Search Results (4,198)

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

Poly(3-thienylboronic acid) (PThBA) has recently been suggested as a conducting polymer with affinity for saccharides. In this study, thin films of this compound were deposited onto gold electrodes. The system obtained was studied as a possible chemical sensor. The measurements were performed by impedance spectroscopy using potassium ferro/ferricyanide as a redox mediator. The thickness of the polymer and the deposition of the adhesive sublayer were optimized to achieve a compromise between the blocking of defects in the polymer layer and the unnecessary increase in the internal resistance of this conductometric sensor. A comparative study of the influence of fructose, glucose, and sorbitol on transversal polymer resistance was conducted. The binding constants for these saccharides were extracted from the concentration dependencies of sensor conductance. Among them, sorbitol showed the highest affinity with a binding constant up to ~15,000 L·mol⁻¹, followed by fructose (~8700 L·mol⁻¹) and glucose (~4500 L·mol⁻¹). In order to exclude the contribution of the analyte tautomers on the obtained binding constants, measurements of ethylene glycol were also performed. The effects of pH and the redox state of PThBA on its affinity properties were studied, revealing higher affinities at alkaline pH and in oxidized state of the chemosensitive polymer. The developed system has the capacity to be applied in chemical sensors and virtual sensor arrays with electrical affinity control. Full article

The sugar alcohol erythritol occurs naturally in fruits and fermented foods, is used as a sweetener, and is also endogenously synthesized via the pentose-phosphate pathway and metabolized into erythronate. Untargeted metabolomic studies have associated elevated plasma erythritol and erythronate concentrations with metabolic disorders, while weight loss has been linked to decreased plasma erythritol concentrations. In this trial, two complementary analyses were performed to identify predictors of fasting erythritol and erythronate concentrations across different populations and to assess changes in these metabolites following bariatric surgery-induced weight loss. Fasting plasma samples from 30 lean adolescents, 50 lean adults, and 138 adults with obesity (including 15 who had undergone bariatric surgery) were analyzed to measure erythritol, erythronate, glucose, and insulin concentrations. Across all populations, age but not body mass index (BMI), glucose, or insulin, was a significant predictor of fasting erythritol concentrations. Fasting erythronate concentrations were associated with both age and BMI. Post-surgery, change in BMI but not fasting glucose or insulin was a predictor of changes in fasting erythritol concentrations, while time was the only predictor of changes in fasting erythronate concentrations. Although the metabolic processes regulating the endogenous erythritol and erythronate production remain unclear, our findings suggest that age-related physiological changes may influence fasting concentrations of both erythritol and erythronate. Full article

Background/Objectives: Understanding the relationship between metabolism and eating behavior may improve how we treat and prevent obesity. Fibroblast growth factor 21 (FGF21) is a hormone secreted by the liver with a putative role in energy expenditure, energy intake, and weight regulation. In this secondary analysis, we studied how fasting FGF21 is correlated with eating behavior and decision making, as measured by the Three-Factor Eating Questionnaire (TFEQ) and the Iowa Gambling Task (IGT), respectively. Methods: Participants (n = 98; women = 19; white = 31) were medically healthy, between 18 and 55 years of age, weight-stable 6 months before admission, and had normal glucose regulation. Women were premenopausal and not pregnant. Pearson partial correlations were determined, accounting for age, sex, and body fat percentage. A mediation analysis examining whether the association between hunger and IGT score was mediated by FGF21 values was performed using general linear models. Results: In partial correlations adjusted for age, sex, and body fat percentage, we found that fasting FGF21 concentrations were positively correlated with hunger susceptibility (sum of internal and external cues) (partial r = 0.26, p = 0.02) and internal hunger (partial r = 0.22, p = 0.04), disinhibition (partial r = 0.27, p = 0.01), and better decision making (higher IGT scores) (partial r = 0.40, p = 0.0001). We also found a correlation between hunger susceptibility and better decision making, including the same covariates (partial r = 0.25, p = 0.03). However, this correlation was mediated (36%) by fasting FGF21. Conclusions: In this study, participants with greater susceptibility to hunger cues had higher IGT scores (better decision making) in the setting of higher fasting FGF21 concentrations. This provides further evidence of the role of FGF21 in the interplay between eating behavior and decision making. Further studying this topic may improve our understanding of the complex relationship between assessing energy requirements and cognitive processes related to eating behavior. Full article

