Review
Hematology
Laura L. Swystun, Alison Michels, David Lillicrap
Summary: Quantitative abnormalities in factor VIII (FVIII) and its binding partner, von Willebrand factor (VWF), are associated with increased bleeding or thrombosis risk. The clearance of VWF-FVIII is influenced by pathways regulated by receptors such as CLEC4M, stabilin-2, and SCARA5. These receptors have been shown to bind and clear VWF-FVIII in both in vitro and in vivo models, and genetic variants in CLEC4M, STAB2, and SCARA5 have been linked to VWF-FVIII phenotypes and the risk of venous thromboembolism in patients.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Genetics & Heredity
Victor Olsavszky, Carsten Sticht, Christian D. Schmid, Manuel Winkler, Sebastian A. Wohlfeil, Ana Olsavszky, Kai Schledzewski, Cyrill Geraud, Sergij Goerdt, Thomas Leibing, Philipp-Sebastian Koch
Summary: The loss of a single Stabilin scavenger receptor, and particularly both receptors, significantly alters the transcriptomic profile of LSECs, potentially affecting their specific functions, such as interactions with ECM, inflammation, and peripheral blood clearance.
Article
Hematology
Christine Hough, Colleen Notley, Aomei Mo, Barbara Videl, David Lillicrap
Summary: Substantial phenotypic heterogeneity exists in endothelial cells, and there is a reciprocal relationship between levels of FVIII and VWF. In some endothelial cells, high levels of FVIII co-localize with VWF and are released together.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Pierre Chelle, Alfonso Iorio, Andrea N. Edginton
Summary: This study evaluates a personalized limited sampling approach (Personalized LSA) for more accurate estimation of the terminal half-life of FVIII concentrates in patients with hemophilia A using population PK modeling.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biochemistry & Molecular Biology
Marie Cade, Javier Munoz-Garcia, Antoine Babuty, Louis Pare, Denis Cochonneau, Karim Fekir, Mathias Chatelais, Marie-Francoise Heymann, Anna Lokajczyk, Catherine Boisson-Vidal, Dominique Heymann
Summary: This study discovered that recombinant human FVIII has direct biological activities on endothelial cells, including decreased cell adhesion, regulation of transcriptomic and protein profiles, increased vascular permeability, and enhanced monocyte adhesion. The findings highlight new functions of FVIII in regulating vascular permeability and leukocyte adhesion and migration.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Hematology
Maria Isabel Bravo, Alba Perez, Aida Raventos, Salvador Grancha, Juan Ignacio Jorquera, Nora Viviana Butta, Maria Teresa Alvarez-Roman, Montserrat Costa, Todd Willis, Victor Jimenez-Yuste
Summary: The study demonstrates that pdFVIII/VWF provides higher protection against FVIII inhibitors, both in in vivo and ex vivo experiments. The data suggest that the FVIII+VWF complexes formed in pdFVIII/VWF concentrates are more effective in combating inhibitors.
Article
Hematology
Olav Versloot, Emma Iserman, Pierre Chelle, Federico Germini, Andrea N. Edginton, Roger E. G. Schutgens, Alfonso Iorio, Kathelijn Fischer
Summary: This study aimed to establish reference values for FVIII/IX concentrates in a large cohort of hemophilia patients. Results showed that EHL concentrates had longer THL than standard half-life concentrates, and THL was dependent on age, concentrate type, blood group, and inhibitor history.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Medicine, Research & Experimental
Caixia Zhou, Yashu Kuang, Qinyu Li, Yunhao Duan, Xiuxiang Liu, Jinnan Yue, Xiaoli Chen, Jie Liu, Yuzhen Zhang, Lin Zhang
Summary: This study demonstrates that EC-expressing S1pr2 tightly controls post-ischemic angiogenesis and blood flow perfusion recovery. The inhibition of S1pr2 can enhance post-ischemic angiogenesis and improve blood flow in peripheral artery disease, offering a novel therapeutic intervention.
