Recent studies have revealed robust metabolic changes during cell differentiation. Mitochondria, the organelles where many vital metabolic reactions occur, may play an important role. Here, we report the involvement of SIRT3-regulated mitochondrial stress in osteoblast differentiation and bone formation. In both the osteoblast cell line MC3T3-E1 and primary calvarial osteoblasts, robust mitochondrial biogenesis and supercomplex formation were observed during differentiation, accompanied by increased ATP production and decreased mitochondrial stress. Inhibition of mitochondrial activity or an increase in mitochondrial superoxide production significantly suppressed osteoblast differentiation. During differentiation, SOD2 was specifically induced to eliminate excess mitochondrial superoxide and protein oxidation, whereas SIRT3 expression was increased to enhance SOD2 activity through deacetylation of K68. Both SOD2 and SIRT3 knockdown resulted in suppression of differentiation. Meanwhile, mice deficient in SIRT3 exhibited obvious osteopenia accompanied by osteoblast dysfunction, whereas overexpression of SOD2 or SIRT3 improved the differentiation capability of primary osteoblasts derived from SIRT3-deficient mice. These results suggest that SIRT3/SOD2 is required for regulating mitochondrial stress and plays a vital role in osteoblast differentiation and bone formation.

BackgroundAs social media becomes increasingly popular online venues for engaging in communication about public health issues, it is important to understand how users promote knowledge and awareness about specific topics.ObjectiveThe aim of this study is to examine the frequency of discussion and differences by race and ethnicity of cancer-related topics among unique users via Twitter.MethodsTweets were collected from April 1, 2014 through January 21, 2015 using the Twitter public streaming Application Programming Interface (API) to collect 1% of public tweets. Twitter users were classified into racial and ethnic groups using a new text mining approach applied to English-only tweets. Each ethnic group was then analyzed for frequency in cancer-related terms within user timelines, investigated for changes over time and across groups, and measured for statistical significance.ResultsObservable usage patterns of the terms "cancer", "breast cancer", "prostate cancer", and "lung cancer" between Caucasian and African American groups were evident across the study period. We observed some variation in the frequency of term usage during months known to be labeled as cancer awareness months, particularly September, October, and November. Interestingly, we found that of the terms studied, "colorectal cancer" received the least Twitter attention.ConclusionsThe findings of the study provide evidence that social media can serve as a very powerful and important tool in implementing and disseminating critical prevention, screening, and treatment messages to the community in real-time. The study also introduced and tested a new methodology of identifying race and ethnicity among users of the social media. Study findings highlight the potential benefits of social media as a tool in reducing racial and ethnic disparities.

Results from recent studies suggest that aberrant microRNA expression is common in numerous cancers. Although miR-338-3p has been implicated in hepatocellular carcinoma, its role in gastric cancer is unknown. To this end, we report that miR-338-3p is downregulated in both gastric cancer tissue and cell lines. Forced expression of miR-338-3p inhibited cell proliferation and clonogenicity and induced a G 1 -S arrest as well as apoptosis in gastric cancer cells. Furthermore, P-Rex2a (PREX2) was identified as a direct target of miR-338-3p, and silencing P-Rex2a resulted in the same biologic effects of miR-338-3p expression in gastric cancer cells. Furthermore, both enforced expression of miR-338-3p or silencing of P-Rex2a resulted in activation of PTEN, leading to a decline in AKT phosphorylation. Also, miR-338-3p markedly inhibited the in vivo tumorigenicity in a nude mouse xenograft model system. These results demonstrate that miR-338-3p affects gastric cancer progression through PTEN-AKT signaling by targeting P-Rex2a in gastric cancer cells, which posits miR-338-3p as a novel strategy for gastric cancer treatment.