Search Results (1,356)

Background/Objectives: The RTK-RAS signaling cascade is a central axis in colorectal cancer (CRC) pathogenesis, governing cellular proliferation, survival, and therapeutic resistance. Somatic alterations in key pathway genes—including KRAS, NRAS, BRAF, and EGFR—are pivotal to clinical decision-making in precision oncology. However, the integration of these genomic events with clinical and demographic data remains hindered by fragmented resources and a lack of accessible analytical frameworks. To address this challenge, we developed AI-HOPE-RTK-RAS, a domain-specialized conversational artificial intelligence (AI) system designed to enable natural language-based, integrative analysis of RTK-RAS pathway alterations in CRC. Methods: AI-HOPE-RTK-RAS employs a modular architecture combining large language models (LLMs), a natural language-to-code translation engine, and a backend analytics pipeline operating on harmonized multi-dimensional datasets from cBioPortal. Unlike general-purpose AI platforms, this system is purpose-built for real-time exploration of RTK-RAS biology within CRC cohorts. The platform supports mutation frequency profiling, odds ratio testing, survival modeling, and stratified analyses across clinical, genomic, and demographic parameters. Validation included reproduction of known mutation trends and exploratory evaluation of co-alterations, therapy response, and ancestry-specific mutation patterns. Results: AI-HOPE-RTK-RAS enabled rapid, dialogue-driven interrogation of CRC datasets, confirming established patterns and revealing novel associations with translational relevance. Among early-onset CRC (EOCRC) patients, the prevalence of RTK-RAS alterations was significantly lower compared to late-onset disease (67.97% vs. 79.9%; OR = 0.534, p = 0.014), suggesting the involvement of alternative oncogenic drivers. In KRAS-mutant patients receiving Bevacizumab, early-stage disease (Stages I–III) was associated with superior overall survival relative to Stage IV (p = 0.0004). In contrast, BRAF-mutant tumors with microsatellite-stable (MSS) status displayed poorer prognosis despite higher chemotherapy exposure (OR = 7.226, p < 0.001; p = 0.0000). Among EOCRC patients treated with FOLFOX, RTK-RAS alterations were linked to worse outcomes (p = 0.0262). The system also identified ancestry-enriched noncanonical mutations—including CBL, MAPK3, and NF1—with NF1 mutations significantly associated with improved prognosis (p = 1 × 10⁻⁵). Conclusions: AI-HOPE-RTK-RAS exemplifies a new class of conversational AI platforms tailored to precision oncology, enabling integrative, real-time analysis of clinically and biologically complex questions. Its ability to uncover both canonical and ancestry-specific patterns in RTK-RAS dysregulation—especially in EOCRC and populations with disproportionate health burdens—underscores its utility in advancing equitable, personalized cancer care. This work demonstrates the translational potential of domain-optimized AI tools to accelerate biomarker discovery, support therapeutic stratification, and democratize access to multi-omic analysis. Full article

Calcium microcapsules were developed by spray-drying using mannoproteins (MPs) extracted from brewer’s spent yeast, xanthan gum (XG), and maltodextrin as encapsulating materials. The formulas included 11 g of calcium, 24 g of MP, and 0, 2, 4, or 8 g of XG 100 g⁻¹ solids, obtaining C1, C2, C3, and C4 microcapsules, respectively. Maltodextrin was added to complete 100 g of solids. Calcium intestinal (IB), colonic (CB), and total bioaccessibility (TB) were estimated after a simulated gastrointestinal digestion followed by in vitro colonic fermentation. The macromolecules of microcapsules interacted by ionic and hydrophobic forces. Microcapsules C1 and C2 showed a spherical shape. However, the addition of XG to the formulation contributed to the formation of concavities in the microcapsules. All microcapsules had higher IB than the control (CaCl₂), probably due to the calcium-chelating peptides dialyzed from MP. Moreover, C1 and C2 showed the highest IB values (≈23%). However, C3 and C4 showed the highest CB values (≈11%), attributing this effect to the short-chain fatty acids produced during colonic fermentation. Finally, C1 and C2 showed the highest TB (31.8 ± 0.1 and 32.0 ± 0.4%, respectively). The use of MP allowed for obtaining a supplement with high calcium bioaccessibility. Full article

