International immunopharmacology
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Int. Immunopharmacol. · Apr 2021
Inhibition of extracellular signal-regulated kinase/calpain-2 pathway reduces neuroinflammation and necroptosis after cerebral ischemia-reperfusion injury in a rat model of cardiac arrest.
Cerebral ischemia-reperfusion injury (CIRI) is the leading cause of poor neurological prognosis after cardiopulmonary resuscitation (CPR). We previously reported that the extracellular signal-regulated kinase (ERK) activation mediates CIRI. Here, we explored the potential ERK/calpain-2 pathway role in CIRI using a rat model of cardiac arrest (CA). ⋯ Inflammation activation and necroptosis involved in CA/CPR-induced CIRI were regulated by the ERK/calpain-2 signaling pathway. Inhibition of that pathway can reduce neuroinflammation and necroptosis after CIRI in the CA model rats.
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Int. Immunopharmacol. · Feb 2021
Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review.
Both pembrolizumab and lenvatinib demonstrate antitumor activity and safety in cancers. However, whether their combination is safer and more effective than monotherapies remains unknown. A systematic review was performed to assess the safety and efficacy of pembrolizumab plus lenvatinib versus their respective monotherapies in solid cancers. ⋯ Compared with their monotherapies, pembrolizumab plus lenvatinib showed more promising antitumor activity and resulted in higher ORRs and significant survival benefits in the above cancers. Toxicities were manageable, with no unexpected safety issues.
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Int. Immunopharmacol. · Feb 2021
Diagnostic utility of C-reactive protein to albumin ratio as an early warning sign in hospitalized severe COVID-19 patients.
C-reactive protein-to-albumin ratio (CAR) has been used as an indicator of prognosis in various diseases. Here, we intended to assess the CAR's diagnostic power in early differentiation of hospitalized severe COVID-19 cases. In this retrospectively designed study, we evaluated 197 patients in total. ⋯ Age (OR = 1.046, P = 0.003), CAR (OR = 1.264, P = 0.037), and AST (OR = 1.029, P = 0.037) were independent risk factors for severe COVID-19 based on the multivariate logistic regression analysis. ROC curve analysis assigned 0.9 as the cut-off value for CAR for differentiation of severe COVID-19 (area under the curve = 0.718, 69.1% sensitivity, 70.8% specificity, P < 0.001). CAR is a useful marker in early differentiation of severity in patients hospitalized due to COVID-19 that have longer hospital stay and higher mortality.
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Int. Immunopharmacol. · Feb 2021
Thyroid function abnormality induced by PD-1 inhibitors have a positive impact on survival in patients with non-small cell lung cancer.
Thyroid function abnormality (TFA) is a common immune-related adverse event (irAEs), but the association between it and the efficacy of programmed cell death protein 1 (PD-1) inhibitor in advanced non-small cell lung cancer (NSCLC) is finitely understood. ⋯ TFA-irAEs is associated with enhanced PD-1 inhibitor efficacy in advanced NSCLC patients and it may be a biomarker for antitumor immune response.
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Int. Immunopharmacol. · Feb 2021
Aggravation of autism-like behavior in BTBR T+tf/J mice by environmental pollutant, di-(2-ethylhexyl) phthalate: Role of nuclear factor erythroid 2-related factor 2 and oxidative enzymes in innate immune cells and cerebellum.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder which manifests itself in early childhood and is distinguished by recurring behavioral patterns, and dysfunction in social/communication skills. Ubiquitous environmental pollutant, di-2-ethylhexyl phthalate (DEHP) is one of the most frequently used plasticizers in various industrial products, e.g. vinyl flooring, plastic toys, and medical appliances. DEHP gets easily released into the environment and leads to human exposure through various routes. ⋯ Our data show that DEHP treatment causes worsening of autism-like behavior in BTBR mice which is associated with enhancement of oxidative stress in innate immune cells and cerebellum with concomitant lack of antioxidant protection. DEHP also causes oxidative stress in C57 mice in both innate immune cells and cerebellar compartment, however there is Nrf2-mediated induction of enzymatic antioxidants which protects them from upregulated oxidative stress. This proposes the notion that ubiquitous environmental pollutants such as DEHP may be involved in the pathogenesis/progression of ASD through dysregulation of antioxidant-antioxidant balance in innate immune cells and cerebellum.