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A new therapeutic approach to erectile dysfunction： urotensin-II receptor high affinity agonist ligands

Asian Journal of Andrology 2015年第1期17卷 81-85,I0008,I0009页

作者： Roberta d'emmanuele di Villa Bianca emma Mitidieri Erminia Donnarumma Ferdinando Fusco Nicola Longo Giuseppe De Rosa Ettore Novellino Paolo Grieco Vincenzo Mirone Giuseppe Cirino Raffaella sorrentino Department of Pharmacy University of Naples Federico II Via D. Montesano 49 Naples Italy Interdepartmental Centre for sexual Medicine University of Naples Federico II Via S. Pansini 5 Naples Italy Department of Neurosciences Human Reproduction and Odontostomatology University of Naples Federico II Via S. Pansini 5 Naples Italy.

Urotensin-II （U-II） is a cyclic peptide that acts through a G protein-coupled receptor （urotensin-II receptor [UTR]） mainly involved in cardiovascular function in humans. The urotensinergic system is also implicated in the urogenital tract. Indeed, U-II relaxes human corpus cavernosum strips and causes an increase in intracavernous pressure （ICP） in rats. In light of this, the U-II/UTR pathway can be considered a new target for the treatment of erectile dysfunction. On this hypothesis, herein we report on two new UTR high affinity-agonists, P5U （H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH） and UPG84（H-Asp-c[Pen-Phe-DTrp-Orn-（pNH2） Phe-Cys]-Val-OH）. The effects of P5U and UPG84 were each compared separately with U-II by monitoring the ICP in anesthetized rats. Intracavernous injection of U-II （0.03-1 nmol）, P5U （0.03-1 nmol） or UPG84 （0.03-1 nmol） caused an increase in ICP. P5U, in particular, elicited a significant increase in ICP as compared to U-II. The observed effect by using P5U at a dose of 0.1 nmol per rat was comparable to the effect elicited by U-II at a dose of 0.3 nmol. Moreover, UPG84 at the lowest dose （0.03 nmol） showed an effect similar to the highest dose of U-II （1 nmol）. Furthermore, UPG84 was found to be more effective than P5U. Indeed, while the lowest dose of P5U （0.03 nmol） did not affect the ICP, UPG84, at the same dose, induced a prominent penile erection in rat. These compounds did not modify the blood pressure, which indicates a good safety profile. In conclusion, UPG84 and P5U may open new perspectives for the management of erectile dysfunction.

关键词： erectile dysfunction intracavernous pressure rat urotensin-II urotensin-II ligands

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China's Bitcoin Revolution

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城市漫步（上海版、英文） 2016年第10期 52-58页

作者： Noelle Mateer Holly Li emma Huang Xinyu Li 不详

When Eric Mu says that the village of Moyu in western sichuan is remote,he means *** more Tibetan than Han,the tiny settlement s让s in a valley among soaring mountains and deep *** village is only connected to neighboring com・munities by a rickety suspension bridge,which wobbles above river rapids *** crossed it ***'ll never cross it *** was terrifying,he *** in Moyu is *** Mu is there,he runs-passing along winding roads and through tunnels that pierce the mountains,some as long as 3 *** coworkers entertain themselves with mahjong and *** of the villagers grow corn.

关键词： mountains winding Tibetan

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Ultrathin monolithic 3D printed optical coherence tomography endoscopy for preclinical and clinical use

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Light(science & Applications) 2020年第1期9卷 753-762页

作者： Jiawen Li simon Thiele Bryden C.Quirk Rodney W.Kirk Johan W.Verjans emma Akers Christina A.Bursill stephen J.Nicholls Alois M.Herkommer Harald Giessen Robert A.McLaughlin Australian Research Council Centre of Excellence for Nanoscale BioPhotonics Adelaide Medical SchoolUniversity of AdelaideAdelaideSA 5005Australia Institute for Photonics and Advanced sensing The University of AdelaideAdelaideSA 5005Australia Institute of Applied Optics(ITO)and Research Center sCoPE University of Stuttgart70569 StuttgartGermany south Australian Health and Medical Research Institute(sAHMRI) AdelaideSA 5000Australia Royal Adelaide Hospital AdelaideSA 5000Australia Monash Cardiovascular Research Centre Monash UniversityMelbourneVIC 3168Australia th Physics Institute and Research Center sCoPE University of Stuttgart70569 StuttgartGermany

