Search Results (9,840)

Breast cancer is a common and chronic condition, and despite improvements in diagnosis, treatment, and prevention, the number of cases of breast cancer is rising annually. New therapeutic drugs that target specific checkpoints should be created to fight breast cancer. Mandragora autumnalis possesses substantial cultural value as a herb and is regarded as one of the most significant medicinal plants; however, little is known about its anticancerous biological activity and chemopreventive molecular pathways against the triple-negative breast cancer (MDA-MB-231) cell line. In this study, the antioxidant, anticancer, and underlying molecular mechanisms of the Mandragora autumnalis ethanolic leaves extract (MAE) were evaluated, and its phytochemical composition was determined. Results indicated that MAE diminished the viability of MDA-MB-231 cells in a concentration- and time-dependent manner. Although MAE exhibited 55% radical scavenging activity at higher concentrations in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the attenuation of its cytotoxic effects in MDA-MB-231 cells with N-acetylcysteine (NAC) co-treatment suggests a potential role of oxidative stress. Additionally, MAE caused an increase in the tumor suppressor p53. Moreover, this extract caused a significant decrease in the expression of Ki-67 (a cellular proliferation marker), MMP-9 (matrix metalloproteinase-9, an enzyme involved in extracellular matrix degradation and metastasis), and STAT-3 (a transcription factor regulating cell growth and survival). Also, MAE altered cell cycle, cell migration, angiogenesis, invasion, aggregation, and adhesion to suppress cellular processes linked to metastasis. All of our research points to MAE’s potential to function as an anticancer agent and opens up new possibilities for the development of innovative triple-negative breast cancer treatments. Full article

ECIS-based impedance biosensors have been extensively studied in various fields including cancer research, microbiology, and immunology. However, most studies have primarily focused on monitoring cellular behavior through impedance changes, with relatively less emphasis on interpreting the biological significance of impedance signals. In this study, we employed a multi-well array impedance biosensor to conduct IC₅₀ (half-maximal inhibitory concentration) analysis, a widely used metric for evaluating drug efficacy and toxicity in biological and pharmacological research. Specifically, we assessed the IC₅₀ values of puromycin, an aminonucleoside antibiotic known to inhibit protein synthesis. NIH/3T3 fibroblasts were exposed to various concentrations of puromycin, and real-time impedance monitoring was performed. Cell viability was assessed, and the IC₅₀ value of puromycin for NIH/3T3 cells was determined to be 3.96 µM using capacitance-based impedance analysis. Our findings demonstrate that the multi-well array impedance biosensor provides a rapid and quantitative method for drug toxicity evaluation, offering a valuable platform for drug screening and biocompatibility assessment. Full article

Surface-enhanced Raman scattering (SERS) has emerged as a powerful signal amplification strategy to address the inherent limitations of conventional flow-based diagnostic methods such as lateral flow analysis (LFA) and vertical flow analysis (VFA). By incorporating SERS-active nanostructures into these platforms, SERS-integrated LFA and VFA systems have significantly improved sensitivity, specificity, and multiplexing performance while maintaining the simplicity and portability of conventional approaches. In this review, we summarize recent advances in SERS-enhanced flow-based diagnostics with a focus on exogenous and endogenous disease detection. Exogenous targets include viral antigens, bacterial pathogens, and foodborne contaminants such as mycotoxins and antibiotic residues. Endogenous applications include therapeutic drug monitoring, inflammation profiling, cancer biomarker detection, and exosome-based molecular subtyping. We highlight the structural differences between LFA and VFA approaches and their impact on analytical performance, and explore the advantages of SERS-integrated platforms for rapid and multiplexed detection in complex biological matrices. Finally, we provide an overview of key technical challenges, such as signal reproducibility, matrix interference, and device integration, and discuss future directions for clinical implementation of SERS-based flow diagnostics in point-of-care settings. Full article

