Article
Hematology
Natalia Colas-Algora, Pablo Munoz-Pinillos, Cristina Cacho-Navas, Jose Avendano-Ortiz, Gema de Rivas, Susana Barroso, Eduardo Lopez-Collazo, Jaime Millan
Summary: This study compared the responses of human lung microvascular endothelial cells to different inflammatory mediators and found that IL-6 and IL-1 beta play a major role in the pathological increase in permeability of the pulmonary microvasculature. Simultaneous inhibition of IL-1 and IL-6R can significantly alleviate the impact of cytokine storms on the pulmonary microvessels. These findings have important implications for finding the best anti-inflammatory treatments for critically ill acute respiratory distress syndrome patients.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Cell Biology
Longxiang Huang, Yuanjing Li, Zhe Cheng, Zi Lv, Suxin Luo, Yong Xia
Summary: Increased expression of PCSK9 during sepsis activates the TLR4/MyD88/NF-κB and NLRP3 pathways, inducing inflammation, vascular endothelial dysfunction, and decreased survival rates. Inhibition of PCSK9 may be a potential clinical therapeutic target to improve vascular endothelial function in sepsis.
Article
Medicine, Research & Experimental
Jie Luo, Mengyu Zhang, Zhaoxin Wang, Lei Yan, Yanhong Liu
Summary: This study found that patients with cerebral infarction had increased levels of anti-beta(2)GPI antibodies and increased expression of NLRP3 in neutrophils, suggesting a role for inflammatory cell death in this condition. It was determined that anti-beta(2)GPI/beta(2)GPI can induce neutrophil pyroptosis, leading to the release of IL-1 beta. The mechanism involves the double-stranded RNA-dependent protein kinase/p38MAPK/NLRP3 pathway. Pyroptotic neutrophils also release high mobility group box protein 1, which promotes inflammation in endothelial cells.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Vichuda Charoensaensuk, Yen-Chou Chen, Yun-Ho Lin, Keng-Liang Ou, Liang-Yo Yang, Dah-Yuu Lu
Summary: This study found that the extract THSG from Polygonum multiflorum Thunb. can alleviate the inflammatory response and cell apoptosis caused by P. gingivalis infection in brain endothelial cells. THSG exerts its inhibitory effects on NF-κB p65 and antiapoptotic properties through inhibiting the ROS pathway. The results suggest that THSG could be a potential herbal medicine to prevent the risk of developing cerebrovascular diseases from infection of periodontal bacteria.
Article
Biochemistry & Molecular Biology
Kuo Shen, Yanhui Jia, Xujie Wang, Jinxin Zhang, Kaituo Liu, Jing Wang, Weixia Cai, Jin Li, Shaohui Li, Ming Zhao, Yunchuan Wang, Dahai Hu
Summary: ADSCs exosomes can polarize macrophages to an anti-inflammatory phenotype by regulating the expression of Nrf2 and HO-1, improving inflammation and organ injury in sepsis models.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Immunology
Sarang Tartey, Prajwal Gurung, Rajendra Karki, Amanda Burton, Paul Hertzog, Thirumala-Devi Kanneganti
Summary: Studies have shown that SYK plays a crucial role in driving neutrophil infiltration and wound healing responses in Ptpn6(spin) mice, while deletion of Ets2 can ameliorate inflammatory skin diseases in these mice. Furthermore, Ets-2 drives IL-1 alpha-mediated inflammatory signaling in neutrophils of Ptpn6(spin) mice.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Immunology
John G. Noel, Seth W. Ramser, Lori Pitstick, Holly S. Goetzman, Elizabeth L. Dale, Andrew Potter, Mike Adam, S. Steven Potter, Jason C. Gardner
Summary: This study demonstrates that the burn wound is the primary source of G-CSF and IL-6 secretion, and their secretion is independent through an IL-1/MyD88-dependent mechanism. IL-1/MyD88 signaling mediates postburn anemia by inducing G-CSF and IL-6 secretion, leading to impaired medullary erythropoiesis and limiting the access of erythroid cells to iron. Neutralizing IL-1a/b antibodies attenuate features of postburn anemia and restore deficits caused by burn injury.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Min Hee Yang, In Jin Ha, Jae-Young Um, Kwang Seok Ahn
Summary: Albendazole has been shown to inhibit the activation of oncogenic transcription factors STAT3 and STAT5 in gastric cancer cells through multiple mechanisms, including suppressing phosphorylation of JAK1/2 and Src, increasing SHP-1 protein levels, and inducing an imbalance of GSH/GSSG leading to elevated levels of reactive oxygen species.
