Search Results (10,431)

Acrylamide is a heat-induced food contaminant that can be formed through the Maillard reaction between reducing sugars and asparagine in carbohydrate-rich foods. It is recognized as having carcinogenic, neurotoxic, and reproductive risks, prompting global regulatory and research attention. This review synthesizes recent advances (2013–2025) in understanding acrylamide’s formation mechanisms, detection methods, mitigation strategies, and health implications. Analytical innovations such as LC–MS/MS have enabled detection at trace levels (≤10 µg/kg), supporting process optimization and compliance monitoring. Effective mitigation strategies combine cooking adjustments, ingredient reformulation, and novel technologies, including vacuum frying, ohmic heating, and predictive modeling, which can achieve up to a 70% reduction in certain food categories. Dietary polyphenols and fibers also hold promise, lowering acrylamide formation and bioavailability through carbonyl trapping and enhanced detoxification. However, significant gaps remain in bioavailability assessment, analysis of metabolic fate (glycidamide conversion), and standardized global monitoring. This review emphasizes that a sustainable reduction in dietary acrylamide requires a multidisciplinary framework integrating mechanistic modeling, green processing, regulatory oversight, and consumer education. Bridging science, industry, and policy is essential to ensure safer food systems and minimize long-term public health risks. Full article

Iron is an essential nutrient for piglets, but iron sources vary greatly in bioavailability, and their effects on intestinal health remain unclear. In this study, 21-day-old weaned piglets were used to compare the effects of different iron sources (ferrous sulfate (FeSO₄), ferric ammonium citrate (FAC), and ferrous glycinate (Fe-Gly)) on growth performance, intestinal inflammation, and gut microbiota. Compared to the FeSO₄ group, the Fe-Gly group significantly increased the body weight of piglets at 35 days (p < 0.05), promoted the average daily feed intake (ADFI) and average daily gain (ADG) of piglets from day 21 to 35 (p < 0.01), and also markedly reduced the diarrhea rate of piglets (p < 0.01). Meanwhile, although FAC increased growth performance-related indicators (ADG, ADFI) in piglets, there was no significant statistical difference compared with FeSO₄ (p > 0.10). Moreover, Fe-Gly supplementation significantly elevated serum iron levels and total iron-binding capacity (p < 0.01), while significantly reducing the iron content in colonic chyme (p < 0.0001). Both the Fe-Gly and FAC significantly improved the anti-inflammatory and antioxidant capacities of the piglets (p < 0.01). Interestingly, Fe-Gly primarily increased the abundance of Lactobacillus, thereby reducing the abundance of harmful bacteria such as Escherichia coli. Functional prediction using PICRUSt2 revealed that Fe-Gly supplementation tended to elevate the relative abundance of gut bacteria capable of carbohydrate metabolism and amino acid synthesis. In conclusion, this study demonstrated that dietary Fe-Gly supplementation improved systemic iron status, effectively reduce residual iron in the intestine, inhibit the proliferation of pathogenic bacteria in the gut, promote the growth performance and intestinal health of piglets, and reduce the diarrhea rate. Full article

Punicalagin, the major polyphenol in pomegranate peel, shows broad bioactivity but suffers from poor oral bioavailability. Whether hepatic or intestinal first-pass processes dominate this limitation remains unresolved. We developed a quantitative UPLC-MS/MS workflow to dissect punicalagin’s first-pass disposition and elimination in rats. Sprague–Dawley rats received punicalagin by intravenous, portal vein, oral, or intraduodenal dosing; plasma exposure was quantified by UPLC-MS/MS and analyzed noncompartmentally. We also profiled urinary and fecal excretion of punicalagin and key metabolites (punicalin, ellagic acid, urolithin C and urolithin A) to define biotransformation and clearance. Punicalagin displayed an absolute oral bioavailability of ~3.49%. First-pass analysis revealed modest hepatic extraction (~13.94%) but near-complete intestinal extraction (95.95%), identifying intestinal first-pass metabolism as the dominant barrier to systemic exposure. Consistently, parent and metabolites were eliminated mainly in feces, whereas urine contained only trace conjugated urolithin A. Collectively, these findings demonstrate that the poor oral bioavailability of punicalagin is driven primarily by extensive intestinal first-pass metabolism rather than hepatic clearance, and that its feces-dominant elimination is compatible with widespread hydrolysis and microbiota-mediated conversion within the gut. This work provides a pharmacokinetic framework to guide strategies aimed at improving oral delivery and systemic exposure of punicalagin. Full article

