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Regulation of PM_(2.5)on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol

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Journal of Environmental Sciences 2024年第4期138卷 288-300页

作者： Shanshan Chen Wenqi Chen Zhiping li Jianwei Yue ken kin lam yung Ruijin li Institute of Environmental Science Shanxi UniversityTaiyuan 030006China Institute of Judicial Identification Techniques for Environmental Damage Shanxi University and Shanxi Unisdom Testing Technology Co.Ltd.Taiyuan 030006China Department of Biology Hong Kong Baptist UniversityHong KongChina Shanxi Yellow River laboratory Taiyuan 030006China

Fine particulate matter(PM_(2.5))exposure is associated with cardiovascular disease(CVD)morbidity and mortality.Mitochondria are sensitive targets of PM_(2.5),and mitochondrial dysfunction is closely related to the occurrence of CVD.The epigenetic mechanism of PM_(2.5)-triggered mitochondrial injury of cardiomyocytes is unclear.This study focused on the mi R-421/SIRT3 signaling pathway to investigate the regulatory mechanism in cardiac mitochondrial dynamics imbalance in rat H9c2 cells induced by PM_(2.5).Results illustrated that PM_(2.5)impaired mitochondrial function and caused dynamics homeostasis imbalance.Besides,PM_(2.5)up-regulated mi R-421 and down-regulated SIRT3 gene expression,along with decreasing p-FOXO3a(SIRT3 downstream target gene)and p-Parkin expression and triggering abnormal expression of fusion gene OPA1 and fission gene Drp1.Further,mi R-421 inhibitor(mi R-421i)and resveratrol significantly elevated the SIRT3 levels in H9c2 cells after PM_(2.5)exposure and mediated the expression of SOD2,OPA1 and Drp1,restoring the mitochondrial morphology and function.It suggests that mi R-421/SIRT3 pathway plays an epigenetic regulatory role in mitochondrial damage induced by PM_(2.5)and that mi R-421i and resveratrol exert protective effects against PM_(2.5)-incurred cardiotoxicity.

关键词： Fine particulate matter Rat H9c2 cells Mitochondrial damage MiR-421 SIRT3 Resveratrol

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Effects of common prebiotics on iron status and production of colonic short-chain fatty acids in anemic rats

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Food Science and Human Wellness 2021年第3期10卷 327-334页

作者： Fan Zhang ken k.l.yung Chi kongYeung Division of Science and Technology BNU-HKBU United International CollegeZhuhaiGuangdongChina Department of Biology Hong Kong Baptist UniversityHong KongChina Animal Science Department California Polytechnic State UniversitySan Luis ObispoCaliforniaUSA

Prebiotics may enhance iron absorption,and one plausible mechanism involves the production of shortchain fatty acids(SCFA)in the colon by intestinal microflora.The objectives of this study were to determine the effects of common commercially-available prebiotics including fructooligosaccharide(FOS),inulin,FOS-inulin mixture,galactooligosaccharide(GOS),and lactulose on the iron status of anemic rats,and to monitor changes in the production of colonic SCFA.Anemic Sprague-Dawley rats receiving a lowiron diet(12μg Fe/g diet)were supplemented with or without prebiotics(5%m/V in drinking water)for 5 weeks.Hemoglobin concentration in rats supplemented with GOS after 3 weeks(4.3 g/dl)was significantly higher than rats without supplementation(3.7 g/dl),while FOS also significantly increased hemoglobin concentration after 4 weeks(4.1 g/dl vs.3.7 g/dl).All other prebiotics showed no effects.Anemic rats showed lower overall SCFA production in the colon than normal rats,and only FOS signifi cantly increased the production of the three main SCFA(acetic acid,propionic acid and isobutyric acid)identifi ed in anemic rats,with other prebiotics showing no noticeable trends.Our results suggest that GOS and FOS may slightly improve iron status of anemic rats,but the role of SCFA in the colon is not clear.

