Search Results (5,680)

This paper analyzes the role of cereal products in the diet of individuals with disorders of carbohydrate metabolism, with particular emphasis on their impact on postprandial glycemia and the risk of developing type 2 diabetes (T2D). Cereal products, as the main source of dietary carbohydrates, also provide dietary fiber, minerals, B vitamins, and key bioactive compounds such as β-glucans, arabinoxylans, resistant starch (RS), and polyphenols. These components may reduce the rate of starch digestion and glucose absorption in the small intestine by increasing the viscosity of intestinal contents or by directly inhibiting digestive enzymes such as α-glucosidase. It has been shown that fermentation of these compounds by the gut microbiota leads to the production of short-chain fatty acids (SCFAs), which improve insulin sensitivity and stimulate the secretion of incretin hormones such as GLP-1. A literature review confirms that regular consumption of whole-grain products is associated with a reduced risk of T2D, whereas refining processes and excessive grain fragmentation lead to an increased glycemic index of products. Based on clinical guidelines and a narrative synthesis of the available literature, minimally processed whole-grain products were identified as a fundamental component of dietary therapy for diabetes, which is illustrated by the cereal product pyramid presented in the paper. This review involved a comprehensive literature search in PubMed, Scopus, and Web of Science using relevant keywords. Peer-reviewed articles, reviews, and meta-analyses (mainly 2000–2025) were included based on their relevance. Full article

Fruit and vegetable processing by-products, such as peels and pomace, are rich in antioxidant polyphenols and represent promising sources of functional ingredients, but how their galloyl-based polyphenols interact with starch remains insufficiently understood. In this study, corilagin with three non-free galloyl moieties and 1,2,3,4,6-O-pentagalloyl glucose with five free galloyl moieties were used as model polyphenols to clarify how galloyl moiety number and accessibility modulate their complexation with high-amylose maize starch (HAMS). Size-exclusion chromatography showed that both polyphenols preferentially complexed with amylose, while FTIR confirmed that complex formation occurred mainly through non-covalent interactions. The two polyphenols induced distinct changes in HAMS structure. Corilagin disrupted short-range order and produced no detectable crystalline structure, whereas 1,2,3,4,6-O-pentagalloyl glucose enhanced molecular order and induced V-type crystallization. Isothermal titration calorimetry revealed more binding sites but weaker affinity for corilagin, with thermodynamic signatures indicating hydrogen bonding and van der Waals interactions. By contrast, 1,2,3,4,6-O-pentagalloyl glucose showed stronger affinity and hydrophobic interaction-dominated binding. Molecular dynamics simulations further confirmed that 1,2,3,4,6-O-pentagalloyl glucose formed a more stable association with the amylose helix than corilagin. These results indicate that galloyl moiety characteristics markedly influence starch–polyphenol interaction mechanisms, providing guidance for the utilization of polyphenol-rich agro-processing by-products in functional starch-based foods. Full article

