Identification of antioxidant peptides from a bioactive peptide database PWDB of walnut family protein hydrolysates.

This study provides the first comparative evaluation of Bisphenol A (BPA) and its derivatives, Bisphenol F (BPF) and Bisphenol S (BPS), with oxidative stress, lipid accumulation, and apoptosis levels in fibroblast cells. WST-1 and LDH assays revealed that while all compounds induced dose-dependent cytotoxic effects, BPA resulted in a more significant decrease in cellular viability compared with BPF and BPS. In addition, BPA demonstrated a more significant dose-dependent elevation in DCF fluorescence intensity, indicating a greater level of oxidative damage compared with BPF and BPS. Flow cytometry analyses showed that all bisphenols led to a decrease in cell viability in a dose-dependent manner, which correlated with an increase in the apoptosis and necrosis rate. All exposure groups of BPA, BPF, and BPS were determined to have diminished sizes and a more crescent nuclei morphology. Malondialdehyde (MDA) levels in the BPA group were significantly higher than in the BPF and BPS groups. The lipid droplets were markedly higher in the BPA group when compared with the BPF and BPS groups, indicating that the accumulation of neutral lipids was greater in BPA-treated fibroblast cells. These results uncover that both BPA and its analogues cause cellular toxicity, but their toxicity levels can vary. Accordingly, further studies are needed to elucidate further risk assessment categories.

Trimetazidine alleviates heart failure after myocardial infarction by promoting PINK1/parkin-mediated mitophagy and suppressing GPX4-dependent ferroptosis.

Cell-based therapies using macrophages for tumor-targeted drug delivery show great promise, but are hindered by limited drug loading, complex fabrication, and premature payload release. Current hitchhiking strategies often suffer from low cargo retention, nanoparticle endocytosis, and detachment. A universal, simplified system balancing high loading, controlled release, and cellular localization is urgently needed. Here, we report a macrophage-anchored gated nanofibers platform (MAGF) that addresses these challenges via polyphenol-gated electrospun nanofibers. Doxorubicin-loaded PLGA nanofibers are fabricated via electrospinning and coated with a Fe3⁺-tannic acid (TA) supramolecular network, forming a pH-responsive polyphenol gate. This design enables ultra-high drug loading (∼25wt.%) and minimizes premature leakage under physiological conditions. Importantly, the nanofibers stably adhere to the macrophage surface without internalization, preserving cellular viability, motility, and tumor-homing capacity. Molecular dynamics and density functional theory simulations reveal that strong TA-drug interactions suppress release at neutral pH but dissociate in acidic tumor environments, ensuring site-specific activation. In vivo, MAGF-loaded macrophages demonstrate enhanced drug accumulation in melanoma tumors, significant inhibition of both primary growth and lung metastasis, and favorable biosafety. This work introduces a robust and cell-compatible delivery platform that bridges synthetic nanotechnology with living-cell therapy, offering a generalizable strategy for next-generation, tumor-targeted chemotherapy.

Parkinson’s disease (PD) is an intractable progressive neurodegenerative disease with poor prognosis in elder patients, which is largely attribute to the deficiency of ultimate pathogenesis. Longitudinal studies have indicated a pivotal role of natural killer (NK) cells, yet the systematic and detailed information of circulating NK cells in PD is largely unknowable. To explore the role of NK cells in PD, we isolated mononuclear cells from peripheral blood (PBMCs) by Ficoll-based density gradient centrifugation, and detected the content of total resident NK cells in healthy donors (HD-NKs) and PD patients (PD-NKs) and the concomitant subsets by flow cytometry (FCM) assay. Then, we took advantage of our well-established “3ILs”-based strategy for ex vivo NK cell expansion and activation, and followed by cellular viability and cytotoxicity assessment. By conducting RNA-sequencing (RNA-SEQ) and multifaceted bioinformatics analyses, we compared the transcriptomic signatures of expanded HD-NKs and PD-NKs. Compared to HD-NKs, PD-NKs showed increase in resident NK cells but minimal differences in expanded NK cells, together with diversity in the subpopulations of NK cells (CD16+, NKG2D+, NKp46+). Interestingly, PD-NKs revealed a moderate higher percentage of apoptotic cells and cytotoxicity upon the co-cultured Nalm6 and U937 tumor cell lines. Despite with high conservations in gene expression pattern and genetic variations, PD-NKs revealed multifaceted diversity in gene set-associated immune response and metabolism. Overall, our data revealed the multidimensional biological and transcriptomic signatures of resident and expanded NK cells generated from peripheral blood of PD patients and HDs. Our findings would provide new references for the further development of NK cell-based biomarkers for PD diagnosis and novel immunotherapy for neurodegenerative diseases.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-26756-w.

