1.The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer
Xin-Die WANG ; Da-Li FENG ; Xiang CUI ; Su ZHOU ; Peng-Fei ZHANG ; Zhi-Qiang GAO ; Li-Li ZOU ; Jun WANG
Progress in Biochemistry and Biophysics 2025;52(4):804-819
Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.
2. Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis
Zheng-Yang SUN ; Nan-Nan LIU ; Xue-Fei FAN ; Su-Huan CHEN ; Xiao-Yu CHEN ; Zheng-Yang SUN ; Wu-Qi CHEN ; Guang-Yi CHEN ; Yu-Bao SHAO ; Xiao-Yu CHEN
Chinese Pharmacological Bulletin 2024;40(2):292-298
Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L
3. Effects of Tao Hong Si Wu decoction on IncRNA expression in rats with occlusion of middle cerebral artery
Li-Juan ZHANG ; Chang-Yi FEI ; Chao YU ; Su-Jun XUE ; Yu-Meng LI ; Jing-Jing LI ; Ling-Yu PAN ; Xian-Chun DUAN ; Li-Juan ZHANG ; Chang-Yi FEI ; Chao YU ; Su-Jun XUE ; Yu-Meng LI ; Jing-Jing LI ; Xian-Chun DUAN ; Dai-Yin PENG ; Xian-Chun DUAN ; Dai-Yin PENG
Chinese Pharmacological Bulletin 2024;40(3):582-591
Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.
4.Exploration of the Treatment of Antibiotic-Associated Diarrhea in Children from the Perspective of Spleen
Hao-Dong SU ; Hao-Ling ZHENG ; Ling-Juan LIU ; Fei LUO ; Xiu-Lan DONG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):1058-1062
Antibiotic-associated diarrhea(AAD)in children is a type of diarrhea that occurs after the use of antibiotics in children,and its pathogenesis is closely related to the intestinal flora.The medication of antibiotics can affect the metabolic function of the intestinal flora and the immune function of the body,and then leads to the occurrence of AAD.In the view of Chinese medicine,AAD in children is mainly involved the spleen,and the etiology of the disease is due to the weakness of the spleen and stomach of the body constitution together with the attack of the pestilential pathogen and the accumulation of drug toxin.The pathogenesis of ADD in children is characterized by spleen deficiency with predominant dampness,deficiency of spleen qi,and insufficiency of spleen yang.Spleen deficiency is the root cause of pediatric AAD,and spleen and intestinal flora have commonality,so the treatment of pediatric AAD can be performed from the perspective of the spleen.The treatment of pediatric ADD from the spleen follows the principle of strengthening and activating the spleen,and the regulation of the spleen for achieving the purpose of treating the disease from the root can be achieved by the methods of strengthening spleen and draining dampness,strengthening spleen and replenishing qi,and strengthening spleen and warming yang separately with the fundamental prescriptions of Shenlin Baizhu Powder,Sijunzi Decoction,and Fuzi Lizhong Pills.
