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Evaluation of the combined activity of benzimidazole arylhydrazones as new anti-Parkinsonian agents:monoamine oxidase-B inhibition,neuroprotection and oxidative stress modulation

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Neural Regeneration Research 2021年第11期16卷 2299-2309页

作者： Neda Anastassova Denitsa Aluani Anton Kostadinov Miroslav Rangelov Nadezhda Todorova nadya hristova-avakumova Maria Argirova Nikolay Lumov Magdalena Kondeva-Burdina Virginia Tzankova Denitsa Yancheva Institute of Organic Chemistry with Centre of Phytochemistry Bulgarian Academy of SciencesSofiaBulgaria Department of Pharmacology Pharmacotherapy and ToxicologyFaculty of PharmacyMedical University of SofiaSofiaBulgaria Institute of Biodiversity and Ecosystem Research Bulgarian Academy of SciencesSofiaBulgaria Department of Medical Physics and Biophysics Faculty of MedicineMedical University of SofiaSofiaBulgaria

Neuroprotective drugs and selective monoamine oxidase inhibitors can slow down the progression and improve symptoms of Parkinson’s disease(PD).Since there is an implication of oxidative stress in the pathophysiological mechanisms of the disease,the compounds possessing an ability to reduce the oxidative stress are prime candidates for *** our current study is focused on the development of new multi-target PD drugs capable of inhibiting the activity of monoamine oxidase-B while exerting neuroprotective and antioxidant properties.A small series of benzimidazole derivatives containing hydroxy and methoxy arylhydrazone fragments has been synthesized and the neurotoxicity of the compounds has been evaluated in vitro on neuroblastoma SH-SY5Y cells and on isolated rat brain synaptosomes by measuring the cell viability and the levels of reduced glutathione and a good safety profile has been *** 2-hydroxy-4-methoxy substituted arylhydrazone 7 was the least toxic on neuronal SH-SY5Y cells and showed the lowest neurotoxicity in rat brain *** neuroprotective properties of the test compounds were further assessed using two models:H2O2-induced oxidative stress on SH-SY5Y cells and 6-hydroxydopamine-induced neurotoxicity in rat brain *** 7 showed more pronounced neuroprotective activity on SH-SY5Y cells,compared to the referent melatonin and *** also preserved the synaptosomal viability and the reduced glutathione levels;the effects were stronger than those of rasagiline and comparable to *** the tested compounds were capable to inhibit human monoamine oxidase-B enzyme to a significant extent,however,compound 7 exerted the most prominent inhibitory activity,similar to selegiline and *** carried out molecular docking studies revealed that the activity is related to the appropriate molecular structure enabling the ligand to enter deeper in the narrow and highly lipophylic active site pocket of th

关键词： antioxidants benzimidazoles density functional theory hydr

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Drain fluid biomarkers for prediction and diagnosis of clinically relevant postoperative pancreatic fistula:A narrative review

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World Journal of Gastrointestinal Surgery 2022年第10期14卷 1089-1106页

作者： nadya Rykina-Tameeva Jaswinder S Samra Sumit Sahni Anubhav Mittal Northern Clinical School University of SydneySt Leonards 2065Australia

Clinically relevant postoperative pancreatic fistula(CR-POPF)has continued to compromise patient recovery post-pancreatectomy despite decades of research seeking to improve risk prediction and *** current diagnostic criteria for CR-POPF requires elevated drain fluid amylase to present alongside POPFrelated complications including infection,haemorrhage and organ *** worrying sequelae necessitate earlier and easily obtainable biomarkers capable of reflecting evolving *** fluid has recently emerged as a promising source of biomarkers as it is derived from the pancreas and hence,capable of reflecting its postoperative *** present review aims to summarise the current knowledge of CR-POPF drain fluid biomarkers and identify gaps in the field to invigorate future research in this critical area of clinical *** findings may provide robust diagnostic alternatives for CR-POPF and hence,to clarify their clinical utility require further reports detailing their diagnostic and/or predictive accuracy.

