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关键词： co-occurrence   genetics   hidradenitis suppurativa   HLA   non-HLA   psoriasis   PSO-SH  

摘要： Background: Select patients are diagnosed with both psoriasis (PSO) and hidradenitis suppurativa (HS), leading to a unique disease pattern. Genetic risk factors remain unidentified. Methods: The study harnessed an international collection of patients with PSO and HS (PSO-SH). Clinical and genetic data were collected and analyzed. Results: Eighty-seven PSO-SH patients (70% female) were identified. They had a high number of comorbidities (89%) and worse general physical health compared to PSO-only (OR: 3.09;95% CI: 1.56-6.12) or HS-only (OR: 2.5;95% CI: 1.23-5.00) patients. PSO-SH patients were at significantly higher risk of having Crohn's disease (OR: 4.6-11.9;95% CI). Data revealed the highest overall genetic risk score for PSO-SH patients (PSO-polygenic risk score;108.22), followed by PSO (101.18), HS (99.84), and healthy controls (98.58). High non-human leukocyte antigen scores were associated with an increased risk for developing both PSO and HS, indicating a distinct biological profile compared to HS-only and PSO-only individuals. Limitations: Some clinical information was collected retrospectively. Conclusions: This study highlights a shared genetic susceptibility of HS and PSO at non-human leukocyte antigen loci. Recognizing PSO-SH patients as a distinct patient group with high morbidity and increased risk for developing Crohn's disease will help to improve patient management. ( J Am Acad Dermatol 2025;92:1303-11.)

关键词： Health care associated infection   LPS-induced TNF-alpha   Multi-organ dysfunction syndrome   Sepsis  

摘要： The present study estimated lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) levels and its association with health care associated infection (HAI) and duration of multi-organ dysfunction syndrome (MODS). LPS-induced TNF-alpha levels were estimated in 67 children on day 3 of MODS. Variables recorded were Pediatric Index of Mortality (PIM-3), cultures, diagnosis, HAI, days of MODS, survivors and non-survivors. Of 67 children, 37 (52.2%) were male and 27 (40.2%) expired. Sixty-three (94%) children had reduced TNF-alpha levels (<200 pg/ml);23.11 (10.38, 40.59). The median number of days in MODS was 7 (5, 12) and prolonged MODS (>= 7 d) was observed in 49/67 (73.1%) children. Forty-five (67.1%) children had HAI, among these 33/45 (73.3%) had ventilator associated pneumonia (VAP). TNF-alpha levels were significantly lower in children with MODS, prolonged MODS, children who developed HAI and non-survivors as compared to healthy children (p <0.0001), children with MODS <7 d (p=0.01), children without HAI (p=0.009) and survivors (p=0.04), respectively. HAI was independently associated with reduced levels of TNF-alpha (p=0.01).

关键词： Schizophrenia   Interleukin 33   IL-33   Soluble interleukin 33 receptor   sST2   Alarmins   Neuroinflammation  

摘要： Schizophrenia is a multi-aetiologic disease. Inflammation have recently been involved in its pathophysiology. Recent research suggests that inflammation may be a key factor in its pathophysiology. Alarmins, interleukin-33 (IL-33), its soluble receptor sST2 and the ratio IL-33/sST2, have been investigated as neuroinflammation biomarkers. However, data on alarmins in schizophrenia remain scarce and conflicting, with findings varying across studies. The aim of this systematic review consists of analysing the relationships between IL-33, its sST2 and the ratio IL-33/sST2 in schizophrenia. The authors follow the PRISMA recommendations. The keywords IL-33 OR interleukin-33 OR sST2 OR soluble ST2 OR IL-33/sST2 were intersected with the Boolean operator AND with the key words schizophrenia OR psychosis OR psychotic disorder. The search was carried out in PubMed/MEDLINE, EMBASE, PsycInfo, Scopus and Web of Science. Despite the initial search yielding 115 publications, only five studies met inclusion criteria, comprising 107 healthy controls (HC) and 267 patients, highlighting the limited data available. IL-33 and its sST2 were significantly increased in patients with an acute relapse compared to HC, while patients in clinical remission had levels comparable to those of HC. No consistent relationship was found between antipsychotic treatment and IL-33 or sST2 levels, raising questions about the influence of medication on these markers. The quality of evidence was low to moderate (10 +/- 1, with an evidence level of 3 +/- 0, according to the Oxford Centre for Evidence-Based Medicine criteria). This systematic review highlights the possibility that IL-33 and sST2 play a role in the pathophysiology of schizophrenia, particularly in relation to neuroinflammation and neuronal dysfunction. However, the controversial and inconsistent findings suggest the need for larger, well-controlled studies. Additionally, the lack of mechanistic insight into how these alarmins contribute to schi

