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Catalpol Prevents Glomerular Angiogenesis Induced by Advanced Glycation End Products via Inhibiting Galectin-3

当代医学科学(英文) 2023年第4期43卷 668-678页

作者： Wei-xiang SUN Yu-yan GAO Ying CAO Jin-fu LU Gao-hong LV hui-qin xu Jiangsu Key Laboratory for High-Tech Research and Development of Veterinary Biopharmaceuticals Jiangsu Agri-animal Husbandry Vocational CollegeTaizhou 225300China Department of Chinese Pharmaceutical Technology School of Animal PharmacyJiangsu Agri-animal Husbandry Vocational CollegeTaizhou 225300China Department of Pharmacology School of PharmacyNanjing University of Chinese MedicineNanjing 210023China Jiangsu Key laboratory of Pharmacology and Safety Evaluation for Chinese Material Medica Nanjing University of Chinese MedicineNanjing 210023China Department of Pharmacology School of PharmacyNanjing University of Chinese Medicine Hanlin CollegeTaizhou 225300China

Objective:The main characteristics of diabetic nephropathy(DN)at the early stage are abnormal angiogenesis of glomerular endothelial cells(GECs)and macrophage infiltration.Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand,advanced glycation end products(AGEs).Catalpol,an iridoid glucoside extracted from Rehmannia glutinosa,has been found to ameliorate vascular inflammation,reduce endothelial permeability,and protect against endothelial damage in diabetic milieu.However,little is known about whether catalpol could exert an anti-angiogenesis and anti-inflammation effect induced by AGEs.Methods:Mouse GECs(mGECs)and RAW 264.7 macrophages were treated with different concentrations of AGEs(0,50,100,200 and 400μg/mL)for different time(0,6,12,24 and 48 h)to determine the optimal concentration of AGEs and treatment time.Cells were treated with catalpol(10μmol/L),GB1107(1μmol/L,galectin-3 inhibitor),PX-478(50μmol/L,HIF-1αinhibitor),adenovirus-green fluorescent protein(Ad-GFP)[3×10^(7)plaque-forming unit(PFU)/mL]or Ad-galectin-3-GFP(2×10^(8)PFU/mL),which was followed by incubation with 50μg/mL AGEs.The levels of galectin-3,vascular endothelial growth factor A(VEGFA)and pro-angiogenic factors angiopoietin-1(Ang-1),angiopoietin-2(Ang-2),tunica interna endothelial cell kinase-2(Tie-2)were detected by enzyme-linked immunosorbent assay(ELISA).Cell counting kit-8(CCK-8)assay was used to evaluate the proliferation of these cells.The expression levels of galectin-3,vascular endothelial growth factor receptor 1(VEGFR1),VEGFR2,and hypoxia-inducible factor-1α(HIF-1α)in mGECs and those of galectin-3 and HIF-1αin RAW 264.7 macrophages were detected by Western blotting and immunofluorescence(IF)staining.The rat DN model was established.Catalpol(100 mg/kg)or GB1107(10 mg/kg)was administered intragastrically once a day for 12 weeks.Ad-galectin-3-GFP(6×10^(7)PFU/mL,0.5 mL)or Ad-GFP(6×10^(6)PFU/mL,0.5 mL)was injected into the tail vein of rats 48 h before the sacrifice of the animals.The expression of gale

关键词： catalpol glomerular angiogenesis advanced glycation end products galectin-3

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Parallel profiling of antigenicity alteration and immune escape of SARS-CoV-2 Omicron and other variants

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Signal Transduction and Targeted Therapy 2022年第3期7卷 770-779页

作者： Cong Sun Yin-Feng Kang Yuan-Tao Liu Xiang-Wei Kong hui-qin xu Dan Xiong Chu Xie Yi-Hao Liu Sui Peng Guo-Kai Feng Zheng Liu Mu-Sheng Zeng State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineDepartment of Experimental ResearchSun Yat-sen University Cancer CenterSun Yat-sen UniversityGuangzhou 510060P.R.China Cryo-electron Microscopy Center Southern University of Science and TechnologyShenzhen 518000 GuangdongP.R.China Medical Laboratory of the Third affiliated Hospital of Shenzhen University Shenzhen 518000 GuangdongP.R.China Institute of Precision Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080 GuangdongP.R.China Clinical Trials Unit The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080 GuangdongP.R.China Department of Endocrinology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080 GuangdongP.R.China

SARS-CoV-2 variants have evolved a variety of critical mutations,leading to antigenicity changes and immune escape.The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resis... 详细信息

关键词： variants antigenicity Omi

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C-peptide and Diabetic Encephalopathy

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Chinese Medical Sciences Journal 2011年第2期26卷 119-125页

作者： Xiao-jun Cai hui-qin xu Yi Lu Department of Pharmacy Wuxi People＇s Hospital Wuxi Jiangsu 214023 China Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing 210029 China

With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic encephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cognitive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glu-cose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronal loss and damaged cognitive functions. Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system, hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide deficiency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients. Those findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.

