Review
Medicine, Research & Experimental
Jing Wen, Dale Creaven, Xiangshu Luan, Jiemin Wang
Summary: Immunotherapy, including immunostimulation and immunosuppression, has made significant progress in the past decade. Immunostimulation has been proven effective in anti-cancer treatment, while immunosuppression is used to treat autoimmune diseases and inflammation. The use of extracellular vesicle-based immunotherapy, with newly-invented simplified isolation methods and potent triggered immune responses, has gained attention. However, more balanced research on the three main types of extracellular vesicles (exosomes, microvesicles, and apoptotic bodies) is needed. This article summarizes the current status and possible mechanisms of immunotherapies based on each type of vesicle. The apoptotic body shows promising potential in immunosuppressive and anti-inflammatory therapies.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Cell & Tissue Engineering
Qinyu Ma, Mengmeng Liang, Yutong Wu, Fei Luo, Zaisong Ma, Shiwu Dong, Jianzhong Xu, Ce Dou
Summary: The study identified the molecular profile of apoptotic bodies (ABs) derived from osteoclasts at different differentiation stages, showing marked differences in protein cargo and high similarity to parental cells. Functionally, pOC-ABs promoted endothelial progenitor cell differentiation and endothelial cell formation, while mOC-ABs induced osteogenic differentiation of mesenchymal stem cells and facilitated osteogenesis via RANKL reverse signaling, highlighting the important biological roles of ABs in coupling bone formation with resorption during bone remodeling.
Article
Cell Biology
Tao Jiang, Yanmin Xia, Wenzhe Wang, Jinbo Zhao, Wenhao Liu, Shiyu Liu, Songtao Shi, Bei Li, Xiaoning He, Yan Jin
Summary: Apoptotic bodies (ABs) released by transplanted human umbilical cord MSCs (UC-MSCs) convert macrophages from a pro-inflammatory to an anti-inflammatory state, ameliorating acute lung injury (ALI) in a mouse model. This effect is mediated by the interaction between programmed cell death 1 ligand 1 (PDL1) on UC-MSCs-derived ABs and programmed cell death protein 1 (PD1) on host macrophages, leading to the reprogramming of macrophage metabolism. The potential clinical implications of developing therapeutic strategies for ALI patients are suggested.
CELL PROLIFERATION
(2023)
Review
Biochemistry & Molecular Biology
Irina V. Kholodenko, Roman V. Kholodenko, Alexander G. Majouga, Konstantin N. Yarygin
Summary: It has been found that transplanted mesenchymal stem cells can undergo rapid apoptosis and be cleared by host cells while still exhibiting therapeutic effects. These effects may be mediated by the phagocytosis of apoptotic stem cells by host cells. This review focuses on the functions and therapeutic mechanisms of apoptotic mesenchymal stem cells and mesenchymal stem cell-derived apoptotic bodies.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jianwei Liu, Hui Xue, Shilei Bai, Jie Wang, Yue Zhang, Liu Liu, Lei Zhang, Zhao Yang, Kui Wang
Summary: With recent advances in immunotherapy, particularly PD-1 inhibitors, the treatment of hepatocellular carcinoma patients has reached a new stage. However, there are few reports on spontaneous bacterial peritonitis (SBP) after PD-1 inhibitor therapy in intermediate-to-advanced stage HCC. This article presents two clinical cases of SBP after successful PD-1 inhibitor therapy, highlighting the need for close monitoring and early treatment of SBP in patients with large or giant HCC and large tumor diameter.
