Search Results (2,730)

Background: Arterial hypertension in childhood is an increasing health concern, often associated with structural and functional cardiovascular or renal alterations. This study aimed to investigate the prevalence and type of non-stenotic renal artery anatomical variants in children with systemic hypertension and to assess their possible association with cardiac involvement. Methods: A total of 107 children and adolescents with hypertension (mean age 15.4 ± 2.7 years) were evaluated. Hypertension was defined as blood pressure persistently above the 95th percentile for over one year, confirmed by 24 h ambulatory blood pressure monitoring. Patients with known secondary causes were excluded. All underwent renal vascular imaging by CT or MRI and echocardiographic assessment of left ventricular morphology and function. Results: Renal artery anatomical variants were found in 69 of 107 patients (65%), mainly unilateral or bilateral accessory polar arteries. Other anomalies found (left renal vein narrowing or duplication, severe left renal artery stenosis) were excluded from the statistical analysis. Normal renal vasculature was observed in only 32%. Left ventricular hypertrophy was detected in 41%, highlighting a significant prevalence of target-organ involvement. No statistically significant differences were found in terms of hypertension or hypertrophy between patients with renal artery anatomical variants and those without. However, patients with renal anomalies more frequently required dual antihypertensive therapy (p = 0.025). Conclusions: Renal artery anatomical variants, even in the absence of overt stenosis, may contribute to the pathogenesis of pediatric hypertension and complicate its management. Systematic evaluation of renal vasculature should be considered in the diagnostic workup to improve risk stratification and guide management strategies. Full article

Lumbar spinal stenosis (LSS) is caused by multiple degenerative changes including the hypertrophy of the ligamentum flavum (LFH). Inflammation and fibrosis contribute to LFH and glucocorticoid drugs (GCDs) are generally used to manage LSS symptoms. However, a thorough understanding of the molecular mechanisms exerted by GCD in ligamentum flavum (LF) cells remains incomplete. Primary human LF cells were isolated from surgical specimens and stimulated with pro-inflammatory agents (IL-1α, IL-1β, LPS) or the profibrotic cytokine TGFβ1, in the presence or absence of dexamethasone. Gene and protein expression levels of inflammatory, fibrotic, and ossification-related markers were analysed using RT-qPCR and Western blotting. Dexamethasone significantly suppressed the expression of key pro-inflammatory, fibrotic, and ossification markers (IL-6, COX2, COL3A1, MMPs, TNFRSF11b) in both acute and prolonged models of LF inflammation. However, under TGFβ1 stimulation, dexamethasone attenuated inflammatory gene expression but failed to reduce the expression of major fibrosis-associated genes, such as COL3A1, bFGF, and POSTN. Dexamethasone effectively suppresses inflammation-mediated fibrosis in LF-derived cells, indicating its potential to both prevent and reverse LFH progression in the context of LSS. However, its limited efficacy against TGFβ1-driven fibrotic pathways highlights the need for combination therapies targeting both inflammation and fibrosis for more comprehensive management of LFH. These findings support further exploration of corticosteroids as therapeutic agents for hypertrophic ligament disorders. Full article

Objectives: Downregulation of the endogenous gasotransmitter hydrogen sulfide (H₂S) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). While prophylactic H₂S supplementation prevents PAH initiation in different rat models, its ability to reverse fully established PAH and pulmonary vascular structural remodeling is unknown. In this study, we aimed to test whether H₂S donor therapy can reverse the existing PAH in a chronic-hypoxia rat model. Methods: After 3 weeks of hypoxia exposure, rats with established hypoxia-induced pulmonary hypertension (HPH) were randomized to receive either continued hypoxia alone or hypoxia plus the H₂S donor NaHS (56 μmol/kg·d, ip) for an additional 6 weeks. Pulmonary artery pressure, pulmonary artery muscularization, and right ventricular hypertrophy were assessed. Furthermore, the cell proliferation (Ki-67 and PCNA), ERK1/2 phosphorylation, and persulfidation of the endothelin type A receptor (ETAR) were examined and detected in rat lung tissues and pulmonary artery smooth muscle cells (PASMCs). Results: H₂S therapy effectively reversed established HPH and pulmonary artery structural remodeling, reducing RVSP, mPAP, and the proportion of fully muscularized small pulmonary arteries by 13.8%, 12.0%, and 62.7%, respectively. Moreover, the PAT/PET ratio was normalized to normoxic levels. The right ventricular hypertrophy index decreased by 29.2%. Mechanistically, H₂S therapy suppressed PASMC proliferation, reduced ERK1/2 phosphorylation, and enhanced ETAR persulfidation. Furthermore, dithiothreitol-mediated reduction of ETAR persulfidation abrogated these antiproliferative effects of H₂S therapy, establishing persulfidation as an obligatory mechanism. Conclusions: H₂S donor therapy effectively reverses established HPH and pulmonary vascular structural remodeling by inhibiting PASMC proliferation, which is linked to enhanced ETAR persulfidation. These data provide preclinical proof-of-concept for H₂S-based interventions in patients with manifest PAH. Full article

Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) occurs mainly by inhalation. Studies indicate that respiratory allergic reactions are induced by this pesticide. This study analyzed the effects of chronic inhalation exposure to 2,4-D in the trachea of rats. We exposed the animals during six months to three different concentrations of 2,4-D used for crop spraying. Animals exposed to low concentrations had an increase in the mast cells count, showing that this herbicide can cause allergic reactions in the airways. The tracheal epithelium thickness, the nuclear area and number of nucleolar organizing regions increased proportionally to the exposure concentration and in correlation with each other. These histological tissue changes correspond to epithelial hypertrophy and increased cell activity and multiplication, and show an adaptation to tissue damage caused by 2,4-D. There was a tendency for inversion in the mucus pattern to acid and a decrease in goblet cells in the groups exposed to 2,4-D, which alters the protective mechanisms of the respiratory tract. The 2,4-D induced adaptations in the tracheal epithelium associated with an increase in herbicide concentrations, which may compromise mucociliary function and predispose the epithelium to additional lesions over time. Therefore, it should be used with appropriate respiratory protection equipment to avoid injury. Full article

Background/Objectives: Acromegaly is a systemic connective tissue disease driven by chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess; yet, the female reproductive tract—especially the extracellular matrix (ECM)-rich cervix—has been poorly studied. We aimed to compare uterine and cervical morphology in women with acromegaly versus healthy controls and a gynecologic disease comparator, testing the hypothesis of selective cervical hypertrophy. Methods: We performed a retrospective case–control study of reproductive-age women who underwent pelvic ultrasound: acromegaly (n = 33), healthy controls (n = 45), and adenomyosis without acromegaly (n = 44). Uterine body measurements were obtained by TAUS/TVUS; cervical biometry was performed transvaginally in all cases. Volumes were estimated using the ellipsoid formula, and a uterus-to-cervix (U:C) volume ratio was calculated. Group differences were analyzed with Mann–Whitney tests and Bonferroni correction. Results: A total of 122 women were included. Uterine body length, width, AP size, and volume did not differ between acromegaly and either comparison group (all p-values non-significant). In contrast, cervical length, width, AP thickness, and volume were significantly higher in acromegaly than in healthy controls, with a corresponding reduction in the U:C volume ratio, indicating disproportionate cervical enlargement. Compared with adenomyosis, women with acromegaly again showed larger cervical width, AP thickness, and volume, together with altered U:C indices, whereas cervical length did not differ, suggesting a pattern not explained by nonspecific pelvic pathology. Conclusions: Women with acromegaly demonstrate a distinct uterine phenotype characterized by selective cervical hypertrophy with preserved uterine corpus size—an ECM-centric “acromegalic uteropathy.” This noninvasive morphometric signature may have diagnostic and procedural relevance and warrants confirmation in prospective studies. Full article

