is a plant commonly used for the treatment of several pathologies, such as diarrhoea, ulcers, pain, stomach aches, fevers, and gout. Our study focused on the use of
for the treatment of gout disease. ...We first studied the chemical composition of a methanolic extract of the aerial parts and demonstrated its xanthine oxidase (XO) inhibitory activity. Then, we performed a fractionation and evaluated the most XO inhibitory active fractions by UV measurement. Purification of some fractions allowed the determination of the inhibitory activity of pure compounds. We demonstrated that spiraeoside, a glycosylated flavonoid, possesses an activity around 25 times higher than allopurinol, used as a reference in the treatment of gout disease. In order to easily and quickly identify potent inhibitors in complex matrix, we developed a complementary strategy based on an HPLC method and an Effect Directed Assay (EDA) method combining HPTLC and biochemical assays. The HPLC method, capable of determining compounds exhibiting interactions with the enzyme, could be an efficient strategy for evaluating potent enzyme inhibitors in a complex mixture. This strategy could be applied for quantitative assays using LC/MS experiments.
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•We measured the ABC-4 of organic acids using their effects on wheat and soybean meal.•A mixture of feed ingredients resulted in the addition of their ABC-4 values proportionally to their level of ...inclusion.•No difference of ΔABC-4 was observed between wheat and soybean meal for the selected organic acids.•HMTBA was as acidifying as formic acid when comparison is made on equimolar basis.•Inclusion of 1kg of methionine hydroxyl analogue (88% purity) per ton of diet would supply −4876 mEq H+.
The objective of this study was to measure the ABC-4 values for organic acids using their compensating effects on various feedstuffs ABC-4 values and to propose a model predicting organic acids ABC-4 values using acid characteristics such as pKa and molecular weight. Measurements of the amount of HCl required to lower the pH of 1kg of sample to pH 4.0 were determined as the ABC-4 on a 0.5g sample of feed ingredient (wheat, soybean meal and dicalcium phosphate). A substitution of HCl 0.1N by an organic acid: dl-2-hydroxy-4-methylthiobutyric acid (HMTBA), formic acid, butyric acid or malic acid was realized with three different proportions (11.7, 23.5 or 35.2 mEq H+). The amount of HCl needed to lower the pH at 4 was recorded and the new ABC’-4 determined. The acidifying effect of organic acids was calculated for wheat and soybean as the difference between ABC’-4 and ABC-4. Results indicated that ABC-4 determined for wheat was lower than ABC-4 of soybean meal and dicalcium phosphate. A mixture of these ingredients resulted in the addition of their ABC-4 values proportionally to their level of inclusion. The ΔABC-4 obtained for organic acids showed a significant difference between these acids with HMTBA and formic acid having the highest acidifying effect on equivalent dose base. The slopes obtained from the linear regression of ΔABC-4 in function of the amount of organic acid added, were not significantly different between wheat and soybean meal for all selected organic acids. Based on these observations and knowing that purity, pKa and molar mass of the acid itself can affect the amount of H+ released, an equation was proposed to predict the ABC-4 of organic acids. HMTBA is as acidifying as formic acid on equimolar basis. Inclusion of 1kg of HMTBA per ton of diet would supply −4876 mEq H+. This study allowed feed formulation using ABC-4 of ingredients and acids for optimal weaned pig performance.
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Obesity, a recognized risk factor for breast cancer in postmenopausal women, is associated with higher mortality rates regardless of menopausal status, which could in part be explained by therapeutic ...escape. Indeed, adipose microenvironment has been described to influence the efficiency of chemo- and hormonal therapies. Residual cancer stem cells could also have a key role in this process. To understand the mechanisms involved in the reduced efficacy of hormonal therapy on breast cancer cells in the presence of adipose secretome, human adipose stem cells (hMAD cell line) differentiated into mature adipocytes were co-cultured with mammary breast cancer cells and treated with hormonal therapies (tamoxifen, fulvestrant). Proliferation and apoptosis were measured (fluorescence test, impedancemetry, cytometry) and the gene expression profile was evaluated. Cancer stem cells were isolated from mammospheres made from MCF-7. The impact of chemo- and hormonal therapies and leptin was evaluated in this population. hMAD-differentiated mature adipocytes and their secretions were able to increase mammary cancer cell proliferation and to suppress the antiproliferative effect of tamoxifen, confirming previous data and validating our model. Apoptosis and cell cycle did not seem to be involved in this process. The evaluation of gene expression profiles suggested that STAT3 could be a possible target. On the contrary, leptin did not seem to be involved. The study of isolated cancer stem cells revealed that their proliferation was stimulated in the presence of anticancer therapies (tamoxifen, fulvestrant, doxorubicine) and leptin. Our study confirmed the role of adipocytes and their secretome, but above all, the role of communication between adipose and cancer cells in interfering with the efficiency of hormonal therapy. Among the pathophysiological mechanisms involved, leptin does not seem to interfere with the estrogenic pathway but seems to promote the proliferation of cancer stem cells.
