Search Results (1,087)

Fresh pork remains susceptible to psychrotrophic spoilage during superchilled storage. Although oregano essential oil (OEO), nisin, and active absorbent pads have each been studied, their effects on spoilage-community proliferation and concurrent quality loss remain poorly resolved. Here, we coupled longitudinal 16S rRNA gene profiling with conventional microbiological and quality measurements to evaluate a poly(vinyl alcohol)/soy protein isolate pad containing OEO-loaded soluble soybean polysaccharide-nisin nanoparticles (PS-NPs). Pork was stored at −1 °C for 24 days without a pad (CK), with a nanoparticle-free pad (PS), or with PS-NPs. Bacterial communities in CK and PS-NPs were profiled alongside total viable count, TVB-N, TBARS, protein carbonyls, color, water-holding capacity, and sensory quality. Compared with CK, PS-NPs slowed the increase in viable counts and delayed physicochemical and sensory deterioration. On day 24, Pseudomonas relative abundance was 39.48% with PS-NPs and 51.02% in CK. TBARS and protein carbonyl contents were 36.96% and 19.44% lower than CK, respectively, while cooking loss was 28.49% versus 32.18%. Among the evaluated taxon-quality pairs, Pseudomonas psychrophila showed the strongest positive association with protein carbonyl content. Unlike earlier performance-focused studies, this work links packaging-associated community shifts with concurrent chemical, physical, and sensory changes under superchilling. The findings support PS-NPs as a preservation strategy. Full article

Inflammasomes are central mediators of innate immune defense but can also drive pathological inflammation and pyroptotic cell death in numerous diseases. While several small-molecule inhibitors have been described, many selectively target individual inflammasomes or act through the adaptor protein ASC, leaving ASC-independent pathways unaffected. We previously identified thiomuscimol as a broad-spectrum inflammasome inhibitor that blocks both ASC-dependent and ASC-independent activation, although the structural basis for this activity remains unclear. Here, we examined the structure–activity relationship of thiomuscimol using related compounds and synthetic analogs. In primary macrophages, inflammasome activation and pyroptosis were assessed by live cell imaging of ASC speck formation, gasdermin D-mediated dye uptake, and cellular ATP levels. Structurally related sulfur-containing molecules, including taurine and isothiazole, failed to inhibit inflammasome activation, indicating that neither the sulfur in an electron-rich environment nor the heterocyclic scaffold confer activity. Replacement of the primary amine with a carbonyl group abolished activity, whereas substitution with a secondary amine preserved inhibitory potency comparable to thiomuscimol. Incorporation of the amine into an annulated piperidine ring reduced potency and revealed sensitivity to the precise positioning of the amine within the ring. Together, these findings identify key structural features required for thiomuscimol-mediated inflammasome inhibition and provide a framework for future studies to define its mechanism of action and guide the development of improved inhibitors. Full article

Background: Despite extensive development of liposomal antibiotics, the structural determinants governing their stability, release, and biological activity remain poorly understood. This study investigated how the cholesterol content and drug-to-lipid ratio affect membrane organization and thereby determine the physicochemical and biological properties of linezolid-loaded liposomes. Methods: Nine liposomal formulations, varying in their cholesterol content (10–30 wt%) and drug-to-lipid ratios (1–5%), were prepared by thin-film hydration. Membrane organization was analyzed by ATR-FTIR spectroscopy and principal component analysis. Liposomes were further characterized by particle size, ζ-potential, encapsulation efficiency, storage stability, in vitro release in phosphate buffer with and without bovine serum albumin, antibacterial activity against B. subtilis, and antimycobacterial activity in an ex vivo PBMC-derived Mycobacterium tuberculosis granuloma model. Results: The cholesterol content and drug-to-lipid ratio markedly altered membrane interfacial organization, particularly the hydration of the carbonyl and phosphate regions. These structural changes correlated with differences in storage stability, protein-responsive release, and antibacterial activity. Functional behavior was non-monotonic, as 30-L showed the highest overall storage stability, while the apparent release depended jointly on the cholesterol content, drug loading, and medium. BSA altered the composition-dependent release pattern instead of producing a uniform effect. In the exploratory granuloma model, the formulations 10-S, 10-L, and 30-M reduced M. tuberculosis CFU by >99%, whereas free linezolid produced approximately 60% inhibition. Conclusions: Membrane interfacial organization is a key determinant of the functional performance of liposomal linezolid, establishing a structure–property–function relationship that provides a mechanistic basis for the rational design of liposomal antibiotic delivery systems for tuberculosis therapy. Full article

