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Teaching an old dog new tricks:reactivated developmental signaling pathways regulate ABCB1 and chemoresistance in cancer

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Cancer Drug Resistance 2021年第2期4卷 424-452页

作者： Wing-Kee Lee Frank Thévenod Institute for Physiology Pathophysiology and ToxicologyZBAFWitten/Herdecke UniversityWitten 58453Germany

Oncogenic multidrug resistance(MDR)is a multifactorial phenotype intimately linked to deregulated expression of detoxification *** efflux transporters,particularly the MDR P-glycoprotein ABCB1,represent a central mechanism by which not only chemotherapeutic drugs are extruded or sequestered to prevent drug delivery to their intracellular targets,but also for inhibiting apoptotic cell death cues,such as removal of proapoptotic *** cell populations exhibiting the MDR phenotype co-exist within a tumor,such as cells forming the bulk tumor cell mass,cancer stem cells,and cancer persister *** key to regulation of ABCB1 expression is the cellular transcriptional *** signaling pathways(e.g,Hedgehog,Notch,Wnt/β-catenin,TGFβ,PITX2)are pivotal in governing cell proliferation,survival,differentiation and guiding cell migration during embryogenesis,and their reactivation during carcinogenesis,which is of particular significance for tumor initiation,progression,and metastasis,also leads to the upregulation of *** pathways also drive and maintain cancer cell stemness,for which ABCB1 is used as a *** this review,the contribution of canonical and non-canonical developmental signaling pathways in transcriptional regulation of ABCB1 to confer MDR in cancer is delineated.

关键词： Drug resistance ABC transporters transforming growth factor beta tumor heterogeneity tumor cell biology

Non-coding RNAs in exercise immunology:A systematic review

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Journal of Sport and Health Science 2024年第3期13卷 311-338,I0002页

作者： Mona Kotewitsch Melina Heimer Boris Schmitz Frank C.Mooren Department of Rehabilitation Sciences Faculty of HealthUniversity of Witten/HerdeckeWitten 58455Germany DRV Clinic Konigsfeld Center for Medical RehabilitationEnnepetal 58256Germany

Regular physical exercise has been recognized as a potent modulator of immune function,with its effects including enhanced immune surveillance,reduced inflammation,and improved overall *** strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs(ncRNAs)also involved in immune system regulation,heterogeneity in individual study designs and analyzed exercise protocols exists,and a condensed list of functional,exercise-dependent ncRNAs with known targets in the immune system is missing from the literature.A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical *** combined approaches were used:(a)a systematic literature search for“ncRNA and exercise immunology”,(b)and a database search for microRNAs(miRNAs)(miRTarBase and DIANA-Tarbase v8)aligned with known target genes in the immune system based on the Reactome database,combined with a systematic literature search for“ncRNA and exercise”.Literature searches were based on PubMed,Web of Science,and SPORTDiscus;and miRNA databases were filtered for targets validated by in vitro experimental *** were eligible if they reported on exercise-based interventions in healthy *** duplicate removal,95 studies were included reporting on 164 miRNAs,which were used for the qualitative *** studies reporting on long-noncoding RNAs(lncRNAs)or circular RNAs were also *** were analyzed using ordering tables that included exercise modality(endurance/resistance exercise),acute or chronic interventions,as well as the consistency in reported change between *** criteria were defined as“validated”with 100%of≥3 independent studies showing identical direction of regulation,“plausible”(≥80%),or“suggestive”(≥70%).For resistance exercise,upregulation of miR-206 was validated while downregulation of miR-133a appeared *** endurance exer

关键词： Immune system Inflammation MicroRNA ncRNA Physical exercise

Impact of mobile health and medical applications on clinical practice in gastroenterology

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World Journal of Gastroenterology 2020年第29期26卷 4182-4197页

作者： Sven Kernebeck Theresa S Busse Maximilian D Bottcher Jurgen Weitz Jan Ehlers Ulrich Bork Didactics Educational Research in Health Science Faculty of HealthWitten/Herdecke UniversityWitten 58455Germany Department of GI- Thoracic-and Vascular SurgeryDresden Technical UniversityUniversity Hospital DresdenDresden 01307Germany

Mobile health apps (MHAs) and medical apps (MAs) are becoming increasinglypopular as digital interventions in a wide range of health-related applications inalmost all sectors of healthcare. The surge in demand for digital medical solutionshas been accelerated by the need for new diagnostic and therapeutic methods inthe current coronavirus disease 2019 pandemic. This also applies to clinicalpractice in gastroenterology, which has, in many respects, undergone a recentdigital transformation with numerous consequences that will impact patients andhealth care professionals in the near future. MHAs and MAs are considered tohave great potential, especially for chronic diseases, as they can support the selfmanagementof patients in many ways. Despite the great potential associated withthe application of MHAs and MAs in gastroenterology and health care in general,there are numerous challenges to be met in the future, including both the ethicaland legal aspects of applying this technology. The aim of this article is to providean overview of the current status of MHA and MA use in the field ofgastroenterology, describe the future perspectives in this field and point out someof the challenges that need to be addressed.