5.Effects of Gegen Qinlian Decoction on PERK/ATF4/CHOP Signaling Pathway in Pancreatic Tissue of Mice with Type 2 Diabetes Mellitus
Xiaowen GUAN ; Yonglin LIANG ; Xiangdong ZHU ; Fei SU ; Yuanyuan ZHANG ; Yanhui ZHAI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):97-103
Objective To observe the effects of Gegen Qinlian Decoction on pancreatic endoplasmic reticulum stress in mice with type 2 diabetes mellitus(T2DM);To explore its mechanism of action in the treatment of T2DM.Methods Totally 75 SPF male db/db mice were randomly divided into model group,metformin group,and Gegen Qinlian Decoction high-,medium-,low-dosage groups,with 15 mice in each group.15 db/m mice were set as the blank group.The administration groups received corresponding medicine for gavage for 12 weeks.Body mass,fasting blood glucose(FBG)and glycated hemoglobin(HbA1c)in mice were detected,HE staining was used to observe the pathological changes of pancreatic tissue,the apoptosis of islet cells was determined by TUNEL staining,Western blot was used to detect pancreatic tissue glucose regulatory protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)protein expression,RT-PCR was used to detect pancreatic tissue PERK,ATF4,CHOP mRNA expressions.Results Compared with the blank group,the body mass,FBG and HbA1c contents in the model group significantly increased(P<0.01);the pancreatic tissue structure was incomplete,with blurry boundaries and vacuoles inside,leading to a significant increase in pancreatic islet cells apoptosis(P<0.01);the expressions of GRP78,p-PERK,ATF4,and CHOP proteins in pancreatic tissue significantly increased(P<0.01),and the mRNA expressions of PERK,ATF4 and CHOP significantly increased(P<0.01).Compared with the model group,the body mass,FBG and HbA1c contents of mice in each administration group significantly decreased(P<0.05,P<0.01);pathological changes in pancreatic tissue was reduced,and islet cells apoptosis decreased to varying degrees(P<0.05,P<0.01);the expressions of GRP78,p-PERK,ATF4 and CHOP proteins in pancreatic tissue significantly decreased(P<0.01)in Gegen Qinlian Decoction high-and medium-dosage groups and the metformin group,and the expressions of PERK,ATF4 and CHOP mRNA significantly decreased(P<0.05,P<0.01).Conclusion Gegen Qinlian Decoction may decreased pancreatic islet cells apoptosis,protect pancreatic cell function,and delay the progression of T2DM by inhibiting the endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway,and down-regulating the expressions of related genes and proteins.
6.Joinpoint regression analysis of hand, foot, and mouth disease trends in Zhangjiakou City, Hebei Province from 2013 to 2022
Fei SUN ; Xiaoli HAN ; Tong SU ; Xiaoyan LUO ; Wen GAO ; Tianman WANG ; Qichen LIU ; Dong YAN ; Jinqin LI
Shanghai Journal of Preventive Medicine 2024;36(9):858-861
ObjectiveTo analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Zhangjiakou City, Hebei Province from 2013 to 2022, so as to provide a basis for HFMD prevention, control, and evaluation of intervention effectiveness. MethodsHFMD data of Zhangjiakou City from 2013 to 2022 were collected. Descriptive statistics and the Joinpoint regression model were used to analyze the trend of the epidemic. ResultsThe incidence of HFMD in Zhangjiakou was predicted to decrease with APC=-14.86% in 2013‒2022. The top five regions with the highest incidence showed varying trends: Qiaodong District (APC=-26.21%), Qiaoxi District (APC=-18.29%), Xuanhua District (APC=-14.28%), Chicheng District (APC=-18.68%), and Zhuolu County (APC=51.43% in 2013‒2016, APC=-14.27% in 2016‒2022), indicating a downward trend. Three age groups showed an upward trend in incidence: the 0-year-old group (APC=-42.82% in 2013‒2016, APC=16.54% in 2016‒2022), the 7-year-old group (AAPC=9.60%), and the 9-year-old group (AAPC=12.76%). HFMD cases occurred throughout the year, peaking from June to August, with July being the most significant month. The male-to-female ratio was1.40∶1, with no statistical difference (χ2=5.932, P>0.05). A high incidence was in children under 5 years old, with those aged 1‒4 years being the main affected group. In terms of occupation, scattered children (6 245 cases, 57.65%) and preschool children (3 653 cases, 33.72%) were the most affected. A total of 504 laboratory-confirmed cases were reported, with a detection rate of 4.65% (504/10 832). The composition of confirmed cases included CoxA 16 (193 cases, 38.29%), EV71 (75 cases, 14.88%), and other enteroviruses (236 cases, 46.83%). ConclusionFrom 2013 to 2022, HFMD in Zhangjiakou City showed a downward trend with clear seasonal, regional, and occupational distributions. It is suggested that epidemic monitoring should be strengthened, etiological detection should be enhanced, and education efforts in key areas should be improved. High-incidence counties should analyze data and conduct risk assessments effectively.
