Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways

Matcha green tea (MGT) is a natural product that is currently used as a dietary supplement and may have significant anti-cancer properties. However, the molecular mechanism(s) underpinning its potential health benefits remain largely unknown. Here, we used MCF7 cells (an ER(+) human breast cancer cell line) as a model system, to systematically dissect the effects of MGT at the cellular level, via i) metabolic phenotyping and ii) unbiased proteomics analysis. Our results indicate that MGT is indeed sufficient to inhibit the propagation of breast cancer stem cells (CSCs), with an IC-50 of ~0.2 mg/ml, in tissue culture. Interestingly, metabolic phenotyping revealed that treatment with MGT is sufficient to suppress both oxidative mitochondrial metabolism (OXPHOS) and glycolytic flux, shifting cancer cells towards a more quiescent metabolic state. Unbiased label-free proteomics analysis identified the specific mitochondrial proteins and glycolytic enzymes that were down-regulated by MGT treatment. Moreover, to discover the underlying signalling pathways involved in this metabolic shift, we subjected our proteomics data sets to bio-informatics interrogation via Ingenuity Pathway Analysis (IPA) software. Our results indicate that MGT strongly affected mTOR signalling, specifically down-regulating many components of the 40S ribosome. This raises the intriguing possibility that MGT can be used as inhibitor of mTOR, instead of chemical compounds, such as rapamycin. In addition, other key pathways were affected, including the anti-oxidant response, cell cycle regulation, as well as interleukin signalling. Our results are consistent with the idea that MGT may have significant therapeutic potential, by mediating the metabolic reprogramming of cancer cells

Numerical simulation of oil-water two-phase flow in a horizontal duct with a Venturi flow meter

The progressive depletion of on-shore and light-oil reserves is forcing an increased use of transitional and heavy oils, which implies new challenges both during the extraction and the transportation. Focusing on the latter, a technique to reduce the pressure drop is water injection in the oil stream to create the so-called core annular flow (CAF), a flow regime with an oil core enveloped in a water annulus wetting the pipe wall, so that the apparent viscosity of the mixture is considerably reduced. Behaviour of CAF in ducts with non-uniform sections is still under research. This work is devoted to a CFD investigation about the pressure drop, pressure gradients, velocity profiles and in situ volume fractions in a duct including a Venturi flow meter. Unsteady RANS simulations were carried out using the Volume-Of-Fluid interFoam solver of OpenFOAM. Numerical results were experimentally validated for oil superficial velocities in the range 0.25-0.75 m/s and water superficial velocities in the range 0.44-1.10 m/s and comparisons between different approaches and sensitivity analyses were performed. Satisfactory agreement was found for the pressure drop and pressure gradients, and also for the in situ volume fraction with respect to the predictions of the Arney correlation

Mitochondrial fission as a driver of stemness in tumor cells : mDIVI1 inhibits mitochondrial function, cell migration and cancer stem cell (CSC) signalling

Mitochondria are dynamic organelles frequently undergoing fission and fusion events to maintain their integrity, bioenergetics and spatial distribution, which is fundamental to the processes of cell survival. Disruption in mitochondrial dynamics plays a role in cancer. Therefore, proteins involved in regulating mitochondrial dynamics are potential targets for treatment. mDIVI1 is an inhibitor of the mitochondrial fission protein DRP1, which induces i) mitochondrial oxidative stress and ii) effectively reduces mitochondrial metabolism. We show here that mDIVI1 is able to inhibit 3D tumorsphere forming capacity, cell migration and stemness-related signalling in breast cancer cells, indicating that mDIVI1 can potentially be used for the therapeutic elimination of cancer stem cells (CSCs)

Characterization of plug and slug multiphase flows by means of image analysis

Multiphase flow is involved in a wide range of applications, and among the flow patterns that a multiphase mixture may develop in its flow, the intermittent one is particularly complex both in behaviour and for analysis. Experimental analysis about the characteristics of the flow structures (plugs and slugs) is therefore still mandatory for a detailed description of the phenomenon. In this work an image-based technique for the determination of the plug/slug characteristics was applied to air-water, oil-air and three-phase oil-water-air flows in horizontal ducts with different diameters, with superficial velocities of the phases in the range 0.2-2.1 m/s. The technique is based on the acquisition of a video of the flow and the conversion of each frame (or part of it) into a Boolean signal, in which the non-zero part represents the structure of interest. Concatenation of such signals along the singleton dimension creates a space-time representation of the flow, from which information about the flow velocities, the structure lengths and frequencies and the void fraction can be extracted. Focus here is particularly on the performances of the technique when using high-speed videos. The results were also compared with the predictions of the drift-flux model

Identification of natural products and FDA-approved drugs for targeting cancer stem cell (CSC) propagation

