Increase in flavan-3-ols by silencing flavonol synthase mRNA affects the transcript expression and activity levels of antioxidant enzymes in tobacco

Aims: Accumulating evidence suggests that atherosclerotic progression depends on persistent and chronic inflammation in the arterial walls. MicroRNA-155 is reportedly involved in cardiovascular disease and has been implicated as a pro-inflammation regulator. Although some researchers have focused on microRNA-155 as an atherosclerosis regulator, the mechanisms by which microRNA-155 functions as a putative pro-atherosclerosis microRNA are largely unknown. This study aims to analyze microRNA-155's effects on atherosclerotic inflammation and to explore its mechanism. Methods: MicroRNA-155's effects on atherosclerotic inflammation were observed along with the expression and activity levels of SOCS1, STAT3 and NF-κB though microRNA-155 inhibition or overexpression. Results: Highly expressions of microRNA-155 in oxLDL-stimulated macrophages and atherosclerosis mice were inversely correlated with SOCS1 expression. Ectopic microRNA-155 overexpression significantly promoted inflammatory cytokine and chemokine production and atherosclerosis progression. We then observed microRNA-155's functional role in the atherosclerotic pathophysiological process in vivo and in vitro. The observation revealed that by enhancing STAT3 and NF-κB signaling and facilitating immune inflammation by targeting SOCS1, microRNA-155 plays a promotable role in atherosclerosis progression. Conclusions: microRNA-155 works as a promoter in the atherosclerotic procession. Its mechanism may include enhancing inflammatory response in atherosclerosis by increasing STAT3 and NF-κB signaling via targeting SOCS1.

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Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment

Molecules ◽

10.3390/molecules27010148 ◽

2021 ◽

Vol 27 (1) ◽

pp. 148

Author(s):

Xiang Li ◽

Yuhui Wang ◽

Man Li ◽

Huipeng Wang ◽

Xiongwei Dong

Keyword(s):

Antioxidant Enzymes ◽

Metal Complexes ◽

Cancer Cells ◽

Chelating Agents ◽

Activity Levels ◽

Biological Functions ◽

Ros Homeostasis ◽

Anti Cancer ◽

Clinical Drugs ◽

New Perspective

Reactive oxygen species (ROS) are rapidly eliminated and reproduced in organisms, and they always play important roles in various biological functions and abnormal pathological processes. Evaluated ROS have frequently been observed in various cancers to activate multiple pro-tumorigenic signaling pathways and induce the survival and proliferation of cancer cells. Hydrogen peroxide (H2O2) and superoxide anion (O2•−) are the most important redox signaling agents in cancer cells, the homeostasis of which is maintained by dozens of growth factors, cytokines, and antioxidant enzymes. Therefore, antioxidant enzymes tend to have higher activity levels to maintain the homeostasis of ROS in cancer cells. Effective intervention in the ROS homeostasis of cancer cells by chelating agents or metal complexes has already developed into an important anti-cancer strategy. We can inhibit the activity of antioxidant enzymes using chelators or metal complexes; on the other hand, we can also use metal complexes to directly regulate the level of ROS in cancer cells via mitochondria. In this review, metal complexes or chelators with ROS regulation capacity and with anti-cancer applications are collectively and comprehensively analyzed, which is beneficial for the development of the next generation of inorganic anti-cancer drugs based on ROS regulation. We expect that this review will provide a new perspective to develop novel inorganic reagents for killing cancer cells and, further, as candidates or clinical drugs.

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Effect of a Peptide Construct on Differentiated Macrophage MMP-2 and MMP-9 Levels of Varicose Patients

Current Pharmaceutical Design ◽

10.2174/1381612825666191029105203 ◽

2020 ◽

Vol 25 (40) ◽

pp. 4303-4309

Author(s):

Golnaz Esfandiari ◽

Azim S. Biranvand ◽

Adeleh Poursaleh ◽

Naser Kakavandi ◽

Fahimeh Fattahi ◽

...

