Vortioxetine’s Therapeutic Potential: Cardiac Responses to Chronic Unpredictable Mild Stress in a Rat Model

Arquivos Brasileiros de Cardiologia, Год журнала: 2025, Номер 122(2)

Опубликована: Янв. 1, 2025

Abstract Background Stress arises in response to threats or challenges, affecting both physical and mental health. While its harmful effects on the heart are widely recognized, cellular-level investigations remain limited. Antidepressants, including vortioxetine (VOR), known impact cardiovascular system. VOR, used treat major depressive disorder, is considered a promising option for patients with disease due anti-inflammatory antioxidant properties, which may reduce cardiac damage. Objectives This study aimed assess of chronic unpredictable mild stress (CUMS) rat hearts evaluate VOR’s potential protective against stress-induced Methods Twenty-eight male Wistar Albino rats were divided into four groups. The CUMS group experienced random daily 6 weeks, while CUMS+VOR received VOR treatment alongside stress. control groups not exposed Heart samples examined histopathologically immunohistochemically. Results showed increased hyperemia, hemorrhage, edema, vacuolar degeneration, mononuclear cell infiltrations, reduced troponin IL-10 caspase-3 NF-κB expressions compared (p≤0.001). improved these findings, normalizing histopathological immunohistochemical results. Conclusions caused significant damage rats, by alleviating pathological changes.

Язык: Английский

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Ferroptosis, a Regulated Form of Cell Death, as a Target for the Development of Novel Drugs Preventing Ischemia/Reperfusion of Cardiac Injury, Cardiomyopathy and Stress-Induced Cardiac Injury

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 897 - 897

Опубликована: Янв. 11, 2024

The hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is about 6% and has not decreased recent years. leading cause of death these ischemia/reperfusion (I/R) cardiac injury. It quite obvious that there an urgent need to create new drugs for the treatment STEMI based on knowledge pathogenesis I/R injury, particular, molecular mechanism ferroptosis. In this study, it was demonstrated ferroptosis involved development antitumor drug-induced cardiomyopathy, diabetic septic inflammation. There indirect evidence participates stress-induced activation AMPK, PKC, ERK1/2, PI3K, Akt prevents inhibition HO-1 alleviates roles GSK-3β NOS regulation require further study. stimulation Nrf2, STAT3 TLR4 NF-κB promotes cardiomyocytes. MiR-450b-5p miR-210-3p can increase tolerance cardiomyocytes hypoxia/reoxygenation through Circ_0091761 RNA, miR-214-3p, miR-199a-5p, miR-208a/b, miR-375-3p, miR-26b-5p miR-15a-5p aggravate

Язык: Английский

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The Multifaceted Role of Endothelial Sirt1 in Vascular Aging: An Update

Cells, Год журнала: 2024, Номер 13(17), С. 1469 - 1469

Опубликована: Сен. 1, 2024

NAD+-dependent deacetylase sirtuin-1 (Sirt1) belongs to the sirtuins family, known be longevity regulators, and exerts a key role in prevention of vascular aging. By aging, expression levels Sirt1 decline with severe impact on function, such as rise endothelial dysfunction, which turn promotes development cardiovascular diseases. In this context, activity preventing senescence is particularly important. Given counteracting senescence, great efforts have been made deepen knowledge about intricate cross-talks interactions other molecules, order set up possible strategies boost prevent or treat The aim review provide proper background regulation function endothelium discuss recent advances regarding therapeutic targeting counteract

Язык: Английский

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NF-κB-Specific Suppression in Cardiomyocytes Unveils Aging-Associated Responses in Cardiac Tissue

