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.Shaoyaotang Alleviates Damage of Tight Junction Proteins in Caco-2 Cell Model of Inflammation by Regulating RhoA/ROCK Pathway
Nianjia XIE ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Yuting YANG ; Bo ZOU ; Da ZHAO ; Yi LU ; Mingsheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):70-77
ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang (SYD) on the lipopolysaccharide (LPS)-induced damage of tight junction proteins in the human colorectal adenocarcinoma (Caco-2) cell model of inflammation via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. MethodsCaco-2 cells were grouped as follows: Blank, model (LPS, 10 mg·L-1), SYD-containing serum (10%, 15%, and 20%), and inhibitor (Fasudil, 25 μmol·L-1). After 24 hours of intervention, the cell viability in each group was examined by the cell-counting kit 8 (CCK-8) method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of RhoA, ROCK2, claudin-5, and zonula occludens-1 (ZO-1) in cells of each group. ResultsCompared with the blank group, the model group showcased a marked reduction in the cell viability (P<0.01), elevations in the levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), declines in both mRNA and protein levels of ZO-1 and claudin-5 (P<0.01), and rises in mRNA and protein levels of RhoA and ROCK2 (P<0.01). Compared with the model group, the Shaoyaotang-containing serum (10%, 15%, and 20%) groups had enhanced cell viability (P<0.01), lowered levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), up-regulated mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and down-regulated mRNA and protein levels of RhoA and ROCK2 (P<0.01). Moreover, the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), higher mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and lower mRNA and protein levels of RhoA and ROCK2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.
3.Shaoyaotang Alleviates Damage of Tight Junction Proteins in Caco-2 Cell Model of Inflammation by Regulating RhoA/ROCK Pathway
Nianjia XIE ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Yuting YANG ; Bo ZOU ; Da ZHAO ; Yi LU ; Mingsheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):70-77
ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang (SYD) on the lipopolysaccharide (LPS)-induced damage of tight junction proteins in the human colorectal adenocarcinoma (Caco-2) cell model of inflammation via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. MethodsCaco-2 cells were grouped as follows: Blank, model (LPS, 10 mg·L-1), SYD-containing serum (10%, 15%, and 20%), and inhibitor (Fasudil, 25 μmol·L-1). After 24 hours of intervention, the cell viability in each group was examined by the cell-counting kit 8 (CCK-8) method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of RhoA, ROCK2, claudin-5, and zonula occludens-1 (ZO-1) in cells of each group. ResultsCompared with the blank group, the model group showcased a marked reduction in the cell viability (P<0.01), elevations in the levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), declines in both mRNA and protein levels of ZO-1 and claudin-5 (P<0.01), and rises in mRNA and protein levels of RhoA and ROCK2 (P<0.01). Compared with the model group, the Shaoyaotang-containing serum (10%, 15%, and 20%) groups had enhanced cell viability (P<0.01), lowered levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), up-regulated mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and down-regulated mRNA and protein levels of RhoA and ROCK2 (P<0.01). Moreover, the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), higher mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and lower mRNA and protein levels of RhoA and ROCK2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.
4.Visual analysis of hot topics in concussion field by finite element method:Improvements in brain injury models,test methods and protective devices
Weidong LUO ; Lihua ZOU ; Da HUANG
Chinese Journal of Tissue Engineering Research 2024;28(34):5487-5493
BACKGROUND:Concussions caused by contact sports or traffic accidents are far more serious and common than people think,and have attracted widespread attention and high attention from the media,medical and sports circles in recent years. OBJECTIVE:To visualize the hot spots and trends in the field of concussion by using the method of bibliometrics,so as to provide some reference for the research in this field in China. METHODS:Based on the core collection database of Web of Science,the keyword retrieval strategy was(TS=(Concussion))AND TS=(Finite element).CiteSpace 6.2.R4 visualization tool was used to visually analyze the author,country,institution,keywords,cited documents,etc. RESULTS AND CONCLUSION:A total of 215 articles were included,with a general upward trend in the number of publications and citations.The distribution of disciplines involves biomedical engineering,biophysics,sports science,clinical neurology,neuroscience and other disciplines,showing a trend of interdisciplinary integration.The author with the most publications is Gilchrist M from University College Dublin,Ireland,the institution with the most publications is the University of Ottawa,and the country with the most publications is the United States.Key word analysis shows that the focus of research is on the establishment of brain injury models to simulate and predict concussion injuries;analysis of concussion injury mechanism;optimal design of protective equipment and devices.Through literature co-citation analysis,it is found that the prediction and evaluation of brain injury is the knowledge base and research hotspot in this field.The research hotspot of finite element application in the field of concussion injury mainly focuses on the prediction of head injury,combined with the exploration of brain injury mechanism and the design and improvement of protective equipment.With the progress of artificial intelligence and materials science,future research hotspots in the field of concussion injury will focus on the improvement of brain injury models,test methods and protective equipment.
