Beangibbs0676

Spinal cord injury is pathologically characterized by the loss of motor function caused by neurons apoptosis. Store-operated calcium entry (SOCE) is widely known to dictate the apoptosis of various cell types. To examine SOCE in spinal cord injury and explore the role of SOCE in apoptosis, patients with spinal cord injury (SCI) and SCI mouse models were included. Expression of SOCE components and apoptosis-related proteins were examined by Western blotting. Calcium imaging was used to assess SOCE activity. As a result, we confirmed the enhanced levels of ORAI1 and STIM1 in SCI patients and SCI mouse models. In vitro study, tunicamycin impaired the viability of VSC4.1 cells (motoneuron-neuroblastoma hybrid cell line) and increased SOCE activity, the effects of which could be abolished by 2-APB. Furthermore, tunicamycinreduced BCL-2/BAX ratio was also reversed by 2-APB. Additionally, EdU assay and DCFH-DA staining confirmed the regulatory role of 2-APB in proliferation and ROS production. Of note is the improved hindlimb motor function and alleviated depression by 2-APB administration. Therefore, we conclude that SOCE may contribute to the pathogenesis of SCI by exacerbating the apoptosis of motoneurons.The treatment of cancer depends on the activity of the cytochrome P450 enzyme family, which is essentially carried out by the CYP3A4 and CYP3A5 enzymes. The aim of our study was to investigate whether the CYP3A4 polymorphism could contribute to protein activity and their influence to the response of cancer cells to treatment. The variability of CYP3A4 cDNA profiles between the cancer cell lines parental HT-29 and resistant HT-29-OxR adenocarcinoma was detected using denaturing gradient gel electrophoresis (DGGE). Subsequently, sequence analysis of CYP3A family members (CYP3A4, CYP3A5) confirmed polymorphism of the CYP3A4 gene in studied cancer cell lines. Variations at the gene expression level, the protein level and the activity of CYP3A4 protein in 12 cancer cell lines were observed, also different response to drug treatments between cell line HT-29 and oxaliplatin-resistant cell line HT-29-OxR. The variability of CYP3A might affect the efficiency of anti-cancer drugs in general and have an impact on metabolism.Lung adenocarcinoma (LUAD) with extremely high morbidity as well as mortality is still in the exploration stage of pathogenesis and treatment. This study aimed to screen and identify differentially expressed genes (DEGs) associated with LUAD via bioinformatics analysis. Three LUAD microarray datasets, GSE116959, GSE68571 and GSE40791, were selected from the Gene Expression Omnibus (GEO) database to analyze the DEGs. 128 DEGs were identified in all, incorporating 36 upregulated and 92 downregulated. Function and pathway enrichment analyses showed that metabolic pathways were their main signaling pathways. After that, seven hub genes including VWF, SPP1, PECAM1, TOP2A, CDK1, UBE2C and KIF23 were mined by the protein-protein interaction (PPI) network. Gene expression analysis, TNM and survival analysis of these hub genes were performed via Gene Expression Profiling Interactive Analysis (GEPIA) online database. Further analysis indicated that TOP2A, CDK1, UBE2C and KIF23 were related to the stage of LUAD patients and overall survival. Then, we verified the relative expression levels of TOP2A, CDK1, UBE2C and KIF23 in LUAD cell lines by qRT-PCR. In conclusion, this study indicated that the four hub genes screened out by bioinformatics analysis were differentially expressed in LUAD compared to normal sample and might be prognostic markers of LUAD.Neuroblastoma (NB) is an extracranial solid malignancy in childhood. More and more studies have demonstrated that circRNAs are essential regulators of various tumors. This study conducted to explore the role and mechanism of circular RNA CUT-like homeobox 1 (circCUX1) in NB. The levels of circCUX1, miR-338-3p and plant homeodomain finger protein 20 (PHF20) were detected by qRT-PCR or Western blot. Cell proliferation and apoptosis were evaluated by colony formation assay, flow cytometry and Western blot analysis. Cell migration and invasion were examined via transwell assay. Glycolysis was expressed by measuring the extracellular acidification rate (ECAR). The interaction among circCUX1, miR-338-3p and PHF20 were validated by dual-luciferase reporter assay and RNA Immunoprecipitation assay. Besides, xenograft experiment was performed to assess tumor growth in vivo. circCUX1 and PHF20 were up-regulated, while miR-338-3p was down-regulated in NB tissues and cells. Knockdown of circCUX1 suppressed the progression and glycolysis of NB cells. circCUX1 triggered NB progression and glycolysis by regulating miR-338-3p. Additionally, down-regulation of miR-338-3p promoted NB progression and glycolysis via targeting PHF20. Moreover, circCUX1 sponged miR-338-3p to regulate PHF20 expression. Furthermore, circCUX1 silencing hindered tumor growth in vivo. circCUX1 depletion suppressed tumor progression and glycolysis in NB by regulating miR-338-3p/PHF20 axis, suggesting a potential biomarker for NB treatment.Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, but effective treatment strategies remain lacking. The objective of this study was to screen underlying therapeutic targets by investigating the molecular mechanisms of AAA using mouse models. The mRNA (GSE109639) and miRNA (GSE51229 and GSE54943) expression profiles of mouse AAA models were downloaded from Gene Expression Omnibus database. A total of 1367 differentially expressed genes (DEGs) were identified between AAA and sham group, 490 of which were used for constructing the Protein-Protein Interaction (PPI) network. NTF3, GNG2 and ITGA7 in the PPI network were suggested to be hub genes according to their ranking of topological features. Furthermore, hub gene GNG2 was enriched in module 1, while ITGA7 was enriched in module 3. Eighteen differentially expressed miRNAs (DEMs) were shared in two datasets, 6 of which were predicted to regulate 130 DEGs (i.e. mmu-miR-677-ITGA7, mmu-miR-350-NTF3 and mmu-miR-292-3p-GNG2) to establish the miRNA-mRNA regulatory network. Function enrichment analysis showed NTF3 was involved in cell motion and MAPK signaling pathway; ITGA7 affected extracellular matrix (ECM)-receptor interaction; GNG2 participated in cell proliferation and chemokine signaling pathway. In conclusion, miRNAs regulating the expressions of NTF3, GNG2 and ITGA7 may represent underlying targets for treatment of AAA.

