Search Results (30,905)

Temporomandibular disorders (TMDs) are the prevalent causes of orofacial pain and dysfunction of the temporomandibular joint (TMJ) and masticatory muscles. Previous studies have revealed that proinflammatory cytokines play a key role in promoting inflammation, pain, and degeneration within the TMJ. In this context, the present systematic review synthesizes current evidence on various cytokines involved in the pathophysiology of TMDs and evaluates their associations with clinical signs and structural TMJ damage. A PRISMA-guided search (PROSPERO: CRD420251163290) was conducted in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library to identify human-based, in vivo, and in vitro studies (January 2014 to September 2025) that assessed the roles of proinflammatory cytokines in TMDs. The following data were extracted from the identified studies: cytokine profiles, sampling methods, clinical outcomes, and TMJ structural changes. Study quality and risk of bias were systematically evaluated. A total of 15 studies (clinical, animal, and mechanistic) were included in the review. Tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) consistently emerged as the major contributors to synovitis, cartilage degradation, nociceptive sensitization, and bone resorption. Human studies showed that high levels of TNF-α, IL-1β, and IL-6 and chemokines such as C-C motif chemokine ligand 2 (CCL2) and regulated on activation, normal T-cell expressed and secreted (RANTES) were associated with TMJ pain, restricted mandibular motion, crepitus, malocclusion, and erosive changes on imaging. An increased ratio of TNF to soluble TNF receptor in synovial fluid correlated with both pain and condylar damage, suggesting that loss of cytokine control contributes to progressive joint destruction. TMDs, particularly inflammatory and degenerative subtypes, are cytokine-driven pathologies rather than purely mechanical disorders. TNF-α, IL-1β, and IL-6 are the promising candidate biomarkers of local inflammation and structural joint pathology. Standardized longitudinal studies are required to validate cytokine-based diagnostics and develop anti-cytokine therapeutics. Full article

Background/Objectives: The objective of this investigation was to assess the prevalence of sarcopenia and identify its related risk factors in patients with rheumatoid arthritis (RA) using data from the nationally representative 2008–2011 Korea National Health and Nutrition Examination Survey (KNHANES). Methods: We analyzed data from the 2008–2011 KNHANES to identify the factors associated with sarcopenia in patients with RA. Sarcopenia was defined as the ratio of appendicular skeletal muscle mass to total body weight (multiplied by 100), with cut-offs of <29.0% for men and <22.9% for women. To identify the specific factors independently associated with sarcopenia, a multivariate logistic regression model was employed, accounting for sample weights and the complex survey design. Results: Among 238 patients with RA included in the analysis, 44 (weighted prevalence: 22.7%) had sarcopenia. The sarcopenia group had a higher proportion of males (55.0% vs. 15.3%, p < 0.001), body mass index (BMI) (26.1 vs. 23.3 kg/m², p < 0.001), and waist circumference (86.9 vs. 79.0 cm, p < 0.001) than the non-sarcopenia group. After adjustment for potential confounders, including age, sex, obesity, physical activity, and daily protein intake, male sex (odds ratio [OR]: 4.17; 95% confidence interval [CI]: 1.48–11.77, p = 0.007) and obesity (OR: 3.06; 95% CI: 1.16–8.07, p = 0.024) were independently associated with sarcopenia. In sex-specific analyses, low physical activity was significantly associated with sarcopenia only in male patients (OR: 13.00; 95% CI: 1.90–88.75, p = 0.012). Conclusions: Our findings indicate that being male and having a higher BMI are significant independent indicators of sarcopenia risk within the Korean RA population. This highlights their critical role in the development of sarcopenia among RA patients. Full article

