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Early prediction of growth patterns after pediatric kidney transplantation based on height-related single-nucleotide polymorphisms

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中华医学杂志(英文版) 2024年第10期137卷 1199-1206页

作者： Feng Yi Feng Yonghua Hu Mingyao Xu Hongen Wang Zhigang Xu Shicheng Yan Yongchuang Feng Chenghao Li Zhou Feng Guiwen Shang Wenjun Department of Renal Transplantation The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China precision medicine center Academy of Medical Science Zhengzhou University Zhengzhou Henan China

Background: Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods: A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of zhengzhou university were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results: The 110 children were divided into two groups according to change in height-for-ageZ-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796).Conclusions: A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.

关键词： Growth Machine learning Pediatric kidney transplantation Single-nucleotide polymorphism

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Targeting ferroptosis and ferritinophagy:new targets for cardiovascular diseases

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 1-22页

作者： Yi LUAN Yang YANG Ying LUAN Hui LIU Han XING Jinyan PEI Hengdao LIU Bo QIN Kaidi REN Clinical Systems Biology Research Laboratories Translational Medicine Centerthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China State Key Laboratory for Artificial Microstructures and Mesoscopic Physics School of PhysicsPeking UniversityBeijing100871China School of Laboratory medicine Xinxiang Medical UniversityXinxiang453003China Quality Management Department Henan No.3 Provincial People’s HospitalZhengzhou450052China Department of Cardiology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China center for Translational medicine the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Henan Key Laboratory of precision Clinical Pharmacy Zhengzhou UniversityZhengzhou450052China Henan Engineering Research center for Application&Translation of precision Clinical Pharmacy Zhengzhou UniversityZhengzhou450052China

Cardiovascular diseases(CVDs)are a leading factor driving mortality worldwide.Iron,an essential trace mineral,is important in numerous biological processes,and its role in CVDs has raised broad discussion for decades.Iron-mediated cell death,namely ferroptosis,has attracted much attention due to its critical role in cardiomyocyte damage and CVDs.Furthermore,ferritinophagy is the upstream mechanism that induces ferroptosis,and is closely related to CVDs.This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy,and the regulatory pathways and molecular targets involved in ferritinophagy,and to determine their roles in CVDs.Furthermore,we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs.Collectively,this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

关键词： Cardiovascular disease Iron Ferroptosis Ferritinophagy Therapeutic target

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Commentary:Gut microbiota reduce the risk of hyperuricemia and gout in the human body

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Acta Pharmaceutica Sinica B 2024年第1期14卷 433-435页

作者： Lin Wang Jianping Ye Metabolic Disease Research center Zhengzhou University Affiliated Zhengzhou Central HospitalZhengzhou 450007China Research center for Basic medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Gout,a prevalent and painful metabolic disease often associated with obesity and aging,is caused by the deposition of urate crystals in joints,bones,or soft tissues1.Urate is an intermediate metabolite within the purine degradation pathway,predominantly derived from uric acid under physiological pH levels.Hyperuricemia occurs due to excessive uric acid production or insufficient excretion2,which is associated with various chronic diseases,including type 2 diabetes.

关键词： Uric acid Gout Microbiota Gut Uricase

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Commentary:Mammokine directs beige adipocytes to reserve energy for milk production in breast

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1472-1476页

作者： Lina Tang Jianping Ye Metabolic Disease Research center Zhengzhou University Affiliated Zhengzhou Central HospitalZhengzhou 450007China Research center for Basic medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Beige/brown adipocytes play a crucial role in regulating the body’s overall energy balance.The thermogenic function is under the influence of various tissues,including the brain,muscles,and liver.However,the breast t... 详细信息

关键词： Beige Breast Epitheliail cells scRNA-seq Thermogenesis

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The key mediator of diabetic kidney disease:Potassium channel dysfunction

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Genes & Diseases 2024年第4期11卷 188-200页

作者： Jia Guo Chaojie Zhang Hui Zhao Yufan Yan Zhangsuo Liu Nephrology Research center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Key Laboratory of precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province ZhengzhouHenan 450052China Research center for Kidney Disease ZhengzhouHenan 450052China

Diabetic kidney disease is a leading cause of end-stage renal disease,making it a global public health concern.The molecular mechanisms underlying diabetic kidney disease have not been elucidated due to its complex pathogenesis.Thus,exploring these mechanisms from new perspectives is the current focus of research concerning diabetic kidney disease.lon channels are important proteins that maintain the physiological functions of cells and organs.Among ion channels,potassium channels stand out,because they are the most common and important channels on eukaryotic cell surfaces and function as the basis for cell excitability.Certain potassium channel abnormalities have been found to be closely related to diabetic kid-ney disease progression and genetic susceptibility,such as KATp,Kca,Kir,and Kv.In this review,we summarized the roles of different types of potassium channels in the occurrence and devel-opment of diabetic kidney disease to discuss whether the development of DKD is due to potas-sium channel dysfunction and present new ideas for the treatment of DKD.