Solanum elaeagnifolium has been utilized for its analgesic, anti-inflammatory, and antioxidant properties to treat a range of conditions, including pain and inflammation. It possesses antibacterial, insecticidal, and molluscicidal properties as well. To investigate the pharmacological potential of the S. elaeagnifolium extract, in vitro, in vivo, and in silico studies were used. Albumin denaturation, heat-induced anti-haemolytic action, and lipooxygenase inhibition were the three techniques used to test anti-inflammatory effectiveness. The phenolic chemicals utilized were identified through the use of high-performance liquid chromatography (HPLC). The effectiveness of the extract in lowering problems connected to diabetes was further evaluated by evaluating fructosamines, carbonyl groups, and β-amyloid formations in albumin glycation. Regarding in vivo studies, the Writhing test and the tail flick test were the two techniques used to evaluate analgesic activity. For docking analysis, we used the following identifiers: cyclooxygenase (PDB ID: 6COX), lipooxygenase (PDB ID: 3V99) and VC1 domain of the receptor for advanced glycation products (PDB ID: 7LMW). The most prevalent phenolic chemicals, according to HPLC analysis, were 3,4-dihydroxybenzoic acid (4.78%), caffeic acid (1.28%), gallic acid (8.18%), ursolic acid (2.6%), syringic acid (1.78%), quercetin (24.09%), catechin (6.67%), and p-coumaric acid (20.49%). Significant suppression of albumin glycation and fructosamine production was demonstrated by the extract, indicating that it may help lessen difficulties associated with diabetes. Furthermore, the extract demonstrated a strong anti-inflammatory impact, with an IC₅₀ of 146 ± 1.17 μg/mL for lipooxygenase inhibition, 87.64 ± 5.35 μg/mL for anti-haemolytic action, and 86.94 ± 1.63 μg/mL for albumin denaturation inhibition. A similar analgesic effect to those of analgesic medications was also demonstrated by SEFE extract. Reinforcing the relevance of the observed effects, the in silico study of the tested activities validated these findings. These findings indicate significant pharmacological promise in the management of diabetes consequences, including inflammation and protein glycation, as well as an analgesic. Full article

While Alzheimer’s disease (AD) is primarily considered a disorder of protein aggregation, converging evidence from clinical, neuropathological, and mechanistic studies strongly supports the notion that brain endothelial dysfunction is a primary and early event in AD pathogenesis. Brain endothelial pathways are among the most differentially expressed in human AD brains. Brain endothelial alterations precede amyloid deposition and cognitive deficits in experimental AD models and closely parallel the degree of neuronal loss in human AD brains. Despite growing evidence to support brain endothelial contributions to neurodegeneration, studies examining the potential of the brain endothelium as a druggable target in AD have been scarce. Further, there has been a relative paucity of validated fluid biomarkers that can reliably measure brain endothelial injury in AD, independently of overt vascular disease or disruption to other cerebrovascular constituents. In this perspective, we propose a brain endothelial glycocalyx-centric model of AD in which brain endothelial dysfunction, driven predominantly by non-enzymatic glycation and carbonyl stress, acts as a key upstream regulator of aberrant protein trafficking, blood–brain barrier instability, and dysregulated neuro-immune cascades. Further, recent evidence suggests the presence of direct interactions of the brain endothelium with key pathways involved in neuronal survival and synaptic signaling, highlighting potential direct contributions of brain endothelial disturbances to cognitive impairment. Within this framework, we identify several brain endothelial axes, including reduction in carbonyl stress, improved glycation-dependent signaling, attenuation of advanced glycation end-product (AGE)-mediated toxicity, and enhanced endothelial glycocalyx stability and resilience as potential therapeutic approaches in AD. Modulating brain endothelial glycation has potential as a novel therapeutic strategy in AD which may complement other disease-modifying treatments, particularly in the earliest preclinical stages. In conclusion, this framework positions the brain endothelium as a mechanistic hub linking metabolic stress to aberrant protein aggregation and neurodegeneration in AD with potential therapeutic implications in AD and other neurodegenerative disorders. Full article