Article
Biotechnology & Applied Microbiology
Irene Barguilla, Ugutz Unzueta, Jose Vicente Carratala, Olivia Cano-Garrido, Antonio Villaverde, Alba Hernandez, Neus Ferrer-Miralles
Summary: Bacterial inclusion bodies (IBs) are protein complexes that appear under stress conditions and recent research has shown their potential as biomaterials for cell growth promotion. In this study, the cytotoxicity, oxidative stress, and genotoxicity of different protein formats were analyzed in eukaryotic cells. The results demonstrate that natural IBs and soluble protein nanoparticles are non-toxic materials for eukaryotic cells.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Sun Woong Kim, Jun Sik Yoon, Junyong Park, Yong Jin Jung, Jae Seung Lee, Jisoo Song, Han Ah Lee, Yeon Seok Seo, Minjong Lee, Jin Myung Park, Dae Hee Choi, Moon Young Kim, Seong Hee Kang, Jin Mo Yang, Do Seon Song, Sung Won Chung, Minseok Albert Kim, Hee Joon Jang, Hyunwoo Oh, Cheol-Hyung Lee, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Jeong-Hoon Lee
Summary: Empirical treatment with carbapenem does not reduce in-hospital mortality compared to treatment with TGCs for patients with a first presentation of SBP. However, among critically ill patients with high CLIF-SOFA scores, empirical carbapenem treatment was significantly associated with lower in-hospital mortality than TGCs.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Hae-Seul Choi, Kwang-Hyun Baek
Summary: Apoptosis is a structured cell death process involving cell morphology and biochemical changes, and the ubiquitin-proteasome system regulates the protein levels. Targeting UPS enzymes and controlling proteasomal degradation of apoptotic proteins could be a unique approach for cancer treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Chemistry, Multidisciplinary
Min Zhou, Yong-Jiang Li, Yu-Cheng Tang, Xin-Yan Hao, Wen-Jie Xu, Da-Xiong Xiang, Jun-Yong Wu
Summary: Extracellular vesicles (EVs), including apoptotic bodies (ABs), have emerged as promising candidates for various biomedical applications. ABs, derived from parent cells during the final stages of apoptosis, possess diverse sources and stable morphological features. They accommodate more functional biomolecules due to their larger volume and exhibit advantageous interactions with recipient cells through their predominant body surface ratio. ABs hold great potential in modulating and alleviating symptoms of numerous diseases, and have also been applied in disease diagnosis, immunotherapy, regenerative therapy, and drug delivery.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemical Research Methods
Adria Lopez-Cano, Paula Sicilia, Clara Gaja, Anna Aris, Elena Garcia-Fruitos
Summary: Recombinant protein production in bacteria often leads to the formation of inclusion bodies (IBs). While strategies to minimize aggregation have been developed, many heterologous proteins still form aggregates. The detergent NLS is effective in solubilizing proteins from IBs, but its impact on protein quality has not been evaluated. This study compared the activity of antimicrobial proteins solubilized with NLS from IBs to those solubilized without detergent, and found that protein activity was impaired by NLS. The results suggest that the solubilization protocol used for IBs can impact the final protein quality.
Article
Gastroenterology & Hepatology
Marika Haderer, Philip Neubert, Eva Rinner, Annika Scholtis, Lucile Broncy, Heidi Gschwendtner, Arne Kandulski, Vlad Pavel, Alexander Mehrl, Christoph Brochhausen, Sophie Schlosser, Karsten Guelow, Claudia Kunst, Martina Mueller
Summary: In patients with liver cirrhosis, thinning of colonic mucus allows bacteria to come into contact with epithelial cells, leading to degradation of cell junctions. Patient-derived SBP-inducing bacteria exhibit a novel bacterial protease activity responsible for cleaving E-cadherin structures.
Article
Multidisciplinary Sciences
Matyas Abel Tsegaye, Jianping He, Kyle McGeehan, Ireland M. Murphy, Mati Nemera, Zachary T. Schafer
Summary: The anti-apoptotic protein c-FLIP shows downregulation in tumor tissue compared to adjacent normal tissue, suggesting potential distinct roles apart from its canonical function. Detachment from extracellular matrix (ECM) signals an elevation in c-FLIP transcription, while oncogenic signaling blocks this increase. Downregulation of c-FLIP promotes luminal filling in mammary acini and inhibits colony formation in cancer cells exposed to ECM-detachment, indicating a context-dependent role for c-FLIP during tumorigenesis.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Jingru Huangfu, Caili Hao, Zongbo Wei, I. Michael Wormstone, Hong Yan, Xingjun Fan
Summary: The study reveals that cFLIP is a critical gene regulating lens epithelial cell survival, with an important impact on the response to TNF alpha stimulation.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Junjie Gou, Hongjiao Li, Jingjing Bi, Xingchen Pang, Xiang Li, Yi Wang
Summary: Cytosine arabinoside (Ara-C) is a standard therapeutic agent for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, drug resistance remains a clinical problem. This study found that apoptotic bodies (ABs) from Ara-C-induced cells carried IGF2BP3, which promoted cell survival by activating signaling pathways. High levels of IGF2BP3 in ABs from MDS/AML patients were associated with poor overall survival.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Analytical
Emma B. Hartnett, Mengli Zhou, Yi-Nan Gong, Yu-Chih Chen
Summary: The study developed a label-free method to classify cell death status using machine learning and image processing. It enables the precise categorization of live, apoptotic, and necrotic cells and allows for tracking the time dynamics of cell death process, enhancing the understanding of cell death regulation at the molecular level.
