Article
Biology
Shasha Xu, Yu Zhang, Xingjie Liu, Huisheng Liu, Xinya Zou, Linlin Zhang, Jing Wang, Zhiwei Zhang, Xiang Xu, Mingxia Li, Kairui Li, Shuyue Shi, Ying Zhang, Zhichao Miao, Jie Zha, Yong Yu
Summary: In this study, researchers identified four subsets of innate lymphoid cells (ILC2s) in the mouse acute inflammatory lung and found a distinct activation subset, marked by the transcription factor Nr4a1, which paradoxically expresses both tissue-resident memory T cell and effector/central memory T cell signature genes. They also discovered that programmed cell death protein-1 (PD-1) negatively modulates the activation of Nr4a1+ILC2s. The findings suggest that activated ILC2s are a heterogenous population and provide insights into the role of PD-1 in modulating the activity of ILC2s.
Review
Medicine, General & Internal
E. J. de Fraiture, N. Vrisekoop, L. P. H. Leenen, K. J. P. van Wessem, L. Koenderman, F. Hietbrink
Summary: Infections in trauma patients can lead to high morbidity and mortality rates. Understanding the functions and characteristics of neutrophils, the key cells in the inflammatory cascade after trauma, is important for the development of effective treatments. Recent advances in analyzing neutrophil phenotype and function have made it possible to identify patients at risk for infectious complications, allowing for timely interventions to be made.
FRONTIERS IN MEDICINE
(2022)
Article
Immunology
Xijie Dong, Chuntao Wang, Xinghua Liu, Xiangjun Bai, Zhanfei Li
Summary: Severe trauma disrupts immune homeostasis and leads to fluctuation in circulating immune-cell count. Study found that alterations in circulating immune-cell count within 7 days post-trauma are related to subsequent sepsis and mortality.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Bert A. 't Hart, Antonio Luchicchi, Geert J. Schenk, Joep Killestein, Jeroen J. G. Geurts
Summary: Multiple sclerosis is a significant neurological disease in young adults, with medications targeting the immune system showing satisfactory results for relapsing MS but carrying serious adverse effects. There is still a high unmet need for safe and effective drugs for progressive MS patients. The poor predictive validity of MS animal models in translating pathogenic mechanisms into treatments has led to calls for improvement in these models.
Article
Biochemistry & Molecular Biology
Angelantonio Maglio, Carolina Vitale, Corrado Pelaia, Maria D'Amato, Luigi Ciampo, Eliana Sferra, Antonio Molino, Giulia Pelaia, Alessandro Vatrella
Summary: In this observational multicenter retrospective study, the effectiveness of mepolizumab and benralizumab in severe asthmatics treated for 12 months in a real-life setting was evaluated. The study found that 30.12% of patients on mepolizumab and 40% of patients on benralizumab achieved disease remission after 12 months. These results confirm the efficacy of anti-IL-5 biologic drugs in the treatment of severe eosinophilic asthma in a real-life setting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Surgery
Getasha D. Doobay, Elizabeth S. Miller, Camille G. Apple, Tyler J. Loftus, Kolenkode B. Kannan, Philip A. Efron, Alicia M. Mohr
Summary: This study showed that propranolol could reduce the expression of HMGB1, G-CSF, and neutrophil elastase, resulting in a decreased mobilization of hematopoietic progenitor cells in response to chronic stress and trauma.
JOURNAL OF SURGICAL RESEARCH
(2021)
Article
Public, Environmental & Occupational Health
Arielle Kaim, Moran Bodas, Dan Bieler, Irina Radomislensky, Gerrit Matthes, Adi Givon, Heiko Trentzsch, Christian Waydhas, Rolf Lefering
Summary: This study compared the performance of trauma registries in Germany and Israel. The results showed significant differences between the two registries, with German trauma patients having higher injury severity, greater need for intensive care, and higher mortality rate. Further research is needed to uncover similarities and differences between the two trauma systems.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Public, Environmental & Occupational Health
Jafar Bakhshaie, James Doorley, Mira Reichman, Ryan Mace, David Laverty, Paul E. Matuszewski, A. Rani Elwy, Amirreza Fatehi, Lucy C. Bowers, Thuan Ly, Ana-Maria Vranceanu
Summary: The study aimed to develop a mind-body program for patients with acute orthopedic injuries and explored the barriers and facilitators of implementing the program in three orthopedic trauma centers. Lack of knowledge and comfort addressing psychosocial factors, organizational cultures, and limited resources were identified as major barriers, while fitting with clinic structure and patients' basic needs were found to be facilitators. Recommendations to enhance implementation included providing knowledge/tools for providers, streamlining recruitment procedures, creating a learning collaborative, tailoring the study protocol, and dedicating research staff.
