treating an intractable grim prognosis dire need effective therapeutic advances.

Язык: Английский

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Biosynthesis and Regulatory Mechanisms of Bioactive Compounds in Salvia miltiorrhiza, a Model System for Medicinal Plant Biology

Critical Reviews in Plant Sciences, Год журнала: 2021, Номер 40(3), С. 243 - 283

Опубликована: Май 4, 2021

Salvia miltiorrhiza is one of the most well known species in genus Lamiaceae with great economic, academic and medicinal value. It was recorded as a traditional Chinese medicine material first about second century BC later many other ancient books. can be clinically used alone or mixed herbs to treat heart cardiovascular diseases beneficial for management diseases. In last 30 years, S. has been studied intensively model system plant biology. With available whole genome sequence four lines large number transcriptome, sRNAome metabolome data, progresses have made biosynthesis regulatory mechanisms bioactive compounds, such tanshinones, phenolic acids, flavonoids, prenylquinones. this review, recent results biosynthetic pathways compounds were summarized. The effects biotic abtiotic factors, hormones, transcription factors noncoding RNAs on compound overviewed. mechanism cross-talk coordination among different progress metabolic engineering synthetic biology various are also reviewed discussed.

Язык: Английский

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Tanshinone IIA ameliorates experimental diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress in cardiomyocytes via SIRT1

Phytotherapy Research, Год журнала: 2023, Номер 37(8), С. 3543 - 3558

Опубликована: Май 1, 2023

Abstract Diabetic cardiomyopathy (DCM) is a common complication in patients with diabetes, and ultimately leads to heart failure. Endoplasmic reticulum stress (ERS) induced by abnormal glycolipid metabolism critical factor that affects the occurrence development of DCM. Additionally, upregulation/activation silent information regulation 2 homolog‐1 (SIRT1) has been shown protect against Tanshinone II A (Tan IIA), main active component Salviae miltiorrhizae radix et rhizome (a valuable Chinese medicine), protective effects cardiovascular disease diabetes. However, its role mechanisms diabetes‐induced cardiac dysfunction remain unclear. Therefore, we explored whether Tan IIA alleviates ERS‐mediated DCM via SIRT1 elucidated underlying mechanism. The results suggested alleviated pathological changes hearts diabetic mice, ameliorated cytopathological morphology cardiomyocytes, reduced cell death rate, inhibited expression ERS‐related proteins mRNA. agonist activities glucose‐regulated protein 78 (GRP78). Furthermore, opposite under inhibitor. knockdown was siRNA‐SIRT1 transfection, degree GRP78 acetylation increased. Cumulatively, inhibiting ERS upregulating expression.

Язык: Английский

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