Discovery of 5-Phenylthiazol-2-amine Derivatives as Novel PI4KIIIβ Inhibitors with Efficacious Antitumor Activity by Inhibiting the PI3K/AKT Axis

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

To develop novel PI4KIIIβ inhibitors and explore their antitumor activity, a series of 5-phenylthiazol-2-amine derivatives were synthesized by structural modifications PIK93. Biological assay results indicated that compounds 16 43 exhibited superior selective inhibitory antiproliferative activity than Mechanistic studies revealed the two inhibit PI3K/AKT pathway more effectively, thereby inducing cancer cell apoptosis, cycle arrest in G2/M phase autophagy. Importantly, vivo toxicity pharmacodynamics showed safety to commercially available axis inhibitor alpelisib, obviously small lung H446 xenograft models. Overall, this work highlights therapeutic potential treatment tumors, provides candidates viable drug development strategies for inhibitors.

Language: Английский

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Inhibition of the Sp1/PI3K/AKT signaling pathway exacerbates doxorubicin-induced cardiomyopathy

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 119960 - 119960

Published: April 1, 2025

Language: Английский

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Evaluation of exo-long noncoding RNA MALAT1 in OSCC in comparison to dysplastic and normal: A cross-sectional study

Journal of Oral Biology and Craniofacial Research, Journal Year: 2025, Volume and Issue: 15(1), P. 123 - 128

Published: Jan. 1, 2025

This study explores the role of MALAT1 as a valuable target for creating minimally-invasive diagnostic methods and personalized treatments in management OSCC. It focuses on evaluating exosomal progression dysplasia to OSCC by influencing PI3K/AKT pathway. cross-sectional evaluated expression pathway components exosomes derived from plasma samples patients with various stages oral dysplasia, compared normal. RNA concentration was estimated, real-time polymerase chain reaction (qPCR) used quantitative analysis. Gene levels MALAT1, PI3K, AKT1, PTEN were analysed across groups using one way ANOVA Post-hoc Tukey analysis performed pairwise comparisons assess correlations between components. found be overexpressed comparison normal, significantly (p < 0.001∗). There no significant change pattern dysplastic yet, association corelation PI3K/AKT/PTEN 0.001∗) among individuals As well all three showed stands out key player complex landscape pathogenesis, impacting tumorigenesis, metastasis, treatment outcomes through multifaceted molecular mechanisms. Continued research into MALAT1's regulatory roles its interactions within tumor microenvironment holds promise uncovering novel therapeutic targets biomarkers that could redefine future.

Language: Английский

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Conditional knockdown of hepatic PCSK9 ameliorates high-fat diet-induced liver inflammation in mice

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Instruction Accumulating evidence has shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with inflammation in the vascular system. However, roles of PCSK9 hepatic remain unclear. Because mainly expressed liver and modulates lipid uptake through low-density lipoprotein receptor family members, present study aimed to elucidate effect conditional knockdown on hyperlipidemia-induced underlying mechanisms action. Methods PCSK9flox/flox mice were bred ALB-Cre + obtain (−/−) , (+/−) (+/+) mice. These fed a high-fat diet for weeks induce inflammation. The effects investigated by molecular biological techniques. Moreover, findings verified vitro using HepG2 cells. Results Discussion Conditional remarkably decreased plasma levels total cholesterol alleviated injury. Mechanistically, significantly reduced pro-inflammatory factors downregulating expression Toll-like receptors, mitogen-activated protein kinase (MAPK), phosphoinositide-3 kinase/protein B, which subsequently attenuated downstream molecules, namely nuclear factor kappa-B activator protein-1. related confirmed lipid-loaded cells together siRNA, alirocumab (anti-PCSK9 antibody), and/or p38-MAPK inhibitor. attenuates following hyperlipidemia induction modulating multiple signaling pathways; this suggests targeting knockdown/inhibition appropriate agents useful not only treating but also ameliorating

Language: Английский

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A Carbon-Based Nanomaterial with Dichotomous Effects: Antineoplastic on Oral Cancer Cells and Osteoinductive/Chondroinductive on Dental Pulp Stem Cells

Journal of Functional Biomaterials, Journal Year: 2025, Volume and Issue: 16(3), P. 109 - 109

