Immunomodulation is the primary biological activity of polysaccharides. We have previously demonstrated that Bangia fusco-purpurea polysaccharide (BFP) can modulate the immune function of immunosuppressed mice and increase the abundance of Lactobacillus murinus. However, the underlying mechanisms remain unclear. In the present study, we aimed to elucidate the L. murinus-mediated immunomodulatory effect of BFP. Co-culture of L. murinus and BFP revealed that BFP promoted the proliferation of L. murinus at the concentrations of 0.5%–2.0%. We established a mouse L. murinus depletion model, in which L. murinus was administered via gavage. Treatment with L. murinus significantly increased macrophage phagocytosis and the levels of immune-related factors in mice, including interleukin (IL)-2, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). These results suggested that L. murinus contributes to the immunomodulatory effect of BFP. Given the important role of macrophages in innate and adaptive immunity, we further confirmed that L. murinus can enhance immune function. Under lipopolysaccharide (LPS)-induced inflammatory conditions, L. murinus stimulated the elevation of IL-10 expression, consequently promoted macrophages polarization toward the anti-inflammatory M2 type, which in turn prevented the overactivation of the inflammatory response and reversed the LPS-induced inflammation. It also maintained the balance between pro- and anti-inflammatory responses, thus playing a role in regulating immune function. Finally, transcriptomic sequencing and pathway validation revealed that L. murinus regulates IL-10 through the macrophage/mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) signaling axis. Overall, these results suggest that the immunomodulatory mechanism of the BFP may involve L. murinus-induced regulation of IL-10 through the macrophage/MAPK/NF-κB signaling axis.
The modulation of lysosome-dependent autophagy as a critical protective mechanism affecting the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a growing area of concern. The current research was designed to evaluate the effect of plant sterol ester of u03B1-linolenic acid (PS-ALA) on lysosomal function and autophagy in preventing the occurrence of hepatic steatosis using in vivo and in vitro models. Our result showed that treatment with PS-ALA significantly alleviated lipid and free cholesterol (FC) accumulation in a high-fat and high-cholesterol diet (HFCD) feeding mice and reduced the levels of FC, free fatty acid, and triglyceride by 66.7%, 70.4%, and 58.3% in oleic acid/cholesterol (OA/Cho)-treated HepG2 cells. In addition, we found that HFCD or OA/Cho damaged lysosomal function and blocked autophagy characteristics by increased LC3u2161 and p62 accumulation. Administration of PS-ALA significantly promoted lysosome biogenesis, alleviated the damage of lysosomes, activated autophagy, and accelerate lysosome-dependent lipid degradation in OA/Cho-induced cells. Further molecular mechanism study revealed that PS-ALA intervention reduced the expression level of phosphorylation mTORC1 by 34% in the liver and induced subsequent nuclear translocation of TFEB. Activation of mTORC1 by MHY1485 markedly abolished PS-ALA-induced lysosome biogenesis and autophagy in OA/Cho-induced cells, leading to lipid accumulation. Our findings support the suitability of PS-ALA as a therapeutic strategy for MASLD upon its beneficial effect on lysosomal function and autophagy via inhibiting mTORC1 signaling.
Peripheral neuropathy is a common side effect of cisplatin; however, there is no definitive treatment for this condition. In humans, u03B2-hydroxy-u03B2-methyl-butyrate (HMB) is an endogenous metabolite of leucine. To date, none data is available about the effects of HMB on cisplatin-induced peripheral neuropathy (CIPN). Herein, oral administration of HMB considerably alleviated cisplatin-induced hyperalgesia in Wistar rats, a symptom of peripheral neuropathy affecting the extremities of the limbs. The primary mechanism of CIPN is apoptosis in the sensory neurons of the dorsal root ganglion (DRG) arising from the accumulation of platinum (Pt). HMB mitigated CDDP-induced neurotoxicity in DRG neurons through reducing Pt accumulation within these cells, as evidenced by the recovery of cell viability and reduced apoptosis. In addition, HMB treatment down-regulated the levels of copper transporter 1 (CTR1), a key molecule mediates the influx of cisplatin. And artificial recovery of CTR1 expression by CTR1-overexpression plasmids transfection abrogated the inhibition of HMB on Pt accumulation in DRG neurons. Moreover, enhanced ubiquitylation, arising from increased NEDD4L expression, mediated the down-regulation of CTR1 by HMB. Finally, as evidenced by the data from lung cancer model in vivo and in vitro, HMB did not interfere with cisplatinu2019s ability to induce tumor cell death. These findings suggest that HMB can alleviate CIPN by destabilizing CTR1 in DRG neurons without affecting cisplatinu2019s chemotherapeutic effects. Therefore, HMB could be developed as an adjuvant therapy to relieve neurotoxicity in cisplatin-based treatment protocols.