Infant clothing represents a critical yet overlooked exposure pathway for heavy metals, with significant implications for child health and sustainable consumption. This study investigates cadmium (Cd) and chromium (Cr) contamination in 33 textile samples, integrating in vitro bioaccessibility assays, cytotoxicity analysis, and risk assessment models to evaluate dermal exposure risks. Results reveal that 80% of samples exceeded OEKO-TEX Class I limits for As (mean 1.01 mg/kg), Cd (max 0.25 mg/kg), and Cr (max 4.32 mg/kg), with infant clothing showing unacceptable hazard indices (HI = 1.13) due to Cd (HQ = 1.12). Artificial sweat extraction demonstrated high bioaccessibility for Cr (37.8%) and Ni (28.5%), while keratinocyte exposure triggered oxidative stress (131% ROS increase) and dose-dependent cytotoxicity (22–59% viability reduction). Dark-colored synthetic fabrics exhibited elevated metal loads, linking industrial dye practices to health hazards. These findings underscore systemic gaps in textile safety regulations, particularly for low- and middle-income countries reliant on cost-effective apparel. We propose three policy levers: (1) tightening infant textile standards for Cd/Cr, (2) incentivizing non-toxic dye technologies, and (3) harmonizing global labeling requirements. By bridging toxicological evidence with circular economy principles, this work advances strategies to mitigate heavy metal exposure while supporting Sustainable Development Goals (SDGs) 3 (health), 12 (responsible consumption), and 12.4 (chemical safety). Full article

Incorporation of lanthanide (Ln) and actinide (An) ions into the human body poses significant chemotoxic and radiotoxic risks, necessitating effective decorporation strategies. This study investigates the displacement of biologically relevant ligands from trivalent ions of europium, Eu(III), and curium, Cm(III), in artificial biofluids by various complexing agents, i.e., ethylenediaminetetraacetic acid (EDTA), ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), diethylenetriaminepentaacetic acid (DTPA), and spermine-based hydroxypyridonate chelator 3,4,3-LI(1,2-HOPO) (HOPO). Utilizing a modified unified bioaccessibility method (UBM) to simulate gastrointestinal conditions, we conducted concentration-dependent displacement experiments at both room and body temperatures. Time-resolved laser-induced fluorescence spectroscopy (TRLFS) supported by ²H nuclear magnetic resonance (NMR) spectroscopy and thermodynamic modelling revealed the complexation efficacy of the agents under physiological conditions. Results demonstrate that high affinity, governed by complex stability constants and ligand pK_a values, is critical to overcome cation and anion competition and leads to effective decorporation. Additionally, there is evidence that cyclic ligands are inferior to linear ligands for this application. HOPO and DTPA exhibited superior displacement efficacy, particularly in the complete gastrointestinal tract simulation. This study highlights the utility of in vitro workflows for evaluating decorporation agents and emphasizes the need for ligands with optimal binding characteristics for enhanced chelation therapies. Full article

Large language models (LLMs) are increasingly being applied to clinical tasks, but it remains unclear whether medical-specific models consistently outperform smaller, generalpurpose ones. This study investigates that assumption in the context of cardiovascular disease (CVD) risk assessment. We fine-tuned eight LLMs—both general-purpose and medical-specific—using textualized data from the Behavioral Risk Factor Surveillance System (BRFSS) to classify individuals as “High Risk” or “Low Risk”. To provide actionable insights, we integrated a Retrieval-Augmented Generation (RAG) framework for personalized recommendation generation and deployed the system within an interactive chatbot interface. Notably, Gemma2, a compact 2B-parameter general-purpose model, achieved a high recall (0.907) and F1-score (0.770), performing on par with larger or medical-specialized models such as Med42 and BioBERT. These findings challenge the common assumption that larger or specialized models always yield superior results, and highlight the potential of lightweight, efficiently fine-tuned LLMs for clinical decision support—especially in resource-constrained settings. Overall, our results demonstrate that general-purpose models, when fine-tuned appropriately, can offer interpretable, high-performing, and accessible solutions for CVD risk assessment and personalized healthcare delivery. Full article