Published: March 19, 2025

Background: Oral cancer is an aggressive malignancy with modest survival rates. It also causes disfigurement following surgical removal of the tumor, thus highlighting need for new treatment and tissue repair modalities. Carbon-based nanomaterials have emerged as promising tools in both anticancer regenerative therapies. Objectives: We aimed to synthesize a carbon-based nanomaterial (CBN) test its antineoplastic effects, well potential capacity. Materials Methods: A carbon nanomaterial, obtained by ball milling graphite flakes, was functionalized polyvinylpyrrolidone (CBN/PVP). Its physicochemical properties were explored X-ray diffraction (XRD), attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR), micro-Raman spectroscopy, fluorescent scanning electron microscopy, wettability analysis. For effects investigation, oral cells treated CBN/PVP examined MTT migration assays, cell-cycle ROS production analyses. Gene expression determined qPCR. To examine pro-regenerative capacity CBN/PVP, dental pulp stem cell cultures (DPSCs) subjected osteo- chondro-induction. Results: Lower concentrations (50, 100 μg/mL) applied on exerted remarkable cytotoxic induced G1 arrest, reduced invasion different mechanisms, including downregulation PI3K/AKT/mTOR pathway. In contrast, addition 50 µg/mL DPSCs stimulated their proliferation. significantly enhanced osteogenic (p < 0.05) chondrogenic 0.01) induction DPSCs. Conclusions: The novel displays unique characteristics, making it suitable therapies concomitantly.

Language: Английский

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Oral cancer: Current and new drug delivery system

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 429 - 450

Published: Jan. 1, 2025

Language: Английский

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Comprehension of PTEN-Regulated MicroRNA Profiling in Oral Premalignant Lesions: A Critical Link to Early Detection of Oral Squamous Cell Carcinoma

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Oral premalignant lesions represent the most prevalent observed within oral cavity. These generally remain asymptomatic until they advance to more severe stages, at which point their progression squamous cell carcinoma (OSCC) becomes evident. Addressing this transformation necessitates further investigative efforts. The PTEN (phosphatase and tensin homolog) gene functions as a crucial tumor suppressor, with its expression regulated by variety of complex mechanisms, including transcriptional, post-transcriptional, post-translational processes. MicroRNAs (miRNAs) are significant modulators play an integral role in transition from OSCC. This review evaluates impact miRNA dysregulation on examines continuum model suppression. It posits that loss functionality may transpire without alterations DNA sequence, particularly through mechanisms associated regulation. Furthermore, discourse elucidates structural interactions between miRNAs, context lesions, influence rate Such insights for informing treatment strategies. also explores potential targeting specific miRNAs restore functionality, intending improve clinical outcomes patients diagnosed By elucidating these regulatory interactions, analysis aims identify pathways conducive development targeted therapeutic

Language: Английский

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Liposome of Phlorizin promote the repair of carotid atherosclerosis in rats by regulating inflammation and the Nrf2 signaling pathway

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2025, Volume and Issue: unknown, P. 159613 - 159613

Published: April 1, 2025

Language: Английский

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A bibliometric analysis of programmed cell death in oral cancer literature: research patterns and emerging trends (2000–2024)

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 22, 2025

Language: Английский

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Molecular Mechanisms in the Carcinogenesis of Oral Squamous Cell Carcinoma: A Literature Review

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 621 - 621

Published: April 25, 2025

The tumor microenvironment (TME) plays a crucial role in the development, progression, and metastasis of oral squamous cell carcinoma (OSCC). TME comprises various cellular acellular components, including immune cells, stromal cytokines, extracellular matrix, microbiome, all which dynamically interact with cells to influence their behavior. Immunosuppression is key feature OSCC TME, regulatory T (Tregs), myeloid-derived suppressor (MDSCs), tumor-associated macrophages (TAMs) contributing an environment that allows evade surveillance supports angiogenesis. microbiome also pivotal pathogenesis, as dysbiosis, or imbalances microbiota, can lead chronic inflammation, promotes carcinogenesis through production pro-inflammatory cytokines reactive oxygen species (ROS). Pathogens like Porphyromonas gingivalis Fusobacterium nucleatum have, hence, been implicated OSCC-driven they induce activate oncogenic pathways, modulate responses. In this review, we discuss how interplay between immunosuppression microbiome-driven inflammation creates tumor-promoting OSCC, leading treatment resistance poor patient outcomes, explore potential therapeutic implication better understanding etiology molecular changes.

Language: Английский

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