Search Results (6,180)

Ovarian cancer remains a top mortality contributor within gynecological cancers because patients receive diagnoses late in the disease course and conventional treatment resistance along with high recurrence rates cause poor outcomes. Aberrant regulation of autophagy and apoptosis has a critical role in the development, progression, chemoresistance, and immune escape from ovarian cancer. Recent evidence has demonstrated a complicated and dynamic crosstalk between autophagy and apoptosis, during which autophagy can act as a cytoprotective or cell death-promoting process depending on tumor stage and therapeutic context. In parallel, apoptosis functions as a tightly regulated form of programmed cell death that is essential for eliminating damaged or malignant cells and serves as a major tumor-suppressive mechanism in ovarian cancer. The PI3K/AKT/mTOR signaling pathway is the most active and clinically relevant pathway in the management of ovarian cancer as a master regulator of both autophagy and apoptosis, suppressing apoptotic cell death while promoting cytoprotective autophagy under chemotherapeutic stress. Bioactive natural products derived from plants, marine sources, and dietary intake have emerged as potential modulators of the autophagy-apoptosis crosstalk. Curcumin, resveratrol, quercetin, berberine, and epigallocatechin gallate are known to have the ability to restore apoptotic signaling, block pro-survival autophagy, and sensitize ovarian cancer cells to chemotherapy through the regulation of key pathways including PI3K/AKT/mTOR, AMPK, MAPK, p53, and Bcl-2 family proteins. In this review, we provide an updated understanding of the molecular mechanisms through which bioactive natural products modulate autophagy–apoptosis crosstalk in ovarian cancer. We also highlight the translational challenges, therapeutic potential, and future directions for the integration of natural product-based strategies in precision medicine for ovarian cancer. Full article

Aim: To report on the clinical and genetic spectrum of retinopathy associated with CDHR1 variants in a Hungarian cohort. Methods: A retrospective cohort study was conducted at a single tertiary care referral center. The study enrolled nine patients harboring biallelic variants in the CDHR1 gene. Detailed clinical history, multimodal imaging, electroretinography, and molecular genetics are presented. Results: We identified four CDHR1 variants predicted to cause loss-of-function and five phenotypes (cone dystrophy, central areolar choroidal dystrophy, cone-rod dystrophy, rod-cone dystrophy, and late-onset macular dystrophy). The most frequent variant was the synonymous CDHR1 c.783G>A (p.Pro261=) variant (10/18 alleles, 55.6%). A novel splice acceptor site variant, CDHR1 c.349-1G>A, and a novel intronic variant, CDHR1 c.1168-10A>G, were also detected. Fundus examination revealed macular atrophy with or without peripheral retinal changes. Full-field electroretinography, available in seven patients, demonstrated decreased light-adapted and extinguished dark-adapted responses in both the rod-cone dystrophy group and patients with macular involvement. OCT imaging indicated ellipsoid zone disruption with foveal sparing in two out of nine patients and severe retinal damage in rod-cone dystrophy cases. Conclusions: The predominant clinical manifestations of cone dystrophy, cone-rod dystrophy, and macular dystrophy in the Hungarian patient cohort showed heterogeneity, with a rod-cone dystrophy phenotype observed in five of nine cases (55.6%). The natural history of CDHR1-associated retinopathy typically follows a slow progression, providing a therapeutic window, which makes the disease a candidate for gene therapy. Full article

