Utilizing network pharmacology and experimental validation to investigate the underlying mechanism of Denglao Qingguan decoction against HCoV-229E.

Background: Denglao Qingguan decoction (DLQGD) has been extensively utilized for the treatment of colds, demonstrating significant therapeutic efficacy. Human Coronavirus 229E (HCoV-229E) is considered a crucial etiological agent of influenza. However, the specific impact and underlying mechanisms of DLQGD on HCoV-229E remain poorly understood. Methods: Active ingredients and targets information of DLQGD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), literature search, and Swiss ADEM database. The Genecard database was used to collect HCoV-229E related targets. We built an "ingredient-target network" through Cytoscape. Protein - Protein interaction (PPI) networks were mapped using the String database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were enriched using the DAVID database. Then, we used molecular docking techniques to verify the binding activity between the core compounds and the core gene targets. Finally, in vitro experiments were conducted to validate DLQGD's antiviral activity against HCoV-229E and assess its anti-inflammatory effects. Results: In total, we identified 227 active components in DLQGD. 18 key targets involved in its activity against HCoV-229E. Notably, the core active ingredients including quercetin, luteolin, kaempferol, ß-sitosterol, and apigenin, and the core therapeutic targets were CXCL8, RELA, MAPK14, NFKB1, and CXCL10, all associated with HCoV-229E. KEGG enrichment results included IL-17 signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway and so on. The core active ingredients and the core therapeutic targets and Human Aminopeptidase N (ANPEP) all showed good binding activity by molecular docking verification. In vitro, DLQGD exhibited anti-HCoV-229E activity and anti-inflammatory effects. Conclusion: Our study suggests that DLQGD has both effects of anti-HCoV-229E and anti-inflammatory. The core active ingredients (quercetin, luteolin, kaempferol, ß-sitosterol, apigenin) and the core therapeutic targets (CXCL8, RELA, MAPK14, NFKB1, CXCL10) may play key roles in the pharmacological action of DLQGD against HCoV-229E.

Circulating lncRNA DANCR as a potential auxillary biomarker for the diagnosis and prognostic prediction of colorectal cancer.

Studies have shown that long non-coding RNAs (lncRNAs) play vital roles in the development of cancer, including colorectal cancer (CRC). Our purpose is to validate the diagnostic value of serum differentiation antagonizing non-protein coding RNA (DANCR) in CRC by focusing on its expression and clinical application. lncRNA expression profiles of CRC patients were obtained and analyzed by repurposing the publically available microarray data. Tissue or serum specimens were obtained from 40 patients with primary CRC, 10 patients with recurrent CRC, 40 patients with colorectal polyps, and 40 healthy controls. It was found that DANCR level in the CRC tissue and serum was significantly increased, and serum DANCR expression was decreased in post-operative patients as compared with that in pre-treatment patients and recurrent patients. In addition, serum DANCR expression was significantly correlated with different TNM stages. Correlation analysis of DANCR and other diagnostic indicators showed that the serum DANCR expression level was significantly correlated with CA199 but not with CEA in CRC patients. As for diagnostic efficiency by ROC analysis, the area under the curve (AUC) of serum DANCR was higher than that of CEA and CA199 in CRC group vs. colorectal polyp group. Simultaneous detection of DANCR, CEA and CA199 yielded the highest sensitivity and AUC as compared with either of them alone. Taken together, serum DANCR was up-regulated in CRC patients and high expression of DANCR may prove to be a potential biomarker for the diagnosis of CRC.

Dysregulation of serum microRNA-574-3p and its clinical significance in hepatocellular carcinoma.

Objectives To explore microRNA-574-3p expression in serum of patients with hepatocellular carcinoma and investigate correlations between serum microRNA-574-3p expression and the development and prognosis of hepatocellular carcinoma. Design and methods Serum samples were collected from 70 patients with primary hepatocellular carcinoma, 40 patients with cirrhosis and 45 healthy controls. Serum microRNA-574-3p expression levels were detected by real-time quantitative polymerase chain reaction. The linearity, specificity and reproducibility were evaluated. In addition, the diagnostic value of microRNA-574-3p and its correlations with clinicopathologic features were assessed. Results The relative expression of microRNA-574-3p in hepatocellular carcinoma patients, cirrhosis patients and healthy controls was 2.306 (1.801-3.130), 1.362 (0.994-1.665) and 1.263 (0.765-1.723), respectively, indicating that it was significantly higher in hepatocellular carcinoma patients than that in the other two groups ( U = 439.5, 514.5, both P < 0.0001) and was significantly correlated with hepatitis B virus DNA copies ( U = 383.0, P = 0.018). In hepatitis B virus-positive hepatocellular carcinoma patients, the relative expression of microRNA-574-3p was significantly correlated with hepatitis B virus DNA concentration ( r = 0.348, P = 0.022). Compared with healthy control group, AUCROC of serum microRNA-574-3p in hepatocellular carcinoma group was 0.837 with 95% CI: 0.763-0.910. Combining microRNA-574-3p, AFU and alpha-fetoprotein together, the sensitivity was highest compared with other markers alone or combined. Conclusions The relative expression of serum microRNA-574-3p in hepatocellular carcinoma patients was significantly higher than that in cirrhosis patients and healthy controls, and it may be an important biomarker in the auxiliary diagnosis of hepatocellular carcinoma.

A peptide probe for the detection of neurokinin-1 receptor by disaggregation enhanced fluorescence and magnetic resonance signals.

We report a novel peptide probe for the detection of neurokinin-1 receptor using disaggregation-caused signal enhancement. The probe was obtained via the aggregation of a modified substance P in a terpyridine-Fe (II) complex with Gd (III)-DOTA into well-defined nanostructures, which effectively weaken ligand fluorescence and slow the exchange rate of inner-sphere water molecules. This probe disaggregates upon binding to the neurokinin-1 receptor and activates the contrast agents to generate a fluorescent signal that positively enhances magnetic resonance imaging contrast and allows for the detection of overexpressed receptors on tumor cells and the identification of lung cancer using serum samples.