Search Results (21,258)

This study aimed to optimize the ultrasonic-assisted extraction of polyphenols from Archidendron clypearia and to evaluate their anti-hyperuricemic effects. Polyphenols from medicinal plants have attracted increasing attention due to their potential roles in regulating uric acid metabolism. In this study, single-factor experiments combined with Box–Behnken response surface methodology were employed to optimize extraction conditions, and an entropy weighting method was applied to integrate total polyphenols and Archidendrin I into a comprehensive evaluation index. The bioactivity of the obtained extract was further assessed through in vitro assays and a hyperuricemic mouse model. The optimal extraction conditions were determined to be 50% ethanol, a liquid-to-material ratio of 30, and 31 min of sonication, yielding 175 mg GAE/g DW of total polyphenols and 80.34 mg/g DW of Archidendrin I. The extract exhibited significant xanthine oxidase inhibitory activity, reduced serum uric acid levels, regulated urate transporters (URAT1, GLUT9, and ABCG2), and alleviated renal and hepatic injury in hyperuricemic mice. These findings indicate that the optimized process enables efficient extraction of polyphenols from Archidendron clypearia, and the resulting extract exerts beneficial regulatory effects on uric acid metabolism, highlighting its potential as a natural agent for hyperuricemia management. Full article

Background/Objectives: Diabetic foot ulcers (DFUs) are a common and challenging complication of diabetes, significantly impacting the quality of life for patients due to impaired wound healing. Exploring effective and targeted therapies for DFUs is therefore both important and meaningful. Sulforaphane (SFN), a natural bioactive compound found in cruciferous vegetables, shows promise in this area. However, its role and underlying mechanisms in promoting wound healing in DFUs have not been fully understood. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured under high-glucose conditions to establish an in vitro diabetic model. Cell viability, inflammation, apoptosis, and mitochondrial function were assessed. The expression and activation of Nrf2 were examined following SFN treatment. Additionally, Nrf2 overexpression was performed to validate its role in mediating the protective effects of SFN under high-glucose stress. Results: High-glucose conditions significantly reduced HUVEC viability and increased inflammation, apoptosis, and mitochondrial dysfunction. Treatment with SFN effectively counteracted these detrimental effects. SFN robustly activated Nrf2 signaling, and overexpression of Nrf2 recapitulated the protective effects of SFN, attenuating cellular damage under high-glucose conditions. Conclusions: SFN activates Nrf2 expression and protects HUVECs from high-glucose-induced injury by improving cell viability, mitochondrial function, and inflammatory response. These findings suggest that SFN may serve as a promising targeted therapy for diabetic foot ulcers. Full article

Background/Objectives: Poor aqueous solubility limits the oral absorption and bioavailability of many active pharmaceutical ingredients. Simple formulation approaches suitable for hospital and community pharmacy compounding are therefore needed. This study aimed to develop and evaluate melt-filled hard capsules containing nifedipine, a model of poorly water-soluble BCS class II drug, using polyethylene glycol (PEG) carriers to improve dissolution performance. Methods: PEG blends of different molecular weights (PEG 400, PEG 1500, and PEG 4000) were prepared by melt mixing, followed by incorporation of nifedipine and manual filling into hard gelatin capsules. The formulations were characterized regarding mass variation, drug content, in vitro dissolution, rheological behavior, and solid-state properties using Fourier transform infrared (FTIR) spectroscopy. Dissolution profiles were kinetically modeled and compared with pure nifedipine. Results: All capsules met pharmacopoeial requirements for mass uniformity and showed acceptable drug content. PEG-based melt-filled formulations exhibited markedly enhanced dissolution compared with crystalline nifedipine. Faster drug release was associated with lower-molecular-weight PEGs and reduced viscosity, with the PEG 400/PEG 1500 blend demonstrating the most rapid dissolution. Rheological analysis confirmed shear-thinning behavior, while FTIR findings suggested intermolecular interactions and partial amorphization of nifedipine within the PEG matrices. Conclusions: This study provides a translational adaptation of solid dispersion principles into a compounding-compatible melt-filling approach. Full article

