Expression Atlas update: gene and protein expression in multiple species.

The EMBL-EBI Expression Atlas is an added value knowledge base that enables researchers to answer the question of where (tissue, organism part, developmental stage, cell type) and under which conditions (disease, treatment, gender, etc) a gene or protein of interest is expressed. Expression Atlas brings together data from >4500 expression studies from >65 different species, across different conditions and tissues. It makes these data freely available in an easy to visualise form, after expert curation to accurately represent the intended experimental design, re-analysed via standardised pipelines that rely on open-source community developed tools. Each study's metadata are annotated using ontologies. The data are re-analyzed with the aim of reproducing the original conclusions of the underlying experiments. Expression Atlas is currently divided into Bulk Expression Atlas and Single Cell Expression Atlas. Expression Atlas contains data from differential studies (microarray and bulk RNA-Seq) and baseline studies (bulk RNA-Seq and proteomics), whereas Single Cell Expression Atlas is currently dedicated to Single Cell RNA-Sequencing (scRNA-Seq) studies. The resource has been in continuous development since 2009 and it is available at https://www.ebi.ac.uk/gxa

Concurrent Driver Gene Mutations as Negative Predictive Factors in Epidermal Growth Factor Receptor-Positive Non-Small Cell Lung CancerResearch in context

Background: Tyrosine kinase inhibitors (TKIs) are clinically effective in non-small cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) oncogene mutations. Genetic factors, other than EGFR sensitive mutations, that allow prognosis of TKI treatment remain undefined. Methods: We retrospectively screened 423 consecutive patients with advanced NSCLC and EGFR 19del or 21L858R mutations. A total of 71 patients whose progression-free survivals (PFS) were shorter than 6 months or longer than 24 months were included and stratified into separate groups. Genetic background discrepancy was analysed in the two groups using next generation sequencing (NGS). Findings: Sensitive EGFR mutations of 19del or 21L858R were detected by NGS in all patients; the 21L858R mutation was the major type. The most frequent accompanying somatic mutations were TP53, RB1, MAP2K. ALK fusion, MET amplification, and BRAF V600E were found only in the short PFS group. Concurrent pretreament T790 M mutation was found in both groups, but was proportionally higher in the short PFS group. In the short PFS group, patients had significantly more driver gene mutations than in long PFS group (P = 0·018). The numbers of concomitant somatic mutations, EGFR pathway-related mutations, and tumor mutation burden (TMB) were not significantly different between the two groups. Interpretation: Co-occuring driver gene mutations were negative predictive factors of TKI therapy in EGFR-mutated patients. This study highlights the importance of exploring co-occuring genomic alterations before initiation of EGFR-TKIs. Keywords: Non-small cell lung cancer, Epidermal growth factor receptor tyrosine kinase inhibitor, Predictive factor, Co-occurring mutation

Co-Occurrence of Pheochromocytoma-Paraganglioma and Cyanotic Congenital Heart Disease: A Case Report and Literature Review

Pheochromocytoma and paraganglioma (PHEO-PGL) and cyanotic congenital heart disease (CCHD) are both rare diseases. We reported a 30-year-old patient with a right adrenal gland nodule and a retroperitoneal mass and history of functional single atrium and ventricle. 123I-metaiodobenzylguanidine scintigraphy showed intense uptake in both lesions. Laboratory investigation demonstrated elevated urinary norepinephrine. Preoperative α-blockade was initiated. A successful open resection of right adrenal and retroperitoneal masses was performed. Pathological examination confirmed PHEO-PGL. Postoperative urinary norepinephrine returned to normal level. A systematic case review in English publications in PubMed and EMBASE suggested a hypothesis that there may exist a possible link between PHEO-PGL and hypoxia from CCHD, which was also indicated in our case. Due to higher risk for PHEO-PGL, a lower threshold of suspicion should be considered in CCHD patients. Therefore, active screening and early treatment of PHEO-PGL are recommended in CCHD patients and clinicians should keep on a long-term follow-up to monitor PHEO-PGL recurrence if hypoxia is not corrected

table_1_Co-Occurrence of Pheochromocytoma-Paraganglioma and Cyanotic Congenital Heart Disease: A Case Report and Literature Review.DOCX

