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Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways

World Journal of Hepatology 2023年第11期15卷 1237-1249页

作者： Adriana Camargo Ferrasi Samara vitória Granja Lima aline Faria Galvani Jeany Delafiori Flavia Luísa Dias-Audibert Rodrigo Ramos Catharino Giovanni Faria Silva Roberta Rodrigues Praxedes Driele Bretones Santos Dayane Trevisan de Macedo Almeida Estela Oliveira Lima Department of Internal Medicine Sao Paulo State UniversityBotucatu 18618-686Brazil Innovare Biomarkers Laboratory University of CampinasCampinas 13083-877Brazil

BACKGROUND Chronic Hepatitis C(CHC)affects 71 million people globally and leads to liver issues such as fibrosis,cirrhosis,cancer,and death.A better understanding and prognosis of liver involvement are vital to reduce morbidity and *** accurate identification of the fibrosis stage is crucial for making treatment decisions and predicting *** used to grade fibrosis include histological analysis and imaging but have *** markers such as molecular biomarkers can offer valuable insights into *** To identify potential biomarkers that might stratify these lesions and add information about the molecular mechanisms involved in the *** Plasma samples were collected from 46 patients with hepatitis C and classified into fibrosis grades F1(n=13),F2(n=12),F3(n=6),and F4(n=15).To ensure that the identified biomarkers were exclusive to liver lesions(CHC fibrosis),healthy volunteer participants(n=50)were also *** untargeted metabolomic technique was used to analyze the plasma metabolites using mass spectrometry and database *** analyses were performed to identify differential biomarkers among *** Six differential metabolites were identified in each grade of *** six-metabolite profile was able to establish a clustering tendency in patients with the same grade of fibrosis;thus,they showed greater efficiency in discriminating *** This study suggests that some of the observed biomarkers,once validated,have the potential to be applied as prognostic ***,it suggests that liquid biopsy analyses of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to fibrosis grade.

关键词： Chronic Hepatitis C Fibrosis Metabolome Biomarkers Plasma Liquid biopsy

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Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil:A national survey

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World Journal of Gastroenterology 2016年第33期22卷 7587-7594页

作者： Bruno Squarcio Sanches Gustavo Miranda Martins Karine Lima Bianca Cota Luciana Dias Moretzsohn Laercio Tenorio Ribeiro Helenice P Breyer Ismael Maguilnik aline Bessa Maia Joffre Rezende-Filho Ana Carolina Meira Henrique Pinto Edson Alves Ramiro Mascarenhas Raissa Passos Julia Duarte de Souza Osmar Reni Trindade Luiz Gonzaga Coelho Instituto Alfa de Gastroenterologia Hospital das ClínicasUniversidade Federal de Minas Gerais Unigastro e Clínica Santa Fé Hospital de Clínicas Universidade Federal do Rio Grande do Sul Fundacao Hospital Adriano Jorge Hospital das Clínicas Universidade Federal de Goiás Hospital Geral Roberto Santos

AIM To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular *** The primary antibiotic resistance rates of Helicobacter pylori(H. pylori) were determined from November 2012 to March 2015 in the Southern,South-Eastern,Northern,North-Eastern,and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female,mean age 43 years(range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using Geno Type Helico DR(Hain Life Science,Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies,multiplex amplification,and reverse hybridization. RESULTS Clarithromycin resistance was found in 83(16.9%) patients,and fluoroquinolone resistance was found in 66(13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones(P = 0.55 and P = 0.06,respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3%(21/490) of patients. The A2147 G mutation was present in 90.4%(75/83),A2146 G in 16.9%(14/83) and A2146 C in 3.6%(3/83) of clarithromycin-resistant patients. In 10.8%(9/83) of clarithromycin-resistant samples,more than 01 mutation in the 23 S r RNA gene was noticed. In fluoroquinolone-resistant samples,37.9%(25/66) showed mutations not specified by the Geno Type Helico DR test. D91 N mutation was observed in 34.8%(23/66),D91 G in 18.1%(12/66),N87 K in 16.6%(11/66) and D91 Y in 13.6%(9/66) of cases. Among fluoroquinolone-resistant samples,37.9%(25/66) showed mutations not specified by the Geno Type Helico DR test. CONCLUSION The H. pylori clarithromycin resistance rate in Brazil is

