Search Results (1,199)

Background: Type 2 diabetes (T2DM) is a chronic metabolic disease closely associated with insulin resistance (IR) and disturbances in glucose and lipid metabolism. Bioactive peptides derived from food are attracting increasing research attention as candidates for nutritional supplements or functional food ingredients that improve metabolic health. This study evaluated the functional food-related properties of YPWTQ (CP4), a novel peptide derived from donkey blood, and its ability to alleviate insulin resistance in HepG2 cells. Methods: CP4 was characterized based on its hemolytic activity, stability under simulated gastrointestinal digestion conditions, inhibitory activity against α-glucosidase and Pancreatic lipase, and free radical scavenging capacity (DPPH·, ABTS⁺·, and O₂⁻·). Its effects on glucolipid metabolism and oxidative stress were examined in a glucosamine-induced insulin-resistant HepG2 cell model. Candidate signaling pathways associated with CP4 treatment were explored through transcriptomic and metabolomic analyses, combined with RT-qPCR technology. Results: CP4 exhibited low hemolytic activity and remained stable after 4 h of simulated gastrointestinal digestion. It inhibited α-glucosidase and Pancreatic lipase and exhibited antioxidant activity. In insulin-resistant HepG2 cells, CP4 increased glucose consumption, glycogen content, and cell survival, while reducing triglyceride accumulation, malondialdehyde levels, and reactive oxygen species (ROS) production. Mult omics analysis indicates that these phenotypic effects may be associated with coordinated changes in the PI3K-Akt, AGE-RAGE, Rap1, and Ras signaling pathways, as well as related genes and metabolites. Conclusions: These findings suggest that CP4, as a food-derived bioactive peptide candidate, warrants further investigation into its potential applications in the field of metabolic health. Full article

Background/Objectives: Gastrointestinal (GI) bleeding in patients with malignancy is frequently refractory to endoscopic and conservative management. Transarterial embolization (TAE) is an established treatment option, but whether the presence of contrast extravasation on preprocedural computed tomography (CT) influences outcomes remains unclear. This study aimed to evaluate the efficacy and safety of TAE for malignancy-related GI bleeding in patients with and without CT-detected contrast extravasation. Methods: From January 2012 to December 2023, 40 consecutive patients who underwent TAE for malignancy-related GI bleeding were retrospectively analyzed and categorized into CT extravasation (n = 25) and CT no-extravasation (n = 15) groups based on preprocedural CT findings. Technical success, clinical success, 30-day mortality, overall survival (OS), and procedure-related complications were compared between groups, and factors associated with OS were evaluated using Cox regression. Results: The technical and clinical success rates were 100% (40/40) and 82.5% (33/40), respectively. Clinical success did not differ between the CT extravasation and no-extravasation groups (84.0% [21/25] vs. 80.0% [12/15]; p = 0.747). Two of 40 patients (5.0%) died within 30 days, one in each group (p = 0.708). OS did not differ significantly (log-rank p = 0.707; median, 147 vs. 187 days). A shock index > 1 was independently associated with worse OS (hazard ratio, 2.308; 95% confidence interval, 1.071–4.972; p = 0.033). No major procedure-related complications occurred. Conclusions: TAE achieved high technical success and comparable short-term clinical outcomes in patients with and without CT extravasation. Hemodynamic instability, rather than CT extravasation, was independently associated with OS. Full article

