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Translational approaches: From fatty liver to non-alcoholic steatohepatitis

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World Journal of Gastroenterology 2014年第27期20卷 9038-9049页

作者： natalia Rosso Norberto C Chavez-Tapia Claudio Tiribelli Stefano Bellentani Fondazione Italiana Fegato 34149 Trieste Italy Obesity and Digestive Diseases Unit Médica Sur Clinic and FoundationMexico 14050 México Department of Medical Sciences University of Trieste Department of Gastroenterology and endoscopy Azienda USL di ModenaOspedale "Ramazzini" 41012 Carpi (Modena) Italy

Over the past few decades, non-alcoholic fatty liver disease(NAFLD) has become one, if not the most common,cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis(NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.

关键词： Fatty Liver Obesity Metabolic syndrome Inflammatio

Cellulose Nanoparticles extracted from Sugarcane Bagasse and Their Use in Biodegradable Recipients for Improving Physical Properties and Water Barrier of the Latter

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Materials Sciences and Applications 2020年第1期11卷 81-133页

作者： Antonio Jedson Caldeira Brant natalia Naime Ademar Benevolo Lugao Patricia Ponce Instituto de Pesquisas energeticas e Nucleares/IPeN Sao PauloBrazil

The present work firstly aimed to obtain cellulose from sugarcane bagasse by using alkaline methods in pulping/delignifying and, at bleaching stages, using sodium chlorite, glacial acetic acid, and hydrogen peroxide, associated to NaOH/KOH. The process was carried out at temperatures varying from 55°C to 110°C, under magnetic stirring in various steps lasting from 2 h to 12 h. The yields of the two cellulose extracted, SCB24-Na-I and SCB24-Na-II, were 37% and 41%, respectively, from samples of ca. 15 g of the bagasse. Secondly, it is to extract nanoparticles from the obtained celluloses via acid hydrolysis (with 77% H2SO4) to lately be tested as reinforcement in biodegradable packagings. Both celluloses and their respective nanoparticles were characterized by several techniques, among them ATR-FTIR, DSC-TGA, XRD, SeM, and TeM. Despite that the yields of cellulose nanoparticles have been low, the preliminary studies of their use in biodegradable films coated on biodegradable pots were promising.

关键词： Sugarcane Bagasse Cellulose from Alkaline extraction Acid Hydrolysis of Cellulose Celullose Nanoparticles Film-Forming Suspensions Biodegradable Packaging

神经元蜡样质脂褐质沉积病(NCL)的基因型与表型相关性研究(英文)

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北京大学学报（医学版） 2006年第1期38卷 41-48页

作者： Weina JU Anetta WRONSKA Dorota N. MOROZIeWICZ Rocksheng ZHONG natalia WISNIeWSKI Anna JURKIeWICZ Michael FIORY Krystyna e. WISNIeWSKI Lance JOHNSTON W. Ted BROWN Nanbert ZHONG SCL-Molecular Neurogenetic Diagnostic Laboratory Department of Human Genetics Department of Pathological Neurobiology Department of Infant Development New York State Institute for Basic Research in Developmental Disabilities Staten Island NY Department of Neurology SUNY Downstate Health Center Brooklyn NY Summer Student Harvard University Boston MA Batten Disease Support and Research Association Columbus OH 北京大学医学遗传中心、北京大学基础医学院医学遗传学系北京100083

Objective:Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL). Methods:Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (eM) profiles. Results: The most common initial symptom leading to a clinical evaluation was developmental delay (30%) in NCL1, seizures (42.4%) in NCL2, and vision problems (53.5%) in NCL3. eighty-two percent of NCL1 cases had granular osmiophilic deposits (GRODs) or mixed-GROD-containing eM profiles; 94% of NCL2 cases had curvilinear (CV) or mixed-CV-containing profiles; and 91% of NCL3 had fingerprint (FP) or mixed-FP-containing profiles. The mixed-type eM profile was found in approximately one-third of the NCL cases. DNA mutations within a specific CLN gene were further correlated with NCL phenotypes. Seizures were noticed to associate with common mutations 523G>A and 636C>T of CLN2 in NCL2 but not with common mutations 223G>A and 451C>T of CLN1 in NCL1. Vision loss was the initial symptom in all types of mutations in NCL3. Surprisingly, our data showed that the age of onset was atypical in 51.3% of NCL1 (infantile form) cases, 19.7% of NCL2 (late-infantile form) cases, and 42.8% of NCL3 (juvenile form) ***:Our data provide an overall picture regarding the clinical recognition of classical childhood NCLs. This may assist in the prediction and genetic identification of NCL1-3 via their characteristic clinical features.

