Search Results (2,942)

Algal carotenoids play a promising role in handling chronic diseases due to their diverse bioactive properties, including anti-inflammatory, antioxidant, and anticancer effects. This study assesses the activity of the antioxidant xanthophyll diatoxanthin (Dt), derived from marine diatoms, against triple-negative breast cancer (TNBC) cells using in vitro models, gene expression evaluation, and explores its role in potentiating the cytotoxic effect of chemotherapy. Dt exhibited selective activity against MDA-MB-231 and BT-549 TNBC cells at concentrations ≥12.5 ng/mL, with maximal effects observed at 25 ng/mL while sparing human umbilical vein endothelial cells (HUVECs) at these doses. When combined with doxorubicin (0.1–0.5 μM), Dt enhanced the anti-tumor efficacy in both TNBC cell lines, further reducing cell viability compared with doxorubicin alone (p < 0.05–0.001). Dt also exerted its activity in inhibiting migration and chemotaxis by approximately 30–50% compared with the controls (p < 0.01) and suppressing 3D-tumor spheroid growth at day 12 (up to >50% reduction, p < 0.001). Notably, secretome analysis revealed Dt-induced changes in inflammatory, oxidative and angiogenic mediators, highlighting its ability to modulate the TNBC microenvironment. Dt also downregulated key pro-survival, pro-angiogenic and pro-tumorigenic genes in both TNBC cell lines, supporting its role in disrupting oncogenic pathways. Angiogenesis-related genes were significantly reduced. Dt also decreased the expression of angiogenic mediators in HUVECs, supporting Dt’s role in inhibiting tumor vascularization. Results on gene expression regulation were also confirmed by RNA-Seq analysis. These findings pose Dt as a promising chemopreventing candidate in the challenging fight against TNBC, a well-known type of cancer that is aggressive and resistant to conventional therapies, targeting critical pathways for tumor survival, such as inflammation, angiogenesis, tumor cell growth, and cell migration. Given its selective activity against TNBC cells, ability to enhance chemotherapy efficacy, and modulation of the tumor microenvironment, Dt holds promise as a complementary drug for cancer prevention and interception. Future studies should focus on validating these effects in vivo and exploring Dt’s potential in combinatorial treatment strategies for cancer. Full article

Background: Cardiogenic shock (CS) and post-cardiac arrest syndrome (PCAS) are frequently associated with a systemic inflammatory response resulting from ischemia–reperfusion injury, endothelial dysfunction, and microcirculatory impairment. This inflammatory biology may be further amplified by temporary mechanical circulatory support (tMCS) through blood–surface interactions and shear-related hemolysis. Extracorporeal cytokine adsorption has therefore been proposed as an adjunctive strategy to attenuate hyperinflammation and facilitate shock reversal in selected patients. Methods: We conducted a narrative review, guided by a targeted PubMed and Scopus search and reference screening, to summarize the current pathophysiological concepts and clinical evidence on extracorporeal cytokine adsorption in CS-, PCAS-, and tMCS-supported states. Results: Across porous polymer hemoadsorption cartridges (e.g., CytoSorb^®), membrane-based or hybrid filters with adsorptive properties (e.g., oXiris^®), and selective approaches targeting inflammatory mediators (e.g., PentraSorb^® CRP), available studies most consistently report short-term physiological effects, including reduced vasopressor demand, improved metabolic stabilization, and modulation of inflammatory markers. However, evidence of benefits to clinically relevant endpoints remains inconsistent in various clinical settings, and randomized data are limited. Conclusions: Extracorporeal cytokine adsorption is a biologically plausible adjunct in inflammation-driven acute cardiovascular syndromes, but current evidence does not support routine use. Phenotype-guided patient selection, early timing, and adequately powered, mechanism-informed randomized trials are required to define clinical efficacy and safety in defined patient populations. Full article

