Search Results (327)

Background/Objectives: Oxidative stress is a major contributor to the pathogenesis of cardiovascular diseases, including hypertension, ischemic cardiomyopathy, and heart failure. MicroRNAs (miRNAs) have been extensively investigated in various contexts, and some of them have been identified to play a role in cardiovascular disease. This narrative review focuses on miR-103 and miR-155, two miRNAs implicated in the modulation of oxidative stress and cardiovascular remodeling. Methods: The following queries were used in PubMed since inception until May 2026: ((“miR-155” OR “microRNA-155” OR miR155) AND (“oxidative stress” OR ROS OR “reactive oxygen species”) AND (“cardiovascular disease” OR cardiovascular OR cardiac OR heart OR vascular)); ((“miR-103” OR “microRNA-103” OR miR103) AND (“oxidative stress” OR ROS OR “reactive oxygen species”) AND (“cardiovascular disease” OR cardiovascular OR cardiac OR heart OR vascular)). Results: A total of seven citations for miR-103 and 79 citations for miR-155 were identified. Reviews and papers about diseases other than those on cardiac/vascular involvement were excluded. miR-155 emerges as a potential regulator of inflammatory-redox signaling, whereas miR-103 appears more closely linked to cell fate and metabolic pathways. In both cases, available evidence supports a context-dependent role that challenges simplistic classification as pro- or antioxidant miRNAs. Conclusions: Available evidence suggests that both miR-103 and miR-155 are important regulators of oxidative stress-related pathways in cardiovascular disease. Nevertheless, the context-dependent effects observed across different cardiovascular disorders raise concerns regarding the safety of systemic miRNA modulation-based therapeutic strategies. Future studies should clarify the determinants of this context-dependent behavior and identify the specific conditions under which these miRNAs exert protective or harmful effects, which might pave the way for the development of miRNA-based therapeutic strategies targeting oxidative stress and cardiovascular remodeling. Full article

Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure in which the ejection fraction remains within the normal range (≥50%); however, patients still experience typical symptoms of heart failure. One of the most common manifestations in this population is exercise intolerance, which in some cases may be the only presenting symptom. Exercise intolerance refers to a reduced capacity to perform physical activity. Several processes, including impaired cGMP–PKG signaling, increased collagen deposition, endothelial dysfunction, increased arterial stiffness, pulmonary hypertension, and vascular remodeling, contribute to the pathophysiology of HFpEF. The disruption of these fundamental physiological processes significantly impairs exercise capacity, leading to attenuated increases in heart rate, stroke volume, and/or contractility, along with abnormal ventricular–vascular coupling during exertion. When EI is suspected, a spectrum of diagnostic modalities—from simple, low-cost tools such as the 6 min walk test to advanced imaging—can be used to evaluate its presence and its association with HFpEF. When EI in HFpEF is diagnosed, management should focus on addressing this limitation to improve quality of life and reduce morbidity and mortality. Exercise training and pharmacological therapies, such as SGLT2 inhibitors, may be beneficial in this population. In conclusion, EI is a common manifestation of HFpEF that significantly impacts patients’ quality of life. Understanding its underlying mechanisms and addressing it appropriately are essential to improving patient outcomes. Full article

Erythropoiesis-targeted doping remains a major challenge for sports medicine because pharmacological and genetic manipulation of erythropoiesis can improve oxygen transport and endurance performance while increasing the risk of serious cardiovascular complications. Erythropoiesis-targeting strategies extend beyond recombinant erythropoietin (EPO) to include hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), modified erythropoietin receptor (EPOR) agonists, transforming growth factor beta (TGF-β) signaling inhibitors, cytoprotective EPO derivatives, and gene- or cell-based approaches, and require complementary detection strategies based on direct analytical methods and the Athlete Biological Passport (ABP). Although they may enhance oxygen delivery and endurance performance, excessive stimulation of erythropoiesis may increase blood viscosity, impair vascular function, and elevate the risk of hypertension, thromboembolic complications, and other cardiovascular (CV) events. Erythropoiesis-targeted doping has evolved beyond recombinant EPO into a diverse group of pharmacological and genetic strategies that require increasingly sophisticated detection approaches. A thorough understanding of their molecular mechanisms and cardiovascular consequences is essential for improving anti-doping surveillance and protecting athlete health. This review summarizes current erythropoiesis-targeting agents, their mechanisms of action, detection strategies, cardiovascular risks, and implications for anti-doping practice. Full article

