Mechanisms of Oxidative Stress in Metabolic Syndrome

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7898 - 7898

Published: April 26, 2023

Metabolic syndrome is a cluster of conditions associated with the risk diabetes mellitus type 2 and cardiovascular diseases (CVDs). closely related to obesity. Increased adiposity promotes inflammation oxidative stress, which are precursors various complications involving metabolic components, namely insulin resistance, hypertension, hyperlipidemia. An increasing number studies confirm importance stress chronic in etiology syndrome. However, few have reviewed mechanisms underlying role contributing In this review, we highlight by reactive oxygen species (ROS) increase mitochondrial dysfunction, protein damage, lipid peroxidation, impair antioxidant function Biomarkers can be used disease diagnosis evaluation severity.

Language: Английский

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The interaction between ferroptosis and inflammatory signaling pathways

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 21, 2023

Abstract Ferroptosis is an iron-dependent regulated cell death driven by excessive lipid peroxidation. Inflammation one common and effective physiological event that protects against various stimuli to maintain tissue homeostasis. However, the dysregulation of inflammatory responses can cause imbalance immune system, dysfunction death. Recent studies have pointed out activation inflammation, including multiple inflammation-related signaling pathways, lead ferroptosis. Among related signal transduction we focused on five classical namely, JAK-STAT, NF-κB, inflammasome, cGAS-STING MAPK expounded their roles in To date, many agents shown therapeutic effects ferroptosis-related diseases modulating aforementioned pathways vivo vitro. Moreover, regulatory these iron metabolism peroxidation been described detail, contributing further understanding pathophysiological process Taken together, targeting inflammation will provide appropriate ways intervene ferroptosis diseases.

Language: Английский

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Ethyl carbamate triggers ferroptosis in liver through inhibiting GSH synthesis and suppressing Nrf2 activation

Redox Biology, Journal Year: 2022, Volume and Issue: 53, P. 102349 - 102349

Published: May 22, 2022

Humans are inevitably exposed to ethyl carbamate (EC) via consumption of fermented food and beverages. EC, known as an environmental toxin, can cause oxidative stress-mediated severe toxicity, but the underlying mechanisms remain unveiled. Ferroptosis is a newly identified ROS-mediated non-apoptotic cell death characterized by iron accumulation excessive lipid oxidation. In this study, we first found that EC triggered ferroptosis in liver cells detection decreased viability, GSH, GPX4 Ferritin levels, well increased MDA contents. inhibitor ferrostatin-1 (Fer-1) pretreatment rescued ferroptotic damage, indicating was critical for EC-caused death. Furthermore, GSH synthesis precursor N-acetylcysteine displayed significant anti-ferroptotic properties suggested depletion might be main under exposure. EC-triggered mainly depended on suppressed inhibition SLC7A11 GCLC expressions. Notably, blocked Nrf2 activation repression phosphorylation modification nuclear translocation, which further resulted occurrence. We also observed EC-induced dysfunction inflammation, accompanied with stress, downregulated signaling Balb/c mice, could effectively reversed Fer-1 tBHQ pretreatment. Together, our study indicated new mechanism attributed inactivation depletion.

Language: Английский

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Molecular mechanisms of ferroptosis and relevance to inflammation

Inflammation Research, Journal Year: 2022, Volume and Issue: 72(2), P. 281 - 299

Published: Dec. 19, 2022

Language: Английский

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How location and cellular signaling combine to activate the NLRP3 inflammasome

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(11), P. 1201 - 1214

Published: Sept. 20, 2022

Abstract NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) is a cytosolic innate immune sensor of cellular stress signals, triggered by infection sterile inflammation. Upon detection an activating stimulus, NLRP3 transitions from inactive homo-oligomeric multimer into active multimeric inflammasome, which promotes the helical oligomeric assembly adaptor molecule ASC. ASC oligomers provide platform for caspase-1 activation, leading to proteolytic cleavage activation proinflammatory cytokines in IL-1 family gasdermin D, can induce lytic form cell death. Recent studies investigating both requirement structure have revealed complex regulation multiple steps involved its activation. This review presents perspective on biochemical processes controlling inflammasome with particular emphasis structural role organelles. We also highlight latest research metabolic control this inflammatory pathway discuss promising clinical targets intervention.

