Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma / 医学前沿

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

Molecular mechanism of SARS-Cov-2 components caused ARDS in murine model

COVID-19 has become a major challenge to global health, and until now, no efficient antiviral agents have been developed. The SARS-CoV-2 infection is characterized by pulmonary and systemic inflammation in severe patients, and acute respiratory distress syndrome (ARDS) caused respiratory failure contributes to most mortalities. There is an urgent need for developing effective drugs and vaccines against SARS-CoV-2 and COVID-19 caused ARDS. However, most researchers cannot perform SARS-CoV-2 related researches due to lacking P3 or P4 facility. We developed a non-infectious, highly safety, time-saving SARS-CoV-2 components induced murine model to study the SARS-CoV-2 caused ARDS and cytokine storm syndrome (CSS). We also investigated mAbs and inhibitors which potentially neutralize the pro-inflammatory phenotype of COVID-19, and found that anti-IL-1, anti-IL-6, anti-TNF, anti-GM-CSF mAbs, p38 inhibitor, and JAK inhibitor partially relieved CSS. Besides, anti-IL-6, anti-TNF, anti-GM-CSF mAbs and inhibitors of p38, ERK, and MPO somewhat reduced neutrophilic alveolitis in the lung. In all, we established the murine model mimic of COVID-19, opening a biosafety and less time-consuming avenue for clarifying the mechanism of ARDS and CSS in COVID-19 and developing the therapeutic drugs.

Study on mutation in V_(79) cells and transformation in NIH/3T3 cells induced by the extract 261-B_2-3 of Alternaria alternata / 中国病理生理杂志

The extract 261-B_2-3 of Alternaria alternata isolated from the corn in Linxian county which is an area with high incidence of esophageal cancer induced 6-thioguanine-resistant mutants in V_(79) cells and transformation in NIH/3T3 cells. There is mutation activity in presence or absence of rat-liver-microsome prepar-ations. Treated with a range of eoncentration(32ug/ml, 64ug/ml, 128ug/ml) of the extract, high rate of transformation different from the rate treated by solvent control, is found.The results show that this extract contains direct mutagen. The high infestationincidence of Alternaria alternata in the corn of Linxian county might play an important role in the causation ofesophageal cancer in this area.