关键词： Helicobacter pylori Microbial drug resistance Clarithromycin Fluoroquinolones Molecular diagnostic techniques

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In vitro induced pluripotency from urine-derived cells in porcine

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World Journal of Stem Cells 2022年第3期14卷 231-244页

作者： Kaiana Recchia Lucas Simões Machado Ramon Cesar Botigelli Naira Caroline Godoy Pieri Gabriela Barbosa Raquel vasconcelos Guimarães de Castro Mariana Groke Marques Laís vicari de Figueiredo Pessôa Paulo Fantinato Neto Flávio vieira Meirelles aline Fernanda de Souza Simone Maria Massami Kitamura Martins Fabiana Fernandes Bressan Department of Surgery Faculty of Veterinary Medicine and Animal SciencesUniversity of São PauloPirassununga 13635-000São PauloBrazil Department of Pharmacology and Biotechnology Institute of BioscienceSão Paulo State UniversityBotucatu 18618-689São PauloBrazil Department of veterinary Medicine Faculty of Animal Sciences and Food EngineeringUniversity of São PauloPirassununga 13635-000São PauloBrazil Embrapa Suínos e Aves Empresa Brasileira de Pesquisa AgropecuáriaConcordia 89715-899Santa CatarinaBrazil Department of Animal Sciences Faculty of Animal Sciences and Food EngineeringUniversity of São PauloPirassununga 13635-000São PauloBrazil

BACKGROUND The generation of induced pluripotent stem cells(iPSC)has been a game-changer in translational and regenerative medicine;however,their large-scale applicability is still hampered by the scarcity of accessible,safe,and reproducible *** porcine model is a large biomedical model that enables translational applications,including gene editing,long term in vivo and offspring analysis;therefore,suitable for both medicine and animal *** To reprogramme in vitro into pluripotency,and herein urine-derived cells(UDCs)were isolated from porcine *** The UDCs were reprogrammed in vitro using human or murine octamer-binding transcription factor 4(OCT4),SRY-box2(SOX2),Kruppel-like factor 4(KLF4),and C-MYC,and cultured with basic fibroblast growth factor(bFGF)*** characterize the putative porcine iPSCs three clonal lineages were submitted to immunocytochemistry for alkaline phosphatase(AP),OCT4,SOX2,NANOG,TRA181 and SSEA 1 *** transcripts related to the pluripotency(OCT4,SOX2 and NANOG)were analyzed via reverse transcription quantitative realtime polymerase chain reaction in different time points during the culture,and all three lineages formed embryoid bodies(EBs)when cultured in suspension without bFGF *** The UDCs were isolated from swine urine samples and when at passage 2 submitted to in vitro *** of putative iPSCs were obtained only from UDCs transduced with the murine factors(mOSKM),but not from human factors(hOSKM).Three clonal lineages were isolated and further cultured for at least 28 passages,all the lineages were positive for AP detection,the OCT4,SOX2,NANOG markers,albeit the immunocytochemical analysis also revealed heterogeneous phenotypic profiles among lineages and passages for NANOG and SSEA1,similar results were observed in the abundance of the endogenous transcripts related to pluripotent *** the clonal lineages when cultured in suspension without

关键词： Induced pluripotent stem cells Noninvasive Pluripotency Reprogramming Urine Porcine

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The Loss of Heterozygosity of FHIT Gene in Sporadic Breast Cancer

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Journal of Oncology Research 2021年第2期3卷 33-39页

