Article
Biochemistry & Molecular Biology
Jonas Nimphy, Sara Ibrahim, Rania Dayoub, Marion Kubitza, Michael Melter, Thomas S. Weiss
Summary: Inflammasomes and innate immune cells contribute to liver injury by activating Kupffer cells and releasing cytokines including IL-6, IL-1β, and TNFα. ALR, a hepatotropic co-mitogen, has anti-oxidative and anti-apoptotic properties and attenuates NAFLD and cholestasis. The expression of ALR is reduced in NAFLD and cholestasis, but the regulation mechanisms are not fully understood. This study revealed that IL-1β reduces ALR expression through decreased Egr-1 binding and diminished HNF4a expression, independent of c-Jun activation. This suggests that IL-1β may contribute to disease progression in NAFLD and cholestatic liver injury by lowering ALR levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Li -Li Huang, Fei-Yang Luo, Wen-Qi Huang, Hui Guo, Qi Liu, Ling Zhang, Ai-Shun Jin, Hang Sun
Summary: This study investigated the role and mechanism of action of augmenter of liver regeneration (ALR) in hepatocellular carcinoma (HCC) using in vitro and in vivo models. The results showed that ALR-specific monoclonal antibody can inhibit tumor growth in nude mice and suppress HCC cell proliferation. Therefore, ALR-specific monoclonal antibody may be a novel therapy for HCC.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Review
Gastroenterology & Hepatology
Alok Kumar Verma, Akanksha Sharma, Nithyananthan Subramaniyam, Chandrashekhar R. Gandhi
Summary: Augmenter of liver regeneration (ALR) is a protein that is expressed more abundantly in the liver than other organs. It plays important roles in protein folding, cytochrome c reductase activity, and protein Fe/S maturation. ALR deficiency in hepatocytes leads to oxidative stress, impaired ATP synthesis, and increased apoptosis/necrosis. Individuals with one functional ALR allele may be susceptible to disorders involving compromised mitochondrial function.
JOURNAL OF HEPATOLOGY
(2022)
Review
Pharmacology & Pharmacy
Yuan Dong, Yuejie Zhang, Yingmei Feng, Wei An
Summary: Non-alcoholic fatty liver disease (NAFLD) affects a quarter of the global population and can be alleviated and protected against by the augmenter of liver regeneration (ALR), a key factor in liver regulation and lipid metabolism.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Yue-Juan Liao, Yi-Xin Ma, Li-Li Huang, Zheng Zhang, Fang-Yan Tan, Li-Li Deng, Dan Cao, Xu-Jia Zeng, Gui-Quan Yu, Xiao-Hui Liao
Summary: This study demonstrates the important role of augmenter of liver regeneration (ALR) in acute kidney injury (AKI) and its inhibitory effect on necroptosis caused by ischemia-reperfusion. ALR overexpression reduces the expression of injury molecules and inflammation-associated factors, as well as inhibits the expression of necroptosis-related proteins. These findings suggest that ALR has a protective effect against AKI and regulate necroptosis.
Article
Medicine, Research & Experimental
Juan Jose Cabrera-Galvan, Eduardo Araujo, Mercedes de Mirecki-Garrido, David Perez-Rodriguez, Borja Guerra, Haidee Aranda-Tavio, Miguel Guerra-Rodriguez, Yeray Brito-Casillas, Carlos Melian, Maria Soledad Martinez-Martin, Leandro Fernandez-Perez, Carlota Recio
Summary: SOCS2 plays a crucial role in the progression of hepatocellular carcinoma (HCC), and its deficiency increases the risk of developing chemically-induced HCC and is associated with the regulation of oncogenic and inflammatory responses mediated by STAT5 and STAT3. Therefore, SOCS2 may serve as an attractive target molecule and potential biomarker for HCC treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Dongju Zhu, Jie Zhong, Xuefeng Gong, Xiang Wu
Summary: Mitochondrial damage leads to increased ROS production, activating the inflammasome and causing AKI. Mitophagy plays a protective role in AKI by regulating mitochondrial quality and reducing ROS production. ALR reduces mtROS production and NLRP3 inflammasome activation through the PINK1/Parkin mitophagy pathway, alleviating IR-induced apoptosis.
Article
Biochemistry & Molecular Biology
Mingzhe Zheng, Ziwei Ai, Yuanyuan Guo, Yujiao Chen, Ping Xie, Wei An
Summary: This study reveals the critical role of augmenter of liver regeneration (ALR) in the progression of hepatocellular carcinoma (HCC) driven by nonalcoholic steatohepatitis (NASH). By regulating ALR ubiquitination-mediated degradation, the balance of mitochondrial dynamics is disrupted, leading to impaired oxidative phosphorylation and ATP synthesis, and promoting the transition of hepatocytes from steatosis to malignant HCC phenotype.