Background/Objectives: The intranasal (IN) route of administration is a promising non-invasive approach for brain targeting, bypassing the blood–brain barrier and enhancing bioavailability. Citalopram hydrobromide (CT), a widely prescribed sparingly water-soluble selective serotonin reuptake inhibitor (SSRI), faces challenges with oral and intravenous administration, including delayed onset, adverse effects, and patient compliance issues. Methods: This study aimed to develop a novel thermoresponsive polymeric micelle (PM) system based on Pluronic^® copolymers (Pluronic F127 and Poloxamer 188) improving CT’s solubility, stability, and nasal permeability for enhanced antidepressant efficacy. A preliminary study was conducted to select the optimized formulation. The preparation process involved using the thin-film hydration method, followed by freeze-drying. Comprehensive evaluations of optimized formulation characteristics included Z-average, polydispersity index (PdI), thermal behavior (lower critical solution temperature, LCST), encapsulation efficiency, X-ray powder diffraction (XRPD), thermodynamic solubility, and biological stability. Additionally, in vitro CT release and CT permeability in nasal conditions were studied. Stability under storage was also evaluated. Results: The optimized CT-PM formulation showed nanoscale micelle size (Z-average of 31.41 ± 0.99 nm), narrow size distribution (polydispersity index = 0.241), and a suitable thermal behavior for intranasal delivery (lower critical solution temperature (LCST) ~31 °C). Encapsulation efficiency reached approximately 90%, with an amorphous structure confirmed via XRPD, leading to a 95-fold increase in CT solubility. The formulation demonstrated appropriate biological and physical stability. In vitro studies showed a 25-fold faster CT release from optimized formulation compared to the initial CT, while CT-PM permeability in nasal conditions increased four-fold. Conclusions: This novel nanoscale thermosensitive formulation is a value-added strategy for nasal drug delivery systems, offering enhanced drug solubility, rapid drug release, stability, and improved permeability. This smart nanosystem represents a promising platform to overcome the limitations of conventional CT administration, improving therapeutic outcomes and patient compliance in depression management. Full article

Surgical procedures trigger dynamic inflammatory responses that influence postoperative pain, wound healing, and long-term outcomes. Conventional therapies rely on the systemic delivery of anti-inflammatory and analgesic agents, which often lack spatiotemporal precision and carry significant side effects. Inflammation-responsive hydrogels offer a promising alternative by enabling localized, stimulus-adaptive drug release aligned with the evolving biochemical milieu of surgical wounds. These smart biomaterials respond to endogenous triggers, such as reactive oxygen species, acidic pH, and proteolytic enzymes, allowing precise modulation of inflammation and tissue repair. This narrative review outlines the pathophysiological features of perioperative inflammation and the design principles of responsive hydrogel systems, including pH-, reactive oxygen species-, enzyme-sensitive, and multi-stimuli platforms. We evaluated the integration of key payloads, NSAIDs, corticosteroids, α₂-adrenergic agonists, and biologics, highlighting their therapeutic synergy and translational relevance. Preclinical studies across soft tissue, orthopedic, thoracic, and abdominal models have demonstrated the efficacy of these systems in modulating immune responses, reducing pain, and enhancing regeneration. Despite these encouraging results, challenges remain, including trigger fidelity, surgical compatibility, and regulatory readiness. Future advances in biosensor integration, logic-based design, and artificial intelligence-guided formulation may accelerate clinical translation. Inflammation-responsive hydrogels represent a transformative strategy for precise perioperative care. Full article

Localized therapeutic action and targeted drug release offer compelling advantages over traditional systemic drug administration. This is particularly important for nitric oxide (NO), whose biological effects vary greatly depending on concentration and cellular environment. Light-sensitive NO donors are promising for achieving precise, on-demand NO release. However, their efficiency and photostability are limited by competing photophysical processes and the generation of reactive oxygen species (ROS). In this study, we investigate hybrid systems composed of photosensitive nitric oxide (NO) donors and silver island films (SIFs). The influence of localized surface plasmon on non-radiative relaxation pathways and ROS generation is the main focus of the paper. Upon excitation at 500 nm, we observed several-fold increase in NO release, attributed to resonant interactions between the plasmonic field and the dye molecules. By tuning the thickness of a SiO₂ buffer layer, we identified key parameters affecting process efficiency: the spectral overlap between the plasmon resonance and the sensitizer’s absorption band, and the distance between the nanoparticle and the molecule. Additionally, singlet oxygen generation increase was observed. These findings demonstrate the potential of plasmonic enhancement to controllably boost photochemical activity in organic systems, paving the way for advanced applications in phototherapy and biomedical diagnostics. Full article