Ulcerative colitis is characterized by inflammation, oxidative stress, and excessive free radical production. This study investigated the antioxidant, anti-inflammatory, and protective effects of N-acetylcysteine (NAC), Tiron, and their fixed-ratio combination in acetic acid-induced colitis. An integrated approach was used, combining ligand–ligand docking, acellular antioxidant and protein-denaturation assays, and an in vivo model in male Wistar rats. Colitis was induced by intrarectal administration of 3% acetic acid after 14 days of intraperitoneal pretreatment with NAC, Tiron, or NAC–Tiron. Docking analysis suggested physicochemical compatibility through non-covalent interactions. In vitro, NAC, Tiron, and their combination showed antioxidant and anti-denaturation activities. NAC–Tiron displayed greater activity than the individual compounds in selected endpoints, particularly 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, but did not consistently outperform them across the other assays. In vivo, NAC, Tiron, and NAC–Tiron attenuated macroscopic and histological colonic damage, reduced inflammatory cell infiltration and edema, decreased lipid peroxidation and protein carbonylation, and helped preserve superoxide dismutase (SOD) activity, reduced glutathione (GSH), and total thiols. The treatments also attenuated increases in C-reactive protein (CRP) and free iron without evident worsening of the measured systemic biochemical parameters. Overall, these findings provide an exploratory proof of concept for fixed-ratio NAC–Tiron co-administration but do not establish pharmacological synergy or superiority over standard therapies. Full article

This study investigated the effects of honeysuckle extract (HE) on the oxidative stability, storage quality, and myofibrillar protein functionality of raw rabbit meat during a 5-day storage period at 4 °C. Raw rabbit meat was treated with HE (1–7% w/v; HE1–HE7) or deionized water (control) and stored for 5 days. pH and color parameters were analyzed, lipid and protein oxidation profile of raw rabbit meat were investigated, and the physicochemical characteristics of rabbit myofibrillar protein (MP) were analyzed. Results showed that HE treatment significantly decreased the levels of TBARS, TVB-N and TVC compared to the control group. Further studies revealed that HE treatment significantly reduced the protein carbonyl level while increasing sulfhydryl content. In addition, HE treatment increased the WHC and solubility and reduced the surface hydrophobicity of rabbit MP during refrigerated storage. Taken together, HE serves as a potent natural preservative for raw rabbit meat, effectively suppressing oxidative and microbial deterioration to maintain storage quality and extend shelf life. Full article

