Search Results (1,529)

Background: The dissolution of oral solid dosage forms is a key determinant of drug bioavailability, yet traditional testing methods do not capture the real-time surface dynamics of drug release. This study introduces a novel framework combining surface dissolution imaging (SDi2) with an interpretable, dual-wavelength convolutional neural network (CNN) to predict and understand dissolution behavior. Methods: Eight tablet formulations containing acetylsalicylic acid, sodium salicylate, or salicylamide, combined with either lactose or methylcellulose, were analyzed under two distinct, compendial conditions (pH 1.2 and pH 6.8). Results: Our final CNN model, which synergistically processes spectral images (280 nm for API release and 520 nm for structural changes), temporal data, and formulation composition, accurately predicted dissolution profiles, achieving a coefficient of determination of 0.89 and a root mean square error (RMSE) of 11.57. To overcome the “black-box” nature of deep learning, we employed Gradient-weighted Class Activation Mapping (Grad-CAM) to interpret the model’s predictions. The analysis revealed that the model focused on tablet edges at 280 nm, consistent with surface dissolution, and on bulk regions at 520 nm, reflecting structural changes including erosion and gel-layer growth. Conclusions: These findings suggest that integrating real-time imaging with explainable AI methods can support better understanding of dissolution processes in pharmaceutical formulation development. Full article

Blood metabolism in dairy cows is crucial for milk quality, functioning primarily through the “blood–milk” metabolic axis. Allium mongolicum Regel (AMR), a functional Allium herb, has been shown to regulate on ruminant lipid metabolism. This study investigated the impact of AMR ethanol extract (AME) on lactation performance, blood lipid parameters, and blood–milk metabolomes. Twelve mid-lactation Holsteins (606 ± 11 kg; milk yield 33.14 ± 2.08 kg/d) of parity 2–3 were assigned to either a basal diet (CON) or a diet supplemented with 54 g/d of AME (AEE). Results indicated that AME significantly decreased plasma triglycerides (TG), C15:0, C16:1, C18:1 n-9 c, C18:3 n-6, monounsaturated fatty acids (p < 0.05) and significantly increased C18:2 n-6 c, polyunsaturated fatty acids (p < 0.05). Lactation performance, including the average daily dry matter intake, daily yields of milk fat, protein and lactose, remained unaffected by the AME addition (p > 0.05). Metabolomic profiling revealed that AME significantly enriched the glycerophospholipid metabolism pathway in plasma, upregulating key phospholipid precursors such as L-serine and Sphinganine. Concurrently, milk metabolomics showed an upregulation of short-chain Acylcarnitines. Plasma TG correlated negatively with both plasma L-serine and milk Acylcarnitines, whereas low-density lipoprotein correlated positively with these energy-driven milk metabolites. These findings suggest that AME may contribute to remodeling the plasma lipid metabolic profile in a manner that could facilitate plasma-to-milk lipid flux. This appears to occur through enhanced hepatic lipid processing and increased mammary lipid utilization, offering preliminary insights into potential nutritional strategies for supporting lipid metabolism in dairy cows. Full article

Since differential scanning calorimetry (DSC) is an excellent method for studying phase transformations in the solid state, the purpose of this study was to assess the suitability of DSC as a method for detecting physicochemical transformations occurring in solid drug products during storage, extending also beyond their expiration date. Based on the DSC measurements of 34 commercial drug products, they were divided into three groups characterized by the fact that the DSC curves show: (I) as dominant endothermic peaks reflecting active pharmaceutical ingredients (APIs) melting, with no additional peaks from excipients, (II) in addition to the peaks reflecting APIs melting, additional peaks related to the excipients, and (III) two peaks characteristic of lactose monohydrate dehydration and melting. Analysis of the temperature ranges and the shape of the DSC peaks showed no significant differences between the six series of measurements performed between 2011 and 2022, suggesting that physicochemical changes in drug products could not be detected during storage. Only the use of principal component analysis (PCA) made it possible to separate the DSC curves obtained during long-term storage of drug products. This allows DSC to be used to detect the first signs of deterioration, but only for drug formulations in group one. Of the drug products in groups two and three, this is only possible for 14 products. It follows that the suitability of DSC for identifying physicochemical changes in products stored for long periods of time is affected by the API content and complex composition of the tablet matrix. Full article

