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Replication factor C 5 (RFC5) is involved in a variety of biological functions of cancer.However, the expression pattern of RFC5 and the underlying mechanisms in colorectal cancer (CRC) remain elusive. Here, we show that RFC5 is significantly upregulated in CRC tissues and cells. Patients with CRC and increased RFC5 levels have an unfavorable prognosis. RFC5 can promote the proliferation, migration, and invasion of CRC cells and inhibit the apoptosis of CRC cells. Additionally, upstream of RFC5, we constructed the competing endogenous RNA network and confirmed that RFC5 in this network was inhibited by miR-3614-5p by directly targeting its 3′-untranslated regions. We verified that circ_0038985, which is positively correlated with RFC5, directly targeted miR-3614-5p. Overexpression of circ_0038985 promoted CRC cell migration and invasion, and these effects were partially reversed by the reintroduction of miR-3614-5p. Moreover, we found that RFC5 may promote the vascular endothelial growth factor A (VEGFa)/vascular endothelial growth factor receptor 2 (VEGFR2)/extracellular signal-regulated protein kinase (ERK) pathway. The knockdown of RFC5 reduced CRC tumorigenesis in vivo.Collectively, these data demonstrate that the circ_0038985/miR-3614-5p/RFC5 axis plays a critical role in the progression of CRC, and RFC5 may promote CRC progression by affecting the VEGFa/VEGFR2/ERK pathway.

BackgroundChronic rhinosinusitis (CRS), whose prevalence and pathogenesis are age-related, is characterized by nasal tissue eosinophil infiltration. CD40-CD40 ligand (CD40L) pathway involves in the eosinophil-mediated inflammation, and inducible co-stimulator (ICOS)–ICOS ligand (ICOSL) signal can strengthen CD40-CD40L interaction. Whether CD40-CD40L and ICOS-ICOSL have a role in the development of CRS remains unknown.ObjectivesThe aim of this study is to investigate the association of CD40-CD40L and ICOS-ICOSL expression with CRS and underlying mechanisms.MethodsImmunohistology detected the expression of CD40, CD40L, ICOS, and ICOSL. Immunofluorescence was performed to evaluate the co-localizations of CD40 or ICOSL with eosinophils. Correlations between CD40-CD40L and ICOS-ICOSL as well as clinical parameters were analyzed. Flow cytometry was used to explore the activation of eosinophils by CD69 expression and the CD40 and ICOSL expression on eosinophils.ResultsCompared with the non-eCRS subset, ECRS (eosinophilic CRS) subset showed significantly increased CD40, ICOS, and ICOSL expression. The CD40, CD40L, ICOS, and ICOSL expressions were all positively correlated with eosinophil infiltration in nasal tissues. CD40 and ICOSL were mainly expressed on eosinophils. ICOS expression was significantly correlated with the expression of CD40-CD40L, whereas ICOSL expression was correlated with CD40 expression. ICOS-ICOSL expression positively correlated with blood eosinophils count and disease severity. rhCD40L and rhICOS significantly enhanced the activation of eosinophils from patients with ECRS. Tumor necrosis factor–α (TNF-α) and interleukin-5 (IL-5) obviously upregulated CD40 expression on eosinophils, which was significantly inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor.ConclusionsIncreased CD40-CD40L and ICOS-ICOSL expressions in nasal tissues are linked to eosinophils infiltration and disease severity of CRS. CD40-CD40L and ICOS-ICOSL signals enhance eosinophils activation of ECRS. TNF-α and IL-5 regulate eosinophils function by increasing CD40 expression partly via p38 MAPK activation in patients with CRS.

Background: Whether the CD40-CD40 ligand (CD40L) and inducible co-stimulatory molecule (ICOS)-ICOS ligand (ICOSL) signals are involved in chronic rhinosinusitis (CRS) development needs further investigation. Objectives: To investigate the association of CD40-CD40L and ICOS-ICOSL expression with CRS and underlying mechanisms. Methods: Immunohistology detected the expression of CD40, CD40L, ICOS, and ICOSL. Immunofluorescence was performed to evaluate the co-locations of CD40 or ICOSL with eosinophils. Correlations between CD40-CD40L and ICOS-ICOSL as well as clinical parameters were analyzed. Flow cytometry was used to explore the activation of eosinophils by CD69 expression and the CD40 and ICOSL expression on eosinophils. Results: Compared with the Non-eCRS subset, ECRS (Eosinophilic chronic rhinosinusitis) subset showed significantly increased CD40, ICOS, and ICOSL expression. The CD40, CD40L, ICOS, and ICOSL expressions were all positively correlated with eosinophil infiltration in nasal tissues. CD40 and ICOSL were mainly expressed on eosinophils. ICOS expression was significantly correlated with the expression of CD40-CD40L, while ICOSL expression was correlated with CD40 expression. ICOS-ICOSL expression positively correlated with blood eosinophils count and disease severity. rhCD40L and rhICOS significantly enhanced the activation of eosinophils from ECRS patients. TNF-α and IL-5 obviously upregulated CD40 and ICOSL expression on eosinophils, which was significantly inhibited by the p38 MAPK inhibitor. Conclusions: Increased CD40-CD40L and ICOS-ICOSL expression in nasal polyps are linked to eosinophils infiltration and disease severity of CRS. CD40-CD40L and ICOS-ICOSL signals enhance eosinophils activation of ECRS. TNF-α and IL-5 regulate eosinophils function by increasing CD40 and ICOSL expression partly via p38 MAPK activation in CRS patients.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. Nasal polyps (NPs) is one of the main manifestations which cause diverse clinical symptoms of CRS. We conducted a bibliometric and visual analysis of CRS and NPs articles published between 2003 and 2022 to provide researchers with the current state of research and potential directions. Method: We used a systematic search strategy to search relevant articles in the databases of the Web of Science from 2003 to 2022. VOSviewers, Bibliometrix R package, and CiteSpace were used to perform the bibliometric analysis. Results: 3,907 publications, including 3,266 “articles” and 641 “reviews” were retrieved. The USA made the highest contributions to global research, followed by China; furthermore, Northwestern University, Capital Medical University, and Sun Yat-Sen University had the highest number of publications. A total of 12,894 authors participated in this research, with the most published author being Bachert C., followed by Schleimer Robert P. and Schlosser Rodney J.. And the authors with the most co-citations were Bachert C., Fokkens W.J., and Gevaert P. 428 journals had published the articles of this research. Moreover, the journal with the most publications was the International Forum Of Allergy & Rhinology and the Journal Of Allergy And Clinical Immunology received the most citations. “Covid-19”, “biologic”, and “type 2 inflammation” were the top current research hotspots. Conclusion: The United States and Northwestern University were the leading country and institution in researching CRS and NPs. And Bachert C. is the most influential expert. The International Forum Of Allergy & Rhinology published the most articles, and the Journal Of Allergy And Clinical Immunology got the highest number of citations. Moreover, “Covid-19”, “biologic”, and “type 2 inflammation” were the trending topics.