Search Results (390)

Adipose tissue expansion in obesity is accompanied by extracellular matrix (ECM) remodeling, regulated by matrix metalloproteinases (MMPs). Visceral adipose tissue (VAT) is metabolically more active than subcutaneous adipose tissue (SAT). However, depot-specific differences in proteolytic activity and protein glycooxidation remain incompletely characterized. In this case–control study, we assessed the activity of six matrix metalloproteinases (MMP-1, -2, -7, -9, -11, and -13) using a fluorescence resonance energy transfer (FRET) assay and quantified advanced glycation- and glycooxidation-related markers in paired VAT, SAT, and plasma samples obtained from 40 patients with obesity and 21 non-obese controls. The activities of all assessed MMPs were greater in patients with obesity than in the control group (p < 0.01 for all MMPs). Direct tissue-compartment comparisons showed that MMP activity and glycooxidation-related markers were most pronounced in VAT, with markedly higher values in obese individuals compared with controls. In VAT of obese individuals, median MMP activity was approximately 50–60% higher compared with controls. Amyloid cross-β-structure, vesperlysine, and pentosidine were significantly elevated in VAT in obesity, whereas plasma levels were markedly lower and showed limited group differences. No significant differences were observed between obese participants with and without metabolic syndrome. Obesity is associated with a depot-specific molecular profile characterized by enhanced proteolytic and glycooxidative activity predominantly within visceral adipose tissue. These findings highlight the importance of tissue-compartment-specific assessment in obesity. Full article

The exact mechanisms of skin involvement in type 1 diabetes (DM1) remain poorly understood. This study aimed to evaluate the relationship between antioxidants, oxidative stress, protein glycation, and glycoxidation, as well as matrix metalloproteinase (MMP) activity, in the skin of rats with DM1, while investigating whether insulin administration improves skin homeostasis. Male Wistar rats were assigned to three groups: control, diabetes, and diabetes treated with insulin. Significantly higher expression of GSH (gluthatione) and GSH-Px (glutathione peroxidase), elevated levels of AGE (Advanced Glycation End products), DT (dityrosine), KN (kynurenine), NFKN (N-formylkynurenine) and ONOO- (peroxynitrite), as well as increased activity of GLU (β-D-glucuronidase), NADPH oxidase (NOX) and MMP-1, -2, -3, -7, -9, -11 and -13 were observed in the skin of rats with DM1. Insulin treatment normalizes the skin’s antioxidant barrier and eliminates oxidative stress. It also reduces the intensity of protein glycation and glycoxidation, though not to the levels observed in the control group. Summarizing, in diabetic skin there is a complex interaction between the thiol antioxidant barrier, oxidative damage, protein glycation and glycoxidation as well as MMP expression. Insulin restores physiological balance in skin cells; however, glycation and ECM remodeling are still more pronounced than in healthy skin. Full article

Background/Objectives: This longitudinal study examined the association between sleep duration, sleep difficulties, and sleeping place at one year (t1) and corresponding characteristics at 4/5 years of age (t2). Methods: Data were collected from 2018 to 2021 (t1) and from 2021 to 2024 (t2) in the LIFE Child cohort study conducted in Leipzig, Germany. Parents completed the Brief Infant Sleep Questionnaire at t1 and the Child Sleep Habits Questionnaire at t2. Associations between sleep characteristics at t1 and t2 were estimated using linear and logistic regression models. All associations were adjusted for child sex, age at t2, and maternal education. Results: The analyses showed significant associations between shorter sleep durations, later sleep onset times, more frequent nightly awakenings and bed sharing and room sharing at t1 and more sleep difficulties at t2. A shorter sleep duration at t2 was predicted by shorter sleep and more parent-perceived sleep difficulties at t1. Bed sharing and room sharing at t1 were significantly associated with a lower probability of sleeping alone at t2. Conclusions: These results indicate that sleep duration, sleep difficulties, and sleeping places are already stable in early childhood. Full article

