1.Chidamide triggers pyroptosis in T-cell lymphoblastic lymphoma/leukemia via the FOXO1/GSDME axis.
Xinlei LI ; Bangdong LIU ; Dezhi HUANG ; Naya MA ; Jing XIA ; Xianlan ZHAO ; Yishuo DUAN ; Fu LI ; Shijia LIN ; Shuhan TANG ; Qiong LI ; Jun RAO ; Xi ZHANG
Chinese Medical Journal 2025;138(10):1213-1224
BACKGROUND:
T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL.
METHODS:
HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse.
RESULTS:
The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo .
CONCLUSIONS
This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans
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Pyroptosis/drug effects*
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Forkhead Box Protein O1/genetics*
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Aminopyridines/pharmacology*
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Animals
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Mice
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Benzamides/pharmacology*
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Cell Line, Tumor
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
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Phosphate-Binding Proteins/metabolism*
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Histone Deacetylase Inhibitors/pharmacology*
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Jurkat Cells
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Histone Deacetylases/metabolism*
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Apoptosis/drug effects*
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Gasdermins
2.Root rot and control of Panax quinquefolium: a review.
Rao-Jing LI ; Jia-le LIU ; Jian ZHANG ; Juan CHEN
China Journal of Chinese Materia Medica 2025;50(9):2317-2323
Panax quinquefolium, also known as American ginseng, is a perennial herb in the Araliaceae family. It has the effects of replenishing Qi and nourishing Yin, clearing heat and generating saliva. Additionally, it has protective effects on the nerves, improves myocardial ischemia and hypoxia, regulates metabolism, enhances the body's immunity, and is known as "green gold". However, with the development of the industry and the expansion of planting scales, P. quinquefolium faces serious disease issues that are difficult to prevent and control. Among these, root rot, often referred to as "plant cancer", is one of the most destructive plant diseases affecting the yield and quality of P. quinquefolium. P. quinquefolium root rot is caused by the fungi Fusarium(genus) and Ilyonectria(genus), which severely affect the root system and limit the production and quality of P. quinquefolium, thus restricting the development of the P. quinquefolium industry. In recent years, research on P. quinquefolium root rot has attracted significant attention and made some progress. However, the mechanisms of interaction between the root rot pathogens and the host plant remain unclear. This paper reviews the research progress on the pathogens, infection cycle, disease prevalence, pathogenesis, and biological control of P. quinquefolium root rot to provide prospects for future research, aiming to provide references for the in-depth study and effective control of root rot, and to promote the green and healthy development of the P. quinquefolium industry.
Panax/microbiology*
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Plant Diseases/prevention & control*
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Plant Roots/microbiology*
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Fusarium/pathogenicity*
4.Correlation of serum metabolites and clinical features in patients with peripheral T-cell lymphoma
Yishuo DUAN ; Jun RAO ; Jing XIA ; Naya MA ; Shijia LIN ; Fu LI ; Shuhan TANG ; Sha ZHOU ; Yunjing ZENG ; Xinlei LI ; Dezhi HUANG ; Qiong LI ; Bangdong LIU ; Xianlan ZHAO ; Jin WEI ; Xi ZHANG
Journal of Army Medical University 2024;46(4):352-358
Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P<0.05),and elevated D-glucose 6-phosphate content(P<0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P<0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P<0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P<0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P<0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P<0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P<0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P<0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.
5.Expert consensus on the bi-directional screening for Mycobacterium tuberculosis and human immunodeficiency virus
Xin SHEN ; Yinzhong SHEN ; Eryong LIU ; Dingyong SUN ; Dongmin LI ; Yun HE ; Jinge HE ; Lin XU ; Bin CHEN ; Chengliang CHAI ; Lianguo RUAN ; Yong GAO ; Aihua DENG ; Zhen NING ; Jing CHEN ; Xiaofeng LIU ; Kaikan GU ; Lixin RAO
Shanghai Journal of Preventive Medicine 2024;36(4):327-336
Tuberculosis (TB) and human immunodeficiency virus infection / acquired immune deficiency syndrome (HIV/AIDS) are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years, with the promotion and application of new TB and HIV detection technologies worldwide, TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening, summarizes important progress of research and applications, and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.