Background/Objectives: Cervical cancer, primarily driven by persistent high-risk HPV infection, remains a major global health issue. Xiao-ai-fei honey ointment, a traditional Uyghur multi-ingredient preparation, has shown clinical promise in cancer treatment, but its mechanisms against cervical cancer are not fully understood. This study aimed to investigate the potential molecular mechanisms of ethanolic extract of Xiao-ai-fei honey ointment (XAFHO) in cervical cancer using network pharmacology, single-cell RNA sequencing, and experimental validation. Methods: Differentially expressed genes (DEGs) in cervical cancer were identified from TCGA database. Active components and corresponding targets of XAFHO were retrieved from the TCMSP database, and disease targets were obtained from GeneCard, OMIM, and the TTD. Intersection targets were subjected to multivariate Cox and LASSO regression to construct a prognostic model. Immune infiltration, TMB, and MSI were compared between risk groups. Single-cell RNA-seq data were analyzed to determine cellular origins and inter-cellular communication. In vitro assays were performed on HeLa and SiHa cells to assess the anti-cancer activity of XAFHO. Molecular docking evaluated binding affinities between active compounds and core targets. The expression and functional roles of FASN and SPP1 were further validated by RT-qPCR, Western blotting, and siRNA transfection. Results: Sixty-three potential XAFHO targets were identified, and an 11-gene prognostic model was established, effectively stratifying patients into high- and low-risk groups with significantly different overall survival (AUC > 0.7). The high-risk group exhibited an immunosuppressive microenvironment and higher TMB. Single-cell analysis revealed that FASN and ACACA were predominantly expressed in tumor cells, while SPP1 was enriched in macrophages/monocytes. Tumor cells communicated with immune cells via the TGFB1–TGFβR1/R2 axis, promoting immune evasion. In vitro, XAFHO significantly inhibited proliferation, colony formation, migration, and invasion of cervical cancer cells. Molecular docking confirmed the strong binding of quercetin, kaempferol, and isorhamnetin to FASN and SPP1 (binding energy < –6.0 kcal/mol). Functional validation indicated that upregulated FASN and SPP1 contribute to malignant behaviors in cervical cancer cells. Conclusions: This study integrates network pharmacology with single-cell and experimental approaches to demonstrate that XAFHO exerts multi-target and multi-cell anti-cervical cancer effects, potentially by modulating lipid metabolism and immune-related pathways via FASN and SPP1. These findings provide a scientific basis for the therapeutic application of XAFHO in cervical cancer. Full article

Background: Clear aligner therapy (CAT) is increasingly popular due to aesthetic and functional advantages. Recent advances allow direct 3D printing of aligners, raising questions about their cytotoxicity and biocompatibility under intraoral conditions. Objectives: To review and synthesize current evidence on the cytotoxicity and biocompatibility of 3D-printed and thermoformable orthodontic aligners, and to identify factors affecting cellular responses. Eligibility criteria: Original research published from 2021 to 2026 evaluating the safety of orthodontic aligners; conference abstracts, editorials, and review papers were excluded. Sources of evidence: Medline (via PubMed), Scopus, Web of Science, and the Cochrane Library; search terms “aligner” AND “biocompatibility”; last search conducted on 31 January 2026. Charting methods: Data on authors, publication year, material type, experimental model, cytotoxicity assessment (extraction solvent, incubation period, cell line, and cell exposure), and main results were extracted independently by two reviewers. Results: Fourteen in vitro studies were included, seven on thermoformable aligners and seven on directly 3D-printed aligners; no clinical trials were identified. Material composition, post-processing, and oral environmental factors influenced cytotoxicity. Some materials exhibited acceptable biocompatibility, whereas others showed varying cytotoxic effects, indicating inconsistencies across studies. Conclusions: Directly 3D-printed and thermoformable aligners show potential for safe intraoral use, but evidence is limited to in vitro studies. Further standardized in vitro and in vivo research is needed to reliably assess cytotoxicity and ensure patient safety before widespread clinical implementation. Full article