Myocardial and vascular injury secondary to SARS-CoV-2 infection and vaccination has emerged as a clinically relevant phenomenon, with distinct but overlapping mechanisms. Myocardial injury in COVID-19 results from a complex interplay between direct viral effects and immune-mediated inflammation, supported by histopathological studies revealing macrophage-rich infiltrates, microthrombosis, and supporting fibrosis in isolated areas. In contrast, vaccine-associated myocarditis—reported predominantly following mRNA vaccines—has a self-limiting clinical course, with mechanisms likely involving molecular mimicry, aberrant immune activation, or hypersensitivity reactions, although these pathways require further validation. Although mRNA vaccines have been associated with a small increase in myocarditis, particularly in young men, the risk is significantly lower than that associated with COVID-19 infection, and the cardiovascular benefits of vaccination far outweigh these rare adverse events in most populations. After the end of the pandemic, the number of patients with severe forms of COVID-19 has decreased significantly, but we consider that cardiac involvement remains an important issue for the acute and long-term prognosis of patients with SARS-CoV-2 infection. Our paper synthesizes the latest epidemiological and mechanistic evidence on the link between COVID-19, vaccination, and myocardial and/or vascular injuries, highlighting the clinical implications and providing practical recommendations for management, as well as future perspectives on risk assessment, targeted immunotherapy, advanced diagnostic tools, and long-term monitoring. Full article

Background: Radiation therapy is a critical treatment modality for craniofacial tumors and metastatic lesions, particularly gliomas. While effective, it poses significant risks of neurotoxicity, which adversely affects patient quality of life. This review aims to explore the mechanisms underlying radiation-induced neurodegeneration (RIN) and its clinical implications, focusing on the interplay between radiation exposure, cognitive decline, and potential therapeutic strategies. Methods: A comprehensive literature review was conducted, analyzing studies on radiation effects on the central nervous system (CNS), including mechanisms of injury, clinical outcomes, and emerging therapeutic approaches. Key areas of interest included the role of inflammation, vascular damage, neurogenesis impairment, and genetic predispositions in the context of radiation therapy. Results: The findings indicate that radiation induces a complex cascade of neurobiological changes, including vascular injury, microglial activation, and neurogenesis dysfunction, leading to cognitive impairments. The severity of these effects is influenced by patient age, treatment regimens, and individual genetic factors. Additionally, emerging biomarkers in cerebrospinal fluid may provide insights into individual susceptibility to radiation-induced neurotoxicity. Therapeutic strategies such as neuroprotective agents, anti-inflammatory treatments, and advanced radiation techniques show promise in mitigating cognitive decline. Conclusions: Radiation-induced neurodegeneration is a multifaceted process with significant implications for patients undergoing radiation therapy. The underlying mechanisms include endothelial cell apoptosis leading to blood–brain barrier breakdown, chronic inflammation, and the destruction of neural progenitor cells in the hippocampus, which collectively trigger cognitive decline and progressive degeneration. A better understanding of these mechanisms is crucial for developing effective preventative and therapeutic strategies. Future research should focus on identifying high-risk patients and exploring innovative approaches to minimize cognitive impacts while maximizing the efficacy of radiation treatment. Full article

Maqui (Aristotelia chilensis) is a berry native to southern Chile, recognized for its high content of phenolic compounds, particularly delphinidin-type anthocyanins, which confer strong antioxidant and anti-inflammatory properties and have generated growing interest as a functional food. Its scientific relevance has increased due to advances in understanding its biological mechanisms, including the Nrf2 signaling pathway, modulation of systemic inflammation, improvement in mitochondrial function, and potential applications in cardiometabolic, renal, and vascular health. Objective: The objective of this study is to analyze the available evidence on maqui in relation to its nutritional composition, bioactive profile, antioxidant and anti-inflammatory mechanisms, bioavailability, and emerging clinical applications in the prevention and/or treatment of chronic non-communicable diseases. Main findings: Maqui is rich in delphinidins, dietary fiber, and antioxidant micronutrients and modulates key oxidative stress and inflammatory pathways, including Nrf2-HO-1 and NF-κB. Preclinical and early clinical evidence supports its cardiometabolic and nephroprotective effects, with improvements in glycemic control, lipid metabolism, oxidative stress, and endothelial function. Conclusions: Maqui shows considerable potential as a Chilean functional food with antioxidant and anti-inflammatory effects relevant to human health. However, robust clinical trials and formulations with enhanced bioavailability are required to consolidate its therapeutic application. Full article

