Search Results (6,246)

Background: Colorectal cancer (CRC) demonstrates substantial clinical and biological diversity across age groups, ancestral backgrounds, and treatment settings, alongside a rising incidence of early-onset disease (EOCRC). The mitogen-activated protein kinase (MAPK) pathway is a major driver of CRC development and therapy response; however, the distribution and prognostic value of MAPK alterations across distinct patient subgroups remain unclear. Methods: We analyzed 2515 CRC tumors with harmonized demographic, clinical, genomic, and treatment metadata. Patients were stratified by ancestry (Hispanic/Latino [H/L] vs. non-Hispanic White [NHW]), age at diagnosis (early-onset [EO] vs. late-onset [LO]), and FOLFOX chemotherapy exposure. MAPK pathway alterations were identified using a curated gene set encompassing canonical EGFR-RAS-RAF-MEK-ERK signaling components and regulatory nodes. Conversational artificial intelligence (AI-HOPE and AI-HOPE-MAPK) enabled natural language-driven cohort construction and exploratory analytics; findings were validated using Fisher’s exact testing, chi-square analyses, and Kaplan–Meier survival estimates. Results: MAPK pathway disruption demonstrated marked heterogeneity across ancestry and treatment contexts. Among EO H/L patients, FGFR3, NF1, and RPS6KA6 mutations were significantly enriched in tumors not receiving FOLFOX, whereas PDGFRB alterations were more frequent in FOLFOX-treated EO H/L tumors relative to EO NHW counterparts. In late-onset H/L disease, NTRK2 and PDGFRB mutations were more common in non-FOLFOX tumors. Distinct MAPK-associated alterations were also observed among NHW patients, particularly in non-FOLFOX settings, including AKT3, FGF4, RRAS2, CRKL, DUSP4, JUN, MAPK1, RRAS, and SOS1. Survival analyses provided borderline evidence that MAPK alterations may be linked to improved overall survival in treated EO NHW patients. Conversational AI markedly accelerated analytic throughput and multi-parameter discovery. Conclusions: Although MAPK alterations are pervasive in CRC, their distribution varies meaningfully by ancestry, age, and treatment exposure. These findings highlight NF1, MAPK3, RPS6KA4, and PDGFRB as potential biomarkers in EOCRC and H/L patients, supporting the need for ancestry-aware precision oncology approaches. Full article

Background: Sarcopenia is a clinically important complication of chronic liver disease (CLD), but its underlying mechanisms may differ according to disease etiology. Quantitative MRI biomarkers, including proton density fat fraction (PDFF) and magnetic resonance elastography (MRE), may help characterize etiology-specific patterns of muscle loss. This study aimed to explore etiology-specific associations between MRI-derived biomarkers and sarcopenia, with a particular focus on metabolic dysfunction-associated steatohepatitis (MASH) and viral hepatitis. Methods: This retrospective single-center study included 131 CLD patients (77 with MASH, 54 with viral hepatitis) who underwent MRI, including PDFF and MRE. Sarcopenia was defined by L2 skeletal muscle index thresholds (<42 cm²/m² for men, <38 cm²/m² for women). Muscle identification was performed by automatic threshold-based segmentation by a single observer. Multivariable logistic regression analyses incorporating interaction terms were performed to evaluate whether associations between MRI biomarkers and sarcopenia differed by etiology. Results: Sarcopenia was present in 56% of patients. In the overall cohort, older age (OR = 1.05, p = 0.01), lower PDFF (OR = 0.93, p = 0.03), and lower liver stiffness (OR = 0.51, p = 0.006) were independently associated with sarcopenia. A significant interaction between BMI and disease etiology was observed (p = 0.02). Subgroup analyses suggested that in MASH, sarcopenia was associated with aging, hepatic fat depletion, and lower stiffness. In contrast, in viral hepatitis, it tended to be associated with higher stiffness and lower BMI. Conclusion: MRI-derived hepatic fat and stiffness reflect distinct etiologic patterns of sarcopenia in CLD—metabolically depleted in MASH and fibrosis-related in viral hepatitis. These findings suggest that sarcopenia in MASH and viral hepatitis may reflect different underlying phenotypic patterns, highlighting the importance of considering disease etiology in imaging-based sarcopenia assessment. The results should be interpreted as hypothesis-generating and warrant validation in prospective studies. 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