Prion diseases are fatal neurodegenerative disorders that affect humans and animals, caused by the conformational conversion of the normal cellular prion protein (PrP^C) into its misfolded, infectious isoform PrP^Sc. Recently, camel prion disease (CPrD) was identified in dromedary camels (Camelus dromedarius) in Algeria. Due to the potential implications for animal and human health, as well as the possible socio-economic impact in Mediterranean regions where camels play a pivotal role as a source of food, in-depth characterization of camel prions is important to increase our understanding of camel prion disease. We developed a neuronal cell line model for studying the molecular features of camel prion infection. We genetically edited mouse neuronal CAD5 cells to generate CAD5 PrP knockout (KO) cells. We then used lentiviral transduction to generate CAD5 cells expressing camel PrP (CAD5-camel-PrP). Following infection of these cells with a CPrD-positive camel brain homogenate, we observed PrP^Sc signals at various passages, as indicated by immunoblotting analysis. RT-QuIC (Real-Time Quaking-Induced Conversion) assays further supported these findings, demonstrating transient prion conversion activity in the CPrD-infected CAD5-camel-PrP cells. Taken together, our data describe the first neuronal cell line permissive to camel prion infection, a novel in vitro tool for mechanistic studies of camel prion disease. Full article

Background: The Xiao Zhong Zhi Tong Patch (XZZTP) has been extensively utilized in China to alleviate many diseases associated with bacterial inflammation. However, its pharmacological mechanism and active components remain unclear. Methods: The anti-inflammatory effects of XZZTP were evaluated in vivo and in vitro models. The characterization of XZZTP and its transdermal components was performed using LC-MS/MS. The underlying pharmacological mechanism was predicted through network pharmacology using the identified transdermal components and verified by Western blotting. Molecular docking and molecular dynamics simulations were performed on key targets to screen active components. Results: XZZTP showed a swelling inhibition rate of 45.96% in xylene-induced ear edema mice in vivo. In vitro, the inflammatory mediators NO, TNF-α, and PGE2 were concentration-dependently reduced by XZZTP in the LPS-induced RAW 264.7 macrophages model, with inhibition rates of 56.53%, 53.75%, and 48.49% at 200 µg/mL, respectively. LC-MS/MS identified 126 chemical components (97 newly reported) in XZZTP, including 52 transdermal potential active components, among which a new iridoid and its isomer were reported for the first time. Network pharmacology analysis demonstrated that XZZTP mainly downregulated the PI3K/AKT/HIF-1 signaling pathway to alleviate bacterial inflammation. The protein expression of core targets p-PI3K, p-AKT, and HIF-1α in the LPS-induced RAW 264.7 macrophages was significantly reduced after XZZTP intervention. Eight active components were screened via molecular docking, and molecular dynamics simulations of three representative complexes validated stable binding interactions, supporting their therapeutic potential. Conclusions: These findings provide a theoretical basis for XZZTP as a potential agent to ameliorate bacterial inflammation-related diseases, serving as a reference for its further application. Full article

Allergic anisakiasis (AA), caused by the ingestion of fish contaminated with Anisakis larvae, has emerged as a growing global health concern due to the increasing consumption of raw or undercooked seafood. Anisakis simplex is identified as the primary etiologic species, responsible for gastrointestinal symptoms, IgE-mediated (Type I) or cell-mediated (Type IV) manifestations, and gastro-allergic anisakiasis (GAA), a unique clinical overlap between parasitic infection and acute IgE-mediated food allergy. In this review, we analyzed the epidemiology of Anisakis simplex allergy, the main diagnostic methods to confirm a diagnosis of food allergy, its clinical manifestations, and how these differ in different countries around the world. This multidisciplinary synthesis provides, for the first time, an integrated understanding of Anisakis-induced disease mechanisms across human, animal, and cellular levels. The persistence of allergenic proteins despite standard food processing underscores the need for improved diagnostic tools, public health surveillance, and preventive strategies—particularly in populations with high seafood consumption or occupational exposure. A comprehensive approach combining clinical, molecular, and immunological perspectives is essential to address the expanding global burden of allergic anisakiasis. Full article

