scholarly journals Potential Applications of NRF2 Modulators in Cancer Therapy

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 193 ◽  
Author(s):  
Emiliano Panieri ◽  
Aleksandra Buha ◽  
Pelin Telkoparan-Akillilar ◽  
Dilek Cevik ◽  
Demetrios Kouretas ◽  
...  
Keyword(s):  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Related Factor ◽  
Oxygen Species ◽  
Dual Roles ◽  
Xenobiotic Stress ◽  
Cancer Initiation ◽  
Potential Applications ◽  
Context Specific ◽  
Risk Of Cancer

The nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation. Thus, a better understanding of the mechanisms that control NRF2 functions and the most appropriate context of its activation is a prerequisite for the development of effective therapeutic strategies based on NRF2 modulation. In line of principle, the controlled activation of NRF2 might reduce the risk of cancer initiation and development in normal cells by scavenging reactive-oxygen species (ROS) and by preventing genomic instability through decreased DNA damage. In contrast however, already transformed cells with constitutive or prolonged activation of NRF2 signaling might represent a major clinical hurdle and exhibit an aggressive phenotype characterized by therapy resistance and unfavorable prognosis, requiring the use of NRF2 inhibitors. In this review, we will focus on the dual roles of the NRF2-KEAP1 pathway in cancer promotion and inhibition, describing the mechanisms of its activation and potential therapeutic strategies based on the use of context-specific modulation of NRF2.

Trilobatin Protects Cardiomyocytes from Hypoxia/ Reperfusion Injury by Regulating the Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 133-138
Author(s):  
Wenyu Chen ◽  
Hui He
Keyword(s):  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cellular Injury ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
H9c2 Cells ◽  
Natural Plant ◽  
Induced Changes

Trilobatin is a natural plant-derived glycosylated flavonoid that has been shown to exhibit multiple beneficial pharmacologic activities including protection of heart against H/R-induced cardiomyocyte injury. However, the molecular mechanisms underlying protection from H/R-induced cardiomyocyte injury remain unknown. Using H9C2 cells as a model, we examined the effect of trilobatin on H/R-induced cellular injury, apoptosis, and generation of reactive oxygen species. The results showed that trilobatin protected H9C2 cells not only from cell death and apoptosis, but also counteracted H/R-induced changes in malondialdehyde, superoxide dismutase, glutathione, and glutathione peroxidase. The evaluation of the mechanism underlying the effect of trilobatin on protection from H/R-induced cellular injury suggested changes in the regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

scholarly journals Evaluation of Toxicity and Antioxidant Property of Cassia fistula Stem Bark Extracts in Zebrafish

2020 ◽  
Vol 10 (03) ◽  
pp. 109-115
Author(s):  
Shreya Udaya ◽  
Nishith Babu ◽  
Dechamma Pandyanda Nanjappa ◽  
Krithika Kalladka ◽  
Gunimala Chakraborty ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Antioxidant Properties ◽  
Ethanol Extract ◽  
Antioxidant Property ◽  
Stem Bark ◽  
Oxygen Species ◽  
Cassia Fistula ◽  
Potential Applications ◽  
Ethanol Extracts ◽  
Stress Models

Abstract Objective This study was aimed at evaluating the toxicity and the antioxidant property of Cassia fistula stem bark extracts in zebrafish. Materials and Methods Crude aqueous and ethanol extracts of C. fistula stem bark were obtained following a standard solvent-based extraction method. The toxicity of these extracts on zebrafish embryonic development was determined and the LC50 values were calculated. Finally, the antioxidant property of C. fistula stem bark extracts was determined in arsenic-induced oxidative stress models of zebrafish. Results The aqueous extract of C. fistula stem bark showed a slightly larger LC50 value (213.6 ppm) compared with the ethanol extract (LC50 = 63.5 ppm), suggesting a lower toxicity of the aqueous extract. A significant reduction of reactive oxygen species (ROS) signal was observed in arsenic-exposed embryos treated with the aqueous extract, but not the ethanol extract, indicating that the antioxidant activity is present only in the aqueous extract of C. fistula stem bark. Conclusion Identification of antioxidants from natural sources is desirable because of increasing safety concerns associated with synthetic antioxidants. This study demonstrated that aqueous extract from C. fistula stem bark possesses antioxidant properties, which can be further characterized for mechanism of action and potential applications.

scholarly journals NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuan Wang ◽  
Jun Cai ◽  
Lei Zhao ◽  
Dejun Zhang ◽  
Guojie Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Bioinformatics Analysis ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Self Renewal ◽  
Tumor Relapse ◽  
The Past ◽  
Overwhelming Evidence ◽  
Novel Therapeutic Strategies

