Reactive oxygen species (ROS) ubiquitously exist in mammalian cells to participate in various cellular signaling pathways. The intracellular ROS levels are dependent on the dynamic balance between ROS generation and elimination. In this review, we summarize reported studies about the influences of magnetic fields (MFs) on ROS levels. Although in most cases, MFs increased ROS levels in human, mouse, rat cells, and tissues, there are also studies showing that ROS levels were decreased or not affected by MFs. Multiple factors could cause these discrepancies, including but not limited to MF type/intensity/frequency, exposure time and assay time-point, as well as different biological samples examined. It will be necessary to investigate the influences of different MFs on ROS in various biological samples systematically and mechanistically, which will be helpful for people to get a more complete understanding about MF-induced biological effects. In addition, reviewing the roles of MFs in ROS modulation may open up new scenarios of MF application, which could be further and more widely adopted into clinical applications, particularly in diseases that ROS have documented pathophysiological roles.

Radiotherapy is effective on a large number of cancer types and is one of the most frequently administrated treatments for cancer patients. The anticancer efficacy of X-ray radiotherapy has been frequently correlated with reactive oxygen species (ROS) elevation, which is also a limiting factor for its toxicity on normal tissues. Here, we found that although 4-10 Gy X-rays could significantly reduce cell numbers in both MDA-MB-231 and MCF-7 breast cancer cells, the ROS level changes are less in MCF-7 cells than in MDA-MB-231 cells. Moreover, although both the ROS scavenger N-acetyl-L-cysteine (NAC) and 1 T static magnetic field (SMF) could reduce X-ray-induced ROS elevation, they did not prevent X-ray-induced cell number reduction or cell death increase, which is significantly different from cisplatin. These results demonstrate that although the anticancer efficacy of cisplatin on two breast cancer cell lines is dependent on ROS, the anticancer efficacy of X-ray is not. Moreover, by testing 19 different cell lines, we found that 1 T SMF could effectively reduce ROS levels in multiple cell lines by 10-20%, which encourages further studies to investigate whether SMF could be used as a potential “physical antioxidant” in the future.

Several members of the NIMA-related kinase (NEK) family have been implicated in tumor progression; however, the role and underlying mechanisms of NEK8 in gastric cancer (GC) remain unclear. This study revealed a significant upregulation of NEK8 in GC, identifying it as an independent prognostic marker in patients with GC. Consistent with these findings, NEK8 silencing substantially impeded GC aggressiveness both in vitro and in vivo, while its overexpression produced the opposite effect. Gene Ontology enrichment analysis and metabolic profiling indicated that the impact of NEK8 on GC is primarily associated with reprogramming asparagine metabolism and modulating the mTORC1 pathway. Specifically, NEK8 knockdown suppressed asparagine synthesis by downregulating asparagine synthetase (ASNS) expression in GC cells. A strong correlation was observed between NEK8 levels and ASNS expression in human GC cells and tissue samples. Mechanistically, NEK8 directly interacts with ASNS, phosphorylating it at the S349 site, which inhibits its ubiquitination and subsequent degradation. Moreover, substituting the ASNS-S349 site with alanine abrogated the pro-tumorigenic effects of ASNS-WT overexpression. Additionally, asparagine was identified as an activator of the mTORC1 pathway, with reintroducing asparagine after NEK8 silencing restoring mTORC1 activity. Collectively, these findings demonstrate that NEK8-mediated asparagine synthesis and activation of the mTORC1 pathway play a critical role in promoting GC progression.

Background: The present study aimed to investigate the expression level, biological function, and underlying mechanism of transmembrane protein 176B (TMEM176B) in gastric cancer (GC). Methods: TMEM176B expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). The function of TMEM176B was determined by various in vitro assays including colony formation, 5-ethynyl-2ʹ-deoxyuridine (EdU), Transwell, and flow cytometry. Bioinformatics techniques were then used to elucidate the signaling pathways associated with TMEM176B activity. Tumor formation experiments were conducted on nude mice for in vivo validation of the preceding findings. TMEM176B expression was cross-referenced to clinicopathological parameters and survival outcomes. Results: It was observed that TMEM176B was overexpressed in GC cells and tissues. Targeted TMEM176B abrogation inhibited colony formation, proliferation, migration, and invasion but promoted apoptosis in GC cell lines while TMEM176B overexpression had the opposite effects. Subsequent experimental validation disclosed an association between TMEM176B and the phosphatidylinositol 3-carboxykinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling axis. Moreover, TMEM176B affects GC cancer progression by regulating asparagine synthetase (ASNS). The in vivo assays confirmed that TMEM176B is oncogenic and the clinical data revealed a connection between TMEM176B expression and the clinicopathological determinants of GC. Conclusion: The foregoing results suggest that TMEM176B significantly promotes the development of gastric cancer and is an independent prognostic factor of it.