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hsa-mir-183 is frequently methylated and related to poor survival in human hepatocellular carcinoma

World Journal of Gastroenterology 2017年第9期23卷 1568-1575页

作者： Sumadi Lukman Anwar Till Krech Britta Hasemeier Elisa Schipper Nora Schweitzer Arndt Vogel Hans Kreipe Reena Buurman Britta Skawran Ulrich Lehmann Ulrich Lehmann Institute of PathologyMedizinische Hochschule Hannover Department of Surgery Faculty of Medicine Universitas Gadjah Mada Department of Gastroenterology Hepatology and EndocrinologyMedizinische Hochschule Hannover Institute of Human Genetics Medizinische Hochschule Hannover

To screen clinically relevant microRNAs (miRNAs) silenced by DNA methylation in human hepatocellular carcinoma (HCC).METHODSKnockdown of DNA methyltransferases (DNMTs) using siRNAs and miRNA profiling in HCC cell lines were performed to identify DNA hypermethylation-mediated miRNA downregulation. Confirmation using individual quantitative real-time PCR (qRT-PCR) assays was then performed followed by DNA methylation quantification at the promoter of the miRNA genes. Quantification of DNA methylation and miRNA expression was then performed in primary HCC tumor samples and related with clinicopathological *** profiling after DNMT knockdown in HCC cell lines revealed upregulation of miR-23, miR-25 and miR-183. After qRT-PCR confirmation and CpG island methylation quantification of these miRNAs in cell lines, further analysis in primary HCC specimens showed that hsa-miR-183 is hypermethylated in 30% of HCC (n = 40). Expression of mature miR-183 showed an inverse correlation with DNA methylation levels. In HCC cells, DNMT knockdown and 5-aza-2’-deoxycytidine treatment reduced methylation and stimulated expression of miR-183. In HCC patients, hypermethylation at hsa-miR-183 promoter significantly correlates with poor survival (log-rank test P = 0.03). DNA methylation analysis in healthy liver, benign liver tumors (hepatocellular adenoma and focal nodular hyperplasia) and their corresponding adjacent tissues showed absence of hypermethylation supporting the notion that aberrant methylation at hsa-miR-183 is specific for the malignant transformation of *** data indicate that hypermethylation of hsa-miR-183 is a frequent event in HCC and potentially useful as a novel surrogate diagnostic and prognostic marker.

关键词： hsa-miR-183 DNA methylation DNMT knockdown microRNA microarray

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Blastoids:a new model for human blastocyst development

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Signal Transduction and Targeted Therapy 2021年第7期6卷 1946-1947页

作者： Heiner Niemann Bob Seamark medizinische hochschule hannover(MHH) HannoverGermany Flinders University College of Medicine and Public HealthAdelaideSAAustralia

Recently,two research groups report in Nature1,'2 the ex-vivo production of blastocyst-like structures,called blastoids,that exhibit many of the landmarks in human early development found in viable blastocysts(Fig.1).The formation of a blastocyst is a critical step in early embryo development denoting a key change from the early cleavage stages to ***,the blastocyst,differentiated from the early cleavage stages,is a fluid filled vesicular structure comprised of cells of now,three distinct cell lineages,namely those of the trophoblast,the outer enclosing cell layer,and those of the inner cell mass(ICM)with the hypoblast and epiblast,found in the central fluid filled cavity(the blastocoel).

关键词： filled cavity outer

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DNA methylation,microRNAs,and their crosstalk as potential biomarkers in hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第24期20卷 7894-7913页

作者： Sumadi Lukman Anwar Ulrich Lehmann Department of Surgery Faculty of Medicine Universitas Gadjah MadaYogyakarta 55281Indonesia Institute of Pathology Medizinische Hochschule HannoverD30625 HannoverGermany

Epigenetic alterations have been identified as a major characteristic in human *** in the field of epigenetics have contributed significantly in refining our knowledge of molecular mechanisms underlying malignant *** methylation and microRNA expression are epigenetic mechanisms that are widely altered in human cancers including hepatocellular carcinoma(HCC),the third leading cause of cancer related mortality *** DNA methylation and microRNA expression patterns are regulated in developmental stage specific-,cell type specific-and tissue-specific *** aberrations are inferred in the maintenance of cancer stem cells and in clonal cell evolution during *** availability of genome-wide technologies for DNA methylation and microRNA profiling has revolutionized the field of epigenetics and led to the discovery of a number of epigenetically silenced microRNAs in cancerous cells and primary *** of these microRNAs affects several key signalling pathways in hepatocarcinogenesis suggesting that modulation of DNA methylation and/or microRNA expression can serve as new therapeutic targets for *** evidence shows that aberrant DNA methylation of certain microRNA genes is an event specifically found in HCC which correlates with unfavorable ***,it can potentially serve as a biomarker for detection as well as for prognosis,monitoring and predicting therapeutic responses in HCC.