Background/Objectives: Image-guided adaptive brachytherapy is a core component of definitive treatment for locally advanced cervical cancer (LACC). However, implantation remains challenging in bulky, asymmetric, or anatomically complex tumors, where standard applicator geometry or purely straight interstitial trajectories may be insufficient for individualized target coverage. This study evaluated the real-world implementation of a patient-specific 3D-printed template-guided adaptive brachytherapy workflow for complex LACC. Methods: We retrospectively reviewed 120 consecutive patients with FIGO 2018 stage IB3–IVA cervical cancer treated with definitive chemoradiotherapy followed by high-dose-rate image-guided brachytherapy between March 2023 and March 2025. All patients were treated using a patient-specific 3D-printed template-guided hybrid intracavitary/interstitial workflow integrating CT/MRI-based target assessment, individualized catheter trajectory planning, template fabrication, implantation verification, and adaptive treatment planning. Straight-channel or curved-channel guidance was selected according to residual tumor geometry and pelvic anatomy, with flexible plastic interstitial catheters used for curved or anatomically constrained trajectories. Procedural deliverability, dosimetry, toxicity, early clinical outcomes, and exploratory dose–outcome patterns were analyzed. Results: The median HR-CTV volume was 55.9 cm³, and the median HR-CTV D90 was 92.9 Gy EQD2. Median organ-at-risk D2cc values remained within contemporary institutional and guideline-consistent constraints. A total of 555 template-guided HDR brachytherapy fractions were delivered. The median applicator-and-catheter placement time was 4.21 min per fraction, with a median of 7.25 implanted channels. Minor and major insertion-related bleeding occurred in 10.8% and 1.7% of patients, respectively. At a median follow-up of 20.1 months, estimated 3-year overall survival, progression-free survival, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival were 77.9%, 76.8%, 94.3%, 98.0%, and 86.2%, respectively. Late grade ≥ 3 gastrointestinal and genitourinary toxicities occurred in 2.5% and 1.7% of patients, respectively, with no grade 4–5 events. Exploratory dose–outcome analyses suggested hypothesis-generating dose–outcome patterns, but these findings were not intended to define or validate a clinical dose threshold. Conclusions: This real-world implementation study supports the feasibility of patient-specific 3D-printed template-guided adaptive brachytherapy for complex LACC. By translating CT/MRI-based individualized trajectory planning into template-guided intracavitary/interstitial catheter placement, this workflow achieved guideline-consistent target coverage, acceptable organ-at-risk doses, efficient procedural delivery, and low severe toxicity within the available follow-up. Dose–outcome findings remain exploratory and require validation in more mature cohorts. Full article

Peritoneal carcinomatosis (PC) is a common, prognostically unfavorable manifestation of advanced gastrointestinal and gynecological malignancies whose treatment is constrained by the blood-peritoneal barrier, which limits drug penetration even when cytoreductive surgery is combined with systemic chemotherapy. This review evaluates current intraperitoneal treatment modalities and emerging technologies for overcoming this limitation, based on recent clinical trials and meta-analyses identified through Scopus and PubMed. We sequentially examine conventional intraperitoneal chemotherapy (IPC); hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian, gastric, and colorectal cancers, with attention to patient selection and the peritoneal cancer index as determinants of survival benefit; pressurized intraperitoneal aerosol chemotherapy (PIPAC) and its electrostatic precipitation variant (ePIPAC); and photodynamic and photothermal therapy for tumor treatment. Novel strategies are also discussed, including IPC combined with immune checkpoint inhibitors, optical dosimetry, and nanomedicine-based drug delivery as tools for improving treatment precision. Overall, management of PC is transitioning toward a personalized, multimodal approach: HIPEC and PIPAC provide standardized platforms for regional therapy, but future progress depends on integrating advanced drug delivery systems, immunotherapy, and real-time intraoperative monitoring, with standardization of protocols through large multicenter trials remaining a priority for translating these modalities into clinical practice. Full article

Gallbladder cancer (GBC) is the most common biliary tract malignancy and is among the most lethal gastrointestinal cancers. Since its inclusion in cancer staging manuals, the GBC Tumour–Node–Metastasis (TNM) classification has undergone repeated revisions intended to improve anatomical precision and prognostic discrimination. This narrative review traces the evolution of GBC staging across AJCC editions and the 2025 UICC TNM update and critically examines whether these refinements have translated into clinically meaningful risk stratification. In the 2025 UICC TNM 9 grouping, Stage IA corresponds to T1aN0M0 and Stage IB to T1bN0M0, while T2aN0M0 and T2bN0M0 remain Stage IIA and IIB, respectively. Structured literature searches were performed to identify historical staging documents, population-based analyses, validation studies, and prognostic reports relevant to stage migration, survival discrimination, and emerging staging modifiers. Successive changes, including T-category refinement and the transition from nodal location to nodal burden, have improved anatomical resolution. However, available validation studies suggest that gains in overall prognostic performance remain modest, with reported concordance indices often remaining near 0.66. Contemporary evidence increasingly shows that tumour location, adequacy of lymphadenectomy, number of positive lymph nodes, lymph node ratio, log odds of positive lymph nodes, obstructive jaundice, residual disease status, and selected molecular alterations may capture inter-patient heterogeneity beyond anatomy alone. Future staging refinement should therefore preserve TNM as a common anatomical language while developing validated parallel modifiers that support more individualized prognostication and treatment selection. Full article

