Acute lung injury (ALI) is a common clinical emergency and all-trans retinoic acid (ATRA) can alleviate organ injury. Therefore, the present study investigated the role of ATRA in ALI. Lipopolysaccharide (LPS)-induced ALI rats were treated with ATRA and the arterial partial pressure of oxygen (PaO 2 ), lung wet/dry weight (W/D) ratio and protein content in the bronchial alveolar lavage fluid (BALF) were measured to evaluate the effect of ATRA on ALI rats. Alveolar macrophages were isolated from the BALF. The phagocytic function of macrophages was detected using the chicken erythrocyte phagocytosis method and flow cytometry. The viability of macrophages was measured using a Cell Counting Kit-8 assay, and apoptosis was analyzed using a TUNEL assay and flow cytometry. The expression levels of Toll-like receptor 4 (TLR4) and cluster of differentiation (CD)14 on the macrophage membrane were detected by immunofluorescence staining. The protein levels of TLR4, CD14, phosphorylated (p)-65, p65, p-IκBα and IκBα were analyzed using western blotting. The concentrations of IL-6, IL-1β and macrophage inflammatory protein-2 in the plasma of rats were detected by ELISA. Macrophages were treated with IAXO-102 (TLR4 inhibitor) to verify the involvement of CD14/TLR4 in the effect of ATRA on ALI. ATRA provided protection against LPS-induced ALI, as evidenced by the increased PaO 2 and reduced lung W/D ratio and protein content in the BALF. ATRA enhanced macrophage phagocytosis and viability and reduced apoptosis and inflammation in ALI rats. Mechanically, ATRA inhibited CD14 and TLR4 expression and NF-κB pathway activation. ATRA enhanced macrophage phagocytosis and reduced inflammation by inhibiting the CD14/TLR4-NF-κB pathway in LPS-induced ALI. In summary, ATRA inactivated the NF-κB pathway by inhibiting the expression of CD14/TLR4 receptor in the alveolar macrophages of rats, thus enhancing the phagocytic function of macrophages in ALI rats, improving the activity of macrophages, inhibiting apoptosis, reducing the levels of inflammatory factors, and consequently playing a protective role in ALI model rats. This study may offer novel insights for the clinical management of ALI.
Background Cancer stem cell (CSC) and ferroptosis play critical roles in cancer development, but the underlying mechanisms remain unclear. Cervical cancer induces a great mortality and an increased incidence globally. Zinc oxide nanoparticle is the nanomaterial that has been applied in industrial products and targets multiple cancer cell types and cancer stem cells. Here, we aimed to explore the effect of ZON on CSC and ferroptosis of cervical cancer. Methods In the present study, we identified that the treatment of ZON in vitro inhibited the proliferation of cervical cancer cells. Results The ZON stimulated the apoptosis of cervical cancer cells. The tumor growth of cervical cancer cells was attenuated by ZON in the xenograft mouse model in vivo. Meanwhile, ZON represses cell invasion and migration of cervical cancer. Crucially, the sphere formation numbers were repressed by ZON. Meanwhile, the SP ratio of cervical cancer cells was inhibited by ZON. The expression of CSC markers, including Sox-2, Oct3/4, and Nanog, was suppressed by circFoxo3 inhibition. Moreover, the ferroptosis was enhanced by ZON in cervical cancer cells. About the mechanism, we observed that ZON enhanced miR-506-3p expression and CD164 was a target of miR-506-3p, in which ZON inhibited CD164 expression by promoting miR-506-3p in cervical cancer cells. We validated that CD164 reversed miR-506-3p-mediated stemness and ferroptosis in cervical cancer cells. ZON repressed stemness and reduced ferroptosis of cervical cancer cells by targeting CD164. ZON inhibits cell growth of cervical cancer in vivo by targeting CD164. Conclusions In brief, we concluded that ZON regulated the ferroptosis, proliferation, invasion, and steaminess of cervical cancer by miR-506-3p/CD164 signaling. Our finding provides new insights into the mechanism by which ZON regulates ferroptosis and steaminess of cervical cancer by a miR-506-3p/CD164 axis.
Aims: CD4+ T cells play crucial roles as both mediators and regulators of the pathogenesis of rheumatoid arthritis (RA). However, the characteristics of CD4+ T cell subpopulations in the earliest stage of RA development remain unclear. Hence, we determined the proportions and absolute counts of circulating CD4+ T cell subsets in patients with seropositive undifferentiated arthritis (SUA), the early and preclinical stage of RA. Methods: Peripheral blood samples and clinical information were collected from 177 patients with SUA, 104 patients with RA, and 120 healthy controls. All patients were newly diagnosed and untreated. Proportions and absolute counts of CD4+ T cell subpopulations were determined by flow cytometric analysis. Results: In patients with SUA, percentages and absolute counts of circulating regulatory T (Treg) cells were decreased significantly and Th17/Treg cell ratios were abnormally increased, whereas Th17 cell numbers were similar to those in healthy controls. In addition, sex-based differences in circulating Treg cells were observed, with female SUA patients having lower proportions and absolute counts of Treg cells than those in males. Moreover, female patients with SUA had higher erythrocyte sedimentation rates and 28-joint Disease Activity Scores than those in males. Conclusion: Immune tolerance deficiency resulting from an abnormal reduction in circulating Treg cells might be the most crucial immunological event in the earliest stage of RA. The sex-specific disparity in Treg cells should also be considered for immunoregulatory and preventive strategies targeting early RA.
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