Search Results (162)

Cardiac devices have transformed the management of heart failure, ventricular arrhythmias, ischemic cardiomyopathy, and valvular heart disease. Technologies such as cardiac resynchronization therapy (CRT), conduction system pacing, left ventricular assist devices (LVADs), and implantable cardioverter-defibrillators have contributed to abated global cardiovascular risk through action onto pathophysiological processes such as mechanical unloading, electrical resynchronization, or hemodynamic optimization, respectively. While their clinical benefits are well established, their long-term molecular and structural effects on the myocardium remain under investigation. Cardiac devices dynamically interact with myocardial and vascular biology, inducing molecular and extracellular matrix adaptations that vary by pathology. CRT enhances calcium cycling and reduces fibrosis, but chronic pacing may lead to pacing-induced cardiomyopathy. LVADs and Impella relieve ventricular workload yet alter sarcomeric integrity and mitochondrial function. Transcatheter valve therapies influence ventricular remodeling, conduction, and coronary flow. Understanding these remodeling processes is crucial for optimizing patient selection, device programming, and therapeutic strategies. This narrative review integrates the current knowledge on the molecular and structural effects of cardiac devices, highlighting their impact across different disease settings. Full article

Human induced pluripotent stem cell-derived cardiomyocytes (iCMs) provide a powerful platform for investigating cardiac biology. However, structural, metabolic, and electrophysiological immaturity of iCMs limits their capacity to model adult cardiomyocytes. Currently, no universally accepted criteria or protocols for effective iCMs maturation exist. This study aimed to identify practical culture conditions that promote iCMs maturation, thereby generating more physiologically relevant in vitro cardiac models. We evaluated the effects of short- and long-term culture in media supplemented with various stimulatory compounds under 2D conditions, focusing on intracellular content and localization of slow skeletal troponin I (ssTnI) and cardiac troponin I (cTnI) isoforms. Our findings demonstrate that the multicomponent metabolic maturation medium (MM-1) effectively enhances the transition toward a more mature iCM phenotype, as evidenced by increased cTnI expression and formation of cross-striated myofibrils. iCMs cultured in MM-1 more closely resemble adult cardiomyocytes and are compatible with high-resolution single-cell techniques such as electron microscopy and patch-clamp electrophysiology. This work provides a practical and scalable approach for advancing the maturation of iPSC-derived cardiac models, with applications in disease modeling and drug screening. Full article

Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article

Sudden cardiac death (SCD) is a major public health concern, being a leading cause of death worldwide. SCD is particularly alarming for individuals with apparently good health, as it often occurs without preceding warning signs. Unfortunately, traditional autopsy methods frequently fail to identify the precise cause of death in these cases, highlighting the need for advanced techniques to elucidate underlying mechanisms. Recent advances in molecular biology over the past few years, particularly in proteomics, transcriptomics, and metabolomics techniques, have led to an expanded understanding of gene expression, protein activity, and metabolic changes, offering valuable insights into fatal cardiac events. Combining multi-omics methods with bioinformatics and machine learning algorithms significantly enhances our ability to uncover the processes behind lethal cardiac dysfunctions by identifying new useful biomarkers (like cardiac myosin-binding protein C, acylcarnitines, or microRNAs) to reveal molecular pathways linked to SCD. This narrative review summarizes the role of multi-omics approaches in forensic diagnosis by exploring current applications in unexplained cases and the benefits of integrating merged techniques in otherwise negative autopsies. We also discuss the potential for developing personalized and preventive forensic medicine, the technical limitations of currently available methods, and the ethical considerations arising from these advancements. Full article

The study of metabolic abnormalities regarding mitochondrial respiration and energy production has significantly advanced our understanding of cell biology and molecular mechanisms underlying cardiovascular diseases (CVDs). Mitochondria provide 90% of the energy required for maintaining normal cardiac function and are central to heart bioenergetics. During the initial phase of heart failure, mitochondrial number and function progressively decline, causing a decrease in oxidative metabolism and increased glucose uptake and glycolysis, leading to ATP depletion and bioenergetic starvation, finally contributing to overt heart failure. Compromised mitochondrial bioenergetics is associated with vascular damage in hypertension, vascular remodeling in pulmonary hypertension and acute cardiovascular events. Thus, mitochondrial dysfunction, leading to impaired ATP production, excessive ROS generation, the opening of mitochondrial permeability transition pores and the activation of apoptotic and necrotic pathways, is revealed as a typical feature of common CVDs. Molecules able to positively modulate cellular metabolism by improving mitochondrial bioenergetics and energy metabolism and inhibiting oxidative stress production are expected to exert beneficial protective effects in the heart and vasculature. This review discusses recent advances in cardiovascular research through the study of cellular bioenergetics in both chronic and acute CVDs. Emerging therapeutic strategies, specifically targeting metabolic modulators, mitochondrial function and quality control, are discussed. Full article

