Search Results (1,818)

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, yet the association between folic acid (FA) intake and CRC risk remains controversial. This study investigated the effects of varying dietary FA levels on colorectal carcinogenesis and the underlying mechanisms. Methods: BALB/c mice were fed diets containing FA at <0.1, 2.0, 6.0, 8.0, or 20.0 mg/kg for 14 weeks. After 4 weeks, colorectal tumorigenesis was induced using the azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Tumor multiplicity, maximum tumor diameter, tumor volume, colorectal length, histopathology, and cell proliferation were assessed. Mechanistic assessments included uracil misincorporation, thymidylate synthase (TS), telomere attrition, genome-wide DNA methylation, RAP1 signaling, immune-related markers, and inflammatory cytokines in colorectal tissues. Results: Both FA deficiency (<0.1 mg/kg) and excess (8.0/20.0 mg/kg) increased colorectal tumor burden, with increased tumor number, larger maximum diameter, greater tumor volume, shortened colorectal length, and enhanced cell proliferation, whereas the 6.0 mg/kg diet group showed the lowest tumor burden. FA deficiency reduced TS expression, elevated deoxyuridine monophosphate (dUMP) levels, decreased deoxythymidine monophosphate (dTMP) levels, increased uracil misincorporation, and exacerbated telomere attrition, as evidenced by shortened telomeres and increased damage. In contrast, excessive FA intake induced Rap1 GTPase-activating protein (RAP1GAP) hypermethylation, reduced Rap1GAP expression, enhanced RAP1 activity, and upregulated programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) expression. Conclusions: Dietary FA can exhibit a U-shaped association with colorectal carcinogenesis, with protective effects observed within an optimal range. FA deficiency and excess may drive tumor development through distinct molecular pathways involving uracil misincorporation-induced telomere attrition and DNA methylation-mediated immunosuppression, respectively. Full article

Flocs, visible particles formed in sugar-sweetened beverages, reduce clarity and consumer acceptance of products. Their presence can be caused not only by different types of trace impurities in the sugar but also by interactions among beverage components. In this review, scientific reports on acid beverage flocs (ABFs) and alcohol flocs are summarized, the main pathways for their formation are described, and practical options for detecting them and preventing their formation in beverages are compiled. Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 and related guidance, literature searches of Scopus, Web of Science (WoS), PubMed, Food Science and Technology Abstracts (FSTA), CAB Abstracts, and International Commission for Uniform Methods of Sugar Analysis (ICUMSA) resulted in the inclusion of 56 studies. In various types of beverages, complexes formed between proteins (Ps) and polyphenols (PPs) often initiate haze and floc formation, while polysaccharides (dextran, pectin, and starch), silica or silicates, and inorganic ions influence charge balance, particle bridging, and floc growth rate. Ethanol in alcohol beverages can further destabilize colloids and promote aggregation. For beet sugars, saponin–protein interactions are a likely pathway for the formation of ABF, but the available evidence is not consistent. In cane sugars, the reported roles of proteins, polysaccharides, silica, and starch in floc formation vary considerably between studies. For quality assurance, ICUMSA floc tests (GS2-40 and GS2-44) should be complemented by turbidity or haze measurement and colloid characterization such as light scattering, ζ–potential, and infrared IR-based analytical methods supported by chemometrics. Risk mitigation works best as a two-level strategy that combines impurity removal during sugar production and stabilization steps in beverage formulation and storage, including the use of clarification agents and control of pH, temperature, ionic strength, and oxygen exposure. Standardized reporting and validation of rapid predictors against ICUMSA benchmarks remain essential. Full article