关键词： Biomarkers Clinically relevant postoperative pancreatic fistula Diagnosis Drain fluid Prediction

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Blood Microbiota and Cancer: Cell Wall-Deficient L-Forms of Bacteria and Fungi as Cancer-Promoting Environment

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Journal of Biosciences and Medicines 2022年第9期10卷 148-159页

作者： nadya Markova Department of Infectious Microbiology Institute of Microbiology Bulgarian Academy of Sciences Sofia Bulgaria

In recent years, valuable experience and insights have been gained into L-forms (cell-wall-deficient variants) of bacteria and fungi and their disease-trigger potential in cases with chronic infections, autism spectrum disorders, autoimmune and neurodegenerative diseases. Based on the concept of “internal” blood microbiota, consisting of L-forms and its relevance to health and disease, the current study aims to outline the profile of dysbiotic disorders in three cancer patients (with endometrial cancer, breast cancer and acute myeloid leukemia), all in a phase before chemotherapy. Venous blood samples from the patients and from one control healthy person, were microbiologically studied. The used novel methodology of blood microbiota assessment was based on the following phases: isolation of L-forms, development and propagation, cultivation and conversion of L-forms into classical bacteria and fungi, as well as their identification with MALDI-TOF method. From the patients were isolated L-forms of opportunistic bacteria (Enterococcus faecalis, Esherichia coli, Enterobacter cloacae and Pseudomonas oryzihabitans) and fungi such as Rhodotorula mucilaginosa, Aspergillus fumigatus and Mucorales. In conclusion, the common feature found for the three cancer patients was the isolation from the blood of highly associated communities consisting of morphologically indistinguishable L-bodies, which through reversion in broth, were identified as distinct bacterial and fungal species. Unlike classic bacteria or fungi causing sepsis and bacteremia/fungemia, the presence of L-forms in blood is hidden, it does not demonstrate clinical signs nor it can be detected by conventional methods. It should be noted, however, that the dysbiotic blood microbiota shows unique and individual characteristics for the concrete cancer patient, correlates to the common state of the organism and tumor localization in the body, as well as it outlines the cancer promoting role of L-forms in processes of m

关键词： L-Forms Blood Microbiota Cancer Patients

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A feasibility study of seabed cover classification standard in generating related geospatial data

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Geo-Spatial Information Science 2019年第4期22卷 304-313,I0007页

作者： Dewayany Sutrisno Rizka Windiastuti nadya Octaviani Aninda W.Rudiastuti Badan Informasi Geospasial-Division of Research Center for researchpromotion and cooperationWest JavaIndonesia

This article assesses the feasibility of generating the geospatial data from a national classification *** this case,the National Standardization Agency(Badan Standardisasi Nasional)of Indonesia created and published a national seabed cover classification standard called SNI 7987–2014 but has not developed corresponding geospatial *** data on seabed cover can be generated by integrating related thematic data,such as those on seafloor surficial sediments,coastal ecosystems,and coastal *** consideration for these issues,this research evaluated the feasibility of using SNI 7987–2014 as a means of generating seabed cover geospatial data at scales of 1:250,000 and 1:50,*** this end,the documentation accompanying the standard was evaluated via descriptive quantitative analysis through weighted scoring,and logical testing,after which overlay,feature selection based on the scored method and remote sensing analysis were carried out to develop the geospatial data *** showed that the feasibility levels of using the prototypes for generating data at scales of 1:250,000 and 1:50,000 were 87.5%and 86.5%,respectively,indicating that SNI 7987–2014 can be fully used as the basis for generating geospatial data on seabed cover.

关键词： Standard seabed cover classification geospatial data integration feasibility

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Target morphology and cell memory:a model of regenerative pattern formation

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Neural Regeneration Research 2015年第12期10卷 1901-1905页

作者： Nikolai Bessonov Michael Levin nadya Morozova Natalia Reinberg Alen Tosenberger Vitaly Volpert Institute of Problems of Mechanical Engineering Russian Academy of Sciences Department of Biology Tufts Center for Regenerative & Developmental BiologyTufts University Laboratoire Epigénétique et Cancer Institut des Hautes Etudes Scientiques Unité de Chronobiologie Théorique Faculté des SciencesUniversité Libre de BruxellesCampus Plaine Institut Camille Jordan UMR 5208 CNRSUniversity Lyon 1

