Cutting Edge: LAG3 Dimerization Is Required for TCR/CD3 Interaction and Inhibition of Antitumor Immunity.

Lymphocyte activation gene 3 (LAG3) is an inhibitory receptor that plays a critical role in controlling T cell tolerance and autoimmunity and is a major immunotherapeutic target. LAG3 is expressed on the cell surface as a homodimer but the functional relevance of this is unknown. In this study, we show that the association between the TCR/CD3 complex and a murine LAG3 mutant that cannot dimerize is perturbed in CD8+ T cells.

Thiolated Polymeric Hydrogels for Biomedical Applications: A Review.

Hydrogels are a three-dimensional (3D) network of hydrophilic polymers. The physical and chemical crosslinking of polymeric chains maintains the structure of the hydrogels even when they are swollen in water. They can be modified with thiol by thiol epoxy, thiol-ene, thiol-disulfide, or thiol-one reactions.

Rosuvastatin, Perindopril and Ezetimibe loaded instant release buccal films: Development and in vitro characterization.

Background: Rosuvastatin Calcium and Ezetimibe are used to control cholesterol level while Perindopril Erbumine is used to treat hypertension. Hepatic metabolism reduces the therapeutic effect of these drugs.

Objective: Instant release buccal films (IRBFs) could possibly be a solution to this issue.

Formulation and evaluation of sustained release ocular inserts of betaxolol hydrochloride using arabinoxylan from Plantago ovata.

The purpose of the current studies was to develop ocular insert of betaxolol hydrochloride (BXH), using arabinoxylan (AX) as a film former. The inserts were prepared by sandwiching I mg of BXH between two films of AX. Six different formulations of ocular inserts were prepared in such a way that first three formulations contained varying concentrations of AX along with glycerol as plasticizer, whereas, rest of the formulations were added with 0.

Synthesis of Thiol-Modified Hemicellulose, Its Biocompatibility, Studies, and Appraisal as a Sustained Release Carrier of Ticagrelor.

Nature has always been considered as the primary source of pharmaceutical ingredients. A variety of hemicelluloses, as well as their modified forms, have been under investigation. Herein, a study was designed to explore the biocompatibility of hemicellulose and its modified form (thiolated hemicellulose) as well as its potential as a pharmaceutical excipient.

An Insight into the Role of Artificial Intelligence in the Early Diagnosis of Alzheimer's Disease.

Background: The complication of Alzheimer's disease (AD) has made the development of its therapeutic a challenging task. Even after decades of research, we have achieved no more than a few years of symptomatic relief. The inability to diagnose the disease early is the major hurdle behind its treatment.

Fabrication of polyvinyl alcohol based fast dissolving oral strips of sumatriptan succinate and metoclopramide HCL.

Migraine is a throbbing condition, usually associated with nausea and vomiting and requires concurrent administration of anti-migraine along with anti-emetic therapy. The current study was undertaken with an aim to fabricate fast dissolving oral strips (FDOSs) containing Sumatriptan succinate (anti-migraine) and Metoclopramide HCl (anti-emetic) in combination without involving any superdisintegrant. Hydrophilic polymer polyvinyl alcohol (PVA) was used alone with three concentrations of 100, 125, and 150 mg using variable concentrations of glycerol.

Solid Lipid Nanoparticles of Mycophenolate Mofetil: An Attempt to Control the Release of an Immunosuppressant.

Introduction: Organ transplantation is a critically important procedure, which requires immune modulation by using immunosuppressants. Development of nanoparticles is an emerging and beneficial engineering process to increase the dissolution rate of poorly soluble immunosuppressants as well as to provide controlled release for better therapeutic outcomes.

Method: Currently, the nanoprecipitation method was employed to fabricate β-cyclodextrin (βCD) facilitated mycophenolate mofetil (MMF)-loaded solid lipid nanoparticles (SLNPs).

Nanoparticles Based Intranasal Delivery of Drug to Treat Alzheimer's Disease: A Recent Update.

Alzheimer Association Report (2019) stated that the 6th primary cause of death in the USA is Alzheimer's Disease (AD), which leads to behaviour and cognitive impairment. Nearly 5.8 million peoples of all ages in the USA have suffered from this disease, including 5.

Enhancement of Oral Bioavailability of Ibandronate Through Gastroretentive Raft Forming Drug Delivery System: In Vitro and In Vivo Evaluation.

Background: Bisphosphonates have very low bioavailability and cause irritation of the esophagus and stomach. This study was planned to improve the oral bioavailability of ibandronate through the formation of a raft in the stomach. Bisphosphonate-induced irritation of the esophagus and stomach is prevented by the formation of a raft.

