Search Results (10)

Background/Objectives: Hyperlipidemia is a silent threat lurking in the bloodstream of millions worldwide. The nano-based platform has emerged as a promising drug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recently as an antihyperlipidemic candidate that could supersede the available antihyperlipidemic drugs. Our goal was to optimize albumin-based nanoparticles loaded with Repaglinide for parenteral delivery and conduct in silico and in vivo studies to explore the efficacy of Repaglinide for the management of hyperlipidemia along with its anti-diabetic effect. Methods: The impact of three independent factors, the albumin%, acetone volume, and glutaraldehyde/albumin, on the particle size, zeta potential, and entrapment efficiency was investigated. Results: The optimized formulation was spherical, homogenous of an average diameter (~181.86 nm) with a narrow size distribution, a zeta potential of −24.26 mV, and 76.37% as the EE%. The in vitro release of Repaglinide from nanoparticles showed a sustained release pattern for 168 h, with an initial burst release after 24 h, and was fitted to the Fickian diffusion mechanism. A molecular docking simulation showed a strong affinity to several protein targets, and the results were very promising, where Repaglinide gave a score of −7.70 Kcal/mol compared to Mevastatin (−6.71 Kcal/mol) and Atorvastatin (−8.36 Kcal/mol). On conducting in vivo studies on animal models, the optimized formula recorded a statistically significant decrease in the serum levels of total cholesterol, triglyceride, and low-density lipoproteins, with an increased high-density lipoprotein. Conclusions: This study suggested albumin nanoparticles as potential nanocarriers for the parenteral delivery of Repaglinide to ameliorate its antihyperlipidemic benefits, especially in diabetic patients. Full article

Objectives: Lower urinary tract symptoms (LUTSs) related to benign prostatic hyperplasia (BPH) are common in older men, and alpha-adrenoceptor blockers continue to be a key part of managing these symptoms. This study aimed to formulate injectable poly (lactic-co-glycolic acid) (PLGA) in situ-forming implants (ISFIs) loaded with silodosin (SLD) to address symptoms associated with BPH. This method, which ensures prolonged therapeutic effects of SLD, is intended to decrease dosing frequency and improve treatment outcomes, leading to better patient adherence. Methods: An appropriate solvent with favorable PLGA solubility, viscosity, and in vitro release profile was selected. Additionally, an I-optimal design was employed as an optimization technique. An in vivo study in albino male rats was conducted to investigate prostate-specific antigens (PSAs), prostate weight and prostatic index, histopathology, and SLD pharmacokinetics. Results: The optimized formulation showed experimental values of 29.25% for the initial burst after 2 h and 58.23% for the cumulative release of SLD after 10 days. Pharmacokinetic data revealed that the SLD–ISFI formulation had lower C_max and higher AUC values than subcutaneous (SC) pure SLD and oral commercial SLD capsule, indicating the controlled-release impact and improved bioavailability of the ISFI systems. SLD–ISFI produced a marked drop in the prostatic index by 2.09-fold compared to the positive control. Serum PSA level decreased significantly from 0.345 ± 0.007 to 0.145 ± 0.015 ng/mL after SLD–ISFI injection compared to the positive control. Conclusions: This study indicated that the optimized SLD–ISFI formulation proved its efficacy in managing BPH. Full article

