Psoriasis is a chronic inflammatory disease that affects up to 3% of the global population. In recent years, monoclonal antibodies targeting key cytokines underlying skin lesions and joint involvement in the course of psoriasis, i.e., TNF-α, IL-17, and IL-23, have been increasingly used due to their high effectiveness and favorable safety profile. Numerous studies have been conducted analyzing the influence of cytokine inhibitors on non-specific inflammatory markers. However, only a limited number of studies on the effect of methotrexate (MTX) therapy on blood-count-derived inflammatory indices in patients with plaque psoriasis have been published so far. The study aims to analyze and compare the impact of methotrexate and biological drugs on the dynamics of selected blood-count-derived inflammatory indices in psoriatic patients. The analysis involved 182 patients receiving biological therapy, which resulted in a total of 219 treatment cycles (TCs) and 48 patients treated with therapeutic doses of MTX (48 TCs). In the biological subgroup, there were six TCs with an inhibitor of IL-12/23, 58 TCs with IL-17A inhibitors, 22 TCs with an inhibitor of IL-17AF, 113 TCs with IL-23 inhibitors, and 20 TCs with TNF-alfa inhibitors. A comparison between patients receiving biological treatment regardless of the drug and patients receiving MTX was conducted. Themajor factors determining the duration of MTX therapy were older age at the time of therapy initiation, a later onset of psoriasis, and a higher burden of comorbidities. Furthermore, the strongest impact on the average inflammatory state over time in patients treated with methotrexate was associated with comorbidities, male gender, and older age. Contrary to MTX therapy, patients receiving biological drugs were characterized by lower values of most assessed blood-count-derived inflammatory biomarkers at week 40 compared to baseline. It was confirmed that biologics and MTX treatment modify the dynamics of blood-count-derived inflammatory biomarkers in a different manner.

Still’s disease (SD) is a rare chronic autoinflammatory disease manifested by the development of high peak fever, joint involvement (arthralgias and arthritis), and the appearance of a salmon-colored maculopapular rash. The 2024 EULAR guidelines unified the diagnostic criteria for Still’s disease including fever ≥39°C (102.2°F), recurrent erythematous rash, musculoskeletal involvement, neutrophilic leukocytosis, and elevated CRP and ferritin. If S100 or interleukin (IL)18 levels can be determined, their elevated values will point in favor of SD. Also, treatment strategy have been modified with the administration of biologics of IL-1 or IL-6 inhibitors if glucocorticoids (GCs) are ineffective, and the use of methotrexate (MTX) is considered if biologic therapy cannot be initiated.This case report focuses on the situation of timely diagnosis of SD and resistance to standard therapy with GCs (including pulse therapy) and MTX. Due to insufficient availability of biologics, based on the existing experience of colchicine prescription in SD in the scientific literature, the patient’s therapy was modified with the addition of colchicine at a dose of 1 mg orally per day, after the administration of which regression of clinical manifestations and normalization of acute-phase markers were noted.This clinical experience demonstrates the feasibility of colchicine administration as an alternative to biologics to reduce disease activity if SD is refractory to GC and MTX therapy.

