Toona sinensis fruit polyphenols alleviate cerebral ischemia-reperfusion injury in rats by inhibiting MAPK signaling pathways and NLRP3 inflammasome/pyroptosis

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119375 - 119375

Published: Jan. 1, 2025

Language: Английский

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Mushrooms, Microdosing, and Mental Illness: The Effect of Psilocybin on Neurotransmitters, Neuroinflammation, and Neuroplasticity

Neuropsychiatric Disease and Treatment, Journal Year: 2025, Volume and Issue: Volume 21, P. 141 - 155

Published: Jan. 1, 2025

The incidence of mental health disorders is increasing worldwide. While there are multiple factors contributing to this problem, neuroinflammation underlies a significant subset psychiatric conditions, particularly major depressive and anxiety disorders. Anti-inflammatory interventions have demonstrated benefit in these conditions. Psilocin, the active ingredient mushrooms Psilocybe genus, both potent serotonin agonist anti-inflammatory agent, increases neuroplasticity, decreases overactivity default mode network. Studies using hallucinogenic doses psilocin under supervision therapist/guide consistently benefits individuals with depression end-of-life anxiety. Microdosing psilocybin sub-hallucinogenic has also mood disorders, may offer safe, less expensive, more available alternative full for as well other medical conditions which inflammation principal pathophysiology.

Language: Английский

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Causal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) study

Diabetology & Metabolic Syndrome, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 7, 2025

Research indicates that there may be an association between plasma lipidome levels and the incidence of diabetic retinopathy (DR) in patients. However, potential causality this relationship is yet to determined. To investigate matter further, we employed a two-sample Mendelian randomization (MR) analysis comprehensively assess DR. Summary statistics for lipid DR were obtained from Genome-Wide Association Studies (GWAS) Catalog database FinnGen Consortium, respectively. We conducted MR analysis, statistical performed using inverse variance weighted (IVW) with addition MR-Egger, median (WM), constrained maximum likelihood model averaging (cML-MA) test causal associations Heterogeneity was checked Cochran's Q statistic. The Pleiotropy Residual Sum Outlier (MR-PRESSO) global MR-Egger regression used detect horizontal pleiotropy. robustness our findings assessed leave-one-out funnel plots. further reliability results, linkage disequilibrium score regressions, colocalization reverse also performed. Analysis pooled results after correction false discovery rate (FDR) revealed five associated risk. Phosphatidylcholine (16:0_16:0) [OR = 0.869 (0.810 0.933), Pfdr 0.006], phosphatidylcholine (16:0_20:2) 0.893 (0.834 0.956), 0.043] phosphatidylethanolamine (18:0_20:4) 0.906 (0.863 0.951), 0.006] protective against DR, whereas sphingomyelin (d36:1) 1.120 (1.061 1.183), (d40:1) 1.081 (1.031 1.134), greater risk Further sensitivity did not reveal heterogeneity or In summary, genetic evidence suggests specific These provide valuable insights into relationships potentially informing future prevention treatment strategies.

Language: Английский

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KLF12 inhibits lipopolysaccharide-induced inflammatory responses, oxidative stress, pyroptosis, and endoplasmic reticulum stress in human airway epithelial cells through inhibition of the NF-κB pathway

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 119917 - 119917

Published: Feb. 1, 2025

Language: Английский

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Curcumin inhibits the activity of ubiquitin ligase Smurf2 to promote NLRP3‑dependent pyroptosis in non‑small cell lung cancer cells

International Journal of Oncology, Journal Year: 2025, Volume and Issue: 66(3)

Published: Feb. 13, 2025

Non‑small cell lung cancer (NSCLC) is a malignant tumor of significant clinical relevance. Curcumin has been investigated for its potential anticancer properties, as it reported to act through multiple cancer‑related targets and pathways. The present study aimed explore the effects curcumin in NSCLC using both vitro vivo models. lines (specifically, A549 NCI‑H1299 cells), mouse model established subcutaneous injection cells, were utilized evaluate intervention. treatment with on NOD‑like receptor pyrin domain‑containing 3 (NLRP3) ubiquitination, pyroptosis pyroptosis‑associated factors also evaluated. In addition, Smad ubiquitination regulatory factor 2 (Smurf2) was analyzed via series knockdown overexpression experiments, vivo, at investigating association NLRP3. results obtained from these experiments showed that inhibited growth, promoted reduced level NLRP3 ubiquitination. reversed curcumin‑induced increase vivo. Additionally, Smurf2 interacted alterations expression levels influenced pyroptosis. Moreover, molecular docking analysis demonstrated could bind directly Smurf2, which subsequently led an inhibition activity. Knockdown enhanced curcumin's ability stabilize promote pyroptosis, whereas negated effects. animal model, volumes weights, addition decreased Ki67 increased factors. Similarly, or by overexpression, respectively. conclusion, findings activity, thereby promoting NLRP3‑dependent cells. have provided mechanistic insights into role NSCLC, opening avenue therapeutic application.

