Search Results (460)

Colchicine is a potent alkaloid with well-established anti-inflammatory properties. It shows significant promise in treating classic immune-mediated inflammatory diseases, as well as associated cardiovascular diseases, including atherosclerosis. However, its clinical use is limited by a narrow therapeutic window, dose-limiting systemic toxicity, variable bioavailability, and clinically significant drug–drug interactions, partly mediated by modulation of P-glycoprotein and cytochrome P450 3A4 metabolism. This review explores advanced delivery strategies designed to overcome these limitations. We critically evaluate lipid-based systems, such as solid lipid nanoparticles, liposomes, transferosomes, ethosomes, and cubosomes; polymer-based nanoparticles; microneedles; and implants, including drug-eluting stents. These systems ensure targeted delivery, improve pharmacokinetics, and reduce toxicity. Additionally, we discuss chemical derivatization approaches, such as prodrugs, codrugs, and strategic ring modifications (A-, B-, and C-rings), aimed at optimizing both the efficacy and safety profile of colchicine. Combinatorial nanoformulations that enable the co-delivery of colchicine with synergistic agents, such as glucocorticoids and statins, as well as theranostic platforms that integrate therapeutic and diagnostic functions, are also considered. These innovative delivery systems and derivatives have the potential to transform colchicine therapy by broadening its clinical applications while minimizing adverse effects. Future challenges include scalable manufacturing, long-term safety validation, and the translation of research into clinical practice. Full article

Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt and NF-κB signaling pathways, and by inducing mitochondrial apoptosis through reactive oxygen species generation and cytochrome c release. However, its clinical application is hindered by its systemic and hemolytic toxicity, rapid degradation in plasma, poor pharmacokinetics, and immunogenicity, necessitating the development of targeted delivery strategies to enable safe and effective treatment. Nanoparticle-based delivery systems have emerged as a promising strategy for overcoming these challenges, offering improved tumor targeting, reduced off-target effects, and enhanced stability. This review provides a comprehensive overview of the mechanisms through which melittin exerts its anticancer effects and evaluates the development of various melittin-loaded nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic systems. It also summarizes the preclinical evidence for melittin nanotherapy across a wide range of cancer types, highlighting both its cytotoxic and immunomodulatory effects. The potential of melittin nanoparticles to overcome multidrug resistance and synergize with chemotherapy, immunotherapy, photothermal therapy, and radiotherapy is discussed. Despite promising in vitro and in vivo findings, its clinical translation remains limited. Key barriers include toxicity, manufacturing scalability, regulatory approval, and the need for more extensive in vivo validation. A key future direction is the application of computational tools, such as physiologically based pharmacokinetic modeling and artificial-intelligence-based modeling, to streamline development and guide its clinical translation. Addressing these challenges through focused research and interdisciplinary collaboration will be essential to realizing the full therapeutic potential of melittin-based nanomedicines in oncology. Overall, this review synthesizes the findings from over 100 peer-reviewed studies published between 2008 and 2025, providing an up-to-date assessment of melittin-based nanomedicine strategies across diverse cancer types. Full article

Flavonoids constitute a broad class of naturally occurring chemical compounds classified as polyphenols, widely present in various plants, fruits, and vegetables. They share a common flavone backbone, composed of two aromatic rings (A and B) connected by a three-carbon bridge forming a heterocyclic ring (C). One representative flavonoid is chrysin, a compound found in honey, propolis, and passionflower (Passiflora spp.). Chrysin exhibits a range of biological activities, including antioxidant, anti-inflammatory, anticancer, neuroprotective, and anxiolytic effects. Its biological activity is primarily attributed to the presence of hydroxyl groups, which facilitate the neutralization of free radicals and the modulation of intracellular signaling pathways. Cellular uptake of chrysin and other flavonoids occurs mainly through passive diffusion; however, certain forms may be transported via specific membrane-associated carrier proteins. Despite its therapeutic potential, chrysin’s bioavailability is significantly limited due to poor aqueous solubility and rapid metabolism in the gastrointestinal tract and liver, which reduces its systemic efficacy. Ongoing research aims to enhance chrysin’s bioavailability through the development of delivery systems such as lipid-based carriers and nanoparticles. Full article