Current psoriatic arthritis (PsA) therapies, from conventional agents (e.g. methotrexate) to targeted biologics (e.g. TNF and IL-17 inhibitors), demonstrate distinct therapeutic profiles. Vunakizumab (SHR-1314) is a novel humanized monoclonal antibody targeting IL-17A. The phase 2 trial evaluated the efficacy and safety of vunakizumab in patients with active PsA. Patients aged 18-75 years with a confirmed diagnosis of active PsA were randomized (1:1:1) to receive either subcutaneous vunakizumab 120 mg (n = 38), vunakizumab 240 mg (n = 37), or placebo (n = 37) at weeks 0, 2, 4, and 8. At week 12, patients on placebo were switched to vunakizumab (1:1 re-randomized to 120 mg or 240 mg through week 20), while vunakizumab groups continued treatment. The primary end point was American College of Rheumatology 20% improvement (ACR20) response rate at week 12. At week 12, ACR20 response rates were higher in the vunakizumab 120 mg (47.4%) or 240 mg (59.5%) groups vs placebo group (21.6%; p = 0.02 and p = 0.001, respectively). Also, improvements were sustained through 24 weeks and were noted in patients who switched from placebo after week 12. Treatment-emergent adverse events (TEAEs) incidence exhibited analogous frequencies between vunakizumab (73.7% [120 mg], 64.9% [240 mg]) and placebo (70.3%) during the 12-week core treatment period, and no severe TEAEs occurred. Vunakizumab demonstrated superior efficacy to placebo and was well tolerated with an acceptable safety profile in patients with active PsA. The findings support proceeding to a phase 3 study. www. clinicaltrials.gov; NCT05055934.

To investigate whether an anti-interleukin-6 (IL-6) receptor antibody (MR16-1) can prevent retinal and optic nerve dysfunction, as well as myelitis, in a mouse model of myelitis induced by immunization with aquaporin-4 (AQP4) peptide. Mice immunized with AQP4 peptide received MR16-1 or vehicle. Retinal function was assessed by electroretinography (ERG), including b-wave, a-wave, and positive scotopic threshold response (pSTR) amplitudes. Histologic analysis evaluated inflammatory cell infiltration and aberrant Müller cell activation (punctate pattern of glial fibrillary acidic protein staining). Blood-retinal barrier (BRB) integrity was assessed using Evans blue dye, IgG leakage, and transendothelial electrical resistance (TEER) in primary mouse retinal microvascular endothelial cells (mRMECs) exposed to mouse serum. AQP4 peptide immunization led to reductions in ERG b-wave and pSTR amplitudes and increased inflammatory cell infiltration, Müller cell alteration, and retinal vascular permeability. MR16-1 treatment significantly mitigated these changes, suppressing reductions in pSTR and b-wave amplitude, preventing inflammation and aberrant Müller cell activation, and reducing vascular leakage. The improvement of a-wave amplitude was not significant. Serum from MR16-1-treated mice did not reduce mRMEC TEER, while serum from AQP4 peptide-immunized mice reduced it. IL-6 receptor blockade with MR16-1 has the potential to suppress AQP4 peptide immunization-related retinal and optic nerve dysfunction and pathology, likely by protecting BRB integrity and suppressing inflammation. These findings support the therapeutic potential of IL-6 inhibition in preserving visual function in neuromyelitis optica spectrum disorder (NMOSD). IL-6 receptor blockade may be a viable strategy for preventing visual impairment in patients with NMOSD.

Time to lift the moratorium on IL-23 inhibitors for axial psoriatic arthritis.

Network pharmacology and experimental validation identify the targets of Marsdenia tenacissima in neutrophilic asthma treatment.

In vitro gastrointestinal digests of 4-methylbenzoquinone-modified β-lactoglobulin exhibit antioxidant and anti-inflammatory activities in macrophages.

Lymphocyte alterations and elevated complement signaling are key features of refractory myasthenia gravis.

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, represents a novel approach to systemic psoriasis treatment, offering the advantages of oral administration and selective inhibition of cytokine signaling pathways involved in psoriasis pathogenesis. This review evaluates the efficacy and safety of deucravacitinib based on findings from phase III clinical trials, including POETYK PSO-1, PSO-2, PSO-4, and long-term extension studies. In these trials, deucravacitinib demonstrated superior efficacy compared to placebo and apremilast, with a significantly higher proportion of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75). Long-term data suggest sustained efficacy through 3 years of continuous treatment. Deucravacitinib was well tolerated, with a safety profile characterized by low rates of serious adverse events, including infections and major cardiovascular events. The most common adverse events included nasopharyngitis, upper respiratory tract infections, and acne, with herpes zoster occurring at a low incidence. The results of the phase III trials support deucravacitinib as an effective oral alternative to biologic therapies, with sustained efficacy and a favorable safety profile. Future studies should explore head-to-head comparisons with interleukin (IL)-17 and IL-23 inhibitors to define their role in psoriasis management better.

