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.Platelet-rich plasma injection combined with warm acupuncture and moxibustion for treating patients with knee osteoarthritis and cold dampness obstruction syndrome
Xiang SHANG ; Fei WANG ; Qiqi YANG ; Tianxin JIANG ; Fen ZHANG ; Sanbing WU ; Yonghui YANG ; Fei LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):270-279
Objective:
To determine the clinical efficacy of platelet-rich plasma (PRP) injection combined with warm acupuncture and moxibustion for treating patients with knee osteoarthritis and cold dampness obstruction syndrome.
Methods:
One hundred and twenty-eight patients with knee osteoarthritis and cold dampness obstruction syndrome who visited the Rehabilitation Department and Orthopedics Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine from January 2023 to March 2024 and who met the inclusion and exclusion criteria were randomly divided into an experimental (n=64) and control group (n=64) using the random number table method. The experimental group was treated with PRP injection combined with warm acupuncture and moxibustion, whereas the control group was treated with normal saline injection combined with warm acupuncture and moxibustion treatment. PRP and normal saline injections were administered once every two weeks, a total of four times. Patients were treated with warm acupuncture and moxibustion once a day, six times a week, for four consecutive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Traditional Chinese Medicine (TCM) syndrome, visual analog scale (VAS), and Lysholm scores were determined before treatment, at week 4 and week 8 of treatment, and week 16 of follow-up. Serum interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), bone gla protein(BGP), and cartilage oligomeric matrix protein (COMP) levels were compared between the two groups before and after 8 weeks of treatment. The clinical efficacy and safety indicators between the two groups were also compared.
Results:
There was no statistical difference in baseline data such as gender, age, disease duration, and body mass index between the two groups of patients. Compared with before treatment, both groups showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm scores at 4, 8, and 16 weeks after treatment. After treatment, serum IL-6, MMP-3, TNF-α, and COMP levels decreased, whereas serum OPG and BGP levels increased (P<0.05). Compared with the control group, patients in the experimental group showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm score at 4, 8, and 16 weeks after treatment. Compared with the control group, patients in the experimental group showed decreased serum IL-6, MMP-3, TNF-α, and COMP levels and an increase in serum OPG and BPG levels after treatment (P<0.05). The total effective rate of the experimental group was 91.94%, higher than that of the control group (81.97%; P<0.05).
Conclusion
PRP injection combined with warm acupuncture and moxibustion can improve various TCM symptoms, improve knee joint function and bone metabolism, and reduce inflammation in patients with knee osteoarthritis and cold dampness obstruction syndrome.
3.An advanced machine learning method for simultaneous breast cancer risk prediction and risk ranking in Chinese population: A prospective cohort and modeling study
Liyuan LIU ; Yong HE ; Chunyu KAO ; Yeye FAN ; Fu YANG ; Fei WANG ; Lixiang YU ; Fei ZHOU ; Yujuan XIANG ; Shuya HUANG ; Chao ZHENG ; Han CAI ; Heling BAO ; Liwen FANG ; Linhong WANG ; Zengjing CHEN ; Zhigang YU
Chinese Medical Journal 2024;137(17):2084-2091
Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.
4.Preliminary study on delaying aging induced thymus degeneration in SAMP6 mice with Bazi Bushen capsule
Zhao-Dong LI ; Yin-Xiao CHEN ; Bo-Yang GONG ; Zhe XU ; Zhi-Xian YU ; Yue-Xuan SHI ; Yan-Fei PENG ; Yu-Hong BIAN ; Yun-Long HOU ; Xiang-Ling WANG ; Shu-Wu ZHAO
Chinese Pharmacological Bulletin 2024;40(6):1186-1192
Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P<0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P<0.01);the proportion of CD3+T cells apparently increased(P<0.05);the level of p16 protein signifi-cantly decreased(P<0.05);the level of Bcl-2 pro-tein significantly increased(P<0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P<0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P<0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.
5.Establishment and Evaluation Strategy of an in Vitro Cell Model of Bone Marrow Microenvironment Injury in Mouse Acute Graft-Versus-Host Disease
Jia-Yi TIAN ; Pei-Lin LI ; Jie TANG ; Run-Xiang XU ; Bo-Feng YIN ; Fei-Yan WANG ; Xiao-Tong LI ; Hong-Mei NING ; Heng ZHU ; Li DING
Journal of Experimental Hematology 2024;32(2):617-624
Objective:To establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2%,5%,and 10%recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2%and 5%was significantly reduced(P<0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P<0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P<0.05),the most significant difference was at a serum concentration of 10%(P<0.001,P<0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10%(P<0.01,P<0.001,P<0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.
