Pentacyclic triterpenes, potential novel therapeutic approaches for cardiovascular diseases.

Cardiovascular diseases (CVDs) involve dysfunction of the heart and blood vessels and have become major health concerns worldwide. Multiple mechanisms may be involved in the occurrence and development of CVDs. Although therapies for CVDs are constantly being developed and applied, the incidence and mortality of CVDs remain high.

The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD.

Metabolic-associated fatty liver disease (MAFLD) is a globally prevalent chronic hepatic disease. Previous studies have indicated that the activation of the signal transducer and activator of transcription3 (STAT3) plays a vital role in MAFLD progression at the very beginning. However, the specific association between STAT3 and abnormal hepatic metabolism remains unclear.

Network pharmacology and molecular docking analysis on Shenfu Qiangxin indicate mTOR is a potential target to treat heart failure.

Background: Heart failure (HF) is one of the major causes of mortality worldwide with high recurrence rate and poor prognosis. Our study aimed to investigate potential mechanisms and drug targets of Shenfu Qiangxin (SFQX), a cardiotonic-diuretic traditional Chinese medicine, in treating HF.

Methods: An HF-related and SFQX-targeted gene set was established using disease-gene databases and the Traditional Chinese Medicine Systems Pharmacology database.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

Ethnopharmacological Relevance: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated.

Aim Of The Study: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation.

Unraveling the Intricate Network of lncRNAs in Corneal Epithelial Wound Healing: Insights Into the Regulatory Role of linc17500.

Purpose: Epigenetic mechanisms orchestrate a harmonious process of corneal epithelial wound healing (CEWH). However, the precise role of long non-coding RNAs (lncRNAs) as key epigenetic regulators in mediating CEWH remains elusive. Here, we aimed to elucidate the functional contribution of lncRNAs in regulating CEWH.

Involvement of plasminogen activator inhibitor-1 in p300/p53-mediated age-related atrial fibrosis.

Plasminogen activator inhibitor-1 (PAI-1), a key regulator of the fibrinolytic system, is also intimately involved in the fibrosis. Although PAI-1 may be involved in the occurrence of atrial fibrillation (AF) and thrombosis in the elderly, but whether it participated in aging-related atrial fibrosis and the detailed mechanism is still unclear. We compared the transcriptomics data of young (passage 4) versus senescent (passage 14) human atrial fibroblasts and found that PAI-1 was closely related to aging-related fibrosis.

IL-6/gp130/STAT3 signaling contributed to the activation of the PERK arm of the unfolded protein response in response to chronic β-adrenergic stimulation.

Prolonged activation of the PERK branch of the unfolded protein response (UPR) promotes cardiomyocytes apoptosis in response to chronic β-adrenergic stimulation. STAT3 plays a critical role in β-adrenergic functions in the heart. However, whether STAT3 contributed to β-adrenoceptor-mediated PERK activation and how β-adrenergic signaling activates STAT3 remains unclear.

Sacubitril/valsartan reduces susceptibility to atrial fibrillation by improving atrial remodeling in spontaneously hypertensive rats.

Aim: Sacubitril/valsartan (Sac/Val, LCZ696), the world's first angiotensin receptor-neprilysin inhibitor (ARNi), has been widely used in the treatment of heart failure. However, the use of Sac/Val in the treatment of atrial fibrillation (AF), especially AF with hypertension, has been less reported. We investigated the effect of Sac/Val on atrial remodeling and hypertension-related AF.

Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice.

Notopterol is a naturally occurring furanocoumarin compound found in the root of Notopterygium incisum. Hyperuricemia involves the activation of chronic inflammation and leads to cardiac damage. Whether notopterol has cardioprotective potential in hyperuricemia mice remains elusive.

STAT3 signaling promotes cardiac injury by upregulating NCOA4-mediated ferritinophagy and ferroptosis in high-fat-diet fed mice.

High-fat diet (HFD) intake provokes obesity and cardiac anomalies. Recent studies have found that ferroptosis plays a role in HFD-induced cardiac injury, but the underlying mechanism is largely unclear. Ferritinophagy is an important part of ferroptosis that is regulated by nuclear receptor coactivator 4 (NCOA4).

Quantitative late gadolinium enhancement cardiac magnetic resonance analysis of the relationship between ablation parameter and left atrial tissue lesion following pulmonary vein isolation.

Background: The impact of ablation parameters on acute tissue lesion formation after pulmonary vein isolation (PVI) has not been sufficiently evaluated in patients with atrial fibrillation. Radiofrequency ablation lesion can be visualized by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). We sought to quantitatively analyze the relationship between ablation parameter and tissue lesion following PVI at different segments of pulmonary vein (PV) using LGE-CMR.

ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury.

Cuproptosis resulting from copper (Cu) overload has not yet been investigated in diabetic cardiomyopathy (DCM). Advanced glycosylation end products (AGEs) induced by persistent hyperglycemia play an essential role in cardiotoxicity. To clarify whether cuproptosis was involved in AGEs-induced cardiotoxicity, we analyzed the toxicity of AGEs and copper in AC16 cardiomyocytes and in STZ-induced or db/db-diabetic mouse models.

Efficiency and safety of high-power ablation guided by Lesion size index: An ex vivo porcine heart study.

Background: Although Lesion size index (LSI) has been reported to highly predict radiofrequency lesion size in vitro, its accuracy in lesion size and steam pop estimation has not been well investigated for every possible scenario.