Background: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating skeletal muscle weakness and fatigue, leading to reduced functional independence and impaired quality of life (QoL). Although exercise has historically been discouraged due to concerns about symptom exacerbation, emerging evidence suggest that structured exercise programs may be safe and beneficial in clinically stable patients. This systematic review critically evaluates current evidence on exercise and physical activity interventions in MG, focusing on effectiveness, safety, and impact on functional outcomes, fatigue, and QoL. Materials and Methods: A systematic review was conducted following PRISMA guidelines. Searches were performed in PubMed, Web of Science, Google Scholar, Scopus and ScienceDirect for studies published between 2015 and 2025. Keywords included MG, physical activity, aerobic training, resistance training, and respiratory muscle training. Methodological quality was assessed using the Downs and Black checklist. Results: Eight controlled studies met the inclusion criteria, encompassing aerobic, resistance, combined, and respiratory muscle training interventions. Sample sizes ranged from small pilot studies to moderate-size randomized controlled trials. Overall, exercise interventions were well tolerated, with no evidence of sustained symptoms exacerbation. Aerobic and combined programs consistently improved functional capacity, muscle strength, and activities of daily living. Respiratory muscle training demonstrated improvements in pulmonary function and inspiratory muscle strength, although findings were more heterogeneous. Study quality ranged from poor to excellent, with common limitations including small sample size, short follow-up duration, and heterogeneity in exercise programs. Conclusions: Current evidence supports the safety and potential efficacy of individualized, symptom-guided exercise interventions in clinically stable MG. Regular physical activity exercise may reduce secondary deconditioning, improve functional outcomes, and enhance QoL. However, larger, high-quality randomized controlled trials with standardized programs and longer follow-up periods are required to strengthen clinical recommendations and clarify long-term effects. Full article

Background/Objectives: This systematic review examined whether oral vitamin D supplementation improves vitamin D status, health, and exercise outcomes in indoor-training aquatic athletes. Methods: We systematically reviewed randomized, placebo-controlled trials (>2 weeks) investigating vitamin D supplementation in competitive swimmers and divers. Six eligible trials (n = 246) were included and summarized descriptively. Results: Supplementation (2000–5000 IU/day for 12 weeks to 6 months) consistently increased serum 25(OH)D compared with placebo, with average increases up to 9.3 ng/mL. While higher doses occasionally improved muscle strength and lean mass, evidence showed no consistent benefits for swimming performance, immune function, or bone turnover. Additionally, higher body mass index (BMI) correlated with smaller 25(OH)D increases. Conclusions: Vitamin D effectively corrects deficiencies in aquatic athletes but lacks consistent ergogenic benefits. Therefore, in practice, supplementation should serve primarily as a targeted corrective measure for deficiency to support fundamental musculoskeletal health, rather than a generalized strategy for performance enhancement. Full article

Betaine-homocysteine methyltransferase (BHMT) is an enzyme involved in one-carbon metabolism and plays a crucial role in maintaining liver health. In this study, we investigated the impact of liver-specific deletion of BHMT on liver dysfunction using a mouse model. We generated BHMT floxed mice and bred them with albumin Cre to generate liver-specific BHMT knockout (BHMT LKO) mice. Liver tissues harvested from six-month-old chow-fed BHMT floxed and LKO mice were characterized through histological, biochemical, and molecular analyses. BHMT LKO mice displayed a complete loss of hepatic expression of BHMT mRNA, protein and enzyme activity. Histopathological analysis revealed the development of hepatic steatosis in BHMT LKO mice compared to the floxed mice. These morphological changes were supported by biochemical analysis showing elevated levels of hepatic triglycerides in conjunction with a profound decrease in the methylation potential (i.e., reduced S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio), which was mainly driven by a six- to sevenfold increase in SAH levels. BHMT LKO mice also exhibited increased lipid peroxidation and lysosomal dysfunction compared to floxed mice. Early signs of inflammation were seen in the livers of BHMT LKO mice of both sexes, as evident from significant increase in CD68-positive cells and interleukin 1β levels. Additionally, there was a moderate increase in fibrosis, as evidenced by the upregulated expression of α-smooth muscle actin and collagen II levels and the histological assessment of picrosirius red-stained liver sections of BHMT LKO mice of both sexes compared to their respective counterparts. These findings demonstrate that hepatic BHMT deficiency promotes lipid accumulation, lysosomal/proteasomal dysfunction, and early inflammatory and fibrotic changes in the liver by reducing the methylation potential. Collectively, our results underscore BHMT as a critical regulator of liver homeostasis and a potential therapeutic target in liver-related disorders. Full article