关键词： DNA methylation MicroRNA Epigenetics Hepatocellular carcinoma Biomarker

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Ultrasound findings in autoimmune hepatitis

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World Journal of Gastroenterology 2018年第15期24卷 1583-1590页

作者： Yi Dong Andrej Potthoff Christoph Klinger Ana Paula Barreiros Dariusz Pietrawski Christoph F Dietrich Department of Ultrasound Zhongshan Hospital Fudan University Department of Gastroenterology Hepatology and Endocrinology Medizinische Hochschule Hannover Department of Internal Medicine 1 Klinikum Ludwigsburg German Organ Transplantation Foundation Region Mitte Department of Internal Medicine 2 Caritas-Krankenhaus Bad Mergentheim

Ultrasound findings in autoimmune hepatitis(AIH) have not been reported systematically so far. The use of reliable and accurate noninvasive methods for determining fibrosis stage is important in evaluation of treatment efficacy and fibrosis regression in AIH. Imaging plays an important role in detection of complications and ruling out other possible causes of chronic liver diseases. Ultrasound elastography cutoff values in AIH patients are not the same as those in patients with chronic viral hepatitis or non-alcoholic fatty liver disease. AIH is characterized by wide fluctuations in inflammatory activity. Here we report on current knowledge of ultrasound findings in AIH.

关键词： Autoimmune hepatitis Fibrosis stage Ultrasound Elastography Chronic liver diseases

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A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin

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Translational Neurodegeneration 2022年第1期11卷 532-546页

作者： Neelam Younas Leticia Camila Fernandez Flores Franziska Hopfner Günter U.Höglinger Inga Zerr Prion Research Group Department of NeurologyNational Reference Center for Surveillance of TSEUniversitätsklinikum Göttingen:Universitätsmedizin GöttingenGeorg-August UniversityGöttingenGermanyRobert-Koch-Strasse 4037075 GöttingenGermany hannover Medical School Medizinische Hochschule HannoverHannoverGermany German Center for Neurodegenerative Diseases(DZNE) MunichGermany German Center for Neurodegenerative Diseases(DZNE) GöttingenGermany.

Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood-brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. Exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. In this review, we aim to discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer’s and Parkinson’s diseases. In the later part, we discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.

关键词： Alzheimer’s disease Central nervous system Diagnosis Exosomes Blood-brain barrier Parkinson’s disease

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Implementation of a Return to Work Strategy in Germany—Are There Changes in Work-Related Rehabilitation Measures and Employment Status in Chronic Conditions?

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Open Journal of Therapy and Rehabilitation 2016年第1期4卷 55-66页

作者： Cornelia Gerdau-Heitmann Monika Schwarze Abt. Technik und Gesundheit für Menschen (TGM) Jade Hochschule Oldenburg Oldenburg Germany Klinik für Rehabilitationsmedizin Medizinische Hochschule Hannover Hanover Germany

Objectives: Aging workforces with increasing numbers of chronic conditions require health initiatives with greater workplace focus. A regional pension insurance introduced a Return To Work (RTW) strategy for insurants with chronic conditions. The objective was to identify the degree of implementation of work related measures in medical rehabilitation and the extent of RTW outcomes. Methods: 5883 insurants were considered. Severe Restriction of Work Ability (SRWA), Work-related Medical Rehabilitation (WMR), and Case Management (CM) were examined for 2008 and 2012. An Index of Employment status (IoE) was used in a logistic regression. Results: Utilization of WMR raised from 12.3% in 2008 to 66.1% in 2012. The proportion of insurants with SRWA and WMR grew from 8% up to 40.1%. In 2008, 14.7% of insurants with SRWA received WMR;in 2012, it grew to 76.6%. On the other hand, in 2012 26% got WMR without SRWA and 12.2% had SRWA and got no WMR. CM was not conducted in 2008 but reached 20.2% in 2012. Across all indications, WMR resulted in positive RTW as measured by IoE: OR = 0.75 (KI-95%: 0.67 - 0.86). Conclusion: WMR was successfully implemented according to the German guideline. There is a need to optimize the linkage between SRWA and WMR and CM to provide need-based care.