6.Study on the protective effect of soybean phospholipid powder on nerve injury
Mengli ZHOU ; Xianyue RAO ; Jing FANG ; Hao WANG
Acta Universitatis Medicinalis Anhui 2024;59(5):797-802
Objective To investigate the protective effects and mechanisms of soybean phospholipid powder on nerve cells in vitro and rats neural tissues.Methods In the cell experiments, the cytotoxicity of soybean phospho-lipid powder with different concentrations on mouse microglia cells (BV2) and rat adrenal pheochromocytoma (PC12) cells was observed by cell counting kit-8(CCK-8) assay.The effect of soybean phospholipid powder on the NO level of BV2 cells was analyzed by NO determination experiment, and the synaptic growth of PC12 cells was observed under the microscope.In the animal experiment, the cognitive dysfunction of rat was simulated by scopol-amine rat model.Then the learning and memory abilities of rat were tested by Morris water maze experiment;hipp-ocampal tissue morphology and nerve cell density of scopolamine model mice were observed by hematoxylin-eosin staining (HE) staining.Results Soybean phospholipid powder had no obvious cytotoxicity on BV2 cells and PC12 cells within the concentration of 1000μg/ml.Compared with the control group, the NO secretion of BV2 cells pre-treated with soybean phospholipid powder significantly decreased (P<0.01) , and the neuronal synapse growth of PC12 cells significantly increased (P <0.01) .In comparison to the model group, soybean phospholipid powder significantly improved the learning and memory ability of scopolamine model rats (P<0.05) , reduced the neuronal damage in dentate gyrus (DG), cornu ammonis3 (CA3), cornu ammonis1 (CA1) areas of hippocampus, and in-creased the density of nerve cells (P<0.001).Conclusion Soybean phospholipid powder can play a neuropro-tective role by reducing neuroinflammation and promoting neuronal synapse growth at the cellular level, and im-prove the learning and memory ability of rats with cognitive impairment, reduce hippocampal tissue damage.
7.Study on the mechanism of electroacupuncture stimulation to activate the acupoint effect and promote skeletal muscle repair
Yuting HUANG ; Jun LIAO ; Tianyu RAO ; Kezhi LIU ; Jia LIN ; Yuye LIN ; Chufan ZENG ; Guojun ZHANG ; Xia ZHANG ; Xiubing TONG ; Jingyu ZHANG ; Yu KAN ; Yanping FANG ; Xianghong JING ; Xuan WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(8):1160-1170
Objective To investigate the mechanism of inducing macrophage polarization induced by acupoint effect of electroacupuncture to promote the repair of acute skeletal muscle injury.Methods 45 SD rats were randomly divided into blank group,model group,electroacupuncture group(EA group),sodium chrominate group (DSCG group) and electroacupuncture+sodium chrominate group (hereinafter referred to as EA+DSCG group),with 9 rats in each group. The rats in the EA group and the EA+DSCG group were subjected to EA intervention at the right "Chengshan" (BL57) and "Yanglingquan"(GB34),with a frequency of 2 Hz/100 Hz. The gait changes of rats were recorded by animal gait analyzer. The morphological changes of the right gastrocnemius were observed by HE staining. The changes of mast cell aggregation and degranulation in local skin muscles of "chengshan" point were observed by toluidine blue staining. The expressions of Pax7,MyoD and skin mast cells and 5-HT in the right gastrocnemius were detected by immunofluorescence method. The positive expressions of CD68 and CD206 in right gastrocnemius macrophage was observed by immunohistochemical staining.Results Compared with blank group,the wiggle time of the right hind leg in model group and DSCG group increased,stride length decreased,HE staining showed inflammatory cell infiltration,myocyte enlargement,degeneration and necrosis. The degranulation rate of local skin mast cells in "Chengshan" (BL57) area increased,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD,CD68 and CD206 increased (P<0.05). Compared with model group,the wiggle time of the right hind leg in EA group and EA+DSCG group decreased,stride length increased,HE staining showed that inflammatory cell infiltration was reduced,muscle cells were uniform in size and arranged neatly. Mast cell degranulation rate increased significantly in EA group,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased (P<0.05). Compared with EA+DSCG group,the degranulation rate of mast cells and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased in EA group (P<0.05). Conclusion EA "Chengshan" (BL57) and "Yanglingquan" (GB34) can stimulate acupuncture points to locally induce mast cell degranulation,promote the polarization of macrophages,and then activate muscle satellite cells to play the regulatory process of repairing skeletal muscle injury.
8.Research progression on non-coding RNA in regulating epilepsy autophagy reaction
Yang LI ; Xueyi RAO ; Jun CHEN ; Jing GAN
Chongqing Medicine 2024;53(16):2549-2553
Epilepsy is one of common diseases of nervous system,which is mainly manifested as repeat-ed abnormal neuronal discharges in the brain.If it cannot be effectively controlled,it can cause irreversible neuronal damage in the brain.Non-coding RNAs plays an important role in the development and progression process of epilepsy and are involved in regulating autophagy,apoptosis,neuroinflammation,synaptic remode-ling and other physiological and pathological processes,especially in the regulation of autophagy in epileptic neuronal cells.This article reviews the regulatory relationship between microRNA and long non-coding RNAs,circRNAs in non-coding RNAs with autophagy in the occurrence and development of epilepsy to pro-vide a direction for the precise treatment and prevention of epilepsy.