Pediatric obesity is a growing public health concern, significantly increasing the risk of metabolic and cardiovascular comorbidities. Background/Objectives: This study aims to explore the burden of obesity, its associated comorbidities, and resting metabolic rate (RMR) assessed by indirect calorimetry among children and adolescents in a cohort of 223 participants from Nord-East of Romania. Methods: A cross-sectional study was conducted among 223 children and adolescents (aged 4–18 years) who were diagnosed with obesity at Saint Mary Emergency Children’s Hospital Iași. Anthropometric measurements, clinical assessment, and biochemical parameters were recorded. RMR was measured by indirect calorimetry, using the Fitmate Pro Metabolic Technology (Cosmed, Rome, Italy), under a stable environment for 15 min, following a fasting period of minimum 6–8 h. Data were analyzed using SPSS 22.0, applying descriptive statistics and Pearson correlations. Results: A total of 223 participants were included in the analysis, with a mean age of 12.03 ± 3.32 years (range 4–17 years) and a mean body mass index (BMI) of 31.21 ± 5.84 kg/m². The average RMR was 1687.5 ± 425.5 kcal/day, with higher values in males compared with females. RMR showed significant positive correlations with age (r = 0.60), BMI (r = 0.51), waist circumference (r = 0.67), and fat mass measured with a three-site formula technique (r = 0.51) and systolic (r = 0.45) and diastolic blood pressure (r = 0.19), all with p < 0.001. A weak inverse correlation was observed between RMR and the fitness index (r = −0.24, p < 0.001), indicating an association between lower fitness scores and higher RMR values. RMR showed no significant correlation with fasting glucose or lipid levels, indicating that metabolic rate was more influenced by body composition than by biochemical markers. Conclusions: Pediatric obesity is strongly linked to multiple comorbidities, emphasizing the need for early detection and targeted interventions. Higher BMI and central adiposity were associated with increased RMR. Indirect calorimetry provides valuable insights into the metabolic profile of children with obesity and can inform individualized management strategies. Full article

Understanding how contextual variables shape differences in match demands in youth football is essential for optimising performance and player development. Objective: This study aimed to compare physical and competitive performance according to playing position, match location, match result, and opponent quality in the physical and competitive performance of U21 football players from a professional Chilean club. Methods: Twenty male U21 players (19.2 ± 1.2 years) were monitored during 11 official matches using 10 Hz GPS devices (WIMU Pro™) and post-match Rating of Perceived Exertion (RPE). Variables included total distance (TD), high-speed running (HSR > 20 km/h), metres per minute (MM), accelerations/decelerations (N°AC/N°DC > 3 m·s⁻²), player load (PL), and peak velocity (PV). Contextual variables were classified by playing position, home/away, win/loss, and opponent quality (higher vs. lower rank). Results: Significant between-group differences were found across all contextual factors (p < 0.05). Midfielders (MFs) covered greater TD and reported higher RPE, while full-backs (FBs) and wingers (WGs) reached higher HSR and PV. Away and lost matches showed greater RPE, PL, and N°AC/N°DC, alongside more goals conceded. Facing higher-ranked opponents increased RPE and HSR but reduced explosive actions. Conclusions: Physical performance in U21 football is strongly modulated by contextual factors. Coaches should adjust training load and tactical strategies according to match conditions and positional roles to optimise adaptation and competitive readiness in developmental categories. Full article

(1) Background: The synthetic eleven-amino acid peptide P₁₁-4, derived from DMP-1, self-assembles into β-sheet tapes, ribbons, fibrils, and fibers that form a 3D matrix enriched with calcium-binding sites. This study investigated whether P₁₁-4 modulates gene and protein expression or induces adverse metabolic alterations in odontoblast-like cells. (2) Methods: MDPC-23 cells were cultured under standard conditions and stimulated with different concentrations of P₁₁-4, followed by assessments of cell viability using the MTT assay, proliferation and migration, cytoplasmic calcium kinetics, reactive oxygen species (ROS) production, osteogenic differentiation-related gene expression via PCR array, and expression of the pro-inflammatory cytokine interleukin-6 (IL-6) using confocal microscopy and flow cytometry. (3) Results: The MTT assay showed that P₁₁-4 at 6.3, 12.6, and 25.2 µmol/L was non-cytotoxic and did not alter MDPC-23 cell proliferation or migration. Only the 25.2 µmol/L concentration induced a detectable Ca²⁺ influx and a slight increase in ROS. Among the 84 genes examined, P₁₁-4 at 6.3 µmol/L upregulated 79 genes, including transcription factors, signaling molecules, and extracellular matrix-related proteins. Furthermore, P₁₁-4 did not increase IL-6 expression under any condition tested. (4) Conclusion: P₁₁-4 markedly modulates mineralization-associated gene regulation without causing metabolic damage in odontoblast-like cells. Full article

