Life sciences
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Colorectal cancer (CRC) is one of the most common malignancies in the world. Emerging evidence has shown that dysregulation of tripartite motif (TRIM) family proteins is strongly correlated with the tumorigenesis of CRC. Here, we evaluated the biological roles of TRIM66, a member of TRIM family, in the progression of CRC. ⋯ Knockdown of TRIM66 reduced the activation of JAK2/STAT3 signaling pathway in CRC cells. Treatment with AG490, an inhibitor of JAK2/STAT3 signaling pathway, enhanced the inhibitory effects of TRIM66 knockdown on cell proliferation, migration and invasion. These findings suggested that knockdown of TRIM66 exhibited anti-tumor activity through inhibiting the JAK2/STAT3 signaling pathway in CRC cells.
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In prostate cancer development, the androgen receptor (AR) signaling plays a crucial role during both formation of early prostate lesions and progression to the lethal, incurable castration resistant stage. Accordingly, numerous approaches have been developed to inhibit AR activity including androgen deprivation therapy, application of the AR antagonists as well as the use of taxanes. However, these treatments, although effective initially, resistance inevitably occur for most of the patients within several years and limiting the therapeutic efficacy. ⋯ Accumulating evidences have suggested that synthesis of AR splicing variants, in particular, the constitutively active AR-V7, is one of the most important mechanisms that contribute to the abnormal AR signaling. In addition, clinical data also highlight the potential of using AR-V7 as a predictive biomarker and a therapeutic target in metastatic castration resistant prostate cancer (mCRPC). In this review, we summarize the recent findings concerning the specific role of AR-V7 in CRPC progression, drug resistance and its potential value in clinical assessment.
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The activation of the angiotensin (Ang) II after acute kidney injury (AKI) triggers oxidative stress and inflammatory cascade which involved not only the kidneys but also the brain. Ang II through the Ang II type 1 receptor (AT1R) may have deleterious effects on hippocampal synaptic transmission and cognitive functions under uremic encephalopathy. The present study was conducted to examine the effects of AT1R antagonist on AKI-induced cognitive and synaptic plasticity impairment. ⋯ The present study conclusively demonstrated a protective role of AT1R antagonist losartan in hippocampal complication and neurocognitive dysfunction after AKI via modulating oxidative stress.