Regulatory T cells (Tregs), particularly their phenotypically distinct subpopulations, are critical for the establishment of maternal immune tolerance during embryo implantation. Despite advances in assisted reproductive technologies, implantation failure remains a frequent and often unexplained clinical challenge. Variations in Treg frequency and phenotype have been proposed to influence implantation success, particularly under differing hormonal conditions. This study aimed to investigate peripheral blood Treg levels and their subpopulations on the day of blastocyst transfer in both stimulated in vitro fertilization (IVF/ICSI) cycles involving controlled ovarian hyperstimulation (COH) and true natural cycles with frozen embryo transfer (FET), and to examine their associations with systemic hormone levels and anti-Müllerian hormone (AMH). A prospective observational study was conducted including women undergoing IVF/ICSI with fresh embryo transfer (ET) and women undergoing natural cycle FET. Peripheral blood samples were collected on the day of ET and analyzed using 13-colour flow cytometry, enabling detailed subdivision of Tregs into multiple subpopulations based on the expression of differentiation and chemokine markers, including CXCR5. In addition, because common $\gamma$-chain cytokines may influence pregnancy success by modulating the balance between suppressive Treg and non-Treg subsets, intracellular STAT5 signaling was assessed using phospho-specific flow cytometry. Serum estradiol, progesterone, FSH, LH, and AMH levels were measured in parallel. Significant differences were observed in Treg subpopulation distributions between women who conceived and those who did not. Higher frequencies of naïve CXCR5⁻ Tregs were associated with clinical pregnancy, independent of age, and correlated with serum progesterone levels. Moreover, both naïve Treg frequency and enhanced IL-7-dependent STAT5 signaling in naïve Tregs from women undergoing COH were associated with AMH levels, suggesting a link between ovarian reserve and Treg homeostasis mediated by signal transducer and activator of transcription 5 (STAT5) signaling. In conclusion, Treg subpopulations, particularly CXCR5⁻ naïve Tregs, appear to play a central role in implantation success following ET. Their distribution differs between stimulated and natural cycles and is influenced by systemic progesterone levels and STAT5 signaling. These findings suggest that peripheral Treg profiling may represent a potential biomarker of implantation competence and could inform personalized approaches in assisted reproduction. Full article

Background and Objectives: The Gustave Roussy Immune (GRIm) score, reflecting systemic inflammation and nutritional status, has emerged as a simple and reproducible prognostic biomarker in various malignancies. However, its prognostic interaction with tumor microenvironmental factors remains unclear in gastric cancer. The primary aim of this study was to evaluate the prognostic value of the GRIm score in patients with resectable gastric adenocarcinoma, while the secondary aim was to determine whether integrating the GRIm score with tumor microenvironment–related pathological markers could improve prognostic stratification. Materials and Methods: This retrospective study analyzed 188 patients with resectable gastric adenocarcinoma treated at the Trakya University Faculty of Medicine between 2007 and 2018. GRIm scores were calculated from preoperative lactate dehydrogenase (LDH), albumin, and neutrophil-to-lymphocyte ratio (NLR) values. Pathologic parameters, including programmed death-ligand 1 (PD-L1) expression (combined positive score [CPS] ≥ 1 vs. <1), tumor–stroma ratio (TSR; stromal component ≥ 50% vs. <50%), and tumor-infiltrating lymphocyte (TIL) density (CD8+ ≥ 10% vs. <10%), were evaluated on surgical specimens. Survival outcomes were assessed using Kaplan–Meier and multivariate Cox analyses. Results: The study population had a mean age of 61.8 years and was predominantly male (72.3%). Patients with low GRIm scores had significantly longer disease-free survival (DFS; 24 vs. 12 months; p = 0.004) and overall survival (OS; 32 vs. 19 months; p = 0.006). In multivariate analysis, the GRIm score remained an independent predictor for both disease-free survival (p = 0.035) and overall survival (p = 0.044). Among combined models, the GRIm–TSR classification provided the most pronounced stratification (median DFS = 35 vs. 12 months; OS = 45 vs. 19 months; p = 0.014 and 0.001, respectively), retaining independent prognostic significance (hazard ratio [HR] = 1.23; p = 0.005). Integrating GRIm with PD-L1 and TIL density also improved prognostic discrimination. Conclusions: The GRIm score is a robust and cost-effective biomarker that independently predicts disease-free survival and overall survival in resectable gastric adenocarcinoma. Its combination with microenvironmental markers—PD-L1, TIL, and TSR—captures complementary biological dimensions of tumor aggressiveness, offering an integrative and clinically feasible framework for individualized risk assessment and postoperative management. Prospective multicenter validation is warranted. Full article

