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This study aims to develop, characterize, and evaluate the best statin-loaded Collagen Silver nanoparticle-coated polycaprolactone nanofibers by electrospinning technique. The characterization and evaluation results reveal that nanofibers had shown an aligned Collagen Silver nanoparticle-coated polycaprolactone nanofibers distribution of fibers and aliment of collagen and silver nanoparticle coating material on the surface of the nanofibers. Furthermore, the electrospun nanofibers have shown no interaction between the drug and collagen and PCL polymeric material and have demonstrated controlled drug release for 360 h and significant degradation for 60 days of the study. In vitro, among the nanofiber treatment groups and the control groups, Pravastatin Collagen Silver nanoparticle-coated polycaprolactone nanofibers have shown cell proliferation and migration of NHDF cells and blood vessel development in the CAM assay and potential anti-bacterial activity against S. aureus and E. coli. In vivo, the Pravastatin Collagen Silver nanoparticle-coated polycaprolactone nanofibers have demonstrated improved wound recovery, reepithelization, fibroblast cell proliferation, angiogenesis, and ECM remodeling and enhanced VEGF-sprouting in the excised tissues of streptozotocin-induced diabetic rats for 7, 14, and 21 days of the study. Therefore, the developed Pravastatin Collagen Silver nanoparticle-coated polycaprolactone nanofibers could be a promising wound-dressing platform for effectively treating and managing diabetic wounds. Highlights * Nanofiber wound dressings provide numerous structural features in biomaterials. * Polycaprolactone can release the repurposed statin molecules into the wound site in a controlled manner. * In diabetic wounds, ECM tissue remodeling stimulates repair and vessel growth. * Pravastatin has been demonstrated to improve angiogenesis and ECM secretion for wound healing in diabetic conditions. KEYWORDS diabetic wounds, electrospinning, hypoxic microenvironment, nanofibers, pro-angiogenesis, re-epithelization, wound dressing, 1 | INTRODUCTION The most prevalent cause of death in diabetic individuals is diabetic wounds. Unfortunately, the bulk of the treatment options in the market do not entirely address how [...]

Background: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML. Methods: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels. Results: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models. Conclusions: In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies. [ABSTRACT FROM AUTHOR]

Objective: The present study evaluated the oral tissue expression of micro‐RNA (miRNAs) linked to the potential malignant evolution of oral lichen planus (OLP). Furthermore, the correlation between OLP severity and miRNAs expression was assessed, and possible predictors of miRNAs in OLP patients were identified. Methods: The present study enrolled 41 patients with OLP (median age 58 years) and 42 healthy controls (median age 59 years). In each patient, miRNA levels (miR‐7a‐3p,‐7a2‐3p,‐7a‐5p,‐21‐3p,‐21‐5p,‐100‐3p,‐100‐5p,‐125b‐2‐3p,‐125b‐5p,‐200b‐3p,‐200b‐5p) were assessed and analyzed through reverse transcription polymerase chain reaction. Clinical parameters and the eventual presence of OLP symptoms, signs, and disease severity scores in each patient were reported using an anamnestic questionnaire. Results: In comparison with healthy controls, OLP patients showed significantly higher miR‐7a‐3p,‐7a‐2‐3p,‐21‐3p, miR‐21‐5p and miR‐100‐5p levels (p < 0.05) and significantly lower miR‐125b‐2‐3p,‐125b‐5p,‐200b‐3p, and ‐200b‐5p levels (p < 0.05). Furthermore, OLP symptoms and signs and disease severity scores were significantly correlated and were also predictors of all analyzed miRNAs (p < 0.05). Conclusions: In comparison with healthy subjects, OLP patients exhibited unbalanced oral miRNAs expression linked to the risk of potential malignant evolution of OLP. Furthermore, some miRNAs were correlated with OLP extent and were significant predictors of OLP symptoms, signs, and disease severity scores. [ABSTRACT FROM AUTHOR]

Objective: Evaluation of contemporary disinfection techniques, Moringa Oleifera (M.Oleifera), Phycocyanin activated by photodynamic therapy (PDT), and Chitosan, on S.mutans survival rate and bond integrity of composite to carious-affected dentin (CAD). Methods: The in vitro study was conducted at King Saud University and concluded within three months. Sixty mandibular teeth with cavities extending to the middle third of the dentin were sterilized. S.mutans was inoculated onto the CAD surface of twenty samples. The samples were randomly divided into four groups (n: 15) based on various disinfection regimes. Group-1 received 2% CHX, Group-2 Phycocyanin activated by photodynamic therapy (PDT), Group-3 Chitosan, and Group-4 M.oleifera. S.mutans survival rate was calculated. Ten CAD samples from each group were restored using composite. The bond integrity of samples was assessed using a Universal testing machine (UTM) and failure mode using a stereomicroscope. Analysis of variance (ANOVA) and Tukey's Post Hoc test were used to calculate statistical significance (p=0.05). Results: Group-2 samples subjected to Phycocyanin activated using PDT, displayed minimal survival rate (0.24 ± 0.05 CFU/ml) of S.mutans.Group-1 samples treated with CHX exhibited the highest count of S.mutans (0.69 ± 0.12 CFU/ml). The most robust bond was observed in Group-3 (Chitosan) samples (19.33 ± 0.47 MPa). In contrast, SBS values were lowest in Group-1 (CHX) treated study samples (13.17 ± 1.88 MPa). Conclusion: Chitosan, Phycocyanin activated by PDT, and Moringa Oleifera extract exhibit potential as viable substitutes for chlorhexidine (CHX) in clinical settings, presenting the possibility of better eradication of S.mutans and greater adhesive strength to CAD. [ABSTRACT FROM AUTHOR]

To date, little is known concerning the circulating levels of biochemically relevant metabolites (antioxidants, oxidative/nitrosative stress biomarkers, purines, and pyrimidines) in patients with primary myelofibrosis (PMF), a rare form of myeloproliferative tumor causing a dramatic decrease in erythropoiesis and angiogenesis. In this study, using a targeted metabolomic approach, serum samples of 22 PMF patients and of 22 control healthy donors were analyzed to quantify the circulating concentrations of hypoxanthine, xanthine, uric acid (as representative purines), uracil, β-pseudouridine, uridine (as representative pyrimidines), reduced glutathione (GSH), ascorbic acid (as two of the main water-soluble antioxidants), malondialdehyde, nitrite, nitrate (as oxidative/nitrosative stress biomarkers) and creatinine, using well-established HPLC method for their determination. Results showed that PMF patients have dramatic depletions of both ascorbic acid and GSH (37.3- and 3.81-times lower circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001), accompanied by significant increases in malondialdehyde (MDA) and nitrite + nitrate (4.73- and 1.66-times higher circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001). Additionally, PMF patients have remarkable alterations of circulating purines, pyrimidines, and creatinine, suggesting potential mitochondrial dysfunctions causing energy metabolism imbalance and consequent increases in these cell energy-related compounds. Overall, these results, besides evidencing previously unknown serum metabolic alterations in PMF patients, suggest that the determination of serum levels of the aforementioned compounds may be useful to evaluate PMF patients on hospital admission for adjunctive therapies aimed at recovering their correct antioxidant status, as well as to monitor patients' status and potential pharmacological treatments. [ABSTRACT FROM AUTHOR]