关键词：神经元蜡样质脂褐质沉积病基因型表型基因 CLN 突变

Batumin—A Selective Inhibitor of Staphylococci—Reduces Biofilm Formation in Methicillin Resistant <i>Staphylococcus aureus</i>

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Open Journal of Medical Microbiology 2015年第4期5卷 193-201页

作者： Larisa Churkina Mario Vaneechoutte elena Kiprianova natalia Perunova Lilja Avdeeva Oleg Bukharin Department of Antibiotics Institute of Microbiology and Virology National Academy of Sciences of Ukraine Kyiv Ukraine Laboratory for Bacteriology Research Faculty of Medicine & Health Sciences Ghent University Ghent Belgium Institute of Cellular and Intracellular Symbiosis Ural Branch of Russian Academy of Sciences Orenburg Russian Federation

The antibiotic batumin, produced by Pseudomonas batumici, has been shown to be highly active against 123 type and reference strains and clinical isolates of 30 Staphylococcus species (including MRSA and small colony variants—(SSCVs) of S. aureus, S. epidermidis and S. haemolyticus). Batumin activity against these bacteria did not depend on the species, origin or resistance to other antibiotics and its MIC was 0.0625 - 0.5 mg/ml. Batumin influence on biofilm formation was studied in clinical isolates of S. aureus, S. epidermidis and S. intermedius. Addition of batumin at a concentration of half of the MIC in the broth, i.e. 0.125 μg/ml, decreased the biofilm of 16 out of 20 S. aureus strains to varying degrees. Batumin was more effective against Staphylococcus strains with strong biofilm formation. Using atomic-force microscopy, it could be shown that batumin reduced the number of S. aureus ATCC 25923 adherent cells more than fourfold. The adherent cells of staphylococci were visualized as monolayers of separate islets. A detailed study of the surface of bacterial cells treated with batumin allowed to establish significant reduction of their roughness values. Observed values were typical for planktonic S. aureus cells. The obtained data explain one of the mechanisms of the antimicrobial activity of batumin, which is based оn preventing the formation of S. aureus biofilm. As such, batumin could be considered as an agent offering opportunities for the treatment of staphylococcal biofilm-associated infections.

关键词： Batumin Staphylococci SSCVs Biofilm

Manifestation of Key Molecular Genetic Markers in Pharmacocorrection of endogenous Iron Metabolism in MCF-7 and MCF-7/DDP Human Breast Cancer Cells

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CellBio 2013年第4期2卷 217-227页

作者： Vasyl’ Chekhun natalia Lukianova Dmytro Demash Tetiana Borikun Svyatoslav Chekhun Yulia Shvets Department of Mechanisms of Antitumor Therapy R.E. Kavetsky Institute of Experimental Pathology Oncology and Radiobiology NAS of Ukraine Kyiv Ukraine

effects of the nanocomposite and its components (magnetic fluid, cisplatin) on the level of endogenous iron exchange and the key links of genetic and epigenetic regulation of apoptotic program of sensitive and resistant MCF-7 cells were examined. We showed genetic and epigenetic mechanisms of action of nanocomposite of magnetic fluid and cisplatin. Nanocomposite caused elevation of number of cells in apoptosis in sensitive and especially resistant MCF-7 cells compared to cisplatin alone. It was proved that impact of nanocomposite on MCF-7/S and MCF-7/DDP cells caused more significant changes in expression of apoptosis regulators p53, Bcl-2 and Bax. We also suggested that changes in endogenous iron homeostasis and activation of free radical processes caused significant impact on apoptosis. Those changes included changes in methylation and expression of transferrin, its receptors, ferritin heavy and light chains (predominantly in resistant cell line), which caused activation of free radical synthesis and development of oxidative stress. We also showed that nanocomposite impact resulted into significant changes in expression of miRNA-34a and miRNA-200b, which regulated apoptosis, cell adhesion, invasion and activity of ferritin heavy chains gene. Thus, use of nanocomposite containing cisplatin and ferromagnetic as exogenous source of Fe ions caused changes of endogenous iron levels in sensitive and resistant cells allowing to increase specific activity of cytostatics and overcome factors, which promoted MDR development. Pharmacocorrection of endogenous iron metabolism allowed increasing antitumor activity of cisplatin and overcoming drug resistance.

