Metabolites and fragments of bacterial cells play an important role in the formation of immune homeostasis. Formed in the course of evolution, symbiotic relationships between microorganisms and a macroorganism are manifested, in particular, in the regulation of numerous physiological functions of the human body by the innate immunity receptors. Low molecular weight bioregulators of bacterial origin have recently attracted more and more attention as drugs in the prevention and composition of complex therapy for a wide range of diseases of bacterial and viral etiology. Signaling networks show cascades of causal relationships of deterministic phenomena that support the homeostasis of multicellular organisms at different levels. To create networks, data from numerous biomedical and clinical research databases were used to prepare expert systems for use in pharmacological and biomedical research with an emphasis on muramyl dipeptides. Muramyl peptides are the fragments of the cell wall of Gram-positive and Gram-negative bacteria. Binding of muramyl peptides with intracellular NOD2 receptors is crucial for an immune response on pathogens. Depending on the microenvironment and duration of action, muramyl peptides possess positive or negative regulation of inflammation. Other factors, such as genetic, pollutions, method of application and stress also contribute and should be taken into account. A system biology approach should be used in order to systemize all experimental data for rigorous analysis, with the aim of understanding intrinsic pathways of homeostasis, in order to define precise medicine therapy and drug design.
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http://dx.doi.org/10.3390/microorganisms10081526 | DOI Listing |
Front Immunol
December 2024
Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Lipoteichoic acid (LTA) and peptidoglycan (PGN) are considered as key virulence factors of , which is a representative sepsis-causing Gram-positive pathogen. However, cooperative effect of LTA and PGN on nitric oxide (NO) production is still unclear despite the pivotal roles of NO in initiation and progression of sepsis. We here evaluated the cooperative effects of LTA (SaLTA) and muramyl dipeptide (MDP), the minimal structure of PGN, on NO production in both a mouse macrophage-like cell line, RAW 264.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
The Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Wuchang, 169 Donghu Road, Hubei Province, China. Electronic address:
Macrophages are present in all tissues and body compartments under homeostatic physiological conditions. Importantly, they play a key role in pathological inflammatory processes when disturbed. They can quickly produce large amounts of inflammatory cytokines in response to danger signals.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Neuroscience, McKnight Brain Institute, University of Florida, 1149 SW Newell Drive, Gainesville, FL 32610, USA.
Receptor-interacting serine/threonine protein kinase 2 (RIPK2) is a kinase that is essential in modulating innate and adaptive immune responses. As a downstream signaling molecule for nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs), it is implicated in the signaling triggered by recognition of microbe-associated molecular patterns by NOD1/2 and TLRs. Upon activation of these innate immune receptors, RIPK2 mediates the release of pro-inflammatory factors by activating mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB).
View Article and Find Full Text PDFJ Med Chem
November 2024
Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China.
Vancomycin and norvancomycin have diminished antibacterial efficacy due to acquired or intrinsic resistance from mutations in the terminal dipeptide of lipid II in Gram-positive bacteria or failure to penetrate into the periplasm in Gram-negative bacteria. Herein, we rationally designed and synthesized a series of vancomycin analogues bearing single amine or guanidine functionality, altering various linkers and modification sites, to combat the resistance. Extensive antibacterial screening was performed to delineate a comprehensive SAR.
View Article and Find Full Text PDFACS Appl Mater Interfaces
November 2024
Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, P.R. China.
The clinical efficacy of cancer vaccines is closely related to immunoadjuvants that play a crucial role in magnifying and prolonging the immune response. Muramyl dipeptide (MDP), a minimal and conserved peptidoglycan found in almost all bacteria, can trigger robust immune activation by uniquely antagonizing the nucleotide-binding oligomerization domain 2 (NOD2) pathway. However, its effectiveness has been hindered by limited solubility, poor membrane penetration, and rapid clearance from the body.
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