Psychotic symptoms, including delusions and hallucinations, frequently complicate the course of Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), and frontotemporal dementia (FTD). Their presence accelerates decline, worsens outcomes, and complicates management. Cognitive screening in such patients is essential yet challenging due to attentional fluctuation, impaired insight, and diagnostic overlap. Addenbrooke’s Cognitive Examination III (ACE-III) is a multidomain tool with higher sensitivity than the MMSE. Evidence indicates that ACE-III captures disorder-specific cognitive-psychotic profiles: memory impairment in AD with delusions of theft, visuospatial and attentional deficits in DLB with hallucinations, or executive dysfunction in FTD with paranoid ideation. Mini-ACE (M-ACE), a shorter derivative, is useful in acute psychiatric or advanced dementia settings. This review synthesizes evidence on ACE-III and M-ACE in psychosis-related neurodegeneration, highlights their role in differentiating from primary psychiatric psychoses, and identifies knowledge gaps, particularly in atypical AD variants, mixed dementia, and autosomal dominant AD. ACE-III emerges as a practical and informative tool, but psychosis-specific normative data and longitudinal studies are needed. Full article

High-performance athletes are increasingly exposed to frequent trans-meridian travel, leading to profound circadian desynchronization and gastrointestinal distress. This review examines the complex interplay between the host’s central circadian system and the gut microbiota (GM), both of which exhibit synchronised daily oscillations essential for homeostasis. Rapid time-zone transitions, such as those anticipated for the 2026 FIFA World Cup, induce a state of “gut jet lag,” characterised by the loss of rhythmic microbial functions and impaired intestinal barrier integrity. Circadian misalignment is associated with increased systemic inflammation and disrupted metabolic regulation, which may contribute to impairments in cognitive performance, sleep quality, and muscle recovery. Critically, travel-induced dysbiosis may reduce the production of microbial metabolites, specifically short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate. These SCFAs serve as energy substrates that may enhance glucose uptake, lipid oxidation, and glycogen storage in skeletal muscle. Evidence suggests that travel-related stressors—including dehydration, psychological stress, and shifts toward highly processed diets—further exacerbate the loss of beneficial taxa. To mitigate these effects, this article proposes evidence-informed strategies: timed light exposure to reset the master clock, chronobiotic meal timing to entrain peripheral tissues, and targeted symbiotic supplementation to restore SCFA-producing populations. Integrating these personalised, evidence-informed protocols may support the optimisation of physiological resilience and performance. Full article

Background: The Danish National Survey of Diet and Physical Activity (DANSDA) is Denmark’s national dietary surveillance system, providing population-level data to support evidence-based government advisory tasks and policymaking, research, and education. Methods: DANSDA 2021–2024 is a cross-sectional survey based on a simple random sample of citizens aged 4–80 years from the Danish Civil Registration System. Home visits included structured interviews covering socio-economic status, family composition, ethnicity, lifestyle behaviors and attitudes, health and non-communicable diseases, dietary supplement use, and measurements of anthropometrics and blood pressure. Dietary intake was recorded using a digital or paper-based seven-day food record and a food frequency questionnaire. Physical activity was measured with a pedometer and a seven-day step diary. Participants aged 40–70 years were offered blood sampling for glucose and lipid analyses. Results: A total of 4223 individuals participated, with 3824 providing valid food records (97.4% were digital). The response rate was 26.3%. The overall underreporting rate was 24%. The sample was skewed by age, education, income, household type, and region; these variables and sex were used to generate weighting factors. Nearly 1000 blood samples were analyzed for glucose and lipids, with surplus material stored in a biobank. Conclusions: DANSDA 2021–2024 provides comprehensive data on diet, physical activity, anthropometry, blood pressure, and blood glucose and lipids. Despite declining response rates and underrepresentation of individuals with lower education and income, weighting procedures support its continued use for national monitoring and research. Strengthening participation and representativeness should be a priority in future survey cycles. Full article