关键词：糖尿病脑病 C肽胰岛素样生长因子神经细胞凋亡神经元损伤并发症生活方式

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Cancer organoids:A platform in basic and translational research

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Genes & Diseases 2024年第2期11卷 614-632页

作者： Xin Ma qin Wang Guozheng Li hui Li Shouping xu Da Pang Department of Breast Surgery Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081China Sino-Russian Medical Research Center Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081China Heilongjiang Academy of Medical Sciences HarbinHeilongjiang 150086China Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China) College of Pharmacy of Harbin Medical UniversityHarbinHeilongjiang 150086China

An accumulation of previous work has established organoids as good preclinical models of human tumors,facilitating translation from basic research to clinical practice.They are changing the paradigm of preclinical cancer research because they can recapitulate the heterogeneity and pathophysiology of human cancers and more closely approximate the complex tissue environment and structure found in clinical tumors than in vitro cell lines and animal models.However,the potential applications of cancer organoids remain to be comprehensively summarized.In the review,we firstly describe what is currently known about cancer organoid culture and then discuss in depth the basic mechanisms,including tumorigenesis and tumor metastasis,and describe recent advances in patient-derived tumor organoids(PDOs)for drug screening and immunological studies.Finally,the present challenges faced by organoid technology in clinical practice and its prospects are discussed.This review highlights that organoids may offer a novel therapeutic strategy for cancer research.

关键词： Drug assays Immunotherapy Mechanism research Organoids Precision medicine

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Systematic review and network meta-analysis of different nonsteroidal anti-inflammatory drugs for juvenile idiopathic arthritis

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World Journal of Clinical Cases 2024年第12期12卷 2056-2064页

作者： Tao Zeng Jian-Zhong Ye hui qin Qian-Qian xu College of Medicine Jingchu University of Technology JingmenJingmen 448000Hubei ProvinceChina

BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.

关键词： Non-steroidal anti-inflammatory drugs Juvenile idiopathic arthritis Network meta-analysis Systematic review

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Height and body mass index trajectories from 1975 to 2015 and prevalence of stunting,underweight and obesity in 2016 among children in Chinese cities:findings from five rounds of a national survey

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World Journal of Pediatrics 2024年第4期20卷 404-412页

作者： Xin‑Nan Zong hui Li Ya‑qin Zhang Department of Growth and Development Capital Institute of PediatricsBeijing 100020China

Background A more comprehensive assessment of growth and nutrition in children is required in China due to rapid socioeconomic processes.We aimed to investigate height and body mass index(BMI)trajectories from 1975 to 2015 and the prevalence of stunting and obesity in 2016 among children in Chinese cities.Methods A total of 904,263 children from birth to 6.9 years were collected from a series of nationally representative surveys in China.Height and BMI trajectories and prevalence of stunting,underweight,overweight and obesity were assessed.Results The average height level of Chinese urban children under 7 years presented a positive secular trend from 1975 to 2015;however,a slowing tendency occurred in 2005‒2015.An apparent increase was observed at the 5th,50th and 95th percentiles of BMI in urban children aged 3 years and older,with a more prominent increase at the 95th percentile.The total prevalence of stunting and underweight under 7 years was 1.4%and 2.0%,respectively.The total prevalence of overweight and obesity under 7 years was 12.6%and 4.3%,respectively,with 12.7%and 4.9%for boys,12.6%and 3.6%for girls,12.1%and 4.0%in urban areas and 13.1%and 4.5%in suburban rural areas.Conclusions The average height level of Chinese urban children has reached World Health Organization child growth standards since 2005 and presented a slowing tendency in secular trend in 2005‒2015.More attention and efforts and public health interventions should be urgently made to combat overweight and obesity among preschool children.

关键词： Body mass index Children Height Obesity Stunting

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Insight into vertical piezoelectric characteristics regulated thermal transport in van der Waals two-dimensional materials

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Rare Metals 2024年第2期43卷 770-779页

作者： Dong-Hai Wei E Zhou Jin-Yuan xu hui-Min Wang Chen Shen Hong-Bin Zhang Zhen-Zhen qin Guang-Zhao qin State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body College of Mechanical and Vehicle EngineeringHunan UniversityChangsha410082China Hunan Key Laboratory for Micro-Nano Energy Materials and Device and School of Physics and Optoelectronics Xiangtan UniversityXiangtan411105China Institute of Materials Science Technical University of DarmstadtAlarich-Weiss-Str.264287DarmstadtGermany School of Physics and Microelectronics Zhengzhou UniversityZhengzhou450001China