This study evaluated the effect of clockwise reciprocation motion used in the original Optimum Torque Reverse kinematics, compared with clockwise continuous rotation, on the cyclic fatigue strength of nickel–titanium rotary instruments (NiTi) with different metallurgical characteristics. A total of 120 instruments, ProFile and EndoSequence in sizes 25/.04, 30/.04, and 35/.04, were tested under continuous rotation or reciprocation motions (n = 10 per subgroup). Instruments were examined by optical and scanning electron microscopy to exclude manufacturing defects. Phase transformation temperatures were determined by differential scanning calorimetry, and cyclic fatigue testing was conducted using a custom device simulating a curved canal with a 6 mm radius and an 86° curvature. The time to fracture was recorded, and the number of cycles to fracture was calculated. Statistical comparisons were performed using the Mann–Whitney U test with a significance level of p < 0.05. Differential scanning calorimetry showed that ProFile instruments were fully austenitic at the test temperature, while EndoSequence instruments exhibited a mixed R-phase and austenitic structure. Clockwise reciprocation motion significantly increased cyclic fatigue resistance in all groups compared with clockwise continuous rotation. Time to fracture increased by 241.3% to 337.5%, and EndoSequence instruments consistently demonstrated higher fatigue resistance. The greatest relative improvement was observed in ProFile 35/.04, with a 422.4% increase in the number of cycles to fracture. Overall, the reciprocation motion markedly enhanced cyclic fatigue strength irrespective of metallurgical phase composition, indicating a practical mechanical benefit that may reduce the risk of instrument separation during endodontic procedures. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and abnormal α-synuclein aggregation. Circulating microRNAs (miRNAs) have emerged as promising biomarkers and potential modulators of PD-related molecular pathways. In this study, we investigated the expression levels of four candidate miRNAs—miR-15a-5p, miR-16-5p, miR-139-5p, and miR-34a-3p—in patients with PD compared with healthy controls. A total of 47 PD patients and 45 age- and sex-matched controls were enrolled. Plasma miRNA levels were quantified using standardized RNA extraction, cDNA synthesis, and qPCR protocols. We observed marked upregulation of miR-15a-5p and robust downregulation of both miR-139-5p and miR-34a-3p in PD patients, whereas miR-16-5p showed no significant difference between groups. Target gene prediction and functional enrichment analysis identified 432 unique genes, with enrichment in biological processes related to protein ubiquitination and catabolic pathways, and signaling cascades such as mTOR, PI3K-Akt, MAPK, and Hippo pathways, all of which are implicated in neurodegeneration. Elevated miR-15a-5p may contribute to pro-apoptotic mechanisms, while reduced miR-139-5p and miR-34a-3p expression may reflect impaired mitochondrial function, diminished neuroprotection, or compensatory regulatory responses. Together, these dysregulated circulating miRNAs provide novel insight into PD pathophysiology and highlight their potential as accessible, non-invasive biomarkers. Further longitudinal studies in larger and more diverse cohorts are warranted to validate their diagnostic and prognostic value and to explore their utility as therapeutic targets. Full article

Background and Objectives: The anatomically demanding structure of curved root canals increases the technical difficulty of retreatment procedures. This study aimed to evaluate the retreatment efficacy of various rotary and reciprocating instruments in curved root canals obturated with cold and warm techniques regarding root canal filling material removal, apical transportation, and retreatment time. Materials and Methods: Sixty-four curved mesial root canals of mandibular molars with Vertucci type IV morphology were prepared using the ProTaper Gold system and obturated with AH Plus sealer using either the single-cone (SC) (n = 32) or continuous wave vertical compaction (CWC) (n = 32) technique. Each group was divided into four subgroups (n = 8) and retreated using MicroMega Remover (MM Remover), ProTaper Universal Retreatment (PTUR), Reciproc (Rec), and Hedstrom file systems. Micro-computed tomography was used to assess residual filling material volume and apical transportation. The time required for retreatment was recorded. The level of statistical significance was set at p < 0.05. Results: Across both obturation techniques, the MM Remover and PTUR groups demonstrated shorter retreatment times compared with the CWC–Hedstrom group (p < 0.05). No statistically significant differences were observed among the file systems in terms of filling material removal and apical transportation (p > 0.05). Conclusions: All tested instruments effectively preserved root canal anatomy within clinically acceptable apical transportation limits. The MM Remover and PTUR systems achieved significantly shorter retreatment times, indicating clinical advantages in efficiency. None of the evaluated systems achieved complete removal of the filling materials in either obturation technique. This study provides one of the first comparative evaluations of the MM Remover system, supporting its applicability in complex canal configurations. Full article