Background: Recurrence poses a major challenge in epithelial ovarian cancer (EOC), often occurring despite optimal first-line therapy. Dormant cancer cells are believed to play a key role, yet the mechanisms driving their reactivation remain unclear. This study examined whether exosomes released by normal peritoneal mesothelial cells (PMCs) and fibroblasts (PFBs) undergoing iatrogenic senescence after carboplatin and paclitaxel exposure contribute to EOC recurrence. Methods and Results: Senescent PMCs and PFBs secreted markedly more exosomes, identified by CD9, CD63, and CD81, compared with young cells. Exosomes from both cell types more effectively reactivated dormant EOC cells (pEOCs, A2780, OVCAR-3, SKOV-3) than non-exosomal medium constituents. Importantly, senescent PMC-derived exosomes most strongly reactivated pEOCs and SKOV-3, whereas those from senescent PFBs exerted greater effects on pEOCs, OVCAR-3, and SKOV-3. Kinetic studies of exosome internalization revealed that this process was generally more efficient in the presence of exosomes derived from senescent cells compared with those from young donor cells. Compositional analysis revealed distinct profiles between young and senescent exosomes compared in two variants: young PMCs/senescent PMCs and young PFBs/senescent PFBS. Senescent PMC exosomes displayed reduced miR-210-3p, miR-409-3p, and miR-421, alongside elevated MMP1, MMP3, and VEGF, while senescent PFB exosomes showed increased amphiregulin and osteopontin but lower MMP1, MMP3, TIMP1, bFGF, VEGF, and HGF. Functionally, senescent PMC exosomes enhanced pEOC migration, invasion, and spheroid formation, and induced the expression of CCL11 and ABCB1. Senescent PFB exosomes promoted migration and upregulated CCL11, TGF-β1, BIRC5, and CHEK1. Conclusions: These findings suggest that therapy-induced senescence in peritoneal cells may contribute to EOC recurrence by reactivating dormant tumor cells through exosomal signaling. Full article

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease in children requiring long-term management, yet real-world data on treatment patterns remain limited. Objective: To evaluate treatment trends and factors associated with topical non-steroidal medication use in pediatric AD. Methods: We retrospectively analyzed 3982 children with AD treated at a tertiary referral center in Thailand between 2015 and 2024. Demographic data, healthcare coverage, and prescribed treatments were reviewed. Multivariable logistic regression was used to identify factors associated with topical non-steroidal use. Results: The median age was 7 years, with no sex difference. The most commonly prescribed treatments were antihistamines (75.0%), topical corticosteroids (47.6%), moisturizers (43.9%), systemic immunosuppressants (15.7%), topical non-steroidal agents including topical calcineurin inhibitors, phosphodiesterase-4 inhibitors, and Janus kinase (JAK) inhibitors (12.7%), and biologics (0.1%). Moderate-potency corticosteroids predominated. Adolescents were less likely to receive topical non-steroidal agents than infants (OR 0.66, 95% CI 0.50–0.87), whereas patients under the Civil Servant Medical Benefit Scheme (CSMBS) had higher access than those under the Universal Coverage Scheme (UCS) (OR 8.40, 95% CI 5.76–12.25). Conclusions: Pediatric AD management was dominated by conventional therapies, with limited access to advanced treatments. Age and healthcare coverage strongly influenced prescribing patterns, highlighting the need for more equitable access. Full article

Garlic (Allium sativum L.) belongs to the Allium genus and is one of the main bulbous plants consumed fresh, powdered, or cooked. Numerous studies have shown that garlic exhibits antihyperlipidaemic, antioxidant, anti-inflammatory, cardiovascular disease preventive, antihypertensive, antibacterial, antiviral, antifungal, antiparasitic, antidiabetic, anticarcinogenic, hepatoprotective, immunomodulatory, and hypoglycaemic effects. Moreover, studies on polyphenols detected in garlic reveal strong anticancer properties in various cell lines. The aim of this review is to summarise the current state of knowledge regarding the anticancer properties and shared molecular mechanisms of action of garlic-derived polyphenolic compounds. Our analysis demonstrates that the polyphenol content in garlic is highly variable and depends on numerous factors, including the part of the plant, processing methods, place of cultivation, and other conditions. Additionally, garlic contains polyphenols that exhibit anticancer activity in preclinical models, the properties of which have been demonstrated in in vitro studies. The anticancer mechanism of action varies depending on the type of polyphenol. Several polyphenols from garlic such as e.g., catechin, quercetin, and kaempferol activate peroxisome proliferator-activated receptors, which appear to contribute to at least part of garlic’s anticancer activity. The primary mechanism of garlic’s anticancer properties relies on reactive oxygen species-dependent toxicity and/or apoptosis, and Nrf2 is also implicated in the mechanism of action of garlic polyphenols. Our review provides evidence that under in vitro conditions, polyphenols present in garlic may exhibit anticancer properties. Garlic is not only a valuable culinary ingredient but also a natural medicine. Regular consumption in moderate amounts may offer numerous health benefits. Full article

