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Madecassic acid suppresses osteoclast differentiation and bone resorption by inhibiting RANKL-induced NF-κB,JNK and NFAT signaling pathways

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Rheumatology & Autoimmunity 2023年第4期3卷 220-229页

作者： Peiru Su xiangya luo Chunping Zeng Lin Zhou Department of Endocrinology Key Laboratory of Biological Targeting DiagnosisTherapy and Rehabilitation of Guangdong Higher Education InstitutesThe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouGuangdongChina

Background:Overproduction and activation of osteoclasts result in various bone diseases,such as osteoporosis,Paget's disease,and rheumatoid ***,inhibiting osteoclast formation and overactivation may effectively prevent osteoclast-related bone diseases,especially *** acid,one of the most important active ingredients in Centella asiatica,has various biological effects,but its role in osteoclastogenesis remains ***:RAW 264.7 cells were stimulated with receptor activator of nuclear factor(NF)-κΒligand(RANKL,25 ng/mL)to differentiate into multinucleated ***,osteoclasts were treated with or without varying concentrations of madecassic acid(1,2.5,5,and 10μmol/L).Results:Madecassic acid significantly inhibited RANKL-induced osteoclastogenesis in a concentration-dependent *** addition,it reduced the percentage of bone resorptive area compared with the control,confirming that madecassic acid can inhibit osteoclast ***,luciferase reporter gene studies indicate that madecassic acid could decrease the transcriptional activity of NF of activated T cells(NFAT)and NF-κB in a dose-dependent *** real-time polymerase chain reaction results show that madecassic acid attenuated the expression of osteoclast-associated genes,including V-ATPase-d2,cathepsin K,tartrate-resistant acid phosphatase(TRAP),NFAT cytoplasmic 1(NFATc1).Western blot analysis shows that madecassic acid inhibited RANKL-mediated degradation of IκBαand NFATc1 expression,as well as phosphorylation of c-Jun N-terminal kinase(JNK)in RAW 264.7 ***:Madecassic acid inhibited osteoclast formation and function in vitro by suppressing NF-κB,JNK,and NFAT signaling pathways,indicating its potential as a novel drug for the treatment of osteoclast-related bone diseases,especially osteoporosis.

关键词： madecassic acid nuclear factor-κB osteoclastogenesis osteoclasts RANKL

Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

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Biomedical and Environmental Sciences 2024年第7期37卷 762-773页

作者： Yamei Li Xiang Xiao Jie Wang Yixu Liu Xiongfeng Pan Haibin Yu Jiayou luo Miyang luo Department of Epidemiology and Health Statistics School of Public HealthUniversity of South ChinaHengyang 421001HunanChina Department of Maternal and Child Health Xiangya School of Public HealthCentral South UniversityChangsha 410008HunanChina Supervision and Inspection Department of Shanghai Healthcare Security Bureau Shanghai 200003China Department of Epidemiology and Health Statistics Xiangya School of Public HealthCentral South UniversityChangsha 410008HunanChina

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically ***-analyses of the genetic variants were conducted using at least five data *** epidemiologic credibility of the significant associations was graded using the Venice *** Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing *** identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the *** meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

关键词： Nonalcoholic fatty liver disease Genetic association study Genetic variant Systematic review Meta-analysis

Parboiled rice supplementation alleviates high-fat diet-induced hyperlipidemia by regulating genes and gut microbiota in mice

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Food Science and Human Wellness 2024年第3期13卷 1422-1438页

作者： Xiuxiu Wu Tianyi Guo Biao Li Shuai Han Zuomin Hu Yi luo Dandan Qin Yaping Zhou Feijun luo Qinlu Lin National Research Center of Rice Deep Process and Byproducts Hunan Provincial Key Laboratory of Grain-oil Deep Process and Quality ControlHunan Provincial Key Laboratory of Forestry Edible Resources Safety and ProcessingCentral South University of Forestry and TechnologyChangsha 410004China College of Life Science and Technology Central South University of Forestry and TechnologyChangsha 410004China Department of Clinical Medicine Medical College of XiangyaCentral South UniversityChangsha 410008China

Dietary parboiled rice(PR)has a low risk of disease,but little is known about the contribution of PR to the prevention of *** potential role and underlying mechanisms of PR in hyperlipidemia were evaluated in this *** C57BL/6J mice were fed with a normal diet,high-fat diet(HFD)containing refined rice(HFDRR)or PR(HFDPR).It was found that PR intervention improved lipid accumulation in *** data analysis revealed that 27 genes were up-regulated(mostly involved in lipid breakdown)and 86 genes were down-regulated(mostly involved in inflammatory responses)in the HFDPR group compared to the HFDRR *** 15 differentially expressed genes(DEGs)were validated by quantitative real-time PCR(RT-qPCR),while protein interaction network showed that protein tyrosine phosphatase receptor type C(PTPRC)has a central *** gut microbiota of mice was also altered after different dietary treatments,with higher ratio of Firmicutes and Bacteroidetes,increased abundances of Ruminococcaceae,Lachnospiraceae,Christensenellaceae,Porphyromonadaceae,Rikenellaceae and Prevotellaceae,and decreased abundances of Lactobacillaceae,Peptostreptococcaceae,Erysipelotrichaceae and Actinobacteria in the HFDRR *** addition,it was observed that PPAR signaling pathway may act as a bridge between DEGs and differential gut *** results suggested that PR can prevent hyperlipidemia by modulating liver genes and gut microbiota.