Background: Salt-sensitive blood pressure (SSBP) represents a prevalent yet underrecognized hypertensive phenotype, in which blood pressure (BP) and volume status are disproportionately influenced by dietary sodium intake. Beyond BP elevation alone, salt sensitivity reflects a convergence of renal sodium handling abnormalities, neurohormonal activation, vascular dysfunction, and inflammatory pathways that link excessive sodium exposure to progressive kidney injury and adverse cardiac remodeling. Given its association with chronic kidney disease (CKD) and the association of heart failure with preserved ejection fraction (HFpEF), improved recognition of SSBP has direct clinical relevance. Objective: This narrative review aims to synthesize current mechanistic and clinical evidence on SSBP, focusing on pathophysiology, cardiorenal interactions, diagnostic challenges, and phenotype-guided therapeutic strategies with practical applicability. Methods: A narrative literature review was conducted using PubMed, Scopus, and Web of Science from inception through January 2026. Experimental, translational, and clinical studies, along with relevant guideline documents, were integrated to provide conceptual and clinical interpretation rather than quantitative analysis. Key Findings: Impaired renal sodium excretion, intrarenal RAAS activation, sympathetic overactivity, endothelial dysfunction, and immune-mediated inflammation contribute to sodium retention, microvascular dysfunction, and fibrotic remodeling across the kidney–heart axis. These pathways are strongly supported by experimental and translational data, but direct interventional clinical validation remains limited for several mechanisms. Clinically, salt-sensitive individuals often exhibit non-dipping BP patterns, albuminuria, salt-induced edema, and a predisposition to HFpEF. Dynamic BP monitoring combined with targeted laboratory assessment improves identification of this phenotype and supports individualized management. Conclusions: Early recognition of SSBP enables targeted interventions beyond uniform sodium restriction. Phenotype-guided strategies integrating lifestyle modification, RAAS blockade, thiazide-like diuretics, mineralocorticoid receptor antagonists, and sodium-glucose co-transporters 2 inhibitors (SGLT2i) may improve cardiorenal outcomes. Emerging precision tools (e.g., wearable blood-pressure sensors, digital sodium tracking technologies, etc.) remain exploratory but may further refine individualized management. Full article

Vitamin D, a fat-soluble secosteroid traditionally recognized for skeletal health, exerts pleiotropic effects on cardiovascular physiology and disease. Circulating 25-hydroxyvitamin D [25(OH)D], the principal biomarker of vitamin D status, is frequently suboptimal worldwide, particularly in older adults, individuals with darker skin pigmentation, and populations at higher latitudes. Observational studies consistently associate low 25(OH)D concentrations with increased risk of hypertension, atherosclerosis, myocardial infarction, heart failure, arrhythmias, stroke, and cardiovascular mortality. Mechanistic investigations have revealed that vitamin D modulates cardiomyocyte calcium handling, endothelial function, vascular smooth muscle proliferation, inflammation, oxidative stress, and renin–angiotensin–aldosterone system activity, establishing biologically plausible links to cardiovascular outcomes. Despite these associations, large randomized trials of vitamin D supplementation have failed to demonstrate reductions in major cardiovascular events, likely due to heterogeneity in baseline status, dosing regimens, intervention timing, genetic variability, and underlying comorbidities. Vitamin D may function more effectively as a biomarker of cardiovascular risk rather than a universal therapeutic agent, with deficiency reflecting systemic vulnerability rather than acting as a dominant causal factor. Emerging evidence supports precision approaches targeting individuals with severe deficiency, high renin activity, early endothelial dysfunction, or specific genetic profiles, potentially in combination with lifestyle or pharmacologic interventions. Future research should focus on defining optimal dosing strategies, intervention timing, and mechanistic biomarkers to identify subpopulations most likely to benefit, integrating vitamin D therapy into multifaceted cardiovascular prevention frameworks. This systematic review synthesizes molecular, observational, and clinical trial evidence, critically evaluating the current understanding of vitamin D in cardiovascular medicine and highlighting opportunities for targeted, personalized interventions. Vitamin D represents a complex, context-dependent modulator of cardiovascular health, offering both prognostic insight and potential therapeutic value when appropriately applied. Full article

