Introduction: This research work was carried out as a joint project between the People’s Republic of China and Mongolia. Mongolian contract number is CHN-2022/278, Chinese contract number is YS2021YFE010725. The title of the project is “The underlying mechanism of the synergistic effect of Arsenic Trioxide and Interferon Alpha on the treatment of Arsenic Resistant Acute Promyelocytic Leukemia”. The main executing organisation of Mongolia is the Mongolian Academy of Medical Sciences, and the project implementing organisation of the Chinese is Zhejiang University School of Medicine, and the People’s Hospital of Hangzhou Medical College, China.
PML nuclear bodies (NB) are disrupted in PML-RARα–driven acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) cures 70% of patients with APL, driving PML-RARα degradation and NB reformation. In non-APL cells, arsenic binding to PML also amplifies NB formation. Yet, the actual molecular mechanism(s) involved remain elusive. Methods: PML and PML-RARα condensate dynamics were examined using live-cell time-lapse imaging, confocal and STED super-resolution microscopy, and FRAP analysis in GFP-tagged PmlKO MEFs before and after arsenic trioxide (ATO) treatment.
Here, we establish that PML NBs display some features of liquid–liquid phase separation and that ATO induces a gel like transition. PML fusion to RARα altered its distribution in the nucleus, as GFP-PML-RAR α localised into many tiny dots with diam diameter below 100 nm in PmlKO MEFs. The basal dynamics of GFP-PML-RARα at these microdots were increased compared with PML at NBs, with a t1/2 of 1.37 minutes and, importantly, no immobile fraction. Here again, ATO treatment drastically decreased PML RARα exchange rates, closer to the dynamics of PML. Thus, ATO therapy drives the gel-like transition of both PML- or PML-RARα–driven condensates. Conclusion These findings show that arsenic trioxide (ATO) converts both PML and PML-RARα condensates from a liquid-like, highly dynamic state into a gel-like, immobilized structure, revealing a key biophysical mechanism underlying ATO’s therapeutic action in APL.

Introduction: In Mongolia, ancient lama doctors and maarambas called it rdo dug in Tibetan. The direct translation of arsenic in Mongolian is stone poison, and the common word is arsenic. Natural arsenic is extracted from stone poison and gold sulphur. It was used as a distinction between red poison and white stone poison. However, there is no specific study of stone arsenic based on ancient medical scriptures and books. Therefore, we have chosen this topic to collect, analyse, and summarise information about arsenic from ancient medical texts written in Tibetan and Mongolian. The purpose of the research work is to collect information and facts from ancient traditional medical scriptures and books written in Tibetan and Mongolian, and to clarify their uses and some terms. Methods: Source study method: The source-study method includes research activities of books, literary works, sources, and papers. We made a historical study on the date and the authors and their literary works in order of the written period, starting from the earliest, thus comparing special, innovative, and creative ideas in terms of content and mentality with other original literary works by using research materials per the research goal and objectives. Comparative method: Comparison is a fundamental tool of analysis. It sharpens our powers of description and plays a central role in concept formation by bringing suggestive similarities and contrasts among sources into focus. Conclusion The study found that there are many references to arsenic in ancient traditional medical scriptures and books written in Tibetan and Mongolian. The Tibetan name for arsenic is rdo dug, the Mongolian name is khuntsel, and the Latin name is arsenic. It was revealed that it is included in several formulas and is also the main ingredient in some traditional formulas.