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Background This study aims to identify a predictive model to predict survival outcomes of osteosarcoma (OS) patients. Methods A RNA sequencing dataset (the training set) and a microarray dataset (the validation set) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. Differentially expressed genes (DEGs) between metastatic and non-metastatic OS samples were identified in training set. Prognosis-related DEGs were screened and optimized by support vector machine (SVM) recursive feature elimination. A SVM classifier was built to classify metastatic and non-metastatic OS samples. Independent prognosic genes were extracted by multivariate regression analysis to build a risk score model followed by performance evaluation in two datasets by Kaplan-Meier (KM) analysis. Independent clinical prognostic indicators were identified followed by nomogram analysis. Finally, functional analyses of survival-related genes were conducted. Result Totally, 345 DEGs and 45 prognosis-related genes were screened. A SVM classifier could distinguish metastatic and non-metastatic OS samples. An eight-gene signature was an independent prognostic marker and used for constructing a risk score model. The risk score model could separate OS samples into high and low risk groups in two datasets (training set log-rank p less then 0.01, C-index = 0.805; validation set log-rank p less then 0.01, C-index = 0.797). Tumor metastasis and RS model status were independent prognostic factors and nomogram model exhibited accurate survival prediction for OS. Additionally, functional analyses of survival-related genes indicated they were closely associated with immune responses and cytokine-cytokine receptor interaction pathway. Conclusion An eight-gene predictive model and nomogram were developed to predict OS prognosis.Background Laparoscopy induces adhesion due to ischemia-reperfusion injury. However, the detail pathomechanism is poorly understood. This study aimed to investigate the impact of laparoscopy on mast cell and mesothelium morphological changes in the rat. Methods Forty-nine males of Sprague-Dawley Rattus norvegicus were divided into four groups a) control and b) intervention groups P1, P2, and P3 that underwent 60 min laparoscopic using carbon dioxide (CO2) insufflation at 8, 10, and 12 mmHg groups, respectively. Serum hydrogen peroxide (H2O2), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and oxidative stress index (OSI) levels were determined 24 h after laparoscopy. Histopathological analyses of mast cell infiltration and degranulation and mesothelium thickness in the liver, greater omentum, mesenterium, small intestine, and peritoneum were performed 7 days after the procedure. Results H2O2, MDA, and OSI levels were significantly increased in the intervention groups compared with the control (p less then 0.05), while the SOD and CAT levels were decreased in the intervention groups compared with the control (p less then 0.05). Mast cell infiltration and degranulation were higher in the intervention groups than in control (p less then 0.05), while the mesothelium thickness was significantly lower in the laparoscopic groups than in control (p less then 0.05). Interestingly, the decrease in mesothelium thickness was strongly associated with the increase in mast cell infiltration and degranulation (p less then 0.01). Conclusions Our study shows that laparoscopy in rats increases mast cell infiltration and degranulation, which also results in and correlates with a decrease in mesothelial thickness.Background The RNA-binding protein Musashi-2 (MSI2) has been implicated in the tumorigenesis and tumor progression of some human cancers. MSI2 has also been reported to suppress tumor epithelial-to-mesenchymal transition (EMT) progression in breast cancer, and low MSI2 expression is associated with poor outcomes for breast cancer patients; however, the underlying mechanisms have not been fully investigated. This study investigated the expression and phenotypic functions of two major alternatively spliced MSI2 isoforms (MSI2a and MSI2b) and the potential molecular mechanisms involved in triple-negative breast cancer (TNBC) progression. Methods The Illumina sequencing platform was used to analyze the mRNA transcriptomes of TNBC and normal tissues, while quantitative reverse transcription-polymerase chain reaction and immunohistochemistry validated MSI2 isoform expression in breast cancer tissues. The effects of MSI2a and MSI2b on TNBC cells were assayed in vitro and in vivo. RNA immunoprecipitation (RIP) and RNins in TNBC, that its downregulation is associated with TNBC progression and poor prognosis and that MSI2a expression inhibited TNBC invasion by stabilizing TP53INP1 mRNA and inhibiting ERK1/2 activity. Overall, our study provides new insights into the isoform-specific roles of MSI2a and MSI2b in the tumor progression of TNBC, allowing for novel therapeutic strategies to be developed for TNBC.Background Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is endemic in Niger but complicated by the presence of Schistosoma bovis, Schistosoma curassoni and S. haematobium group hybrids along with various Bulinus snail intermediate host species. Establishing the schistosomes and snails involved in transmission aids disease surveillance whilst providing insights into snail-schistosome interactions/compatibilities and biology. Methods Infected Bulinus spp. were collected from 16 villages north and