Biomedicines, Год журнала: 2025, Номер 13(1), С. 224 - 224

Опубликована: Янв. 17, 2025

Background/Objectives: Aging is associated with structural and functional changes in the heart, including hypertrophy, fibrosis, impaired contractility. Cellular mechanisms such as senescence, telomere shortening, DNA damage contribute to these processes. Nuclear factor kappa B (NF-κB) has been implicated mediating cellular responses aging tissues, increased NF-κB expression observed hearts of rodents. Therefore, suspected play an important regulatory role molecular processes occurring heart during aging. This study investigates vivo aging-related cardiac alterations, focusing on senescence events. Methods: Young old wild-type (WT) transgenic male mice cardiomyocyte-specific suppression (3M) were used assess function, morphology, markers, lipofuscin deposition, damage, apoptosis. Results: Kaplan–Meier analysis revealed reduced survival 3M compared WT. Echocardiography showed evidence eccentric both diastolic systolic dysfunction mice. Both aged WT exhibited more pronounced hypertrophic cardiomyocytes from Additionally, senescence-associated β-galactosidase activity, p21 protein expression, (marked by phosphorylated H2A.X) elevated young Conclusions: The leads remodeling, dysfunction, process. These findings suggest that plays a critical aging, influencing pathways. implications for development therapeutic strategies aimed at mitigating age-related cardiovascular diseases.

Язык: Английский

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The role of the transcription factor NF-kB in the pathogenesis of inflammation and carcinogenesis. Modulation capabilities

Pharmacia, Год журнала: 2025, Номер 72, С. 1 - 13

Опубликована: Фев. 20, 2025

The nuclear factor kappa B (NF-kB) signaling module is a complex and highly interconnected molecular network with important functions in all nucleated cells. Most chronic diseases caused by lifestyle factors appear to be related inflammation. NF-kB plays major role the pathogenesis of inflammation its intimate mechanism. This transcription participates evolution diabetes complications. In T1D (Type 1 Diabetes), proinflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis (TNF), CD40L secreted immune cells islets induce activation β-cells through both canonical noncanonical roads. increases expression genes, including TNF-α, IL-1β, IL-6, MCP-1, ICAM-1, that initiate promote atherosclerosis. particular, severity lethality acute lung injury or respiratory distress syndrome (ALI/ARDS) pneumonia sepsis primarily associated an NF-kB-mediated “cytokine storm,” which massive polymorphonuclear (PMN) extravasation subsequent release cause rapid deterioration due widespread coagulation. Nuclear translocation p65 can several genes involved induction EMT (epithelial-to-mesenchymal transition). has been confirmed various types cancer, brain, breast, lung, gastric cancer. Cutaneous T-cell lymphoma (CTCL) encompasses group lymphoproliferative disorders characterized invasive neoplastic T skin clinical prognoses. early stages CTCL, cell proliferation are stimulated autocrine production TNFα, leading increased resistance apoptosis. Bladder cancer second most common genitourinary often recurrent and/or chemoresistant after resection. critical normal physiology bladder patients have pathologically active induced cytokines, chemokines, hypoxia, enhancing carcinogenesis progression disease.

Язык: Английский

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The chemical composition analysis of Yixin Tongmai Granules using UHPLC-MS/MS and exploration of its potential mechanism in treatment of coronary artery disease based on network pharmacology and molecular docking

Medicine, Год журнала: 2025, Номер 104(8), С. e41620 - e41620

Опубликована: Фев. 21, 2025

Yixin Tongmai Granules (YTG) is a popular Chinese herbal granules for the treatment of coronary artery disease (CAD), but its molecular pharmacological mechanism still unclear. This article explores CAD from perspective network pharmacology. We analyzed chemical composition YTG using UHPLC-MS/MS and identified 131 ingredients. The relative drug content 33 ingredients exceeded 0.5%. These were further screened SwissADME platform with ADME criteria. Using HIT database SwissTargetPrediction platform, high probability targets these generated. Venn Diagram, 96 effective associated identified, involving 14 core study imported into STRING obtained through topology analysis: TP53, STAT3, transcription factor Jun, MAPK3, MAPK1, AKT1, SRC, MYC, BCL2, p65, TNF, ESR2. Then enrichment analysis Metascape indicated that, in system anti-CAD, principal pathways are “Lipid Atherosclerosis”, “Pathways cancer”, “AGE-RAGE signaling pathway diabetic complications.” Next, affinities between their examined individually docking. Finally, based on deep mining PubMed literature, this investigated relationship each target CAD, ingredients, inferred main YTG, namely Tanshinone IIA, Cryptotanshinone, Caffeic acid, Denshensu, Ononin, Formononetin.