关键词： Iron Non-digestible oligosaccharides Short-chain fatty acids Prebiotics Rat

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Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

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Military Medical Research 2024年第2期11卷 206-227页

作者： Guang-Hui Deng Chao-Feng Wu Yun-Jia li Hao Shi Wei-Chao Zhong Mu-keng Hong Jun-Jie li Jia-Min Zhao Chang liu Meng-Chen Qin Zhi-Yun Zeng Wei-Min Zhang ken kin lam yung Zhi-Ping lv lei Gao Department of Gastroenterology Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou 510515China Department of Hepatology Cancer CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China Shenzhen Traditional Chinese Medicine Hospital Shenzhen 518033GuangdongChina Department of Biology Hong Kong Baptist UniversityKowloon TongKowloonHong Kong SAR 999077China

Background:Nonalcoholic fatty liver disease(NAFlD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFlD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFlD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ElISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFlD.The expression of Cav-1 was decreased in NAFlD hepatocytes(Plism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFlD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFlD patients and healthy volunteers(Plusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It i

关键词： Caveolin-1 Nonalcoholic fatty liver disease Iron metabolism Ferritin Oxidative stress

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Novel small molecules and nanomaterials as potential treatments of neurodegeneration

Novel small molecules and nanomaterials as potential treatme...

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中国神经科学学会第十届全国学术会议

作者： ken k.l.yung Department of Biology Hong Kong Baptist University

Neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases can cripple lives to varying degrees:from minor disability to loss of movement or memory.At present,there are only limited therapies for neurodegenerative diseases.We have adopted latest interdisciplinary designs and synthesis of novel small molecules and nanoparticles and then combine these novel materials to develop novel and potential treatments.First,small molecules have been found to arrest aggregations of beta-amyloid proteins.Secondly,magnetic iron oxide nanoparticles（MNPs） possess a magnetic characteristic and allow for easy manipulation by changing the magnetic field and/or other physical parameter.The in vitro cell separation could be easily driven by a conventional magnet after magnetic labelling of these cells with MNPs.To increase the efficacy and specificity of the separation from a mixed cell culture,antibodies against specific cell markers were conjugated to MNPs and a significant success in cell separation was achieved.Furthermore,our data also strongly supported that nanoparticles could be an efficient delivery agents for drug delivery for gene modulatory agents such as small interfering RNA（siRNAs）.In summary,it is believed that small molecules and nanoparticles can act as potential and effective devices for different therapeutic approaches for neurodegenerative diseases.

关键词： nanoparticles drug delivery cell separation brain neurodegenerative diseases

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Absorbed Bioactive Compounds Replicate GuanxinⅡ-Induced Endothelium-Associated in/ex vivo Vasodilation

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Chinese Journal of Integrative Medicine 2024年第5期30卷 387-397页

作者： XU Min lIU Hao SU Meng-qing lI lan YU Ai-ling CHEN ken HUANG Yun-ke ZHAO Qiu-long HUANG Wen-ya HUANG Xi Institute of Traditional Chinese Medicine Related Comorbid Depression Nanjing University of Chinese MedicineNanjing 210029China Department of Gynecology Women's HospitalZhejiang University School of MedicineHangzhou 310053China

Objective:To develop an interference-free and rapid method to elucidate GuanxinⅡ(GXⅡ)'s representative vasodilator absorbed bioactive compounds(ABCs)among enormous phytochemicals.Methods:The contents of ferulic acid,tanshinol,and hydroxysafflor yellow A(FTA)in GXⅡ/rat serum after the oral administration of GXⅡ(30 g/kg)were detected using ultra-performance liquid chromatography-mass spectrometry.Totally 18 rats were randomly assigned to the control group(0.9%normal saline),GXⅡ(30 g/kg)and FTA(5,28 and 77 mg/kg)by random number table method.Diastolic coronary flow velocity-time integral(VTI),i.e.,coronary flow or coronary flow-mediated dilation(CFMD),and endothelium-intact vascular tension of isolated aortic rings were measured.After 12 h of exposure to blank medium or 0.5 mmol/l H_(2)O_(2),endothelial cells(ECs)were treated with post-dose GXⅡof supernatant from deproteinized serum(PGSDS,300μl PGSDS per 1 m l of culture medium)or FTA(237,1539,and 1510 mg/m l)for 10 min as control,H_(2)O_(2),PGSDS and FTA groups.Nitric oxide(NO),vascular endothelial growth factor(VEGF),endothelin-1(ET-1),superoxide dismutase(SOD),malondialdehyde(MDA)and phosphorylated phosphoinositide 3 kinase(p-PI3k),phosphorylated protein kinase B(p-AkT),phosphorylated endothelial nitric oxide synthase(p-e NOS)were analyzed.PGSDS was developed as a GXⅡproxy of ex vivo herbal crude extracts.Results:PGSDS effectively eliminates false responses caused by crude GXⅡpreparations.When doses equaled the contents in GXⅡ/its post-dose serum,FTA accounted for 98.17%of GXⅡ-added CFMD and 92.99%of PGSDS-reduced vascular tension.In ECs,FTA/PGSDS was found to have significant antioxidant(lower MDA and higher SOD,Plial function-protective(lower VEGF,ET-1,Plaxation,endothelial NO levels and phosphorylated PI3k/Akt/e NOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-l-arginine methyl ester(l-NA,e NOS inhibitor)and wortmannin(PI3k/AkT inhibitor),respectively,indicating an endothelium-depende

