Search Results (346)

Cell replacement therapy is a promising investigational approach for Parkinson’s disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD. Full article

Honokiol (HON) and magnolol (MAG), hepatoprotective neolignans from Magnolia spp., are promising candidates for mitigating liver damage associated with long-term parenteral nutrition (PN). However, their clinical use is limited by poor aqueous solubility. This study aimed to develop a multifunctional nanoemulsion platform based on clinically used lipid nanoemulsions (Lipofundin^®/Lipidem^®), enriched with omega-3 fatty acids and loaded with HON, MAG, or a combination of both. Nanoemulsions were prepared using a two-step homogenization process. Pre-emulsions containing HON, MAG, or both neolignans were first obtained using high-shear homogenization, then mixed in a 1:1 volume ratio with Lipofundin or Lipidem and subsequently subjected to high-pressure homogenization. All nanoemulsions met pharmacopeial standards and literature-recommended quality criteria. The formulations showed mean droplet diameters below 500 nm, PFAT5 values below the 0.05% limit, and PDI values < 0.2. Strongly negative zeta potentials (≤−30 mV) confirmed stability. The formulations were non-hemolytic, fully compatible with PN admixtures for 24 h, and non-cytotoxic in THLE-2 cells. Furthermore, all developed nanoemulsions demonstrated lower in vitro hepatotoxicity than clinically used reference formulations, indicating their promising clinical potential. However, further in vivo studies are required to confirm their therapeutic benefits and hepatoprotective effect during parenteral nutrition (PN). Full article

Doxycycline (DOX) is a well-characterized antibiotic, and its pharmacokinetic behavior has recently attracted renewed scientific interest. Its absorption occurs mainly in the small intestine, while ions such as Fe³⁺ and Al³⁺ readily form complexes, particularly under acidic conditions, thereby reducing the fraction of free drug available for absorption. The present study provides a systematic investigation of how such interactions influence the dissolution and intestinal permeability of DOX. A dynamic in vitro protocol was implemented, incorporating an online transition from gastric to intestinal conditions in combination with Franz diffusion cells. This integrated system enables real-time monitoring of early DOX absorption-related processes, providing a more comprehensive understanding of potential pharmacokinetic interactions during its coadministration with iron or aluminum supplements. To ensure reliable quantification, a rapid, economical, and environmentally compatible HPLC-FLD method was developed and validated, employing a Hypersil Gold C18 column (50 mm × 4.6 mm, 5 μm; Thermo) and a mobile phase consisting of acetonitrile—20 mM NaH₂PO₄ (pH 2) 15:85 v/v. Overall, a practical and efficient framework was established for investigating factors that influence the bioavailability of doxycycline, supporting the broader evaluation of drug, excipient, and drug supplement interactions. Full article

The hybrid approach remains a compelling strategy for designing molecules that combine enhanced biological activity with a favorable safety profile. Marine peptides, in particular, have attracted significant attention due to their well-documented broad spectrum of biological activities. Peptides derived from rays have been recognized for their diverse biological activities. Notably, physicochemical properties of these peptides support practical application without requiring further refinement of the mature molecule or specialized formulations. In this study, we present two new chimeric peptides, PK01# and PK02#, which incorporate an opioid pharmacophore linked to a short amino acid sequence derived from the skate Raja porosa. Those compounds interact with the opioidergic system, specifically targeting the mu-opioid receptor (MOR). Furthermore, the compounds were evaluated for their effects on cancer cell viability through in vitro MTT assays (as an exploratory endpoint) and for their binding compatibility with EGFR via in silico docking. Both compounds showed limited effects on cell viability in HeLa, SAS, and PANC-1 cells, while PK02# induced a minor reduction in metabolic activity in glioblastoma cells without reaching IC50 values or significant cytotoxic thresholds. Interestingly, the structures of these hybrid compounds offer valuable insights into the role of phenylalanine residues within their sequences, which appear to be critical for both biological activity and receptor interaction. Moreover, these findings may support future structural optimization of peptide hybrids focused on receptor modulation and biological profiling. Full article

