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Book ; Online ; Thesis: Identifizierung neuer Substanzen für die zielgerichtete Behandlung der MACC1-vermittelten Metastasierung

Yan, Shixian [Verfasser]

2022

Author's details	Shixian Yan
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	English
Publisher	Medizinische Fakultät Charité - Universitätsmedizin Berlin
Publishing place	Berlin
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Long non-coding RNA Homeobox D gene cluster antisense growth-associated long noncoding RNA/microRNA-182-5p/Homeobox protein A10 alleviates postmenopausal osteoporosis via accelerating osteoblast differentiation of bone marrow mesenchymal stem cells.

Huang, YeJian / Tao, MingGao / Yan, ShiXian / He, XueMing

Journal of orthopaedic surgery and research

2023 Volume 18, Issue 1, Page(s) 726

Abstract: Background: Studies have illuminated that long non-coding RNA (lncRNA) influences bone cell differentiation and formation. Nevertheless, whether lncRNA Homeobox D gene cluster antisense growth-associated long noncoding RNA (HAGLR) was implicated in ... ...

Abstract	Background: Studies have illuminated that long non-coding RNA (lncRNA) influences bone cell differentiation and formation. Nevertheless, whether lncRNA Homeobox D gene cluster antisense growth-associated long noncoding RNA (HAGLR) was implicated in postmenopausal osteoporosis (PMOP) was yet uncertain. Purpose: The research was to explore HAGLR's role in the osteogenic differentiation (OD) process of bone marrow mesenchymal stem cells (BMSCs). Methods: BMSCs were isolated from mouse bone marrow tissues and identified by electron microscope and flow cytometry. HAGLR, microRNA (miR)-182-5p, and homeobox protein A10 (Hoxa10) levels in BMSCs were detected. Mouse BMSC OD process was induced, and calcium deposition and alkaline phosphatase content were analyzed, as well as expressions of runt-related transcription factor 2, osteopontin, and osteocalcin, and cell apoptosis. Bilateral ovaries were resected from mice to construct the ovariectomized model and bone mineral density, maximum bending stress, maximum load, and elastic modulus of the femur were tested, and the femur was histopathologically evaluated. Chondrocyte apoptosis in the articular cartilage of mice was analyzed. Analysis of the interaction of HAGLR, miR-182-5p with Hoxa10 was conducted. Results: HAGLR and Hoxa10 were down-regulated and miR-182-5p was elevated in PMOP patients. During the BMSC OD process, HAGLR and Hoxa10 levels were suppressed, while miR-182-5p was elevated. Promotion of HAGLR or suppression of miR-182-5p accelerated OD of BMSCs. Inhibition of miR-182-5p reversed the inhibitory effect of HAGLR on BMSC OD. In in vivo experiments, up-regulating HAGLR alleviated PMOP, while silencing Hoxa10 reversed the effects of upregulating HAGLR. HAGLR performed as a sponge for miR-182-5p, while miR-182-5p targeted Hoxa10. Conclusion: In general, HAGLR boosted the OD process of BMSCs and relieved PMOP via the miR-182-5p/Hoxa10 axis. These data preliminarily reveal the key role of HAGLR in PMOP, and the research results have a certain reference for the treatment of PMOP.
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Bone Marrow Cells/metabolism ; Cell Differentiation/genetics ; Cells, Cultured ; Genes, Homeobox ; Mesenchymal Stem Cells/metabolism ; MicroRNAs/metabolism ; Multigene Family ; Osteoblasts/metabolism ; Osteogenesis/genetics ; Osteoporosis, Postmenopausal/genetics ; Osteoporosis, Postmenopausal/therapy ; Osteoporosis, Postmenopausal/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Homeobox A10 Proteins/genetics
Chemical Substances	MicroRNAs ; Mirn182 microRNA, human ; Mirn182 microRNA, mouse ; RNA, Long Noncoding ; HOXA10 protein, human (140441-81-2) ; Homeobox A10 Proteins ; long non-coding RNA HOXD-AS1, human
Language	English
Publishing date	2023-09-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2252548-8
ISSN	1749-799X ; 1749-799X
ISSN (online)	1749-799X
ISSN	1749-799X
DOI	10.1186/s13018-023-04203-8
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Article ; Online: Identification of unique long non-coding RNAs as putative biomarkers for chromophobe renal cell carcinoma.

Wu, Guanlin / Xia, Pengfei / Yan, Shixian / Chen, Dongming / Xie, Lei / Fan, Gang

Personalized medicine

2020 Volume 18, Issue 1, Page(s) 9–19

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Biomarkers, Tumor ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/mortality ; Carcinoma, Renal Cell/pathology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms/genetics ; Kidney Neoplasms/mortality ; Kidney Neoplasms/pathology ; Protein Interaction Maps ; RNA, Long Noncoding/biosynthesis ; Survival Analysis
Chemical Substances	Biomarkers, Tumor ; RNA, Long Noncoding
Language	English
Publishing date	2020-10-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2299146-3
ISSN	1744-828X ; 1741-0541
ISSN (online)	1744-828X
ISSN	1741-0541
DOI	10.2217/pme-2020-0020
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Article ; Online: Discovery of tetrazolo-pyridazine-based small molecules as inhibitors of MACC1-driven cancer metastasis.