Here, we report the identification of key compounds that effectively inhibit the anchorage-independent growth and propagation of cancer stem cells (CSCs), as determined via screening using MCF7 cells, a human breast adenocarcinoma cell line. More specifically, we employed the mammosphere assay as an experimental format, which involves the generation of 3D spheroid cultures, using low-attachment plates. These positive hit compounds can be divided into 5 categories: 1) dietary supplements (quercetin and glucosamine); 2) FDA-approved drugs (carvedilol and ciprofloxacin); 3) natural products (aloe emodin, aloin, tannic acid, chlorophyllin copper salt, azelaic acid and adipic acid); 4) flavours (citral and limonene); and 5) vitamins (nicotinamide and nicotinic acid). In addition, for the compounds quercetin, glucosamine and carvedilol, we further assessed their metabolic action, using the Seahorse to conduct metabolic flux analysis. Our results indicate that these treatments can affect glycolytic flux and suppress oxidative mitochondrial metabolism (OXPHOS). Therefore, quercetin, glucosamine and carvedilol can reprogram the metabolic phenotype of breast cancer cells. Despite having diverse chemical structures, these compounds all interfere with mitochondrial metabolism. As these compounds halt CSCs propagation, ultimately, they may have therapeutic potential

Oxidative Stress Biomarkers and Peripheral Endothelial Dysfunction in Rheumatoid Arthritis: A Monocentric Cross-Sectional Case-Control Study

Previous studies have suggested that oxidative stress may heighten atherosclerotic burden in rheumatoid arthritis (RA), but direct evidence is lacking. Objective: To evaluate the relationship between established plasma oxidative stress biomarkers and peripheral endothelial dysfunction (ED), a marker of early atherosclerosis, in RA. Methods: Paroxonase-1 (PON-1), protein-SH (PSH), and malondialdehyde (MDA) were measured in 164 RA patient s and 100 age- and sex-matched healthy controls without previous cardiovascular events. Peripheral ED, evaluated by flow-mediated pulse amplitude tonometry, was defined by log-transformed reactive hyperemia index (Ln-RHI) values < 0.51. Results: PON-1 activity and PSH concentrations were significantly reduced in RA patients compared to controls. In regression analysis, increased plasma MDA levels were significantly associated with reduced Ln-RHI [B coefficient (95% CI) = −0.003 (−0.005 to −0.0008), p = 0.008] and the presence of peripheral ED (OR (95% CI) = 1.75 (1.06–2.88), p = 0.028). Contrary to our expectations, increased PON-1 activity was significantly associated, albeit weakly, with the presence of ED (OR (95% CI) = 1.00 (1.00–1.01), p = 0.017). Conclusions: In this first evidence of a link between oxidative stress and markers of atherosclerosis, MDA and PON-1 showed opposite associations with peripheral vasodilatory capacity and the presence of ED in RA. Further studies are needed to determine whether this association predicts atherosclerotic events in the RA population

Possible added value of thyroglobulin antibody (TgAb) testing in the evaluation of thyroidal status of subjects with overweight or obesity

Purpose: An increase in serum TSH concentrations in the absence of thyroid disease, named isolated hyperthyrotropinemia, is frequently observed in subjects with obesity. It is directly associated with body mass index, and it is reversible following weight loss. Autoimmune hypothyroidism is frequently associated with obesity, it is usually progressive and needs replacement treatment with L-thyroxine. The aim of this study was to investigate the role of thyroglobulin antibodies (TgAb) to define the thyroidal status in subjects with overweight or obesity. Methods: This is a retrospective study including 749 consecutive adult patients with overweight or obesity. Of those, 76 were excluded from the analysis due to hyperthyroidism, previous thyroidectomy or radioiodine therapy for hyperthyroidism, hemiagenesis or drug-induced hypothyroidism. Serum thyrotropin (TSH), free thyroxine (FT4), free 3,5,3'-triiodothyronine (FT3), TgAb and thyroperoxidase antibodies (TPOAb) were measured in all patients. Results: Out of 673 patients, 408 did not have thyroid disease. Among patients with thyroid disease (n = 265), 130 had nodular disease with no humoral signs of thyroid autoimmunity and 135 (20%) had autoimmune thyroiditis, defined by the presence of TPOAb and/or TgAb. The prevalence of hyperthyrotropinemia, either directly measured or presumed based on L-thyroxine treatment at the time of data collection, was 63.9% in patients with both TgAb and TPOAb, 47.1% in those with isolated positivity of TPOAb, 42.8% in patients with isolated positivity of TgAb, and 14.5% in those with no detectable TgAb or TPOAb. Conclusions: Our results confirm a high prevalence of autoimmune thyroiditis (20%) in patients with obesity. TgAb may be associated with hypothyroidism in the absence of TPOAb. TgAb measurement may turn helpful to unravel a proportion of subjects that may have or may develop primary hypothyroidism requiring specific substitutive treatment