Design, Synthesis, Evaluation, and Molecular Docking Study of Ascorbic Acid Dual-Coated Omeprazole Pellets and the Antioxidative Effect of Ascorbic Acid on Omeprazole-Induced Renal Injury in an Animal Model.

The present study was carried out to investigate the antioxidant effect of ascorbic acid on omeprazole (O.P.)-induced acute kidney infection (AKI). Design of experiment (DoE) was employed to fabricate formulations (P1-P8) by the extrusion spheronization technique, and they were evaluated using various analytical techniques. P1-P8 formulations have % drug loading ranging from 56.34 ± 1.10 to 98.67 ± 1.05%, encapsulation efficiency from 70.98 ± 0.96 to 98.67 ± 1.05%, percentage drug release varying from 36.56 ± 1.34 to 93.45 ± 1.45%, Hausner's ratio ranging from 1.026 ± 0.05 to 1.065 ± 0.02%, and Carr's index varying from 2.3 ± 0.07 to 6.1 ± 0.06 g/mL. The optimized formulation (P6) was dual-coated with Eudragit L-100 (5% w/v) and ascorbic acid (2% w/v). A smooth uniform morphology was found after coating, and particle size nonsignificantly changed from 85.31 ± 77.43 to 101.99 ± 65.56 µm. IR spectra showed omeprazole characteristic peaks confirming drug loading, and peaks at 1747.40 and 1611.51 cm-1 confirmed ascorbic acid and Eudragit L-100 coating. X-ray diffraction (XRD) analysis confirmed the crystalline nature, and thermal degradation studies until 500 °C demonstrated increased stability after coating. Cytotoxicity analysis with 97% cell viability revealed the nontoxic behavior of pellets. In vitro dissolution studies of coated pellets showed <20% drug release at pH 1.2 and 99.54% at pH 6.8. Animal studies showed that pure omeprazole showed a nonsignificant decrease in weight, urine output, and fecal output compared to rodents on ascorbic acid pellets. Increased uric acid and creatinine levels in the group on pure omeprazole indicated AKI. Histopathological studies of renal cells also supported these results. The integration of experimental pellet formulation with molecular docking simulations has unveiled the potential of ascorbic acid and omeprazole as highly promising therapeutic agents for addressing oxidative stress and inflammation.

Synthesis, In Silico Study, and Anti-Cancer Activity of Thiosemicarbazone Derivatives.

Thiosemicarbazones are known for their biological and pharmacological activities. In this study, we have synthesized and characterized 3-Methoxybenzaldehyde thiosemicarbazone (3-MBTSc) and 4-Nitrobenzaldehyde thiosemicarbazone (4-NBTSc) using IR, 1HNMR and 13C NMR. The compound's in vitro anticancer activities against different cell lines were evaluated. Molecular docking, Insilco ADMET, and drug-likeness prediction were also done. The test compounds showed a comparative IC50 and growth inhibition with the standard drug Doxorubicin. The IC50 ranges from 2.82 µg/mL to 14.25 µg/mL in 3-MBTSc and 2.80 µg/mL to 7.59 µg/mL in 4-NBTSc treated cells. The MTT assay result revealed, 3-MBTSc inhibits 50.42 and 50.31 percent of cell growth in B16-F0 and EAC cell lines, respectively. The gene expression showed that tumor suppressor genes such as PTEN and BRCA1 are significantly upregulated in 7.42 and 5.33 folds, and oncogenes, PKC, and RAS are downregulated -7.96 and -7.64 folds, respectively in treated cells. The molecular docking performed on the four targeted proteins (PARP, VEGFR-1, TGF-ß1, and BRAFV600E) indicated that both 4-NBTSc and 3-MBTSc potentially bind to TGF-ß1 with the best binding energy of -42.34 Kcal/mol and -32.13 Kcal/mol, respectively. In addition, the test compound possesses desirable ADMET and drug-likeness properties. Overall, both 3-MBTSc and 4-NBTSc have the potential to be multitargeting drug candidates for further study. Moreover, 3-MBTSc showed better activity than 4-NBTSc.

Perception, Knowledge, and Attitude of Individuals from Different Regions of Saudi Arabia toward Dental Implants and Bone Grafts.