Background: Monitoring skeletal muscle mass (SMM) during radiotherapy (RT) is important, as SMM loss is associated with poorer clinical outcomes. Cone-beam CT (CBCT), acquired before each RT fraction, offers the potential to track the lumbar skeletal muscle index (LSMI) over time. However, CBCT has lower image quality than conventional CT. This study assessed the agreement between CT and CBCT and evaluated the reliability of LSMI measurements in patients with head and neck squamous cell carcinoma. Methods: Patients who underwent both CT and CBCT on the same day during RT were included. The cross-sectional muscle area at C3 was measured, converted to L3, and used to calculate the LSMI. Two researchers analyzed all scans, with one repeating the measurements. Agreement and reliability were quantified using intraclass correlation coefficients (ICCs) and visualized with Bland–Altman plots. Results: LSMI measurements showed excellent agreement between CBCT and CT (ICC: 0.97–0.99; 95% CI: 0.95–0.99). The intrarater (ICC: 0.99; 95% CI 0.98–0.99) and interrater reliability (ICC: 0.97; 95% CI: 0.66–0.99) were high. Bland–Altman plots, however, revealed wide limits of agreement. Conclusion: CBCT provides reliable LSMI measurements and agrees well with CT, but the observed variability suggests cautious interpretation. When both modalities are available, CT remains the preferred standard for SMM assessment. Full article

This study aims to establish a protocol for measuring the postauricular muscle reflex (PAMR) and to characterize both short- and mid-latency responses under controlled conditions in adults with normal hearing. PAMR electromyography was recorded in 43 adults with normal hearing. Auditory stimuli (50 ms, 80–100 dB(A)) were presented at four frequencies (500, 1000, 2000, and 4000 Hz), with systematic variation in stimulation side (ipsilateral/contralateral) and eye position (forward/rotated). The influence of these factors on PAMR amplitude and latency was analyzed using linear mixed-effects models. A short-latency PAMR (10–25 ms) was observed in all but one participant in at least one frequency. Reflex amplitude was significantly affected by stimulation side, eye position, frequency, and intensity. Contralateral stimulation produced stronger responses than ipsilateral stimulation. Additionally, a mid-latency PAMR (37–50 ms) was identified in 91% of participants, exhibiting lower amplitude and a higher detection level compared to the short-latency response. The mid-latency reflex was also significantly influenced by experimental conditions. The data shows that PAMR can be reliably recorded under controlled conditions in normal-hearing adults and that both short- and mid-latency components are influenced by auditory and oculomotor factors. These results provide us with normative data that can serve as a reference for future investigations in clinical populations, such as cochlear implant users and individuals with hearing loss. Full article

Objective: To characterize the distribution of FCR severity across survivorship time intervals in bladder cancer survivors. Methods: A cross-sectional study of 79 patients utilized the validated 9-item FCR Inventory-Short Form (FCRI-SF) to assess overall FCR severity. Primary analysis employed Spearman’s correlation coefficient to evaluate the relationship between time elapsed since the first procedure and total FCR scores. Patients were stratified into four temporal groups (<1, 1–2, 2–5, and >5 years). Inter-group variability in FCR scores was assessed using Levene’s test for equality of variances. Subgroup analyses compared FCR scores across clinical subgroups, including tumor grade and smoking history, using the Mann–Whitney U test. Multivariate logistic regression identified independent predictors of clinically significant FCR (total score ≥13). Results: Median patient age was 72.0 years (IQR 66.0–78.0), with a median of 24.0 months post-diagnosis. Clinically significant FCR (score ≥13) was prevalent in 55.7% of the cohort. Spearman correlation analysis revealed no significant relationship between months elapsed and FCR severity (rho = 0.068, p = 0.552). Patients in the 12–24 month window exhibited the highest variability (Levene’s test, p = 0.058), representing a period of clinical divergence. High-Grade disease and smoking cessation motivated by diagnosis were associated with higher FCR scores. In the multivariate logistic regression model, history of tumor recurrence was the sole independent predictor of clinically significant FCR (aOR 3.28, 95% CI 1.11–9.68, p = 0.031), whereas age and gender were not significantly associated. Conclusions: FCR severity did not demonstrate a significant association with time elapsed since diagnosis in this cross-sectional sample. The 1–2 year interval demonstrated greater inter-individual variability in FCR scores. Findings highlight the need for long-term, structured survivorship support, particularly targeting the 12–24 month post-diagnosis window. Full article