Immunomodulation is the primary biological activity of polysaccharides. We have previously demonstrated that Bangia fusco-purpurea polysaccharide (BFP) can modulate the immune function of immunosuppressed mice and increase the abundance of Lactobacillus murinus. However, the underlying mechanisms remain unclear. In the present study, we aimed to elucidate the L. murinus-mediated immunomodulatory effect of BFP. Co-culture of L. murinus and BFP revealed that BFP promoted the proliferation of L. murinus at the concentrations of 0.5%u20132.0%. We established a mouse L. murinus depletion model, in which L. murinus was administered via gavage. Treatment with L. murinus significantly increased macrophage phagocytosis and the levels of immune-related factors in mice, including interleukin (IL)-2, tumor necrosis factor-u03B1 (TNF-u03B1), and interferon-u03B3 (IFN-u03B3). These results suggested that L. murinus contributes to the immunomodulatory effect of BFP. Given the important role of macrophages in innate and adaptive immunity, we further confirmed that L. murinus can enhance immune function. Under lipopolysaccharide (LPS)-induced inflammatory conditions, L. murinus stimulated the elevation of IL-10 expression, consequently promoted macrophages polarization toward the anti-inflammatory M2 type, which in turn prevented the overactivation of the inflammatory response and reversed the LPS-induced inflammation. It also maintained the balance between pro- and anti-inflammatory responses, thus playing a role in regulating immune function. Finally, transcriptomic sequencing and pathway validation revealed that L. murinus regulates IL-10 through the macrophage/mitogen-activated protein kinase/nuclear factor-u03BAB (MAPK/NF-u03BAB) signaling axis. Overall, these results suggest that the immunomodulatory mechanism of the BFP may involve L. murinus-induced regulation of IL-10 through the macrophage/MAPK/NF-u03BAB signaling axis.
Imperatae Rhizoma belongs to the Poaceae family and is the rhizome of the perennial plant Imperata cylindrica. As a versatile traditional Chinese medicinal herb that is both edible and medicinal, it is used to treat hematuria, damp-heat jaundice, vomiting, and bleeding. Atopic dermatitis (AD) is an inflammatory dermatitis characterized by chronic, recurrent, pruritic conditions. However, the adverse effects of current mainstream therapies include commonly used medications seriously affect the quality of patientsu2019 life. This study investigates the role of Imperatae Rhizoma extract (IRE) in AD and underlying mechanisms. Using a dinitrochlorobenzene-induced AD mouse model, we found that IRE alleviates AD symptoms by reducing skin dryness, itching, and ear swelling, and modulating epidermal thickening and mast cell infiltration. The liquid chromatography-mass spectrometry combined with the self-built database identification revealed 14 components in IRE, primarily consisting of phytosterols and triterpenes. Network pharmacology suggests IREu2019s anti-inflammatory effects may involve the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-u03BAB (PI3K/AKT/NF-u03BAB) pathway. In vitro, IRE mitigated the activation of this pathway, inhibiting NO and inducible nitric oxide synthase (iNOS) expression, and reducing tumor necrosis factor-u03B1 and interleukin-6 release. IRE also enhanced human immortalized keratinocyte cell line HaCaT cell migration, promoting skin healing, and showed inhibitory effects on Staphylococcus aureus on the surface of skin. In conclusion, IRE may serve as a potential treatment for AD by reducing inflammation through the PI3K/AKT/NF-u03BAB pathway and regulating skin microbiota. This research not only provides a theoretical basis for the application of IRE in the treatment of AD, but also offers a new direction for the development of food and medicine homologous natural compound-based therapies in dermatology.
