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1.
Antioxidants (Basel) ; 11(1)2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35052640

RESUMO

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L-1) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L-1) and an aqueous extract (CAE, 100 µg mL-1) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53-115%) and fatty acid synthase activity (59-93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD.

2.
Food Funct ; 12(14): 6309-6322, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34085683

RESUMO

This work is aimed to evaluate the nutritional composition, and the techno-functional and in vitro physiological properties of flours made using six different insect species and the sensorial feasibility of including them in bakery products. The insect flours exhibited high protein and fat contents as their main components, highlighting the presence of chitin in ant samples. The techno-functional properties showed high oil holding, swelling, and emulsifying capacities in all the analysed insect flours, whereas their bulk density, hydration properties, and foaming capacity showed average values and no gelation capacity. Moreover, these edible insect flours exhibited effective hyperglycaemia and hyperlipidaemia properties, which together with their high antioxidant capacity are associated with beneficial in vitro physiological effects. The beetle and caterpillar flours stand out in these properties, and thus were selected to make a cupcake. The sensory evaluation confirmed that the edible beetle powder can be successfully included in baked goods to provide excellent sensory properties and very high acceptance. Thus, these insect flours may be of great interest to the food industry as a healthy source of protein, exerting a positive impact on functional and sensory food properties, and with a potential role in the prevention of diseases associated with hyperglycaemia and hyperlipidaemia.


Assuntos
Insetos Comestíveis/química , Valor Nutritivo , Animais , Antioxidantes/química , Formigas/química , Quitina/análise , Besouros/química , Gorduras na Dieta/análise , Proteínas na Dieta/análise , Manipulação de Alimentos/métodos , Indústria Alimentícia/métodos , Gryllidae/química , Humanos , Lepidópteros/química , Locusta migratoria/química , Microscopia Eletrônica de Varredura/métodos , Mariposas/química , Tenebrio/química
3.
Foods ; 10(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808664

RESUMO

This study aimed to model and optimize a green sustainable extraction method of phenolic compounds from the coffee husk. Response surface methodology (RSM) and artificial neural networks (ANNs) were used to model the impact of extraction variables (temperature, time, acidity, and solid-to-liquid ratio) on the recovery of phenolic compounds. All responses were fitted to the RSM and ANN model, which revealed high estimation capabilities. The main factors affecting phenolic extraction were temperature, followed by solid-to-liquid ratio, and acidity. The optimal extraction conditions were 100 °C, 90 min, 0% citric acid, and 0.02 g coffee husk mL-1. Under these conditions, experimental values for total phenolic compounds, flavonoids, flavanols, proanthocyanidins, phenolic acids, o-diphenols, and in vitro antioxidant capacity matched with predicted ones, therefore, validating the model. The presence of chlorogenic, protocatechuic, caffeic, and gallic acids and kaemferol-3-O-galactoside was confirmed by UPLC-ESI-MS/MS. The phenolic aqueous extracts from the coffee husk could be used as sustainable food ingredients and nutraceutical products.

4.
Cancers (Basel) ; 13(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803160

RESUMO

Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic approach in the management of several pathologies, including central nervous system diseases. Previously, we demonstrated the therapeutic potential of human adipose-derived MSCs for neurological sequelae of oncological radiotherapy using the intranasal route as a non-invasive delivery method. However, a comprehensive investigation of the safety of intranasal MSC treatment should be performed before clinical applications. Here, we cultured human MSCs in compliance with quality control standards and administrated repeated doses of cells into the nostrils of juvenile immunodeficient mice, mimicking the design of a subsequent clinical trial. Short- and long-term effects of cell administration were evaluated by in vivo and ex vivo studies. No serious adverse events were reported on mouse welfare, behavioral performances, and blood plasma analysis. Magnetic resonance study and histological analysis did not reveal tumor formation or other abnormalities in the examined organs of mice receiving MSCs. Biodistribution study reveals a progressive disappearance of transplanted cells that was further supported by an absent expression of human GAPDH gene in the major organs of transplanted mice. Our data indicate that the intranasal application of MSCs is a safe, simple and non-invasive strategy and encourage its use in future clinical trials.

