Search Results (1,284)

Congenital heart disease (CHD) is the most common anatomical malformation occurring in live-born infants and an increasing cause of morbidity and mortality all over the world. Population-based observations have described associations between maternal cardiometabolic disorders and the risk of CHD in offspring. The present article is a narrative review. The aim of this study was to review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD in offspring, with particular attention paid to first trimester disturbances of fetal cardiac development and the influence of genetic, epigenetic and environmental factors. Studies have shown that maternal diabetes is a risk factor associated with nearly all subtypes of CHDs in offspring, while obesity and overweight are associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. Diabetes and obesity share several phenotypes, which could be transmissible from mother to fetus via the placenta. This means that an increase in maternal glucose could be responsible for the prevalence of CHD in newborns of obese women. On the other hand, maternal diabetes may induce epigenetic modifications in the developing fetus. DNA methylation changes can impact gene expression patterns relevant to heart development. The abovementioned studies are heterogenous, express different opinions and are often difficult to compare. Therefore, the results from these meta-analyses must be interpreted with caution. Optimal diabetes control is responsible for the prevention of oxidative stress in diabetic pregnancies, and a deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHDs by identifying at-risk pregnancies and primary prevention of diseases by improving preconception management. Full article

Background: Diabetes mellitus (DM) is an emerging public health challenge in Africa, driven by rapid urbanisation, changing lifestyles and socio-economic transitions. As the global prevalence rises, evidence on the burden and determinants of DM across African countries remains fragmented and inconsistent. Objective: We aimed to synthesize evidence from existing systematic reviews and meta-analyses on the prevalence and determinants of diabetes mellitus across African populations, thereby informing targeted interventions and policy actions. Methods: This umbrella review followed the PRISMA guidelines and included systematic reviews and meta-analyses of studies, published up to December 2024, that reported on DM prevalence and/or risk factors for DM in adults across four African countries. The literature was retrieved from PubMed, Scopus, Web of Science and African Journals Online (AJOL). Quality assessment was conducted using the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews, version 2) tool, and only moderate- to high-quality reviews were retained. Random-effects models were used to estimate the pooled prevalence and odds ratios (ORs), while heterogeneity, publication bias and sensitivity analyses were also conducted. Findings: Seven reviews were included, covering four countries: Ethiopia, South Africa, Nigeria and Ghana. The pooled prevalence of diabetes mellitus was 9.0% (95% CI: 6.0–12.0%), with significant heterogeneity (I² = 99.8%). Among the determinants, only family history of DM (OR:5.11, 95% CI: 2.96–8.85), hypertension (OR: 2.52; 95% CI: 1.65–3.83), obesity (OR: 3.04; 95% CI: 1.92–4.82), physical inactivity (OR: 3.32; 95% CI: 1.99–5.54), smoking (OR: 2.59; 95% CI: 1.23–5.47), unhealthy diet (OR: 4.77; 95% CI: 1.73–13.18) and urban residence (OR: 5.81; 95%CI: 4.41–7.65), showed a statistically significant association. Sensitivity analysis confirmed the robustness of pooled prevalence, and no significant publication bias was detected. Conclusions: Diabetes mellitus prevalence in Africa is rising and approaching the global averages. The heterogeneity in risk factors underscores the need for localised, context-specific strategies. Full article

