Onychomycosis and nail psoriasis are nail disorders that often require systemic antifungal therapy. Oral treatments are associated with adverse effects due to first-pass metabolism and potential drug interactions. Topical drug delivery to the nail, known as transungual drug delivery, offers a promising alternative but presents challenges due to the nail’s dense, keratinized structure, which restricts drug penetration. As a result, achieving effective therapeutic concentrations at the site of infection is difficult. Additional barriers, such as reduced blood supply to the nail bed and alterations in nail morphology, further hinder drug delivery. This review highlights current advances in transungual drug delivery, focusing on strategies to overcome the nail plate barrier. These include the use of chemical penetration enhancers, physical and mechanical techniques, and innovative drug delivery systems designed to improve drug diffusion. The importance of pre-treating the nail plate, such as filing, to increase permeability is also discussed. Recent developments in nail sampling techniques are explored. Transungual delivery systems can provide localized therapy with minimal systemic exposure, offering a safer and more targeted approach for treating nail disorders like onychomycosis and psoriasis. Enhanced drug permeation through the nail is essential for successful treatment, achievable through optimized formulation strategies and penetration-enhancing techniques.
Abstract: Rheumatoid arthritis (RA) is a complex autoimmune disease characterised by chronic joint inflammation that necessitates effective management strategies. In recent years, medicinal plants of the Fabaceae family have gained considerable attention for their potential therapeutic roles in managing inflammatory disorders, including RA. This review examines the anti-arthritic potential of Fabaceae plants and elucidates their underlying mechanisms of action. A comprehensive literature search was conducted across PubMed and ISI Web of Knowledge databases for publications from 1990 to 2023, using keywords, such as Faba-ceae, medicinal plants, arthritis, phytochemicals, and mode of action. The analysis revealed that phytoconstituents, such as flavonoids, alkaloids, and polyphenols, contribute signifi-cantly to the anti-inflammatory, antioxidant, and immunomodulatory activities of Fabaceae members. These bioactive compounds alleviate RA symptoms by downregulating pro-in-flammatory mediators and modulating key molecular targets, including TNF-α, COX-2, and NF-κB signalling pathways. Moreover, antioxidant-rich extracts from Fabaceae species help neutralize reactive oxygen species, thereby mitigating oxidative stress–induced joint dam-age. While evidence from preclinical studies supports their therapeutic potential, clinical validation remains limited. Collectively, the findings underscore the promise of Fabaceae plants as valuable natural sources for developing safe and effective anti-arthritic agents, war-ranting further pharmacological and clinical investigations to establish their efficacy and safety profiles.
Abstract: ISGylation has traditionally been examined in the context of antiviral immunity, where it is widely recognized as a protective interferon-stimulated response. This protective dimension may be considered the “yang” of ISGylation, reflecting its role in viral restriction, immune defense, and maintenance of cellular homeostasis. Numerous reviews have emphasized this antiviral and beneficial function while contrasting it with emerging evidence implicating ISGylation in cancer-associated pathways, where its effects remain less clearly defined, often context-dependent, and potentially pathogenic. This disease-promoting dimension may represent the “yin” of ISGylation, in which the same regulatory system may contribute to oncogenic signaling, immune evasion, tumor–stromal interactions, or cancer cell cooperation. However, existing literature has largely treated these opposing roles as parallel but separate phenomena. This review proposes a unifying perspective by examining ISGylation as a dynamic regulatory system whose functional outcome is shaped by cellular context, disease state, and intercellular communication. Recent findings are synthesized on the dual activities of ISG15, both as an intracellular ubiquitin-like modifier and as a free, secreted molecule with cytokine-like properties. While intracellular ISGylation affects viral restriction, immune signaling, and oncogenic pathways, increasing evidence suggests that unconjugated ISG15 can be released from cells and participate in immune modulation beyond the cell of origin. Notably, this review highlights the underexplored role of exosome-mediated ISG15 trafficking as a potential mechanism of cell-to-cell communication. This mode of signaling may be particularly relevant in the tumor microenvironment, where ISGylation could influence immune evasion, tumor–stromal crosstalk, and cooperative cancer cell behavior in ways that are not yet fully appreciated. By integrating intracellular and extracellular dimensions, this review reframes the “protective versus pathogenic” dilemma as a yin–yang regulatory balance and suggests that ISGylation’s therapeutic potential may be embedded in its intertwined intracellular and intercellular communication networks in viral infection and cancer.