Lactiplantibacillus plantarum is one of the most studied probiotic organisms due to its adaptability, gastrointestinal tolerance, antimicrobial activity, and health-promoting properties. However, the survival and efficacy of this probiotic can be significantly reduced during processing, storage, and gastrointestinal transit, limiting its effectiveness in food, nutraceutical, and pharmaceutical products. Synbiotic formulations, which are prepared by combining probiotics with prebiotics, have emerged as a promising approach to enhance the survival and efficacy of probiotics. In this context, encapsulation technologies play a crucial role in protecting probiotic cells from environmental and physiological stresses and in enabling controlled release at targeted sites within the gastrointestinal tract. This review describes recent developments in encapsulation strategies for L. plantarum-based synbiotic formulations, including traditional methods such as spray drying, freeze drying, extrusion and emulsion-based systems, as well as emerging methods such as nanoencapsulation and hydrogel-based delivery systems. The properties of commonly used encapsulating materials, and functional applications in food, nutraceutical and pharmaceutical products are also described. Furthermore, current challenges and future prospects are also highlighted. Overall, encapsulation represents an effective strategy to improve the stability, delivery and therapeutic potential of L. plantarum-based synbiotic formulations. Full article

Dietary interventions using probiotics actively regulate metabolism in obesity and type 2 diabetes. This study aimed to characterize two novel co-isolated strains, P. pentosaceus BGI-N8 and P. acidilactici BGI-N9, using an integrated genome–phenotype approach. Whole-genome sequencing established their preliminary safety and functional genotypes, followed by in vitro assays measuring gastrointestinal tolerance, adhesion, and metabolic enzyme activity. Genomic analysis revealed that both strains achieved genome-based safety levels, and no high-confidence transferable AMR determinants and canonical virulence factors were identified. Functional annotation showed that BGI-N8 and BGI-N9 contain essential genes for gastrointestinal adaptation, including F0F1-ATPase, the dltA-D operon, and the opp transport system. Phenotypically, BGI-N9 exhibited superior acid resistance (79.3% survival at pH 2.0), while both strains showed robust auto-aggregation (>70%) and high adhesion to HT-29 cells (ranged from 5.4 to 5.9 adherent bacteria per cell). Furthermore, the strains displayed inhibitory activity against selected indicator pathogens (88.6–97.6% inhibition). Notably, BGI-N8 and BGI-N9 showed comparable α-glucosidase inhibitory activities, with inhibition rates of 44.53% and 39.94%, respectively, Both strains also exhibited comparable cholesterol-removal capacities under the tested conditions, with removal rates of 68.76% and 74.49%. Overall, these genomic and phenotypic results supported the potentials of BGI-N8 and BGI-N9 as candidate probiotic strains with distinct complementary strengths in glycolipid regulation, providing a theoretical basis for their synergistic application. Further mechanistic, safety, and in vivo studies are required to validate their metabolic-health-related relevance. Full article

This study evaluates the combined antibacterial activity (AA) of lactic acid bacteria (LAB) and UV-C light-activated gallic acid (AGA) against two common enteropathogens (Escherichia coli and S. Typhimurium) in terms of microbial growth and survival during gastrointestinal simulation (GS). The LAB were selected based on their capacity to ferment soy and whey concentrates in monoculture and co-culture. The resulting LAB-fermented medium (LABF) was evaluated for its antibacterial properties against enteropathogens and combined with AGA to determine its effects during the GS. Results indicated that the whey solution supported the highest growth of LAB co-culture (>10⁷ CFU/mL). LABF showed AA in a dose-dependent manner, achieving >2-log reductions. Although AGA exhibited strong AA, when combined with LABF, its antimicrobial activity under GS was null, with a complete microbial recovery after 24 h of GS. Therefore, the application of LABF plus AGA in the in vitro gastrointestinal system needs further study to avoid loss of antibacterial activity during gastric transit. Full article