Despite the growing body of work on molecular components required for regenerative repair,we still lack a deep understanding of the ability of some animal species to regenerate their appropriate complex anatomical structure following damage.A key question is how regenerating systems know when to stop growth and remodeling-what mechanisms implement recognition of correct morphology that signals a stop condition？In this work,we review two conceptual models of pattern regeneration that implement a kind of pattern *** the first one,all cells communicate with each other and keep the value of the total signal received from the other *** a part of the pattern is amputated,the signal distribution *** difference fromthe original signal distribution stimulates cell proliferation and leads to pattern regeneration,in effect implementing an error minimization process that uses signaling memory to achieve pattern *** the second model,we consider a more complex pattern organization with different cell *** tissue contains a central（coordinator）cell that controls the tissue and communicates with the other central *** of them keeps memory about the signals received from other central *** values of these signals depend on the mutual cell location,and the memory allows regeneration of the structure when it is *** purpose of these models is to suggest possible mechanisms of pattern regeneration operating on the basis of cell memory which are compatible with diverse molecular implementation mechanisms within specific organisms.

关键词： target morphology pattern regeneration cell memory morphogenesis cell signaling mathematical modeling agent-based model

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Novel Approach to Microbiological Study of Chronic Inflammations at Upper Respiratory Tract: Research of Blood L-Form Microbiota

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Open Journal of Medical Microbiology 2021年第3期11卷 144-156页

作者： nadya Markova Institute of Microbiology Bulgarian Academy of Sciences Sofia Bulgaria

Background: The recognition of human blood microbiota, consisting of cell wall-deficient microbes (L-forms), is a major challenge today in the field of microbiology. There are accumulating data confirming the concept of “internal” blood L-form microbiota and its significance for health and diseases. Finding out whether the blood microbiota can be of diagnostic and prognostic importance for detection and evaluation of chronic infections anywhere in the body is a major objective. In the context of chronically infected upper respiratory tract (URT), the aim of the current study was to understand whether a local infection can be a source for entry of bacteria and fungi in the blood. Methods: Blood samples from six persons with chronic inflammations in URT diagnosed with hypertrophied adenoids, chronic sinusitis, nasal polyps, chronic naso-pharyngitis and one control healthy person were studied. Blood microbiota assessment methodology that be used, included three phases: 1) isolation of L-form cultures from blood-development and propagation;2) cultivation directed to conversion of L-forms into bacterial and fungal cultures;3

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Around the World in 20 Days

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英语学习 1999年第9期 24-26页

作者： nadya Labi 天涯

大家可能都看过法国作家儒勒·凡尔纳的小说或改编的影视作品《八十天环游地球》,今天,又是英国人完成了乘热气球二十天环游地球的壮举。

关键词：《八十天环游地球》 In Around the World in 20 Days World

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Study on the Development of Lactic Acid Bacteria in Bread Dough Enriched with Zinc and Selenium

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Journal of Food Science and Engineering 2017年第10期7卷 497-504页

作者： Denka Zlateva Dana Stefanova nadya Ninova-Nicolova Department of Commmodity Science Faculty of Economics University of Economics Varna 9000 Bulgaria LB Bulgaricum PLC Research & Development Center Sofia 1225 Bulgaria

The incorporation of lyophilized lactic acid bacteria in dough formulation is a current trend in bread making in order toachieve quality improvement and extension of shelf life of bread. Another major aspect for today＇s bread making industry is anincrease of the biological value of bread, by addition of mineral substances that are deficient in bread （such as zinc and selenium）.This is an effective approach to combat the existing mineral deficiency in population nutrition. The aim of the present study is toinvestigate the development of lactic acid bacteria in a medium enriched with zinc and selenium. It was found that the addition ofZnSO4-7H20 in an amount of 0.174 g/kg flour and Na2SeO3.5H20 in an amount of 880.28 μg/kg flour （alone and in combination） didnot inhibit the development of lactic acid bacteria used as starter cultures in bread dough formulation. It was found that the growth ofthe lactococcal component of the applied starters is dominant. The results reveal the possibility of obtaining bread with increasedbiological value and improved quality.

关键词： Bread dough, lactic acid bacteria, starter cultures, zinc, selenium.