Methods: Initially, radiofrequency ablations were performed on porcine myocardial slabs at various power, CF, and time settings with blinded LSI. Subsequently, radiofrequency power at 20, 30, 40, 50, and 60 W was applied at CF values of 5, 10, 20, and 30 g to reach target LSIs of 4, 5, 6, and 7.

Acetyltransferase p300 regulates atrial fibroblast senescence and age-related atrial fibrosis through p53/Smad3 axis.

Atrial fibrosis induced by aging is one of the main causes of atrial fibrillation (AF), but the potential molecular mechanism is not clear. Acetyltransferase p300 participates in the cellular senescence and fibrosis, which might be involved in the age-related atrial fibrosis. Four microarray datasets generated from atrial tissue of AF patients and sinus rhythm (SR) controls were analyzed to find the possible relationship of p300 (EP300) with senescence and fibrosis.

Anti-angiogenic properties of microRNA-29a in preclinical ocular models.

Abnormal neovascularization is an important cause of blindness in many ocular diseases, for which the etiology and pathogenic mechanisms remain incompletely understood. Recent studies have revealed the diverse roles of noncoding RNAs in various biological processes and facilitated the research and development of the clinical application of numerous RNA drugs, including microRNAs. Here, we report the antiangiogenic activity of microRNA-29a (miR-29a) in three animal models of ocular neovascularization.

Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice.

Diabetic cardiomyopathy (DCM) is a severe complication of diabetes mellitus that is characterized by aberrant myocardial structure and function and is the primary cause of heart failure and death in diabetic patients. Endothelial dysfunction plays an essential role in diabetes and is associated with an increased risk of cardiovascular events, but its role in DCM is unclear. Previously, we showed that S-nitroso-L-cysteine(CSNO), an endogenous S-nitrosothiol derived from eNOS, inhibited the activity of protein tyrosine phosphatase 1B (PTP1B), a critical negative modulator of insulin signaling.

Cirsiliol regulates mitophagy in colon cancer cells via STAT3 signaling.

Background: Mitophagy is a type of selective autophagy for dysfunctional mitochondria and plays a key role in tumorigenesis and cancer progression. However, whether mitophagy plays a role in colon cancer remains unclear. Cirsiliol is a natural product and has been found to exert anti-cancer effects in multiple tumors.

Preexisting Cardiovascular Risk Factors and Coronary Artery Atherosclerosis in Patients with and without Cancer.

Cancer survivors suffer a higher risk of coronary artery atherosclerosis (CAA). Whether cancer patients had increased baseline CAA burden prior to cardiotoxic therapy remains unclear. We conducted a case-control study, and 286 consecutive patients were finally included.

IL-6/STAT3 Signaling Promotes Cardiac Dysfunction by Upregulating FUNDC1-Dependent Mitochondria-Associated Endoplasmic Reticulum Membranes Formation in Sepsis Mice.

Aims: Cytokine storm is closely related to the initiation and progression of sepsis, and the level of IL-6 is positively correlated with mortality and organ dysfunction. Sepsis-induced myocardial dysfunction (SIMD) is one of the major complications. However, the role of the IL-6/STAT3 signaling in the SIMD remains unclear.

Shikonin suppresses colon cancer cell growth and exerts synergistic effects by regulating ADAM17 and the IL‑6/STAT3 signaling pathway.

Signal transducer and activator of transcription 3 (STAT3) activation is associated with drug resistance induced by anti‑epidermal growth factor receptor (anti‑EGFR) therapy in the treatment of colon cancer. Thus, the combined inhibition of EGFR and STAT3 may prove beneficial for this type of cancer. STAT3 has been proven to play a critical role in colon cancer initiation and progression, and is considered the primary downstream effector driven by interleukin‑6 (IL‑6).

Connexin 43 participates in atrial electrical remodelling through colocalization with calcium channels in atrial myocytes.

Atrial fibrillation (AF) is associated with atrial conduction disturbances caused by electrical and/or structural remodelling. In the present study, we hypothesized that connexin might interact with the calcium channel through forming a protein complex and, then, participates in the pathogenesis of AF. Western blot and whole-cell patch clamp showed that protein levels of Cav1.

Activation of PKCα participates in the reduction of Ikur in atrial myocytes induced by tumour necrosis factor-α.

The atrial-specific ultra-rapid delayed rectifier K current (Ikur) plays an important role in the progression of atrial fibrillation (AF). Because inflammation is known to lead to the onset of AF, we aimed to investigate whether tumour necrosis factor-α (TNF-α) played a role in regulating Ikur and the potential signalling pathways involved. Whole-cell patch-clamp and biochemical assays were used to study the regulation and expression of Ikur in myocytes and in tissues from left atrial appendages (LAAs) obtained from patients with sinus rhythm (SR) or AF, as well as in rat cardiomyocytes (H9c2 cells) and mouse atrial myocytes (HL-1 cells).

MicroRNA-184 negatively regulates corneal epithelial wound healing via targeting , , and .

Background: MicroRNAs (miRNAs) play critical roles in corneal development and functional homeostasis. Our previous study identified miR-184 as one of the most highly expressed miRNAs in the corneal epithelium. Even though its expression level plummeted dramatically during corneal epithelial wound healing (CEWH), its precise role in mediating corneal epithelial renewal was unresolved.

MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A.

Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mouse model of oxygen-induced proliferative retinopathy (OIR).