US food regulatory agencies have adopted a preference for researchers and testing labs to use ‘acid-adapted challenge cultures’ when performing inoculated validation studies of food processes that involve acidic treatments to accustom the cultures to acidic pH so that they will not be easily affected during processing. We evaluated acid adaptation in regard to the processing of South African style air-dried beef, notably biltong and droëwors, using a mixture of five serovars of Salmonella as well as a unique serovar isolated from dried beef (Salmonella Typhimurium 1,4,[5],12:i:-). Acid adaptation was obtained by growing cultures in tryptic soy (TS) broth containing 1% glucose. Non-adapted cultures were obtained by growth in TS broth without glucose or in TS broth with 1% glucose but buffered with 0.2 M phosphate buffer. Processes included biltong (dried solid beef) and droëwors (ground, sausage-style). Each trial was performed twice and triplicate samples were examined at each sampling point (i.e., n = 6). Statistical analysis was applied using analysis of variance (ANOVA) or one-way repeated measures (RM-ANOVA) and the Holm–Sidak test for pairwise multiple comparisons to determine significant differences (p < 0.05). We observed that in all processes examined (eight trials), treatments using acid-adapted cultures were more sensitive to the biltong and droëwors processes, giving greater reductions (5.3-log reduction) than when non-adapted cultures were used (3.8-log reduction). Acid adaptation leads to stressed conditions in Salmonella resulting in sensitization to the multiple hurdles found in biltong and droëwors processing (acid/vinegar, salt, desiccation). Based on our data, the use of non-adapted Salmonella cultures to achieve desired challenge culture process lethality could result in more robust processing conditions and a greater level of safety in these products as intended by US regulatory guidance. Full article

Background: Colorectal cancer (CRC) is significantly associated with multiple metabolic diseases, with plasma metabolites potentially mediating this relationship. This large-scale metabolomics study aims to (1) quantify the genetic correlations and causal effects between 10 metabolic disease-related phenotypes and CRC risk; (2) identify the plasma metabolites mediating these effects; and (3) explore downstream regulatory genes and druggable targets. Methods: Using linkage disequilibrium score regression and two-sample Mendelian randomization, we assessed the causal relationships between each metabolic trait and CRC. A total of 1091 plasma metabolites and 309 metabolite ratios were identified and analyzed for mediating effects by a two-step MR approach. Colocalization analyses evaluated shared genetic loci. The findings were validated in the UK Biobank for metabolite-trait associations. The expression of candidate genes was explored using data from TCGA, GTEx, and GEO. A FADS1-centered protein–protein interaction (PPI) network was constructed via STRING. Results: BMI, waist circumference, basal metabolic rate, insulin resistance and metabolic syndrome exhibited both genetic correlation and causal effects on CRC. Five plasma metabolites—mannonate, the glucose/mannose ratio, plasma free asparagine, 1-linolenoyl-2-linolenoyl-GPC (18:2/18:3), and the mannose/trans-4-hydroxyproline ratio—were identified as shared central mediators. A colocalization analysis showed rs174546 linked CRC and 1-linolenoyl-2-linoleoyl-GPC. Validation in the UK Biobank confirmed the associations between phosphatidylcholine (the lipid class of this metabolite), adiposity measures, and CRC risk. An integrative analysis of TCGA, GTEx, and GEO revealed consistent upregulation of FADS1/2/3 and FEN1 in CRC, with high FADS1 expression predicting a poorer prognosis and showing the distinct cell-type expression in adipose and colon tissue. The PPI network mapping uncovered nine FADS1 interacting proteins targeted by supplements such as α-linolenic acid and eicosapentaenoic acid. Conclusions: This study systematically reveals, for the first time, the shared intermediary plasma metabolites and their regulatory genes in the causal pathway from metabolic diseases to CRC. These findings provide candidate targets for subsequent functional validation and biomarker development. Full article