Tissue engineering is a growing field with multidisciplinary players in cell biology, engineering, and medicine, aiming to maintain, restore, or enhance functions of tissues and organs. The extracellular matrix (ECM) plays fundamental roles in tissue development, maintenance, and repair, providing not only structural support, but also critical biochemical and biomechanical cues that regulate cell behavior and signaling. Although its specific composition varies across different tissue types and developmental stages, matrix molecules influence various cell functional properties in every tissue. Given the importance of ECM in morphogenesis, tissue homeostasis, and regeneration, ECM-based bioscaffolds, developed through tissue engineering approaches, have emerged as pivotal tools for recreating the native cellular microenvironment. The aim of this study is to present the main categories of these scaffolds (i.e., natural, synthetic, and hybrid), major fabrication techniques (i.e., tissue decellularization and multidimensional bioprinting), while highlighting the advantages and disadvantages of each category, focusing on biological activity and mechanical performance. Scaffold properties, such as mechanical strength, elasticity, biocompatibility, and biodegradability are essential to their function and integration into host tissues. Applications of ECM-based bioscaffolds span a range of engineering and regenerative strategies, including cartilage, bone, cardiac tissue engineering, and skin wound healing. Despite promising advances, challenges remain in standardization, scalability, and immune response modulation, with future directions directed towards improving ECM-mimetic platforms. Full article

Background/Objectives: Cardiac aging involves the progressive structural and functional decline of the myocardium. Endurance training is a well-recognized non-pharmacological intervention that counteracts this decline, yet the molecular mechanisms driving exercise-induced cardiac rejuvenation remain inadequately elucidated. This study aimed to identify key effector genes and regulatory pathways by integrating human cardiac aging transcriptomic data with multi-omic exercise response datasets. Methods: A systems biology framework was developed to integrate age-downregulated genes (n = 243) from the GTEx human heart dataset and endurance-exercise-responsive genes (n = 634) from the MoTrPAC mouse dataset. Thirty-seven overlapping genes were identified and subjected to Enrichr for pathway enrichment, KEA3 for kinase analysis, and ChEA3 for transcription factor prediction. Candidate effector genes were ranked using ToppGene and ToppNet, with integrated prioritization via the FLAMES linear scoring algorithm. Results: Pathway enrichment revealed complementary patterns: aging-associated genes were enriched in mitochondrial dysfunction and sarcomere disassembly, while exercise-responsive genes were linked to protein synthesis and lipid metabolism. TTN, PDK family kinases, and EGFR emerged as major upstream regulators. NKX2-5, MYOG, and YBX3 were identified as shared transcription factors. SMPX ranked highest in integrated scoring, showing both functional relevance and network centrality, implying a pivotal role in mechano-metabolic coupling and cardiac stress adaptation. Conclusions: By integrating cardiac aging and exercise-responsive transcriptomes, 37 effector genes were identified as molecular bridges between aging decline and exercise-induced rejuvenation. Aging involved mitochondrial and sarcomeric deterioration, while exercise promoted metabolic and structural remodeling. SMPX ranked highest for its roles in mechano-metabolic coupling and redox balance, with X-inactivation escape suggesting sex-specific relevance. Other top genes (e.g., KLHL31, MYPN, RYR2) form a regulatory network supporting exercise-mediated cardiac protection, offering targets for future validation and therapy. Full article