Betalains are natural red colorants characterized by their stability to anthocyanins, particularly in acidic foods. Beetroot stalks are a good source of betalains, with higher bioactive components than the whole root. Hence, the current study aims to investigate the potential use of beetroot stalk water extract (BSE) as a functional colorant for raspberry-flavored stirred yogurt. For this purpose, the betalains of BSE and their stability at pH 4 and 5 were investigated in addition to the phenolic and flavonoid content. Furthermore, the antioxidant and antimicrobial activities of BSE were characterized. Subsequently, BSE was added to raspberry-flavored stirred yogurt at concentrations of 1 (T1), 2 (T2), and 5% (T3) to study the stability of betalains, the physicochemical properties, the nutritional value, and the viability of lactic acid bacteria during storage (14 days/4 °C). BSE showed a considerable amount of betalains (456.82 mg/L) and phenolics (139.87 mg/g), with a high content of chlorogenic and ferulic acids. The betalains showed greater stability at pH 4 than pH 5 after 14 days of cold storage (275.05 and 247.00 mg/L, respectively). Applying BSE resulted in a functional beverage with high phenolic content (116.55 ± 1.23 mg/g) and flavonoids (71.77 ± 0.57 mg/g) in T3 (5%) compared to the control (95.11 ± 1.12 and 64.72 ± 0.29 mg/g, respectively). The beverages shared high DPPH scavenging activity (IC₅₀ = 71.68 ± 1.30– 69.18 ± 0.48) compared with the control (78.47 ± 3.27 µL/mL). BSE significantly increased the betalain level in yogurt from 44.19 ± 0.05 mg/L to 67.86 ± 0.54 mg/L, resulting in pale red beverages with a redness value of 6.38–9.68 on day 1. By day 14, the redness of the treatments decreased by 6–18% compared with the first day, reaching 5.25 ± 0.03 (T1), 7.87 ± 0.03 (T2), and 8.43 ± 0.05 (T3) due to the degradation of betalains. Generally, BSE is a promising natural colorant when added to stirred yogurt, and it has preferable physical and sensory properties, as it improves the stability of the red color throughout cold storage and increases the nutritional quality. The use of beet stalks as a natural and functional colorant is presented for the first time in the current investigation. Full article

Urokinase receptors regulate the interplay between inflammation, immunity, and blood clotting. The soluble urokinase plasminogen activator system is an immunologic regulator affecting endothelial function and its related receptor; the soluble urokinase plasminogen activator receptor (suPAR) has been reported to impact kidney injury. This work aims to measure serum levels of suPAR in COVID-19 patients and correlate the measurements with variable clinicolaboratory parameters and patient outcomes. In this prospective cohort study, 150 COVID-19 patients and 50 controls were included. The circulating suPAR levels were quantified by Enzyme-linked immunosorbent assay (ELISA). Routine COVID-19 laboratory assessments, including CBC, CRP, LDH, serum creatinine, and estimated glomerular filtration rates, were performed. The need for oxygen therapy, CO-RAD score, and survival rates was assessed. Bioinformatic analysis and molecular docking were run to explore the urokinase receptor structure/function and to characterize molecules as potential anti-suPAR therapeutic targets, respectively. We found higher circulating suPAR levels in COVID-19 patients vs. controls (p < 0.001). Circulating suPAR levels positively correlated with COVID-19 severity, the need for O₂ therapy, the total leukocytes count, and the neutrophils to lymphocyte ratio, while they were negatively correlated with the O₂ saturation level, albumin, blood calcium, lymphocytic count, and GFR. In addition, the suPAR levels were associated with poor prognostic outcomes such as a high incidence of acute kidney injury (AKI) and mortality rate. Kaplan–Meier curves showed a lower survival rate with higher suPAR levels. The logistic regression analysis confirmed the significant association of suPAR levels with the occurrence of AKI related to COVID-19 and with increased mortality probability within three months of COVID-19 follow-up. Some compounds that can act similarly to uPAR were discovered and tested by molecular docking to identify the possible ligand–protein interactions. In conclusion, higher circulating suPAR levels were associated with COVID-19 severity and could be considered a putative predictor of AKI development and mortality. Full article

This study assessed the possible protective role of green synthesized zinc oxide nanoparticles using Moringa olifera leaf extract (MO-ZNPs) in acrylamide (ACR)-induced reproductive dysfunctions in male rats. ACR (20 mg/kg b.wt/day) and/or MO-ZNPs (10 mg/kg b.wt/day) were given orally by gastric gavage for 60 days. Then, sperm parameters; testicular enzymes; oxidative stress markers; reproductive hormones including testosterone, luteinizing hormone (LH)-estradiol, and follicle-stimulating hormone (FSH) concentration; testis histology; steroidogenesis-related gene expression; and apoptotic markers were examined. The findings revealed that MO-ZNPs significantly ameliorated the ACR-induced decline in the gonadosomatic index and altered the pituitary–gonadal axis, reflected by decreased serum testosterone and FSH with increased estradiol and LH, and sperm analysis disruption. Furthermore, a notable restoration of the tissue content of antioxidants (catalase and reduced glutathione) but depletion of malondialdehyde was evident in MO-ZNPs+ACR-treated rats compared to ACR-exposed ones. In addition, MO-ZNPs oral dosing markedly rescued the histopathological changes and apoptotic caspase-3 reactions in the testis resulting from ACR exposure. Furthermore, in MO-ZNPs+ACR-treated rats, ACR-induced downregulation of testicular steroidogenesis genes and proliferating cell nuclear antigen (PCNA) immune-expression were reversed. Conclusively, MO-ZNPs protected male rats from ACR-induced reproductive toxicity by suppressing oxidative injury and apoptosis while boosting steroidogenesis and sex hormones. Full article

