Search Results (1,464)

Perturbations in the tightly regulated processes of VLDL biosynthesis and secretion can directly impact both liver and cardiovascular health. Patients with metabolic disorders have an increased risk of developing hepatic steatosis, which can lead to cirrhosis. These associated metabolic risks underscore the importance of discerning the role of different cellular proteins involved in VLDL biogenesis, transport, and secretion. Small VCP-Interacting Protein (SVIP) has been identified as a component of VLDL transport vesicles and VLDL secretion. This study evaluates the cellular effects stemming from the CRISPR-Cas9-mediated depletion of SVIP in rat hepatocytes. The SVIP-knockout (KO) cells display an increased VLDL retention with elevated intracellular levels of ApoB100 and neutral lipid staining. RNA sequencing studies reveal an impaired PPARα and Nrf2 signaling in the SVIP KO cells, implying a state of metabolic reprograming, with a shift from fatty acid uptake, synthesis, and oxidation to cells favoring the activation of glucose by impaired glycogen storage and increased glucose release. Additionally, SVIP KO cells exhibit a transcriptional profile indicative of acute phase response (APR) in hepatocytes. Many inflammatory markers and genes associated with APR are upregulated in the SVIP KO hepatocytes. In accordance with an APR-like response, the cells also demonstrate an increase in mRNA expression of genes associated with protein synthesis. Together, our data demonstrate that SVIP is critical in maintaining hepatic lipid homeostasis and metabolic balance by regulating key pathways such as PPARα, Nrf2, and APR. Full article

Childhood obesity increases chronic disease risk, but no comprehensive synthesis has evaluated the impact of school-based combined nutrition education and physical activity interventions on cardiometabolic biomarkers in children aged 3 to 12 years. This systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251085194). Five databases were systematically searched through June 2025. Twelve randomized controlled trials involving 18,231 children were included and assessed using the PEDro scale. Ten trials demonstrated significant improvements in at least one cardiometabolic biomarker. Blood pressure (8 studies) outcomes showed systolic reductions of 1.41–6.0 mmHg in six studies. Glucose metabolism (5 studies) improved in two studies with reductions of 0.20–0.22 mmol/L. Lipid profiles (7 studies) improved in three studies, including total cholesterol (−0.32 mmol/L). Insulin levels (5 studies) decreased significantly in two investigations. Anthropometric improvements included BMI and body fat. Physical activity increased by >45 min/week and dietary habits improved significantly. Programs with daily implementation (90-min sessions 4x/week), longer duration (≥12 months), family involvement (parent education), and curriculum integration (classroom lessons) showed superior effectiveness. Interventions targeting children with overweight/obesity demonstrated higher changes compared to the general population. However, methodological limitations included a lack of assessor blinding, absence of subject/therapist blinding, and inadequate retention rates. School-based interventions combining nutrition and physical activity can produce significant improvements in cardiometabolic biomarkers, supporting comprehensive, sustained multicomponent programs for early chronic disease prevention. Full article

Background and Objectives: The management of type 2 diabetes (T2D) extends beyond glycemic control, requiring a more global strategy that includes optimization of body composition, even more so in the context of sarcopenia and visceral adiposity, as they contribute to poor outcomes. Past reviews have typically been focused on weight reduction or glycemic effectiveness, with limited inclusion of new therapies’ effects on muscle and fat distribution. In addition, the emergence of incretin-based therapies and dual agonists such as tirzepatide requires an updated synthesis of their impacts on body composition. This review attempts to bridge the gap by taking a systematic approach to how current blood-glucose lowering therapies affect lean body mass, fat mass, and the risk of sarcopenia in T2D patients. Materials and Methods: Between January 2015 and March 2025, we conducted a narrative review by searching the PubMed, Scopus, and Web of Science databases for English-language articles. The keywords were combinations of the following: “type 2 diabetes,” “lean body mass,” “fat mass,” “body composition,” “sarcopenia,” “GLP-1 receptor agonists,” “SGLT2 inhibitors,” “tirzepatide,” and “antidiabetic pharmacotherapy.” Reference lists were searched manually as well. The highest precedence was assigned to studies that aimed at adult type 2 diabetic subjects and reported body composition results. Inclusion criteria for studies were: (1) type 2 diabetic mellitus adult patients and (2) reporting measures of body composition (e.g., lean body mass, fat mass, or muscle function). We prioritized randomized controlled trials and large observational studies and excluded mixed diabetic populations, non-pharmacological interventions only, and poor reporting of body composition. Results: Metformin was widely found to be weight-neutral with minimal effects on muscle mass. Insulin therapy, being an anabolic hormone, often leads to fat mass accumulation and increases the risk of sarcopenic obesity. Incretin-based therapies induced substantial weight loss, mostly from fat mass. Notable results were observed in studies with tirzepatide, demonstrating superior reduction not only in fat mass, but also in visceral fat. Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) promote fat loss but are associated with a small yet significant decrease in lean muscle mass. Conclusions: Blood-glucose lowering therapies demonstrated clinically relevant effects on body composition. Treatment should be personalized, balancing glycemic control, cardiovascular, and renal benefits, together with optimal impact on muscle mass along with glycemic, cardiovascular, and renal benefits. Full article