9.Clinical symptoms and epidemiological characteristics of 57 patients with tsutsugamushi disease in Yunxi County, Shiyan City, Hubei Province in 2022
Xiao XIONG ; Shiping HAN ; Meihe CAI ; Qin ZHAO ; Yanping ZHONG ; Jing MAO ; Junjie YANG ; Xinhua LIU ; Kangxiao LIU ; Rong RAO ; Feifei LEI ; Fangmin SONG ; Huabing TAN
Chinese Journal of Endemiology 2024;43(5):388-392
Objective:To analyze the clinical symptoms and epidemiological characteristics of patients with tsutsugamushi disease (TD) in Utica County, Shiyan City, providing reference for scientific prevention and control of TD.Methods:The information of 57 TD patients admitted to the Department of Infectious Diseases of the People's Hospital of Utica County in Shiyan City from January to December 2022 was collected, including age, gender, occupation, clinical manifestations (tarsus or chigger, high fever, rash and accompanying syndromes), laboratory and imaging test results, and field work and travel history. Blood samples and body crusts were collected, and enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) were used to detect antibodies against Orientia tsugamushi (Ot-Ab-IgM) and Orientia tsutsugamushi (Ot). The scores of each patient were calculated using the TD Diagnostic Scale. A score of ≥8.5 was considered a clinical diagnosis of TD. According to the number of system functional damages (0, 1, 2, ≥3), 57 patients were divided into 4 groups, A, B, C, and D, TD was analyzed for system functional damages of each system.Results:Among the 57 TD patients, 26 (45.61%) were male and 31 (54.39%) were female, and the proportion of patients aged 40 - 79 years was 92.98% (53/57); farmers accounted for 89.47% (51/57). May was the peak of TD incidence, with 19 cases, which accounted for 33.33% (19/57) of the total number of patients affected that year. Fifty-four patients had a history of fieldwork or field trips before the onset of the disease. The incidence of high fever in 57 TD patients was 100.00%(57/57), the detection rate of body scorch or chiggers was 80.70% (46/57), and the incidence rate of rash was 98.25% (56/57); the incidence rate of tsutsugamushi disease triad (accompanied by scabs, high fever, and rash) was 80.70% (46/57); the incidence of eosinophil decline was 100.00%(57/57), and 77.19% (44/57) of TD patients experienced multiple-system functional damage (MSFD). The TD score diagnostic scale for 57 patients ranged from 8.5 to 10.5 points. After being hospitalized for 1 - 5 days, all TD patients experienced a decrease in body temperature to the normal range, and the damage to various systems functional gradually recovered.Conclusions:TD has become one of the most common natural infectious diseases in Utopia County, Shiyan City, Hubei Province. The patients are mainly middle-aged and elderly people, and the triple syndrome is a typical clinical manifestation. Asymptomatic injuries to the blood system, liver and kidneys are the most common.
10.Application of GLIM criteria for malnutrition diagnosis in 5 236 elderly inpatients
Jingsi SONG ; Chunyan DU ; Shi QIU ; Junchi YE ; Na YU ; Zhiyong RAO ; Xiaofan JING
Chinese Journal of Clinical Nutrition 2024;32(3):150-155
Objective:To analyze the nutritional status of elderly inpatients using Global Leadership Initiative on Malnutrition (GLIM) criteria.Methods:A total of 5 236 elderly patients (aged 65 years or older) who were hospitalized at the West China Hospital, Sichuan University from March 2021 to March 2022 were included. The nutritional status was analyzed using the GLIM diagnostic criteria for malnutrition.Results:The rate of patients at nutritional risk was 30.29%, and the incidence of malnutrition as per GLIM criteria was 15.64%. The levels of hemoglobin, albumin, triglycerides, and cholesterol, and body mass index of the malnutrition group were lower compared with the non-malnutrition group, and the differences were statistically significant ( P<0.05). The non-malnutrition group had significantly shorter hospital stay and lower hospitalization costs compared with the malnutrition group ( P<0.001). Conclusions:The GLIM criteria is suitable for evaluating the nutritional status in elderly inpatients. The incidence of malnutrition in elderly inpatients is relatively high, which deserves attention in clinical management.


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