关键词： Parboiled rice Blood lipids Transcriptome Gut microbiota PPAR Signaling pathway

Pannexins in the musculoskeletal system:new targets for development and disease progression

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Bone Research 2024年第2期12卷 255-269页

作者： Yan luo Shengyuan Zheng Wenfeng Xiao Hang Zhang Yusheng Li Department of Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Clinical Medicine Xiangya Medicine SchoolCentral South UniversityChangshaHunan 410008China Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhen 518055China

During cell differentiation,growth,and development,cells can respond to extracellular stimuli through communication ***(Panx)family and connexin(Cx)family are two important types of channel-forming *** family contains three members(Panx1-3)and is expressed widely in bone,cartilage and *** there is no sequence homology between Panx family and Cx family,they exhibit similar configurations and *** to Cxs,the key roles of Panxs in the maintenance of physiological functions of the musculoskeletal system and disease progression were gradually revealed ***,we seek to elucidate the structure of Panxs and their roles in regulating processes such as osteogenesis,chondrogenesis,and muscle *** also focus on the comparison between Cx and *** a new key target,Panxs expression imbalance and dysfunction in muscle and the therapeutic potentials of Panxs in joint diseases are also discussed.

关键词： skeletal diseases system

Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide

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Neural Regeneration Research 2024年第7期19卷 1532-1540页

作者： Qin Huang Minping Wei Xianjing Feng Yunfang luo Yunhai Liu Jian Xia Department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Neurology Peking University People’s HospitalBeijingChina Clinical Research Center for Cerebrovascular Disease of Hunan Province Central South UniversityChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Hemorrhagic transformation is a major complication of large-artery atheroscle rotic stroke(a major ischemic stro ke subtype)that wo rsens outcomes and increases *** of the gut microbiota is an important feature of stroke,and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation *** aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in largearte ry atheroscle rotic stro *** observational retrospective study was *** May 2020 to September 2021,blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy,as well as 16 healthy *** with stro ke who developed hemorrhagic transfo rmation(n=15)were compared to those who did not develop hemorrhagic transformation(n=17)and with healthy *** gut microbiota was assessed through 16S ribosomal ribonucleic acid *** also examined key components of the lipopolysaccharide pathway:lipopolysaccharide,lipopolysaccharide-binding protein,and soluble *** observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transfo rmation group compared with the healthy *** patients with ischemic stro ke who developed hemorrhagic transfo rmation exhibited altered gut micro biota composition,in particular an increase in the relative abundance and dive rsity of members belonging to the Enterobacteriaceae *** lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transfo rmation ***,lipopolysaccharide-binding protein,and soluble CD14 concentrations were associated with increased abundance of Enterobacte ***,the role of the gut microbiota in hemorrhagic transformation was evaluated using

关键词： gut microbiota hemorrhagic transformation inflammation lipopolysaccharide stroke

Bioactive peptides alleviating oxidative stress-associated diseases by targeting the Nrf2 signaling pathway

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Food Science and Human Wellness 2024年

作者： Dandan Qin Zuomin Hu Shuai Han Yi luo Feiyan Yang Tiantian Xie Feijun luo Hunan Key Laboratory of Grain-oil Deep Process and Quality Control， Hunan Key Laboratory of Forestry Edible Resources Safety and Processing， College of Food Science and Engineering， Central South University of Forestry and Technology Department of Gastroenterology， xiangya Hospital， Central South University

Oxidative stress is caused by an imbalance of the antioxidant defense system and excessive production of free radicals， which can damage biological macromolecules such as proteins， lipids and nucleic acids， which can cause aging， ischemia-reperfusion injury， inflammatory injury， liver and kidney injury and other diseases. The nuclear factor erytheroid-2-related factor 2 (Nrf2) is a major regulator of redox balance. The Nrf2 pathway also exerts a central function in cell apoptosis， oxidative stress damage and metabolic diseases. Bioactive peptides are small molecular peptides composed of amino acid residues. They have many biological activities and play important physiological roles in human body. Antioxidant peptide is a kind of peptide which can reduce oxidative stress damage. They are safe， non-toxic and easily absorbed. In this review， we summarized the mechanism of bioactive peptides in regulating oxidative stress， especially antioxidant peptides， through regulating the Nrf2 signaling pathway and the expressions of oxidative stress-related genes， to alleviate oxidative stress-induced damage. The paper will provide valuable reference to investigators in the antioxidant peptide field and also promote the applications of antioxidant peptides in the oxidative stress-associated diseases.