Background/Objectives: Ulcerative colitis (UC) involves inflammatory response, oxidative stress, changes in metabolites, and the gut microbiota. Jingangteng capsule (JGTC) has been utilized clinically for the treatment of inflammatory diseases for many years. However, the efficacy of JGTC in ameliorating UC remains unclear, and the underlying mechanisms have not yet been elucidated. This study aims to investigate the effect and mechanism of JGTC on UC. Methods: The chemical compositions of JGTC were examined using ultra-high-performance liquid chromatography with quadrupole time-of-fight mass spectrometry. The anti-UC effect of JGTC was evaluated by assessing the disease activity index (DAI), colon length, intestinal barrier recovery, and inflammatory factors in a dextran sulfate sodium (DSS)-induced colitis model. Mechanisms were investigated through fecal 16S rDNA sequencing, metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), Western blotting, and network pharmacology analysis. Results: JGTC significantly reduced the DAI scores in UC mice, increased their body weight and colon length (p < 0.001), repairing damaged intestinal tissue. It decreased the levels of inflammatory cytokines TNF-α, IL-6, IL-1β, and LPS (p < 0.01, p < 0.001), alleviating intestinal inflammation. It also raised the expression of tight junction proteins ZO-1, Claudin-1, and Occludin (p < 0.05, p < 0.001), thereby enhancing intestinal barrier function. Fecal metabolomic analysis revealed that the favorable alterations in amino acid and lipid metabolites were more pronounced. Heat maps showed strong correlations between pharmacological indicators and gut microbiota, as well as between the main differential metabolites and gut microbial communities. UPLC-QTOF-MS detection yielded 33 components of JGTC, and network pharmacology analysis based on these components predicted pathways of action of JGTC in UC. Functional pathways closely associated with significantly differential metabolites and metabolic pathways were also investigated. The PI3K-AKT-mTOR pathway was one of them, which is consistent with the conclusions drawn from network pharmacology. JGTC significantly modulated key factors in this pathway, inhibiting the expression of PI3K, Akt, PDK1, and mTOR, while augmenting the expression of PTEN (p < 0.05, p < 0.01, p < 0.001). It also mitigated the levels of related oxidative stress factors MDA, MPO, and D-LA, and raised SOD levels (p < 0.01, p < 0.001). Conclusions: JGTC improved the excessive inflammatory response in UC by regulating intestinal flora and metabolic disorders, affecting the PI3K-AKT-mTOR signaling pathway, restoring intestinal tissue damage and intestinal barrier, and inhibiting inflammatory and oxidative stress factors. Full article

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucidated. This study investigated the effects and mechanisms of a 20% ethanolic extract of Petasites japonicus leaves (EPJ) on dextran sulfate sodium (DSS)-induced colitis and depression-like behaviors. The physiological compounds identified in the EPJ were citric acid, chlorogenic acid, caffeic acid, fukinolic acid, 3,5-dicaffeoylquinic acid, quercetin 3-O-β-D-glucose-6″-acetate, 4,5-dicaffeoylquinic acid, kaempferol-3-O-(6″-acetyl)-β-glucopyranoside, and pedunculoside. EPJ significantly alleviated DSS-induced colitis, as evidenced by improvements in body weight loss (87.41% vs. 76.02% in the DSS group), colon length (5.75 vs. 4.34 cm), intestinal permeability (52.80 vs. 163.01 μg/mL), and myeloperoxidase (MPO) activity (0.24 vs. 0.67 U/mg) (p < 0.05). Histological analysis further confirmed recovery of goblet cells and attenuation of muscle layer thickening. EPJ also reversed DSS-induced gut microbiota dysbiosis and contributed to the restoration of microbial homeostasis. Behavioral assessments showed that EPJ effectively ameliorated depression-like behaviors. EPJ improved antioxidant systems in colon and brain tissues by modulating malondialdehyde (MDA) levels and reduced glutathione (GSH) and superoxide dismutase (SOD) activity. EPJ further upregulated tight junction protein expression and suppressed TLR4/NF-κB inflammatory pathway activation in both colon and brain tissues. Moreover, EPJ modulated serum stress-related hormones, normalized hypothalamic–pituitary–adrenal (HPA) axis dysregulation, regulated the BDNF/TrkB signaling pathway, and modulated tryptophan–kynurenine metabolism. Collectively, these findings suggest that EPJ exerts protective effects against DSS-induced colitis and depression-like behaviors. Full article