Background/Aim: Routine ultrasonography now detects gallbladder polyps (GBPs) more often, but reported prevalence varies across populations. Jeju Island has South Korea’s highest obesity prevalence and red meat consumption, suggesting a rapid nutritional transition similar to that reported in Native Hawaiians. This study aimed to first analyze risk factors influencing GBP prevalence, including birthplace, and second compare clinical variables between JNs and JMs. Methods: Between May 2018 and October 2023, 28,751 individuals underwent medical checkups at Jeju National University Hospital. GBPs were diagnosed via ultrasonography, and risk factors including age, sex, birthplace, metabolic syndrome, hepatitis B virus antigen (HBsAg) positivity, lipid profiles, and alcohol consumption were assessed using univariate and multivariate logistic regression. Results: After exclusions, 15,219 participants were analyzed. The overall prevalence of GBPs was 10.3%. Male participants had a higher prevalence than females (11.4% vs. 9.1%, p < 0.001). The younger age group (20–49 years) showed the highest prevalence, while those aged ≥70 years had the lowest (11.6% vs. 8.6%, p = 0.001). Jeju Natives (JNs) exhibited a significantly higher prevalence than Jeju migrants (JMs) (10.6% vs. 9.0%, p = 0.004). Multivariate analysis identified female sex [odds ratio (OR) = 0.644, p < 0.001], age ≥ 70 years (OR = 0.601, p < 0.001), JN birthplace (OR = 1.260, p = 0.015), HBsAg positivity (OR = 1.347, p = 0.040), and high-risk alcohol drinking (OR = 0.758, p = 0.001) as independent predictors. Notably, the 60–69 age group did not reach statistical significance in the optimized model (p = 0.158). Compared to JMs, JNs were older and had a higher prevalence of fatty liver disease, a higher BMI, and higher levels of AST and GGT, but lower levels of HDL-cholesterol and triglycerides. Conclusions: GBPs are more prevalent among JNs compared to JMs, with birthplace emerging as a novel independent risk factor. Fatty liver disease, BMI, and reduced HDL-cholesterol were associated with GBP risk. These findings hypothesize that dietary and metabolic health factors may be potential pathways for the higher GBP prevalence among JNs, though direct dietary assessment is required for confirmation. Full article

Background/Objectives: This study aimed to estimate self-reported prevalence of HIV and gonorrhea among primary healthcare attendees in Riyadh and to identify key demographic, behavioral, and clinical predictors, acknowledging that diagnoses were based on participant self-report rather than laboratory confirmation. Methods: A cross-sectional survey was conducted between March and July 2023 across 48 primary healthcare centers in Riyadh. A total of 14,239 adult participants (aged ≥18 years) completed an electronically administered questionnaire that included self-reported prior diagnoses of HIV and gonorrhea. Multivariable logistic regression models were used to identify independent predictors of self-reported HIV and gonorrhea. Results: The self-reported prevalence of HIV was 2.6% (95% CI: 2.35–2.87%), and gonorrhea was 3.1% (95% CI: 2.83–3.40%). Several factors were independently associated with higher odds of self-reported infection. Younger age (<50 years) increased risk (HIV: AOR = 2.19; gonorrhea: AOR = 1.57), as did female sex (HIV: AOR = 1.67; gonorrhea: AOR = 1.59), higher education (HIV: AOR = 1.29; gonorrhea: AOR = 1.23), married status (HIV: AOR = 1.76,; gonorrhea: AOR = 1.49,), and insurance coverage (HIV: AOR = 2.01,; gonorrhea: AOR = 1.88). Behavioral and clinical factors included smoking (HIV: AOR = 4.79,; gonorrhea: AOR = 2.41,), hypertension (HIV: AOR = 2.58; gonorrhea: AOR = 1.49,), obesity (HIV: AOR = 11.55; gonorrhea: AOR = 9.02), hypercholesterolemia (HIV: AOR = 2.24; gonorrhea: AOR = 2.53,), and heart disease (HIV: AOR = 11.31; gonorrhea: AOR = 8.77). The notably high associations for obesity and heart disease should be interpreted with caution, as they may be influenced by detection bias or residual confounding within the healthcare-seeking sample. Conclusions: This study provides key insights into the self-reported burden and predictors of HIV and gonorrhea in Saudi Arabia. While identifying significant demographic and metabolic risk profiles, the high magnitude of certain clinical associations must be interpreted with caution due to potential detection bias and residual confounding. Given the reliance on self-reported data, these findings should be viewed as an epidemiological baseline rather than absolute prevalence. Prioritizing clinical context over statistical values and strengthening integrated, laboratory-based surveillance within primary care will be essential for improving early detection and evidence-based prevention strategies in the region. Full article

