Search Results (3,045)

Protein turnover and extracellular proteolysis continuously generate diverse peptide fragments within biological systems, yet the metabolic and pharmacological implications of these peptides remain incompletely understood. Among these transporters, members of the solute carrier family 15 (SLC15), including peptide transporter 1 (PEPT1/SLC15A1) and peptide transporter 2 (PEPT2/SLC15A2), mediate the proton-coupled uptake of dipeptides, tripeptides, and structurally related compounds across cellular membranes. While these transporters have been extensively studied in the context of intestinal peptide absorption and drug delivery, their potential roles in cancer biology remain incompletely understood. Tumor microenvironments are characterized by extensive proteolysis and dynamic metabolic remodeling, processes that can generate diverse peptide fragments derived from extracellular matrix proteins and intracellular protein turnover. These peptides may accumulate locally and potentially serve as substrates for cellular peptide transport systems. Once internalized through peptide transporters, dipeptides are typically hydrolyzed into free amino acids that can support biosynthetic pathways, energy metabolism, and cellular growth. In addition to their potential metabolic roles, certain endogenous dipeptides have also been reported to influence cellular signaling pathways and redox homeostasis. The broad substrate specificity of peptide transporters has also attracted significant interest in pharmacology because numerous clinically used drugs exploit these transport systems for efficient cellular uptake. This property raises the possibility that peptide transporters may be utilized for transporter-mediated drug delivery strategies, including the development of peptide-modified prodrugs or dipeptide–drug conjugates. In this review, we summarize the molecular characteristics and physiological functions of dipeptide transport systems with a particular focus on the SLC15 transporter family. We then discuss emerging evidence linking peptide transporters to tumor metabolism and the tumor microenvironment. Finally, we highlight current progress and future perspectives in exploiting peptide transport systems for transporter-mediated drug delivery and therapeutic targeting in cancer. Full article

Wheat processing generates large volumes of co-products, particularly wheat bran (WB) and wheat germ (WG), which remain underutilized despite their high content of dietary fiber, phenolic compounds, bioactive peptides, and lipophilic antioxidants. Although their composition and processing have been widely investigated, an integrated and application-oriented evaluation of these fractions remains limited. This review provides a structured and critical analysis of WB, raw and defatted WG, and wheat germ oil (WGO), linking composition, processing strategies, and functional performance within a unified framework. Conventional and emerging technologies, including enzymatic hydrolysis, fermentation, thermomechanical treatments, and supercritical CO₂ extraction, are discussed in terms of selectivity, impact on techno-functional properties, and scalability. An evidence-grading approach is introduced to distinguish bioactivities supported by chemical assays, cell-based models, animal studies, or human data, enabling a more rigorous interpretation of health-related effects. Across applications, these co-products have been incorporated into food systems and related sectors, primarily showing improvements in nutritional composition, oxidative stability, and product performance under experimental conditions. However, translation to an industrial scale remains constrained by techno-economic limitations, regulatory requirements, and stability challenges. This work highlights the need for integrated processing strategies aligned with industrial feasibility to support the development of sustainable cereal biorefineries. Full article

Alzheimer’s disease (AD) develops as a progressive dementia condition through the step-by-step breakdown of nerve cells. Neurodegeneration in this context primarily results from metal ions, including copper, iron, zinc, and aluminum, building up in the system. The aggregation of amyloid-beta (Aβ) peptides and oxidative stress generation stem from metal ion involvement acting as defining characteristics of Alzheimer’s disease pathology. We developed a comprehensive mathematical model based on 24 coupled ordinary differential equations (ODEs) to represent the interactions between metal ions, Aβ peptides, reactive oxygen species (ROS), antioxidant defenses, and tau protein phosphorylation. The mathematical model monitors how metal ion concentrations change over time and examines their competitive binding effects, which trigger a series of reactions, resulting in oxidative stress and subsequent tau protein damage. The model uses analytical and numerical mathematical methods to expose nonlinear behaviors and threshold effects while offering mechanistic insights into the course of disease development. This model functions as a quantitative framework for assessing how therapeutic interventions that target metal dyshomeostasis and oxidative stress can potentially affect outcomes. Full article

