PLGA Nanoparticles Based Mucoadhesive Nasal In Situ Gel for Enhanced Brain Delivery of Topiramate.

Oral Topiramate therapy is associated with systemic adverse effects including paresthesia,abdominal pain, and fluctuations in plasma levels. The purpose of this research was to develop an intranasal in situ gel based system comprising Topiramate polymeric nanoparticles and evaluate its potential both in vitro and in vivo. Poly (lactic-co-glycolic acid) (PLGA)nanoparticles prepared by nanoprecipitation method were added into the in situ gelling system of Poloxamer 407 and HPMC K4M.

Immunotherapeutic approaches for Alzheimer's disease: Exploring active and passive vaccine progress.

Alzheimer's disease (AD) is the most common neurodegeneration having non-effective treatments. Vaccines or monoclonal antibodies are two typical immunotherapies for AD. Due to Aβ neurotoxicity, most of the treatments target its generation and deposition.

Machine learning-based virtual screening and molecular modelling studies for identification of butyrylcholinesterase inhibitors as anti-Alzheimer's agent.

Butyrylcholinesterase (BChE) is a hydrolase involved in the metabolism and detoxification of specific esters in the blood. It is also implicated in the progression of Alzheimer's disease, a type of dementia. As the disease progresses, the level of BChE tends to increase, opting for a major role as an acetylcholine-degrading enzyme and surpassing the role of acetylcholinesterase.

Reversal of biological age in multiple rat organs by young porcine plasma fraction.

Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young adult pigs rejuvenates old rat tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n = 613 tissue samples.

Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction.

Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young pigs rejuvenates old rat tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n=613 tissue samples.

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.

DNA methylation networks underlying mammalian traits.

Using DNA methylation profiles ( = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors.

Edge Modification and Site-Selective Functionalization of Graphene Quantum Dots: A Versatile Technique for Designing Tunable Optoelectronic and Sensing Devices.

This work successfully traces the imprints of zigzag/armchair-edge modification and site-selective functionalization by different chemical species in dictating the structural, electronic, and optical properties of low-symmetry structural isomers of graphene quantum dots (GQDs). Our time-dependent density functional theory-based computations reveal that the electronic band gap reduction is greater for zigzag-edge functionalization than for armchair-edge modification by chlorine atoms. The computed optical absorption profile of functionalized GQDs exhibits an overall red shift with respect to their pristine counterpart, with the shift being more pronounced at higher energies.

Techno-Economic Assessment and Sensitivity Analysis of Glycerol Valorization to Biofuel Additives via Esterification.

Glycerol is a valuable feedstock, produced in biorefineries as a byproduct of biodiesel production. Esterification of glycerol with acetic acid yields a mixture of mono-, di-, and triacetins. The acetins are commercially important value-added products with a wide range of industrial applications as fuel additives and fine chemicals.

Coumarin linked thiazole derivatives as potential α-glucosidase inhibitors to treat diabetes mellitus.

Diabetes is a leading cause of kidney failure, blindness, heart attacks and lower limb amputation. Prevalence of diabetes is rising globally. α-glucosidase is validated target for controlling hyperglycemia because of its role in catalysing hydrolysis of carbohydrates to glucose in GIT.

Identifying potential neuroprotective polyphenols targeting endoplasmic reticulum stress through an approach.

The endoplasmic reticulum (ER) is essential in many cellular processes, including protein processing, lipid metabolism, and calcium storage. Dysregulation of ER function has been linked with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, etc. The primary pathological alteration explicated in the diseases is the accumulation of misfolded proteins in the neuronal cells.

Pharmacological Features of 18β-Glycyrrhetinic Acid: A Pentacyclic Triterpenoid of Therapeutic Potential.

L. (belonging to the family Leguminosae), commonly known as Licorice, is a popular medicinal plant that has been used in traditional medicine worldwide for its ethnopharmacological efficacy in treating several ailments. Natural herbal substances with strong biological activity have recently received much attention.

Solvent Free Upgrading of 5-Hydroxymethylfurfural (HMF) with Levulinic Acid to HMF Levulinate Using Tin Exchanged Tungstophosphoric Acid Supported on K-10 Catalyst.

The manufacture of high-value products from biomass derived platform chemicals is becoming an integral part of the biorefinery industry. In this study, we demonstrate a green catalytic process using solvent free conditions for the synthesis of hydroxymethylfurfural (HMF) levulinate from HMF and levulinic acid (LA) over tin exchanged tungstophosphoric acid (DTP) supported on K-10 (montmorillonite K-10 clay) as the catalyst. The structural properties of solid acid catalysts were characterized by using XRD, FT-IR, UV-vis, titration, and SEM techniques.

