Subject(s)
COVID-19 , Pneumonia , Humans , Inflammation/genetics , Lung , SARS-CoV-2 , Serologic TestsABSTRACT
Gastric cancer has the second highest incidence among all the malignancies in China, just below lung cancer. Gastric cancer is likewise one of the main sources of cancer related passings. Gastric cancer therefore remains a huge threat to human health. The primary reason is absence of high sensitivity and specificity for early detection while the pathogenesis of GC is stayed muddled. During the last few decades, a lot of GC related genes have been identified. To find candidate GC related variant in these GC related genes, we conducted this case-control study. 29 tagSNPs located in 7 GC related genes were included. 228 gastric cancer patients and 299 healthy controls were enrolled. Significant differences were found between the genotype frequencies of EFNA1 rs4971066 polymorphism between gastric cancer patients and healthy controls. The result indicated that ephrin-A1 tagSNP rs4971066 GT/TT genotypes was significantly associated with reduced susceptibility of gastric cancer development.
ABSTRACT
BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1ß and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.
Subject(s)
COVID-19/pathology , Hemorrhage/pathology , Lung Transplantation , Lung/pathology , Lymph Nodes/pathology , Pulmonary Fibrosis/pathology , B-Lymphocytes/pathology , B-Lymphocytes/ultrastructure , B-Lymphocytes/virology , COVID-19/genetics , COVID-19/metabolism , COVID-19/surgery , Chromatography, Liquid , Flow Cytometry , Gene Expression Profiling , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Killer Cells, Natural/pathology , Killer Cells, Natural/ultrastructure , Killer Cells, Natural/virology , Lung/metabolism , Lung/ultrastructure , Lung/virology , Lymph Nodes/metabolism , Lymph Nodes/ultrastructure , Lymph Nodes/virology , Macrophages, Alveolar/pathology , Macrophages, Alveolar/ultrastructure , Macrophages, Alveolar/virology , Male , Middle Aged , Monocytes/pathology , Monocytes/ultrastructure , Monocytes/virology , Neutrophils/pathology , Neutrophils/ultrastructure , Neutrophils/virology , Nitric Oxide Synthase Type II/metabolism , Proteomics , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/surgery , RNA-Seq , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/pathology , T-Lymphocytes/ultrastructure , T-Lymphocytes/virology , Tandem Mass SpectrometryABSTRACT
ARHGEF18 has been identified as upregulated in the lung tissues of rat models of pulmonary artery hypertension introduced by hypoxia or monocrotaline (MCT). We used online SNP function prediction tools to screen the candidate SNPs that might be associated with the regulation of the ARHGEF18 expression. The result suggested that rs3745357 located in the 3'-untranslated region of ARHGEF18 is probably a genetic modifier in the process. In the present study, we aimed to investigate the association between ARHGEF18 rs3745357 polymorphism and nonidiopathic pulmonary arterial hypertension susceptibility (niPAH). A total of 293 participants were included in the case-control study (117 patients and 176 healthy controls). The rs3745357 variant was discriminated by using cleaved amplification polymorphism (CAP) sequence-tagged site technology. Although the overall allele and genotype frequencies of rs3745357 in niPAH patients were close to those of the control group, significant differences have been identified when we further divided the niPAH patients into subgroups with or without coronary heart disease (CHD). Rs3745357 C allele frequency was significantly higher in niPAH patients without CHD history (p = 0.001), while the frequency was significantly lower in niPAH patients with CHD history (p = 0.017) when compared to control subjects. The distribution of genotype frequencies was also quite different. After adjustment by gender and age, significant differences were found between patients with CHD history and controls. The results suggest that the ARHGEF18 rs3745357 variant may be used as a marker for the genetic susceptibility to niPAH.