Article
Biochemistry & Molecular Biology
Suzan Abdu, Nouf Juaid, Amr Amin, Mohamed Moulay, Nabil Miled
Summary: This study investigated the therapeutic effects of the phytochemical crocin alone or in combination with sorafenib in rats induced with hepatocellular carcinoma (HCC) and in human liver cancer cell line (HepG2). The results showed that the combination treatment of crocin and sorafenib had significant therapeutic effects in reducing liver toxicity, impeding HCC development, and improving liver functions.
Article
Cell & Tissue Engineering
Yuan Dong, Weining Kong, Wei An
Summary: Cell-based therapeutic approaches have shown to be effective in treating acute liver injury, but face limitations including stemness loss, aberrant differentiation, and low engraftment. Transplanting ALR-transfected LEPCs into ALI mice significantly protected against injury, reducing ALT and AST levels and inflammation, highlighting potential for clinical therapy.
Article
Chemistry, Applied
Malka M. Samra, Muhammad Asim Raza Basra
Summary: In this study, two new meloxicam complexes with Mg(II) and Sr(II) were synthesized and characterized. The complexes showed effective biological activities and enhanced safety index. The Mg(II) complex demonstrated the highest inhibitory effects in inflammation and analgesic assays, and showed higher potential to bind with proteins and cleave DNA compared to meloxicam alone. Molecular docking analysis suggested the Mg(II) complex had the highest anti-inflammatory effect.
APPLIED ORGANOMETALLIC CHEMISTRY
(2023)
Article
Oncology
Jing Zhang, Sili Chen, Ye Li, Weichun Xiao, Wei An
Summary: Both lfALR and sfALR protect mitochondria by promoting PINK1/Parkin-dependent mitophagy through FOXO3a activation, indicating a novel mechanism for mitochondrial protection.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Chemistry, Physical
Elisa Fiume, Dilshat U. Tulyaganov, Avzal Akbarov, Nigora Ziyadullaeva, Andrea Cochis, Alessandro C. Scalia, Lia Rimondini, Enrica Verne, Francesco Baino
Summary: The study characterizes a novel silicate bioactive glass with good cytocompatibility and strong pro-osteogenic properties in vitro and in vivo. Implantation of the glass induced clear osteogenic effects at the defect site, with complete resorption of the material and formation of new tissue observed after 3 months.
Article
Gastroenterology & Hepatology
Chunyan Liu, Lintao Wang, Mengzhen Xu, Yajie Sun, Zhen Xing, Junfeng Zhang, Chunming Wang, Lei Dong
Summary: This study successfully transformed the spleen into a liver-like organ by directly reprogramming the splenic fibroblasts into hepatocytes. This method, which does not require cell or tissue transplantation, provides a potential therapeutic approach for the treatment of end-stage liver diseases.
Review
Biochemistry & Molecular Biology
Vikas Sud, Andrew Abboud, Samer Tohme, Yoram Vodovotz, Richard L. Simmons, Allan Tsung
Summary: Acute inflammation is essential for tissue repair, but excessive inflammation can be detrimental. IL-17A plays a crucial role in acute inflammation, especially following surgery, sepsis, or traumatic injury. Further research on IL-17A in acute inflammation may lead to new therapeutic approaches.
Article
Gastroenterology & Hepatology
Hamza O. Yazdani, Christof Kaltenmeier, Kristin Morder, Juik Moon, Madelyn Traczek, Patricia Loughran, Ruben Zamora, Yoram Vodovotz, Feng Li, James H-C. Wang, David A. Geller, Richard L. Simmons, Samer Tohme
Summary: Exercise training preconditioning mitigates the inflammatory response to liver ischemia/reperfusion injury, protecting the liver from injury and metastases. By reducing neutrophil infiltration and NET formation, exercise training alters the complexity of hepatic inflammatory mediator networks and promotes an increase in tumor-suppressing T cells within the tumor microenvironment.
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
Immunology
Erica L. Heipertz, Jourdan Harper, Dinesh G. Goswami, Charlie A. Lopez, Jose Nellikappallil, Ruben Zamora, Yoram Vodovotz, Wendy E. Walker
Summary: IRF3 plays a detrimental role in sepsis, with IRF3-KO mice being protected in a relevant model. The role of IRF3 primarily affects IL-6-related inflammatory programs.
JOURNAL OF IMMUNOLOGY
(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
Biochemistry & Molecular Biology
Jillian Bonaroti, Sultan Abdelhamid, Upendra Kar, Jason Sperry, Ruben Zamora, Rami Ahmd Namas, Todd McKinley, Yoram Vodovotz, Timothy Billiar
Summary: The immune response following trauma plays a crucial role in clinical outcomes, with excessive or sustained inflammation potentially leading to organ damage. Studying the dynamic patterns of immune mediator responses in human trauma is essential for understanding the pathophysiology of traumatic injury.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Oncology
Asmita Chopra, Ruben Zamora, Yoram Vodovotz, Jacob C. Hodges, Derek Barclay, Randall Brand, Richard L. Simmons, Kenneth K. Lee, Alessandro Paniccia, Pranav Murthy, Michael T. Lotze, Brian A. Boone, Amer H. Zureikat
Summary: Baseline inflammatory profiles are associated with response to neoadjuvant therapy in pancreatic ductal adenocarcinoma (PDAC), and an upregulated inflammatory status is associated with a poor response to NAT. Further analysis into the role of inflammatory mediators as predictors of chemotherapy response is warranted.