TRANSLATIONAL BEHAVIORAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Susana Rojo-Tolosa, Maria Victoria Gonzalez-Gutierrez, Gonzalo Jimenez-Galvez, Jose Antonio Sanchez-Martinez, Laura Elena Pineda-Lancheros, Jose Maria Galvez-Navas, Alberto Jimenez-Morales, Cristina Perez-Ramirez, Concepcion Morales-Garcia
Summary: This study aimed to evaluate the clinical improvement of patients with severe uncontrolled asthma (SUA) treated with anti-interleukin 5 (IL5) therapies and search for biomarkers associated with the treatment response. The results showed significant improvements in asthma control, lung function, and the use of oral corticosteroids after 12 months of treatment with IL5 biological therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Nicholas A. Schmitz, Ritesh P. Thakare, Chun-Shiang Chung, Chang-Min Lee, Jack A. Elias, Chun Geun Lee, Brian W. LeBlanc
Summary: The study found that Chit1 plays a counterproductive role in interfering with fungal clearance, with chitobiose potentially impairing neutrophil function and increasing the burden of Candida in the kidney.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Moe Takemura, Masaya Yamaguchi, Momoko Kobayashi, Tomoko Sumitomo, Yujiro Hirose, Daisuke Okuzaki, Masayuki Ono, Daisuke Motooka, Kana Goto, Masanobu Nakata, Narikazu Uzawa, Shigetada Kawabata
Summary: The gene bgaA in Streptococcus pneumoniae has been identified as a multifunctional virulence factor that affects glycan metabolism, bacterial adherence, and resistance to neutrophil-mediated killing. Deletion of bgaA reduces bacterial association with human cells and enhances neutrophil-mediated killing in human blood. In a mouse sepsis model, the absence of bgaA leads to increased host immune response, suppressed tissue damage, and blood coagulation. Therefore, BgaA could be a potential target for drug design and vaccine development against pneumococcal infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Lisa Wrba, Rebecca Halbgebauer, Julian Roos, Markus Huber-Lang, Pamela Fischer-Posovszky
Summary: Despite efforts to improve patient outcomes, trauma remains a significant issue in clinical practice and society, particularly among younger individuals. Adipose tissue plays an essential role in regulating the posttraumatic inflammatory response, both through its secretory products and as an immune target of injured remote organs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Allergy
Genevieve Pelletier, Krystelle Godbout, Marie-Eve Boulay, Louis-Philippe Boulet, Mathieu C. Morissette, Andreanne Cote
Summary: This study investigates the increase in FeNO levels in a subgroup of severe asthma patients after initiation of anti-IL5/IL5R therapy. The results showed that although FeNO levels increased temporarily, it did not affect clinical outcomes. Further research is needed to understand the underlying mechanisms.
JOURNAL OF ASTHMA AND ALLERGY
(2022)
Review
Immunology
Natalie K. Boyd, Chengwen Teng, Christopher R. Frei
Summary: Drug repurposing is an alternative method to traditional drug discovery processes, utilizing the potential of existing drugs to improve drug development efficiency.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Genetics & Heredity
Chiara De Luca, Anuj S. Gupta, Alex Bortvin
Summary: Although animals have developed TE-targeting defenses, LINE-1 still thrives in humans and mice. ORF1p interacts with TE RNAs, genic mRNAs, and stress granule proteins. ORF1p also associates with the CCR4-NOT deadenylation complex and PRKRA, without affecting the stability and translation of LB-localized mRNAs. The study shows that PRKRA elevates ORF1p levels and LINE-1 retrotransposition.
Article
Critical Care Medicine
Todd O. McKinley, Greg E. Gaski, Ruben Zamora, Li Shen, Qing Sun, Rami A. Namas, Timothy R. Billiar, Yoram Vodovotz
Summary: Recent studies have shown that early analysis of dynamic immune response coordination can differentiate patients who are significantly tolerant or sensitive to hemorrhage.
