Nrf2 modulation in breast cancer

Reactive oxygen species (ROS) are identified to control the expression and activity of various essential signaling intermediates involved in cellular proliferation, apoptosis, and differentiation. Indeed, ROS represents a double-edged sword in supporting cell survival and death. Many common pathological processes, including various cancer types and neurodegenerative diseases, are inflammation and oxidative stress triggers, or even initiate them. Keap1-Nrf2 is a master antioxidant pathway in cytoprotective mechanisms through Nrf2 target gene expression. Activation of the Nfr2 pathway benefits cells in the early stages and reduces the level of ROS. In contrast, hyperactivation of Keap1-Nrf2 creates a context that supports the survival of both healthy and cancerous cells, defending them against oxidative stress, chemotherapeutic drugs, and radiotherapy. Considering the dual role of Nrf2 in suppressing or expanding cancer cells, determining its inhibitory/stimulatory position and targeting can represent an impressive role in cancer treatment. This review focused on Nrf2 modulators and their roles in sensitizing breast cancer cells to chemo/radiotherapy agents

Antioxidant activity and ACE-inhibitory of Class II hydrophobin from wild strain Trichoderma reesei

International audienceThere are several possible uses of the Class II hydrophobin HFBII in clinical applications. To fully understand and exploit this potential however, the antioxidant activity and ACE-inhibitory potential of this protein need to be better understood and have not been previously reported. In this study, the Class II hydrophobin HFBII was produced by the cultivation of wild type Trichoderma reesei. The crude hydrophobin extract obtained from the fermentation process was purified using reversed-phase liquid chromatography and the identity of the purified HFBII verified by MALDI-TOF (molecular weight: 7.2 kDa). Subsequently the antioxidant activities of different concentrations of HFBII (0.01–0.40 mg/mL) were determined. The results show that for HFBII concentrations of 0.04 mg/mL and upwards the protein significantly reduced the presence of ABTS+ radicals in the medium, the IC50 value found to be 0.13 mg/mL. Computational modeling highlighted the role of the amino acid residues located in the conserved and exposed hydrophobic patch on the surface of the HFBII molecule and the interactions with the aromatic rings of ABTS. The ACE-inhibitory effect of HFBII was found to occur from 0.5 mg/mL and upwards, making the combination of HFBII with strong ACE-inhibitors attractive for use in the healthcare industry

New insight on biological interaction analysis: new nanocrystalline mixed metal oxide SPME fiber for GC-FID analysis of BTEX and its application in human hemoglobin-benzene interaction studies.

Nanocrystalline mixed metal oxides (MMO) of various metal cations were synthesized and were used for coating a piece of copper wire as a new high sensitive solid phase micro extraction (SPME) fiber in extraction and determination of BTEX compounds from the headspace of aqueous samples prior to GC-FID analysis. Under optimum extraction conditions, the proposed fiber exhibited low detection limits, and quantification limits, good reproducibility, simple and fast preparation method, high fiber capacity and high thermal and mechanical durability. These are some of the most important advantages of the new fiber. The proposed fiber was used for human hemoglobin upon interaction with benzene. Binding isotherm, Scatchard and Klotz logarithmic plots were constructed using HS-SPME-GC data, accurately. The obtained binding isotherm analyzed using Hill method. The Hill parameters have been obtained by calculating saturation parameter from the ratio of measured chromatographic peak areas in the presence and absence of hemoglobin. In this interaction, Hill coefficient and Hill constant determined as (nH = 6.14 and log KH = 6.47) respectively. These results reveal the cooperativity of hemoglobin upon interaction with benzene

Overview on differential scanning calorimetry applications for early stage of cancers: brief report