Language: Английский

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Ferroptosis, necroptosis, and pyroptosis in calcium oxalate crystal-induced kidney injury

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 167791 - 167791

Published: March 1, 2025

Kidney stones represent a highly prevalent urological disorder worldwide, with high incidence and recurrence rates. Calcium oxalate (CaOx) crystal-induced kidney injury serves as the foundational mechanism for formation progression of CaOx stones. Regulated cell death (RCD) such ferroptosis, necroptosis, pyroptosis are essential in pathophysiological process injury. Ferroptosis, newly discovered RCD, is characterized by its reliance on iron-mediated lipid peroxidation. Necroptosis, widely studied programmed necrosis, initiates necrotic phenotype that resembles apoptosis appearance. Pyroptosis, type RCD involves gasdermin protein, accompanied inflammation immune response. In recent years, increasing amounts evidence has demonstrated significant processes involved Herein, we summed up roles Furthermore, delved into curative potential targeting

Language: Английский

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The Effects of Xialiqi Capsules in Regulating the Pyroptosis of Prostate Epithelial Cells Via NLRP3/Caspase-1 Pathway for the Treatment of Chronic Prostatitis

American Journal of Men s Health, Journal Year: 2025, Volume and Issue: 19(2)

Published: March 1, 2025

Chronic prostatitis (CNP) is a prevalent inflammatory disorder among men. The Xialiqi capsule has been reported to alleviate the clinical symptoms of CNP patients, which may be related its anti-inflammatory effect; yet, exact mechanism action remains unclear. In this study, human normal prostate epithelial cells (RWPE-2 cells) were categorized into control group, model an inhibitor along with high, medium, and low drug-containing serum groups (5%, 10%, 15%, respectively). With exception cell pyroptosis models created by stimulating lipopolysaccharide (100 ng/mL) adenosine triphosphate (5 mM). Subsequently, NOD-like receptor 3 ( NLRP3 ) (MCC950) utilized intervene according their respective groups. Post-administration MCC950 serum, improvement in viability was noted group medium-high dosage (by 20.5%, 38.2%, 73.2%). Transmission electron microscopy indicated reduction features characteristic pyroptosis. Levels nitric oxide, interleukin-18 (IL-18), tumor necrosis factor-α cellular supernatant decreased significantly (60.7%, 21.6%, 33.7%, 41.8%; 49.2%, 54.8%, 53.5%, 69.3%; 31.3%, 44.4%, 38.1%, 51.2%). Immunofluorescence showed reduced fluorescence intensity Cysteine aspartate protease-1 (Caspase-1) proteins, Western Blot analysis revealed significant decline expression NLRP3, pro-Caspase-1, gasdermin D (20.5%, 45.9%, 58.1%, 74.8%; 23.2%, 36.7%, 51.6%, 51.9%; 15.4%, 28.6%, 33.1%, 39.2%). vitro experiments suggest that treat regulating reducing factor release via inhibiting NLRP3/Caspase-1 signaling pathway. This study offers novel approach for future treatment traditional Chinese medicine preparations, deserving further promotion.

Language: Английский

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Nitric Oxide Mediates Negative Feedback on the TXNIP/NLRP3 Inflammasome Pathway to Prevent Retinal Neurovascular Unit Dysfunction in Early Diabetic Retinopathy

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Autophagy: a double-edged sword in ischemia–reperfusion injury

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: April 7, 2025

Abstract Ischemia–reperfusion (I/R) injury describes the pathological process wherein tissue damage, initially caused by insufficient blood supply (ischemia), is exacerbated upon restoration of flow (reperfusion). This phenomenon can lead to irreversible damage and commonly observed in contexts such as cardiac surgery stroke, where temporarily obstructed. During ischemic conditions, anaerobic metabolism tissues organs results compromised enzyme activity. Subsequent reperfusion exacerbates mitochondrial dysfunction, leading increased oxidative stress accumulation reactive oxygen species (ROS). cascade ultimately triggers cell death through mechanisms autophagy mitophagy. Autophagy constitutes a crucial catabolic mechanism within eukaryotic cells, facilitating degradation recycling damaged, aged, or superfluous organelles proteins via lysosomal pathway. essential for maintaining cellular homeostasis adapting diverse conditions. As self-degradation clearance mechanism, exhibits dualistic function: it confer protection during initial phases injury, yet potentially exacerbate later stages. paper aims elucidate fundamental I/R highlighting its dual role regulation effects on both organ-specific systemic responses. By comprehending their implications organ function, this study seeks explore potential therapeutic interventions modulation clinical settings.

Language: Английский

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Regulation of pyroptosis by natural products in ulcerative colitis: mechanisms and therapeutic potential

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 9, 2025

Ulcerative colitis (UC), a chronic inflammatory bowel disease, is driven by dysregulated immune responses and persistent intestinal inflammation. Pyroptosis, caspase/gasdermin-mediated cell death that exacerbates mucosal damage through excessive cytokine release epithelial barrier disruption. Although pyroptosis considered to be key mechanism in the pathogenesis of UC, systematic assessment role natural products targeting pathway remains critical research gap. The purpose this review investigate regulatory effects on UC elucidate mechanisms action potential therapeutic effects. Key findings highlight polyphenols (e.g., resveratrol), flavonoids Quercetin), terpenoids as promising agents inhibit NLRP3 inflammasome activation, suppress gasdermin D cleavage, restore integrity, thereby reducing pro-inflammatory preclinical models. Current evidence shows enhanced efficacy safety when these compounds are combined with standard therapies, but clinical translation requires overcoming three barriers: limited human trial data, uncharacterized polypharmacology, suboptimal pharmacokinetics needing formulation refinement. Future should prioritize standardized animal-to-human translational models, mechanistic studies synergistic pathways, rigorous validation harness full pyroptosis-targeted therapies.

Language: Английский

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