BET in hematologic tumors:Immunity,pathogenesis,clinical trials and drug combinations

The bromodomain and extra-terminal(BET)proteins act as“readers”for lysine acetylation and facilitate the recruitment of transcriptional elongation complexes.BET protein is associated with transcriptional elongation of genes such as c-MYC and BCL-2,and is involved in the regulation of cell cycle and apoptosis.Meanwhile,BET inhibitors(BETi)have regulatory effects on immune checkpoints,immune cells,and cytokine expression.The role of BET proteins and BETi in a variety of tumors has been studied.This paper reviews the recent research progress of BET and BETi in hematologic tumors(mainly leukemia,lymphoma and multiple myeloma)from cellular level studies,animal studies,clinical trials,drug combination,etc.BETi has a promising future in hematologic tumors,and future research directions may focus on the combination with other drugs to improve the efficacy.

Review of Baduanjin and resistance exercise for the mental health of patients with hematologic malignancies

Patients with hematological tumors experience physical and psychological stress,and negative psychological states.Baduanjin,an emerging psychological rehabil-itation method combined with resistance exercise,has received widespread attention.This study reviews the current status of the application of Baduanjin combined with resistance exercise in improving the negative psychological state of patients with hematological tumors and discusses its problems and prospects.Through a literature review and comprehensive analysis,the application of Baduanjin and resistance exercise in the psychological rehabilitation of patients with hematological tumors was identified and evaluated.The results showed that Baduanjin with resistance exercise had a positive effect on improving negative psychological states of patients with hematological tumors,which can alleviate anxiety,depression,and other adverse emotions,and improve quality of life.However,there is a lack of unified and standardized exercise intervention programs for practical application,and patient participation and compliance must be improved.Baduanjin combined with resistance exercise can potentially improve the negative psychological status of patients with hematological tumors;however,it is still necessary to further standardize and improve the exercise program improving patient participation and compliance.Future studies should strengthen theoretical exploration and empirical research,providing more effective psychological rehabilitation strategies for patients with hematological tumors.

Targeting and Internalization of Sterically Stabilized Liposome Modified with ZCH-4-2E8

Sterically stabilized liposome （SL） modified with 2E8 monoclonal antibody （2E8-SL） was prepared in order to evaluate its targeting ability and internalization efficiency against tumor cells with high expression of CD19.2E8 was coupled to the surface of SL using post-insertion technique. The shape of liposomes was observed under a transmission electronic microscope. The average size of liposomes was determined by using the Zetasizer instrument. The binding and internalization of 2E8-SL against tumor cells with higher expression of CD 19 were tested by flow cytometry and confocal microscopy. The mean diameter of 2E8-SL was 121.25 nm. 2E8-SL was stable after up to 24 days in various buffers. 2ES-SL showed specific binding to tumor cells with high expression of CD19, including B cells in peripheral blood mononuclear cells （PBMCs）. 2E8-SL could efficiently internalize into Nalm6 cells with CD19 high expression. It is suggested that 2E8-SL may serve as useful delivery carrier of anti-cancer drugs targeting to hematological malignant tumors with CD 19 high expression.

Research progress on anti-tumor properties of Marsdenia tenacissima

Tongguanteng （Marsdenia tenacissima）, which is mainly distributed in the Yunnan and Guizhou provinces of China, wasfirst recorded in Diannanbencao by Lan Mao of the Ming dynasty of China. According to recent pharmacological studies,the chemical composition of Tongguanteng （Marsdenia tenacissima） is complex and contains C21 steroidal saponins,polysaccharides, alkaloids, and other molecules, which show anti-cancer effects on various tumor cell lines. It inhibitstumor cell proliferation and growth mainly by increasing the expression of apoptosis- and cell cycle-related proteins topromote apoptosis and arrest tumor cells in the G2/M or S phase. Downregulation of the expression of vascularendothelial growth factor-2/A and matrix metalloprotease-2/9 suppresses the formation of the tumor microvasculature,leading to tumor malnutrition, increased expression of interleukin-2, glutathione peroxidase, catalase, and superoxidedismutase, and decreased interleukin-10 and malondialdehyde expression, thereby enhancing immunity andantioxidation in the body. Additionally, inhibition of epidermal growth factor receptor, hepatocyte growth factor receptor,and tyrosine-protein kinase receptor activation enhances the anti-tumor efficacy of epidermal growth factorreceptor-tyrosine kinase inhibitors as well as inhibits P-glycoprotein and cytochrome P450 to increase the concentrationof anti-tumor drugs in tumor cells.

Human Endogenous Retroviruses and Hematological Malignant Tumors

Human endogenous retrovirus(HERV)gene sequences are remnants of retroviruses that infected the ancestors of humans millions of years ago and were integrated into human chromosomes,accounting for approximately 8%-9%of the human genome.Most integrated HERVs have lost their coding capacity and remain silent due to frame shifts,mutations,and sequence deletions or insertions over the millions of years,but their expression is highly regulated by epigenetic and host defense mechanisms.However,there are still some HERV genes that have intact open reading frames due to recent integration into the human genome or positive selective pressure.The abnormal activation of HERVs may contribute to diseases or their pathology,such as malignant tumors,autoimmune diseases,and nervous system diseases.The occurrence and development of hematological malignant tumors(HMTs)is a complex process involving interactions of multiple genetic and environmental factors.The abnormal activation of HERVs may contribute to the pathology of HMTs via indirect mechanisms.In this review,we address the discovery of endogenous retroviruses in vertebrates,and the classification and genomic structure of HERVs.Among HERV family members,HERV-K is the latest type of HERV integrated into the human genome and it has the strongest transcriptional activity.We explore the currently known expression of HERV-K proto-oncogenes in HMTs and further address potential research and therapeutic approaches.However,much remains to be learned about not only the impact of HERVs on the occurrence of HMTs,but also the potential value of HERVs as diagnostic and therapeutic targets for HMTs.