Liver fibrosis, the progressive accumulation of scar tissue resulting from chronic liver disease, is increasingly recognized as a multi-system condition, the effects of which extend beyond the liver, affecting brain health. Dementia, characterized by progressively impaired cognition sufficient to impede daily functioning, is a major global health issue with incompletely defined risk factors and pathogenic precursors. To examine the relationship between liver fibrosis and cognitive outcomes, we conducted a comprehensive PubMed literature search, and human studies published in English were included. Evidence is synthesized on the pathophysiology and clinical significance of liver fibrosis, types of dementia, and studies supporting the association between liver fibrosis and cognitive impairment. Meta-analytic data indicate that liver fibrosis is associated with an approximately 30% increased risk of incident dementia (pooled hazard ratio ~1.3), with progressively higher risks across more advanced fibrosis stages. Putative pathomechanisms, potentially modulated by age and sex, include chronic systemic and neuro-inflammation, insulin resistance, vascular dysfunction, and a perturbed intestinal microbiota–liver–brain axis. Non-invasive liver fibrosis diagnostics, advanced neuroimaging, and biomarkers represent key tools for assessing risk. In conclusion, liver fibrosis is a systemic condition that can affect brain health. Early detection, thorough risk assessment and interventions, such as lifestyle changes, metabolic therapies, and antifibrotic treatments, may help protect neural function. Key research gaps are identified, with suggestions for improving understanding of liver fibrosis’s connection to dementia or cognitive impairment. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer subtype and, in most cases, it is incidentally diagnosed, as early-stage disease is often asymptomatic. Therefore, the identification of stable, noninvasive biomarkers is a major unmet clinical need. Urinary microRNAs (miRNAs) have emerged as promising candidates since they are extraordinarily stable in urine and show a close relationship with tumour biology. Methods: In this study, urinary expression levels of five miRNAs (miR-15a, miR-15b, miR-16, miR-210, and miR-let-7b) were analysed in RCC patients before surgery, 5 days after, and one month after surgery, and compared to healthy controls. Results: Non-parametric analyses revealed significant postoperative decreases for miR-15a (p = 0.002), miR-16 (p = 0.025), miR-210 (p = 0.030), and in the overall miRNA Sum (p = 0.002), suggesting that these miRNAs are directly linked to tumour presence. In the comparison between preoperative and one-month postoperative samples, miR-let-7b (p = 0.049) and the global miRNA Sum (p = 0.037) remained significantly reduced after intervention, indicating a partial normalisation of urinary miRNA profiles. Correlation analyses demonstrated positive associations between specific miRNAs and clinical parameters such as age, ischemia time, and surgical time, reinforcing their potential relevance to tumour biology and treatment response. Conclusions: These findings support urinary miRNAs as promising, minimally invasive biomarkers for ccRCC diagnosis and postoperative monitoring. Full article

