Basic research and opportunities for translational advancement in the field of mammalian ∼12-hour ultradian chronobiology DOI Creative Commons
William Dion, Bokai Zhu

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 20, 2024

Repetitive variations, such as oscillation, are ubiquitous in biology. In this mini review, we present a general summary of the ∼24 h circadian clock and provide fundamental overview another biological timekeeper that maintains ∼12 oscillations. This oscillator is proposed to function independently regulate ultradian rhythms relevant both protein homeostasis liver health. Recent studies exploring these humans discussed, followed by our proposal mammary gland physiology represents promising area for further research. We conclude highlighting potential translational applications chronobiology.

Language: Английский

Leptin Receptor Deficiency–Associated Diabetes Disrupts Lacrimal Gland Circadian Rhythms and Contributes to Dry Eye Syndrome DOI Creative Commons
Xiaoting Pei,

Mengru Ba,

Tingting Yang

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(1), P. 19 - 19

Published: Jan. 8, 2025

Purpose: This study investigated the impact of hyperglycemia in type 2 diabetes mellitus (T2DM) on circadian rhythms and function lacrimal glands (LGs) contributing to dry eye syndrome. We assessed effects gene expression, immune cell recruitment, neural activity, metabolic pathways, evaluated effectiveness insulin restoring normal LG function. Methods: Using a T2DM mouse model (db/db mice), transcriptomic changes LGs were analyzed through RNA sequencing over 24-hour period. Rhythmic expression core clock genes, pathways evaluated. The treatment these parameters also assessed. Results: Hyperglycemia disrupted genes LGs, leading 50% reduction rhythmic expression. was associated with altered impaired changes. Insulin lowered blood glucose levels but did not restore or tear secretion, exacerbating syndrome diabetic mice. Conclusions: significantly disrupts glands, limited efficacy regulation suggests that hyperglycemia-induced dysfunction is solely dependent levels, highlighting need for therapies targeting ocular complications.

Language: Английский

Citations

1
Chronic sleep deprivation impairs retinal circadian transcriptome and visual function DOI

Shenzhen Huang,

Wenxiao Zhang,

Shuting Xuan

et al.

Experimental Eye Research, Journal Year: 2024, Volume and Issue: 243, P. 109907 - 109907

Published: April 21, 2024

Language: Английский

Citations

7
Exploring Immune Cell Diversity in the Lacrimal Glands of Healthy Mice: A Single-Cell RNA-Sequencing Atlas DOI Open Access

Qiwei Fan,

Ruyu Yan,

Yan Li

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1208 - 1208

Published: Jan. 19, 2024

The lacrimal gland is responsible for maintaining the health of ocular surface through production tears. However, our understanding immune system within currently limited. Therefore, in this study, we utilized single-cell RNA sequencing and bioinformatic analysis to identify analyze cells molecules present glands normal mice. A total 34,891 were obtained from mice classified into 18 distinct cell clusters using Seurat clustering. Within these populations, 26 different subpopulations identified, including T cells, innate lymphocytes, macrophages, mast dendritic B cells. Network revealed complex cell-cell interactions between with particularly significant observed among plasma Interestingly, found be main source ligands Thy1 signaling pathway, while M2 macrophages identified as primary target pathway. Moreover, some validated immunohistological techniques. Collectively, findings highlight abundance provide valuable insights complexity its relevance associated diseases.

Language: Английский

Citations

6
Long-term PM2.5 exposure disrupts corneal epithelial homeostasis by impairing limbal stem/progenitor cells in humans and rat models DOI Creative Commons

Shengjie Hao,

Zhijian Chen, Yuzhou Gu

et al.

Particle and Fibre Toxicology, Journal Year: 2023, Volume and Issue: 20(1)

Published: Sept. 27, 2023

Limbal stem/progenitor cells (LSPCs) play a crucial role in maintaining corneal health by regulating epithelial homeostasis. Although PM2.5 is associated with the occurrence of several diseases, its effects on LSPCs are not clearly understood.