关键词： ultra-performance liquid chromatography-mass spectrometry endothelium-dependent vasodilation herbal extract GuanxinⅡ absorbed bioactive compound

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Small interfering RNA specific for NMDA receptor one protects dopam inergic neurons in rats after six-hydroxydopamine lesion

Small interfering RNA specific for NMDA receptor one protect...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： ken k.l.yung Tyler C.H.lEUNG Department of Biology Hong Kong Baptist UniversityKowloon TongHong Kong SAR

＜正＞Parkinson’s disease（PD） is a common motor disorder in human.Degeneration of dopaminergic neurons in the substantia nigra is the cause of PD.After dopamine denervation,an over-activity of glutamatergic pathways has been implicated in the neuropathology in PD.One of the possible causes of cell death of dopaminergic neurons in PD is suggested to be glutamate-mediated excitocytotoxicity.The excitocytotoxic cell death is mainly mediated by ionotropic glutamate receptors,including N-methyl-D-aspartate（NMDA） receptors.Blockage of NMDA receptors is believed to have therapeutic values in treatments of PD.In the present study,unilateral 6-hydroxydoapmine-leisoned rats were employed as an animal model for the investigation of the efficacy of NR1 specific siRNA（NRl-siRNA） in neuroprotection and amelioration of the motor symptoms of PD.Two parameters indicating motor deficits in the 6-OHDA-lesioned rats, i.e.,apomorphine-induced contralateral rotations and muscular rigidity were assessed.After a single dose of NRl-siRNA, the rats showed significant ameliorations in both the rotation numbers and muscular rigidity.In addition,siRNA administration was found to delay the decrease of tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra. Down-regulations of NRl proteins in the striatum were found by immunofluorescence and Western blot analysis.The present results implicate that a single dose of NRl-siRNA reduces the level of NRl expression,and provides neuroprotection and thus results in amelioration of motor symptoms in the rat model of PD.

关键词： glutamate receptor basal ganglia Parkinson’s disease

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峭崖眺远:王铁崖与中国国际法学

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中国法律评论 2024年第3期 159-164页

作者：杨肯北京大学法学院

“爱祖国、爱国际法、爱北大、爱学生”是学生对王铁崖一生风采的概括。也正因为如此,他在时代风雨中擎起大旗,让北大国际法学在五四运动的延长线上赓续成长,让中国的国际法学为世人尊重。壹“一心一意要学国际法”王铁崖于1913年在福... 详细信息

“爱祖国、爱国际法、爱北大、爱学生”是学生对王铁崖一生风采的概括。也正因为如此,他在时代风雨中擎起大旗,让北大国际法学在五四运动的延长线上赓续成长,让中国的国际法学为世人尊重。壹“一心一意要学国际法”王铁崖于1913年在福州出生。其父王寿昌(1864—1926年)在洋务运动中被选为官费生赴巴黎学习法语与国际法,回国后为张之洞所用。民国后,王寿昌任外交部驻福建特派交涉员。

关键词：国际法学爱祖国王铁崖洋务运动张之洞交涉员王寿昌五四运动

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An integrative analysis of miRNA and mRNA expression in the brains of Alzheimer's disease transgenic mice after real-world PM_(2.5)exposure

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Journal of Environmental Sciences 2022年第12期34卷 25-40页

作者： Pengfei Fu Yufei Zhao Chuan Dong Zongwei Cai Ruijin li ken kin lam yung Department of Biology Hong Kong Baptist UniversityHong Kong SARChina Golden Meditech Center for NeuroRegeneration Sciences Hong Kong Baptist UniversityHong Kong SARChina Institute of Environmental Science Shanxi UniversityTaiyuan 237016China State key laboratory of Environmental and Biological Analysis Hong Kong Baptist UniversityHong Kong SARChina