Varicella-Zoster Virus (VZV) is one of the most important pathogens in ophthalmology. Reactivation may involve the adnexa (blepharoconjunctivitis, pseudomembranous conjunctivitis), cornea (dendritic keratitis, nummular and necrotizing stromal keratitis, disciform endotheliitis, neurotrophic ulcers, mucous-plaque keratitis) and sclera (episcleritis, anterior scleritis). Uveal inflammation ranges from anterior uveitis—with iris atrophy, trabeculitis-induced glaucoma and complicated cataract—to posterior necrotizing syndromes: acute retinal necrosis in immunocompetent hosts and progressive outer retinal necrosis in immunosuppressed patients, often complicated by occlusive vasculitis, macular edema, retinal detachment and phthisis. Optic nerve and cranial nerve involvement (optic neuritis, neuroretinitis, III/IV/VI palsies) and orbital inflammation may occur even without cutaneous signs (“zoster sine herpete”), making PCR-based intraocular diagnostics essential. Management relies on early, high-dose antivirals (acyclovir or valacyclovir), judicious corticosteroids and timely surgical intervention when required. Universal childhood varicella vaccination and recombinant zoster vaccination in adults ≥50 years have reduced VZV incidence and ocular complications in settings with high vaccine coverage, though rare post-vaccine keratitis or uveitis underscore the need for ongoing vigilance. In this review, we synthesize current knowledge on varicella-zoster virus ocular disease, with a focus on host–pathogen interactions that drive both injury and defense. Full article

Peripartum depression (PPD) represents one of the most prevalent and disabling psychiatric conditions among women, yet its underlying biology remains poorly integrated across medical disciplines. Emerging evidence highlights PPD as a prototypical disorder of the heart–brain axis, where neuroendocrine changes, immune activation, and cardiovascular dysregulation converge to shape maternal vulnerability. During pregnancy and the postpartum period, abrupt fluctuations in estrogen, progesterone (P4), and placental corticotropin-releasing hormone (CRH) interact with a sensitized hypothalamic–pituitary–adrenal (HPA) axis, altering neural circuits involved in mood regulation, stress reactivity, and maternal behavior. Parallel cardiovascular adaptations, including endothelial dysfunction, altered blood pressure variability, and reduced heart rate variability (HRV), suggest a profound perturbation of autonomic balance with potential long-term implications for maternal cardiovascular health. Neuroinflammation, microglial activation, and systemic cytokine release further mediate the bidirectional communication between the heart and the brain, linking emotional dysregulation with vascular and autonomic instability. Evidence also indicates that conditions such as preeclampsia and peripartum cardiomyopathy share biological pathways with PPD, reinforcing the concept of a unified pathophysiological axis. This review synthesizes current knowledge on the neurobiological, cardiovascular, endocrine, and inflammatory mechanisms connecting PPD to maternal heart–brain health, while discussing emerging biomarkers and therapeutic strategies aimed at restoring integrative physiology. Understanding PPD as a multisystem heart–brain disorder offers a transformative perspective for early detection, risk stratification, and personalized intervention during one of the most biologically vulnerable periods of a woman’s life. Full article

Neovascular diseases, such as neovascular ophthalmopathy, atherosclerosis, and tumors, are characterized by pathological angiogenesis, leading to the formation of leaky, tortuous, and immature blood vessels, often accompanied by chronic inflammation and tissue damage. Among the multiple drivers of angiogenesis in these conditions, the role of oxidized low-density lipoprotein (oxLDL) has garnered increasing attention. Formed from low-density lipoprotein (LDL) under oxidative stress, oxLDL acts as a cross-organ biomarker that systemically impacts multiple organs via the circulatory system, exerting a pivotal pro-angiogenic effect. This review focuses on elucidating the common molecular mechanisms by which oxLDL and its downstream lipid peroxidation products accumulate in disease-specific microenvironments. This accumulation activates inflammatory and oxidative stress pathways in macrophages and endothelial cells, modulating their functional reprogramming and thereby driving pathological neovascularization. Our aim is to provide an integrated framework for understanding the complex role of oxLDL as a cross-organ biomarker in multisystem neovascular diseases and to offer a theoretical basis for its potential as a therapeutic target. Full article

