Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells.

Triple-negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes. Recently, the activation of NF-κB, which is involved in the growth and survival of malignant tumors, has been demonstrated in TNBC, suggesting that NF-κB may serve as a new therapeutic target. In the present study, we examined whether dimethyl fumarate (DMF), an NF-κB inhibitor, induces apoptosis in TNBC cells and enhances the apoptosis-inducing effect of paclitaxel and adriamycin. Cell survival was analyzed by the trypan blue assay and apoptosis assay. Protein detection was examined by immunoblotting. The activation of NF-κB p65 was correlated with poor prognosis in patients with TNBC. DMF induced apoptosis in MDA-MB-231 and BT-549 cells at concentrations that were non-cytotoxic to the normal mammary cell line MCF-10A. Furthermore, DMF inhibited NF-κB nuclear translocation and Survivin, XIAP, Bcl-xL, and Bcl-2 expression in MDA-MB-231 and BT-549 cells. Moreover, DMF enhanced the apoptosis-inducing effect of paclitaxel and adriamycin in MDA-MB-231 cells. These findings suggest that DMF may be an effective therapeutic agent for the treatment of TNBC, in which NF-κB is constitutively active. DMF may also be useful as an adjuvant therapy to conventional anticancer drugs.

The Relationship of Dry Eye Disease with Depression and Anxiety: A Naturalistic Observational Study.

PURPOSE: In recent years, the relationship between dry eye disease (DED) and psychiatric disorders has been gaining attention. The relationship between dry eye symptoms and psychiatric symptoms has been reported in multiple retrospective studies. However, in previous studies there have been limitations to these observations, such as a lack of close examination of either DED or mood symptoms. METHODS: In this study, we evaluated the psychological state and social functionality of DED patients by administering validated psychiatric tests as well as ophthalmologic examinations twice during the course of DED treatment. Forty subjects (61.3 ± 18.1-years old) received the primary psychiatric assessments and 26 received the secondary psychiatric assessments. RESULTS: In a cross-sectional examination, we found patients with depressive and/or anxiety symptoms had higher Dry Eye Related Quality of Life Score (DEQ) scores, whereas the objective symptoms of DED did not differ between groups. We also found a positive relationship between depression/anxiety scores and DED subjective symptoms. On the other hand, in longitudinal examination, we found psychiatric symptoms had no impact on subjective and objective DED symptoms throughout the course of DED symptoms. CONCLUSIONS: We found depression and anxiety were related to the subjective symptoms of DED but not the objective symptoms. TRANSLATIONAL RELEVANCE: It is important to pay attention to psychiatric symptoms in patients with DED and an investigation into appropriate treatment strategies for patients with DED in combination with psychiatric symptoms is needed in the future.

Effects of a perilymphatic fistula on the passive vibration response of the basilar membrane.

In this study, a three-dimensional finite-element model of the passive human cochlea was created. Dynamic behavior of the basilar membrane caused by the vibration of the stapes footplate was analyzed considering a fluid-structure interaction with the cochlear fluid. Next, the effects of a perilymphatic fistula (PLF) on the vibration of the cochlea were examined by making a small hole on the wall of the cochlea model. Even if a PLF existed in the scala vestibuli, a traveling wave was generated on the basilar membrane. When a PLF existed at the basal end of the cochlea, the shape of the traveling wave envelope showed no remarkable change, but the maximum amplitude became smaller at the entire frequency range from 0.5 to 5kHz and decreased with decreasing frequency. In contrast, when a PLF existed at the second turn of the cochlea, the traveling wave envelope showed a notch at the position of the PLF and the maximum amplitude also became smaller. This model assists in elucidating the mechanisms of hearing loss due to a PLF from the view of dynamics.