关键词： Mobile health Health applications Medical applications Technology Telemedicine Mobile applications Smartphone eHealth mHealth Digital biomarker Electronic health records

Noninvasively diagnosing coronary artery disease with 61-channel MCG data

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Chinese Science Bulletin 2014年第11期59卷 1123-1128页

作者： Tuo Chen Chen Zhao Shiqin Jiang Peter Van Leeuwen Dietrich Grnemeyer School of Electronics and Information Engineering Tongji University Grnemeyer Institute for Microtherapy Faculty of HealthUniversity Witten/Herdecke

Magnetocardiography(MCG) has been investigated as a tool for noninvasive detection of coronary artery disease(CAD). In this study, the area ratio of positive and negative magnetic induction extracted from an extrema circle in the magnetocardiogram was analyzed at specific time points in the cardiac cycle: P maximum, R peak, J point, T onset, T peak and T end. The area of the positive proportion of the magnetic field relative to the total area within a circle encompassing the field extrema was determined and proposed for fast-speed CAD diagnosis. MCG was performed with a 61-channel biomagnetometer in a shielded environment in 38 healthy subjects and 15 CAD patients. A notable difference in area ratio was found between healthy and CAD subjects at the peak time of T wave: 0.416 ± 0.090 versus0.465 ± 0.065(p = 0.013). Using a cutoff value of 0.4506resulted in a sensitivity and specificity of 86.7 % and 73.8 %,respectively. This approach may enable a fast-speed CAD diagnosis in a clinical setting.

关键词：冠心病诊断通道冠状动脉疾病 CAD 心动周期峰值时间面积率

Current status of emergency treatment of chemical eye burns in workplaces

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International Journal of Ophthalmology(English edition) 2021年第2期14卷 306-309页

作者： Kevin Claassen Dominique Rodil Dos Anjos Horst Christoph Broding Faculty of Health Department of Human Medicine Occupational Medicine and Corporate Health ManagementWitten/Herdecke University

Chemical eye burns present an avoidable,but frequent,occupational injury with potentially detrimental consequences for the quality of life and occupational rehabilitation of the injured.A periodical review of guidelines is required to assure the optimal emergency *** reviewed the literature with emphasis on current German guidelines,primarily *** the crucial first-line measure,the injury prevention has failed and an eye burn has been sustained,the immediate and copious rinsing of the eye is the pivotal emergency treatment *** the immediacy and sufficiency of the emergency rinsing are largely unanimous,there is an ongoing debate about the benefits and risks of specific rinsing solutions,and regular updates on guidelines and recommendations for the emergency treatment are *** easiest and readily available rinsing solution is tap water,which fulfils the crucial criteria conveniently in most industrialized countries:purity,sterility,and neutral p *** rinsing solutions are proposing higher osmolality to stabilize the physiological p H,because of their superior buffering ***,there is no compelling evidence for a substantial benefit,and some reports suggest that there could be unwanted side *** combination with the substantially increased expenditure and a more complex handling procedure,currently a general recommendation of any other solution than tap water is not warranted.

关键词： eye burns occupational medicine emergency treatment rinse solutions

Peritonitis and pneumoperitoneum after successful emergency pericardiocentesis in the case of a Chilaiditi syndrome

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Journal of Geriatric Cardiology 2019年第1期16卷 60-62页

作者： Michael Schulte-Hermes Oliver Klein-Wiele Marc Vorpahl Melchoir Seyfarth Department of Cardiology Pneumologand AngiologyUniversity of Witten/HerdeckeProsper Hospital.RecklinghausenMiihlenstrRecklinghausenGermany Department of Cardiology Katholisches Klinikum EssenPhilippusstiflHulsmannstrafteEssenGermany Department of Cardiology Helios University Hospital and University of Witten/HerdeckeWuppertalArrenbergerstrWuppertalGetmany

Pericardiocentesis is a common therapeutic procedure for pericardial tamponade due to pericardial effusion as well as a diagnostic procedure to obtain fluid for cytopathologic *** methods include ultrasound or fluoroscopic guidance,which generally result in high success rates(over 95%).[1,2].The complication rate of pericardiocentesis is low with reported incidences of l%-2%.[3]In the past,the most common indications for pericardiocentesis include uremia,tuberculous pericarditis or malignant pericardial ***,with the increasing number of catheter-based interventional cardiac procedures,iatrogenic pericardial effusions are becoming more frequent[4-6].

