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8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

Acta Pharmaceutica Sinica B 2023年第5期13卷 2152-2175页

作者： Damijan Knez Daniel Diez-Iriepa Mourad Chioua Andrea Gottinger Milica Denic Fabien Chantegreil Florian Nachon Xavier Brazzolotto Anna Skrzypczak-Wiercioch Ane Meden Anja Pilar janko kos Simon akelj Jure Stojan Kinga Saat Julia Serrano Ana Patricia Fernández Aitana Sánchez-García Ricardo Martínez-Murillo Claudia Binda Francisco López-Muoz Stanislav Gobec JoséMarco-Contelles University of Ljubljana Faculty of PharmacyLjubljana 1000Slovenia Laboratory of Medicinal Chemistry(Institute of Organic Chemistry CSIC)Madrid 28006Spain Departamento de Química Orgánicay Química Inorgánica Alcaláde HenaresMadrid 28871Spain Department of Biology and Biotechnology University of PaviaPavia 27100Italy Département de Toxicologie et Risques Chimiques Institut de Recherche Biomédicale des ArméesParis 91220France Department of Animal Anatomy and Preclinical Sciences University Centre of Veterinary Medicine JU-UAUniversity of Agriculture in KrakowKrakow 30-059Poland Institute of Biochemistry Faculty of MedicineUniversity of LjubljanaLjubljana 1000Slovenia Department of Pharmacodynamics Chair of PharmacodynamicsFaculty of PharmacyJagiellonian University Medical CollegeKrakow 30-688Poland Department of Translational Neurobiology Neurovascular Research GroupCajal Institute(CSIC)Madrid 28002Spain Biotechnology and Vegetal Biology Department Escuela Técnica Superior de Ingeniería AgronómicaAlimentaria y de BiosistemasUniversidad Politécnica de MadridMadrid 28040Spain Faculty of Health Camilo JoséCela University of Madrid(UCJC)Neuropsychopharmacology Unit“Hospital 12 de Octubre”Research InstituteMadrid 28692Spain

We describe the development of quinolylnitrones(QNs)as multifunctional ligands inhibiting cholinesterases(ChEs:acetylcholinesterase and butyrylcholinesterase—h BChE)and monoamine oxidases(hMAO-A/B)for the therapy of neurodegenerative diseases.We identified QN 19,a simple,low molecular weight nitrone,that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde.Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition,yet unexpectedly showed potent inhibition of h BChE(IC50=1.06±0.31 nmol/L)and h MAO-B(IC_(50)=4.46±0.18μmol/L).The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding,which was further studied by enzyme kinetics.Compound 19 acted as a free radical scavenger and biometal chelator,crossed the blood—brain barrier,was not cytotoxic,and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease.In addition,in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination.Importantly,chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice,underscoring the disease-modifying effect of QN 19.

关键词： Quinolylnitrone Butyrylcholinesterase Monoamine oxidase B Alzheimer's disease Multifunctional ligands 6-Hydroxydopamine model Passive avoidance task Novel object recognition

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抗组织蛋白酶B单克隆抗体可变区基因的克隆和序列分析

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广西医科大学学报 2002年第5期19卷 628-630页

作者：樊晓晖 Kopitar-Jerala Natasa Ales Premzl janko kos 广西医科大学基础学院微生物学与免疫学教研室南宁530021 Department of Biochemistry and Molecular Biology Jotzef Stear Institate

目的 :为制备基因工程抗体 ,需要对组织蛋白酶 B单抗可变区基因的核苷酸序列进行分析。方法 :利用 RT- PCR技术扩增 2 A2抗组织蛋白酶 B单克隆抗体可变区基因 ,测序并和已报道的小鼠免疫球蛋白的基因库进行比较。结果 :2 A2抗组织蛋白... 详细信息

目的 :为制备基因工程抗体 ,需要对组织蛋白酶 B单抗可变区基因的核苷酸序列进行分析。方法 :利用 RT- PCR技术扩增 2 A2抗组织蛋白酶 B单克隆抗体可变区基因 ,测序并和已报道的小鼠免疫球蛋白的基因库进行比较。结果 :2 A2抗组织蛋白酶 B单克隆抗体可变区基因的克隆和序列分析及比较结果没有发现有害的基因突变。结论 :2

关键词：组织蛋白酶B 单克隆抗体可变区基因序列分析克隆

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Sol-gel derived B_(2)O_(3)-CaO borate bioactive glasses with hemostatic,antibacterial and pro-angiogenic activities

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Regenerative Biomaterials 2024年第1期3卷 108-118页

作者： Kai Zheng Faina Bider Mahshid Monavari Zhiyan Xu Christina janko Christoph Alexiou Ana M.Beltran Aldo R.Boccaccini Jiangsu Province Engineering Research Center of Stomatological Translational Medicine College of StomatologyNanjing Medical UniversityNanjing 210029China Jiangsu Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjing 210029China Institute of Biomaterials University of Erlangen-Nuremberg91058 ErlangenGermany Department of Oto-Rhino-Laryngology Head and Neck SurgerySection of Experimental Oncology and Nanomedicine(SEON)Else Kroener-Fresenius-Stiftung ProfessorshipUniversitaetsklinikum Erlangen91058 ErlangenGermany Departamento de Ingenier�ıa y Ciencia de los Materiales y del Transporte Escuela Politecnica

