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Animal Nutrition 2024年第1期16卷 251-266页

作者： Pengju Wang Lv-hui Sun xu Wang qinghua Wu Aimei Liu Hubei Key Laboratory of Diabetes and Angiopathy Medicine Research Institute Xianning Medical College Hubei University of Science and Technology Hubei Hongshan Laboratory College of Animal Science and Technology Huazhong Agricultural University National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues Huazhong Agricultural University College of Life Science Yangtze University

T-2 toxin is one of the most widespread and toxic fungal toxins in food and feed. It can cause gastrointestinal toxicity, hepatotoxicity, immunotoxicity, reproductive toxicity, neurotoxicity, and nephrotoxicity in humans and animals. T-2 toxin is physicochemically stable and does not readily degrade during food and feed processing. Therefore, suppressing T-2 toxin-induced organ toxicity through antidotes is an urgent issue. Protective agents against the organ toxicity of T-2 toxin have been recorded widely in the literature, but these protective agents and their molecular mechanisms of detoxification have not been comprehensively summarized. In this review, we provide an overview of the various protective agents to T-2 toxin and the molecular mechanisms underlying the detoxification effects. Targeting appropriate targets to antagonize T-2 toxin toxicity is also an important option. This review will provide essential guidance and strategies for the better application and development of T-2 toxin antidotes specific for organ toxicity in the future.

关键词： T-2 toxin Organ toxicity Protective agent Detoxification mechanism

Low expression of fatty acid oxidation related gene ACADM indicates poor prognosis of renal clear cell carcinoma and is related to tumor immune infltration

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Oncology Research 2024年第3期32卷 545-561页

作者： JIECHUAN QIU TIANMIN YANG YANNING SUN KAI SUN YINGKUN xu qinghua XIA Department of Urology Shandong Provincial Hospital A fliated to Shandong First Medical UniversityJinan250021China Depatment of Urology Shandong Provincial HospitalCheeloo College of MedicineShandong UniversityJinan250021China Depatment of Breast and Thyroid Surgery The First Afiliated Hospital of Chongqing Medical UniversityChongqing400042China

This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.

关键词： Kidney renal clear cell carcinoma Acyl CoA dehydrogenase medium chain Immune infiltration Fatty acid oxidation Prognosis

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

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Animal Models and Experimental Medicine 2024年第3期7卷 259-274页

作者： Huirong xu Meiyue Dong Ruikun Du Chengcheng Zhang Zinuo Chen Guangyu Tian qinghua Cui Kejian Li College of Traditional Chinese Medicine Shandong University of Traditional Chinese MedicineJinanChina Innovative Institute of Chinese Medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinanChina Qingdao Academy of Chinese Medical Sciences Shandong University of Traditional Chinese MedicineQingdaoChina College of Pharmacy Shandong University of Traditional Chinese MedicineJinanChina

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

关键词： network pharmacology pharmacodynamical material basis serum pharmacochemistry viral pneumonia YangshenDingzhi granules

Diagnostic Study of an Extreme Explosive Cyclone over the Kuroshio/Kuroshio Extension Region

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Journal of Ocean University of China 2024年第3期23卷 605-617页

作者： ZHANG Shuqin LIAO qinghua LIU Chunlei GAO Xiaoyu LONG Jingchao LI Pengyuan xu Jianjun College of Ocean and Meteorology Guangdong Ocean UniversityZhanjiang 524088China South China Sea Institute of Marine Meteorology Guangdong Ocean UniversityZhanjiang 524088China CMA-GDOU Joint Laboratory for Marine Meteorology Guangdong Ocean UniversityZhanjiang 524088China Key Laboratory of Climate Resources and Environment in Continental Shelf Sea and Deep Sea of Department of Education of Guangdong ProvinceGuangdong Ocean UniversityZhanjiang 524088China State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesBeijing 100081China Department of Marine Meteorology Ocean-Atmosphere Interaction and Climate LaboratoryKey Laboratory of Physical OceanographyOcean University of ChinaQingdao 266100China