Background: Mitochondrial dysfunction is a central event in the pathogenesis of ischemic stroke. The roles of specific mitochondrial complex subunits, such as NDUFA4 and NDUFB3, in cerebral ischemia–reperfusion injury remain poorly defined. This study aims to investigate the dynamic expressions and functional impact of NDUFA4 and NDUFB3 in ischemic stroke. Methods: A transient middle cerebral artery occlusion (MCAO) model was established in male C57BL/6J mice. Label-free quantitative proteomics and Western blotting were employed to analyze protein expression in the ischemic penumbra. Highly differentiated PC12 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) or glutamate excitotoxicity to mimic ischemic injury in vitro. The functional consequences of NDUFB3 knockdown and overexpression were assessed by measuring ATP levels, reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and apoptosis. The involvement of the JNK-mediated mitochondrial apoptotic pathway was also examined. Results: Proteomic analysis revealed a significant upregulation of NDUFA4 and NDUFB3 in the ischemic penumbra of MCAO mice, as verified by western blot. In highly differentiated PC12 cells, both OGD/R and glutamate exposure induced a time-dependent increase in these proteins in mitochondrial fractions. Functional studies demonstrated that NDUFB3 knockdown significantly rescued OGD/R-induced mitochondrial dysfunction, as indicated by restored ATP production, reduced ROS generation, and stabilized ΔΨm. Furthermore, NDUFB3 silencing attenuated apoptosis by inhibiting JNK phosphorylation and decreasing BAX levels. Conversely, overexpression of NDUFB3 alone was sufficient to induce mitochondrial abnormalities, including loss of ΔΨm and elevated oxidative stress in highly differentiated PC12 cells. Conclusions: Ischemic injury triggers the upregulation of mitochondrial complex subunits NDUFA4 and NDUFB3. While this may initially act as a compensatory response, our findings identify NDUFB3 as a critical mediator of ischemic stroke pathology, whose overexpression drives mitochondrial dysfunction and apoptosis. In contrast, the suppression of NDUFB3 provides protection against ischemic injury. Therefore, NDUFB3 may be a potential candidate therapeutic target for reducing mitochondrial damage in ischemic stroke, but this role requires further validation in additional experimental and translational models. Full article

Bauhinia forficata leaves were subjected to ultrasonic pretreatment and subsequently dried using a refractance window (RW) and tray drying (TD). The physical, chemical, and biological properties of the dried leaves were evaluated under both drying methods, with and without ultrasound. RW combined with ultrasound (RW-US) resulted in the shortest drying time (90 min) and the lowest values of water activity (0.21), color difference (ΔE = 0.61), and maximum shear force (14.72 N), indicating improved drying efficiency and texture preservation. In addition, the RW-US samples exhibited the highest water solubility capacity (13.75%), water absorption capacity (5.56 g water/g dry matter), and swelling power (9.95%). With respect to structural changes, thickness showed the greatest percentage reduction during drying. The RW-US treatment also preserved bioactive compounds more effectively, yielding the highest total polyphenol content (61.96 mg GAE/g extract), flavonoid content (308.44 mg QE/g extract), antioxidant activity (60.50% by DPPH• and 70.15% by ABTS•+), and chlorophyll content (2.65 mg/g), the values of which were closest to those of fresh leaves. None of the extracts showed cytotoxic effects, with respect to hypoglycemic activity, the best treatments were RW, RW-US, and TD, which resulted in glucose reductions of 51.64%, 41.95% and 39.70%, respectively. Overall, RW-US drying preserved most of the physical, chemical, and biological properties, resulting in the production of a potential functional ingredient for foods. Full article

Natural deep eutectic solvents (NADESs) coupled with ultrasound-assisted extraction (UAE) were evaluated as an extraction technique for phenolic compounds from Crataegus monogyna leaves and flowers. Nine well-known hydrophilic NADESs were investigated as green extraction media, and their extractability was assessed in terms of major individual compounds, total flavan-3-ols and proanthocyanidins, as well as antioxidant activity. Water and ethanol–water solutions (70% and 50%, v/v) were used as reference solvents. An HPLC method was developed and partially validated for the quantitative determination of key individual components, including chlorogenic acid, hyperoside, vitexin, vitexin-2″-O-rhamnoside, and vitexin 2″-O-(4‴-O-acetyl)-rhamnoside. The subsequent chemometric analysis of the datasets revealed that the NADES systems choline chloride:urea:water (1:1:6) and choline chloride:glucose:water (5:2:25) exhibited pronounced extraction performance for all investigated metabolites, while preserving high antioxidant activity of the extracts. Pearson correlation coefficients and corresponding p-values demonstrated strong and statistically significant relationships among the majority of the investigated parameters: solvents’ physicochemical properties, the yield of phenolic compounds, and the antioxidant activity of the hawthorn extracts. The results highlight the potential of choline chloride based NADESs containing urea or glucose as alternative solvents for the green production of hawthorn-derived ingredients for functional foods, nutraceuticals, and herbal preparations, thereby contributing to the development of scalable, application-oriented extraction technologies. Full article