Background: Vitamin D deficiency is common in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Whether vitamin D status influences tumor aggressiveness and clinical outcomes remains uncertain. This review examines current evidence on the prevalence, determinants, clinical associations, and clinical relevance of vitamin D deficiency in GEP-NENs. Methods: A narrative and critical review of the literature was conducted using the PubMed/MEDLINE, Scopus, and Web of Science databases. Clinical studies, observational cohorts, translational research, selected mechanistic studies, and current clinical guidelines addressing vitamin D metabolism and neuroendocrine neoplasms were evaluated. Results: Vitamin D deficiency has been reported in approximately 60–80% of patients with GEP-NENs. Low serum 25-hydroxyvitamin D concentrations likely reflect multiple disease-related factors, including malabsorption, pancreatic exocrine insufficiency, chronic diarrhea, previous gastrointestinal surgery, and nutritional impairment. Several observational studies have linked lower vitamin D status with markers of more aggressive disease, including higher Ki-67 proliferation index values and shorter progression-free survival. Nevertheless, the available data are heterogeneous, predominantly observational, and do not support a causal relationship between vitamin D deficiency and tumor progression. At present, the main clinical rationale for assessing vitamin D status is to support metabolic care, preserve bone health, and prevent osteoporosis. Conclusions: Vitamin D deficiency is a frequent and clinically relevant comorbidity in patients with GEP-NENs. Although lower vitamin D status has been associated with markers of more aggressive disease, current findings do not support vitamin D supplementation as an anticancer treatment strategy. Prospective clinical and translational studies are needed to clarify the biological and clinical significance of vitamin D signaling in GEP-NENs. Full article

Gastrinoma is a rare neuroendocrine tumor in dogs that arises from functional pancreatic non-β cells and secretes excessive gastrin. Gastrinoma in dogs has a high metastasis rate at diagnosis, and curative treatment is often difficult. There are few reports describing the long-term outcomes of surgical treatment in dogs with gastrinoma, and no established method for monitoring disease progression has been reported. We report here the cases of two adult dogs with pancreatic gastrinoma treated with surgical resection. Pharmacological therapy using proton pump inhibitors was administered to control gastrointestinal symptoms caused by hypergastrinemia. Multiple surgeries were performed to reduce the volume of primary and metastatic gastrinoma lesions. Serial serum gastrin concentrations were used as an adjunctive monitoring marker during follow-up. Changes in serum gastrin concentrations were used to support decisions regarding further imaging. Additional surgery was performed based on serum gastrin concentrations, clinical signs, and diagnostic imaging findings. A total of four surgeries were performed in Case 1 and three surgeries in Case 2. Both dogs maintained well-controlled gastrointestinal symptoms and showed long-term survival. The changes in serum gastrin concentrations in these cases suggest that serial serum gastrin measurement may be useful for monitoring recurrence or tumor progression in canine gastrinoma. Full article

Rushan acid whey is an underutilized by-product of a traditional fermented dairy food and may contain probiotic lactic acid bacteria. This study screened cholesterol-lowering strains from Rushan acid whey and evaluated Limosilactobacillus fermentum A001-A-08 for functional traits, preliminary safety, and lipid-lowering potential in high-fat-diet-induced zebrafish. A001-A-08 showed cholesterol removal, bile salt hydrolase activity, acid/bile/simulated gastrointestinal tolerance, auto-aggregation, gamma-hemolysis, and a mostly susceptible antibiotic profile. A 10⁶ CFU/mL bath concentration maintained larval survival, heart rate, and morphology and enabled intestinal localization during the observation period. In high-fat zebrafish, A001-A-08 reduced Oil Red O-stained lipid accumulation, improved hepatic morphology, lowered TC and TG, and increased HDL-C. Transcriptomic, metabolomic, qRT-PCR, and 16S rRNA sequencing analyses indicated that these phenotypic changes were associated with alterations in lipid transport, lipoprotein assembly, bile acid-related metabolism, selected metabolite features, and gut microbial composition. These findings support A001-A-08 as a promising Rushan acid whey-derived probiotic candidate, while genome-level safety assessment, mammalian oral-administration studies, and food-matrix validation remain necessary before functional-food application. Full article

The prebiotic concept now extends past inulin and fructo-oligosaccharides to diverse dietary compounds for selective gut microbial utilization and health promotion. This review explores Pleurotus eryngii as a source of prebiotic substrates, with a focus on how preparation methods and molecular traits affect its digestive stability, fermentability and food applicability. The tested materials include various mushroom-derived fractions: polysaccharides (native and modified), β-glucan extracts, powders, hydrolysates, protein co-extracts, exopolysaccharides and composite matrices. Many fractions survive upper gastrointestinal digestion and produce short-chain fatty acids whose profiles vary with the substrate during fecal fermentation. Animal studies have demonstrated their positive impacts on intestinal barriers, immunity and metabolism, and these ingredients fit well into multiple food formulations. Rather than treating Pleurotus eryngii as a uniform polysaccharide product, evaluations should be performed for each individual preparation. Existing data supports Pleurotus eryngii as a promising source of structurally diverse candidate prebiotic substrates, with a consistent biological rationale linking digestive persistence, microbial fermentation, short-chain fatty acid production, microbiota modulation and gut-related host responses. Further research is required to verify the microbiota-related causal mechanisms, assess finished food products and implement human microbiota intervention trials. Full article