Background/Objectives: Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine–metabolic disorder of multifactorial etiology, driven by interactions among hyperandrogenism, metabolic dysfunction, oxidative stress, and chronic low-grade inflammation that interact to promote reproductive dysfunction and increase risk of cardiometabolic complications. Although the combination of letrozole and high-fat diet (LET + HFD) represents a widely used experimental approach for inducing a PMOS-like phenotype in rats, its multisystem pathophysiological features remain incompletely characterized. The present study aimed to characterize reproductive, cardiometabolic, hormonal, inflammatory, oxidative, and morphometric alterations associated with a LET + HFD-induced PMOS-like phenotype in rats. Methods: PMOS-like model was induced in rats over a 21-day period of orally administered letrozole combined with a high-fat diet. Results: Body weight gain was higher, while uterine weight was lower in the PMOS group compared with controls. Metabolic parameters suggested insulin resistance, while hormonal profiling revealed increased total testosterone and LH levels, accompanied by reduced FSH, estradiol, and progesterone levels. Elevated triglycerides and reduced HDL levels were also observed in the PMOS group. Morphometric analysis revealed numerous atretic and large thin-walled cystic follicles in the ovaries, accompanied by thinning of the uterine luminal and glandular epithelium, stromal layer, and hypoplasia of endometrial glands. Both the longitudinal diameter and cross-sectional area of cardiomyocytes were increased in the PMOS group, together with nuclear hypertrophy and enhanced myocardial collagen deposition. In addition, altered oxidative stress markers, including increased lipid peroxidation and reduced glutathione levels, were observed, whereas IL-6, IL-1β, and IL-23 were not significantly altered. Conclusions: The LET + HFD model reproduces key reproductive and cardiometabolic features of PMOS, extending beyond reproductive dysfunction to involve oxidative and structural alterations in multiple organs. These findings support its use for investigating PMOS pathophysiology and evaluating potential preventive and therapeutic strategies. Full article

Introduction: Bispecific antibodies (BsAbs) are a promising and potent therapeutic intervention for relapsed or refractory (R/R) hematologic malignancies, including acute lymphoblastic leukemia (ALL), multiple myeloma (MM), and B-cell lymphomas. These recombinant molecules are designed to target two distinct antigens or epitopes. While BsAbs have shown significant efficacy in managing hematologic malignancies, toxicities must be carefully monitored and their safety profiles require further investigation. This meta-analysis investigates cardiovascular adverse effects associated with seven BsAbs across multiple clinical trials. Methods: A systematic literature review identified seven BsAbs, blinatumomab, elranatamab, epcoritamab, glofitamab, mosunetuzumab, talquetamab, and teclistamab, analyzing 25 clinical trials (Phase I–III) that included monotherapy regimens. The cardiovascular adverse events studied were arrhythmias, heart failure, blood pressure changes, and myocardial infarctions. A meta-analysis using the R meta package calculated proportions and 95% confidence intervals (CIs) and employed a random-effects model to assess heterogeneity. Results: Among 3215 patients, pooled analysis revealed significant findings with 13.6% cardiac arrhythmia (95% CI 10.1–18.2%, p = 0.05), 13.3% hypotension (95% CI 10–17.3%, p < 0.0001), 10.2% tachycardia (95% CI 7.6–13.5%, p = 0.0003), and 3.4% sudden death (95% CI 0–80%, p = 0.046). Less frequent events were hypertension (8%), acute myocardial infarction (1.5%), heart failure (1.4%), and atrial fibrillation (1.3%). Discussion: As BsAbs see increased use in R/R hematologic malignancies, cardiovascular complications must be closely monitored. This analysis highlights hypotension, cardiac arrhythmias, tachycardia, and sudden death as significant adverse effects. Although study heterogeneity and limited patient-level data may have influenced incidence estimates, these findings support routine cardiovascular monitoring and underscore the need for prospective studies to identify high-risk patients and optimize prevention and management strategies. Oncologists, cardiologists, and pharmacists should establish strategies for early detection and management to optimize patients’ outcomes. Full article

