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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: 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]

Photophysical studies of 4-Dicyanomethylene-2,6-Dimethyl-4H-Pyran (DDP) dye with globular proteins, Human Serum Albumin (HSA) and Bovine Serum Albumin (BSA) were carried out in aqueous solution. An isosbestic point resulted on the addition of serum albumins, which signifies a complex or an equilibrium state of DDP dye with albumin. Addition of BSA to DDP dye results in a fluorescence enhancement accompanied with a significant hypsochromic shift, whereas with that of HSA, a fluorescence quenching with a considerable blue shift resulted. Excited state studies of DDP dye with serum albumins portray that the role of binding sites of dye with albumins vary considerably and the nature of interaction is presumably attributed to combined hydrogen-bonding and hydrophobic interactions. Molecular docking studies of DDP dye with albumins and two other derivatives 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM) dye and 4-(Dicyanomethylene)-2-methyl-6-(4-t-buyl)-4H-pyran (DCT) dyes with BSA and HSA elucidates that the hydrogen-bonding interaction accompanied with several hydrophobic, pi–pi an pi–alkyl interactions coexist between dye and albumins. The binding energy, intermolecular energy and stability of the DDP, DCM and DCT dyes through docking techniques with albumins authenticate that the dye predominantly acts as hydrogen-bonding acceptor site and the protein molecule as the donor. DDP dye prefers to exist in four different binding sites of HSA, whereas, in the case of BSA, the most preferred site is found to be hydrophobic domain (site I). Interestingly, the most preferred site of DCT dye is III A subdomain of HSA, whereas DCM dye is oriented towards I B subdomain. DDP and DCT are smaller in size and reside in the domain preferred for smaller ligands (II A and IIIA) as resulted in several drugs-HSA interaction whereas DCM dye which is categorized as medium to larger ligand based on the extended structure resides in the most favoured site IB. Fluorescence techniques in combination with molecular docking methods elucidate binding characteristics and the domain in which the dye resides in a micro heterogeneous environment is established in this study.

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]

Objective: This study aims to determine the efficacy of the Acacia arabica (Lam.) Willd. and Cinnamomum camphora (L.) J. Presl. vaginal suppository in addressing heavy menstrual bleeding (HMB) and their impact on participants' health-related quality of life (HRQoL) analyzed using machine learning algorithms. Method: A total of 62 participants were enrolled in a double-dummy, singlecenter study. They were randomly assigned to either the suppository group (SG), receiving a formulation prepared with Acacia arabica gum (Gond Babul) and camphor from Cinnamomum camphora (Kafoor) through two vaginal suppositories (each weighing 3,500 mg) for 7 days at bedtime along with oral placebo capsules, or the tranexamic group (TG), receiving oral tranexamic acid (500 mg) twice a day for 5 days and two placebo vaginal suppositories during menstruation at bedtime for three consecutive menstrual cycles. The primary outcome was the pictorial blood loss assessment chart (PBLAC) for HMB, and secondary outcomes included hemoglobin level and SF-36 HRQoL questionnaire scores. Additionally, machine learning algorithms such as k-nearest neighbor (KNN), AdaBoost (AB), naive Bayes (NB), and random forest (RF) classifiers were employed for analysis. Results: In the SG and TG, the mean PBLAC score decreased from 635.322 ± 504.23 to 67.70 ± 22.37 and 512.93 ± 283.57 to 97.96 ± 39.25, respectively, at postintervention (TF3), demonstrating a statistically significant difference (p < 0.001). A higher percentage of participants in the SG achieved normal menstrual blood loss compared to the TG (93.5% vs 74.2%). The SG showed a considerable improvement in total SF-36 scores (73.56%) compared to the TG (65.65%), with a statistically significant difference (p < 0.001). Additionally, no serious adverse events were reported in either group. Notably, machine learning algorithms, particularly AB and KNN, demonstrated the highest accuracy within cross-validation models for both primary and secondary outcomes. Conclusion: The A. arabica and C. camphora vaginal suppository is effective, costeffective, and safe in controlling HMB. This botanical vaginal suppository provides a novel and innovative alternative to traditional interventions, demonstrating promise as an effective management approach for HMB. [ABSTRACT FROM AUTHOR]

