A New Strategy to Fight Metallodrug Resistance: Mitochondria-Relevant Treatment through Mitophagy to Inhibit Metabolic Adaptations of Cancer Cells.

Metabolic adaptations can help cancer cells to escape from chemotherapeutics, mainly involving autophagy and ATP production. Herein, we report a new rhein-based cyclometalated IrIII complex, Ir-Rhein, that can accurately target mitochondria and effectively inhibit metabolic adaptations. The complex Ir-Rhein induces severe mitochondrial damage and initiates mitophagy to reduce the number of mitochondria and subsequently inhibit both mitochondrial and glycolytic bioenergetics, which eventually leads to ATP starvation death. Moreover, Ir-Rhein can overcome cisplatin resistance. Co-incubation experiment, 3D tumor spheroids experiment and transcriptome analysis reveal that Ir-Rhein shows promising antiproliferation performance for cisplatin-resistant cancer cells with the regulation of platinum resistance-related transporters. To our knowledge, this is a new strategy to overcome metallodrug resistance with a mitochondria-relevant treatment.

[Study on the risk factors related to severe acute respiratory syndrome among close contactors in Beijing].

OBJECTIVE: To understand the risk factors on severe acute respiratory syndrome (SARS) among their contacts and to develop effective strategy for its control. METHODS: Available epidemiological data of SARS cases and close contacts were reviewed and analyzed by SPSS. RESULTS: Out of the 2195 close contacts, 138 (6.3%) were diagnosed as SARS. Among colleagues and classmates of SARS patients, the infection rate was 0.36% versus 31.71% in contacts among families and hospitals, 0.77% in schools. No one was infected among 459 close contacts to SARS in the working unit. CONCLUSIONS: Among close contacts, factors that facilitating transmission would include: time, extent, frequency and place of contact to the patients, as well as factors related to close contacts as way, time of isolation and age. One of the epidemiological characteristics was that SARS were as clustered in the family among those close contacts. It is important to control the spread of SARS through supervision on the close contacts to patients.