Investigating the neurodevelopmental toxicity of graphene oxides using 3D human brain organoids and zebrafish models: emphasis on GABAergic neuron alterations at single-cell resolution.

Background: Long noncoding RNA (lncRNA) hox transcript antisense intergenic RNA (HOTAIR) is implicated in the progression of gastric cancer (GC) by promoting the microRNA-217 (miR-217)-glypican-5 (GPC5) axis. Quercetin (QCT), a well-known flavonoid, has demonstrated anticancer effects against various malignancies, including GC. However, the impact of QCT on HOTAIR expression and its downstream mediators remains unclear. Objectives: This study aimed to elucidate the antitumor mechanisms of QCT and its regulatory effects on the HOTAIR/miR-217/GPC5 axis in AGS and MKN-45 GC cell lines. Methods: Cellular viability, apoptosis, cell cycle progression, invasion, and oxidative stress markers were assessed using the MTT assay, annexin V-FITC/PI staining, real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and spectrophotometry. Expression levels of HOTAIR, miR-217, and GPC5 were quantified. Results: The QCT significantly downregulated HOTAIR and GPC5 while upregulating miR-217 in both cell lines (P < 0.001). The QCT induced dose-dependent apoptosis and cell cycle arrest, and reduced invasion through upregulation of TP53/PTEN (P < 0.05). Oxidative stress modulation displayed lineage-specific differences, with a marked reduction in malondialdehyde (MDA) in MKN-45 cells (P = 0.013). AGS cells exhibited greater sensitivity to QCT than MKN-45 cells. Conclusions: These findings highlight QCT’s ability to inhibit GC progression via the HOTAIR/miR-217/GPC5 axis, with molecular heterogeneity influencing therapeutic response. The QCT emerges as a promising candidate for further investigation as a multifaceted agent against GC, though validation in preclinical models is necessary.

Nearly all cell models explicitly or implicitly deal with the biophysical constraints that must be respected for life to persist. Despite this, there is almost no systematicity in how these constraints are implemented, and we lack a principled understanding of how cellular dynamics interact with them and how they originate in actual biology. Computational cell biology will only overcome these concerns once it treats the life-death boundary as a central concept, creating a theory of cellular viability. We lay the foundation for such a development by demonstrating how specific geometric structures can separate regions of qualitatively similar survival outcomes in our models, offering new global organizing principles for cell fate. We also argue that idealized models of emergent individuals offer a tractable way to begin understanding life's intrinsically generated limits.

