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.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
		                        		
		                        			
		                        			 Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC. 
		                        		
		                        		
		                        		
		                        	
3.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
		                        		
		                        			
		                        			 Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC. 
		                        		
		                        		
		                        		
		                        	
4.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
		                        		
		                        			
		                        			 Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC. 
		                        		
		                        		
		                        		
		                        	
5.Iron overload regulates atherosclerotic activity of foam cells induced by oxLDL
Xiaoyan WANG ; Xiaoyi ZOU ; Xiang ZHU ; Ting WANG ; Yetao QIANG ; Siyuan ZHOU ; Peng ZHANG ; Ping ZHANG
The Journal of Practical Medicine 2024;40(3):295-301
		                        		
		                        			
		                        			Objective To explore the roles of iron overload in pro-atherogenic activation of foam cells.Methods RAW264.7 and MOVAS cells were stimulated by oxLDL,ferrimine citrate and deferoxamine respectively.Prussian Blue and Oil Red O staining were used to detect iron deposition and foam cell.CCK-8 test,DHE probe,ELISA,RT-qPCR were performed to detect the cell death rate,reactive oxygen species(ROS)generation,lipid peroxidation molecules[glutathione peroxidase(GSH),glutathione peroxidase 4(GPX4),malondialdehyde(MDA)content]and the mRNA level of ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABCG1),inductible nitris oxide synthase(iNOS),arginase-1(Arg-1),α-smooth muscle actin(α-SMA),smooth muscle 22 alpha(SM22a),osteopontin(OPN),Interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α).Results Iron overload could reduced reverse cholesterol transporters(ABCA1 and ABCG1),promote foam cells generation,increased cell death rate,induced the expression of lipid peroxidation molecules(GSH,GPX4,MDA),and promoted pro-inflammatory M1 marker of macrophage and synthetic marker expression of vascular smooth muscle cell(VSMC)and inflammatory cytokines(IL-1β,TNF-α).Conclusion Iron overload promotes the generation of foam cells derived from macrophages and smooth muscle cells and transform them into pro-atherosclerotic phenotype,aggravates cell lipid peroxidation and inflammatory reaction,which contributes to the progress of atherosclerosis.
		                        		
		                        		
		                        		
		                        	
6.Lipopolysaccharide induces aging phenotype of hematopoietic stem cells in bone marrow and spleen of young mice
Ke BAI ; Mi ZOU ; Qiang ZHAN ; Yingxin HUANG ; Zhenyu JU ; Zhiyang CHEN
Chinese Journal of Pathophysiology 2024;40(1):38-46
		                        		
		                        			
		                        			AIM:This study aim to investigate the effects of lipopolysaccharide(LPS)-induced inflammation on the aging phenotype of hematopoietic stem/progenitor cells(HSPCs)in the bone marrow(BM)and spleen of mice.METHODS:(1)Young(2-month old)wild-type(WT)mice were treated with LPS to establish an actue inflammation model.The percentage of HSPCs in the BM and spleen of mice after LPS stimulation,as well as the ratio of mature cells in peripheral blood(PB)and spleen,were analyzed using flow cytometry.The proliferation of HSPCs in the BM and spleen was evaluated by examining the expression of the proliferation marker Ki67.In addition,changes in CD45 expression on HSPCs in the spleen of mice following LPS exposure were investigated by flow cytometry.(2)The percentage of HSPCs in BM and mature cells in PB and spleen of both young(2-month old)and old(24-month old)WT mice were analyzed by flow cytometry.(3)The transcriptome changes of hematopoietic stem cells(HSCs)after LPS stimulation was performed by an in silico analysis.RESULTS:(1)Mice exposed to LPS exhibited a significant increase in the percentage of HSPCs in BM and a marked elevation in the percentages of myeloid cells in PB and spleen compared to the mice in control group(P<0.05).(2)LPS exposure resulted in increased spleen weight and cell counts(P<0.05),along with a higher per-centage of HSPCs in the spleen compared to controls(P<0.05).(3)LPS stimulation promoted the proliferation of HSPCs in the BM and spleen(P<0.05).(4)The expression of CD45 was reduced on HSPCs from spleen of mice after LPS stimu-lation(P<0.01).(5)In comparison to young mice,aged mice showed an increase in spleen weight and a higher percent-age of HSPCs in the spleen(P<0.05).(6)Aged mice,in comparison to young mice,demonstrated a significantly higher percentage of HSPCs in the BM and myeloid skewing in the PB and spleen(P<0.01).(7)The silico analysis revealed up-regualtion of reactive oxygen species(ROS)and apoptosis signaling in HSPCs following LPS stimulation.CONCLU-SION:Young HSPCs stimulated by LPS exhibited an increase in cell number,a bias towards myeloid differentiation,en-hanced extramedullary hematopoiesis,and elevated levels of ROS and apoptosis,all of which collectively manifested the aging phenotype of HSPCs.
		                        		
		                        		
		                        		
		                        	
7.Effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis of rats with ischemia-reperfusion induced injury
Yang ZHAI ; Xue-Ni MO ; Hong-Li TENG ; Yue-Qiang HU ; Guang-Shan ZHENG ; Wei MA ; Peng YANG ; Xiao-Ping MEI ; Min ZOU ; Kai-Hua WANG
Chinese Traditional Patent Medicine 2024;46(3):795-802
		                        		
		                        			
		                        			AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P<0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P<0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.
		                        		
