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HMGB1 reduce DNA damage by binding KU70 to activate NHEJ pathway in colorectal cancer cells after radiation

by Xiuxin Liu, Yuhui Han, Ruixue Kuang, Wenjiong Sheng, Yan Zhang, Xinyu Jia, Xiaoxiao Gao, Yanchao Ma

DNA damage-induced by radiotherapy is a critical factor in promoting the death of colorectal cancer cells (CRC). Although high mobility group box 1 (HMGB1) reportedly plays a vital role in tumor radioresistance by modulating DNA damage repair, the precise mechanisms remain unclear. In this study, HMGB1 knockdown markedly enhanced cell apoptosis after radiation. HMGB1 downregulation significantly inhibited DNA damage repair and reactive oxygen species (ROS)-mediated redox homeostasis after irradiation in CRC cells. Mechanistically, HMGB1 interacts with KU70 via its region spanning residues 95–163. This interaction subsequently activates the non-homologous end joining (NHEJ) pathway to facilitate DNA damage repair, ultimately leading to reduced radiation-induced cell apoptosis. KU70 silencing showed the same effect as HMGB1 depletion mediated cell apoptosis and DNA damage response both in vitro and in vivo. Additionally, HMGB1 and KU70 were overexpressed in CRC tissues. Analysis of the GEPIA database indicated that elevated levels of both genes showed a trend toward association with poor patient prognosis, although this did not reach statistical significance. The current study revealed that HMGB1 may promote DNA damage repair through KU70 and its mediated NHEJ pathway to affect apoptosis in CRC cells after irradiation. Thus, targeting the HMGB1/KU70/NHEJ axis may be a potential therapeutic target to promote the response of CRC to radiotherapy and in-depth study of the specific mechanism of this axis in CRC radioresistance will help to the develop more effective treatment strategies.

Mobile phone MIMO antenna array miniaturization-based low SAR research in the combined EMF

by Wen-Qi Hou, Yu-Xin Li, Ming-Fei Luo, Wen-Ying Zhou, Mai Lu

Due to the diversification of media functions of mobile phones, users can make calls and access the internet simultaneously, which has significantly increased the usage time of mobile phones. The exposure dose of the users in the combined electromagnetic fields (EMF) should be further quantified to better evaluate the public exposure safety. Different from most conventional EMF safety studies that only focus on a single frequency, this work not only discusses the mobile phone simultaneously operated in fourth-generation (4G) and fifth-generation (5G) mobile communications radiation impact on users, but also verifies that the miniaturized mobile phone multiple-input multiple-output (MIMO) antenna array can significantly reduce the specific absorption rate (SAR) absorbed by users. In this article, a miniaturized mobile phone MIMO antenna array is employed as the radiation source, and multi-pose human models are established to simulate the practical utilization of a smartphone. A systematic analysis of the SAR absorbed by the human model is conducted in both single and combined EMF scenarios. The results indicate that the peak SAR in various tissues under multi-frequency exposure is 1.02 to 15.85 times higher than that under single-frequency exposure.

Effects of ascorbic acid on intestinal flora and metabolites of C57 mice exposed to formaldehyde in digestive tract

by Xin Ling, Ziyan Hao, Yixuan Shi, Yuting Li, Kehan Wang, Yunshan Zhang, Yue Wang

The diversity of microbiota and metabolites plays a key role in regulating metabolism, host immune response, neurobehavioral effects and detoxification mechanism in the digestive tract gut. Formaldehyde (FA) affects the gastrointestinal tract and its microbiota, whereas ascorbic acid (VC) improves gut health and selectively promotes microbial growth. In this study, we employed 16S rRNA sequencing and non-targeted metabolomics approaches to investigate these interactions. Our results demonstrated that Lachnospiraceae_NK4A136_group, Lactobacillus, Ligilactobacillus, Clostridiales_unclassified, and other microflora significantly decreased following FA exposure, whereas the intestinal flora changed in the exact opposite way following VC administration. And compared with FA group, the number of 492 ions were regulated, in which 382 feature was up-regulated and 304 feature was down-regulated in FA + 150 mg VC group. In addition, a correlation between gut microbiota and metabolites was observed. These results reveal the effects of FA or VC on the gastrointestinal tract and its microbiota, and our understanding in the treatment of FA-induced damage to the digestive tract.
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