Explosive cyclones(ECs)occur frequently over the Kuroshio/Kuroshio Extension region.The most rapidly intensified EC over the Kuroshio/Kuroshio Extension region during the 42 years(1979-2020)of cold seasons(October-April)was studied to reveal the variations of the key factors at different explosive-developing stages.This EC had weak low-level baroclinicity,mid-level cyclonic-vorticity advection,and strong low-level water vapor convergence at the initial explosive-developing stage.The low-level baroclinicity and mid-level cyclonic-vorticity advection increased substantially during the maximum-deepening-rate stage.The diagnostic analyses using the Zwack-Okossi equation showed that diabatic heating was the main contributor to the initial rapid intensification of this EC.The cyclonic-vorticity advection and warm-air advection enhanced rapidly in the middle and upper troposphere and contributed to the maximum rapid intensification,whereas the diabatic heating weakened slightly in the mid-low troposphere.The relative contribution of the diabatic heating decreased from the initial explosive-developing stage to the maximum-deepening-rate stage due to the enhancement of other factors(the cyclonic-vorticity advection and warm-air advection).Furthermore,the physical factors contributing to this EC varied with the explosive-developing stage.The non-key factors at the initial explosive-developing stage need attention to forecast the rapid intensification.

关键词： explosive cyclone diabatic heating cyclonic-vorticity advection rapid intensification the Kuroshio/Kuroshio Extension region

Application of Global Leadership Initiative on Malnutrition criteria in patients with liver cirrhosis

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Chinese Medical Journal 2024年第1期137卷 97-104页

作者： Minjie Jiang Juan Chen Muchen Wu Jing Wu Xiaotong xu Juan Li Can Liu Yaping Zhao Xin Hua qinghua Meng Department of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing 100069China Department of Medical Oncology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of Nutrition Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:The Global Leadership Initiative on Malnutrition(GLIM)criteria were published to build a global consensus on nutritional diagnosis.Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria.However,there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings.This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition,as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods:This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1,2018,and February 28,2022,at Beijing You-An Hospital,Capital Medical University.Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography(CT)examination during hospitalization were included in the study.These patients were randomly divided into a modeling group(cohort 1,667 patients)and a validation group(cohort 2,335 patients).In cohort 1,optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index(L3-SMI)were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups.Next,patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002(NRS-2002),and malnutrition was diagnosed by GLIM criteria.Additionally,the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1.Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results:The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients.Based on the cut-off values,31.63%(68/215)of the male patients and 23.3%(28/120)of the female patients had CT-determined sarcopenia in cohort 2.The prevalence of GL

关键词： Malnutrition Liver cirrhosis Sarcopenia Clinical outcomes GLIM criteria

Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

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Food Science and Human Wellness 2024年第4期13卷 2289-2309页

作者： Jie Zhang Shuang Yang Baocai xu Zihui Qin Xinyi Guo Ben Wei qinghua Wu Kamil Kuca Tushuai Li Wenda Wu School of Biology and Food Engineering Changshu Institute of TechnologySuzhou 215500China Center for Clinical Mass Spectrometry School of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary MedicineNanjing Agricultural UniversityNanjing 210095China Department of Chemistry Faculty of ScienceUniversity of Hradec KraloveHradec Kralove 50003Czech Republic College of Life Science Yangtze UniversityJingzhou 434025China Wuxi Medical College Jiangnan UniversityWuxi 214122China Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch Wuxi 214013China

Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

关键词： Aflatoxin B_(1) Podocyte inflammation miRNA-9 Chemokine(C-X-C motif)receptor 4 RelA ubiquitin-dependent degradation

Anemoside B4 inhibits SARS-CoV-2 replication in vitro and in vivo

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Chinese Herbal Medicines 2024年第1期16卷 106-112页

作者： Mingyue Xiao Ronghua Luo qinghua Liang Honglv Jiang Yanli Liu Guoqiang xu Hongwei Gao Yongtang Zheng Qiongming xu Shilin Yang College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Jiangsu Key Laboratory of Neuropsychiatric Diseases and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Soochow UniversitySuzhou 215123China College of Pharmacy Guangxi University of Chinese MedicineNanning 530000China

Objective: Anemoside B4(AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro.Methods: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8(CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore,label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type Ⅰ IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining.Results: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein(N), Spike protein(S), and 3C-like protease(3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon(IFN)-β response via the activation of retinoic acid-inducible gene Ⅰ(RIG-1) like receptor(RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism.Conclusion: Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

