1.Mechanism prediction and verification of Xihuang pill against diffuse large B-cell lymphoma
Ruyi HUANG ; Jinyu LI ; Wenqi LIN ; Xin JIANG ; Yanling CHEN ; Weikun HUANG ; Lin YANG
China Pharmacy 2026;37(2):161-167
OBJECTIVE To investigate the mechanism of Xihuang pill (XHP) against diffuse large B-cell lymphoma (DLBCL). METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP, GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics (MD) simulation were conducted to verify the interactions between core components and core targets, and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay, flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components (e.g., 17 beta-estradiol, quercetin) and ten core targets [e.g., tumor protein 53 (TP53), proto-oncogene tyrosine-protein kinase Src (SRC)] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis (P<0.05). Molecular docking, MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail:stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells; compared with control group, XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells, and significantly down- regulated the expressions of SRC protein, phosphorylated (p)-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells (P<0.05). CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.
2.Prognosis of deep lamellar keratoplasty versus penetrating keratoplasty in the treatment of stromal corneal dystrophy
Ruyi JING ; Yingxin CHEN ; Lei CAO
Chinese Journal of Tissue Engineering Research 2025;29(8):1626-1633
BACKGROUND:The traditional surgical treatment for stromal corneal dystrophy is penetrating keratoplasty.In recent years,more and more doctors are considering using deep lamellar keratoplasty to treat stromal corneal dystrophy.Few studies comparing penetrating keratoplasty and deep lamellar keratoplasty for stromal corneal dystrophy have been reported in China. OBJECTIVE:To compare the clinical efficacy of deep lamellar keratoplasty and penetrating keratoplasty in the treatment of stromal corneal dystrophy. METHODS:Fifty-seven patients(57 eyes)diagnosed with stromal corneal dystrophy and admitted at the General Hospital of Northern Theater Command from January 2000 to January 2018 were selected,including 18 males and 39 females,aged(52.9±20.0)years.They were divided into two groups based on the surgical procedure:21 cases(21 eyes)in the deep lamellar keratoplasty group and 36 cases(36 eyes)in the penetrating keratoplasty group.A 12-month follow-up was conducted to observe the best-corrected visual acuity,corneal endothelial cell density,corneal grafttransparency,intraoperative and postoperative complications,and recurrence of the original disease. RESULTS AND CONCLUSION:Visual acuity at 1,3,6,and 12 months postoperatively was higher than preoperatively in both groups(P<0.05).The postoperative best-corrected visual acuity between the two groups showed no significant difference(P>0.05).With the prolongation of postoperative time,the corneal endothelial cell density gradually decreased in the two groups,and the annual loss rate of corneal endothelial cell density in the penetrating keratoplasty group was higher than that of the deep lamellar keratoplasty group at 6 and 12 months postoperatively(P<0.05),while there was no significant difference in corneal grafttransparency between the two groups at 12 months postoperatively(P>0.05).There were six cases of complications in the deep lamellar keratoplasty group and 14 cases of complications in the penetrating keratoplasty group.There was no recurrence in 57 cases within 12 months after surgery,and the difference in recurrence rates between the two groups at 5 years after surgery was not significant(P>0.05).The graftsurvival rates at 5 years after surgery in the penetrating keratoplasty group and the deep lamellar keratoplasty group were 83%and 86%,respectively,and there was no significant difference between the two groups(P>0.05).To conclude,deep lamellar keratoplasty could be considered as an alternative to penetrating keratoplasty in the treatment of stromal corneal dystrophy.