关键词： CD4(+) T cells   cytotoxic T cells   human toxoplasmosis   toxoplasma gondii  

摘要： Toxoplasma gondii is a highly versatile parasite that infects most warm-blooded animals and is a major cause of retinochoroiditis and uveitis in humans. The pathophysiology of these conditions remains poorly understood. Both parasite virulence and host inflammatory response contribute to the development of ocular disease. While CD4(+) T cells play a critical role in host resistance to Toxoplasma infection, their kinetics and effector functions, as well as their contribution to the clinical outcome of the infection, including ocular involvement, remain poorly understood. To address this question, we investigated the immune response during acute and convalescent toxoplasmosis and stratified patients further based on the presence or absence of ocular disease. We found that T. gondii infection leads to decreased and increased proportions of central and effector memory CD4(+) T cells, respectively. Applying unsupervised analysis, distinct CD4(+) T-cell subsets were determined. Among 50 clusters, 10 produced cytotoxic proteins (granzyme B and perforin) and one produced cytokines upon antigen-specific stimulation. We observed that proportions of five CD4(+) T-cell clusters out of 50 were different during acute disease between T. gondii-infected patients with and without ocular lesions. Interestingly, three of the five displayed a cytotoxic signature indicating their possible involvement in ocular immunopathology. Taken together, our results reveal that during T. gondii infection, CD4(+) T cells not only develop a Th1 cytokine profile, but also acquire previously unappreciated cytotoxic capacity/function. These results, while underscoring the complexity of the CD4(+) T-cell response to T. gondii, suggest that specific subsets may be involved in the development of pathology and provide possible targets for therapeutic intervention.

关键词： Biologics   Inflammation   IL-23   Pyoderma gangrenosum   Wound healing  

摘要： Pyoderma gangrenosum is a severe ulcerative disease with a great need for novel therapies. A major barrier to the development of novel therapies is a lack of understanding of disease pathogenesis. We present the results of a proof-of-concept open-label clinical trial of IL-23p19 antagonism with tildrakizumab in pyoderma gangrenosum. Gene expression analysis identified proinflammatory genes associated with IFN responses and dendritic cell activity, including IFI27, XBP1, SAA1 LGALS3, and signal transducer and activator of transcription 3 significantly downregulated in lesional tissue after 12 weeks of therapy. Immunohistochemistry confirmed reduction in IL-17A- and IL-17F-positive cells as well as reduction in TNF-a-, C5a-, and IL-1B-positive cells in week 12 samples compared with those at baseline. Significant reduction in serum inflammation was observed through serum proteomics, with IL-8, IL-6, and CASP-8 levels reduced comparable with those in healthy controls at week 12. Clinical outcomes demonstrated significant reduction in ulcer size, pain, itch, and QOL outcomes in line with the molecular findings. Differential expression of key inflammatory cytokines such as IL8, CXCL5, PD-L1, SPP1, and matrix metalloproteinase 1 was observed in tissue and serum when stratified by clinical responders and nonresponders. These data provide insights into the clinical relevance of alterations in molecular markers in pyoderma gangrenosum and the potential for the identification of clinically relevant biomarkers of disease activity.

