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We also evaluated MCT1 and MCT4 expression and oxidative markers (JC1 staining and Bec index) in tumour-derived spindle cell cultures and CD14+ monocytic cells. Finally, we quantified the intratumoural and circulating levels of lactate in a series of 17 subjects with GCTB. In sharp contrast to the benign histological features of GCTB, we found a high expression of glycolytic markers, with particular reference to MCT4. Unexpectedly, this was mainly confined to the giant cell, not proliferating cell component. MLT-748 Accordingly, GCTB patients showed higher levels of blood lactate as compared to healthy subjects. In conclusion, taken together, our data indicate that GCTB is characterized by a highly glycolytic metabolism of its giant cell component, opening new perspectives on the pathogenesis, the natural history, and the treatment of this lesion. Protein phosphatase methylesterase 1 has been identified as a novel gene in skeletal muscle that is upregulated in response to neurogenic atrophy in mice. Western blot analysis confirms that Ppme1 is expressed during both muscle cell proliferation and differentiation. Additionally, the Ppme1 promoter is active in muscle cells, while mutation of a conserved E-box element prevents full induction of the Ppme1 reporter gene, suggesting that Ppme1 is transcriptionally regulated by myogenic regulatory factors. Interestingly, immunofluorescence analysis indicates that Ppme1 is localized to both the cytoplasm and the nucleus, while cell fractionation shows that Ppme1 is found only in the cytoplasm. Functional studies reveal that inhibition of Ppme1 using ABL127 or AMZ30 attenuates muscle cell differentiation. Interestingly, inhibition of Ppme1 by ABL127 led to a significant increase in AP-1 reporter activity, as well as, increases in ERK1/2, c-Jun, Ppme1, and PP2A protein levels in differentiating muscle cells. In contrast, AMZ30 treated cells showed a significant decrease in AP-1 reporter activity and a decrease in ERK1/2 and p38 phosphorylation levels. Finally, co-immunoprecipitation studies show that ABL127, but not AMZ30, causes disruption of the endogenous interaction between Ppme1 and PP2A. The data in this study show for the first time that Ppme1 is expressed in skeletal muscle and is upregulated in response to neurogenic atrophy. Furthermore, these findings suggest that Ppme1 may act as a sentinel of the MAP kinase signaling pathway and may indirectly regulate the ERK1/2 and p38 branches via a non-canonical mechanism leading to inhibition of muscle cell differentiation. Alprazolam is used in the treatment of patients with anxiety disorders comorbid with alcohol use disorder. Some proportion of these patients does not respond adequately to treatment with alprazolam, while many of them experience dose-dependent adverse drug reactions. Results of the previous studies have shown that CYP3A is involved in the biotransformation of alprazolam, the activity of which is dependent, inter alia, on the polymorphism of the encoding gene. OBJECTIVE The objective of our study was to investigate the effect of 99366316G>A polymorphism of the CYP3A4 gene on the concentration/dose indicator of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder, using findings on enzymatic activity of CYP3A (as evaluated by the 6-beta-hydroxy-cortisol/cortisol ratio measurement) and on CYP3A4 expression level obtained by measuring the miR-27b plasma concentration levels in patients with anxiety disorders comorbid with alcoholism. MATERIAL AND METHODS Our study enrolled 105 patientsAt the same time, correlation analysis revealed a statistically significant relationship between the alprazolam concentration and the miR-27b plasma concentration rs = 0.28, p = 0.003. CONCLUSION The effect of genetic polymorphism of the CYP3A4 gene on the efficacy and safety profiles of alprazolam was demonstrated in a group of 105 patients with anxiety disorders comorbid with alcohol use disorder. At the same time, miR-27b remains a promising biomarker for assessing the level of CYP3A4 expression, because it correlates with the encoded isoenzyme's activity. As an important transcription factor family, DREB transcription factors play important roles in response to abiotic stresses. In this study, we identified wheat DREB genes at genome-level, and characterized the functions of TaDREB genes. Totally, there are 210 TaDREB genes, which can be divided into 6 subgroups. Some of these genes display tissue-specific expression patterns. Among them, the expression of three TaDREB3 homoeologous genes is induced by abiotic stresses. Meanwhile, as alternatively spliced genes, they generate three isoforms respectively. Transcripts I and II encode DREB proteins, while transcript III does not generate DREB proteins. Transgenic Arabidopsis over-expressing TaDREB3-AI displayed enhanced resistance to drought, salt and heat stresses. The physical indexes and the expression of stress-related genes further verified the functions in response to abiotic stresses. Our results lay a foundation for further study of wheat DREB genes. Especially, our findings indicate that TaDREB3 genes can be used for crop genetic improvement. Valgus-varus Deformity (VVD) is an outward or inward deviation of the tibiotarsus or tarsometatarsus, which results in physical distress of chickens and economic loss in poultry industry. While the etiology and pathogenesis of VVD at the molecular level are still not fully understood so far. Here, based on a case/control design with VVD birds and normal birds, we identified genes and lncRNAs which associated with VVD using RNA sequencing. Transcriptome analysis revealed 231 differentially expressed mRNAs and 23 differentially expressed lncRNAs between case and control of leg cartilage. We identified the cis- and trans-regulatory targets of the differentially expressed lncRNAs, and we constructed a functional lncRNA-mRNA co-expression network. Analysis of the network showed that the differentially expressed mRNAs and the target genes of the differentially expressed lncRNAs were enriched in the signaling pathways associated with bone development, including p53, MAPK, Toll-like receptor, Jak-STAT, Hedgehog, and PPAR.