Search Results (945)

As an emerging natural source of DPP-IV inhibition strategy, we report for the first time the use of Lithobates catesbeianus skin gelatin (LSG) as a novel source for DPP-IV inhibitory peptides in this study. Through enzymatic hydrolysis with multiple proteases, the papain-treated hydrolysate exhibited superior performance in hydrolysis degree, protein recovery, and DPP-IV inhibition, with 93.47% of peptides under 1 kDa. Subsequent separation and peptidomics analysis identified 13 previously unreported peptides. Molecular docking and in silico screening pinpointed four candidate peptides, i.e., LGPQR, RGFDQ, RGPVGP, and RLDDVT, which were then synthesized and functionally validated. Enzyme kinetic studies revealed that these peptides acted via competitive or mixed-type inhibition mechanisms. Notably, this study uncovered the bio-functional potential of amphibian-derived gelatin and provided a new strategy for natural DPP-IV inhibitor discovery through integrated enzymatic, computational, and biochemical approaches. This work pioneered the use of amphibian skin gelatin in antidiabetic peptide discovery and laid the foundation for its application in functional foods. Full article

In this multicenter, nonrandomised comparative study, we evaluated the potential effectiveness of a program to promote the safe use of dipeptidyl peptidase-4 (DPP-4) inhibitors led by community pharmacists. The program facilitated early detection of gastrointestinal adverse events (GIAEs) in patients newly prescribed DPP-4 inhibitors and facilitated timely communication with physicians. Community pharmacists reviewed patient conditions and provided relevant information to physicians as needed. GIAE monitoring based on the program was conducted in 35 patients at 10 pharmacies in Japan (intervention group) between March and August 2024. The proportion of pharmacist interventions was compared with that in 451 patients from March to August 2023, before program implementation (baseline cohort). The primary outcome, pharmacist intervention rate, was significantly higher in the intervention group (5 out of 35 patients, 14.3%) than in the baseline cohort (0 out of 451 patients, 0.0%) (p < 0.001). GIAEs were identified in 13 out of 35 patients (37.1%) in the intervention group; information for five patients (14.3%) was shared with physicians, resulting in discontinuation of the DPP-4 inhibitor in one patient and addition of supportive therapy in others. Most GIAEs occurred within the first 1–2 weeks of therapy, highlighting the need for early intervention. Thus, proactive involvement of community pharmacists may improve the care process in these cases and contribute to healthcare coordination and diabetes care quality. Full article

This study evaluates biogas production through the anaerobic digestion of food waste (FW), cow dung (CD), and green waste (GW), with the primary objective of determining the efficacy of co-digesting these organic wastes commonly generated by households and small farms in Central Queensland, Australia. The investigation focuses on both experimental and technoeconomic aspects to support the development of accessible and sustainable energy solutions. A batch anaerobic digestion process was employed using a 1 L jacketed glass digester, simulating small-scale conditions, while technoeconomic feasibility was projected onto a 500 L digester operated without temperature control, reflecting realistic constraints for decentralized rural or residential systems. Three feedstock mixtures (100% FW, 50:50 FW:CD, and 50:25:25 FW:CD:GW) were tested to determine their impact on biogas yield and methane concentration. Experiments were conducted over 14 days, during which biogas production and methane content were monitored. The results showed that FW alone produced the highest biogas volume, but with a low methane concentration of 25%. Co-digestion with CD and GW enhanced methane quality, achieving a methane yield of 48% while stabilizing the digestion process. A technoeconomic analysis was conducted based on the experimental results to estimate the viability of a 500 L biodigester for small-scale use. The evaluation considered costs, benefits, and financial metrics, including Net Present Value (NPV), Internal Rate of Return (IRR), and Dynamic Payback Period (DPP). The biodigester demonstrated strong economic potential, with an NPV of AUD 2834, an IRR of 13.5%, and a payback period of 3.2 years. This study highlights the significance of optimizing feedstock composition and integrating economic assessments with experimental findings to support the adoption of biogas systems as a sustainable energy solution for small-scale, off-grid, or rural applications. Full article

