Search Results (25,520)

The demand for antimicrobial and biocompatible materials in biomedical applications continues to grow, particularly in the context of wound care and textiles. This study explores the development of multifunctional coatings by applying magnesium (Mg) nanoparticles onto medical-grade cotton textiles using magnetron sputtering—a solvent-free and environmentally sustainable technique. A comprehensive material characterization confirmed the formation of Mg, MgO and Mg(OH)₂/MgH₂ phases, along with generally consistent particle coverage and increased fiber surface roughness. The antibacterial testing revealed the effective inhibition of both Gram-positive and Gram-negative bacteria—except Enterococcus faecalis. Additionally, the growth of the fungus Candida albicans and the microalgae Prototheca spp. was reduced by over 80%. Importantly, a cytocompatibility evaluation using human umbilical vein endothelial cells (HUVECs) demonstrated not only non-toxicity but a significant increase in cell viability after 72 h, particularly in samples treated for 20 and 60 min, indicating a potential cytoprotective and proliferative effect. These findings highlight the dual functionality of plasma-sputtered Mg nanoparticle coatings, offering a promising strategy for the development of eco-friendly, antimicrobial and cell-supportive medical textiles. Full article

Cannabidiol (CBD) has been reported in medical applications for various indications. The enzymatic metabolism of CBD is not fully understood in the different routes of administration. This research aimed to identify the CBD metabolites after incubation of CBD with derived hepatocyte cells (HepG2), bronchial epithelial cells (NCI-H358), alveolar cells (A549), and alveolar macrophage cells (NR8383). A liquid chromatography–mass spectrometry technique was developed to quantify the CBD and its metabolites. Molecular docking was employed to evaluate the binding affinity of CBD with different cytochrome P-450 (CYP-450) enzymes and further predict the implication of drug–drug interactions. CBD and major metabolites of CBD were also docked with cannabinoid receptors. The results revealed that only HepG2 cells metabolized CBD to 7-hydroxy-CBD (7-OH-CBD) and 7-carboxy-CBD (7-COOH-CBD), whereas other respiratory cell lines and alveolar macrophages were found to have mainly CBD in the incubated samples without any metabolites. The CYP2C19 and CYP3A4 enzymes were responsible for CBD conversion to hydroxylated CBD metabolites. The 7-OH-CBD and 7-COOH-CBD metabolites were found to bind to cannabinoid receptors with different affinities. The relative abundance of CBD and major metabolites may indicate the potential route of CBD administration. Full article

Fridericia platyphylla, a member of the Bignoniaceae family, is widely recognized as a rich source of flavonoids with significant biopharmacological potential. This study aimed to perform a chemical annotation of its metabolites and to evaluate the antitumor activity of the hydroalcoholic extract from its leaves. The chemical diversity of this specimen was analyzed using liquid chromatography coupled with tandem mass spectrometry and Molecular Networking. Fifteen significant phenolic compounds were annotated, including phenolic acid derivatives, flavonoid glycosides, and flavone aglycones. Furthermore, the antiproliferative activities against human cervical cell lines, adenocarcinoma HPV 18 positive (HeLa) and carcinoma HPV 16 positive (SiHa), in vitro, exhibited distinct inhibitory effects, with IC₅₀ values of 44.78 and 66.97 µg mL⁻¹, respectively. The extract inhibited cell migration and exhibited cytotoxic effects by reducing the viability of HeLa and SiHa cells, suggesting its potential as a therapeutic candidate for cervical cancer. Therefore, given the significant antiproliferative and anti-migratory activity, these results open up prospects for investigating F. platyphylla leaf extract in the development of alternative therapies for cervical cancer. Full article