Type 2 diabetes mellitus (T2DM) is a major global health burden characterized by insulin resistance, progressive pancreatic β-cell dysfunction, and chronic metabolic dysregulation. Marine seaweeds have emerged as a valuable source of bioactive natural products, particularly polyphenols and polysaccharides, with promising potential for diabetes management. This review focuses on three major contributions: first, the structural diversity of seaweed-derived polyphenols and polysaccharides; second, their multi-target mechanisms of glucose regulation; and third, the structure–activity relationships governing their bioactivities. Current evidence shows that these compounds may help manage type 2 diabetes in several ways, including inhibition of α-amylase and α-glucosidase, attenuation of oxidative stress and chronic inflammation, enhancement of insulin secretion and insulin sensitivity, regulation of lipid metabolism, and modulation of gut microbiota. Key structural determinants such as degree of polymerization, hydroxyl group density, sulfation level, molecular weight, and chemical modifications are discussed in relation to their functional properties. By linking chemical structure with biological function, these findings highlight marine seaweeds as a rich reservoir of multi-target therapeutic candidates for T2DM management and provide a scientific basis for their development as functional food ingredients or lead compounds for novel diabetes management drugs. Full article

Coconut kernel fiber (CKF) is a by-product of coconut oil processing; it is rich in protein and serves as a potential source of bioactive peptides. In this study, from the enzymatic hydrolysis products of CKF (CKFH), a low-molecular-weight CKFH component (LW-CKFH, 1–3 kDa), exhibiting 74.49% α-glucosidase inhibition and restoring glucose metabolism in IR-HepG2 cells to 71.37% of normal levels. In a type 2 diabetes (T2DM) mouse model, LW-CKFH alleviated insulin resistance and enhanced insulin sensitivity by repairing liver damage, thereby improving glucose and lipid metabolism and reducing inflammation; its effects on improving insulin resistance and sensitivity reached 75.43% and 75.47% of the efficacy of metformin, respectively. Molecular docking analysis identified FDLPAR, LPFPRPAGPR, and ANVFNPR as key active peptides responsible for inhibiting α-glucosidase activity. Furthermore, LW-CKFH exhibited good gastrointestinal digestibility and processing stability, while significantly reducing the glucose release rate from bread (>50%), indicating its suitability for the development of hypoglycemic or low-GI functional foods. LW-CKFH was particularly suitable as a functional ingredient for fruits, vegetables, grains, and dairy products to develop low-GI or hypoglycemic foods. This study provides new insights into the high-value utilization of the coconut processing by-product CKF. Full article

Background and Objectives: Nowadays synthetic sweeteners are widely used as sugar substitutes in beverages, processed foods, and pharmaceutical products, largely due to their low caloric content and perceived benefits for weight management and glycemic control. Their consumption has increased markedly over recent decades, paralleling global efforts to reduce added sugar intake and combat obesity and diabetes. This review examines the regulation of artificial sweeteners, their impact on vulnerable populations, and the increased concern about their health effects, including metabolic effects, effects on gut microbiota and neurological and behavioral issues. Materials and Methods: A comprehensive search was performed across multiple electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar, to identify studies relevant to synthetic sweeteners and human health. Results: While considered safe, artificial sweeteners are linked to potential influence on hormonal responses, affecting glucose homeostasis and insulin secretion, as well as effects on gut microbiota composition and glucose metabolism. However, the results reveal inconsistencies of the impact of artificial sweeteners on vulnerable populations, as well as their effects on the human gut microbiota, neurological behavior and endocrine effects and evidence remain limited. Conclusions: Continuous human trials, post-market surveillance and regulatory evaluations are therefore essential to ensure the safety of sugar substitutes for consumers’ health. Full article

