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.

Current status and future perspectives of metabolic network models of industrial microorganisms / 生物工程学报

Genome-scale metabolic network model (GSMM) is an extremely important guiding tool in the targeted modification of industrial microbial strains, which helps researchers to quickly obtain industrial microbes with specific traits and has attracted increasing attention. Here we reviewe the development history of GSMM and summarized the construction method of GSMM. Furthermore, the development and application of GSMM in industrial microorganisms are elaborated by using four typical industrial microorganisms (Bacillus subtilis, Escherichia coli, Corynebacterium glutamicum, and Saccharomyces cerevisiae) as examples. In addition, prospects in the development trend of GSMM are proposed.

Long-term effectiveness and safety of rituximab for the treatment of pemphigus / 中华皮肤科杂志

Objective:To assess the long-term effectiveness and safety of rituximab (RTX) for the treatment of pemphigus, and to evaluate the effect of RTX on immune indices.Methods:A retrospective study was conducted, and patients with pemphigus who received monotherapy or combination therapy with RTX (375 mg/m 2 body surface area, once a week for 4 consecutive weeks) were collected from the Department of Dermatology, Peking University First Hospital from February 2008 to July 2017. Levels of autoantibodies and proportion of B cells in patients were determined at baseline and different follow-up time points, and their changes and relationship with therapeutic effect were analyzed. Time-to-event outcomes (disease control, complete remission and relapse) were estimated using the Kaplan-Meier method. The median ( M) as well as 25th ( P25) and 75th ( P75) percentile values were calculated for repeatedly measured immune indices (autoantibodies and B cells) , and the median level of immune indice-time curve was drawn. Results:A total of 53 patients of Han nationality with pemphigus were included, including 40 with pemphigus vulgaris and 13 with pemphigus foliaceus. The male to female ratio was 0.96∶1, the median age was 37.4 years, and the median duration of disease was 13.4 months at baseline. The median follow-up duration ( P25, P75) was 37.5 (25.0, 54.7) months. Forty-eight (90.6%) patients achieved disease control, and the time to disease control was 1.7 (1.1, 3.2) months. Thirty-eight (71.7%) patients achieved complete remission, and the time to complete remission was 13.1 (9.6, 27.5) months. During the follow up, 12 of the 38 (31.6%) patients who had complete remission experienced recurrence, with the time to recurrence being 12.4 (4.8, 19.8) months. The median immune indice level-time curve showed that anti-Dsg1 and Dsg3 autoantibody levels decreased when skin lesions resolved, but increased when skin lesions relapsed. The most common severe adverse reaction was pulmonary infection, with a mortality rate of 3.8% (2/53) . Conclusions:RTX shows marked long-term effectiveness for the treatment of pemphigus. Pulmonary infection during treatment is worthy of the highest attention. The autoantibody levels can serve as an index for evaluating the effectiveness of RTX in the treatment of pemphigus.