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c-Jun N-terminal kinase (JNK) plays a key role in the regulation of neuronal apoptosis. Previous studies have revealed that forkhead transcription factor (FOXO3a) is a critical effector of JNK-mediated tumor suppression. However, it is not clear whether the JNK/FOXO3a pathway is involved in neuronal apoptosis in the developing rat brain after hypoxia-ischemia (HI). In this study, we generated an HI model using postnatal day 7 rats. Fluorescence immunolabeling and Western blot assays were used to detect the distribution and expression of total and phosphorylated JNK and FOXO3a and the pro-apoptotic proteins Bim and CC3. We found that JNK phosphorylation was accompanied by FOXO3a dephosphorylation, which induced FOXO3a translocation into the nucleus, resulting in the upregulation of levels of Bim and CC3 proteins. Furthermore, we found that JNK inhibition by AS601245, a specific JNK inhibitor, significantly increased FOXO3a phosphorylation, which attenuated FOXO3a translocation into the nucleus after HI. Moreover, JNK inhibition downregulated levels of Bim and CC3 proteins, attenuated neuronal apoptosis and reduced brain infarct volume in the developing rat brain. Our findings suggest that the JNK/FOXO3a/Bim pathway is involved in neuronal apoptosis in the developing rat brain after HI. Agents targeting JNK may offer promise for rescuing neurons from HI-induced damage.

Objective: Timely application of surfactant replacement therapy is critical for neonates with respiratory distress syndrome (RDS). Presently, early clinical decision on surfactant use relies solely on ventilator parameters. However, ventilator parameters are unable to truly recapitulate the extent of surfactant deficiency. Lung ultrasound has been increasingly used in the early prediction of surfactant use in recent years, but its predictive value remains unclear. Therefore, we conducted this study to examine its predictive value in surfactant use and determine the optimal timing and cutoff value. Methods: Studies on neonates with respiratory distress or diagnosed with RDS were collected from PubMed, Embase, Cochrane Library, and Web of Science. Primary outcomes included sensitivity, specificity, and positive and negative predictive values of lung ultrasound. Results: Ten eligible studies with 1162 participants were included. The sensitivity and specificity of lung ultrasound in predicting surfactant use were 0.86 (95% CI: 0.81–0.90) and 0.82 (95% CI: 0.71–0.90), respectively. Lung ultrasound performed within 1–3 h after birth had a sensitivity of 0.89 (95% CI: 0.79–0.95) and a Youden's index of 0.67. Compared with a lung ultrasound score (LUS) cutoff of ≤6/7, ≤8, >5, >6/7, and >8, a LUS cutoff of ≤5 had higher Youden's index (0.73) and sensitivity (0.94, 95% CI: 0.85–0.97) in predicting surfactant use. Conclusions: Lung ultrasound is effective for predicting surfactant use in neonates. Lung ultrasound within 1–3 h after birth and a LUS cutoff of 5 are recommended. However, the symptoms and oxygenation of the neonatal patients must also be considered. [ABSTRACT FROM AUTHOR]

Cultivars of rice (Oryza sativa L.), especially of the type with large spikelets, often fail to reach the yield potential as expected due to the poor grain-filling on the later flowering inferior spikelets (in contrast to the earlier-flowering superior spikelets). The present study showed that the size and grain weight of superior spikelets (SS) was greater than those of inferior spikelets (IS), and the carbohydrate supply should not be the major problem for the poor grain-filling because there was adequate amount of sucrose in IS at the initial grain-filling stage. High resolution two-dimensional gel electrophoresis (2-DE) in combination with Coomassie-brilliant blue (CBB) and Pro-Q Diamond phosphoprotein fluorescence stain revealed that 123 proteins in abundance and 43 phosphoproteins generated from phosphorylation were significantly different between SS and IS. These proteins and phosphoproteins were involved in different cellular and metabolic processes with a prominently functional skew toward metabolism and protein synthesis/destination. Expression analyses of the proteins and phosphoproteins associated with different functional categories/subcategories indicated that the starch synthesis, central carbon metabolism, N metabolism and cell growth/division were closely related to the poor grain-filling of IS. Functional and expression pattern studies also suggested that 14-3-3 proteins played important roles in IS poor grain-filling by regulating the activity of starch synthesis enzymes. The proteome and phosphoproteome obtained from this study provided a better understanding of the molecular mechanism of the IS poor grain-filling. They were also expected to be highly useful for improving the grain filling of rice. [ABSTRACT FROM AUTHOR]

Two new peptides, MCh-1 and MCh-2, along with three known trypsin inhibitors (MCTI-I, MCTI-II and MCTI-III), were isolated from the seeds of the tropical vine Momordica charantia. The sequences of the peptides were determined using mass spectrometry and NMR spectroscopy. Using a strategy involving partial reduction and stepwise alkylation of the peptides, followed by enzymatic digestion and tandem mass spectrometry sequencing, the disulfide connectivity of MCh-1 was elucidated to be CysI-CysIV, CysII-CysV and CysIII-CysVI. The three-dimensional structures of MCh-1 and MCh-2 were determined using NMR spectroscopy and found to contain the inhibitor cystine knot (ICK) motif. The sequences of the novel peptides differ significantly from peptides previously isolated from this plant. Therefore, this study expands the known peptide diversity in M. charantia and the range of sequences that can be accommodated by the ICK motif. Furthermore, we show that a stable two-disulfide intermediate is involved in the oxidative folding of MCh-1. This disulfide intermediate is structurally homologous to the proposed ancestral fold of ICK peptides, and provides a possible pathway for the evolution of this structural motif, which is highly prevalent in nature. [ABSTRACT FROM AUTHOR]

Two new peptides, MCh-1 and MCh-2, along with three known trypsin inhibitors (MCTI-I, MCTI-II and MCTI-III), were isolated from the seeds of the tropical vine Momordica charantia. The sequences of the peptides were determined using mass spectrometry and NMR spectroscopy. Using a strategy involving partial reduction and stepwise alkylation of the peptides, followed by enzymatic digestion and tandem mass spectrometry sequencing, the disulfide connectivity of MCh-1 was elucidated to be CysI-CysIV, CysII-CysV and CysIII-CysVI. The three-dimensional structures of MCh-1 and MCh-2 were determined using NMR spectroscopy and found to contain the inhibitor cystine knot (ICK) motif. The sequences of the novel peptides differ significantly from peptides previously isolated from this plant. Therefore, this study expands the known peptide diversity in M. charantia and the range of sequences that can be accommodated by the ICK motif. Furthermore, we show that a stable two-disulfide intermediate is involved in the oxidative folding of MCh-1. This disulfide intermediate is structurally homologous to the proposed ancestral fold of ICK peptides, and provides a possible pathway for the evolution of this structural motif, which is highly prevalent in nature. [ABSTRACT FROM AUTHOR]