1.Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairs de novo synthesis of glutathione.
Fu'an XIE ; Yujia NIU ; Xiaobing CHEN ; Xu KONG ; Guangting YAN ; Aobo ZHUANG ; Xi LI ; Lanlan LIAN ; Dongmei QIN ; Quan ZHANG ; Ruyi ZHANG ; Kunrong YANG ; Xiaogang XIA ; Kun CHEN ; Mengmeng XIAO ; Chunkang YANG ; Ting WU ; Ye SHEN ; Chundong YU ; Chenghua LUO ; Shu-Hai LIN ; Wengang LI
Journal of Pharmaceutical Analysis 2025;15(1):101068-101068
Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [15N2]-cystine and [13C5]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.
3.Chinese Medicine Regulates Hepatocellular Carcinoma-related Signaling Pathways: A Review
Chun YU ; Fen GAO ; Lanlan ZHENG ; Cai GUO ; Yanfang HE ; Jiaojiao XIE ; Xuan ZHANG ; Yanhua MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):232-243
Hepatocellular carcinoma (HCC) is a common tumor in the digestive tract, the formation mechanism of which remains to be fully elucidated. Although surgery, radiation, chemotherapy, targeted therapy, and immunotherapy have achieved significant results in the treatment of HCC, these methods are accompanied by a considerable number of adverse reactions and complications. In recent years, Chinese medicine has shown remarkable efficacy in the treatment of HCC, and both basic experiments and clinical studies have confirmed the effectiveness of Chinese medicine, which exerts therapeutic effects via multiple components and multiple targets. However, the pathogenesis of HCC is exceptionally complex and not fully understood, which means that studies remain to be carried out regarding the specific mechanism of Chinese medicine in preventing and treating HCC. Network pharmacology and molecular biology can be employed to decipher the mechanism of Chinese medicine in the treatment of diseases. Studies have shown that Chinese medicine can regulate various pathways such as the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Hedgehog, Wnt/β-catenin, nuclear factor-κB (NF-κB), Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), and transforming growth factor-β (TGF-β)/Smad signaling pathways. Chinese medicine can exhibit its anti-HCC effects by inducing cell apoptosis, inhibiting cell proliferation and migration, and blocking the cell cycle via the above pathways. However, the specific mechanisms remain to be systematically studied. This study comprehensively reviews the regulatory effects of Chinese medicine on HCC-related signaling pathways to reveal the molecular mechanisms of Chinese medicine in the treatment of HCC. This view holds the promise of providing new targets, new perspectives, and new therapies for HCC treatment and advancing the modernization and development of Chinese medicine.
4.Expression and clinical significance of cell cycle protein-dependent kinase 1 and aurora kinase A in the serum of patients with hepatitis B virus-related hepatocellular carcinoma
Yanfang HE ; Jiaojiao XIE ; Lanlan ZHENG ; Cai GUO ; Yanhua MA
Journal of Clinical Hepatology 2024;40(7):1390-1396
Objective To investigate the value of serum cell cycle protein-dependent kinase 1(CDK1)and aurora kinase A(AURKA)in the diagnosis of patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC).Methods A total of 50 HBV-HCC patients,50 patients with hepatitis B virus-related liver cirrhosis(HBV-LC),and 50 chronic hepatitis B(CHB)patients who were hospitalized in Department of Gastroenterology,Gansu Provincial Hospital,from June 2022 to December 2023 were enrolled,and 50 healthy individuals,matched for age and sex,who received physical examination at Physical Examination Center during the same period of time were enrolled as control group.Related data were recorded for all patients,including age,sex,complications,and the results of routine blood test,liver function,and coagulation for the first time after admission.ELISA was used to measure the serum levels of CDK1 and AURKA.