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PurposeHypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical neuronal cells and astrocytes.MethodsPrimary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay.ResultsAll MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes (P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05).ConclusionPretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting ERK pathways.

The plant Dendropanax morbifera Léveille (D. morbifera), a subtropical broad-leaved evergreen tree, have been used in folk medicine for the treatment of infectious diseases, skin diseases, and other maladies. However, the effect of extracts from D. morbifera in vascuar diseases has not yet been reported. In this study, BrdU assay revealed that extracts from D. morbifera inhibit significantly the proliferation rate of Rat Aortic Smooth Muscle Cells (RAoSMCs) by -40% in treated samples compared to controls. Notably, 2-D wound healing assay and 3-D boyden chamber assay showed the significant reduction of RAoSMCs migration induced by serum in nano extracts treated groups by -50%. We further observed that the phosphorylated levels of Akt and ERK were significantly reduced by 70% in extracts treated RAoSMCs. Moreover, the expression levels of matrix metalloproteinase (MMP) 2 and 9 were significantly reduced by extracts from D. morbifera. Our results suggest that extracts from D. morbifera inhibit proliferation and migration in RAoSMCs via the modulation of phosphorylated levels of Akt and ERK. Subsequently, the reduced MMP2 and 9 expression might result to reduced migration of RAoSMCs.

Background: Bronchial hyperresponsiveness (BHR), an important physiological feature of asthma, is a prognostic marker of childhood asthma.Purpose: We aimed to investigate the factors associated with BHR in adolescents with childhood asthma.Methods: Two hundred and fifteen adolescents (≥13 years of age; 149 males, 66 females) who were diagnosed with asthma during childhood were enrolled, underwent methacholine challenge tests, and were divided into the BHR group (<25 mg/mL of provocation concentration causing a 20% fall in forced expiratory volume in 1 second [FEV₁] [PC₂₀], n=113) or non-BHR group (≥25 mg/mL of PC₂₀, n=102). We examined longitudinal changes in BHR and the risk factors for its persistence in the 108 adolescents for whom baseline data, including methacholine PC₂₀ at age 6 years, were available. Multivariate logistic regression analyses were performed to assess the factors associated with BHR in adolescents.Results: Mold sensitization (adjusted odds ratio [aOR], 5.569; <i>P</i>=0.005) and increased blood eosinophil count (aOR, 1.002; <i>P</i>=0.026) were independently associated with BHR in boys but not girls. The odds of BHR decreased by 32% with each 1-year increase in age in boys (aOR, 0.683; <i>P</i>=0.010) but not girls. A reduced FEV₁/forced vital capacity ratio (<90%) was independently related with BHR in female patients only (aOR, 7.500; <i>P</i>=0.007). BHR decreased with age throughout childhood. A low methacholine PC₂₀ at age 6 years was independently associated with persistent BHR throughout childhood in male and female patients, whereas early mold sensitization was a risk factor for persistent BHR in male patients only (aOR, 7.718; <i>P</i>=0.028).Conclusion: Our study revealed sex-specific differences in the factors associated with BHR in adolescents with childhood asthma. Our findings suggest the risk factors that might affect asthma transition from childhood to adolescence and adulthood.

PurposeFrequent desaturation due to immature incoordination of suck-swallow-breathing in preterm infants can influence multiple organs such as the heart, lungs, and brain, which can then affect growth and development. Most notably in preterm infants, feeding desaturation may even affect pulmonary function during gavage feeding. Because respiratory muscle activities may reflect the work required during respiration, we evaluated the differences in these activities between full-term and preterm infants with feeding desaturation, and investigated the correlations with clinical variables.MethodsNineteen preterm infants with feeding desaturation (group 1) and 19 age-matched full-term infants (group 2) were evaluated. Oromotor function was evaluated using video recording. The root-mean-squre (RMS) envelope of the electromyography signal was calculated to quantify the activities of muscles involved in respiration. The differences in RMS between both groups and the correlation with clinical variables including gestational age (GA), birth weight (BW), and Apgar scores (AS) at 1 and 5 minutes after birth were evaluated.ResultsThe RMS values of the diaphragm (RMS-D) and rectus abdominis (RMS-R) were significantly greater in group 1 compared to group 2, and the 1- and 5-min AS were significantly lower in group 1 compared to group 2. RMS-D and RMS-R were inversely correlated with GA, BW, 1- and 5-min AS in all infants.ConclusionThis study showed that respiratory muscle activities were augmented during feeding in preterm infants compared to full-term infants. Additionally, respiratory muscle activities were inversely correlated with all clinical variables.

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