5.Application of deep learning image reconstruction combined with computer-aided diagnosis in CT screening of pulmonary nodules
Jing LU ; Tao LI ; Bimiao WEI ; Hang CHEN ; Da ZOU ; Hongfeng LIANG
Journal of Practical Radiology 2024;40(1):135-139
Objective To analyze the effects of deep learning image reconstruction(DLIR)and adaptive statistical iterative recon-struction V(ASIR-V)on the imaging quality of chest CT in patient with pulmonary nodules,and to evaluate the differences based on different image reconstruction techniques in the detection of efficiency of computer-aided diagnosis(CAD)for pulmonary nodules.Methods The image data of pulmonary nodules of eighty patients with chest CT screening were reconstructed with ASIR-V 80%,DLIR-low(DLIR-L),DLIR-medium(DLIR-M)and DLIR-high(DLIR-H)images,respectively.The objective image quality and sub-jective image quality of the four groups were compared and analyzed.Objective image quality includes CT value of region of interest(ROI),noise,signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR)and image average gradient.The diagnostic efficacy of CAD in detecting pulmonary nodules of reconstructed images among four groups were further evaluated.Results There were no signifi-cant difference in CT value of ROI of reconstructed images among the four groups(P>0.05).The noise,SNR and CNR of DLIR-H images were similar to those of ASIR-V 80%(P>0.05),but significantly better than those of DLIR-L and DLIR-M(P<0.05).The average gradient of DLIR-L,DLIR-M and DLIR-H images were significantly higher than those of ASIR-V 80%(P<0.05).The subjective image quality scores of DLIR-L,DLIR-M and DLIR-H images were significantly higher than those of ASIR-V 80%(P<0.05),and the subjective image quality score of DLIR-H image was the highest.CAD showed the highest true positive rate in DLIR-H images for detecting pulmonary nodules(P<0.05),and CAD showed the highest false positives per capita in ASIR-V 80%images for detecting pulmonary nodules(P<0.05).Conclusion The noise,SNR and CNR of DLIR-H images are similar to those of ASIR-V 80%,with the significantly higher image clarity and subjective image quality scores.DLIR-H has advantages in CAD detection of pulmonary nodules,which is an ideal image reconstruction technology for chest CT pulmonary nodule screening.
6.Risk factors of complicating pulmonary hypertension in patients with chronic obstructive pulmonary disease:a meta-analysis
Xun ZOU ; Xiaohong TANG ; Da JING ; Yang YANG
Chongqing Medicine 2024;53(11):1711-1716
Objective To systematically evaluate the risk factors for complicating pulmonary hyperten-sion (PH) in the patients with chronic obstructive pulmonary disease (COPD).Methods The databases of PubMed,Embase,Cochrane Library,VIP,CNKI,China Biomedical Literature Service System and Wanfang Database were retrieved by computer.The retrieval time limitation was from the establishment of the database to September 2023.The literatures on the risk factors for complicating PH in the patients with COPD was col-lected and the meta analysis was conducted by using the RevMan 5.3 software.Results A total of 18 articles were included,including 8 prospective studies and 10 retrospective studies,with a total of 4361 COPD pa-tients,including 8 risk factors.The meta analysis results showed that the risk factors with statistical signifi-cance included C-reactive protein (CRP)[OR(95%CI)=2.17 (1.49-3.14)],interleukin-6 (IL-6)[OR(95%CI)=2.07 (1.59-2.70)],tumor necrosis factor-α (TNF-α)[OR(95%CI)=1.69 (1.28-2.22)],brain na-triuretic peptide (BNP)[OR(95%CI)=1.58 (1.35-1.85)],D-dimer (D-D)[OR(95%CI)=2.58 (1.99-3.35)],forced expiratory volume in one second (FEV1)[OR(95%CI)=2.49 (1.93-3.20)]and mean plate-let volume (MPV)[OR(95%CI)=1.69 (1.19-2.39)].Conclusion CRP,IL-6,TNF-α,BNP,D-D,FEV1 and MPV are the risk factors for complicating PH in COPD patients.
