Article
Biochemistry & Molecular Biology
Natsumi Ogawa, Shingo Nakajima, Kenya Tamada, Natsuki Yokoue, Haruki Tachibana, Miwa Okazawa, Takahiro Oyama, Hideaki Abe, Hiroaki Yamazaki, Atsushi Yoshimori, Akira Sato, Takanori Kamiya, Takehiko Yokomizo, Fumiaki Uchiumi, Takehiko Abe, Sei-ichi Tanuma
Summary: The spasmolytic drug trimebutine has shown potential as an anti-inflammatory agent in experiments, reducing the production of various proinflammatory factors and significantly decreasing mortality in a mouse model of sepsis. Studies have found that trimebutine exerts its anti-inflammatory effects by inhibiting TLR signaling pathways and NF-kappa B activity.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Cardiac & Cardiovascular Systems
Yanan Zhang, Jimin Wu, Erdan Dong, Zhanli Wang, Han Xiao
Summary: Toll-like receptors (TLRs) are important in innate immune response, identifying pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). They play a role in cardiac hypertrophy, which contributes to heart failure. Targeting TLR signaling may be effective against pathological cardiac hypertrophy, making it necessary to study TLR mechanisms in this process.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Medicine, Research & Experimental
Lianghui Zhan, Jingru Zheng, Jianbiao Meng, Danting Fu, Lisha Pang, Chunlian Ji
Summary: This study found that TLR4 deficiency can reduce inflammatory responses and apoptosis, improve intestinal damage, regulate intestinal flora, and alleviate LPS-induced intestinal barrier dysfunction.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Zhen Wang, Menglin Liu, Di Ye, Jing Ye, Menglong Wang, Jianfang Liu, Yao Xu, Jishou Zhang, Mengmeng Zhao, Yongqi Feng, Shuwan Xu, Wei Pan, Zhen Luo, Dan Li, Jun Wan
Summary: The study revealed an upregulation of Il12a in septic patients, while Il12a deletion exacerbated sepsis-induced cardiac dysfunction and injury mainly by affecting macrophage activity and the NF-κB signaling pathway. The findings suggest Il12a as a potential target for treating sepsis-induced cardiac dysfunction.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Immunology
Niloofar Deravi, Mohadeseh Poudineh, Marzieh Pirzadeh, Hanie Yavarpour-Bali, Hoda Mehrabi, Gisou Erabi, Amene Saghazadeh, Nima Rezaei
Summary: Endothelial cells play a critical role in innate immune and inflammatory responses, and Toll-like receptors (TLRs) are key in activating innate mechanisms in ECs. Endothelial dysfunction may lead to tissue damage in various diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Saahithh Redddi Patlola, Gary Donohoe, Declan P. McKernan
Summary: Toll-like receptors (TLRs) are pattern recognition receptors that protect the brain from self and foreign antigens/pathogens and can elicit a harmful or beneficial immune response. TLR activation has been associated with neurodegenerative diseases and cytokine imbalance in schizophrenia. This review explores the current literature on TLRs, their potential role in schizophrenia pathogenesis, factors affecting TLR activity and their impact on cognitive performance in schizophrenia.
Review
Immunology
Mengyuan Kou, Liying Wang
Summary: This review focuses on Toll-like receptor 9 (TLR9), an important intracellular pattern recognition receptor in the immune system. TLR9 can recognize CpG DNA in endosomes, but it can also be expressed on the membrane surface of certain immune and non-immune cells, where it plays an immunomodulatory role. This review provides a theoretical reference for the application of TLR9 modulators.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Rennan Guo, Jingjing Wang, Wen Tang, Dong Xiao
Summary: This study reveals that Rnf144b plays a role in preventing inflammatory responses and cardiac dysfunction in sepsis. Up-regulation of Rnf144b expression in septic patients and its deficiency leading to exacerbated inflammatory cytokine production and impaired TBK1 activation suggest its protective functions.