Target of rapamycin (TOR) is a conserved protein kinase that integrates nutrient and energy signals to control growth and metabolism, yet its proteome-level impact in microalgae remains poorly understood. Here, we conducted quantitative proteomics analysis of the unicellular red alga Cyanidioschyzon merolae under rapamycin-induced TOR inactivation to characterize global changes in protein abundance. TOR inhibition triggered widespread metabolic remodeling, including coordinated shifts in carbon and nitrogen allocation, and pronounced changes in protein synthesis, photosynthesis, and energy metabolism. Specifically, proteins associated with ribosome biogenesis and ribosomal subunits declined broadly, indicating impaired translation, alongside pronounced reductions in photosynthetic components, including PSI/PSII subunits and chlorophyll biosynthesis enzymes. In contrast, triacylglycerol (TAG) biosynthesis and starch metabolism were enhanced, indicating a shift towards carbon storage. Notably, a diacylglycerol acyltransferase (DGAT; CMQ199C) and a UDP-glucose pyrophosphorylase (UGP; CMS159C) were strongly induced (2.02-fold and 3.48-fold, respectively), identifying them as candidate targets for enhancing TAG and starch accumulation. Proteins associated with nitrogen assimilation were also upregulated, supporting TOR-dependent regulation of nitrogen metabolism at the protein level. Together, these results indicate that TOR orchestrates proteome-level reprogramming in C. merolae, coordinating growth, energy production, and carbon storage across interconnected metabolic pathways. Full article

This study developed a two-step statistically integrated optimization framework to identify the effects of key fermentation medium components controlling hyaluronic acid (HA) biosynthesis by Streptococcus zooepidemicus. As an initial phase, the Plackett–Burman design was employed to identify the most influential components among yeast extract, casein, peptone, beef extract, MgSO₄·7H₂O, K₂HPO₄, KH₂PO₄, and (NH₄)₂SO₄ by conducting 12 fermentation runs, and 30 g/L of glucose was used as the carbon source. Among the eight ingredients, yeast extract, MgSO₄·7H₂O, and KH₂PO₄ were identified as the most significant factors in enhancing HA production. The following steps were based on the selection of the best carbon and yeast extract sources. Sucrose was selected as the optimal carbon source among glucose and lactose, and Tastone 900-Baker’s yeast extract was selected as the optimal nitrogen source among various yeast extract sources. The final phase of the optimization procedure employed the Box–Behnken design to determine the optimal concentrations of three ingredients: yeast extract (10–30 g/L), MgSO₄·7H₂O (0.2–2.0 g/L), and KH₂PO₄ (1–4 g/L). The results depicted that the optimized media formulation, composed of 30.0 g/L of yeast extract, 1.16 g/L of MgSO₄·7H₂O, and 4.0 g/L of KH₂PO₄, enhanced HA production and biomass OD600 to 545.9 mg/L with 1250–1500 kDa and 2.53 OD600 in a 250 mL shake flask scale, which was around a 10-fold increase in HA production compared with run #10 of Plackett–Burman (57.42 mg/L). This study provided preliminary results for future process conditions optimization, scale-up studies, and techno-economic evaluation. Full article