Background: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. Methods: Four-week-old male C57BL/6 mice were fed a high-fat diet and intraperitoneally injected with streptozotocin (35 mg/kg) to establish an obese T2DM model. Mice were randomized into control, T2DM and T2DM+Ang-(1-7) groups (n = 6). Body weight and blood glucose were recorded weekly. At 10 weeks, blood glucose, serum inflammatory factors, lipid profiles, and pancreatic β-cell insulin secretion were detected; serum metabolite alterations were analyzed via untargeted metabolomics. Results: 1. Ang-(1-7) intervention decreased blood glucose (p < 0.05) and CRP levels (p < 0.01), and alleviated dyslipidemia (p < 0.05 or p < 0.01), as well as β-cell morphology and insulin expression in obese T2DM mice. 2. Non-targeted metabolomics analysis suggested that Ang-(1-7) may alleviate abnormal amino acid metabolic pathways by regulating levels of metabolites such as L-valine, L-proline, L-histidine, and glutamic acid. This intervention also tended to reduce multiple lipid metabolites, including Omega-3 Arachidonic Acid Ethyl Ester, phosphatidylcholine, and glycerophosphocholine, thereby participating in the modulation of lipid metabolism balance. KEGG enrichment analysis further indicated that Ang-(1-7) was involved in the regulation of protein digestion and the absorption pathway, as well as the HIF-1 signaling pathway related to oxidative stress, bile acid metabolism pathway, and other signaling pathways, and improving the insulin secretion pathway, pyrimidine metabolism, and TCA cycle energy metabolism pathway. Conclusions: Ang-(1-7) may partially improve metabolic disturbances in obese T2DM mice, which is potentially associated with the modulation of multiple metabolic processes, including amino acid metabolism, lipid metabolism, insulin secretion, and TCA cycle energy metabolism. Full article

Evidence on hospitalised COVID-19 patients during the Omicron BA.5 wave from Eastern European, vaccine-heterogeneous cohorts remains limited. We conducted a retrospective single-centre cohort study of 395 consecutive adults admitted with laboratory-confirmed COVID-19 to a tertiary infectious-diseases unit in western Romania between 1 July and 31 October 2022. Median age was 72 years (IQR 65–81); 33.2% were unvaccinated, 42.8% had documented prior SARS-CoV-2 infection, and 41.3% were obese. Multivariable logistic regression identified independent predictors of in-hospital mortality and post-acute symptom burden. In-hospital mortality was 15.7% (62/395). Vaccination was independently associated with lower mortality (adjusted odds ratio [aOR] 0.55, 95% CI 0.30–0.99; p = 0.048), as was each 1% increase in admission SpO₂ (aOR 0.83, 95% CI 0.76–0.92; p < 0.001), whereas COPD independently increased mortality risk (aOR 2.42, 95% CI 1.15–5.10; p = 0.020). Interleukin-6 was the most discriminating admission biomarker for in-hospital mortality (AUROC 0.70). Bloodstream bacterial co-infection, detected in 22.5% of patients tested on clinical suspicion, was dominated by gut-derived organisms with case-fatality ≥30%. At discharge, 90.1% reported persistent symptoms, most commonly cognitive (24.6%). Prior SARS-CoV-2 infection independently predicted post-acute symptom burden (aOR 2.96, 95% CI 1.75–5.01; p < 0.001), with a specific cardiopulmonary signature. In this BA.5 cohort, vaccination remained protective; IL-6 was the most informative admission biomarker; bloodstream infections suggested gut translocation; and prior infection was an independent determinant of early post-acute symptom burden. Full article