Objective: Developing foundational biomaterial platforms for cultured meat research requires 3D co-culture systems capable of supporting multiple relevant cell types in a spatially organized manner. This study aimed to establish a compartmentalized tri-culture hydrogel disc incorporating a lipid-containing barrier phase as a proof-of-concept in vitro model. Methods: Beeswax/alginate (Bw/Algi) hydrogels were fabricated and evaluated for morphology and cytocompatibility as a lipid-containing scaffold component. Fucoidan/alginate (Fu/Algi) hydrogels were prepared at varying fucoidan concentrations and screened to identify conditions compatible with C2C12 viability and early-stage differentiation. A composite beeswax/fucoidan/alginate disc (Bw/Fu/Algi) was then assembled by casting cell-laden Fu/Algi regions (myoblasts, fibroblasts, and endothelial cells), separated by Bw/Algi barrier layers and ionically crosslinked with CaCl₂. Scaffold performance was assessed using standard assays for morphology, cytocompatibility, myogenic marker expression, protein production, and thermal stability. Results: Bw/Algi supported cytocompatible C2C12 attachment and growth, while Fu/Algi exhibited concentration-dependent effects on myogenic marker expression, enabling selection of an optimized fucoidan concentration for 3D assembly. The final Bw/Fu/Algi disc maintained viable compartmentalized tri-culture and supported indirect co-culture through spatial separation by the Bw barrier. Myogenic regions exhibited myogenic marker expression with measurable protein production, and differential scanning calorimetry confirmed structural stability under heating. Conclusion: This work establishes a Bw/Fu/Algi tri-culture disc integrating a lipid-containing barrier component with hydrogel-based myogenic compartments, providing a preliminary platform for multicellular in vitro modeling and scaffold design relevant to cultured meat research. Full article

Hyperlipidemia-associated obesity is frequently accompanied by hepatic injury, bile acid dysregulation, gut microbial remodeling, and anxiety-like behavioral alterations. As emerging functional food ingredients, postbiotics and dietary herbs (DH) may provide practical dietary strategies for metabolic health management, but the most suitable postbiotic form and its compatibility with DH remain unclear. In this study, FB 3-14-derived postbiotics were first screened in vitro for cholesterol micellar binding. Inactivated bacterial cells (Postcell) exhibited the strongest cholesterol-binding capacity and were therefore selected for in vivo validation, alone or in combination with DH, in a high-fat, high-cholesterol (HFHC) mouse model. Consistently, Postcell showed superior efficacy in attenuating body weight gain, jejunal triglyceride accumulation, and hepatic dysfunction compared with other postbiotic forms. Importantly, Postcell_DH exerted broader metabolic benefits, including reductions in weight gain, food efficiency, bile acid dysregulation, and neuroinflammation. Multi-omics analysis further indicated that these effects may be mediated through remodeling of the gut microbiota and metabolome, particularly pathways involved in bile acid and tryptophan metabolism. Notably, Clostridioides and taurochenodeoxycholate-7-sulfate were negatively associated with total cholesterol (TC) and leptin, whereas Clostridium_sensu_stricto_1 and 3-Hydroxyindolin-2-1-sulfate were negatively correlated with brain inflammatory level, lipid, and bile acid-related index. This study supports a practical postbiotic–herbal combination strategy relevant to functional food and dietary supplement development for hyperlipidemia-associated metabolic disturbances. Full article

Background/Objectives: Curcuma longa is widely recognized for its antioxidant, antimicrobial, and wound-related biological effects. The present study aimed to compare two extracts prepared from organic turmeric powder (Curcuma longa), using distilled water (CUR-H₂O) and 96% ethanol (CUR-EtOH), in terms of extraction yield, phytochemical profile, antimicrobial activity, and in vitro biological behavior relevant to future oral-health-oriented applications. Methods: The extracts were prepared by maceration followed by ultrasound-assisted processing, concentration, and lyophilization. Their antioxidant potential (AOP) was evaluated by DPPH assay, total phenolic content (TPC) by the Folin–Ciocalteu method, and targeted polyphenolic profile by UHPLC-MS. Antimicrobial activity was assessed by broth microdilution against Streptococcus mutans, Streptococcus oralis, and Candida albicans. In vitro biological activity was investigated on HaCaT keratinocytes. Results: CUR-EtOH extract showed a higher extraction yield than CUR-H₂O (5.13% vs. 2.01%), higher AOP (69.54 ± 0.49% vs. 53.35 ± 0.30%), and a higher TPC (163.87 ± 0.32 vs. 78.05 ± 0.28 mg GAE/g dry extract). Consistent with these TPC results, UHPLC-MS revealed a richer targeted polyphenolic profile in CUR-EtOH extract, particularly in terms of p-coumaric and ferulic acid derivatives. CUR-EtOH extract was more active against the tested oral streptococci, especially S. mutans (MIC 10 µL vs. 60 µL for CUR-H₂O), whereas CUR-H₂O extract showed a slightly better antifungal effect against C. albicans (MIC 60 µL vs. 80 µL). In HaCaT cells, CUR-H₂O extract exhibited the more favorable compatibility profile, while CUR-EtOH extract showed stronger cytotoxicity, despite promoting faster wound-gap closure at 10 µg/mL. Conclusions: The extraction solvent strongly influenced both the chemical profile and biological behavior of the turmeric-powder-derived extracts. These findings suggest that solvent selection may be used to tailor the balance between antimicrobial efficacy and epithelial compatibility in future turmeric-powder-derived preparations intended for oral-health-oriented applications. Full article

