Notch signaling: A possible therapeutic target and its role in diabetic foot ulcers

Begum, Farmiza; Keni, Raghuvir; Ahuja, Tejas N.; Beegum, Fathima; Nandakumar, Krishnadas; Shenoy, Rekha R

doi:10.1016/j.dsx.2022.102542

Cited by 9 publications

(4 citation statements)

References 35 publications

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“…The prolonged formation of collagen may lead to abnormal scar formation on the healed wound (Goulding 2015 ). Epithelium formation, fibroblast formation, collagen formation, and angiogenesis are considered hallmarks of wound healing, which have been observed in the normal and treated groups (Begum et al 2022 ). Angiogenesis was confirmed through immunostaining using the CD-31 marker (Fig.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the cellular and molecular effects of dehydrozingerone formulation on various days of diabetic wound repair

Begum,

Nandakumar,

Shenoy

2024

3 Biotech

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Cases of diabetes are significantly increasing year by year, attracting the attention of medical professionals and researchers to focus on diabetes and its underlying complications. One among such are diabetic wounds which are difficult to heal, creating severe implications in the day-to-day chores of not only patients, but also family members. Dehydrozingerone (DHZ) is known to possess various effects like anti-inflammatory, anti-microbial, antioxidant, and wound-healing properties. The effect of DHZ on different phases of diabetic wound healing remains untested. Hence, this study was proposed to find out the effect of oral and topical formulation of DHZ on day 5, 10 and 15 of diabetic wound healing. Excisional wounds were created on the dorsal side of animals using punch biopsy to mimic human diabetic wounds. Topical DHZ gel (100 mg in 1 gm of gel) was prepared using 1% Carbopol 934 and was applied twice a day. The treated groups had increased percentage of wound closure; western blotting suggested that DHZ significantly increased ERK and JNK levels and decreased TNF and MMP 2 and 9 levels. From histopathological studies, it was observed that angiogenesis, collagen formation, granulation tissue formation, and fibroblast proliferation were improved on days 5, 10, and 15 of diabetic wound healing. These findings indicate that DHZ (both systemic and topical) are effective during the early phases of wound healing which gets impaired in diabetic wounds. Dehydrozingerone accelerated diabetic wound healing by regulating the various hallmarks of wound healing process.

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Section: Discussionmentioning

confidence: 99%

Investigation of the cellular and molecular effects of dehydrozingerone formulation on various days of diabetic wound repair

Begum,

Nandakumar,

Shenoy

2024

3 Biotech

Self Cite

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“…Among other types of diabetic neuropathies, diabetic polyneuropathy is most common condition that frequently leads to foot ulceration (De Gregorio et al 2020). In the diabetic population, foot disorders contribute to around 85 percent of all amputation cases (Begum et al 2022). In the next decades, the cases will exacerbate if no effective medications are applied.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Reveals the Potential of Dolastatin 16 as Diabetic Wound Healing Agent

Luthfiana,

Utomo

2023

Preprint

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Dolastatin 16, a marine cyclic depsipeptide, was first isolated from the sea hare Dolabella Auricularia by Pettit et al. Since its bioactivity lacks of information, target identification is the indispensable strategy to reveal the potential target and mechanism of action of Dolastatin 16. Network pharmacology was utilized to identify the target associated with the disease, gene ontology, and KEGG pathway. The results demonstrated Matrix Metalloproteinase-9 (MMP9) as a potential target of Dolastatin 16 via network pharmacology analysis. The target was also mainly involved in TNF signaling pathway and foot ulceration-associated diabetic polyneuropathy. Further, the binding mode and dynamic behavior of the complex was investigated by molecular docking and molecular dynamics studies. In docking study, a native ligand (a hydroxamate inhibitor) and (R)-ND-336 were used as the ligand controls, demonstrating the binding energies of -6.6 and − 8.9 kcal/mol, respectively. The Dolastatin 16 complex showed the lowest binding energy of -9.7 kcal/mol, suggesting its higher potential as an inhibitor. Molecular dynamics also validated the stability of MMP9-Dolastatin complex throughout the simulation process. Dolastatin 16 may act as a MMP9 inhibitor and have potential to accelerate the wound healing process in diabetic foot condition.

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“…Further investigations allowed for attributing this effect to exo-mediated uptake of LINC01435—A long noncoding RNA—that suppresses the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Considering the role of the Notch pathway in angiogenesis, the authors extended the inspection of potential antiangiogenetic targets to various players engaged in Notch signalling, including the HDACs family [ 88 , 89 , 90 ]. This analysis highlighted the overexpression of HDAC8 in HUVECs, promoted by the nuclear translocation of the transcription factor YY1.…”

Section: Involvement Of Hdac8 In Different Diseasesmentioning

confidence: 99%

A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors

Fontana

Cursaro

Carullo

et al. 2022

IJMS

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Histone deacetylases (HDACs) are epigenetic enzymes which participate in transcriptional repression and chromatin condensation mechanisms by removing the acetyl moiety from acetylated ε-amino group of histone lysines and other non-histone proteins. In recent years, HDAC8, a class I HDAC, has emerged as a promising target for different disorders, including X-linked intellectual disability, fibrotic diseases, cancer, and various neuropathological conditions. Selective HDAC8 targeting is required to limit side effects deriving from the treatment with pan-HDAC inhibitors (HDACis); thus, many endeavours have focused on the development of selective HDAC8is. In addition, polypharmacological approaches have been explored to achieve a synergistic action on multi-factorial diseases or to enhance the drug efficacy. In this frame, proteolysis-targeting chimeras (PROTACs) might be regarded as a dual-targeting approach for attaining HDAC8 proteasomal degradation. This review highlights the most relevant and recent advances relative to HDAC8 validation in various diseases, providing a snapshot of the current selective HDAC8is, with a focus on polyfunctional modulators.

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Notch signaling: A possible therapeutic target and its role in diabetic foot ulcers

Cited by 9 publications

References 35 publications

Investigation of the cellular and molecular effects of dehydrozingerone formulation on various days of diabetic wound repair

Investigation of the cellular and molecular effects of dehydrozingerone formulation on various days of diabetic wound repair

Network Pharmacology Reveals the Potential of Dolastatin 16 as Diabetic Wound Healing Agent

A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors

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