1.HDAC6 inhibitor ACY-738 induces apoptosis and autophagy in diffuse large B-cell lymphoma cells through P53 acetylation
Peijie JIANG ; Jinyi LIU ; Guancui YANG ; Jiarun LI ; Xiaolong TIAN ; Shijie YANG ; Jin WEI ; Xi ZHANG
Chinese Journal of Hematology 2025;46(5):437-444
Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.
2.HDAC6 inhibitor ACY-738 induces apoptosis and autophagy in diffuse large B-cell lymphoma cells through P53 acetylation
Peijie JIANG ; Jinyi LIU ; Guancui YANG ; Jiarun LI ; Xiaolong TIAN ; Shijie YANG ; Jin WEI ; Xi ZHANG
Chinese Journal of Hematology 2025;46(5):437-444
Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.
3.Knowledge, attitude, practice and influencing factors on influenza and influenza vaccine among pregnant women in Suzhou
Rui WANG ; Yuanyuan ZHANG ; Cheng LIU ; Pengwei CUI ; Feng XU ; Jiarun JIANG ; Liling CHEN ; Haibing YANG ; Fang LIU
Chinese Journal of Epidemiology 2024;45(12):1672-1678
Objective:To understand the current knowledge, attitude, and practice (KAP) on influenza and influenza vaccine among pregnant women in Suzhou and to analyze its influencing factors to provide technical support data for public health strategies for promoting influenza vaccination in pregnant women.Methods:A questionnaire was designed, and a stratified sampling method was used to conduct a face-to-face survey among pregnant women at different stages of pregnancy who received antenatal examinations at different levels of medical institutions in Suzhou, Jiangsu Province, in 2023. KAP status and influencing factors were analyzed by χ2 test and logistic regression analysis. Results:A total of 2 195 valid questionnaires were collected in this survey. The M( Q1, Q3) of knowledge about influenza and influenza vaccine among pregnant women in Suzhou was 7.60 (5.23, 9.80) points, and the score range was 0.20-14.71 points, the passing rate was 34.12%, the awareness rate of influenza vaccine was 57.45%, and the vaccination rate of influenza vaccine was 1.91% within one year before the survey. The willingness to receive influenza vaccine during pregnancy was only 3.57%. Multivariate analysis of influenza and influenza vaccine-related knowledge scores showed that the passing rate was positively correlated with education level and gestational age. In contrast, family income was negatively correlated with living in rural areas, working as migrant workers, and having no medical insurance. Multivariate analysis of vaccination intention showed that decreased effectiveness of influenza vaccine and increased adverse reactions decreased vaccination intention during pregnancy. Conclusions:The pregnant women in Suzhou pay more attention to influenza, and vaccination rates and intentions are generally low. Pregnant women with early and second trimester of pregnancy, low education, living in rural areas, working as migrant workers, and not purchasing medical insurance are the key groups to popularize the knowledge about influenza and influenza vaccine.
4.Problems and Suggestions in the Registration and Approval of Chemical Preparations in Medical Institutions of Guangdong Province
Jiarun CHEN ; Xiaoli SHEN ; Xiaoying WANG ; Yingzhu JIANG
China Pharmacy 2019;30(22):3030-3034
OBJECTIVE: To provide reference for ensuring clinical drug safety and promoting the development of characteristic chemical preparations in medical institutions. METHODS: From three aspects such as registration declaration of new preparations, supplementary application declaration and re-registration declaration, the problems found during the technical review of registration of chemical preparation in medical institutions of Guangdong province have been summed up, the causes of above problems also have been analyzed, and the relevant suggestions have been given at the same time. RESULTS & CONCLUSIONS: There were deficiencies in the registration declaration of new preparations, such as insufficient basis for the title, the lack of key process parameters in the study of preparation process and the failure of stability test conditions to meet the requirements of the Pharmacopoeia, etc. There were deficiencies in the supplementary application declaration, such as the unreasonable formulation of drug, the interaction between the drugs packing material and the drug, and unreasonable setting of storage conditions. There were deficiencies in the re-registration declaration, such as the supply of existing drugs on the market, the lack of production conditions for the formulation unit, the inability to purchase the original excipient materials, and the incomplete attention items. The main reasons were that the lack of technical guidelines for the research of chemical preparations, imperfection of the Standards for the Quality Management of Pharmaceutical Preparation in Medical Institutions and authorized preparation of chemical agents not allowed in Measures for the Registration and Administration of Pharmaceutical Preparation in Medical Institutions, and some kinds of chemical preparations could not adapt to the development of the new situation. The solutions are to improve the regulations of medicinal preparation in medical institutions and develop chemical preparations selectively based on safety and efficiency. In the future, the problems can be solved by formulating the technical guidelines for the research of chemical preparations in medical institutions, refining the rules for the retention of samples in finished products, increasing the requirements for continuous stability inspections, allowing authorized chemical preparations to be commissioned and prepared, phasing out the chemical preparations that do not adapt to the new situation, and developing valuable chemical preparations, to provide safe and effective chemical preparations for clinical use.

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