Background and Objectives: The hypertrophic adaptation of the diaphragm to inspiratory muscle training (IMT) remains insufficiently characterized, particularly in healthy and athletic populations. To address this gap, we conducted a meta-analysis and meta-regression to evaluate the effects of IMT on diaphragm thickness and identify potential moderating factors. Materials and Methods: A systematic search was conducted across PubMed, MEDLINE, Embase, CINAHL, and SPORTDiscus as well as Google Scholar (gray literature) through November 2025. Eight studies involving 203 healthy participants met the inclusion criteria. A random-effects model was used to calculate pooled effect sizes and meta-regression estimates. Results: IMT produced a statistically significant moderate increase in diaphragm muscle thickness, with a standardized mean difference (SMD) of Hedges’ g = 0.52 (95% CI: 0.19 to 0.85; p < 0.05). Subgroup analyses indicated that IMT with 50% maximal inspiratory pressure (MIP) produces a statistically significant effect (p = 0.0069), whereas fitness status and age did not significantly influence outcomes (p = 0.589 and p = 0.126, respectively). Meta-regression analyses revealed that only baseline MIP value (β = 0.030; 95% CI: 0.009 to 0.050; p = 0.004) was associated with diaphragm hypertrophy. Conclusions: IMT with 50% of MIP elicits meaningful diaphragmatic hypertrophy in healthy individuals. This response appears independent of fitness status or age, but is significantly influenced by baseline inspiratory muscle strength (MIP). These findings support the utility of IMT in enhancing respiratory muscle morphology in health and performance contexts. Full article

Background/Objectives: Fabry disease (FD) is a lysosomal storage disorder characterized by progressive renal and cardiac involvement and an increased burden of cardiovascular and cerebrovascular events. While cardiac magnetic resonance imaging (CMR) has significantly advanced structural assessment, circulating biomarkers reflecting disease-related cardiac manifestations remain incompletely understood. We therefore investigated adiponectin and leptin, two adipokines involved in inflammatory, metabolic, and fibrotic pathways, in relation to cardiac involvement and analyzed long-term lipid trajectories in FD. Methods: This longitudinal observational study included 49 patients with FD with 149 study visits. Circulating adiponectin, leptin, NT-proBNP, and conventional lipid parameters were assessed longitudinally and stratified by FD-specific therapy status and sex. Multivariable linear regression was performed to evaluate independent associations with log-transformed NT-proBNP values. Results: Adiponectin was positively associated with NT-proBNP, reflecting cardiac involvement, independent of age, sex, BMI, and eGFR (p < 0.001). Higher adiponectin levels were observed in patients with left ventricular hypertrophy or low T1 and those with fibrosis, detected by CMR (p = 0.009 and p < 0.001, respectively). This association was mainly seen in patients receiving FD-specific therapy, raising the question of whether this reflects underlying organ involvement or treatment effects. Leptin demonstrated weaker, inverse associations. Adiponectin, leptin, Triglycerides, total cholesterol, and HDL- and LDL-cholesterol levels remained stable over long-term follow-up, irrespective of FD-specific therapy or sex. Conclusions: In FD, adiponectin appears to be associated with cardiac involvement, and conventional lipid parameters remained unchanged over time. These findings suggest that alterations in adipokines, rather than progressive dyslipidemia, may reflect disease-related cardiac manifestations. Full article

Pathological cardiac hypertrophy is a critical factor leading to cardiomyopathy and ultimately heart failure. While several signaling pathways controlling cardiac hypertrophy have been identified, the molecular mechanisms underlying their precise regulation remain incompletely understood. Strip1, a structural component of STRIPAK complexes, has been implicated in various cellular functions; however, its role in cardiomyocytes is uncharacterized. Here we identify Strip1 as a potent anti-hypertrophic factor, controlling cell size and the hypertrophic gene program in neonatal rat ventricular cardiomyocytes (NRVCMs). STRIP1 expression was found to be significantly reduced in human dilated and ischemic cardiomyopathies (DCM/ICM), as well as in murine stress model induced by transverse aortic constriction (TAC). In a knockdown model with morpholino-driven STRIP1 reduction in zebrafish in vivo, impaired cardiac function and heart failure–like features were observed. Interestingly, Strip1 localized to the nucleolus in NRVCMs, suggesting a putative nuclear/epigenetic role in cardiomyocytes. Furthermore, our data support association of Strip1 with cardiac STRIPAK complex, modulating kinase activities, including MST1/MST2 and MST4. Mechanistically, Strip1 appears to influence prohypertrophic signaling, including Hippo- and Calcineurin/NFAT-related pathways, which may contribute to pathological cardiac remodeling. Collectively, these findings establish Strip1 as an important modulator of cardiomyocyte hypertrophy and a potential therapeutic target for cardiomyopathy and heart failure. Full article