关键词： Chronic Conditions Return to Work (RTW) Work-Related Medical Rehabilitation (WMR) Case Management (CM) Severe Restrictions of Work Ability (SRWA)

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Pharmacokinetics of Micafungin in Adult Patients with Invasive Candidiasis and Candidemia

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Open Journal of Medical Microbiology 2012年第3期2卷 84-90页

作者： Nasrullah A. Undre Paul Stevenson Ernst-Rüdiger Kuse Ignace Demeyer Astellas Pharma Europe Ltd. Staines-upon-Thames UK Formerly of Astellas Pharma GmbH Munich Munich Germany medizinische hochschule hannover Hannover Germany Onze Lieve Vrouw Ziekenhuis Aalst Belgium

Micafungin is an efficacious and well-tolerated echinocandin with in vitro and in vivo activity against a broad range of Candida species. The objective of this randomized, double-blind study was to examine the pharmacokinetic parameters of micafungin and its metabolites in a subset of adult patients with invasive candidiasis or candidemia. The study was conducted at 27 sites in four countries, including eight in Europe. Micafungin 100 mg/day or liposomal amphotericin B 3 mg/kg/day were administered once daily as a 1-hour infusion in a blinded manner. The minimum duration of therapy was 14 days. To define plasma analyte (micafungin and metabolites) concentration-time profiles, serial blood samples were collected after the first dose (Day 1), and at the end of therapy (EOT). For patients who received treatment for longer than 2 weeks, an additional profile was obtained during Week 2. To determine plasma trough analyte concentrations, blood samples were collected immediately prior to dosing on Day 2, Week 2, and EOT. In 20 evaluable, micafungin-treated patients, plasma micafungin concentrations peaked at completion of the 1-hour infusion and then declined biexponentially. Plasma concentrations of the micafungin metabolites (M-1, M-2, and M-5) remained low (<1 μg/mL) throughout the study. The mean half-life and clearance of micafungin were largely unchanged with repeated dosing up to 28 days, and no evidence of micafungin accumulation was observed. These data provide further support for the predictability of micafungin pharmacokinetics in adult patients with invasive candidiasis and candidemia.

关键词： Micafungin Pharmacokinetics Invasive Candidiasis Candidemia

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复发性腰椎间盘突出脊髓造影CT诊断标准

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放射学实践 1990年第4期5卷 170-172页

作者： B.Haubitz 李贵林 Abteilung Neuroradiologie Zentrum RadiologieMedizinische Hochschule Hannover 同济医科大学附属同济医院

复发性椎间盘突出与瘢痕组织的鉴别诊断至今仍很困难,若无磁共振断层扫描,则普通脊髓造影和脊髓造影CT的联合应用是最好的诊断方法。

关键词：椎间盘突出脊髓造影 CT 诊断

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老年患者脑供血动脉剥离

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世界核心医学期刊文摘（神经病学分册） 2005年第1期1卷 23-24页

作者： Ahl B. Bokemeyer M. Ennen J.C. 王英鹏 Department of Neurology Medizinische Hochschule Hannover D-30623 Hannover Germany Dr.

Cervical artery dissection (CAD) is being increasingly diagnosed due to improved neuroimaging methods. The mean age of patients with CAD is about 40 years, with a peak between 40 and 45 years of age. Proven data on the incidence of CAD in older patients are missing. Therefore, whether CAD should also be considered as a probable cause of cerebral ischemic events in the elderly was investigated. All consecutive patients referred to our clinic with a diagnosis of cerebral ischemia from January 1999 until June 2000 were thoroughly assessed for the presence of CAD. In addition, the records of all stroke patients treated in our department fromJanuary 1995 to December 1998 were analysed retrospectively for a diagnosis of CAD. A total of 34 patients (11 women) had suffered from internal carotid (n=29) or vertebral artery (n=5) dissection. Their mean (SD) age was 50.3 (14.6) years, with 32.4% being older than 60 years. Clinical presentation of CAD did not differ depending on the patients’ age. The results show that CAD is a possible cause of cerebral ischemia in the elderly and thus has also to be considered in the diagnostic investigation in this patient group.

关键词：脑供血动脉脑缺血患者颈内动脉临床资料颈动脉剥离影像学技术诊断率门诊治疗住院治疗

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肝脏的超声分段及其对肝段切除的意义

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放射学实践 1992年第4期7卷 156-158页

作者： S.A.A.Qaiyumi H.Milbradt A.Weimann G.Steinhoff M.Prokop M.Galanski 乐桂蓉 medizinische hochschule hannover Abt. Diagnostische Radiologie Konstanty-Gutschow-Str. 8 3000 Hannover 61 FRG 同济医科大学附属同济医院

〈正〉肝脏部分切除方面的进展,要求放射学能准确描述肝转移的部位。这不仅用CT扫查,而且用有经验的超声检查也是可能的。近年来随着显像方法和手术技术的不断改进,肝脏外科已达到了一新的水平。目前已可能进行针对性的肝脏部分切除而... 详细信息

〈正〉肝脏部分切除方面的进展,要求放射学能准确描述肝转移的部位。这不仅用CT扫查,而且用有经验的超声检查也是可能的。近年来随着显像方法和手术技术的不断改进,肝脏外科已达到了一新的水平。目前已可能进行针对性的肝脏部分切除而无严重并发症发生。肝部分切除术是以功能性外科肝段解剖学为基础,因此,

关键词：肝超声波诊断

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