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Immune checkpoint inhibitor-induced severe epidermal necrolysis mediated by macrophage-derived CXCL10 and abated by TNF blockade.
Nat Commun
December 2024
Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.
View Article and Find Full Text PDFImpact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis.
Front Immunol
December 2024
Division of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL, United States.
Background: The impact of steroid-sparing immunosuppressive agents (SSIAs) for immune-related adverse events (irAEs) on tumor outcome is not well-known. This systematic review evaluates tumor outcomes for corticosteroid (CS) monotherapy versus CS with SSIA (CS-SSIA) for irAE treatment with a focus on melanoma.
Methods: Search was conducted through 1/5/23 using PubMed, Embase, Cochrane CENTRAL, and Web of Science.
Fexuprazan safeguards the esophagus from hydrochloric acid-induced damage by suppressing NLRP1/Caspase-1/GSDMD pyroptotic pathway.
Front Immunol
December 2024
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Introduction: Proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are widely used to manage gastric acid-related disorders by inhibiting hydrochloric acid (HCl) secretion from parietal cells in the stomach. Although PPIs are known to have anti-inflammatory properties beyond their role in inhibiting gastric acid secretion, research on P-CABs is lacking. In this study, we aimed to investigate whether all available P-CABs exhibit anti-inflammatory effects in gastroesophageal reflux-induced esophagitis and to elucidate the underlying mechanisms.
View Article and Find Full Text PDFSulfonamide-Pyrazole derivatives as next-generation Cyclooxygenase-2 enzyme inhibitors: From molecular design to in vivo efficacy.
Int J Biol Macromol
December 2024
Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt. Electronic address:
The current research focuses on the design and synthesis of celecoxib analogues incorporating sulphonamide pyrazole moieties 4, 5, 6a-e, and 7a-f with the aim of achieving a broad range of COX-2 selectivity in vitro. Among these, compounds 6b-d, 7a, 7e, and 7d exhibited potent inhibition, with IC values ranging between 0.05 and 0.
View Article and Find Full Text PDFActivation of aryl hydrocarbon receptor ameliorates degranulation of LL-37 induced mast cells in rosacea through enhancing autophagy.
Int Immunopharmacol
December 2024
Department of Dermatology, The First Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Immunodermatology, Ministry of Education Key Laboratory of Immunodermatology, National Joint Engineering Research Center for Diagnosis and Treatment of Immunologic Skin Diseases, The First Hospital of China Medical University, Shenyang, China.
Background: Activation of the aryl hydrocarbon receptor (AhR) ameliorates LL-37-induced rosacea-like dermatitis in mice, whereas mast cells and cytokine overexpression are prominent features in rosacea skin.
Objective: To evaluate the potential mechanisms of AhR activation on autophagy and degranulation of mast cells in rosacea.
Methods: LL-37 treated mast cells were used to mimic rosacea.
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