Chile boasts a rich variety of native endemic melliferous flora, recognized internationally for the excellent taste and biological properties of its honeys. While honey production occurs across various regions, the southern zone, particularly near native rainforests, yields highly valued honeys that often lack comprehensive analytical characterization. This study was focused on seven apiaries near Lake Ranco in the Los Rios Region, collecting two honey samples from each location over two consecutive harvesting seasons, totaling 20 samples. Key parameters analyzed included botanical origin, total carbohydrates, glucose/fructose ratio, total phenolic compounds, antioxidant/antiradical activity and 5-hydroxymethylfurfural (HMF) content. The results indicated a significant influence of three native species, Eucryphia cordifolia, Caldcluvia paniculata, and Weinmannia trichosperma, on the antioxidant activity of the honeys. The physicochemical parameters measured, along with the concentration and activity of the compounds responsible for this activity, establish a very characteristic pattern for the monofloral honeys of these three species. This information could serve as a foundation for constructing a map to help differentiate Chilean honeys based on their natural biological attributes helpful for consumer health, generating distinctive profiles that would contribute to accurately guaranteeing their geographical origin and, consequently, increase their specific value. Full article

The central cholinergic system is an important player in the control of motor function, appetite, the reward system, attention, memory and learning. Its participation in neurological diseases (e.g., Alzheimer’s and Parkinson’s disease, epilepsy) and in psychiatric diseases (e.g., schizophrenia, depression) makes it a preferred study subject for drug development. The present review summarizes salient features of the central cholinergic synapses that will guide future studies. Cholinergic synapses are defined by the presence of choline acetyltransferase (ChAT), the vesicular ACh transporter (VAChT), the high-affinity choline transporter CHT-1 and the presence of PRiMA-coupled acetylcholinesterase (AChE). The firing frequency of cholinergic fibers is reflected in high-affinity choline uptake activity, which also responds to variations in ChAT, VAChT and AChE activities conferring considerable plasticity to cholinergic responses. The availability of glucose and choline can limit ACh synthesis and release under conditions of high ACh turnover. Future studies will focus on rapid methods to measure ACh release and a deeper understanding of cholinergic plasticity during development, aging and dementia. Full article

Non-invasive glucose monitoring remains a persistent challenge in the scientific literature due to the complexity of biological samples and the limitations of traditional optical methods. Although advances have been made in the use of near-infrared (NIR) spectrophotometry, the direct application of the Lambert–Beer Law (LBL) to such systems has proven problematic, particularly due to the non-linear behavior observed in complex organic solutions. In this context, the objective of this work is to propose and validate a methodology for the determination of the extinction coefficient of glucose in blood, taking into account the limitations of the LBL and the specificities of molecular interactions. The method was optimized through an iterative process to provide consistent results over multiple replicates. Whole blood and plasma samples from two individuals were analyzed using spectrophotometry in the 700 nm to 1400 nm. The results showed that glucose has a high spectral sensitivity close to 975 nm.The extinction coefficients obtained for glucose (${\alpha }_g$) ranged from −0.0045 to −0.0053, and for insulin (${\alpha }_i$) from 0.000075 to 0.000078, with small inter-individual variations, indicating strong stability of these parameters. The non-linear behaviour observed in the relationship between absorbance, glucose and insulin concentrations might be explained by the changes imposed by both s and p orbitals of organic molecules. In order to make the LBL valid in this context, the extinction coefficients must be functions of the analyte concentrations, and the insulin concentration must also be a function of glucose. A regression model was found which allows to differentiate glucose from insulin concentration, by considering the cuvette thickness and sample absorbance at 965, 975, and 985 nm. It can also be concluded from experiments that wavelength of approximately 975 nm is more suitable for blood glucose calculation by using photometry. The final spectra are consistent with those reported in mid-infrared validation studies, suggesting that the proposed model encompasses the key aspects of glucose behavior in biological media. Full article