Background/Objectives: Image quality of mammograms in breast cancer screening is strongly operator-dependent, particularly in the mediolateral oblique (MLO) projection where adequate visualisation of the pectoralis major muscle serves as a surrogate marker of posterior tissue inclusion. Current positioning assessment is predominantly qualitative and subject to inter-observer variability. This study aimed to quantitatively evaluate pectoral muscle visualisation and compression force variability among radiographers participating in a national screening programme. Methods: A retrospective observational study was conducted at Clinical Hospital Center Rijeka in January and February 2020. A total of 464 digital MLO mammograms were analysed. Images from nine radiographers were randomly retrieved from the institutional Picture Archiving and Communication System (PACS). Pectoral muscle length and width were measured using a standard clinical workstation with an integrated distance measurement tool. Additional variables included radiographer gender, breast side (LMLO vs. RMLO), imaging order, and applied compression force. Statistical analyses included Welch’s ANOVA, one-way ANOVA, t-tests, and appropriate post hoc comparisons. Results: Across all MLO projections, the combined mean pectoral muscle width was 41.0 ± 11.4 mm and the mean length was 134.3 ± 21.7 mm. Significant inter-operator differences were observed in pectoral muscle width (p < 0.001) and length (p = 0.023). Mean muscle width ranged from 35.0 mm to 54.2 mm, and mean length from 126.5 mm to 139.4 mm across radiographers. No significant differences were found with respect to radiographer gender, breast side, or imaging order (all p > 0.05). Compression force differed significantly among radiographers (p < 0.001), ranging from 117.0 ± 18.3 N to 184.8 ± 33.9 N. Conclusions: This study demonstrates significant inter-operator variability in both pectoral muscle visualisation and applied compression force during MLO mammography. These findings indicate that important technical aspects of mammographic examination remain strongly operator-dependent and highlight the need for more consistent positioning practices within screening programmes. Quantitative measurement of pectoral muscle dimensions may serve as a practical and objective approach for monitoring positioning quality and supporting quality assurance in routine clinical practice. Full article

Objective: Seaweed and microalgae provide antioxidants, polyunsaturated fatty acids, and bioactive compounds that may enhance exercise performance and accelerate recovery. However, evidence remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of algae-derived supplementation on exercise performance and physiological recovery outcomes in healthy and athletic adults. Methods: This review was registered in PROSPERO (CRD420251166723) and conducted in accordance with PRISMA 2020 guidelines. PubMed, Web of Science, Embase, Cochrane Library, EBSCO, and CNKI were systematically searched for randomized controlled trials (RCTs) evaluating algae supplementation in exercise contexts. Inclusion and exclusion criteria were defined based on the PICOS framework. Primary outcomes included VO₂max, Time to exhaustion (TTE), maximal power output (WRmax), Time-Trial (TT) performance, and creatine kinase (CK). Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were performed. Results: Twenty-two RCTs (n = 822) investigating Spirulina, Chlorella, brown-algal polysaccharides, or astaxanthin met inclusion criteria. Algae supplementation showed a suggestive improvement in VO₂max (SMD = 0.88, 95%CI: 0.00–1.75) and significantly improved in TTE (SMD = 1.06, 95%CI: 0.16–1.96), with smaller effects on WRmax (SMD = 0.29, 95%CI: 0.03–0.55), and no significant benefit for TT performance (SMD = −0.27, 95%CI: −0.74 to 0.21). Regarding recovery, CK concentrations were significantly reduced (SMD = −0.78, 95%CI: −1.28 to −0.28). Subgroup analysis suggested greater effects for Chlorella supplementation, higher dosages, and aerobic training contexts; reductions in muscle-damage markers were more evident following resistance exercise. Sensitivity analyses supported the robustness of the main findings with minimal evidence of publication bias. Conclusions: Algae-derived supplements—particularly Spirulina and Chlorella—may modestly enhance aerobic exercise performance and attenuate exercise-induced muscle damage under certain conditions. Effects appear to depend on algae species, dosing strategies, intervention duration, and training modality. High-quality, multi-center RCTs incorporating mechanistic endpoints are needed to clarify optimal application and to develop athlete-specific recommendations. Full article

