Search Results (25,014)

Continuous glucose monitoring (CGM)-based interventions have been predominantly conducted in people with established diabetes. Recently, there has been an increasing interest in using CGM for clinical and research purposes in people without diabetes. In this review, we describe the current evidence regarding the use of CGM in people at high risk of diabetes. To date, there is no strong evidence to support the global implementation of CGM in individuals who are at risk of developing diabetes. However, there are promising results highlighting the benefits of CGM in specific populations such as people living with obesity, prediabetes, gestational diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, other endocrinopathies, and genetic syndromes. Also, CGM has shown promising potential in people with positive islet autoantibodies and pre-symptomatic type 1 diabetes, those treated with medications that induce hyperglycaemia or diabetes, and individuals receiving solid organ transplantation who are at risk of post-transplant diabetes mellitus. However, larger studies are needed to confirm these preliminary results. CGM-derived data are not currently validated for the diagnosis of diabetes. There is no CGM-derived definition of normoglycaemia in people without diabetes. Looking to the future, CGM metrics, in tandem with physical activity, dietary intake, and clinical parameters, and eventually bioinformatics, may inform personalised risk scores for precision prevention of individuals at risk. We conclude that further research is needed to clarify the indications, drawbacks, and feasibility of CGM use in people at high risk of diabetes to identify those groups who could benefit most from this technology. Full article

This study evaluated the effects of dietary olive leaf extract (OLE) on Nile tilapia (Oreochromis niloticus) juveniles, focusing on growth parameters, centesimal composition, biochemical responses, and lipid peroxidation. OLE was extracted with 60% ethanol (1:20 w/v). Five diets, containing 34% crude protein and 8% lipids, were tested: a control (0 g/kg) and four with increasing OLE levels (0.25, 0.5, 1, and 2 g/kg). The 46-day trial included 225 fish (0.56 ± 0.11 g) distributed in 15 tanks. Growth performance was not affected, except for a higher condition factor in OLE0.25. This dose also resulted in lower moisture and higher lipid content, while all OLE treatments increased crude protein in fish. Muscle glycogen decreased in all OLE-fed groups, and liver glycogen was reduced in OLE0.25. Plasma triglycerides decreased in OLE0.5 and OLE0.25, while total plasma protein was lower in OLE2.0. Liver triglycerides were lower in OLE0.25 and higher in OLE0.5, whereas glucose showed a glycemic peak in OLE2.0. Hepatic lipid peroxidation was reduced in OLE2.0. Overall, dietary OLE did not compromise the growth performance of Nile tilapia, and 0.25 g/kg promoted beneficial effects on centesimal composition, biochemical parameters, and lipid peroxidation, highlighting its potential as a functional ingredient in aquafeeds. Full article

Background: Continuous insulin infusion protocols are essential for managing decompensated diabetic dogs, but comparative data between variable and fixed infusion rates are limited. Methods: This prospective observational study evaluated the glycemic response of 21 diabetic dogs treated with a fixed-dose continuous-rate infusion (CRI) of regular insulin at 0.05 IU/kg/h for 12 h. Capillary blood glucose was measured hourly. Statistical analyses included Wilcoxon signed-rank tests, Friedman test, Mann–Whitney U, and Kruskal–Wallis tests. Results: A significant reduction in glucose concentration occurred during the first five hours of infusion (p < 0.0001), followed by a stabilization phase with no further significant changes. No differences in glycemic response were found by sex or breed. The protocol was well tolerated, with no hypoglycemic events observed. Conclusions: A fixed-dose CRI of 0.05 IU/kg/h offers a safe and effective option for acute glycemic control in diabetic dogs, including those with early ketoacidosis. The standardized approach simplifies management without compromising efficacy and supports its inclusion in emergency treatment protocols. Full article