Cadmium (Cd) contamination in agricultural systems poses significant ecotoxicological risks through bioaccumulation in food chains. While lime-based amendments are widely applied for Cd immobilization, mechanistic understanding of bioavailability control pathways remains limited. This study employed a meta-analysis methodology based on 260 datasets from 55 publications to systematically investigate the mechanisms and differences in the effectiveness of calcium hydroxide, calcium carbonate, and calcium oxide in regulating Cd migration in acidic soil–plant systems. The study revealed that lime-based materials synergistically regulated Cd migration through two processes: chemical fixation and ionic competition. Results showed lime application reduced soil available Cd by 33.0%, decreased grain Cd by 44.8%, increased soil pH by 15.6%, and enhanced exchangeable Ca by 35.2%. Chemical fixation was evidenced by Cd transformation from labile to stable forms (residual Cd: +29.5%, acid-soluble Cd: −17.5%). Ionic competition was quantitatively confirmed through strong negative correlation between exchangeable Ca and grain Cd (R² = 0.704). Among the materials, Ca(OH)₂ exhibits the highest efficiency in rapid pedogenic passivation (58.7% reduction in available Cd), whereas CaCO₃ demonstrates superior long-term grain Cd attenuation (65.7% inhibition) via sustained Ca²⁺ release and rhizosphere-regulated dissolution. This study advances mechanistic understanding of Cd bioavailability control and establishes quantitative frameworks for predicting ecotoxicological outcomes, providing scientific basis for optimizing remediation strategies to minimize Cd transfer through agricultural food chains. Full article

Dissolved organic matter (DOM) in salt lake brines comprises organic compounds dissolved in high-salinity aquatic systems. With complex composition and diverse sources, DOM significantly influences biogeochemical cycles, mineral formation, and resource development in salt lakes. However, few studies have investigated the characteristics and sources of DOM in salt lake brines. In this study, a DOM sample (YC-4) from brine of Shanxi Yuncheng Salt Lake was isolated and characterized using FT-ICR-MS, nuclear magnetic resonance spectroscopy, three-dimensional fluorescence spectroscopy, and parallel factor analysis. The results demonstrate that YC-4 DOM exhibits rich chemical diversity, primarily composed of lignin/CRAM-like compounds (54.26%), tannins (16.75%) and proteins (13.43%). The predominant carbon forms in YC-4 DOM were aliphatic C-O bonded compounds (33.74%), aliphatic compounds (24.31%), and carboxylic acid compounds (23.95%). YC-4 DOM consists of five fluorescent components: marine-like humic substances, two types of humic-like substances, fulvic-like substances, and one protein-like substance. The fluorescence signature, characterized by high fluorescence index (FI 1.99), low humification index (HIX 0.66), and high biological index (BIX 1.27), collectively indicates that the DOM in Yuncheng Salt Lake brine is predominantly autochthonous, weakly humified, and highly bioavailable. This study reveals the DOM feature within the “human–environment coupled system” of Yuncheng Salt Lake. The findings provide a scientific basis for the sustainable utilization of its brine DOM resources and further enrich the theoretical system of DOM biogeochemical cycle in high-salinity lake system. Full article