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烘焙处理对红松松籽植物化学成分和品质影响及变化规律研究

烘焙处理对红松松籽植物化学成分和品质影响及变化规律研究

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作者： nadya Mara Adelina 东北林业大学

学位级别：硕士

红松同砧嫁接（Grafted Pinus koraiensis on the same scions,PK）和樟子松异砧嫁接红松（Grafted tris on Pinus koraiensis rootstocks,PKS）是我国东北地区主要红松树种。烘焙处理是松籽产品最常采用的加工方式,有关烘焙处理对两种... 详细信息

红松同砧嫁接（Grafted Pinus koraiensis on the same scions,PK）和樟子松异砧嫁接红松（Grafted tris on Pinus koraiensis rootstocks,PKS）是我国东北地区主要红松树种。烘焙处理是松籽产品最常采用的加工方式,有关烘焙处理对两种红松松籽成分、品质特性和生物活性方面的影响尚未见报道。本研究以PK和PKS松籽为原料,进行不同烘焙处理（温度130、150、180℃,时间10、20、30 min）,对两种松籽壳、皮、仁的成分、品质和抗氧化性进行研究,比较营养成分、生物活性成分、感官品质及抗氧化活性受烘焙条件影响的变化模式,分析烘焙处理影响成分含量和产品品质变化的原因。为提高松籽加工利用水平,进一步开发利用嫁接红松松籽提供依据。主要研究结果如下:烘焙处理对PK和PKS加工副产物壳、皮中活性成分和抗氧化性影响。烘焙后松籽壳、皮中总多酚、总黄酮和原花青素含量及抗氧化活性（FRAP,ABTS和DPPH）均有所提高,PK松籽中活性成分和抗氧化指标高于PKS,皮中活性成分含量和抗氧化活性高于外壳（p＜0.05）。采用HPLC对关键酚类化合物（抗氧化活性较好）进行定量分析,结果表明,PK种籽衣在150℃30min条件下的抗氧化活性最高,香草酸和儿茶素是决定松籽壳和种籽衣抗氧化活性强弱的最主要化合物（在PK和PKS中分别为6.052 mg/g和3.418 mg/g）。相关性分析结果显示,活性物质含量与抗氧化活性指标之间具有高度相关性,而总酚类化合物与FRAP之间的相关性最高（r=0.941）。经中低温度、短时间烘焙处理（150℃ 20 min或者30min）的松籽壳、皮具有作为抗氧化性原料进一步利用的潜能。烘焙处理对PK和PKS松仁中化学成分和抗氧化性的影响。未经烘焙处理的PK和PKS化学成分中除灰分外,其他成分均存在显著差异。PK和PKS均富含脂肪和蛋白质,含量分别为61.89%、22.39%和59.65%、25.23%。烘焙使松仁中蛋白质和碳水化合物含量显著减少,这与发生美拉德反应有关。PK和PKS中的脂肪酸组成相似,其中亚油酸的比例最大,占40%以上。多不饱和脂肪酸和饱和脂肪酸含量经烘焙处理略有降低。丙二醛是脂质氧化的产物,在较高的烘焙温度下含量升高并在180℃ 30min烘焙条件下达到最高（PK和PKS的6倍）。在烘焙过程中,生物活性成分含量和抗氧化性逐渐提高。采用HPLC测定酚酸和黄酮含量变化结果表明,没食子酸是PK和PKS松仁中决定抗氧化活性高低的主要化合物,并在180℃ 20min条件下达到最高（在PK和PKS中分别为113.817和108.148 μg/g）。多元分析表明,适度烘焙（150℃ 20min）既不会造成松仁营养成分过多损失,又能促进其抗氧化能力的提高。烘焙处理对PK和PKS松仁品质的影响。采用仪器测定和感官分析方法评价烘焙处理对两种松仁品质的影响。烘焙处理显著影响了松仁的颜色（L*,a*和b*值）和质构特性,可以检测到棕褐色出现和质地逐渐变脆。松仁的香气特征采用顶空固相微萃取（HS-SPME）结合气相色谱-质谱法（GC-MS）和电子鼻（E-nose）检测其挥发性成分,在未处理和烘焙处理下PK和PKS仁中共鉴定出286种挥发性化合物,烘焙温度升高和烘烤时间延长显著降低了萜烯和芳烃的含量,在烘烤后期醛,呋喃,糠醛,吡嗪和吡咯成分逐渐形成,此时PKS松仁的相应成分含量高于PK。电子鼻检测到的香气特征表明,相比时间,温度带来的影响更大。基于感官分子网络,探讨了感官分析与仪器分析之间的相关性。研究表明,中度烘焙条件（150℃ 20min）具有更适宜的品质特征。烘烤处理对美拉德反应程度的影响。烘焙过程中发生美拉德反应,对其前体即蛋白质和糖,以及反应的变化程度进行了评估。单糖组成分析表明,葡萄糖和果糖是参与美拉德反应的主要还原糖。通过蛋白质组成和分子量分析,烘焙过程中从PK和PKS仁中提取的总蛋白逐渐减少,白蛋白和球蛋白作为松仁中的主要蛋白质组分在烘焙过程中含量逐渐降低,而松仁中谷蛋白含量较低,随烘焙处理而增加。SDS-PAGE电泳结果表明,在烘焙后期分子量为23、33和53 kDa的蛋白组分缺失,这可能是蛋白质受热变性结构发生改变以及发生美拉德反应的结果。FTIR光谱分析表明PK和PKS松仁蛋白的二级结构中β-折叠居多。荧光光谱显示样品荧光强度随着温度和烘焙时间的增加而下降,同时检测到美拉德反应的中间产物（5-羟甲基糠醛）和终产物（游离和结合的美拉德反应产物）的形成。以上结果可以用于评价美拉德反应程度及其对体系植物化学成分变化的影响。