Background: Crimean–Congo hemorrhagic fever (CCHF) is a severe zoonotic viral infection with high mortality rates. This study aimed to examine the prognostic value of new-generation inflammatory markers—CRP/albumin ratio (CAR), D-dimer/albumin ratio (DAR), D-dimer/fibrinogen ratio (DFR), and triglyceride-glucose index (TGI)—in predicting mortality among patients diagnosed with CCHF. Methods: This prospective study involved 76 patients with a positive polymerase chain reaction test for CCHF and 38 age- and sex-matched healthy controls between 15 April 2023 and 15 October 2024. Participants’ demographic, clinical, and laboratory data at presentation were recorded. Results: CAR, DAR, DFR, and TGI levels were significantly higher in the patient group compared to the control group (all p < 0.001). Furthermore, when mortal cases were compared with survivors, all of these markers were found to be significantly higher in the mortal group (p = 0.005, p = 0.004, p = 0.001, and p = 0.003, respectively). In Kaplan–Meier analysis, survival time was significantly shorter in patients with higher levels of these parameters (p < 0.001 for all). In the Receiver Operating Characteristic analysis conducted to differentiate mortal cases from survivors, DFR and TGI were identified as the markers with the highest predictive power (area under the curve: 0.938 and 0.899, respectively). Conclusions: Inflammatory markers CAR, DAR, DFR and TGI may serve as significant prognostic tools to predict mortality in CCHF. Full article

Introduction: After total pancreatectomy, patients inevitably develop pancreatogenic diabetes with marked glycemic variability and high risk of malnutrition due to both endocrine and exocrine insufficiency. Weight loss and malnutrition can occur even in those with adequate dietary intake and plausible pancreatic enzyme replacement. We hypothesized that glycemic variability is associated with nutritional decline. Methods: We retrospectively analyzed 14 patients who underwent continuous glucose monitoring (CGM) after total pancreatectomy. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), and patients were classified into malnutrition-risk progression or nutrition-maintaining groups. Then, we evaluated glycemic indices, dietary intake, anthropometry, and pancreatic enzyme replacement therapy (PERT). Results: Insulin use, PERT dose, and dietary intake were approximately comparable between groups. In contrast, the malnutrition-risk progression group showed significantly higher mean glucose and time above range, and lower time in range (TIR). Importantly, TIR consistently showed an inverse association with malnutrition-risk progression across models adjusted for clinical covariates, including time since pancreatectomy, primary diagnosis, insulin regimen, and pancrelipase dose. These findings indicate that the observed relationship between lower TIR and worsening GNRI was independent of dietary intake and adequacy of enzyme replacement therapy, underscoring TIR as a clinically meaningful indicator of nutritional decline in this population. Conclusions: Hyperglycemia and reduced TIR were significantly associated with worsening GNRI after total pancreatectomy, independent of dietary intake or PERT. CGM-based glycemic metrics may help identify patients at risk of malnutrition and guide postoperative management. Full article

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a serious health problem worldwide. Moreover, increased systemic and cerebrovascular inflammation is one of the major pathophysiological features of T2DM, and a growing body of evidence emphasizes T2DM with memory and executive function decline. Bioactive sphingolipids regulate a cell’s survival, inflammatory response, as well as glucose and insulin signaling/metabolism. Moreover, current research on the role of sphingosine kinases (SPHKs) and sphingosine-1-phosphate receptors (S1PRs) in T2DM is not fully understood, and the results obtained often differ. The aim of the present study was to evaluate the effect of metformin (anti-diabetic agent, MET) on the brain’s sphingosine-1-phosphate-related signaling and ultrastructure in diabetic mice. Our results revealed elevated mRNA levels of genes encoding sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate receptor 3 (S1PR3), which was accompanied by downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) in the hippocampus of diabetic mice. Simultaneously, upregulation of genes encoding pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was observed. Administration of MET significantly reversed changes in mRNA levels in the hippocampus and reduced Sphk2, Il6, and Tnf, with concomitant upregulation of S1pr1 gene expression. Ultrastructural analysis of diabetic mice hippocampus revealed morphological alterations in neurons, neuropil, and capillaries that were manifested as mitochondria swelling, blurred synaptic structure, and thickened basal membrane of capillaries. The use of MET partially reversed those changes. Our research emphasizes the important role of insulin sensitivity modulation by metformin in the regulation of SPHKs and S1PRs and inflammatory gene expression in a murine model of T2DM. Full article