5.
Food Funct ; 12(3): 1097-1110, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33427263

RESUMO

The dietary fibre and phenolic contents and the functional properties of extruded coffee parchment flour were studied to evaluate its possible use as an ingredient rich in dietary fibre (DF) with potential antioxidant, hypoglycaemic and hypolipidemic properties in extruded products. Coffee parchment flour treated at 160-175 °C and 25% moisture feed showed higher DF (84.3%) and phenolic contents (6.5 mg GAE per g) and antioxidant capacity (32.2 mg TE per g). The extrusion process favoured the release of phenolic compounds from the fibre matrix. Phytochemicals liberated during in vitro simulated digestion exhibited enhanced antioxidant capacity and attenuated reactive oxygen species in intestinal cells (IEC-6). However, the physicochemical and techno-functional properties were just affected by extrusion at high temperature, although extruded coffee parchment flours exhibited lower bulk density and higher swelling capacity than non-extruded ones. Extruded coffee parchment preserved the glucose adsorption capacity and enhanced the α-amylase in vitro inhibitory capacity (up to 81%). Moreover, extruded coffee parchment maintained the ability to delay glucose diffusion and exhibited improved capacity to retard starch digestion in the gastrointestinal tract. The extrusion of coffee parchment flours preserved the cholesterol-binding ability and augmented the capacity of this ingredient to bind bile salts, favouring the inhibition of pancreatic lipase by coffee parchment. These discoveries generate knowledge of the valorisation of coffee parchment as a food dietary fibre ingredient with antioxidant, hypoglycaemic, and hypolipidemic properties that are enhanced by the release of phenolic compounds from the fibre matrix through the production of extruded products.


Assuntos
Antioxidantes/farmacologia , Café/química , Manipulação de Alimentos , Resíduos Industriais , Animais , Antioxidantes/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Digestão , Células Epiteliais/efeitos dos fármacos , Glucose/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Mucosa Intestinal , Compostos Fitoquímicos , Ratos , Temperatura
6.
Foods ; 11(1)2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-35010198

RESUMO

Plants are the main natural source of numerous phytochemicals, although only a certain amount have been isolated and identified [...].

8.
Int J Mol Sci ; 21(18)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916960

RESUMO

STIM1 is an endoplasmic reticulum (ER) protein that modulates the activity of a number of Ca2+ transport systems. By direct physical interaction with ORAI1, a plasma membrane Ca2+ channel, STIM1 activates the ICRAC current, whereas the binding with the voltage-operated Ca2+ channel CaV1.2 inhibits the current through this latter channel. In this way, STIM1 is a key regulator of Ca2+ signaling in excitable and non-excitable cells, and altered STIM1 levels have been reported to underlie several pathologies, including immunodeficiency, neurodegenerative diseases, and cancer. In both sporadic and familial Alzheimer's disease, a decrease of STIM1 protein levels accounts for the alteration of Ca2+ handling that compromises neuronal cell viability. Using SH-SY5Y cells edited by CRISPR/Cas9 to knockout STIM1 gene expression, this work evaluated the molecular mechanisms underlying the cell death triggered by the deficiency of STIM1, demonstrating that STIM1 is a positive regulator of ITPR3 gene expression. ITPR3 (or IP3R3) is a Ca2+ channel enriched at ER-mitochondria contact sites where it provides Ca2+ for transport into the mitochondria. Thus, STIM1 deficiency leads to a strong reduction of ITPR3 transcript and ITPR3 protein levels, a consequent decrease of the mitochondria free Ca2+ concentration ([Ca2+]mit), reduction of mitochondrial oxygen consumption rate, and decrease in ATP synthesis rate. All these values were normalized by ectopic expression of ITPR3 in STIM1-KO cells, providing strong evidence for a new mode of regulation of [Ca2+]mit mediated by the STIM1-ITPR3 axis.


Assuntos
Sinalização do Cálcio , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Mitocôndrias/metabolismo , Proteínas de Neoplasias/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Técnicas de Inativação de Genes , Humanos , Proteínas de Neoplasias/genética , Molécula 1 de Interação Estromal/genética
9.
Sci Rep ; 10(1): 6580, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313105