关键词： Nanocomposite Iron Metabolism Apoptosis ROS Drug Resistance Breast Cancer Cells

Linagliptin alleviates fatty liver disease in diabetic db/db mice

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World Journal of Diabetes 2016年第19期7卷 534-546页

作者： Svetlana V Michurina Irina Ju Ishenko Vadim V Klimontov Sergey A Archipov natalia e Myakina Marina A Cherepanova eugenii L Zavjalov Galina V Koncevaya Vladimir I Konenkov Laboratory of Functional Morphology Scientific Institute of Clinical and Experimental Lymphology Laboratory of endocrinology Scientific Institute of Clinical and Experimental Lymphology SPF-vivarium Institute of Cytology and Genetics of Siberian Branch of Russian Academy of Sciences Laboratory of Clinical Immunogenetics Scientific Institute of Clinical and Experimental Lymphology

AIM To study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease(NAFLD) in db/db mice. MeTHODS Male diabetic db /db mice(***-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl peptidase 4(DPP4) inhibitor linagliptin(10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. Intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals. We estimated the changes in hepatocytes, sinusoidal cells, liver microvasculature and lymphatic roots. Hepatic staining for lymphatic vessel endothelial hyaluronan receptor-1(LYVe-1) was assessed by immunohistochemistry. ReSULTS In 18-wk-old diabetic mice, liver steatosis(predominantly microvesicular and mediovesicular steatosis) was accompanied by dilation of the roots of the lymphatic system, interlobular blood vessels and bile canaliculi. Compared to saline-treated mice, linagliptin-treated mice exhibited a reduction in the mean numeral densities of hepatocytes with lipid droplets(92.4% ± 1.7% vs 64.9% ± 5.8% per field of view, P = 0.0002) and a lower proportion of hepatocytes with a high density of lipid droplets(20.7% ± 3.6% vs 50.4% ± 3.1%, P = 0.0007). We observed heterogeneous hepatocytes and relatively preserved cell structures in the linagliptin group. Dilation of blood and lymphatic vessels, as well as ultrastructural changes in the hepatocyte endoplasmic reticulum and mitochondria, were alleviated by linagliptin treatment. In intact and placebo-treated mice, immunohistochemical staining for LYVe-1 was observed in the endothelial cells of interlobular lymphatic vessels and on the membranes of some endothelial sinusoidal cells. We observed an enlarged LYVe-1 reaction area in linagliptin-treated mice compared to intact and placebo-treated mice. The improvement in the structural parameters of the liver in linagliptin-treated mice was independe

关键词： Diabetes Obesity Non-alcoholic fatty liver disease Dipeptidyl peptidase 4 Linagliptin

Clarifying sub-genomic positions of QTLs for flowering habit and fruit quality in U.S. strawberry (Fragaria×ananassa) breeding populations using pedigree-based QTL analysis

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Horticulture Research 2017年第1期4卷 85-93页

作者： Sujeet Verma Jason D Zurn natalia Salinas Megan M Mathey Beatrice Denoyes James F Hancock Chad e Finn Nahla V Bassil Vance M Whitaker IFAS/Department of Horticulture University of FloridaGulf Coast Research and Education Center14625 CR 672Wimauma33598FLUSA USDA-ARS National Clonal Germplasm Repository 33447 Peoria RoadCorvallis97333ORUSA Department of Horticulture Oregon State University4017 Agriculture and Life Sciences BuildingCorvallis97331ORUSA Department of Horticulture UMR 1332 Biologie du Fruit et PathologieINRAUniv.BordeauxVillenave d’OrnonF-33140France Michigan State University East Lansing48824MIUSA USDA-ARS HCRU3420 NW Orchard AvenueCorvallis97330ORUSA

