Article
Biophysics
Andressa R. Pereira, Flavio M. Shimizu, Osvaldo N. Oliveira Jr
Summary: The composition of Langmuir monolayers, specifically the relative concentration of cholesterol, plays a crucial role in modulating the effects of the antineoplastic drug paclitaxel. The dependence on cholesterol concentration for these monolayers simulating lipid rafts is non-monotonic, affecting surface pressure and compressibility modulus differently. The physiological action of paclitaxel may vary depending on its interaction with membrane penetration or membrane elasticity changes.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2021)
Article
Chemistry, Analytical
Minggang Tian, Yaru Sun, Xiuqi Kong, Baoli Dong
Summary: Studying the phase separation of ER membranes is crucial for understanding the fundamental biology of ER. However, NIR ratiometric imaging of ER phase behaviors has not been explored in living cells and diverse tissues. In this study, we developed a polarity-responsive NIR fluorescent probe to visualize the phase behavior in ER membranes and revealed different phase behaviors in different tissues.
ANALYTICAL CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Bin Du, Wanying Zhu, Lili Yu, Yuehua Wang, Mei Zheng, Jingshu Huang, Guopeng Shen, Jie Zhou, Hanchun Yao
Summary: This study synthesized nanoparticles to target drug-resistant cells by modifying them with α-tocopherol polyethylene glycol 2000 succinate (TPGS(2k)). The nanoparticles co-loaded with doxorubicin (DOX) and simvastatin (SV) were designed to deplete cholesterol in lipid rafts, inhibit drug efflux, and re-sensitize drug-resistant cells to DOX. The research shows promising results for using these nanoparticles as a new strategy to combat drug resistance.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Maria Blaszczyk, Agata Koziol, Anna Palko-Labuz, Kamila Sroda-Pomianek, Olga Wesolowska
Summary: Cholesterol is an important component of mammalian cell membranes, and together with sphingomyelin, it forms lipid rafts, which play a role in signal transduction. Altered cholesterol levels are associated with various diseases. This study investigated compounds that affect cellular cholesterol homeostasis. These compounds were found to be cytotoxic to colon cancer cells and decreased cellular cholesterol levels. The interaction of these compounds with model membranes was visualized, and certain compounds were found to affect the size and shape of lipid domains. The importance of membrane interactions for the anticancer potency of these compounds, especially betulin derivatives, was suggested.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Article
Biochemistry & Molecular Biology
Elizabeth Dustin, Edna Suarez-Pozos, Camryn Stotesberry, Shulan Qiu, Juan Pablo Palavicini, Xianlin Han, Jeffrey L. Dupree
Summary: 3-O-sulfogalactosylceramide, or sulfatide, is reduced in the normal appearing white matter (NAWM) in Multiple Sclerosis (MS), suggesting a role in the disease progression. Previous studies have shown the essential role of sulfatide in myelin and axonal integrity, and in the stable tethering of myelin proteins. In this study, using an adult-onset model of sulfatide depletion, progressive axonal degeneration with myelin sparing is observed, and the anchoring of neurofascin155, a myelin paranodal protein, is found to be sulfatide-dependent. These findings indicate that sulfatide depletion can trigger axonal degeneration independent of demyelination.
Article
Biochemistry & Molecular Biology
Orsolya Geda, Tamas Tabi, Peter P. Lakatos, Eva Szoko
Summary: This study investigated the effects of DIMEB, HPBCD, RAMEA, and HPACD on ganglioside and cholesterol levels in rat brain synaptosomes. HPBCD showed selective cholesterol depletion capability, while RAMEA and HPACD selectively depleted gangliosides.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
V. N. Nesterov, E. S. Bogdanova, O. A. Rozentsvet
Summary: The study investigated the lipid composition and fatty acids in detergent-resistant membranes of chloroplasts and mitochondria in salt-accumulating halophyte plants of the Amaranthaceae family, Salicornia perennans and Suaeda salsa. The composition of lipids in detergent-resistant membranes differed from total lipids, mainly in the abundance of cerebrosides and sterols. Under salt stress, there was a significant increase in the relative content of cerebrosides in detergent-resistant chloroplast membranes of S. perennans and detergent-resistant mitochondrial membranes of S. salsa, while the relative content of sterols decreased. These results indicate the involvement of detergent-resistant membranes in the interaction of chloroplasts and mitochondria in the cellular response of halophytes to salinity.