Simultaneous values of glucose rate of change (RoC) and glucose can be presented in a dynamic glucose region plot, and risk spaces can be specified for (RoC, glucose) values expected to remain in the target range (glucose 3.9–10.0 mmol/L) or leave or return to the target range within the next 30 min. We downloaded continuous glucose monitoring (CGM) data for 60 days from persons with type 1 diabetes using two different systems for automated insulin delivery (AID), A (n = 65) or B (n = 85). The relative distribution of (RoC, glucose) values in risk spaces was compared. The fraction of all (RoC, glucose) values anticipated to remain in the target range in the next 30 min was higher with system A (62.5%) than with system B (56.8%) (difference 5.7, 95% CI (2.2–9.2%), p = 0.002). The fraction of (RoC, glucose) values in the target range with a risk of progressing to the above range (glucose > 10.0 mmol/L) was slightly lower in system A than in B (difference −1.1 (95% CI: −1.8–−0.5%, p < 0.001). Dynamic glucose region plots and the concept of risk spaces are novel strategies to obtain insight into glucose homeostasis and to demonstrate clinically relevant differences comparing two AID systems. Full article

Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article

With increasing popularity of food delivery services, the microbial safety of transported meals should be ensured. An effect of the type of a meal (cooked rice; mashed potatoes; mushroom sauce), inner primary packaging (sugarcane bagasse [SB] tray; polypropylene [PP] tray), secondary container (polyester/polyethylene foam/aluminum foil [PPA] bag; PP box) on the time interval of the internal hot ready-to-eat (RTE) meal temperature decrease to the value critical for Bacillus cereus growth (40 °C) was tested during a simulated delivery; in aliquot samples of the same meals, B. cereus growth was quantified presuming a natural contamination of the meals. Type of a meal had no effect on the tested time interval (p > 0.05). Packaging a meal in the PP tray as compared to the SB tray and inserting primary trays into the PP box instead of PPA bag delayed (p < 0.05) the internal meal temperature decrease by 50 and 15 min, respectively. Average B. cereus counts in the naturally contaminated meals after the four-hour culturing at 40 °C was 2.99 log CFU·g⁻¹. It was concluded that a hot RTE meal delivered up to four hours under the tested conditions is not likely to facilitate B. cereus growth above unacceptable levels. Full article

The tensile strength of the umbilical cord (UC) is influenced by its composition—including collagen, elastin, and hyaluronan—contributing to its unique biomechanical properties. This experimental in vitro study aimed to evaluate the UC’s mechanical behavior under varying strain rates and to characterize its viscoelastic response. Twenty-nine UC specimens, each 40 mm in length, were subjected to uniaxial tensile testing and randomly assigned to three traction speed groups: Group A (n = 10) at 8 mm/min, Group B (n = 7) at 12 mm/min, and Group C (n = 12) at 16 mm/min. Four different parameters were analyzed: the ultimate tensile strength and its corresponding elongation, the elastic modulus defined as the slope of the linear initial portion of the stress–strain plot, and the elongation at the end of the test (at break). While elongation and elongation at break did not differ significantly between groups (one-way ANOVA), Group C showed a significantly higher ultimate tensile strength (p = 0.047). A linear relationship was observed between test speed and stiffness (elastic modulus), with the following regression equation: y = 0.3078e^4.425x. These findings confirm that the UC exhibits nonlinear viscoelastic properties and strain-rate-dependent stiffening, resembling non-Newtonian behavior. This novel insight may have clinical relevance during operative deliveries, where traction speed is often overlooked but may play a role in preserving cord integrity and improving neonatal outcomes. Full article

Incorporating probiotics into edible films offers an effective strategy for delivering viable microorganisms to the body. This study aimed to develop edible films based on three types of pregelatinized cassava starch—pregelatinized native starch (PNS), hydroxypropyl distarch phosphate (HDP), and hydroxypropyl starch (HS)—as carriers for Bacillus coagulans (BC). The interactions between probiotic powder and the polymer matrix, as well as the viability of B. coagulans during film drying and subsequent storage, were evaluated to assess the effectiveness of the films as protective delivery systems at room temperature (25 °C). The addition of BC altered the amorphous-to-ordered structure of the starch matrices. Surface morphology analysis showed BC aggregates on PNS films, whereas HDP and HS films retained smooth surfaces. Incorporation of BC increased the tensile strength and Young’s modulus of PNS films but reduced their elongation at break. Additionally, BC decreased both the light transmittance and water contact angle in PNS films, while 1% BC increased the contact angle in HDP and HS films. BC had no significant effect on the solubility of PNS films but enhanced the solubility of HDP and HS films. Notably, B. coagulans maintained viability around 8 log CFU/g after 90 days of storage at room temperature, supporting the potential of pregelatinized starch-based films as effective probiotic carriers. Full article

Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), remains a therapeutic challenge due to its aggressive nature, limited treatment options, and high recurrence rates. Current therapies, including chemotherapy and immune checkpoint inhibitors, face resistance driven by tumor heterogeneity, immunosuppressive signaling, and dysregulated redox pathways. This review explores silibinin’s potential to modulate the tumor immune microenvironment (TIME) and overcome therapeutic resistance in TNBC. Silibinin exerts multifaceted anticancer effects by suppressing PD-L1 expression through the inhibition of JAK/STAT3 signaling and MUC1-C interaction, attenuating NF-κB-driven inflammation, and downregulating CCL2-mediated recruitment of tumor-associated macrophages (TAMs). Additionally, silibinin disrupts redox adaptation by targeting the Nrf2-EGFR-MYC-TXNIP axis, enhancing oxidative stress and chemosensitivity. Preclinical studies highlight its ability to inhibit epithelial–mesenchymal transition (EMT), reduce cancer stem cell (CSC) populations, and synergize with existing therapies like PD-1 inhibitors. Despite its low bioavailability, advanced formulations such as liposomes and nanoparticles show promise in improving delivery and efficacy. By reshaping TIME through dual antioxidant and immunomodulatory mechanisms, silibinin emerges as a viable adjunct therapy to reverse immunosuppression and chemoresistance in TNBC. Full article

Background/Objectives: Increasing the solid-state landscape of an active pharmaceutical ingredient (API) by generating new crystalline forms (e.g., polymorphs, cyclodextrin (CD) inclusion complexes, co-crystals, and salts) can yield products with significantly enhanced biopharmaceutical properties (especially increased water solubility), thereby improving API delivery and extending its lifetime. The aim of this study was the isolation of new solid forms of the poorly water-soluble non-steroidal anti-inflammatory drug fenbufen (FBF), for which relatively few solid phases have been reported to date. Further motivation for the study is the recent finding that it has potential for repurposing to treat acute pancreatitis. Methods: Interventions for generating new solid forms of FBF included (a) polymorph screening with a variety of solvent media, (b) attempts to form solid inclusion complexes with the native cyclodextrins α-, β-, and γ-CD using various preparative methods, and (c) co-crystallization with a series of coformers to produce co-crystals and/or molecular salts. Results: No new polymorphic forms of FBF were identified, but screening with CDs resulted in isolation and characterization of a new solid inclusion complex with γ-CD. However, co-crystallization of FBF with the water-soluble coformer isonicotinamide yielded two new products, namely a 1:1 co-crystal and an unusual multi-component ionic co-crystal, whose aqueous solubility indicated significant enhancement of FBF solubility. Conclusions: Due to its extremely low water solubility, FBF presented challenges during the study aimed at modifying its crystalline form. However, two new supramolecular forms, a co-crystal and an ionic co-crystal, were isolated, the latter phase having potential for further formulation owing to its significantly enhanced solubility. Full article

Bacterial cellulose (BC), an extracellular polysaccharide synthesized by various bacterial strains. It exhibits high tensile strength, water retention, crystallinity, and biocompatibility, making it valuable in biomedical, cosmetic, food, textile, and paper industries. This study examined the effects of six carbon sources on BC production by Komagataeibacter sucrofermentans, identifying fructose as the most effective. A Box–Behnken experimental design was employed to investigate the effects of three variables (fructose concentration, temperature, and cultivation time) on cellulose yield. The optimized cultivation conditions were: fructose concentration of 227.5 g/L, temperature of 28.0 °C, and cultivation time of 295 h, resulting in a BC yield of 63.07 ± 2.91 g/L. Subsequently, BC’s potential as a bacteriophage carrier was assessed. Escherichia coli phage T4 and Staphylococcus aureus phage vB_SauS_CS1 (CS1) were immobilized within BC hydrogels, and their antibacterial activities were assessed through in vitro experiments. These findings suggest BC’s promise as a phage delivery platform for biomedical applications. Full article

Cancer remains a leading global health challenge, necessitating the exploration of novel therapeutic strategies. Vitexin (apigenin-8-C-β-D-glucopyranoside), a natural flavonoid glycoside with a molecular weight of 432.38 g/mol, is derived from plants such as mung bean, beetroot, and hawthorn. This compound features a distinctive C-glycosidic bond at the 8-position of its apigenin backbone, contributing to its enhanced metabolic stability compared to O-glycosidic flavonoids. Preclinical studies demonstrate that vitexin modulates critical cellular processes such as cell cycle progression, apoptosis, autophagy, metastasis, angiogenesis, epigenetic modifications, and tumor glycolysis inhibition. It exerts its effects by targeting key signaling pathways, including phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and signal transducer and activator of transcription 3 (STAT3), and shows potential for combination therapies to enhance efficacy and overcome resistance. Advances in nanotechnology further enhance its bioavailability and delivery potential. This review comprehensively examines the current evidence on vitexin’s anticancer mechanisms, highlighting its multi-target therapeutic potential and future research directions. Full article