Coronavirus disease 2019 (COVID-19) and other respiratory viral infections, such as influenza and respiratory syncytial virus (RSV), elicit both common and virus-specific host responses. Here, we present an integrative analysis leveraging the COVID-19 Host Genetics Initiative (HGI) GWAS data (freeze 7) and publicly available multi-omics datasets (including influenza/RSV human challenge transcriptomes and plasma proteomics) to construct an explainable AI model for comparing host infection mechanisms between COVID-19 and other viral illnesses. We identified shared antiviral pathways (type I interferon (IFN) signaling) active in host responses to all three viruses, as well as virus-specific mechanisms: for instance, SARS-CoV-2 infection induced uniquely strong coagulation and renin-angiotensin system dysregulation, along with sustained AP-1/MAPK activation, whereas influenza provoked more robust T-cell activation, and RSV triggered an excessive neutrophil-driven inflammatory response. Genetic risk pathway fingerprints from GWAS highlight that COVID-19 severity is associated with variants in IFN and inflammatory pathways, while host genetic effects in influenza point to distinct receptor usage (sialic acid biosynthesis) with minimal overlap. Mendelian randomization (MR) pinpointed key causal proteins for COVID-19 severity, including ABO (blood group glycosyltransferase) and inflammatory mediators, suggesting that host glycomic and immune factors modulate disease outcomes. Our explainable machine learning model integrated these multi-omic features to accurately distinguish COVID-19 from other viral infections, with SHAP interpretation confirming the predominance of the above mechanisms in model predictions. In summary, this cross-omics study provides a comprehensive comparative map of host responses in COVID-19 versus influenza and RSV, yielding biologically interpretable insights into both common antiviral defenses and unique pathogenic pathways. These findings inform the development of targeted therapies (IL-6 or MAPK inhibitors for COVID-19) and broad-spectrum antivirals (enhancing IFN responses) to mitigate severe respiratory viral diseases.

Psoriasis is a chronic inflammatory skin condition characterized by the hyperproliferation of keratinocytes that results in erythematous and scaly plaques on the epidermal surface. Conventional therapeutic approaches exhibit drawbacks such as inadequate skin penetration, low drug bioavailability, and undesirable side effects. Nanoformulations emerge as a novel strategy to enhance drug delivery for treating psoriatic lesions with modified cyclodextrins (CDs), offering significant potential to improve their efficacy in the field of medicine. Cyclodextrins are well-known as versatile excipients that improve solubility, dissolution rate, chemical stability, and bioavailability through the formation of inclusion complexes. Furthermore, the chemical modifications of cyclodextrins such as sulfation, methylation, and hydroxypropylation have further enhanced their utility in topical formulations. Modified cyclodextrins enhance the delivery of anti-psoriatic agents such as TNF-α or IL-17 inhibitors and target key inflammatory pathways in psoriasis while reducing systemic exposure and minimizing side effects like immunosuppression, infections, and gastrointestinal disturbances. Additionally, modified cyclodextrins help to repair the epidermal barrier by increasing the efficacy of anti-inflammatory and keratinocyte-modulating medications. This article highlights the capabilities of modified cyclodextrins for revolutionizing the transformation of more effective and targeted therapies for psoriasis by identifying the limitations of current therapies and exploring the innovative applications of modified cyclodextrins in nanoformulations.