While industrial-scale dairy fermentations often employ pasteurized milk as the substrate, many farmhouse and traditional production practices apply raw milk derived from a variety of mammals. Certain artisanal production systems rely on the autochthonous microbiota of the milk, fermentation vessels, equipment and/or environment to initiate milk coagulation. While the technological properties of lactic acid bacteria associated with dairy fermentations are well described, their interactions with other organisms during fermentation and cheese ripening are poorly investigated. This study presents an overview of the microbial ecology of raw and pasteurized milk used in the production of Irish farmhouse cheeses using metagenomic and culture-based approaches. Metagenomic analysis of four raw milk-derived cheeses established the dominant presence of either lactococci or Streptococcus spp. and with a secondary population of various lactobacilli. Interestingly, the Brie sample was also demonstrated to possess significant proportion of Hafnia spp. This was corroborated in culture-based analysis where Hafnia isolates were also identified. Furthermore, we report on the motility phenotype, lactose utilization ability and metabolic products of isolates of Hafnia paralvei and Hafnia alvei, and determine that these strains could grow in a non-antagonistic manner on plates with strains of Lactococcus lactis and Streptococcus thermophilus. As artisanal and farmhouse production systems are often associated with protected or regionally significant products, it is essential to develop a clear understanding of the microbial communities within and the complex relationships between the community members. Full article

The common metabolic disorder, lactose intolerance, is often treated with oral lactase enzyme supplements, which can frequently cause gastrointestinal instability. This work utilizes Malbranchea cinnamomea’s AA9 lytic polysaccharide monooxygenase (LPMO) to target β-lactose (β-lactose) in an investigation of a new enzymatic approach for lactose breakdown. Potential possibilities for lactose breakdown are AA9 LPMOs, copper-dependent enzymes that oxidatively cleave glycosidic bonds in polysaccharides. We employed a combined in silico method that incorporated molecular docking, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. Docking studies revealed that β-lactose formed hydrogen bonds with key residues SER100, ASN54, and ARG56, exhibiting a greater binding affinity (−5.4 kcal/mol) toward LPMO compared to the control citric acid (−4.9 kcal/mol). Upon DFT analysis, (LPMO) showed excellent stability and appropriate reactivity for enzyme interaction. The higher stability of the LPMO-β-lactose complex was highlighted by MD simulation over 100 ns, which showed lower root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, greater structural compactness, and reduced solvent accessibility when compared to the control. These collective findings suggest that β-lactose interacts efficiently with the AA9 LPMO active site, supporting its potential as a novel enzymatic target for lactose degradation. This computational study provides a theoretical foundation for developing alternative therapeutic strategies for lactose intolerance, though further in vitro and in vivo investigations are required to validate these findings. Full article

Background: The Mediterranean diet (MedDiet) has been associated with anti-inflammatory effects and potential benefits in several chronic conditions. However, adherence to the MedDiet and its relationship with lifestyle factors and disease severity across different rheumatological diseases remain poorly characterized. Objectives: This study aimed to evaluate differences in MedDiet adherence among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and fibromyalgia (FM), and to explore its association with cardiovascular comorbidities, bowel habits, and disease-related outcomes. Methods: In this monocentric cross-sectional study, adherence to the MedDiet was assessed using the 14-item PREDIMED questionnaire. Self-reported data on sociodemographic characteristics, cardiovascular comorbidities, bowel habits, and dietary behaviors were collected through questionnaires. Disease activity and severity were assessed using validated disease-specific measures. Differences in MedDiet adherence across diagnostic groups were evaluated using non-parametric tests. Multivariable models were performed to examine associations between MedDiet adherence and cardiovascular comorbidities or disease outcomes, adjusting for potential confounders including age, sex, BMI, smoking status, and educational level. Results: A total of 422 participants were included (RA n = 165, PsA n = 85, FM n = 172). Significant differences in MedDiet adherence were observed across diagnostic groups (p < 0.001), with the highest adherence in RA, intermediate values in PsA, and the lowest in FM. Compared with the other groups, a higher proportion of FM participants reported food intolerances (46.5%) and restrictive diets, including lactose-free (34.9%) and gluten-free (15.1%) diets. In the FM group, high adherence to the MedDiet was significantly associated with lower FIQR scores (β = −16.9; 95% CI −32.1 to −1.7; p = 0.01) and lower PDS scores (β = −4.34; 95% CI −7.81 to −0.86; p = 0.01). Sensitivity analyses using the continuous PREDIMED score confirmed these associations. Conclusions: Adherence to the MedDiet differs across rheumatological diseases, with the lowest adherence observed in FM. Higher adherence was associated with lower disease severity and impact in FM. These findings highlight the potential relevance of nutritional counselling in rheumatological diseases and support the need for longitudinal and interventional studies evaluating the role of the MedDiet within multidisciplinary disease management. Full article