The gastrointestinal epithelium forms a critical barrier that regulates nutrient absorption while preventing the translocation of harmful luminal contents. Disruption of this barrier initiates a coordinated wound healing response involving epithelial restitution, proliferation, and differentiation. Focal adhesion kinase (FAK) is central to this process, regulating focal adhesion (FA) turnover and cytoskeletal dynamics required for epithelial migration. Activation of FAK via phosphorylation at tyrosine 397 (Y397) promotes cell motility, proliferation, and survival, whereas loss of function impairs mucosal repair and exacerbates tissue injury. Effective wound healing also requires tight regulation of reactive oxygen species (ROS). The nuclear factor erythroid 2-related factor 2 (NRF2) pathway governs antioxidant defenses by inducing cytoprotective genes, including SOD1, CAT, GCLC, GCLM, and NQO1, restoring redox homeostasis and limiting inflammation. NRF2 deficiency results in increased oxidative stress, heightened inflammatory signaling, and delayed wound healing. While both FAK and NRF2 are independently essential for gastrointestinal wound healing, their mechanistic relationship remains unclear. Emerging evidence suggests that they may be functionally linked through redox-dependent signaling where FAK-mediated ROS production may promote NRF2 activation, while NRF2-driven antioxidant responses maintain conditions necessary for sustained FAK signaling. This coordinated interaction highlights a redox-sensitive feedback mechanism critical for efficient gastrointestinal wound repair. Full article

Since decades, surgery of pancreatic adenocarcinoma is confronted with two major challenges. First, the prognosis of pancreatic adenocarcinoma is the worst of all gastrointestinal malignancies, characterized by late diagnosis and aggressive tumor biology. Second, postoperative mortality and morbidity have been exceptionally high, giving pancreatic resection a reputation of being one of the most dangerous procedures. This narrative review concentrates on the progress in decreasing postoperative mortality by centralization and standardization, the exertion of extended resections for local tumor clearance and multimodal strategies to improve oncologic survival. Research regarding surgical techniques, especially robotic assistance, indicated further progress in minimizing the perioperative trauma. Multimodal treatment concepts have been implemented with adjuvant therapy in resectable and neoadjuvant regimen in borderline and locally advanced cancer. However, significant problems have to be solved. Postoperative morbidity remains high, hindering the administration of adjuvant therapy, and toxicity is an essential factor in neoadjuvant strategies. Despite neoadjuvant therapies, resection rates of locally advanced carcinoma are modest and tumor progression hinders resection of borderline and resectable carcinomas. Obviously, deficits in understanding tumor biology are a central obstacle in improving resection rates and overall survival. Hence, improvement in selection of patients for surgical resection apart from using preoperative anatomical findings is mandatory. The progression of current standards, future developments and the status of surgery in multimodal concepts to treat pancreatic adenocarcinoma are delineated using historical and recent reports, registry data, meta-analysis and randomized controlled trials. Full article

The growing demand for plant-based functional foods has encouraged the development of non-dairy fermented beverages able to deliver viable microorganisms and improve the technological and nutritional value of plant matrices. This study aimed to develop a prototype fermented peanut beverage using Lactiplantibacillus plantarum strains and to evaluate their technological performance, stability, and functional potential. Two plant derived strains, L. plantarum F1B and LpAv, and the commercial probiotic L. plantarum 299v were assessed in animal-free culture media and used to ferment peanut extract supplemented with sucrose and yeast extract. Fermented beverages were characterized through microbiological, physicochemical, rheological, peptide profile, refrigerated storage, and simulated gastrointestinal digestion. The selected formulation allowed all strains to reach pH ≤ 4.5 after 6.5 h, with LAB counts of 8.6–9.0 log CFU/mL. Lactic acid was the main fermentation product, and oxalic acid levels were significantly reduced. Fermentation increased peptide signals and improved rheological behavior, generating pseudoplastic beverages with higher viscosity than the control. LAB counts remained ≥8 log CFU/mL after 28 days at 4 °C, although gastrointestinal resistance after storage was strain-dependent. Taken together, L. plantarum strains showed promising technological and functional properties for developing fermented peanut-based beverages. The nutritional properties of peanut, together with the fact that it supports the growth and survival of LAB in a fermented beverage, positions peanuts as a candidate which deserves further studies in the space of fermented functional foods. Full article