Psoriasis and psoriatic arthritis (PsA) occasionally coexist with antinuclear antibody (ANA) positivity, cutaneous lupus erythematosus (CLE), or systemic lupus erythematosus (SLE), creating one of the most challenging therapeutic overlap scenarios in immunodermatology. Divergent immune pathways-IL-23/Th17-driven psoriatic inflammation versus type I interferon-mediated autoimmunity-generate unique vulnerabilities when systemic treatments are used. To synthesize treatment outcomes, lupus-related safety signals, and mechanistic insights across systemic therapies in patients with psoriasis or PsA who also exhibit ANA positivity, CLE, or SLE. A systematic review following PRISMA 2020 guidelines was conducted across PubMed/MEDLINE, Embase, the Cochrane Library, Scopus, and ClinicalTrials.gov from database inception through 31 October 2025. Thirty-three eligible reports (29 unique clinical studies; 1429 patients) were included and organized into six prespecified overlap subgroups. Mechanistic and translational studies-including ustekinumab and deucravacitinib SLE trial data and reports of IL-17 inhibitor-associated CLE-were reviewed separately to provide contextual interpretation. IL-23 inhibitors were consistently associated with a favorable cross-disease safety profile, with no clear signal for CLE worsening, SLE flares, or drug-induced autoimmunity. IL-17 inhibitors maintained strong psoriatic efficacy but were associated with an increased frequency of de novo or exacerbated CLE. TNF-α inhibitors showed the strongest association with ANA seroconversion, anti-dsDNA induction, drug-induced lupus, and lupus flares. Ustekinumab demonstrated a stable safety profile across lupus-spectrum disease despite variable efficacy in formal SLE trials. TYK2 inhibition provided dual modulation of IL-23 and type I interferon pathways and showed emerging utility in psoriasis or PsA coexisting with CLE or SLE. Apremilast, methotrexate, and mycophenolate mofetil remained reliable non-biologic systemic options. Phototherapy was associated with potential risk in ANA-positive or lupus-susceptible populations and therefore requires careful consideration. Interpretation is limited by the predominantly observational nature and heterogeneity of the available evidence. IL-23 inhibition and TYK2 inhibition appear to offer a balanced profile of efficacy and lupus-related safety in psoriatic disease complicated by lupus-spectrum autoimmunity. IL-17 inhibitors and TNF-α inhibitors may be associated with higher risk in CLE- or SLE-prone patients and therefore warrant particular caution. Personalized treatment strategies should integrate the relative dominance of psoriatic versus lupus disease, ANA/ENA profile, CLE subtype, and underlying mechanistic considerations. Prospective, biomarker-driven studies are needed to guide therapy in this increasingly recognized overlap population (PROSPERO registration: CRD420251241279).

Abstract INTRODUCTION With advances in treatment, the population of people living with inflammatory bowel disease (IBD) is living to an older age, unmasking malignancies that may or may not be associated with the treatment exposure. While some IBD therapies, particularly thiopurines, have been associated with increased risk of lymphoproliferative disorders, data suggest that anti-TNF monotherapy, Ustekinumab, and Vedolizumab carry low malignancy risk, even in patients with a history of previous malignancies. TNF, IL-12, and IL-23 are variably involved in cancer development, with inhibition potentially raising the risk of malignancy. Previously, studies have not shown worsening malignancy potential with newer therapies. TNF historically was associated with lymphomas, but meta-analyses in the past have associated that with thiopurine therapy. This review summarizes existing studies on the incidence of malignancies on patients on biologic therapy for IBD. METHODS PubMed, Cochrane, Embase, Scopus, Web of Science, and Google Scholar were explored for studies from origin till June 2025. 15 studies were included for review, including studies on anti-TNF, with and without thiopurines, IL-23 inhibitors, and JAK inhibitors. PRISMA guidelines were adhered to, and the Cochrane risk of bias was used. RESULTS Incidence of lymphoma (in 100 PPY) with thiopurines was 0.9 and 0.7 with and without anti-TNF agents. It was 0.2 for JAK-2 inhibitors and < 0.1 for the rest of the agents. For non-melanoma skin cancers, thiopurines have an incidence of 0.4, followed by < 0.1 for the rest of the biologics. An overall incidence of 0.2 was seen with JAK inhibitors for NSCLC. Incidence was double in the population >65 years of age. No difference was seen with gender or type of IBD. DISCUSSION Immunomodulatory agents alone or in combination with anti-TNF agents were associated with a higher risk of malignancy, most commonly lymphoma, followed by non-melanoma skin cancer and then non-small cell lung cancer. This was followed by anti-TNF monotherapy and then JAK inhibitors. Vedolizumab and Ustekinumab showed the most favorable malignancy profiles, even in patients with prior cancer with Vedolizumab comparatively safer. Across the groups, those aged > 65 years had the highest incidence of malignancy. So far, clinical trial evidence does not show a meaningful increase in overall cancer risk with S1P receptor modulators (ozanimod, etrasimod) in IBD patients. Kaposi sarcoma has been reported in one case linked to ozanimod.