Язык: Английский

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Social Determinants of Health in Cardio-Oncology

JACC CardioOncology, Год журнала: 2024, Номер 6(3), С. 331 - 346

Опубликована: Май 7, 2024

Addressing the need for more equitable cardio-oncology care requires attention to existing disparities in cardio-oncologic disease prevention and outcomes. This is particularly important among those affected by adverse social determinants of health (SDOH). The intricate relationship SDOH, cancer diagnosis, outcomes from cardiotoxicities associated with oncologic therapies influenced sociopolitical, economic, cultural factors. Furthermore, mechanisms cell signaling epigenetic effects on gene expression link SDOH CVD-related complications therapies. To mitigate these disparities, a multifaceted strategy needed that includes access, policy, community engagement improved screening management. Interdisciplinary teams must also promote humility competency leverage new technology foster collaboration addressing impact

Язык: Английский

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Inflammaging, immunosenescence, and cardiovascular aging: insights into long COVID implications

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 11

Опубликована: Июнь 26, 2024

Aging leads to physiological changes, including inflammaging-a chronic low-grade inflammatory state with significant implications for various systems, particularly cardiovascular health. Concurrently, immunosenescence-the age-related decline in immune function, exacerbates vulnerabilities pathologies older individuals. Examining the dynamic connections between immunosenescence, inflammation, and aging, this mini-review aims disentangle some of these interactions a better understanding their complex interplay. In context associated inflammaging compromises vascular integrity contributing atherosclerosis, endothelial dysfunction, arterial stiffening, hypertension. The aging system's amplifies oxidative stress, fostering an environment conducive atherosclerotic plaque formation. Noteworthy markers, such as high-sensitivity C-reactive protein, interleukin-6, interleukin-1β, interleukin-18, tumor necrosis factor-alpha emerge key players triggering signaling pathways intensifying immunosenescence. review we aim explore molecular cellular mechanisms underlying shedding light on nuanced contributions diseases. Furthermore, reciprocal relationship immunosenescence inflammaging, revealing self-reinforcing cycle that intensifies risks. This opens avenues potential therapeutic targets break mitigate dysfunction address Long COVID, introducing additional layer complexity Our stimulate continued exploration advance our within realm

Язык: Английский

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Impact of the environmental pollution on cardiovascular diseases: From epidemiological to molecular evidence

Heliyon, Год журнала: 2024, Номер 10(18), С. e38047 - e38047

Опубликована: Сен. 1, 2024

Язык: Английский

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Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis

Antioxidants, Год журнала: 2024, Номер 13(2), С. 232 - 232

Опубликована: Фев. 14, 2024

Atherosclerosis is a multifactorial disease of medium and large arteries, characterized by the presence lipid-rich plaques lining intima over time. It main cause cardiovascular diseases death worldwide. Redox imbalance lipid peroxidation could play key roles in atherosclerosis promoting bundle responses, including endothelial activation, inflammation, foam cell formation. The oxidation polyunsaturated fatty acids generates various products such as reactive carbonyl species (RCS), 4-hydroxy alkenals, malondialdehyde, acrolein. RCS covalently bind to nucleophilic groups nucleic acids, phospholipids, proteins, modifying their structure activity leading progressive dysfunction. Protein lipoxidation non-enzymatic post-translational modification proteins RCS. Low-density lipoprotein (LDL) apolipoprotein B (apoB) major role Moreover, oxidized LDLs are source RCS, which form adducts on huge number depending oxidative stress intensity, nature targets, availability detoxifying systems. Many systems affected lipoxidation, extracellular matrix components, membranes, cytoplasmic cytoskeletal transcription factors, other components. mechanisms involved lipoxidation-induced vascular dysfunction not fully elucidated. In this review, we focus protein during atherogenesis.

Язык: Английский

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