关键词： Bowel perforation Chilaiditi syndrome Pericardiocentesis Peri to nitis

Gene therapeutic approaches to inhibit hepatitis B virus replication

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World Journal of Hepatology 2015年第2期7卷 150-164页

作者： Maren Gebbing Thorsten Bergmann Eric Schulz Anja Ehrhardt Institute of Virology and Microbiology Center for Biomedical Education and Research(ZBAF)Department of Human MedicineFaculty of HealthUniversity Witten/Herdecke58453 WittenGermany

Acute and chronic hepatitis B virus(HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammation of the liver and over years this can lead to cirrhosis and the development of hepatocellularcarcinomas. Currently available therapeutics for chronically infected individuals aim at reducing viral replication and to slow down or stop the progression of the disease. Therefore, novel treatment options are needed to efficiently combat and eradicate this disease. Here we provide a state of the art overview of gene therapeutic approaches to inhibit HBV replication. We discuss non-viral and viral approaches which were explored to deliver therapeutic nucleic acids aiming at reducing HBV replication. Types of delivered therapeutic nucleic acids which were studied since many years include antisense oligodeoxynucleotides and antisense RNA, ribozymes and DNAzymes, RNA interference, and external guide sequences. More recently designer nucleases gained increased attention and were exploited to destroy the HBV genome. In addition we mention other strategies to reduce HBV replication based on delivery of DNA encoding dominant negative mutants and DNA vaccination. In combination with available cell culture and animal models for HBV infection, in vitro and in vivo studies can be performed to test efficacy of gene therapeutic approaches. Recent progress but also challenges will be specified and future perspectives will be discussed. This is an exciting time to explore such approaches because recent successes of gene therapeutic strategies in the clinic to treat genetic diseases raise hope to find alternative treatment options for patients chronically infected with HBV.

关键词： Gene therapy Hepatitis B virus Antisense nucleic acid RNA interference Designer nuclease Ribozyme DNAzyme Dominant negative mutant External guide sequence DNA vaccination

Role of homologous recombination/recombineering on human adenovirus genome engineering:Not the only but the most competent solution

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Engineering Microbiology 2024年第1期4卷 90-107页

作者： Lisa-Marie Dawson Montaha Alshawabkeh Katrin Schröer Fatima Arakrak Anja Ehrhardt Wenli Zhang Virology and Microbiology Center for Biomedical Education and Research(ZBAF)School of MedicineFaculty of HealthWitten/Herdecke UniversityStockumer Str.1058453 WittenGermany

Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly ***,adenoviruses have garnered significant interest as a versatile tool in gene therapy,tumor treatment,and vaccine vector *** the past two decades,the advent of recombineering,a method based on homologous recombination,has notably enhanced the utility of adenoviral vectors in therapeutic *** review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these ***,it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.

关键词： Adenoviral vector Gene therapy Homologous recombination Oncolytic virus Vaccine vector

Complementary and alternative medicine in pediatrics in Turkey

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World Journal of Pediatrics 2014年第4期10卷 299-305页

作者： Candan Ozturk Hulya Karatas Alfred Längler Tim Schütze Rebekka Bailey Tycho Jan Zuzak Istanbul Sabahattin Zaim university Faculty of Health SciencesHead of Nursing DepartmentIstanbulTurkey Harran university School of HealthPediatric Nursing DepartmentSanliurfa Turkiye Gemeinschaftskrankenhaus Department for Integrative Pediatric and Adolescent MedicineHerdeckeGermany university of witten/herdecke Faculty of HealthCentre for Integrative MedicineWittenGermany university Children's Hospital Department of Pediatric Oncology and HematologyEssenGermany

Background:Complementary and alternative medicine(CAM)is applied both to children and adults widely throughout the world.A previous pan-European survey showed a surprisingly high CAM-use in Turkish *** review aimed to survey information on the use of CAM in pediatrics in *** sources:A narrative,non-systematic review was conducted by melding expert opinions with a thorough and balanced review of available *** unrestricted literature search using the key words,"alternative","complementary","integrative","prevalence"and"pediatric"or"children"and"Turkey"was performed by internet search in March,2012 using PubMed and Google ***:CAM use was examined in general pediatrics,pediatric oncology,patients with asthma,and patients with diabetes.A frequency of CAM use was 87%in Turkish pediatric patients,with a mean of 60%.The primary sources of information about CAM are family and *** with patients/parents and health care professionals showed that most parents do not speak about CAM use with their physicians or ***:CAM is extensively used in Turkish pediatric *** might be due to Turkey's status as a developing country in which a traditional medical system still dominates in comparison to developed ***,larger studies are required to prove an extensive use of CAM in Turkey,as this review article does not have the capacity for in-depth *** about CAM and its related topics is essential for physicians and nurses in order to meet the patients'wish for a competent consultation concerning all aspects of a possible therapy.

关键词： acupuncture alternative medicine herbal medicine homeopathy mind-body