RUSSIAN JOURNAL OF PLANT PHYSIOLOGY
(2023)
Article
Biology
Zixuan Yuan, Mahmud Arif Pavel, Hao Wang, Jerome C. Kwachukwu, Sonia Mediouni, Joseph Anthony Jablonski, Kendall W. Nettles, Chakravarthy B. Reddy, Susana T. Valente, Scott B. Hansen
Summary: The study reveals that hydroxychloroquine (HCQ) inhibits the entry of SARS-CoV-2 virus through two distinct mechanisms, which are influenced by tissue cholesterol levels. This finding provides new insights into the potential use of HCQ in clinical settings.
COMMUNICATIONS BIOLOGY
(2022)
Article
Virology
Naoyuki Iida, Madoka Kawahara, Riku Hirota, Yoshio Shibagaki, Seisuke Hattori, Yuko Morikawa
Summary: The cell-cell contact between HIV-1-infected and uninfected cells forms a virological synapse (VS) to allow for efficient HIV-1 transmission. Mass spectrometry revealed the recruitment of various molecules, including ATP-related enzymes, protein translation factors, and charged multivesicular body protein 4B, to the VS. Further exploration showed that vimentin plays a role in HIV-1 transmission through the recruitment of CD4 to the cell-cell interface.
Review
Cell Biology
Bor Luen Tang
Summary: Cholesterol plays important structural and regulatory roles in animal cells, and is crucial for post-injury axon regrowth. Depletion and inhibition of cholesterol synthesis can enhance axon regeneration, possibly by interfering with axon growth inhibitory signals and enhancing neuronal survival signaling processes.
NEURAL REGENERATION RESEARCH
(2022)
Article
Biology
Anna Olivieri, Rebecca S. Lee, Federica Fratini, Cyrianne Keutcha, Mudit Chaand, Valentina Mangano, Francesco Celani, Stefania Mochi, Cecilia Birago, Silvio Paone, Felicia Grasso, Valentina Tirelli, Mario Falchi, Estela Shabani, Stefania Bertoncini, Bienvenu Sodiomon Sirima, Elisabetta Pizzi, David Modiano, Manoj T. Duraisingh, Marta Ponzi
Summary: The study utilizes the floating properties of microdomain-associated proteins to identify a host protein, ART4, crucial for Plasmodium falciparum invasion. It further confirms the role of microdomains in the process of malaria parasite infection.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Micaela G. Fosdick, Pratik Rajesh Chheda, Phuong M. Tran, Alex Wolff, Ronal Peralta, Michael Y. Zhang, Robert Kerns, Jon C. D. Houtman
Summary: This study explores the structural components of GML necessary for its suppression of human T cell activation through an extensive structure activity relationship analysis. It was found that an acyl chain with 12-14 carbons, a polar head group, an ester linkage, and a single laurate group at any position are all necessary for GML to inhibit protein clustering, calcium signaling, and cytokine production.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Physical
Jordan A. Doumanov, Kirilka Mladenova, Vesselina Moskova-Doumanova, Tonya D. Andreeva, Svetla D. Petrova
Summary: This article reviews the current understanding of hBest1 surface organization, interactions with membrane lipids in model membranes, and its association with microdomains of cellular membranes, which are important for modulation of channel activity in cells.
ADVANCES IN COLLOID AND INTERFACE SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Johanna Detzner, Gottfried Pohlentz, Johannes Muthing
Summary: This review discusses the clinical impact of Enterohemorrhagic Escherichia coli (EHEC) infections, focusing on the vesicular packaging of Shiga toxin (Stx) in the intestine and blood stream, as well as the extraintestinal complications and therapeutic options. The role of epithelial cells of the colon and kidneys in the infection process is also addressed. The review highlights the importance of Stx-binding glycosphingolipids (Gb3Cer and Gb4Cer) and their distribution in primary human kidney and colon epithelial cells. The susceptibility of primary renal and colonic epithelial cells to Stx is discussed, suggesting a resilience of the intestinal epithelium against the human-pathogenic Stx subtypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Anran Lu, Jing Yang, Xiangyu Huang, Xinmei Huang, Guihu Yin, Yiqin Cai, Xiuli Feng, Xiaofei Zhang, Yin Li, Qingtao Liu
Summary: This study investigated the role of vimentin and lipid metabolism in the replication of H9N2 avian influenza virus. It was found that disruption of vimentin and lipid rafts significantly inhibited viral infection. Furthermore, high cholesterol levels and low HMGCR phosphorylation levels were associated with viral replication. These findings provide potential targets for antiviral treatment against influenza viruses.