The urgent demand of extreme(ultra-high/low)thermal conductivity materials is triggered by the high-power device,where exploring the theories and mechanisms of regulating thermal transport properties plays a key role.Herein,we elaborately investigate the effect of vertical(out-of-plane)piezoelectric characteristics on thermal transport,which is historically undiscovered.The different stacking-order(AA and AB)bilayer boron nitride(Bi-BN)in two-dimensional(2D)materials are selected as study cases.By performing state-of-the-art first-principles calculations,it is found that the polarization charge along the out-of-plane orientation ascends significantly with the increasing piezoelectric response in AB stacked Bi-BN(Bi-BN-AB)followed by the enhanced interlayer B–N atomic interactions.Consequently,the amplitude of phonon anharmonicity in Bi-BN-AB increases larger than that in the AA stacked Bi-BN(Bi-BN-AA),resulting in the dramatic weakening of the thermal conductivity by 20.34%under 18%strain.Our research reveals the significant role of the vertical(out-of-plane)piezoelectric characteristic in regulating thermal transport and provides new insight into accurately exploring the thermal transport performance of 2D van der Waals materials.

关键词： Thermal conductivity Piezoelectric effect 2D materials Bilayer BN Strain engineering

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Multistep continuous flow synthesis of Erlotinib

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Chinese Chemical Letters 2024年第4期35卷 371-375页

作者： hui Jin qin Cai Peiwen Liu Yan Chen Derong Wang Weiping Zhu Yufang xu xuhong Qian State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of Chemical BiologySchool of PharmacyEast China University of Science and TechnologyShanghai 200237China

Erlotinib is an orally administered, highly effective, specific epidermal growth factor receptor tyrosine kinase inhibitor, used to treat non-small cell lung cancer and pancreatic cancer. The traditional synthetic methods for Erlotinib exhibit long reaction time and safety concern. Herein, we describe a novel five-step route for the synthesis of Erlotinib in flow. These five steps comprise etherification, nitration, reduction,addition and cyclization reactions. All steps were optimized and converted to continuous flow process,which drastically reduces the reaction time and considerably improves the process safety as well as the total yield. Enabled by five continuous flow units, Erlotinib is efficiently afforded with an E-factor of 38,an overall yield of 83%, and a total residence time of 25.1 min. Majority steps in this process have been optimized for quantitative conversion, which offers the possibility of telescoping the entire process.

关键词： Erlotinib Continuous flow synthesis Microchannel flow reactor Process optimization Continuous nitration Continuous hydrogenation

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Vasculopathy in dermatomyositis

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Chinese Medical Journal 2024年第2期137卷 247-249页

作者： hui xu Jie Qian Department of Rheumatology Affiliated Hospital of Nantong UniversityNantongJiangsu 226001China

To the Editor:Dermatomyositis(DM)is a rare autoimmune disease characterized by specific cutaneous manifestations and proximal muscle weakness,in which abnormalities of nailfold capillary(NFC)and serum levels of vascular biomarkers are common.Dynamic changes in vascular lesions play an important role in the occurrence and development of DM and reflect the disease activity and treatment efficacy.Due to the diversity of clinical manifestations in DM patients,vascular involvement is often under-evaluated,causing the treatment of refractory vascular damage challenging.This review aims to explore the mechanisms,clinical manifestations,and treatment options of vasculopathy in DM to achieve early recognition and improve prognosis.

关键词： involvement clinical myositis

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Capturability-based Fuzzy Footstep Planner for a Biped Robot with Centroidal Compliance

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Journal of Bionic Engineering 2024年第1期21卷 84-100页

作者： Zihan xu qin Fang Yong Ren Chengju Liu Robot and Artificial Intelligence Lab(RAIL) College of Electronic and Information EngineeringTongji UniversityShanghai 201804China Applied Technology College Soochow UniversitySuzhou 215000China

Compliance motion and footstep adjustment are active balance control strategies from learning human subconscious behaviors.The force estimation without direct end-actuator force measurement and the optimal footsteps based on complex analytical calculation are still challenging tasks for elementary and kid-size position-controlled robots.In this paper,an online compliant controller with Gravity Projection Observer(GPO),which can express the external force condition of perturbations by the estimated Projection of Gravity(PoG)with estimation covariance,is proposed for the realization of disturbance absorption,with which the robustness of the humanoid contact with environments can be maintained.The fuzzy footstep planner based on capturability analysis is proposed,and the Model Predictive Control(MPC)is applied to generate the desired steps.The fuzzification rules are well-designed and give the corresponding control output responding to complex and changeable external disturbances.To validate the presented methods,a series of experiments on a real humanoid robot are conducted.The results verify the effectiveness of the proposed balance control framework.

关键词： Biped walking Centroidal compliance Gravity projection observer Fuzzy footstep planner

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