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Filename: Session/Session.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Function: formatAIDetailSummary
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Filename: controllers/Detail.php
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Acute ammonia neurotoxicity caused by intraperitoneal administration of ammonium salts is mediated by overactivation of N-methyl-D-aspartate (NMDA) receptors, with ensuing generation of free radicals and extracellular accumulation of cyclic GMP (cGMP) arising from stimulation of nitric oxide (NO) synthesis. In this study, infusion of ammonium chloride or NMDA into the striata of rats via microdialysis probes increased the contents of cyclic GMP and hydroxyl radicals in the microdialysates. Co-infusion of taurine virtually abolished both the ammonia- and NMDA-induced accumulation of cGMP. Taurine also attenuated accumulation of hydroxyl radicals evoked by either treatment. This result is the first evidence of a potential of taurine to attenuate the effects of NMDA receptor overactivation by ammonia in vivo and points to the inhibition of the NMDA receptor-mediated NO synthesis as a possible mechanism of its neuroprotective action. Taurine or its blood-brain barrier penetrating analogues may be applicable in treatment of ammonia-induced neurological deficits.
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http://dx.doi.org/10.1016/s0014-2999(03)01667-4 | DOI Listing |
Autophagy
December 2024
Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Immune checkpoint inhibitors, especially those targeting CD274/PD-L1yield powerful clinical therapeutic efficacy. Thoughmuch progress has been made in the development of antibody-basedCD274 drugs, chemical compounds applied for CD274degradation remain largely unavailable. Herein,baicalein, a monomer of traditional Chinese medicine, isscreened and validated to target CD274 and induces itsmacroautophagic/autophagic degradation.
View Article and Find Full Text PDFJ Adv Res
December 2024
Department of Pathology, Xuzhou Medical University, Xuzhou, China. Electronic address:
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a crucial mechanism in antiviral defense and innate immunity pathway. Ferroptosis, characterized by iron dependence and lipid peroxidation, represents a specialized form of cell death. A burgeoning collection of studies has demonstrated that the cGAS-STING signaling pathway participates in the homeostatic regulation of the organism by modulating ferroptosis-associated enzyme activity or gene expression.
View Article and Find Full Text PDFCell Rep
December 2024
Cellular Degradation Biology Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Convergence Research Center for Dementia, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea; AUTOTAC Bio, Inc., Changkkyunggung-ro 254, Jongno-gu, Seoul 03077, Republic of Korea; Ischemic/Hypoxic Disease Institute, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea. Electronic address:
The human body reacts to tissue damage by generating damage-associated molecular patterns (DAMPs) that activate sterile immune responses. To date, little is known about how DAMPs are removed to avoid excessive immune responses. Here, we show that proteasomal dysfunction induces the release of mitochondrial DNA (mtDNA) as a DAMP that activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway and is subsequently degraded through the N-degron pathway.
View Article and Find Full Text PDFMol Cell
December 2024
Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan. Electronic address:
Viral mimicry driven by endogenous double-stranded RNA (dsRNA) stimulates innate and adaptive immune responses. However, the mechanisms that regulate dsRNA-forming transcripts during cancer therapy remain unclear. Here, we demonstrate that dsRNA is significantly accumulated in cancer cells following pharmacologic induction of micronuclei, stimulating mitochondrial antiviral signaling (MAVS)-mediated dsRNA sensing in conjunction with the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway.
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
December 2024
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:
Mitochondrial DNA (mtDNA), a circular double-stranded DNA located within mitochondria, plays a pivotal role in mitochondrial-induced innate immunity, particularly via the cyclic GMP-AMP synthase (cGAS)-STING pathway, which recognizes double-stranded DNA and is crucial for pathogen resistance. Recent studies elucidate the interplay among mtDNA, the cGAS-STING pathway, and neutrophil extracellular traps (NETs) in the context of cancer. mtDNA uptake by recipient cells activates the cGAS-STING pathway, while mtDNA leakage reciprocally regulates NET release, amplifying inflammation and promoting NETosis, a mechanism of tumor cell death.
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