Aortic stenosis (AS) and atherosclerosis are progressive cardiovascular conditions that frequently coexist and share multiple clinical and molecular features. Medical therapies have shown effectiveness in preventing and treating atherosclerosis and its consequences. For AS, effective pharmacological therapies remain limited. Understanding the shared risk factors and mechanisms between the two conditions may provide opportunities for therapeutic repositioning in AS. We performed a narrative review focusing on studies published from 2005 to 2025. Inclusion criteria encompassed clinical trials, experimental models, and molecular studies addressing overlapping risk factors, pathological pathways, and treatment approaches for AS and atherosclerosis. AS and atherosclerosis share key risk factors, including age, hypertension, hyperlipidemia, and diabetes. Molecular mechanisms, such as chronic inflammation, endothelial dysfunction, oxidative stress, lipid accumulation, and calcific remodeling, are common to both. Pathways involving the renin-angiotensin system, Notch signaling, and osteogenic mediators contribute to disease progression. Several drug classes, notably proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipoprotein(a) (Lp(a)) lowering therapies, anti-inflammatory agents, and immunomodulators, show potential for repositioning in AS management. The substantial overlap in risk factors and molecular mechanisms between AS and atherosclerosis supports a rationale for therapeutic repositioning. Targeting shared pathways could lead to innovative strategies for slowing AS progression and improving patient outcomes. Full article

Endoscopic ultrasound (EUS)-guided drainage using lumen-apposing metal stents (LAMSs) has become the standard for managing pancreatic fluid collections (PFCs), especially walled-off necrosis (WON). However, LAMS-specific adverse events (AEs), including bleeding, stent occlusion, and infection, remain a concern. To mitigate these complications, some experts advocate placing coaxial double-pigtail plastic stents (DPPSs) within LAMSs. This narrative review critically examines the evidence from retrospective and prospective studies, one RCT, and recent meta-analyses on this combined approach. While the routine use of coaxial double-pigtail plastic stents (DPPSs) within LAMSs is not universally supported, emerging data suggest benefits in select high-risk scenarios, such as large WON, debris-rich cavities, or disconnected pancreatic duct syndrome (DPDS), in which coaxial DPPS within LAMSs can reduce occlusion, infection, and recurrence. In addition, the type of LAMS appears to influence safety outcomes: the SPAXUS stent shows lower bleeding and migration rates than the Hot AXIOS. We propose a pragmatic algorithm for the patient-tailored use of coaxial DPPS and discuss technical innovations to improve outcomes. While evidence is still evolving, personalized strategies and future high-quality studies are needed to define the optimal role of coaxial DPPS within LAMSs in the EUS-guided drainage of PFCs. Full article

Microbial metabolites offer a multitude of mechanisms for alleviating diabetes, particularly type 2 diabetes (T2D). However, the metabolites of yeasts recognised as safe remain under-explored and are receiving less attention in the treatment of T2D. In addition to the recognised probiotic status of certain yeasts, their genetic feature is responsible for many of the effects observed. Branched and non-branched short-chain fatty acids, bioactive peptides, carotenoids, and polysaccharides (β-glucans, mannans, and peptides derived from them) have vital properties that modulate intestinal permeability, soothe inflammation, and directly influence insulin sensitivity. Their action mechanism ranges from hepatic lipogenesis via the induction of hormone-sensitive lipase and the inhibition of α-glucosidase or DPP-IV to promoting the secretion of GLP-1 (Glucagon-Like Peptide-1) and GIP (Gastric Inhibitory Polypeptide), orchestrating immune modulation, and nourishing the gut microbiota. The richness of the yeast metabolome suggests that a concentrated fermentate could be developed to potentiate the functional effects in vitro in the treatment of T2D. The purpose of this review is to take stock of the current state of knowledge of probiotic yeast metabolites and outline their potential for the treatment of diabetes via the development of food supplements or nutraceuticals. Full article