Background/Objectives: We developed a telehealth-enabled fiber-bundle endomicroscopy platform and evaluated its preclinical feasibility for targeted fluorescence imaging in cervical cancer models. Methods: The platform integrates a portable fiber-bundle endomicroscopy (FBE) system, fluorescein isothiocyanate (FITC)-labeled candidate peptides, and a secure web-based telehealth platform for remote consultation. The FBE probe achieved a field of view of 1,700 µm and a lateral resolution of 4 µm, enabling cellular-level fluorescence imaging in a compact, portable format. Four FITC-labeled peptides (SHS1*, SHS2*, FPP*, and CRL*) were evaluated in A549, SiHa, and CaSki cell lines. Ex vivo testing was performed on commercial cervical tissue-array samples. The telehealth platform was assessed for secure medical-image/video transmission and end-to-end latency in a simulated remote-consultation setting. Results: Among the tested probes, FPP*-FITC and CRL*-FITC showed higher fluorescence-positive fractions in the p16-overexpressing cervical cancer cell lines than in the A549 comparator line, with the strongest signals observed in CaSki cells. In ex vivo testing, CRL*-FITC generated higher fluorescence intensity in malignant cervical tissue-array samples than in non-malignant comparator tissues, with a reported 4.6- to 7.4-fold difference in mean signal intensity (p < 0.001). The telehealth platform supported the secure transmission of medical images and video and demonstrated an end-to-end latency of <500 ms in a simulated remote consultation setting. Conclusions: These results support the technical and preclinical feasibility of integrating targeted fluorescence imaging, portable fiber-bundle endomicroscopy, and telehealth into a single platform. This study should therefore be interpreted as a preclinical feasibility study evaluating optical, molecular, and telehealth integration, rather than as a clinically validated cervical cancer screening test. Full article

The efficacy of postbiotics varies significantly between different strains and preparation processes. We aimed at evaluating the effect of an innovative postbiotic product (iPB) generated through the sequential fermentation of Lacticaseibacillus rhamnosus GG and Lacticaseibacillus paracasei NPB-01, compared to single-strain postbiotics, on epithelial barrier integrity and innate immunity in human enterocytes using a Caco-2-cell-based experimental model by measuring human enterocyte proliferation and differentiation (lactase expression), tight junction proteins (occludin and zonula occludens 1, ZO-1), and mucus protein Mucin-2 (Muc-2) expression. The modulatory action on the major innate immunity peptide, Human Beta-Defensin 2 (HBD-2), production was also assessed. The iPB exposure resulted in a higher up-regulation of human enterocyte proliferation and differentiation, as suggested by higher lactase expression, and of occludin, ZO-1, and MUC2 expression compared with the single-strain postbiotics, suggesting a beneficial synergistic action in modulating the epithelial gut barrier. Furthermore, iPB induced a higher production of HBD-2, suggesting a synergistic enhancement of innate immune response. Our findings suggested that the sequential fermentation process could act as a biotechnological catalyst, optimizing the gut-barrier-protective properties and the immunomodulatory action of Lacticaseibacillus strains. This study introduces iPB as a high-performance postbiotic candidate for the prevention and management of conditions characterized by alterations in epithelial gut barrier and innate immunity. Full article

Fermented foods and probiotics represent complementary yet distinct components of human nutrition. Fermented foods are shaped by biochemical transformations driven by microbial metabolism, whereas probiotics are live microorganisms that may confer health benefits to the host. In both cases, bacteria, yeasts, and filamentous fungi mediate key metabolic activities that generate bioactive compounds and modulate host–microbiota interactions. During fermentation, microbial communities synthesize organic acids, peptides, exopolysaccharides, vitamins, and other metabolites that enhance food safety, sensory attributes, and potential health-promoting properties. Several microbial products, such as bacteriocins, reuterin, hydroxylated fatty acids, and exopolysaccharides, exhibit antimicrobial, immunomodulatory, antioxidant, and cholesterol-lowering activities. Advancing our understanding of microbial metabolism in fermented foods is essential for developing next-generation functional foods and nutraceuticals that leverage microbial biotransformations to support human health. Nonetheless, multiple challenges limit the translation of these advances into commercial products. Inadequately controlled fermentation may introduce microbiological or chemical hazards, regulatory frameworks governing microbial use in foods remain insufficiently defined, and standardized procedures for microbial strain handling and characterization are still lacking. This narrative review integrates current evidence on the nutraceutical properties of fermented foods and probiotics, while also examining the associated safety considerations and the technological factors that influence fermentation processes. Full article