Background: The aim of this study was to evaluate the diagnostic and prognostic performance of albumin-based inflammatory–nutritional indices in hyperemesis gravidarum (HG) and to determine their associations with disease severity and risk of re-hospitalization. Methods: This retrospective case–control study included 246 women with HG and 246 gestational-age-matched healthy pregnant controls at 6–16 weeks of gestation. Disease severity was classified as mild, moderate, or severe using the Pregnancy-Unique Quantification of Emesis (24 h scale) (PUQE-24) score. A comprehensive panel of albumin-based inflammatory indices—including C-reactive protein-to-albumin ratio (CAR), fibrinogen-to-albumin ratio (FAR), neutrophil-to-albumin ratio (NAR), leukocyte-to-albumin ratio (LAR), neutrophil percentage-to-albumin ratio (NPAR), monocyte-to-albumin ratio (MAR), hemoglobin–albumin–lymphocyte–platelet (HALP) score, modified HALP (m-HALP) score, prognostic nutritional index (PNI) score, systemic immune-inflammation index-to-albumin (SII/Alb), and systemic inflammatory response index-to-albumin (SIRI/Alb)—was calculated from routine complete blood count and serum biochemistry results obtained at diagnosis. Receiver operating characteristic analysis, along with univariate and multivariate logistic regression models, was performed to evaluate diagnostic performance and identify predictors of severe HG and re-hospitalization. Results: Albumin-based indices exhibited severity-associated alterations, with an overall trend toward worsening immuno-nutritional status across increasing HG severity. Among these, m-HALP score demonstrated the strongest inverse correlations with PUQE-24 score, ketonuria grade, length of hospital stay, and re-hospitalization risk (r = −0.74 to −0.52; all p < 0.001) and achieved the highest discriminative accuracy for both severe HG (AUC 0.864, 95% CI 0.836–0.892, p < 0.001) and re-hospitalization (AUC 0.722, 95% CI 0.675–0.766, p < 0.001). In multivariable analysis, higher HALP, m-HALP, and PNI were independently associated with a lower likelihood of severe HG. For re-hospitalization, higher m-HALP and HALP were independently associated with a lower risk, whereas higher NPAR, higher ketonuria grade, and higher PUQE-24 score were independently associated with an increased risk of re-hospitalization. Conclusions: Albumin-based indices, particularly m-HALP, demonstrated robust diagnostic and prognostic performance in HG compared with conventional biomarkers. These readily available, cost-neutral composite biomarkers enable objective severity stratification and accurate identification of patients at elevated risk of recurrent hospitalization, offering immediate potential to guide personalized, evidence-based clinical management. Full article

Pulmonary embolism (PE) is one of the most serious complications of antiphospholipid syndrome (APS), a systemic autoimmune disorder defined by thrombotic events and persistent antiphospholipid antibodies (aPLA). PE occurs in 11–20% of patients and may constitute the initial clinical manifestation. Young and middle-aged women are most frequently affected, and triple-positive aPLA profiles markedly increase the risk of recurrence and long-term morbidity, including chronic thromboembolic pulmonary hypertension (CTEPH). This review article summarizes current evidence on the epidemiology, pathophysiology, diagnostic approach, and management of PE in APS. Key mechanisms include anti-β2-glycoprotein I-mediated endothelial and platelet activation, complement engagement, and neutrophil extracellular trap formation, resulting in immunothrombosis. Diagnostic pathways follow standard PE algorithms; however, chronically elevated D-dimer levels and lupus anticoagulant-related aPTT prolongation require careful interpretation and consideration. Long-term vitamin K antagonist therapy remains the standard of care, whereas direct oral anticoagulants are not recommended in high-risk APS. Future directions include improved risk stratification through detailed aPLA profiling and the use of emerging biomarkers, early screening for CTEPH, and the development of targeted therapies such as complement inhibition and anti-NETosis strategies. Full article