This study formulated and characterized metformin-loaded chitosan nanoparticles (NPs) using the ionic gelation technique and evaluated the drug release kinetics. Characterization confirmed successful drug encapsulation, with Fourier-transform infrared spectroscopy (FTIR) indicating compatibility, and X-ray diffraction (XRD) showing attenuation of characteristic metformin reflections consistent with reduced crystalline contribution after encapsulation. Particle sizes ranged from 74.28 to 86.82 nm. The NPs exhibited stable zeta potentials (+42.38 to +49.06 mV) and high entrapment efficiencies (68.42–81.26%). In vitro drug release studies at pH 7.4 and pH 2.0 demonstrated an initial burst release, followed by sustained release over 24 h. The cumulative drug release ranged from 81.92% to 97.72% at pH 7.4 and 89.4% to 98.1% at pH 2.0, with a faster release at pH 2.0. Drug release kinetics followed first-order for batch MN1, while batches MN2 and MN3 best fitted into the Higuchi model, indicating diffusion-controlled release through the chitosan polymeric network. The formulated metformin nanoparticles demonstrated significant potent dose-related and time-dependent cytotoxic effect against ovarian cancer cell lines and in vivo blood glucose lowering effect compared to the conventional dosage forms and control (p < 0.05). These findings highlight the potential of metformin-loaded chitosan NPs for sustained drug delivery, which may enhance patient compliance by reducing dosing frequency. Future studies should further explore their clinical applications. Full article

The production of cultivated meat relies on in vitro animal cell growth and requires the use of scaffolds that structurally resemble key features of the extracellular matrix (ECM), providing mechanical support and biochemical cues for cell adhesion, proliferation, and differentiation. Electrospinning has emerged as a promising technique for manufacturing three-dimensional edible scaffolds because it is robust, versatile, and capable of producing nanofibers with a high surface area-to-volume ratio, tunable porosity, and ECM-like fibrous architectures. Natural biopolymers are promising candidates for the fabrication of electrospun scaffolds, combining biocompatibility, biodegradability, and processing compatibility with food-grade requirements. However, the absence of fully food-grade electrospinning systems, coupled with limited scalable green-processing strategies, remains a critical barrier to industrial translation. In this context, this review presents recent advances in the food-grade electrospinning of natural biopolymers focused on cultivated meat production. Furthermore, scientific gaps in the development of fully edible scaffolds are discussed, along with the need for alternatives to animal-derived materials and synthetic carrier polymers, considering sustainability, consumer acceptance, and the translation from laboratory-scale studies to industrial systems. Finally, this review outlines a strategic roadmap to accelerate the transition from proof-of-concept studies toward scalable, regulatory-compliant, and industrially viable electrospinning technologies for cultivated meat production. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in the world. The disease progresses from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The modern concept of “multiple parallel hits” interprets disease progression as the result of the synergistic action of lipotoxicity, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, proinflammatory signals, and gut–liver axis dysfunction. Against the background of the limited translation of preclinical data from animal models due to interspecies differences, the importance of human-oriented in vitro platforms compatible with controlled design and high-throughput screening is increasing. The current review analyzes MASLD models based on the HepG2 cell line, systematizing steatosis induction protocols, evaluating the metabolic characteristics and limitations of this cell, and comparing 2D monocultures, 3D systems, and co-cultures. HepG2 has been shown to demonstrate a predictable steatogenic response to free fatty acids (FFAs) and is convenient for reproducing early stages of pathogenesis and primary pharmacological selection of compounds. At the same time, key limitations of the model are highlighted, namely tumor origin, glycolytic shift (Warburg effect), reduced β-oxidation, impaired very-low-density lipoprotein (VLDL) assembly and secretion, and sharply reduced cytochrome P450 (CYP450) activity, as well as limited reproducibility of fructose-induced de novo lipogenesis (DNL). Comparative analysis demonstrates an increase in physiological relevance with the transition from 2D to 3D and multicomponent co-cultures, accompanied by increased complexity and cost, but allowing for the modeling of inflammation and fibrogenesis. The review justifies approaches to selecting the appropriate platform based on the specific research task. Full article