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder in which systemic pathophysiological alterations significantly contribute to disease progression and non-motor manifestations, such as depression and anxiety. The microbiota–gut–brain axis represents a critical bidirectional pathway in which intestinal dysbiosis and epithelial barrier disruption catalyze central neuroinflammation. This scoping review synthesizes evidence from 43 empirical and analytical studies across 28 countries and maps the findings under the WHO International Classification of Functioning (ICF) framework. Pathophysiological data reveal a profound taxonomic shift in patients with ALS, characterized by severe depletion of neuroprotective, butyrate-producing genera (Akkermansia and Prevotella) and enrichment of pro-inflammatory Enterobacteriaceae. This dysbiotic state leads to structural damage to the intestinal mucosa, alteration of Paneth cells, and downregulation of tight junction proteins (zonulin), triggering a “leaky gut” phenomenon. Subsequent systemic translocation of lipopolysaccharides (LPS) induces TLR4-mediated endotoxemia, microglial hyperactivation, and accelerated motor neuron apoptosis. Conversely, therapeutic modulation via Fecal Microbiota Transplantation (FMT), psychobiotics, and metabolic interventions (ketogenic or Mediterranean diets) has demonstrated significant efficacy in restoring epithelial integrity, mitigating mitochondrial hypermetabolism, and reducing emotional distress. This review identifies a critical research gap in the microstructural characterization of the enteric nervous system in ALS. Incorporating microbiome-targeted biomarkers into clinical protocols is crucial for implementing a stratified, multi-systemic therapeutic strategy aimed at enhancing patient prognosis and psychological well-being. Full article

The intricate relationship between the heart and the brain has transitioned from historical, cardio-centric theories to a modern, circuit-based, bi-directional framework known as neurocardiology. This review provides a comprehensive anatomical, physiological, and clinical synthesis of the bidirectional heart–brain axis, highlighting how disruptions in one organ systematically impact the other. Structurally, the heart–brain axis operates as a closed-loop feedback network. Vagal parasympathetic control dominates at rest, driven by an asymmetrical fiber distribution where sensory afferents actively supply interoceptive data to the brainstem. Hemodynamically, cerebral blood flow delivery is linked to cardiac output in an age-dependent fashion with the related vascular dysfunction. Clinically, brain-to-heart pathologies like acute brain injury trigger life-threatening catecholamine surges, neuroinflammation, and myocardial stunning, including Takotsubo cardiomyopathy. Conversely, heart-to-brain pathways reveal that atrial fibrillation and heart failure can independently trigger cardioembolic stroke, long-term neuroinflammation, and a profound, progressive burden of cognitive decline. The heart and brain are inexorably linked through complex structural, mechanical, and paracrine pathways. Ameliorating clinical outcomes demands integrated cross-specialty diagnostic screening, digital rhythm monitoring, and holistic neurocardioprotective therapeutic strategies. Full article

Background/Objectives: Time-varying low-frequency electromagnetic fields (LF-EMFs), including pulsed electromagnetic fields (PEMFs) and sinusoidal low-frequency electromagnetic fields, have been investigated as modulators of tissue repair and vascular remodeling. Although numerous studies report pro-angiogenic effects in endothelial systems, the underlying mechanisms remain incompletely understood. This review synthesizes evidence for LF-EMF-induced endothelial angiogenesis and evaluates emerging mechanistic explanations. Methods: Literature was identified through searches of PubMed, Web of Science, and Google Scholar through March 2026. Peer-reviewed studies emphasizing in vitro endothelial angiogenesis models were prioritized, with selected in vivo studies included when relevant to mechanistic interpretation. The review was conducted as a narrative synthesis rather than a systematic review or meta-analysis. Results: Experimental evidence indicates that LF-EMF exposure can enhance endothelial proliferation, migration, sprouting, tube formation, and survival across diverse model systems. Reported mechanisms include modulation of growth factor signaling, calcium-dependent pathways, nitric oxide production, cytoskeletal remodeling, and mechanotransduction. Reexamination of early ultrastructural studies suggests that membrane ruffling, vacuole formation, and vesicular structures observed following LF-EMF exposure may be interpreted within the framework of macropinocytosis and vesicular trafficking, providing a potential mechanistic link between electromagnetic stimulation and endothelial morphogenesis. Conclusions: Current evidence supports the conclusion that LF-EMFs can modulate key endothelial processes involved in angiogenesis and vascular remodeling. Membrane trafficking and macropinocytosis provide a biologically plausible framework linking historical observations with contemporary endothelial cell biology, although direct experimental validation is needed. Future progress will require standardized exposure paradigms and mechanistic studies using physiologically relevant angiogenesis models. Full article