Parkinson’s disease (PD) is recognized as one of the most common neurodegenerative disorders globally. The primary factor contributing to this condition is the loss of dopaminergic neurons, which results in both motor and nonmotor symptoms. The etiology of neurodegeneration remains unclear. However, it is characterized by the elevated production of reactive oxygen species, which subsequently leads to oxidative stress, lipid peroxidation, mitochondrial dysfunction, and inflammation. The investigation of the applicability of natural compounds and their derivatives to various diseases is becoming increasingly important. The possible role of curcumin from Curcuma longa L. and its derivatives in the treatment of PD has been partially investigated, but there are no data on the action of synthetic cyclic C₅-curcuminoids and chalcones tested in a Parkinson’s model. Two chalcones and five synthetic cyclic C₅-curcuminoids with potential antioxidant properties were investigated in an in vitro model of 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in differentiated SH-SY5Y cells. Reactive oxygen species (ROS) production, total antioxidant capacity, antioxidant enzyme activity, thiol and ATP levels, caspase-3 activity, and cytokine release were examined after treatment with the test compounds. Based on these results, one cyclic chalcone (compound 5) and three synthetic cyclic C₅-curcuminoids (compounds 9, 12, and 13) decreased oxidative stress and apoptosis in our in vitro model of neurodegeneration. Compounds 5 and 9 were also successful in decreasing the production of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α), while promoting the release of anti-inflammatory cytokines (IL-4 and IL-10). These findings indicate that these two compounds exhibit potential antioxidant, anti-apoptotic, and anti-inflammatory properties, rendering them promising candidates for drug development. Full article

Schwann cells (SCs) are the primary glial cells of the Peripheral Nervous System (PNS), which insulate and provide protection and nutrients to the axons. Technological and experimental advances in neuroscience, focusing on the biology of SCs, their interactions with other cells, and their role in the pathogenesis of various diseases, have paved the way for exploring new treatment strategies that aim to harness the direct protective or causative properties of SCs in neurological disorders. SCs express cytokines, chemokines, neurotrophic growth factors, matrix metalloproteinases, extracellular matrix proteins, and extracellular vesicles, which promote the inherent potential of the injured neurons to survive and accelerate axonal elongation. The ability of SCs to support the development and functioning of neurons is lost in certain hereditary, autoimmune, metabolic, traumatic, and toxic conditions, suggesting their role in specific neurological diseases. Thus, targeting, modifying, and replacing SC strategies, as well as utilizing SC-derived factors and exosomes, have been considered novel therapeutic opportunities for neuropathological conditions. Preclinical and clinical data have demonstrated that SCs and SC-derived factors can serve as viable cell therapy for reconstructing the local tissue microenvironment and promoting nerve anatomical and functional recovery in both peripheral and central nerve injury repair, as well as in peripheral neuropathies. However, despite the promising successes of genetic engineering of SCs, which are now in preclinical and clinical trials, improving tactics to obtain ‘repair’ SCs and their products from different sources is the key goal for future clinical success. Finally, further development of innovative therapeutic approaches to target and modify SC survival and function in vivo is also urgently needed. Full article

Background/Objectives: Alterations in immunoinflammatory activation may constitute a pathogenetic mechanism in neurodevelopmental disorders (NDDs). Blood cell count (CBC) parameters and hematological inflammatory indices (neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio) are now assuming a greater role as potential biomarkers for NDDs. Methods: In this retrospective observational study, we gathered data on 135 medication-free individuals aged 6 to 17 years: 90 with NDDs (34 with autism spectrum disorder (ASD), 29 with attention-deficit/hyperactivity disorder, 14 with intellectual disability, and 13 with tic disorder) and 45 typically developed controls. The variables analyzed were compared using analysis of variance including Bonferroni posthoc testing for pairwise comparisons Significance was defined as p < 0.05. Results: The analysis of variance revealed statistical significance for all evaluated CBC parameters, as well as for the lymphocyte-to-monocyte ratio. Notably, subjects with ASD exhibited increased values of neutrophils, lymphocytes, monocytes, and eosinophils compared to both typically developing subjects and other NDDs. The lymphocyte-to-monocyte ratio was found to be lower in the tic disorder group compared to typically developing subjects. The elevated lymphocyte and monocyte levels in ASD subjects might reflect chronic low-grade inflammation. Conclusions: Consistent with the evidence in literature, statistically significant differences between the NDD group and typically developed subjects in the CBC parameters were found. The principal limitations of this investigation are the restricted sample size and the exclusion of specific NDD subtypes. Future research is needed to evaluate CBC parameters and inflammatory indices in a broader spectrum of NDDs to better understand the immunoinflammatory response specific to each disorder. Full article

