Host–microbe interactions in the nasal cavity of dogs with chronic idiopathic rhinitis DOI Creative Commons
Zhe Wang, Lyndah Chow, Sunetra Das

и другие.

Frontiers in Veterinary Science, Год журнала: 2024, Номер 11

Опубликована: Авг. 12, 2024

Chronic rhinitis (CR) is a frustrating clinical syndrome in dogs and our understanding of the disease pathogenesis limited. Increasingly, host–microbe interactions are considered key drives sites persistent mucosal inflammation such as nasal oral cavities. Therefore, we applied next generation sequencing tools to interrogate abnormalities present nose with CR compared immune microbiome profiles those healthy dogs. Host cell transcriptomes were evaluated by RNA sequencing, while microbial communities assessed 16S rRNA sequencing. Correlation analysis was then used identify significant between how these altered animals CR. Notably, observed downregulation multiple genes associated ciliary function CR, suggesting previously undetected role for dysfunction this syndrome. We also found upregulation related TNF-α interferon pathways. The significantly dogs, overrepresentation several potential pathobionts. Interactome revealed correlations bacteria genus Porphyromonas upregulated host inflammatory responses well defective which correlated Streptococcus abundance. These findings provide new insights into canine model indicate presence potentially causal relationships pathobionts development dysfunction.

Язык: Английский

The immune mechanism of the nasal epithelium in COVID-19–related olfactory dysfunction DOI Creative Commons
Shunmei Chen,

Shufen Wang

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июль 17, 2023

During the first waves of coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) infection, olfactory dysfunction (OD) was reported as a frequent clinical sign. The nasal epithelium is one front-line protections against viral infections, and immune responses mucosa may be associated with OD. Two mechanisms underlying OD occurrence in COVID-19 have been proposed: infection sustentacular cells inflammatory reaction epithelium. former triggers latter likely prolongs These two alternative act parallel; more important for because are to entry point SARS-CoV-2 than neurons susceptible early injury. Furthermore, abundantly express transmembrane protease, serine (TMPRSS2) play major role has revealed crucial roles cells. This review aims elucidate how contribute COVID-19–related Understanding aid development improved medical treatments

Язык: Английский

Процитировано

11
Live imaging of airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread DOI Creative Commons
Mark E. Becker, Laura Martin‐Sancho, Lacy M. Simons

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 2, 2024

SARS-CoV-2 initiates infection in the conducting airways, where mucociliary clearance inhibits pathogen penetration. However, it is unclear how impacts spread after established. To investigate viral at this site, we perform live imaging of infected differentiated primary human bronchial epithelium cultures for up to 12 days. Using a fluorescent reporter virus and markers cilia mucus, longitudinally monitor mucus motion, ciliary infection. Infected cell numbers peak 4 days post infection, forming characteristic foci that tracked movement. Inhibition MCC using physical genetic perturbations limits foci. Later deteriorates. Increased secretion accompanies motion defects, but vectorial resume removal, suggesting may mediate deterioration. Our work shows while can facilitate initial subsequent decreases inhibit spread, revealing complex interplay between MCC.

Язык: Английский

Процитировано

4
Betrayal From the Core: Centriolar and Cytoskeletal Subversion by Infectious Pathogens DOI Open Access

Himanshi Amita,

Zidhan Subair,

Tulasiram Mora

и другие.

Cytoskeleton, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Microbes and parasites have evolved several means to evade usurp the host cellular machinery mediate pathogenesis. Being major microtubule-organizing center (MTOC) of cell, centrosome is targeted by multiple viral nonviral pathogens their assembly trafficking within cell. This review examines consequence such targeting associated cytoskeletal machinery. We also amassed a substantial body evidence viruses utilizing cilia airway epithelium infection hijacking for efficient entry, replication, egress. While infections been demonstrated induce structural, functional, numerical aberrations in centrosomes, ciliary dysfunction, current literature increasingly supports notion pro-viral role these organelles. Although less explored, impact bacterial parasitic on structures has addressed very briefly. Mechanistically, molecular pathways responsible effects remain largely uncharacterized many instances. Future research focusing centriolar triad comprising centrosome, cilia, satellites will undoubtedly provide vital insights into tactics employed infectious agents subvert centriole cytoskeleton-based

Язык: Английский

Процитировано

0
Spatial transcriptomics of the epipharynx in long COVID identifies SARS-CoV-2 signalling pathways and the therapeutic potential of epipharyngeal abrasive therapy DOI Creative Commons
Kensuke Nishi, Shohei Yoshimoto,

Takayuki Tanaka

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 12, 2025

Abstract In this study, the critical role of epipharynx in managing long-term coronavirus disease 2019 (COVID-19), and particular, how residual SARS-CoV-2 RNA affects signalling pathways were investigated via spatial gene expression analysis (Visium HD). Moreover, we hypothesize that epipharyngeal abrasive therapy (EAT) targeting could improve long COVID symptoms by modulating local inflammation expression. We conducted a comparative profiles three patients with two control individuals without COVID-19. Residual was detected COVID, along activation epithelial immune cells. After EAT, viral either completely cleared or significantly reduced. T-cell receptor suppressed; levels proinflammatory cytokines, such as interleukin-6 tumour necrosis factor-α, reduced; excessive antibody production mitigated. Histology showed EAT effectively eliminated inflamed, dysfunctional ciliated epithelium. This study clarifies has effects on response epipharynx, emphasizing need to focus chronic epipharyngitis potential cause COVID. Furthermore, may offer promising approach alleviating persistent symptoms.

Язык: Английский

Процитировано

0
Optical Imaging of Cilia in the Head and Neck DOI Open Access
Elizabeth Lee,

Lidek Chou,

Zhongping Chen

и другие.