Endoscopic sinus surgery (ESS) is commonly performed to treat chronic rhinosinusitis and selected sinonasal tumors, yet postoperative complications such as neo-osteogenesis and restenosis remain frequent, largely due to impaired mucosal regeneration after extensive epithelial and bony tissue loss. Successful nasal epithelial repair requires a microenvironment that preserves cell viability, phenotype, and barrier integrity. Conventional culture substrates often lack physiological relevance or rely on animal-derived components, limiting translational applicability. In this study, we evaluated nanofibrillar cellulose (NFC) hydrogel (GrowDex^®) as a xeno-free scaffold for primary human nasal epithelial cells (NECs). NECs isolated from healthy donor tissue were characterized by immunofluorescence and qPCR for basal, goblet, and ciliated cell markers. Cells embedded in NFC were assessed for viability, cytotoxicity, epithelial morphology, and barrier function. Transepithelial electrical resistance (TEER) and FITC-dextran permeability assays were used to quantify barrier integrity and compared with collagen- and polylysine-based controls. NECs cultured in NFC maintained high viability, stable epithelial morphology, and preserved subtype-specific marker expression without detectable cytotoxicity. NFC-supported cultures demonstrated enhanced barrier formation, indicated by higher TEER values and reduced paracellular permeability relative to controls, and sustained structural integrity during extended culture. These findings identify NFC hydrogel as a biocompatible, non-animal scaffold that supports functional human nasal epithelium regeneration and may contribute to advanced tissue engineering strategies for craniofacial bone repair. Full article

Polyvinylidene fluoride (PVDF) membranes are used in ultrafiltration systems for car wash water reuse, where frequent alkaline cleaning is required to maintain operational flux rates. Although NaOH-induced degradation of virgin PVDF membranes has been reported, its relevance under real industrial conditions remains poorly understood. This study investigates the long-term exposure of tubular PVDF membranes to alkaline car wash detergents and evaluates how the resulting structural changes influence permeate quality. During several months of pilot-scale operation with synthetic car wash wastewater and daily alkaline cleaning (pH > 11.5), permeate fluxes remained stable at 50–70 LMH despite pronounced membrane aging. Structural analyses revealed enlarged pore size, increased water permeability and reduced dextran retention, while FTIR confirmed dehydrofluorination of the polymer matrix. Despite the extensive degradation of the membrane skin layer, permeate turbidity, dissolved organic carbon, and surfactant concentrations remained stable throughout the operation. This stability was attributed to the persistent fouling layer, which acted as an effective secondary separation barrier and compensated for the loss of intrinsic membrane selectivity. These findings demonstrate that substantial PVDF degradation does not necessarily compromise permeate quality in car wash ultrafiltration systems, highlighting the dominant role of fouling-controlled separation under long-term alkaline cleaning regimes. Full article

Cerium oxide nanoparticles (CeO₂NPs) possess unique physicochemical properties that make them promising compounds for medical and industrial applications. However, variations in synthesis methods, particle size, and surface characteristics may influence their potential toxicity. This study provides a comparative analysis of CeO₂NPs synthesized via three methods (citric, dextran, and uncoated modifications) to evaluate their toxicity, antioxidant mechanisms, and genoprotective potential using a panel of Escherichia coli-based lux-biosensors. Our data indicate that all of the tested CeO₂NPs exhibit high biocompatibility with no significant toxicity or genotoxicity at physiological concentrations (10⁻⁴–10⁻² M). The citrate-modified nanoparticles demonstrated pronounced catalase-mimetic activity, acting as the most effective scavengers against hydrogen peroxide. Conversely, the dextran-modified nanoparticles exhibited the highest antimutagenic potential, reducing dioxidine-induced DNA damage by over 56%. Thus, beyond establishing biocompatibility, this study highlights the potential of using specific CeO₂NP modifications for targeted therapy depending on the oxidative pathway involved. This suggests their potential for application as antioxidant and antimutagenic agents in both human and veterinary medicine. Full article

In this study, a novel combination strategy of sodium trimetaphosphate (STMP) phosphorylation and dextran (DX) glycosylation was employed to modify soy protein isolate (SPI). The phosphorylated protein–dextran conjugate (TSPI-DX) was successfully prepared and then was used as an emulsifier to prepare the astaxanthin emulsion, with the aim to enhance the emulsion delivery performance. Structural analysis revealed that phosphorylation and glycosylation altered the microenvironment of the side chains, leading to changes in protein secondary structure, which consequently loosened the protein architecture and enhanced molecular flexibility. The functional properties of TSPI-DX, including its solubility, emulsifying activity (EAI) and emulsifying stability (ESI), were markedly enhanced. Furthermore, the concurrent modification through phosphorylation and the Maillard reaction yielded a synergistic effect, boosting the DPPH radical scavenging rate by 86.5% and increasing the ferric-ion reducing power nearly fourfold. The astaxanthin emulsion prepared by modified SPI also exhibited several advantages. The TSPI-DX emulsion exhibited a markedly smaller mean particle size and a larger absolute Zeta-potential value. Consequently, with the higher electrostatic repulsion and steric hindrance among the droplets, the astaxanthin emulsion prepared by TSPI-DX demonstrated superior encapsulation efficiency and stability across various conditions, including storage, oxidation, thermal, and pH challenges. Moreover, in vitro digestion experiments revealed that the modified SPI emulsion facilitated a higher extent of lipolysis and astaxanthin bioaccessibility. Therefore, this work proposes a novel strategy for constructing plant-protein emulsion systems with enhanced delivery and release capabilities. Full article