Background/Objectives: Accurate blood glucose forecasting is critical for closed-loop insulin delivery systems to support effective disease management in people with type 1 diabetes (T1D). While long short-term memory (LSTM) neural networks have shown strong performance in glucose prediction tasks, the relative performance of individualized versus aggregated training remains underexplored. Methods: In this study, we compared LSTM models trained on individual-specific data to those trained on aggregated data from 25 T1D subjects using the HUPA UCM dataset. Results: Despite having access to substantially less training data, individualized models achieved comparable prediction accuracy to aggregated models, with mean root mean squared error across 25 subjects of 22.52 ± 6.38 mg/dL for the individualized models, 20.50 ± 5.66 mg/dL for the aggregated models, and Clarke error grid Zone A accuracy of 84.07 ± 6.66% vs. 85.09 ± 5.34%, respectively. Subject-level analyses revealed only modest differences between the two approaches, with some individuals benefiting more from personalized training. Conclusions: These findings suggest that accurate and clinically reliable glucose prediction is achievable using personalized models trained on limited individual data, with important implications for adaptive, on-device training, and privacy-preserving applications. Full article

Collagen peptides derived from fish skin may be limited in food applications due to undesirable flavors. To investigate the effects of Maillard reaction modification on their physicochemical and flavor properties, collagen peptides from tilapia skin were prepared via enzymatic hydrolysis, followed by the Maillard reaction with four reducing sugars (xylose, ribose, glucose and glucosamine) through a combined procedure involving simultaneous enzyme inactivation and Maillard reaction at 100 °C. The resultant Maillard reaction products (MRPs) were characterized by analyzing free amino groups, peptide size distribution and color difference, while the reaction progression was monitored using UV absorption and fluorescence spectroscopy. The flavor profile of MRPs was analyzed through quantitative descriptive sensory evaluation and GC-MS coupled with principal component analysis. Among the four reducing sugars tested, glucosamine-induced Maillard reaction products exhibited the most pronounced physicochemical and sensory improvements. Specifically, glucosamine-MRPs showed the greatest reduction in free amino groups (0.69 μmol/L) and a notable decrease in high-molecular-weight peptides (3.31%), accompanied by an increase in low-molecular-weight fractions. Colorimetric analysis revealed a marked color change (ΔE = 31.78), and spectral analysis further confirmed intensified UV absorbance and fluorescence intensity in the glucosamine group, indicating advanced reaction progression. Sensory evaluation demonstrated a significant reduction in bitterness and enhancement of umami and saltiness. Moreover, GC-MS analysis revealed that the glucosamine-treated group exhibited the most favorable volatile profile, characterized by an increase in aromatic compounds and a substantial decrease in undesirable odorants. This study provides a theoretical basis for controlling the undesirable flavor of collagen peptides through low-extent Maillard reactions by different reducing sugars. Full article

Background/Objectives: Melanoma cells enhance glycolysis and expand lysosomes to support energy metabolism, proliferation, and metastasis. However, lysosomal membrane permeabilization (LMP) causes cathepsin leakage into cytosol triggering cytotoxicity. This study investigated the antimelanoma effect of 2-deoxy-D-glucose (2DG), an inhibitor of glycolytic enzyme hexokinase-2, in combination with cathepsin C-dependent LMP inducer L-leucyl-L-leucine methyl ester (LLOMe) and cathepsin C-independent LMP-inducers mefloquine and siramesine. Methods: The viability of A375 and B16 melanoma cells and primary fibroblasts was measured by crystal violet. Apoptosis, necrosis, and LMP were assessed by flow cytometry; caspase activation, mitochondrial depolarization, superoxide production, and energy metabolism were analyzed by fluorimetry, and expression of cathepsins and hexokinase-2 was evaluated by immunoblot. Appropriate inhibitors, antioxidant, and energy boosters were used to confirm cell death type and mechanism. Results: LLOMe triggered LMP, mitochondrial depolarization, and mitochondrial superoxide production, while suppressing oxidative phosphorylation. 2DG suppressed glycolysis and, together with LLOMe, synergized in ATP depletion, caspase activation, and mixed apoptosis and necrosis in A375 cells. Inhibitors of lysosomal acidification, cysteine cathepsins, and caspases, as well as antioxidant and energy boosters, reduced 2DG+LLOMe-induced toxicity. Cathepsins B, C, and D were lower, while hexokinase-2 was higher in A375 cells than fibroblasts. Accordingly, 2DG exhibited lower while LLOMe exhibited higher toxicity against fibroblasts than A375 and B16 cells. However, mefloquine and siramesine induced stronger LMP in A375 cells than in fibroblasts and showed melanoma-selective toxicity when combined with 2DG. Conclusions: 2DG-mediated glycolysis inhibition in combination with lysosomal destabilization induced by mefloquine and siramesine, but not with non-selectively toxic LLOMe, may be promising antimelanoma strategy. Full article