Stem-cell behavior is governed not solely by intrinsic genetic programs but by highly specialized microenvironments—or niches—that integrate structural, biochemical, and mechanical cues to regulate quiescence, self-renewal, and differentiation. This review traces the evolution of stem-cell niche biology from foundational embryological discoveries to its current role as a central determinant in tissue regeneration and disease. We describe the cellular and extracellular matrix architectures that define adult stem-cell niches across diverse organs and dissect conserved signaling axes—including Wnt, BMP, and Notch—that orchestrate lineage commitment. Emphasis is placed on how aging, inflammation, fibrosis, and metabolic stress disrupt niche function, converting supportive environments into autonomous drivers of pathology. We then examine emerging therapeutic strategies that shift the regenerative paradigm from a stem-cell-centric to a niche-centric model. These include stromal targeting (e.g., FAP inhibition), which are engineered scaffolds that replicate native niche mechanics, extracellular vesicles that deliver paracrine cues, and composite constructs that preserve endogenous cell–matrix interactions. Particular attention is given to cardiac, hematopoietic, reproductive, and neurogenic niches, where clinical failures often reflect niche misalignment rather than intrinsic stem-cell deficits. We argue that successful regenerative interventions must treat stem cells and their microenvironment as an inseparable therapeutic unit. Future advances will depend on high-resolution niche mapping, mechanobiologically informed scaffold design, and niche-targeted clinical trials. Re-programming pathological niches may unlock regenerative outcomes that surpass classical cell therapies, marking a new era of microenvironmentally integrated medicine. Full article

Albumin is the most abundant protein synthesized exclusively by the hepatocytes in the liver. Once secreted into plasma, it helps in the maintenance of osmotic pressure, as well as the exertion of defensive roles such as anti-oxidative and anti-inflammatory functions. Dysregulation in the synthesis and clearance of albumin is observed in various hepatic and extra-hepatic diseases. Abnormal levels of albumin could be either a cause or an effect of various pathological ailments, including hepatic, cardiac, renal, neurological, etc. Owing to its long half-life and multiple binding sites in its heart-shaped structure, it interacts with various internal agents, such as hormones, or external substances like drugs, which is why transportation can be one of its many functions. Additionally, albumin’s drug interactions, as well as displacement of albumin–drug binding, could have serious clinical consequences, and careful considerations should be made in determining an appropriate drug regimen to achieve a desired therapeutic outcome with minimal side effects. Moreover, albumin also undergoes several post-translational modifications that can influence its physiological roles, including drug binding and antioxidant functions. Furthermore, it has a complicated role in physiology, where it can help in maintaining plasma oncotic pressure and prevent endothelial cell apoptosis but can have adverse effects on the lungs and kidneys. These adverse effects are mainly attributed to ER stress and inflammasome activation. This narrative review provides an overview of the general biology of albumin and its effects in physiology, with a focus on its beneficial and adverse effects and the underlying molecular mechanisms. Full article

Cardiovascular diseases are among the major global health problems. For example, sudden cardiac death (SCD) accounts for approximately 4 million deaths worldwide. In particular, an SCD event can subtly change the electrocardiogram (ECG) signal before onset, which is generally undetectable by the patient. Hence, timely detection of these changes in ECG signals could help develop a tool to anticipate an SCD event and respond appropriately in patient care. In this sense, this work proposes a novel computational methodology that combines the maximal overlap discrete wavelet packet transform (MODWPT) with stacked autoencoders (SAEs) to discover suitable features in ECG signals and associate them with SCD prediction. The proposed method efficiently predicts an SCD event with an accuracy of 98.94% up to 30 min before the onset, making it a reliable tool for early detection while providing sufficient time for medical intervention and increasing the chances of preventing fatal outcomes, demonstrating the potential of integrating signal processing and deep learning techniques within computational biology to address life-critical health problems. Full article

Cardiac tumors represent rare neoplasms, but they include a very wide range of neoplasia—first primary benign and malignant cardiac tumors, then cardiac metastases, with these latter ones being far more common in adulthood. These diagnoses may be challenging because of frequently non-specific signs and symptoms; for example, their clinical management may be difficult because of the site and because of possible hemodynamic or arrhythmogenic consequences, independent from their biology. Cardiac tumors may be asymptomatic and incidentally diagnosed, or they may cause heart failure, life-threatening arrhythmias, or even sudden cardiac death. Although they may still represent a post-mortem finding, the evolution and the larger use of cardiac imaging tools, initially echocardiography, has progressively and significantly increased their in vivo detection. Magnetic resonance imaging and computed tomography may give crucial information as to the composition and localization of cardiac masses, useful for investigating them and for planning surgery. Histology is mandatory for the definite and differential diagnosis of the cardiac masses, for assessing predictive factors in malignancies, and for then establishing the appropriate management of patients. Modern techniques applied to histology, including immunohistochemistry and molecular biology, may be required to characterize cardiac tumors, to properly classify them and to assess predictive and/or prognostic markers. Surgical procedures, including minimally invasive surgery, have also dramatically evolved in the last decades, allowing adequate treatment in most cardiac tumors. Finally, biopsy may be useful in selected cases, particularly when radical surgery is not feasible, and histological diagnosis is fundamental for other possible therapeutic approaches. The scope of this review covers advancements in the imaging diagnosis, histology, and treatment of primary and secondary cardiac tumors. Full article