Psoriasis is a chronic systemic inflammatory disease primarily affecting the skin, yet it is increasingly recognized for its systemic implications, particularly its strong association with type 2 diabetes mellitus (T2DM). This review synthesizes recent mechanistic and clinical evidence to elucidate the shared pathways linking psoriasis and T2DM, as well as to explore therapeutic strategies for this comorbidity. We conducted a narrative review of studies published between January 2020 and October 2025, encompassing preclinical models, clinical trials, and high-quality reviews that address pathogenesis and treatment.Key findings indicate that shared genetic loci and molecular pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, the IL-23/Th17 axis, and mitochondrial dysfunction associated with the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, contribute to both cutaneous inflammation and systemic metabolic dysregulation.Additionally, adipokine imbalances and chronic low-grade inflammation exacerbate insulin resistance and psoriatic skin pathology. Therapeutically, IL-17/IL-23 inhibitors, metformin, glucagon-like peptide 1(GLP-1)receptor agonists, and other immunomodulatory strategies demonstrate potential in addressing both dermatologic and metabolic features.These insights reinforce the notion of psoriasis as a systemic disorder with significant metabolic consequences, highlighting the need for integrated, multidisciplinary management. Future research should concentrate on precise gene-environment interactions, biomarker validation, and the development of treatments that simultaneously target both skin and metabolic pathology to advance precision medicine for patients with psoriasis-T2DM comorbidity.

Moderate-to-severe plaque psoriasis is a chronic inflammatory disease with high prevalence that significantly impacts patients’ quality of life. In recent years, interleukin-17 inhibitors have emerged as one of the most effective biologic therapeutic options for the management of this condition. The aim of this study was to comprehensively evaluate the efficacy and safety of IL-17 inhibitors in patients with moderate-to-severe plaque psoriasis through a systematic review and narrative meta-analysis of the available literature. An exhaustive search was conducted in international electronic databases, identifying randomized controlled trials and observational studies evaluating secukinumab, ixekizumab, brodalumab, and bimekizumab. The results demonstrate that treatment with IL-17 inhibitors is associated with significant clinical improvement, evidenced by high rates of PASI 75, PASI 90, and PASI 100 responses, as well as rapid reduction of cutaneous inflammatory activity. In addition, a favorable safety profile was observed, with mostly mild to moderate adverse events and a low rate of treatment discontinuation, with mucocutaneous infections being the most frequently reported adverse event. Overall, the available evidence supports IL-17 inhibitors as a highly effective and safe therapeutic option for the treatment of moderate-to-severe plaque psoriasis, consolidating their role as a first-line alternative in the current management of this disease.