Background: Cancer-associated fibroblasts (CAFs) are key mediators of metastatic progression in non-small cell lung cancer (NSCLC). Fibroblast activation protein (FAP) serves as the hallmark of CAF activation. However, the upstream regulation of FAP remains elusive, limiting stroma-targeted therapy development. Methods: ⁶⁸Ga-FAP inhibitor (FAPI)-04 PET/CT imaging was performed on 61 NSCLC patients to evaluate the clinical significance of FAP. CAFs and normal fibroblasts (NFs) were isolated from patient tissues. Bioinformatic analysis and qRT-PCR were employed to screen and validate miRNAs. Functional assays (CCK-8, collagen contraction, wound healing, transwell co-culture) were utilized to investigate the role of miR-624-5p in regulating fibroblast activation and the effects on the metastatic potential of NSCLC cells. The targeting relationship between miR-624-5p and FAP was validated using FISH, dual-luciferase assay, and Western blotting. Results: ⁶⁸Ga-FAPI-04 uptake was higher in advanced NSCLC (p < 0.001) and correlated with tumor size, lymph node metastases, and distant metastases (p < 0.05). Isolated primary CAFs significantly enhanced the migration and invasion of A549 and PC9 cells compared to NFs (p < 0.001). We identified miR-624-5p as a significantly downregulated miRNA in CAFs (p < 0.001). Functionally, miR-624-5p overexpression inhibited CAF proliferation and collagen contraction (p < 0.01) and reduced the proliferation, migration, and invasion capabilities of A549 and PC9 cells (p < 0.001). Mechanistically, miR-624-5p bound to FAP mRNA and negatively regulated FAP expression (p < 0.001), thus suppressing CAF activation and tumor metastasis. Conclusions: Our findings establish miR-624-5p as a novel upstream regulator that suppresses FAP expression, consequently inhibiting CAF activation and its pro-metastatic function. Targeting the miR-624-5p/FAP axis represents a promising therapeutic strategy for NSCLC metastasis. Full article

Background/Objectives: Nurses are susceptible to compassion fatigue due to the nature of their professional responsibilities. Factors contributing to this vulnerability include daily patient interactions and organizational elements within their work environment, as well as work-related stress and sociodemographic characteristics, including age, marital status, years of professional experience, and, notably, gender. This research investigates the relationship between compassion fatigue and the levels of anxiety and depression, as well as the professional quality of life among nurses providing care to dementia patients in Greece. Methods: A cross-sectional survey was carried out with 115 nurses working in dementia care centers in Greece. The Hospital Anxiety and Depression Scale (HADS), the Professional Quality of Life Scale (ProQOL-5), and the participants’ personal, demographic, and professional information were all included in an electronic questionnaire. Multiple regression analysis was used. Results: A total of 42.6% of nurses rated their working environment as favorable. Additionally, 23.5% of the sample exhibited high levels of compassion satisfaction, whereas 46.1% demonstrated low levels of burnout. Female gender (p = 0.022) and a higher family income (p = 0.046) was positively associated with compassion satisfaction. Regression analysis indicated that elevated symptoms of anxiety and depression were found to correlate with decreased compassion satisfaction, increased burnout, and heightened secondary post-traumatic stress. Conclusions: Engaging in the care of patients with dementia, particularly throughout the pandemic period, has underscored a pronounced susceptibility to compassion fatigue, physical fatigue, pain, psychological stress, and a reduced quality of life. These results highlight the importance for nursing management to adopt specific organizational measures, including proper staffing levels, balancing workloads, and conducting routine mental health assessments. Full article

