PI3K/AKT signaling pathway associates with pyroptosis and inflammation in patients with endometriosis

Journal of Reproductive Immunology, Journal Year: 2024, Volume and Issue: 162, P. 104213 - 104213

Published: Feb. 9, 2024

Endometriosis (EMS) is known to be closely associated with inflammation. We evaluate the possible mechanism linking PI3K/AKT signaling pathway pyroptosis and inflammation in EMS. collected 30 patients undergoing laparoscopic for endometriosis as EMS group those surgery uterine fibroids control group, from whom we serum, normal endometrium, eutopic endometrium ectopic endometrium. Transmission electron microscopy (TEM) was used observe internal structure of endometrial cells. Western Blot detect protein expression PI3K, P-PI3K, AKT, P-AKT, NLRP3, Caspase-1, GSDMD, GSDMD-N. Immunohistochemistry (IHC) staining GSDMD-N proteins. Immunofluorescence (IF) Quantitative real-time polymerase chain reaction (qRT-PCR) analyze mRNA levels ELISA serum IL-1β, IL-18, TLR4, NF-κB. found that activation significantly increased level cellular inflammatory factors. Our results suggest there a positive correlation between pyroptosisas well patients.

Language: Английский

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Echinatin protects from ischemic brain injury by attenuating NLRP3-related neuroinflammation

Neurochemistry International, Journal Year: 2024, Volume and Issue: 175, P. 105676 - 105676

Published: Feb. 7, 2024

Language: Английский

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Dihydroquercetin Ameliorates Neuronal Ferroptosis in Rats After Subarachnoid Hemorrhage via the PI3K/AKT/Nrf2/HO‐1 Pathway

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(1)

Published: Jan. 1, 2025

ABSTRACT Subarachnoid hemorrhage (SAH) is a specific type of stroke. Dihydroquercetin (DHQ), flavonoid, known for its various pharmacological properties. This study aimed to explore the roles and mechanisms DHQ in influencing progression SAH. A rat SAH model was established using endovascular perforation technique. Following induction, administered orally 1 h later. Assessments included scores, neurological function, brain swelling, blood‐brain barrier (BBB) integrity, neuronal damage, apoptosis levels, inflammation, indicators ferroptosis treatments. The HT22 cells were exposed hemin simulate SAH‐like conditions under vitro settings. Cell counting kit‐8 assays, flow cytometry, enzyme?linked immunosorbent assay, BODIPY 581/591 C11 staining, western blot analysis, biochemical kits employed evaluate potential effects DHQ. Moreover, responsible protective effect examined by analysis. vivo findings revealed that mitigated impairments, BBB disruption, injury at 24 post‐SAH. also reduced degeneration, following enhanced cell survival exposure. Mechanistically, activated phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2‐related 2 (Nrf2) signaling rats hemin‐treated exert neuroprotective effects. In conclusion, this reveals can effectively decrease permeability, edema, dysfunctions, post‐SAH activating PI3K/AKT/Nrf2/HO‐1 pathway.

Language: Английский

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GSDMD-mediated mitochondrial dysfunction in marginal cells: A potential driver of inflammation and stria vascularis damage in CIHL

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(11)

Published: March 11, 2025

Inflammation is among the known causes of cisplatin-induced hearing loss (CIHL), but its exact pathophysiological mechanisms remain unclear. Herein, we demonstrated that pyroptosis—a recently identified inflammatory type regulated cell death dependent on gasdermin D (GSDMD)—was activated in cochleae cisplatin-treated mice, causing CIHL. Meanwhile, treatment with GSDMD inhibitor necrosulfonamide alleviated CIHL these mice. To further examine role GSDMD-mediated pyroptosis CIHL, conducted experiments Gsdmd- deficient mice . Gsdmd −/− significantly lower cochlear damage than control and appeared to be invulnerable Furthermore, stria vascularis (SV), not hair cells (HCs), played a dominant In marginal (MCs) SV, cisplatin induced caspase-dependent cleavage, pore-forming N-terminal rapidly localized mitochondria, leading abnormal mitochondrial aggregation oxidative stress. The consequent dysfunction MCs might result severe progression inflammation, SV damage, HC loss. Notably, pharmacological inhibition using FDA-approved drug disulfiram effectively symptoms Collectively, findings offer broad avenue for inhibiting pyroptosis-induced ototoxicity provide valuable theoretical insights clinical management

Language: Английский

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Crosstalk Between Cell Death and Spinal Cord Injury: Neurology and Therapy

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(12), P. 10271 - 10287

Published: May 7, 2024

Language: Английский

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Interleukin-18 in chronic pain: Focus on pathogenic mechanisms and potential therapeutic targets

Pharmacological Research, Journal Year: 2024, Volume and Issue: 201, P. 107089 - 107089

Published: Jan. 29, 2024

Chronic pain has been proven to be an independent disease, other than accompanying symptom of certain diseases. Interleukin-18 (IL-18), a pro-inflammatory cytokine with pleiotropic biological effects, participates in immune modulation, inflammatory response, tumor growth, as well the process chronic pain. Compelling evidence suggests that IL-18 is upregulated occurrence Antagonism or inhibition expression can alleviate and development And located microglia, while IL-18R mostly astrocytes spinal cord. This indicates interaction between microglia mediated by IL-18/IL-18R axis involved In this review, we described role mechanism different types review provides strong potential therapeutic target management.

Language: Английский

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TXNIP Regulates NLRP3 Inflammasome-Induced Pyroptosis Related to Aging via cAMP/PKA and PI3K/Akt Signaling Pathways

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 8051 - 8068

Published: March 9, 2024

Language: Английский

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MAPK signaling pathway in spinal cord injury: Mechanisms and therapeutic potential

Experimental Neurology, Journal Year: 2024, Volume and Issue: 383, P. 115043 - 115043

Published: Nov. 8, 2024

Language: Английский

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Unravelling the Neuroprotective Effects of Taxifolin against Scopolamine-Induced Dementia in male Sprague Dawley rats: A Comprehensive Preclinical Investigation

Brain Disorders, Journal Year: 2025, Volume and Issue: 17, P. 100203 - 100203

Published: Feb. 21, 2025

Language: Английский

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Certolizumab enhances spinal cord injury recovery in rats through inhibition of the TNF-α signaling pathway and neuronal apoptosis

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Spinal cord injury (SCI), which is characterized by motor and/or sensory dysfunction, presents a significant health challenge resulting from mechanical trauma. Secondary injury, follows the trauma and driven factors such as inflammation, plays critical role in SCI pathophysiology. Scientific evidence indicates that treatment strategies aimed at modulating inflammation during acute phase of alleviate seconder injury. In this regard, present study seeks to evaluate effectiveness certolizumab, monoclonal antibody targeting TNF-α widely used various inflammatory diseases, model. study, Control, Trauma, Trauma + Certolizumab groups were established, each comprising eight male rats. One hour after induction, rats group administered 10 µg dissolved saline intraperitoneally, while Control received an equivalent volume saline. After Modified Tarlov Scoring was performed on seventh day experiment, all sacrificed. The effects certolizumab neuroinflammation apoptosis model evaluated using histological, biochemical, molecular analyses blood tissue samples obtained downregulated expression TNF-α, NF-κB, IL-6. addition, evidenced TUNEL assay, Caspase-3 (an apoptotic marker), Score results, effectively suppressed inflammation-induced neural alleviated locomotor deficits. exerts neuroprotective effect against secondary damage through inhibition apoptosis.

Language: Английский

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