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Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer

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Genes & Diseases 2024年第3期11卷 400-416页

作者： Meijia Yu Yiming Wu Qingfang Li Weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei Laboratory of Aging research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Gynecology and Obstetrics Development and Related Disease of Women and Children Key Laboratory of Sichuan ProvinceKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationWest China Second HospitalSichuan UniversityChengduSichuan 610041China Department of Obstetrics and Gynecology The First Affiliated HospitalArmy Medical UniversityChongqing 400038China

Ovarian cancer is the tumor with the highest mortality among gynecological *** have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the ***-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid *** are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor ***,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian *** found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor *** by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in *** of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.

关键词： CSF-1R Ovariancancer Paclitaxel PLX3397 Targeted therapy Tumor-associated macrophages

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Epidemiology of congenital diaphragmatic hernia among 24 million Chinese births:a hospital-based surveillance study

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World Journal of Pediatrics 2024年第7期20卷 712-722页

作者： Zhi-Yu Chen Jing Tao Wen-Li Xu Yu-Yang Gao Wen-Yan Li Zhen Liu Jia-Yuan Zhou Li Dai National center for birth defects Monitoring West China Second University HospitalSichuan UniversityNo.17 Section 3 RenminnanluChengdu 610041China The Joint Laboratory for Pulmonary Development and Related Diseases West China Institute of Women and Children’s HealthWest China Second University HospitalSichuan UniversityChengduChina Key Laboratory of birth defects and Related Diseases of Women and Children Ministry of EducationSichuan UniversityChengduChina NHC Key Laboratory of Chronobology Sichuan UniversityChengduChina Med‑X center for Informatics Sichuan UniversityChengduChina

Background The prevalence of congenital diaphragmatic hernia(CDH)varies across countries,with limited information available on its epidemiology in *** study aimed to investigate the prevalence,time trends,and perinatal outcomes of CDH in China,as well as its associated malformations and potential associations with maternal and infant *** This study included all birth and CDH cases from the Chinese birth defects Monitoring Network between 2007 and 2019,with CDH cases classified as either isolated or *** employed the joinpoint regression model to calculate the trends of prevalence and the annual percent change,with Poisson regression used for adjusted prevalence rate ratios.A P value≤0.05 was considered statistically *** A total of 4397 CDH cases were identified among 24,158,029 births in the study period,yielding prevalence rates of 1.82,1.13 and 0.69 per 10,000 for overall,isolated,and associated CDH,*** prevalence of each type of CDH increased over *** prevalence of overall CDH varied significantly by infant sex(male ***,1.91/10,000 vs.1.63/10,000),maternal residence(urban ***,2.13/10,000 vs.1.45/10,000),maternal age(birth and perinatal death than those with isolated *** The increasing prevalence and high perinatal mortality rate of CDH highlight the need for further etiological,epidemiological,and clinical studies among the Chinese population.

关键词： China Congenital diaphragmatic hernia Epidemiology Prevalence

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Advances in metal-organic framework-derived single-atom catalysts for biomedicine

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Nano Materials Science 2024年第4期6卷 396-412页

作者： Li Qiu Yingxi Lin Jun Song Chen Hong Luo Rui Wu Department of Ultrasound West China Second University Hospital Sichuan University Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and birth defects of Ministry of Education Sichuan University School of Materials and Energy University of Electronic Science and Technology of China Interdisciplinary Materials research center Institute for Advanced Study Chengdu University

As a alternative for natural enzymes, nanozymes has shown enzyme-like activity and selectivity in the field of various kinds of biomedical application, which has attracted considerable research interest. Recently, single-atom catalysts(SACs) have been extensively studied due to their similar active centers, coordination environment and better stability to natural enzymes. Metal-organic frameworks(MOFs) have been demonstrated as highly promising precursors for the synthesis of various types of SACs. MOF-derived SACs can not only significantly enhance the catalytic activity, but also improve the selectivity of nanozymes due to tunable coordination environment and structure, thereby receiving widespread attention in biomedicine. This review provided an overview of the preparation strategies for MOF-derived SACs, and then detailed the latest research progress of the SACs in the biomedical field for cancer, antibacterial, antioxidation and biosensors. Finally, the challenges and potential future opportunities of MOF-derived SACs in biomedical applications are proposed.