(1) Background: Epidemiological studies link ozone (O₃) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O₃ were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related to impaired glucose tolerance and insulin resistance were screened through the Comparative Toxicogenomics Database (CTD), and verified using quantitative real-time PCR. In addition, liver histopathological observations and the determination of basic biochemical indicators were conducted, and targeted metabolomics analysis was performed on the liver to verify glycogen levels and gene expression. In vitro validation was conducted with HepG2 and Min6 cell lines. (3) Results: Fasting blood glucose and insulin resistance were elevated following O₃ exposure. Given that the liver plays a critical role in glucose metabolism, we further investigated hepatocyte apoptosis and alterations in glycogen metabolism, including reduced glycogen levels and genetic dysregulation. Metabolomics analysis revealed abnormalities in fructose metabolism and glycogen synthesis in the livers of the O₃-exposed group. In vitro studies demonstrated that oxidative stress enhances both liver cell apoptosis and insulin resistance in pancreatic islet β cells. (4) Conclusions: O₃ triggers prediabetes symptoms via hepatic metabolic dysfunction and hepatocyte apoptosis. The identified metabolites and genes offer potential as early biomarkers and therapeutic targets. Full article

Films of a Ni/Al-layered double hydroxide intercalated with reduced graphene oxide were deposited, by means of a simple and rapid electrochemical synthesis, on Pt electrodes previously submitted to a special cleaning procedure. The aim of the research was to determine whether the better electrocatalytic properties of the Ni(III)/Ni(II) couple, due to the presence of the carbon nanomaterial, as compared to the Ni/Al-LDH alone, could allow glucose detection at physiological pHs, as normally LDHs work as redox mediators in basic solutions. Chronoamperometric experiments were carried out by applying a potential of 1.0 V vs. SCE to the electrode soaked in solutions buffered at pHs from 5.0 to 9.0 to which glucose was continuously added. The steady-state currents increased as the pH solution increased, but at pH = 7.0 the modified electrode exhibited a fast and rather sensitive response, which was linear up to 10.0 mM glucose, with a sensitivity of 0.56 A M⁻¹ cm⁻² and a limit of detection of 0.05 mM. Our results suggest the potential application of Ni/Al-LDH(ERGO) composite for the non-enzymatic detection of glucose or other oxidizable analytes under biological conditions. Full article

Cirrhosis remains a significant global health burden, responsible for nearly 4% of annual deaths worldwide. Despite progress in antiviral therapies and public health measures, its prevalence has plateaued, particularly in regions affected by viral hepatitis, alcohol misuse, and metabolic syndrome. This review presents a comprehensive synthesis of the multifactorial drivers of cirrhosis, including hepatocyte injury, liver stellate cell activation, and immune-mediated inflammation. The emphasis is on the central role of metabolic dysfunction, characterized by mitochondrial impairment, altered lipid and glucose metabolism, hormonal imbalance, and systemic inflammation, in exacerbating disease progression. While current therapies may slow the progression of early-stage disease, they are very often ineffective in reversing established fibrosis. Emerging molecular strategies offer promising alternatives by targeting key pathogenic pathways. These include AMPK activators (e.g., metformin, AICAR), FGF21 analogs, and mitochondria-targeted agents (e.g., MitoQ, urolithin A, NAD+ precursors) to restore bioenergetic balance and reduce oxidative stress. Other approaches, such as mesenchymal stem cell therapy, inflammasome inhibition, and hormonal modulation, aim to suppress fibrogenesis and restore liver homeostasis. The integration of systems biology and multi-omics profiling supports patient stratification and precision medicine. This review highlights a shift toward mechanism-based interventions that have the potential to alter cirrhosis outcomes and improve patient survival. Full article