Design, mechanism, delivery and therapeutics of canonical and Dicer-substrate siRNA.

Upon the discovery of RNA interference (RNAi), canonical small interfering RNA (siRNA) has been recognized to trigger sequence-specific gene silencing. Despite the benefits of siRNAs as potential new drugs, there are obstacles still to be overcome, including off-target effects and immune stimulation. More recently, Dicer substrate siRNA (DsiRNA) has been introduced as an alternative to siRNA.

Development and optimization of flurbiprofen loaded microsponges; an in-vitro evaluation.

Current study was designed with the aim to employ quasi emulsification, and double emulsification techniques for the development of Flurbiprofen (FLB) loaded micro sponges, followed by their physicochemical evaluation. FTIR interpretations exhibited compatibility of ingredients, while crystallographic analysis revealed crystalline nature of pure drug, which was masked upon incorporation into microsponges. Optical microscope and SEM have exposed spherical and spongy surfaces of prepared micro sponges.

Development of thiomer based buccal films for the enhancement of bioavailability: An in-vivo analysis.

Present work was conducted to improve the bioavailability of Tizanidine HCl (TZN) by formulating mucoadhesive buccal films (MBFs) using novel thiolated arabinoxylan (TAX) as film former. MBF's were prepared by solvent casting technique followed by their evaluation for surface morphology and folding endurance. Moreover, pharmacokinetic parameters including C, t, t and AUC were determined after administering standard oral solution (SOS) and MBFs of TZN at a dose of 1mg/kg.

Antibiotic resistance pattern shown by various pathogens, causing infections in neonates.

This study was schemed to comprehend the latest kaleidoscopic trends of bacterial resistance in neonatal pathogens against all those antibiotics commonly employed as empirical therapy in neonates. The methodological approach included; isolation and subsequent identification of those pathogens having caused bacterial infections in neonates, application of antibiotic sensitivity testing and finally construing the conclusion depicting patterns of antibiotic resistance by various pathogens, isolated from neonatal biological samples. Antibiotic resistance patterns was evident in gram-positive as well as in gram-negative bacteria in all the eight species identified in this study.

Synthesis and biological evaluation of new tetramethylpyrazine-based chalcone derivatives as potential anti-Alzheimer agents.

In the current study, a series of new ligustrazine-based chalcones was synthesized. For insertion of tetramethylpyrazine (TMP, also designated as ligustrazine) in chemical backbone of chalcone, a new ligustrazine-based aldehyde was prepared. New ketones were synthesized for inclusion of quinazolin-4-yl amino and pyrazin-2-yl amino moieties.

Discovery of potential anticancer multi-targeted ligustrazine based cyclohexanone and oxime analogs overcoming the cancer multidrug resistance.

The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor.

Synthesis and mechanistic studies of curcumin analog-based oximes as potential anticancer agents.

The incidence of cancer can be decreased by chemoprevention using either natural or synthetic agents. Apart from synthetic compounds, numerous natural products have exhibited promising potential to inhibit carcinogenesis in vivo. In this study, α, β-unsaturated carbonyl-based anticancer compounds were used as starting materials to synthesize new oxime analogs.

Stability, Intracellular Delivery, and Release of siRNA from Chitosan Nanoparticles Using Different Cross-Linkers.

Chitosan (CS) nanoparticles have been extensively studied for siRNA delivery; however, their stability and efficacy are highly dependent on the types of cross-linker used. To address this issue, three common cross-linkers; tripolyphosphate (TPP), dextran sulphate (DS) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-TPP/DS/PGA nanoparticles by ionic gelation method. The resulting nanoparticles were compared with regard to their physicochemical properties including particle size, zeta potential, morphology, binding and encapsulation efficiencies.

Development of Chitosan Nanoparticles as a Stable Drug Delivery System for Protein/siRNA.

Chitosan nanoparticles (CS NPs) exhibit good physicochemical properties as drug delivery systems. The aim of this study is to determine the modulation of preparative parameters on the physical characteristics and colloidal stability of CS NPs. CS NPs were fabricated by ionic interaction with dextran sulphate (DS) prior to determination of their storage stability.

Comparative characterization and cytotoxicity study of TAT-peptide as potential vectors for siRNA and Dicer-substrate siRNA.

Recently, a newly discovered Dicer-substrate siRNA (DsiRNA) demonstrates higher potency in gene silencing than siRNA but both suffer from rapid degradation, poor cellular uptake and chemical instability. Therefore, Tat-peptide was exploited to protect and facilitate their delivery into cells. In this study, Tat-peptide was complexed with siRNA or DsiRNA through simple complexation.