Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Alzheimer's disease.

Alzheimer's disease (AD) is a multifaceted, advancing neurodegenerative illness that is responsible for most cases of neurological impairment and dementia in the aged population. As the disease progresses, affected individuals may experience cognitive decline, linguistic problems, affective instability, and behavioral changes. The intricate nature of AD reflects the altered molecular mechanisms participating in the affected human brain. MicroRNAs (miRNAs, miR) are essential for the intricate control of gene expression in neurobiology. miRNAs exert their influence by modulating the transcriptome of brain cells, which typically exhibit substantial genetic activity, encompassing gene transcription and mRNA production. Presently, comprehensive studies are being conducted on AD to identify miRNA-based signatures that are indicative of the disease pathophysiology. These findings can contribute to the advancement of our understanding of the mechanisms underlying this disorder and can inform the development of therapeutic interventions based on miRNA and related RNA molecules. Therefore, this comprehensive review provides a detailed holistic analysis of the latest advances discussing the emerging role of miRNAs in the progression of AD and their possible application as potential biomarkers and targets for therapeutic interventions in future studies.

Chitosan coated clove oil-based nanoemulsion: An attractive option for oral delivery of leflunomide in rheumatoid arthritis.

Rheumatoid arthritis (RA), a distressing inflammatory autoimmune disease, is managed mainly by Disease-modifying antirheumatic drugs (DMARDs), e.g. leflunomide (LEF). LEF (BCS class II) has limited solubility and adverse effects following its systemic exposure. The appealing antirheumatic properties of both clove oil and chitosan (CS) were exploited to design oral leflunomide (LEF)-loaded nanoemulsion (NE) system to augment the therapeutic action of LEF and decrease its systemic side effects as well. Different LEF-NEs were prepared using clove oil, Tween® 20 (surfactant), and PEG 400(co-surfactant) and characterized by thermodynamic stability, percentage transmittance, cloud point, size analysis, and drug content. Optimized LEF-NE was subjected to CS coating forming LEF-CS-NE that exhibited nanometric size range, prolonged drug release, and good physical stability. In vivo anti-rheumatic activity of pure LEF, market LEF, and LEF-CS-NE was assessed utilizing a complete Freund's adjuvant (CFA) rat model. Treatment with LEF-CS-NE reduced edema rate (48.68% inhibition) and caused a marked reduction in interleukin-6 (IL-6) (510.9 ± 2.48 pg/ml), tumor necrosis factor- α (TNF-α) (397.3 ± 2.53 pg/ml), and rheumatoid factor (RF) (42.58 ± 0.49 U/ml). Furthermore, LEF-CS-NE reduced serum levels of glutamic pyruvic transaminase (GPT) to (83.19%) and glutamic oxaloacetic transaminase (GOT) to (40.68%) compared to the control + ve group. The effects of LEF-CS-NE were also superior to both pure and market LEF and showed better results in histopathological studies of paws, liver, kidney, lung, and heart. The remarkable therapeutic and safety profile of LEF-CS-NE makes it a potential oral system for the management of RA.