Cellular senescence is a permanent cell cycle arrest that plays a critical role in the development and pathogenesis of age-related diseases. This paper aims to present the biological mechanisms of cellular senescence and the role of the senescence-associated secretory phenotype (SASP) in the pathogenesis of atherosclerosis, as well as to discuss therapeutic strategies targeting senescent cells in cardiovascular diseases. Different types of cellular senescence are described, including replicative, stress-induced, and oncogene-induced senescence, along with the composition and regulation of SASP and its impact on chronic inflammation, endothelial dysfunction, vascular remodeling, and plaque destabilization. The involvement of senescent endothelial cells, vascular smooth muscle cells, and macrophages in the initiation and progression of atherosclerosis is also discussed. The paper reviews current research on senolytic and senomorphic therapies and highlights emerging approaches such as immunosenolytic and epigenetic interventions. The therapeutic potential of these strategies in reducing chronic vascular inflammation and improving plaque stability, as well as their limitations and challenges in clinical application, is emphasized. Full article

Long COVID-19 syndrome (or so-called post-COVID-19) is indicated by miscellaneous symptoms, usually starting 3 months from the COVID-19 infection and lasting for at least 2 months, which cannot be explained by an alternative diagnosis. There has been more and more reports addressing the audiovestibular dysfunction related to long COVID-19 syndrome. Emerging evidence suggests that the linkage between audiovestibular dysfunction and long COVID-19 syndrome might rely on (a) direct inner ear system damage related to viral invasion and consequent inflammation, (b) micro thromboembolic events, which might result from the COVID-19-induced autoimmune reaction against endothelial cells, and consequent transient-ischemia and hypoxia of the auditory pathways, (c) the disturbed nerve conduction in vestibulocochlear nerves due to viral invasion, and finally (d) altered auditory cortex function, either imbalanced central gain or neurotransmitter disturbance. However, most of the aforementioned mechanism remained hypothetic and still needed further studies to approve or refute. This systematic review synthesizes current evidence on the characteristics, pathophysiology, diagnostic approaches, and management of audiovestibular dysfunction related to long COVID-19 syndrome. Literature searches across PubMed, Embase, ClinicalKey, Web of Science, and ScienceDirect (up to 15 December 2025) were conducted in accordance with PRISMA guidelines. Through this systematic review, we provided a schematic diagram of the physiopathology of long COVID-19 syndrome-related audiovestibular dysfunction. Further, we summarized the currently available diagnostic tools to explore the audiovestibular function in such patients. The currently available treatment, either pharmacotherapy or nonpharmacotherapy, mainly tackles idiopathic audiovestibular dysfunction but not specifically long COVID-19 syndrome-related audiovestibular dysfunction. Timely recognition and intervention may prevent progression to permanent hearing loss or vestibular disability, improving quality of life. Trial registration: PROSPERO CRD420251265741. Full article

Hypertension has been traditionally known to be highlighted by mean blood pressure; however, emerging evidence exhibits that blood pressure variability (BPV), including short-term, day-to-day, and visit-to-visit fluctuations can have an implication across multiple body systems. Elevated BPV reflects repetitive hemodynamic stress, affecting the physiologic hemostasis contributing to vascular injury and end organ damage. This narrative review is a compilation of recent evidence on the prognostic value of BPV, explained by pathophysiology, various devices with its measurement approaches, and, essentially, the clinical implication of BPV and the use of such devices utilizing artificial intelligence. A comprehensive literature search across PubMed, Cochrane Library, Scopus, and Web of Science were conducted, focusing on observational studies, cohorts, randomized trials, and meta-analyses. Higher BPV has been associated with an increased risk of cardiovascular mortality, stroke, coronary events, and heart failure, the progression of chronic kidney disease, cognitive decline, and preeclampsia, among other end organ damage, despite mean blood pressure. The various pathophysiologic mechanisms include autonomic dysregulation, arterial stiffness, endothelial dysfunction, circadian rhythm alteration, and systemic inflammation, which result in vascular remodeling and multisystem damage. Antihypertensive medications such as calcium channel blockers and renin–angiotensin–aldosterone system inhibitors seem to reduce BPV; randomized trials have not specifically investigated their BPV-reducing effects. The aim of this review is to highlight that BPV is a dynamic marker of multisystem risk, and question how various AI-based devices can aid continuous BPV monitoring and patient specific risk stratification. Full article