Background/Objectives: Umami peptides enhance flavor and contribute to appetite regulation (satiety) and metabolic health. By signaling to the orbitofrontal cortex, umami has been shown to improve cognitive function in Alzheimer’s disease dementia. This taste boosts the immune system and induces saliva secretion. However, the molecular mechanisms linking umami peptides to systemic physiology remain poorly understood. This study provides the first integrated analysis of neurological, immunological, and endocrinological pathways activated by umami peptides. Methods: Novel umami peptides were identified using machine-learning and deep-learning analyses from a library of marine-derived bioactive peptides. T1R1-T1R3 heterodimer is the dominant receptor for umami taste transmission in humans, expressed on taste cells, intestinal cells, and hypothalamic tanycytes. Molecular docking confirmed the binding of novel ligands to the T1R1-T1R3 receptor complex. New candidates and experimentally validated umami peptides, identified by sensomics approaches from tauco, chicken soup, pufferfish, and dry-cured ham, were analyzed using gene ontology. Results: The functional enrichment analysis revealed crosstalk among key signaling processes, including glutamatergic and opioidergic pathways. In addition to the role of µ1 opioid receptor (OPRM1), hub gene intersections highlight cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and the anorexigenic pro-opiomelanocortin (POMC) neurons as potential regulators of the gut–brain axis in satiety signaling. Chemokine-encoding genes, melanin-concentrating hormone (MCH), oxytocin (OXT), and neurotensin (NTS) were other key target genes. Conclusions: The identified targets reveal the coordinated crosstalk between peripheral and central umami signaling that may contribute to the regulation of feeding behavior, satiety, cognition, memory, learning, and immune function. These network-based insights generate hypotheses and guide the design of nutritional and drug-like effectors for metabolic and cognitive health. Full article

Background and aims: Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the progressive dilation of the aorta, culminating in rupture. At present, there are no pharmacological treatments to prevent AAA development or reduce rupture rate. A recent study showed that patients prescribed Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have significantly lower risks of mortality, AAA repair, and acute abdominal aortic syndrome. Semaglutide is a GLP-1RA with increased agonist capacity and longer half-life, compared to earlier generations of GLP-1RAs. In this study, we aimed to investigate the role and mechanisms of semaglutide in the prevention of AAA development and rupture in a murine model. Methods: AAA was induced in apolipoprotein-E-deficient mice, by continuous subcutaneous infusion of angiotensin II. Treatment with semaglutide (12 µg/kg) began seven days after disease induction (rescue trial) or simultaneously with disease induction (prophylactic trial). At experimental endpoint, aortic diameter was measured by high-frequency ultrasound and the aortic tissue was collected for histological analysis. Results: Prophylactic treatment with semaglutide drastically reduced mortality by dissection and rupture during the first seven days of disease development, but did not affect AAA formation at 28 days. Histological evaluation of the aorta at day seven showed a normal vessel wall thickness with a trend for a higher content of collagen in the aortic wall in mice treated with semaglutide, compared to controls. Conclusions: Semaglutide prevents aortic rupture and dissection in the early phases of AAA development in the angiotensin II mouse model, likely by promoting the maintenance of an adequate proportion of collagen in the vessel wall. Full article

Background/Purpose: Rectal neuroendocrine tumors (NETs) with distant metastases are uncommon, and evidence supporting the effectiveness of peptide receptor radionuclide therapy (PRRT) in this population remains limited, particularly in Asian cohorts. This study aimed to evaluate the clinical role and real-world outcomes of PRRT in Japanese patients with somatostatin receptor-positive metastatic rectal NETs. Methods: We retrospectively analyzed 20 patients with metastatic rectal NETs who underwent PRRT at the University Hospital Basel (Switzerland) and Yokohama City University Hospital (Japan) between April 2015 and May 2023. The primary endpoint was progression-free survival (PFS), and secondary endpoints included disease control rate (DCR), overall response rate (ORR), overall survival (OS), and adverse events (AEs). Exploratory subgroup analyses were performed according to clinical characteristics, including changes in serum neuron-specific enolase (NSE). Results: The median PFS was 18.9 months (95% CI, 13.5–24.3), and the median OS was 30.3 months (95% CI, 18.9–41.7). The DCR was 80.0%, and the ORR was 15.0%. Treatment responses included partial response in 3 patients, stable disease in 13, progressive disease in 3, and not evaluable in 1. The most common AEs were lymphopenia and anemia, and no secondary malignancies were observed. No clinical factors were significantly associated with PFS; however, higher baseline NSE levels showed a trend toward shorter PFS. Patients with post-treatment declines in NSE showed more favorable treatment responses. Conclusions: PRRT may provide durable disease control with a favorable safety profile in Japanese patients with metastatic rectal NETs. However, these findings should be interpreted with caution given the small sample size and heterogeneous patient population. Baseline NSE elevation and early post-treatment declines may serve as potential prognostic indicators. These results are hypothesis-generating and warrant validation in larger, multicenter studies. Full article