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and the least significant difference Bonferroni test was used for further comparison between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.The Spearman correlation analysis was used to investigate the correlation between CDK1 and AURKA,and the receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to investigate the value of CDK1 and AURKA in the diagnosis of HBV-HCC.Results There were significant differences in liver function parameters between the HBV-HCC patients and the control group(all P<0.05);there were significant differences between the CHB group and the HBV-HCC group in albumin,Glb,direct bilirubin,aspartate aminotransferase(AST),gamma-glutamyl transpeptidase(GGT),and alkaline phosphatase(all P<0.05);there were significant differences between the HBV-LC group and the HBV-HCC group in Glb,AST,and GGT(all P<0.05).The HBV-HCC group had significantly higher serum levels of CDK1 and AURKA than the HBV-LC group,the CHB group,and the control group(all P<0.05).There was a significant positive correlation between CDK1 and AURKA in the overall study population and the HBV-HCC patients(r=0.526 6 and 0.815 2,P<0.001).With the control group as reference,CDK1 had an AUC of 0.832 3 in the diagnosis of HBV-HCC,with a sensitivity of 92.86%and a specificity of 75%,and AURKA had an AUC of 0.886 6 in the diagnosis of HCC,with a sensitivity of 95.80%and a specificity of 74%.With the CHB group as reference,CDK1 had an AUC of 0.833 3 in the diagnosis of HBV-HCC,with a sensitivity of 93.75%and a specificity of 75%,and AURKA had an AUC of 0.972 7 in the diagnosis of HBV-HCC,with a sensitivity of 95.83%and a specificity of 91.67%.With the HBV-LC group as reference,CDK1 had an AUC of 0.608 5 in the diagnosis of HBV-HCC,with a sensitivity of 66.67%and a specificity of 54.17%,and AURKA had an AUC of 0.762 2 in the diagnosis of HBV-HCC,with a sensitivity of 95.83%and a specificity of 47.92%.Conclusion The serum levels of CDK1 and AURKA increase with the progression of hepatitis B-associated chronic liver disease,and significant increases in serum CDK1 and AURKA have a certain value in the diagnosis of HBV-HCC.
5.Exploration on the TCM Pathogenesis of Pulmonary Fibrosis Based on the Theory of"Lung Connecting to Large Intestine"
Yawei DONG ; Zhongbo ZHU ; Fan YANG ; Quan MA ; Hongmei LI ; Yanmei ZHANG ; Lanlan HE ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):19-23
Pulmonary fibrosis is a respiratory system disorder characterized by damage to alveolar epithelial cells,pathological proliferation and transformation of fibroblasts,excessive deposition of extracellular matrix,leading to structural damage and loss of function in lung tissues,with a high mortality rate and limited effective treatment methods.This article was based on the TCM understanding of"lung connecting to large intestine",namely the theory of"lung and the large intestine being interior-exterior related",and set the modern medical understanding of"lung connecting to large intestine",namely the theory of"gut-lung axis"as the key.Combining the TCM pathogenesis of pulmonary fibrosis and the related mechanisms of"gut-lung axis"in pulmonary fibrosis,it preliminarily expounded the connotation of TCM regulating the"gut-lung axis"to treat pulmonary fibrosis,aiming to provide new ideas for clinical treatment of pulmonary fibrosis through the"gut-lung axis".