AbstractExperimental and clinical studies over the past two decades have provided overwhelming evidence that human cancers, including prostate cancer (PCa), harbor cancer stem cells (CSCs) that sustain tumor growth, drive tumor progression and mediate therapy resistance and tumor relapse. Recent studies have also implicated NUMB as a PCa suppressor and an inhibitor of PCa stem cells (PCSCs); however, exactly how NUMB functions in these contexts remains unclear. Here, by employing bioinformatics analysis and luciferase assays and by conducting rescue experiments, we first show that NUMB is directly targeted by microRNA-9-5p (miR-9-5p), an oncogenic miR associated with poor prognosis in many malignancies. We further show that miR-9-5p levels are inversely correlated with NUMB expression in CD44+ PCSCs. miR-9-5p reduced NUMB expression and inhibited numerous PCSC properties including proliferation, migration, invasion as well as self-renewal. Strikingly, overexpression of NUMB in CD44+ PCSCs overcame all of the above PCSC properties enforced by miR-9-5p. Taken together, our results suggest that inhibiting the expression of the oncomiR miR-9-5p and overexpressing NUMB may represent novel therapeutic strategies to target PCSCs and PCa metastasis.

scholarly journals Oxidative Stress and Inflammation in Renal and Cardiovascular Complications of Diabetes

Biology ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 18
Author(s):  
Amelia Charlton ◽  
Jessica Garzarella ◽  
Karin A. M. Jandeleit-Dahm ◽  
Jay C. Jha
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Tissue Injury ◽  
Cardiovascular Complications ◽  
Therapeutic Strategies ◽  
Cellular Damage ◽  
Antioxidant Defenses ◽  
Pathological State ◽  
Oxygen Species ◽  
Emerging Therapies

Oxidative stress and inflammation are considered major drivers in the pathogenesis of diabetic complications, including renal and cardiovascular disease. A symbiotic relationship also appears to exist between oxidative stress and inflammation. Several emerging therapies target these crucial pathways, to alleviate the burden of the aforementioned diseases. Oxidative stress refers to an imbalance between reactive oxygen species (ROS) and antioxidant defenses, a pathological state which not only leads to direct cellular damage but also an inflammatory cascade that further perpetuates tissue injury. Emerging therapeutic strategies tackle these pathways in a variety of ways, from increasing antioxidant defenses (antioxidants and Nrf2 activators) to reducing ROS production (NADPH oxidase inhibitors and XO inhibitors) or inhibiting the associated inflammatory pathways (NLRP3 inflammasome inhibitors, lipoxins, GLP-1 receptor agonists, and AT-1 receptor antagonists). This review summarizes the mechanisms by which oxidative stress and inflammation contribute to and perpetuate diabetes associated renal and cardiovascular disease along with the therapeutic strategies which target these pathways to provide reno and cardiovascular protection in the setting of diabetes.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals LINKING INTERACTIVE OPTIMIZATION FOR URBAN PLANNING WITH A SEMANTIC 3D CITY MODEL

2018 ◽  
Vol IV-4 ◽  
pp. 179-186 ◽  
Author(s):  
N. Schüler ◽  
G. Agugiaro ◽  
S. Cajot ◽  
F. Maréchal
Keyword(s):  
Urban Planning ◽  
Data Model ◽  
Active Management ◽  
Specific Information ◽  
Exploration Process ◽  
Interactive Optimization ◽  
Potential Applications ◽  
City Model ◽  
Definition Of ◽  
Context Specific

<p><strong>Abstract.</strong> The cities in which we live are constantly evolving. The active management of this evolution is referred to as urban planning. The according development process could go in many directions resulting in a large number of potential future scenarios of a city. The planning support system URB<sup>io</sup> adopts interactive optimization to assist urban planners in generating and exploring those various scenarios. As a computer-based system it needs to be able to efficiently handle all underlying data of this exploration process, which includes both methodology-specific and context-specific information. This article describes the work carried out to link URB<sup>io</sup> with a semantic city model. Therefore, two key requirements were identified and implemented: (a) the extension of the CityGML data model to cope with many scenarios by the proposition of the Scenario Application Domain Extension (ADE) and (b) the definition of a data model for interactive optimization. Classes and features of the developed data models are motivated, depicted and explained. Their usability is demonstrated by walking through a typical workflow of URB<sup>io</sup> and laying out the induced data flows. The article is concluded with stating further potential applications of both the Scenario ADE and the data model for interactive optimization.</p>

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