ANALYTICAL CHEMISTRY
(2022)
Review
Cell Biology
Sergio D. Catz, Kenneth R. McLeish
JOURNAL OF LEUKOCYTE BIOLOGY
(2020)
Article
Urology & Nephrology
Michael L. Merchant, Michelle T. Barati, Dawn J. Caster, Jessica L. Hata, Liliane Hobeika, Susan Coventry, Michael E. Brier, Daniel W. Wilkey, Ming Li, Ilse M. Rood, Jeroen K. Deegens, Jack F. Wetzels, Christopher P. Larsen, Jonathan P. Troost, Jeffrey B. Hodgin, Laura H. Mariani, Matthias Kretzler, Jon B. Klein, Kenneth R. McLeish
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2020)
Article
Cell Biology
Ferenc Kolonics, Erika Kajdacsi, Veronika J. Farkas, Daniel S. Veres, Delaram Khamari, Agnes Kittel, Michael L. Merchant, Kenneth R. McLeish, Akos M. Lorincz, Erzsebet Ligeti
Summary: Extracellular vesicles (EVs) play important roles in intercellular communication, with both anti-inflammatory and proinflammatory effects. These vesicles are customizable based on environmental factors, including reducing reactive oxygen, increasing cytokines, activating endothelial cells, and promoting coagulation.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Anjali A. Satoskar, John P. Shapiro, Mikayla Jones, Cherri Bott, Samir V. Parikh, Sergey V. Brodsky, Lianbo Yu, Haikady N. Nagaraja, Daniel W. Wilkey, Michael L. Merchant, Jon B. Klein, Tibor Nadasdy, Brad H. Rovin
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Adrienne Bushau-Sprinkle, Michelle T. Barati, Kenneth B. Gagnon, Syed Jalal Khundmiri, Kathleen Kitterman, Bradford G. Hill, Amanda Sherwood, Michael Merchant, Shesh N. Rai, Sudhir Srivastava, Barbara Clark, Leah Siskind, Michael Brier, Jessica Hata, Eleanor Lederer
Article
Medicine, General & Internal
Dawn J. Caster, Erik A. Korte, Michael L. Merchant, Jon B. Klein, Michelle T. Barati, Ami Joglekar, Daniel W. Wilkey, Susan Coventry, Jessica Hata, Brad H. Rovin, John B. Harley, Bahram Namjou-Khales, Kenneth R. McLeish, David W. Powell
Summary: Research suggests that autoantibodies targeting podocyte and glomerular cell proteins may contribute to the development of immune complex formation in lupus nephritis.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Samantha M. Morrissey, Anne E. Geller, Xiaoling Hu, David Tieri, Chuanlin Ding, Christopher K. Klaes, Elizabeth A. Cooke, Matthew R. Woeste, Zachary C. Martin, Oscar Chen, Sarah E. Bush, Huang-Ge Zhang, Rodrigo Cavallazzi, Sean P. Clifford, James Chen, Smita Ghare, Shirish S. Barve, Lu Cai, Maiying Kong, Eric C. Rouchka, Kenneth R. McLeish, Silvia M. Uriarte, Corey T. Watson, Jiapeng Huang, Jun Yan
Summary: COVID-19 patients exhibit a population of low-density inflammatory neutrophils expressing intermediate levels of CD16, which play a role in the associated coagulopathy, systemic inflammation, and ARDS. Monitoring the frequency of this LDN subset in the circulation may serve as an adjunct clinical marker for disease status and progression, as it is associated with D-dimer, ferritin, IL-6, and TNF-alpha levels.