Preclinical and clinical diagnostics increasingly rely on techniques to visualize internal organs at high resolution via *** endoscopic probes are necessary for imaging small luminal or delicate organs without causing trauma to ***,current fabrication methods limit the imaging performance of highly miniaturized probes,restricting their widespread *** overcome this limitation,we developed a novel ultrathin probe fabrication technique that utilizes 3D microprinting to reliably create side-facing freeform micro-optics(single-mode *** this technique,we built a fully functional ultrathin aberration-corrected optical coherence tomography *** is the smallest freeform 3D imaging probe yet reported,with a diameter of 0.457 mm,including the catheter *** demonstrated image quality and mechanical flexibility by imaging atherosclerotic human and mouse *** ability to provide microstructural information with the smallest optical coherence tomography catheter opens a gateway for novel minimally invasive applications in disease.

关键词： smallest utilize overcome

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Hypoglycemia, Hyperglycemia and Astaxanthin: An <i>in Vitro</i>Alzheimer’s Disease Model

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Advances in Alzheimer's Disease 2019年第3期8卷 27-38页

作者： Julie Griffith shauna Northrup emma Cieslik Marie Kelly-Worden Biology Department Ball State University Muncie USA

Alzheimer’s Disease is projected to increase to 30 million people in the next 30 years and the rate of diabetes mellitus is projected to rise also. Hyperglycemia is commonly observed in patients with diabetes mellitus, and hypoglycemia is a common consequence due to insulin therapy. Previous research has shown a potential link between Alzheimer’s disease and diabetes. This study sought to determine if Astaxanthin (ATX) could prevent mitochondrial dysfunction from the compounded effects of amyloid β (Aβ) plaque and hypoglycemia or hyperglycemia. Growth patterns, ATP production, and ROs generation were examined in 2 μM, 5 μM, 25 μM (hypoglycemic groups), 2 mM, 5 mM (normal groups), and 25 mM glucose (hyperglycemic group), and then treated with or without ATX or Aβ. When hypoglycemia groups and the hyperglycemia group were treated with ATX, their growth patterns were either comparable to control or increased. ATX and Aβ treated cells demonstrated increased growth patterns over cells treated with Aβ alone. Aβ alone treated groups overall had significantly less growth than controls (p β demonstrated low levels of average fluorescence generated by ROs production as determined by Mitosox assay while ATX groups actually produced higher to normal levels of ROs. Cells grown in the presence of Aβ and ATX generally produced more ROs than just Aβ groups. Thus, hypoglycemia and hyperglycemia do appear to compound the effects of Aβ on hippocampal cells. ATX treatment demonstrated promise with increased cellular growth, which promoted usage of ATP by the cell and ROs production. This growth was present even in the presence of Aβ, suggesting that ATX is able to overcome the negative effects of Aβ.

关键词： ATP Luciferase Assay ROs Production Amyloid Beta Astaxanthin Diabetes Mellitus

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Myocarditis and pericarditis following mRNA vaccination in autoimmune inflammatory rheumatic disease patients: A single‐center experience

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Rheumatology & Autoimmunity 2022年第2期2卷 92-97页

作者： shreeya Patel emma Wu Maninder Mundae Keith Lim Department of Rheumatology Western HospitalFootscrayVictoriaAustralia

Introduction:The mRNA vaccines Comirnaty(Pfizer/BioNTech)and spikevax(Moderna)are considered safe and highly effective against sARs‐***,they are also associated with a small increased risk of pericarditis and *** is concern about an increased risk of these complications in patients with autoimmune inflammatory rheumatic diseases(AIRD).Case Report:We describe three patients with pre‐existing AIRD who developed myocarditis or pericarditis shortly after receiving their first dose of the Pfizer‐BioNTech *** first case is a 31‐year‐old female with systemic lupus erythematosus(sLE)and anti‐phospholipid syndrome(APLs)who presented 7 days after receiving the Pfizer‐BioNTech vaccine and was diagnosed with myopericarditis following a positive troponin and abnormal transthoracic echocardiogram(TTE).The second case is a 29‐year‐old man with seronegative inflammatory arthritis and APLs who presented 7 days after receiving the first dose of the Pfizer‐BioNTech *** troponin and TTE were unremarkable however his ECG showed widespread sT ***,the third case is a 34‐year‐old man with Behcet's disease with a history of recurrent *** developed a recurrence of symptoms approximately 7 days after his Pfizer‐BioNTech vaccine and self‐commenced prednisolone at *** had normal laboratory and radiological *** patients received prednisolone resulting in a quick recovery and resolution of ***:In this review we discuss the association between myocarditis,pericarditis and mRNA COVID‐19 vaccines,those who are at greatest risk and current clinical *** also discuss the possible increased risk in AIRD patients and the current research supporting this.