JOURNAL OF IMMUNOTHERAPY
(2021)
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)
Article
Immunology
Ali Mubin Aral, Ruben Zamora, Derek Barclay, Jinling Yin, Fayten El-Dehaibi, Vasil E. Erbas, Liwei Dong, Zhaoxiang Zhang, Huseyin Sahin, Vijay S. Gorantla, Yoram Vodovotz
Summary: This study used a systems biology approach to investigate the effects of tacrolimus on inflammatory networks in vascularized composite allotransplantation (VCA). Results revealed the significant roles of specific mediators such as interleukin-1β, interleukin-18, and interleukin-6 in different tissues after TAC treatment. Statistical analysis showed significant alterations in 24/27 inflammatory mediators between control and TAC-treated groups over time in peripheral blood, skin, and/or muscle. Virtual VCA and Virtual Animal analyses identified the skin as a key control point of dynamic inflammatory networks.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ruben Zamora, Sangeeta Chavan, Theodoros Zanos, Richard L. Simmons, Timothy R. Billiar, Yoram Vodovotz
Summary: The study used network analysis to define the spatiotemporal dynamics of 20 LPS-induced inflammatory mediators in different organs of mice, suggesting varying levels of TLR4 dependence in inflammation across different tissues. The computational analyses provided insights into the role of TLR4-dependent tumor necrosis factor in early inflammation, followed by interleukin-17A in later stages, potentially derived from specific T cell populations.
MOLECULAR MEDICINE
(2021)
Article
Oncology
Lena Vodovotz, Ruben Zamora, Derek A. Barclay, Yoram Vodovotz, Jinling Yin, Julie Bitner, John Florida, Efthymios D. Avgerinos, Ulka Sachdev
Summary: The study aimed to investigate the role of inflammation in superficial venous reflux in varicose veins using computational network modeling and measurement of immune mediators in plasma. Results showed significant differences in age, BMI, and clinical severity scores between groups. Plasma concentrations of most cytokines were lower in patients than in control subjects, while certain chemokines were higher in patients. Interleukin (IL)-17A and interferon gamma were found to be more interconnected in venous insufficiency, suggesting a potential role for pathogenic Th17 cells in varicose veins.
ANNALS OF TRANSLATIONAL MEDICINE
(2021)
Article
Immunology
Ashti M. Shah, Ruben Zamora, Sebastian Korff, Derek Barclay, Jinling Yin, Fayten El-Dehaibi, Timothy R. Billiar, Yoram Vodovotz
Summary: Trauma/hemorrhagic shock followed by resuscitation leads to inflammation and organ dysfunction, with TLR4 playing a role in binding damage-associated molecular pattern molecules. TLR4-null mice showed more localized expression of inflammatory mediators compared to wild type mice. IL-17A showed positive correlations with GM-CSF, IL-10, and TNF in the kidney and gut.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Raphael J. Crum, Scott A. Johnson, Peng Jiang, Jayati H. Jui, Ruben Zamora, Devin Cortes, Mangesh Kulkarni, Archana Prabahar, Jennifer Bolin, Eric Gann, Eric Elster, Seth A. Schobel, Dale Larie, Chase Cockrell, Gary An, Bryan Brown, Milos Hauskrecht, Yoram Vodovotz, Stephen F. Badylak
Summary: The comprehensive analysis of wound healing process in a novel canine model of VML, compared with a nine-patient cohort of combat-associated VML, provides a translational framework and model system for future studies investigating novel therapies for human VML.
TISSUE ENGINEERING PART A
(2022)
Article
Cardiac & Cardiovascular Systems
Katherine M. Reitz, Andrew D. Althouse, Daniel E. Forman, Brian S. Zuckerbraun, Yoram Vodovotz, Ruben Zamora, Robert L. Raffai, Daniel E. Hall, Edith Tzeng
Summary: This article introduces a study on the effect of metformin on non-diabetic patients, with the aim of evaluating its impact on patients' functional status, vascular disease progression, systemic inflammation, and more.
BMC CARDIOVASCULAR DISORDERS
(2023)
Review
Medicine, Research & Experimental
Ashti M. Shah, Ruben Zamora, Yoram Vodovotz
Summary: A systematic review explores the role of interleukin (IL)-17A in acute inflammatory diseases and suggests that it is centrally involved in inflammation propagation. Using biological network analysis and computational methodologies, IL-17A is implicated in the cross-tissue spread of inflammation, partly regulated by neural mechanisms. The study also proposes a possible link between chronic inflammation and IL-17A-mediated acute inflammation, indicating that insights from computational modeling of acute inflammatory diseases may aid in the diagnosis and treatment of chronic inflammation.
WIRES MECHANISMS OF DISEASE
(2023)