Background/Objectives: Assessing treatment response in neuroendocrine tumors (NETs) remains challenging. The multifactorial mechanism of action of peptide receptor radionuclide therapy (PRRT) further complicates response evaluation, particularly in the absence of standardized criteria. This study aimed to compare different imaging-based response assessment methods after PRRT and to explore their relationship with clinical outcomes, particularly progression-free survival (PFS). Methods: In this single-center retrospective study, we analyzed NET patients treated with PRRT between 2020 and 2024 who underwent [⁶⁸Ga]Ga-DOTATOC PET/CT before and after therapy, with a minimum follow-up of 12 months. Five response criteria were evaluated: (a) Krenning Score changes; (b) adapted PERCIST criteria (MORE); (c) ZP-normalized parameter; (d) qualitative visual PET assessment; and (e) RECIST-based morphological response on contrast-enhanced CT. Imaging findings were correlated with clinical outcomes. Nonparametric analyses were performed using the MedCalc^® software. Results: Thirty-one patients (median age 63 years; 17 males) with NET were evaluated after PRRT. Post-PRRT PET/CT was performed at a median of 3 months. Response rates varied across methods, with higher rates noted using functional imaging (MORE 66%, Visual PET 68%, ZP 70%) compared to RECIST (40%) and Krenning score (21%). After a median follow-up of 37 months, 58% of patients experienced disease progression. Although no significant association was found between the response criteria and progression (p > 0.05), functional imaging showed a trend toward better correlation with longer progression-free survival. Conclusions: Functional PET-based responsecriteria suggest association with progression-free survival compared to RECIST criteria and Krenning score changes. However, given the exploratory nature of the study and its methodological limitations, these observations should be considered hypothesis-generating only. They do not provide definitive evidence of superiority over established assessment methods and therefore should not be interpreted as practice-changing. Full article

Background: Depression and anxiety are prevalent mental health disorders that substantially impact quality of life. The association of incretin mimetics, including glucagon-like peptide-1 (GLP-1) receptor agonists, with symptoms of depression and anxiety remain underexplored in Saudi Arabia. This study was conducted to assess the association between GLP-1 receptor agonist use and symptoms of depression and anxiety and to identify related factors. Methods: A cross-sectional study using convenience sampling was conducted among adults (≥18 years) treated with GLP-1 receptor agonists at King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. Data were collected using a questionnaire developed by the research team, in addition to the Arabic versions of the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7). Results: A total of 235 participants were included, of whom 48.5% used GLP-1 receptor agonists for both glycemic control and weight loss. Only 31.9% had undergone psychiatric evaluation prior to initiating therapy, and 14.9% had a diagnosed psychiatric disorder. The mean anxiety score (GAD-7) was 4.82 ± 5, and the mean depression score (PHQ-9) was 6.13 ± 4.95. Multivariable analysis showed that higher odds of more severe depression were associated with using diabetes medications for weight loss in addition to diabetes treatment, a history of psychiatric disorders, and holding a bachelor’s degree. Exercising for 101–150 min per week was associated with lower odds of depression. Regarding anxiety, participants who exercised 101–150 min per week had significantly lower odds of anxiety compared with those who did not exercise, while a history of psychiatric disorders was associated with higher odds of more severe anxiety. Conclusions: This study’s findings highlight the importance of integrating both routine psychiatric screening and follow-up into diabetes and obesity management to enhance both psychological well-being and metabolic outcomes. They also reflect the benefit of physical activity for mental health, emphasizing the need to encourage exercise among individuals with diabetes or obesity. Full article