Myocardial ischemia represents a state of reduced coronary perfusion with oxygenated blood, insufficient to meet the metabolic demands of the myocardium. Both acute and chronic ischemia trigger a cascade of cellular events that lead to disturbances in ionic balance, mitochondrial function and energy metabolism. During ischemia, cardiomyocytes (CMs) shift from aerobic to anaerobic metabolism, resulting in adenosine triphosphate (ATP) depletion, loss of ionic homeostasis and calcium (Ca²⁺) overload that activate proteases, phospholipases and membrane damage. Reperfusion restores oxygen supply and prevents irreversible necrosis but paradoxically initiates additional injury in marginally viable myocardium. The reoxygenation phase induces excessive production of reactive oxygen species (ROS), endothelial dysfunction and a strong inflammatory response mediated by neutrophils, platelets and cytokines. Mitochondrial dysfunction and opening of the mitochondrial permeability transition pore (mPTP) further amplify oxidative stress and inflammation and trigger apoptosis and necroptosis. Understanding these intertwined cellular and molecular mechanisms remains essential for identifying novel therapeutic targets aimed at reducing reperfusion injury and improving myocardial recovery after ischemic events. Full article

Endothelial cell (EC) barrier integrity is tightly regulated by the activity of the non-muscle myosin light chain kinase (nmMLCK) under diverse pathological inflammatory conditions (pneumonia, sepsis) and exposure to mechanical stress. Inflammatory stimuli, including lipopolysaccharide (LPS), cytokines, and damage-associated molecular patterns (DAMPs), increase EC permeability through nmMLCK-dependent EC paracellular gap formation. However, the exact mechanisms by which nmMLCK regulates vascular barrier dysfunction in acute lung injury (ALI) remain incompletely understood. We hypothesized that inflammation-induced ROS results in the peroxynitrite-mediated nitration of nmMLCK that contributes to EC barrier disruption. Human lung EC exposure to either the peroxynitrite donor, SIN-1, or to LPS, triggered significant nmMLCK nitration, which was abolished by the oxidant scavenger, MnTMPyP. Mass spectrometry of SIN-1-treated nmMLCK identified multiple nitrated tyrosines. Nitration of Y1410 proved a critical PTM as site-directed substitution with alanine (Y1410A) abolished both SIN-1- and LPS-induced nmMLCK nitration. nmMLCK nitration disrupts wild-type nmMLCK interaction with Kindlin-2, a cytoskeletal regulator of vascular barrier stability, whereas EC transfected with the Y1410A nmMLCK mutant exhibited preserved Kindlin-2 binding, reflected by alterations in trans-EC electrical resistance (TEER). Consistent with these observations, LPS-challenged murine lungs displayed enhanced nmMLCK nitration and diminished nmMLCK-Kindlin-2 association. Functionally, SIN-1 markedly impaired EC barrier integrity (TEER), which was not observed in ECs expressing the Y1410A mutant. Together, these findings suggest that nmMLCK nitration at Y1410 is a critical molecular mechanism contributing to vascular leakage, highlighting this modification as a potential therapeutic target to reduce inflammation-induced vascular permeability. Given nmMLCK’s established role in barrier regulation, we hypothesized that LPS-induced peroxynitrite formation may promote the nitration of nmMLCK tyrosine residues: a PTM that potentially contribute to nmMLCK’s regulation of EC barrier integrity. Full article