Safflower (Carthamus tinctorius L.) is a multipurpose economic crop. Flavonoid glycosides are its key bioactive constituents, and several glycosyltransferases involved in their biosynthesis have been identified. The glycosyltransferase 84 subfamily represents a specialized branch with diverse functions, involved not only in catalyzing flavonoid glycosylation but also in the biosynthesis of auxins, tannins, and other compounds. However, this subfamily remains poorly characterized in safflower. In this study, two UGT84 subfamily genes, UGT84A28 and UGT84B3, were screened based on expression patterns and phylogenetic evolution analysis. Recombinant proteins were induced and purified using prokaryotic expression systems. Functional characterization was subsequently conducted through enzymatic assays in vitro and transient expression in tobacco leaves. Molecular docking was employed to investigate the binding modes of UGTs with UDP-glucose. The results indicated that both UGTs demonstrated glycosylation activity at the flavonoid 7-OH position. Notably, when luteolin was employed as the aglycone, both enzymes also exhibited 3′-O-glycosylation activity. Combined with amino acid sequence alignment, we propose that residues A351/T343 and G263/F254, which affect spatial conformation and hydrogen bonding ability, may be one of the reasons for the functional differences between these two enzymes. These findings provide new insights into the catalytic diversity of glycosyltransferases. Full article

Alzheimer’s disease (AD) requires early and accurate identification of affected brain regions, which can be achieved through the detection of specific biomarkers to enable timely intervention. Carbon nanomaterials (CNMs), including graphene derivatives, carbon nanotubes, graphitic carbon nitride, carbon black, fullerenes, and carbon dots, offer high conductivity, large electroactive surface area, and versatile surface chemistry that enhance biosensor performance. While such properties benefit a wide range of transduction principles (e.g., electrochemical, optical, and plasmonic), this review focuses on their role in electrochemical biosensors. This review summarizes CNM-based electrochemical platforms reported from 2020 to mid-2025, employing aptamers, antibodies, and molecularly imprinted polymers for AD biomarker detection. Covered topics include fabrication strategies, transduction formats, analytical performance in complex matrices, and validation. Reported devices achieve limits of detection from the femtomolar to picogram per milliliter range, with linear ranges typically spanning 2–3 orders of magnitude (e.g., from femtomolar to picomolar, or from picogram to nanogram per milliliter levels). They exhibit high selectivity against common interferents such as BSA, glucose, uric acid, ascorbic acid, dopamine, and non-target peptides, along with growing capabilities for multiplexing and portable operation. Remaining challenges include complex fabrication, limited long-term stability and reproducibility data, scarce clinical cohort testing, and sustainability issues. Opportunities for scalable production and integration into point-of-care workflows are outlined. Full article

Background/Objectives: The longitudinal associations between different modalities of sedentary behaviors (SBs) and sedentary patterns (SPs) with metabolic syndrome (MetS) in children and adolescents are unclear. We aimed to analyze the cross-sectional and longitudinal (2-year follow-up) association between SB and SP with the MetS score in Spanish children and adolescents. Methods: 76 children (34 females) and 186 adolescents (94 females) were included for SB analyses, and 175 children (82 females) and 188 adolescents (95 females) for SP. Children and adolescents were aged 6–11.9 years and 12–17.9 years, respectively. SB were assessed by a self-reported questionnaire and SP were determined by accelerometry. The MetS score was computed from the waist circumference, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose levels. Different linear regression models were implemented to examine cross-sectional, longitudinal, and change associations of SB and SP with MetS. Results: Total daily SB, educative daily SB, and mean SB were longitudinal and inversely associated with MetS (β = −0.001, all p < 0.05) in male adolescents, while other daily SB was longitudinal and inversely associated with MetS (β = −0.002, all p < 0.05) in female adolescents. Changes in screen and other daily SB were directly associated with MetS in female adolescents (β = 0.001 to 0.002, all p < 0.05). In contrast, changes in educative daily SB were inversely associated with MetS in female adolescents (β = −0.001, all p < 0.05). Conclusions: Few associations between SB modalities and the MetS score were found, mainly in adolescents and often in unexpected directions. In male adolescents, total and educative daily SB were negatively associated with MetS. In female adolescents, other daily SB and changes in educative daily SB showed negative associations, while changes in screen-based and other daily SB were positively associated with MetS. No associations were found between SP and MetS. Given the low evidence available to date, more longitudinal studies analyzing SB and SP simultaneously are needed to reach solid conclusions. Full article