3.Ultrasonic characteristics of hip joints in preterm infants with different gestational ages
Min CHEN ; Ruyi CAI ; Jing WANG ; Lei XIA ; Xia CHI ; Jun QIAN
Journal of Clinical Medicine in Practice 2025;29(9):70-74
Objective To analyze the results of ultrasonic examinations of hip joints in preterm infants,clarify the developmental characteristics of hip joints across different gestational ages.Meth-ods A total of 881 preterm infants who attended the Child Healthcare Outpatient Clinic of Nanjing Maternity and Child Health Care Hospital between January 2023 and April 2024 were enrolled.The first ultrasonic examination of the hip joints was performed at a corrected gestational age of 4 to 6 weeks.The Graf classification method was employed to categorize the ultrasonic findings.Differences in hip joint development among preterm infants of varying gestational ages were compared,and rele-vant influencing factors were statistically analyzed.Results A total of 1,762 hip joints were exam-ined,with 30 cases of abnormal hip joints detected,yielding an abnormality detection rate of 3.4%(30/881).Among these,26 hips were classified as type Ⅱa and 8 as type Ⅱb.Statistically signifi-cant differences were observed in the detection of left-sided abnormal hip joints between preterm in-fants of other gestational age groups and late preterm infants(P<0.05).A statistically significant difference was found in the classification of right-sided hip joints between preterm infants of different genders(P<0.05),while no significant difference was observed for left-sided hip joints(P>0.05).Statistically significant differences were noted in the detection rates of bilateral abnormal hip joints among preterm infants with varying birth weights(P<0.05).Advanced maternal age was found to influence the development of left-sided hip joints inpreterm infants,whereas factors such as assisted reproductive technology,breech presentation,and nulliparity had no significant impacts on abnormal hip joint development in preterm infants.Conclusion Ultrasonic technology demonstrates signifi-cant advantages in screening for developmental dysplasia of the hip(DDH)in preterm infants.Dif-ferent gestational ages exert a notable influence on the development of left-sided hip joints in preterm infants.Female preterm infants exhibit a higher risk of right-sided hip joint abnormalities compared to the left side.Breech presentation,assisted reproductive technology,and nulliparity are not risk factors for DDH in preterm infants.However,higher birth weight in preterm infants and advanced maternal age are associated with abnormal hip joint development.Clinical attention should focus on high-risk factors,and enhanced dynamic ultrasonic monitoring of hip joints in preterm infants is war-ranted to facilitate early intervention and treatment.
4.Effect of slurry proportion on the microstructure and properties of dental lithium disilicate ceramics manufactured through 3D printing.
Baoxin LIN ; Xiaoxuan CHEN ; Ruyi LI ; Qianbing WAN ; Xibo PEI
West China Journal of Stomatology 2025;43(2):175-182
OBJECTIVES:
This study aims to use 3D prin-ting technology based on the principle of stereo lithography apparatus (SLA) to shape dental lithium disilicate ceramics and study the effects of different slurry proportions on the microstructure and properties of heat-treated samples.
METHODS:
The experimental group comprised lithium disilicate ceramics manufactured through SLA 3D printing, and the control group comprised lithium disilicate ceramics (IPS e.max CAD) fabricated through commercial milling. An array of different particle sizes of lithium disilicate ceramic powder materials (nano and micron) was selected for mixing with photocurable acrylate resin. The proportion of experimental raw materials was adjusted to prepare five groups of ceramic slurries for 3D printing (Groups S1-S5) on the basis of rheological properties, stability, and other factors. Printing, debonding, and sintering were conducted on the experimental group with the optimal ratio, followed by measurements of microstructure, crystallographic information, shrinkage, and mechanical properties.
RESULTS:
Five groups of lithium disilicate ceramic slurries were prepared, of which two groups with high solid content (75%) (Groups S2 and S3) were selected for 3D printing. X-ray diffraction and scanning electron microscopy results showed that lithium disilicate was the main crystalline phase in Groups S2 and S3, and its microstructure was slender, uniform, and compact. The average grain sizes of Groups S2 and S3 were (559.79±84.58) nm and (388.26±61.49) nm, respectively (P<0.05). Energy spectroscopy revealed that the samples in the two groups contained a high proportion of Si and O elements. After heat treatment, the shrinkage rate of the two groups of ceramic samples was 18.00%-20.71%. Test results revealed no statistical difference in all mechanical properties between Groups S2 and S3 (P>0.05). The flexural strengths of Groups S2 and S3 were (231.79±21.71) MPa and (214.86±46.64) MPa, respectively, which were lower than that of the IPS e.max CAD group (P<0.05). The elasticity modulus of Groups S2 and S3 were (87.40±12.99) GPa and (92.87±19.76) GPa, respectively, which did not significantly differ from that of the IPS e.max CAD group (P>0.05). The Vickers hardness values of Groups S2 and S3 were (6.53±0.19) GPa and (6.25±0.12) GPa, respectively, which were higher than that of the IPS e.max CAD group (P<0.05). The fracture toughness values of Groups S2 and S3 were (1.57±0.28) MPa·m0.5 and (1.38±0.17) MPa·m0.5, respectively, which did not significantly differ from that of the IPS e.max CAD group (P>0.05).