6.Analysis of ABO serological phenotype and molecular biology results of 256 blood donors with ambiguous blood group
Lanlan CHEN ; Yanhua ZHANG ; Jin CHE ; Feng LI ; Jingmin MA ; Jiahong ZHANG
Chinese Journal of Blood Transfusion 2024;37(7):766-772
Objective To correctly identify the blood group of ABO and study its molecular biological characteristics.Methods Blood samples from blood donors with discrepancies in forward and reverse typing using the microplate method were subjected to both saline tube agglutination test for serological identification and polymerase chain reaction-sequence specific primers(PCR-SSP)for genotyping.Additionally,direct sequencing of exons 1 to 7 of the ABO gene was performed on some donor samples to analyze their blood phenotype,genotype and gene sequence.Results For 256 samples showing discrepancy between forward and reverse typing in microwell method,119 were identified as normal ABO blood types,90 were weakened ABO antibodies and 47 were ABO subtypes by serology tube test.According to the PCR-SSP genotyping test,233 of 256(91.02%)were consistent with serological phenotype and genotype,17 of 256(6.64%)were inconsistent,and 6 samples can′t read genotype based on the kit result typing table.A total of 17 genotypes were identified in 250 samples as AO1 in 56,AO2 in 58,AA in 50,BO1 in 31,BO2 in 17,BB in 8,O1O1 in 2,O1O2 in 7,AB in 13,AO4 in 1,A205O2 in 1,A205A in 1,A201A in 1,O1O4 in 1,O2O2 in 1,A201B in 1 and A205B in 1.Sequencing of exons 1 to 7 of the ABO gene was carried out in 78 samples,and 29 ABO alleles were detected,seven of which were common alleles(?A101,?A102,?A104,?B101,?O01,?O02,?O04),22 of which were rare alleles(?A201,?A205,?Ax01,?Ax03,?Ax13,?Ax19,?Ax22,?Ael10,?B305,?Bel03,?Bel06/?Bx02,?Bw07,?Bw12,?Bw17,?Bw37,?O05,?O26,?O61,?B(A)04,?B(A)07,?cisAB01 and ?cisAB01var).In addition,six rare allele mutation sites were identified(c.101A>G;c.103_106delG;c.146_147insGC;c.259G>T;c.322C>T;c.932T>C).Conclusion The identification of ambiguous ABO blood group requires the combination of serological testing and molecular biological examination to correctly identify the blood type and ensure the safety of clinical blood transfusion.
7.Research progress of type 2 diabetes mellitus combined with sarcopenia
Chenglan XU ; Bingli LIU ; Lanlan JIANG ; Jianhua MA
Chinese Journal of Diabetes 2024;32(10):782-784
Sarcopenia is an age-related degenerative disease.Type 2 diabetes mellitus(T2DM)is a senile disease.These two diseases often coexist.Early identification and intervention of T2DM combined with sarcopenia can improve the quality of life to a certain extent.This article reviews the research progress of T2DM combined with sarcopenia.
8.Evaluation of current status in implementation of WS 582-2017 Specifications for testing of quality control in X and γ ray stereotactic radiotherapy system
Wei CHEN ; Jinxin JU ; Zhibin ZHANG ; Qiao MA ; Xingjiang CAO ; Xiangyong FAN ; Xindi WEI ; Zihao ZHANG ; Lanlan TIAN ; Tianyuan QIU ; Jin WANG
Chinese Journal of Radiological Medicine and Protection 2024;44(12):1043-1048
Objective:To investigate WS 582-2017 Specifications for testing of quality control in X and γ ray stereotactic radiotherapy system (hereinafter referred to as WS 582-2017) with respect to its current status, existing problems and evaluation since its implementation in Beijing, Chongqing, Jiangsu and Sichuan. Methods:The evaluation of this standard was carried out by means of field survey, questionnaire survey and expert seminar. In accordance with the WS 582-2017 implementation assessment programme, a total of 153 professionals involved in the implementation of WS 582-2017 from 80 radiological health technical service institutions, health supervision institutions and medical institutions of two municipalities and two provinces were surveyed in 2023. The investigation was carried out by using a combination of cluster sampling and stratified sampling and through sampling professionals with of different institution characteristics and different technical titles. The general survey method was used for Jiangsu province, while the cluster sampling method was used for others, with 153 individulas from 80 institutions being sampled for the investigation.Results:The awareness rate of WS 582-2017 was 80.39%, of which 90.85% considered it to be scientific and rigorous, 81.05% considered it to be operational and 97.39% considered it to be in consistency with the relevant regulatory standards, 90.20% considerd it to have played an important role in promoting radiological protection optimization for radiotherapy, 90.85% considered the implementation of it to have played a significant role in the quality control of standarded testing of radiotherapy equipment, and 86.93% considered the implementation of it to have played a significant role in enhancing the professional competence of relevant technicians.Conclusions:The overall implementation of WS 582-2017 in two municipalities and two provinces is good, with scientific and operable technical contents and the remarkable effect achieved in its implementation. However, the WS 582-2017 needs to be further improved in some areas, and training on the standard needs to be strengthened to improve the awareness rate of it.
