Identification of key genes associated with poor prognosis and neoplasm staging in gastric cancer.

BACKGROUND: Gastric cancer (GC) is highly biologically and genetically heterogeneous disease with poor prognosis. Increasing evidence indicates that biomarkers can serve as prediction and clinical intervention. Therefore, it is vital to identify core molecules and pathways participating in the development of GC. METHODS: In this study, GSE54129, GSE56807, GSE63089, and GSE118916 were used for identified overlapped 75 DEGs. GO and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed DEGs mainly enriched in biological process about collagen-containing extracellular matrix and collagen metabolic. Next, protein-protein interaction network was built and the hub gene was excavated. Clinicopathological features and prognostic value were also evaluated. RESULTS: Hub genes were shown as below, FN1, COL1A2, COL1A1, COL3A1, COL4A1, COL6A3, COL5A2, SPARC, PDGFRB, COL12A1. Those genes were upregulation in GC and related to the poor prognosis (except COL5A2, P = .73). What is more, high expression indicated worse T stage and tumor, node, metastasis stage in GC patients. Later, the results of 25 GC tumor specimens and 34 normal tissues showed that FN1, COL3A1, COL4A1, SPARC, COL5A2, and COL12A1 were significantly upregulated in cancer samples. CONCLUSION: Our study systematically explored the core genes and crucial pathways in GC, providing insights into clinical management and individual treatment.

Identification of hub genes and key pathways of paraquat-induced human embryonic pulmonary fibrosis by bioinformatics analysis and in vitro studies.

OBJECTIVE: Paraquat (N,N0-dimethyl-4,40-bipyridinium dichloride;PQ) is a highly toxic pesticide, which usually leads to acute lung injury and subsequent development of pulmonary fibrosis. The exact mechanism underlying PQ-induced lung fibrosis remain largely unclear and as yet, no specific treatment drugs have been approved. Our study aimed to identify its potential mechanisms of PQ-induced fibrosis through a modeling study in vitro studies and bioinformatics analysis. METHODS: Gene expression datasets associated with PQ-induced lung fibrosis were obtained from the Gene Expression Omnibus, wherefrom differentially expressed genes (DEGs) were identified using GEO2R. Functional enrichment analyses were performed using the Database for Annotation Visualization and Integrated Discovery. The DEGs analyzed by a protein-protein interaction network was constructed with the Search Tool for the Retrieval of Interacting Genes database. MCODE, a Cytoscape plugin, was subsequently used to identify the most significant modules. The expression of the key genes in PQ-induced pulmonary fibrotic tissues was verified by reverse transcription-quantitative PCR (RT-qPCR). RESULTS: Two datasets were analyzed and revealed 92 overlapping DEGs. Functional analysis demonstrated that these 92 DEGs were enriched in the 'TNF signaling pathway', 'CXCR chemokine receptor binding', and 'core promoter binding'. Moreover, nine hub genes were identified from the protein-protein interaction network formed from the DEGs. These results suggested that the TNF signaling pathway and nine hub genes are possibly involved in PQ-induced lung fibrosis progression. CONCLUSIONS: This integrative analysis identified candidate genes and pathways potentially involved in PQ-induced lung fibrosis, and could benefit future development of novel approaches for controlling and treating this disease.

Polydatin relieves paraquat-induced human MRC-5 fibroblast injury through inhibiting the activation of the NLRP3 inflammasome.

BACKGROUND: Paraquat (PQ) is a herbicide that is highly toxic to the lungs and kidneys. When it enters the body, it will disrupt the balance of the microenvironment in the body, induce a large number of inflammatory factors and cause cell damage. Polydatin (PD), resveratrol glycoside, has multiple pharmacological effects. However, the protective effect of PD on human embryo lung fibroblast damage caused by PQ poisoning has not been reported. The purpose of this study was to investigate the regulatory effect of PD on human embryo lung fibroblast damage caused by PQ poisoning. METHOD: The optimal experimental concentration of PQ for human embryonic lung fibroblast MRC-5 was 100 µmol/L, and then the cells of 100 µmol/L PQ group were treated with different concentrations of PD for 24 h. MTT assay to detect MRC-5 cell viability and flow cytometry to detect apoptosis. The corresponding kit was used to detect the contents of glutathione peroxidase (GSH-PX), malondialdehyde (MDA) and superoxide dismutase (SOD). Enzyme-linked immunosorbent assay (ELISA) to detect the levels of related inflammatory factors tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). Western blot detection of NLRP3 inflammatory body activation-related protein expression. RESULTS: Compared with the PQ group, cell activity, GSH-Px content, and SOD content in PD intervention group were significantly increased, while apoptosis, MDA content, inflammatory factor level, and activation-related proteins of the NLRP3 inflammasome were significantly reduced and were dose-dependent. CONCLUSIONS: PD can relieve PQ-induced human MRC-5 fibroblasts injury by reducing the inflammatory response, improving the antioxidant stress capacity, and inhibiting the activation of the NLRP3 inflammasome.

Acute cerebral infarction following a Trimeresurus stejnegeri snakebite: A case report.

RATIONALE: Acute cerebral infarction after snake bites is rare. The underlying mechanism causing the thrombotic process remains complex and unknown. PATIENT CONCERNS: We herein describe a 49-year-old female who was bitten by a Trimeresurus stejnegeri. After 4 days of biting, she developed acute ischemic infarct. DIAGNOSIS: The patient exhibited right side weakness and speech disturbances. Brain computed tomography (CT) scan showed no sign about cerebral hemorrhage symptoms, and brain magnetic resonance imaging (MRI) showed acute ischemic infarct in the left territory. The patient confirmed a diagnosis of acute cerebral infarction following a T. stejnegeri bite. INTERVENTIONS: The patient received an injection of polyvalent anti-snake venom serum, neuroprotective therapy, and anti-platelet aggregate treatment. OUTCOMES: At the 3-month follow-up visit, the patient's left lower extremity swelling disappeared, the right limb muscle strength recovered, and the modified Rankin scale (mRS) score was 4 points. LESSONS: The patient was diagnosed with acute ischemic infarct interrelated to snake bite; further investigations were needed to ascertain mechanism. The clinicians should pay more attention to identify potential victims of neurologic complications, to reduce the mortality rate of snake bite.