Background/Objectives: Micropapillary urothelial carcinoma of the urinary bladder (MPUC) represents a rare but highly aggressive histological variant of urothelial carcinoma (UC), frequently presenting at an advanced stage of disease. Although data on histological variants consistently suggest inferior oncological outcomes, the independent prognostic role of the micropapillary variant remains controversial. Methods: The present work synthesizes the findings of a large meta-analysis evaluating histological variants of UC and a separate meta-analysis focusing exclusively on MPUC, and further examines the most recent cohort-based evidence published between 2016 and 2025. Results: The presence of any histological variant in UC treated with radical cystectomy is associated with significantly worse recurrence-free survival, disease-specific survival, and overall survival, as reflected by pooled hazard ratios (HRs). For the micropapillary variant specifically, a modest increase in overall mortality has been demonstrated (pooled HR ≈ 1.20); however, results from adjusted analyses dedicated to MPUC remain inconsistent. Conclusions: Micropapillary urothelial carcinoma is consistently associated with adverse pathological features and poorer oncological outcomes. However, whether micropapillary morphology independently predicts prognosis beyond established factors such as pathological stage and nodal status remains uncertain, as adjusted analyses across studies have yielded inconsistent results. Part of the observed survival disadvantage may be explained by stage migration, although an intrinsic residual risk cannot be definitively ruled out. This review integrates contemporary population-based registry analyses with prior meta-analytic evidence to provide a clinically oriented synthesis of the prognostic and therapeutic implications of MPUC. In addition, we propose minimal reporting standards aimed at improving comparability across future studies and strengthening risk stratification and treatment decision-making. Full article

The biological compatibility of endodontic sealers is a key determinant of periapical tissue healing. This in vitro study investigated the cytotoxic, pro-inflammatory, and redox-related effects of eight endodontic sealers on human periodontal ligament fibroblasts (HPdLFs): Biopulp (Chema-Elektromet), AH Plus (Dentsply Sirona), MTA Fillapex (Angelus), EndoSeal MTA (Maruchi), GuttaFlow (Coltène), AH Plus Bioceramic (Dentsply Sirona), TotalFill BC (FKG Dentaire SA), and BioRoot TM (Septodont). Cells were exposed for 24 h to 10-fold-diluted sealer extracts prepared in accordance with the manufacturers’ instructions, while control samples underwent identical procedures without sealer contact. Oxidative stress biomarkers, antioxidant defense parameters, protein oxidation indices, apoptotic activity (caspase-3), pro-inflammatory cytokines (IL-1, IL-6), and cell viability (MTT assay) were assessed. Under the applied conditions, all materials induced only limited global oxidative stress, with most alterations reflecting selective protein and glycoxidative modifications. Nevertheless, AH Plus, MTA Fillapex, and the calcium hydroxide-based Biopulp exhibited a less favorable redox profile and greater protein oxidation compared with calcium silicate-based sealers. AH Plus and EndoSeal MTA were associated with increased IL-6 release, whereas EndoSeal MTA moderately elevated IL-1 levels. BioRoot TM demonstrated the lowest cytokine expression, and TotalFill BC preserved high cell viability. Caspase-3 activity remained comparable across all experimental groups, indicating minimal induction of apoptosis. Full article

Progression in understanding the relationships among cardiovascular, kidney, and metabolic diseases necessitates reappraising these concepts. Here, this narrative review explains the evolution of the ideas behind cardiovascular-kidney-metabolic syndrome (CKMS), focusing both on the impact of kidney disease on the cardiovascular system and metabolic syndrome and, conversely, on the effects of metabolic syndrome on cardiovascular and kidney diseases. Merging these concepts has resulted in a holistic approach more pertinent to managing the increased pressure from civilization diseases. In light of recent guidelines, early laboratory assessment is critical for risk stratification by improved patient classification, enabling individualized therapeutic strategies. Moreover, understanding the molecular mechanisms common to these systemic disorders not only enhances diagnostic accuracy but also facilitates the implementation of preventive measures that target multiple organ pathologies simultaneously. This review summarizes selected laboratory parameters that may support the diagnosis and management of cardiovascular-kidney-metabolic syndrome, aligning current knowledge with emerging clinical recommendations. Full article