Nonsteroidal anti-inflammatory drug-based therapies are the cause of 20–30% cases of gastric lesions in chronic users worldwide. Co-medication with omeprazole (OMP) is the most commonly used option to prevent these lesions, although this carries risks of its own; thus, alternatives are being explored, such as dietary antioxidant therapies. The objective of this study was to evaluate the gastroprotective activity of quinoa (Chenopodium quinoa Willd.) on ibuprofen (IBP)-induced gastric ulcers in a rat model. Quinoa cookies were formulated with heat-treated quinoa using microwave radiation. The intestinal bioaccessibility of phenols and flavonoids, and the antioxidant activity of microwaved quinoa cookies (MQCs) were notably higher than quinoa cookies without thermal treatment (RQCs): 132% TPC, 52% TFC, 1564% TEAC vs. 67% TPC, 24% TFC, and 958% TEAC, respectively. Basal diets were supplemented with MQCs (20%) and quercetin (Q, 0.20%) as a reference flavonoid and administered for 30 days. Gastric lesions were induced by intragastric IBP doses, with OMP treatment as a positive control. Gastric damage index (macroscopic study), histological score (microscopic study), and plasma antioxidant enzyme activity (SOD and CAT) were evaluated. Macroscopic results showed that the addition of MQCs, Q, and OMP decreased the gastric damage index (GDI) by 50%, 40%, and 3%, respectively, as compared to IBP (GDI 100%). Histological analyses showed neutrophil infiltration and congested blood vessels in IBP-treated tissues; in contrast, the experimental diet groups showed lower infiltration for MQC > OMP > Q, respectively. A significant increase in SOD and CAT enzyme activity was observed in the MQC and Q groups as compared to the IBP group. We conclude that a reduction in the GDI and histological score was observed in IBP-induced murine models fed diets containing 20% MQC and 0.20% Q, demonstrating a preventive gastroprotective effect. Full article

The Stability Toolkit for the Appraisal of Bio/Pharmaceuticals’ Level of Endurance (STABLE) is introduced and proposed as a comprehensive tool and software to evaluate the stability of active pharmaceutical ingredients (APIs) under various stress conditions. In the pharmaceutical industry, stability testing is a critical step in the drug development process, ensuring the quality, safety, and efficacy of APIs. Traditional stability tests—such as real-time, accelerated, and forced degradation testing—often face challenges, including inconsistent interpretation and implementation across different regions and organizations. STABLE addresses these challenges by providing a standardized and holistic approach to assessing drug stability across five key stress conditions: oxidative, thermal, acid-catalyzed hydrolysis, base-catalyzed hydrolysis, and photostability. Beyond its role as an evaluation tool, STABLE also serves as a practical guide for chemists, encouraging a more complete and thoughtful approach to stability studies. While many investigations focus solely on acid- and base-catalyzed hydrolysis, other critical conditions—such as photostability—are often underexplored or entirely omitted. By highlighting the importance of evaluating all relevant degradation pathways, STABLE promotes more robust and informed stability testing protocols. The index utilizes a color-coded scoring system to quantify and compare stability, facilitating consistent assessments across different APIs. This paper discusses the methodology of STABLE, including the scoring system and specific criteria applied under each condition. This tool is introduced to reflect intrinsic degradation susceptibility under forced conditions. The software is freely available as an open-source tool at bit.ly/STABLE2025, enabling broader accessibility and implementation across the pharmaceutical research community. Full article