Ulcerative colitis (UC) is a highly prevalent chronic non-specific intestinal inflammatory disorder for which effective therapeutic options are urgently needed. The active component cimigenoside (CIM) possesses promising anti-inflammatory bioactivity; however, its therapeutic efficacy and underlying molecular mechanism against UC remain to be fully elucidated. The present study aimed to investigate the effects and possible mechanisms of CIM on dextran sodium sulfate (DSS)-induced UC. Mice received drinking water containing 2.5% DSS to induce a UC model, and were then treated with different dosages of CIM for 10 consecutive days. The results found that CIM restored the colonic length, alleviated pathological damage to the colon, preserved intestinal mucosal barrier integrity, and inhibited colonic oxidative stress and inflammatory responses in DSS-induced mice. Additionally, DSS induction reduced the expression of sirtuin 3 (SIRT3) protein in the colonic tissues of mice; however, this was improved by treatment with CIM. Notably, the above protective roles of CIM on DSS-induced UC were unavailable in SIRT3-knockout (SIRT3-KO) mice. Notably, the docking score of CIM binding to SIRT3 is −11.3 kcal/mol, suggesting that CIM could directly bind to SIRT3. Collectively, CIM directly binds to SIRT3 and upregulates its protein expression, which in turn inhibits colonic inflammation and oxidative stress, thereby exerting anti-UC effects. Full article

In patients, extraintestinal manifestations of inflammatory bowel disease (IBD) are attenuated ventricular contractile function and arrhythmia. To determine the mechanism of IBD-induced changes in ventricular function, we used a mouse model of dextran sodium sulfate (3.5% weight/volume; 7 days)-induced colitis. Changes in cardiac function were quantified in isolated ventricular myocytes (VM) by cell shortening, imaging of [Ca²⁺]_i, reactive oxygen species (ROS), and t-tubular density. During colitis, VMs exhibited attenuated cell-shortening and altered Ca²⁺-handling properties. A prolonged Ca²⁺ transient (CaT) rise time correlated with an increased coefficient of variation in the subcellular Ca²⁺ release and an attenuated t-tubular density. T-tubular loss was accompanied by increased ROS production, calpain-2 (CAPN2) expression, junctophilin-2 (JPH-2) cleavage, and autophagy. Inhibition of Angiotensin-converting enzyme during colitis (Perindopril: 3 mg/kg/day) prevented the increase in CAPN2, ROS production, autophagy, and t-tubular remodeling. It failed, however, to restore full length JPH-2. We conclude that, during IBD, the angiotensin II (AngII)-induced loss of t-tubular integrity and altered cellular Ca²⁺ handling can be prevented by suppression of the AngII-dependent increase in CAPN2 and autophagy and thus suppression of AngII signaling might benefit IBD patients with cardiac manifestations of the disease. Full article