关键词： Biomedicine MOF-Derived SAC nanozymes Catalytic mechanisms

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Exosomal let-7a-5p derived from human umbilical cord mesenchymal stem cells alleviates coxsackievirus B3-induced cardiomyocyte ferroptosis via the SMAD2/ZFP36 signal axis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第5期25卷 422-437页

作者： Xin LI Yanan HU Yueting WU Zuocheng YANG Yang LIU Hanmin LIU Department of Pediatric Pulmonology and Immunology West China Second University HospitalSichuan UniversityChengdu 610041China Key Laboratory of birth defects and Related Diseases of Women and Children(sichuan University) Ministry of EducationChengdu 610041China NHC Key Laboratory of Chronobiology(sichuan University) Chengdu 610041China The Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital Sichuan University and School of Life Sciences of Fudan UniversityWest China Institute of Women and Children's HealthWest China Second University HospitalSichuan UniversityChengdu 610041China sichuan birth defects clinical research center West China Second University HospitalSichuan UniversityChengdu 610041China Department of Pediatrics the Third Xiangya HospitalCentral South UniversityChangsha 410013China

Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and ***,its pathogenesis is still unclear,and effective treatments are *** study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular *** echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac *** CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione) peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 ***-7a-5p was enriched in hucMSCs-exo,and the inhibitory ffect of hucMSCs-exoa-ie-pmimo on CVB3-induced ferroptosis was higher than that of hucMSCs-exommie N(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)***-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 *** SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related ***,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe^(2+)*** conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 ***-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.

关键词： Exosome Let-7a-5p Mothers against decapentaplegic homolog 2(SMAD2) Coxsackievirus B3(CVB3) Ferroptosis

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Precise genome-editing in human diseases:mechanisms,strategies and applications

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1065-1085页

作者： Yanjiang Zheng Yifei Li Kaiyu Zhou Tiange Li Nathan J.VanDusen Yimin Hua Key Laboratory of birth defects and Related Diseases of Women and Children of MOE Department of PediatricsWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Department of Cardiovascular Surgery West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pediatrics Herman B Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisIN 46202USA

Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and *** continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic *** genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo ***,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target *** this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and ***,we discuss the landmark events in the history of precise ***,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human ***,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and ***,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.

关键词： precise generating editing

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Dietary protein sources, gut microbiome, and puberty timing in children: findings from a cohort study

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3167-3169页

作者： Yujie Xu Jingyuan Xiong Xiaoyu Wang Fang He Guo Cheng Laboratory of Molecular Translational Medicine Center for Translational MedicineKey Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationMaternal&Child Nutrition CenterWest China Second University HospitalSichuan UniversityChengduSichuanP.R.China West China School of Public Health and West China Fourth Hospital and Healthy Food Evaluation research center Sichuan UniversityChengduP.R.China

Dear Editor,Developing countries are in a critical term of nutritional transition,marked by a sharp increase in the consumption of animal-source *** China,the intake of calories from animalsource foods in children tri... 详细信息

关键词： intake finding children

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Emerging delivery systems based on aqueous two-phase systems:A review

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Acta Pharmaceutica Sinica B 2024年第1期14卷 110-132页

作者： Yaowen Zhang Yankun Luo Jingqi Zhao Wenzhuo Zheng Jun Zhan Huaping Zheng Feng Luo State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China School of StomatologySichuan UniversityChengdu 610041China Department of Obstetrics and Gynecology West China Second University HospitalSichuan UniversityChengdu 610041China Key Laboratory of birth defects and Related Diseases of Women and Children(sichuan University) Ministry of EducationChengdu 610041China Department of Dermatology Rare Diseases CenterInstitutes for Systems GeneticsFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Department of Prosthodontics West China School of StomatologySichuan UniversityChengdu 610041China

The aqueous two-phase system(ATPS)is an all-aqueous system fabricated from two immiscible aqueous *** is spontaneously assembled through physical liquid-liquid phase separation(LLPS)and can create suitable templates like the multicompartment of the intracellular *** structures containing multiple compartments make it possible to endow materials with advanced *** to the properties of ATPSs,ATPS-based drug delivery systems exhibit excellent biocompatibility,extraordinary loading efficiency,and intelligently controlled content release,which are particularly advantageous for delivering drugs in ***,we will systematically review and evaluate ATPSs as an ideal drug delivery *** on the basic mechanisms and influencing factors in forming ATPSs,the transformation of ATPSs into valuable biomaterials is ***,we concentrate on the most recent cutting-edge research on ATPS-based delivery ***,the potential for further collaborations between ATPS-based drug-carrying biomaterials and disease diagnosis and treatment is also explored.