Pathological cardiac hypertrophy, a major contributor to heart failure, is characterized by an abnormal increase in the size of atria and ventricles. In the context of ventricular hypertrophy, the right ventricle (RV) exhibits less resistance to hypertrophy than the left one (LV). Insulin-like growth factors (IGF-1 and IGF-2) are critical for cell growth and provide cardioprotective effects. Pregnancy-associated plasma protein-A (PAPP-A) is a protease that cleaves insulin-like growth factor-binding protein-4 (IGFBP-4) and enhances IGF bioavailability. This study investigated PAPP-A-mediated IGFBP-4 proteolysis—one possible mechanism of IGF release regulation in rat models of right ventricular (RVH) and left ventricular (LVH) hypertrophy. RVH was induced with monocrotaline, and LVH via renovascular hypertension (1 Kidney 1 Clip (1K1C) model). Systolic blood pressure was measured using tail-cuff plethysmography. Heart morphometry was used to assess the mass of cardiac chambers. Cardiomyocyte purity was confirmed via troponin I immunocytochemistry. Plasma natriuretic type-B peptide (BNP) and C-terminal IGFBP-4 (CT-IGFBP-4) concentrations were quantified by fluoroimmunoassay. RVH and LVH were successfully modelled, with 1.6-fold and 1.3-fold increases in RV (p < 0.0001) and LV masses (p < 0.05), respectively. Plasma BNP was 2–3 times higher in LVH versus control rats. Hypertrophied cardiomyocytes secreted significantly more BNP than controls, showing 3.3-fold and 4.1-fold increases in LVH and RVH, respectively. PAPP-A-mediated IGFBP-4 proteolysis was 4-fold higher in RVH compared to control, but unaffected in LVH. These findings suggest that PAPP-A-specific elevation of IGFBP-4 proteolysis occurs predominantly in RVH, suggesting a differential IGF bioavailability in both ventricles and highlighting PAPP-A as a potential target to increase RVH resistance to hypertrophy. Full article

Energy thriftiness and metabolic adaptations have had a crucial role in the emergence and spreading of the Homo lineage in the world. A higher-energy demand was required not only for the growing body mass, encephalization and human proliferation, but also for the survival adaptations to the environmental stresses. Because lean body mass lacks the energy-storage capacity required to supply the body’s demands, dedicated fat-storing cells originated. To feed such fat stores, the hominid evolution developed “meat-adaptive” genes to detect, digest and metabolize higher fat diets, and body-fat stores can be affected by lifestyle through hormonal-controlled daily energy balance. In energy surplus conditions, hypertrophy and hyperplasia of adipocytes can occur, with hypertrophic adipocyte signaling both a neo-adipocyte differentiation (leading to hyperplasia) and a local macrophage density (resident + infiltrated macrophages) for fat surplus scavenging. Adiposity-induced inflammation is caused by fat-overstored (hypertrophied) adipocytes that may operate as an overactive endocrine organ secreting an array of pro-inflammatory adipokines that, in combination with resident-macrophage activity and infiltrated blood-recruited, monocyte-derived macrophages, amplify the inflammatory process by spurting pro-inflammatory cytokines into the bloodstream. From an evolutionary perspective, obese humans represent a natural selection overexpressing the “thrifty” genes evolved for efficient food collection and fat deposition intended to help in survival in prolonged periods of famine. However, genetically speaking, obesity is a polygenic multifactorial disorder. Considering the rapidity of obesity-epidemic growth worldwide, epigenetic sets forth the key assumption of the mismatch between our human genome molded over thousands of generations, coping with the unprecedented dietary and physical conditions. Consequently, obesity would be due to our evolutionary-adapted polygenic-charge expressed by a deteriorated lifestyle characterized by high energy-dense food intake coupled with a reduction in caloric expenditure stemming from new mobility-reducing technologies. As a model of lifestyle change (LiSM), our 28-year on-going longitudinal study (“Moving for Health”) has shown effectiveness in the reduction not only of obesity but especially of its comorbidities, in a (10 week to 3 year) length-dependent LiSM. However, a disappointing progressive decrease in compliance with the study has been observed and attributed to the resistance of people to change their actual “obesogenic” lifestyle, basically represented by the individuals’ demand for labor-saving technologies and convenient, affordable, palatable foods. Full article