6.Efficacy of visualized precise lung expansion for determining intersegmental plane in thoracoscopic segmentectomy
Hongchun BIAN ; Xue WU ; Huixia WANG ; Fei WANG ; Qiang SONG ; Xiaoxia WANG ; Long-Xiang ZHANG ; Wei ZHANG ; Zhiqiang ZOU ; Chengjie GAO
Chinese Journal of Anesthesiology 2024;44(4):401-405
Objective:To evaluate the efficacy of visualized precise lung expansion for determining the intersegmental plane in thoracoscopic segmentectomy.Methods:Sixty-four American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, regardless of gender, aged 33-77 yr, with body mass index of 16-34 kg/m 2, undergoing elective thoracoscopic segmentectomy under general anesthesia, were included. They were preoperatively reconstructed with 3D CT bronchovascularization to reconstruct the pulmonary vasculature, bronchus, and the virtual intersegmental planes of the lungs. The patients were divided into 2 groups ( n=32 each) using a random number table method: visualized precise lung expansion group (group V) and modified expansion and atrophy group (group E). Group V used visualized precision lung expansion to determine the intersegmental planes, and group E used the modified expansion and atrophy method to determine the intersegmental planes. The intraoperative intersegmental plane determination time, target segmental bronchus identification and treatment time, anesthesia time, operation time, postoperative air leakage, pulmonary atelectasis, fever, occurrence of lung infection, postoperative 24 h drainage volume, drain removal time and hospitalization time were recorded in the two groups. Results:Compared with group E, the intersegmental plane determination time, target segment bronchial identification and treatment time, anesthesia time and operation time were significantly shortened in group V( P<0.05).There were no significant differences between groups in the 24 h postoperative drainage volume, drain removal time, hospitalization time or incidence of postoperative pulmonary complications ( P>0.05). Conclusions:Compared with the modified expansion and atrophy method, visualized precise lung expansion can effectively shorten the intersegmental plane determination time in thoracoscopic segmentectomy.
7.Effects of Didang Decoction-containing serum on high glucose-induced injury of rat glomerular endothelial cells
Bao-Lu LUO ; Quan-Gen CHU ; Jun CHU ; Fei-Xiang LI ; Jing CHEN ; Yue-Qi WANG
Chinese Traditional Patent Medicine 2024;46(9):2930-2935
AIM To investigate the protective effects of Didang Decoction-containing serum on rat glomerular endothelial cells(RGECs)following high glucose injury.METHODS Rats were given distilled water or Didang Decoction by gavage to prepare the blank serum or Didang Decoction-containing serum.CCK8 method was used to screen the glucose concentration for the modeling and serum concentration of the drug.The RGECs were divided into the blank group,the model group,Didang Decoction group(10%Didang Decoction medicated serum),Dapagliflozin group(normal serum+2 μmol/L Dapagliflozin)and Didang Decoction+Dapagliflozin group(10%Didang Decoction medicated serum+2 μmol/L Dapagliflozin).24 hrs after the drug treatment,the RGECs had their mRNA and protein expressions of Nrf2,HO-1 and NQO-1 detected by RT-qPCR method and Western blot method;their Nrf2 fluorescence expression detected by immunofluorescence method;and their SOD activity and MDA level detected by colorimetric method.RESULTS Compared with the blank group,the model group displayed decreased mRNA and protein expressions of Nrf2,HO-1 and NQO-1 as well as the activity of SOD(P<0.01),and increased MDA level(P<0.01).Compared with the model group,the groups intervened with the drugs showed increased mRNA and protein expressions of Nrf2,HO-1 and NQO-1 as well as the activity of SOD(P<0.05,P<0.01),and decreased MDA level(P<0.01).CONCLUSION Didang Decoction-containing serum can protect RGECs from high glucose injury through activating the Nrf2 signaling pathway.
8.Analysis of Helicobacter pylori infection in the natural population of Sanya City
Shi-Mei HUANG ; Lian-Guo LAN ; Da-Ya ZHANG ; Run-Xiang CHEN ; Xiao-Dong ZHANG ; Chen CHEN ; Fan ZENG ; Da LI ; Xian-Feng HUANG ; Qi WANG ; Shi-Ju CHEN ; Lei GAO ; Jun-Tao ZENG ; Fei-Hu BAI
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(2):141-145
Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5%.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P<0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P>0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.
9. Effect of miR-141-5p/ZNF705A on adhesion of bone marrow mesenchymal stem cells in chronic myeloid leukemia cell-derived exosomes
Jing BAO ; Han XU ; Wan-Jie WANG ; Ting-Ting XU ; Ji-Fei DAI ; Rui-Xiang XIA
Chinese Pharmacological Bulletin 2024;40(3):506-514
Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.
10.Role of Ferroptosis in Osteoarthritis and Traditional Chinese Medicine Intervention: A Review
Xiaojing GUO ; Huan QIN ; Dongliang XIANG ; Yan WANG ; Li ZHANG ; Bo ZHANG ; Shujin WANG ; Xiaotong LI ; Mingyue ZHAO ; Shanhong WU ; Fei PEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):263-272
Osteoarthritis (OA) is characterized by articular cartilage degeneration, synovial hyperplasia, hyperosteogeny, and narrowing of joint space, which can be caused by trauma, inflammation, and other factors. With the increasing global population aging, the incidence of OA is rising year by year, making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex, including oxidative stress, autophagy, and apoptosis. Recent studies have found that ferroptosis, a new type of cell death, is also an important pathogenic factor in OA, characterized by a series of complex changes such as iron ion accumulation, glutathione (GSH) depletion, and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation, delay extracellular matrix (ECM) degradation, and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement, but there are limitations. Traditional Chinese medicine (TCM) has been widely used in the treatment of various diseases because of its low cost, low drug resistance, and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets, multiple levels, and aspects, but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism, lipid peroxidation, cysteine/glutamate transporter system Xc- (system Xc-)/GSH/glutathione peroxidase 4 (GPX4) pathway, nicotinamide adenine dinucleotide phosphate(NADPH)/ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10) pathway, tumor protein p53 in OA, and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs.


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