Background: Porcine epidemic diarrhea virus (PEDV) remains a major threat to the global swine industry, highlighting the urgent need for safe and effective next-generation vaccines. mRNA vaccines have emerged as a promising platform due to their rapid development and favorable safety profile. Objectives: This study aimed to design and perform the preliminary evaluation of a PEDV multi-epitope mRNA vaccine using an immunoinformatics-guided strategy combined with experimental validation. Methods: Immunoinformatics tools were used to identify B-cell and cytotoxic T lymphocyte (CTL) epitopes from the PEDV spike (S), membrane (M), and nucleocapsid (N) proteins. Selected epitopes were assembled into a multi-epitope antigen (E). mRNA constructs encoding S1, S2, and antigen E were synthesized via in vitro transcription and encapsulated into lipid nanoparticles (LNPs). Expression was evaluated in HEK293T cells, and immunogenicity was assessed in mice measuring antigen-specific antibody responses and cytokine levels following immunization. Results: The mRNA constructs exhibited high structural integrity and efficient intracellular translation. The LNP formulations showed good physicochemical stability and delivery efficiency. Immunization with the antigen E mRNA-LNP formulation induced significantly higher PEDV-specific IgG levels compared with control groups. Elevated cytokine levels further indicated activation of both humoral and cellular immune responses. Conclusions: This study presents a feasible workflow for the development of a PEDV multi-epitope mRNA vaccine. The antigen E construct demonstrated favorable immunogenicity in a mouse model, supporting its potential as a promising construct for further investigation and optimization. Although further studies are required to validate antigen expression at the protein level and to further characterize immune mechanisms, these findings provide preliminary evidence supporting the feasibility of multi-epitope mRNA vaccines for PEDV prevention. Full article

Introduction: Gastric cancer is a prevalent and aggressive malignancy driven by complex signaling networks. Estrogen receptor-α36 (ER-α36), a membrane-localized receptor, mediates non-genomic signaling and promotes tumor progression. ER-α36 can interact with epidermal growth factor receptor (EGFR) to activate downstream mitogen-activated protein kinase (MAPK) signaling, but the detailed mechanism in gastric cancer remains unclear. This study aimed to explore whether ER-α36 promotes gastric cancer progression by regulating serum and glucocorticoid-regulated kinase 1 (SGK1)-mediated Erk1/2 activation. Methods: We collected 53 human gastric adenocarcinoma specimens and detected ER-α36 expression by immunohistochemistry. Bioinformatics analysis was used to identify ER-α36-related kinases. Gastric cancer cell lines (SGC7901, HGC27, NCI-N87, and MFC) were used for in vitro studies. Western blotting, qRT-PCR, immunofluorescence, co-immunoprecipitation (Co-IP), wound healing, MTT, and Transwell invasion analyses, and nude mouse orthotopic tumor models were applied to investigate the function and mechanism of the ER-α36/SGK1/Erk1/2 axis. Results: ER-α36 was positively expressed in 62.3% of gastric adenocarcinoma tissues and was associated with poor differentiation and prognosis. SGK1 was identified as a key kinase downstream of ER-α36. ER-α36, SGK1, and p-Erk1/2 were co-upregulated in gastric cancer tissues and cells. ER-α36 regulated Raf/MEK1/2/Erk1/2 phosphorylation in an SGK1-dependent manner. EGF-induced Erk1/2 activation required both ER-α36 and SGK1. Overexpression of ER-α36 promoted the proliferation, migration, and invasion of gastric cancer cells, while SGK1 knockdown abolished these oncogenic effects. In vivo experiments confirmed that ER-α36 promoted gastric tumor growth and EGFR/Erk signaling, which was attenuated by SGK1 knockdown. Conclusions: ER-α36 contributes to the malignant progression of gastric adenocarcinoma by activating the Erk1/2 pathway through SGK1. The ER-α36–SGK1–Erk1/2 axis may serve as a novel therapeutic target for gastric cancer. Full article