Glucose-responsive insulin delivery systems that effectively regulate insulin retention and release in response to real-time fluctuation of glucose levels are highly desirable for diabetes care with minimized risk of hypoglycemia. Herein, we report a class of glucose-sensitive copolymer microgels, prepared from a simple one-pot precipitation copolymerization of 4-vinylphenylboronic acid (VPBA), 2-(dimethylamino) ethyl acrylate (DMAEA), and oligo(ethylene glycol) methyl ether methacrylate (M_w = 300, MEO₅MA), for gated glucose-responsive insulin release within the physiologically desirable glucose level range. The composition of the p(VPBA-DMAEA-MEO₅MA) copolymer microgels were analyzed using NMR and FTIR spectra. The cis-diols of glucose can reversibly bind with the −B(OH)₂ groups of the VPBA component in the microgels, resulting in the formation of negatively charged boronate esters that induce the volume phase transition of the microgels. The DMAEA component is incorporated to reduce the pK_a of VPBA, thus improving the glucose sensitivity of the microgels at physiological pH. The neutral hydrophilic MEO₅MA component is used to tune the onset of the glucose responsiveness of the microgels to the physiologically desirable levels. The more the MEO₅MA component copolymerized in the microgels, the greater the glucose concentration required to initiate the swelling of the microgels to trigger the release of insulin. When the onset of the glucose response was tuned to 4−5 mM, the copolymer microgels retained insulin effectively in the hypo-/normo-glycemic range but also released insulin efficiently in response to the elevation of glucose levels in the hyperglycemic range, which is essential for diabetes management. The copolymer microgels display no cytotoxicity in vitro. Full article

Ancient grains, including wild rice, millet, fonio, teff, quinoa, amaranth, and sorghum, are re-emerging as vital components of modern diets due to their dense nutritional profiles and diverse health-promoting bioactive compounds. Rich in high-quality proteins, dietary fiber, essential micronutrients, and a broad spectrum of bioactive compounds such as phenolic acids, flavonoids, carotenoids, phytosterols, and betalains, these grains exhibit antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and immunomodulatory properties. Their health-promoting effects are underpinned by multiple interconnected mechanisms, including the reduction in oxidative stress, modulation of inflammatory pathways, regulation of glucose and lipid metabolism, support for mitochondrial function, and enhancement of gut microbiota composition. This review provides a comprehensive synthesis of the essential nutrients, phytochemicals, and functional properties of ancient grains, with particular emphasis on the nutritional and molecular mechanisms through which they contribute to the prevention and management of chronic diseases such as cardiovascular disease, type 2 diabetes, obesity, and metabolic syndrome. Additionally, it highlights the growing application of ancient grains in functional foods and nutrition-sensitive dietary strategies, alongside the technological, agronomic, and consumer-related challenges limiting their broader adoption. Future research priorities include well-designed human clinical trials, standardization of compositional data, innovations in processing for nutrient retention, and sustainable cultivation to fully harness the health, environmental, and cultural benefits of ancient grains within global food systems. Full article

The demand for biomass has been growing in recent years for several reasons, related to environmental, economic, and social trends. In the context of global climate changes and the depletion of natural resources, the recycling of plant biomass waste is a promising strategy for sustainable development that contributes to minimizing waste, improving resource efficiency, and achieving the goal of creating a circular economy. One of the highly demanded products of agricultural waste recycling is glucose. Glucose is an important organic substrate that allows a number of value-added products to be obtained. In this review, we focused on the commercially significant products of glucose oxidation: gluconic and glucaric acids. This review summarized the latest available data on the scope of the application of each product as well as the methods of their production. The capabilities and limitations of currently used methods of synthesis were highlighted. Full article