Article
Biochemistry & Molecular Biology
Shweta Khandibharad, Shailza Singh
Summary: In this study, we identified a phosphatase SHP-1 as a point of intervention of IL-10 and IL-12 reciprocity in leishmaniasis and designed synthetic peptides with high binding affinity.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Dhiraj Kumar Sah, Pham Ngoc Khoi, Shinan Li, Archana Arjunan, Jae-Uk Jeong, Young Do Jung
Summary: EGCG can inhibit the invasion ability of bladder cancer cells induced by IL-1β by suppressing the expression of uPAR through the inhibition of ERK1/2, JNK, AP-1, and NF-κB activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Critical Care Medicine
QiXing Chen, Yang Yang, XiaoLiang Wu, ShiYue Yang, Yan Zhang, Qiang Shu, XiangMing Fang
Summary: The study found that TREM-2 can prolong the survival of elderly septic patients by regulating the IL-23/IL-17A immune pathway, providing new therapeutic targets in sepsis.
Article
Cell Biology
Ahmed Shamloul, Gustav Steinemann, Kerrin Roos, Celine Huajia Liem, Jonathan Bernd, Thorsten Braun, Andreas Zakrzewicz, Janine Berkholz
Summary: The methyltransferase Smyd1 plays a crucial role in regulating IL-6 expression and secretion in endothelial cells by increasing NF-kappa B activity and promoting H3K4 trimethylation within the IL-6 promoter in response to LPS stimulation.
Article
Biochemistry & Molecular Biology
Nadeem Akhter, Ajit Wilson, Reeby Thomas, Fatema Al-Rashed, Shihab Kochumon, Areej Al-Roub, Hossein Arefanian, Ashraf Al-Madhoun, Fahd Al-Mulla, Rasheed Ahmad, Sardar Sindhu
Summary: IL-8/MCP-1 expression in adipose tissue is elevated in obesity. The synergistic effect of ROS/TNF-alpha can drive the expression of chemokines in monocytic cells, potentially through inducing ER stress, HIF1A stabilization, and signaling via NF-kappa B/ERK-1,2. NAC may have a therapeutic significance in inhibiting oxidative stress-driven IL-8/MCP-1 expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Claire E. Depew, Jordan A. Rixon, Stephen J. McSorley
Summary: Hepatic CD4 tissue-resident memory T cells (TRM) are crucial for protection against Salmonella infection, and a study has found that local inflammation in the liver enhances the formation of CD4 TRM. The researchers developed a system to directly visualize the formation of hepatic TRM and found that liver inflammation also boosts the effectiveness of a subunit Salmonella vaccine. Surprisingly, IL-2 and IL-1 were found to play a role in enhancing CD4 TRM formation. This knowledge is important for developing a more effective vaccine against invasive nontyphoidal salmonellosis (iNTS).
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Critical Care Medicine
Yuichi Akama, Eun Jeong Park, Naoko Satoh-Takayama, Arong Gaowa, Atsushi Ito, Eiji Kawamoto, Samuel Darkwah, Michael G. Appiah, Phyoe Kyawe Myint, Hiroshi Ohno, Hiroshi Imai, Motomu Shimaoka
Summary: This study reveals the role of ILC2s in lung injury in sepsis, showing a gradual restoration of IL-13 production in the lungs of sepsis mice. Despite the high expression of stimulatory receptors ST2 and inducible T-cell costimulator on ILC2s in sepsis, IL-13 production is reduced with high PD-1 inhibitory receptor expression.
Review
Medicine, General & Internal
Ha-Yeun Chung, Ralf A. Claus
Summary: The breakdown of sphingomyelin to ceramide by acid sphingomyelinase is tightly regulated during stress response, triggering immune response and tissue repair following severe infection. The secretion of the enzyme disrupts the biophysical context of cellular membranes, affecting the functional assembly and reorganization of proteins and receptors. Lysosomotropic agents could potentially act as inhibitors of this process.
FRONTIERS IN MEDICINE
(2021)
Review
Medicine, General & Internal
Ralf A. Claus, Markus H. Graeler
Summary: Sphingolipids are a highly diverse group of lipids with mass spectrometry being a valuable tool for their qualitative and quantitative identification, especially in biomedical applications. Therefore, considering the entire experimental strategy is crucial, from sample collection and preparation to data analysis and interpretation. Expert opinions suggest that mass spectrometry plays a key role in investigating cellular and compartment-specific stress responses, with the integration of multiple datasets being crucial for understanding human health and disease response.