Article
Respiratory System
Peter Van Mourik, Paul van Haaren, Evelien Kruisselbrink, Cemil Korkmaz, Hettie M. Janssens, Karin M. de Winter-de Groot, Cornelis K. van der Ent, Marne C. Hagemeijer, Jeffrey M. Beekman
JOURNAL OF CYSTIC FIBROSIS
(2020)
Article
Immunology
Maaike Nederend, Arthur H. van Stigt, J. H. Marco Jansen, Shamir R. Jacobino, Sylvia Brugman, Cornelis A. M. de Haan, Louis J. Bont, R. J. Joost van Neerven, Jeanette H. W. Leusen
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Allergy
Inge Van de Walle, Karen Silence, Kevin Budding, Liesbeth Van de Ven, Kim Dijkxhoorn, Elisabeth de Zeeuw, Cafer Yildiz, Sofie Gabriels, Jean-Michel Percier, Johanna Wildemann, Jan Meeldijk, Peter J. Simons, Louis Boon, Linda Cox, Rob Holgate, Rolf Urbanus, Henny G. Otten, Jeanette H. W. Leusen, Christophe Blanchetot, Hans de Haard, C. Erik Hack, Peter Boross
Summary: ARGX-117 is a promising new complement inhibitor that uniquely targets both the classical and lectin pathways by binding to the Sushi-2 domain of C2. It prevents complement-mediated cytotoxicity in in vitro models for autoimmune hemolytic anemia and antibody-mediated rejection of organ transplants.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Niklas Baumann, Thies Roesner, J. H. Marco Jansen, Chilam Chan, Klara Marie Eichholz, Katja Klausz, Dorothee Winterberg, Kristina Mueller, Andreas Humpe, Renate Burger, Matthias Peipp, Denis M. Schewe, Christian Kellner, Jeanette H. W. Leusen, Thomas Valerius
Summary: The study shows that inhibiting glutaminyl cyclase can enhance the immunotherapeutic effects on tumor cells. Inhibition of glutaminyl cyclase reduces the specific signal of CD47 at the SIRP alpha binding site, leading to increased efficiency of tumor cell phagocytosis and ADCC reactions mediated by antibodies.
Article
Infectious Diseases
Arthur H. van Stigt, Katrien Oude Rengerink, Kitty W. M. Bloemenkamp, Wouter de Waal, Sabine M. P. J. Prevaes, Thuy-My Le, Femke van Wijk, Maaike Nederend, Anneke H. Hellinga, Christianne S. Lammers, Gerco den Hartog, Martijn J. C. van Herwijnen, Johan Garssen, Leon M. J. Knippels, Lilly M. Verhagen, Caroline G. M. de Theije, Alejandro Lopez-Rincon, Jeanette H. W. Leusen, Belinda Van't Land, Louis Bont
Summary: The PRIMA cohort aims to identify novel functions of components in human milk that are protective against respiratory tract infections and allergic diseases early in life through an observational, prospective, and multi-center birth study. It will provide new insights into immunomodulatory components in human milk by collecting and analyzing human milk samples in relation to clinical data.
BMC INFECTIOUS DISEASES
(2022)
Article
Oncology
Tassilo L. A. Wachsmann, Anne K. Wouters, Dennis F. G. Remst, Renate S. Hagedoorn, Miranda H. Meeuwsen, Eline van Diest, Jeanette Leusen, Jurgen Kuball, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: This study compared the activity of CAR T cells and engineered TCR T cells in targeting CD20 antigen, and found that CAR T cells were more potent in the short term but their expansion was impaired with increased antigen exposure, while eTCR T cells performed better under high antigenic pressure.