Investigate the cellular response of human nucleus pulposus (HNP) cells to serum deprivation, focusing on the role of high mobility group box1(HMGB1) in regulating autophagy and apoptosis, and elucidate the time-dependent activation of autophagy shifting toward apoptosis under nutrient stress. Additionally, the study evaluated the impact of autophagy inhibition by chloroquine (CQ) on apoptosis progression. HNP samples were obtained from the human biobank with exemption from IRB screening (IRB number DC25SASI0012) to evaluate the impact of nutritional deprivation. Comprehensive analyses encompassed detailed evaluations of cellular morphology, viability, DNA integrity, and metabolic function, providing an integrated view of cellular status. Western blotting (WB), fluorescence-activated cell sorting (FACS), and immunofluorescence (IF) were used to detect LC3, P62, HMGB1, and cleaved caspase-3. Real-time quantitative polymerase chain reaction (RT-qPCR) further revealed changes in gene expression related to autophagy (LC3, P62) and apoptosis (caspase-3), highlighting cellular stress responses. Serum deprivation markedly reduced HNP cell viability, altered morphology, and suppressed metabolic activity, while inducing a time-dependent increase in autophagy, peaking at 48 h. Furthermore, elevated LC3-II, decreased P62, and increased cytoplasmic translocation of HMGB1 indicate activation of HMGB1-mediated autophagy. Simultaneously, cleaved caspase-3 levels rose, suggesting HMGB1’s involvement in shifting the balance toward apoptosis. IF and RT-qPCR confirmed enhanced LC3 and cleaved caspase-3 expression, while FACS analysis revealed increased apoptotic cell populations with declining serum levels. These findings highlight a crucial interplay between autophagy and apoptosis regulated by HMGB1 under nutrient-deprived conditions. Eventually, CQ treatment inhibited autophagic flux by blocking LC3-II degradation, thereby amplifying apoptosis. Serum deprivation potently induced HMGB1-mediated autophagy-apoptosis interplay in HNP cells, with CQ enhancing apoptosis by inhibiting autophagy. Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-23026-7.

Beyond simple inhibition: Unveiling the non-monotonic impact and multi-level mechanisms of aged microplastics on sludge anaerobic digestion.

The development of new titanium alloys for dental implants aims to eliminate potentially cytotoxic elements while achieving mechanical properties compatible with bone, particularly a low elastic modulus. This study evaluates the in vitro biocompatibility and mechanical performance of a newly developed β-type Ti-20Zr-3Mo-3Sn (Ti2033) alloy, in comparison with Ti-14Zr and Ti-6Al-4V, two reference alloys used in oral implantology. Mechanical properties were assessed by tensile testing and hardness measurements, while biocompatibility was evaluated using MTT and wound healing assays on osteoblastic cells (Saos-2). Ti2033 exhibits a significantly reduced Young's modulus (52 GPa), nearly 50% that of the reference alloys, thereby improving mechanical compatibility with bone. Although its ultimate tensile strength (825MPa) and hardness (300 HV) are slightly lower, Ti2033 shows good ductility (elongation at rupture: 10%). No cytotoxic effects were observed, and cellular viability and migration were comparable among the three alloys. These findings suggest that Ti2033 combines mechanical performance and biocompatibility, making it a promising candidate for endosseous dental implant applications.

Introduction: Diabetic kidney disease (DKD) is one of the most common complication of type 2 diabetes mellitus (T2DM) and confers increased risk of myocardial infarction, stroke, and heart failure. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and guideline-directed moderate physical training (PT) reduce major adverse cardiovascular events. This study investigated whether this combination provides cardiorenal benefit through improved vascular compliance, renal perfusion, and redox balance. Methods: Male wistar rats were allocated into six groups: controls, GLP-1RA, T2DM, T2DM+PT, T2DM+GLP-1RA and T2DM+PT+GLP-1RA. Interventions lasted 28 days. Renal function (inulin clearance, serum creatinine), microalbuminuria, renal hemodynamics, oxidative biomarkers (urinary peroxides, lipid peroxidation, nitrates, tissue thiols, catalase), and mitochondrial enzyme activity (citrate synthase) were evaluated. In parallel, HK-2 cells were cultured under normoglycemic (5.5 mM) or hyperglycemic (30 mM) conditions and treated with semaglutide (400 nM) for up to 4 days. Cell viability was assessed using MTT assay. Results: The combination of semaglutide and PT in type 2 diabetic rats significantly improved glomerular filtration rate, reduced serum creatinine, microalbuminuria, renal oxidative stress, and vascular resistance, while enhancing renal blood flow and citrate synthase activity. In vitro, semaglutide attenuated high-glucose-induced cytotoxicity in HK-2 cells, preserving cellular viability. Conclusion: Combined treatment with semaglutide and moderate physical training attenuated the progression of DKD induced by T2DM. These findings reinforce the superior renoprotective effects of the combined therapy compared to isolated interventions, particularly through improved renal hemodynamics and reduced oxidative stress. Overall, the data highlights the therapeutic potential of this strategy in mitigating DKD progression and cardiovascular disease.