Acute myeloid leukemia (AML) is a complex blood cancer that primarily affects relapsing or refractory patients receiving conventional chemotherapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) have anticancer properties with restricted clinical efficacy attributable to cyclooxygenase (COX)-induced toxicities. To address this issue, a group of benzylamide analogs of the classical NSAIDs (NSI-1–NSI-9) were developed and synthesized to mask the carboxylic acid moiety and minimize COX-induced adverse effects while maintaining anticancer activity. The cytotoxic effect of such substances has been demonstrated in some leukemia cell lines (HL-60, MV4-11, KG1a, and K562). NSI-5 exerted the highest anti-leukemic activity among these sulindac analogs, as determined at a sub-micromolar level in all cell lines studied, by IC50. This mechanistic data also demonstrated that NSI-5 induced apoptosis that was dose-dependent, especially in HL-60 cell lines, and increased the sub-G1 cell fraction. This apoptotic process was also accompanied by a significant decrease in mitochondrial membrane potential, which is characteristic of the induction of the intrinsic apoptotic process. Interestingly, NSI-5 decreased the intracellular reactive oxygen species (ROS) and the expression of most antioxidants (catalase and glutathione synthetase), as well as the redox balance. Gene characterization in vitro also suggested activation of apoptotic pathways, where expression of Bax, Bak1, and Caspase-3 increased, suggesting a potential p53-independent apoptotic pathway, in contrast to control for Bcl-2 expression. Collectively, these findings indicate that NSI-5 is a promising in vitro anti-leukemic lead compound, with activity associated with mitochondrial dysfunction and altered redox regulation. The observed effects are consistent with previously reported COX-independent activity of structurally related NSAID derivatives, and support further investigation of NSI-5 in preclinical models. Full article

Diabetic wounds are a common and severe complication of diabetes mellitus, characterized by delayed healing due to persistent inflammation, impaired angiogenesis, and cellular dysfunction. Conventional therapeutic approaches remain limited in efficacy. In recent years, exosomes have attracted considerable attention in wound healing and regenerative medicine because of their crucial role in intercellular communication and tissue repair. However, rapid clearance of exosomes in vivo greatly limits their therapeutic efficacy. To address this critical limitation, we engineered a decellularized extracellular matrix (dECM)-based hydrogel system functionalized with exosomes derived from skin-derived precursor cells (SKPs). This biomimetic scaffold was designed to serve as a local exosome-delivery platform at the wound site, with the aim of improving exosome utilization and augmenting their regenerative effects. Comprehensive in vitro characterization demonstrated that the exosome-loaded composite hydrogels exhibited robust pro-angiogenic activity, as evidenced by enhanced endothelial cell proliferation, migration, and tube formation. Moreover, the hydrogels displayed significant antibacterial effects against wound-relevant pathogens and potent reactive oxygen species (ROS)-scavenging capacity, thereby mitigating oxidative damage. Notably, the composite hydrogels also promoted the phenotypic polarization of macrophages toward the pro-regenerative M2 phenotype. In parallel, in vivo studies using a streptozotocin-induced diabetic rat wound model confirmed that treatment with the composite hydrogels significantly accelerated wound closure rates compared to control groups. Histological and immunohistochemical analyses revealed enhanced angiogenesis, as evidenced by increased CD31-positive microvessel density, as well as improved collagen deposition, re-epithelialization, and an attenuated local inflammatory microenvironment characterized by reduced pro-inflammatory cytokine expression and elevated M2 macrophage infiltration. Collectively, the SKPs exosome-loaded dECM based composite hydrogels developed in this study represent a potential therapeutic strategy for the treatment of diabetic wounds. Full article