Diseases caused by pathogenic microorganisms in Bombyx mori have long been a major constraint on the sustainable development of sericulture. Current preventive strategies remain substantially constrained by issues of drug resistance and environmental compatibility. In recent years, the application of nanomaterials for pathogenic microorganism control has garnered escalating attention. Among these, chitosan–silver nanoparticles (CS-Ag NPs), as an emerging class of nanocomposites, integrate the biocompatibility and biodegradability of chitosan with the robust antimicrobial activity of silver nanoparticles, thereby exhibiting considerable potential for preventing pathogenic infections. Nevertheless, the efficacy of CS-Ag NPs against B. mori pathogens has not previously been documented. In this study, CS-Ag NPs were successfully synthesized via chemical reduction. Their antiviral activity was validated using quantitative PCR. The inhibitory efficacy of CS-Ag NPs against Bacillus bombysepticus and Serratia marcescens was evaluated through in vitro inhibition zone assays and bacterial growth curve analysis, with the minimum inhibitory (MIC) concentration for both pathogens determined. Notably, CS-Ag NPs exhibited no significant inhibitory effect on filamentous fungi, potentially due to the impaired ability of nanoparticles to penetrate fungal cell walls. Preliminary mechanistic investigations into the antimicrobial mechanism of CS-Ag NPs were conducted from the perspectives of oxidative stress. Our data showed that CS-Ag NPs could effectively alleviate ROS accumulation induced by the pathogen. In summary, our work systematically investigates the potential of CS-Ag NPs in controlling pathogens and enables the preliminary elucidation of their antibacterial mechanisms. These findings establish a theoretical foundation for the development of pharmaceuticals against pathogenic microorganisms and also offer novel insights into the ecofriendly management of diseases. Full article

Background/Objectives: Compounded vaginal creams are widely used for conditions such as hormone replacement therapy, vaginal dryness, low libido, vaginal infections, etc. Recent research highlights the potential of using anhydrous bases to extend shelf life, particularly when combined with self-emulsifying and mucoadhesive properties that improve mucosal retention and enhance drug bioavailability. This study provides in vitro and ex vivo evaluation of an anhydrous vaginal base. Methods: Key quality indicators such as irritation potential, leakage potential, pH compatibility, mucoadhesion, and self-emulsification were assessed using the chorioallantoic membrane Hen’s Egg Test, MTT assay, texture analysis, and fluorescence microscopy. Results: The anhydrous vaginal base demonstrated high cell viability (>78%) and non-irritant potential (IS = 2.5) in in vitro assays. It maintained physiological vaginal pH (4.56 ± 0.05), showed strong mucoadhesive properties comparable to commercial products, and exhibited minimal leakage. Ex vivo studies confirmed its prolonged retention on vaginal tissues. The anhydrous vaginal base formed stable emulsions upon contact with vaginal fluid simulant, effectively distributing both lipophilic and hydrophilic compounds. Conclusions: Compared to water-containing bases, an anhydrous vaginal base shows advantages: longer retention time and lower leakage; adaptability to varying vaginal fluid levels; and efficient dispersion of both hydrophilic and lipophilic active pharmaceutical ingredients. These features support its potential use in compounded vaginal products, minimizing stability risks and enhancing patient compliance and therapeutic outcomes. Full article