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猫眼草黄素对破骨细胞分化及自噬作用的研究

现代医药卫生 2022年第9期38卷 1441-1445页

作者：苏珮茹罗香雅曾春平周琳广州医科大学附属第五医院/广州市加速康复腹部外科重点实验室/广州医科大学第五临床医学院广东广州510700

目的研究猫眼草黄素对破骨细胞分化的影响及自噬在其中的作用。方法采用核转录因子-κB受体活化因子配体(RANKL)诱导小鼠单核巨噬细胞RAW264.7分化成破骨细胞,空白组给予完全培养基,模型组给予含50.0 ng/mL RANKL的培养基,A~F组给予不... 详细信息

目的研究猫眼草黄素对破骨细胞分化的影响及自噬在其中的作用。方法采用核转录因子-κB受体活化因子配体(RANKL)诱导小鼠单核巨噬细胞RAW264.7分化成破骨细胞,空白组给予完全培养基,模型组给予含50.0 ng/mL RANKL的培养基,A~F组给予不同水平猫眼草黄素(0.5、1.0、2.5、5.0、10.0、20.0μmol/L)+含50.0 ng/mL RANKL的培养基。染色后计数破骨细胞数目,同时通过Western blot检测自噬相关蛋白LC3、ATG5的表达情况。结果C~F组破骨细胞数量与模型组比较,差异有统计学意义(P0.05)。与空白组比较,模型组自噬相关蛋白LC3Ⅱ表达及LC3Ⅱ/LC3Ⅰ比值增加(P0.05)。在干预3、5 d时,自噬相关蛋白LC3的表达较模型组明显下降(P<0.05)。结论猫眼草黄素对破骨细胞的分化有抑制作用,且呈剂量依赖性,其可能通过自噬途径发挥抑制作用。

关键词：猫眼草黄素破骨细胞自噬骨质疏松

Monte Carlo method for evaluation of surface emission rate measurement uncertainty

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Nuclear Science and Techniques 2024年第7期35卷 126-136页

作者： Yuan-Qiao Li Min Lin Li-Jun Xu Rui luo Yu-He Zhang Qian-Xi Ni Yun-Tao Liu China Institute of Atomic Energy Beijing102413China National Key Laboratory for Metrology and Calibration Techniques Beijing102413China Department of Radiation Oncology Hunan Cancer HospitalChangsha410031China The Affiliated Cancer Hospital of xiangya School of Medicine Central South UniversityChangsha410031China

The aim of this study is to evaluate the uncertainty of 2πα and 2πβ surface emission rates using the windowless multiwire proportional counter *** study used the Monte Carlo method (MCM) to validate the conventional Guide to the Expression of Uncertainty in Measurement (GUM) method.A dead time measurement model for the two-source method was established based on the characteristics of a single-channel measurement system,and the voltage threshold correction factor measurement function was indirectly obtained by fitting the threshold correction *** uncertainty in the surface emission rate was calculated using the GUM method and the law of propagation of *** MCM provided clear definitions for each input quantity and its uncertainty distribution,and the simulation training was realized with a complete and complex mathematical *** results of the surface emission rate uncertainty evaluation for four radioactive plane sources using both methods showed the uncertainty’s consistency E_(n)<0.070 for the comparison of each source,and the uncertainty results of the GUM were all lower than those of the ***,the MCM has a more objective evaluation process and can serve as a validation tool for GUM results.

关键词： Surface emission rate Monte Carlo method Metrology Probability distribution function Dead time Low-energy loss correction Least-squares method

麦考酚吗乙酯联合来氟米特与麦考酚吗乙酯单药维持治疗狼疮肾炎的疗效对比

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新医学 2017年第12期48卷 853-858页

作者：罗香雅刘琪陈瑞林林泽英黄文辉广州医科大学附属第二医院风湿免疫科广州510260

目的比较麦考酚吗乙酯(MMF)联合来氟米特与MMF单药维持治疗狼疮肾炎的疗效和安全性。方法收集经诱导治疗达到完全缓解或部分缓解后的44例Ⅲ~Ⅴ型狼疮肾炎患者临床资料,按其治疗方案分为多靶点组21例与单药组23例,2组在相同的综合治疗基... 详细信息

目的比较麦考酚吗乙酯(MMF)联合来氟米特与MMF单药维持治疗狼疮肾炎的疗效和安全性。方法收集经诱导治疗达到完全缓解或部分缓解后的44例Ⅲ~Ⅴ型狼疮肾炎患者临床资料,按其治疗方案分为多靶点组21例与单药组23例,2组在相同的综合治疗基础上,多靶点组予MMF 0.5 g每日2次联合来氟米特10 mg/d,单药组予MMF 0.5 g每日2次,总观察时间18个月,比较治疗前后疗效(主要观察终点为肾脏复发)及安全性。结果 2组治疗后均未出现死亡和终末期肾病患者。多靶点组维持治疗狼疮肾炎的无复发生存率高于单药组(95%vs.70%,P0.05)。2组患者的不良反应以感染及胃肠道症状最为常见,组间不良反应发生率比较差异无统计学意义(P>0.05)。结论 MMF联合来氟米特多靶点维持治疗狼疮肾炎预防肾脏复发和维持肾脏完全缓解均优于MMF单药治疗。

关键词：麦考酚吗乙酯来氟米特狼疮肾炎维持治疗肾脏复发