Review
Biochemistry & Molecular Biology
Katrin Colleselli, Anna Stierschneider, Christoph Wiesner
Summary: While inflammation is crucial for human survival in response to infection and injury, prolonged inflammation can be fatal. Toll-like receptors (TLRs) are important in initiating inflammatory processes, and TLR2, in particular, has been extensively studied and known to recognize a wide range of pathogens through heterodimerization. However, many unanswered questions still remain about the mechanisms of TLR2 in both health and disease. This review provides an up-to-date overview of TLR2, including its homo- and heterodimers, and discusses its pro- and anti-inflammatory properties and recent findings in infectious and neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Patricia G. G. Valles, Andrea Fernanda Gil Lorenzo, Rodrigo D. D. Garcia, Valeria Cacciamani, Maria Eugenia Benardon, Valeria Victoria Costantino
Summary: Acute kidney injury (AKI) is a common and devastating condition with no effective pharmacological treatment. Toll-like receptor 4 (TLR4) and its ligands play a crucial role in the pathogenesis of AKI by mediating inflammatory responses. Excessive activation of TLR4 can lead to chronic inflammation. This review discusses the role of TLR4 in ischemic/reperfusion-induced AKI and sepsis-associated AKI, as well as its potential signaling patterns in kidney injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Arturo Orlacchio, Pellegrino Mazzone
Summary: Pancreatic cancer is a lethal form of cancer characterized by its aggressiveness and metastatic potential. Toll-like receptors play a pivotal role in inflammation and immune response, and can be potential targets for cancer therapy. Studies have shown that TLRs play an important role in the progression of pancreatic cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Ao Wei, Jingjing Liu, Dihua Li, Yanmin Lu, Lei Yang, Yuzhen Zhuo, Wencong Tian, Hongliang Cong
Summary: The study demonstrated that syringaresinol (SYR) exerts a protective effect on sepsis-induced cardiac dysfunction through the ER/SIRT1/NLRP3/GSDMD pathway. These findings provide a new insight into the treatment of sepsis-induced cardiac dysfunction.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Patrick Thon, Katharina Rump, Annika Knorr, Birte Dyck, Dominik Ziehe, Matthias Unterberg, Hartmuth Nowak, Lars Bergmann, Alexander Wolf, Maha Bazzi, Jennifer Orlowski, Marcus Peters, Alexander Zarbock, Thorsten Brenner, Michael Adamzik, Tim Rahmel, Bjoern Koos
Summary: We established a diagnostic assay to quantify the phosphorylation of TLR-4, which can be used in both cell culture and clinical samples of sepsis patients, enabling large-scale stratification of sepsis patients based on their TLR-4 activation status.
Article
Cardiac & Cardiovascular Systems
Denitsa Meteva, Ramona Vinci, Claudio Seppelt, Youssef S. Abdelwahed, Daniela Pedicino, Gregor Nelles, Carsten Skurk, Arash Haghikia, Ursula Rauch-Kroehnert, Teresa Gerhardt, Elisabeth Straessler, Yingjie Zhao, Felix Golla, Michael Joner, Himanshu Rai, Adelheid Kratzer, Hector Giral Arnal, Giovanna Liuzzo, Jens Klotsche, Filippo Crea, Ulf Landmesser, David M. Leistner, Nicolle Kraenkel
Summary: This study identified distinct Toll-like receptor 2 (TLR2)-mediated neutrophil activation in patients with acute coronary syndrome (ACS) and an intact fibrous cap (IFC-ACS). The activation was triggered by elevated levels of soluble hyaluronic acid and resulted in the release of active matrix metalloproteinase 9 (MMP9), promoting endothelial cell loss-triggered thrombosis.
EUROPEAN HEART JOURNAL
(2023)
Article
Medicine, Research & Experimental
Ai Tanaka, Kohei Anada, Masataka Yasue, Takuya Honda, Hiroyuki Nakamura, Toshihiko Murayama
Summary: Changes in sphingolipid metabolism in the brain can affect various cellular functions. In this study, we investigated the roles of CerK and C1P in multiple sclerosis. Our results showed that CerK knockout improved motor dysfunction and demyelination in a multiple sclerosis mouse model. Additionally, CerK knockout also had an impact on gender differences in mice.