Background: Sarcoidosis is a multisystem inflammatory disorder characterized by non-caseating granulomas, most commonly affecting the lungs and intrathoracic lymph nodes. Angiotensin-converting enzyme (ACE) levels and calcium abnormalities are recognized biomarkers, while ^18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is increasingly used to assess disease activity. However, neither provides sufficient diagnostic accuracy alone. Therefore, this study aimed to investigate the relationship between FDG-PET/CT metabolic findings and serum ACE and calcium (Ca²⁺) levels as surrogate indicators of inflammatory metabolic intensity in sarcoidosis. Methods: In this retrospective single-center study, 127 patients with pulmonary sarcoidosis who underwent PET/CT at diagnosis were evaluated. Demographic and clinical data, ACE, and Ca²⁺ levels were recorded. FDG uptake in mediastinal, pulmonary, and extrapulmonary sites was analyzed, and correlations with biomarkers were assessed. Results: The cohort included 89 females (70.1%) and 38 males (29.9%), mean age 51.3 ± 11.9 years. FDG uptake was most frequent in mediastinal lymph nodes (84.3%) and lung parenchyma (40.9%). ACE levels correlated weakly with total SUVmax (r = 0.214, p = 0.019). Calcium levels correlated with extrapulmonary SUVmax (r = 0.327, p = 0.001) and were higher in patients with extrapulmonary involvement (p = 0.045). No associations were found between symptom presence and biomarkers or SUVmax values. Conclusions: FDG-PET/CT metabolic parameters, particularly total and extrapulmonary SUVmax, demonstrated modest yet statistically significant associations with ACE and calcium levels. These findings suggest that a combined biomarker-imaging approach may provide complementary information regarding inflammatory metabolic intensity and systemic involvement; however, the results should be interpreted as exploratory and require validation in prospective studies. Full article

Background: The development of lung cancer is strongly influenced by oxidative stress (OS), which results when the balance between oxidants and antioxidants is disturbed. Evaluation of both specific redox markers such as thiol/disulfide homeostasis (TDH) and overall indicators including total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) may provide a more comprehensive view of oxidative imbalance in lung cancer. We examined OS indices and TDH in patients with lung cancer versus healthy controls. Methods: Eighty participants were enrolled, consisting of 40 patients with newly diagnosed lung cancer and 40 age- and sex-matched healthy controls. Serum levels of native thiol (NT), total thiol (TT), and disulfide were determined using an automated spectrophotometric method. Additionally, TAS, TOS, and the OSI were evaluated to provide an overall assessment of oxidative balance. Routine hematological and biochemical parameters were compared between groups. Results: White blood cell and neutrophil counts were notably higher in lung cancer patients compared with controls (p < 0.05). NT and TT levels were remarkably decreased, whereas disulfide levels, TOS, and OSI were significantly elevated in the lung cancer group (p < 0.05). TAS levels tended to be lower in patients, although not reaching statistical significance. No significant association was observed between oxidative parameters and tumor stage or localization. Conclusions: Patients with lung cancer exhibited a marked oxidative imbalance, characterized by elevated oxidant burden and impaired TDH. Combined assessment of TAS, TOS, OSI, and thiol/disulfide parameters may provide valuable insight into the oxidative pathophysiology of lung cancer and hold potential as complementary biomarkers for disease evaluation. Further large scale studies are needed to confirm these findings. Full article

Background: Autism Spectrum Disorder (ASD) is a type of neurodevelopmental disorder, and its exact causes are currently unknown. Neuroimaging research suggests that its clinical features are closely linked to alterations in brain functional network connectivity, yet the specific patterns and mechanisms underlying these abnormalities require further clarification. Methods: We recruited 36 children with ASD and 36 age- and sex-matched typically developing (TD) controls. Resting-state EEG data were used to construct static and dynamic low- and high-order functional networks across four frequency bands (δ, θ, α, β). Graph-theoretical metrics (clustering coefficient, characteristic path length, global efficiency, local efficiency) and state entropy were applied to characterize network topology and dynamic transitions between integration and segregation. Additionally, between-frequency networks were built for six band pairs (δ-θ, δ-α, δ-β, θ-α, θ-β, α-β), and network global measures quantified cross-frequency interactions. Results: Low-order networks in ASD showed increased δ and β connectivity but decreased θ and α connectivity. High-order networks demonstrated increased δ connectivity, reduced α connectivity, and mixed alterations in θ and β. Graph-theoretical analysis revealed pronounced α-band topological disruptions in ASD, reflected by a lower clustering coefficient and efficiency and higher characteristic path length in both low- and high-order networks. Dynamic analysis showed no significant entropy changes in low-order networks, while high-order networks exhibited time- and frequency-specific abnormalities, particularly in δ and α (0.5 s window) and δ (6 s window). Between-frequency analysis showed enhanced β-related coupling in low-order networks but widespread reductions across all band pairs in high-order networks. Conclusions: Young children with ASD exhibit coexisting hypo- and hyper-connectivity, disrupted network topology, and abnormal temporal dynamics. Integrating hierarchical, dynamic, and cross-frequency analyses offers new insights into ASD neurophysiology and potential biomarkers. Full article