CONCLUSIONS
The combination of lithium disilicate ceramic powders with different particle sizes can yield a slurry with high solid content (75%) and suitable viscosity and stability. The dental lithium disilicate ceramic material is successfully prepared by using 3D printing technology. The 3D-printed samples show a small shrinkage rate after heat treatment. Their microstructure conforms to the crystal phase of lithium disilicate ceramics, and their mechanical properties are close to those of milled lithium disilicate ceramics.
Printing, Three-Dimensional
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Dental Porcelain/chemistry*
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Ceramics/chemistry*
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Materials Testing
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Particle Size
5.Base on the"One Qi Circulation"Theory to Treat Heart Failure with Reduced Ejection Fraction
Ruyi LIN ; Hui CHEN ; Lili RUAN
Journal of Zhejiang Chinese Medical University 2025;49(10):1332-1335
[Objective]To analyze the etiology and pathogenesis of heart failure with reduced ejection fraction(HFrEF)by using the"One Qi Circulation"theory,and explore the corresponding therapeutic strategies in traditional Chinese medicine.[Methods]Based on the"One Qi Circulation"theory,the causes of HFrEF fraction are analyzed in conjunction with the clinical manifestations of patients.The treatment principles and the selection of formulas and drugs are specifically discussed in combination with the characteristics of drug use in the"One Qi Circulation"theory,and the application of the method of benefiting the heart,strengthening the spleen and promoting diuresis is elaborated.Finally,a clinical case was listed for verification.[Results]The"One Qi Circulation"theory considers that water-cold and earth-dampness are the basic pathogenesis of heart failure,and Yang-decline and fire-defeat are the keys to the exacerbation of the condition.The ultimate goal is to restore the state of"One Qi Circulation".The method of benefiting the heart,strengthening the spleen and promoting diuresis is refined from this,which takes drying the earth,warming the water and protecting the middle Qi as the basic principles.The cited case involved an HFrEF patient exhibiting water-cold and earth-dampness with Yang deficiency and water overflow,treated by invigorating the spleen and promoting diuresis,warming Yang and benefiting the heart,and the symptoms of the patients were relieved.[Conclusion]The application of the method of benefiting the heart,strengthening the spleen and promoting diuresis based on the"One Qi Circulation"theory on treating HFrEF fraction is practical and effective,and it provides much inspiration for improving the prognosis and reducing the recurrence rate of the disease,providing new ideas and methods for the clinical diagnosis and treatment of HFrEF fraction.