Keyword(s):

Gene Expression ◽

Varicose Veins ◽

Docking Studies ◽

Activity Levels ◽

Matrix Remodeling ◽

The Matrix ◽

Enzyme Functions ◽

Catalytic Functions ◽

Gene Expression Levels ◽

Expression And Activity

Background: The Matrix Metalloproteinase (MMPs) secreted from macrophages can affect the extracellular matrix remodeling process and improve varicose veins. Aim: The aim of this study was to investigate the MMP-2 and MMP-9 gene expression and activity levels in the differentiated macrophages M2 of subjects with varicose veins, and to evaluate a peptide construct on their catalytic functions. Methods: The macrophages were differentiated from the monocytes using M-CSF. The MMP-2 and MMP-9 gene expression and activity levels were measured by RT-qPCR and Zymography techniques, respectively. A peptide construct (ESLCG) was predicted with bioinformatics tools, and was prepared for the study of enzyme functions as compared to Batimastat. Furthermore, the docking studies were obtained for the evaluation of interactions between peptide construct, Batimastat and enzyme 3D structures. Results: The results showed significant increases in MMP2 and MMP9 gene expression levels (P <0.001 and P <0.004, respectively) and gelatinolytic activities (P <0.001 and P <0.0001, respectively) in the macrophages. In agreement with the inhibitory effects of Batimastat, the peptide construct inhibited the MMP-2 and MMP-9 gelatinolytic activities up to 6.8 and 6.5 folds in the concentration of 150 µM. The docking analyses showed that the Lys187, Arg98, Leu49, Gly189, Leu190, Met97, Tyr53 and Phe57 residues of MMP-2 and the Leu187, His190, Glu402, His401, His405 and His411 residues of MMP-9 are interacted with the atoms of Batimastat and ESLCG peptide. Conclusion: The ESLCG peptide may be applied as an inhibitor of MMP-2 and MMP-9 enzymes in the subjects with varicose veins.

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Calcineurin expression and activity is regulated by the intracellular redox status and under hypertension in human neutrophils

Journal of Endocrinology ◽

10.1530/joe-12-0106 ◽

2012 ◽

Vol 214 (3) ◽

pp. 399-408 ◽

Cited By ~ 2

Author(s):

Gonzalo Alba ◽

Consuelo Santa-María ◽

María Edith Reyes-Quiroz ◽

Rajaa El Bekay ◽

Isabel Geniz ◽

...

Keyword(s):

De Novo ◽

Redox Status ◽

Human Neutrophils ◽

Pyrrolidine Dithiocarbamate ◽

Activity Levels ◽

Ang Ii ◽

Activity Increase ◽

Expression And Activity ◽

Intracellular Redox Status ◽

Intracellular Redox

Calcineurin (protein phosphatase 2B) (CN) comprises a family of serine/threonine phosphatases that play a pivotal role in signal transduction cascades in a variety of cells, including neutrophils. Angiotensin II (Ang II) increases both activity andde novosynthesis of CN in human neutrophils. This study focuses on the role that intracellular redox status plays in the induction of CN activity by Ang II. Bothde novosynthesis of CN and activity increase promoted by Ang II were downregulated when cells were treated withl-buthionine-(S,R)-sulfoximine, an inhibitor of synthesis of the antioxidant glutathione. We have also investigated the effect of pyrrolidine dithiocarbamate and phenazine methosulfate, which are antioxidant and oxidant compounds, respectively, and concluded that the intracellular redox status of neutrophils is highly critical for Ang II-induced increase of CN expression and activity. Results obtained in neutrophils from hypertensive patients were very similar to those obtained in these cells on treatment with Ang II. We have also addressed the possible functional implication of CN activation in the development of hypertension. Present findings indicate that downregulation of hemoxygenase-1 expression in neutrophils from hypertensive subjects is likely mediated by CN, which acts by hindering translocation to the nucleus of the transcription factorNRF2. These data support and extend our previous results and those from other authors on modulation of CN expression and activity levels by the intracellular redox status.

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