Dry-cured ham is a traditional food in the Mediterranean diet, which, in addition to its sensory qualities, is a natural source of bioactive peptides generated during the curing process through the action of endogenous enzymes on muscle and sarcoplasmic proteins. These low-molecular-weight peptides have attracted growing interest due to their multiple bioactivities, including antihypertensive, antioxidant, antimicrobial, antidiabetic, and anti-inflammatory effects described in vitro, in vivo, and in preliminary human studies. The identification of specific sequences, such as AAPLAP, KPVAAP, and KAAAAP (ACE inhibitors), SNAAC and GKFNV (antioxidants), RHGYM (antimicrobial), and AEEEYPDL and LGVGG (dipeptidyl peptidase-IV and α-glucosidase inhibitors), has been possible thanks to the use of peptidomics techniques, tandem mass spectrometry, and bioinformatics tools that allow their activity to be characterized, their digestive stability to be predicted, and their bioavailability to be evaluated. This review article summarizes current knowledge on the bioactivities of peptides derived from dry-cured ham, advances in their functional characterization, and challenges associated with their application in functional foods and nutraceuticals, with the aim of providing a comprehensive overview of their potential in health promotion and chronic disease prevention. Full article

Emerging evidence suggests that vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors exert synergistic immunomodulatory, anti-inflammatory and antioxidant actions. Moreover, intervention studies showed that combination therapy based on the concomitant use of vitamin D and DPP-4 inhibitors (VIDPP-4i) may preserve beta-cell function in patients with type 1 diabetes mellitus (T1D) and latent autoimmune diabetes in adults (LADA). These effects are particularly relevant in the context of beta-cell replacement strategies, whose long-term efficacy can be hampered by various factors, such as immune-mediated graft rejection, inadequate vascularization, hypoxia, trauma-induced cell apoptosis, fibrosis, host immune response, and recurrence of autoimmunity. Based on preclinical and clinical studies conducted in the fields of autoimmune diabetes and solid organ/cell transplantation, the present narrative review aims to describe the rationale behind the investigation of VIDPP-4i combination therapy as an adjuvant treatment strategy to enhance the efficacy of novel beta-cell replacement therapies for T1D. In this regard, we discuss the potential immune and metabolic mechanisms through which vitamin D and DPP-4 inhibitors can promote the long-term function and survival of transplanted islets in patients with T1D receiving various types of beta-cell replacement therapies, including therapeutic approaches using encapsulated stem cell-derived beta cells. Full article

Background/Objectives: Patients with diabetes mellitus face increased risk of severe outcomes and mortality from COVID-19. Dipeptidyl peptidase-4 (DPP-4) inhibitors, widely used antidiabetic agents, are hypothesized to affect COVID-19 outcomes via anti-inflammatory and immune-modulating mechanisms. However, real-world evidence, especially in Korean populations, remains limited. Methods: We conducted a retrospective cohort study using Korea’s nationwide Health Insurance Review and Assessment (HIRA) database. Adults with diabetes hospitalized for confirmed COVID-19 between 1 March 2021, and 28 February 2022, were included and stratified by DPP-4 inhibitor use. The primary outcome was 30-day all-cause mortality. Cox proportional hazards models adjusted for age, sex, and comorbidities estimated hazard ratios (HRs). Subgroup analyses examined angiotensin receptor blocker (ARB) and insulin use. Results: Among 16,134 eligible patients, 7082 received DPP-4 inhibitors. The 30-day mortality rate was lower in DPP-4 inhibitor users than non-users (4.3% vs. 10.3%, p < 0.0001). Adjusted analyses showed DPP-4 inhibitor use was associated with reduced mortality risk (adjusted HR: 0.455; 95% CI: 0.414–0.499). Subgroup analyses yielded consistent results across ARB and insulin users. Kaplan-Meier curves demonstrated higher survival probability in the DPP-4 inhibitor group. Conclusions: In this nationwide Korean cohort, DPP-4 inhibitor use was associated with lower mortality among hospitalized diabetic patients with COVID-19. While these findings suggest a potential benefit, causality cannot be confirmed due to the observational design. Prospective studies are needed to verify these associations and explore underlying mechanisms. Full article