Protein-polyphenol-based delivery vehicles are effective strategies for encapsulating bioactive compounds, thereby enhancing their solubility and bioaccessibility. In this study, dihydromyricetin/soy protein isolate (DHM/SPI) complexes were used as emulsifiers to prepare Pickering emulsions for DHM delivery. The results show that DHM and SPI form negatively charged complexes through hydrogen bonding, and the complex size decreases and stabilizes with increasing DHM addition. The size of the emulsion droplets was inversely related to the concentration of DHM addition (c), particle concentration (w), and ionic strength (i). Conversely, the increasing oil phase concentration (φ) was positively correlated with droplet size. The CLSM results confirmed the expected oil-in-water emulsion, while the rheological behavior of the Pickering emulsion highlighted its elastic, gel-like network structure and non-Newtonian fluid properties. Moreover, DHM effectively slowed lipid oxidation in the emulsion, and the bioaccessibility of DHM reached 33.51 ± 0.31% after in vitro simulated digestion. In conclusion, this emulsion system shows promising potential for delivering DHM and harnessing its bioactive effects. Full article

The treatment of inflammatory bowel diseases (IBDs), particularly ulcerative colitis and Crohn’s disease, remains a challenge. As the available therapeutic options have limited efficacy and various side effect, there is a need to identify new inflammatory modulators that can influence IBD. Natural polyphenols and polyphenol-rich extracts have been found to have preventive and therapeutic potential, including various anti-inflammatory effects. In this study, the inhibition of the formation of mediators associated with intestinal inflammation, remodelling, and angiogenesis by the spent hop extract (SHE), a polyphenol-rich extract from Humulus lupulus L., and its flaxseed polysaccharide-based encapsulates was examined using tumour necrosis factor alpha (TNF-α)-stimulated human small intestinal epithelial (HIEC-6) and large intestinal epithelial (CCD841CoN) cells. Also, we assessed the activity of the tested agents after in the vitro-simulated gastrointestinal digestion process. SHE strongly inhibited the expression of pro-inflammatory cytokines, mainly IL-1β and TNF-α, as well as the expression and activity of type IV collagenases (MMP-2 and MMP-9); these effects resulted from the suppression of NF-κB, ERK and Akt signalling pathways. We also proved the protective effect of encapsulation process against the reduction in the bioaccessibility of SHE, observed under the influence of digestion process. Our results provide initial evidence on the potential utility of SHE and its encapsulates in IBD. Full article

Ginger (Zingiber officinale Roscoe) has been widely recognized for its antioxidant properties, primarily attributed to its phenolic compounds such as gingerols and shogaols. However, limited data exist regarding how different pharmaceutical forms influence the bioaccessibility and antioxidant efficacy of these compounds. This study aimed to evaluate the antioxidant capacity and bioaccessibility of ginger in different pharmaceutical forms—capsules (20 mg, 40 mg, and 80 mg), a pure powdered extract, and a liquid formulation—standardized to ≥6% gingerols. The phenolic profile of each formulation was characterized using HPLC-DAD (High-Performance Liquid Chromatography with Diode Array Detection), followed by the evaluation of antioxidant capacity through DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ORAC (Oxygen Radical Absorbance Capacity) assays, and the assessment of bioaccessibility via an in vitro digestion model. The results demonstrated that antioxidant activity was positively correlated with extract concentration and was highest in the liquid formulation (426.0 ± 0.05 µmol Trolox equivalents (TE) and 11,336.7 ± 0.20 µmol TE in the DPPH and ORAC assays, respectively). The bioaccessibility of 6-gingerol and 6-shogaol significantly increased in the liquid form, reaching 23.44% and 11.31%, respectively, compared to ≤4% in the pure extract. These findings highlight the influence of the formulation matrix on compound release and support the use of liquid preparations to enhance the functional efficacy of ginger-derived nutraceuticals. This standardized comparative approach, using formulations derived from the same extract, offers new insights into how the delivery matrix influences the functional performance of ginger compounds, providing guidance for the development of more effective nutraceutical strategies. Full article