Background/Objectives: Nobiletin, one of the main components of citrus peel, exhibits potent antioxidant, anti-inflammatory, and metabolic regulatory properties. However, its effect on obesity-associated vasculopathay remains unknown. We aim to investigate the effect of nobiletin in ameliorating oxidative stress and endothelial dysfunction induced by a high-fat diet (HFD). Methods: Male C57BL/6J mice were fed a HFD (60 kcal% fat) or normal chow for four months and orally administered with vehicle or nobiletin (50 mg/kg/day) for 8 weeks. Vasoreactivity in aortas was measured on a wire myograph. Primary rat aortic endothelial cells (RAECs) were isolated from Sprague-Dawley rats for in vitro study. Protein expressions were detected by Western blot. Superoxide production was determined by fluorescence imaging. Results: Exposure to high glucose increased the phosphorylation of JNK (Tyr185) and decreased the protein expressions of Nrf2 and HO-1, as well as downregulated the phosphorylation of AMPK and eNOS (Ser1177) in RAECs. This led to reduced nitric oxide (NO) generation and elevation of oxidative stress. High glucose induction also impaired the endothelium-dependent relaxations (EDRs) in murine aortas. These high glucose-induced impairments were restored by co-treatment of nobiletin (1 μM or 10 μM) whereas effects of nobiletin were abolished by AMPK inhibitor Compound C. The DIO-induced diabetic animal model showed increased body weight and blood pressure, imbalance of glucolipid metabolism, impaired EDRs, and elevated oxidative stress in aortas. AMPK/eNOS and Nrf2/HO-1 pathways were downregulated in aortas from DIO mice. Oral administration of nobiletin could at least partially reverse the above damage. Conclusions: Nobiletin ameliorates endothelial dysfunction by reducing oxidative stress and enhancing NO bioavailability upon activation of AMPK/eNOS and Nrf2/HO-1 pathways in obese diabetic mice. Full article

Background: Gallbladder carcinoma (GBC) represents one of the most aggressive malignancies of the hepatobiliary system, evolving along a continuum from chronic inflammation to preneoplastic lesions and invasive cancer. This progression is frequently associated with gallstones and chronic cholecystitis and shares common pathogenic mechanisms with systemic inflammatory and metabolic disorders. Despite its relatively low incidence, GBC is characterized by poor prognosis, largely due to late-stage diagnosis and limited understanding of its molecular underpinnings. Methods: We conducted an observational study including 60 adult patients with radiologically suspected gallbladder cancer (GBC). Patients with disseminated disease, ongoing oncologic treatment, or synchronous malignancies were excluded. Fasting venous blood samples were collected to evaluate tumor markers and biochemical parameters, including carcinoembryonic antigen (CEA) and carbohydrate antigen CA 19-9. Surgical specimens were analyzed histopathologically and staged according to the European Society for Medical Oncology TNM classification system. Statistical analysis was performed using SPSS software (version 26.0), with appropriate parametric or non-parametric tests applied based on data distribution, and a p-value < 0.05 considered statistically significant. Results: Based on histological findings, patients were stratified into benign gallbladder disease (GBD) and GBC groups. CA 19-9 demonstrated higher mean serum levels with lower variability compared to CEA, suggesting superior sensitivity and diagnostic stability for gallbladder adenocarcinoma. In contrast, CEA levels exhibited greater fluctuation, limiting its reliability as a standalone biomarker. Importantly, the combined use of CA 19-9 and CEA improved diagnostic accuracy, supporting a multimarker approach for better clinical stratification. Our findings highlight the diagnostic value of CA 19-9 as a robust biomarker in GBC and support the integration of combined biomarker panels. Beyond tumor markers, the study identified a strong interplay between systemic inflammation and metabolic comorbidities, with obesity and hypertension significantly associated with chronic gallbladder pathology, and diabetes mellitus contributing to increased risk of acute inflammatory episodes. Elevated inflammatory markers, leukocytosis, and cholestatic enzyme alterations further supported the presence of a systemic inflammatory milieu. Multivariate analysis revealed that C-reactive protein (CRP), as a marker of systemic inflammation, was significantly influenced by a combination of clinical and biochemical variables, including age, hemoglobin, hypertension, amylase, CA 19-9, and CEA, explaining over 50% of its variability and up to 85% in advanced fibrotic changes. Additionally, platelet counts were significantly reduced in adenocarcinoma and correlated specifically with CA 19-9 levels, suggesting a potential link between tumor burden, inflammation, and platelet dynamics. Conclusions: Therefore, the observed associations between chronic inflammation, metabolic dysregulation, and tumor marker expression suggest a potential link between gallbladder carcinogenesis and systemic cardiometabolic pathways, opening new perspectives for early detection and targeted therapeutic strategies. Full article