<p>Pheochromocytoma and paraganglioma (PHEO-PGL) and cyanotic congenital heart disease (CCHD) are both rare diseases. We reported a 30-year-old patient with a right adrenal gland nodule and a retroperitoneal mass and history of functional single atrium and ventricle. ¹²³I-metaiodobenzylguanidine scintigraphy showed intense uptake in both lesions. Laboratory investigation demonstrated elevated urinary norepinephrine. Preoperative α-blockade was initiated. A successful open resection of right adrenal and retroperitoneal masses was performed. Pathological examination confirmed PHEO-PGL. Postoperative urinary norepinephrine returned to normal level. A systematic case review in English publications in PubMed and EMBASE suggested a hypothesis that there may exist a possible link between PHEO-PGL and hypoxia from CCHD, which was also indicated in our case. Due to higher risk for PHEO-PGL, a lower threshold of suspicion should be considered in CCHD patients. Therefore, active screening and early treatment of PHEO-PGL are recommended in CCHD patients and clinicians should keep on a long-term follow-up to monitor PHEO-PGL recurrence if hypoxia is not corrected.</p

PAMs ameliorates the imiquimod-induced psoriasis-like skin disease in mice by inhibition of translocation of NF-κB and production of inflammatory cytokines

<div><p>Psoriasis is a chronic and persistent inflammatory skin disease seriously affecting the quality of human life. In this study, we reported an ancient formula of Chinese folk medicine, the natural plant antimicrobial solution (PAMs) for its anti-inflammatory effects and proposed the primary mechanisms on inhibiting the inflammatory response in TNF-α/IFN-γ-induced HaCaT cells and imiquimod-induced psoriasis-like skin disease mouse model. Two main functional components of hydroxysafflor Yellow A and allantoin in PAMs were quantified by HPLC to be 94.2±2.2 and 262.9±12.5 μg/mL respectively. PAMs could significantly reduce the gene expression and inflammatory cytokines production of Macrophage-Derived Chemokine (MDC), IL-8 and IL-6 in TNF-α/IFN-γ-induced HaCaT cells. PAMs also significantly ameliorates the psoriatic-like symptoms in a mouse model with the evaluation scores for both the single (scales, thickness, erythema) and cumulative features were in the order of blank control < Dexamethasone < PAMs < 50% ethanol < model groups. The results were further confirmed by hematoxylin-eosin staining, RT-qPCR and immunohistochemistry. The down-regulated gene expression of <i>IL-8</i>, <i>TNF-α</i>, <i>ICAM-1 and IL-23</i> in mouse tissues was consistent with the results from those of the HaCaT cells. The inhibition of psoriasis-like skin inflammation by PAMs was correlated with the inactivation of the translocation of P65 protein into cellular nucleus, indicating the inhibition of the inflammatory NF-κB signaling pathway. Taken together, these findings suggest that PAMs may be a promising drug candidate for the treatment of inflammatory skin disorders, such as psoriasis.</p></div

Effects of PAMs on erythema, scaling and thickening in imiquimod-induced mouse skin.

<p>A: Phenotypical presentation of mouse back skin after 6 days’ treatment. B: The scores of scales, thickness, erythema and the cumulative scores are shown for each group. The data are shown as mean± S.D (n = 6). Significant differences compared to model group: *<i>p</i> < 0.05.</p

PAMs ameliorates the psoriasis-like symptoms and skin inflammation in imiquimod-induced mice.

<p>A: Histopathological investigation in each group (×100). Black arrows represent the presence of horny layer and granular layer. B: Immunohistochemistry analysis was performed for Ki67 and ICAM-1 protein of the back skin of psoriatic mice, PAMs treatment could effectively decrease the expression of Ki67 and ICAM-1 protein (×100). Red arrows represent the overexpression of Ki67 and ICAM-1 protein. C: Epidermal thickness was measured. Data are the mean values ± SD (n = 5). D: PAMs treatment led to the significant decrease of TNF-α levels in the serum of each group. #<i>p</i> < 0.05 <i>vs</i> control group; *<i>p</i> < 0.05 <i>vs</i> model group. Bar = 100 μm.</p

Inhibitory effects of PAMs on NF-κB activation and nuclear translocation in HaCaT cells.

<p>A: Cellular localization of p65 was analyzed by immunofluorescence staining. HaCaT cells were pretreated with or without 3.0% (v/v) PAMs or 1.5% (v/v) ethanol for 6 h and incubated with TNF-α and IFN-γ (each 10.0 ng/mL) for 30 min, later, the cells were incubated with anti-p65 and Cy3-conjugated secondary antibodies subsequently. Arrows indicate that NF-κB does not translocate to the nucleus. Images are representative of three independent experiments. B: The translocation rate was counted. ##<i>p</i> < 0.01 vs control group; **<i>p</i> < 0.01 vs model group. Bar = 50μm.</p

Primer sequences of mouse genes by quantitative real-time PCR.

<p>Primer sequences of mouse genes by quantitative real-time PCR.</p