Boron carbide (B₄C)-reinforced metal matrix composites (MMCs) are promising candidates for biomedical implants due to their mechanical properties and potential biological compatibility. In this study, in vitro biocompatibility and cytotoxicity of B₄C-reinforced CoCrMo, Ti, and 17-4 PH alloys were systematically evaluated using human osteoblast (HOB) cells. Composites were fabricated via powder metallurgy with varying B₄C reinforcement ratios (CoCrMo and Ti: 5–10 wt%; 17-4 PH: 3–12 wt%). Extracts prepared according to ISO 10993-12 standards were applied at different concentrations (100%, 50%, 25%, 12.5%) to assess cell viability using the MTT assay over 24, 48, and 72 h. Results demonstrated a clear dose-dependent cytotoxic effect across all composite systems. Ti composites exhibited the highest biocompatibility, with cell viability largely preserved even at higher B₄C ratios. CoCrMo composites showed moderate cytotoxicity, which decreased upon extract dilution, indicating low-concentration compatibility. In contrast, 17-4 PH composites revealed significant cytotoxicity at higher extract concentrations, exacerbated by increasing B₄C content. Literature-supported findings confirm that B₄C incorporation enhances hardness, wear resistance, and elastic modulus, yet excessive reinforcement can induce local stress and particle detachment, affecting cellular tolerance. Diluted extracts of Ti and CoCrMo composites maintained cell viability at a biocompatible level consistent with ISO 10993-5 criteria. These results highlight the promising biocompatibility of B₄C-reinforced Ti and CoCrMo alloys for biomedical applications and provide a biological basis for the design of next-generation composite implants. Full article

Fusarium wilt, caused by Fusarium oxysporum f. sp. niveum (Fon), severely restricts the sustainable development of the global watermelon industry. While conventional chemical fungicides of this disease have triggered prominent ecological issues, Bacillus-based microbial biocontrol, which combines inherent environmental compatibility with stable control efficacy, has emerged as a key green alternative to chemical management. However, the biocontrol potential of Bacillus sonorensis against this disease has not yet been fully investigated. In this study, we isolated 56 bacterial strains from healthy watermelon rhizosphere soil, and obtained a Fon-antagonistic strain A-5 with the strongest activity (70.15% mycelial inhibition rate), which was identified as B. sonorensis via polyphasic taxonomic analysis. In vitro assays showed that the sterile fermentation filtrate of strain A-5 had a maximum 81.05% inhibition rate against Fon, and its volatile organic compounds also significantly suppressed Fon growth, with broad-spectrum antifungal activity against four common phytopathogenic fungi. Functional tests confirmed that strain A-5 could secrete cell wall-degrading enzymes, produce siderophores and synthesize indole-3-acetic acid, and 17 antimicrobial secondary metabolite biosynthetic gene clusters were identified in its genome. Pot experiments verified that strain A-5 had a 78.04% relative control efficacy against watermelon Fusarium wilt, which significantly reduced seedling disease incidence and upregulated defense-related antioxidant enzyme activities in watermelon leaves. In general, B. sonorensis A-5 is a promising novel biocontrol agent for green management of watermelon Fusarium wilt. Full article

Braided nerve guidance conduits (NGCs) composed of decellularized porcine small intestinal submucosa (SIS) were developed to achieve an appropriate balance between mechanical performance and biological compatibility for peripheral nerve repair. This study aimed to compare four SIS-braided conduits with silicone tubes in terms of bending compliance, tensile strength, swelling behavior, and cytocompatibility. SIS-braided conduit exhibited a favorable combination of flexibility, tensile strength, and dimensional stability. In vitro evaluations using PC12 and SW10 cells demonstrated that SIS-braided conduit supported neurite outgrowth and Schwann cell adhesion, confirming its favorable cytocompatibility. Based on these findings, SIS-braided conduits and silicone tubes were subsequently evaluated in a rat sciatic nerve defect model. Functional recovery assessed using the Sciatic Functional Index suggested preliminary functional recovery in the SIS-braided conduit, and histological analyses revealed evidence of axonal regeneration and myelin formation within the conduit. Overall, the results indicate that the integration of mechanical robustness with biological activity is essential for the design of nerve graft substitutes. The conduit braided from decellularized small intestinal submucosa represents a promising biodegradable alternative, a considerable biodegradable alternative to conventional non-degradable silicone conduits for peripheral nerve repair. Full article