7.Dosimetric comparison of anal sphincter and its substructures with different radiotherapy techniques for rectal cancer
Geng LI ; Fei DENG ; Yong-Jun LI ; Da-Li FENG ; Xin LI ; Zhuo KONG ; Ji-Ping WANG ; Min ZOU
Chinese Medical Equipment Journal 2024;45(8):63-67
Objective To compare the dosimetric effects of volume modulated arc therapy(VMAT)and intensity modulated radiation therapy(I M RT)on the anal sphincter(AS)and its sub-structures in neoadjuvant radiotherapy for rectal cancer to facilitate the selection of radiotherapy techniques.Methods Fifty rectal cancer patients receiving neoadjuvant radiotherapy were selected,and 2 types of radiotherapy plans,including coplanar double full-arc VMAT and coplanar seven-field homo-geneous IMRT,were designed based on the CT images of the patients,respectively.Under the premise of ensuring that the irradiated doses to the target area and the major organs at risk reached the standard and met the clinical requirements,AS and its substructures were added as the organs at risk for dosimetric evaluation.The absolute dose parameters and relative dose parameters of AS and its substructures were counted by dose-volume histograms.Statistical analysis was performed using IBM SPSS 22.0 software.Results The VMAT plan had the relative dose parameters V20,V30,and V40 of AS and its substructures lower those of the IMRT plan,the differences were statistically significant(P<0.05),while the differences in V5 and V 10 were not statistically significant(P>0.05).The VMAT plan had the absolute dose parameterDmeanlower while the D2%slightly higher than those of the IMRT plan,the differences were statistically significant(P<0.05).The difference in D98%between the two plans was not statistically significant(P>0.05).Conclusion During rectal cancer radiotherapy VMAT generally behaves better than IMRT in protecting AS and its sub-structures and decreasing injuries of AS and its sub-structures dosimetrically.[Chinese Medical Equipment Journal,2024,45(8):63-67]
8.Application of multi-disciplinary team model in the management of hospi-tal antimicrobial management
Lin-Li PAN ; Da-Wei WU ; Shan-Shan LIU ; Jie PANG ; Xiu-Zhen ZOU
Chinese Journal of Infection Control 2024;23(6):719-724
Objective To explore the application effect of multi-disciplinary team(MDT)model in hospital antimi-crobial management.Methods Relevant data on antimicrobial use in hospitalized patients in a hospital from January 2021 to December 2022 were analyzed retrospectively,January-December 2021 adopted conventional management mode and was as the control group,January-December 2022 adopted MDT management model and was as the inter-vention group.Antimicrobial therapy relevant indicators between two groups of patients were compared.Results After adopting the MDT management model,pathogen detection rate before the therapeutic antimicrobial use in the intervention group(73.62%)was higher than that in the control group(70.56%),difference was statistically sig-nificant(P<0.001).Pathogen detection rate related to healthcare-associated infection diagnosis was 87.98%in the control group and 88.89%in the intervention group,with no statistically significant difference between two groups(P>0.05).Pathogen detection rate before combined use of key antimicrobial agents in the intervention group(93.94%)was higher than that in the control group(92.00%),difference was statistically significant(P<0.05).Antimicro-bial use rate in hospitalized patients and use rate of prophylactic antimicrobial agents in class Ⅰ incision surgery de-creased from 38.03%and 21.03%to 32.78%and 10.30%,respectively,with statistically significant differences(both P<0.05).The amount and intensity of antimicrobial use in hospitalized patients in the intervention group de-creased.The implementation rate of bundled prevention and control measures for multidrug-resistant organism(MDRO)after intervention was significantly higher than that of the control group,with statistically significant differences(all P<0.05).MDRO detection rate decreased from 34.70%to 32.37%,difference was statistically significant(P=0.027).there was no significant change in the MDRO case infection rate.Conclusion The MDT model can effectively improve the standardized management of antimicrobial agents,promote the rational use of anti-microbial agents in clinical practice,and prevent bacterial resistance.