Osteoarthritis in dogs is commonly managed with non-steroidal anti-inflammatory drugs (NSAIDs), nutraceuticals, and other medications aimed at alleviating pain and inflammation. Although NSAIDs are generally considered the most effective option, their use is contraindicated in certain conditions due to adverse side effects. Consequently, there has been growing interest in alternative or complementary therapies, such as acupuncture, laser therapy, and their combination. Laser acupuncture involves stimulating traditional acupuncture points with low-intensity laser light, producing anti-inflammatory, analgesic, anti-edematous, and bio-stimulatory effects. In this study, 19 dogs with osteoarthritis were assigned to two groups: 10 received laser acupuncture treatment (Group T) using a dual-wavelength system delivering continuous and pulsed, synchronized emissions, while 9 served as controls (Group C). After 30 days, only Group T showed significant improvement (p < 0.01), with reduced pain and improved joint mobility. Significant reductions in LDH and CPK were observed in Group T, along with changes in inflammatory markers (IL-6 and IL-10, though not TNF-α) and a significant increase in biological antioxidant potential. These preliminary findings indicate that laser acupuncture, applied according to a standardized protocol and adapted to the site of disease, may represent a viable non-invasive therapeutic option for canine osteoarthritis, particularly in cases where pharmacological treatment is contraindicated or ineffective. Further large-scale, randomized controlled trials are warranted to confirm these results and establish long-term efficacy. Full article

Self-assembled nanoparticles formed with amphiphilic block or graft copolymers are being extensively studied for their use in a variety of biological and industrial applications, including targeted drug delivery. This study reports a novel strategy to tune the structure of self-assembled nanoparticles for enhancing the cellular uptake by varying the hydrophilic ratio of amphiphilic graft copolymers. We synthesized poly(aspartic acid) (PAsp) substituted with octadecyl chains (C18) at varying degrees of substitution (DS), ranging from 4.5 to 37.5 mol%, which could form self-assemblies in an aqueous solution. As the DS increased, a morphological transition was observed—from spherical assemblies (DS 4.5 and 9.1) to rod-like (DS 19.0), vesicular (DS 25.7), and lamellar-like structures (DS 37.6). Further, Trans-Activator of Transcription (TAT) as the cell penetrating peptide to the synthesized amphiphilic graft copolymers leads to an enhanced cellular uptake of the biomimetic self-assembly. In particular, the lamellar-like self-assemblies resulted in a 1.3-fold increase of cellular uptake, as compared to the spherical self-assemblies, and a 3.6-fold increase, as compared to the vesicles. Therefore, tuning the structure of poly(aspartic acid)s’ self-assemblies was proven as an effective strategy to enhance the cellular uptake, while minimizing invasive cell damage. This new strategy to tune the morphologies of self-assemblies will serve to improve the cell penetrating activity for targeted drug delivery. Full article

Sterol biosynthesis is crucial for the function of biological membranes and an important target for anti-protozoan/anti-fungal drugs. In the trypanosomatid parasite Leishmania major, the deletion of sterol C14-demethylase (C14DM) results in hypersensitivity to heat, increased plasma membrane fluidity, profound mitochondrial dysfunctions, and reduced virulence in mice. In this study, we show that C14DM-null mutants are defective in their tolerance to membrane-disrupting agents and osmotic stress and their ability to form autophagosomes. In addition, C14DM-null mutants exhibit a heightened sensitivity to anti-trypanosomatid drugs including antimony, ethidium bromide, and pentamidine. The combination of itraconazole (a C14DM antagonist) and pentamidine synergistically inhibits the growth of Leishmania parasites. These findings reveal new insight into the roles of sterol synthesis in protozoan pathogens and highlight the potential of using drug combinations to achieve better treatment outcomes. Full article

