Publications by authors named "Anthony L Walker"

Since the early 20th century, the increase in non-communicable diseases such as diabetes, heart disease, stroke, and cancer compared to infectious diseases has led to chronic illnesses becoming a leading cause of global morbidity and mortality [...

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Article Synopsis
  • The PI3K-Akt-mTOR signaling pathway is linked to various inflammatory skin conditions, which can lead to ineffective treatments for diseases like acne and psoriasis.
  • Understanding how this pathway operates has spurred the creation of new therapeutic strategies, but more research is needed to fully grasp its regulatory functions.
  • Some natural and synthetic compounds show promise in inhibiting this pathway, highlighting their potential for treating persistent skin inflammatory disorders.
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Psoriasis is a chronic autoimmune inflammatory skin disorder characterized by epidermal hyperplasia and aberrant immune response. In addition to aberrant cytokine production, psoriasis is associated with activation of the Akt/mTOR pathway. mTOR/S6K1 regulates T-lymphocyte activation and migration, keratinocytes proliferation and is upregulated in psoriatic lesions.

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The skin is the largest organ of the integumentary system, strategically located at the interface of the body's internal and external environment. [..

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This article contains supplemental datasets of the recently published related research article by Roy et al., [1]. It provides in-depth data not included in the original co-submission on the biophysical, molecular docking, and biological characterization of newly synthesized flavonol-based analogs of fisetin, a natural dietary small molecule with anticancer and anti-inflammatory properties.

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Due to hurdles, including resistance, adverse effects, and poor bioavailability, among others linked with existing therapies, there is an urgent unmet need to devise new, safe, and more effective treatment modalities for skin cancers. Herein, a series of flavonol-based derivatives of fisetin, a plant-based flavonoid identified as an anti-tumorigenic agent targeting the mammalian targets of rapamycin (mTOR)-regulated pathways, were synthesized and fully characterized. New potential inhibitors of receptor tyrosine kinases (c-KITs), cyclin-dependent kinase-2 (CDK2), and mTOR, representing attractive therapeutic targets for melanoma and non-melanoma skin cancers (NMSCs) treatment, were identified using inverse-docking, in vitro kinase activity and various cell-based anticancer screening assays.

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The mammalian or mechanistic target of rapamycin (mTOR) and associated phosphatidyl-inositiol 3-kinase (PI3K)/protein kinase B (Akt) pathways regulate cell growth, differentiation, migration, and survival, as well as angiogenesis and metabolism. Dysregulation of these pathways is frequently associated with genetic/epigenetic alterations and predicts poor treatment outcomes in a variety of human cancers including cutaneous malignancies like melanoma and non-melanoma skin cancers. Recently, the enhanced understanding of the molecular and genetic basis of skin dysfunction in patients with skin cancers has provided a strong basis for the development of novel therapeutic strategies for these obdurate groups of skin cancers.

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