关键词： anemoside B4 interferon RNA metabolism quantitative proteomics SARS-CoV-2

CircR-ZC3HC1 mediates MiR-384-5p/SIRT1 axis to promote neuronal autophagy and relieves ischemic stroke

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BIOCELL 2024年第3期48卷 491-499页

作者： MIN SHEN XIAOMAN xu GUANGLING SUN LIANGZHU WANG TAO YING HANG SU WEI WANG qinghua CAO ZHEZHE SUN Department of Neurology The First Affiliated Hospital of Ningbo UniversityNingbo315010China School of Medicine Ningbo UniversityNingbo315211China

Objective:Circular RNAs(circRNAs)have been shown to involve in pathological processes of ischemic stroke(IS),including autophagy.This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in IS and the related mechanisms.Methods:Expression of circR-ZC3HC1 in blood samples of IS patients and healthy controls was detected.Hippocampal neurons were treated with oxygen and glucose deprivation(OGD)to establish IS in vitro model.The expression of LC3 and p62 and the number of autophagosomes were examined to evaluate the autophagy level of OGD induced neurons using western blotting and transmission electron microscope.Cell apoptosis rate and the expression of cleaved caspase-3,Bax,and Bcl-2 were assessed byﬂow cytometry and western blotting.The binding relationships among circR-ZC3HC1,miR-384-5p,and SIRT1 were predicted and veriﬁed.Results:Low expression of circR-ZC3HC1 was found in blood samples of IS patients and OGD-treated neurons.Overexpressed circR-ZC3HC1 or inhibited miR-384-5p expression promoted autophagy and inhibited apoptosis of OGD-treated neurons,which could be reversed by further 3-MA treatment.Mechanistically,circR-ZC3HC1 targeted miR-384-5p to mediate SIRT1 expression.miR-384-5p overexpression or SIRT1 knockdown in the presence of circR-ZC3HC1 overexpression in OGD-treated neurons lead to reduced autophagy and enhanced apoptosis.Conclusion:Collectively,circR-ZC3HC1 promoted neuronal autophagy to attenuate IS via miR-384-5p/SIRT1 axis.

关键词： Ischemic stroke circR-ZC3HC1 miR-384-5p SIRT1 Autophagy

Biological function of miRNA-145-5p in angiotensin II induced renal inflammation

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BIOCELL 2024年第4期48卷 601-611页

作者： BIN LI YUCHENG SHENG XIAOYING xu SHENGCUN WANG HONGYAN SONG JINGYUAN LI HAONAN JI qinghua WANG XIAODI ZHOU LONGJU QI Department of Pediatrics Affiliated Hospital of Nantong UniversityNantong226001China Department of Science and Education Affiliated Nantong Hospitalof Nantong UniversityNantong226001China Laboratory Animal Center Nantong UniversityNantong226001China Department of Gynecology and Obstetrics and Department of Oncology Hai’an Hospital Affiliated to Nantong UniversityNantong226600China

Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise of miR-145-5p in addressing renal pathologies has been discerned.This investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inﬂammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and downregulation.Furthermore,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)analysis.Results:AngII incubation induced an upregulation of miR-145-5p and inﬂammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ratio.Conversely,inhibition of miR-145-5p heightened the levels of inﬂammatory factors and cell cycle regulators induced by AngII incubation.Reduced expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII stimulation.Moreover,ectopic miR-145-5p expression demonstrated a reduction in inﬂammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall proliferation.Conclusion:MiR-145-5p exhibited inhibitory effects on the inﬂammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.

关键词： miR-145-5p Kidney Angiotensin II Cell cycle Inflammation

Predictive value of T cell receptor repertoire profiling for immunosuppressive therapy in severe aplastic anemia

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Genes & Diseases 2024年第1期11卷 95-98页

作者： Cunte Chen Yuling Zhang Dongpei Lu Zelong Zhang Jun Yang Xiaowei Chen Ming Zhou Wenjian Mo Caixia Wang qinghua Cai Yumiao Li Ruiqing Zhou Shilin xu Wei Zhou Tingfen Deng Shiyi Pan Yanli xu Shunqing Wang Yuping Zhang Department of Hematology Guangzhou First People's HospitalSouth China University of TechnologyGuangzhouGuangdong 510180China Guangzhou Junruikang Biotechnology Co. LtdGuangzhouGuangdong 510700China

Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).

关键词： anemia aplastic interferon