Targeting Noncanonical Pyroptosis With a Small Molecular Inhibitor Alleviates Inflammation in the LPS-Induced Keratitis Mouse Model

Zhang, Yun; Zhou, Nenghua; Yan, Jiao; Lin, Guifeng; Li, Xun; Gao, Sheng; Zhou, Pei; Liu, Jingming; Nan, Jinshan; Zhang, Meixia; Yang, Shengyong

doi:10.1167/iovs.64.1.1

Cited by 3 publications

(2 citation statements)

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“…The selected dosage for the corneal stroma injection was 2 μL of the diluent at a concentration of 1.5 × 10 8 colony forming unit (CFU)/mL, based on the bacterial keratitis mouse model by Chojnacki et al 26 and our preliminary experiments. [27][28][29] Corneal scrapings of the mice were performed 1 day after the injection, and positive for weak acid-fast staining indicated the mouse model was established successfully. All animal studies followed the guidelines of the Association for Research in Vision and Ophthalmology and were approved by the Institutional Animal Care and Use Committee.…”

Section: Establishment Of a Mouse Model Of Nocardiamentioning

confidence: 99%

Whole Genome Sequencing Highlights the Pathogenic Profile in Nocardia Keratitis

Guo,

Zhang,

Chen

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.Nocardia keratitis is a serious and sight-threatening condition. This study aims to reveal the virulence and antimicrobial resistance gene profile of Nocardia strains using whole genome sequencing. METHODS.Whole-genome sequencing was performed on 23 cornea-derived Nocardia strains. Together with genomic data from the respiratory tract and the environment, 141 genomes were then utilized for phylogenetic and pan-genome analyses, followed by virulence and antibiotic resistance analysis. The correlations between virulence genes and pathogenicity were experimentally validated, including the characteristics of Nocardia colonies and clinical and histopathological evaluations of Nocardia keratitis mice models. RESULTS.Whole-genome sequencing of 141 Nocardia strains revealed a mean of 220 virulence genes contributed to bacterial pathogenesis. The mce gene family analysis led to the categorization of strains from the cornea into groups A, B, and C. The colonies of group C had the largest diameter, height, and fastest growth rate. The size of corneal ulcers and the clinical scores showed a significant increase in mouse models induced by group C. The relative expression levels of pro-inflammatory cytokines (CD4, IFN-γ , IL-6Rα, and TNF-α) in the lesion area exhibited an increasing trend from group A to group C. Antibiotic resistance genes (ARGs) spanned nine distinct drug classes, four resistance mechanisms, and seven primary antimicrobial resistance gene families. CONCLUSIONS.Whole genome sequencing highlights the pathogenic role of mce gene family in Nocardia keratitis. Its distribution pattern may contribute to the distinct characteristics of the growth of Nocardia colonies and the clinical severity of the mice models.

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Section: Establishment Of a Mouse Model Of Nocardiamentioning

confidence: 99%

Whole Genome Sequencing Highlights the Pathogenic Profile in Nocardia Keratitis

Guo,

Zhang,

Chen

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…The compound J114, also referred to as N-(3-hydroxyphenyl)-2-(1H-indol-6-yl) acetamide, exhibited the inhibition of caspase-1 activation and IL-1β release by directly disturbing the interaction of NLRP3 or AIM2 with the adaptor protein ASC and inhibited ASC oligomerization in human THP-1 macrophages [140]. This compound prevented acute corneal inflammation and cell injury by inhibiting the noncanonical pyroptosis signaling pathway in mice [141]. Compounds like 4-sulfonic calix [6]arene, 4-sulfonic calix [8]arene, and suramin have been identified as the inhibitors of dsDNA-triggered inflammatory responses mediated by the AIM2 inflammasome.…”

Section: Inflammasomes As Therapeutic Targetsmentioning

confidence: 99%

A Perfect Storm: The Convergence of Aging, Human Immunodeficiency Virus Infection, and Inflammasome Dysregulation

Thirugnanam,

Rout

2024

CIMB

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The emergence of combination antiretroviral therapy (cART) has greatly transformed the life expectancy of people living with HIV (PWH). Today, over 76% of the individuals with HIV have access to this life-saving therapy. However, this progress has come with a new challenge: an increase in age-related non-AIDS conditions among patients with HIV. These conditions manifest earlier in PWH than in uninfected individuals, accelerating the aging process. Like PWH, the uninfected aging population experiences immunosenescence marked by an increased proinflammatory environment. This phenomenon is linked to chronic inflammation, driven in part by cellular structures called inflammasomes. Inflammatory signaling pathways activated by HIV-1 infection play a key role in inflammasome formation, suggesting a crucial link between HIV and a chronic inflammatory state. This review outlines the inflammatory processes triggered by HIV-1 infection and aging, with a focus on the inflammasomes. This review also explores current research regarding inflammasomes and potential strategies for targeting inflammasomes to mitigate inflammation. Further research on inflammasome signaling presents a unique opportunity to develop targeted interventions and innovative therapeutic modalities for combating HIV and aging-associated inflammatory processes.

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