The multiple roles of interferon regulatory factor family in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 9, 2024

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores diverse functions nine mammalian IRF members, each featuring conserved domains essential for interactions with other factors cofactors. These allow IRFs to modulate broad spectrum processes, encompassing host defense, response, cell development. Conversely, their pivotal role in regulation implicates them pathophysiology various diseases, such as infectious autoimmune disorders, metabolic cancers. In this context, display dichotomous nature, functioning tumor suppressors promoters, contingent upon specific disease milieu. Post-translational modifications IRFs, including phosphorylation ubiquitination, play crucial modulating function, stability, activation. As prospective biomarkers therapeutic targets, present promising opportunities intervention. Further research is needed elucidate precise mechanisms governing regulation, potentially pioneering innovative strategies, particularly cancer treatment, where equilibrium activities paramount importance.

Language: Английский

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Role of macrophage polarization in heart failure and traditional Chinese medicine treatment

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 18, 2024

Heart failure (HF) has a severe impact on public health development due to high morbidity and mortality is associated with imbalances in cardiac immunoregulation. Macrophages, major cell population involved immune response inflammation, are highly heterogeneous polarized into M1 M2 types depending the microenvironment. macrophage releases inflammatory factors chemokines activate remove harmful substances, while anti-inflammatory inhibit overactive promote tissue repair. restrict each other maintain homeostasis. The dynamic balance of closely related Traditional Chinese Medicine (TCM) yin-yang theory, imbalance yin yang will result pathological state organism. Studies have confirmed that TCM produces positive effects HF by regulating polarization. This review describes critical role polarization fibrosis, angiogenesis electrophysiology course HF, as well potential mechanism regulation preventing treating thereby providing new ideas for clinical treatment scientific research design HF.

Language: Английский

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Navigating the Landscape of Coronary Microvascular Research: Trends, Triumphs, and Challenges Ahead

Reviews in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 25(8)

Published: Aug. 16, 2024

Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the microcirculation that impair myocardial perfusion. CMD plays a pivotal role in numerous cardiovascular diseases, including ischemia with non-obstructive coronary arteries, heart failure, acute syndromes. This review summarizes recent advances pathophysiology, assessment, treatment strategies, as well ongoing challenges future research directions. Signaling pathways implicated pathogenesis include adenosine monophosphate-activated protein kinase/Krüppel-like factor 2/endothelial nitric oxide synthase (AMPK/KLF2/eNOS), nuclear erythroid 2-related 2/antioxidant response element (Nrf2/ARE), Angiotensin II (Ang II), endothelin-1 (ET-1), RhoA/Rho kinase, insulin signaling. Dysregulation these leads endothelial dysfunction, hallmark CMD. Treatment strategies aim reduce oxygen demand, improve microcirculatory function, restore homeostasis through mechanisms vasodilation, anti-inflammation, antioxidant effects. Traditional Chinese medicine (TCM) compounds exhibit therapeutic potential multi-targeted actions. Small molecules regenerative approaches offer precision therapies. However, remain translating findings clinical practice developing effective pharmacotherapies. Integration engineering microfabrication, tissue AI presents opportunities advance diagnosis, prediction,

Language: Английский

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Cardioprotective Effects of Jiming Formula on Improving Myocardial Metabolism in Mice with Myocardial Infarction Via the Ampk/Sirt1/Pgc-1α Pathway

Published: Jan. 1, 2025

Background: Heart failure remains a leading cause of morbidity and mortality worldwide. Mitochondrial dysfunction is an important pathological characteristic heart failure. Abnormal energy metabolism closely related to the progression prognosis failure, regulating myocardial has become attractive treatment strategy for managing Jiming Formula (JMF), as traditional Chinese medicine Formula, been proven be effective in treating clinical practice.Purpose: This study integrated targeted-metabolomics transcriptomics investigate cardioprotective properties JMF against MI underlying molecular mechanism mice.Method: We initially established UHPLC-QTRAP-MS/MS method analyzing components. The protective effects mice were further identified using echocardiography, hematoxylin eosin (HE) staining, Masson Wheat Germ Aglutinin (WGA) staining. Differential genes expression detected technology, cardiac metabolites quantified LC-ESI-MS/MS system. morphology function evaluated transmission electron microscopy ATP assays. Finally, western blot immunofluorescence used on AMPK/SIRT 1/PGC-1 α signaling pathway.Results: A total 191 40 components aqueous extract rat plasma, ensuring quality JMF. improved survival rates quantitative manner, reduced adverse remodeling mitochondrial damage. protected cardiomyocytes from apoptosis hypertrophy. Transcriptomics analysis showed improvement Tricarboxylic Acid cycle (TCA) mice. Targeted-metabolomics was applied subsequently, revealed that substrate content various pathways glucose metabolism. also poor metabolic cardiomyocytes, enhanced aerobic oxidation production. Enzyme assays increased activity key glycolytic enzymes respiratory complex I IV. Furthermore, activated AMPK/SIRT1/PGC-1 pathway, resulting upregulation GLUT4, PKM2, CPT1A PPAR-α protein levels, while reducing GLUT1 level.Conclusion: provides new perspective with JMF, which may activation AMPK/SIRT1/PGC-1α pathway respiration capacity. These results provide valuable insights into pharmacological mechanisms offering alternative options ischemic cardiovascular diseases.