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(6), С. 2059 - 2059

Опубликована: Март 18, 2025

Background/Objectives: Cilia are hair-like organelles with various mechanosensory and chemosensory functions. In particular, motile cilia generate directional fluid flow important for multiple processes. Motile ciliopathies have serious clinical implications, including developmental respiratory disorders. Evaluating the most suitable imaging methods studying ciliary structure function has great significance. Methods: Here, we provide an overview of function, modalities, applications in ciliopathic diseases. Results: Optical become a crucial tool providing high-resolution, non-invasive capabilities that valuable vivo applications. coherence tomography (OCT) is well suited visualization anatomy quantitative studies microfluidic flow. Conclusions: A deeper understanding biology can lead to novel approaches diagnosing, treating, monitoring ciliopathies, contributing more effective individualized care.

Язык: Английский

Процитировано

0
DNA methylation changes during acute COVID-19 are associated with long-term transcriptional dysregulation in patients’ airway epithelial cells DOI Creative Commons
Marey Messingschlager, Sebastian D. Mackowiak, Maria Theresa Vöelker

и другие.

EMBO Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Abstract Molecular changes underlying the persistent health effects after SARS-CoV-2 infection remain poorly understood. To discern gene regulatory landscape in upper respiratory tract of COVID-19 patients, we performed enzymatic DNA methylome and single-cell RNA sequencing nasal cells patients ( n = 19, scRNA-seq 14) controls 14, 10). In addition, resampled a subset these for transcriptome analyses at 3 7) 12 months 5) post followed expression differentially regulated genes over time. Genome-wide methylation analysis revealed 3112 methylated regions between controls. Hypomethylated affected immune genes, while hypermethylated were associated with governing ciliary function. These not only downregulated acute phase disease but sustained repressed up to ciliated cells. Validation an independent cohort collected 6 15) indicated symptom-dependent transcriptional repression genes. We therefore propose that hypermethylation observed may exert long-term effect on expression, possibly contributing post-acute sequelae.

Язык: Английский

Процитировано

0
Longitudinal improvements in clinical and functional outcomes following initiation of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis DOI Creative Commons
Kadambari Vijaykumar, Hui Min Leung,

Amilcar Barrios

и другие.

Heliyon, Год журнала: 2024, Номер 10(8), С. e29188 - e29188

Опубликована: Апрель 1, 2024

Use of elexacaftor/tezacaftor/ivacaftor (ETI) for treatment cystic fibrosis (CF) has resulted in unprecedented clinical improvements necessitating development outcome measures monitoring disease course. Intranasal micro-optical coherence tomography (μOCT) previously helped detect and characterize mucociliary abnormalities patients with CF. This study was done to determine if μOCT can define the effects ETI on nasal clearance monitor changes conferred understand mechanistic CFTR modulators beyond activation.

Язык: Английский

Процитировано

1
Dynamic micro-optical coherence tomography enables structural and metabolic imaging of the mammalian cochlea DOI Creative Commons
Hinnerk Schulz‐Hildebrandt, Svetolik Spasić, Fang Hou

и другие.

Frontiers in Molecular Neuroscience, Год журнала: 2024, Номер 17

Опубликована: Окт. 10, 2024

Sensorineural hearing loss (SNHL) is caused by damage to the mechanosensory hair cells and auditory neurons of cochlea. The development imaging tools that can directly visualize or provide functional information about a patient’s cochlear critical identify pathobiological defect determine cells’ receptiveness emerging SNHL treatments. However, cochlea’s small size, embedded location within dense bone, sensitivity perturbation have historically precluded high-resolution clinical imaging. Previously, we developed micro-optical coherence tomography (μOCT) as platform for otologic in animal models human cochleae. Here report on advancing μOCT technology obtain simultaneously acquired co-localized images cell viability/metabolic activity through dynamic (DμOCT) intracellular motion. DμOCT obtains cross-sectional ATP-dependent movement organelles cytoskeletal polymerization acquiring sequential computing intensity fluctuation frequency metrics pixel-wise basis. Using customized benchtop system, demonstrate detailed resolution anatomical metabolic features organ Corti, via an apical cochleostomy, freshly-excised adult mouse Further, show capable capturing rapid changes metabolism following ototoxic insult induce death actin stabilization. Notably, few 6 frames be used reconstruct with sufficient detail discern individual their state. Taken together, these results motivate future probe cellular diagnosis humans.

Язык: Английский

Процитировано

0
Host–microbe interactions in the nasal cavity of dogs with chronic idiopathic rhinitis DOI Creative Commons
Zhe Wang, Lyndah Chow, Sunetra Das

и другие.

Frontiers in Veterinary Science, Год журнала: 2024, Номер 11

Опубликована: Авг. 12, 2024

Chronic rhinitis (CR) is a frustrating clinical syndrome in dogs and our understanding of the disease pathogenesis limited. Increasingly, host–microbe interactions are considered key drives sites persistent mucosal inflammation such as nasal oral cavities. Therefore, we applied next generation sequencing tools to interrogate abnormalities present nose with CR compared immune microbiome profiles those healthy dogs. Host cell transcriptomes were evaluated by RNA sequencing, while microbial communities assessed 16S rRNA sequencing. Correlation analysis was then used identify significant between how these altered animals CR. Notably, observed downregulation multiple genes associated ciliary function CR, suggesting previously undetected role for dysfunction this syndrome. We also found upregulation related TNF-α interferon pathways. The significantly dogs, overrepresentation several potential pathobionts. Interactome revealed correlations bacteria genus Porphyromonas upregulated host inflammatory responses well defective which correlated Streptococcus abundance. These findings provide new insights into canine model indicate presence potentially causal relationships pathobionts development dysfunction.

Язык: Английский

Процитировано

0