Diet is a major modifiable determinant of gastrointestinal (GI) health, influencing disease risk and progression through coordinated effects on the gut microbiome, immune regulation, epithelial barrier integrity, oxidative balance, and epigenetic mechanisms. This narrative review synthesizes epidemiological, mechanistic, and clinical evidence from the past decade to examine bidirectional relationships between dietary patterns and seven common GI disorders: celiac disease, irritable bowel syndrome (IBS), Crohn’s disease, ulcerative colitis, Helicobacter pylori-associated gastritis, peptic ulcer disease, and lactose intolerance. Western dietary patterns, characterized by high intake of ultra-processed foods and saturated fats and low fiber consumption, are consistently associated with microbial dysbiosis, impaired barrier function, and enhanced inflammatory signaling. In contrast, Mediterranean and plant-forward dietary patterns show protective associations across multiple GI conditions. Mechanistically, diet influences GI pathophysiology largely through microbiome-derived metabolites, particularly short-chain fatty acids, which regulate epithelial homeostasis, immune tolerance, and inflammatory pathways. Condition-specific dietary strategies remain clinically important. Gluten exclusion is essential in celiac disease, low- fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) approaches provide evidence-based symptom control in IBS, and exclusive enteral nutrition or targeted exclusion diets support remission induction in Crohn’s disease. Selected probiotics and emerging postbiotics may provide adjunctive benefits in specific contexts. Despite growing evidence, dietary research remains limited by methodological heterogeneity and interindividual variability. Precision nutrition approaches integrating microbiome profiling and artificial intelligence represent a promising translational direction. Overall, dietary patterns—rather than isolated nutrients—form the foundation of GI dietary therapy. Full article

Colostrum is the primary source of nutrients for newborn piglets, significantly influencing their growth, health and survival. This study examines the relationship between sow litter weight gain and the fatty acid composition of colostrum, including crude protein, lactose, calculated gross energy and total solids. The n-6:n-3 fatty acid ratio was higher in low-performing sows (p < 0.05), suggesting that a lower ratio, associated with higher n-3 fatty acid content, may positively impact litter weight gain. Specific fatty acids such as myristic acid (C14:0), pentadecanoic acid (C15:0), palmitic acid (C16:0), palmitoleic acid (C16:1), margaric acid (C17:0), elaidic acid (C18:1n9t), linoleic acid (C18:2n6c), α-linolenic acid (C18:3n3), behenic acid (C22:0), docosadienoic acid (C22:2) and eicosapentaenoic acid (C20:5n3) were also found in lower concentrations in the colostrum of low-performing sows (p < 0.05). The study suggests that the content of n-3 fatty acids and perhaps the n-6:n-3 ratio of the colostrum and the content of some special fatty acids could serve as a selection criterion for improving litter performance in the future. Full article

The rising demand for plant-based, lactose-free functional beverages amid gut health concerns positions finger millet (FM, Eleusine coracana) as a promising substrate. This study assessed sprouting and fermentation inoculum effect: dairy starters (Streptococcus thermophilus and Lactobacillus bulgaricus) or backslopping with commercial Mageu on microbial growth, fermentation dynamics, nutrition, antioxidants, color, and texture of FM beverages. Microbial growth increased modestly over 48 h OD₆₀₀ = 0.169–0.201, peaking in non-sprouted FM with dairy starters (ND) at OD600 = 0.201). ND showed the fastest pH decline (ΔpH = 2.19), while sprouted FM with dairy starters (SD) or backslopping (SB) had controlled acidification. Total titratable acidity increased from 0.14 to 0.66%, with the highest total soluble solids in sprouted substrates (SD = 11.26 °Brix; SB = 10.97 °Brix). Proximate analysis revealed SB had high crude fiber (2.86%) and SD highest protein (4.02%). Sprouted beverages excelled in minerals (SB Ca = 27.00 mg/100 g; SD Ca = 25.75 mg/100 g), while ND or non-sprouted FM fermented spontaneously (NS) had high Fe (4.31%, 2.65%) and K (48.08%, 38.32%). ND showed peak antioxidants: phenolics 10.54 µg/mL, DPPH 87.80%, FRAP 21.24 µM Fe²⁺/g, ABTS 79.09%. Sprouted beverages displayed distinct color (L* = 37.67–39.65, C* = 25.94–27.03) versus commercial Mageu (L* = 57.89, C* = 14.50) and favorable texture (firmness 12.78–13.40 g, secondary peak force ~−7.2 g). Controlled fermentation of sprouted FM yields nutrient-dense, antioxidant-rich, vegetarian beverages with superior attributes, affirming its functional potential. Full article