(1) Interest in the
family has risen as some members have shown anti-inflammatory properties and interesting compounds. In this regard, we decided to investigate the antioxidant and anti-inflammatory ...properties of
, a
not yet extensively studied, in the context of osteoarthritis. (2) The
Ethanol extract (LS-E) was used to test the production of reactive oxygen species (ROS) by leucocytes, the IL1β and PGE2 production by peripheral blood mononuclear cells (PBMCs), the production of EP4, and the activation of NFκB in THP-1, as well as the IL1β-activated normal human knee articular chondrocytes (NHAC-Kn) gene expression, grown in monolayers or maintained in alginate beads. (3) Organic acids, caffeoylquinic acids, quercetin and luteolin, compounds frequently found in this family were identified. The LS-E exhibited inhibited ROS formation. The LS-E did not affect NFκB activation and IL1β secretion but dampened the secretion of PGE2 by PBMCs and the presence of EP4 in THP-1. It also modulated the expression of NHAC-Kn in both models and inhibited the expression of several proteases and inflammatory mediators. (4)
might supply interesting antioxidant protection against cartilage damages and lessen joint inflammation, notably by decreasing PGE2 secretion in the synovial fluid. Moreover, it could act directly on chondrocytes by decreasing the expression of proteases and, thus, preventing the degradation of the extracellular matrix.
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Blood vessel-on-a-chip models aim at reproducing vascular functions. However, very few efficient methods have been designed to address the need for biological replicates in medium- to high-throughput ...screenings. Here, vessels-on-chip were designed in polydimethylsiloxane-glass chips using the viscous finger patterning technique which was adapted to create channels with various internal diameters inside a collagen solution and to simultaneously seed cells. This method was refined to create blood vessels composed of two concentric, distinct, and closely appositioned layers of human endothelial and perivascular cells arranged around a hollow lumen. These approaches allowed the formation of structurally correct blood vessels-on-chips which were constituted of either only endothelial cells or of both cell types in order to distinguish the vascular barrier reactivity to drugs in the presence or not of perivascular cells. The established vessels showed a tight vascular barrier, as assessed by immunostaining of the adherens junctions, and were reactive to the natural vasopermeant thrombin and to inflammatory cytokines. The presence of perivascular cells markedly increased the tightness of the vascular barrier and lowered its response to thrombin. The design allowed us to simultaneously challenge in real-time several tens of 3D-reconstituted, multicellular blood vessels in a standard multiwell plate format suitable for high-throughput drug screening.
Phenanthrenoids have been widely described, in the Juncaceae family, for theirbiological properties such as antitumor, anxiolytic, anti-microbial, spasmolytic, and antiinflammatoryactivities. The ...Juncaceae family is known to contain a large variety ofphenanthrenoids possessing especially anti-inflammatory and cytotoxic properties. Luzulasylvatica, a Juncaceae species, is widely present in the Auvergne region of France, but has neverbeen studied neither for its phytochemical profile nor for its biological properties. We investigatedthe phytochemical profile and evaluated the potential anti-inflammatory activities of L. sylvaticaaerial parts extracts. A bioassay-guided fractionation was carried out to identify the most activefractions. Nine compounds were isolated, one coumarin 1 and eight phenanthrene derivatives (2-9), including four new compounds (4, 5, 8 and 9), from n-hexane and CH2Cl2, fractions. Theirstructures were established by HRESIMS, 1D and 2D NMR experiments. The biological properties,especially the anti-inflammatory/antioxidant activities (ROS production) and antiproliferativeactivity on THP-1, a monocytic leukemia cell line, of each compound, were evaluated. Threephenanthrene derivatives 4, 6, and 7 showed very promising antiproliferative activities.Phenanthrene derivatives.