This study discloses the noncovalent immobilization of a bienzyme cascade composed of glucose oxidase (GOx) and horseradish peroxidase (HRP) onto magnetically responsive polyamide microparticles (PA MPs). Porous PA6, PA4, and PA12 MPs containing iron fillers were synthesized via activated anionic ring-opening polymerization in suspension, alongside neat PA6 MPs used as a reference. Four hybrid catalytic systems (GOx/HRP@PA) were prepared through sequential adsorption of HRP and GOx onto the various PA MP supports. The initial morphologies of the supports and the hybrid biocatalysts were characterized by SEM, followed by evaluation of the catalytic performance using a two-step glucose oxidation cascade process. Among all systems, the GOx/HRP@PA4-Fe complex exhibited the highest activity, being approximately 1.5 times greater than the native enzyme dyad, followed by the PA6-supported system with slightly inferior performance. All systems obeyed Michaelis–Menten kinetics, with the immobilized cascades displaying higher Kₘ and Vₘₐₓ values than the non-immobilized enzyme pair while maintaining comparable catalytic efficiencies, CE (CE = k_cat/Kₘ). Subsequently, the immobilized and native enzyme systems were employed for the polymerization of aniline. According to UV–VIS, complete monomer conversion was achieved within 24 h for selected catalysts, and FTIR analysis confirmed the formation of polyaniline in the emeraldine base form without the use of template molecules. These findings highlight the potential of Fe-containing polyamide microparticles as efficient supports for the sustainable, enzyme-mediated synthesis of intrinsically conductive aromatic polymers. Full article

Ganoderma lucidum polysaccharides (GLPs) are natural compounds with a broad spectrum of biological activities. β-1,3-glucosyltransferase (GL20535) plays an important role in polysaccharide synthesis by catalyzing the transfer of UDP-glucose to extend sugar chains, but its underlying mechanism remains unclear. In this study, the regulatory mechanism of GL20535 in polysaccharide synthesis was elucidated by overexpressing and silencing gl20535 in G. lucidum. Overexpression of gl20535 resulted in maximum increases of 18.08%, 79.04%, and 18.01% in intracellular polysaccharide (IPS), extracellular polysaccharide (EPS), and β-1,3-glucan contents, respectively. In contrast, silencing gl20535 resulted in maximum reductions of 16.97%, 30.20%, and 23.56% in IPS, EPS, and β-1,3-glucan contents, respectively. These phenomena in the overexpression strains were attributed to gl20535-mediated promotion of UDP-glucose synthesis in the sugar donor pathway and upregulation of the expression of glycoside hydrolase genes. The opposite trend was observed in the silenced strains. In mycelial growth studies, neither overexpression nor silencing of gl20535 affected biomass and cell wall thickness. Furthermore, the GL20535 isozyme gene gl24465 remained unaffected in gl20535-overexpressed strains but was upregulated in gl20535-silenced strains, suggesting a compensatory regulatory relationship. These findings reveal the regulatory role of GL20535 on gene expression in the GLPs synthesis pathway and deepen our understanding of GL20535 function in the polysaccharide network of edible and medicinal fungi. Full article

As tumor research has deepened, the deregulation of cellular metabolism has emerged as yet another recognized hallmark of cancer. Tumor cells adapt different biochemical pathways to support their rapid growth, proliferation, and invasion, resulting in distinct anabolic and catabolic activities compared with healthy tissues. Certain metabolic shifts, such as altered glucose and glutamine utilization and increased de novo fatty acid synthesis, are critical early on, while others may become essential only during metastasis. These metabolic adaptations are closely shaped by, and in turn remodel, the tumor microenvironment, creating favorable conditions for their spread. Anticancer metabolic strategies should integrate pharmacological approaches aimed at inhibiting specific biochemical pathways with well-defined dietary interventions as adjunctive therapies, considering also the role of gut microbiota in modulating diet and treatment responses. Given the established link between the consumption of foods rich in saturated fatty acids and sugars and an increased cancer risk, the effects of diet cannot be ignored. However, current evidence from controlled and multicenter clinical trials remains insufficient to provide definitive clinical recommendations. Further research using modern omics methods, such as metabolomics, proteomics, and lipidomics, is necessary to understand the changes in the metabolic profiles of various cancers at different stages of their development and to determine the potential for modifying these profiles through pharmacological agents and dietary modifications. Therefore, clinical trials should combine standard treatments with novel approaches targeting metabolic reprogramming, such as inhibition of specific enzymes and transporters or binding proteins, alongside the implementation of dietary restrictions that limit nutrient availability for tumor growth. However, to optimize therapeutic efficacy, a precision medicine approach should be adopted that balances the destruction of cancer cells with the protection of healthy ones. This approach, among others, should be based on cell type-specific metabolic profiling, which is crucial for personalizing oncology treatment. Full article