Dilated cardiomyopathy is characterized by progressive left ventricular dilation and impaired systolic function, with inflammation recognized as a key contributor to disease onset and adverse outcomes. C-reactive protein reflects systemic biochemical inflammation, whereas Delta Neutrophil Index represents the circulating immature neutrophil fraction and provides a cellular dimension of inflammatory burden. The combined diagnostic and prognostic value of these two biomarkers in dilated cardiomyopathy has not been adequately explored. This retrospective study included one hundred and fifty patients with dilated cardiomyopathy and one hundred and fifty age-, diabetes-, and hypertension-matched controls. Demographic, laboratory, and echocardiographic measurements were analyzed. The diagnostic and prognostic performances of C-reactive protein, Delta Neutrophil Index, and their combined model were assessed using logistic regression, receiver operating characteristic curve analysis, reclassification metrics, calibration testing, and decision curve analysis. Additional analyses were performed for patients with left ventricular ejection fraction below twenty percent, and mortality predictors were examined within the dilated cardiomyopathy cohort. Both C-reactive protein and Delta Neutrophil Index levels were significantly higher in patients with dilated cardiomyopathy than in controls and were further elevated in those with severely reduced ejection fraction. Delta Neutrophil Index remained independently associated with severe left ventricular dysfunction (ejection fraction ≤ 20%) in multivariable analysis (odds ratio 2.51). Each biomarker showed an independent association with the presence of dilated cardiomyopathy, and their combined model achieved the highest diagnostic accuracy. In receiver operating characteristic analysis, the area under the curve was 0.895 for Delta Neutrophil Index, 0.691 for C-reactive protein, and increased to 0.920 for the combined model, with a sensitivity of 81.3% and specificity of 92.0%. Delta Neutrophil Index was independently associated with severe left ventricular dysfunction and mortality, while C-reactive protein, age, ejection fraction, urea, and sodium also contributed to mortality risk. Delta Neutrophil Index was independently associated with mortality (odds ratio 2.51), while C-reactive protein, age, ejection fraction, urea, and sodium also contributed to mortality risk. The combined model provided significant improvement in risk reclassification and demonstrated superior calibration and greater net clinical benefit across a wide range of decision thresholds. C-reactive protein and Delta Neutrophil Index offer complementary diagnostic and prognostic information in dilated cardiomyopathy. Their combined use enhances diagnostic discrimination, strengthens risk stratification, and improves identification of patients at high risk for severe ventricular dysfunction and mortality. Incorporation of these accessible biomarkers into clinical evaluation may support earlier recognition and more tailored management of high-risk individuals. Full article