Abstract Rationally engineered mixed‑dimensional heterostructures enable synergistic and interfacial effects that are inaccessible to single components. Here we construct a 2D/1D/3D Ti3C2Tx/MWCNTs‑COOH/UiO‑66 nanohybrid and deploy it as an electrocatalytic interface for the differential‑pulse‑voltammetric (DPV) detection ofloxacin in aquatic foods. In this architecture, 2D Ti3C2Tx MXene acts as a highly conductive scaffold, while 1D carboxyl-functionalized multi-walled carbon nanotubes (MWCNTs-COOH) are intercalated between MXene sheets to suppress restacking and build rapid electron pathways. The 3D metal-organic framework UiO-66, is anchored onto the MXene/MWCNTs network, providing abundant adsorption and recognition sites. resulting in hybrid materials with superior electrocatalytic activity. The mixed‑dimensional heterointerfaces promote fast charge transport and strong ofloxacin preconcentration. Under optimized conditions, the Ti3C2Tx/MWCNTs-COOH/UiO-66 modified electrochemical sensor demonstrated excellent performance for ofloxacin detection, delivering the wide linear range (0.04–50.0 μmol/L) and a low limit of detection of 0.018 μmol/L (S/N = 3). The sensor also exhibits excellent anti-interference, repeatability, reproducibility, and stability. Recoveries of 95.9%~110.0% and the agreement with a reference HPLC method in real samples analysis, substantiate its practical utility for monitoring ofloxacin residues in aquatic foods. This work illustrates a generalizable route to leverage mixed‑dimensional MXene/MOF architectures for signal amplification in electrochemical antibiotic sensing.
Abstract This study systematically investigates the structural characteristics and neuroprotective effects of pectic polysaccharides isolated from defatted walnut kernels (WKP). Three fractions—WKP-W, WKP-S1, and WKP-S2—were obtained via DEAE-52 chromatography. Structural analysis revealed that WKP-S1 (15% uronic acid, 72.13 kDa) is rich in rhamnogalacturonan-I (RG-I) domains with a backbone primarily composed of →4)-β-D-GalpA-(1→ and →2,4)-α-L-Rhap-(1→. In contrast, WKP-S2 (68% uronic acid, 45.61 kDa) exhibits a hybrid homogalacturonan-RG-I (HG-RG-I) structure with partially methyl- and O-acetyl-esterified GalA residues. Bioactivity evaluation in an Aβ42-expressing Drosophila model demonstrated that all WKP fractions ameliorated Alzheimer’s disease (AD)-related symptoms, including extended lifespan, improved locomotor function, reduced Aβ42 aggregation, and enhanced antioxidant defenses. Notably, WKP-S1 exhibited the most potent neuroprotective effects among the tested fractions, underscoring the critical role of RG-I domains and side-chain architecture in mediating bioactivity. Transcriptomic analysis further revealed the upregulation of neuroprotective genes (Jon25Biii, Jon99Fi, Jon99Fii) associated with serine hydrolase activity and oxidative stress mitigation. These findings highlight the structure–activity relationship of walnut pectic polysaccharides and support the potential of RG-I-enriched fractions as multi-target therapeutic candidates for AD.
Vast quantities of by-products generated during plant-based food processing operations represent a rich yet underutilized source of dietary fiber (DF) and bioactive compounds. These offer immense potential for gut health modulation and sustainable resource utilization. This comprehensive review systematically elucidates the classification, advanced extraction technologies, and diverse health-promoting mechanisms of DF derived from these plant-derived processing residues. A central focus of this work is its in-depth examination of the synergistic interactions between DF and polyphenols, uncovering their profound potential in enhancing bioavailability and biological activityu2014a perspective that contributes to a more comprehensive understanding of their combined impact on health. The review further delineates DFu2019s crucial role in regulating metabolic functions, including glucose homeostasis, lipid metabolism, and intestinal barrier integrity, primarily mediated through gut microbiota-derived short-chain fatty acids and immune-modulatory pathways. This review also explores the application of precision nutrition frameworks to develop individualized fiber interventions. Leveraging host genetics and microbiome variability, it proposes a refined paradigm for future personalized health management. The integration of advanced extraction technologies with detailed mechanistic insights into fiber-polyphenol interactions provides a robust foundation for the development of innovative functional foods and the high-value utilization of these plant-based processing by-products.
Abstract Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is a prevalent global chronic gastrointestinal disorder with rising incidence, burdening healthcare and patients; current treatments are often ineffective. Thus, there is an urgent need to find efficient therapeutic approaches or drugs. Tea polyphenols(TP), natural compounds derived from China's millennia-old tea culture, have demonstrated potent anti-inflammatory and antioxidant properties. Network pharmacology analysis revealed that tea polyphenols exert therapeutic effects on ulcerative colitis (UC) by modulating inflammation and reactive oxygen species (ROS) -mediated signaling pathways. However, their clinical application is severely limited by suboptimal targeting efficacy, low bioavailability and adverse effects. To address these challenges, we developed oral tea polyphenol nanoparticles (TP-NPs) to enhance therapeutic delivery efficiency. Thermodynamic analysis and release kinetics showed that TP-NPs significantly improve the stability and sustained-release properties of tea polyphenols, maintaining prolonged therapeutic concentrations. Both in vitro and in vivo studies demonstrated that TP-NPs exhibit strong resistance to gastric acid and preferentially accumulate at sites of intestinal inflammation. In a murine model of UC, TP-NPs effectively reduced colonic ROS levels, thereby mitigating oxidative stress-induced damage. These findings highlight the dual anti-inflammatory and antioxidant properties of TP-NPs, underscoring their potential as an innovative therapeutic strategy for UC.