Sol-gel borate bioactive glasses(BGs)are promising ion-releasing biomaterials for wound healing applications.Here,we report the synthesis of a series of binary B_(2)O_(3)-CaO borate BGs(CaO ranging from 50 to 90mol%)using a sol-gel-based method.The influence of CaO content in B_(2)O_(3)-CaO borate BG on morphology,structure and ion release behavior was investigated in detail.Reduced dissolution(ion release)and crystallization could be observed in borate BGs when CaO content increased,while the morphology was not significantly altered by increasing CaO content.Our results evidenced that the ion release behavior of borate BGs could be tailored by tuning the B_(2)O_(3)/CaO molar ratio.We also evaluated the in vitro cytotoxicity,hemostatic,antibacterial and angiogenic activities of borate BGs.Cytocompatibility was validated for all borate BGs.However,borate BGs exhibited composition-dependent hemostatic,antibacterial and angiogenic activities.Generally,higher contents of Ca in borate BGs facilitated hemostatic activity,while higher contents of B_(2)O_(3) were beneficial for pro-angiogenic activity.The synthesized sol-gel-derived borate BGs are promising materials for developing advanced wound healing dressings,given their fast ion release behavior and favorable hemostatic,antibacterial and angiogenic activities.

关键词： borate glasses sol-gel processing glass composition wound healing

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人-鼠嵌合抗人组织蛋白酶B抗体体外抑制组织蛋白酶B活性的试验

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临床检验杂志 2004年第5期22卷 352-353页

作者：樊晓晖 Kopitar-Jerala Natasa Premzl Ales kos janko 广西医科大学微免教研室南宁530021 斯洛文尼亚Jozef Stefan研究所

目的　体外试验人鼠嵌合抗人组织蛋白酶B(抗CatB)抗体对CatB的抑制作用。方法　培养 1株分泌人鼠嵌合抗人CatB抗体细胞 ,收集细胞培养上清 ,分离纯化人鼠嵌合抗人CatB抗体 ,用于体外抑制CatB活性试验。结果　该抗体在体外能抑制Cat... 详细信息

目的　体外试验人鼠嵌合抗人组织蛋白酶B(抗CatB)抗体对CatB的抑制作用。方法　培养 1株分泌人鼠嵌合抗人CatB抗体细胞 ,收集细胞培养上清 ,分离纯化人鼠嵌合抗人CatB抗体 ,用于体外抑制CatB活性试验。结果　该抗体在体外能抑制CatB活性。结论　抗CatB抗体能特异结合CatB并抑制其酶活性 ,将可能用于CatB过度表达的癌症治疗。

关键词：抗体体外抑制组织蛋白酶B 抗C 嵌合活性体外试验体细胞分离纯化分泌

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抗人组织蛋白酶B嵌合抗体的研制及体外抑制组织蛋白酶B活性的试验

抗人组织蛋白酶B嵌合抗体的研制及体外抑制组织蛋白酶B活性的试验

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中国科协第五届青年学术年会

作者：樊晓晖 Kopitar-Jerala Natasa Premzl Ales kos janko 广西医科大学微生物与免疫学教研室

目的:制备抗人组织蛋白酶B人-鼠嵌合抗体,体外试验:C62A2人-鼠嵌合抗人组织蛋白酶B抗体对组织蛋白酶B的抑制作用。

关键词：组织蛋白酶B 嵌合抗体抑制酶活性

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抗人组织蛋白酶B人-鼠嵌合抗体的表达及体外对癌细胞浸润的抑制效应

抗人组织蛋白酶B人-鼠嵌合抗体的表达及体外对癌细胞浸润的抑制效...

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广西微生物学会2003年学术年会

作者：樊晓晖 Kopitar-Jerala Natasa Premzl Ales kos janko 广西医科大学微免教研室斯洛文尼亚Jozef Stefan研究所

组织蛋白酶B属于半胱氨酸蛋白酶,通常位于细胞溶酶体内,细胞癌变后,它过度表达并分泌到细胞外,激活其它酶分解细胞外基质而促进肿瘤细胞扩散,因此和肿瘤细胞远处转移有关。组织蛋白酶B单克隆抗体能特异和组织蛋白酶B结合,封闭酶活性中心...

