Identifying the Neurogenetic Framework of Crohn's Disease Through Investigative Analysis of the Nucleotide-binding Oligomerization Domain-containing Protein 2 Gene Mutation

Sakibuzzaman,; Moosa, Syed Ahmad; Akhter, Mahabuba; Trisha, Ipsita Hamid; Talib, Khandokar A

doi:10.7759/cureus.5680

Cited by 4 publications

(1 citation statement)

References 34 publications

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“…For many years, scientists have been aware of the value of the MDP molecule in terms of its potential use in the treatment of many diseases given its signaling pathway ( 14 , 15 ). However, many approaches have shown that the MDP molecule exhibits high pyrogenicity and rapid excretion from the body; therefore its structure was modified to exclude several side effects and prolong its presence in the body while not altering its affinity to the NOD2 receptor ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

Muramyl dipeptide-based analogs as potential anticancer compounds: Strategies to improve selectivity, biocompatibility, and efficiency

Iwicka

Hajtuch²,

Dzierzbicka³

et al. 2022

Front. Oncol.

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According to the WHO, cancer is the second leading cause of death in the world. This is an important global problem and a major challenge for researchers who have been trying to find an effective anticancer therapy. A large number of newly discovered compounds do not exert selective cytotoxic activity against tumorigenic cells and have too many side effects. Therefore, research on muramyl dipeptide (MDP) analogs has attracted interest due to the urgency for finding more efficient and safe treatments for oncological patients. MDP is a ligand of the cytosolic nucleotide-binding oligomerization domain 2 receptor (NOD2). This molecule is basic structural unit that is responsible for the immune activity of peptidoglycans and exhibits many features that are important for modern medicine. NOD2 is a component of the innate immune system and represents a promising target for enhancing the innate immune response as well as the immune response against cancer cells. For this reason, MDP and its analogs have been widely used for many years not only in the treatment of immunodeficiency diseases but also as adjuvants to support improved vaccine delivery, including for cancer treatment. Unfortunately, in most cases, both the MDP molecule and its synthesized analogs prove to be too pyrogenic and cause serious side effects during their use, which consequently exclude them from direct clinical application. Therefore, intensive research is underway to find analogs of the MDP molecule that will have better biocompatibility and greater effectiveness as anticancer agents and for adjuvant therapy. In this paper, we review the MDP analogs discovered in the last 10 years that show promise for antitumor therapy. The first part of the paper compiles the achievements in the field of anticancer vaccine adjuvant research, which is followed by a description of MDP analogs that exhibit promising anticancer and antiproliferative activity and their structural changes compared to the original MDP molecule.

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Section: Introductionmentioning

confidence: 99%

Muramyl dipeptide-based analogs as potential anticancer compounds: Strategies to improve selectivity, biocompatibility, and efficiency

Iwicka

Hajtuch²,

Dzierzbicka³

et al. 2022

Front. Oncol.

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NOD2 is involved in regulating odontogenic differentiation of DPSCs suppressed by MDP through NF-κB/p65 signaling

et al. 2022

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Effect of Toll-like receptor-2, -4, -5, -7, and NOD2 stimulation on potassium channel conductance in intestinal epithelial cells

Cosme

Soares‐da‐Silva

Magro

2022

American Journal of Physiology-Gastrointestinal and Liver Physi

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Disproportionate activation of pattern recognition receptors plays a role in inflammatory bowel disease (IBD) pathophysiology. Diarrhea is a hallmark symptom of IBD, resulting at least in part from an electrolyte imbalance that may be caused by changes in potassium channel activity. We evaluated the impact of Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain 2 (NOD2) stimulation on potassium conductance of the basolateral membrane in human intestinal epithelial cells (IECs) and the role of potassium channels through electrophysiological assays under short-circuit current in Ussing chambers. TLRs and NOD2 were stimulated using specific agonists, and potassium channels were selectively blocked using triarylmethane-34 (TRAM-34), adenylyl-imidodiphosphate (AMP-PNP) and BaCl2. Potassium conductance of the basolateral membrane decreased upon activation of TLR2, TLR4 and TLR7 in T84 cells (mean ± SEM, -11.2 ± 4.5, -40.4 ± 7.2 and -19.4 ± 5.9 respectively) and in Caco-2 cells (-13.1 ± 5.7, -55.7 ± 7.4 and -29.1 ± 7.2, respectively). In contrast, activation of TLR5 and NOD2 increased basolateral potassium conductance, both in T84 cells (18.0 ± 4.1 and 18.4 ± 2.8, respectively) and in Caco-2 cells (21.2 ± 8.4 and 16.0 ± 3.6, respectively). TRAM-34 and AMP-PNP induced a decrease on basolateral potassium conductance upon TLR4 stimulation in both cell lines. Both KCa3.1- and Kir6- channels appear to be important mediators of this effect in IECs, and could be potential targets for therapeutic agent development.

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Identifying the Neurogenetic Framework of Crohn's Disease Through Investigative Analysis of the Nucleotide-binding Oligomerization Domain-containing Protein 2 Gene Mutation

Cited by 4 publications

References 34 publications

Muramyl dipeptide-based analogs as potential anticancer compounds: Strategies to improve selectivity, biocompatibility, and efficiency

Muramyl dipeptide-based analogs as potential anticancer compounds: Strategies to improve selectivity, biocompatibility, and efficiency

NOD2 is involved in regulating odontogenic differentiation of DPSCs suppressed by MDP through NF-κB/p65 signaling

Effect of Toll-like receptor-2, -4, -5, -7, and NOD2 stimulation on potassium channel conductance in intestinal epithelial cells

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