Yan, Shixian / Schöpe, Paul Curtis / Lewis, Joe / Putzker, Kerstin / Uhrig, Ulrike / Specker, Edgar / von Kries, Jens Peter / Lindemann, Peter / Omran, Anahid / Sanchez-Ibarra, Hector E / Unger, Anke / Zischinsky, Mia-Lisa / Klebl, Bert / Walther, Wolfgang / Nazaré, Marc / Kobelt, Dennis / Stein, Ulrike

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 168, Page(s) 115698

Abstract: Metastasis is directly linked to poor prognosis of cancer patients and warrants search for effective anti-metastatic drugs. MACC1 is a causal key molecule for metastasis. High MACC1 expression is prognostic for metastasis and poor survival. Here, we ... ...

Abstract	Metastasis is directly linked to poor prognosis of cancer patients and warrants search for effective anti-metastatic drugs. MACC1 is a causal key molecule for metastasis. High MACC1 expression is prognostic for metastasis and poor survival. Here, we developed novel small molecule inhibitors targeting MACC1 expression to impede metastasis formation. We performed a human MACC1 promoter-driven luciferase reporter-based high-throughput screen (HTS; 118.500 compound library) to identify MACC1 transcriptional inhibitors. HTS revealed 1,2,3,4-tetrazolo[1,5-b]pyridazine-based compounds as efficient transcriptional inhibitors of MACC1 expression, able to decrease MACC1-induced cancer cell motility in vitro. Structure-activity relationships identified the essential inhibitory core structure. Best candidates were evaluated for metastasis inhibition in xenografted mouse models demonstrating metastasis restriction. ADMET showed high drug-likeness of these new candidates for cancer therapy. The NFκB pathway was identified as one mode of action targeted by these compounds. Taken together, 1,2,3,4-tetrazolo[1,5-b]pyridazine-based compounds are effective MACC1 inhibitors and pose promising candidates for anti-metastatic therapies particularly for patients with MACC1-overexpressing cancers, that are at high risk to develop metastases. Although further preclinical and clinical development is necessary, these compounds represent important building blocks for an individualized anti-metastatic therapy for solid cancers.
MeSH term(s)	Animals ; Humans ; Mice ; Gene Expression Regulation, Neoplastic ; Neoplasm Metastasis ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Promoter Regions, Genetic ; Trans-Activators/antagonists & inhibitors
Chemical Substances	MACC1 protein, human ; Trans-Activators
Language	English
Publishing date	2023-10-21
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.115698
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Article ; Online: Wnt signalling pathway in bladder cancer.

Wu, Guanlin / Weng, Weidong / Xia, Pengfei / Yan, Shixian / Zhong, Cheng / Xie, Lei / Xie, Yu / Fan, Gang

Cellular signalling

2020 Volume 79, Page(s) 109886

Abstract: Bladder cancer (BC) is one of the most common tumours of the urinary system and is also known as a highly malignant tumour. In addition to conventional diagnosis and treatment methods, recent research has focused on studying the molecular mechanisms ... ...

Abstract	Bladder cancer (BC) is one of the most common tumours of the urinary system and is also known as a highly malignant tumour. In addition to conventional diagnosis and treatment methods, recent research has focused on studying the molecular mechanisms related to BC, in the hope that new, less toxic and effective targeted anticancer drugs and new diagnostic markers can be discovered. It is known that the Wingless (Wnt) signalling pathway and its related genes, proteins and other substances are involved in multiple biological processes of various tumours. Clarifying the contribution of the Wnt signalling pathway in bladder tumours will help establish early diagnosis indicators, develop new therapeutic drugs and evaluate the prognosis for BC. This review aims to summarise previous studies related to BC and the Wnt signalling pathway, with a focus on exploring the participating substances and their mechanisms in the regulation of the Wnt signalling pathway to better determine how to promote new chemotherapeutic drugs, potential therapeutic targets and diagnostic biomarkers.
MeSH term(s)	Animals ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/metabolism ; Wnt Signaling Pathway
Chemical Substances	Neoplasm Proteins
Language	English
Publishing date	2020-12-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2020.109886
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Article: MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients.