关键词：松籽烘焙处理植物化学成分品质特性美拉德反应

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Advancing male age differentially alters levels and localization patterns of PLCzeta in sperm and testes from different mouse strains

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Asian Journal of Andrology 2021年第2期23卷 178-187页

作者： Junaid Kashir Bhavesh V Mistry Maha Adel Gumssani Muhammad Rajab Reema Abu-Dawas Falah AlMohanna Michail Nomikos Celine Jones Raed Abu-Dawud nadya Al-Yacoub Kevin Coward F Anthony Lai Abdullah M Assiri College of Medicine Alfaisal UniversityRiyadh 11533Saudi Arabia Department of Comparative Medicine King Faisal Specialist Hospital and Research CentreRiyadh 11211Saudi Arabia College of Medicine QU HealthQatar UniversityDoha PO Box 2713Qatar Nuffield Department of Women’s and Reproductive Health University of OxfordLevel 3Women’s CentreJohn Radcliffe HospitalOxford OX39DUUnited Kingdom Biomedical Research Centre Qatar UniversityDoha PO Box 2713Qatar

Sperm-specific phospholipase C zeta(PLCζ)initiates intracellular calcium(Ca2+)transients which drive a series of concurrent events collectively termed oocyte *** investigations have linked abrogation and absence/reduction of PLCζwith forms of male infertility in humans where oocyte activation ***,very few studies have examined potential relationships between PLCζand advancing male age,both of which are increasingly considered to be major effectors of male *** efforts in humans may be hindered by inherent PLCζvariability within the human population,alongside a lack of sufficient controllable ***,utilizing immunoblotting,immunofluorescence,and quantitative reverse transcription PCR(qRT-PCR)we examined for the first time PLCζprotein levels and localization patterns in sperm,and PLCζmRNA levels within testes,from mice at 8 weeks,12 weeks,24 weeks,and 36 weeks of age,from two separate strains of mice,C57BL/6(B6;inbred)and CD1(outbred).Collectively,advancing male age generally diminished levels and variability of PLCζprotein and mRNA in sperm and testes,respectively,when both strains were ***,advancing male age altered the predominant pattern of PLCζlocalization in mouse sperm,with younger mice exhibiting predominantly post-acrosomal,and older mice exhibiting both post-acrosomal and acrosomal populations of PLCζ.However,the specific pattern of such decline in levels of protein and mRNA was ***,our results demonstrate a negative relationship between advancing male age and PLCζlevels and localization patterns,indicating that aging male mice from different strains may serve as useful models to investigate PLCζin cases of male infertility and subfertility in humans.

关键词： ageing fertilization male infertility oocyte activation phospholipase C zeta sperm

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