Language: Английский

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Specific inhibition of the NLRP3 inflammasome suppresses immune overactivation and alleviates COVID-19 like pathology in mice

EBioMedicine, Journal Year: 2021, Volume and Issue: 75, P. 103803 - 103803

Published: Dec. 31, 2021

The Coronavirus Disease 2019 (COVID-19) pandemic has been a great threat to global public health since 2020. Although the advance on vaccine development largely achieved, strategy alleviate immune overactivation in severe COVID-19 patients is still needed. NLRP3 inflammasome activated upon SARS-CoV-2 infection and associated with severity. However, processes by which involved disease remain unclear.We infected THP-1 derived macrophages, knockout mice, human ACE2 transgenic mice live Biosafety Level 3 (BSL-3) laboratory. We performed quantitative real-time PCR for targeted viral or host genes from mouse tissues, conducted histological immunofluorescence analysis tissues. also injected intranasally AAV-hACE2 intraperitoneally inhibitor MCC950 before as indicated.We have provided multiple lines of evidence that plays an important role response invasion lungs. Inhibition attenuated release related pro-inflammatory cytokines cell cultures mice. pathology induced lung tissues was reduced Nlrp3-/- compared wild-type C57BL/6 Finally, specific inhibition alleviated excessive inflammation thus like mice.Inflammatory activation stimulator immunopathology. Targeting promising intervention against disease.This work supported grants Bureau Frontier Sciences Education, CAS (grant no. QYZDJ-SSW-SMC005 Y.G.Y.), key project "Light West China" Program (to D.Y.) Yunnan Province (202001AS070023 D.Y.).

Language: Английский

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Molecular Mechanisms of Inflammation in Sarcopenia: Diagnosis and Therapeutic Update

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2359 - 2359

Published: Aug. 1, 2022

Sarcopenia is generally an age-related condition that directly impacts the quality of life. It also related to chronic diseases such as metabolic dysfunction associated with diabetes and obesity. This means everyone will be vulnerable sarcopenia at some point in their Research find precise molecular mechanisms implicated this can increase knowledge for better prevention, diagnosis, treatment sarcopenia. Our work gathered most recent research regarding inflammation new therapeutic agents proposed target its consequences pyroptosis cellular senescence. Finally, we compared dual X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), ultrasound (US) techniques diagnose follow up on sarcopenia, indicating respective advantages disadvantages. goal scientific evidence presented here help guide future understand involved strategies, translation into clinical practice.

Language: Английский

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Role of XBP1 in regulating the progression of non-alcoholic steatohepatitis

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(2), P. 312 - 325

Published: March 12, 2022

Non-alcoholic steatohepatitis (NASH) is associated with the dysregulation of lipid metabolism and hepatic inflammation, though underlying mechanisms remain unclear. We aimed to investigate role X-box binding protein-1 (XBP1) in progression NASH.

Language: Английский

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Gut liver brain axis in diseases: the implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 6, 2023

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In past few decades, breakthrough progress has been made in gut liver brain axis, mainly through understanding its formation mechanism increasing treatment strategies. this review, we discuss various complex networks including barrier permeability, hormones, microbial metabolites, vagus nerve, neurotransmitters, immunity, toxic β-amyloid (Aβ) metabolism, epigenetic regulation gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet nanotechnology application regulate Besides, some special treatments targeting gut-liver include farnesoid X receptor (FXR) agonists, takeda G protein-coupled 5 (TGR5) glucagon-like peptide-1 (GLP-1) antagonists fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain embraces cognitive behavioral therapy (CBT), antidepressants tryptophan metabolism-related therapies. liver-brain contains Aβ future, better interactions will promote development novel preventative strategies discovery precise therapeutic targets multiple diseases.

Language: Английский

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Salidroside Ameliorates Alzheimer's Disease by Targeting NLRP3 Inflammasome-Mediated Pyroptosis

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 21, 2022

Amyloid β-protein (Aβ) is reported to activate NLRP3 inflammasomes and drive pyroptosis, which subsequently involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). To date, AD unfortunately insufficiently elucidated. Therefore, this study was conducted explore whether Salidroside (Sal) treatment could benefit by improving pyroptosis. Firstly, two animal models AD, induced, respectively, Aβ1-42 D-galactose (D-gal)/AlCl3, have been created assist our appreciation pathophysiology. We then confirmed that pyroptosis related Sal can slow progression inhibiting Subsequently, we established D-gal Nigericin-induced PC12 cells injury model vitro verify blocks mainly targeting inflammasome. For vivo studies, observed Aβ accumulation, Tau hyperphosphorylation, neurons hippocampal damage, cognitive dysfunction mice, caused bilateral injection into hippocampus treatments with combine AlCl3. Besides, accumulated promotes inflammasome activation, leads activation release a pro-inflammatory cytokine, interleukin-1 beta (IL-1β). Notably, both accumulation hyperphosphorylation decreased inhibited downregulating expression IL-1β IL-18, be attributed Sal. further found reverse increased protein TLR4, MyD88, NF-κB, P-NF-κB, NLRP3, ASC, cleaved Caspase-1, GSDMD, IL-1β, IL-18 vitro. The underlying mechanism may through TLR4/NF-κB/NLRP3/Caspase-1 signaling pathway. Our highlights importance inflammasome-mediated how administration pharmacological doses inhibit ameliorate AD. Thus, conclude plays significant role therapeutic drug for

Language: Английский

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