This study presents the development of a TiO₂ nanowire-based electrochemical sensor for the selective and sensitive detection of hydrogen peroxide (H₂O₂) under neutral pH conditions, with a particular focus on its application in analyzing plant stress. The sensor exhibited a linear detection range of 0–0.5 mM, a sensitivity of 0.0393 mA · mM⁻¹, and a detection limit of 2.8 μM in phosphate-buffered saline solution (PBS, pH 7.4). This work’s main novelty lies in the systematic investigation of the relationship between TiO₂ nanostructure morphology, which is controlled by hydrothermal synthesis parameters, and the resulting sensor performance. Interference studies confirmed excellent selectivity in the presence of common electroactive species found in plant samples, such as NaCl, KNO₃, glucose, citric acid, and ascorbic acid. Real sample analysis using barley plant extracts grown under salt stress and treated with Fe₃O₄ nanoparticles confirmed the sensor’s applicability in complex biological matrices, enabling accurate quantification of endogenously produced H₂O₂. Endogenous H₂O₂ concentrations were found to range from near-zero levels in control and Fe₃O₄-only treated plants, to elevated levels of up to 0.36 mM in salt-stressed samples. These levels decreased to 0.25 and 0.15 mM upon Fe₃O₄ nanoparticle treatment, indicating a dose-dependent mitigation of stress. This finding was supported by genome template stability (GTS) analysis, which revealed improved DNA integrity in Fe₃O₄-treated plants. This study takes an integrated approach, combining the development of a nanostructured sensor with physiological and molecular stress assessment. The urgent need for tools to detect stress at an early stage and manage oxidative stress in sustainable agriculture underscores its relevance. Full article

This study investigates the valorization of carrot discard, a carbohydrate-rich agricultural residue, for the production of 2,3-butanediol (2,3-BDO). The fermentation process was evaluated using two strains, Bacillus licheniformis DSM 8785 and Bacillus amyloliquefaciens DSM 7. Two process configurations were compared: separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF). Additionally, to determine substrate and product inhibition thresholds, fermentation assays were conducted in semi-defined media with glucose concentrations ranging from 20 to 120 g/L. The SHF strategy proved more effective than the SSF configuration. Under the SHF configuration, B. amyloliquefaciens demonstrated superior performance, yielding 16.7 g/L of 2,3-BDO. In contrast, B. licheniformis was notable for its high capacity for acetoin synthesis, producing 24.2 g/L of acetoin in addition to 10.9 g/L of 2,3-BDO. Therefore, these findings demonstrate that carrot discard is a viable feedstock for the co-production of 2,3-BDO and acetoin. Full article

2-Phenylethanol (2-PE), an aromatic alcohol with a rose-like fragrance, is widely used in the food, pharmaceutical, and high-end cosmetic industries. In this study, a high-yield 2-PE-producing strain was isolated and identified as Saccharomyces cerevisiae based on morphological characterization and taxonomic identification. Fermentation medium components (carbon and nitrogen sources) were optimized through single-factor experiments in shaking flasks, and fermentation medium with 40 g/L glucose, 5 g/L malt extract, 1.75 g/L corn steep liquor, 2.5 g/L yeast extract, 5 g/L malt extract, 1.75 g/L corn steep liquor was considered suitable for 2-PE production. RT-qPCR results indicated that corn steep liquor activates expression of genes related to the shikimate pathway and Ehrlich pathway (pha2, aro4, aro8, and aro9), thereby promoting the synthesis of 2-PE through these pathways. Excess yeast extract inhibited the expression of aro8 and aro9, while enhancing the expression of tdh3 and adh2, thus promoting the de novo synthesis of 2-PE. Furthermore, fermentation in a 5 L bioreactor was applied to investigate the effects of feeding strategies, inoculum proportion, and pH on 2-PE production. With a pH of 5.5 and10% inoculum proportion, the supplementation of the substrate L-Phe led to a 2-PE production of 4.81 g/L after 24 h of fermentation. Finally, in situ product recovery (ISPR) techniques was applied to alleviate 2-PE cytotoxicity, achieving a production of 6.41 g/L. This process offers a promising strategy for producing 2-PE efficiently and naturally, paving the way for further industrial applications in food, pharmaceutical, and cosmetic sectors. Full article