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.

The pathogenesis of hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC） is complicated with the crosstalk of multiple factors and the multi-step processes. The main mechanisms underlying the HBV-induced HCC include:①integration of HBV DNA into the host hepatocyte genome to alter gene function at the insertion site，resulting in host genome instability and expression of carcinogenic truncated proteins;②HBV gene mutations at S，C，and X coding regions in the genome;③HBV X gene-encoded HBx protein activates proto-oncogenes and inhibits tumor suppressor genes，leading to the HCC occurrence. In this article，the recent research progress on the molecular mechanism of HBV-induced HCC is comprehensively reviewed，so as to provide insights into the prevention，early prediction and postoperative adjuvant therapy of HCC.
Carcinoma, Hepatocellular ; Hepatitis B/complications* ; Hepatitis B virus/genetics* ; Hepatocytes ; Humans ; Liver Neoplasms

Promyelocytic leukemia (PML) protein, a tumor suppressor, plays an important role in patients with acute promyelocytic leukemia (APL) receiving arsenic trioxide (AsO) therapy. APL is a M3 subtype of acute myeloid leukemia (AML), which is characterized by expression of PML-RARα (P/R) fusion protein, leading to the oncogenesis. AsO is currently used as the first-line drug for patients with APL, and the mechanism may be:AsO directly binds to PML part of P/R protein and induces multimerization of related proteins, which further recruits different functional proteins to reform PML nuclear bodies (PML-NBs), and finally it degraded by SUMOylation and ubiquitination proteasomal pathway. Gene mutations may lead to relapse and drug resistance after AsO treatment. In this review, we discuss the structure and function of PML proteins; the pathogenesis of APL induced by P/R fusion protein; the involvement of PML protein in treatment of APL patient with AsO; and explain how PML protein mutations could cause resistance to AsO therapy.
Antineoplastic Agents ; therapeutic use ; Arsenic Trioxide ; therapeutic use ; Drug Resistance, Neoplasm ; genetics ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Mutation ; Oncogene Proteins, Fusion ; metabolism ; Promyelocytic Leukemia Protein ; chemistry ; genetics ; metabolism

In our previous work, we found that trivalent dimethylarsinous acid (DMA(III)) have high affinity binding to cysteine residue 13 of rat hemoglobin. However, it is still unknown why arsenic intermediate metabolite DMA(III) has high binding affinity for Cysl3 but not for other cysteine residues 93, 140, 111 and 125. In order to better understand the molecular mechanism of DMA(III) with rat hemoglobin, we have done current study. So, SD rats were divided into control and arsenic-treated groups randomly. Arsenic species in lysate of red blood cells were analyzed by HPLC-ICP-MS, and then determined by a hybrid quadrupole TOF MS. In addition, trivalent DMA(III) binds to different cysteine residues in rat hemoglobin alpha and beta chains were also simulated by Molecular Docking. Only Cys13 in alpha chain is able to bind to DMA(III) from the experiment results. Cys13 of alpha chain in rat hemoglobin is a specific binding site for DMA(III), and we found that amino acids compose pockets structure and surround Cys13 (but not other cysteine residues), make DMA(III) much easy to bind cysteine 13. Taken together, the DMA(III) specific binding to Cys13 is related to spatial structure of Cys13.
Animals ; Arsenic ; metabolism ; Binding Sites ; Cacodylic Acid ; analogs & derivatives ; chemistry ; Chromatography, High Pressure Liquid ; Cysteine ; metabolism ; Hemoglobins ; metabolism ; Mass Spectrometry ; Peptide Fragments ; metabolism ; Rats

In our previous work, we found that trivalent dimethylarsinous acid (DMA(III)) have high affinity binding to cysteine residue 13 of rat hemoglobin. However, it is still unknown why arsenic intermediate metabolite DMA(III) has high binding affinity for Cysl3 but not for other cysteine residues 93, 140, 111 and 125. In order to better understand the molecular mechanism of DMA(III) with rat hemoglobin, we have done current study. So, SD rats were divided into control and arsenic-treated groups randomly. Arsenic species in lysate of red blood cells were analyzed by HPLC-ICP-MS, and then determined by a hybrid quadrupole TOF MS. In addition, trivalent DMA(III) binds to different cysteine residues in rat hemoglobin alpha and beta chains were also simulated by Molecular Docking. Only Cys13 in alpha chain is able to bind to DMA(III) from the experiment results. Cys13 of alpha chain in rat hemoglobin is a specific binding site for DMA(III), and we found that amino acids compose pockets structure and surround Cys13 (but not other cysteine residues), make DMA(III) much easy to bind cysteine 13. Taken together, the DMA(III) specific binding to Cys13 is related to spatial structure of Cys13.

OBJECTIVETo purify the arsenic-binding proteins (As-BP) in hamster plasma after a single oral administration of arsenite (iAs(III)).

METHODSArsenite was given to hamsters in a single dose. Three types of HPLC columns, size exclusion, gel filtration and anion exchange columns, combined with an inductively coupled argon plasma mass spectrometer (ICP MS) were used to purify the As-BP in hamster plasma. SDS-PAGE was used to confirm the arsenic-binding proteins at each purification step.

RESULTSThe three-step purification process successfully separated As-BP from other proteins (ie, arsenic unbound proteins) in hamster plasma. The molecular mass of purified As-BP in plasma was approximately 40-50 kD on SDS-PAGE.

CONCLUSIONThe three-step purification method is a simple and fast approach to purify the As-BP in plasma samples.

Administration, Oral ; Animals ; Arsenic ; blood ; Arsenites ; administration & dosage ; pharmacokinetics ; Carrier Proteins ; blood ; Chromatography, High Pressure Liquid ; methods ; Cricetinae

OBJECTIVETo detect common environmental pollutants in human body.

METHODSUrine samples were collected from 80 healthy subjects. Chromatography mass spectrometry (GC-MS), HPLC and ELISA were applied to detect several common environmental pollutants in urine samples.

RESULTSDBP and methylbenzene were present in 75.3% and 41.2% of urine samples. The methanal and AFM1 were found in most of urine samples (approximately 91≊97%). By contrast, PCBs, CPZ, 4, 5-DCC were found in less than 5 samples, but there was no TMT detected.

CONCLUSIONSome of the environmental pollutants including carcinogens are detected in urine samples in this study.

Adolescent ; Adult ; Aged ; Environmental Exposure ; Environmental Pollutants ; urine ; Humans ; Middle Aged ; Young Adult