Abstract This study investigated the combined effects of sunflower oil (SO) and coconut oil (CO) at 3% and 6% (w/w) on the in-vitro starch digestibility and functional properties of five rice varieties (XKL, XKS, NG46, NP, and YPT) that had a wide variety of amylose (AM) content and molecular fine structure. Structural, physicochemical, and textural characteristics were analyzed using size exclusion chromatography (SEC), fluorophore-assisted carbohydrate electrophoresis (FACE), X-ray diffraction (XRD), small-angle X-ray scattering (SAXS), scanning electron microscopy (SEM), a rapid visco analyzer (RVA), differential scanning calorimetry (DSC), texture profile analysis (TPA) and in vitro digestion. Pronounced varietal differences were observed in starch structure and digestion behavior. The low-AM variety NG46 showed the fastest digestion rate coefficient (k = 1.7 min⁻¹). The XRD results confirmed the formation of starch–lipid complexes, indicated by the appearance of V-type diffraction pattern, with the highest relative crystallinity (Rc) in YPT (17.5%) with 6% CO. Incorporation of CO markedly increased the undigested starch fraction (Cres), reaching 23.4% in YPT cooked with 6% CO. In contrast, SO moderately increased resistant starch (RS) but improved textural quality by balancing hardness and stickiness. Overall, 6% CO combined with the high AM, long-chain indica variety YPT was most effective for forming starch–lipid complexes and enhancing RS content, whereas 3% SO improved consumer-preferred texture without greatly reducing digestibility. These findings provide insight into optimizing oil type, concentration, and rice variety to achieve desirable nutritional and functional properties in cooked rice.
Abstract The texture of soft materials, such as yogurt, emerges from the complex interplay of their constituent molecules. While polysaccharides are widely used to modulate texture, achieving predictable outcomes is hindered by their structural heterogeneity. Here, we demonstrate that pectin molecular weight (Mw) acts as a master regulator for designing customizable yogurt textures through precise control of casein network assembly. By fractionating lemon pectin into discrete MW fractions, we achieved distinct viscoelastic landscapes in yogurt systems: intermediate Mw (20.01 kDa) induced weak, flowable gels by disrupting optimal pectin-protein interactions (electrostatic and hydrophobic interactions), whereas high and lower Mw (40.09 and 7.77 kDa) reinforced the network through enhanced protein-protein binding (disulfide bonding). This reveals a non-monotonic (U-shaped) dependence of gel strength on pectin chain length. Our findings provide a mechanistic framework for Mw-directed texture engineering, offering practical guidelines for developing texture-tunable foods tailored for vulnerable populations, such as the elderly and individuals with dysphagia. This work thereby advances the intersection of food science and human wellness.
Abstract Sleep is essential for maintaining physiological homeostasis, and sleep deprivation can lead to severe health problems including ferroptosis-driven intestinal damage. Due to the complexity of the intestinal microenvironment, research on intestinal ferroptosis remains in its early stages. Moreover, the relationship between 7,8-dihydroxyflavone and ferroptosis has not yet been clearly defined. This study aims to explore the regulatory role of 7,8-dihydroxyflavone on ferroptosis in sleep-deprived mice. The results revealed that 7,8-dihydroxyflavone alleviates colonic ferroptosis by activating the Nrf2 signaling pathway. 7,8-dihydroxyflavone treatment mitigated weight loss, colon shortening, and the reduction of tight junction proteins in sleep-deprived mice. In colonic epithelial cells, 7,8-dihydroxyflavone suppressed ferroptosis, and this protective effect was dependent on Nrf2 activation. Transcriptomic analysis further demonstrated that 7,8-dihydroxyflavone modulates Nrf2 and its downstream antioxidant targets through the TrkB-Akt signaling cascade. Together, these findings identify 7,8-dihydroxyflavone as a promising therapeutic candidate for preventing intestinal ferroptosis induced by sleep deprivation via the TrkB-Akt-Nrf2 pathway.