Article
Medicine, Research & Experimental
Alexander H. Staudacher, Vasilios Liapis, Nicole L. Wittwer, William Tieu, Hiu Chun Lam, Jeanette Leusen, Michael P. Brown
Summary: The interaction between Fc and Fc gamma R is not essential for the diagnostic or therapeutic applications of chDAB4 conjugates, as tumor-associated macrophages mainly respond to endogenous signals rather than functional expression of Fc gamma R during phagocytosis.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Immunology
Chilam Chan, Marta Lustig, Niklas Baumann, Thomas Valerius, Geert van Tetering, Jeanette H. W. Leusen
Summary: The expression of checkpoint molecules by tumor cells hampers the clinical responses to therapeutic antibodies. Myeloid checkpoint inhibition in combination with IgA-based treatment could significantly enhance IgA therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Niklas Baumann, Christian Arndt, Judith Petersen, Marta Lustig, Thies Roesner, Katja Klausz, Christian Kellner, Miriam Bultmann, Lorenz Bastian, Fotini Vogiatzi, Jeanette H. W. Leusen, Renate Burger, Denis M. Schewe, Matthias Peipp, Thomas Valerius
Summary: Antibody-based immunotherapy is increasingly used to treat acute lymphoblastic leukemia (ALL) patients. This study investigates the effects of CD38 antibodies, targeting T-ALL cells expressing CD38, on tumor cell killing through antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cell-mediated cytotoxicity (ADCC). The study shows that IgA2 variants of CD38 antibodies are more effective in killing tumor cells through myeloid cells. The interactions between CD47 and SIRP alpha negatively regulate ADCP and ADCC. Additionally, treatment with all-trans retinoic acid (ATRA) enhances CD38 expression and further enhances ADCP and ADCC.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Biliana Todorova, Ophelie Godon, Eva Conde, Caitlin M. Gillis, Bruno Iannascoli, Odile Richard-Le Goff, Daniel Fiole, Lubka T. Roumenina, Jeanette H. W. Leusen, Andrew J. Murphy, Lynn E. Macdonald, Laurent L. Reber, Friederike Joensson, Pierre Bruhns
Summary: In mouse models of active systemic anaphylaxis, IgG-allergen immune complexes predominantly accumulate in the lungs. The accumulation of allergens in the lungs does not rely on IgG receptors, complement component C1q, neutrophils, or macrophages. Neutrophils and monocytes recruited to the lungs capture high amounts of allergens, leading to downregulation of surface IgG receptors and activation.
JOURNAL OF IMMUNOLOGY
(2022)
Correction
Immunology
Chilam Chan, Marta Lustig, Niklas Baumann, Thomas Valerius, Geert Van Tetering, Jeanette H. W. Leusen
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Firas Hamdan, Michaela Feodoroff, Salvatore Russo, Manlio Fusciello, Sara Feola, Jacopo Chiaro, Gabriella Antignani, Francesca Greco, Jeanette Leusen, Erkko Ylosmaki, Mikaela Gronholm, Vincenzo Cerullo
Summary: Immune checkpoint inhibitors have shown clinical success in cancer treatment, but there is room for improvement. Researchers have developed an oncolytic adenovirus, Ad-Cab, to enhance the efficacy of PD-L1 checkpoint inhibitors. By adding somatic mutations to increase natural killer (NK) cell activation, they further improved the effectiveness of the therapy. The modified adenovirus demonstrated targeted release in the tumor microenvironment and better tumor killing.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Oncology
Marjolein C. Stip, J. H. Marco Jansen, Maaike Nederend, Maria Tsioumpekou, Mitchell Evers, Patricia A. Olofsen, Friederike Meyer-Wentrup, Jeanette H. W. Leusen
Summary: The transgenic mouse model expressing human Fc alpha RI is a valuable tool for studying the efficacy of IgA immunotherapy against infectious diseases and cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Cell Biology
Maria Tsioumpekou, Danielle Krijgsman, Jeanette H. W. Leusen, Patricia A. Olofsen
Summary: Neutrophils are important immune cells that make up 50-70% of the white blood cell population. In infection and cancer, neutrophil numbers increase due to the secretion of various substances by cells present in the inflamed tissue or tumor microenvironment. The function of neutrophils in cancer has gained attention, as they can have both pro-tumor and anti-tumor effects, depending on the cytokine environment in the tumor microenvironment.
Article
Medicine, Research & Experimental
Simone Mester, Mitchell Evers, Saskia Meyer, Jeannette Nilsen, Victor Greiff, Inger Sandlie, Jeanette Leusen, Jan Terje Andersen
Summary: In this study, it was demonstrated that ABD-fused IgA1 binds human FcRn pH-dependently and is rescued from cellular degradation in a receptor-specific manner in the presence of albumin. Furthermore, the presence of ABD led to an extended half-life of IgA1 in human FcRn transgenic mice, with the light chain fusion showing the longest half-life. The study suggests that an ABD, which does not interfere with albumin binding to human FcRn, may be used to extend the half-life of IgA.
