Extracellular vesicle-transmitted miR-671-5p alleviates lung inflammation and injury by regulating the AAK1/NF-κB axis.

Mesenchymal stem cells regulate remote intercellular signaling communication via their secreted extracellular vesicles. Here, we report that menstrual blood-derived stem cells alleviate acute lung inflammation and injury via their extracellular vesicle-transmitted miR-671-5p. Disruption of this abundantly expressed miR-671-5p dramatically reduced the ameliorative effect of extracellular vesicles released by menstrual blood-derived stem cells on lipopolysaccharide (LPS)-induced pulmonary inflammatory injury. Mechanistically, miR-671-5p directly targets the kinase AAK1 for post-transcriptional degradation. AAK1 is found to positively regulate the activation of nuclear factor κB (NF-κB) signaling by controlling the stability of the inhibitory protein IκBα. This study identifies a potential molecular basis of how extracellular vesicles derived from mesenchymal stem cells improve pulmonary inflammatory injury and highlights the functional importance of the miR-671-5p/AAK1 axis in the progression of pulmonary inflammatory diseases. More importantly, this study provides a promising cell-based approach for the treatment of pulmonary inflammatory disorders through an extracellular vesicle-dependent pathway.

p38-mediated FOXN3 phosphorylation modulates lung inflammation and injury through the NF-κB signaling pathway.

NF-κB activates the primary inflammatory response pathway responsible for methicillin-resistant Staphylococcus aureus (MRSA)-induced lung inflammation and injury. Here, we report that the Forkhead box transcription factor FOXN3 ameliorates MRSA-induced pulmonary inflammatory injury by inactivating NF-κB signaling. FOXN3 competes with IκBα for binding to heterogeneous ribonucleoprotein-U (hnRNPU), thereby blocking ß-TrCP-mediated IκBα degradation and leading to NF-κB inactivation. FOXN3 is directly phosphorylated by p38 at S83 and S85 residues, which induces its dissociation from hnRNPU, thus promoting NF-κB activation. After dissociation, the phosphorylated FOXN3 becomes unstable and undergoes proteasomal degradation. Additionally, hnRNPU is essential for p38-mediated FOXN3 phosphorylation and subsequent phosphorylation-dependent degradation. Functionally, genetic ablation of FOXN3 phosphorylation results in strong resistance to MRSA-induced pulmonary inflammatory injury. Importantly, FOXN3 phosphorylation is clinically positively correlated with pulmonary inflammatory disorders. This study uncovers a previously unknown regulatory mechanism underpinning the indispensable role of FOXN3 phosphorylation in the inflammatory response to pulmonary infection.

[Value of Multiparameter Flow Cytometry in Diagnosis of Non-Hodgkin's Lymphoma].

OBJECTIVE: To explore the value of multiparameter flow cytometry in diagnosis of non-Hodgkin's lymphoma (NHL). METHODS: Twenty patients with NHL admitted in Traditional Chinese Medicine Hospital of Zhengzhou from January 2009 to August 2014 years were enrolled into this study, among them 13 cases received lymnode puncture, 2 cases were given bone marrow aspiration, 2 cases received peripheral blood examination, 3 cases suffered lymphnode biopsy. RESULTS: After FCM immune typing and cytological smear, 6 cases was confirmed to be B-SLL, 1 case was B-NHL, 1 case was FL, 5 cases was DLBCL, 2 cases was T-NHL, 3 cases was T-LBL, 1 case was NK/T-NHL, 1 case was PTun. CONCLUSION: Multiparameter flow cytometry is valuable for diagnosis of non-Hodgkin's of lymphoma.

Value of detection of serum human epididymis secretory protein 4 and carbohydrate antigen 125 in diagnosis of early endometrial cancer of different pathological subtypes.

This study explored the value of detection of human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) from serum in diagnosis of early endometrial cancer of different pathological subtypes and discussed the mechanism of HE4 and CA125 in diagnosis. In this study, enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to detect HE4 and CA125 from serum in endometrial cancer and control groups. Besides, the concentration of HE4 and CA125 was compared in these two groups, and the expression of CA125 and HE4 and clinicopathological characteristics in patients with endometrial cancer were also analyzed. Compared with the control group, the expression of HE4 was much higher in serum of patients with endometrial cancer, while there was no obvious change in the expression of CA125. The threshold detection value was acquired by receiver operating characteristic analysis method, that is, 141.5 pmol/L and 54.5 U/L, respectively. When comparing the concentration of HE4 in patients with endometrial cancer at the early stage (stage I) with healthy people, the difference therein had statistical significance, but there was no obvious difference in CA125. HE4 and CA125 in diagnosis of endometrial cancer in the stages I and II were found with no statistically significant difference. The difference of HE4 in the stages II and III had statistical significance while the difference of CA125 had no statistical significance. The specificity of both HE4 and CA125 was 95%, and the sensitivity of HE4 to uterine papillary serous carcinomas was higher than that to endometrioid adenocarcinoma. Thus, the serum HE4 is much better than CA125 in detecting the endometrial cancer at an early stage.