Subarachnoid hemorrhage (SAH) is a critical neurological emergency and one of the leading causes of stroke. Neuronal demise serves as the primary factor contributing to early brain injury (EBI) following SAH. This study aims to investigate the molecular mechanism underlying Hirudin's impact on EBI after SAH, with a particular focus on pyroptosis. The SAH rat model was established by performing intravascular puncture, followed by the administration of Hirudin and Nod-like receptor protein 3 (NLRP3) agonist Nigericin into the lateral ventricle. The SAH grading, neurological score, brain water content, blood-brain barrier (BBB) permeability, neuronal damage, inflammatory reaction, neuronal death, distribution of microglia marker Iba-1 and expression levels of NLRP3 inflammasomal-related proteins were evaluated at 72 h post-SAH. Hirudin treatment significantly ameliorated neurological scores and attenuated brain edema, BBB permeability, inflammatory response, microglia activation, and pyroptosis in SAH rats. Additionally, Hirudin treatment downregulated the expression levels of NLRP3 inflammasomal- related proteins, such as NLRP3, apoptosis- associated speck-like protein (ASC) and cleaved caspsase-1. However, Nigericin partially counteracted the aforementioned effects of Hirudin, indicating that Hirudin exerted its inhibitory effect on pyroptosis by modulating the NLRP3 inflammasome pathway. The neuroprotective effect of Hirudin on EBI following SAH is attributed its ability to inhibit pyroptosis mediated by NLRP3 inflammasome, suggesting its potential as a promising therapeutic approach for SAH. Keywords: Subarachnoid hemorrhage, Early brain injury, Hirudin, pyroptosis, Nod-like receptor protein 3 (NLRP3) inflammasome.

• MeSH
• hematoencefalická bariéra účinky léků   metabolismus   MeSH
• hirudiny * farmakologie   MeSH
• inflamasomy * metabolismus   MeSH
• krysa rodu Rattus MeSH
• poranění mozku * metabolismus   farmakoterapie   etiologie   patologie   MeSH
• potkani Sprague-Dawley MeSH
• protein NLRP3 * metabolismus   MeSH
• pyroptóza * účinky léků   fyziologie   MeSH
• subarachnoidální krvácení * metabolismus   farmakoterapie   komplikace   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hirudiny * MeSH
• inflamasomy * MeSH
• Nlrp3 protein, rat MeSH Prohlížeč
• protein NLRP3 * MeSH

This study aimed to establish a rat model of chronic wounds to observe the effects of hyperbaric oxygen (HBO) on chronic wound repair and pyroptosis and explore the potential role of pyroptosis in the pathogenesis of chronic wounds. Sprague-Dawley (SD) rats were randomly divided into acute wound group (control group), chronic wound group (model group), chronic wound + HBO treatment group (HBO group), and chronic wound + VX-765 (IL-converting enzyme/Caspase-1 inhibitor) treatment group (VX-765 group). After 7 days of respective interventions, the wound healing status was observed, and wound tissue specimens were collected. Hematoxylin and eosin (HE) staining was used to observe the pathological changes in wound tissues. Transmission electron microscopy was used to observe the changes in cellular ultrastructure. Immunofluorescence was used to observe the expression and localization of vascular endothelial growth factor A (VEGF-A) and the N-terminal domain of gasdermin D (GSDMD-N). Western blot was conducted to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteine-requiring aspartate protease-1 (Caspase-1), VEGF-A, and GSDMD-N proteins in wound tissues. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of NLRP3, Caspase-1, and GSDMD genes. Enzyme-linked immunosorbent assay (ELISA) was performed to observe the expression of the inflammatory cytokines interleukin-1 beta (IL-1beta) and IL-18. The results showed that the HBO group had a faster wound healing rate and better pathology improvement compared to the model group. The expression level of VEGF-A was higher in the HBO group compared to the model group, while the expression levels of NLRP3, Caspase-1, GSDMD, IL-1beta, and IL-18 were lower than those in the model group. HBO can effectively promote the healing of chronic wounds, and the regulation of pyroptosis may be one of its mechanisms of action. Keywords: Hyperbaric oxygen, Pyroptosis, Chronic wounds, Inflammatory.

• MeSH
• hojení ran * fyziologie   účinky léků   MeSH
• hyperbarická oxygenace * metody   MeSH
• krysa rodu Rattus MeSH
• potkani Sprague-Dawley MeSH
• protein NLRP3 metabolismus   MeSH
• proteiny vázající fosfáty metabolismus   MeSH
• pyroptóza * fyziologie   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• protein NLRP3 MeSH
• proteiny vázající fosfáty MeSH

To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating cryptorchidism-induced infertility. Spermatogonial GC-1 cells were heat stimulated to simulate the heat hurt microenvironment of cryptorchidism. The cell viability was assayed by CCK-8, and cellular DNA damage was detected by gamma-H2AX immunofluo-rescence assay. Flow cytometry was employed to assess pyroptosis index, while western blot, ELISA and PCR were used to examine the expressions of pyroptosis-related proteins (Caspase-1, IL-1beta, NLRP3) and cGAS-STING pathway proteins (cGAS, STING). After STING silencing by siRNA, the expressions of pyroptosis-related proteins were determined. Pyroptosis occurred after heat stimulation of cells. Morphological detection found cell swelling and karyopyknosis. According to the gamma-H2AX immunofluorescence (IFA) assay, the endonuclear green fluorescence was significantly enhanced, the gamma-H2AX content markedly increased, and the endonuclear DNA was damaged. Flow cytometry revealed a significant increase in pyroptosis index. Western blot and PCR assays showed that the expressions of intracellular pyrogenic proteins like Caspase-1, NLRP3 and GSDMD were elevated. The increased STING protein and gene expressions in cGAS-STING pathway suggested that the pathway was intracellularly activated. Silencing STING protein in cGAS-STING pathway led to significantly inhibited pyroptosis. These results indicate that cGAS-STING pathway plays an important role in heat stress-induced pyroptosis of spermatogonial cells. After heat stimulation of spermatogonial GC-1 cells, pyroptosis was induced and cGAS-STING pathway was activated. This study can further enrich and improve the molecular mechanism of cryptorchidism.

• MeSH
• acetáty * MeSH
• chromogranin A MeSH
• fenoly * MeSH
• kaspasa 1 MeSH
• kryptorchismus * MeSH
• lidé MeSH
• nukleotidyltransferasy MeSH
• protein NLRP3 MeSH
• pyroptóza MeSH
• signální transdukce MeSH
• spermatogonie MeSH
• úpal * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetáty * MeSH
• chromogranin A MeSH
• fenoly * MeSH
• GC 1 compound MeSH Prohlížeč
• kaspasa 1 MeSH
• nukleotidyltransferasy MeSH
• protein NLRP3 MeSH