Language: Английский

Citations

11
Chronic Jet Lag Disrupts Circadian Rhythms and Induces Hyperproliferation in Murine Lacrimal Glands via ROS Accumulation DOI Creative Commons

Shenzhen Huang,

Wenxiao Zhang,

Mengru Ba

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(1), P. 12 - 12

Published: Jan. 7, 2025

Purpose: Chronic jet lag (CJL) is known to disrupt circadian rhythms, which regulate various physiological processes, including ocular surface homeostasis. However, the specific effects of CJL on lacrimal gland function and underlying cellular mechanisms remain poorly understood. Methods: A model was established using C57BL/6J mice. Extraorbital glands (ELGs) were collected at 3-hour intervals for RNA extraction high-throughput sequencing. Circadian transcriptomic profiles analyzed, functional annotations performed. Hydrogen peroxide levels total antioxidant capacity in tear fluid measured chemometric assays. Immunofluorescence used assess cell proliferation, apoptosis, immune infiltration ELGs, reactive oxygen species (ROS) accumulation. The potential therapeutic alpha-lipoic acid (ALA) CJL-induced oxidative stress pathological changes ELGs also investigated. Results: significantly disrupted locomotor activity, altered body temperature modified diurnal oscillations ELGs. Transcriptomic analysis revealed extensive rhythmic gene expression, phase shifts, pathway clustering response CJL. disruption core clock transcription associated with ELG hyperproliferation increased ROS tert-Butyl hydroperoxide promoted ALA effectively reduced mitigated hyperproliferation. Conclusions: These findings uncover novel molecular pathways affected by highlight therapies, such as ALA, preserving health under conditions rhythm disruption.

Language: Английский

Citations

0
Antibiotic-Induced dysbiosis of the ocular microbiome affects corneal circadian rhythmic activity in mice DOI Creative Commons
Xinwei Jiao, Yán Li,

Yu Hu

et al.

Mucosal Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Mechanisms of Extraorbital Lacrimal Gland Aging in Mice: An Integrative Analysis of the Temporal Transcriptome DOI Creative Commons
Jiangman Liu,

Hongli Si,

Duliurui Huang

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2023, Volume and Issue: 64(12), P. 18 - 18

Published: Sept. 11, 2023

This study used high-throughput RNA sequencing (RNA-Seq) and bioinformatics analysis to investigate the altered transcriptome profile of aging lacrimal glands in mice that occurs over course a 24-hour cycle.Male C57BL/6J aged 12 weeks (young) 20 months (aging) were housed pathogen-free setting with 12-hour light/12-hour dark cycle. Throughout cycle, mouse extraorbital (ELGs) collected at eight time points three-hour intervals. To prepare for RNA-Seq, whole mRNA was extracted. Differentially expressed genes (DEGs) young groups subjected bioinformatic based on diurnal patterns. Furthermore, cell populations which significant DEGs express signaling pathways occur validated single-cell (scRNA-seq) level.The total composition significantly ELGs compared during 864 upregulated 228 downregulated DEGs, primarily enriched inflammatory pathways. Further comparative point-to-point revealed underwent alterations temporal several pathways, including inflammation-related, metabolism-related, mitochondrial bioenergetic function-associated, synaptome neural activity-associated, processes-associated, DNA processing-associated fibrosis-associated Most these occurred separately distinct populations.Transcriptome profiles undergo considerable time-dependent changes; this finding offers comprehensive source information better understand pathophysiology gland its underlying mechanisms.

Language: Английский

Citations

10
Sleep deprivation induces corneal endothelial dysfunction by downregulating Bmal1 DOI Creative Commons
Yani Wang, Qun Wang, Shengqian Dou

et al.