Background/Objectives: Chronic complications of diabetes mellitus are closely associated with increased oxidative stress and the formation of advanced glycation end products (AGEs). This study aimed to investigate the antioxidant and antiglycation potential of hesperetin-7-O-glucoside (HCD) and diosmetin-7-O-glucoside (DCD) formulations complexed with cyclodextrins, using in vitro and in silico experimental models to evaluate their efficacy in mitigating hyperglycemia-induced molecular damage. Methods: Antioxidant activity was assessed using chemical and erythrocyte-based oxidative stress models, whereas antiglycation activity was evaluated in BSA–fructose, BSA–methylglyoxal, and arginine–methylglyoxal models. Results: Both formulations showed measurable antioxidant effects, with concentration-dependent behavior observed in some of the evaluated assays. In the DPPH assay, HCD and DCD achieved maximum inhibition values of 30.71% and 26.61%, respectively. Furthermore, DCD exhibited higher total antioxidant capacity (102.80 µg vitamin C equivalents/mL) and nitric oxide scavenging activity (37.89%) than HCD. In a cellular model, both formulations (200 µg/mL) significantly reduced AAPH-induced hemolysis, with DCD providing superior protection (7.05% vs. 16.63% for HCD). Under oxidative stress induced by high glucose concentration in erythrocytes, HCD and DCD reduced non-protein thiol levels, and HCD significantly increased catalase enzyme activity. Regarding antiglycation activity, DCD demonstrated superior efficacy relative to HCD in the BSA-fructose system, achieving 43.23% inhibition. DCD also displayed concentration-dependent inhibition of fructosamine formation (up to 47.99%) and BSA glycation by methylglyoxal (up to 45.20%). Both formulations significantly reduced carbonylated protein levels and preserved free thiol groups. In the arginine–methylglyoxal model, DCD and HCD reached 44.03% and 48.82% inhibition, respectively. Molecular docking revealed high binding affinity of both flavonoids to the protein active site (−9.00 kcal/mol for hesperetin-7-O-glucoside and −9.04 kcal/mol for diosmetin-7-O-glucoside), suggesting a structural protective role. Conclusions: The HCD and DCD formulations demonstrated antioxidant and antiglycation activities that may contribute to attenuating molecular alterations associated with chronic hyperglycemia through complementary mechanisms, including antioxidant effects, protection against protein carbonylation, and inhibition of glycation. While these findings highlight the potential of the evaluated formulations, additional mechanistic and in vivo studies are required to establish their pharmacological applicability. Full article

Mycotoxin contamination of cereal-based pig feeds is a persistent threat to swine health and global pork safety. Pigs are uniquely susceptible to mycotoxicosis, and the principal toxins—aflatoxins (AFs), deoxynivalenol (DON), zearalenone (ZEN), fumonisins (FUMs), and ochratoxin A (OTA)—cause impaired growth, reproductive failure, hepato- and nephrotoxicity, immunosuppression, and carry-over residues in edible tissue. Anti-mycotoxin feed additives, including mineral adsorbents, biotransforming agents, and multicomponent mycotoxin-detoxifying agents (MMDAs) combining clays, phytogenic antioxidants (curcumin, silymarin), and postbiotics (yeast cell wall, hydrolyzed yeast), constitute the primary mitigation strategy. Beyond animal health, these agents play underappreciated roles in both the circular economy (CE)—enabling safe valorization of by-product feed ingredients and reducing feed waste—and in the life cycle assessment (LCA) sustainability profile of pork production, where feed conversion ratio (FCR) drives 22–95% of greenhouse gas emissions. Field-based in vivo studies in sows and weaned piglets, integrating plasma oxidative stress biomarkers (TBARS, protein carbonyls, total antioxidant capacity) with performance and reproductive endpoints, provide the most comprehensive real-world evidence for MMDA efficacy to date. This review synthesizes mycotoxin toxicology, anti-mycotoxin agent mechanisms, clinical evidence, and the CE/LCA sustainability framework, proposing integrated mycotoxin management as a One Health imperative in modern swine production. Full article