Despite advancements in psoriasis therapeutics, biologic discontinuation and switching still happen frequently, with the most common reasons being lack of efficacy or treatment intolerance. Conventional teaching has been to switch out of the class (inter-class switching) for primary non-responders and to stay in the class (intra-class switching) for secondary non-responders. Previous real-world studies have reported success with intra-class switching within the IL-17 inhibitor class, but data have been limited to secukinumab, ixekizumab, and brodalumab. Using retrospective data from cases selected for moderate-to-severe psoriasis who failed prior IL-17 therapy, we report our real-world experience using bimekizumab in 50 patients who failed a prior IL-17 inhibitor, in which 82% achieved an IGA 0/1. By demonstrating achievement of stringent benchmarks, such as IGA 0/1 and sPGAxBSA 100 in these selected patients, we challenge the conventional teaching of primary vs secondary non-responders class switching, and have found bimekizumab to be a viable option in those who have failed IL-17 inhibitor therapy in the past.

Severe forms of systemic JIA (sJIA), also called paediatric-onset Still's disease are associated with two major life-threatening complications: macrophage activation syndrome (MAS) and severe lung disease. Patients are usually resistant to conventional synthetic (cs) DMARDs, biologic (b) DMARDs, and targeted synthetic (ts) DMARDs. Recently, allogeneic haematopoietic stem cell transplantation (HSCT) has been performed in a small number of patients with refractory and life-threatening disease. We aimed to report outcomes and complications of allogeneic HSCT in patients with severe, refractory sJIA treated at our centre. We conducted a retrospective, observational, single-centre study in a tertiary paediatric immunology care centre (Necker Hospital, Paris, France). We report three sJIA patients who underwent allogeneic HSCT at a median age of 3.5 years. All had recurrent MAS; two had lung disease and the HLA-DRB1*15 haplotype, associated with severe delayed hypersensitivity to IL-1/IL-6 inhibitors. Donors were matched sibling donors for the first and third patient, and matched unrelated donor for the second patient. They presented multiple post-graft complications: graft-vs-host disease, infections, thrombotic microangiopathy and severe inflammatory complications on previously affected organs, such as skin and lungs. At a median follow-up of 22 months (20-33) after transplantation, they were all in remission with full-donor chimerism and were off immunosuppressive treatment. Allogeneic HSCT can be an effective salvage therapy in patients with refractory sJIA. However, the risk of post-transplant endothelial complications and severe inflammation in previously affected organs, such as joints, skin and lungs deserves particular attention.

While plasma transfusion is a key resuscitation strategy, its mechanisms of benefit beyond coagulopathy correction remain unclear. Solvent detergent plasma, which contains high glycine levels and lacks inflammatory mediators, may offer advantages over fresh frozen plasma by preserving endothelial integrity and reducing inflammation. This study aimed to test whether plasma containing a high dose of glycine is superior to standard plasma in improving outcomes after traumatic shock by mitigating endothelial damage and inflammation. Anesthetized, fully instrumented Wistar rats (n = 11 per group) were randomly assigned to receive plasma, glycine-supplemented plasma, or crystalloid following polytraumatic injury and shock. The primary outcome was endothelial leakage of the lung. Inflammation and organ failure, as determined by biochemistry and histopathology, were secondary outcomes. Glycine-supplemented plasma, but not plasma, prevented an increase in pulmonary vascular leakage in comparison to crystalloid. Glycine-supplemented plasma resulted in lower systemic levels of syndecan-1 than crystalloid (p < .05). Glycine-supplemented plasma caused less lung injury compared with standard plasma (p < .001) and crystalloids (p < .001). Preservation of the endothelial barrier was associated with lower IL-6 levels and less acidosis in the glycine-supplemented plasma group than in the crystalloid group (p < .05). Glycine-supplemented plasma is superior to standard plasma in preventing endothelial permeability, glycocalyx shedding, and lung injury, which may be mediated via inhibition of IL-6 or improvement of acid-base balance. The use of solvent detergent plasma for trauma resuscitation may be more beneficial than standard plasma, partly due to glycine content.

Hepatoprotective potential of Diospyros melanoxylon (Roxb.) leaf extract by inhibition of IL-6, COX-2, and 5-LOX expression in paracetamol intoxicated rats.

Synthesis of 7-azaindoles and their pro-angiogenic and anti-inflammatory activities.