The cultivated strawberry(Fragaria×ananassa)is consumed worldwide for its flavor and nutritional *** analysis of commercially important traits in strawberry are important for the development of breeding methods and tools for this *** several quantitative trait loci(QTL)have been previously detected for fruit quality and flowering traits using low-density genetic maps,clarity on the sub-genomic locations of these QTLs was *** discoveries in allo-octoploid strawberry genomics led to the development of the IStraw90 single-nucleotide polymorphism(SNP)array,enabling high-density genetic maps and finer resolution QTL *** this study,breeder-specified traits were evaluated in the eastern(Michigan)and Western(Oregon)United States for a common set of breeding populations during 2 *** QTLs were validated for soluble solids content(SSC),fruit weight(FWT),pH and titratable acidity(TA)using a pedigree-based QTL analysis *** fruit quality,a QTL for SSC on linkage group(LG)6A,a QTL for FWT on LG 2BII,a QTL for pH on LG 4CII and two QTLs for TA on LGs 2A and 5B were *** addition,a large-effect QTL for flowering was detected at the distal end of LG 4A,coinciding with the FaPFRU *** haplotype analysis in the FaPFRU region indicated that the homozygous recessive genotype was highly predictive of seasonal *** probes in the FaPFRU region may help facilitate marker-assisted selection for this trait.

关键词： breeding straw Fragaria

Rebamipide and Pantoprazole Combination in NSAIDs-Gastropathy Treatment

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Journal of Pharmacy and Pharmacology 2017年第3期5卷 153-157页

作者： Maher Mbarki Helen Sklyarova Krystyna Aksentiychuk1 natalia Kharchenko eugene Sklyarov Department of Therapy No. 1 and Medical Diagnostics Lviv National Medical University Named After Danylo Halytsky Lviv79010 Ukraine Department of Gastroenterology Dietology and Endoscopy Shupyk National Medical Academy of Postgraduate Education Kyiv04112 Ukraine

Seimatoric acid and colletonoic acid:Two new compounds from the endophytic fungi,Seimatosporium *** Colletotrichum sp.

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Chinese Chemical Letters 2014年第12期25卷 1577-1579页

作者： Hidayat Hussain natalia Root Farah Jabeen Ahmed Al-Harrasi Ahmed Al-Rawahi Manzoor Ahmad Zahid Hassan Ghulam Abbas Fazal Mabood Afzal Shah Amin Badshah Amjad Khan Riaz Ahmad Ivan R.Green Siegfried Draeger Barbara Schulz Karsten Krohn Department of Chemistry University of PaderbornWarburger Strasse 100Paderborn 33098Germany UoN Chair of Oman's Medicinal Plants and Marine Natural Products University of NizwaP.O.Box 33Postal Code 616Birkat Al MauzNizwaOman Department of Chemistry University of MalakandChakdaraDir(L)Pakistan Department of Chemistry CIITAbbottabad CampusAbbottabad 22060Pakistan Department of Chemistry Quaid-i-Azam UniversityIslamabad 45320Pakistan Department of Biotechnology Quaid-i-Azam UniversityIslamabad 45320Pakistan Department of Chemistry and Polymer Science University of StellenboschP/Bag X1Matieland 7602South Africa Institute of Microbiology University of BraunschweigSpielmannstraβe 7Braunschweig 38106Germany

A new metabolite,named seimatoric acid（1）,representing a new oxobutanoic acid derivative has been isolated from Seimatosporium sp., in addition to four known compounds viz.,2-hydroxymethyl-4β,5α,6β-trihydroxycyclohex-2-enone（2）,（-）-phyllostine（3）,（＋）-epiepoxydon（4） and（＋）-epoxydon monoacetate（5）.Similarly one new benzoic acid derivative,named colletonoic acid（6） was isolated from the ethyl acetate fraction of Colletotrichum *** structures of the new compounds were elucidated by detailed ^1 H NMR,^13C NMR,COSY,*** spectroscopic analysis,and *** acid（1）was also isolated from another taxonomical unidentified fungal strain 4295 in *** structures of the known compounds were elucidated by their spectral data comparison to literature *** studies showed that colletonoic acid（6） showed good antibacterial,antifungal,and antialgal activities.

关键词： Seimatosporium sp. Colletotrichum sp. Activity Natural product