The aim of the study was to design injectable long-acting poly (lactide-co-glycolide) (PLGA)-based in situ gel implants (ISGI) loaded with the anti-diabetic alogliptin. Providing sustained therapeutic exposures and improving the pharmacological responses of alogliptin were targeted for achieving reduced dosing frequency and enhanced treatment outputs. In the preliminary study, physicochemical characteristics of different solvents utilized in ISGI preparation were studied to select a proper solvent possessing satisfactory solubilization capacity, viscosity, water miscibility, and affinity to PLGA. Further, an optimization technique using a 2³ factorial design was followed. The blood glucose levels of diabetic rats after a single injection with the optimized formulation were compared with those who received daily oral alogliptin. N-methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO), as highly water-miscible and low viscous solvents, demonstrated their effectiveness in successful ISGI preparation and controlling the burst alogliptin release. The impact of increasing lactide concentration and PLGA amount on reducing the burst and cumulative alogliptin release was represented. The optimized formulation comprising 312.5 mg of PLGA (65:35) and DMSO manifested a remarkable decrease in the rats’ blood glucose levels throughout the study period in comparison to that of oral alogliptin solution. Meanwhile, long-acting alogliptin-loaded ISGI systems demonstrated their feasibility for treating type 2 diabetes with frequent dosage reduction and patient compliance enhancement. Full article

Bioethanol-derived biomass is a green sustainable source of energy that is highly recommended as an efficient alternative to the replacement of fossil fuels. However, this type of bioethanol production is always expensive with very low bioethanol concentration. Therefore, this work aims to represent a facile and green approach for bioethanol production with high concentration and purity as well as reasonable cost from corn stover (CS). The goal of this study is to characterize CS and its treated samples with maleic acid (CSM) using various characterization analyses, such as proximate and ultimate analysis, HHV, TGA, FTIR, SEM, and CHNS. The bioethanol production stages: Pretreatment, enzymatic degradation, fermentation, and finally bioethanol separation and purification via the pervaporation process, which have been investigated and optimized are associated with the economic analysis. The optimum operating condition of the pretreatment process was 2% maleic acid, 1:20 solid-to-liquid ratio at 45 psi, 120 °C, and 1 h of operation in the autoclave. This process contributes to 53 and 45% lignin and hemicellulose removal, 98% cellulose recovery, and a glucose yield of 741 mg/dL. The yeast isolate succeeded in the production of 1230 mg/dL of bioethanol. This isolated yeast strain was close to Pichia nakasei with a similarity of 98%, and its amplified 18S rRNA gene sequence was deposited in GenBank with the accession number MZ675535. Poly (MMA-co-MA) membrane was synthesized, characterized, and its efficiency for increasing the bioethanol concentration was evaluated using the integrated pervaporation technique. The techno-economic analysis is presented in detail to evaluate the process profitability, which achieves a considerable profit for the whole duration of the project without any losses as it reaches a net profit of USD 1 million in 2023, reaching USD 2.1 million in 2047 for a company with a capacity of 32 thousand tons per year. The sequential strategy offers a promising approach for efficient bioethanol production under mild and environmentally friendly conditions that enable its implication industrially. Full article

Clonazepam (CLZ), an antipsychotic drug reported for its efficiency in managing anxiety-related disorders, is being marketed only as conventional tablets. Some patients have abstention to swallow the conventional tablets; therefore, the proposed study was aimed at developing a buccal lozenge tablet by direct compression of two types of optimized granules. Conazepam’s water solubility was first enhanced by a solid dispersion technique for a fast and better dissolution of type 1 granules, while the impact of gelling polymers was investigated on controlled-release type 2 granules. The optimized formulae met the acceptable pharmacopeial limits for tablets’ evaluation. A differential scanning calorimetry study revealed the compatibility between the drug and used excipients. All formulae gave a burst release of CLZ in the first hour of investigation, followed by a sustained release over 24 h. The formula that showed the highest prolonged in vitro release (99.0 + 0.1%), following the Higuchi diffusion model (R² = 0.99), was then selected for further study. The formula succeeded in controlling the induced stress in a rat model with a significant impact on the behavioral tests throughout the experiment. The results were further confirmed by a pharmacokinetic study that showed a significant increase in Cmax, Tmax, and AUC (1.5, 2, and 3.9 folds), respectively, compared to oral suspension. The newly proposed delivery system has proven a better efficacy with a reduced dosing frequency. Full article