作者： Lisiane Silveira Zavalhia Andrea Pires Souto Damin Grasiela Agnes aline Weber Taís Frederes Kramer Alcalde Laura Marinho Dorneles Guilherme Watte Adriana vial Roehe Research Laboratory in Pathology Graduate Program in PathologyFederal University of Health Sciences of Porto Alegre(UFCSPA)Brazil Department of Gynecology and Obstetrics of Federal University Rio Grande do Sul(UFRGS)Porto AlegreBrazil Research Laboratory in Molecular Biology Federal University of Health Sciences of Porto Alegre(UFCSPA)Rio Grande do SulBrazil Department of Respiratory Medicine and Thoracic Surgery Irmandade da Santa Casa de Misericordia de Porto AlegreRio Grande do SulBrazil Department of Pathology Graduate Programa in PathologyFederal University of Health Sciences of Porto Alegre(UFCSPA)Porto AlegreBrazil

*** is a potential tumor suppressor *** the precise FHIT molecular mechanism of action is not well understood,evidences suggest that Fhit protein reduced levels are involved in mammary *** aim of this study was to investigate if FHIT LOH could influence on sporadic breast cancer(BC)biological behavior,through its association with prognostic factors for sporadic *** tissue and peripheral blood samples were analyzed using the microsatellite marker *** findings were associated with clinicopathological parameters including overall *** was detected in 31.1%(52/167)of the informative BC’*** clinical and pathological characteristics we have found no significant association with FHIT LOH *** mean follow-up time was 80 *** the Cox regression analysis two parameters remained associated with BC’s risk of death:TNM stage III and Iv-HR=3.74(95%CI,1.16-12.1)P=0.027 and disease relapse HR=3.14(CI 95%1.26-7.80)P=*** study shows that FHIT LOH by itself is not a prognostic factor for sporadic *** researches are required to elucidate the functional role of FHIT LOH concerning to BC.

关键词： Breast cancer D3S1300 LOH Survival Loss of heterozygosity

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Towards a Comprehensive Search of Putative Chitinases Sequences in Environmental Metagenomic Databases

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Natural Science 2014年第5期6卷 323-337页

作者： aline S.Romao-Dumaresq Adriana M.Fróes Rafael R.C.Cuadrat Floriano P.Silva Alberto M.R.Dávila Laboratório de Biologia Computacional e Sistemas Instituto Oswaldo Cruz(IOC)FIOCRUZRio de JaneiroBrazil Laboratório de Bioquímica de Proteínas e Peptídeos Instituto Oswaldo Cruz(IOC)FIOCRUZRio de JaneiroBrazil Pólo de Biologia Computacional e Sistemas Instituto Oswaldo Cruz(IOC)FIOCRUZRio de JaneiroBrazil

Chitinases catalyze the hydrolysis of chitin, a linear homopolymer of β-(1,4)-linked N-acetylglucosamine. The broad range of applications of chitinolytic enzymes makes their identification and study very promising. Metagenomic approaches offer access to functional genes in uncultured representatives of the microbiota and hold great potential in the discovery of novel enzymes, but tools to extensively explore these data are still scarce. In this study, we develop a chitinase mining pipeline to facilitate the comprehensive search of these enzymes in environmental metagenomic databases and also to explore phylogenetic relationships among the retrieved sequences. In order to perform the analyses, UniprotKB fungal and bacterial chitinases sequences belonging to the glycoside hydrolases (GH) family-18, 19 and 20 were used to generate 15 reference datasets, which were then used to generate high quality seed alignments with the MAFFT program. Profile Hidden Markov Models (pHMMs) were built from each seed alignment using the hmmbuild program of HMMER v3.0 package. The best-hit sequences returned by hmmsearch against two environmental metagenomic databases (Community Cyberinfrastructure for Advanced Microbial Ecology Research and Analysis—CAMERA and Integrated Microbial Genomes—IMG/M) were retrieved and further analyzed. The NJ trees generated for each chitinase dataset showed some variability in the catalytic domain region of the metagenomic sequences and revealed common sequence patterns among all the trees. The scanning of the retrieved metagenomic sequences for chitinase conserved domains/signatures using both the InterPro and the RPS-BLAST tools confirmed the efficacy and sensitivity of our pHMM-based approach in detecting putative chitinases sequences. These analyses provide insight into the potential reservoir of novel molecules in metagenomic databases while supporting the chitinase mining pipeline developed in this work. By using our chitinase mining pipeline, a larg