组织蛋白酶B属于半胱氨酸蛋白酶,通常位于细胞溶酶体内,细胞癌变后,它过度表达并分泌到细胞外,激活其它酶分解细胞外基质而促进肿瘤细胞扩散,因此和肿瘤细胞远处转移有关。组织蛋白酶B单克隆抗体能特异和组织蛋白酶B结合,封闭酶活性中心,对抑制肿瘤细胞扩散有一定作用。因其为鼠源性异种蛋白,限制了它在人体的应用,制备抗组织蛋白酶B嵌合抗体,将大大降低抗体用于人体而引起的排斥反应而促进它的抗癌应用。本文利用基因工程的方法,将构建的人-鼠嵌合抗体基因转染中国仓鼠卵巢细胞并得到表达,体外能抑制一株组织蛋白酶B过度分泌的癌细胞株的浸润作用,现报道如下:

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In polytocous mammals,weakling neonates,but not their stronger littermates,benefit from specialized foraging

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Current Zoology 2019年第6期65卷 675-683页

作者： janko SKOK Maja PREVOLNIK POVSE Faculty of Agriculture and Life Sciences University of Maribor2311 HoceSlovenia

Adjusting foraging strategies is a common phenomenon within groups of animals competing for the same resource.In polytocous mammals,neonates concurrently compete for limited milk and alternate between two foraging(suckling)strategies:adaptable exploratory foraging with random sampling of teats,and ordered foraging with a tendency towards exploiting a particular suckling position.Some theoretical(game theory)models have shown that weaker siblings in particular benefit from foraging specialization(suckling order).Neonate piglets establish a well-defined suckling order that develops gradually and fluctuates throughout the lactation period,implying the existence of inter-individual differences in foraging strategies.We therefore analyzed suckling behavior in pigs to determine whether one foraging strategy was more beneficial to neonates in terms of their body weight and foraging environment.We found that intermediate and heavy littermates tended to adjust their suckling strategy according to the foraging environment;however,the selected foraging strategy did not affect their overall growth performance.Lighter individuals that consumed significantly less milk did not greatly alternate their foraging strategy according to the foraging environment but their growth rate was significantly higher whenever they performed less-exploratory foraging behavior.Although suckling order appeared to be a relatively stable behavioral phenotype,it was beneficial exclusively for weaklings.These results confirm theoretical predictions and indicate that specializing in a suckling position is a beneficial strategy for weaker,light neonates.These findings suggest that physically weaker neonates might have driven the evolution of neonatal foraging specialization.

关键词： neonatal foraging strategy pig polytocous mammals suckling

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David Lloyd George and the Balfour Declaration： Assessing the Role of Individuals in Historic Policy Making

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Fudan Journal of the Humanities and Social Sciences 2018年第3期11卷 389-410页

作者： janko Scepanovic SIRPA Fudan University Shanghai People's Republic of China

The 1917 Balfour Declaration remains one of the most controversial policy statements of the wartime British Government. Historically it has been praised as the highest diplomatic act of the First World War that helped restore a home for the Jewish people in Palestine. Its critics point out that it planted seeds of future discord between the Palestinians and Israelis. There are also historians who suggest that what Britain really wanted was to secure vital geostrategic interests in the Eastern Mediterranean. The reality is that the process and decision making leading up to the Balfour Declaration was very complicated. This paper will focus on the role and influence of Britain’s Prime Minister David Lloyd George whose leadership and personal drive made a difference in securing the Anglo-Zionist Alliance. By looking at the theories on the role of individuals on policy making and testing them on the case of Lloyd George, it will be demonstrated that, in spite of certain arguments to the contrary, leaders with right strength of personality, determination, strong beliefs, interest in foreign policy, and the right placement in the state bureaucracy can make a huge impact. These elements, combined with shifting attitude of British policymakers toward the imperial burdens during the early twentieth century, and rising influence of national movements enabled Britain to not only secure a vital strategic outpost in Palestine, but also restore therein a homeland for the Jews.

关键词：历史学家估计巴勒斯坦官僚主义英国人外交政策犹太人决策者

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Proper ties of core-EP order in rings with involution

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Frontiers of Mathematics in China 2019年第4期14卷 715-736页

作者： Gregor DOLINAR Bojan KUZMA janko MAROVT Burcu UNGOR University of Ljubljana Faculty of Elec trical Engineering Trzaska 25 SI-1000 Ljubljana Slovenia University of Primorska Glagoljaska 8 SI-6000 Koper Slovenia University of Maribor Faculty of Economics and Business Razlagova 14 SI-2000 Maribor Slovenia IMFM Jadranska 19 SI-1000 Ljubljana Slovenia Faculty of Sciences Ankara University 06100 Tandogan Ankara Turkey

We study properties of a relation in *-rings, called the core-EP (pre)order which was introduced by H. Wang on the set of all n × n complex matrices [Linear Algebra Appl., 2016, 508: 289-300] and has been recently generalized by Y. Gao, J. Chen, and Y. Ke to *-rings [Filomat, 2018, 32: 3073- 3085]. We present new characterizations of the core-EP order in *-rings with identity and introduce the notions of the dual core-EP decomposition and the dual core-EP order in *-rings.

关键词： Drazin inverse core-EP decomposition pre-order ring

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地图投影知识库系统的设计考虑

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测绘译丛 1991年第2期 30-36页

作者： janko.,P 孙群

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