Background/Objectives: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway is a critical mediator of immune regulation, inflammation, and cancer progression. Although implicated in colorectal cancer (CRC) pathogenesis, its molecular heterogeneity and clinical significance remain insufficiently characterized—particularly within early-onset CRC (EOCRC) and across diverse treatment and demographic contexts. We present AI-HOPE-JAK-STAT, a novel conversational artificial intelligence platform built to enable the real-time, natural language-driven exploration of JAK/STAT pathway alterations in CRC. The platform integrates clinical, genomic, and treatment data to support dynamic, hypothesis-generating analyses for precision oncology. Methods: AI-HOPE-JAK-STAT combines large language models (LLMs), a natural language-to-code engine, and harmonized public CRC datasets from cBioPortal. Users define analytical queries in plain English, which are translated into executable code for cohort selection, survival analysis, odds ratio testing, and mutation profiling. To validate the platform, we replicated known associations involving JAK1, JAK3, and STAT3 mutations. Additional exploratory analyses examined age, treatment exposure, tumor stage, and anatomical site. Results: The platform recapitulated established trends, including improved survival among EOCRC patients with JAK/STAT pathway alterations. In FOLFOX-treated CRC cohorts, JAK/STAT-altered tumors were associated with significantly enhanced overall survival (p < 0.0001). Stratification by age revealed survival advantages in younger (age < 50) patients with JAK/STAT mutations (p = 0.0379). STAT5B mutations were enriched in colon adenocarcinoma and correlated with significantly more favorable trends (p = 0.0000). Conversely, JAK1 mutations in microsatellite-stable tumors did not affect survival, emphasizing the value of molecular context. Finally, JAK3-mutated tumors diagnosed at Stage I–III showed superior survival compared to Stage IV cases (p = 0.00001), reinforcing stage as a dominant clinical determinant. Conclusions: AI-HOPE-JAK-STAT establishes a new standard for pathway-level interrogation in CRC by empowering users to generate and test clinically meaningful hypotheses without coding expertise. This system enhances access to precision oncology analyses and supports the scalable, real-time discovery of survival trends, mutational associations, and treatment-response patterns across stratified patient cohorts. Full article

Microbeads of raspberry extract were produced using encapsulation matrices alginate + pea protein isolate + psyllium mucilage, alginate + pea protein isolate + psyllium mucilage + okra, and alginate + pea protein isolate + psyllium mucilage + Aloe ferox gel + gallic acid using freeze-drying method. The microbeads were characterised and assessed for their effectiveness on the release, bioaccessibility, of anthocyanin components and antioxidant activities during in vitro digestion. Alginate + pea protein isolate + psyllium mucilage + Aloe ferox gel + gallic acid matrix showed the highest encapsulation efficiency of 91.60% while the lowest encapsulation efficiency was observed in alginate + pea protein isolate + psyllium mucilage + okra (69.94%). Scanning electron microscope images revealed spherical shapes and varying surface morphologies for different encapsulation matrices. Despite the differences observed in Fourier transform infrared spectra, microbeads showed similar thermal degradation patterns. X-ray diffractograms showed amorphous structures for different encapsulation matrices. Comparatively, alginate+ pea protein isolate + psyllium mucilage + Aloe ferox gel + gallic acid microbeads exhibited the highest bioaccessibility for total phenols (93.14%), cyanidin-3-O-sophoroside (54.61%), and cyanidin-3-O-glucoside (55.30%). The encapsulation matrices of different biopolymer combinations (alginate+ pea protein isolate+ psyllium mucilage, alginate + pea protein isolate + psyllium mucilage + okra, and alginate + pea protein isolate + psyllium mucilage + Aloe ferox gel + gallic acid) enhanced anthocyanin stability and protected it against in vitro degradation of bioactive compounds. Full article