Fine particulate matter(PM_(2.5))is associated with increased risks of Alzheimer's disease(AD),yet the toxicological mechanisms of PM_(2.5)promoting AD remain unclear.In this study,wildtype and APP/PS1 transgenic mice(AD mice)were exposed to either filtered air(FA)or PM_(2.5)for eight weeks with a real-world exposure system in Taiyuan,China(mean PM_(2.5)concentration in the cage was 61μg/m~3).We found that PM_(2.5)exposure could remarkably aggravate AD mice's ethological and brain ultrastructural damage,along with the elevation of the pro-inflammatory cytokines(Il-6 and TNF-α),Aβ-42 and ACh E levels and the decline of Ch AT levels in the brains.Based on high-throughput sequencing results,some differentially expressed(DE)m RNAs and DE mi RNAs in the brains of AD mice after PM_(2.5)exposure were screened.Using RT-q PCR,seven DE mi RNAs(mmu-mi R-193b-5p,122b-5p,466h-3p,10b-5p,1895,384–5p,and 6412)and six genes(Pcdhgb8,Unc13b,Robo3,Prph,Pter,and Tbata)were evidenced the and verified.Two mi RNA-target gene pairs(mi R-125b-Pcdhgb8 pair and mi R-466h-3p-Il-17Rα/TGF-βR2/Aβ-42/ACh E pairs)were demonstrated that they were more related to PM_(2.5)-induced brain injury.Results of Gene Ontology(GO)pathways and kyoto Encyclopedia of Genes and Genomes(kEGG)pathways predicted that synaptic and postsynaptic regulation,axon guidance,Wnt,MAPk,and m TOR pathways might be the possible regulatory mechanisms associated with pathological response.These revealed that PM_(2.5)-elevated pro-inflammatory cytokine levels and PM_(2.5)-altered neurotransmitter levels in AD mice could be the important causes of brain damage and proposed the promising mi RNA and m RNA biomarkers and potential mi RNA-m RNA interaction networks of PM_(2.5)-promoted AD.

关键词： Fine particulate matter mRNAs miRNAs Brain Alzheimer’s disease APP/PS1 transgenic mice

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多系统单频紧组合GNSS-R测高方法

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武汉大学学报（信息科学版） 2024年第1期49卷 146-155页

作者：邓垦周佩元杜兰蔡巍信息工程大学地理空间信息学院河南郑州450001 77120部队四川成都610000 中国科学院精密测量科学与技术创新研究院大地测量与地球动力学国家重点实验室湖北武汉430077 西安测绘总站陕西西安710054

全球卫星导航系统反射测量(global navigation satellite system-reflectometry,GNSS-R)技术可以同时接收导航卫星直射信号和来自水面的反射信号,进而利用伪距、载波相位和信噪比信息实现高时空分辨率的水面高度反演。由于岸基设备特别... 详细信息

全球卫星导航系统反射测量(global navigation satellite system-reflectometry,GNSS-R)技术可以同时接收导航卫星直射信号和来自水面的反射信号,进而利用伪距、载波相位和信噪比信息实现高时空分辨率的水面高度反演。由于岸基设备特别是单频设备在部分受限环境中观测量不足,导致基于载波相位处理的GNSS-R实时测高性能降低,因此提出了一种利用GNSS重叠频率B1C/l1/E1信号的紧组合模型以提升单频GNSS-R的测高性能。首先,从天线极化方式的角度对差分系统间偏差(differential inter-system bias,DISB)进行评估和分析。结果表明,对于左圆极化天线和右圆极化天线组成的短基线,在使用同型号接收机时可以忽略DISB的影响。然后,基于实测北斗三号卫星导航系统/全球定位系统(global positioning system,GPS)/伽利略(Galileo)系统数据评估了多系统紧组合模型下的GNSS-R测高性能。实验结果表明,相比于松组合模型,多系统紧组合模型能够显著减少安装环境对设备的限制,特别是在单系统反射信号观测量不足4个的条件下,紧组合模型GNSS-R水面高度反演在保证厘米级精度的条件下成功率仍高达约94%,从而有效提升恶劣观测条件下GNSS-R测高性能。

关键词： GNSS反射测量差分系统间偏差反射信号多系统紧组合

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Therapeutic potential of prophylactic exercise for intracerebral hemorrhage

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Neural Regeneration Research 2022年第7期17卷 1484-1485页

作者： keita kinoshita kelly k.Chung Hiroshi katsuki ken Arai Neuroprotection Research laboratory Departments of Radiology and NeurologyMassachusetts General Hospital and Harvard Medical SchoolCharlestownMAUSA Department of Chemico-Pharmacological Sciences Graduate School of Pharmaceutical SciencesKumamoto UniversityKumamotoJapan

Exercise and brain health:Physical activity helps promote and maintain our brain health,including memory and cognitive performance.Research has shown that exercise is a safe behavioral intervention that reduces the ri... 详细信息

关键词： diseases Therapeutic hemorrhage

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