Shah, Sahil / DeBerge, Matthew / Iovane, Andre / Yan, Shixian / Qiu, Longhui / Wang, Jiao-Jing / Kanwar, Yashpal S / Hummel, Mary / Zhang, Zheng J / Abecassis, Michael M / Luo, Xunrong / Thorp, Edward B

Pathogens (Basel, Switzerland)

2020 Volume 9, Issue 8

Abstract: Transplantation tolerance is achieved when recipients are unresponsive to donor alloantigen yet mobilize against third-party antigens, including virus. After transplantation, cytomegalovirus (CMV) reactivation in latently-infected transplants reduces ... ...

Abstract	Transplantation tolerance is achieved when recipients are unresponsive to donor alloantigen yet mobilize against third-party antigens, including virus. After transplantation, cytomegalovirus (CMV) reactivation in latently-infected transplants reduces allograft viability. To determine if pre-tolerized recipients are resistant to viral dissemination in this setting, we transfused chemically-fixed donor splenocytes (1-ethyl-3- (3'-dimethyl-aminopropyl)-carbo-diimide (ECDI)-treated splenocytes (ECDIsp)) to induce donor antigen tolerance without immunosuppression. In parallel, we implanted donor islet cells to validate operational tolerance. These pre-tolerized recipients were implanted with murine CMV (MCMV) latently-infected donor kidneys (a validated model of CMV latency) to monitor graft inflammation and viral dissemination. Our results indicate that tolerance to donor islets was sustained in recipients after implantation of donor kidneys. In addition, kidney allografts implanted after ECDIsp and islet implantation exhibited low levels of fibrosis and tubulitis. In contrast, kidney cellular and innate immune infiltrates trended higher in the CMV group and exhibited increased markers of CD8
Keywords	covid19
Language	English
Publishing date	2020-07-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9080607
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Article: MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients

Pathogens. 2020 July 26, v. 9, no. 8

2020

Abstract	Transplantation tolerance is achieved when recipients are unresponsive to donor alloantigen yet mobilize against third-party antigens, including virus. After transplantation, cytomegalovirus (CMV) reactivation in latently-infected transplants reduces allograft viability. To determine if pre-tolerized recipients are resistant to viral dissemination in this setting, we transfused chemically-fixed donor splenocytes (1-ethyl-3- (3′-dimethyl-aminopropyl)-carbo-diimide (ECDI)-treated splenocytes (ECDIsp)) to induce donor antigen tolerance without immunosuppression. In parallel, we implanted donor islet cells to validate operational tolerance. These pre-tolerized recipients were implanted with murine CMV (MCMV) latently-infected donor kidneys (a validated model of CMV latency) to monitor graft inflammation and viral dissemination. Our results indicate that tolerance to donor islets was sustained in recipients after implantation of donor kidneys. In addition, kidney allografts implanted after ECDIsp and islet implantation exhibited low levels of fibrosis and tubulitis. In contrast, kidney cellular and innate immune infiltrates trended higher in the CMV group and exhibited increased markers of CD8⁺ T cell activation. Tolerance induction was unable to prevent increases in MCMV-specific CD8⁺ T cells or dissemination of viral IE-1 DNA. Our data suggest that latently-infected allografts are inherently more susceptible to inflammation that is associated with viral dissemination in pre-tolerized recipients. Thus, CMV latently-infected allografts require enhanced strategies to protect allograft integrity and viral spread.
Keywords	Cytomegalovirus ; DNA ; T-lymphocytes ; allografting ; antigens ; fibrosis ; immunosuppression ; inflammation ; islets of Langerhans ; kidneys ; mice ; model validation ; pathogens ; splenocytes ; viability ; viruses
Language	English
Dates of publication	2020-0726
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9080607
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Up-regulation of NF45 correlates with Schwann cell proliferation after sciatic nerve crush.

Wang, Youhua / Zhou, Shiran / Xu, Hua / Yan, Shixian / Xu, Dawei / Zhang, Yi

Journal of molecular neuroscience : MN

2015 Volume 56, Issue 1, Page(s) 216–227

Abstract: Nuclear factor (NF)45 (also known as interleukin enhancer-binding factor (ILF)2), is a transcription factor that interacts with NF90 to regulate gene expression. It has long been implicated in the regulation of cell proliferation. However, the role of ... ...