Background/Objectives: The use of food waste in nanomaterial development represents an efficient and sustainable strategy for producing value-added products. Methods: In this study, silver nanoparticles (AgNPs) were synthesized from the hydroethanolic and aqueous extracts of buckwheat (Fagopyrum esculentum Moench) hulls, under optimized conditions. The resulting AgNPs were characterized using spectroscopic and microscopic techniques. To evaluate their bioactivity, free radical scavenging assays, cytotoxicity assays against tumor and normal cells, and broth microdilution assays were conducted. Results: AgNPs, synthesized from the hydroethanolic and aqueous buckwheat hull extracts under optimized conditions, were small (mean diameters of 19.97 ± 7.86 and 5.55 ± 1.34 nm, respectively), well dispersed (polydispersity index values of 0.204 and 0.345, respectively), negatively charged, and stable (zeta potential values of −24.10 ± 6.73 and −23.5 ± 10.3 mV, respectively). The latter were more homogenous in shape, being predominantly spherical. Both samples of AgNPs demonstrated remarkable cytotoxic activity against A-375 human malignant melanoma cells (IC₅₀ values below 5 μg/mL). AgNPs derived from the hydroethanolic buckwheat hull extract suppressed the growth of methicillin-resistant Staphylococcus aureus ATCC 43300 and Staphylococcus epidermidis ATCC 12228, with minimum inhibitory concentration (MIC) values of 37.50 and 4.68 μg/mL, respectively. AgNPs derived from the aqueous buckwheat hull extract exhibited higher free radical scavenging activity (EC₅₀ values of 132.6 ± 0.3 and 77.40 ± 3.52 μg/mL in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, respectively). Conclusions: AgNPs synthesized from the buckwheat hull extracts demonstrated notable potential as antimelanoma and antibacterial agents. Full article

The increasing prevalence of obesity, a chronic disease, necessitates the development and evaluation of evidence-based prevention and intervention strategies tailored to heterogeneous populations. Certain fruits, including papaya and pineapple (Ananas comosus), have been investigated as potential dietary components in obesity management. In the context of obesity and chronic low-grade inflammation, bromelain, a proteolytic enzyme derived from pineapple, is a widely studied phytotherapeutic agent that acts through multiple mechanisms intersecting immune and metabolic pathways. This narrative review summarizes current evidence on the effects of bromelain in obesity, low-grade inflammation, and related metabolic disturbances. Searches of the literature were conducted in Google Scholar, PubMed, and Scopus databases. This review incorporates findings from in vitro, animal, and human studies. We outline the mechanisms and evidence supporting the therapeutic efficacy of bromelain, emphasizing its implications for obesity management in clinical settings. Bromelain has been shown to exert significant anti-inflammatory activity and may modulate adipocyte metabolism, potentially alleviating comorbidities associated with excess adiposity. Although its effects on immune cells are relatively well described, the mechanisms underlying bromelain’s actions on adipocytes remain incompletely understood. Full article

Background: Prosthetic candidiasis remains a significant clinical challenge, particularly due to the ability of Candida species to form resilient biofilms on dental prostheses, which limits the efficacy of conventional antifungal treatments. In this context, developing strategies to prevent or reduce biofilm formation is essential. Objectives This study investigates the antifungal and antibiofilm potential of a hydrogel formulation incorporating aminochalcone AM-35 as a candidate for the prevention and treatment of prosthetic candidiasis. Methods: To achieve this, experiments were conducted to determine the minimum inhibitory concentration (MIC) of aminochalcone AM-35 against Candida albicans and Candida tropicalis strains. AM-35 was incorporated into a hydrogel, which was subsequently tested on biofilms formed by these yeast species, both individually and in combination. The experimental disks were sterilized and incubated with C. albicans, C. tropicalis, and a mixture of both strains for 120 h to allow biofilm maturation. After contamination, the samples were divided into four experimental groups: Group 1: Hydrogel; Group 2: Hydrogel+AM-35; Group 3: Sodium hypochlorite (positive control); and Group 4: No treatment. The samples were then subjected to a sonication process to disaggregate the cells, which were then cultured on plates for colony-forming unit (CFU/mL) counts. The hydrogel’s toxicity was evaluated in vivo using the Galleria mellonella model. Results: The hydrogel formulation demonstrated significant antimicrobial activity, with an MIC of 7.8 μg/mL for C. albicans and 3.9 μg/mL for C. tropicalis. Treatment with the hydrogel at a concentration of 39 μg/mL resulted in a significant reduction in the formation and viability of mixed-species biofilms (p < 0.05). Additionally, the results indicated robust activity against C. albicans and C. tropicalis without presenting toxicity in the Galleria mellonella model. In conclusion, the hydrogel formulation exhibited effective antibiofilm activity, significantly reducing the microbial load. Conclusions: These findings open new possibilities for the development of alternative treatments for prosthetic candidiasis. The research suggests that the use of chalcone-based compounds may represent a promising approach in combating fungal infections in dentistry. Full article

