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Circadian disruption and ROS-NLRP3 signaling mediate sleep deprivation-enhanced silica nanoparticle toxicity in lacrimal glands.

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Title: Circadian disruption and ROS-NLRP3 signaling mediate sleep deprivation-enhanced silica nanoparticle toxicity in lacrimal glands.
Authors: Zhang, Wenxiao1 (AUTHOR), Qi, Di2 (AUTHOR), Pei, Xiaoting2 (AUTHOR), Lu, Dingli2 (AUTHOR), Ba, Mengru1 (AUTHOR), Xuan, Shuting3 (AUTHOR), Huang, Duliurui1 (AUTHOR), Yang, Tingting3 (AUTHOR), Yang, Jingwen2 (AUTHOR), Li, Zhijie1,2,3,4 (AUTHOR) tzhijieli@jnu.edu.cn, Huang, Shenzhen1,2,3,4 (AUTHOR) huangshenzhen@zzu.edu.cn
Source: Journal of Nanobiotechnology. 9/2/2025, Vol. 23 Issue 1, p1-29. 29p.
Subjects: Sleep deprivation, Silica nanoparticles, Circadian rhythms, Inflammation, Oxidative stress, Oxidizing agents, Lacrimal apparatus, NLRP3 protein
Abstract: Sleep deprivation (SD) and exposure to engineered nanomaterials such as silica nanoparticles (SiNPs) are emerging risk factors for ocular surface disorders, particularly dry eye disease. However, the molecular mechanisms underlying their combined impact on lacrimal gland function remain unclear. In this study, we investigated the synergistic effects of SD and SiNPs exposure on circadian regulation, oxidative stress, inflammation, and structural integrity of the extraorbital lacrimal glands (ELGs) in C57BL/6J mice. Behavioral and physiological monitoring revealed that SD + SiNPs disrupted circadian locomotor activity and body temperature rhythms. Phenotypic assessments showed reduced tear secretion and ELG atrophy. RNA sequencing identified extensive transcriptomic reprogramming, including altered expression of core clock genes and enrichment of inflammatory and redox-related pathways. Increased reactive oxygen species (ROS) accumulation and γ-H2AX expression indicated oxidative DNA damage. Immunohistochemistry confirmed NLRP3 inflammasome activation, while Western blotting revealed enhanced phosphorylation of JAK2, STAT3, NF-κB p65, and IκBα, alongside upregulation of IL-17A. Elevated malondialdehyde levels further reflected oxidative lipid damage. These findings demonstrate that SD exacerbates SiNPs-induced ELG dysfunction via circadian disruption and activation of the ROS/NLRP3/IL-17A inflammatory axis. While these effects are currently limited to the lacrimal gland, future studies are needed to determine whether similar mechanisms contribute to broader systemic metabolic consequences. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Nanobiotechnology is the property of BioMed Central and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
  Group: Ti
  Data: Circadian disruption and ROS-NLRP3 signaling mediate sleep deprivation-enhanced silica nanoparticle toxicity in lacrimal glands.
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  Label: Authors
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  Data: <searchLink fieldCode="AR" term="%22Zhang%2C+Wenxiao%22">Zhang, Wenxiao</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Qi%2C+Di%22">Qi, Di</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pei%2C+Xiaoting%22">Pei, Xiaoting</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lu%2C+Dingli%22">Lu, Dingli</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ba%2C+Mengru%22">Ba, Mengru</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xuan%2C+Shuting%22">Xuan, Shuting</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Huang%2C+Duliurui%22">Huang, Duliurui</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yang%2C+Tingting%22">Yang, Tingting</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yang%2C+Jingwen%22">Yang, Jingwen</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Zhijie%22">Li, Zhijie</searchLink><relatesTo>1,2,3,4</relatesTo> (AUTHOR)<i> tzhijieli@jnu.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Huang%2C+Shenzhen%22">Huang, Shenzhen</searchLink><relatesTo>1,2,3,4</relatesTo> (AUTHOR)<i> huangshenzhen@zzu.edu.cn</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Nanobiotechnology%22">Journal of Nanobiotechnology</searchLink>. 9/2/2025, Vol. 23 Issue 1, p1-29. 29p.
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  Data: <searchLink fieldCode="DE" term="%22Sleep+deprivation%22">Sleep deprivation</searchLink><br /><searchLink fieldCode="DE" term="%22Silica+nanoparticles%22">Silica nanoparticles</searchLink><br /><searchLink fieldCode="DE" term="%22Circadian+rhythms%22">Circadian rhythms</searchLink><br /><searchLink fieldCode="DE" term="%22Inflammation%22">Inflammation</searchLink><br /><searchLink fieldCode="DE" term="%22Oxidative+stress%22">Oxidative stress</searchLink><br /><searchLink fieldCode="DE" term="%22Oxidizing+agents%22">Oxidizing agents</searchLink><br /><searchLink fieldCode="DE" term="%22Lacrimal+apparatus%22">Lacrimal apparatus</searchLink><br /><searchLink fieldCode="DE" term="%22NLRP3+protein%22">NLRP3 protein</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Sleep deprivation (SD) and exposure to engineered nanomaterials such as silica nanoparticles (SiNPs) are emerging risk factors for ocular surface disorders, particularly dry eye disease. However, the molecular mechanisms underlying their combined impact on lacrimal gland function remain unclear. In this study, we investigated the synergistic effects of SD and SiNPs exposure on circadian regulation, oxidative stress, inflammation, and structural integrity of the extraorbital lacrimal glands (ELGs) in C57BL/6J mice. Behavioral and physiological monitoring revealed that SD + SiNPs disrupted circadian locomotor activity and body temperature rhythms. Phenotypic assessments showed reduced tear secretion and ELG atrophy. RNA sequencing identified extensive transcriptomic reprogramming, including altered expression of core clock genes and enrichment of inflammatory and redox-related pathways. Increased reactive oxygen species (ROS) accumulation and γ-H2AX expression indicated oxidative DNA damage. Immunohistochemistry confirmed NLRP3 inflammasome activation, while Western blotting revealed enhanced phosphorylation of JAK2, STAT3, NF-κB p65, and IκBα, alongside upregulation of IL-17A. Elevated malondialdehyde levels further reflected oxidative lipid damage. These findings demonstrate that SD exacerbates SiNPs-induced ELG dysfunction via circadian disruption and activation of the ROS/NLRP3/IL-17A inflammatory axis. While these effects are currently limited to the lacrimal gland, future studies are needed to determine whether similar mechanisms contribute to broader systemic metabolic consequences. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Nanobiotechnology is the property of BioMed Central and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1186/s12951-025-03630-5
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 29
        StartPage: 1
    Subjects:
      – SubjectFull: Sleep deprivation
        Type: general
      – SubjectFull: Silica nanoparticles
        Type: general
      – SubjectFull: Circadian rhythms
        Type: general
      – SubjectFull: Inflammation
        Type: general
      – SubjectFull: Oxidative stress
        Type: general
      – SubjectFull: Oxidizing agents
        Type: general
      – SubjectFull: Lacrimal apparatus
        Type: general
      – SubjectFull: NLRP3 protein
        Type: general
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      – TitleFull: Circadian disruption and ROS-NLRP3 signaling mediate sleep deprivation-enhanced silica nanoparticle toxicity in lacrimal glands.
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              Text: 9/2/2025
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              Y: 2025
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