Abstract	Nuclear factor (NF)45 (also known as interleukin enhancer-binding factor (ILF)2), is a transcription factor that interacts with NF90 to regulate gene expression. It has long been implicated in the regulation of cell proliferation. However, the role of NF45 in the process of peripheral nervous system regeneration after injury remains poorly understood. Herein, we investigated the spatiotemporal expression of NF45 in a rat sciatic nerve crush model. We detected the up-regulated expression of NF45 in Schwann cell after sciatic nerve crush. What's more, the expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA) exhibited a similar tendency with that of NF45. In cell cultures, we observed increased expression of NF45 during the process of TNF-α-induced Schwann cell proliferation, whereas the protein level of p21 was down-regulated. Interference of NF45 led to enhanced expression of p21 and also impaired proliferation of Schwan cells. Taken together, our data implicated that NF45 was up-regulated in the sciatic nerve after crush, which was associated with proliferation of Schwann cell.
MeSH term(s)	Animals ; Cell Proliferation ; Cells, Cultured ; Male ; Nerve Crush ; Nuclear Factor 45 Protein/genetics ; Nuclear Factor 45 Protein/metabolism ; Peripheral Nerve Injuries/metabolism ; Proliferating Cell Nuclear Antigen/genetics ; Proliferating Cell Nuclear Antigen/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Rats ; Rats, Sprague-Dawley ; Schwann Cells/metabolism ; Schwann Cells/physiology ; Sciatic Nerve/injuries ; Sciatic Nerve/metabolism ; Up-Regulation
Chemical Substances	Nuclear Factor 45 Protein ; Proliferating Cell Nuclear Antigen ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2015-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1043392-2
ISSN	1559-1166 ; 0895-8696
ISSN (online)	1559-1166
ISSN	0895-8696
DOI	10.1007/s12031-014-0484-3
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Article: Illumination/Darkness-Induced Changes in Leaf Surface Potential Linked With Kinetics of Ion Fluxes.

Li, Jinhai / Yue, Yang / Wang, Ziyang / Zhou, Qiao / Fan, Lifeng / Chai, Zhiqiang / Song, Chao / Dong, Hongtu / Yan, Shixian / Gao, Xinyu / Xu, Qiang / Yao, Jiepeng / Wang, Zhongyi / Wang, Xiaodong / Hou, Peichen / Huang, Lan

Frontiers in plant science

2019 Volume 10, Page(s) 1407

Abstract: A highly reproducible plant electrical signal-light-induced bioelectrogenesis (LIB) was obtained by means of periodic illumination/darkness stimulation of broad bean ( ...

Abstract	A highly reproducible plant electrical signal-light-induced bioelectrogenesis (LIB) was obtained by means of periodic illumination/darkness stimulation of broad bean (
Language	English
Publishing date	2019-11-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2613694-6
ISSN	1664-462X
ISSN	1664-462X
DOI	10.3389/fpls.2019.01407
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Article ; Online: A clinically relevant murine model unmasks a "two-hit" mechanism for reactivation and dissemination of cytomegalovirus after kidney transplant.

Zhang, Zheng / Qiu, Longhui / Yan, Shixian / Wang, Jiao-Jing / Thomas, Paul M / Kandpal, Manoj / Zhao, Lihui / Iovane, Andre / Liu, Xue-Feng / Thorp, Edward B / Chen, Qing / Hummel, Mary / Kanwar, Yashpal S / Abecassis, Michael M

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2019 Volume 19, Issue 9, Page(s) 2421–2433

Abstract: Reactivation of latent cytomegalovirus remains an important complication after transplant. Although immunosuppression (IS) has been implicated as a primary cause, we have previously shown that the implantation response of a kidney allograft can lead to ... ...

Abstract	Reactivation of latent cytomegalovirus remains an important complication after transplant. Although immunosuppression (IS) has been implicated as a primary cause, we have previously shown that the implantation response of a kidney allograft can lead to early transcriptional activation of latent murine cytomegalovirus (MCMV) genes in an immune-competent host and to MCMV reactivation and dissemination to other organs in a genetically immune-deficient recipient. We now describe a model that allows us to separately analyze the impact of the implantation effect vs that of a clinically relevant IS regimen. Treatment with IS of latently infected mice alone does not induce viral reactivation, but transplant of latently infected allogeneic kidneys combined with IS facilitates MCMV reactivation in the graft and dissemination to other organs. The IS regimen effectively dampens allo-immune inflammatory pathways and depletes recipient anti-MCMV but does not affect ischemia-reperfusion injury pathways. MCMV reactivation similar to that seen in allogeneic transplants combined with also occurs after syngeneic transplants. Thus, our data strongly suggest that while ischemia-reperfusion injury of the implanted graft is sufficient and necessary to initiate transcriptional reactivation of latent MCMV ("first hit"), IS is permissive to the first hit and facilitates dissemination to other organs ("second hit").
MeSH term(s)	Animals ; Cytomegalovirus Infections/complications ; Disease Models, Animal ; Gene Deletion ; Histones/metabolism ; Immunosuppression Therapy ; Kidney/pathology ; Kidney Transplantation/adverse effects ; Mice ; Mice, Inbred BALB C ; Muromegalovirus/physiology ; Phenotype ; Postoperative Complications/virology ; Proteomics ; Renal Insufficiency/complications ; Renal Insufficiency/surgery ; Reperfusion Injury ; Transplantation, Homologous ; Virus Activation
Chemical Substances	Histones
Language	English
Publishing date	2019-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.15376
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