Background/Objectives: Quiescent leukemia stem cells (LSCs) are self-renewing, pluripotent cells that present a major obstacle to the successful curative treatment of chronic myeloid leukemia (CML). LSCs function independently of BCR::ABL1 signaling and persist following tyrosine kinase inhibitor treatment. The mechanisms enabling LSC survival are a central focus of current CML research. This review details the complex relationship between signaling pathways and discusses recent advancements in energy metabolism research within the pathogenesis of CML. Discussion: Energy metabolism is critical to the biology of CML LSCs. These cells depend on oxidative phosphorylation (OXPHOS) and mitochondrial homeostasis, utilizing fatty acid oxidation as their primary ATP source. Research highlights significant alterations in signaling networks, marked by a dynamic interplay among dominant pathways within the CML clone. While TGF-β-FOXO signaling maintains the self-renewal capacity of quiescent LSCs, proliferating mature CML cells rely heavily on glycolysis and the PI3K/Akt pathway. Furthermore, unique metabolic traits of LSCs underscore the impact of leukemic cell–microenvironment interactions in fostering a permissive niche. Conclusions: Fatty acid oxidation is critical to the survival and self-renewal of CML LSCs. This adaptation of mitochondrial function is closely linked to signaling alterations and entails an adjustment of mitochondrial respiration alongside stimulated OXPHOS. Emerging research unveils many potential targets within metabolic signaling that can be exploited to overcome these survival mechanisms, highlighting the disruption of mitochondrial energy support as a promising strategy to selectively eradicate CML LSCs. Full article

Background: During intrauterine life, the fetus is continuously exposed to rhythmic sensory stimuli; among these, the maternal heartbeat is one of the earliest and most biologically salient, contributing to the early organization of physiological regulation. This exploratory longitudinal observational study examined whether exposure to the maternal heartbeat influences neonatal autonomic activity and whether this response is moderated by prenatal maternal psychological distress. Methods: Sixteen dyads of mother–child were included in the analyses. Pregnant women were first assessed between 24 and 28 weeks of gestation: maternal distress was measured using the Depression Anxiety Stress Scales—21 (DASS-21), and maternal heartbeat recordings were obtained. At 3–4 weeks postpartum, neonates were exposed to recordings of their own mother’s heartbeat. Neonatal heart rate variability (HRV) was assessed using electrocardiography at rest and during the hearing of the maternal heartbeat. Results: Exposure to the heartbeat significantly reduced high-frequency (HF) HRV compared to baseline (p = 0.037), providing evidence for modulation of parasympathetic activity. Importantly, an interaction between condition and maternal distress was observed (p = 0.021), suggesting that neonatal autonomic responses differ as a function of maternal psychological state. Conclusions: Overall, these preliminary findings suggest that neonatal autonomic responses to maternal heartbeat exposure may not be uniform but may vary according to maternal psychological distress, highlighting the potential role of the maternal psychophysiological context in shaping early autonomic regulation. Full article

Background/Objectives: Chronic orofacial pain represents a heterogeneous group of disorders affecting the trigeminal system and remains difficult to treat due to its complex pathophysiology, which involves glial cells in the development and maintenance of persistent pain states. This systematic review aimed to synthesize evidence from animal studies investigating the pathophysiological role of glial cells in chronic orofacial pain. Methods: After registering on PROSPERO, a systematic search of the literature, based on PRISMA guidelines, was conducted to identify experimental animal studies evaluating glial involvement in orofacial pain models. After screening and eligibility assessment, 10 studies met the inclusion criteria. Data regarding experimental models, glial populations investigated, and pain-related behavioral outcomes were extracted and qualitatively synthesized. Results: Activation of satellite glial cells, microglia, and astrocytes was consistently associated with increased neuroinflammatory signaling and enhanced neuronal excitability within trigeminal pathways, demonstrating that both peripheral and central nervous tissues were involved. Several studies reported that pharmacological modulation of glial activity may reduce pain-related behaviors. Conclusions: Glial cells are key modulators of chronic orofacial pain through neuroimmune interactions that contribute to peripheral and central sensitization. Although these findings highlight promising therapeutic targets, further translational research is required to clarify their relevance for human pain conditions. Full article

Background/Objectives: Cystic fibrosis (CF) is a genetic disease whose hallmarks include chronic inflammation of the airways causing tissue damage with increased levels of alarmins in the respiratory secretions, as well as activation of the coagulation/fibrinolytic systems that are linked to inflammation. However, no information is available about the fibrinolytic system and how fibrinolysis is involved in airway injury. On the road to understanding this issue, we determined levels of two key markers, High Mobility Group Box 1 (HMGB1), an alarmin, and D-dimers, associated with fibrin breakdown and airway inflammation, in the sputum from patients with cystic fibrosis. Methods: Sputum samples were collected from 13 individuals with CF and subjected to two different treatment protocols. In the first protocol, the sample was treated with dithiothreitol (DTT) and then centrifuged in order to collect the supernatant (SED). In the second protocol, the sample was centrifuged and the supernatant was obtained (SE). The pellet obtained was treated with DTT and then centrifuged in order to collect the supernatant (SPE). ELISA assays were performed on all samples. Results: HMGB1 and D-dimer levels were significantly lower in supernatants from sputum centrifuged before DTT treatment (SE) compared to those processed after DTT (SPE and SED). However, no significant difference was observed between SPE and SED samples for both markers. D-dimer levels in SED correlated positively with FEV₁ and blood monocyte counts. Conclusions: Direct sputum processing with DTT may be a useful procedure for assessing biomarkers of inflammation and fibrinolysis in CF. Full article