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Breast cancer is the most common cancer among women worldwide. Overweight and obesity are now recognized as established risk factors for this pathology in postmenopausal women. These conditions are ...also believed to be responsible for higher recurrence and mortality rates. Reciprocal interactions have been described between adipose and cancer cells. An adipose microenvironment favors a greater proliferation of cancer cells, their invasion and even resistance to anti-cancer treatments. In addition, the chronic low-grade inflammation observed in obese individuals is believed to amplify these processes. Among the cell types present in the breast, myoepithelial cells (MECs), located at the interface of the epithelial cells and the stroma, are considered "tumor suppressor" cells. During the transition from ductal carcinoma
to invasive cancer, disorganization or even the disappearance of MECs is observed, thereby enhancing the ability of the cancer cells to migrate. As the adipose microenvironment is now considered as a central actor in the progression of breast cancer, our objective was to evaluate if it could be involved in MEC functional modifications, leading to the transition of
to invasive carcinoma, particularly in obese patients. Through a co-culture model, we investigated the impact of human adipose stem cells from women of normal weight and obese women, differentiated or not into mature adipocytes, on the functionality of the MECs by measuring changes in viability, apoptosis, gene, and miRNA expressions. We found that adipose cells (precursors and differentiated adipocytes) could decrease the viability of the MECs, regardless of the original BMI. The adipose cells could also disrupt the expression of the genes involved in the maintenance of the extracellular matrix and to amplify the expression of leptin and inflammatory markers. miR-122-5p and miR-132-3p could also be considered as targets for adipose cells. The metabolite analyses revealed specific profiles that may be involved in the growth of neoplastic cells. All of these perturbations could thus be responsible for the loss of tumor suppressor status of MECs and promote the transition from
to invasive carcinoma.
Some Bupleurum species, such as the
DC. or the
Willd have been extensively studied (especially their roots) for the treatment of inflammation. In contrast, only compounds extracted from the aerial ...parts of
have been studied and showed anti-inflammatory or antiproliferative activities. This study was conducted to investigate the antioxidant, anti-inflammatory, and immunomodulatory effects of
roots.
To tackle the various aspects of inflammation, we studied in vitro a methanolic extract from the roots of
on peripheral blood mononuclear cells (PBMCs), polymorphonuclear neutrophils (PMNs), and the monocytic cells THP-1. Its antioxidant capacities and iron-chelating activity were assessed. The extract was tested on THP-1 differentiation, reactive oxygen species (ROS) production by leukocytes, neutrophils chemotaxis, cytokines, PGE2 production, and NF-κB activation in PBMCs.
The extract showed a decreased ROS production in stimulated cells. It increased PBMC chemokine secretion and up-regulated the differentiation of THP-1 monocytes into macrophage-like cells, indicating a potential interest of the extract in the resolution of acute inflammation. In addition, the analysis of cytokine production suggests that
has immunomodulatory properties.
Cytokines secretion, especially IL-1β and IL-12p70, provided us with a set of indicators suggesting that the extract might be able to drive the polarization of macrophages and lymphocytes toward a Th2 anti-inflammatory profile in excessive inflammation.
Although dietary Met, as the first limiting amino acid (AA), has been extensively studied for poultry, little is known about how the supply and source of free Met affect tissue composition. The ...purpose of this study was to investigate the effect of feeding young broiler chickens with a deficient or sufficient TSAA (Met+Cys) supply, using either dl-Met (dl-Met+ and dl-Met-, for respectively diets sufficient and deficient in TSAA) or dl-2-hydroxy-4-methylthiobutyric acid (HMTBA+ and HMTBA-, for respectively diets sufficient and deficient in TSAA) as a Met source on tissue composition and breast muscle traits. For both Met sources, the deficient diets were formulated to provide true digestible Met:Lys and TSAA:Lys respectively 45% and 30% below that of the sufficient diets. Performance and tissue weights were affected by the Met supply but not by the Met source. In TSAA-deficient chickens, ADG and FCR, and protein content in empty body and pectoralis major muscles (PM) were lower than in TSAA-sufficient chickens (P < 0.05). Reducing the Met content of the diet increased the redness value of PM (a*) and the hue angle (H°; P < 0.01). The source of Met affected body AA composition and the partitioning of body Cys among tissues (P < 0.05). In TSAA-deficient birds, body Cys mass decreased in the commercial carcass and PM, but increased in the rest of the body (P < 0.01). The Met source also had an impact on the Cys mass, which was reduced in the commercial carcass and PM of dl-Met birds, but higher in the rest, especially in the feathers of TSAA-deficient birds (P < 0.05). The Met source, supply, or both altered the AA composition of the empty body, mostly in the commercial carcass. In conclusion, a dietary TSAA deficiency altered performance, tissue composition and quality traits of PM of broilers. There was no impact between dietary dl-Met and dl-HMTBA on performance or muscle weight, although the Met source affected the partitioning of Cys among tissues.
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