Beyond Genes: Epiregulomes as Molecular Commanders in Innate Immunity.

The natural fastest way to deal with pathogens or danger signals is the innate immune system. This system prevents too much inflammation and tissue damage and efficiently eliminates pathogens. The epiregulome is the chromatin structure influenced by epigenetic factors and linked to cis-regulatory elements (CREs). The epiregulome helps to end the inflammatory response and also assists innate immune cells to show specific action by making cell-specific gene expression patterns. This inspection unfolds two concepts: (1) how epiregulomes are shaped by switching the expression levels of genes, manoeuvre enzyme activity and earmark of chromatin modifiers on specific genes; during and after the infection, and (2) how the expression of specific genes (aids in prompt management of innate cell growth, or the reaction to aggravation and illness) command by epiregulomes that formed during the above process. In this review, the consequences of intrinsic immuno-metabolic remodelling on epiregulomes and potential difficulties in identifying the master epiregulome that regulates innate immunity and inflammation have been discussed.

Screening anabolic androgenic steroids in human urine: an application of the state-of-the-art gas chromatography-Orbitrap high-resolution mass spectrometry.

Over the past few decades, anabolic androgenic steroids (AASs) have been abused in and out of competition for their performance-enhancing and muscle-building properties. Traditionally, AASs were commonly detected using gas chromatography-mass spectrometry in the initial testing procedure for doping control purposes. Gas chromatography-Orbitrap high-resolution mass spectrometry (GC-Orbitrap-HRMS) is a new technology that has many advantages in comparison with GC-MS (e.g., a maximum resolving power of 240,000 (FWHM at m/z 200), excellent sub-ppm mass accuracy, and retrospective data analysis after data acquisition). Anti-doping practitioners are encouraged to take full advantage of the updated techniques of chromatography-mass spectrometry to develop sensitive, specific, and rapid screening methods for AASs. A new method for screening a wide range of AASs in human urine using GC-Orbitrap-HRMS was developed and validated. The method can qualitatively determine 70 anabolic androgenic steroids according to the minimum required performance limit of the World Anti-Doping Agency. Moreover, the validated method was successfully applied to detect six metabolites in urine after the oral administration of metandienone, and their excretion curves in vivo were studied. Metandienone M6 (17ß-hydroxymethyl-17α-methyl-18-nor-androst-1,4,13-trien-3-one) has been identified as a long-term urinary metabolite which can be detected up to 7 weeks, thus providing a longer detection window compared with previous studies. This study provides a rationale for GC-Orbitrap-HRMS in drug metabolism and non-targeted screening.

The clinical value of using chloroquine or hydroxychloroquine as autophagy inhibitors in the treatment of cancers: A systematic review and meta-analysis.

BACKGROUND: Autophagy is a mechanism which relies on lysosomes for clearance and recycling of abnormal proteins or organelles. Many studies have demonstrated that the deregulation of autophagy is associated with the development of various diseases including cancer. The use of autophagy inhibitors is an emerging trend in cancer treatment. However, the value of autophagy inhibitors remains under debate. Thus, a meta-analysis was performed, aiming to evaluate the clinical value of autophagy-inhibitor-based therapy. METHODS: We searched for clinical studies that evaluated autophagy-inhibitor-based therapy in cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR), 6-month progression-free survival (PFS) rate, and 1-year overall survival (OS) rate. RESULTS: Seven clinical trials were identified (n = 293). Treatments included 2 combinations of hydroxychloroquine and gemcitabine, 1 combination of hydroxychloroquine and doxorubicin, 1 combination of chloroquine and radiation, 2 combinations of chloroquine, temozolomide, and radiation, and 1 hydroxychloroquine monotherapy. Autophagy-inhibitor-based therapy showed higher ORR (RR: 1.33, 95% confidence interval [CI]: 0.95-1.86, P = .009), PFS (RR: 1.72, 95% CI: 1.05-2.82, P = .000), OS (RR: 1.39, 95% CI: 1.11-1.75, P = .000) values than the therapy without inhibiting autophagy. CONCLUSION: This meta-analysis showed that autophagy-inhibitor-based therapy has better treatment response compared to chemotherapy or radiation therapy without inhibiting autophagy, which may provide a new strategy for the treatment of cancers.