Background: Cancer is the most common cause of death in the world, and it incidence has been increasing for many years in economically developed countries. Early detection of cancers greatly increases the chances for successful treatment. So finding cancers before they start to cause symptoms is a most effective treatment. Recent studies have proposed that blood plasma contains a rich source of disease biomarkers for detecting, diagnosing and monitoring diseases. While some researchers have dismissed the low molecular weight serum peptidome as biological trash, recent work using differential scanning calorimetry has indicated that the peptidome may reflect biological event and contain diagnostic biomarkers. Methods: Differential scanning calorimetry (DSC), a highly sensitive tool for analysis of blood plasma and other biofluids has recently been reported. Louisville Bioscience, Inc. (LBIdx™), The Plasma Thermogram™ (pT™) company has made a significant breakthrough in the analysis of blood plasma using differential scanning calorimetry for clinical monitoring and diagnostic applications. Results: DSC analysis of plasma from diseased individuals revealed significant changes in the thermogram which are suggested to result not from changes in the concentration of the major plasma proteins but from interactions of small molecules or peptides with these proteins. The difference in plasma thermograms between healthy and disease individuals caused this method was recognized as a novel technique for disease diagnosis and monitoring. Conclusion: Measurement of plasma proteins is a powerful clinical is standard medical practice which hope revolutionizes strategies for early cancer detection

The Potential Role of Curcumin in Modulating the Master Antioxidant Pathway in Diabetic Hypoxia-Induced Complications

Oxidative stress is the leading player in the onset and development of various diseases. The Keap1-Nrf2 pathway is a pivotal antioxidant system that preserves the cells’ redox balance. It decreases inflammation in which the nuclear trans-localization of Nrf2 as a transcription factor promotes various antioxidant responses in cells. Through some other directions and regulatory proteins, this pathway plays a fundamental role in preventing several diseases and reducing their complications. Regulation of the Nrf2 pathway occurs on transcriptional and post-transcriptional levels, and these regulations play a significant role in its activity. There is a subtle correlation between the Nrf2 pathway and the pivotal signaling pathways, including PI3 kinase/AKT/mTOR, NF-κB and HIF-1 factors. This demonstrates its role in the development of various diseases. Curcumin is a yellow polyphenolic compound from Curcuma longa with multiple bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Since hyperglycemia and increased reactive oxygen species (ROS) are the leading causes of common diabetic complications, reducing the generation of ROS can be a fundamental approach to dealing with these complications. Curcumin can be considered a potential treatment option by creating an efficient therapeutic to counteract ROS and reduce its detrimental effects. This review discusses Nrf2 pathway regulation at different levels and its correlation with other important pathways and proteins in the cell involved in the progression of diabetic complications and targeting these pathways by curcumin

Theoretical studies on models of lysine-arginine cross-linksderived from α-oxoaldehydes: a new mechanismfor glucosepane formation

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A holistic view of muscle metabolic reprogramming through personalized metabolic modeling in newly diagnosed diabetic patients.

Type 2 diabetes mellitus (T2DM) is a challenging and progressive metabolic disease caused by insulin resistance. Skeletal muscle is the major insulin-sensitive tissue that plays a pivotal role in blood sugar homeostasis. Dysfunction of muscle metabolism is implicated in the disturbance of glucose homeostasis, the development of insulin resistance, and T2DM. Understanding metabolism reprogramming in newly diagnosed patients provides opportunities for early diagnosis and treatment of T2DM as a challenging disease to manage. Here, we applied a system biology approach to investigate metabolic dysregulations associated with the early stage of T2DM. We first reconstructed a human muscle-specific metabolic model. The model was applied for personalized metabolic modeling and analyses in newly diagnosed patients. We found that several pathways and metabolites, mainly implicating in amino acids and lipids metabolisms, were dysregulated. Our results indicated the significance of perturbation of pathways implicated in building membrane and extracellular matrix (ECM). Dysfunctional metabolism in these pathways possibly interrupts the signaling process and develops insulin resistance. We also applied a machine learning method to predict potential metabolite markers of insulin resistance in skeletal muscle. 13 exchange metabolites were predicted as the potential markers. The efficiency of these markers in discriminating insulin-resistant muscle was successfully validated