Understanding the molecular mechanisms underlying host immune responses to SARS-CoV-2 vaccination remains essential, particularly in populations with a high prevalence of obesity. In this cross-sectional study, we evaluated whether body mass index (BMI) is associated with vaccine-induced humoral immunity in a cohort from northeastern Mexico and discuss the findings within a structural immunology framework of spike antigenicity and antibody–epitope interactions. A total of 138 adults were recruited in Reynosa and Matamoros (June 2021–June 2022) and categorized as healthy weight, overweight, or obese according to BMI criteria. Serum anti-SARS-CoV-2 IgG was assessed using an ELISA-based assay, and differences across BMI groups were tested using the Kruskal–Wallis approach. Among all participants, 33.3% were classified as obese and 99.3% (137/138) were seropositive for anti-SARS-CoV-2 IgG. No significant differences in IgG levels were detected between BMI categories (p = 0.20). These results indicate that, in this Mexican cohort—sampled during a period of heterogeneous and often incomplete vaccination schedules—obesity was not associated with reduced detectable anti-SARS-CoV-2 IgG responses. Our findings support the need to integrate population-level serology with mechanistic studies that interrogate antibody quality (e.g., neutralization potency and epitope specificity) to better connect clinical determinants such as obesity with molecular correlates of protection. Full article

Background: Southeast Asian Americans (SEAAs) experience a disproportionately high burden of hepatocellular carcinoma (HCC), with incidence in several subgroups (i.e., Cambodian, Laotian, and Vietnamese individuals) reaching up to nine times that of non-Hispanic Whites. HCC in SEAAs is largely driven by chronic hepatitis B (HBV), hepatitis C (HCV), metabolic dysfunction–associated steatotic liver disease (MASLD), and alcohol-associated liver disease (ALD). Despite established screening guidelines, under-detection and delayed diagnosis remain common. Objective: To summarize epidemiologic patterns, risk factors, screening challenges, and potential interventions aimed at reducing HCC disparities among SEAAs. Design and Methods: This narrative review synthesized evidence from population based epidemiologic studies, community-based interventions, health services research, and policy analyses. Attention was given to studies reporting disaggregated SEAA subgroup data. Findings derived from SEAA specific studies were distinguished from evidence drawn from broader Asian American or general cirrhosis populations, with inferential steps explicitly noted where subgroup specific data were limited. Key Findings: HCC incidence varies widely across SEAA subgroups, with elevated HBV- and HCV-related HCC in Vietnamese, Cambodian, and Laotian communities, and increasing MASLD-related HCC including among lean individuals who fall outside many surveillance frameworks. Screening and surveillance remain suboptimal, with fewer than 30% of patients with cirrhosis receiving recommended semiannual HCC surveillance and even lower uptake among SEAAs. Barriers include low HBV/HCV screening rates, limited disease awareness, language barriers, underinsurance, provider knowledge gaps, and lack of automated EHR-based reminders. Structural challenges such as poverty, transportation barriers, and limited access to specialty care further delay diagnosis. Proposed Interventions: Culturally tailored outreach programs, bilingual navigators, and community-based screening initiatives have demonstrated improved HBV/HCV testing and linkage to care. AI-enabled EHR tools may enhance identification of high-risk patients, streamline follow-up, and increase surveillance adherence. Expanded use of non-invasive fibrosis assessment and recognition of MASLD-related risk in non-obese individuals may support earlier detection. Policy priorities include mandatory Asian subgroup data disaggregation, expanded insurance coverage, and strengthened community-level healthcare infrastructure. Conclusions: SEAAs face a substantial and preventable HCC burden. A coordinated approach combining culturally tailored community engagement, improved provider support systems, and policy reforms is essential to improving early detection and reducing HCC disparities in this diverse population. Full article

