Pandu College

Rheumatoid arthritis is a chronic autoimmune disorder characterized by chronic inflammation of synovial joints, for which methotrexate remains the first-line therapy. However, conventional methotrexate administration is often limited by systemic toxicity and uncontrolled drug release. In this study, a methotrexate-loaded Aloe vera-based emulgel was developed to achieve sustained drug delivery and enhanced anti-inflammatory efficacy. Four emulgel formulations with varying compositions were prepared and evaluated for physicochemical characteristics, including appearance, rheological behavior, spreadability, average globule size, zeta potential, drug content, and in vitro drug release. Aloe vera-containing formulations demonstrated sustained methotrexate release, with more than 60% of the drug released over 6 h, and the release kinetics were best described by the Weibull model. In contrast, non-Aloe vera formulations exhibited rapid drug release (>80% within 2 h) following Michaelis-Menten kinetics, indicating the critical role of Aloe vera in modulating release behavior. The optimized emulgel showed significant anti-inflammatory activity by inhibiting protein denaturation, achieving up to 93% inhibition of bovine serum albumin and 95% inhibition of egg albumin, comparable to diclofenac. Cytotoxicity studies revealed minimal to negligible toxicity toward normal peripheral blood mononuclear cells and splenocytes over 24-96 h, confirming good biocompatibility. Density functional theory calculations indicated stable adduct formation between methotrexate and bioactive constituents of Aloe vera, supporting their role as effective drug carriers. Molecular docking studies further suggested enhanced binding affinity of these adducts toward cyclooxygenase-2 compared to methotrexate alone. Overall, the findings suggest that methotrexate-loaded Aloe vera-based emulgel is a safe and promising therapeutic platform for improved management of rheumatoid arthritis.

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by the selective loss of dopaminergic neurons, resulting in a severe deficiency of dopamine. Monoamine oxidase-B (MAO-B), a key enzyme involved in dopamine catabolism, is an important therapeutic target in PD management. Although berry-derived polyphenols are well known for their antioxidant and neuroprotective properties, their MAO-B inhibitory potential remains inadequately explored. In this study, an integrated in silico approach was employed to investigate 15 major polyphenolic compounds derived from berries as potential MAO-B inhibitors. Molecular docking, density functional theory-based quantum chemical calculations, molecular dynamics (MD) simulations, and binding free energy analyses were performed to elucidate binding affinity, interaction stability, and inhibition mechanisms. In addition, pharmacokinetic profiling, ADMET prediction, and toxicity assessments, including cardiotoxicity, carcinogenicity, and cytochrome P450 isoform inhibition, were conducted to evaluate drug-likeness and safety profiles. While most polyphenols exhibited favorable interactions with MAO-B, kaempferol, ellagic acid, quercetin, and pelargonidin demonstrated superior binding affinities and stable active-site interactions during MD simulations. These findings were further supported by favorable quantum chemical descriptors and lower binding free energy values. Overall, this computational study identifies berry-derived polyphenols as promising MAO-B inhibitors for PD.

In this study, we define new Banach sequence spaces ℓ _p(𝒥) , ℓ _∞(𝒥) , c_0(𝒥) and c(𝒥) using a new regular infinite matrix 𝒥= (𝔧_cd) which is given by 𝔧_cd = {[ 2j_dj_c+2 - 1 1 ≤ d ≤ c; ∀ c,d = 1,2,3,⋯; ; 0 otherwise, ]. where j= (j_d) is Jacobsthal number sequence. We also introduce various topological, inclusion relations, α -, β -, γ - duals, matrix mappings and Schauder bases of newly generated sequence spaces. Lastly, compactness of matrix operators on related sequence spaces have been provided using the concept of measure of noncompactness.

Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are caused largely by protein fibril misfoldings, their aggregation, mitochondrial dysfunction and irregularity in cell signalling pathways. Due to the presence of the blood brain barrier and poor target specificity, the traditional therapeutics showed limited success. In recent times, with the progress in computational biology and artificial intelligence a structurally precise, highly stable de novo microproteins with tunable binding affinity have been designed to treat such deleterious diseases. These engineered small proteins through selective binding with the amyloid protein fibrils as well as by enhancing mitochondrial function and proteostasis prevent the onset and progression of neural disorders. This review highlights de novo design of microproteins, their mechanisms of action, challenges and future prospects in neurodegenerative pathologies. Collectively, de novo designed microproteins represent a promising candidate in curing of neural diseases.