Article
Biotechnology & Applied Microbiology
Anjana Jeyaram, Tek N. Lamichhane, Sheng Wang, Lin Zou, Eshan Dahal, Stephanie M. Kronstadt, Daniel Levy, Babita Parajuli, Daphne R. Knudsen, Wei Chao, Steven M. Jay
Article
Multidisciplinary Sciences
Feng Wu, Jian-Ying Wang, Wei Chao, Carrie Sims, Rosemary Ann Kozar
SCIENTIFIC REPORTS
(2020)
Article
Critical Care Medicine
Kerri Lopez, Andrew Suen, Yang Yang, Sheng Wang, Brittney Williams, Jing Zhu, Jiang Hu, Gary Fiskum, Alan Cross, Rosemary Kozar, Catriona Miller, Lin Zou, Wei Chao
Summary: The study demonstrated that exposure to hypobaria after polytrauma worsened cardiac dysfunction and endothelial injury, indicating a potential physiological second hit following traumatic injury.
Article
Biochemistry & Molecular Biology
Fengqian Chen, Lin Zou, Brittney Williams, Wei Chao
Summary: TLRs play an important role in host defense against pathogens, but targeting them for sepsis treatment has yielded mixed clinical trial results. Future sepsis treatments will need to consider the complexity of sepsis pathogenesis and the heterogeneity of septic patients for more effective interventions.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Immunology
Jerod Brammer, Myeongjin Choi, Scott M. Baliban, Adrienne R. Kambouris, Gary Fiskum, Wei Chao, Kerri Lopez, Catriona Miller, Yousef Al-Abed, Stefanie N. Vogel, Raphael Simon, Alan S. Cross
Summary: This study showed that infection with Pseudomonas aeruginosa following a burn injury significantly increased mortality in mice, with detection of bacteria in distal organs, elevated levels of proinflammatory cytokines, and a significant increase in serum HMGB1 concentrations associated with postburn mortality. Treatment with a peptide inhibitor of HMGB1 increased survival time, indicating a potential therapeutic target for reducing postburn mortality.
INFECTION AND IMMUNITY
(2021)
Article
Critical Care Medicine
Briana K. Shimada, Liron Boyman, Weiliang Huang, Jing Zhu, Yang Yang, Fengqian Chen, Maureen A. Kane, Nagendra Yadava, Lin Zou, W. Jonathan Lederer, Brian M. Polster, Wei Chao
Summary: This study identified a broad mitochondrial protein remodeling, inactivation of pyruvate dehydrogenase (PDH), and impaired pyruvate-fueled oxidative phosphorylation during sepsis-induced cardiomyopathy. These findings provide a molecular framework for further exploration and understanding of the pathogenesis of sepsis-induced cardiomyopathy.
Article
Immunology
Lin Zou, Junyun He, Lili Gu, Rami A. Shahror, Yun Li, Tuoxin Cao, Sheng Wang, Jing Zhu, Huang Huang, Fengqian Chen, Xiaoxuan Fan, Junfang Wu, Wei Chao
Summary: The study found that sepsis survivors may develop encephalopathy and neurological dysfunction, which are associated with extracellular miRNAs and the TLR7 sensor. Experimental results showed that sepsis can lead to BBB disruption, excessive neuroinflammatory responses in the brain, and impaired motor coordination and neurological function in neurobehavioral testing.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Critical Care Medicine
Jerod Brammer, Gideon Wolf, Scott M. Baliban, Jessica C. Allen, Myeongjin Choi, Adrienne R. Kambouris, Raphael Simon, Gary Fiskum, Wei Chao, Kerri Lopez, Catriona Miller, Nevil J. Singh, Alan S. Cross
Summary: The World Health Organization estimates that around 180,000 deaths occur annually due to burn-related injuries. Many survivors of burn traumas ultimately die from bacterial infections that cause sepsis during treatment. This study provides evidence for the first time that a fluid-filled pocket, called subeschar seroma, forms postburn even in the absence of infection, and it supports the growth of Pseudomonas aeruginosa (PA) bacteria and contains inflammatory cytokines and chemokines. The recruitment of immature immune cells to the seroma may contribute to the sequestration of critical immune cells and promote PA-mediated sepsis.