Background/Objectives: Lung cancer tumors are the most frequent malignant tumors and the primary cause of cancer-related deaths. Despite the improvement in survival related to the implementation of immunotherapy, a significant proportion of patients fail to demonstrate satisfactory response. As a result, the need for new biomarkers, which will predict patient response, as well as for novel therapeutic targets, is urgent. SHP-2 is an intracellular signal transduction molecule, modifying signal transduction of numerous intracellular cascades, acting primarily as an oncogene. In this study we analyzed the expression pattern of SHP-2 in a cohort of non-small-cell lung cancer cases and attempted to correlate it with available clinicopathological parameters. Methods: We performed immunohistochemistry for SHP-2 detection in a cohort of 258 NSCLC cases. H-score was estimated and statistical analyses correlated it with survival and other clinicopathological and molecular parameters. Results: SHP-2 expression was observed in 60 cases (23.3%), with an H-score ranging from 150 to 300. Positive samples were distributed among the three major histological subtypes, without statistically significant differences. Statistical analysis revealed significant positive correlation of SHP-2 expression with smoking, PD-L1 levels, and KRAS mutations. Moreover, positive SHP-2 immunohistochemistry was associated with better clinical outcome in both the total cohort and in the group of patients who received immunotherapy. Finally, the simultaneous presence of SHP-2 expression and KRAS mutation was correlated with prolonged survival. Conclusions: Our findings indicate that SHP-2 could be a useful prognostic factor and a very reliable biomarker in predicting response to immune checkpoint inhibitors. Full article

Background/Objectives: Hypertensive disorders of pregnancy, particularly preeclampsia and eclampsia, are associated with high maternal and fetal morbidity and mortality, with maternal obesity representing a major, modifiable risk factor. This study aimed to estimate the association between obesity and preeclampsia/eclampsia (PEC) in obstetric hospitalizations in the state of São Paulo, Brazil, and to examine risk trends across maternal age groups and between two distinct temporal cohorts. Methods: This population-based observational study analyzed 2,338,934 obstetric hospitalizations using data from the Hospital Information System of the Unified Health System (SIH/SUS). PEC and obesity diagnoses were coded according to the International Classification of Diseases, 10th Revision (ICD-10). Logistic regression models were applied to estimate associations adjusted for maternal age, complemented by adjusted marginal predictions. Results: PEC occurred more than twice as often among women with obesity than without (5.4% vs. 2.2%; OR 2.13, 95% CI 1.84–2.47) and was associated with longer hospital stays (3.52 vs. 2.70 days) and higher costs (R$797.91 vs. R$602.69). The absolute risk difference between obese and non-obese women declined from 24.7% to 13.6% at age 20 between the 2017–2019 and 2023–2025 cohorts, while the relative risk gradient remained stable across all ages. Conclusions: Obesity is strongly associated with increased PEC risk, longer hospitalization, and higher costs. The observed attenuation in absolute risk differences in the most recent cohort reinforces the need for preventive interventions, nutritional surveillance, and public health policies aimed at reducing hypertensive complications during pregnancy for both obese and non-obese women. Full article

Background/Objectives: There is increasing evidence on the effect of obesity on lung function in children with and without respiratory diseases. The aim of was to evaluate the prevalence of overweight and obesity and their impact on lung function parameters among healthy children. Methods: Six hundred and seventy-one healthy Bulgarian school children (339 males) aged 7–18 years were included in the study. All participants completed anthropometric measurements, including standing height, weight, and BMI. The studied group underwent comprehensive pulmonary function assessment. Results: The overweight and obese children group consisted of 131—overweight, 97, and obese, 34, children, accounting for 19.5% or every fifth child. The highest prevalence of overweight was at the ages of 10, 11, 12 and 17 years, and that of obesity was 7, 10 and 14 years, respectively. We compared normal weight, overweight and obese children in every age group and found that an increase in weight was associated with increased height and increased lung function parameters, such as FVC, FEV₁, PEF, and FEF₅₀. To overcome the effect of height, we compared normal weight and overweight obese children in height groups and found nonsignificant differences in the spirometric indices. Only in the 130–139 cm group the obese children had lower values of FEV₁(L): 1.78 ± 0.13 vs. 1.91 ± 0.19 (NS) in children with normal weight. Conclusions: The increase in weight is associated with height growth, and the same pattern is observed for the mean spirometry indices, with lowest values found only in obese 7-year-old children. Full article