9.Ultra-fast track anesthesia management for transcatheter mitral valve edge-to-edge repair
Zhi-Yao ZOU ; Da ZHU ; Yi-Ming CHEN ; Shou-Zheng WANG ; Jian-Bin GAO ; Jing DONG ; Xiang-Bin PAN ; Ke YANG
Chinese Journal of Interventional Cardiology 2024;32(5):250-256
Objective To retrospectively analyze the ultra-fast track anesthesia(UFTA)methods and perioperative anesthesia management experiences of transcatheter mitral valve edge-to-edge repair(TEER)in the treatment of functional mitral regurgitant.Methods In this retrospective study,patients underwent the TEER procedure and received UFTA in Fuwai Yunnan Hospital,from May 2022 to September 2022 for heart failure combined with moderate to severe or severe functional mitral regurgitant were included.Baseline,preoperative complications,cardial function and anesthesia classification,amino-terminal probrain natriuretic peptide(NT-proBNP),ultrasound examination results,surgery time,extubation time,intraoperative anesthetic and vasoactive drug,complications related to TEER and UFTA,perioperative,and postoperative 30-day and one-year follow-up data were collected.All perioperative clinical data were recorded and analyzed.Results A total of 30 patients were enrolled,11 patients(36.7%)were female,mean age was(63.6±6.1)years,NYHA classification IV 14 patients(46.7%),left ventricular ejection fraction(LVEF)(36.0±8.1)%,the end-diastolic volume of the left ventricle(66.0±8.2)mm,mitral regurgitation 4+14 patients(56.7%),3+17 patients(43.3%),NT-proBNP(1 934.1±1 973.5)pg/ml,1 patient(3.3%)used high-dose vasoactive drugs during surgery.All patients did not experience nausea,vomiting,delirium,respiratory depression,perioperative transesophageal echocardiography-related gastrointestinal bleeding,pericardial effusion,cerebrovascular accidents,emergency surgery or secondary intervention,or other serious adverse events within 24 hours after surgery.No 30-day all-cause death occurred;the mean postoperative hospital stay was(7.4±2.8)days.All patients completed one-year follow-up,LVEF(37.6±11.1)%,the end-diastolic volume of the left ventricle(63.2±8.6)mm,mitral regurgitation 2+7 patients(23.3%),1+23 patients(76.7%),NT-proBNP(1 949.2±2 576.6)pg/ml.Conclusions Ultra-fast track anesthesia can be safely applied to TEER in treating functional mitral regurgitant patients.
10.Establish a Graded Method to Avoid HLA Class I Antibodies Cor-responding Antigen and Combining HLAMatchmaker Application in Improving the CCI Value after Platelet Transfusion for Patients with IPTR
Su-Qing GAO ; Yun-Ping XU ; Chang-Ru LUO ; Da-Cheng LI ; Long PEN ; Tong LIU ; Qiong-Cai ZOU
Journal of Experimental Hematology 2024;32(1):242-249
Objective:To establish a graded method to avoid mean fluorescence intensity(MFI)threshold of HLA Class I antibodies corresponding antigen,and the HLAMatchmaker program has been used to select the minimum mismatch value of donor-patient epitopes.Evaluate the application value of combining both methods in selecting HLA compatible platelets(PTL)for patients with immune platelet transfusion failure(IPTR)in improving platelet the corrected count increment(CCI).Methods:A total 7 807 PLT cross-matching compatible were performed by the solid-phase red cell adherence(SPRCA)method for 51 IPTR patients.The Luminex single antigen flow cytometry was used to detect HLA Class I antibodies in patients,and detected the MFI value for different specificity antigens of HLA Class I antibodies,was graded into strong positive group(MFI>4 000,level 1),medium positive group(1 000<MFI 4 000,2),weak positive group(500<MFI≤1 000,3),and one negative control group(MFI≤500).The results of 7 807 SPRCA their negative/positive reaction wells were enrolled and statistically analyzed in different grades and the four groups,the statistical differences between the four groups were compared.Multiple applications for the select HLA Class I compatible donor events were made for patients in two cases,and HLAMatchmaker program was used to calculate the number of HLA Class I epitopes mismatches between the donors and patients.The donor with the minimum number of epitopes mismatches was selected,while avoiding the corresponding antigens of HLA Class I antibodies in levels 1 and 2,the provision of HLA compatible platelets for IPTR.After the transfusions,the CCI value of the platelet transfusion efficacy evaluation index was calculated,and the clinical evaluation of the transfusion effect was obtained through statistical analysis.Results:There were statistically significant differences in the positive results of SPRCA immunoassay among the strong positive group,medium positive group,and weak positive group of 51 IPTR patients with different specific of HLA-I class antibodies and corresponding antigens(all P<0.001).The positive results showed a range from high to low,with strong positive group>medium positive group>weak positive group.There were a statistical difference among between the strongly positive or moderately positive groups and the negative control group(P<0.001).There was no statistical difference between the weakly positive group and the negative control group(P>0.05).The strong positive group was set as the corresponding specific HLA Class I site corresponding antigen grade 1 avoidance threshold,the medium positive group as the grade 2 avoidance thresholds,and the weak positive group as the grade 3 avoidance threshold.In the case of donor platelet shortage,it is not necessary to avoid the weak positive group.Avoiding the strategy of donor antigens and HLAMatchmaker program scores≤7 corresponding to HLA Class I antibodies of levels 1 and 2,with CCI values>4.5 × 109/L within 24 hours,can obtain effective clinical platelet transfusion conclusions.Conclusion:When selecting HLA Class I compatible donors for IPTR patients,the grading avoids HLA Class I antibodies corresponding to donor antigens,and the donor selection strategy with the minimum scores of HLAMatchmaker program is comprehensively selected.The negative result confirmed by platelet cross-matching experiments has certain practical application value for improving platelet count in IPTR patients.

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