IL23A (Interleukin 23 Subunit Alpha)

These include combinatorial and sequential treatment strategies, next-generation biologics and oral agents, immunometabolic modulation, selective targeting of pathogenic immune cell populations and upstream inflammatory, immune tolerance-based approaches. It is with hope that these developments highlight a shift from incremental therapeutic expansion towards a integrated, targeted and ultimately, more informed treatment approach.

In this article, we discuss the clinical and histopathologic findings of cutaneous adverse reactions to newer medications, including those recently approved to treat inflammatory skin diseases, such as dupilumab for atopic dermatitis and IL-12/-23 and IL-23 specific inhibitors for psoriasis, as well as those with oncologic indications, including immune checkpoint inhibitors, mogamulizumab, and enfortumab vedotin.

Therefore, this narrative review aims to provide a consolidated mechanistic overview of bacterial infection-induced carcinogenesis and to highlight emerging phytochemical and nanotechnology strategies as potential therapeutic approaches. Additionally, phytochemical-based interventions and nanotechnology strategies are discussed as potential alternative therapeutic approaches to counteract bacteria-induced carcinogenesis.

Thiazolidinedione agonists (pioglitazone, rosiglitazone) have modest but clinically significant anti-psoriatic efficacy when combined with traditional systemic medicines, resulting in cardiometabolic benefits. Future directions include patient biomarker stratification, dual/selective agonists (glitazars), and sensible combination with biologics that target tumor necrosis factor-alpha/IL-17/IL-23. This review reframes PPARs as key players in the relationship between psoriasis and metabolic syndrome by synthesizing molecular understanding and clinical data.

A murine psoriasis model was induced by 6-day continuous topical imiquimod (IMQ) application; cellular models were established by stimulating keratinocyte lines with tumor necrosis factor-alpha (TNF-α)/interleukin-17A (IL-17A)...siNrf2 abolished Nef-mediated inhibition of NF-κB/ERK phosphorylation, cytokine down-regulation and ΔΨm loss. Neferine ameliorates psoriasis by inducing oxidative stress-driven apoptosis in hyper-proliferative keratinocytes and by activating Keap1-Nrf2-mediated anti-inflammatory signaling to block the IL-23/IL-17 axis, offering a promising small-molecule strategy for psoriasis management.

Therefore, this work aimed to evaluate the potential effect of enzymatically-modified isoquercitrin (EMIQ, 50 and 100 mg/kg body weight "b.wt", administered orally for 8 days), in comparison with methotrexate (MTX, a synthetic drug), against imiquimod (IMQ)-induced psoriatic lesions in female BALB/c mice. Moreover, oral administration of EMIQ prevented significantly (P < 0.001) the vascular permeability associated with augmented Evans blue leakage and dermal accumulation of degranulated mast cells, suggesting a reduction in inflammation and edema. Taken together, our study demonstrated that EMIQ can alleviate psoriasis and may be considered as a promising strategy for psoriasis treatment via targeting IL-23/IL-17A axis and mast cell degranulation.

In addition, J2H-1802 significantly reduced serum tumor necrosis factor-α (TNF-α) levels and suppressed pro-inflammatory cytokine expression, including IL-1β, IL-6, IL-17, and TNF-α, in psoriatic skin. J2H-1802 alleviates both local and systemic inflammatory features of psoriasis, suggesting its potential as a therapeutic candidate for targeting IL-23/Th17-mediated inflammatory pathways.

Selective TYK2 inhibitors, such as deucravacitinib, envudeucitinib, and zasocitinib, act through a unique allosteric mechanism by binding to the regulatory pseudokinase domain (JH2) rather than the enzyme's catalytic domain...Clinical trials (POETYK PSO-1 and PSO-2) and long-term extension studies demonstrate that deucravacitinib provides superior efficacy compared to the first-generation oral small molecule apremilast, with high and sustained response rates...Selective TYK2 inhibition bridges the therapeutic gap, providing an optimal balance of efficacy and oral convenience. With the potential to improve patient adherence and quality of life, these agents represent a promising option to become a first-line oral systemic therapy for psoriasis.

In addition, neurotrophic therapies preserving BBB integrity may reduce secondary neuronal damage. Therefore, a future precision cardio-neuroprotective paradigm will rely on the integration of anti-inflammatory, molecular, and neurovascular strategies aimed at limiting systemic cytokine propagation and restoring bidirectional homeostasis through the heart-brain axis.

Current evidence supports a stepwise, phenotype-driven approach in which systemic retinoids remain first-line systemic therapy, while biologics represent a rational and increasingly evidence-supported option for moderate-to-severe, treatment-resistant, or syndromic disease. Further controlled studies are needed to define optimal sequencing, duration, and combination strategies for long-term management.

Despite the immunogenetics incriminating the IL-23/IL-17 axis, clinical evidence confirming the role of IL-23/IL-17/inhibition in BS therapy is still limited including disappointing results with secukinumab in trials for Behçet's uveitis. However, emerging evidence from small-scale retrospective studies, prospective trials, and case reports indicates that IL-23/IL-17 axis inhibition may benefit mucocutaneous and articular manifestations, as well as neuro-Behçet's disease and the licensed PDE4 inhibitor apremilast regulates multiple aspects of IL-23/17 axis and neutrophil biology...Herein, we discuss IL-23/IL-17 axis inhibition in BS and why it should be used cautiously and be limited to mucocutaneous and/or articular manifestations at this juncture. Further randomized controlled trials are imperative to dissect the IL-23/IL-17 axis in BS including high-dose anti-IL-23 therapy antagonism given that neutrophils are an abundant source of IL-23 and consider novel strategies including IL-23R antagonism.

Sex is a crucial biological variable in CIPN, influencing drug efficacy through sex-specific neuroimmune mechanisms and hormonal regulation. These findings underscore the necessity of incorporating sex as a key variable in analgesic development and clinical practice to achieve personalized pain management in CIPN patients.