Extracellular vesicles (EVs) are mediators of intercellular communication and serve as promising tools for drug discovery and targeted therapies. These lipid bilayer-bound nanovesicles facilitate the transfer of functional proteins, RNAs, lipids, and other biomolecules between cells, thereby influencing various physiological and pathological processes. This review outlines the molecular mechanisms governing EV biogenesis and cargo sorting, emphasizing the role of key regulatory proteins in modulating selective protein packaging. We explore the critical involvement of EVs in various disease microenvironments, including cancer progression, neurodegeneration, and immunological modulation. Their ability to cross biological barriers and deliver bioactive cargo makes them desirable candidates for precise drug delivery systems, especially in neurological and oncological disorders. Moreover, this review highlights advances in engineering EVs for the delivery of RNA therapeutics, CRISPR-Cas systems, and targeted small molecules. The utility of EVs as diagnostic tools in liquid biopsies and their integration into personalized medicine and companion diagnostics are also discussed. Patient-derived EVs offer dynamic insights into disease states and enable real-time treatment stratification. Despite their potential, challenges such as scalable isolation, cargo heterogeneity, and regulatory ambiguity remain significant hurdles. Recent studies have reported novel pharmacological approaches targeting EV biogenesis, secretion, and uptake pathways, with emerging regulators showing promise as drug targets for modulating EV cargo. Future directions include the standardization of EV analytics, scalable biomanufacturing, and the classification of EV-based therapeutics under evolving regulatory frameworks. This review emphasizes the multifaceted roles of EVs and their transformative potential as therapeutic platforms and biomarker reservoirs in next-generation precision medicine. Full article

Background/Objectives: This article reports pyrrolidine iminosugars of L-gulose absolute stereochemical configuration that are functionalised via N-alkylation to bear boronate ester and boronic acid pharmacophores. Inclusion of boron pharmacophores has been shown to reduce toxicity profiles of drugs and can expand the range of interactions between drugs and target enzymes. Methods: The synthetic development, detailed spectroscopic analysis, and biological investigation against glycosidase enzymes and cancer cell lines of these novel five-membered ring iminosugars are reported. Results: This family of iminosugars displays selective, moderate-to-weak inhibition (IC₅₀s = 133–501 μM) of β-d-galactosidase (bovine liver) and emerging inhibition of β-d-glucosidases (almond) and (bovine liver). The boronic acid pharmacophore may be suitable for the management of lysosomal storage disorders to support the restoration of biological activity of mutant enzymes via the chaperone-mediated therapy approach. From a structure–activity perspective, the cancer screening revealed slight growth inhibition in a panel of cancer cell lines, with A2780 ovarian carcinoma cells showing the strongest response across all compounds. Beyond the growth inhibition capabilities, the real therapeutic potential of these borylated drugs lies in their switch-on/switch-off activation under BNCT radiotherapeutic conditions. Conclusions: This is an important novel family of drug leads capable of interacting with drug targets via intermolecular and intramolecular interactions, changing shape and electronics. Introduction of organic boron atoms to organic molecules presents significant synthetic and purification challenges, as well as analysis of the equilibria that arise in aqueous systems. We provide a methodology to achieve all this and introduce boron pharmacophores onto carbohydrate scaffolds in a systematic manner to facilitate a more widespread adoption of boron pharmacophores. Full article

Despite their disadvantages, preclinical models in vitro are still crucial for every area of biomedical science. They remain a necessary basis for biological, biochemical, and mechanistic studies of pathophysiology of human disease, evaluation of diagnostic tests, assessment of vaccines, as well as screening of potential and repurposed drugs before they are adapted to clinical use. In contrast to animal models in vivo, preclinical in vitro models are cost and time effective. They are easier to use, and, in most cases, they are not associated with ethical concerns. Therefore, they are extensively used in cancer research. Conditional cell reprogramming (CCR) has been one of the novel technologies utilized as a preclinical model in vitro for various common cancers and other diseases. It may be even more important for the research related to rare cancers—elusive, difficult to study, and with insufficient number of relevant models available. Applications of this technology for the basic and translational studies of rare cancers are described in this article. Evaluation of the mechanisms of tumorigenicity and metastasis in neuroblastoma, neuroendocrine cervical carcinoma, ependymoma and astrocytoma, as well as screening of potential drugs and other therapeutic approaches for the laryngeal and hypopharyngeal carcinoma and adenoid cystic carcinoma, demonstrate that the CCR technology is a potential reliable model for various aspects of rare cancer research in the future. Full article

