Xyloketal B is a natural compound isolated from the mangrove fungus, Xylaria sp. in the South China Sea. In the past decade, studies have shown that xyloketal B exhibits anti-oxidative, anti-inflammatory, and anti-apoptotic abilities and may serve as a treatment for ischemic stroke. Xyloketal B has been shown to interact with both neurons and residential microglial cells and regulate a number of proteins involved in the apoptotic events during ischemia. Such mechanisms include inhibition of specific NADPH oxidase subunits, upregulation of HO-1, increase of Bcl-1/Bax ratio, and downregulation of TLR4 receptor. Both in vitro and in vivo stroke models have validated its potential in preventing ischemia-induced neuronal cell death. This review summarizes our current understanding of the effects of xyloketal B in ischemic conditions. As stroke ranks second in the causes of mortality worldwide and still lacks effective treatment, it is necessary to seek novel therapeutic options. Understanding the role of xyloketal B in ischemic stroke could reveal a new aspect of stroke treatment.
Despite advances in cancer therapeutics, early detection is often the best prognostic indicator for survival (1). Patients with Li Fraumeni syndrome harbor a germline pathogenic variant in the tumor suppressor gene TP53 (2) and face a near 100% lifetime risk of developing a wide spectrum of, often multiple, cancers (3). TP53 mutation carriers routinely undergo intensive surveillance protocols which, although associated with significantly improved survival, are burdensome to both the patient and the health care system (4). Liquid biopsy, the analysis of cell free DNA fragments in bodily fluids, has become an attractive tool for a range of clinical applications, including early cancer detection, because of its ability to provide real time holistic insight into the cellular milieu (5). Here, we assess the efficacy of a multi modal liquid biopsy assay that integrates a targeted gene panel, shallow whole genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a cohort of Li Fraumeni syndrome patients: 196 blood samples from 90 patients, of which 27 were pediatric and 63 were adults. Our integrated analysis was able to detect a cancer-associated signal in 79.4% of samples from patients with active cancer, a 37.5% to 58.8% improvement over each individual analysis. Through longitudinal analysis, we were able to detect cancer-associated signals up to 16 months prior to occurrence of cancer as detected by conventional clinical modalities in 17.6% of TP53 mutation carriers. This study provides a framework for the integration of liquid biopsy into current surveillance methods for patients with Li Fraumeni syndrome.
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