9.Evaluation of current status in implementation of WS 582-2017 Specifications for testing of quality control in X and γ ray stereotactic radiotherapy system
Wei CHEN ; Jinxin JU ; Zhibin ZHANG ; Qiao MA ; Xingjiang CAO ; Xiangyong FAN ; Xindi WEI ; Zihao ZHANG ; Lanlan TIAN ; Tianyuan QIU ; Jin WANG
Chinese Journal of Radiological Medicine and Protection 2024;44(12):1043-1048
Objective:To investigate WS 582-2017 Specifications for testing of quality control in X and γ ray stereotactic radiotherapy system (hereinafter referred to as WS 582-2017) with respect to its current status, existing problems and evaluation since its implementation in Beijing, Chongqing, Jiangsu and Sichuan. Methods:The evaluation of this standard was carried out by means of field survey, questionnaire survey and expert seminar. In accordance with the WS 582-2017 implementation assessment programme, a total of 153 professionals involved in the implementation of WS 582-2017 from 80 radiological health technical service institutions, health supervision institutions and medical institutions of two municipalities and two provinces were surveyed in 2023. The investigation was carried out by using a combination of cluster sampling and stratified sampling and through sampling professionals with of different institution characteristics and different technical titles. The general survey method was used for Jiangsu province, while the cluster sampling method was used for others, with 153 individulas from 80 institutions being sampled for the investigation.Results:The awareness rate of WS 582-2017 was 80.39%, of which 90.85% considered it to be scientific and rigorous, 81.05% considered it to be operational and 97.39% considered it to be in consistency with the relevant regulatory standards, 90.20% considerd it to have played an important role in promoting radiological protection optimization for radiotherapy, 90.85% considered the implementation of it to have played a significant role in the quality control of standarded testing of radiotherapy equipment, and 86.93% considered the implementation of it to have played a significant role in enhancing the professional competence of relevant technicians.Conclusions:The overall implementation of WS 582-2017 in two municipalities and two provinces is good, with scientific and operable technical contents and the remarkable effect achieved in its implementation. However, the WS 582-2017 needs to be further improved in some areas, and training on the standard needs to be strengthened to improve the awareness rate of it.
10.Ferroptosis in Treatment of Liver Fibrosis with Chinese Medicine: A Review
Lanlan ZHENG ; Cai GUO ; Yanfang HE ; Jiaojiao XIE ; Fen GAO ; Chun YU ; Yanhua MA
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):235-244
Hepatic fibrosis characterized by various chronic liver injuries can lead to abnormal activation of hepatic stellate cells, unbalanced production and degradation of extracellular matrix proteins, and excessive deposition that destroys the normal structure of the liver. The aggravated liver fibrosis can cause irreversible cirrhosis and hepatocellular carcinoma, becoming a great challenge to the global health. Ferroptosis is a new form of iron-dependent cell death discovered in recent years, which mainly involves abnormal iron metabolism, lipid peroxide accumulation, and weakening of the antioxidant defense system. A number of studies have reported that inducing ferroptosis in hepatic stellate cells or alleviating ferroptosis in the liver can ameliorate liver fibrosis and reduce liver injury. Chinese medicine widely applied in the treatment of chronic liver diseases has demonstrated good safety, wide therapeutic effects, and easy access compared with Western medicine. Therefore, The intervention of hepatic stellate cells or hepatic ferroptosis by Chinese medicine may be a new direction for the prevention and treatment of liver fibrosis in the future. This paper summarized the various regulatory mechanisms of ferroptosis and expounded how ferroptosis affected the progression of liver fibrosis, providing theoretical support for the prevention and treatment of liver fibrosis with Chinese medicine in the future.

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