Transdermal Delivery of Tofacitinib Citrate via Mannose-Decorated Transferosomes Loaded with Tofacitinib Citrate in Arthritic Joints.

Transdermal drug delivery systems are a promising option for the treatment of rheumatoid arthritis (RA) because they can lower systemic adverse effects of immunosuppressants. Janus kinase (JAK) inhibitors were found to be effective for the treatment of RA by inhibiting the JAK-STAT pathway and preventing autoimmune joint destruction. The aim of this study is to deliver tofacitinib (a JAK 1 and 3 inhibitor) through mannose-decorated transferosomes (MDTs) directly to inflamed joints.

Evaluation of the efficacy of triazavirin versus oseltamivir in management of COVID-19.

To compare the safety and efficacy of triazavirin (TZV) 250 mg capsules versus oseltamivir 75 mg capsules in the treatment of individuals diagnosed with COVID-19. A double-blind, randomized, interventional pilot study was conducted in a parallel design with a 7-day treatment period. The results showed that TZV is superior to oseltamivir regarding length of hospital stay, days until clinical symptoms improvement, and cure of chest pneumonia.

Potential anti-obesity effect of saponin metabolites from adzuki beans: A computational approach.

In contrast to its widespread traditional and popular culinary use to reduce weight, (adzuki beans) was not subjected to sufficient scientific scrutiny. Particularly, its saponins whose role was never investigated before to unveil the beans' antidiabetic and anti-obesity effects. Four vital pancreatic and intestinal carbohydrate enzymes were selected to assess the potency of the triterpenoidal saponins of to bind and activate these proteins through high-precision molecular modeling and dynamics mechanisms with accurate molecular mechanics Generalized Born Surface Area (MMGBSA) energy calculations; thus, recognizing their anti-obesity potential.

Benzimidazole-Based Derivatives as Apoptotic Antiproliferative Agents: Design, Synthesis, Docking, and Mechanistic Studies.

A new class of benzimidazole-based derivatives (-, , and ) with potential dual inhibition of EGFR and BRAF has been developed. The newly synthesized compounds were submitted for testing for antiproliferative activity against the NCI-60 cell line. All newly synthesized compounds -, , and were selected for testing against a panel of sixty cancer cell lines at a single concentration of 10 µM.

Impact of magnesium supplementation on clinical outcome and disease progression of patients with diabetic nephropathy: a prospective randomized trial.

Background: Magnesium (Mg) deficiency is closely linked with proteinuria.

Objectives: To assess the impact of oral Mg citrate supplementation on the clinical outcome of diabetic nephropathy (DN) patients.

Design: This was a prospective, randomized, controlled, open-label study.

Poly(2-Hydroxyethyl Methacrylate) Hydrogel-Based Microneedles for Metformin Release.

The release of metformin, a drug used in the treatment of cancer and diabetes, from poly(2-hydroxyethyl methacrylate), pHEMA, hydrogel-based microneedle patches is demonstrated in vitro. Tuning the composition of the pHEMA hydrogels enables preparation of robust microneedle patches with mechanical properties such that they would penetrate skin (insertion force of a single microneedle to be ≈40 N). Swelling experiments conducted at 20, 35, and 60 °C show temperature-dependent degrees of swelling and diffusion kinetics.

The effect of high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients. A randomized placebo controlled trial.

Non-alcoholic fatty liver (NAFLD) is one of the most common progressive metabolic disorders worldwide. There are increasing scientific interests nowadays for the association between vitamin D status and Non-alcoholic fatty liver. Earlier studies have revealed that vitamin D deficiency is highly prevalent in Non-alcoholic fatty liver patients that contributes to poor outcomes.

Anti-Inflammatory, Antiallergic and COVID-19 Main Protease (M) Inhibitory Activities of Butenolides from a Marine-Derived Fungus .

Amid the current COVID-19 pandemic, the emergence of several variants in a relatively high mutation rate (twice per month) strengthened the importance of finding out a chemical entity that can be potential for developing an effective medicine. In this study, we explored ethyl acetate (EtOAc) extract of a marine-derived fungus afforded three butenolide derivatives, butyrolactones I, VI and V (-), two naphtho--pyrones, TMC-256 A1 () and rubrofusarin B () and methyl -hydroxyphenyl acetate (). Structure identification was unambiguously determined based on exhaustive spectral analyses including 1D/2D NMR and mass spectrometry.

The other side to the use of active targeting ligands; the case of folic acid in the targeting of breast cancer.

Due to its overexpression in cancer cells, the folate receptor (FR) is heavily exploited in the active targeting of nanoparticles (NPs). Its ligand, folic acid (FA) is as a consequence widely used as a NP targeting ligand. Although rather popular and successful in principle, recent data has shown that FA may result in breast cancer initiation and progression, which questions the suitability of FA as NP cancer targeting ligand.

Efficacy and Safety of Metformin Use in Rheumatoid Arthritis: A Randomized Controlled Study.