Background. Cervical spondylosis is a degenerative disorder of the spine, frequently associated with chronic neck pain, reduced mobility, and functional impairment. Patients develop alterations in muscle tone, stiffness, and elasticity, which further contribute to disability. This study aimed to investigate the effects of a 14-day standardized rehabilitation program on the biomechanical and contractile properties of cervical and scapular muscles in patients with cervical spondylosis. Methods. This study used a single-group pre–post observational design on 23 patients (16 women, 7 men; mean age 61.1 ± 14.2 years) diagnosed with cervical spondylosis. All participants completed a standardized rehabilitation treatment that included cervical mobilization, stretching, isometric exercises, scapular stabilization, electrotherapy, ultrasound, thermotherapy, and balneotherapy. Muscle properties were evaluated bilaterally using the MyotonPRO^® device, measuring frequency, stiffness, decrement, relaxation time, and creep. Assessments were performed in a sitting position for the deltoid, upper trapezius and pectoralis major, both at baseline (T0) and after treatment (T1). Handgrip strength was assessed bilaterally with a handheld dynamometer. Results. The deltoid muscle showed a significant reduction in frequency (14.86 → 13.50 Hz, p = 0.034) and stiffness (306.4 → 256.1 N/m, p = 0.014) on the right side, suggesting normalization of tone and passive resistance. The upper trapezius had a significant bilateral decrease in decrement (p < 0.05), reflecting improved elasticity. The pectoralis major displayed the most consistent adaptations, with increased frequency (right side, p = 0.008), improved relaxation bilaterally (p < 0.05), and significant reductions in decrement and creep (p < 0.01). Handheld dynamometry confirmed increased handgrip strength, with a 5.4% improvement on the left side and 7.6% on the right side. Conclusions. In our study measurable changes in muscle parameters were observed following a rehabilitation program in patients with cervical spondylosis. The integration of myotonometry and dynamometry allowed objective assessment of muscle adaptations supporting the clinical value of individualized rehabilitation strategies. Full article

Background/Objectives: Retinitis pigmentosa is a degenerative retinal disease and a major cause of inherited blindness globally. The pro-survival kinase AKT is downregulated in degenerating photoreceptors in retinitis pigmentosa, and its activation has shown neuroprotective effects in retinitis pigmentosa and other neurodegenerative disorders. In this study, we evaluated the therapeutic potential of SC79, a pharmaceutical AKT activator, in two mouse models of retinitis pigmentosa, rd1.GFP and RhoP23H.GFP. Methods: SC79 was administered intravitreally at postnatal day 12 (P12) and analysis was conducted at P16. Results: SC79 at 10 µM was well tolerated in wildtype mice, with no reduction in retinal function or thickness. In rd1.GFP mice, SC79 partially preserved peripheral outer nuclear layer (ONL) thickness, improved rod photoreceptor-driven optomotor contrast sensitivity responses, and improved cone photoreceptor morphology. Immunohistochemistry of retinal sections indicated AKT-related protein expression changes in both sham and SC79-treated rd1.GFP retinas, with sham injections leading to decreases in this pathway and SC79 injections restoring this back to uninjected protein levels or higher, indicating the damage from intravitreal injections can induce AKT-related protein expression changes. In RhoP23H.GFP mice, changes to the visual response from the therapeutic effects of SC79 were not detectable. An increased dosage of SC79 at 100 µM was evaluated in wildtype mice and showed no major toxic effects, although it did not confer neuroprotective benefits in either disease model. Conclusions: These results demonstrate the potential therapeutic effect of AKT pathway modulation for preserving photoreceptors in recessive retinitis pigmentosa, with further optimisation of treatment delivery required. Full article