Cigarette smoking contributes to vascular aging through oxidative stress, inflammation, and extracellular matrix (ECM) remodeling. Cellular senescence has been recognized as an important mechanism linking tobacco exposure to vascular dysfunction, but effective pharmacological strategies targeting this process remain scarce. In this study, we examined whether Rapalink-1, a dual inhibitor of mechanistic target of rapamycin complex 1 and complex 2 (mTORC1 and mTORC2), modulates smoke condensate (SC)-induced senescence in vascular cells. Human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (SMCs) were exposed to SC with or without Rapalink-1. SC increased intracellular reactive oxygen species, induced DNA damage, and promoted senescence-associated changes, including increased senescence-associated β-galactosidase (SA-β-gal) activity, reduced Lamin B1, and elevated p21 expression. These effects were accompanied by increased expression of inflammatory and matrix-remodeling genes associated with the senescence-associated secretory phenotype (SASP). Rapalink-1 co-treatment reduced oxidative stress and DNA damage, attenuated senescence markers, and partially normalized SASP-related and ECM-associated gene expression. Mechanistically, SC activated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling and increased downstream mTOR pathway activity, whereas Rapalink-1 dampened these signaling responses. Together, these findings indicate that dual mTORC1/2 inhibition by Rapalink-1 mitigates smoke condensate-induced senescence and inflammatory responses in vascular cells. Full article

The Mediterranean Diet (MD) is recognized for promoting longevity and reducing the risk of chronic disease, yet the mechanisms underlying these benefits remain uncharacterized. This review highlights the diverse nutritional and phytoactive constituents of the MD and research exploring its complex network of polyphenols. It discusses data evaluating MD-derived constituents formulated into a dietary supplement capsule developed using a systems and network biology framework. Component selection was based on their actions on enzyme systems involved in senescence-related pathways and health preservation. This review highlights how MD components synergistically modulate pathways central to antioxidant activity, cognitive health, and aging. Liquid chromatography–mass spectrometry identified phytochemically diverse constituents in capsules (supplied by DailyColors™, Warwickshire, UK and Sebastopol, CA, USA) derived from primary color groups in sixteen Mediterranean plants. These constituents were mapped to bioactive networks targeting enzymes linked to inflammation, metabolic regulation, and cellular senescence. Preclinical studies demonstrated the modulation of mitochondrial and metabolic health markers, with complementary effects on cytokine inhibition and glucose sensitivity. Two clinical studies confirmed broad proteomic and epigenetic effects on pathways governing immunity, skeletal muscle, cognition, and inflammation. Therefore, this review advances a novel perspective that MD polyphenols act through synergistic, multi-pathway interactions that link dietary patterns to coordinated regulation of longevity and healthy aging. Full article

The present study investigated the effect of Ligula intestinalis L. infection on several components of the antioxidant system and on protein oxidation in the host fish, common bream Abramis brama L. In ligulosed bream, the hepatopancreatic antioxidant system response included a decrease in catalase (CAT) activity, an increase in glutathione S-transferase (GST) activity, and no change in superoxide dismutase (SOD) activity. The contents of molecular antioxidants in the organs of infected bream were inconsistent; for instance, hepatopancreatic α-tocopherol content was significantly lower, whereas retinol content was significantly higher than in uninfected individuals. In contrast, no significant differences were found in the α-tocopherol or retinol content in the skeletal muscles of infected and uninfected fish. The protein oxidation, estimated via protein carbonyl content, was unaffected by ligulosis, as was the activity of proteasomes. However, the activity of calpain, another protease, was significantly higher in the skeletal muscle of infected fish. Overall, the data reveal moderate and tissue-specific alterations in oxidative stress markers in A. brama infected with L. intestinalis, suggesting a complex host–parasite interaction that does not result in severe systemic oxidative damage under the studied conditions. Full article