Background: Polygonatum sibiricum (PS), a perennial herbaceous plant belonging to the Liliaceae family, is widely distributed in China and other East Asian countries. PS has been used as food and medicine for thousands of years, and its rhizomes are rich in Polygonatum sibiricum polysaccharides (PSP), which exhibit various bioactivities, yet their structural features and therapeutic mechanisms against ulcerative colitis (UC) remain unclear. Methods: A homogeneous polysaccharide, PSP-1b (57.45 kDa), was isolated from the rhizomes of PS via ion-exchange and gel filtration chromatography and structurally characterized using chromatographic and spectroscopic methods. In vivo, its effects were evaluated in a dextran sulfate sodium (DSS)-induced mouse model of UC, while in vitro mechanisms were explored using macrophages stimulated with lipopolysaccharide (LPS) and neutrophil extracellular traps (NETs). Results: PSP-1b was identified as a neutral polysaccharide with minimal branching. Its primary structural backbone was largely composed of →4)-β-D-Galp-(1→ residues. A portion of these backbone residues was substituted at the O-6 position by side chains primarily composed of β-D-Galp-(1→ units. In vivo, PSP-1b significantly alleviated DSS-induced colitis by reducing inflammatory cytokine secretion, suppressing colonic macrophage infiltration, and reversing neutrophil extracellular traps (NETs) deposition. In vitro, PSP-1b directly interacted with TLR4, inhibited the MAPK/NF-κB signaling pathway, and attenuated LPS- and NET-induced macrophage polarization and inflammation. Conclusions: PSP-1b as a promising candidate for functional foods or therapeutic agents targeting inflammatory bowel disease. Full article

Phenolamides in bee pollen exhibit notable bioactivities, such as antioxidant, anti-inflammatory, and antimicrobial effects. Ulcerative colitis (UC) is a prevalent intestinal disorder, while the potential effects of phenolamides on UC remain unclear. This study aims to investigate the effects and mechanisms of phenolamide extract (PAE) from apricot bee pollen on dextran sulfate sodium (DSS)-induced UC in mice. Firstly, we analyzed the main compounds of PAE. Mice were treated with PAE (100, 200, and 400 mg/kg bw) both during the 7 days preceding 2.5% DSS induction and throughout the induction period (7 days). The results show that the primary compounds of PAE were isomers of tri-p-coumaroyl spermidine (97.78 ± 2.76%). A biochemical analysis showed that PAE decreased the levels of pro-inflammatory cytokines and increased the activities of antioxidant enzymes. Regarding the gut microbiota, PAE reduced the Bacillota/Bacteroidota ratio. Additionally, PAE elevated beneficial bacteria, including norank_f_Muribaculaceae, norank_o_Clostridia_UCG-014, and Lachnospiraceae_NK4A136_group, while reducing harmful bacteria, including Escherichia-Shigella, Clostridium, and Romboutsia. A quantitative analysis of short-chain fatty acids (SCFAs) demonstrated that PAE intervention promotes the biosynthesis of SCFAs in UC mice. This study first demonstrates that PAE attenuates DSS-induced colitis by modulating gut microbiota and SCFAs, suggesting its potential as a functional dietary supplement for colitis. Full article

Background: The global spread of monkeypox virus (MPXV) highlights an urgent need for thermostable and easily administrable vaccines. Current orthopoxvirus vaccines are limited by cold-chain dependence and inconvenient injection-based delivery. Objectives: This study aimed to develop a dissolvable microneedle (DMN) vaccine against monkeypox based on a replication-deficient orthopoxvirus platform, through systematic formulation screening, stabilization mechanism exploration, and rigorous in vivo immunogenicity evaluation. Methods: A film-based approach was adopted for efficient, high-throughput formulation screening and thermostability assessment. NTV was mixed with excipients and dried into solid films. Stability was monitored via RT-qPCR after storage at 4 °C to 40 °C. The lead formulation was physically characterized, then used to fabricate MVA-BN-loaded DMN patches, which were further evaluated for in vivo immunogenicity via immunization in BALB/c mice. Results: The optimal formulation F2 (containing dextran, L-threonine, and BSA/HSA) showed a potency loss of only ~1 log₁₀ after 2 months at 25 °C, and <1 log₁₀ loss after 1 week at 37 °C. SEM revealed a porous virus-entrapment morphology, and FTIR indicated enhanced hydrogen bonding between the virus and the dextran matrix. The formulation was successfully manufactured into DMNs that dissolved within 5 min. In mice, these DMNs elicited robust MPXV-specific IgG and neutralizing antibody responses, with immunogenicity comparable to that induced by conventional intramuscular injection. Conclusions: This study successfully established a thermostable formulation and dissolvable microneedle delivery platform for replication-deficient orthopoxvirus vaccines against monkeypox. The optimized DMN vaccine induced robust MPXV-specific immune responses in mice with immunogenicity comparable to intramuscular injection, addressing the core limitations of current vaccines and providing a promising solution for monkeypox prevention. Full article