The health-promoting activity of radish microgreens after consumption depends on their bioaccessibility and bioavailability. In this study, we compared the composition of phenolic compounds, their cytoprotective and anti-inflammatory activities in cell lines, and antioxidant properties of the undigested radish microgreens with their fractions obtained after simulated in vitro digestion in the stomach, as well as in the small and large intestine. The results have demonstrated higher levels of total phenolics (by 70.35%) and total hydroxycinnamic acids (3.5 times increase), an increase in scavenging efficiency toward ABTS^•+ and superoxide anion radicals, and an increase in the reduction potential (FRAP method) in the gastric bioaccessible fraction. In contrast, small intestinal digestion negatively affected phenolic content (a reduction of 53.30–75.63%), except for total hydroxycinnamic acids (3-fold increase). Incubation of the non-bioavailable fraction with bacterial enzymes led to further degradation. Undigested microgreens had no negative impact on Caco-2, HT-29, and SH-SY5Y cells’ metabolism at 0.05–2 mg/mL, while all digested samples at 1 mg/mL revealed their cytotoxic potential. All samples used at a non-cytotoxic concentration showed protective activity against H₂O₂ and corticosterone-induced oxidative stress generation as well as reduced proinflammatory cytokines production. Overall, radish microgreens may exhibit a broad spectrum of biological activities when consumed. Full article

This study investigated the functional potential of Campomanesia xanthocarpa leaf and fruit infusions through phytochemical profiling, simulated gastrointestinal digestion, enzyme inhibition assays, and in vivo evaluation of glycemic markers. Leaf infusions exhibited a more diverse phenolic profile, higher total phenolic content, and greater antioxidant capacity compared to fruit infusions. Simulated digestion confirmed the bioaccessibility of key phenolic compounds, particularly glycosylated flavonoids such as quercetin-3-glucoside and kaempferol derivatives, with leaf extracts showing superior gastrointestinal stability. In vitro assays revealed a strong inhibitory activity of leaf infusions against α-amylase and β-glucosidase. In a 32-day trial with healthy dogs, the consumption of biscuits enriched with leaf infusion did not alter fasting glucose or amylase levels but resulted in a significant treatment × time interaction for serum fructosamine, indicating a delayed modulation of glycemic control, potentially associated with antioxidant or anti-glycation activity. These findings highlight the potential of C. xanthocarpa leaves as a functional ingredient in foods aimed at supporting glycemic regulation and metabolic health. Full article

This paper presents a methodology for extracting and simulating arterial pulse waveform signals from Fabry–Perot interferometric measurements, emphasizing a practical approach for noninvasive cardiovascular assessment. A key novelty of this work is the presentation of a complete Python-based processing pipeline, which is made publicly available as open-source code on GitHub (git version 2.39.5). To the authors’ knowledge, no such repository for demodulating these specific interferometric signals to obtain a raw arterial pulse waveform previously existed. The proposed system utilizes accessible Python-based preprocessing steps, including outlier removal, Butterworth high-pass filtering, and min–max normalization, designed for robust signal quality even in settings with common physiological artifacts. Key features such as the rate of change, the Hilbert transform of the rate of change (envelope), and detected extrema guide the signal reconstruction, offering a computationally efficient pathway to reveal its periodic and phase-dependent dynamics. Visual analyses highlight amplitude variations and residual noise sources, primarily attributed to sensor bandwidth limitations and interpolation methods, considerations critical for real-world deployment. Despite these practical challenges, the reconstructed arterial pulse waveform signals provide valuable insights into arterial motion, with the methodology’s performance validated on measurements from three subjects against synchronized ECG recordings. This demonstrates the viability of Fabry–Perot sensors as a potentially cost-effective and readily implementable tool for noninvasive cardiovascular diagnostics. The results underscore the importance of precise yet practical signal processing techniques and pave the way for further improvements in interferometric sensing, bio-signal analysis, and their translation into clinical practice. Full article