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit. Full article

Breast cancer is the most prevalent form of cancer among women globally. The hypoxic microenvironment resulting from the rapid oxygen consumption of rapidly dividing cancer cells causes the accumulation of hypoxia-inducible factor-1α (HIF-1α) due to reduced catalytic activity of prolyl hydroxylase domain 2 (PHD2) and Von Hippel-Lindau (VHL). Under physiological conditions, HIF-1α regulates cell response to hypoxic environments. Activating genes are involved in glycolysis, angiogenesis, and erythropoiesis. However, the sustained hypoxic environment in breast cancer facilitates metastasis, immune evasion, and drug resistance. Consequently, HIF-1α is a key target in breast cancer treatment, and such inhibitors of HIF-1α may prove to be a viable treatment option. Increasing evidence suggests that natural chemicals, such as polyphenols, isothiocyanates, curcumin, and alkaloids, are inhibitors of HIF-1α. Preclinical studies using animal models and breast cancer cell lines indicate significant reductions in angiogenesis, despite challenges of heterogeneity, bioavailability, and dose optimization. This review intends to summarize current evidence on natural inhibitors of HIF-1α and potential future studies. Full article

One of the main challenges facing the pharmaceutical industry today is the low solubility of active pharmaceutical ingredients (APIs), which leads to low bioavailability, reduced therapeutic efficacy, and the need for higher drug doses. Eutectic solvents (ES) offer a promising solution by effectively dissolving APIs, creating API-ES systems that can significantly improve drug solubility and delivery. In this study, three distinct ESs were prepared by combining various components, with their successful formation confirmed through Fourier Transform Infrared Spectroscopy. Key physicochemical properties, including the density, viscosity, and pH of the prepared solvents, were subsequently determined. Ceritinib (CRT), an API utilized in the treatment of non-small cell lung cancer, was then incorporated into the prepared ESs to yield the API-ES systems. A comparative analysis was conducted to assess the release profiles of pure CRT versus CRT within the API-ES systems. Furthermore, the permeability and diffusion coefficient of the drug within these systems were also determined. The results conclusively demonstrated that the formation of the API-ES system increased the solubility of CRT in water. This achievement represents a vital initial step toward optimizing the delivery of this drug and highlights the significant potential for developing a novel, improved pharmaceutical formulation. Full article

Natural products have an invaluable therapeutic effect on human health. Natural antioxidants, including beta-carotene, turmeric, and polyphenols, are recognised for their health benefits but face significant barriers related to insufficient solubility, instability, volatility, and diminished bioavailability, which limit their therapeutic efficacy in drug delivery systems. Therefore, encapsulation of natural products in a carrier addresses the above concern. Drug delivery systems, such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), are promising carriers for effective release, consisting of solid and liquid lipids, which enhance efficiency, stability, and controlled release, thereby minimising bioavailability limitations. This review consolidates current studies on the formulation methodologies, mechanisms of action, and therapeutic applications of NLCs, emphasizing their use in the treatment of conditions such as cancer, neurological disorders, and cardiovascular diseases. The results demonstrate that NLCs substantially enhance the bioavailability and therapeutic efficacy of antioxidants, thereby improving their targeted administration and clinical effects. Nonetheless, difficulties in clinical translation remain, including drug loading capacity, regulatory authorisation, and the need for pervasive research on cytotoxicity. This article highlights important areas for future inquiry, specifically the optimisation of NLC formulations, the enhancement of targeting accuracy, and the resolution of safety issues to enhance their clinical application. Full article

New arylbenzofuran derivatives were designed, synthesized, and evaluated as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Five hybrid compounds (31–35) feature a 2-phenylbenzofuran core linked via a heptyloxy spacer to an N-methylbenzylamine moiety, to enhance interactions within the active site of BChE. Biological evaluation revealed that brominated derivatives 34 and 35 showed the highest cholinesterases (ChE) inhibition compared to their chlorinated analogs, with compound 34 showing the highest activity for both AChE (IC₅₀ = 27.7 μM) and BChE (IC₅₀ = 0.7 μM). These compounds proved to be non-cytotoxic and demonstrated significant antioxidant activity in SH-SY5Y cells exposed to hydrogen peroxide (H₂O₂), highlighting their potential to mitigate oxidative stress: a key pathological factor in Alzheimer’s disease. Structural activity analysis suggests that bromine substitution at position 7 and the presence of a seven-carbon linker are critical for dual ChE inhibition and selectivity towards BChE. ADMET prediction indicates favorable pharmacokinetic properties, including drug-likeness and oral bioavailability. Overall, these findings highlight the potential of the 2-arylbenzofuran as a promising scaffold for multitarget-directed ligands in Alzheimer’s disease therapy. Full article