Background/Objectives: Obesity is a chronic, relapsing disease with a widening gap between clinical need and the availability of specialist care. Artificial intelligence (AI) may enable earlier risk detection, more precise phenotyping, and scalable behavioural support across obesity treatment pathways. This narrative review synthesises contemporary AI applications across the obesity care continuum and evaluates their translational readiness. Methods: A targeted search of PubMed/MEDLINE and Google Scholar (January 2024–January 2026) was conducted, complemented by citation chaining. Evidence was synthesised across four domains: (1) risk prediction and screening, (2) environmental and behavioural determinants, (3) multimodal phenotyping and precision stratification, and (4) AI-enabled lifestyle interventions and behavioural coaching (AIBC). Results: Electronic health record (EHR)-based models demonstrate clinically useful discrimination for early risk identification. Multimodal approaches refine stratification beyond body mass index (BMI)-centric classification. AI-enabled behavioural coaching (AIBC) platforms show emerging evidence of clinically meaningful weight loss, including non-inferiority to human coaching; however, long-term effectiveness, generalisability, and equity remain insufficiently established. Conclusions: AI is positioned to become a core enabler of personalised obesity pathways. Safe translation requires external validation, bias auditing, transparent reporting, human oversight, and post-deployment surveillance aligned with clinical guidelines and regulatory expectations. Full article

Background/Objectives: Obesity is a complex metabolic disorder associated with chronic low-grade inflammation, insulin resistance, and increased risk of metabolic complications. Traditional measures, such as body mass index (BMI), may not detect early metabolic disturbances. Myokines and cytokines, including irisin, C-C Motif Chemokine (CCL2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-15 (IL-15), have been proposed as potential biomarkers. This study aimed to investigate the relationships between these biomarkers and metabolic parameters in adults with varying BMI. Methods: Fifty-one adults (mean age 38 ± 11 years) were stratified by BMI into normal weight, overweight, and obese groups. Serum irisin, CCL2, IL-1β, IL-6, and IL-15 concentrations were measured along with metabolic parameters, including insulin, HOMA-IR, C-peptide, and visceral fat. Statistical analyses included Pearson’s correlation, Kruskal–Wallis ANOVA with Bonferroni correction, and subgroup analyses for insulin resistance (HOMA-IR ≥ 2.5). Results: Irisin concentrations were significantly higher in overweight and obese participants compared with normal-weight individuals (p < 0.001) and positively correlated with insulin (r = 0.77), HOMA-IR (r = 0.63), C-peptide (r = 0.71), and BMI (r = 0.54). In contrast, IL-6 and IL-15 levels did not differ significantly across BMI groups, although IL-15 showed a borderline increase in insulin-resistant individuals (p = 0.048). Both IL-1β and CCL2 were significantly elevated across increasing body-weight categories and showed strong positive correlations with measures of adiposity, visceral fat, and insulin resistance; however, neither marker differed significantly when participants were stratified by insulin-resistance status. Additionally, multivariable linear regression identified irisin as the only independent predictor of insulin resistance, while CCL2 was the strongest predictor of BMI. Principal component analysis (PCA) revealed two dominant components separating metabolic (irisin, HOMA-IR, insulin, BMI) and inflammatory (IL-1β, CCL2) profiles, supporting the distinction between metabolic and inflammatory pathways in obesity. Conclusions: Irisin appears to be a sensitive associative marker of metabolic dysregulation associated with increased body mass and insulin resistance. In contrast, IL-1β and CCL2 reflect obesity-related inflammatory burden rather than early metabolic changes, while IL-6 and IL-15 did not reflect early metabolic alterations in this study. Together, these findings suggest that irisin may serve as an associative biomarker for identifying individuals at risk of obesity-related metabolic disturbances, whereas CCL2 and IL-1β may be more indicative of chronic adipose tissue inflammation. Full article