关键词： Channel dysfunction Diabetic kidney disease End-stage renal disease lon channel Potassium

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Protein translation:biological processes and therapeutic strategies for human diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1048-1064页

作者： Xuechao Jia Xinyu He Chuntian Huang Jian Li Zigang Dong Kangdong Liu Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450000China China-US(Henan)Hormel Cancer Institute ZhengzhouHenan 450000China Department of Pathology and Pathophysiology Henan University of Chinese MedicineZhengzhouHenan 450000China Tianjian Laboratory of Advanced Biomedical Sciences ZhengzhouHenan 450052China Research center for Basic medicine Sciences Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052 HenanChina Provincial Cooperative Innovation center for Cancer Chemoprevention Zhengzhou UniversityZhengzhouHenan 450000China State Key Laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou UniversityZhengzhouHenan 450000China The Collaborative Innovation center of Henan Province for Cancer Chemoprevention ZhengzhouHenan 450000China

Protein translation is a tightly regulated cellular process that is essential for gene expression and protein synthesis.The deregulation of this process is increasingly recognized as a critical factor in the pathogenesis of various human diseases.In this review,we discuss how deregulated translation can lead to aberrant protein synthesis,altered cellular functions,and disease progression.We explore the key mechanisms contributing to the deregulation of protein translation,including functional alterations in translation factors,tRNA,mRNA,and ribosome function.Deregulated translation leads to abnormal protein expression,disrupted cellular signaling,and perturbed cellular functions-all of which contribute to disease pathogenesis.The development of ribosome profiling techniques along with mass spectrometry-based proteomics,mRNA sequencing and single-cell approaches have opened new avenues for detecting diseases related to translation errors.Importantly,we highlight recent advances in therapies targeting translation-related disorders and their potential applications in neurodegenerative diseases,cancer,infectious diseases,and cardiovascular diseases.Moreover,the growing interest lies in targeted therapies aimed at restoring precise control over translation in diseased cells is discussed.In conclusion,this comprehensive review underscores the critical role of protein translation in disease and its potential as a therapeutic target.Advancements in understanding the molecular mechanisms of protein translation deregulation,coupled with the development of targeted therapies,offer promising avenues for improving disease outcomes in various human diseases.Additionally,it will unlock doors to the possibility of precision medicine by offering personalized therapies and a deeper understanding of the molecular underpinnings of diseases in the future.

关键词： translation offering precise

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Bioinspired metal-organic framework nanozyme reinforced with thermosensitive hydrogel for regulating inflammatory responses in Parkinson’s disease

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Nano Research 2024年第2期17卷 858-865页

作者： Xiaowan Fan Tao Zhang Xin Ding Yushuo Gu Qing Li Wei Jiang Kelong Fan Nanozyme Medical center Academy of Medical ScienceZhengzhou UniversityZhengzhou 450001China Department Central-China Branch of National Center for Cardiovascular DiseasesHean Cardiovascular Disease CenterFuwai Central-China HospitalCentral China Fuwai Hospital of Zhengzhou UniversityZhengzhou 450046China Application center for precision medicine the Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide PharmaceuticalsInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China university of Chinese Academy of Sciences Beijing 101408China Department of General Surgery Strategic Support Force Medical CenterBeijing 100101China Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Parkinson’s disease(PD)is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory injury.Anti-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing PD.However,traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and sustainability.Herein,Cu-doping zeolite imidazolate framework-8(ZIF-8)nanozyme is designed to simulate Cu/Zn superoxide dismutase(SOD)by biomimetic mineralization.The nanozyme composite is then integrated into thermosensitive hydrogel(poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid)(PLGA-PEG-PLGA))to form an effective antioxidant system(Cu-ZIF@Hydrogel).The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion,prolonging nanozyme retention time,and modulating antioxidant activity,thus significantly improving the bioavailability of nanozymes.At the cellular and animal levels of PD,we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve cells.Moreover,the Cu-ZIF@Hydrogel significantly alleviate the PD’s behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion site.Therefore,the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.

关键词： bioinspired nanozyme thermosensitive hydrogel Parkinson’s disease oxidative stress neuroinflammatory

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Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

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Acta Pharmaceutica Sinica B 2024年第2期14卷 437-454页

作者： Jiamei Le Yilong Chen Wei Yang Ligong Chen Jianping Ye Shanghai Key Laboratory of Molecular Imaging Zhoupu HospitalShanghai University of Medicine and Health SciencesShanghai 201318China School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai 200093China Metabolic Disease Research center Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhou 450007China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China Research center for Basic medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter proteins.These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions.They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

关键词： Solute carriers(SLCs) Energ ymetabolism ATP production Type 2 diabetes mellitus(T2DM) Glucose homeostasis Polymorphisms

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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical Research center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational Medical center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

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Implications of T cell-mediated tumor killing genes for molecular heterogeneity and clinical stratification in lung adenocarcinoma

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Genes & Diseases 2024年第4期11卷 39-41页

作者： Tong Qiao Beining Yin Jun Liang Li Wei Department of Thoracic Surgery Henan Provincial People's HospitalZhengzhouHenan 450000China Reproductive medicine center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Breast Surgery Henan Provincial People's HospitalZhengzhouHenan 450000China

Due to the profound heterogeneity exhibited amongst patients with lung adenocarcinoma(LUAD),considerable variances in clinical efficacy emerge.1 For the aims of precision medicine,a clinical instrument to delineate distinct disease phenotypes and anticipate susceptibility to intervention is imperative.Cellular cytotoxicity mediated through T lymphocytes constitutes a pivotal mechanism of anti-tumoral immunity and the foundation for cancer immunotherapy.?Numerous genes regulating the sensitivity of tumor cells to killing mediated by T lymphocytes(GSTKKs)are conducive to satisfying the aforesaid medical necessity.

关键词： clinical mediated adenocarcinoma

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