RESUMO

Tumor invasion requires efficient cell migration, which is achieved by the generation of persistent and polarized lamellipodia. The generation of lamellipodia is supported by actin dynamics at the leading edge where a complex of proteins known as the WAVE regulatory complex (WRC) promotes the required assembly of actin filaments to push the front of the cell ahead. By using an U2OS osteosarcoma cell line with high metastatic potential, proven by a xenotransplant in zebrafish larvae, we have studied the role of the plasma membrane Ca2+ channel ORAI1 in this process. We have found that epidermal growth factor (EGF) triggered an enrichment of ORAI1 at the leading edge, where colocalized with cortactin (CTTN) and other members of the WRC, such as CYFIP1 and ARP2/3. ORAI1-CTTN co-precipitation was sensitive to the inhibition of the small GTPase RAC1, an upstream activator of the WRC. RAC1 potentiated ORAI1 translocation to the leading edge, increasing the availability of surface ORAI1 and increasing the plasma membrane ruffling. The role of ORAI1 at the leading edge was studied in genetically engineered U2OS cells lacking ORAI1 expression that helped us to prove the key role of this Ca2+ channel on lamellipodia formation, lamellipodial persistence, and cell directness, which are required for tumor cell invasiveness in vivo.


Assuntos
Cortactina/genética , Proteína ORAI1/genética , Osteossarcoma/genética , Pseudópodes/genética , Proteínas rac1 de Ligação ao GTP/genética , Citoesqueleto de Actina/genética , Complexo 2-3 de Proteínas Relacionadas à Actina/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Movimento Celular/genética , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Pseudópodes/metabolismo
10.
Antioxidants (Basel) ; 9(4)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218124

RESUMO

Twin pregnancies are increasing due to the rise in mothers' childbearing age and have a higher risk of fetal growth restriction (FGR) and prematurity. Therefore, early prediction of these events is important. Our aim was to analyze in the first trimester of pregnancy a possible association between antioxidants, including melatonin, in maternal plasma and the development of fetal complications in twin pregnancies. A single-center, prospective, and observational study was performed in 104 twin-pregnant women. A blood sample was extracted between the 9th and the 11th week of gestation, and plasma was obtained. Antioxidants (thiols, reduced glutathione, phenolic compounds, catalase, superoxide dismutase) and oxidative damage biomarkers (carbonyl groups and malondialdehyde) were assessed by spectrophotometry, and global scores were calculated from these parameters (Antiox-S, Prooxy-S). Melatonin and cortisol were evaluated by a competitive immunoassay. In the first trimester of pregnancy, Antiox-S was significantly lower in women who developed FGR compared to those with normal fetal growth; plasma melatonin was significantly lower in women with preterm compared to those with full-term births and exhibited a positive correlation with birth weight. Maternal cortisol showed a negative correlation with birth weight. We conclude that, for twin gestations, maternal plasma antioxidant status and melatonin could be potential biomarkers to be included in algorithms to predict FGR and preterm labor.

11.
Foods ; 9(3)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178261

RESUMO

Melatonin is a multifunctional antioxidant neurohormone found in plant foods such as lentil sprouts. We aim to evaluate the effect of lentil sprout intake on the plasmatic levels of melatonin and metabolically related compounds (plasmatic serotonin and urinary 6-sulfatoxymelatonin), total phenolic compounds, and plasmatic antioxidant status, and compare it with synthetic melatonin. The germination of lentils increases the content of melatonin. However, the phenolic content diminished due to the loss of phenolic acids and flavan-3-ols. The flavonol content remained unaltered, being the main phenolic family in lentil sprouts, primarily composed of kaempferol glycosides. Sprague Dawley rats were used to investigate the pharmacokinetic profile of melatonin after oral administration of a lentil sprout extract and to evaluate plasma and urine melatonin and related biomarkers and antioxidant capacity. Melatonin showed maximum concentration (45.4 pg/mL) 90 min after lentil sprout administration. The plasmatic melatonin levels increased after lentil sprout intake (70%, p < 0.05) with respect to the control, 1.2-fold more than after synthetic melatonin ingestion. These increments correlated with urinary 6-sulfatoxymelatonin content (p < 0.05), a key biomarker of plasmatic melatonin. Nonetheless, the phenolic compound content did not exhibit any significant variation. Plasmatic antioxidant status increased in the antioxidant capacity upon both lentil sprout and synthetic melatonin administration. For the first time, we investigated the bioavailability of melatonin from lentil sprouts and its role in plasmatic antioxidant status. We concluded that their intake could increase melatonin plasmatic concentration and attenuate plasmatic oxidative stress.