BMC Ophthalmology, Journal Year: 2024, Volume and Issue: 24(1)

Published: June 21, 2024

Abstract Background Sleep deprivation (SD) is a common public health problem that contributes to various physiological disorders and increases the risk of ocular diseases. However, whether sleep loss can damage corneal endothelial function remains unclear. This study aimed determine effect possible mechanism SD on endothelium. Methods Male C57BL/6J mice were subjected establish models. After 10 days, quantitative RT-PCR (qRT-PCR) western blot or immunostaining for expression levels zonula occludens-1 (ZO-1), ATPase Na+/K + transporting subunit alpha 1 (Atp1a1), core clock genes in endothelium evaluated. Reactive oxygen species staining mitochondrial abundance characterized function. The regulatory role Bmal1 was confirmed by specifically knocking down overexpressing basic helix-loop-helix ARNT like protein (Bmal1) vivo. In vitro, stress test conducted cultured human cells upon knockdown. Results damaged barrier pump functions mouse endothelium, accompanied dysfunction. Interestingly, dramatically downregulated gene level. knockdown disrupted function, while overexpression ameliorated dysfunction induced SD. Mitochondrial bioenergetic deficiency mediated an underlying Conclusion downregulation caused led via impairing bioenergetics. Our findings offered insight into how impairs expanded understanding leading

Language: Английский

Citations

3
Corneal Sensory Nerve Injury Disrupts Lacrimal Gland Function by Altering Circadian Rhythms in Mice DOI Creative Commons
Senmao Li, Jingyi Xie,

Jiayan Xiang

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(4), P. 40 - 40

Published: April 16, 2025

To investigate the impact of corneal sensory nerve injury on lacrimal gland function, focusing mechanisms involving superior salivatory nucleus (SSN), circadian rhythm disruption, immune microenvironment alterations, and potential for neural regeneration. A murine model was used to assess with tear secretion measured using phenol red thread test. Transcriptomic analysis glands examined immune-related gene expression. Basic fibroblast growth factor (bFGF) promote regeneration, its effects repair were evaluated. Corneal resulted in a 35% reduction significantly impaired SSN activity, as evidenced by 31% decrease c-FOS-positive neurons choline acetyltransferase (ChAT)-expressing neurons. revealed significant downregulation pathways, including Toll-like receptor (TLR), NOD-like (NLR), T-cell signaling. Circadian expression exhibited phase shifts, 2.13-hour delay peak substantial change number types rhythmic genes, which enriched different signaling pathways. The bFGF treatment restored 22% promoted although fiber density remained 74% lower than that controls. disrupts both central peripheral clock functions gland, leading reduced dysregulation. These findings highlight novel role rhythms neural-immune interactions dysfunction. Neural regeneration strategies, such bFGF, offer therapeutic dry eye syndrome, providing new directions clinical intervention.

Language: Английский

Citations

0
Sleep Deprivation Potentiates Silica Nanoparticle-Induced Circadian Disruption and Lacrimal Gland Dysfunction in Mice DOI
Wenxiao Zhang, Di Qi, Xiaoting Pei

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

Abstract Sleep deprivation and engineered nanomaterials, such as silica nanoparticles, have emerged potential risk factors for ocular surface disorders, including dry eye disease. However, the mechanisms by which sleep exacerbates nanoparticle-induced lacrimal gland dysfunction remain unclear. In this study, combined effects of nanoparticle exposure on circadian rhythms, oxidative stress, inflammation, structural integrity extraorbital were investigated in mice. Male C57BL/6J mice divided into control, nanoparticle-treated, groups. Locomotor activity, core body temperature, tear production, glandular morphology assessed, while RNA sequencing was performed to examine gene expression inflammatory pathways. Oxidative stress evaluated via reactive oxygen species accumulation γ-H2AX expression, inflammation assessed immune cell infiltration NLRP3 inflammasome activation. Silica dampened behavioral temperature these further exacerbated deprivation, also abolished diurnal secretion. Histological transcriptomic analyses revealed reduced size, phase shifts clock elevated DNA damage, increased activation NF-κB, IL-17, JAK-STAT The markedly activated group, linking chronic tissue dysfunction. These findings demonstrate that aggravates injury disrupting homeostasis promoting highlighting importance addressing environmental stressors prevention treatment deprivation-associated

Language: Английский

Citations

0