The present study evaluated the effects of sugarcane-derived polyphenol nutritional supplement on milk production, milk composition, and somatic cell count (SCC) in lactating Holstein cows. A second objective was to evaluate the quality and stability of yogurt produced with milk from supplemented cows. Sixteen cows (20 ± 2 L/d milk, 120 ± 21 days in milk, 550 ± 82 kg body weight) were assigned to either a control group or a polyphenol-supplemented group in a randomized block design for a six-week evaluation period. Milk yield and individual milk samples for composition analysis (fat, protein, lactose, non-fat solids, casein, free fatty acids, and milk urea nitrogen) were recorded weekly, and only SCC was monitored three times per week. Yogurt was produced from pooled milk of each treatment and evaluated for fermentation parameters (pH, titratable acidity), shelf life, and sensory attributes were evaluated using a triangle test (discriminative sensory analysis). Polyphenol supplementation did not significantly affect milk yield or composition (p > 0.05), but reduced SCC considerably (238 × 10³ vs. 593 × 10³ cells/mL; p < 0.01). Yogurt fermentation and storage parameters were not significantly affected by supplementation, although pH and titratable acidity changed considerably over time (p < 0.01). Sensory analysis indicated that only 37.3% of panelists correctly identified differences between yogurts, which did not differ from chance expectation in the triangle test. These results demonstrate that polyphenol supplementation can improve udder health, evidenced by reduced SCC, without compromising milk yield, composition, or yogurt quality. Polyphenols thus represent a promising nutritional supplement for enhancing dairy cow health and maintaining product quality. Full article

Different groups of microorganisms—namely lactic acid bacteria (LAB), coagulase-negative staphylococci (CNS), dairy propionibacteria, yeasts, and molds—play essential roles in producing safe fermented foods of animal and plant origin with high nutritional value and sensory quality. The acquisition of genetic traits with technological relevance by natural horizontal gene transfer (HGT) via transformation, conjugation, phage transduction, and other routes would broaden the spectrum of beneficial activities exerted by individual microbial strains with no limitations for their use in food. Therefore, this critical review aimed to identify the potential for natural genetic improvement of microbial species relevant to food technology, based on reports of natural genetic exchanges occurring in environmental niches and laboratory conditions. Results showed that the species most frequently involved in natural HGT is Lactiplantibacillus plantarum, followed by Streptococcus thermophilus and Lactococcus lactis. Extensive HGT events enabling adaptation to food have been observed in domesticated filamentous fungi. The transferred traits of technological relevance include resistance to various stress factors, exopolysaccharide (EPS) and bacteriocin production, protein and amino acid utilization, phage immunity, lactose and citrate metabolism in dairy species, and use of plant carbohydrates in vegetable adapted species. Methods suitable for detecting HGT events in microbial communities have been developed and can aid in isolating improved strains for use in fermented foods. Full article

This study was aimed at producing galactooligosaccharides (GOS) from Porungo cheese whey in immobilized enzyme bioreactors. The β-galactosidase was produced, concentrated, and immobilized on chitosan–genipin supports. Initially, GOS production was conducted in conical flasks, investigating three different variables: enzyme concentration (50–150 U/mL), Porungo cheese whey concentration (200–400 g/L), and temperature (37–43 °C). The highest GOS yields (15.24%) occurred under intermediate process conditions (100 U/mL, 300 g/L, 40 °C), reaching a GOS concentration of 27.04 g/L. These conditions were then used in a packed-bed column bioreactor operated in batch mode, achieving yields of 19.72%. Repeated batches were carried out, and the system was stable until the fifth cycle, with enzyme activity remaining at 83.56% of the initial level. Continuous bioreactors were conducted, varying feed flow rates (1–3 mL/h), with the highest yields and lactose conversion occurring for the longest residence time (24.63% and 68.38%), respectively, with high GOS concentration (44.14 g/L). Microorganisms isolated from Porungo cheese showed the ability to metabolize the GOS produced, demonstrating its prebiotic potential. This work can contribute to optimizing the production of GOS, an important product for pharmaceuticals and food industries. Full article