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
(2021)
Article
Surgery
Anthony Cyr, Yanjun Zhong, Steven E. Reis, Rami A. Namas, Andrew Amoscato, Brian Zuckerbraun, Jason Sperry, Ruben Zamora, Yoram Vodovotz, Timothy R. Billiar
Summary: Metabolomic analysis revealed significant alterations in circulating plasma sphingolipids following blunt trauma, with different sphingolipid patterns associated with clinical outcomes and inflammatory mediators.
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
(2021)
Article
Immunology
Lukas Schimunek, Haley Lindberg, Maria Cohen, Rami A. Namas, Qi Mi, Jinling Yin, Derek Barclay, Fayten El-Dehaibi, Andrew Abboud, Ruben Zamora, Timothy Robert Billiar, Yoram Vodovotz
Summary: Systemic inflammation following traumatic injury leads to immune dysregulation and multiple organ dysfunction. By studying inflammatory responses in 227 blunt trauma survivors, three distinct endotypes were identified with significant differences in mechanical ventilation requirement, ventilation duration, and MOD. Correlations between IL-17A and other cytokines suggested a role for type 3 immunity in systemic inflammation after injury.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Tianmeng Chen, Matthew J. Delano, Kong Chen, Jason L. Sperry, Rami A. Namas, Ashley J. Lamparello, Meihong Deng, Julia Conroy, Lyle L. Moldawer, Philip A. Efron, Patricia Loughran, Christopher Seymour, Derek C. Angus, Yoram Vodovotz, Wei Chen, Timothy R. Billiar
Summary: The immune response after trauma was investigated using single-cell RNA sequencing, revealing significant changes in gene expression in monocytes in both mice and humans. Human CD14(+) monocytes were classified into 6 signatures, defining two subtypes of trauma patients with differences in recovery, organ dysfunction, and complications. These subtypes were also observed in burn and sepsis patients, indicating a shared immune response pattern in critical illness.
Article
Multidisciplinary Sciences
Nabil Azhar, Rami A. Namas, Khalid Almahmoud, Akram Zaaqoq, Othman A. Malak, Derek Barclay, Jinling Yin, Fayten El-Dehaibi, Andrew Abboud, Richard L. Simmons, Ruben Zamora, Timothy R. Billiar, Yoram Vodovotz
Summary: The study analyzed time course data on multiple inflammatory mediators in the blood of blunt trauma patients and proposed a new control architecture for systemic inflammation. A logical model was created to test this hypothesis, predicting key qualitative features of systemic inflammation in patient sub-groups.
SCIENTIFIC REPORTS
(2021)
Review
Pharmacology & Pharmacy
Matthew A. Borrelli, Heth R. Turnquist, Steven R. Little
Summary: Cardiovascular disease is the leading cause of death worldwide, with myocardial infarction as a significant precipitating event. Recent studies have focused on developing novel biologic delivery systems to effectively treat myocardial infarction, emphasizing sustained or targeted release of biologics. Future developments include targeting the immune system through soluble factor or chemokine delivery, and advancing delivery systems to facilitate synergistic delivery of biologics.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Editorial Material
Immunology
Craig A. Byersdorfer, Heth R. Turnquist
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Gaelen K. Dwyer, Louise M. D'Cruz, Heth R. Turnquist
Summary: Our understanding of the functions of IL-33 in homeostasis and immunity is constantly evolving. IL-33 plays a crucial role in both regulation and the development of inflammatory diseases. It directs a network of key cells that are involved in tissue development, homeostasis, and repair.
ANNUAL REVIEW OF IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Tianmeng Chen, Julia Conroy, Xinjun Wang, Michelle Situ, Rami A. Namas, Yoram Vodovotz, Wei Chen, Harinder Singh, Timothy R. Billiar
Summary: This study investigated the relationship between transcriptomic patterns and open chromatin patterns in circulating leukocytes from trauma patients. The study found that gene expression patterns associated with global epigenetic changes in leukocytes are correlated with worse outcomes in trauma, burns, and sepsis.
Review
Biochemistry & Molecular Biology
Kassandra J. Baron, Heth R. Turnquist
Summary: Based on successful preclinical animal transplant models, adoptive cell therapy with regulatory T cells (Tregs) shows promise in inducing allograft tolerance or reducing the need for immunosuppressive drugs in transplant recipients. Clinical evaluations have shown the ability to expand Tregs ex vivo and safely infuse them in large numbers. However, these trials have not yet achieved drug-free tolerance or significant reduction in immunosuppression needed for solid organ transplant (SOTx) rejection. Strategies to improve Treg therapy effectiveness may involve increasing Treg persistence or orchestrating Treg migration. This review discusses current clinical Treg manufacturing methods and highlights strategies to improve Treg persistence and migration in preclinical studies.