Obesity, an escalating global health crisis, is characterized by adipose tissue hypertrophy and chronic low-grade inflammation. Although anti-obesity drugs can induce weight loss, their use is limited by adverse effects, underscoring the need for safer therapeutic strategies. In this study, we generated a recombinant form of Trichinella spiralis-derived macrophage migration inhibitory factor (rTs-MIF) and investigated its anti-inflammatory and anti-obesity effects via immunometabolic regulation. Male C57BL/6 mice fed a 45% high-fat diet were orally administered rTs-MIF, and its effects were evaluated by measuring fat mass, glucose metabolism, serum cytokines, liver histology, and adipose tissue parameters. In 3T3-L1 cells, we examined the effects of rTs-MIF on adipocyte differentiation, obesity-related gene expression, and intracellular signaling pathways. Oral rTs-MIF suppressed body weight gain, reduced fat mass, improved glucose levels, and decreased the food efficiency ratio. It also lowered pro-inflammatory cytokines and increased markers associated with M2 macrophages. In 3T3-L1 cells, rTs-MIF inhibited adipocyte differentiation and reduced the expression of lipogenic transcription factors and mouse Mif while modulating AKT and p44/42 MAPK signaling. These findings identify rTs-MIF as a potential bioactive candidate that ameliorates obesity by regulating the immune–metabolic axis. Full article

Background and Objectives: Asymmetries in body composition and movement patterns are common in professional basketball due to the sport’s repetitive and unilateral demands. While both structural and functional asymmetries have been independently studied, little is known about their interaction under real training conditions. The aim of this study was to compare structural asymmetries, obtained from bioelectrical impedance analysis, with functional asymmetries, measured through inertial devices in professional basketball players. Methods: Twenty-five male professional basketball players from two Spanish teams were monitored over a two-month period. Structural asymmetries were assessed via the TANITA MC-780MA multi-frequency analyzer, while functional asymmetries were quantified using WIMU Pro™ inertial units during 43 training sessions. Descriptive, correlational, and cluster analyses were performed, followed by linear mixed-effects models adjusted for individual random effects, with statistical significance set at p < 0.05. Results: Descriptive results revealed low overall fat mass and no relevant group-level asymmetries in muscle mass or functional variables, although fat mass asymmetry showed greater variability across players. Correlation analyses indicated weak and non-significant relationships between structural and functional asymmetries. Cluster analysis grouped muscle mass and functional asymmetries together, while fat mass asymmetry formed a distinct cluster. Linear mixed-effects models confirmed significant differences for muscle mass asymmetry and demonstrated high inter-individual variability. Conclusions: Structural and functional asymmetries behave independently, with muscle mass asymmetry showing greater variability and functional relevance. These findings highlight the need for individualized monitoring approaches integrating morphological and functional assessments to optimize performance and reduce injury risk in elite basketball players. Full article

This study explored the effects of Bifidobacterium animalis subspecies lactis CECT 8145 (B. animalis CECT 8145)—in both live probiotic and heat-treated postbiotic form—on metabolic health and digestion in male and female Labrador Retrievers during weight gain and loss. The study consisted of two, seven-week phases: weight gain (200% maintenance energy intake; Phase (1) and weight loss (100% maintenance energy requirement for ideal weight; Phase (2), separated by a 2-week washout period. In each phase, forty-five adult Labrador Retrievers (1.6–12.5 years) were randomly assigned to daily supplementation with live B. animalis CECT 8145 probiotic (PRO, n = 15), heat-treated B. animalis CECT 8145 postbiotic (POST, n = 15), or placebo control (CON, n = 15). Body weight, body condition score, fecal quality and food consumption were monitored throughout the study, and body composition, fecal, and blood samples were analyzed at the beginning and end of each phase. Digestibility was evaluated at the end of each phase. Post-prandial glucose responses were affected by intervention during weight loss, with a 6% reduction in the area under the curve (AUC) in POST compared to CON dogs (p = 0.035). Glucagon was decreased in females supplemented with POST (p = 0.0014), while POST males showed increased glucagon-like peptide-1 (GLP-1) compared to CON (p = 0.016) during weight gain. Serum GGT levels decreased, within the normal reference range, in POST compared to CON dogs during weight gain (post hoc p = 0.041). Fecal isovalerate was also reduced and fat digestibility increased (p = 0.026) in POST compared to CON (p = 0.018) during weight gain. There was a significant association between the group and gastric inhibitory polypeptide (GIP), with a decrease in GIP in POST over time (p = 0.030), and glucagon tended to be decreased in POST compared to CON (p = 0.073). Overall, these findings suggest supplementation with postbiotic B. animalis CECT 8145 may improve certain markers of Labrador retrievers’ metabolic health. Full article