New tale on LianHuaQingWen: IL6R/IL6/IL6ST complex is a potential target for COVID-19 treatment.

LianHuaQingWen (LHQW) improves clinical symptoms and alleviates the severity of COVID-19, but the mechanism is unclear. This study aimed to investigate the potential molecular targets and mechanisms of LHQW in treating COVID-19 using a network pharmacology-based approach and molecular docking analysis. The main active ingredients, therapeutic targets of LHQW, and the pathogenic targets of COVID-19 were screened using the TCMSP, UniProt, STRING, and GeneCards databases. According to the "Drug-Ingredients-Targets-Disease" network, Interleukin 6 (IL6) was identified as the core target, and quercetin, luteolin, and wogonin as the active ingredients of LHQW associated with IL6. The response to lipopolysaccharide was the most significant biological process identified by gene ontology enrichment analysis, and AGE-RAGE signaling pathway activation was prominent based on the interaction between LHQW and COVID-19. Protein-protein docking analysis showed that IL6 receptor (IL6R)/IL6/IL6 receptor subunit beta (IL6ST) and Spike protein were mainly bound via conventional hydrogen bonds. Furthermore, protein-small molecule docking showed that all three active ingredients could bind stably in the binding model of IL6R/IL6 and IL6ST. Our findings suggest that LHQW may inhibit the lipopolysaccharide-mediated inflammatory response and regulate the AGE-RAGE signaling pathway through IL6. In addition, the N-terminal domain of the S protein of COVID-19 has a good binding activity to IL6ST, and quercetin and wogonin in LHQW may affect IL6ST-mediated IL6 signal transduction and a large number of signaling pathways downstream to other cytokines by directly affecting protein-protein interaction. These findings suggest the potential molecular mechanism by which LHQW inhibits COVID-19 through the regulation of IL6R/IL6/IL6ST.

[Therapeutic efficacy of Nexavar on liver cancer and its relation to the expression of Ki-67 and CD34].

OBJECTIVE: To study the therapeutic effects of Nexavar on liver cancer and its relation to the expressions of Ki-67 and CD34. METHODS: Twenty-eight patients with liver cancer were treated with Nexavar. The therapeutic efficacy of Nexavar on liver cancer was observed. Liver cancer tissues were examined for the expressions of Ki-67 and CD34 by immunohistochemistry. Microvessel density (MVD) was calculated according to the expression of CD34. RESULTS: Of 28 patients, none achieved a complete response (CR), 12 had a partial response (PR), 7 had stable disease (SD), and 9 progressive disease (PD). The efficacy of Nexavar was associated significantly with Ki-67 expression. The mean MVD count was 346.03-/+146.98 in PR patients, and 89.14-/+45.66 in PD patients. There was a significant difference in MVD between PR and PD patients. CONCLUSION: There is a better efficacy of Nexavar in treatment of liver cancer in the patients who had Ki-67-positive expression and high MVD count.