Enzyme technology, characterized by high efficiency, environmental compatibility, and precise controllability, has become a pivotal biocatalytic approach for quality enhancement and nutritional improvement in modern food industries. This review summarizes recent advances and underlying mechanisms of enzyme applications in food processing optimization, nutritional enhancement, and functional food development. In terms of process optimization, enzymes such as transglutaminase, laccase, and peroxidase enhance protein crosslinking, thereby markedly improving the texture and stability of dairy products, meat products, and plant-based protein systems. Proteases and lipases play essential roles in flavor development, maturation, and modulation of sensory attributes. From a nutritional perspective, enzymatic hydrolysis significantly improves the bioavailability of proteins, minerals, and dietary fibers, while simultaneously degrading antinutritional factors and harmful compounds, including phytic acid, tannins, food allergens, and acrylamide, thus contributing to improved food safety and nutritional balance. With respect to functional innovation, enzyme-directed production of bioactive peptides has demonstrated notable antihypertensive, antioxidant, and immunomodulatory activities. In addition, enzymatic synthesis of functional oligosaccharides and rare sugars, glycosylation-based modification of polyphenols, and enzyme-assisted extraction of plant bioactive compounds provide novel strategies and technological support for the development of functional foods. Owing to their high specificity and eco-friendly nature, enzyme technologies are driving food and nutrition sciences toward more precise, personalized, and sustainable development pathways. Despite these advances, critical research gaps remain, particularly in the limited mechanistic understanding of enzyme behavior in complex food matrices, the insufficient integration of multi-omics data with enzymatic process design, and the challenges associated with translating laboratory-scale enzymatic strategies into robust, data-driven, and scalable industrial applications. Full article

Doxorubicin (DOX), a widely used chemotherapeutic, is constrained by its nephrotoxicity, characterized by endothelial injury, inflammation, and oxidative stress. Vascular endothelial growth factor (VEGF) signaling in the kidney serves a dual function. Under normal conditions, it supports the survival of glomerular endothelial cells and maintains vascular stability, but when excessively activated, it disrupts angiogenesis and contributes to kidney injury. In this context, we hypothesize that Nanocurcumin (CUR-NP), a nano-formulated curcumin derivative with enhanced bioavailability, can modulate the VEGF pathway and restore regular renal activity. Thus, this study aims to explore the potential protective effect of CUR-NP on DOX-induced renal injury in male rats. Thirty-two Wistar albino rats were used and distributed into four groups. CUR-NP (80 mg/kg dissolved in 1% CMC) was administered by oral gavage for two weeks. A single dose of DOX (15 mg/kg) (i.p.) was injected on day seven of the study. Results showed that DOX increased the circulating creatinine, urea, and urea-nitrogen levels, while pretreatment with CUR-NP markedly alleviated kidney function. In addition, CUR-NP treatment significantly normalized oxidative stress markers in renal tissues, such as NO, GSH, and SOD, and improved renal pro-inflammatory mediators, TNF-α, IL-6, and NF-κB-p65. DOX caused degeneration of glomeruli and tubules with degenerated epithelial lining and casts in their lumens. Conversely, CUR-NP maintained standard tubular and glomerular structure. Immunohistochemistry showed that DOX strongly upregulated VEGF and AhR, while CUR-NP markedly reduced their expression, countering VEGF/AhR pathway disruption and helping restore physiological signaling. Full article

