Plasma exosomal microRNA expression profiles in patients with high-altitude polycythemia.

High-altitude polycythemia (HAPC) is a chronic mountain sickness characterized by multiple severe ill-effects. Its pathogenesis is still unclear, and till date, no study has been conducted to investigate the plasma exome profile of Tibetan patients with HAPC. In this study, we aimed to elucidate the pathogenesis of HAPC by determining the microRNA (miRNA) signatures. We compared the plasma exosome miRNA expression profiles of eight patients with HAPC and eight healthy controls using next-generation miRNA sequencing. Further, we extracted and identified plasma exosomes using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to validate differentially expressed plasma exosomal miRNAs. Finally, we analyzed the diagnostic values of the differentially expressed miRNAs for HAPC using receiver operating characteristic (ROC) curves. We detected 2007 miRNAs from confirmed plasma exosomes, including 1342 known miRNAs and 665 newly predicted miRNAs. We verified the expression of the top 10 differentially expressed miRNAs via qRT-PCR. Patients with HAPC showed significantly upregulated hsa-miR-122-5p, hsa-miR-423-5p, hsa-miR-4433b-3p, hsa-miR-1291, and hsa-miR-106b-5p expression levels, while hsa-miR-200c-3p expression was downregulated. This study may provide background knowledge for future studies on HAPC studies, which may further facilitate the development of novel therapies against this common disease.

Effect of thymalfasin on myeloid-derived suppressor cells in patients with non-small cell lung cancer.

OBJECTIVE: To observe the effect of thymalfasin on myeloid-derived suppressor cells (MDSCs) subsets in peripheral blood of patients with non-small cell lung cancer (NSCLC). METHODS: 50 cases of NSCLC (NSCLC group) diagnosed in Chest Hospital of Jiangxi Province were selected as the research subjects, and 50 healthy subjects who underwent physical examination in our hospital during the same period were selected as the healthy control group. The expression of HLA-DR-CD14-CD33+ MDSCs in peripheral blood mononuclear cells and tumor tissue single cell suspension of NSCLC patients before and after thymalfasin treatment was explored by flow cytometry. RESULTS: The proportion of MDSCs in peripheral blood of NSCLC group was 1.70±0.52%, which was significantly higher than that in peripheral blood (0.51±0.15%) of healthy controls (P < 0.05). The proportion of HLA-DR-CD14-CD33+ MDSCs in the tissues of NSCLC group was 1.65±0.43% before treatment and 1.15±0.50% after treatment (P < 0.05). The proportion of MDSCs in peripheral blood of NSCLC patients before treatment was 1.70±0.52%, and that after treatment was 0.59±0.18% (P < 0.05). CONCLUSION: Thymalfasin can reduce the number of MDSCs in peripheral blood mononuclear cells. The application of thymalfasin in the treatment of NSCLC patients can help to enhance the anti-tumor effect.

Geniposide exerts protective effects on spinal cord injury in rats by inhibiting the IKKs/NF-κB signaling pathway.

BACKGROUND: Spinal cord injury (SCI) is a traumatic condition of the central nervous system , which can cause nerve injury and affect nerve regeneration, thus leading to severe dysfunction of motor and sensory pathways, and unfortunately these effects are irreversible. Inflammatory response constitutes one of the important mechanisms of spinal cord secondary injury. Geniposide (Gen) is reported to possess anti-inflammation and neuronal repair capacities. OBJECTIVES: To investigate the effect and mechanism of Gen on motor function and inflammatory response in SCI rats. METHODS: Sprague-Dawley (SD) rats were randomly grouped, and the SCI model was established by Allen's method. The motor function of rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale. The protective effect of Gen on the injured spinal cord tissues was evaluated by measuring the water content, myeloperoxidase (MPO) activity, and levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6. Moreover, the protein level of the inflammation-related pathway was detected by spectrometry and Western blot assays. RESULTS: Gen significantly promoted the recovery of SCI rats, decreased the edema of spinal cord tissues, reduced the area of cavity, increased the number of NF-200-positive neurons, as well as increased the number of horseradish peroxidase (HRP) retrograde tracing-positive neurons and regenerated axons with myelin sheath. Additionally, compared with the control group, the neutrophil infiltration, contents of TNF-α, IL-1ß, and IL-6, the activity of inhibitor of nuclear factor κB kinase subunit ß (IKKß) kinase, and protein levels of (nuclear factor κB) NF-κB p65 and phosphorylated inhibitor of NF-κB (p-I-κB) in the Gen experimental group were significantly decreased. CONCLUSION: Gen effectively alleviated inflammatory response after SCI by inhibiting the IKKs/NF-κB signaling pathway and promoted the recovery of motor function and axon regeneration in rats. SIGNIFICANCE: This study can provide novel insights for the early and effective intervention of SCI and confer basic data for the treatment of spinal cord secondary injury.