Eccentric (ECC) and concentric (CON) muscle training produce distinct physiological responses, with potential implications for musculoskeletal, metabolic, and cardiovascular health. Therefore, our objective is to synthesize evidence from randomized controlled trials comparing the effects of ECC and CON training on strength, hypertrophy, metabolic function, and cardiovascular health across diverse adult populations. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered in PROSPERO (ID: CRD42024627600). The review included eight randomized controlled trials, pooling data from a total of 441 participants. For strength-related outcomes, six studies (n = 322) were included; for hypertrophy, four studies (n = 210); and for cardiovascular measures, three studies (n = 154). Studies were assessed using the TESTEX scale. Standardized mean differences and random-effects models were applied (p ≤ 0.05). Results indicated that ECC training consistently produced moderate to large improvements in muscle strength (pooled ES = 0.95; I² = 78.6%) and hypertrophy (pooled ES = 0.60; I² = 62.3%), particularly in populations with chronic obstructive pulmonary disease (COPD) and older adults. The rate of force development (RFD) showed large effect sizes for ECC (RFD50: ES = 0.97; RFD100: ES = 0.95) but minimal change for CON (RFD50: ES = 0.04; RFD100: ES = 0.10). Both ECC and CON showed minimal effects on cardiovascular outcomes (heart rate and blood pressure: pooled ES range = −0.16 to 0.00; I² = 41.8%) and limited tendon remodeling (ES = −0.18). In conclusion, ECC exercise demonstrates superior benefits for improving muscular strength, hypertrophy, and power across varied populations, particularly those with clinical conditions such as COPD. Its impact on cardiovascular health and tendon properties, however, appears limited. These findings support the integration of ECC modalities into targeted rehabilitation and performance programs. Full article

Background and Clinical Significance: Subvalvular aortic stenosis (SAS) is the second most common form of aortic stenosis after valvular disease and predominantly affects male patients. It is frequently associated with other congenital cardiac anomalies, such as ventricular septal defect, and is rarely diagnosed during infancy. Instead, SAS typically manifests during childhood or adulthood as a progressive left ventricular outflow tract obstruction, leading to left ventricular hypertrophy and, in many cases, aortic regurgitation. Case Presentation: The first patient was a 61-year-old man presenting with progressive dyspnea, in whom echocardiography revealed severe subaortic stenosis and computed tomography demonstrated aneurysmal dilatation of the ascending aorta. Intraoperatively, the aortic valve was found to be dystrophic with mixed stenotic and regurgitant disease; therefore, subaortic membrane resection, mechanical aortic valve replacement, and ascending aortic replacement with a synthetic graft were performed. The second patient was a 31-year-old man with exertional dyspnea and a discrete subaortic membrane associated with mild ascending aortic dilatation. Surgical treatment consisted of complete membrane resection and aortic valve repair, while the ascending aorta was preserved. Both patients had an uneventful postoperative course and were discharged on the fourth postoperative day. At 3-month follow-up, both were asymptomatic, in normal sinus rhythm, and demonstrated satisfactory echocardiographic findings without residual left ventricular outflow tract obstruction. Conclusions: Surgical intervention remains the definitive treatment for subvalvular aortic stenosis when clinically indicated. Concomitant cardiac or aortic pathology should be addressed during the same procedure to optimize outcomes. When performed with meticulous technique and appropriate patient selection, surgical correction is associated with excellent early recovery and favorable mid-term results, although long-term follow-up remains essential due to the risk of recurrence. Full article