Background/Objectives: Clonazepam (CLZ), a BCS Class II drug, presents significant oral delivery challenges due to its low aqueous solubility. This study explores the systematic development of solid self-emulsifying drug delivery systems (S-SEDDS) using Quality by Design (QbD). The primary objective was to evaluate and compare advanced mathematical optimization frameworks, specifically Derringer’s Desirability Function (D) and Weighted Goal Programming (WGP), to identify a robust formulation that enhances drug solubilization while ensuring superior processability and flowability. Methods: Liquid SEDDS were solidified by adsorption onto a porous matrix (Aerosil^® 200/Lactose). A multi-objective optimization was conducted to define a robust Design Space (DS), comparing D against WGP. The trade-offs between competing Critical Quality Attributes (CQAs), specifically powder flowability (angle of repose, AR), blending efficiency (BE), and CLZ recovery (CR), were evaluated. Characterization included morphology from Environmental Scanning Electron Microscopy (ESEM), droplet size analysis, and pH-dependent dissolution studies. Results: D provided a highly robust baseline, yielding constant optimal coordinates (F2, F3 = +1; F4 = 0) across all sensitivity levels, with a predicted AR of 40.46°, BE of 0.12 and CR of 90.0%. However, WGP successfully refined this solution by allowing a more flexible weighting of goals, achieving a more favorable compromise with an AR of 38.96°, a BE of 0.11, and a CR of 90.23%. The optimized system maintained nanometric droplet sizes (<200 nm) and showed a controlled, pH-independent release profile, reaching 80% drug solubilization at 6 h. Conclusions: Integrating WGP into the QbD framework offers a more versatile and precise optimization than the traditional D for complex pharmaceutical systems. This approach ensures the production of high-quality S-SEDDS, bridging the gap between mathematical modeling and the stringent requirements of industrial solid dosage manufacturing. Full article

The integrated valorization of whey into multifunctional food ingredients is constrained by sequential processing routes and the need for purified lactose and protein fractions. The simultaneous enzymatic conversion of lactose and whey proteins in a single reactor remains underexplored despite the frequent co-formulation of galacto-oligosaccharides (GOS) and whey protein hydrolysates in functional foods. This study evaluated the feasibility of a one-pot enzymatic system using native whey as the sole substrate for the concurrent production of GOS and antioxidant peptide fractions. A batch process combining β-galactosidase from Aspergillus oryzae and Alcalase^® was assessed through a 3² factorial design, analyzing the effects of pH (4.5–6.5) and temperature (40–60 °C) on GOS yield and degree of protein hydrolysis. The system enabled simultaneous transgalactosylation and proteolysis under mildly acidic conditions without significant mutual enzyme inhibition. Multi-response optimization identified pH 6.0 and 59.5 °C as the optimal conditions, yielding 25.7 ± 0.2% GOSs and 10.5 ± 0.3% protein hydrolysis. The antioxidant capacity and emulsifying and foaming properties were strongly dependent on pH, temperature, and reaction time. The results demonstrate that native whey can be directly transformed into a multifunctional ingredient through a one-pot enzymatic strategy, offering a simplified valorization approach. Full article

Alleviating negative energy balance in perinatal yaks is a critical challenge for safeguarding the health of both dams and calves and achieving sustainable development of yak husbandry. While RPG supplementation represents an effective nutritional strategy, its transgenerational benefits, particularly the long-term effects on offspring calf development through maternal intervention, remain largely unexplored. In the present study, low-dose RPG (150 g d⁻¹, L-RPG, n = 6) markedly improved milk composition, elevating protein, fat, lactose, and gross energy contents (p < 0.05), and enhance calf weight gain (21.74%) with activation of the somatotropic axis (increased GH, IGF-1, etc.). Calves in this group also exhibited enhanced antioxidant capacity (higher SOD, CAT, and T-AOC) and improved immune regulation (lower IL-6, TNF-α). Multi-omics analyses revealed that L-RPG enriched beneficial taxa such as Solbacillus, Citricoccus, and Akkermansia muciniphila, optimized the hindgut microbiome, and upregulated serum metabolites including di-O-methylfraxetin and phenylalanyl-histidine. Integrated microbiota–metabolite profiling demonstrated significant cross-talk between the altered bacteria and metabolites. Collectively, supplementing dams with 150 g d⁻¹ RPG improves milk quality, modulates the calf gut microbiota, and reshapes host metabolism, thereby synergistically promoting offspring growth. Our findings provide a comprehensive “maternal nutrition–microbiota–metabolism” framework for understanding RPG’s mode of action and furnish both theoretical insights and practical guidance for dam–calf health management in yak production systems. Full article