关键词： mRNA vaccines myocarditis pericarditis severe acute respiratory syndrome coronavirus 2(sARs‐CoV‐2)

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Relevance of proteolysis and proteasome activation in fatty liver graft preservation: An Institut Georges Lopez-1 vs University of Wisconsin appraisal

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World Journal of Gastroenterology 2017年第23期23卷 4211-4221页

作者： Mohamed Amine Zaouali Arnau Panisello-Roselló Alexandre Lopez Carlos Castro Benítez emma Folch-Puy Agustín García-Gil Teresa Carbonell RenéAdam Joan Roselló-Catafau Experimental Hepatic Ischemia-Reperfusion Unit Institut d’Investigacions Biomèdiques de BarcelonaSpanish National Research Council Research Unit of Biology and molecular anthropology applied to development and Health(UR12Es11) Faculty of PharmacyUniversity of Monastir Tunisia and Institute of Biotechnology of Monastir University of Monastir Centre Hépatobiliaire AP-PHHopital Paul Brousse Hospital Clínico de Zaragoza Facultat Biologia Universitat de Barcelona

To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) *** liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to “ex vivo” normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography. Total free amino acid release was correlated with the activation of the ubiquitin proteasome system (UPs: measured as chymotryptic-like activity and 20s and 19s proteasome), the prevention of liver injury (transaminases), mitochondrial injury (confocal microscopy) and inflammation markers (TNF 1 alpha, high mobility group box-1 (HGMB-1) and PPAR gamma), and liver apoptosis (TUNEL assay, cytochrome c and caspase 3).REsULTsProfiles of free AA (alanine, proline, leucine, isoleucine, methionine, lysine, ornithine, and threonine, among others) were similar for tissue and reperfusion effluent. In all cases, the IGL-1 solution showed a significantly higher prevention of proteolysis than UW (P schemia reperfusion. Livers conserved in IGL-1 presented more effective prevention of ATP-breakdown and more inhibition of UPs activity (measured as chymotryptic-like activity). In addition, the prevention of liver proteolysis and UPs activation correlated with the prevention of liver injury (AsT/ALT) and mitochondrial damage (revealed by confocal microscopy findings) as well as with the prevention of inflammatory markers (TNF1alpha and HMGB) after reperfusion. In addition, the liver grafts preserved in IGL-1 showed a significant decrease in liver apoptosis, as shown by TUNEL assay and the reduction of cytochrome c, caspase 3 and P62 *** comparison of these two preservation solutions suggests that IGL-1 helps to prevent ATP breakdown more effectively than UW and subsequently achieves a hig

关键词： Liver proteolysis Proteasome activation Fatty liver preservation Institut Georges Lopez-1 University of Wisconsin High mobility group box 1 Cold ischemia reperfusion injury

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Resveratrol activation of sIRT1/MFN2 can improve mitochondria function,alleviating doxorubicin-induced myocardial injury

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Cancer Innovation 2023年第4期2卷 253-264页

作者： Qingling Zhang Yunpeng Zhang Bingxin Xie Daiqi Liu Yueying Wang Zandong Zhou Yue Zhang emma King Gary Tse Tong Liu Department of Cardiology Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular DiseaseTianjin Institute of CardiologyThe Second Hospital of Tianjin Medical UniversityTianjinChina Epidemiology Research Unit Cardiovascular Analytics GroupChina-UK CollaborationHong KongChina Kent and Medway Medical school CanterburyKentUK

Background Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different ***,its use is associated with dose-dependent cardiotoxicity,causing irreversible myocardial damage and significantly reducing the patient's quality of life and *** this study,an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial *** study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in *** Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin *** weight,echocardiography,surface electrocardiogram,and myocardial histomorphology were *** mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups(phosphate-buffered saline,doxorubicin,and doxorubicin with resveratrol).Results Compared to the control group,the doxorubicin group showed a lower body weight and higher systolic arterial pressure,associated with reduced left ventricular ejection fraction and left ventricular fractional shortening,prolonged PR interval,and QT *** abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes,increased protein expression levels of α-smooth muscle actin and caspase 3,and reduced protein expression levels of Mitofusin2(MFN2)and sirtuin1(sIRT1).Compared to the doxorubicin group,doxorubicin+resveratrol treatment reduced caspase 3 and manganese superoxide dismutase,and increased MFN2 and sIRT1 expression *** Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial *** ameliorates doxorubicin-induced cardiotoxicity by activating sIRT1/MFN2 to improve mitochondria function.