Honey, as a natural and nutritious sweetener, is one of the most widely consumed foods worldwide. However, the presence of phytotoxins in honey and the influence of honey’s intrinsic sugar matrix on the toxicity of these phytotoxins remain insufficiently explored. An optimized liquid chromatography–quadrupole trap tandem mass spectrometry method was developed to quantify 17 toxic alkaloids in 150 raw honey samples. Camptothecin was identified for the first time in the tested samples and was the most prevalent contaminant (36% detection, max 3.09 μg/kg), which induced cardiac hypertrophy and impaired cardiac function in zebrafish assays. The honey sugar matrix further potentiated these adverse cardiac effects through exacerbating oxidative stress and upregulating pro-inflammatory and pro-apoptotic gene expression, while natural honey partially mitigated such damage by upregulating the key antioxidant gene nrf2, thereby downregulating il-1β and regulating the bcl2/bax expression ratio. This study offers novel insights into honey phytotoxins’ matrix-modulated toxicity, laying a scientific foundation for optimizing safety protocols and matrix-specific risk standards. Full article

Background: The adenoid surface serves as a potential bacterial reservoir for upper respiratory tract pathologies, including Adenoid Hypertrophy (AH) and Otitis Media with Effusion (OME). While dysbiosis is implicated in the pathogenesis of these conditions, it remains unclear whether the microbiome of children with otitis media differs significantly from those with simple hypertrophy when compared against a healthy baseline. This study aimed to characterize the adenoid microbiome in children with adenoid hypertrophy with and without middle ear effusion, contrasting them with a healthy control group. Methods: We conducted a cross-sectional case–control study involving 58 pediatric participants divided into three groups: adenoid hypertrophy, adenoid hypertrophy and otitis media with effusion and healthy controls. Nasopharyngeal swabs were collected, and bacterial community composition was analyzed using 16S rRNA gene V4 sequencing. Alpha and beta diversity metrics, taxonomic composition, and differential abundance were evaluated. Results: Alpha diversity was significantly reduced in both disease groups compared to healthy controls (p < 0.001), indicating a collapse of microbial richness and evenness. Beta diversity analysis revealed a distinct separation between healthy and diseased cohorts; however, the microbial profiles of the AH and AH with OME groups were nearly identical. Taxonomic analysis demonstrated that disease was characterized by the depletion of health-associated commensals, specifically Veillonella, Actinomyces, and Gemella, and a concomitant expansion of Fusobacterium, Haemophilus, and Streptococcus. Conclusions: Adenoid hypertrophy is associated with a profound dysbiotic shift characterized by the loss of protective commensal flora and the dominance of pathobionts. The lack of significant microbial differentiation between the AH and AH with OME groups suggests that the adenoid surface acts as a centralized reservoir of dysbiosis, the composition of which is conserved regardless of the presence of middle ear effusion. These findings highlight the importance of restoring the commensal microbiome in the management of chronic adenoid disease. Full article

Mitochondria comprise ~1/3rd of the volume of an adult ventricular cardiomyocyte. The gene Immt encodes the Mic60/Mitofilin protein that is hypothesized to organize the mitochondrial contact site and cristae organization system (MICOS) complex that generates mitochondrial cristae junctions between the inner and outer membranes. To investigate the function of the Immt gene in the mouse heart, we generated and characterized mice in which this gene was specifically deleted in the mouse heart using a loxP-targeted allele (Immt^fl/fl) and either the constitutive heart-specific Myh6-Cre transgene or the conditional Myh6-MerCreMer transgene, each of which showed lethality in several weeks. Hearts from these mice showed progressive hypertrophic cardiomyopathy and failure with lost contractility and lung edema. At the ultrastructural level, hearts from these mice showed extreme abnormalities in mitochondrial architecture characterized by lost cristae junctions, stacking of the inner mitochondrial membranes, mitophagy and areas with complete absence of mitochondria. Analysis of mitochondria showed loss of the MICOS complex of proteins as well as loss of mitochondrial membrane potential (Δψ) and increased expression of mitophagy proteins and mitochondrial biogenesis transcription factors. Hearts from these mice also showed widespread cardiomyocyte necrosis and induction of the universal mitochondrial stress response at the mRNA level, as well as major alterations in cardiac metabolites, suggesting greater use of glucose, ketones and amino acids. We conclude that the Immt gene is required for cardiac mitochondrial structure and function, although the ensuing mitochondrial stress response provides molecular clues as to how the heart can compensate metabolically and maintain viability for weeks after mitochondria are absent or unfunctional. Full article