Background: Type 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism. On the other hand, the important role of the RANKL/OPG/RANK signaling axis in bone physiology is well established. The aim of this study was to evaluate the levels of receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor kappa-B (RANK) and plasma osteoprotegerin (OPG) levels, in T1D youngsters and to investigate factors that could influence theOPG/RANK/RANKLsignaling axis such as 25-hydroxy vitamin D [25(OH) D], parathormone (PTH) and age.Methods: Serum RANKL, RANK, 25(OH) D, PTH levels and plasma OPG levels, were measured in 71 youngsters with T1D and 50 healthy controls matched for age and gender.Results: Plasma OPG levels were significantly lower (p = 0.025) in T1D patients compared to controls. Serum RANKL levels were significantly higher (p = 0.037), while no differences were observed in serum RANK levels (p = 0.946) between the two groups. Serum 25(OH) D levels found significantly decreased (p < 0.001) while serum PTH levels were significantly elevated (p < 0.001) in T1D patients than in controls.Conclusions: Our results demonstrated that OPG and RANKL may be promising biomarkers for T1D patients. However, their circulating levels were associated with several factors including PTH, 25(OH) D and therefore, may represent an integrative biomarker for a variety of endocrine signaling disturbances observed in T1D.

Nonalcoholic fatty liver disease (NAFLD), the most widespread chronic liver disease worldwide, confers a significant burden on health systems and leads to increased mortality and morbidity through several extrahepatic complications. NAFLD comprises a broad spectrum of liver-related disorders, including steatosis, cirrhosis, and hepatocellular carcinoma. It affects almost 30% of adults in the general population and up to 70% of people with type 2 diabetes (T2DM), sharing common pathogenetic pathways with the latter. In addition, NAFLD is closely related to obesity, which acts in synergy with other predisposing conditions, including alcohol consumption, provoking progressive and insidious liver damage. Among the most potent risk factors for accelerating the progression of NAFLD to fibrosis or cirrhosis, diabetes stands out. Despite the rapid rise in NAFLD rates, identifying the optimal treatment remains a challenge. Interestingly, NAFLD amelioration or remission appears to be associated with a lower risk of T2DM, indicating that liver-centric therapies could reduce the risk of developing T2DM and vice versa. Consequently, assessing NAFLD requires a multidisciplinary approach to identify and manage this multisystemic clinical entity early. With the continuously emerging new evidence, innovative therapeutic strategies are being developed for the treatment of NAFLD, prioritizing a combination of lifestyle changes and glucose-lowering medications. Based on recent evidence, this review scrutinizes all practical and sustainable interventions to achieve a resolution of NAFLD through a multimodal approach.

Purpose: To compare serum humanin concentrations in pregnant women with and without pre-eclampsia (PE). Materials and methods: A case-control study where pregnant women (PE group, n = 37; control group, n = 34) studied through history parameters (gynecological, obstetrical, personal, and family), physical and sonographic examination parameters [body mass index (BMI), blood pressure obstetrical ultrasound], and biochemical/hormonal assays [creatinine, urea, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), uric acid, platelets, urinary protein, and humanin]. Results: There was no difference in basic characteristics between women with PE and control, except in parity and gravidity. Humanin concentrations were higher in women with PE compared to controls (422.2 ± 33.5 vs. 319.1 ± 28.1 pg/ml, p = 0.023). In a binary logistic analysis, humanin was associated with the presence of PE [odds ratio 1.003, 95% confidence interval (CI); 1.000–1.006]. The ability of humanin to discriminate between women with PE and controls was evaluated by receiver operation characteristics (ROC) analysis [area under the curve (AUC) 0.639, 95% CI; 0.510–0.768, p = 0.045]. Conclusions: Serum humanin concentrations are increased in women with PE, compared to women with uncomplicated pregnancies, suggesting a potential protective role of humanin against the oxidative stress and endothelial dysfunction occurring in PE.

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the myocardium that is characterized by phenotypic variability among patients. miR-146a is a small non-coding RNA that is well known for its role in inflammation and myocardial hypertrophy. The aim of this study is to evaluate the role of miR-146a as a candidate genetic factor influencing HCM phenotype. In this study, 140 HCM patients and 112 control individuals were genotyped for the rs2910164 single nucleotide polymorphism in the MIR146A gene; using this data, the correlation between different genotypes and clinical features of the disease were determined. Additionally, plasma levels of miR-146a-5p were determined in 50 HCM patients and 30 control individuals by qPCR. The incidence of GC and CC genotypes were significantly lower in HCM patients (odds ratio (OR)=0.5 [0.3-0.8], p=0.007). The GC/CC genotypes in the dominant genetic model positively correlated with the presence of left ventricle outflow tract (LVOT) obstruction (OR=2.3 [1.2-4.7], p=0.018), a higher left ventricle mass index (118±47g/m2 vs 92±42g/m2, p=0.02), and increased left ventricle end-diastolic diameter (4.66±0.64cm vs 4.39±0.7cm, p=0.026). Atrial fibrillation was significantly higher in patients homozygous for the C allele (OR=10.6 [2-55], p=0.003). Interestingly, the plasma levels of miR-146a-5p were significantly increased in HCM patients with left ventricle outflow tract obstruction. Our findings indicate that the C allele of the rs2910164 single nucleotide polymorphism might be under negative selection in HCM patients. Additionally, plasma levels of miR-146a-5p and GC/CC genotypes are indicative of the obstructive phenotype in HCM patients.

Background/Objectives: Athonian fasting, a rigorous form of intermittent fasting practiced by Christian Orthodox nuns and a subset of the Mediterranean diet, has known health benefits, but its impact on the interplay of adipokines, inflammatory cytokines, and vitamin D status remains under-investigated. This study aimed to elucidate these relationships within this controlled dietary context. Methods: This cross-sectional study examined the interplay of leptin, interleukin-6 (IL-6), and vitamin D in 41 overweight, vitamin D-sufficient Christian Orthodox nuns practicing Athonian fasting. Anthropometric, biochemical, and inflammatory markers were assessed in the nuns (mean age 53.4 ± 17.1 years, median monastery stay 17 years, median BMI 26.8 kg/m²). Results: Analysis revealed significant positive correlations between age and monastery stay (r = 0.615, p < 0.001), age and visceral fat (ρ = 0.791, p < 0.001), age and IL-6 (ρ = 0.647, p < 0.001), and BMI and IL-6 (ρ = 0.622, p < 0.001). Strong associations existed between adiposity (BMI, body fat, visceral fat), leptin, and IL-6. Specifically, body fat showed substantial positive correlations with visceral fat (ρ = 0.858, p < 0.001), leptin (ρ = 0.538, p < 0.001), and IL-6 (ρ = 0.675, p < 0.001). Visceral fat demonstrated strong positive correlations with leptin (ρ = 0.613, p < 0.001) and IL-6 (ρ = 0.741, p < 0.001). A significant positive correlation was also observed between leptin and IL-6 (ρ = 0.507, p = 0.003). Conversely, a significant negative correlation was found between 25(OH)D and PTH (ρ = −0.380, p = 0.016). Multivariate regression analysis did not reveal independent effects of leptin or IL-6 after adjusting for other factors. Conclusions: This study reveals a complex interplay of adiposity, inflammation, and vitamin D status in this unique population of Orthodox monastery fasters. The strong correlations suggest potential targets for interventions aimed at improving metabolic health. Future research should investigate the effects of vitamin D within the context of Athonian fasting.