关键词： cardio-oncology doxorubicin-induced cardiomyopathy mitochondriafunction resveratrol sIRT1 agonists

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Tremor

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英国医学杂志中文版 2014年第5期17卷 337-338页

作者： Pipis Menelaos Dehabadi Mohammad Matthews emma Gould Lawrence Accident and Emergency Department Watford General Hospital Watford WD18 0HB UK Ophthalmology Department Watford General Hospital Neurology Department National Hospital for Neurology and Neurosurgery London UK The stanmore Medical Centre London UK

A middle aged man presents complaining of excessive shaking of his *** examination reveals bilateral hand tremor,right more so than the left,and worse when holding his arms *** remainder of the physical and neurological examinations are *** you should coverTremor is the most common involuntary movement encountered in clinical *** is an unintentional,rhythmic muscle movement that usually affects the hands but can also affect the arms,head,legs,and rarely the *** tremor is the commonest form,but tremor may sometimes be a symptom of an underlying neurological disorder or a manifestation of systemic disease,and patients are often worried about a diagnosis of Parkinson's disease.

关键词：神经系统手部大脑诊断方法

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白蛋白刺激肾小管上皮细胞表达基质金属蛋白酶2和9

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中华肾脏病杂志 2007年第8期23卷 519-523页

作者：孙良忠 Ibrini Juma Parker emma 陈述枚 Johnson Timothy s. El Nahas A. Meguid 中山大学附属第一医院儿科广州510089 sheffield Kidney Institute University of Sheffield Sheffield UK

目的探讨白蛋白对近端肾小管上皮细胞表达基质金属蛋白酶2（MMP-2）和MMP-9的影响。方法大鼠近端肾小管细胞株NRK52E培养至70％或100％融合时，分别给予不同浓度（0．1～1．0g／L）去脂和非去脂牛血清白蛋白（dBsA和BsA）刺激，于24、48... 详细信息

目的探讨白蛋白对近端肾小管上皮细胞表达基质金属蛋白酶2（MMP-2）和MMP-9的影响。方法大鼠近端肾小管细胞株NRK52E培养至70％或100％融合时，分别给予不同浓度（0．1～1．0g／L）去脂和非去脂牛血清白蛋白（dBsA和BsA）刺激，于24、48、72h收集培养液，用明胶酶谱和Western印迹方法检测培养液MMP-2和MMP-9活性和蛋白水平。结果与空白对照组比较，1．0g／LBsA刺激未完全融合NRK52E72h后，MMP-2和MMP-9活性分别上调276％、176％（P〈0．05）。与刺激24h比较，1．0g／LBsA刺激72h，在未完全融合NRK52E的MMP-2和MMP-9活性分别上调536％、148％；在完全融合NRK52E分别上调212％、184％（P〈0．05）。与完全融合NRK52E比较，1．0g／LBsA刺激未完全融合NRK52E 72h，MMP-2活性上调增加了274％，MMP-9活性上调减少了45．1％（P〈0．05）。dBsA刺激结果与BsA类似。结论白蛋白刺激呈剂量和时间依赖性上调近端肾小管细胞表达MMP-2和MMP-9。细胞完全融合可抑制MMP-2表达，促进MMP-9表达。

关键词：白蛋白基质金属蛋白酶类肾小管上皮细胞

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LOD2和LOD3细节层次下IFC至CityGML的模型转换

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扬州大学学报（自然科学版） 2017年第3期20卷 26-30页

作者：虞铭尧庞浩宇 WARDLE emma 墨尔本大学工程学院

基于可视化编程处理软件FME(feature manipulation engine),设计了语义信息过滤和几何信息提取与处理的方法,实现了IFC(industry foundation classes)至LOD2(level of detail 2)以及LOD3细节层次下CityGML(city geography markup language)的模型转换,并通过实验验证了该方法.结果表明:本文提出的方法能够根据表达尺度的需求,有效地将结构复杂的IFC模型转换为不同细节层次的CityGML模型,实现不同比例三维地图中建筑模型的可视化,避免了重复建模.

关键词： IFC CityGML FME 建筑信息模型三维地理信息系统空间数据互操作

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