Zearalenone (ZEA) is a mycotoxin widely present in cereals, feeds, and foods, posing a persistent threat to human and animal health. Hepatic fibrosis is a pathological process characterized by excessive extracellular matrix (ECM) deposition. Chronic liver injury caused by sustained oxidative stress can initiate the development of early hepatic fibrosis. However, whether liver injury induced by ZEA can trigger hepatic stellate cell (HSC) activation and promote early profibrotic responses remains unclear. The aim of this study was to assess whether ZEA-induced liver injury promotes HSC activation and early profibrotic responses. To address this, we established a BALB/c mouse exposure model and used the murine HSC line (JS-1) for in vitro validation. The results showed that ZEA exposure caused structural damage in hepatic tissue and produced an incomplete bridging pattern of collagen thickening suggestive of an early profibrotic tendency. ZEA shaped a proinflammatory microenvironment by activating the IκBα/NF-κB axis and induced the TGF-β1/Smad2/3 pathway, accompanied by Smad7 suppression, thereby promoting HSC activation and the expression of fibrosis-related genes. ZEA also altered autophagy-related markers in liver tissue and JS-1 cells. Pharmacological inhibition with chloroquine partially attenuated ZEA-induced upregulation of α-SMA and collagen I/III, suggesting that autophagy-related processes may be involved in ZEA-associated HSC activation and early ECM deposition. In summary, ZEA promotes HSC activation and early profibrotic changes in the liver and is associated with inflammatory activation, TGF-β1/Smad signaling, and altered autophagy-related activity. These findings provide a basis for further investigation into the mechanisms underlying ZEA-induced early profibrotic remodeling in the liver. Full article

Plant-derived sweet proteins are promising low-calorie natural sweeteners that may reduce dietary sugar intake and prevent non-communicable diseases. Although seven have been identified—thaumatin, miraculin, monellin, mabinlin, brazzein, pentadin, and curculin (neoculin)—only thaumatin is currently approved as a food additive. The development of others requires comprehensive safety assessments, particularly regarding allergenicity. This systematic review aims to investigate and synthesize allergenicity assessment methods (in silico, in vitro, in vivo, and clinical) applied to these seven sweet proteins. The literature searches were conducted following PRISMA guidelines across Scopus, PubMed, and Wiley Online Library databases, up to 30 November 2025, with no time restrictions. The risk of bias in selected studies was evaluated using GRADE. After the selection process, 14 out of 2634 studies met the inclusion criteria. Thaumatin, miraculin, monellin, and brazzein emerged as the most extensively studied proteins. In silico approaches (sequence and structural homology) and in vitro assays (digestibility and cell-based methods) were the most commonly employed methods. In contrast, in vivo studies (animal models) and clinical evaluations (skin prick tests, oral food challenges) were rarely reported. Allergenicity studies on pentadin, mabinlin, and curculin (neoculin) are limited, indicating a research gap that requires further study to support regulatory approval and consumer acceptance. Full article

Adult neural stem cells (NSCs) maintain lifelong neurogenesis, a fundamental process for neuroplasticity, memory and brain homeostasis. Despite decades of research, translating basic NSC biology into effective clinical therapies remains a central challenge. Here we present a narrative review that provides a comprehensive update on the current landscape of adult NSC research, associating molecular mechanisms with the emerging translational technologies. First, we analyze the biological features and neurogenic sequences within canonical niches such as the subventricular lateral zone and the subgranular zone, emphasizing phylogenetic and migratory differences between rodent models and humans. Second, we integrate these mechanisms with the influence of environmental and pathological modulators, describing how aging, metabolic changes, chronic stress and neuroinflammation disrupt NSC quiescence and lineage progression. Finally, we highlight recent technological advances driving the field toward clinical applications. By examining current NSC isolation strategies, induced pluripotent stem cell modeling, direct somatic reprogramming and the use of CRISPR-Cas9-based gene-editing therapies, this review delineates the pathways to overcome existing methodological limitations. Ultimately, we provide an integrated context that connects the modulation of the neurogenic niches with advanced in vitro technologies, offering new perspectives for regenerative medicine and the treatment of neurological disorders. Full article