Background: Cyclin-dependent kinase 4 (CDK4) is a key regulator of cell-cycle progression and an established therapeutic target for breast cancer. Although the unique architecture of its ATP-binding site has enabled the development of highly selective inhibitors, the emergence of acquired resistance highlights the need for alternative therapeutic strategies targeting protein conformational regulation. Methods: The conformational landscape of CDK4 was investigated in this study using accelerated molecular dynamics (aMD) simulations combined with Markov state model (MSM) analysis to identify cryptic conformational states and potential allosteric binding sites. Particular attention was given to the glycine-rich loop (G-loop), a critical structural element that shapes the ATP-binding pocket, and to the effects of compound 8i (1-(2-(3-chlorobenzoyl)hydrazine-1- carbonyl)-N-(pyridin-3-yl)pyrrolidine-2-carboxamide), previously synthesized in our laboratory, on CDK4 dynamics. Results: A distinct conformational transition was identified in which the G-loop shifted toward the N-terminus, resulting in the exposure of a previously unrecognized allosteric pocket adjacent to the catalytic site. Compound 8i interacted with Leu147 and was associated with stabilization of conformational states that favor exposure of the cryptic pocket. Conclusions: These observations suggest that ligand binding may modulate the conformational landscape of CDK4 and favor formation of a cryptic pocket with potential allosteric characteristics. The identified conformational mechanism provides new insights into the dynamic regulation of CDK4 and suggests that stabilization of transient allosteric states represents a promising strategy for the rational design of next-generation CDK4 inhibitors with the potential to overcome resistance in breast cancer therapy. Full article

Background: Post-COVID-19 condition (PCC) remains a public health concern due to persistent metabolic and inflammatory alterations, especially among ICU survivors. Oxidative stress is involved in PCC pathophysiology, and the Mediterranean diet may be associated with redox balance. Objective: To evaluate the association between Mediterranean diet adherence (main exposure variable) and oxidative stress/redox stress biomarkers (primary outcomes) in ICU survivors with persistent symptoms after severe COVID-19. Additionally, body composition and inflammatory markers were explored as secondary outcomes related to redox status. Methods: This cross-sectional study included 123 adult ICU survivors with PCC (51 ± 13.2 years; 53% men; 75% with obesity). Protein carbonyls, TBARS, sulfhydryl groups, glutathione, CRP, albumin, and IL-6 were measured. Diet adherence during post-COVID-19 outpatient follow-up was assessed using MEDAS, and body composition by DXA. Participants were categorized by the median score, and Poisson regression models were applied. Results: The median MEDAS total score was 4 (IQR 2–5), indicating overall low adherence to the Mediterranean diet. Lower adherence was associated with higher glutathione levels (p = 0.04), with no differences in pro-oxidant markers. Higher sulfhydryl levels were associated with lower body fat, higher appendicular skeletal muscle mass, and lower CRP and IL-6. Conclusions: Low adherence was frequent and associated with antioxidant differences. Redox status was also associated with body composition and inflammatory markers. Full article

This pilot study examined longitudinal changes in psychological distress and biomarkers related to stress, inflammation, and biological aging during the first inpatient rehabilitation after Spinal Cord Injury (SCI). We analyzed data from 120 participants in the SwiSCI inception cohort at two timepoints: the beginning of the first post-injury rehabilitation and discharge. A subset of 50 participants representing four distress patterns (high chronic, low, transient, increasing distress) underwent biomarker analyses, including measurements of immune and inflammatory proteins and whole-blood transcriptomic profiling. The results showed that psychological distress, depression, and protein carbonyl content decreased significantly by discharge. In contrast, cortisol levels and telomere length showed no significant changes. Proteomic analyses revealed a broad downregulation of inflammatory proteins (e.g., IFN-γ, IL-10, LIF) at discharge, whereas transcriptomic profiles did not differ between timepoints. The high chronic distress group showed lower expression of six genes involved in adaptive immunity, neural development and apoptosis. Psychological distress was not linearly associated with global biomarker profiles. However, CXCL1 and IL-7 showed low-to-moderate correlations with depression and anxiety, respectively. This pilot study demonstrates the feasibility of integrating psychological and molecular data to investigate biological response following SCI. The findings are exploratory and need validation in larger studies with longer follow-up periods. Full article