		                        		
		                        		
		                        	
8.Giant chronic left ventricular pseudoaneurysm following myocardial infarction with non-obstructive coronary arteries: A case report
Wanwan ZOU ; Enze BIAN ; Qikun ZHU ; Song YANG ; Weizhong ZHUANG ; Huiming GUO ; Yun TENG ; Qiang GAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(12):1865-1866
		                        		
		                        			
		                        			A 55-year-old male patient was admitted to the hospital due to "recurrent chest pain for 8 months, with worsening symptoms for 2 weeks". After admission, comprehensive relevant examinations led to the consideration of a giant chronic left ventricular pseudoaneurysm caused by myocardial infarction with non-obstructive coronary arteries. Surgical treatment was performed at our hospital. We discuss the diagnosis and treatment of this patient.
		                        		
		                        		
		                        		
		                        	
9.Study on the Efficacy and Safety of Modified Huanglian Wendan Decoction in Treating Hypertension Complicated with Sleep Disorders of Phlegm-Heat Harassing the Interior Type
Zu-Qiang WU ; Hui-Ping ZHOU ; Jun ZOU ; Tian CAI ; Shun-Zhi YANG ; Shen-Rong HUANG ; Ai-Lan LUO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(9):2319-2325
		                        		
		                        			
		                        			Objective To investigate the efficacy and safety of Chinese herbal compound modified Huanglian Wendan Decoction in the treatment of hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.Methods A total of 70 patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type were randomly divided into a control group and an observation group,35 cases in each group.The patients in the control group were treated with conventional western medicine,and the patients in the observation group were treated with modified Huanglian Wendan Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The Clinical Global Impression(CGI)score,traditional Chinese medicine(TCM)syndrome score,Pittsburgh Sleep Quality Index(PSQI)score,blood pressure,and serum levels of homocysteine(Hey),interleukin 6(IL-6),interleukin 10(IL-10)and interleukin 8(IL-8)levels in the two groups were observed before and after treatment.Moreover,the safety of medication was evaluated in the two groups.Results(1)After four weeks of treatment,the CGI score of the observation group was(1.63±0.60)points,which was significantly lower than that of the control group[(2.74±0.82)points],and the difference was statistically significant(P<0.01).(2)After treatment,the TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score of the two groups were significantly decreased compared with those before treatment(P<0.01),and the decrease of TCM syndrome score,systolic blood pressure,diastolic blood pressure and PSQI score in the observation group was significantly superior to that in the control group(P<0.05 or P<0.01).(3)After treatment,the levels of serum Hcy,IL-6 and IL-8 in the two groups were significantly decreased compared with those before treatment(P<0.01),and the serum IL-10 level was significantly increased compared with that before treatment(P<0.01).The decrease of serum Hcy,IL-6 and IL-8 levels and the increase of serum IL-10 level in the observation group were significantly superior to those in the control group(P<0.01).(4)During the treatment,no treatment-related adverse reactions or complications occurred in the two groups.Conclusion Modified Huanglian Wendan Decoction has certain efficacy on patients with hypertension complicated with sleep disorders of phlegm-heat harassing the interior type.The decoction can not only reduce the blood pressure and serum Hcy level of the patients,but also regulate the level of inflammatory factors with high safety.
		                        		
		                        		
		                        		
		                        	
10.Construction of a variety of fusion gene probes for soft tissue sarcoma based on TaqMan technique and their clinical diagnostic applications
Shunping CHEN ; Yuan WU ; Shaojun HONG ; Qiang LI ; Jianming WENG ; Zongkai ZOU ; Mingzhi CAI
Chinese Journal of Clinical and Experimental Pathology 2024;40(10):1045-1051
		                        		
		                        			
		                        			Purpose To design PCR combined probes u-sing TaqMan technology to detect the expression of major driver genes in a variety of soft tissue sarcomas at one time,and to dis-cuss whether the combined probes can better assist clinicopatho-logical diagnosis based on histological features and FISH results.Methods Our research group designed 32 pairs of fusion gene probes related to soft tissue sarcoma based on TaqMan tech-nique,involving 10 types of sarcoma.The histopathological specimens of 70 patients with common fusion gene soft tissue sarcoma in our hospital were examined by fusion gene combina-tion,and the histopathological specimens of 30 patients with oth-er soft tissue sarcoma without fusion gene were set as controls.Individual common sarcoma types were analyzed with FISH probe detection.At the same time,the detection performance of the combined probe was evaluated by various methods.Results The soft tissue sarcoma-related fusion gene probe designed by our research group was used to detect the confirmed soft tissue sarcomas,and the results showed that the highest sensitivity was 100%.Among the three types of tumors,protuberant dermatofi-brosarcoma,synovial sarcoma and mucinous liposarcoma were verified by FISH,and the coincidence rate of the two methods was high,with no statistical significance(P>0.05).The re-sults of interlot and intralot reproducibility of protuberous derma-tofibrosarcoma,mucinous liposarcoma and synovial sarcoma were consistent.Three different concentration limits were used to de-tect the positive plasmid of all the fused gene RNA,and 25 cop-ies/μL was the lowest concentration limit.Conclusion Com-bined with the pathological diagnosis results,TaqMan technology can be used to design PCR combined probes for soft tissue sarco-ma,which have high sensitivity and high specificity and good methodological performance,and meet the needs of primary medical institutions for one-time and rapid auxiliary pathological diagnosis of common soft tissue sarcoma.It provides a rapid and reliable method for the detection of multiple fusion genes in clin-ical soft tissue sarcoma.
		                        		
		                        		
		                        		
		                        	
            
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