1.ALKBH3-regulated m1A of ALDOA potentiates glycolysis and doxorubicin resistance of triple negative breast cancer cells.
Yuhua DENG ; Zhiyan CHEN ; Peixian CHEN ; Yaming XIONG ; Chuling ZHANG ; Qiuyuan WU ; Huiqi HUANG ; Shuqing YANG ; Kun ZHANG ; Tiancheng HE ; Wei LI ; Guolin YE ; Wei LUO ; Hongsheng WANG ; Dan ZHOU
Acta Pharmaceutica Sinica B 2025;15(6):3092-3106
Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m1A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m1A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.
2.Study on the design of X-ray Flash-RT equipment with high power petal accelerator
Shuqing LIAO ; Xiaozhong HE ; Liu YANG ; Ruo TANG ; Tao WEI ; Zhuo ZHANG ; Jinshui SHI ; Jianjun DENG
China Medical Equipment 2024;21(1):21-23,28
Objective:To study and design one kind of flash radiotherapy(Flash-RT)equipment with ultra-high dose rate,which can be used in the mechanism research of Flash-RT with ultra-high dose rate.Methods:Based on the technique roadmap of high-power petal accelerator,the Flash-RT equipment can realize the requirement of Flash-RT for ultra-high dose rate and multiple irradiation angles.The corresponding design and research work were carried out on the basis of the overall design of the equipment,the main components and characteristics,the dynamics design of beam,the construction of movable and preliminary experimental platform,etc.Result:The dose rate of the designed equipment can reach to 100 Gy/s at a distance of 0.8 meters from the target point,which is easy to realize the radiotherapy method with multi angles.Conclusion:The designed X-ray equipment based on the technique roadmap of high-power petal accelerator can realize the research for the mechanism of medical Flash-RT equipment with ultra-high dose rate.
3.Research advance of clinical application of X-ray Flash-RT equipment
Ruo TANG ; Xiaozhong HE ; Pengfei ZHU ; Zhuo ZHANG ; Ziping HUANG ; Shuqing LIAO ; Tao WEI ; Liu YANG ; Jinshui SHI
China Medical Equipment 2024;21(1):24-28
The protection effect of flash-radiotherapy(Flash-RT)with super-high dose on normal tissue has obtained wide attention in therapeutic radiology since it was found in 2014 year.The increasing research demand of Flash-RT with super-high dose-rate proposed new challenge for the existing radiotherapy equipment.Based on the demands of FLASH-RT research and clinical application,this review analyzed the proposed new requirement of Flash-RT for equipment,and introduce current scientific facilities with the experimental ability of X-ray FLASH-RT,as well as the situation of the specialized FLASH-RT equipment which were developing.The research of Flash-RT mechanism need the existing equipment with high-energy X-ray source develop toward high power,while the clinical application of Flash-RT demand these transient high-power devices should possess a series of radiotherapy techniques such as multi angle irradiation,conformal radiotherapy and others.Currently,China's X-ray FLASH-RT research is at the forefront of the world,which is expected to achieve the first breakthrough of high-end medical equipment in the X-ray Flash RT field.
4.Exploration on Characteristics of Acupoint Efficacy Based on the Self-developed ACU&MOX-DATA Platform
Sihui LI ; Shuqing LIU ; Qiang TANG ; Ruibin ZHANG ; Wei CHEN ; Hao HONG ; Bingmei ZHU ; Xun LAN ; Yong WANG ; Shuguang YU ; Qiaofeng WU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):64-69
Objective To explore the effects of different acupoints,different target organs,and different interventions on acupoint efficacy based on ACU&MOX-DATA platform;To illustrate and visualize whether the above factors have the characteristics of"specific effect"or"common effect"of acupoint efficacy.Methods The multi-source heterogeneous data were integrated from the original omics data and public omics data.After standardization,differential gene analysis,disease pathology network analysis,and enrichment analysis were performed using Batch Search and Stimulation Mode modules in ACU&MOX-DATA platform under the conditions of different acupoints,different target organs,and different interventions.Results Under the same disease state and the same intervention,there were differences in effects among different acupoints;under the same disease state,the same acupoint and intervention,the responses produced by different target organs were not completely consistent;under the same disease state and acupoint,there were differences in effects among different intervention measures.Conclusion Based on the analysis of ACU&MOX-DATA platform,it is preliminary clear that acupoints,target organs,and interventions are the key factors affecting acupoint efficacy.Meanwhile,the above results have indicated that there are specific or common regulatory characteristics of acupoint efficacy.Applying ACU&MOX-DATA platform to analyze and visualize the critical scientific problems in the field of acupuncture and moxibustion can provide references for deepening acupoint cognition,guiding clinical acupoint selection,and improving clinical efficacy.
5.The Chinese guideline for management of snakebites
Lai RONGDE ; Yan SHIJIAO ; Wang SHIJUN ; Yang SHUQING ; Yan ZHANGREN ; Lan PIN ; Wang YONGGAO ; Li QI ; Wang JINLONG ; Wang WEI ; Ma YUEFENG ; Liang ZIJING ; Zhang JIANFENG ; Zhou NING ; Han XIAOTONG ; Zhang XINCHAO ; Zhang MAO ; Zhao XIAODONG ; Zhang GUOQIANG ; Zhu HUADONG ; Yu XUEZHONG ; Lyu CHUANZHU
World Journal of Emergency Medicine 2024;15(5):333-355
In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.
6.Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration
Wei LIU ; Wenyu WANG ; Chenglong TIAN ; Ming-Zhong SUN ; Shuqing LIU ; Qinlong LIU
The Korean Journal of Physiology and Pharmacology 2024;28(5):479-491
Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.
7.Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration
Wei LIU ; Wenyu WANG ; Chenglong TIAN ; Ming-Zhong SUN ; Shuqing LIU ; Qinlong LIU
The Korean Journal of Physiology and Pharmacology 2024;28(5):479-491
Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.
8.Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration
Wei LIU ; Wenyu WANG ; Chenglong TIAN ; Ming-Zhong SUN ; Shuqing LIU ; Qinlong LIU
The Korean Journal of Physiology and Pharmacology 2024;28(5):479-491
Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.
9.Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration
Wei LIU ; Wenyu WANG ; Chenglong TIAN ; Ming-Zhong SUN ; Shuqing LIU ; Qinlong LIU
The Korean Journal of Physiology and Pharmacology 2024;28(5):479-491
Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.
10.Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration
Wei LIU ; Wenyu WANG ; Chenglong TIAN ; Ming-Zhong SUN ; Shuqing LIU ; Qinlong LIU
The Korean Journal of Physiology and Pharmacology 2024;28(5):479-491
Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.

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