JOURNAL OF BURN CARE & RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Huang Huang, Jing Zhu, Lili Gu, Jiang Hu, Xiujing Feng, Weiliang Huang, Sheng Wang, Yang Yang, Ping Cui, Shao-Hsuan Lin, Andrew Suen, Briana K. Shimada, Brittney Williams, Maureen A. Kane, Yunbo Ke, Chen-Ou Zhang, Anna A. Birukova, Konstantin G. Birukov, Wei Chao, Lin Zou
Summary: Research demonstrates that TLR7 activation can induce pulmonary inflammation and endothelial barrier disruption through sensing extracellular miR-146a-5p, thus contributing to sepsis-associated acute respiratory distress syndrome.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Critical Care Medicine
Ahmad Zeineddin, Feng Wu, Wei Chao, Lin Zou, Roumen Vesselinov, Amanda M. Chipman, Jing Fei Dong, Huang Huang, Shibani Pati, Rosemary A. Kozar
Summary: This study demonstrates that miR-19b and syndecan-1 are biomarkers for endothelial dysfunction independent of resuscitation. There is no strong correlation between miR-19b and syndecan-1 or outcomes. Admission syndecan-1 remains a strong prognostic marker, but its elevation over time suggests a versatile role following hemorrhagic shock that requires further investigation.
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
(2022)
Article
Biochemistry & Molecular Biology
Alex Eli Pottash, Daniel Levy, Anjana Jeyaram, Leo Kuo, Stephanie M. Kronstadt, Wei Chao, Steven M. Jay
Summary: Extracellular vesicles (EVs) are promising therapeutic entities that can regulate multiple signaling pathways in target cells. Among the components of EVs, microRNAs (miRNAs) are commonly implicated and associated with EV-induced biological phenomena. This study utilized sonication to load multiple miRNAs in HEK293T EVs and found that a combination of miR-146a, miR-155, and miR-223 had the most potential in anti-inflammatory outcomes.
Article
Medicine, Research & Experimental
Weihua Ding, Lukas Fischer, Qian Chen, Ziyi Li, Liuyue Yang, Zerong You, Kun Hu, Xinbo Wu, Xue Zhou, Wei Chao, Peter Hu, Tewodros Mulugeta Dagnew, Daniel M. Dubreuil, Shiyu Wang, Suyun Xia, Caroline Bao, Shengmei Zhu, Lucy Chen, Changning Wang, Brian Wainger, Peng Jin, Jianren Mao, Guoping Feng, Mark T. Harnett, Shiqian Shen
Summary: Cortical neural dynamics mediate information processing for the cerebral cortex, playing a crucial role in various biological processes and diseases. Spontaneous pain in neuropathic pain activates a specific area within the primary somatosensory cortex, resulting in synchronized neural dynamics. Manipulating the cortical network or applying clinically effective pain therapies can attenuate this synchronization and alleviate pain-like behavior.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Critical Care Medicine
Jerod Brammer, Gideon Wolf, Scott M. Baliban, Jessica C. Allen, Myeongjin Choi, Adrienne R. Kambouris, Raphael Simon, Gary Fiskum, Wei Chao, Kerri Lopez, Catriona Miller, Nevil J. Singh, Alan S. Cross
Summary: The World Health Organization estimates that approximately 180,000 deaths occur annually from burn-related injuries, with bacterial infections leading to sepsis as the main cause of death. While advancements in burn care continue in high-income countries, low and middle-income countries still face high frequencies of burn injuries and deaths.
JOURNAL OF BURN CARE & RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Stephanie M. Kronstadt, Alex E. Pottash, Daniel Levy, Sheng Wang, Wei Chao, Steven M. Jay
Summary: EVs, as nanosized cell-derived particles, play critical roles in regulating sepsis pathophysiology and have demonstrated anti-inflammatory, anti-apoptotic, and immunomodulatory effects in sepsis models. Future sepsis therapies may involve using EVs to enhance and control therapeutic effects.
ADVANCED THERAPEUTICS
(2021)