Article
Neurosciences
Lena Hansen, Niklas Lohfink, Rajkumar Vutukuri, Roxane-Isabelle Kestner, Sandra Trautmann, Max Hecht, Pia Viktoria Wagner, Daniel Spitzer, Maryam Ibrahim Khel, Jadranka Macas, Nerea Ferreiros, Robert Gurke, Stefan Guenther, Waltraud Pfeilschifter, Kavi Devraj
Summary: This study provides novel data on the expression, localization, and function of S1P receptor 4 (S1P4) in brain microvascular endothelial cells (BMECs). The results show that S1P4 plays an important role in maintaining blood-brain barrier (BBB) permeability, and its downregulation is associated with BBB dysfunction. These findings reveal the therapeutic potential of S1P4 as a novel target for CNS diseases associated with BBB dysfunction.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biology
Yaqin Yan, Jintian Tang, Qinfeng Yuan, Caiyun Liu, Xiaolin Chen, Hao Liu, Junbin Huang, Chonglai Bao, Tom Hsiang, Lu Zheng
Summary: Prohibitins play important roles in fungal virulence by regulating mitophagy, affecting the pathogenicity of Colletotrichum higginsianum.
COMMUNICATIONS BIOLOGY
(2022)
Review
Oncology
Cedric Hermans, Mark T. Reding, Jan Astermark, Robert Klamroth, Maria Elisa Mancuso
Summary: This review examines the methodology of clinical studies on extended-half-life (EHL) factor VIII products and their applicability for personalized prophylaxis. The similarities and differences between the studies are compared to broaden physicians' understanding of each treatment's effectiveness and assist in treatment selection for individual patients.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Kacey J. Prentice, Jani Saksi, Lauren T. Robertson, Grace Y. Lee, Karen E. Inouye, Kosei Eguchi, Alexandra Lee, Ozgur Cakici, Emily Otterbeck, Paulina Cedillo, Peter Achenbach, Anette-Gabriele Ziegler, Ediz S. Calay, Feyza Engin, Gokhan S. Hotamisligil
Summary: This study identifies a hormonal FABP4 complex that regulates extracellular ATP and ADP levels in adipocytes, influencing beta-cell function and potentially playing a key role in the control of lipolysis and development of diabetes. Antibody-mediated targeting of this complex improves metabolic outcomes and provides a promising target against metabolic disease.
Article
Multidisciplinary Sciences
Wenji Piao, Lushen Li, Vikas Saxena, Jegan Iyyathurai, Ram Lakhan, Yigang Zhang, Isadora Tadeval Lape, Christina Paluskievicz, Keli L. Hippen, Young Lee, Emma Silverman, Marina W. Shirkey, Leonardo Riella, Bruce R. Blazar, Jonathan S. Bromberg
Summary: This study reveals the regulatory role of PD-L1 signaling in the transendothelial migration of T cells and highlights the importance of PD-L1 in cell migration and immune regulation.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Christina M. Termini, Amara Pang, Tiancheng Fang, Martina Roos, Vivian Y. Chang, Yurun Zhang, Nicollette J. Setiawan, Lia Signaevskaia, Michelle Li, Mindy M. Kim, Orel Tabibi, Paulina K. Lin, Joshua P. Sasine, Avradip Chatterjee, Ramachandran Murali, Heather A. Himburg, John P. Chute
Summary: Ionizing radiation and chemotherapy deplete hematopoietic stem cells and damage the vascular niche, leading to the secretion of SEMA3A from bone marrow endothelial cells. Inhibition of NRP1 promotes vascular and hematopoietic regeneration through increased expression of R spondin 2, suggesting a potential therapeutic target for improving hematopoietic recovery after myeloablation.
NATURE COMMUNICATIONS
(2021)
Article
Health Care Sciences & Services
Hae Kyung Kim, Carmen Peral, Dario Rubio-Rodriguez, Carlos Rubio-Terres
Summary: According to the analysis, using standard half-life rFVIII instead of extended half-life rFVIII products in Spain could lead to an average annual savings of euro11,227 per patient. Not switching treatment from SHL to EHL rFVIII would result in greater savings per patient (euro53,078). Considering the frequency of rFVIII dispensation in the US, annual savings per patient would increase to euro16,350 in Spain.