Formulation development and evaluation of therapeutic contact lens loaded with ganciclovir.

Purpose: In the present investigation ganciclovir (GAN) loaded microparticles dispersed in hydrogel-based contact lenses were fabricated, characterized and evaluated for eye irritation.

Methods: GAN-Hydroxy Propyl Methyl Cellulose (HPMC) microparticles were prepared by solvent evaporation method and evaluated for entrapment efficiency, drug content and drug release. The Polyhydroxyethylmethacrylate (pHEMA) contact lenses were synthesized by free radical polymerization reaction using crosslinkers like ethylene glycoldimethacrylate and photoinitiator such as IRGACURE 1173, in UVB light, λ 365 nm.

Computational Design, Synthesis, and Pharmacological Evaluation of Naproxen-Guaiacol Chimera for Gastro-Sparing Anti-Inflammatory Response by Selective COX2 Inhibition.

The 4-allyl guaiacol is a natural phenolic molecule that has been widely studied for its antioxidant capacity against reactive-oxygen-species-mediated cellular damage. Therefore, we hypothesized that concomitant use of an antioxidant and NSAID may decrease the risk of gastrointestinal toxicity and make the therapy safer. To address the gastrointestinal toxicity of conventional NSAIDs, a new S-naproxen-4-allyl guaiacol chimera (MAS-1696) was computationally developed, chemically synthesized, and tested for anti-inflammatory effectiveness and gastrointestinal safety.

Kinetic Analysis of Glycerol Esterification Using Tin Exchanged Tungstophosphoric Acid on K-10.

Glycerol acetins (mono-, di-, and tri) are produced via esterification with acetic acid. The acetins are commercially important industrial chemicals including their application as fuel additives, thus significant to environmental sustainability and economic viability of the biorefinery industry. Glycerol esterification with acetic acid was studied using partial tin exchanged tungstophosphoric acid supported on montmorillonite K-10 as catalysts.

A unified multivariate statistical approach for the assessment of deep groundwater quality of rapidly growing city of Maharashtra Province, India, with potential health risk.

The main aim of this research is to assess the consequences of natural and anthropogenic processes on the groundwater quality of 65 deep aquifers of Nagpur city, Maharashtra Province, India, using a unified multivariate statistical approach. The dominant groundwater type recognized is Ca-HCO (recharge waters) in 43.1 and 38.

Current perspectives on interethnic variability in multiple myeloma: Single cell technology, population pharmacogenetics and molecular signal transduction.

Multiple myeloma (MM) is an aggressive cancer characterised by malignancy of the plasma cells and a rising global incidence. The gold standard for optimum response is aggressive chemotherapy followed by autologous stem cell transplantation (ASCT). However, majority of the patients are above 60 years and this presents the clinician with complications such as ineligibility for ASCT, frailty, drug-induced toxicity and differential/partial response to treatment.

Computational design of PD-L1 small molecule inhibitors for cancer therapy.

Drug repurposing opens new avenues in cancer therapy. Drug repurposing, or finding new uses for existing drugs, can substantially reduce drug discovery time and costs. Cheminformatics, genetics, and systems biology advances enable repositioning drugs.

A comprehensive network map of IL-17A signaling pathway.

Interleukin-17A (IL-17A) is one of the member of IL-17 family consisting of other five members (IL-17B to IL-17F). The Gamma delta (γδ) T cells and T helper 17 (Th17) cells are the major producers of IL-17A. Aberrant signaling by IL-17A has been implicated in the pathogenesis of several autoimmune diseases including idiopathic pulmonary fibrosis, acute lung injury, chronic airway diseases, and cancer.

Aphrodisiac Performance of Bioactive Compounds from Linn.: In Silico Molecular Docking and Dynamics Simulation Approach.

Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research.

Effects of active compounds from on quorum sensing mediated virulence and biofilm formation in .

infections are attributed to its ability to form biofilms and are difficult to eliminate with antibiotic treatment. Biofilm formation is regulated by quorum sensing (QS), an intracellular bacterial communication mechanism that allows the activation of numerous virulence factors and secondary metabolites. Targeting the QS pathway is a potential approach that prevents QS-controlled phenotypes and biofilm formation.

and Leptospirosis: New Systems Science Insights on Proteome, Posttranslational Modifications, and Pathogen-Host Interaction.

Leptospirosis is one of the most important zoonotic diseases for planetary health. It is caused by spp., which poses a formidable challenge in both rural and urban geographies.