Given that type 2 diabetes mellitus is common in several ciliopathies, the NME7 gene (non-metastatic cells 7), encoding a recognized member of the ciliome, was studied in connection with glucose metabolism. The aim was to find out whether the variability in the gene is associated with the response to administered glucose during the 3 h oral glucose tolerance test. The study included 1262 individuals with different levels of glucose tolerance. Glycemic curves were categorized according to their shape as monophasic, biphasic, triphasic, and more complex multiphasic. The analysis showed a significant association of five linked NME7 polymorphisms with the biphasic course of the glycemic curve, a shape that has been shown to be metabolically protective. Specifically, minor alleles of rs4656659 and rs2157597 in combination with wild-type alleles of rs10732287, rs4264046, and rs10800438 were more frequent within the biphasic category. Moreover, haplotype analysis confirmed higher insulin sensitivity in carriers of this specific haplotype. In conclusion, a cluster of five linked NME7 polymorphisms showed an association with a biphasic glycemic curve. Considering the health benefits of the biphasic curve in terms of glycoregulation and taking into account the demonstrated link of the NME7 haplotype with insulin sensitivity, variability in the NME7 gene represents another piece of the complex mosaic influencing healthy energy processing. Full article

Background/Objectives: Retinal ischemia–reperfusion (I/R) injury is a common mechanism in glaucoma, diabetic retinopathy, and retinal vein occlusion, leading to progressive loss of retinal ganglion cells (RGCs). This study investigates the regulatory role of miR-21-5p and its interaction with Signal Transducer and Activator of Transcription 3 (STAT3) in retinal I/R injury. Methods: An acute intraocular hypertension (AIH) rat model was used to induce retinal I/R. The interaction between miR-21-5p and STAT3 was examined by dual-luciferase reporter assays. miR-21-5p and STAT3 expression were quantified by qRT-PCR and Western blotting. Retinal morphology, microglial polarization, and RGC survival were assessed by H&E staining and immunofluorescence. In vitro, microglia and RGCs were subjected to oxygen–glucose deprivation/reperfusion (OGD/R), and microglial-conditioned media (MCM) were applied to RGCs. Results: (1) miR-21-5p ameliorated AIH-induced retinal damage in vivo. (2) Overexpression of miR-21-5p inhibits M1 polarization of RM cultured in vitro. (3) MCM from miR-21-5p-overexpressing microglia attenuated OGD/R-induced RGC death. (4) miR-21-5p downregulates STAT3 expression to inhibit RM M1 polarization. (5) miR-21-5p down-regulation of STAT3 levels inhibits M1 polarization and reduces apoptosis of RGCs in retinal microglia of AIH rats. Conclusions: miR-21-5p alleviates retinal I/R injury by restraining microglial M1 polarization through direct repression of STAT3, thereby promoting RGC survival. These findings identify the miR-21-5p/STAT3 axis as a potential therapeutic target for ischemic retinal diseases. Full article

Semaglutide-induced facial changes, or “Ozempic face” popularized by media, have gained increasing recognition since the widespread and growing use of Ozempic (semaglutide) for weight loss. It refers to facial volume depletion and soft tissue laxity following rapid weight loss associated with this medication. Semaglutide use can also cause gastrointestinal side effects, volume loss, and decrease skin quality not only in the face but globally. As the use of Ozempic becomes increasingly popular, more patients are presenting to cosmetic clinics for these undesirable esthetic changes. While cosmetic changes following rapid weight loss is not new, such as those following bariatric interventions, the accessibility and ease of GLP-1, Glucose-like protein-1, makes this a growing concern among the community. It is important for clinicians to recognize these potential effects, counsel patients appropriately, and give options for treatment. This emerging esthetic concern highlights the need for further investigation into underlying causes, risk factors, and potential interventions. Full article