Background: While sphingolipid alterations in obesity and metabolic syndrome (MS) have been extensively studied in plasma, their intracellular regulation within immune cells remains poorly characterized. Here, we introduce a PBMC-based sphingolipidomic approach that provides a novel immunometabolic perspective beyond traditional analyses of circulating lipids. Methods: Targeted sphingolipidomics was performed in peripheral blood mononuclear cells (PBMCs) from normal-weight healthy (NWH) subjects, and patients with essential obesity (EO) or MS. Multivariate integration (principal component analysis [PCA], hierarchical clustering, and partial least squares discriminant analysis [PLS-DA]) was combined with selected univariate models to explore lipid patterns and associations with cardiometabolic variables. Results: PBMC profiling identified a selective intracellular sphingolipid signature, with 10 species significantly altered across groups (FDR < 0.05), including ceramides, dihydroceramides, glycosphingolipids, and ceramide ratio indices. PCA showed that the first two components explained ~72% of total variance, with PC2 driving group separation. EO and MS displayed partial overlap, consistent with a shared metabolic phenotype, while both differed from NWH. Multivariate models highlighted ceramide ratios (e.g., CER16/24, and CER18/24) as key discriminators. Associations with cardiometabolic variables were limited and modest (adjusted R² ≈ 0.06–0.09), indicating that lipid alterations reflect integrated metabolic dysregulation rather than single clinical drivers. Conclusions: PBMC-based sphingolipidomics reveals a distinct intracellular immunometabolic remodeling in EO and MS, capturing aspects not detectable in plasma. These findings support the relevance of immune cell lipid profiling as a potential source of integrative biomarkers and provide insight into immune–metabolic crosstalk underlying metabolic disease. Full article

Objectives: Exposure to high-fat diets in early life plays an important role in metabolic dysfunction-associated steatotic liver disease (MASLD); however, the mechanism remains unclear. In this study, we explore the role of autophagy and ferroptosis in pre-puberty obesity-related MASLD caused by high-fat diets in early life. Methods: Twenty-four male C57BL/6J mice were fed over a 6-week period, and were divided into three groups: control, lactation HFD, and lactation + post-weaning HFD group. AML12 cells were treated with 0.5 mM free fatty acids (palmitic acid:oleic acid = 1:2) for 24 h to establish an in vitro model. Metabolism, autophagy, and ferroptosis-related indicators were detected. Results: Compared to the control group, the body weight, droplet deposition of the liver, Fe²⁺, and MDA level increased significantly in the lactation + post-weaning HFD group. Impaired autophagy, ferroptosis, and AMPK/mTOR/ULK1 pathway protein expression were also found in the lactation + post-weaning HFD group. Additionally, BL-918 (activate autophagy) exposure in AML12 cells may recover FFA-induced ferroptosis and disorder of lipid metabolism. Conclusions: Early-life high-fat-diet exposure induced pre-puberty obesity-related MASLD, possibly via autophagy, which may be regulated by the AMPK/mTOR/ULK1 pathway and mediated by ferroptosis in male mice. Full article

Intermittent fasting confers protection in diverse diseases through various mechanisms, including the clearance of senescent and pathogenic cells, modulation of tissue inflammation and enhancement of stem/progenitor cell niche and functionality. Our previous study demonstrated the beneficial impact of alternate-day fasting (ADF) on xerostomia and sialadenitis, along with an improvement in salivary gland ductal compartments, where salivary gland progenitor cells reside, in non-obese diabetic mice, a spontaneous model of Sjögren’s syndrome (SS). In the present study, we induced SS-associated hyposalivation in KRT5^CreERT2; R26^tdTomato lineage tracing mice by immunizing them with submandibular gland proteins from wild-type C57BL/6 mice. ADF alleviated salivary gland hypofunction, which was accompanied by decreased expression of the senescent cell marker p16^INK4a, reduced protein levels of anti-apoptotic proteins BCL-2, BCL-XL, and MCL-1, and attenuated NLRP3 inflammasome activity in the submandibular glands, particularly within the ductal compartments, of this inducible model. Furthermore, immunofluorescence staining of submandibular gland sections revealed the expression of the acinar cell marker aquaporin 5 in a small subset of Keratin 5⁺ cells in 2 of 9 mice that were subjected to ADF, whereas no such cells were detected in the control mice. Taken together, these findings indicate that ADF favorably modulates the salivary gland progenitor cell niche, potentially by promoting apoptosis-mediated senescent cell clearance, suppressing NLRP3 inflammasome signaling, and promoting Keratin 5⁺ progenitor cell-derived acinar cell replenishment, thereby contributing to the structural and functional restoration of damaged salivary glands in autoimmune exocrinopathy. Full article