To determine the association between pathologic features and molecular classes (BRAF-like, RAS-like, and non-BRAF-like non-RAS-like [NBNR]).

Retrospective review of a merged database containing 676 patients, 84% (571/676) were assigned to a molecular class from publicly accessible sequenced data of thyroid neoplasms.

The merged cohort included 571 neoplasms 353 (62%) BRAF-like, 172 (30%) RAS-like, and 46 (8.1%) NBNR. Lymph node metastasis (any N1 disease) was present in 166/337 (49%) of BRAF-like, 23/164 (14%) of RAS-like, and 0/46 (0%) of NBNR and are significantly different (P < .001). Gross extra-thyroidal extension was observed in 27 patients, including 24/331 (7%) of BRAF-like, 2/160 (1%) of RAS-like, and 1/46 (2%) of NBNR (P = .01). N1B lymph node metastases or T4 disease was present in 74/333 (22%) of BRAF-like, 10/160 (6%) of RAS-like, and 1/46 (2%) of NBNR (P < .0001). Distant metastasis was present in 4/151 (2.6%) of BRAF-like, 2/50 (4%) of RAS-like and 0/46 for NBNR (P = .627). Angioinvecular mutations in thyroid tumors aids in decision-making regarding extent of surgery.

To examine risk factors that might be associated with thyroid eye disease (TED) in patients with Graves' disease (GD), which may guide physicians in the prevention and management of TED.

Medline and Embase were searched for articles discussing risk factors of TED. Comparisons were made between GD patients with and without TED, and between active and inactive TED GD patients. Weighted mean differences (WMDs) and odds ratios (ORs) were determined for continuous and dichotomous outcomes, respectively. Results were pooled with random effects using the DerSimonian and Laird model.

Fifty-six articles were included in the analysis. Smoking, inclusive of current and previous smoking status, was a significant risk factor for TED (OR 2.401; CI 1.958-2.945; P < .001). Statistical significance was found upon meta-regression between male sex and the odds of smoking and TED (β= 1.195; SE= 0.436; P= .013). Other risk factors were also examined, and patients with TED were significantly older than those without TED (WMD 1.350; CI 0.328-2.372; P= .010). While both age (WMD 5.546; CI 3.075-8.017; P < .001) and male sex (OR 1.819; CI 1.178-2.808; P= .007) were found to be significant risk factors for active TED patients compared to inactive TED patients, no statistical significance was found for family history, thyroid status, cholesterol levels, or body mass index.

Factors such as smoking, sex, and age predispose GD patients to TED, and TED patients to active TED. A targeted approach in the management of GD and TED is required to reduce the modifiable risk factor of smoking.

Factors such as smoking, sex, and age predispose GD patients to TED, and TED patients to active TED. A targeted approach in the management of GD and TED is required to reduce the modifiable risk factor of smoking.Horizontal gene transfer is a major force in bacterial evolution. Mobile genetic elements are responsible for much of horizontal gene transfer and also carry beneficial cargo genes. Teniposide Uncovering strategies used by mobile genetic elements to benefit host cells is crucial for understanding their stability and spread in populations. We describe a benefit that ICEBs1, an integrative and conjugative element of Bacillus subtilis, provides to its host cells. Activation of ICEBs1 conferred a frequency-dependent selective advantage to host cells during two different developmental processes biofilm formation and sporulation. These benefits were due to inhibition of biofilm-associated gene expression and delayed sporulation by ICEBs1-containing cells, enabling them to exploit their neighbors and grow more prior to development. A single ICEBs1 gene, devI (formerly ydcO), was both necessary and sufficient for inhibition of development. Manipulation of host developmental programs allows ICEBs1 to increase host fitness, thereby increasing propagation of the element.Calmodulin (CaM) engages in Ca2+-dependent interactions with numerous proteins, including a still incompletely understood physical and functional interaction with the human Na+/H+-exchanger NHE1. Using nuclear magnetic resonance (NMR) spectroscopy, isothermal titration calorimetry, and fibroblasts stably expressing wildtype and mutant NHE1, we discovered multiple accessible states of this functionally important complex existing in different NHE1CaM stoichiometries and structures. We determined the NMR solution structure of a ternary complex in which CaM links two NHE1 cytosolic tails. In vitro, stoichiometries and affinities could be tuned by variations in NHE1CaM ratio and calcium ([Ca2+]) and by phosphorylation of S648 in the first CaM-binding α-helix. In cells, Ca2+-CaM-induced NHE1 activity was reduced by mimicking S648 phosphorylation and by mutation of the first CaM-binding α-helix, whereas it was unaffected by inhibition of Akt, one of several kinases phosphorylating S648. Our results demonstrate a diversity of NHE1CaM interaction modes and suggest that CaM may contribute to NHE1 dimerization and thereby augment NHE1 regulation.