Background: Irisin, a muscle-derived hormone, enhances the energy metabolism by activating the brown adipose tissue and acts as a bone-forming agent across the entire life span. No consistent clinical data in humans have been published so far to highlight if blood irisin as glucose/bone biomarker should be refined based on the vitamin D status (deficient or sufficient). Therefore, we aimed to objectively assess the level of irisin in female adults with abnormal and normal vitamin D status, as reflected by the level of 25-hydroxyvitamin (25OHD) in relationship with glucose and bone metabolic parameters. Methods: This pilot, prospective, exploratory study included eighty-nine menopausal women aged over 50. We excluded subjects with malignancies, bone and metabolic disorders, insulin treatment, and active endocrine disorders. Fasting profile included glycaemia, insulin, and glycated haemoglobin A1c (HbA1c). Then, 75 g oral glucose tolerance test (OGTT) included glycaemia and insulin assay after 60 and 120 min. Bone status involved bone turnover markers and central dual-energy X-ray absorptiometry providing bone mineral density (BMD) and trabecular bone score. Results: Eighty-nine subjects were included in the following two groups depending on 25OHD: vitamin D-deficient (VDD) group (N = 48; 25OHD < 30 ng/mL) and vitamin D-sufficient (VDS) group (N = 41; 25OHD ≥ 30 ng/mL). The two groups had similar age and menopausal period (62.29 ± 10.19 vs. 63.56 ± 8.16 years, respectively; 15.82 ± 9.55 vs. 16.11 ± 9.00 years, p > 0.5 for each). A statistically significant higher body mass index (BMI) was found in VDD vs. VDS group (32.25 ± 5.9 vs. 28.93 ± 4.97 kg/m², p = 0.006). Circulating irisin was similar between the groups as follows: median (IQR) of 91.85 (44.76–121.76) vs. 71.17 (38.76–97.43) ng/mL, p = 0.506. Fasting profile and OGTT assays showed no between-group difference. Median HOMA-IR in VDD group pointed out insulin resistance of 2.67 (1.31–3.29). Lowest mean/median T-scores at DXA for both groups were consistent with osteopenia category, but they were confirmed at different central sites as follows: femoral neck in both groups [VDD versus VDS group: −1.1 (−1.20–−0.90) vs. −1.1 (−1.49–−0.91), p = 0.526, respectively], only at lumbar spine for VDS group (T-score of −1.18 ± 1.13). The correlations between irisin and the mentioned parameters displayed a different profile when the analysis was performed in the groups with different 25OHD levels. In VDD group, irisin levels statistically significantly correlated with serum phosphorus (r = −0.32, p = 0.022), osteocalcin (r = −0.293, p = 0.038), P1NP (r = −0.297, p = 0.04), HbA1c (r = 0.342, p = 0.014), and BMI (r = 0.408, p = 0.003). Conclusions: This pilot study brings awareness in the analysis of irisin in relationship with glucose and bone-related biomarkers correlates, showing a distinct type of association depending on 25OHD level, which might represent an important crossroad in the multitude of irisin-activated signal transduction pathways. Full article

Chronic, low-grade inflammation is a characteristic of metabolic diseases like type 2 diabetes. Despite recommendations to select low- or non-fat dairy foods over full-fat dairy foods for metabolic health, recent research suggests potential anti-inflammatory benefits of dairy fat consumption. We aimed to compare the systemic inflammatory tone (i.e., circulating inflammatory biomarker concentrations and ex vivo peripheral blood mononuclear cell inflammatory responses) of individuals with prediabetes after consuming diets with full-fat (3.25%) or non-fat yogurt. We hypothesized that short-term consumption of three daily full-fat yogurt servings beneficially affects inflammatory tone. Thirteen participants aged 45–75 years completed an eight-week randomized, double-masked, controlled crossover study. The two, three-week experimental diets comprised three daily servings of full-fat or non-fat yogurt and were each preceded by a one-week run-in diet. Following each diet, circulating inflammatory biomarkers and cytokine concentrations in the supernatants of peripheral blood mononuclear cells under control or lipopolysaccharide-stimulated conditions were measured. Compared with non-fat yogurt intake, circulating immature granulocyte concentrations were lower following full-fat yogurt intake, but there were no other differences in leukocyte concentrations. Circulating concentrations of cytokines or other inflammatory markers did not differ by diet. Cell supernatant interleukin-1β concentrations were lower following the full-fat yogurt diet under unstimulated conditions but were not different between diets under stimulated conditions. There were no differences by diet in supernatant concentrations of other cytokines under unstimulated or stimulated conditions. Together, minimal differences in inflammatory tone were observed following the short-term consumption of three daily servings of full-fat or non-fat yogurt in individuals with prediabetes. Full article