Background: Obesity substantially increases cardiovascular risk and contributes to the accumulation of cardiometabolic risk factors. Achieving optimal control of body weight and guideline-recommended targets is essential in high-risk patients, particularly in secondary prevention following acute coronary events. This study aimed to evaluate treatment strategies and lifestyle modifications undertaken by patients with obesity during long-term follow-up. Methods: This analysis included patients enrolled 6–18 months after acute coronary syndrome or coronary revascularization within the multicentre POLASPIRE II study. Standardized EUROASPIRE methodology was applied to collect clinical, anthropometric, and lifestyle-related data. Results: A total of 788 patients (mean age 65.4 ± 8.9 years; 25.8% women) were included, of whom 40.6% had obesity. No significant association between sex and BMI was observed (β = −0.48; 95% CI −1.30 to 0.31; p = 0.20). Increasing age was associated with lower BMI (β = −0.05; 95% CI −0.09 to −0.0001; p = 0.044), and higher education correlated with lower BMI (β = −1.10; 95% CI −2.00 to −0.22; p = 0.015). With advancing age (OR 1.02; 95% CI 1.002–1.033; p = 0.023) and increasing BMI (OR 1.11; 95% CI 1.076–1.138; p = 0.001), the number of risk factors and comorbidities increased. Higher BMI was associated with poorer control of medical risk factors (OR 1.06; 95% CI 1.03–1.10; p < 0.001), whereas patients with higher BMI demonstrated better control of lifestyle-related risk factors (OR 0.95; 95% CI 0.919–0.983; p = 0.003). Conclusions: Obesity is highly prevalent among high-risk cardiovascular patients and is associated with a greater burden of comorbidities and poorer control of medical risk factors. These findings support the need for strengthened, risk-stratified secondary prevention strategies and more personalized therapeutic approaches in patients with obesity. Full article

Little is known about the clinical utility of blood, salivary, and urinary redox biomarkers in critically ill patients with brain injury and secondary organ failure. The aim of the study was to explore total antioxidant and oxidant status in neurocritically ill patients using ferric reducing antioxidant power (FRAP), total antioxidant capacity (TAC), and total oxidant status (TOS) in plasma, saliva, and urine from the study (n = 45) and the healthy control group (n = 49). We analyzed the relationship between well-known biomarkers of organ function and redox status in different biofluids. Plasma FRAP was significantly higher (p < 0.05), but salivary and urinary FRAP were statistically lower in the study group (p < 0.05, p < 0.001) compared with controls. The salivary and urinary TAC were statistically lower (p < 0.05, p < 0.001), while plasma TOS was significantly higher (p < 0.05) in the study group compared with the control group. Circulating redox status did not differ between survivors and non-survivors. Significant associations were observed in non-survivors: salivary TAC correlated with urea and creatinine; salivary FRAP with creatinine, troponin, and CRP; urinary TAC with troponin and P_aO₂/FiO₂ ratio, as well as plasma FRAP with P_aO₂/FiO₂ ratio. The plasma FRAP had a significant effect on survival (AUC = 0.687, p = 0.02), with 69% sensitivity and 83% specificity. Crucial differences in redox status in blood, saliva, and urine were observed between neurocritically ill patients and healthy controls; however, none of the biomarkers differed between survivors and non-survivors. Oxidative and antioxidant status correlated with organ function in non-survivors. Full article

Background/Objectives: This study evaluates a media prevention program conducted in elementary schools. Methods: A one-week media program, carried out with fourth graders in Leipzig, Germany, was evaluated using a non-randomized controlled cluster design. Program participants (experimental group (EG), n = 84 children, 41 parents) and non-participants (control group (CG), n = 19 children, 14 parents) completed questionnaires before the media program (t1), directly after the program (t2, EG only), and 3 months later (t3). The child questionnaire assessed media use frequency, rules at home, perceived and objective media-knowledge, and awareness of dangers on the Internet. The parent questionnaire assessed media-related topics discussed with their children and parents’ confidence regarding media education. Results: In the EG, children’s perceived and objective knowledge and their awareness of dangers on the Internet increased significantly between t1 and t2 and remained stable until t3, while no changes were observed in the CG. The number of children reporting that there exist rules on social media use also increased significantly in the EG but not in the CG. The amount of media-related topics discussed within the family and parents’ confidence regarding media education increased significantly from t1 to t3 in both EG and CG. Children’s media use frequency did not change across time, neither in the EG nor in the CG. Conclusions: Media prevention programs at school can have positive effects on children’s knowledge and awareness of dangers on the Internet and might improve parents’ confidence in and the realization of media education at home. Full article