12.
Foods ; 8(10)2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557849

RESUMO

This work aimed to evaluate the contribution of isoflavones and melatonin to the aqueous extract obtained from the coffee silverskin (CSE) antiglycative properties, which has not been previously studied. To achieve this goal, two model systems constituted by bovine serum albumin (BSA) and reactive carbonyls (glucose or methylglyoxal) in the presence or absence of pure phytochemicals (chlorogenic acid (CGA), genistein, and melatonin) and CSE were employed. Glucose was used to evaluate the effect on the formation of glycation products formed mainly in the early stage of the reaction, while methylglyoxal was employed for looking at the formation of advanced products of the reaction, also called methylglyoxal-derivative advanced glycation end products (AGE) or glycoxidation products. CGA inhibited the formation of fructosamine, while genistein and melatonin inhibited the formation of advanced glycation end products and protein glycoxidation. It was also observed that phenolic compounds from CSE inhibited protein glycation and glycoxidation by forming BSA-phytochemical complexes. CSE showed a significant antiglycative effect (p < 0.05). Variations in the UV-Vis spectrum and the antioxidant capacity of protein fractions suggested the formation of protein-phytochemical complexes. Fluorescence quenching and in silico analysis supported the formation of antioxidant-protein complexes. For the first time, we illustrate that isoflavones and melatonin may contribute to the antiglycative/antiglycoxidative properties associated with CSE. CGA, isoflavones, and melatonin composing CSE seem to act simultaneously by different mechanisms of action.

13.
Antioxidants (Basel) ; 8(8)2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387271

RESUMO

This study aimed to compare the phytochemicals from coffee and cocoa by-products and their relationship with the potential for reducing markers of inflammation, oxidative stress, adipogenesis, and insulin resistance in vitro. We characterized the phytochemical profile of extracts from coffee husk, coffee silverskin, and cocoa shell and evaluated their in vitro biological activity in RAW264.7 macrophages and 3T3-L1 adipocytes. Pearson correlations and principal component regressions were performed to find the contribution of phytochemicals and underlying mechanisms of action. Coffee husk and silverskin extracts were mainly composed of caffeine and chlorogenic acid. Major components in cocoa shell included theobromine and protocatechuic acid. Both coffee and cocoa by-product extracts effectively reduced inflammatory markers in macrophages and adipocytes (NO, PGE2, TNF-α, MCP-1, and IL-6) and the production of reactive oxygen species (21.5-66.4%). Protocatechuic and chlorogenic acids, together with caffeine, were suggested as main contributors against inflammation and oxidative stress. Furthermore, extracts reduced lipid accumulation (4.1-49.1%) in adipocytes by regulating lipolysis and inducing adipocyte browning. Gallic and chlorogenic acids were associated with reduced adipogenesis, and caffeine with adipocyte browning. Extracts from coffee and cocoa by-products also modulated the phosphorylation of insulin receptor signaling pathway and stimulated GLUT-4 translocation (52.4-72.9%), increasing glucose uptake. The insulin-sensitizing potential of the extracts was mainly associated with protocatechuic acid. For the first time, we identified the phytochemicals from coffee and cocoa by-products and offered new insights into their associations with biomarkers of inflammation, oxidative stress, adipogenesis, and insulin resistance in vitro.

14.
Food Funct ; 10(8): 4739-4750, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31309208

RESUMO

Coffee parchment is one of the less studied coffee by-products, being rich in phenolic compounds. The objective of this study was to revalorise coffee parchment, obtaining aqueous extracts rich in phenolic compounds, optimising the extraction conditions using response surface methodology and comprehensively characterising the obtained extracts. A Box-Behnken design was used to maximise the recovery of total phenolic compounds, total flavonoids, total flavanols, total phenolic acids, and total ortho-diphenols, and the antioxidant capacity of coffee parchment extracts. The main factor influencing phenolic compound extraction was temperature, followed by solid-to-solvent ratio and acidity. Optimised heat-assisted extraction conditions were 100 °C, 90 min, 0% citric acid, and 0.02 g mL-1 solid-to-solvent ratio. Under these conditions, the concentrations of phenolic compounds and antioxidant capacity were equivalent to those expected, allowing us to validate the model. The UPLC-ESI-MS/MS phenolic profile exhibited the occurrence of 13 phenolic compounds, with those shown in higher concentrations being chlorogenic acid, vanillic acid, protocatechuic acid, and p-coumaric acid. The findings of this study provide valuable insights into the potential application of a useful, clean, environmentally friendly and cost-effective method to recover phenolic compounds from coffee parchment and, thus, to revalorize the by-product by converting it into high-added value new products to be used in the food and cosmetic industries.