EXPERT REVIEW OF PHARMACOECONOMICS & OUTCOMES RESEARCH
(2021)
Article
Gastroenterology & Hepatology
Manuel Winkler, Theresa Staniczek, Sina Wietje Kuerschner, Christian David Schmid, Hiltrud Schoenhaber, Julio Cordero, Linda Kessler, Arthur Mathes, Carsten Sticht, Michelle Nessling, Alexey Uvarovskii, Simon Anders, Xue-Jun Zhang, Guido von Figura, Daniel Hartmann, Carolin Mogler, Gergana Dobreva, Kai Schledzewski, Cyrill Geraud, Philipp-Sebastian Koch, Sergij Goerdt
Summary: The study reveals that endothelial GATA4 plays a protective role against perisinusoidal liver fibrosis by repressing MYC activation and profibrotic angiocrine signaling. Therapies targeting the GATA4/MYC/PDGFB/PDGFRb axis offer a promising strategy for prevention and treatment of liver fibrosis.
JOURNAL OF HEPATOLOGY
(2021)
Article
Genetics & Heredity
Victor Olsavszky, Carsten Sticht, Christian D. Schmid, Manuel Winkler, Sebastian A. Wohlfeil, Ana Olsavszky, Kai Schledzewski, Cyrill Geraud, Sergij Goerdt, Thomas Leibing, Philipp-Sebastian Koch
Summary: The loss of a single Stabilin scavenger receptor, and particularly both receptors, significantly alters the transcriptomic profile of LSECs, potentially affecting their specific functions, such as interactions with ECM, inflammation, and peripheral blood clearance.
Article
Dermatology
Melanie Schwab, Sabrina Lohr, Jakob Schneider, Michaela Kaiser, Damir Krunic, Doris Helbig, Cyrill Geraud, Peter Angel
Summary: The study demonstrates that loss of PDPN in murine cSCC cells leads to decreased migration and invasion in vitro, highlighting the crucial role of PDPN in cSCC progression. Experiments with Pdpn mutants further reveal the importance of both intra- and extracellular domains in cancer cell invasion. Orthotopic injection of labeled cells into nude mice confirms the impact of PDPN on tumor infiltration into the stroma.
EXPERIMENTAL DERMATOLOGY
(2021)
Editorial Material
Dermatology
Corinne Huebers, Felix Struebing, Maliha Sadick, Sebastian Wohlfeil, Cyrill Geraud, Moritz Felcht
Article
Medicine, Research & Experimental
Sebastian A. Wohlfeil, Verena Haefele, Bianca Dietsch, Celine Weller, Carsten Sticht, Anna Sophia Jauch, Manuel Winkler, Christian David Schmid, Anna Lena Irkens, Ana Olsavszky, Kai Schledzewski, Philipp-Sebastian Reiners-Koch, Sergij Goerdt, Cyrill Geraud
Summary: This study investigates the efficiency and vascularization patterns of different mouse melanoma cell lines in liver metastasis. The highly and moderately metastatic melanomas are associated with gene clusters involved in cell migration and angiogenesis. Sorafenib shows a strong inhibitory effect on vascularization in liver metastasis of melanoma.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Joschka Heil, Victor Olsavszky, Katrin Busch, Kay Klapproth, Carolina de la Torre, Carsten Sticht, Kajetan Sandorski, Johannes Hoffmann, Hiltrud Schoenhaber, Johanna Zierow, Manuel Winkler, Christian David Schmid, Theresa Staniczek, Deborah E. Daniels, Jan Frayne, Georgia Metzgeroth, Daniel Nowak, Sven Schneider, Michael Neumaier, Vanessa Weyer, Christoph Groden, Hermann-Josef Groene, Karsten Richter, Carolin Mogler, Makoto Mark Taketo, Kai Schledzewski, Cyrill Geraud, Sergij Goerdt, Philipp-Sebastian Koch
Summary: The study reveals that endothelial cells in the bone marrow microenvironment play a critical role in hematopoiesis, with overactivation leading to anemia. Activation of the Wnt signaling pathway affects the differentiation of red blood cells.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Marina Roy-Luzarraga, Louise E. Reynolds, Beatriz de Luxan-Delgado, Oscar Maiques, Laura Wisniewski, Emma Newport, Vinothini Rajeeve, Rebecca J. G. Drake, Jesus Gomez-Escudero, Frances M. Richards, Celine Weller, Christof Dormann, Ya-Ming Meng, Peter B. Vermeulen, Dieter Saur, Victoria Sanz-Moreno, Ping-Pui Wong, Cyrill Geraud, Pedro R. Cutillas, Kairbaan Hodivala-Dilke
Summary: This study reveals that endothelial cell focal adhesion kinase (FAK) plays a role in regulating pancreatic ductal adenocarcinoma (PDAC) metastasis and impacting the outcome of gemcitabine treatment. The findings suggest the potential clinical utility of combinatorial endothelial cell FAK targeting with gemcitabine in controlling metastasis in PDAC patients.
