Altered microRNA Expression Correlates with Reduced TLR2/4-Dependent Periodontal Inflammation and Bone Resorption Induced by Polymicrobial Infection

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

ABSTRACT Periodontitis (PD) is a polymicrobial dysbiotic immuno-inflammatory disease. Toll-like receptors (TLRs) are present on gingival epithelial cells and recognize pathogen-associated molecular patterns (PAMPs) pathogenic bacteria, induce the secretion of proinflammatory cytokines, initiate innate adaptive antigen-specific immune responses to eradicate invading microbes. Since PD chronic inflammatory disease, TLR2/TLR4 plays vital role in disease pathogenesis maintaining periodontium during health. Many factors modulate TLR-mediated signaling pathway, including specific miRNAs. The study was designed characterize function TLR2/4 miRNA profile after polybacterial infection with Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia C57BL6/J wild-type, TLR2 −/− , TLR4 mice (n=16/group) using RT-qPCR. selection 15 dominant miRNAs for RT-qPCR analysis based prior NanoString global expression profiling response monobacterial infection. Polybacterial infections established colonization induction bacterial-specific IgG. A significant reduction alveolar bone resorption (ABR) inflammation observed mandibles compared wild-type ( p <0.0001). Periodontal bacteria disseminated from tissue multiple organs (heart, lungs, brain, kidney) limited heart F. nucleatum ), lungs P. gingivalis kidney T. ) mice. diagnostic potential assessed by receiver operating characteristic (ROC) curves. Among miRNAs, three were upregulated mice, two seven Notably, anti-inflammatory miR-146a-5p consistently all Additionally, miR-15a-5p let-7c-5p downregulated Multi-species oral bacterial alters pathways modulating several biomarker periodontium. IMPORTANCE most prevalent immuno-infectious multispecies cavity. (TLR) provide first line defense, one best-characterized pathogens-detection systems play recognizing microbial products. Multispecies periodontal S. induced inflammation, whereas did not increase ABR deficient investigated, miR-146a - 5p, miR-146a-5p, miR-30c-5p, sham-infected controls. uniquely among different groups. (miR-146a, miR-15-a-5p, let-7c-5p) could be markers TLRs-mediated periodontitis.

Language: Английский

Elevated Astrocytic NFAT5 of the hippocampus increases epilepsy susceptibility in hypoxic‐ischemic mice

Epilepsia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal mortality, resulting in injury and persistent seizures that can last into the late period beyond. Effective treatments interventions for infants affected by hypoxia-ischemia remain lacking. Clinical investigations have indicated an elevation nuclear factor activated T cells 5 (NFAT5) whole blood from umbilical cords severely HIBD with epilepsy. Experimental research has demonstrated NFAT5 ambivalent effects on neuroprotection neurologic damage. However, mechanistic role remains unclear. This investigation aims to further clarify epilepsy following insult.

Language: Английский

lncRNA PART1 improves sevoflurane-induced impairments in learning and cognitive function by regulating miR-16-5p expression and reducing neuroinflammation

Toxicology Research, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 31, 2024

Abstract Sevoflurane is a commonly utilized inhalational anesthetic in surgical settings. Nevertheless, sevoflurane has been demonstrated to possess neurotoxic properties. The objective was examine the neuroprotective function of long non-coding RNA prostate androgen-regulated transcript 1 (PART1) sevoflurane-induced neurotoxicity and elucidate its potential mechanism. level PART1 quantified by RT-qPCR. proliferation apoptosis HT22 cells were evaluated through CCK-8 assay flow cytometry, respectively. To assess protein IL-6, IL-1β, TNF-α, ELISA conducted. levels malondialdehyde, nitrite, reduced glutathione along with activity superoxide dismutase determined evaluate oxidative stress. Verification targeting relationship between miR-16-5p performed using dual-luciferase reporter assay. Morris water maze test used impact on learning cognitive rats. decreased sevoflurane-treated suppressed attenuated inhibitory effect cell proliferation. mitigated inflammatory response stress regulation miR-16-5p. damage leading improvement rats subjected exposure. regulate via miR-16-5p, which turn improves function. Consequently, may be promising therapeutic target for neurotoxicity.

Language: Английский