Approximately 5% to 8% of patients with Wilms tumour have bilateral disease. The prevalence of bilateral Wilms tumour (BWT) is higher in individuals with genetic predisposition syndromes than in those without. The goal of therapy is to preserve as much renal tissue as possible without compromising the overall oncological outcomes, utilising neoadjuvant chemotherapy followed by nephron sparing surgery (NSS) if possible. The Children’s Oncology Group (COG) in North America and the International Society of Paediatric Oncology (SIOP) in Europe have developed the main protocols for the treatment of BWT. Both protocols are similar: initial biopsies are not indicated, and they both recommend surgical resection at week 6 or no later than week 12. Chemotherapy includes the use of vincristine and actinomycin-D in both protocols, but the COG approach also includes the use of doxorubicin, which is a cardiotoxic drug with important long-term effects on the cardiac function of childhood cancer survivors. What doxorubicin adds to patients with BWT in terms of radiological tumour response, resectability, long-term renal function and overall survival, is still not very well described and it may be variable depending on the tumour biology. This article describes the current approach for BWT in North America and Europe, focusing on the potential effect that doxorubicin may have on patient outcomes. Full article

Cardiovascular diseases increase among pregnant women and complicate 1–4% of pregnancies worldwide. The incidence of maternal deaths due to cardiovascular causes has increased dramatically, rising from 3% three decades ago to 15% in recent years. The aim of this study is to provide a comprehensive overview of the current status of knowledge in sudden maternal death (SMD) described in the literature and to present two cases of autopsy findings in sudden cardiac death in pregnant women. Among the most common causes of sudden maternal deaths are peripartum cardiomyopathies, aortic dissection, acute myocardial infarction, arrhythmias, ischemic heart disease, and coronary artery dissection, and among the less common causes, we list coronary artery dissection, congenital heart diseases, valvulopathies, hypertension, fibroelastosis, and borderline myocarditis. The Centers for Disease Control and Prevention (CDC) reported that over 80% of pregnancy-related deaths were preventable. To reduce the number of maternal deaths caused by cardiovascular diseases, the implementation of specialized multidisciplinary teams has been proposed. Molecular biology techniques are proving their effectiveness in forensic medicine. PCR or DNA sequencing can be utilized in “molecular autopsy”, which holds particular value in cases of sudden death where the forensic autopsy is negative but there is a suspicion that death was caused by arrhythmia. Susceptibility genes can be analyzed, such as KCNQ1, KCNH2, KCNE1, and KCNE2, which are involved in long QT syndrome, the RYR2 gene implicated in catecholaminergic polymorphic ventricular tachycardia type 1, or the SCN5A gene associated with Brugada syndrome. Early identification of risk factors involved in sudden maternal death prenatally and during pregnancy is essential. At the same time, genetic determinations and molecular biology techniques are absolutely necessary to prevent the occurrence of sudden deaths among close relatives. Full article

The therapeutic potential of presumed cardiac progenitor cells (CPCs) in heart regeneration has garnered significant interest, yet clinical trials have revealed limited efficacy due to challenges in cell survival, retention, and expansion. Priming CPCs to survive the hostile hypoxic environment may be key to enhancing their regenerative capacity. We demonstrate that microRNA-210 (miR-210), known for its role in hypoxic adaptation, significantly improves CPC survival by inhibiting apoptosis through the downregulation of Casp8ap2, a ~40% reduction in caspase activity, and a ~90% decrease in DNA fragmentation. Contrary to the expected induction of Bnip3-dependent mitophagy by hypoxia, miR-210 did not upregulate Bnip3, indicating a distinct anti-apoptotic mechanism. Instead, miR-210 reduced markers of mitophagy and increased mitochondrial biogenesis and oxidative metabolism, suggesting a role in metabolic reprogramming. Furthermore, miR-210 enhanced the secretion of paracrine growth factors from CPCs, with a ~1.6-fold increase in the release of stem cell factor and of insulin growth factor 1, which promoted in vitro endothelial cell proliferation and cardiomyocyte survival. These findings elucidate the multifaceted role of miR-210 in CPC biology and its potential to enhance cell-based therapies for myocardial repair by promoting cell survival, metabolic adaptation, and paracrine signalling. Full article