Editorial Material
Dermatology
Georg Stary, Mario Fabri, Christoffer Gebhardt, Rudiger Eming, Julia Matthias, Artem Vorobyev, Maike Effern, Johanna Strobl, Claudia Gunther, Christina Zielinski, Diana Dudziak, Cyril Geraud, Verena Raker, Monique Butze, Fang Zhao, Yuanyuan Wang, Dennis Gerloff, Nicole L. Bertschi, Evelyn Gaffal, Timo Buhl
EXPERIMENTAL DERMATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Christian David Schmid, Victor Olsavszky, Manuel Reinhart, Vanessa Weyer, Felix A. Trogisch, Carsten Sticht, Manuel Winkler, Sina W. Kurschner, Johannes Hoffmann, Roxana Ola, Theresa Staniczek, Joerg Heineke, Beate K. Straub, Jens Mittler, Kai Schledzewski, Peter ten Dijke, Karsten Richter, Steven Dooley, Cyrill Geraud, Sergij Goerdt, Philipp-Sebastian Koch
Summary: This study established an HHT mouse model with liver vascular malformations and investigated the role of ALK1 signaling in liver vessel formation and metabolic function. The results showed that hepatic endothelial ALK1 signaling protects from development of vascular malformations and preserves organ-specific endothelial differentiation and angiocrine signaling.
Article
Cell Biology
Margaret Tulessin, Rim Sabrina Jahan Sarker, Joscha Griger, Thomas Leibing, Cyrill Geraud, Wilko Weichert, Katja Steiger, Carolin Mogler
Summary: This study comprehensively characterized and compared the vasculature in mouse models used for hepatocarcinogenesis studies. The findings demonstrate that vascular remodeling is an important step in the early phase of liver tumorigenesis in rodent models. This research provides a strong basis for further angiogenesis studies in these experimental models.
Article
Oncology
Anne Zaremba, Philipp Jansen, Rajmohan Murali, Anand Mayakonda, Anna Riedel, Dieter Krahl, Hans Burkhardt, Stefan John, Cyrill Geraud, Manuel Philip, Julia Kretz, Inga Moeller, Nadine Stadtler, Antje Sucker, Annette Paschen, Selma Ugurel, Lisa Zimmer, Elisabeth Livingstone, Susanne Horn, Christoph Plass, Dirk Schadendorf, Eva Hadaschik, Pavlo Lutsik, Klaus Griewank
Summary: Recurrent CTNNB1 exon 3 mutations are associated with a specific type of melanocytic tumors in benign tumors (nevi), which can be used for diagnosis. In advanced disease, there were no distinct characteristics separating CTNNB1-mutant melanomas from other melanomas; however, larger and optimally prospective cohort studies are needed.
Article
Microbiology
Philipp Jansen, Adelaida Creosteanu, Viktor Matyas, Amrei Dilling, Ana Pina, Andrea Saggini, Tobias Schimming, Jennifer Landsberg, Birte Burgdorf, Sylvia Giaquinta, Hansgeorg Mueller, Michael Emberger, Christian Rose, Lutz Schmitz, Cyrill Geraud, Dirk Schadendorf, Joerg Schaller, Maximilian Alber, Frederick Klauschen, Klaus G. Griewank
Summary: In this study, a machine learning algorithm was used to detect fungal elements on digitized histologic sections of human nail specimens, and its performance was compared with that of dermatopathologists. The results demonstrated that the algorithm achieved a comparable sensitivity to the human pathologists. This finding suggests that machine learning algorithms can serve as supportive diagnostic tools to improve the screening efficiency of fungal infections.
Article
Dermatology
Mine Schoeller, Cyrill Geraud
Summary: Vitamin and mineral deficiency can cause various clinical symptoms, with the skin being an important indicator for diagnosis. Deficiency can occur due to inadequate nutrient supply, impaired intestinal absorption, or genetic defects. Factors such as alcoholism, autism, psychiatric illnesses, and eating disorders are associated with deficiency in our region. This article focuses on the specific skin symptoms of scurvy and acrodermatitis enteropathica, which are caused by deficiencies in vitamin C and zinc.