Dihydroartemisinin (DHA), a first-line treatment for uncomplicated malaria, has demonstrated antitumor activity against a variety of human cancers, emphasizing its potential for repurposing as an anticancer agent. However, its short half-life and poor bioavailability hinder its application in cancer therapy. We previously demonstrated that the molecular hybridization of DHA with bile acids (BAs) enhances its anticancer activity by improving stability and reducing toxicity. Based on this rationale, here, we designed and synthesized a library of DHA-based hybrids through conjugation with ursodeoxycholic and chenodeoxycholic bile acids. Different conjugation sites and both cleavable and non-cleavable linkages were explored to enable a comprehensive structure–activity relationship analysis. The resulting BA-DHA hybrids were evaluated in vitro for their anticancer activity against HCT116 and RKO colorectal cancer cell lines. As a result of the synergistic effect of the linker type and conjugation site, the BA-DHA hybrids synthesized via click chemistry emerged as the most active compounds in both cell lines, displaying 2- to 20-fold higher activity than the parent DHA. Mechanistic investigations further revealed that the click-derived BA-DHA hybrids possess enhanced anticancer activity and antimetastatic potential, achieving comparable or even superior efficacy to the parent compound at markedly lower concentrations. Full article

The present study reports the design and physicochemical characterization of a hybrid nanoparticle system for the potential intranasal delivery of galantamine (GAL), aimed at improving its bioavailability. Carbon dots (CDs) were used to load GAL, enhancing its dissolution and stability, and were subsequently incorporated into a poly(lactic-co-glycolic acid)–curcumin (PLGA–Cur) conjugate matrix. The successful formation of the PLGA-Cur conjugate was verified via ¹H-NMR and FTIR spectroscopy, while the loading of GAL and its physical state in the CDs was assessed via FTIR and pXRD, respectively. The resulting GAL-CD/PLGA–Cur nanoparticles were spherical, with particle sizes varying from 153.7 nm to 256.3 nm, a uniform morphology and a narrow size distribution. In vitro release studies demonstrated a multi-phase sustained release pattern extending up to 12 days. Spectroscopic and thermal analyses confirmed successful conjugation and molecular interactions between GAL and the carrier matrix. This proof-of-concept hybrid system demonstrates promising controlled, multi-phase sustained galantamine release in vitro, highlighting the role of curcumin conjugation in modulating polymer structure and release kinetics and providing a foundation for future biological evaluation. Full article

Chromium (Cr) is a highly toxic heavy metal, yet its effects on soil invertebrates—particularly Caenorhabditis elegans (C. elegans)—remain insufficiently understood, especially regarding how soil properties and Cr speciation change regulate its bioavailability and toxicity. In this study, the toxicity of Cr(VI) to the growth, fertility, and reproduction of C. elegans was assessed in six representative agricultural soils following 7, 60, and 120 days of spiked soil aging, following ISO 10872 guidelines. Substantial differences in toxicity were observed among soils after 7 days of aging, with toxicity ranking from low to high as black soil < yellowish-red soil < red soil < yellow–brown soil < fluvo-aquic soil < purple soil. After 60 days of aging, Cr(VI) toxicity decreased markedly, with EC₅₀ values for growth, fertility, and reproduction increasing by 1.04–2.32, 1.04–2.34, and 1.40–2.20 times, respectively. Organic matter (OM) and amorphous aluminum oxides (Al_AO) were identified as the principal soil properties that were significantly correlated with Cr(VI) toxicity and were useful for explaining and estimating toxicity thresholds within the range of soils examined in this study. In addition, the magnitude of the aging effect showed significant positive correlations with both amorphous aluminum oxides (Al_AO) and total aluminum (Al_total), suggesting that Al-bearing minerals may contribute to the time-dependent immobilization of Cr(VI) under the experimental conditions of this study. These findings expand the ecotoxicological database for chromium, improve the prediction of toxicity thresholds under diverse soil conditions, and provide a scientific basis for refining soil environmental quality standards and developing targeted management strategies for Cr-contaminated agricultural soils. Full article