Phycobiliproteins have gained increasing attention for their antidiabetic potential, yet the specific bioactive peptides and their targets and molecular mechanisms have remained unclear. In this study, four peptides with potential hypoglycemic activity were identified through virtual screening. Network pharmacology was employed to elucidate their hypoglycemic mechanism in the treatment of T2DM. A subsequent in vitro assay confirmed that the synthesized peptides, GR-5, SA-6, VF-6, and IR-7, exhibited significant inhibitory activity against α-glucosidase and DPP-IV. In insulin-resistant HepG2 models, all four peptides exhibited no cytotoxicity. Among them, GR-5 demonstrated the most promising therapeutic potential by remarkably enhancing cellular glucose consumption capacity. Furthermore, GR-5 administration substantially increased glycogen synthesis and enzymatic activities of hexokinase and pyruvate kinase with statistically significant improvements compared to the control groups. This study provides novel peptide candidates for T2DM treatment and validates an integrative strategy for targeted bioactive peptide discovery, advancing the development of algal protein-based therapeutics. Full article

Defatting methods are key to modulating the nutritional, functional, and bioactive characteristics of edible insect powders. This study evaluated the effects of mechanical pressing and ethanol-based solvent extraction on Hermetia illucens larvae powder. Solvent-defatted samples (DPSs) showed the highest protein content (54.96 g/100 g), with a 61% increase compared to full-fat powder (FP), and the lowest residual lipid content (3.18 g/100 g). In contrast, mechanical pressing (DPP) preserved higher antioxidant activity (68.30% DPPH inhibition), a 30% increase over FP. DPS also showed greater fiber content (13.90 g/100 g), improved water solubility, emulsification capacity, and reduced water activity (0.269), desirable traits for food formulations. DPP retained higher hygroscopicity and exhibited the highest antioxidant potential among the samples. These findings demonstrate that defatting method selection significantly impacts the techno-functional and nutritional quality of insect powders and should align with the desired end use, whether for protein enrichment, enhanced antioxidant activity, or development of sustainable food ingredients. This work supports the strategic use of Hermetia illucens as a functional, high-protein ingredient and reinforces its role in advancing circular and sustainable food systems. Full article

SARS-CoV and MERS-CoV are two coronaviruses that have received significant attention due to their high pathogenicity and mortality rates in human populations. In this study, we compared their evolutionary dynamics to provide a One Health perspective on their differences in terms of the results of disease control. The phylogenetic network of SARS-CoVs showed that human isolates gathered into a “super-spreader” cluster and were distinct from civet isolates. In contrast, dromedary camel- and human-isolated MERS-CoVs were clustered together. Thus, most clades of MERS-CoV can infect humans, and MERS-CoVs seem to more easily spill over the animal-to-human interface. Additionally, the civet can be easily controlled, while the intermediate host (dromedary camels) of MERS-CoV is an important livestock species, so it is impossible to eliminate all animals. This further leads to difficulties in disease control in MERS. Although MERS-CoVs are endemic to dromedary camels in both the Middle East and Africa, human infections are mainly linked to the Middle East. The nucleotide sequences of the MERS-CoV receptor gen (dipeptidyl peptidase 4 (DPP4)) from 30 Egyptians, 36 Sudanese, and 34 Saudi Arabians showed little difference. These findings suggest that the observed disparities in MERS prevalence between populations in the Middle East and Africa may be more strongly attributed to inadequate disease surveillance and the limited camel-to-human transmission of clade C MERS-CoV in Africa, rather than variations in DPP4 gene. Full article