Article
Biochemistry & Molecular Biology
Julien Vitry, Guillaume Pare, Andrea Murru, Xavier Charest-Morin, Halim Maaroufi, Kenneth R. McLeish, Paul H. Naccache, Maria J. Fernandes
Summary: CLEC12A is a myeloid inhibitory receptor that negatively regulates inflammation in mouse models of autoimmune and autoinflammatory arthritis. The cysteines in the stalk domain of CLEC12A differentially modulate the expression, oligomerisation, and signaling of this inhibitory receptor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Guillaume Pare, Julien Vitry, Michael L. Merchant, Myriam Vaillancourt, Andrea Murru, Yunyun Shen, Sabine Elowe, Mireille H. Lahoud, Paul H. Naccache, Kenneth R. McLeish, Maria J. Fernandes
Summary: CLEC12A modulates neutrophil activation and cytokine production through a specific signaling pathway, potentially serving as a therapeutic target for inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Andras Kallai, Marta Kelemen, Noemi Molnar, Adrienn Tropotei, Balazs Hauser, Zsolt Ivanyi, Janos Gal, Erzsebet Ligeti, Katalin Kristof, Akos M. Lorincz
Summary: The study developed a flow cytometry-based antibiotic susceptibility testing (AST) method, which can produce reliable results a workday earlier than the traditional microdilution method. Results showed that the method is able to detect bacterial growth accurately after 4 hours of incubation, with high consistency compared to the microdilution method.
MICROBIOLOGY SPECTRUM
(2021)
Article
Immunology
Kenneth R. McLeish, Rejeena Shrestha, Aruna Vashishta, Madhavi J. Rane, Michelle T. Barati, Michael E. Brier, Mario Gutierrez Lau, Xiaoling Hu, Oscar Chen, Caitlin R. Wessel, Travis Spalding, Sarah E. Bush, Kenechi Ijemere, C. Danielle Hopkins, Elizabeth A. Cooke, Shweta Tandon, Terri Manning, Silvia M. Uriarte, Jiapeng Huang, Jun Yan
Summary: Neutrophil subsets in COVID-19 patients have distinct functional capabilities, with severe cases showing enhanced phagocytosis and degranulation, while low density neutrophils exhibit impaired functions. These findings contribute to a better understanding of the pathology of COVID-19.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Kenneth R. McLeish, Maria J. Fernandes
Summary: This article introduces the response mechanism of neutrophils to invading pathogens or injured cells and the molecular mechanisms that regulate their response. Among them, inhibitory receptors are a mechanism of response control that interrupts intracellular signaling pathways to control the response of neutrophils. As inhibitory receptors, CLEC12A and DCIR exhibit different molecular and functional mechanisms and are associated with different diseases.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Urology & Nephrology
Jessica R. Gooding, Shipra Agrawal, Susan McRitchie, Zach Acuff, Michael L. Merchant, Jon B. Klein, William E. Smoyer, Susan J. Sumner, John Mahan, Hiren Patel, Richard F. Ransom, Cynthia Pan, Denis F. Geary, Myra L. Chang, Keisha L. Gibson, Franca M. Iorember, Patrick D. Brophy, Tarak Srivastava, Larry A. Greenbaum
KIDNEY INTERNATIONAL REPORTS
(2020)
Article
Urology & Nephrology
Shipra Agrawal, Michael L. Merchant, Jiro Kino, Ming Li, Daniel W. Wilkey, Adam E. Gaweda, Michael E. Brier, Melinda A. Chanley, Jessica R. Gooding, Susan J. Sumner, Jon B. Klein, William E. Smoyer, John Mahan, Hiren Patel, Richard F. Ransom, Cynthia Pan, Denis F. Geary, Myra L. Chang, Keisha L. Gibson, Franca M. Iorember, Patrick D. Brophy, Tarak Srivastava, Larry A. Greenbaum
KIDNEY INTERNATIONAL REPORTS
(2020)
