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Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Columbia University, New York, NY, USA.
Background: The connection between inflammasomes and Alzheimer's disease (AD) has garnered significant interest, with emerging evidence suggesting genetic associations and functional implications. Notably, studies have reported the upregulation of inflammasome components like NLRP1, NLRP3, and Caspase-1 in AD patients. Moreover, genetic polymorphisms in inflammasome-related genes are linked to increased AD risk.
View Article and Find Full Text PDFPinocembrin activation of DPP9 inhibits NLRP1 inflammasome activation to alleviate cerebral ischemia/reperfusion-induced lung and intestinal injury.
Immunol Res
December 2024
Department of Nephrology, Liuzhou Workers Hospital, the Fourth Affiliated Hospital of Guangxi Medical University, No. 156, Heping Road, Liunan District, Liuzhou, 545000, Guangxi Zhuang Autonomous Region, P.R. China.
After stroke, there is a high incidence of acute lung injury and impairment of intestinal barrier function. In this research, the effects of pinocembrin on organ injuries induced by cerebral ischemia-reperfusion were investigated in mice with middle cerebral artery occlusion/reperfusion (MCAO/R) and further explored the possible mechanism. The potential targets of pinocembrin against MCAO/R were obtained by online tools.
View Article and Find Full Text PDFThe Serine Protease DPP9 and the Redox Sensor KEAP1 Form a Mutually Inhibitory Complex.
J Biol Chem
November 2024
Pharmacology Program of the Weill Cornell Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA; Tri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. Electronic address:
Synthetic inhibitors of the serine protease DPP9 activate the related NLRP1 and CARD8 inflammasomes and stimulate powerful innate immune responses. Thus, it seems plausible that a biomolecule similarly inhibits DPP9 and triggers inflammasome activation during infection, but one has not yet been discovered. Here, we wanted to identify and characterize DPP9-binding proteins to potentially uncover physiologically relevant mechanisms that control DPP9's activity.
View Article and Find Full Text PDFComparison of Different Keratinocyte Cell Line Models for Analysis of NLRP1 Inflammasome Activation.
Biomolecules
November 2024
Department of Dermatology and Allergology, University Hospital RWTH Aachen, 52074 Aachen, Germany.
Article Synopsis
- The study focuses on the NLRP1 inflammasome, which is crucial for skin immune response, and aims to evaluate its activation in different keratinocyte cell lines.
- Researchers compared NLRP1 activation, expression, and cell death in primary keratinocytes and immortalized cell lines (HaCaT, HaSKpw, SVTERT) after UVB irradiation or treatment with talabostat.
- Findings indicated that primary keratinocytes showed the highest NLRP1 expression and detectable inflammasome activation, suggesting that they are the preferred model for studying inflammasome activation over immortalized keratinocyte cell lines.
Schwann cell C5aR1 co-opts inflammasome NLRP1 to sustain pain in a mouse model of endometriosis.
Nat Commun
November 2024
Department of Health Science, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy.
Over 60% of women with endometriosis experience abdominopelvic pain and broader pain manifestations, including chronic back pain, fibromyalgia, chronic fatigue, vulvodynia, and migraine. Although the imbalance of proinflammatory mediators, including the complement component C5a, is associated with endometriosis-related pain, the mechanisms causing widespread pain and the C5a role remain unclear. Female mice and women with endometriosis exhibit increased plasma C5a levels and pain.
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