FRONTIERS IN MEDICINE
(2021)
Article
Infectious Diseases
Christina Bahrs, Aurelia Kimmig, Sebastian Weis, Juliane Ankert, Stefan Hagel, Jens Maschmann, Andreas Stallmach, Andrea Steiner, Michael Bauer, Wilhelm Behringer, Michael Baier, Miriam Kesselmeier, Cora Richert, Florian Zepf, Martin Walter, Andre Scherag, Michael Kiehntopf, Bettina Loffler, Mathias W. Pletz
Summary: A prospective cohort study among hospital staff in Jena University Hospital found a low risk of SARS-CoV-2 infection for healthcare workers, possibly due to high compliance in wearing personal protective equipment.
TRANSBOUNDARY AND EMERGING DISEASES
(2022)
Article
Immunology
Rainer Koenig, Amol Kolte, Olaf Ahlers, Marcus Oswald, Veiko Krauss, Daniela Roell, Oliver Sommerfeld, George Dimopoulos, Iraklis Tsangaris, Eleni Antoniadou, Neeraja Jaishankar, Holger Bogatsch, Markus Loeffler, Markus Roedel, Marina Garcia-Moreno, Lorena Tuchscherr, Charles L. Sprung, Mervyn Singer, Frank Brunkhorst, Michael Oppert, Herwig Gerlach, Ralf A. Claus, Sina M. Coldewey, Josef Briegel, Evangelos J. Giamarellos-Bourboulis, Didier Keh, Michael Bauer
Summary: This study suggests that the IFNγ/IL10 ratio could be a potential molecular marker for determining the administration of hydrocortisone in patients with septic shock. The findings were supported by multiple validation sets and experimental studies, indicating the marker's potential clinical utility.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Diana M. Morales-Prieto, Jose M. Murrieta-Coxca, Milan Stojiljkovic, Celia Diezel, Priska E. Streicher, Julian A. Henao-Restrepo, Franziska Roestel, Julia Lindner, Otto W. Witte, Sebastian Weis, Christian Schmeer, Manja Marz
Summary: Extracellular vesicles, specifically small EVs, are involved in neuroinflammation and neurodegenerative diseases. Aging brains show increased neuroinflammation and glial activation, which can be influenced by EVs. Our study demonstrates that sEVs from aged mice can cross the blood-brain barrier and induce glial cell activation in young animals.
Article
Immunology
Nico Andreas, Sebastian Weis, Steffi Kolanos, Sabine Baumgart, Thomas Kamradt, Mathias W. Pletz
Summary: In this case report, a 64-year-old male participant of the CoNAN study was found to have a mild SARS-CoV-2 infection without any measurable antibody response. After vaccination with the ChAdOx1 vaccine 11 months later, no antibodies were detected in six serological tests. However, T-helper cell immunity, specifically SARS-CoV-2-specific Th cells, produced detectable amounts of IFN gamma and TNF six weeks after the infection. A robust T-cell immunity was detectable for at least six months after the infection and was further boosted by the vaccination. These findings suggest that assessing prior infection or vaccine response based solely on antibody detection may have limitations in individual patients.
Article
Immunology
Martin Bernhard Mueller, Max Huebner, Lei Li, Stephanie Tomasi, Valena Liesske, David Effinger, Simon Hirschberger, Kristin Pogoda, Markus Sperandio, Simone Kreth
Summary: This study reveals a novel regulatory network in which miR-125a acts as a central hub to regulate endothelial barrier permeability and monocyte migration. The network involves the modulation of adhesion molecules, phosphatases, and transcription factors, leading to the opening of the endothelial barrier. Furthermore, miR-125a enhances the expression of a chemokine in endothelial cells, while suppressing its own expression in monocytes, resulting in enhanced monocyte chemotaxis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Hannah Kipka, Roland Tomasi, Max Hubner, Uwe Liebchen, Christian Hagl, Klaus T. Wanner, Hanna Mannell, Georg Hofner
Summary: A highly sensitive LC-ESI-MS/MS method for simultaneous quantification of levosimendan and its metabolites was developed and validated. The study revealed constitutional isomers of levosimendan metabolites in surgical patients' samples, which were identified as metamizole metabolites. This research is important for efficient therapeutic drug monitoring (TDM) of cardiac surgery patients even with the additional administration of metamizole.
