Serum Eosinophil-Derived Neurotoxin Better Reflect Asthma Control Status Than Blood Eosinophil Counts.

BACKGROUND: Although several biomarkers have been proposed for eosinophilic asthma, biomarkers for reflecting asthma control status remain controversial. Eosinophil-derived neurotoxin (EDN), a degranulated eosinophil protein, is an emerging biomarker in asthmatic patients. OBJECTIVE: This study analyzed serum EDN concentrations in asthmatics and compared its performance with that of blood eosinophil count as an indicator of asthma control status. METHODS: We enrolled 75 uncontrolled asthmatics, 56 controlled asthmatics, and 43 healthy controls from Asan Medical Center. Serum EDN levels (ng/mL) were measured using an enzyme-linked immunosorbent assay kit. The predictability of EDN for asthma control status was analyzed by univariate and multivariable logistic regression analyses. A receiver operating characteristic (ROC) curve analysis was conducted to compare the performances of a serum EDN level and blood eosinophil count as indicators of uncontrolled asthma status. RESULTS: The mean serum EDN level in the uncontrolled asthma group was higher than that in the controlled asthma and healthy groups (103.2 ± 60.2 vs 60.8 ± 49.7 vs 49.6 ± 28.3 ng/mL, P < .001). Serum EDN level was the significant parameter related to asthma control status in univariate and multivariable analysis (both P < .001). Serum EDN levels correlated with blood eosinophil counts (r = 0.510, P < .001). However, in the ROC analysis, serum EDN level showed a significantly better performance for predicting uncontrolled asthma status (area under the curve, 0.726 vs 0.628, P = .024). CONCLUSIONS: Serum EDN levels significantly differed between patients with controlled and uncontrolled status in adult asthmatics. To our knowledge, this is the first study to identify EDN as a better indicator of asthma control status than blood eosinophil count.

Knock-down of PSAT1 Enhances Sensitivity of NSCLC Cells to Glutamine-limiting Conditions.

BACKGROUND/AIM: Phosphoserine aminotransferase 1 (PSAT1) is an enzyme implicated in serine biosynthesis, and its overexpression has been linked to cancer cell proliferation. Therefore, targeting PSAT1 is considered to be an anticancer strategy. MATERIALS AND METHODS: The viability of non-small cell lung cancer (NSCLC) cells was measured by MTT assay. Protein and mRNA expression were determined by western blot and reverse transcription polymerase chain reaction, respectively. RESULTS: Glutamine-limiting conditions were generated through glutamine deprivation or CB-839 treatment, which induced PSAT1 expression in NSCLC cells. PSAT1 expression induced by glutamine-limiting conditions was regulated by activating transcription factor 4. Knock-down of PSAT1 enhanced the sensitivity of NSCLC cells to glutamine-limiting conditions. Interestingly, ionizing radiation induced PSAT1 expression, and knocking down PSAT1 increased cell sensitivity to ionizing radiation. CONCLUSION: Inhibiting PSAT1 might aid in the treatment of lung cancer, and PSAT1 may be a therapeutic target for lung cancer.

Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithin-induced injury in spinal cord slice culture.

Here, we sought to delineate the effect of EPO on the remyelination processes using an in vitro model of demyelination. We report that lysolecithin-induced demyelination elevated EPO receptor (EpoR) expression in oligodendrocyte progenitor cells (OPCs), facilitating the beneficial effect of EPO on the formation of oligodendrocytes (oligodendrogenesis). In the absence of EPO, the resultant remyelination was insufficient, possibly due to a limiting number of oligodendrocytes rather than their progenitors, which proliferate in response to lysolecithin-induced injury. By EPO treatment, lysolecithin-induced proliferation of OPCs was accelerated and the number of myelinating oligodendrocytes and myelin recovery was increased. EPO also enhanced the differentiation of neural progenitor cells expressing EpoR at high level toward the oligodendrocyte-lineage cells through activation of cyclin E and Janus kinase 2 pathways. Induction of myelin-forming oligodendrocytes by high dose of EPO implies that EPO might be the key factor influencing the final differentiation of OPCs. Taken together, our data suggest that EPO treatment could be an effective way to enhance remyelination by promoting oligodendrogenesis in association with elevated EpoR expression in spinal cord slice culture after lysolecithin-induced demyelination.