Background: Kidney transplantation (KT) improves survival and quality of life in patients with end-stage kidney disease; however, long-term allograft survival remains a major challenge. Brain natriuretic peptide (BNP), a biomarker of cardiorenal stress and volume status, may be associated with early postoperative physiological changes after KT. This study evaluated the association between early postoperative BNP changes and long-term allograft survival, and explored the potential role of BNP-derived parameters in relation to graft outcomes. Methods: This retrospective cohort study included adult recipients of deceased-donor KT between 2009 and 2018. Patients were categorized according to early graft function. Serum BNP levels were measured preoperatively and within postoperative 24 h, and the percentage increase (dBNP ratio) was calculated. Cox regression and receiver operating characteristic analyses were used to identify risk factors for graft failure and evaluate the discriminatory performance of BNP-derived biomarkers, respectively. Results: Among the 179 recipients, postoperative BNP levels and dBNP ratios differed significantly across graft function groups, with higher values in delayed graft function. After multivariate adjustment, the dBNP ratio remained significantly associated with graft failure (hazard ratio, 1.16; 95% confidence interval, 1.10–1.21; p < 0.001). Additionally, the dBNP ratio demonstrated better discriminatory performance for graft failure compared with postoperative BNP alone (area under the curve, 0.815 vs. 0.596; p < 0.001), with an exploratory cutoff of approximately 18%. Recipients with a dBNP ratio ≥ 18% had poorer early graft function, lower longitudinal estimated glomerular filtration rates, and significantly reduced graft survival. Conclusions: An increased early postoperative dBNP ratio was significantly associated with adverse long-term kidney allograft outcomes. However, given the potential for residual confounding, these findings should be interpreted as associative and hypothesis-generating rather than predictive. Full article

Periodontitis is a highly prevalent chronic inflammatory disease with significant oral and systemic consequences, including associations with cardiovascular disease, diabetes, and adverse pregnancy outcomes. Although mechanical debridement remains the cornerstone of therapy, adjunctive antibiotic use is increasingly limited by antimicrobial resistance, biofilm-associated tolerance, pharmacokinetic constraints, and disruption of the commensal microbiome, leading to inconsistent outcomes and disease recurrence. This review highlights the mechanistic limitations of conventional antibiotic therapies in periodontitis and critically examines emerging next-generation therapeutic strategies aimed at overcoming these challenges. Specifically, it explores antimicrobial peptides, quorum sensing inhibitors, nanotechnology-based drug delivery systems, host modulation approaches, and microbiome-targeted therapies, with emphasis on their molecular mechanisms, clinical relevance, and translational potential. By integrating microbial, host, and pharmacological perspectives, this review provides a comprehensive framework for advancing precision-guided periodontal therapy and supports the shift toward targeted, sustainable, and personalized treatment strategies. Full article

Gene therapy relies on safe and efficient delivery systems, yet traditional viral vectors and synthetic polymers often fail to meet these requirements due to immunogenicity and biocompatibility concerns. This review highlights self-assembling short peptides as a highly programmable and biocompatible non-viral platform uniquely positioned to overcome these translational bottlenecks. To provide a comprehensive overview of next-generation gene delivery, we systematically trace the trajectory from fundamental chemistry to clinical applications. First, we elucidate the supramolecular interactions and mechanisms driving peptide–nucleic acid co-assembly. Second, we outline concrete design strategies, detailing how sequence engineering and environmental responsiveness dictate the formation of optimized nanomorphologies. Third, we critically analyze how these nanocarriers navigate critical physiological and intracellular barriers, with a specific focus on cellular uptake, endosomal escape, and cargo release. Finally, we demonstrate the platform’s versatility in emerging frontiers, particularly mRNA vaccines and CRISPR/Cas9 gene editing. We conclude by identifying current obstacles to clinical translation and proposing future directions centered on multifunctional integration and stimuli-responsive design. Full article

The growing production volume of the meat industry has increased the need for revalorization of meat by-products to reduce economic and environmental impacts. Enzymatic hydrolysis of protein-rich meat by-products is an effective strategy for producing hydrolyzates with bioactive potential. Combining sequential enzymatic hydrolysis with γ-glutamyl transpeptidase activity can promote the formation of γ-glutamyl peptides associated with koku perception, a sensory attribute that increases taste intensity, continuity, and palatability. This study aimed to develop porcine liver hydrolyzates enriched in koku-related peptides through enzymatic hydrolysis followed by post-treatment with the transpeptidase Protana Uboost. Substrate specificity assays showed that a 0.2 U/mL enzyme concentration maximized γ-glutamyl dipeptide formation. Sequential hydrolysis using Alcalase and Protana Prime followed by Protana Uboost post-treatment generated the highest levels of koku-related peptides. Moreover, post-treatment significantly enhanced antioxidant capacity in the resulting hydrolyzates, supporting their potential as a functional ingredient. Full article