Article
Multidisciplinary Sciences
Raphael J. Crum, Brydie R. Huckestien, Gaelen Dwyer, Lisa Mathews, David G. Nascari, George S. Hussey, Heth R. Turnquist, John F. Alcorn, Stephen F. Badylak
Summary: Cytokine storm is a life-threatening inflammatory syndrome characterized by elevated proinflammatory cytokines and immune cell hyperactivation. Matrix-bound nanovesicles (MBV) have been shown to down-regulate proinflammatory immune responses. This study assessed the efficacy of MBV in a murine model of influenza-induced acute respiratory distress syndrome and cytokine storm. Intravenous administration of MBV decreased total lung inflammatory cell density, proinflammatory macrophages, and cytokines following viral inoculation, while also increasing the proportion of activated anti-viral T cells. These findings suggest that MBV has immunomodulatory properties that may be beneficial in treating viral-mediated pulmonary inflammation, including diseases such as SARS-CoV-2.
Meeting Abstract
Cell & Tissue Engineering
M. C. Cramer, L. Mathews, G. Hussey, W. Schwarzmann, V. Soman, J. Sembrat, M. Rojas, C. McTiernan, U. Chandran, H. Turnquist, S. F. Badylak
TISSUE ENGINEERING PART A
(2022)
Article
Medicine, Research & Experimental
Gaelen K. Dwyer, Lisa R. Mathews, Jose A. Villegas, Anna Lucas, Anne Gonzalez de Peredo, Bruce R. Blazar, Jean-Philippe Girard, Amanda C. Poholek, Sanjiv A. Luther, Warren Shlomchik, Heth R. Turnquist
Summary: In allogeneic hematopoietic stem cell transplantation (alloHCT), recipient conditioning releases damage-associated molecular patterns (DAMPs) that generate proinflammatory antigen-presenting cells (APCs) secreting IL-12, which drives the response of donor Th1 cells, leading to graft-versus-host disease (GVHD). However, there are other mechanisms through which alloreactive T cell responses are initiated by directly acting on donor CD4(+) T cells. Among these mechanisms, fibroblastic reticular cell-derived DAMP IL-33 plays a critical role by enhancing T cell expansion and differentiation through the activation of T cell signaling pathways in response to alloantigen, resulting in GVHD.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Cell Biology
Junru Wu, Yoram Vodovotz, Sultan Abdelhamid, Francis X. Guyette, Michael B. Yaffe, Danielle S. Gruen, Anthony Cyr, David O. Okonkwo, Upendra K. Kar, Neha Krishnamoorthi, Robert G. Voinchet, Isabel M. Billiar, Mark H. Yazer, Rami A. Namas, Brian J. Daley, Richard S. Miller, Brian G. Harbrecht, Jeffrey A. Claridge, Herbert A. Phelan, Brian S. Zuckerbraun, Par Johansson, Jakob Stensballe, James H. Morrissey, Russell P. Tracy, Stephen R. Wisniewski, Matthew D. Neal, Jason L. Sperry, Timothy R. Billiar
Summary: Trauma is a major cause of death and morbidity worldwide. The analysis of a longitudinal multi-omic dataset from severely injured humans revealed systemic stormpatterns and consumption patterns, as well as two human injury response endotypes. Prehospital thawed plasma is found to rescue traumatic brain injury patients of one endotype, with Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) identified as the most predictive circulating biomarker.
CELL REPORTS MEDICINE
(2021)
Article
Critical Care Medicine
Jinman Cai, Todd McKinley, Isabel Billiar, Mazen S. Zenati, Greg Gaski, Yoram Vodovotz, Danielle S. Gruen, Timothy R. Billiar, Rami A. Namas
Summary: The study revealed that severe injuries are associated with the suppression of certain cytokines known for their tissue protection and regeneration effects, which correlates with adverse clinical outcomes. Thus, the relationship between injury severity and inflammatory mediators diverges with increasing ISS.
TRAUMA SURGERY & ACUTE CARE OPEN
(2021)