Background/Objectives: Diabetes mellitus (DM) is a critical metabolic condition with escalated blood glucose levels caused by insulin resistance, restricted insulin production, and the activity of alpha-amylase and alpha-glucosidase enzymes. Methods: This current work focuses on the synthesis and evaluation of novel Pyrimidine-derived pyrazole-based thiadiazole derivatives to target DM by inhibiting α-amylase and α-glucosidase. Results: The findings exhibited that, except for three compounds, all other synthesized derivatives inhibited α-amylase and α-glucosidase enzymes with IC₅₀ values ranging from 5.17 μM to 29.84 μM on α-amylase and 7.60 μM to 31.62 μM on α-glucosidase, in comparison to the standard drug Acarbose (α-amylase IC₅₀ = 8.25 ± 0.80 μM; α-glucosidase IC₅₀ = 10.75 ± 1.10 μM). Analogs 8g, 8k, and 8b displayed superior or comparable inhibitory activity compared to the reference drug Acarbose. The inhibition potential of the derivatives can be attributed to their stable contacts with crucial amino acid residues of targeted enzymes, as shown through molecular docking analysis. Moreover, DFT-calculated HOMO–LUMO parameters and electrostatic potential (ESP) maps were used to gain complementary insight into the electronic characteristics, charge distribution, and potential interaction behavior of the synthesized derivatives, which supported the molecular docking observations. Conclusions: Experimental outcomes and in silico support display that these derivatives serve as potential leads for anti-diabetic drug development. These potent pyrimidine-derived pyrazole-based thiadiazole derivatives were comparable to an existing diabetic mellitus inhibitor, specifying potential for further therapeutic development and optimization against diabetic mellitus. Full article

Background/Objectives: Type 2 diabetes (T2D)-associated sarcopenia is characterized by impaired insulin signaling, lipotoxicity, oxidative stress, and progressive muscle loss. Although liraglutide improves glucose control and reduces lipid burden, its ability to preserve muscle integrity under diabetic lipotoxic conditions remains limited. This study investigated whether β-hydroxy-β-methylbutyrate (HMB) could enhance liraglutide-mediated protection against high-glucose plus free fatty acid (HG+FFA)-induced injury in skeletal muscle cells. Methods: Differentiated C2C12 myotubes were exposed to HG+FFA to establish a sublethal lipotoxic model and treated with liraglutide, HMB, or their combination. Cell viability, lipid accumulation, myotube morphology, insulin signaling, glucose uptake, mitochondrial function, reactive oxygen species (ROS), antioxidant gene expression, and atrophy-related signaling were assessed. Results: HG+FFA induced marked lipid droplet accumulation, impaired insulin signaling, reduced glucose uptake, disrupted mitochondrial membrane potential, increased ROS production, suppressed antioxidant gene expression, and promoted an atrophic phenotype characterized by increased atrogin-1 and MuRF1 and reduced myogenic markers. Liraglutide alone reduced large lipid droplets and partially improved insulin signaling but showed limited efficacy in preserving the myotube phenotype. HMB alone exerted modest effects on lipid accumulation but preserved myotube area. Notably, combined HMB and liraglutide treatment more effectively reduced lipid burden, restored insulin signaling and glucose uptake, attenuated mitochondrial dysfunction and oxidative stress, restored antioxidant gene expression, and preserved MyHC-positive area and myotube diameter while suppressing atrogin-1/MuRF1 activation. These protective effects were largely attenuated by rapamycin, indicating at least partial dependence on mTOR-associated signaling. Conclusions: Overall, HMB and liraglutide exert complementary protective effects against diabetic lipotoxic and atrophic stress, supporting the potential utility of this combination strategy for T2D-associated sarcopenia. Full article

Steroid glycosides constitute an important class of bioactive molecules, yet their selective synthesis remains challenging. Here, we established a screening platform for nucleotide sugar-dependent glycosyltransferases (GTs) coupled with sucrose synthase (SuSy) for in situ UDP-glucose regeneration, enabling cost-efficient steroid glucosylation. A library of GTs comprising literature-derived enzymes and newly mined archaeal and fungal candidates was constructed using sequence filtering, AlphaFold3 modeling, and docking-guided prioritization. The resulting panel was screened against 31 structurally diverse steroids (androgens, estrogens, pregnanes, and corticosteroids) using crude Escherichia coli lysates as catalysts and UPLC-DAD, LC-MS and NMR analytics. YjiC and OleD glycosyltransferases emerged as the most promiscuous biocatalysts, while Sbaic7OGT and SgUGT74AC1_M7 displayed greater selectivity toward estrogens and selected testosterone derivatives. Product assignment for representative reactions was validated using authenticated reference standards or NMR (1D/2D) analysis, confirming regioisomeric estradiol monoglucosides (3-O- and 17-O-), estrone 3-O-glucoside, and an unexpected product diversification for 17α-testosterone by endogenous E. coli enzyme, where the major product was identified as a 6′-O-acetylated glucoside. Finally, SuSy-coupled cascades were applied in semi-preparative scale and evaluated under optimized conditions and co-immobilization formats. Full article