Non-communicable diseases (NCDs) are the leading global cause of death, causing over 43 million deaths in 2021, including 18 million premature deaths, disproportionately affecting low- and middle-income countries. NCDs also incur significant economic losses, estimated at USD 7 trillion from 2011 to 2025, despite low prevention costs. This study evaluated body mapping indicators: body mass index (BMI), waist circumference, and waist-to-hip ratio—for predicting NCD risk, including hypertension, diabetes, and cardiovascular diseases, using data from a nationally representative survey in Ghana. The study sampled 5775 participants via multistage stratified sampling, ensuring proportional representation by region, urban/rural residency, age, and gender. Ethical approval and informed consent were obtained. Anthropometric and biochemical data, including height, weight, waist and hip circumferences, blood pressure, fasting glucose, and lipid profiles, were collected using standardized protocols. Data analysis was conducted with STATA 17.0, accounting for complex survey design. Significant sex-based differences were observed: men were taller and lighter, while women had higher BMI and waist/hip circumferences. NCD prevalence increased with age, peaking at 60–69 years, and was higher in females. Lower education and marital status (widowed, divorced, separated) correlated with higher NCD prevalence. Obesity and high waist circumference strongly predicted NCD risk, but individual anthropometric measures lacked screening accuracy. Integrated screening and tailored interventions are recommended for improved NCD detection and management in resource-limited settings. Full article

Background/Objectives: Cardiometabolic risk remains a major challenge in patients with type 2 diabetes mellitus (DMT2). This study aimed to evaluate cardiovascular (CV) risk stratification using advanced glycation end-products (AGEs) measured via skin autofluorescence (SAF) and to assess the achievement of evidence-based ABC targets (HbA1c, blood pressure, low-density lipoprotein (LDL) cholesterol) in adults with DMT2 in Dalmatia. Methods: In this single-center cross-sectional study, 251 adults with DMT2 were stratified by CV risk based on SAF measured AGE levels. Clinical, biochemical, and anthropometric data were collected, including ABC goal attainment and medication use. Statistical analyses compared groups and explored predictors of ABC target achievement using regression models adjusted for clinical factors. Results: Only 17.5% of participants achieved all three ABC goals, indicating suboptimal cardiometabolic control. Those with elevated CV risk had higher hip circumference and lower diastolic blood pressure. Use of sodium-glucose cotransporter 2 (SGLT2) inhibitors was positively associated with ABC goal achievement in patients with prior CV or cerebrovascular events, while higher body mass index was negatively associated. SAF measured AGE levels correlated with cardiometabolic risk but showed no significant differences across LDL cholesterol or other traditional markers. Conclusions: SAF AGE measurement shows potential for CV risk stratification in DMT2 beyond traditional factors. The low rate of ABC goal attainment highlights the need for intensified individualized management incorporating novel biomarkers and therapeutics like SGLT2 inhibitors. Further prospective studies are needed to validate these findings and improve prevention of cardiovascular complications in DMT2. Full article

The hyperinsulinemic–euglycemic clamp technique is considered the gold standard for measuring insulin sensitivity in large animals. We developed a practical method for conducting concurrent glucose clamp experiments in a pair of sedated farm swine positioned in a sling. Descriptions of customized equipment and central venous access surgical procedures for blood collection are provided. Personnel functions are described for execution of the clamp protocol. A total of 24 hyperinsulinemic–euglycemic clamp studies were performed over 6 weeks. Infusaports remained functional for 1454 blood samples. There were three CSII catheter occlusions during bolus administration, and the swine showed no signs of infection or disease. IM telazol at 1.0 mg/kg, administered 1–2 h prior (mean of 3.26 mL ± 1.59) was effective in keeping animals comfortable. SpO₂ and heart rate remained within normal ranges. Means ± SD total infused volumes for octreotide, 10% dextrose, and saline were 9.7 ± 0.93 mL, 2328.0 ± 672.8 mL, and 690.3 ± 206.8 mL. Mean blood glucose was maintained between 75.7 and 87.8 mg/dL (CV 3.17%) for the 24 experiments. The GIR infusion rate peaked between 15 and 60 min after insulin bolusing, with insulin C_max of 108.5 pmol/L and t_max at 10 min. All aspects of the protocol were effectively carried out. The animals remained in good health, and the implanted infusion ports remained patent for over 700 blood draws per animal. This method could potentially reduce the number of animals used and the costs of other similar experiments. Full article

