To investigate sepal/petal/lip formation in Oncidium Gower Ramsey, three paleoAPETALA3 genes, O. Gower Ramsey MADS box gene5 (OMADS5; clade 1), OMADS3 (clade 2), and OMADS9 (clade 3), and one PISTILLATA gene, OMADS8, were characterized. The OMADS8 and OMADS3 mRNAs were expressed in all four floral organs as well as in vegetative leaves. The OMADS9 mRNA was only strongly detected in petals and lips. The mRNA for OMADS5 was only strongly detected in sepals and petals and was significantly down-regulated in lip-like petals and lip-like sepals of peloric mutant flowers. This result revealed a possible negative role for OMADS5 in regulating lip formation. Yeast two-hybrid analysis indicated that OMADS5 formed homodimers and heterodimers with OMADS3 and OMADS9. OMADS8 only formed heterodimers with OMADS3, whereas OMADS3 and OMADS9 formed homodimers and heterodimers with each other. We proposed that sepal/petal/lip formation needs the presence of OMADS3/8 and/or OMADS9. The determination of the final organ identity for the sepal/petal/lip likely depended on the presence or absence of OMADS5. The presence of OMADS5 caused short sepal/petal formation. When OMADS5 was absent, cells could proliferate, resulting in the possible formation of large lips and the conversion of the sepal/petal into lips in peloric mutants. Further analysis indicated that only ectopic expression of OMADS8 but not OMADS5/9 caused the conversion of the sepal into an expanded petal-like structure in transgenic Arabidopsis (Arabidopsis thaliana) plants.
The current study analyzed the acute, chronic, and lasting effects of ketamine administration in four inbred mouse strains (C3H/HeHsd, C57BL/6Hsd, FVB/Hsd, and DBA/2Hsd) to evaluate vulnerability to ketamine as a drug of abuse and as a model of schizophrenia. Serum half-life of ketamine was similar between all strains (approximately 13 min). Also, the ratio of brain-to-serum ketamine levels was 3:1. Examination of multiple phases of auditory processing using auditory-evoked potentials (AEPs) following acute ketamine (0, 5, and 20 mg/kg) treatment revealed C3H/HeHsd mice to be most vulnerable to ketamine-induced alterations in AEPs, whereas FVB/Hsd mice exhibited the least electrophysiological sensitivity to ketamine. Overall, the precortical P1-evoked potential component increased in amplitude and latency, whereas the cortically generated N1 and P2 components decreased in amplitude and latency following acute ketamine across all strains. Brain catecholamine analyses indicated that ketamine decreased hippocampus epinephrine levels in C3H/HeHsd but elevated hippocampus epinephrine levels in FVB/Hsd, suggesting one potential mechanism for AEP vulnerability to ketamine. Based on results of the acute study, the immediate and lasting effects of chronic low-dose ketamine on AEPs were examined among C3H/HeHsd (sensitive) and FVB/Hsd (insensitive) mice. We observed a decrement of the N1 amplitude that persisted at least 1 week after the last exposure to ketamine across both strains. This lasting deficit in information processing occurred in the absence of acute changes among the FVB/Hsd mice. Implications for both ketamine abuse and N-methyl-d-aspartate hypofunction models of schizophrenia are discussed.
Pseudolaric acid B (PAB), an acid isolated from the roots of Pseudolarix kaempferi gorden, has shown antitumour effects through multiple mechanisms of action. The objective of this study was to investigate the anticancer effect of PAB on non-small cell lung cancer (NSCLC) and its underlying mechanism. In our experiments, we observed that PAB decreased cell viability, inhibited colony formation, induced cell cycle arrest, impeded scratch healing, and increased apoptosis in H1975 and H1650 cells. Additionally, PAB treatment enhanced the fluorescence intensity of MDC staining in NSCLC cells, upregulated the protein expression of microtubule-associated protein light chain 3 II (LC3 II), and downregulated the expression of sequestosome 1 (SQSTM1/P62). Combined treatment with PAB and chloroquine (CQ) increased the protein expression levels of LC3 II and P62 while decreasing the apoptosis of H1975 and H1650 cells. Moreover, treatment with PAB led to significant mTOR inhibition and AMPK activation. PAB combined with compound C (CC) inhibited autophagy and apoptosis. Furthermore, PAB treatment increased intracellular reactive oxygen species (ROS) levels in NSCLC cells, which correlated with the modulation of the AMPK/mTOR signalling pathway and was associated with autophagy and apoptosis. Finally, we validated the antitumour growth activity and mechanism of PAB in vivo using athymic nude mice bearing H1975 tumour cells. In conclusion, our findings suggest that PAB can induce apoptosis and autophagic cell death in NSCLC through the ROS-triggered AMPK/mTOR signalling pathway, making it a promising candidate for future NSCLC treatment.
To assess the synergetic change of thoracoabdominal motion in COPD patients during incremental exercise testing, and to evaluate the effect of oxygen therapy on thoracoabdominal synergetic motion.30 stable moderate to severe COPD patients performed incremental exercise test with ergometer twice while breathing either air or 30% oxygen. Thoracoabdominal motion (assessed by TCD/VT) was monitored with respigraph during the whole test.18 of 30 patients had TCD/VT > 1.20 during maximal exercise. TCD/VT at maximal exercise (TCD/VTmax) was significantly correlated with FEV1, FVC, MVV and PaCO2(r = -0.66, -0.63, -0.51, and 0.51), but not correlated with DLCO. The thoracoabdominal synergetic motion could be obviously improved with oxygen therapy.The change of thoracoabdominal synergetic motion during exercise in COPD patients was related with ventilatory function and blood gases. Oxygen therapy could obviously ameliorate paradoxical thoracoabdominal motion.
Low compliance with medication is the major cause of poor outcome in schizophrenia treatment. While surgically implantable solvent-cast pellets were produced to improve outcome by increased compliance with medication, this process is laborious and time-consuming, inhibiting its broader application (Siegel et al., Eur J Pharm Biopharm 2006;64:287-293). In this study, the previous fabrication process was translated to a continuous and scalable extrusion method. Extrusion processes were modified based on in vitro release studies, drug load consistency examination, and surface morphology analysis using scanning electron microscopy. Afterward, optimized haloperidol implants were implanted into rats for preliminary analysis of biocompatibility. Barrel temperature, screw speed and resulting processing pressure influenced surface morphology and drug release. Data suggest that fewer surface pores shift the mechanism from bulk to surface PLGA degradation and longer lag period. Results demonstrate that extrusion is a viable process for manufacturing antipsychotic implants.
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