Background/Objectives: The study of biological activity of plants and their metabolites is an important approach for the discovery of new active material. However, little is known of the properties of the Microlicia genus. In addition to natural products, nanotechnology demonstrates considerable potential in pharmacotherapy. The utilization of nanoemulsions holds considerable promise in enhancing the efficacy of drugs, reducing dose, and therefore, lowering of toxic effects. Methods: In this context, antimicrobial and trypanocidal activities were evaluated to the free and encapsulated essential oil from M. graveolens in oil-in-water (o/w) nanoemulsion. Results: This oil is composed mainly of cis-pinocarvyl acetate (~80.0%). The nanoemulsions were prepared by phase inversion method and showed mean particle size of 58 nm, polydispercity index of 0.09, pH 7.8, zeta potential of −21.9 mV, electrical conductivity of 0.38 mS/cm, and good stability. The essential oil was active against all five Gram-positive bacteria tested, and the formulation enhanced this ability. The cytotoxicity effect on L929 cells was also reduced after encapsulation of this oil in o/w nanoemulsion. In addition, the oil and the nanoemulsion were able to inhibit the growth of Trypanosoma cruzi. Conclusions: Thus, the development of a nanoemulsion loaded with M. graveolens essential oil is an easy and low-cost way to obtain and deliver the cis-pinocarvyl acetate compound as well as allow its use in the treatment of diseases caused mainly by the genus Listeria and Staphylococcus. Full article

Dalbergia sissoo is a commercially exploited timber tree also known for its varied phytochemical constituents holding significant importance in folk medicines with documented biological properties. The present study reports the establishment of callus cultures from its leaf explants for the in vitro production of skin therapeutics. The growth parameters of the callus cultures were calculated. The antioxidant potential of the methanolic extracts of leaf and its callus cultures was evaluated through DPPH assay. Calli at third subculture stage showed the highest antioxidant potential (IC₅₀ 273 ± 14.14 µg/mL). A comparative analysis of phytochemical composition was performed using Gas Chromatography–Mass Spectrometry (GC-MS) which revealed the presence of potential skin therapeutic compounds. Out of 146 compounds, only 15 are unique to leaf explants, with the rest being produced in callus cultures. ADME predictions of potential compounds showed their drug likeness properties. The molecular docking of selected phytochemicals such as Chondrillasterol, Stearic acid, and n-Hexadecanoic acid against the tyrosinase enzyme showed better binding affinities than the reference drug (Kojic acid). Molecular dynamics simulation also showed stable conformations of the docked complexes with the target protein. Overall, these investigations unveil for the first time the successful in vitro production of skin therapeutics from D. sissoo, ensuring the sustainable and conservation-friendly utilization of its biomass for medicinal purposes. Full article

Dromedary camels raised under semi-extensive management can act as One Health sentinels for environmental exposures and food chain surveillance, yet serum reference information remains scarce. Our objective was to provide the most comprehensive assessment to date of physiological and toxicological serum profiles in dromedary camels (Camelus dromedarius) from the Canary Islands. We included 114 clinically healthy animals of different sex, age, and reproductive status. Serum samples were analyzed for essential, toxic, and potentially toxic elements using inductively coupled plasma mass spectrometry (ICP-MS). In addition, a high-throughput multi-residue method based on QuEChERS extraction followed by UHPLC-MS/MS and GC-MS/MS was used to screen for 360 organic compounds, including pesticides, veterinary drugs, human pharmaceuticals, and persistent organic pollutants. Essential elements showed biologically consistent variations according to sex, age group, and pregnancy status. Males had higher levels of selenium and copper, while calves showed elevated concentrations of manganese and zinc. Pregnant females exhibited lower iron, zinc, and selenium levels, consistent with increased fetal demand. These results provide preliminary reference values for healthy camels, stratified by physiological status. In contrast, classical toxic elements such as arsenic, mercury, lead, and cadmium were found at very low or undetectable concentrations. Several potentially toxic elements, including barium, strontium, and rare earth elements, were detected sporadically but without toxicological concern. Only 13 organic compounds (3.6%) were detected in any sample, and concentrations were consistently low. The most prevalent was the PAH acenaphthene (55.3%), followed by the fungicide procymidone and the PAH fluorene. Notably, no residues of the usually detected 4,4′-DDE or PCB congeners were found in any sample. These findings confirm the low environmental and dietary exposure of camels under low-intensity farming systems and highlight their value as sentinel species for food safety and environmental monitoring. Full article