关键词： Aqueous two-phase systems Drug delivery systems Biomaterials Microcapsules Microparticles Cell therapy Cancer treatment Organ regeneration

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Pathological BBB Crossing Melanin-Like Nanoparticles as Metal-Ion Chelators and Neuroinflammation Regulators against Alzheimer’s Disease

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research 2024年第1期6卷 687-706页

作者： Qianqian Huang Chaoqing Jiang Xue Xia Yufan Wang Chenxing Yan Xiaorong Wang Ting Lei Xiaotong Yang Wenqin Yang Guo Cheng Huile Gao Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041P.R.China Laboratory of Molecular Translational Medicine Center for Translational MedicineKey Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationDepartment of PediatricsWest China Second University HospitalSichuan UniversityChengdu 610041P.R.China

Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD ***,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of *** this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβ*** vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB *** engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.

关键词： oxidative aggregation chelating

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Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

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Journal of Pharmaceutical Analysis 2024年第3期14卷 321-334页

作者： Rangrang Fan Linrui Cai Hao Liu Hongxu Chen Caili Chen Gang Guo Jianguo Xu Department of Neurosurgery and Institute of Neurosurgery Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China NMPA Key Laboratory for Technical research on Drug Products in Vitro and in Vivo Correlation Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOENational Drug Clinical-Trial InstitutionWest China Second HospitalSichuan UniversityChengdu610041China Department of Immunology School of Basic Medical SciencesXinxiang Medical UniversityXinxiangHenan453000China

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in *** the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in ***,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was *** coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton ***–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its ***,this pH-responsive nanoplatform presents controllable drug release *** in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free *** in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their *** triple-combination therapy approach is promising for efficient and targeted cancer treatment.

关键词： Metformin Glucose oxidase Metabolism disruption Tumor starvation Combination cancer therapy

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RCAN family member 3 deficiency contributes to noncompaction of the ventricular myocardium

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Journal of Genetics and Genomics 2024年第5期51卷 543-553页

作者： Ting Hu Lan Liu He Wang Mei Yang Bocheng Xu Hanbing Xie Ziyuan Lin Xiaolei Jin Ping Wang Yanyan Liu Huaqin Sun Shanling Liu Department of Medical Genetics West China Second University HospitalSichuan UniversityChengduSichuan 610041China Key Laboratory of birth defects and Related Diseases of Women and Children(sichuan University) Ministry of EducationChengduSichuan 610041China Medical College Tibet UniversityLhasaTibet 850000China SCU-CUHK Joint Laboratory for Reproductive Medicine West China Second University HospitalSichuan UniversityChengduSichuan 610041China West China School of Medicine Sichuan UniversityChengduSichuan 610041China

Noncompaction of the ventricular myocardium(NVM),the third most diagnosed cardiomyopathy,is characterized by prominent trabeculae and intratrabecular ***,the genetic etiology of 40%–60%of NVM cases remains ***,we identify two infants with NVM,in a nonconsanguineous family,with a typical clinical presentation of persistent bradycardia since the prenatal period.A homozygous missense variant(R223L)of RCAN family member 3(RCAN3)is detected in both infants using whole-exome *** the zebrafish model,marked cardiac dysfunction is detected in rcan3 deficiency(MO-rcan3^(ATG)-injected)and rcan^(−/−) *** dysplasia of both endocardial and myocardial layers is also detected in rcan3-deficient ***3 R223L variant mRNAs can not rescue heart defects caused by rcan3 knockdown or knockout;however,hRCAN3 mRNAs rescue these ***-seq experiments show that several genes involved in cardiomyopathies are significantly regulated through multiple signaling pathways in the rcan3-knockdown zebrafish *** human cardiomyocytes,RCAN3 deficiency results in reduced proliferation and increased apoptosis,together with an abnormal mitochondrial ***,we suggest that RCAN3 is a susceptibility gene for cardiomyopathies,especially NVM and that the R223L mutation is a potential loss-of-function variant.

关键词： Cardiomyopathy NVM RCAN3 Mitochondrial structure Heartdefects

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