A substantial number of experimental and epidemiological studies support an important role for the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) pathway in the biology of human cancers. Components of this signaling cascade have been found to be deregulated in a wide range of solid tumors and hematologic malignancies, and extensive anti-cancer therapeutic programs are now devoted to the identification of agents that specifically block this molecular pathway. This article focuses on the current knowledge of the alterations of the PI3K/PKB pathway in cancer cells and ongoing drug discovery efforts to therapeutically target it. Particular emphasis is placed on medicinal chemistry activities to identify and develop compounds able to modulate the kinase activity of its main molecular components.
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Objective: To examine the potential of galangin in a mouse model of ovalbumin (OVA)-induced allergic rhinitis (AR), as chronic AR, induced by immunoglobulin-E (IgE), leads to histamine release and nasal inflammation, and although galangin exhibits antiasthmatic and anti-inflammatory potential, its effect on AR is yet to be investigated.
Animals: 126 BALB/c mice.
Methods: AR induction involved sensitizing female mice with OVA (5%, 500 µL, IP) for 14 days.
Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy.
Adv Ther
February 2024
Department of Otorhinolaryngology and Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, China.
Introduction: Our prior clinical study assessed the efficacy and safety of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farina drops on patients with allergic rhinitis (AR) while analyzing the characteristics of adverse reactions. This study was conducted to evaluate the immune cell composition alterations in AR patients before and after SLIT, and to comprehensively investigate the role and changes of antigen-specific immune cells associated with treatment efficacy.
Methods: A total of 68 AR patients who completed 12 months of SLIT were included in the study.
Lipid peroxidation: Reactive carbonyl species, protein/DNA adducts, and signaling switches in oxidative stress and cancer.
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Department of Biochemistry and Molecular Biology, N.I. Pirogov Russian National Research Medical University, 117997, 1 Ostrovityanov Street, Moscow, Russia.
Under the exposure of lipids to reactive oxygen species (ROS), lipid peroxidation proceeds non-enzymatically and generates an extremely heterogeneous mixture of reactive carbonyl species (RCS). Among them, HNE, HHE, MDA, methylglyoxal, glyoxal, and acrolein are the most studied and/or abundant ones. Over the last decades, significant progress has been achieved in understanding mechanisms of RCS generation, protein/DNA adduct formation, and their identification and quantification in biological samples.
View Article and Find Full Text PDFAffected inflammation-related signaling pathways in snake envenomation: A recent insight.
Toxicon
October 2023
College of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi, 330000, PR China. Electronic address:
Snake envenomation is well known to cause grievous pathological signs, including haemorrhagic discharge, necrosis, and respiratory distress. However, inflammatory reactions are also common envenoming manifestations that lead to successive damage, such as oedema, ulceration, lymphadenectasis, systemic inflammatory response syndrome (SIRS) and even multiple organ dysfunction syndrome (MODS). Interference with the inflammatory burst is hence important in the clinical treatment of snake envenomation.
View Article and Find Full Text PDFDNAJB3 attenuates ER stress through direct interaction with AKT.
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Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar.
Metabolic stress involved in several dysregulation disorders such as type 2 diabetes mellitus (T2DM) results in down regulation of several heat shock proteins (HSPs) including DNAJB3. This down regulation of HSPs is associated with insulin resistance (IR) and interventions which induce the heat shock response (HSR) help to increase the insulin sensitivity. Metabolic stress leads to changes in signaling pathways through increased activation of both c-jun N-terminal kinase-1 (JNK1) and the inhibitor of κB inflammatory kinase (IKKβ) which in turn leads to inactivation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2).
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