Assuntos
Fracionamento Químico/métodos , Coffea/química , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Resíduos/análise , Antioxidantes/química , Antioxidantes/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Temperatura Alta , Fenóis/química , Extratos Vegetais/química , Sementes/química , Espectrometria de Massas em Tandem
15.
Food Chem Toxicol ; 132: 110672, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306686

RESUMO

The aim of this study was to evaluate the inhibitory potential of aqueous extracts from coffee silverskin (CSE) and husk (CHE) and their main phenolics on adipogenesis, obesity-related inflammation, mitochondrial dysfunction, and insulin resistance, in vitro. Coffee by-products extracts (31-500 µg mL-1) and pure phenolics (100 µmol L-1) reduced lipid accumulation and increased mitochondrial activity in 3T3-L1 adipocytes. Also reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2 and diminished secretion of pro-inflammatory factors in LPS-stimulated RAW2643.7 macrophages. Cytokine release diminished (tumor necrosis factor α: 23-57%; monocyte chemoattractant protein 1: 42-60%; interleukin-6: 30-39%) and adiponectin increased (7-13- fold) in adipocytes treated with macrophage-conditioned media. ROS scavenging and activation of peroxisome proliferator-activated receptor γ coactivator 1-α pathway counteracted mitochondrial dysfunction. Increases in insulin receptor (1.4 to 4-fold), phosphoinositide 3-kinase (2 to 3-fold) and protein kinase B (1.3 to 3-fold) phosphorylation, in conjunction with a decrease in serine phosphorylation of insulin receptor substrate 1, evoked glucose transporter 4 translocation (8-15-fold) and glucose uptake (44-85%). CSE and CHE phenolics inhibited adipogenesis and elicited adipocytes browning. Suppressing macrophages-adipocytes interaction alleviated inflammation-triggered mitochondrial dysfunction and insulin resistance. CSE and CHE are beneficial in reducing adipogenesis and inflammation-related disorders.


Assuntos
Adipogenia/efeitos dos fármacos , Café/química , Inflamação/patologia , Resistência à Insulina , Mitocôndrias/efeitos dos fármacos , Fenóis/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Meios de Cultivo Condicionados , Camundongos , Mitocôndrias/fisiologia , Fenóis/isolamento & purificação , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
16.
Front Cell Neurosci ; 13: 204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156392

RESUMO

Radiotherapy is a highly effective tool for the treatment of brain cancer. However, radiation also causes detrimental effects in the healthy tissue, leading to neurocognitive sequelae that compromise the quality of life of brain cancer patients. Despite the recognition of this serious complication, no satisfactory solutions exist at present. Here we investigated the effects of intranasal administration of human mesenchymal stem cells (hMSCs) as a neuroprotective strategy for cranial radiation in mice. Our results demonstrated that intranasally delivered hMSCs promote radiation-induced brain injury repair, improving neurological function. This intervention confers protection against inflammation, oxidative stress, and neuronal loss. hMSC administration reduces persistent activation of damage-induced c-AMP response element-binding signaling in irradiated brains. Furthermore, hMSC treatment did not compromise the survival of glioma-bearing mice. Our findings encourage the therapeutic use of hMSCs as a non-invasive approach to prevent neurological complications of radiotherapy, improving the quality of life of brain tumor patients.

17.
Front Immunol ; 10: 1151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231366

RESUMO

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI.

18.
Food Res Int ; 122: 105-113, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31229061

RESUMO

Coffee parchment was evaluated as a potential dietary fiber ingredient. For this purpose, dietary fiber was extracted by enzymatic and non-enzymatic methods and its physicochemical and in vitro hypoglycemic and hypolipidemic properties were investigated. Results revealed that coffee parchment (flakes and flour) was a good source of insoluble dietary fiber (IDF), mainly composed by xylans (35%), lignin (32%), and cellulose (12%). From results, the IDF extraction seemed not to be required the use of enzymes. Coffee parchment did not stand out by its content of phenolic compounds and antioxidant capacity, but milling process improved them. Due to its physical structure, coffee parchment flakes exhibited high oil holding capacity (3.8 mg L-1), gelation capacity (8%) besides hydration properties, including water holding (3.4 mg L-1), absorption (3.0 mg L-1) and swelling (14 mg L-1) capacities. Its flour and water-insoluble residue showed lower capacities. Nevertheless, these coffee parchment samples presented effective in vitro hypoglycemic properties, showing high glucose adsorption capacity (50-200 mmol L-1), and capacity to decrease its diffusion (13%), and to inhibit α-amylase (52%) that led to lower starch digestibility (until 46%); and also, outstanding in vitro hypolipidemic properties, as inhibition of pancreatic lipase (43%) and binding of cholesterol and sodium cholate (16.6 and 35.3 mg g-1, respectively). These results provide valuable information for the potential use of coffee parchment as new food DF ingredient.