AIM: The aim of this study was to assess the perception, knowledge, and attitude of individuals from different regions of Saudi Arabia toward dental implants and bone grafts. MATERIAL AND METHODS: An online, self-oriented, and cross-sectional-based questionnaire with 21 items was given to 1622 individuals from different regions of Saudi Arabia. The questionnaire recorded the perception, knowledge, and attitude of participants and their agreement or rejection of dental implants and various kinds of bone grafts. The responses were compared with age, sex, and educational level. Descriptive statistical analysis was performed for the collected data and P < 0.05 was considered statistically significant. RESULTS: Most of the males (35.8%) and females (39.8%) reported that the major source of data regarding dental implants is friends and families. Majority of the participants (approximately 75% males and 73% females) support the idea that dental implants last for lifetime, whereas majority of the participants (approximately 49% males and 56% females) displayed their unawareness regarding materials used for dental implants. The overall acceptance rates of participants for autografts, alloplasts, xenografts from the cow, xenografts from the horse, and allografts were 40%, 15.9%, 2.5%, 2.2%, and 1.6%, respectively. CONCLUSION: The expense of dental implants was considered the foremost reason for avoiding the procedure. Most of the participants think that fixed dental prostheses last longer than removable prosthesis. Autograft was the most accepted bone graft, whereas allograft was the least accepted bone graft over the responded participants.

Assessment of knowledge and foot self-care practices among diabetes mellitus patients in a tertiary care centre in Makkah, Saudi Arabia: a cross-sectional analytical study.

Introduction: diabetic foot is a common long-term complication of uncontrolled diabetes mellitus. Knowledge about foot self-care practices among diabetic patients in Saudi Arabia is limited. Thus, the aim of this study was to assess the level of patients´ knowledge and practices regarding self-care of diabetic foot among diabetic patients. Methods: a cross-sectional analytical study was conducted using a sample of diabetic patients attending outpatient clinics at Heraa Diabetic Center, Ministry of Health, Makkah City, Saudi Arabia from June 2020 to July 2020. The participants were interviewed through a self-administered questionnaire inquiring sociodemographic factors, patients´ knowledge and practices regarding foot self-care. Results: a total of 409 patients were included in this study. Respondents' ages ranged between 6 and 75 years with a mean of 42.5 years and standard deviation of 13.9 years. Females represented 51.1% of the participants. Type 2 diabetes represented 85.6% of the responses. Overall, most of the participants (72.4%) had a poor level of knowledge whereas only 4.2% expressed a good level of knowledge. Being employed (P = 0.046), type II diabetes patients (P = 0.047) and those whose main source of information was health staff (P = 0.026) were more knowledgeable compared to their peers. Almost two-thirds (63.3%) of patients showed a poor level of practice related to diabetic foot self-care. Conclusion: low level of knowledge and practice of foot care are prevalent among diabetic patients attending outpatient clinics at Heraa Diabetic Center. Designed interventions should be implemented to enhance diabetic foot self-care.

Magnusiomyces capitatus fungemia: The value of direct microscopy in early diagnosis.

Two cases of fungemia caused by Magnusiomyces capitatus, an arthroconidial yeast-like fungus, in non-hematologic immunocompromised patients are described. Both patients died before definite diagnosis of M. capitatus was made. The report highlights that pending confirmation of the isolate by phenotypic and/or molecular methods, the characteristic morphologic features observed in Gram-stained smears of blood culture positive bottles can lead to early preliminary diagnosis, thus significantly reducing time required for initiating appropriate antifungal therapy.

Post-Transcriptional Regulation of Renalase Gene by miR-29 and miR-146 MicroRNAs: Implications for Cardiometabolic Disorders.

Renalase, a recently identified oxidoreductase, is emerging as a novel regulator of cardiovascular and metabolic disease states. The mechanism of regulation of renalase gene, especially at the post-transcriptional level, is completely unknown. We set out to investigate the possible role of microRNAs in regulation of renalase gene in this study. Computational predictions using multiple algorithms coupled with systematic functional analysis revealed specific interactions of miR-29a/b/c and miR-146a/b with mouse and human renalase 3'-UTR (untranslated region) in cultured cells. Next, we estimated miR-29b and miR-146a, as well as renalase expression, in genetically hypertensive blood pressure high and genetically hypotensive blood pressure low mice. Kidney tissues from blood pressure high mice showed diminished (~1.6- to 1.8-fold) renalase mRNA/protein levels and elevated (~2.2-fold) miR-29b levels as compared to blood pressure low mice. A common single nucleotide polymorphism in human renalase 3'-UTR (C/T; rs10749571) creates a binding site for miR-146a; consistently, miR-146a down-regulated human renalase 3'-UTR/luciferase activity in case of the T allele suggesting its potential role in regulation of renalase in humans. Indeed, genome-wide association studies revealed directionally concordant association of rs10749571 with diastolic blood pressure, glucose and triglyceride levels in large human populations (n ≈ 58,000-96,000 subjects). This study provides evidence for post-transcriptional regulation of renalase gene by miR-29 and miR-146 and has implications for inter-individual variations on cardiometabolic traits.