This study addresses the challenge of optimizing envelope retrofit strategies for aged residential buildings across China’s five distinct climate zones. A simulation-based frame work is proposed, applying a standardized Taguchi L27 experimental design to ensure direct comparability across climates. Analysis of variance (ANOVA) and effect size (partial eta squared, η²) are used to identify and quantitatively rank the sensitivity of each retrofit parameter, while interaction analysis reveals the independence or synergy between measures. Technical results are linked with discounted payback period (DPP) analysis to evaluate economic feasibility. The findings show that insulation thickness is most influential in cold climates (η² > 0.95), whereas glazing system upgrades are dominant in warmer regions (η² > 0.97), with parameter interactions generally insignificant. The resulting climate-responsive retrofit priority matrix offers practical guidance for region-specific design and investment decisions. This scalable and replicable method enables policymakers and practitioners to tailor low-carbon, cost-effective retrofit solutions to diverse building and climate contexts, bridging the gap between technical performance and financial viability. Full article

Background/Objectives: Essential amino acid (EAA) supplementation is often employed in sportive and clinical nutrition due to EAAs’ role in muscle mass maintenance and growth. EAAs are also involved in insulin and glucagone regulation in diabetes management, but only few reports investigate their possible implication as dipeptidyl peptidase-IV (DPP-IV) inhibitors and their effect on the stability and secretion of enteroendocrine hormones. A blend of EAAs (called GAF) available as a food supplement, in a specific qualitative and quantitative ratio, was investigated to address its in vitro bioaccessibility, its hypoglycemic properties in vitro and in situ on cellular models, and its safety on intestinal Caco-2 cells. Methods: GAF was subjected to the INFOGEST static digestion protocol, producing the iGAF sample. iGAf DPP-IV inhibitory properties were investigated both in vitro and in situ on Caco-2 cells. Then, STC-1 enteroendocrine cells were employed alone and in co-culture with Caco-2 cells to evaluate iGAF’s impact on glucagon-like peptide 1 (GLP-1) hormone secretion. Results: The study demonstrates that the present EAAs blend is stable and bioaccessible after simulated gastrointestinal digestion, and it is safe at the intestinal cellular level. It inhibits DPP-IV enzyme both in vitro and in situ and promotes GLP-1 secretion by enteroendocrine cells. Conclusions: The sample demonstrated safety at the intestinal level and showed hypoglycemic properties by acting on a dual synergic mechanism that involves DPP-IV enzyme inhibition and GLP-1 hormone stimulation. Full article

Background: Numerous studies have demonstrated the beneficial effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiovascular and renal outcomes in patients with heart failure and chronic kidney disease. However, whether SGLT2 inhibitors are also associated with a reduced risk of tinnitus has not been investigated. Objective: This study aimed to investigate the association between SGLT2 inhibitor therapy and the incidence of tinnitus in patients with type 2 diabetes. Methods: This retrospective cohort study was based on data from a nationally representative database of primary care practices in Germany from 2012 to 2023. Patients with type 2 diabetes who were treated with metformin and additionally received either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor were included. Patients with a previous diagnosis of tinnitus were excluded. The primary outcome was the first tinnitus diagnosis documented by a primary care physician. The SGLT2 and DPP4 cohorts were compared for tinnitus incidence using Kaplan–Meier analysis and multivariable Cox regression. Results: 66,750 patients with SGLT2 inhibitors and 82,830 with DPP4 inhibitors were analyzed. The cumulative 5-year incidence of tinnitus was 1.9% in both groups. The multivariable regression analysis did not show a significant association between SGLT2 therapy and the occurrence of a tinnitus diagnosis (HR: 1.04; 95% CI: 0.89–1.21). Conclusion: There was no difference in tinnitus incidence between patients with SGLT2 or DPP4 inhibitors. The causes could lie in the heterogeneous, not purely vascular, etiology of tinnitus in general practitioners’ practices. Future studies should include further clinical data, including confirmed hearing impairments. Full article