7.Intra-and peri-tumoral radiomics model for predicting the response to concurrent chemoradiotherapy in cervical squamous cell carcinoma based on dynamic contrast-enhanced MRI
Yaying SU ; Dan ZHAO ; Zhiying PANG ; Fei YANG ; Shujun CUI
Journal of Practical Radiology 2024;40(3):411-416
Objective To investigate the correlation between intra-and peri-tumoral radiomics features and the response to con-current chemoradiotherapy(CCRT)in cervical squamous cell carcinoma,and to explore the difference of predictive performance between 2D and 3D radiomics models.Methods The imaging data of 132 patients were analyzed retrospectively and randomly divided into training set(n=92)and validation set(n=40).Radiomics features were extracted based on the dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),the correlation analysis and least absolute shrinkage and selection operator(LASSO)algorithm were used for dimensionality reduction and screening,then the radiomics score was calculated and the logistic model was constructed.The receiver operating characteristic(ROC)curve,internal validation of Bootstrap and Brier score were used to evaluate the discrimina-tion and calibration of the model,and the improvement in predictive performance of 3D model compared with 2D model was evaluated by the integrated discrimination improvement(IDI).Results In the training set,the ROC curve showed that the area under the curve(AUC)of the models(2D-intratumoral,3D-intratumoral,3D-peritumoral,3D-combined)ranged from 0.774 to 0.893.The internal validation of Bootstrap showed the AUC were 0.772,0.860,0.847 and 0.888,respectively,while in the validation set,the AUC were 0.757,0.849,0.824 and 0.887,respectively.The Brier scores indicated that the models were well calibrated.In the training set and the validation set,the IDI values were 0.155 and 0.179,respectively,and the differences were statistically significant(P<0.05).Conclusion The radiomics analysis based on the tumor volume can fully explore the tumor heterogeneity.The intra-and peri-tumoral radiomics combined model shows the best predictive performance,which is important to assist clinicians in developing individualized therapies.
8.Early acute change process after retinal laser injury
Chinese Journal of Primary Medicine and Pharmacy 2024;31(4):627-631
Laser-induced retinal damage is a gradual and progressive process, yet there remains a dire need for safe and effective therapeutic drugs and preventive measures to mitigate and treat this condition. Currently, the exploration of treatment options for laser-induced retinal damage is still in its experimental phase. This review delves into the histopathological, functional, and molecular expression levels of the retina after acute laser injury. It aims to uncover the acute changes that occur following laser injury, identify the optimal window period for intervention, and hypothesize the best time for treatment to rescue residual cells and preserve remaining vision.
9.Development and prospects of predicting drug polymorphs technology
Mei GUO ; Wen-xing DING ; Bo PENG ; Jin-feng LIU ; Yi-fei SU ; Bin ZHU ; Guo-bin REN
Acta Pharmaceutica Sinica 2024;59(1):76-83
Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.
10.Study on the Trend of Out-of-Pocket as a Proportion of Total Health Expenditure in Heilongjiang Province from 2013 to 2022
Chinese Health Economics 2024;43(11):49-52
Objective:To explore the trend of Out-of-Pocket as a proportion of total health expenditure in Heilongjiang Province from 2013 to 2022,assessing the medical economic burden on residents and the equitable distribution of health resources.Methods:It employs statistical description and comparative research methods,collecting data on total health expenditure and Out-of-Pocketfor medical care in Heilongjiang Province from 2013 to 2022.A horizontal comparative analysis is conducted,comparing these trends with other provinces in the Northeast region and at the national level.Results:The Out-of-Pocket proportion in total health expenditure in Heilongjiang Province decreased from 41.56%in 2013 to 28.88%in 2022,indicating a downward trend;however,it remains higher than the national average during the same period.Additionally,the proportion of government health expenditure and social health expenditure has gradually increased,reflecting greater investment in the health sector by both the government and society.Conclusion:Although the Out-of-Pocket proportion in total health expenditure in Heilongjiang Province has decreased,the medical economic pressure on residents remains significant.It is recommended that the government continue to enhance health investment,optimize the health financing model,improve the efficiency of health services,reduce the burden of personal health expenditure,and achieve a more equitable distribution of health resources.

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