Dioscin Alleviates Periodontitis by Inhibiting NLRP3 Inflammasome Activation via Regulation of K⁺ Homeostasis and Mitochondrial Function

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(4), P. 1375 - 1388

Published: Jan. 1, 2024

Gingival inflammation and alveolar bone loss are characteristic manifestations of periodontitis. Interleukin (IL)-1β, the maturation which is mainly regulated by NOD-like receptor protein (NLRP) 3 inflammasome, not only amplifies inflammatory response but also triggers osteoclastogenesis, thereby accelerating progression Dioscin, a natural steroid saponin, has been shown to inhibit NLRP3 inflammasome. Nevertheless, research on effectiveness Dioscin for management periodontitis remains scarce. In this study, was found dramatically reduce integral components ultimately limiting IL-1β secretion. Notably, inhibitory impact inflammasome might be exerted curbing generation mitochondrial (mt) reactive oxygen species (ROS) oxidized (ox) mtDNA, were mediated inhibition K

Language: Английский

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A20 as a Potential Therapeutic Target for COVID‐19

Immunity Inflammation and Disease, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 1, 2025

ABSTRACT Background Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is a major concern due to its astonishing prevalence and high fatality rate, especially among elderly people. Patients suffering from COVID‐19 may exhibit immunosuppression in initial stage of infection, while cytokine storm can occur when progresses stage. This inopportune immune rhythm not only makes patients more susceptible virus but also leads numerous complications resulting excessive production inflammatory factors. A20, which widely accepted as pivotal regulator inflammation, has been shown be implicated processes antiviral responses immunosuppression. Thus, A20 participate regulating pathological COVID‐19. Methods narrative literature review summarizes recent evidence on mechanisms We downloaded single‐cell RNA‐seq data sets healthy individuals with varying severities NCBI GEO database further dissect A20's regulatory these intricate pathways that are closely associated SARS‐CoV‐2 infection. Results might one most critical anti‐infectious anti‐inflammatory factors involved pathogenesis It effectively suppresses damage viral Conclusions Understanding relationship between A20‐regulated signaling provide insight into potential targets for intervention. Precise regulation induce activity an response could mediate become effective treatment.

Language: Английский

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New, potent, small molecule agonists of tyrosine kinase receptors attenuate dry eye disease

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Aug. 25, 2022

Nerve growth factor (NGF), brain-derived neurotrophic (BDNF), and neurotrophin3 (NT-3) bind to tyrosine kinase (Trk) receptors, TrkA, TrkB, TrkC, respectively. This study investigated the efficacy of novel molecule agonists Trk receptors in an vivo model dry eye disease (DED). Small TrkC agonist (C1) a pan-Trk (pan) were synthesized for this. C57BL/6J mice subjected desiccating stress (DS) received bilateral drops C1, pan, or vehicle (2x/day). Dry signs, inflammation expression corneal barrier function, conjunctival goblet cell (GC) densities measured as part DED phenotype. Corneal epithelial lysates collected either western blot RNA extraction. Extracted total RNAs used NanoString analyses. Immunofluorescent staining was performed on whole-mount corneas using anti-TNFAIP3 anti-EP4 antibodies. Compared vehicle, treated with pan C1 showed improved while also increased GC density. analyses revealed upregulation specific mRNA transcripts (Ptger4, Tnfaip3, Il1a Ptger4, Tlr3, Osal1) pan- C1-treated compared vehicle-treated corneas. Western blots that decreased vehicle-induced NFkB nuclear translocation after DS one day EP4 TNFAIP3 protein levels 5 days epithelium lysates. We conclude small-molecule improve by decreasing activation increasing anti-inflammatory molecules EP4. Surprisingly, most efficacious small not TrkA selective but panTrk, suggesting wider exploration TrkB C are warranted efforts treat DED.

Language: Английский

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The impaired unfolded protein‐premelanosome protein and transient receptor potential channels‐autophagy axes in apoptotic melanocytes in vitiligo

Pigment Cell & Melanoma Research, Journal Year: 2021, Volume and Issue: 35(1), P. 6 - 17

Published: Aug. 1, 2021

Vitiligo is an autoimmune skin disease, characterized by depigmentation and epidermal melanocytes loss. The specific mechanisms underlying vitiligo have not been fully understood. As a result, treating dermatological challenge. Recently, much attention has paid to the dysfunction interaction of organelles under environmental stress. impaired could generate misfolded proteins, particularly accumulated toxic premelanosome protein (PMEL) amyloid oligomers, activating system cause melanocyte damage. Unfolded response (UPR) accelerates PMEL accumulation. Herein, we presented narrative review on UPR's role in vitiligo, PMEL-induced attack autophagy caused abnormal activation transient receptor potential (TRP) channels background UPR defects melanocytes. All these were integrated form UPR/PMEL-TRP channels/autophagy axis, providing new understanding pathogenesis.

Language: Английский

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Ubiquitin-specific protease 34 in macrophages limits CD8 T cell-mediated onset of vitiligo in mice

Immunobiology, Journal Year: 2023, Volume and Issue: 228(3), P. 152383 - 152383

Published: April 8, 2023

Language: Английский

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