关键词： IL   WPU   Self-healing   Ionic gel   Sensor  

摘要： In today's burgeoning e-skin trend, ionic liquids (IL) have been incorporated into polymer substrates in significant quantities due to their high conductivity and stability. However, the high substitution resistance of IL is often impeded by the polymer substrates, leading to reduced carrier mobility and sensitivity. Here, we designed a self-healing waterborne polyurethane (WPU) with a polydimethylsiloxane (PDMS) backbone and prepared WPU ion gels through complexation with IL. The increased mobility of the PDMS fragments reduces the glass transition temperature (Tg) and crystallinity of the WPU and increases the carrier transport rate of IL in the WPU substrate, thus improving the electrical conductivity. Additionally, the exchange of disulfide bonds within the backbone, along with ion-dipole interactions, facilitates the rapid repair of the ionic gel when fractured, occurring within five minutes. The resulting ionic gels possess the capability to detect subtle human motion signals, such as facial expressions, heartbeats, and muscle movements.

关键词： Anti-IL-17A   Multiple sclerosis   Psoriasis   Psoriatic arthritis   Ankylosing spondylitis  

摘要： Anti-IL-17A antibodies are used in rheumatological conditions. While not approved for multiple sclerosis (MS), anti-IL-17As reduce new gadolinium-enhancing lesions. Optimal treatment for those with MS and comorbid rheumatological conditions remains unclear. We report safety and efficacy outcomes for anti-IL-17A treatment with and without concurrent MS disease modifying therapy (DMT). Patients with MS and anti-IL-17A use were identified using electronic medical records. Primary outcomes were severe infections and markers of immunosuppression. Secondary outcomes were MS relapses and new MRI lesions. Six patients (median age: 50.1) without recent MS disease activity had anti-IL-17A monotherapy exposures (17.4 total patient-years);seven (median age: 48.2) had concurrent MS DMT use (8.8 patient-years), including anti-CD20 treatment in three patients. One patient on anti-IL-17A monotherapy had a serious infection. No patients had new or worsening lymphopenia. Four of six patients on anti-IL-17A monotherapy had new MS disease activity. No relapses or new MRI lesions occurred during concurrent MS DMT use. No significant safety concerns were identified with anti-IL-17A and MS DMT combination therapy, although exposure duration was limited. More MS disease activity was seen with antiIL-17A monotherapy. Dual therapy with an MS DMT may be reasonable for MS patients who require anti-IL-17A treatment.

关键词： Angelica gigas Nakai   Intestinal barrier function   Permeability   Tight junction   Inflammatory bowel disease  

摘要： BackgroundInflammatory bowel disease (IBD) is a chronic disease that includes Crohn's disease and ulcerative colitis (UC). Tight junctions (TJs) play an important role in intestinal barrier function. In intestinal epithelial cells, TJs are composed of different junction molecules, including claudin and occludin (OCLN), and regulate the paracellular permeability of water, ions, and macromolecules in adjacent cells. The TJ structure also provides a physical barrier to luminal inflammatory molecules, although impaired integrity and structure of the TJ barrier can result in the forcible activation of immune cells and *** study aimed to investigate the protective effects of Angelica gigas Nakai extracts (AGNE) on intestinal barrier and TJ *** exhibited no cytotoxic activity against Caco-2 cells and showed potent antioxidant activity. Moreover, AGNE treatment significantly increased transepithelial electrical resistance (TEER) values and reduced epithelial permeability. In addition, the expression of Zonula Occludens (ZO)-1 and OCLN increased in a concentration-dependent manner with AGNE treatment. Conversely, myosin light chain kinase (MLCK) expression decreased in a concentration-dependent manner upon AGNE treatment. Notably, the most significant improvement was observed in the AGNE 200 mu g/mL group compared to the IL-6 control *** findings highlight the potential usefulness of AGNE as a novel therapeutic agent for maintaining epithelial barrier integrity in IBD.

关键词： Clinical Trial   Rare/orphan diseases   Remission   Randomised controlled trial