To evaluate the efficacy and safety of metformin use in rheumatoid arthritis (RA) patients receiving conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). A prospective, randomized, controlled, single blinded, study was carried on 66 RA patients with moderate and high disease activity state, receiving csDMARDs. Patients were simply randomized to receive either metformin 850 mg twice daily (Metformin group, = 33), or placebo twice daily (Control group, = 33) in addition to their stable anti-rheumatic regimen and followed up for 6 months.

An "eat me" combinatory nano-formulation for systemic immunotherapy of solid tumors.

Tumor immunogenic cell death (ICD), induced by certain chemotherapeutic drugs such as doxorubicin (Dox), is a form of apoptosis potentiating a protective immune response. One of the hallmarks of ICD is the translocation of calreticulin to the cell surface acting as an 'eat me' signal. This manuscript describes the development of a stable nucleic acid-lipid particles (SNALPs) formulation for the simultaneous delivery of ICD inducing drug (Dox) with small interfering RNA (siRNA) knocking down CD47 (siCD47), the dominant 'don't eat me' marker, for synergistic enhancement of ICD.

Mathematical filtration of quaternary mixture to the zero order spectra of its individual components.

Simple accurate and precise validated UV spectrophotometric methods have been described here for the simultaneous determination of Tretinoin (TN) Eusolex (EX) Hydroquinone (HQ) & Hydrocortisone acetate (HC) in their dosage form. Simultaneous determination of these four drugs was a major challenge till now. Each spectrum was filtered alone to its zero-order absorption spectrum (D) form getting spectra typical to each pure component separately.

A genetic insight into vitamin D binding protein and COVID-19.

It's since December 2019 that Corona virus disease (COVID-19) has emerged to be the global issue of concern. A "pandemic"; this is what WHO has declared about the COVID-19 outbreak on March 3rd, 2020. Vitamin D and its deficiency have recently been claimed to be one of the potential factors affecting COVID-19 risks and outcomes [1].

The effect of metformin on indomethacin-induced gastric ulcer: Involvement of nitric oxide/Rho kinase pathway.

Gastric ulcer is a very common disease that represent an economic burden. Non-steroidal anti-inflammatory drugs induce ulcer in old patients and in patients with comorbidities. Indomethacin is widely used to induce gastric ulcer in animal models.

Coenzyme Q10 administration has no effect on sICAM-1 and metabolic parameters of pediatrics with type 1 diabetes mellitus.

: Endothelial dysfunction (ED) plays a key role in the development and progression of microvascular and macrovascular complications in pediatrics with type 1 diabetes mellitus (T1DM). Coenzyme Q10 (CoQ10) is a nutraceutical with a known anti-inflammatory and anti-oxidant activity. This study was conducted to evaluate the potential effect of CoQ10 on ED and various metabolic parameters.

Design and Synthesis of New Quinoxaline Derivatives as Anticancer Agents and Apoptotic Inducers.

The quinoxaline scaffold is a promising platform for the discovery of active chemotherapeutic agents. Three series of quinoxaline derivatives were synthesized and biologically evaluated against three tumor cell lines (HCT116 human colon carcinoma, HepG2, liver hepatocellular carcinoma and MCF-7, human breast adenocarcinoma cell line), in addition to VEGFR-2 enzyme inhibition activity. Compounds , , , and exhibited promising activity against the tested cell lines and weak activity against VEGFR-2.

Descriptive analysis of medication errors reported to the Egyptian national online reporting system during six months.

Objectives: This study analyzes reports to the Egyptian medication error (ME) reporting system from June to December 2014.

Methods: Fifty hospital pharmacists received training on ME reporting using the national reporting system. All received reports were reviewed and analyzed.

Molecular design, synthesis and cell based HCV replicon assay of novel benzoxazole derivatives.

Hepatitis C virus inhibitors based on benzoxazole scaffold were designed based on molecular modeling simulation study including docking into the NS5B polymerase active site. Several compounds showed significant high simulation docking scores relative to the assigned benzimidazole lead compound. The designed compounds were synthesized, structurally elucidated and their antiviral activity was evaluated through cell-based replicon in cultured Huh 5-2 cells.

Discovery of Novel Benzo[a]phenoxazine SSJ-183 as a Drug Candidate for Malaria.

Malaria is a serious infectious disease caused by protozoan parasites in tropical and subtropical regions. Even inhabitants of temperate zones are exposed to the danger of malaria infection because of travel and global warming. Novel, effective, safe, and inexpensive drugs are required to treat malaria and contribute to the global goal of eradication.

Computer based design, synthesis and biological evaluation of novel indole derivatives as HCV NS3-4A serine protease inhibitors.

A series of novel indoles were designed and their molecular modeling simulation study including fitting to a 3D pharmacophore model using CATALYST program and their docking into the NS3 active site was examined as HCV NS3 protease inhibitor. Several compounds showed significant high simulation docking score and fit values. The designed compounds were synthesized and biologically evaluated in vitro using an NS3 protease binding assay, where compounds 10a-k showed significant inhibitory activity (> or =67% inhibition at 100 microg/mL).