In this study, three new 3,7-dihydroxyflavone (1) derivatives with different sugars were designed and synthesised by click chemistry. Click chemistry requires the previously modification of building blocks with azide and alkyne groups and therefore, the 3,7-dihydroxyflavone (1) was first converted in 3,7-(prop-2-yn-yloxy)flavone (2) and acetobromo-α-D-glucose (3) was converted into 2,3,4,6-tetra-O-acetyl-β-glucopyranosyl azide (4). Subsequently, a click reaction was performed via copper-catalysed cycloaddition (CuAAC) between 2 and 4, as well as between 2 and 2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranosyl (AG931) and, 2 and commercial 2-azidoethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl (AG358), resulting in three distinct disubstituted flavone glycosides (5a–5c). Biological assays performed on L929 fibroblast cell lines and human glioblastoma astrocytoma U-251 cell lines indicated cytocompatibility with fibroblasts and reduced metabolic activity of GBM cells in the presence of compound 5b and 5c. To enhance therapeutic effect, improve local drug delivery, and overcome solubility issues of these high molecular weight compounds, the synthesised compounds were encapsulated in polymeric particles (polymersomes, PMs) composed of polylactic acid-polyethylene glycol (PEG-PLA) functionalized, once more by click chemistry, with 0.1 mol% transferrin mimetic (T7—HRPYIAH) peptide. The PMs were prepared by solvent displacement and exhibited stability over 100 days, encapsulation efficiency of 39–93%, and mean size diameters of 120–180 nm. The toxicity assays of the PMs on the U-251 cell line showed a significant decrease in metabolic activity, supporting the potential of this delivery system against GBM. Among the PMs tested, the flavone 5c-based PM demonstrated the highest efficacy. Full article

Background: The timing of anesthesia administration may affect drug efficacy and recovery outcomes. Understanding these variations is important for optimizing anesthetic care. Aim: To assess how spinal anesthesia timing affects block duration, postoperative pain, and CRP and cortisol levels in cesarean deliveries. Methods: Ninety women were divided into three groups based on spinal anesthesia timing: Group A (08:00–16:00), Group B (16:00–00:00), and Group C (00:00–08:00). Standardized spinal anesthesia was administered. Sensory/motor blockade and pain (NRS) were assessed every 10 min. Blood samples for CRP and cortisol were collected preoperatively and at 2, 4, 24, and 48 h post operation. Results: Group C showed shorter sensory and motor blockade than Groups A and B (p < 0.05). The time to first analgesic request was longest in Group A, while Group C reported the highest pain scores (p < 0.05). CRP levels were significantly higher in Group B vs. Group A at 24 and 48 h, and vs. Group C at 48 h (p < 0.05). Group B demonstrated the steepest CRP velocity, indicating a more rapid physiological stress response. BMI differences may have influenced biomarker dynamics. Conclusions: Spinal anesthesia timing significantly impacts block duration, pain experience, and the rate of the physiological stress response. CRP velocity may offer additional insights into perioperative inflammation. Circadian considerations should be integrated into anesthetic planning for cesarean deliveries. Full article

Background: Self-administered orally dissolving films (ODFs) encapsulating inactivated influenza vaccines represent an effective strategy for stimulating mucosal immunity. While this vaccination method offers several advantages over conventional influenza vaccines, a comparative efficacy study remains lacking. Methods: Female BALB/c mice were immunized with inactivated A/PR/8/34 (H1N1) either via orogastric inoculation or through the oral mucosal delivery using pullulan and trehalose-based ODF vaccines. Each group received equivalent antigen doses across three immunizations. Humoral responses and antibody functionality were assessed using sera collected post-immunization. After lethal viral challenge, other immunological and virological parameters were determined in corresponding tissues. Body weight and survival were monitored over a 14-day period after challenge. Results: ODF vaccination elicited significantly higher virus-specific IgA levels, HAI titers, and neutralizing antibody activity than oral gavage. After the viral challenge, ODF-immunized mice exhibited stronger IgG and IgA responses in respiratory tissues, increased antibody-secreting cells in lungs and spleen, and elevated germinal center B cells and CD8⁺ T cell responses. Both vaccination methods reduced lung pro-inflammatory cytokines and provided full protection against lethal challenge; however, the ODF group showed lower cytokine levels, better weight maintenance, and reduced viral loads. Conclusions: ODF vaccination elicits more robust systemic and mucosal immune responses than oral vaccination and may serve as a promising alternative method of influenza vaccine delivery. Full article