关键词： Chitinase Metagenome pHMM Sequence Search

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Features of ^(90)Sr behavior in Crimean lakes with different salinity of their water environment

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Acta Geochimica 2023年第1期42卷 89-102页

作者： N.Yu.Mirzoeva S.I.Arkhipova v.Yu.Proskurnin O.N.Miroshnichenko I.N.Moseichenko A.O.Kovalevsky Institute of Biology of the Southern Seas of RAS SevastopolRussian Federation

The comparative study of technogenic ^(90)Sr behavior features in Crimea lakes’ ecosystems with different levels of salinity was carried out in *** sources of ^(90)Sr input were identified for all the studied lakes:the primary source concerned with atmospheric fallout immediately after the Chernobyl NPP accident and the secondary long-term input of this radionuclide by *** half-life of the ^(90)Sr concentration in the water of the hypers aline Lake Sasyk-Sivash was estimated to vary from 0.8 to 1.1 years after the closure of the North Crimean Canal(NCC).Biogeochemical processes in the lake under the absence of the secondary source of the radionuclide input were shown to decrease in the ^(90)Sr residence time in the water column by 131 *** brackish water bodies,a significant factor influencing the radionuclide concentration in ecosystems of lakes was the pH of their water,while for hypers aline lakes the level of water salinity was the main factor determining ^(90)Sr *** concentration of ^(90)Sr in bottom sediments of studied lakes depended mainly on this radionuclide concentration in a water *** ^(90)Sr distribution factors(Kd) for studied lakes’ bottom sediments varied in a range of n·10^(0)÷n·10^(2) for hypersaline lakes and of n·10^(1)÷n·10^(2) for lakes with brackish *** to the closure of the NCC,the ^(90)Sr redistribution took place in lake ecosystems only under the geochemical processes within the water bodies *** results obtained in this work are of particular importance as a starting point or a basis for further radioecological studies of the Crimean inland waters after the reopening of the NCC and the Dnieper waters re-entering the territory of Crimea in 2022after the 8 years of their absence.

关键词： ^(90)Sr Salt lakes Water Bottom sediments Chernobyl NPP accident Crimea

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Antioxidant Activity and Phytochemical Profile of Spondias tuberosa Arruda Leaves Extracts

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American Journal of Plant Sciences 2015年第19期6卷 3038-3044页

作者： Amanda D.A.Uchoa Weslley F.Oliveira aline P.C.Pereira Alexandre G.Silva Bruna M.P.C.Cordeiro Carolina B.Malafaia Clébia M.A.Almeida Nicácio H.Silva Juliana F.C.Albuquerque Márcia v.Silva Maria T.S.Correia Departamento de Bioquímica Centro de Ciências BiológicasUniversidade Federal de PernambucoRecifeBrazil Instituto Nacional do Semiárido(INSA) Campina GrandeBrazil Departamento de Antibióticos Centro de Ciências BiológicasUniversidade Federal de PernambucoRecifeBrazil

Spondias tuberosa Arruda (umbuzeiro), a Brazilian semiarid plant, is a species of great economic, social, and ecological importance. In folk medicine, the leaves have been used in the treatment of diabetes, inflammation, stomach and uterine pains, and constipation. In this study, the antioxidant properties of ethyl acetate and methanol leaves extracts were evaluated in vitro using different methods: free radicals elimination by DPPH and ABTS assays, and transition metal reduction by phosphomolybdenium assay. In addition, a phytochemical study was also carried out. The methanolic leaves extracts showed the strongest antioxidant activity and the higher values for total phenolic and flavonoids. The results showed that S. tuberosa leaves have antioxidant activity and this seems to be related to the phenolic content.