Protein tyrosine phosphatase receptor sigma (PTPRS) regulates cellular signals involved in hematopoietic stem cell development, synaptic plasticity, and synovium differentiation. The soluble extracellular Ig-like domains of PTPRS have therapeutic potential by binding to a ligand, inhibiting the ligand-binding of endogenous PTPRS. However, the wild-type Ig-like domains have poor solubility, which limits their therapeutic use. In this study, we identified solvent-exposed hydrophobic residues on the surface of PTPRS and mutated the residues to hydrophilic residues for solubility-enhancing engineering. The mutagenesis screening increased its solubility up to five-fold. In addition, the expression yields were also increased by up to 14-fold. The biochemical and functional analysis of the engineered PTPRS showed that the mutant protein had comparable properties to the wild type. Thus, the engineered PTPRS has potential for therapeutic applications where modulation of PTPRS is critical. Full article

Background: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), remains a major public health concern in Latin America. No licensed vaccine exists to prevent or treat T. cruzi infection. Identifying correlates of protection (CoPs) could provide substitute endpoints to guide and accelerate vaccine development. Although most CoPs established to date are antibody-based, their utility has not been demonstrated in T. cruzi vaccine reports. Thus, this study aimed to explore alternative strategies considering the use of immune cells as potential CoPs. Methods: Mice were immunized with a vaccine candidate based on the T. cruzi trans-sialidase protein (TSf) and potentiated with 5-fluorouracil (5FU) to deplete myeloid-derived suppressor cells (MDSCs). Percentages of CD4⁺, CD8⁺, and CD11b⁺Gr-1⁺ cellular biomarkers were assessed by flow cytometry from the peripheral blood of immunized mice, which were subsequently challenged with a high dose of T. cruzi. A machine-learning (ML) model based on decision trees was applied to identify potential CoPs to predict survival by day 25 post-infection. Results: Individual biomarkers obtained from flow cytometry did not show strong predictive performance. In contrast, biomarker engineering led to a combination that integrated biomarkers rationally: summing the percentages of CD8⁺ and CD4⁺ cells and subtracting the percentage of CD11b⁺Gr-1⁺ MDSC-like cells (REB), enhanced the predictive capacity. Subsequent computational analysis and ML application led to the identification of a better and even improved potential Integrative CoP: $2 \ast \%CD{8}^{+}+ {\%CD4}^{+} - {\%CD11b}^{+}{ Gr1}^{+}$(pICoP), which significantly improved the performance of a simple one-level decision-tree model, achieving an average accuracy of 0.86 and an average AUC-ROC of 0.87 for predicting survival in immunized and infected mice. Conclusions: Results presented herein provide evidence that integrating cellular immune biomarkers through rational biomarker engineering, together with ML analysis, could lead to the identification of potential CoPs for a T. cruzi vaccine. Full article

The TMEM16 (Anoctamin) family comprises a group of transmembrane proteins involved in diverse physiological processes, including ion transport and phospholipid scrambling. TMEM16F (Anoctamin 6), a phospholipid scramblase and nonselective ion channel, plays a central role in membrane remodeling, blood coagulation, immune responses, and cell death pathways through its ability to externalize phosphatidylserine in response to elevated intracellular calcium levels. Consequently, modulating TMEM16F activity has emerged as a promising strategy for the development of new therapeutic applications. Despite the functional importance of TMEM16F, TMEM16F modulators have received little study. In a previous study, we generated TMEM16F-specific affibodies by biopanning a phage display library for affibodies that bind to brain-specific TMEM16F (hTMEM16F) variant 1. In this study, we selected six other affibodies from among the 38 previously sequenced affibody candidates and characterized them. After purification, we confirmed that two of these affibodies bound to human TMEM16F with high affinity. To provide functional insights into how these affibodies modulate TMEM16F activity, we tested whether they could exert functional effects at the cellular level. Finally, we show that TMEM16F affibody attenuated the neuronal cell death induced by glutamate and microglial phagocytosis, suggesting that these affibodies might have potential therapeutic and diagnostic applications. Full article