south of the Niamey region, Niger, between 2011 and 2015. From each Bulinus spp., 20-52 cercariae shed were analysed using microsatellite markers and a subset identified using the mitochondrial (mt) cox1 and nuclear ITS1 + 2 and 18S DNA regions. Infected Bulinus spp. were identified using both morphological and molecular analysis (partial mt cox1 region). Results A total of 87 infected Bulinus from 24 sites were found, 29 were molecularly confirmed as B. truncatus, three as B. forskaliiSchistosoma species/forms (S. haematobium and S. haematobium hybrids) were found transmitted only in five villages whereas those causing veterinary schistosomiasis (S. bovis), were found in most villages. Bulinus truncatus was most abundant, transmitting all Schistosoma species, while the less abundant B. forskalii and B. globosus, only transmitted S. bovis. Our data suggest that species-specific biological traits may exist in relation to co-infections, snail-schistosome compatibility and intramolluscan schistosome development.Background Although important advances in treatment strategies have been developed in type 2 diabetes mellitus (T2DM), large gaps exist in achieving glycemic control and preventing complications, particularly in low-and middle-income countries, which suggests a potential effect of social determinants of health (SDH, i.e., education level and socioeconomic status). However, few studies have determined the role of SDH and other determinants of health (ODH, i.e., diabetes knowledge and self-care scores) in achieving T2DM goals during effective multidisciplinary interventions. We aimed to examine a multicomponent integrated care (MIC) program on diabetes care goals and determine the effect of SDH and ODH on T2DM patients. Methods A before-and-after design (a pretest, a 5-month intervention, and a follow-up) was used in a T2DM population from Mexico City. The SDH included education level and socioeconomic status; the ODH included diabetes knowledge, self-care scores, and deltas (i.e., differences between baseline of T2DM. SDH, such as education level, and ODH (diabetes knowledge and self-care scores at baseline) play a key role in improving glycemic control in these settings.Background The biosynthesis of high value-added compounds using metabolically engineered strains has received wide attention in recent years. Myo-inositol (inositol), an important compound in the pharmaceutics, cosmetics and food industries, is usually produced from phytate via a harsh set of chemical reactions. Recombinant Escherichia coli strains have been constructed by metabolic engineering strategies to produce inositol, but with a low yield. The proper distribution of carbon flux between cell growth and inositol production is a major challenge for constructing an efficient inositol-synthesis pathway in bacteria. Construction of metabolically engineered E. coli strains with high stoichiometric yield of inositol is desirable. Results In the present study, we designed an inositol-synthesis pathway from glucose with a theoretical stoichiometric yield of 1 mol inositol/mol glucose. Recombinant E. coli strains with high stoichiometric yield (> 0.7 mol inositol/mol glucose) were obtained. Inositol was successftol from glucose in recombinant E. coli was optimized by metabolic engineering strategies. The metabolically engineered E. coli strains represent a promising method for future inositol production. This study provides an essential reference to obtain a suitable distribution of carbon flux between glycolysis and inositol synthesis.Background Aim was to investigate age-dependent changes in the prostate of castrated dogs in computed tomographic (CT) examination. Thirty-six canine prostates were evaluated in pre- and post-contrast CT scans. Dogs were divided in groups with homogenous prostatic tissue (25/36) and with tissue alterations (11/36). Prostatic attenuation in Hounsfield Units (HU) and prostatic size were measured and a ratio of the prostatic size to the sixth lumbar vertebra was calculated. Additionally, the CT images of the prostate were compared with ultrasound examination. Results In pre-contrast CT scans no significant differences were found in prostatic size between homogenous and altered prostatic tissue groups whereas prostatic attenuation differed significantly in post-contrast CT between these groups. The homogenous tissue pattern of homogeneous prostates could be confirmed in CT images and in ultrasound examination. Concerning prostates with alterations, the results differed between ultrasound and CT examination in four cases of 11 dogs with tissue alterations. Selleckchem fMLP Conclusions CT is beneficial to examine the prostate of castrated dogs. The prostatic attenuation is characteristic for the prostatic morphology, which can vary due to ageing processes. Differences in attenuation and size can be found between prostates of castrated and intact dogs. Using contrast agent, CT can visualize prostatic alterations, which were not seen in ultrasound. The presented results should be considered preliminary until a study with larger sample size and histologic examination of the prostates is performed.Background Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated. Methods To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to T-cell differentiation in both primary T-cells and mice treated with PM. Results We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse.
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