Diabetes mellitus is a complex metabolic disorder whose management has moved from glycemic control to the control of risk factors through the use of new antihyperglycemic drugs with pleiotropic effects. Despite the multiple cardio–renal benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors, their prescription is often avoided due to concerns regarding side effects. This review aims to discuss the multiple benefits of SGLT2 inhibitors in balance with one of the most concerning side effects, the risk of euglycemic diabetic ketoacidosis (EDKA). A literature search was performed to identify and select articles relevant to this topic. We accessed several databases, including PubMed, Web of Science and Scopus, using appropriate keywords. We selected and evaluated randomized controlled trials, retrospective studies, systematic reviews and meta-analysis published between 2014 and 2024 supporting the multifaceted benefits of SGLT2 inhibitors and the limitations of their recommendations and focusing on the risk of EDKA. Initially designed as antidiabetic agents, SGLT2 inhibitors have demonstrated important cardio–renal benefits, these drugs being the first-line medication in patients with established cardiovascular disease, heart failure and chronic kidney disease. SGLT2 inhibitors are associated with some potential side effects, but with contradictory data concerning their prevalence and clinical relevance. From the possible side effects, EDKA is a life-threatening metabolic emergency whose incidence and recognition has increased, in particular with the use of SGLT2 inhibitors. These drugs can cause this disorder through several mechanisms, including reduced insulin secretion and increased glucagon levels, leading to free fatty acid production, which generally occurs in the presence of some risk factors such as reduced dietary carbohydrates, intercurrent illnesses, surgical stress and alcohol consumption. Through awareness of these risk factors as well as of the clinical symptoms, this condition could be promptly avoided or managed and SGLT2 inhibitors could be safely used. Full article

The understanding of oxidative stress is being refined leading to the use of the terms “oxidative distress” and “eustress”. This reflects the dual role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in both pathology and physiology, emphasizing the complexity of the mechanisms influencing the redox status. This review discusses how these redox mechanisms interact with key signaling pathways, specifically the mammalian/mechanistic target of rapamycin (mTOR) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), which are crucial for mitochondrial health and muscle recovery. During exercise, the contraction of skeletal muscles increases ROS production which, through redox signaling, triggers mitochondrial biogenesis, enhances the antioxidant defenses and stimulates glucose metabolism, contributing to cardiovascular function and health. There is a large consensus about the importance of physical exercise in maintaining the redox homeostasis. However, the redox status could be disturbed after an intense and/or long physical effort, and signs such as markers of oxidative distress were identified. In that context, antioxidant strategies are warranted to prevent oxidative damage and help recovery. Given the many factors influencing the redox status of the body, including the training status, the duration and type of exercises and effort, diet, lifestyle, genetic polymorphisms, and circulating cytokines, a personalized approach is necessary. Targeted therapeutic interventions become important for preventing oxidative damage and helping recovery. In this review, we discuss the potential benefits of micro-immunotherapy (MI), as a multi-target approach utilizing signaling molecules, including cytokines at low doses (LD, typically 3–5 centesimal Hahnemannian CH dilutions) and ultra-low doses (ULD, from 6 CH upwards). We focused specifically on the investigational MI medicine 2LMIREG, and propose its application in preventing oxidative distress and restoring redox balance. Additionally, this review explores how the redox status interplays with the immune system, presenting preclinical data on 2LMIREG as a proof-of-concept for a tailored immunoregulatory strategy to enhance both immune and oxidative adaptations. Full article