Chickpea is an important source of plant flavonoids in the diet, and flavonoids from chickpea have hypoglycemic activity. In this study, a male SD rat model of type 2 diabetes mellitus (T2DM) induced by a high-fat high-sugar diet combined with streptozotocin (STZ) was used to investigate the inhibitory effects on the polyol pathway (a branch of glucose metabolism) by chickpea flavonoid extract (CFE). The results demonstrated that CFE significantly lowered fasting blood glucose (FBG) level, and reduced insulin resistance in diabetic rats by elevating the homeostasis model assessment of insulin sensitivity (HOMA-IS) and decreasing the homeostasis model assessment of insulin resistance (HOMA-IR). And CFE relieved oxidative stress through reducing H₂O_2, malondialdehyde (MDA) and carbonylated protein levels, and increasing the activity of glutathione peroxidase (GSH-Px). Moreover, CFE inhibited the polyol pathway by downregulating the aldose reductase (AR) and sorbitol dehydrogenase (SDH) activities, as well as reducing the sorbitol and fructose levels. Meanwhile, CFE also enhanced the antioxidant defense capacity through increasing glutathione reductase (GR) activity and the glutathione (GSH) level, while decreasing the oxidized glutathione (GSSG) level. Further results showed that CFE mitigated reductive stress in T2DM rats via increasing intracellular NAD⁺ content and the NAD⁺/NADH ratio, due to suppressing PARP activity and upregulating Sirt3 activity. Furthermore, CFE regulated the levels of metabolites such as nicotinamide and β-aminobutyric acid, and modulated seven metabolic pathways closely associated with the improvement of diabetes and its complications. Ten key differential metabolites were reversed after CFE intervention, which were strongly correlated with the polyol pathway and oxidative stress in T2DM rats. In summary, CFE possessed hypoglycemic activity and could inhibit the polyol pathway, which was considered a promising natural product for diabetes prevention. Full article

Small-molecule α-dicarbonyl compounds (α-DCs), including glyoxal, methylglyoxal and diacetyl, are electrophilic compounds characterized by two adjacent carbonyls. These compounds ubiquitously occur in various foods and food–medicine homologous herbs, generated via the Maillard reaction, caramelization, lipid peroxidation, and enzymatic reactions during thermal treatment and storage. Upon oral intake, small-molecule α-DCs are rapidly absorbed into systemic circulation, triggering protein and DNA damage, as well as inflammation. They also serve as important precursors to derive other hazards, such as advanced glycosylation end products possessing carcinogenic and genotoxic properties. Small-molecule α-DCs and their derived harmful products accelerate the progression of multiple metabolic diseases, e.g., cancer and diabetes. However, their pathological processes remain poorly elucidated, necessitating highly sensitive and accurate analytical methods. This review also systematically summarizes and discusses the current analytical techniques targeting small-molecule α-DCs. Chromatography and chromatography–mass spectrometry are still frequently used techniques. Given the polarity and weak ultraviolet absorption of small-molecule α-DCs, tedious pretreatment is necessary yet time-consuming. Novel rapid detection techniques such as mass spectrometry probes and direct ionization mass spectrometry have been proposed in recent years. Even so, developing rapid, eco-friendly, highly sensitive and accurate analytical methods remains a key priority for future research. Full article

Objective: This study investigated the effects of three chronic stress exposure models (permanent elimination, forced swimming, and food and water deprivation) on bone oxidative stress, structure, and metabolism in vivo. Methods: Adult rats were exposed to different stress conditions, while control animals were maintained under standard laboratory conditions. Bone morphological and histological parameters, oxidative stress biomarkers, antioxidant defense system, and mineral concentrations were assessed. Results: Stress exposure resulted in significant reductions in body weight, femur weight, and femur length compared to controls. A marked increase in oxidative stress biomarkers was observed in bone tissue, including lipid peroxidation, reactive oxygen species, hydroperoxides, hydrogen peroxide, protein carbonyls, and advanced oxidation protein products. In contrast, antioxidant defenses, including enzymatic activities and levels of glutathione, non-protein thiols, and vitamin C, was significantly decreased. Bone calcium and phosphorus levels were reduced, whereas their plasma concentrations were increased following stress exposure. Histological analysis confirmed the biochemical alterations, suggesting that chronic stress can disrupt bone integrity via oxidative mechanisms. Conclusions: These findings highlight the need for strategies to control and reduce stress-related disorders to maintain skeletal health under various chronic stress conditions. Full article