Introduction: Monoclonal antibodies (mAbs) that target receptor-mediated oncogenic pathways have revolutionized oncology research. Better therapeutic indices are possible with these mAbs for targeted tumor treatment. This review covers receptor-targeted monoclonal antibodies targeting the EGFR, HER2, and VEGF pathways in solid tumors, as well as their therapeutic use and development. Methods: The study searched the scientific literature to identify key FDA-authorized studies on the EGFR, HER2, and VEGF/VEGFR pathways, as well as translational research and mechanistic investigations of these pathways. The focus was on developing next-generation antibody engineering platforms, understanding resistance mechanisms, and using biomarkers to select patients. Results: Therapeutic monoclonal antibodies (mAbs) inhibited carcinogenic signaling pathways, such as RAS/MAPK and PI3K/AKT. When mAbs engage with the immune system, they activate the complement system and induce antibody-dependent cellular cytotoxicity. Clinical trials have shown that biomarker-selected cohorts of patients with colorectal, breast, lung, gastric, and other cancers have improved survival rates without disease recurrence. Mutations, activation of alternative pathways, and changes in the tumor microenvironment may generate intrinsic and acquired resistance, reducing long-term efficacy. Discussion: Resistance patterns highlight the need for adaptable strategies that account for the biology of multiple target organisms. Cell-penetrating platforms, glycoengineering, antibody-drug conjugates, and bispecific antibodies have been developed to improve therapeutic efficacy, decrease escape mechanisms, and increase drug accessibility. Conclusion: Receptor-targeting monoclonal antibodies are crucial in precision oncology. Future advances must include molecular profiling, smart combination approaches, and nextgeneration antibody engineering to improve response durability and patient outcomes.
Introduction: Inflammatory bowel disease, encompassing ulcerative colitis and Crohn's disease, represents a growing global health burden, characterised by chronic intestinal inflammation, oxidative stress, and progressive mucosal barrier dysfunction. This study investigated the anti-colitic potential of the whole alkaloid extract of Linum usitatissimum (ALU) in a murine model of dextran sodium sulphate (DSS)-induced colitis, evaluating its antioxidant, anti-inflammatory, and mucosal-protective properties. Methods: Forty male BALB/c mice were divided into five groups (n = 8): vehicle control, DSS-only, and three DSS groups treated orally with ALU at 50, 100, or 200 mg/kg daily. Clinical activity, colon weight-to-length ratio, H&E histological scoring, and biochemical markers (CAT, GSH, NO, MDA) were assessed on Day 7. Results: DSS induced marked colitis, which ALU reversed dose-dependently; at 200 mg/kg, ALU normalised the colon weight-to-length ratio, restored CAT and GSH levels, reduced NO and MDA, and produced near-complete histological recovery. Discussion: The current study demonstrates that ALU has considerable antioxidant and intestinal anti-inflammatory capabilities. The anti-colitic effect was demonstrated through multiple pathways, including maintaining a stable body weight, reducing the colon weightto-length ratio, restoring endogenous antioxidant defenses, and inhibiting pro-oxidant and pro-inflammatory mediators. Conclusion: These findings show that the entire alkaloid extract from Linum usitatissimum seeds significantly reduces inflammation in the DSS-induced colitis model in vivo, showing its potential as an anti-inflammatory drug for the treatment of inflammatory bowel diseases.