Introduction: The worldwide prevalence of type 2 diabetes mellitus (T2DM) and obesity has been steadily increasing over the past four decades, with projections indicating a significant rise in the number of affected individuals by 2045. Therapeutic interventions in T2DM aim to control blood glucose levels and reduce the risk of complications. Dietary and lifestyle modifications play a crucial role in the management of T2DM and obesity. While conventional medical nutritional therapy (MNT) often promotes a high-carbohydrate, low-fat Mediterranean diet as an elective treatment, low-carbohydrate diets (LCDs), specifically those restricting carbohydrate intake to less than 130 g/day, have gained popularity due to their multifaceted benefits. Scientific research supports the efficacy of LCDs in improving glycemic control, weight loss, blood pressure, lipid profiles, and overall quality of life. However, sustaining these benefits over the long term remains challenging. This trial aimed to compare the effects of a Mediterranean diet vs. a low-carbohydrate diet (carbohydrate intake < 130 g/day) on overweight/obese patients with T2DM over a 16-week period. The study will evaluate the differential effects of these diets on glycemic regulation, weight reduction, lipid profile, and cardiovascular risk factors. Methods: The study population comprises 100 overweight/obese patients with poorly controlled T2DM. Anthropometric measurements, bioimpedance analysis, and blood chemistry assessments will be conducted at baseline and after the 16-week intervention period. Both dietary interventions were hypocaloric, with a focus on maintaining a 500 kcal/day energy deficit. Results: After 16 weeks, both diets had positive effects on various parameters, including weight loss, blood pressure, glucose control, lipid profile, and renal function. However, the low-carbohydrate diet appears to result in a greater reduction in BMI, blood pressure, waist circumference, glucose levels, lipid profiles, cardiovascular risk, renal markers, and overall metabolic parameters compared to the Mediterranean diet at the 16-week follow up. Conclusions: These findings suggest that a low-carbohydrate diet may be more effective than a Mediterranean diet in promoting weight loss and improving various metabolic and cardiovascular risk factors in overweight/obese patients with T2DM. However, it is important to note that further research is needed to understand the clinical implications and long-term sustainability of these findings. [ABSTRACT FROM AUTHOR]

High performance liquid chromatography (HPLC) and second-order derivative spectrophotometry have been used for simultaneous determination of pravastatin (PS) and fenofibrate (FF) in pharmaceutical formulations. HPLC separation was performed on a phenyl HYPERSIL C18 column (125 mm × 4.6 mm i.d., 5 μm particle diameter) in the isocratic mode using a mobile phase acetonitrile/0.1 % diethyl amine (50:50, V/V, pH 4.5) pumped at a flow rate of 1.0 mL min-1. Measurement was made at 240 nm. Both drugs were well resolved on the stationary phase, with retention times of 2.15 and 5.79 min for PS and FF, respectively. Calibration curves were linear (R = 0.999 for PS and 0.996 for FF) in the concentration range of 5-50 and 20-200 µg mL-1 for PS and FF, respectively. Pravastatin and fenofibrate were quantitated in combined preparations also using the second-order derivative response at 237.6 and 295.1 nm for PS and FF, respectively. Calibration curves were linear, with the correlation coefficient R = 0.999 for pravastatin and fenofibrate, in the concentration range of 5-20 and 3-20 µg mL-1 for PS and FF, respectively. Both methods were fully validated and compared, the results confirmed that they were highly suitable for their intended purpose.

A simple, sensitive and accurate HPLC method with high throughput has been developed and validated for the simultaneous determination of irbesartan (IRB) and hydrochlorothiazide (HCT) in combined pharmaceutical dosage forms. The proposed method employed, for the first time, a monolithic column in the analysis. Optimal chromatographic separation of the analytes was achieved on Chromolith® Performance RP-18e column using a mobile phase consisting of phosphate buffer (pH 4)/acetonitrile (50:50, V/V) pumped isocratically at a flow rate of 1.0 mL min-1. The eluted analytes were monitored with a UV detector set at 270 nm. Under the optimum chromatographic conditions, linear relationship with a good correlation coefficient (R ≥ 0.9997) was found between the peak area and the corresponding concentrations of both IRB and HCT in the ranges of 10-200 and 1-20 ng mL-1. The limits of detection were 2.34 and 0.03 ng mL-1 for IRB and HCT, respectively. The intra- and inter-assay precisions were satisfactory as the RSD values did not exceed 3 %. The accuracy of the proposed method was > 97 %. The proposed method had high throughput as the analysis involved a simple procedure and a very short run- -time of < 3 min. The results demonstrated that the method is applicable in the quality control of combined pharmaceutical tablets containing IRB and HCT