关键词： Umbuzeiro Phenolic Compounds Flavonoids Antioxidants

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Determination of isotretinoin in pharmaceutical formulations by reversed-phase HPLC

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Journal of Biomedical Science and Engineering 2010年第5期3卷 454-458页

作者： Carla Aiolfi Guimaraes Farid Menaa Bouzid Menaa Ivo Lebrun Joyce S. Quenca-Guillen aline vivian vatti Auada Lucildes P. Mercuri Paula Ferreira Maria Inês Rocha Miritello Santoro 不详

The development of facile and rapid quantification of biologically active biomolecules such as isotretitoin in therapeutic drugs contained in many generic formu- lations is necessary for determining their efficiency and their quality to improve the human health care. Isotretritoin finds its applications in the maintenance of epithelial tissues. Different processes to date such as normal phase HPLC, or gas chromatrography am- ong others are able to separate and quantify isote- troin. However, the extraction is quite complex and in the case of HPLC, the analysis requires long retention times. In such context, an isocratic reversed- phase high-performance liquid chromatography (HP- LC) technique coupled with an Uv-vis detector is described here for easy separation and quantification of 13-cis-retinoic (isotretinoin) from soft gelatin capsule formulations. The isotretinoin was extracted from three different commercial drug samples with tetrahydrofuran (THF) solvent by a procedure that can be completed in less than 10 minutes. Subsequent separation and quantification were accomplished in less than 5 minutes under isocratic reversed-phase conditions on a Lichrospher RP18 column and a mobile phase consisting of 0.01% TFA/acetonitrile (15/85, v/v) at a flow rate of 1.0 mL/min. Isotretoin was detected for the three samples via its Uv-vis absorbance at 342 nm. The method was validated and the results showed good linearity, precision and accuracy for sensitive and selective quantitative determination of isotretinoin in the different pharmaceutical formulations. We found that the average isotretinoin content in two of the three commercial pro- ducts fell outside the 90-110% United States Pha- rmacopeia specifications. Consequently, the facile extraction and the precise method for the biomole- cule quantification open up tremendous possibilities in improving the quality control of drugs which can exist as different generic brands.

关键词： 13-Cis Retinoic Acid Reversed-Phase Chromatography Isotretitoin Extraction Isotretinoin Quantification Pharmaceuticals Formulation

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新的CT重建技术能够挑战MRI在首诊肺癌的脑转移瘤检测吗?

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国际医学放射学杂志 2018年第2期 247-247页

作者： M.Domitille B.David C.Philippe E.C.Samantha G.v.M.aline v.Alain 王习 Department of Radiology and Medical Imaging Cliniques Universitaires Saint Luc Université Catholique de Louvain

摘要目的评估基于模型的迭代算法重建常规和半剂量CT影像在脑转移瘤的诊断效能。方法采用前瞻性研究历经15个月收集115例经过病理学证实的肺癌病人。使用

关键词：脑转移瘤重建技术标准剂量 CT MRI

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法国西部地区钙化性主动脉瓣狭窄的家族聚集性

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世界核心医学期刊文摘（心脏病学分册） 2006年第7期2卷 31-31页

作者： probst v. Le Scouarnec S. Legendre A. 孙凯 Service de Cardiologie du CHU de Nantes CHU de Nantes HpitalNord Bd Jacques Monod 44093 Nantes Cedex France Dr.

Background -Calcific aortic valve stenosis(CAvS) is the most common valvular defect in developed countries. Unlike mitral valve prolapse, there is no demonstration that a familial factor could play a role in the occurrence of this disease. The aim of this study was to demonstrate a familial aggregation for CAvS. Methods and Results -We used the files of 2527 consecutive patients operated on for CAvS in our institution between 1992 and 2002 to map the distribution of operated CAvS in the western part of France. In a second step, we investigated clinically and genealogically the clusters with the highest rates of operated CAvS to detect familial forms of the disease. The geographic distribution of CAvS is highly heterogeneous, with an average frequency of operated CAvS of 1.13 per 1000 inhabitants but up to 9.38 per 1000 in specific parishes. A screening of the population from the parishes with the highest rate of operated CAvS allowed us to identify 5 families with ≥3 sibs affected by CAvS. A large genealogical analysis performed in one of these families allowed us to link 48 patients who derived from 34 nuclear families. Genealogical information could be traced to a common ancestor within 13 generations. Conclusions -Identification of clusters and large families affected by a classic form of CAvS demonstrates a familial aggregation for this disease.

关键词：家族聚集性二尖瓣脱垂平均发生率家系调查地理分布非均质族性调查法中起

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