Impact of methotrexate-loaded fattigated albumin nanoparticles and pharmaceutical excipients on real-time reactive oxygen species and cell viability in a microfluidic chip system.

Real-time tracking of mRNP complex assembly reveals various mechanisms that synergistically enhance translation repression.

Analysis of the metabolic process of sugarcane juice fermented by Leuconostoc mesenteroides and identification of exopolysaccharides.

Optimizing pilot plant flux by harnessing loach metabolism to overcome biocake steric hindrance.

Mapping the metabolic perturbations associated with palmitate-induced oxidative stress and development of insulin resistance in skeletal muscle cells.

Anthocyanin-sulfated polysaccharide-ovalbumin nanocomplex: Intestinal absorption mechanism and intracellular antioxidant activity in Caco-2 cells.

Reprogramming cysteine metabolism via METTL14-SLC7A11 axis promotes the progression of NAFLD and hepatocellular carcinoma.

ABSTRACTBackgroundOsteosarcopenia, characterised by concurrent bone loss and muscle atrophy, presents a significant challenge in aging populations, particularly in postmenopausal women. The current therapeutic options potentially treat bone and muscle loss independently, highlighting the importance of an integrated approach. This study aimed to investigate the effects of branched‐chain amino acid (BCAA) supplementation on muscle and bone health using ovariectomised (OVX) mice, a model for postmenopausal osteoporosis and sarcopenia.MethodsFemale C57BL/6 mice were divided into sham‐operated and OVX groups, with OVX mice further subdivided to receive 0.25 mg/kg (Low) or 1 mg/kg (High) of BCAA supplementation for 16 weeks. Muscle mass, function and mitochondrial health were assessed alongside bone mineral density (BMD), bone turnover markers and histological evaluations. Additionally, the study explored mechanistic insights into sclerostin modulation and its influence on Wnt signalling through plasma and tissue analyses.ResultsThe hind limb fat mass was increased in the OVX group but reduced with BCAA supplementation, while hindlimb lean mass (p < 0.01) and total lean mass (p < 0.001) were significantly higher in the OVX + High‐BCAA group compared with the OVX group. Gastrocnemius muscle weight was lower in the OVX group but improved (p < 0.05) with both Low‐ and High‐BCAA supplementation. BCAA preserved bone microarchitecture by improving cortical thickness (p < 0.01) and modulating bone turnover markers, including osteocalcin (p < 0.01) levels. Plasma sclerostin levels were regulated, suggesting a role in bone remodelling. In muscle, BCAA enhanced hypertrophy by upregulating MHC expression (p < 0.05) and downregulating atrophy markers such as Atrogin‐1 (Low‐BCAA, p < 0.001; High BCAA, p < 0.001) and MuRF‐1 (Low‐BCAA, p < 0.01; High BCAA, p < 0.001). Additionally, BCAA mitigated the cytotoxic effects of H2O2 in osteocytic MLO‐Y4 cells, reducing sclerostin levels (p < 0.05) and improving cellular viability (p < 0.05). In C2C12 cells, BCAA reversed sclerostin‐induced muscle atrophy (p < 0.01), increasing MHC expression (p < 0.01) and myotube diameter (p < 0.01) while reducing Atrogin‐1 (p < 0.01) and MuRF‐1 (p < 0.001) expression.ConclusionsBCAA supplementation alleviates muscle atrophy and partially preserves bone microarchitecture in OVX mice. Importantly, our data highlight bone‐derived sclerostin as a molecular link that transmits bone signals to muscle; BCAA mitigates osteosarcopenia by modulating this bone‐to‐muscle endocrine axis via Wnt signalling. Although improvements in bone structure were modest, the findings position BCAAs as a promising adjunct therapy targeting the integrated bone–muscle unit.