Alopecia areata (AA) is a type of immune-mediated alopecia. Recent studies have suggested microRNAs’ (miRNAs) implication in several cellular processes, including epidermal and hair follicle biology. Single nucleotide polymorphisms (SNPs) can modify gene expression levels, which may induce an autoimmune response. This case–control study included 480 participants (240 for each case/control group). MicroRNA-34a gene (MIR-34A) rs2666433A/G variant was genotyped using real-time allelic discrimination polymerase chain reaction (PCR). Additionally, circulatory miR-34a levels were quantified by quantitative reverse transcription PCR (qRT-PCR). On comparing between alopecia and non-alopecia cohorts, a higher frequency of A variant was noted among patients when compared to controls—A allele: 28 versus 18% (p < 0.001); A/A genotype: 9 versus 2%; A/G genotype: 39 versus 32% (p < 0.001). A/A and A/G carriers were more likely to develop alopecia under heterozygote comparison (OR = 1.83, 95% CI = 1.14–2.93), homozygote comparison (OR = 4.19, 95% CI = 1.33–13.1), dominant (OR = 2.0, 95% CI = 1.27–3.15), recessive (OR = 3.36, 95% CI = 1.08–10.48), over-dominant (OR = 1.65, 95% CI = 1.04–32.63), and log additive (OR = 1.91, 95% CI = 1.3–2.82) models. Serum miR-34a expression levels were upregulated in alopecia patients with a median and quartile fold change of 27.3 (1.42–2430). Significantly higher levels were more pronounced in A/A genotype patients (p < 0.01). Patients carrying the heterozygote genotype (rs2666433 * A/G) were two times more likely to develop more severe disease grades. Stratified analysis by sex revealed the same results. A high expression level was associated with concomitant autoimmune comorbidities (p = 0.001), in particular SLE (p = 0.007) and vitiligo (p = 0.049). In conclusion, the MIR34A rs2666433 (A/G) variant is associated with AA risk and severity in the studied population. Furthermore, high miR-34a circulatory levels could play a role in disease pathogenesis. Full article

Postbiotics are functional bioactive substances manufactured during fermentation in a food matrix, which can be used to improve human health, but their influence on the adhesion potential and physicochemical cell surface of probiotics is still unclear. We examined the postbiotic influence produced by Escherichia coli Nissle 1917 in functional labneh on cell surface properties (auto-aggregation, hydrophobicity, and co-aggregation) and the adhesion capacities of three probiotic strains. The most commonly detected effects of probiotics, particularly L^syn−7, were an increase in auto-aggregation, hydrophobicity, co-aggregation, and adhesion ability of the tested strains. Lactobacillus rhamnosus with L^syn−7 (59%) presented the highest hydrophobicity, whereas the least adhesion to xylene was detected in L. rhamnosus with LHM. Lactobacillus casei with L^syn−7 showed the highest auto-aggregation after 24 h (60.55%). Moreover, it also has a strong adhesion to Caco-2 cells and effectively prevents the binding of Salmonella Typhimurium to Caco-2 cells. Lactobacillus plantarum with L^syn−7 presented the strongest co-aggregation with Staphylococcus aureus (85.1%), S. typhimurium (85. 02%) and Listeria monocytogenes (77.4%). The adherence potential of tested probiotic strains was highly correlated with auto-aggregation, hydrophobicity, co-aggregation, and competitive inhibition of L. monocytogenes and S. typhimurium. The findings suggest that L^syn−7 can be a candidate to promote the adhesion potential of selected probiotic strains. For the reason that the application of probiotic strains has been more interested in their positive influences in the gastrointestinal tract, it is essential to use some functional compounds, such as postbiotics, to improve adhesion abilities and cell surface properties in terms of bacterial binding. Full article