This study aims to investigate the effects of continuous glucose monitoring (CGM) on glycemic control in patients with diabetes mellitus (DM) and to identify the sociodemographic or health behavioral factors that influence the outcomes. The data were collected from 510 diabetic patients prescribed to use CGM for 12 weeks and analyzed using SPSS 27.0. Paired samples t-tests were used to compare the glycemic control (HbA1c and fasting glucose) and metabolic health (body mass index and total cholesterol) measures of subjects before and after the CGM use, and independent t-tests were conducted to examine whether the effectiveness of CGM differs according to subjects’ sociodemographic and health behavioral characteristics. As a result of this study, the use of CGM resulted in a significant reduction in HbA1c from 8.09 to 7.48 percent (p < 0.001) and in fasting glucose from 152.41 to 137.16 mg/dL (p < 0.001). In the subgroup analysis of CGM effectiveness, fasting glucose reduction was greater in females than in males and in patients with type 2 diabetes than in those with type 1 diabetes. In conclusion, it is essential to consider patient characteristics to enhance the effectiveness of CGM and to expand its use to type 2 diabetes to reduce the social burden of the disease. Full article

The problems of excessive nitrogen fertilizer application and mismatch between varieties and planting density are common in potato production in the dryland farming areas of Loess Plateau, and it is of great significance to select suitable nitrogen application rates and planting densities for the green and sustainable production of dryland potatoes in this area. In this study, Longshu 16 was selected as the potato variety, and we investigated two nitrogen application rates: 200 kg·hm⁻² (N1), 300 kg·hm⁻² (N2); and three planting densities: 37,500 plants·hm⁻² (D1), 52,500 plants·hm⁻² (D2), 67,500 plants·hm⁻² (D3). The effects of different nitrogen fertilization rates and planting densities on photosynthetic characteristics, leaf carbon and nitrogen metabolism enzyme activities, and yield and quality of potato were measured and analyzed. The results showed that during the tuber swelling stage, the activity of ribose-1,5-diphosphate carboxylase oxygenase (Rubisco) in potato leaves was increased by 9.05%. During the starch accumulation stage, the activity of glutamine synthetase (GS) in potato leaves was increased by 3.02~22.34% in N1D2 treatment compared with other treatments, and the activity of glutamate synthase (GOGAT) was increased by 2.83~7.35% compared with other treatments. During the starch accumulation stage, the activity of ADP-glucose pyrophosphorylase (AGPase) in potato leaves was increased by 7.85~31.17% in N1D2 treatment compared with other treatments. The contents of protein, starch, vitamin C, and calcium in potato tubers in N1D2 treatment were the highest, and the yield was the highest in N1D2 treatment. In conclusion, the recommended nitrogen application rate of 200 kg·hm⁻² and planting density of 52,500 plants·hm⁻² in dry-fed potato production improved the yield and quality of potato by enhancing activities of GAPDH, GS, and AGPase. Full article

Background: Metabolic syndrome is a constellation of medical conditions including central obesity, high blood sugar, and high triglycerides known to increase the risk of heart disease, stroke, and type 2 diabetes, with significant sex differences in the syndrome’s incidence and prevalence. These clinical symptoms may be accompanied by cognitive impairment. Methods: In the present experiment, we fed rabbits a diet high in fat and sugar (HFSD), assessed symptoms, and measured changes in cognition using trace eyeblink conditioning. Results: We show that a range of symptoms of metabolic syndrome resulted from HFSD in male and female rabbits and obesity, high blood sugar, and glucose intolerance were higher in male than female rabbits. Specifically, HFSD male rabbits gained more weight and had a higher body-mass index, more body fat, higher fasting glucose levels, and greater glucose intolerance. Importantly, using trace and delay eyeblink conditioning, we show that there was cognitive impairment because of the high-fat and high-sugar diet in both male and female rabbits, but this was greater in HFSD male rabbits than HFSD female rabbits. Conclusions: Metabolic syndrome modeled in rabbits fed a diet high in fat and sugar reflects trends in the adult population including central obesity, high blood sugar, and high triglycerides and cognitive impairment and provides an important model and test bed for assessing interventions. Full article