Article
Biochemistry & Molecular Biology
Stephanie Tomasi, Lei Li, Ludwig Christian Hinske, Roland Tomasi, Martina Amini, Gabriele Strauss, Martin Bernhard Mueller, Simon Hirschberger, Sven Peterss, David Effinger, Kristin Pogoda, Simone Kreth, Max Huebner
Summary: During acute inflammation, the regulatory network driven by miR-125a affects monocyte adhesion and chemotaxis by directly targeting adhesion molecules and chemokine receptors. The levels of miR-125a are influenced by the type of inflammatory stimulus, which in turn strongly impacts the phenotype of human monocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Paul Horn, Sascha Radtke, Uta Barbara Metzing, Ricardo Steidl, Christoph Sponholz, Oliver Sommerfeld, Johannes Roth, Ralf A. Claus, Andreas L. Birkenfeld, Utz Settmacher, Falk Rauchfuss, Christian von Loeffelholz
Summary: This study found that sepsis patients have significant dyslipidemia and the cytokine betatrophin/ANGPTL8 plays an important role in this metabolic disorder. Despite similar mRNA expression levels in adipose tissue, circulating betatrophin/ANGPTL8 is significantly increased in sepsis patients.
Article
Infectious Diseases
Christina Bahrs, Sebastian Weis, Miriam Kesselmeier, Juliane Ankert, Stefan Hagel, Stephanie Beier, Jens Maschmann, Andreas Stallmach, Andrea Steiner, Michael Bauer, Wilhelm Behringer, Michael Baier, Cora Richert, Florian Zepf, Martin Walter, Andre Scherag, Michael Kiehntopf, Bettina Loeffler, Mathias W. Pletz
Summary: This study aims to assess the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital in Germany. The results show that non-patient-related exposure to SARS-CoV-2 posed the highest infection risk for hospital staff members, with contact with household members and colleagues significantly increasing the risk of infection.
Editorial Material
Critical Care Medicine
Rachel E. Powell, Miguel P. Soares, Sebastian Weis
INTENSIVE CARE MEDICINE
(2023)
Article
Physiology
Martin B. Mueller, Clemens Stihl, Annika Schmid, Simon Hirschberger, Rea Mitsigiorgi, Martin Holzer, Martin Patscheider, Bernhard G. Weiss, Christoph Reichel, Max Huebner, Bernd Uhl
Summary: Obstructive sleep apnea (OSA) is a common sleep disorder characterized by recurrent upper airway obstruction and hypoxia. The molecular mechanisms underlying cardiovascular complications in OSA are not well understood. This study established an in vitro model using endothelial cells to investigate the effects of OSA on the vascular endothelium. The findings suggest that OSA activates pro-inflammatory pathways in endothelial cells. This model may contribute to the development of targeted strategies against OSA-induced cardiovascular disease.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Chemistry, Medicinal
Monica J. Bohmer, Jinhua Wang, Eva S. Istvan, Madeline R. Luth, Jennifer E. Collins, Edward L. Huttlin, Lushun Wang, Nimisha Mittal, Mingfeng Hao, Nicholas P. Kwiatkowski, Steven P. Gygi, Ratna Chakrabarti, Xianming Deng, Daniel E. Goldberg, Elizabeth A. Winzeler, Nathanael S. Gray, Debopam Chakrabarti
Summary: Protein kinases have been successful therapeutic targets, especially for cancer treatment, and there is potential to repurpose them as antimalarials. A study discovered BI-2536, a potent inhibitor of human polo-like kinase 1, showing nanomolar antiplasmodial activity. Screening of other PLK1 inhibitors identified more potential antimalarials, and a shared target, PfNEK3, was identified through kinase panel screening. However, there may be additional targets involved as distinct signaling pathways were disrupted by different inhibitors. Genomic analysis of BI-2536-resistant parasites suggested potential inhibition of an aminoacyl-tRNA synthetase.
ACS INFECTIOUS DISEASES
(2023)
Article
Medicine, Research & Experimental
Gloria Asantewaa, Nsoh Godwin Anabire, Michael Bauer, Sebastian Weis, Sophie Neugebauer, Osbourne Quaye, Gideon Kofi Helegbe
Summary: Co-infection of Plasmodium falciparum and hepatitis B virus is increasing among pregnant women in northern Ghana. These co-infections result in unique metabolic alterations, including decreased concentrations of sphingolipids, amino acids, phospholipids, and hexoses, and alterations in pathways related to redox homeostasis. The metabolite PC ae C40:1 shows promise as a discriminatory marker for co-infection, and can potentially be used for diagnosis and treatment of malaria and chronic hepatitis B co-morbidity.