Project description:Background: Chronic hand eczema (CHE) is a debilitating skin condition characterized by pain, itch, and chronic inflammation, with a complex multifactorial origin. Its diverse presentations, including overlapping traits of atopic dermatitis, contact dermatitis, and psoriasis, make diagnosis and treatment particularly challenging. The underlying immune mechanisms of CHE still need to be investigated.Methods: Here we conducted a comprehensive molecular profiling of CHE patients, enrolled without prior selection on etiology and morphology, and performed a phase 2b randomized, multicenter, double-blind, placebo-controlled clinical trial comparing dupilumab to placebo over 16 weeks.Results: We demonstrated that CHE patients may benefit from IL4Rα-blockade, regardless of etiological factors or clinical presentation. Skin transcriptomic and serum profiles of CHE patients closely resemble those seen in both atopic dermatitis and psoriasis, with dysregulated genes affecting keratinocyte differentiation, leucocyte-mediated immunity, cytokine signaling, and mixed type 1, 2, and 3 immunity. The clinical trial included 94 adults with moderate to severe CHE persisting for at least six months and resistant to potent topical corticosteroids. Compared to placebo control, 16-week dupilumab treatment significantly improved clinical severity and quality of life of all CHE patients while largely restoring appropriate transcriptomic and proteomic programs related to skin barrier and immune homeostasis.Conclusion: These findings confirmed the involvement of not only type 2 but also type 1 and type 3 immunity across all CHE patients, and demonstrate that IL-4Rα blockade may offer effective therapeutic perspectives for this highly burdensome condition, independent of an atopic dermatitis background.
Project description:A randomized, double-blind, placebo-controlled trial of netazepide (YF476) in patients with BE without dysplasia was performed. Gene expression before and after treatment with netazepide and with a placebo was measured with RNASeq
Project description:Microarray Analysis of Human Whole Blood and Intestinal Biopsy Samples from a Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Crohn’s Disease
Project description:Interleukin (IL)-23 is implicated in T2 and T17-mediated airway inflammation, supporting a role in asthma. We undertook a Phase II, randomized, double-blind, placebo-controlled, 24-week, parallel-group, multicenter trial to assess the efficacy and safety of risankizumab, an IL23p19 monoclonal antibody, administered subcutaneously (90 mg 4 weekly) in adults with severe asthma. Sputum samples were collected at several timepoints: visit 1B (week -3), visit 2 (week 0 proir to treatment), visit 7 (week 20), visit 8 (week 24, end of treatment), visit 12 (week 40, end of observation). RNA sequencing of sputum cells.
Project description:Diabetes and Arteriosclerosis progression are frequently observed in borderline Type 2 diabetes cases. Onset of complications (arteriosclerosis and renal damage) due to Type 2 diabetes is well documented; it is extremely important to prevent or delay their progression. Type 2 diabetes onset and progression has been controlled through dietary habits and exercise, although these remain insufficient. Chlorella ingestion improves blood glucose and cholesterol concentrations in mice and humans, although no reports have evaluated Chlorella effects in borderline diabetics. Therefore, we conducted a randomized, placebo-controlled trial for borderline diabetics using laboratory results and comprehensive gene analysis as outcomes. Chlorella ingestion suppressed resistin gene expression, suggesting that Chlorella may be useful for preventing diabetes onset and ameliorating arteriosclerosis.
Project description:BrighTNess was a phase III, multicenter, randomized, double-blind, placebo-controlled study that enrolled stage II/III TNBC patients to receive neoadjuvant chemotherapy with paclitaxel followed by doxorubicin/cyclophosphamid (AC), or the same plus carboplatin or carboplatin plus the PARP inhibitor veliparib concurrent with paclitaxel. Whole transcriptome RNA sequencing (RNAseq) was performed on pre-treatment research biopsies.
Project description:Microarray Analysis of Human Whole Blood and Intestinal Biopsy Samples from a Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Crohn’s Disease 329 Crohn's biopsies from multiple regions in the intestine of 87 anti TNFa refractory patients and blood samples from 204 patients at Week 0 prior to drug treatment are included in this study
Project description:We collected airway epithelial brushings for microarray analysis from 42 asthmatics and two control groups – 28 healthy subjects and 16 smokers. A subgroup of 32 asthmatics completed a randomized placebo-controlled trial of fluticasone propionate in which collection of brushings was repeated after 1 week of treatment. Keywords: disease state analysis, clinical trial
Project description:Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity among people living with HIV with a more aggressive course than in the general population. In a recent randomized placebo-controlled trial, we demonstrated that the growth hormone-releasing hormone analogue tesamorelin reduced liver fat and prevented fibrosis progression in HIV-associated NAFLD over one year. In the current study, we leveraged paired liver biopsy specimens from this trial to identify hepatic gene pathways that are differentially modulated by tesamorelin versus placebo to gain key insights into the biological underpinnings of its clinical effects.