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a complex molecular landscape. Despite extensive research, our understanding of the molecular mechanisms remains incomplete, hindering the development of effective therapeutic strategies for this disease. Long non-coding RNAs (lncRNAs) have emerged as crucial factors in cancer biology, regulating key networks across various malignancies. These molecules exert their regulatory functions through interactions with nucleic acids or proteins, thereby influencing signaling pathways within tumor cells. Consequently, lncRNAs play a significant role in key processes like cell proliferation, metastasis, immune evasion, and treatment resistance. This review offers a comprehensive overview of current knowledge regarding lncRNA-mediated mechanisms in HNSCC. The first section explores how lncRNAs influence tumor processes through various modulation mechanisms, including transcriptional and post-transcriptional regulation, chromatin remodeling, and epigenetic modifications. We also highlight the impact of lncRNAs on specific signaling pathways that control essential cellular functions (e.g., proliferation, apoptosis, angiogenesis, invasion, metastasis). Ultimately, this underscores the promising potential of lncRNAs as diagnostic biomarkers and therapeutic targets capable of enhancing patient care in oncology. Gaining a deep understanding of how lncRNAs modulate carcinogenic mechanisms may yield innovative approaches for early detection, personalized treatment, and improved clinical outcomes for HNSCC patients. Full article

Background: The increasing prevalence of antibiotic-resistant bacterial strains highlights the urgent need for new membrane-targeting antimicrobial agents. Bisquaternary ammonium compounds (bisQACs) have attracted attention for their ability to disrupt bacterial membranes more effectively than monoquaternary analogs. Quinuclidine, known for its health-beneficial properties, has previously been explored for monoQAC derivatization, but studies using natural scaffolds to generate bisQACs remain limited. Methods: Here, we synthesized twelve novel quinuclidine-based bisQACs, systematically varying alkyl chain and linker lengths to investigate structure–activity relationships. Results: Several compounds, including 2(QC₁₆)₃, 2(QC₁₆)₄, 2(QC₁₄)₆, and 2(QC₁₆)₆, exhibited strong activity against Staphylococcus aureus (including MRSA), Listeria monocytogenes, and Escherichia coli, with 2(QC₁₆)₆ being the most potent (MICs 5–38 µM). While cytotoxicity was observed on human RPE1 and HEK293 cells, selectivity indices indicated a favorable therapeutic window relative to reference QACs. Conclusions: These compounds also inhibited biofilm formation and induced rapid bacterial killing through a membrane-disruptive mode of action. Molecular docking showed that alkyl chain and linker variations modulate binding to the QacR efflux regulator, revealing a lower potential for efflux-mediated resistance. Overall, quinuclidine-based bisQACs represent promising leads for potent, selectively active next-generation antimicrobials with a reduced likelihood of resistance development. Full article

Objectives: Atherosclerosis is a chronic inflammatory disease characterized by complex pathological mechanisms. Early detection of vulnerable plaques is critical for assessing rupture risk and preventing acute cardiovascular events. Conventional ultrasound contrast agents (UCAs) are limited in their ability to penetrate the vascular wall and unable to provide detailed information on plaque composition and stability. In this study, we developed biosynthetic gas vesicles (GVs) derived from Halobacterium NRC-1 as UCAs for imaging of vulnerable plaques. Methods: These GVs were functionalized with the VHPKQHR peptide (VHP), enabling specific binding to vascular cell adhesion molecule-1 (VCAM-1), a key biomarker of inflammation in atherosclerosis. In vitro evaluation of VHP-GVs was performed through contrast-enhanced ultrasound imaging using agarose gel phantoms and adhesion assays with inflammatory cell models to assess their targeting capability toward VCAM-1. In vivo ultrasound molecular imaging was performed using the Sprague Dawley (SD) rat model of early-stage atherosclerosis in the left common carotid artery to evaluate imaging efficacy. Results: Both in vitro and in vivo experiments demonstrated that VHP-GVs could effectively penetrate the vascular wall into plaques and generate robust ultrasound contrast signals for precise identification of vulnerable regions. Conclusions: This study establishes a promising tool for the early diagnosis and targeted treatment of atherosclerosis, underscoring the translational potential of biosynthetic nanobubbles in clinical practice. Full article