6.Bloodstream infection caused by Trichosporon asahii in an acute leukemia patient:a case report and literature review
Lili CAI ; Zhihang LIN ; Ruyi GUO ; Namei WU ; Qingqing CHEN
Chinese Journal of Infection Control 2025;24(5):609-617
Objective To analyze clinical characteristics and therapeutic strategies for patients with Trichosporon asahii(T.asahii)bloodstream infection(BSI),and provide reference for clinical diagnosis and treatment for such disease.Methods Diagnosis and treatment process of a patient with T.asahii BSI were reported.China National Knowledge Infrastructure(CNKI),Wanfang,PubMed,and Web of Science databases were retrieved using key-words:"Trichosporon asahii"and"bloodstream infection".Patients'age,gender,underlying diseases,immune status,treatment,and clinical outcome as well as antimicrobial susceptibility testing results of T.asahii were ana-lyzed retrospectively.Results The leukemia patient developed T.asahii BSI during chemotherapy,and showed clinical improvement after treatment with fluconazole+flucytosine.A total of 44 cases(43 from literature plus this index case)were analyzed.Among these cases,28 were males,the median age was 54.5 years old.The underlying diseases were predominantly hematological diseases.Catheter,urinary tract,and skin were identified as concurrent culture-positive sites.Azoles exhibited good antimicrobial activity in vitro,with voriconazole showing the strongest activity and associated with significantly higher survival rates.Under the guidance of antimicrobial susceptibility tes-ting results,patients with fluconazole treatment had a higher survival rate.At minimum inhibitory concentrations(MICs)of 4-8 μg/mL of fluconazole,fluconazole combined with other agents was predominantly required.Am-photericin B demonstrated good in vitro activity,but the overall survival rate of patients was low when amphotericin B was used as monotherapy without azoles.Catheters removal,surgical intervention,and neutrophil recovery were influencing factors for enhanced survival rates.Conclusion BSI caused by T.asahii primarily occurs in patients with hematological diseases,with neutropenia being a high-risk factor.Infection sites at catheter,urinary tract,and skin may be infection sources.Clearing the source of infection and promoting the recovery of neutrophils can help to improve survival rates of patients.For voriconazole-intolerant patients,fluconazole monotherapy or in combination with flucytosine/amphotericin B can be used alternatively based on antimicrobial susceptibility testing results.
7.Changing prevalence and antibiotic resistance profiles of carbapenem-resistant Enterobacterales in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Wenxiang JI ; Tong JIANG ; Jilu SHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yuanhong XU ; Ying HUANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yingchun XU ; Xiaojiang ZHANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hong ZHANG ; Chun WANG ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(4):445-454
Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43%(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38%,9.73%,and 8.47%,respectively.The prevalence of CRE strains in Escherichia coli was 1.99%.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)%,followed by blood(20.88±3.40)%and urine(18.40±3.45)%.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)%.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.
8.Changing distribution and antibiotic resistance profiles of the respiratory bacterial isolates in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Ying FU ; Yunsong YU ; Jie LIN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE ; Wenhui HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(4):431-444
Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6%of the isolates were Gram-negative bacteria and 17.4%were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)%and(94.0±0.1)%,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P<0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9%.The prevalence of penicillin-resistant S.pneumoniae was 1.4%.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8%and 41.3%,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7%,20.8%,9.4%,29.8%,and 73.3%,respectively.The prevalence of β-lactamase was 96.1%in Moraxella catarrhalis and 60.0%in Haemophilus influenzae.The H.influenzae isolates from children(<18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P<0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.
9.Research and prospect of application of artificial intelligence technology in oral and maxillofacial surgery
Ruyi CHEN ; Ruoyan ZHANG ; Jun WANG
Chinese Journal of Stomatology 2025;60(1):88-93
Artificial intelligence (AI) technology is a scientific and technological field that focuses on the research and development of systems that simulate, extend, and expand human intelligence activities. This field encompasses various applications such as image recognition, language processing, expert systems, and robotics. The advancement of AI has greatly improved the quality and efficiency of medical work, particularly in areas like medical imaging, clinical decision support, precision medicine, and healthcare management. These advancements have contributed to the establishment of more effective healthcare systems.Within the realm of AI in healthcare, the application of AI technology in oral and maxillofacial surgery continues to evolve, with scenarios such as assisting in the interpretation and analysis of dental medical images, predicting and diagnosing early oral and maxillofacial tumors, aiding in minimally invasive surgery, designing ideal and personalized surgical plans, and simplifying medical management tasks. Oral and maxillofacial surgeons, as well as radiologists, should embrace and utilize these emerging technologies, actively adapting to environmental changes and updates, and driving forward the development of the field of oral and maxillofacial surgery.In summary, the integration of AI into oral and maxillofacial surgery presents significant opportunities for advancing patient care, surgical efficiency, and medical research in this specialized area of medicine. This technological partnership has the potential to reshape the landscape of oral and maxillofacial healthcare, benefiting both practitioners and patients.
10.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):189-207
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 down-regulated metabolites in sera of RIPS 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[13Cs]-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.

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