Language: Английский

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Morus alba L. alleviates influenza viral pneumonia. Evidences of its mechanism of action

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156574 - 156574

Published: Feb. 27, 2025

Language: Английский

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Understanding Acute Coronary Syndrome from the Perspective of Traditional Chinese Medicine

IntechOpen eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

This chapter delves into the understanding of acute coronary syndrome (ACS) from perspective traditional Chinese medicine (TCM). It starts with different thinking frameworks and Western emphasizes holistic concepts “balance,” “harmony,” “regulation” in TCM. explores multiple causes ACS, including internal external factors such as dysfunction organs, wrong emotions, disharmony daily life. The four diagnostic methods TCM provide a comprehensive assessment that goes beyond symptoms captures underlying imbalances pathogenic factors. principles treatment prioritize maintaining balance Yin Yang. focuses on restoring enhancing body’s ability to heal itself through health cultivation, regular diet, life, exercise. acknowledges limitations emergency situations argues for holistic, individualized approach managing ACS by combining medicine. fusion modern science holds great promise creating more effective healthcare system future. also makes people think scientific level about shift behind it.

Language: Английский

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Cardioprotective Effects of the Jiming Formula on Myocardial Metabolism in Mice with Myocardial Infarction via the AMPK/SIRT1/PGC-1α Pathway

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156727 - 156727

Published: April 1, 2025

Language: Английский

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GTS-21 alleviates sepsis-induced atrial fibrillation susceptibility by modulating macrophage polarization and Neuregulin-1 secretion

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 154, P. 114561 - 114561

Published: April 7, 2025

Sepsis-induced atrial fibrillation (AF) is driven by systemic inflammation and macrophage-mediated remodeling, with proinflammatory M1 macrophages playing a key role. This study investigates whether GTS-21, an α7nAChR agonist, can reduce AF susceptibility promoting macrophage polarization towards the anti-inflammatory M2 phenotype. A mouse model of lipopolysaccharide (LPS) (10 mg/kg)-induced sepsis was used to explore relationship between AF. GTS-21 (20 mg/kg) administered assess its impact on 48-h survival incidence. Cardiac function evaluated using echocardiography. Markers myocardial injury, including CK-MB, LDH, cTnI, were measured. Macrophage assessed immunofluorescence, flow cytometry, RT-qPCR, western blotting. Oxidative stress mitochondrial reactive oxygen species (ROS) measurements, electron microscopy, protein expression analysis. Calcium dynamics studied blotting confocal microscopy. In LPS-induced septic mice, improved rates reduced induction rate duration (P < 0.05). Echocardiography showed preserved left ventricular ejection fraction enhanced diastolic function. Mechanistically, it promoted polarization, inhibited NF-κB P65/NLRP3/C-caspase 1 pathway IL-1β release, alleviated oxidative stress. Additionally, structure restored reversing fission fusion, while calcium-handling proteins (NCX-1, RYR2, SERCA2a) regulated prevent intracellular calcium overload, reducing susceptibility. mitigated incidence in mice regulating stress, preserving cardiomyocytes. These findings highlight therapeutic potential treating sepsis-induced

Language: Английский

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The interplay between T lymphocytes and macrophages in myocardial ischemia/reperfusion injury

Molecular and Cellular Biochemistry, Journal Year: 2023, Volume and Issue: 479(8), P. 1925 - 1936

Published: Aug. 4, 2023

Language: Английский

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Shexiang Tongxin dropping pills protect against ischemic stroke-induced cerebral microvascular dysfunction via suppressing TXNIP/NLRP3 signaling pathway

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 322, P. 117567 - 117567

Published: Dec. 19, 2023

Patients with ischemic stroke (IS) often continue to exhibit cerebral microcirculatory dysfunction even after receiving thrombolytic therapy. Enhancing the function of microvascular endothelia represents a pivotal advancement in therapeutic strategy for disturbances. A traditional Chinese medicinal formulation named Shexiang Tongxin Dropping Pills (STDP), has been clinically employed ameliorate abnormalities. Existing literature attests beneficial role STDP on endothelial cells (ECs). Nevertheless, specific impacts and underlying mechanisms rectifying IS-induced warrant further exploration. This investigation seeks delineate effects damage induced by elucidate mechanism involved. Middle artery occlusion reperfusion (MCAO/R) technique was established model mice. The efficacy assessed through laser speckle contrast imaging, behavioral assays, histological evaluations. Biochemical markers brain tissue, including GSH, SOD, MDA, ROS, were quantified using assay kits. In vitro study, oxygen-glucose deprivation (OGD/R) performed bEnd.3 cells. cytoprotective potential then evaluated measuring cell viability, LDH activity, permeability, oxidative stress parameters. Important targets critical pathway verified immunoblotting immunofluorescence both mice slices decrease infarct size, repaired blood flow attenuated neurological deficiency MCAO/R Moreover, abolished MCAO/R-induced which reflected rescuing GSH content, restoration SOD activity T-AOC, reduction MDA ROS. Ex vivo, increased decreased their permeability ODG/R. Mechanistically, significantly suppressed ROS-TXNIP mediated activation NLRP3 inflammasome vivo vitro. improves stroke-induced deficits regulating ROS/TXNIP/NLRP3 signaling pathway.

Language: Английский

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