Assuntos
Café/química , Fibras na Dieta , Adsorção , Colesterol/química , Colesterol/metabolismo , Fibras na Dieta/análise , Fibras na Dieta/metabolismo , Glucose/química , Glucose/metabolismo , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Hipolipemiantes/química , Hipolipemiantes/metabolismo , Colato de Sódio/química , Colato de Sódio/metabolismo
19.
Mol Nutr Food Res ; 63(10): e1801413, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31018035

RESUMO

SCOPE: The aim is to assess the action of an aqueous extract from cocoa shell (CAE) and its main phenolic compounds to prevent the loss of obesity-induced mitochondrial function and insulin sensitivity, targeting inflammation between macrophages-adipocytes in vitro. METHODS AND RESULTS: CAE (31-500 µg mL-1 ) inhibits 3T3-L1 adipocytes lipid accumulation and induces browning during differentiation. LPS-stimulated RAW264.7 macrophages show reduced inducible nitric oxide synthase and cyclooxygenase-2 expression and lowered pro-inflammatory cytokine production when treated with CAE and pure phenolics. Inflammatory crosstalk created by stimulating adipocytes with macrophage-conditioned media (CM) is arrested; CAE diminishes tumor necrosis factor-α (67%) and promotes adiponectin secretion (12.3-fold). Mitochondrial function, measured by reactive oxygen species production, mitochondrial content, and activity, is preserved in CM-treated adipocytes through up-regulating peroxisome proliferator-activated receptor gamma coactivator 1-α expression. Increases in insulin receptor (9-fold), phosphoinositide 3-kinase (3-fold), protein kinase B (4-fold) phosphorylation, and a decrease in insulin receptor substrate 1 serine phosphorylation induce increased glucose uptake (34%) and glucose transporter 4 translocation (14-fold) in CM-induced adipocytes. CONCLUSION: CAE phenolics promote a beige phenotype in adipocytes. Macrophages-adipocytes inflammatory interaction is reduced preventing mitochondrial dysfunction and insulin resistance. For the first time, CAE shows a positive effect on adipogenesis and inflammation-related disorders.


Assuntos
Adipócitos/efeitos dos fármacos , Cacau/química , Macrófagos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Biflavonoides/farmacologia , Catequina/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Hidroxibenzoatos/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Mitocôndrias/metabolismo , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Proantocianidinas/farmacologia , Células RAW 264.7
20.
Mol Ther ; 26(11): 2696-2709, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30195725

RESUMO

Diabetes is a chronic metabolic disorder that affects 415 million people worldwide. This pathology is often associated with long-term complications, such as critical limb ischemia (CLI), which increases the risk of limb loss and mortality. Mesenchymal stromal cells (MSCs) represent a promising option for the treatment of diabetes complications. Although MSCs are widely used in autologous cell-based therapy, their effects may be influenced by the constant crosstalk between the graft and the host, which could affect the MSC fate potential. In this context, we previously reported that MSCs derived from diabetic patients with CLI have a defective phenotype that manifests as reduced fibrinolytic activity, thereby enhancing the thrombotic risk and compromising patient safety. Here, we found that MSCs derived from diabetic patients with CLI not only exhibit a prothrombotic profile but also have altered multi-differentiation potential, reduced proliferation, and inhibited migration and homing to sites of inflammation. We further demonstrated that this aberrant cell phenotype is reversed by the platelet-derived growth factor (PDGF) BB, indicating that PDGF signaling is a key regulator of MSC functionality. These findings provide an attractive approach to improve the therapeutic efficacy of MSCs in autologous therapy for diabetic patients.


Assuntos
Diabetes Mellitus/genética , Inflamação/genética , Células-Tronco Mesenquimais/metabolismo , Proteínas Proto-Oncogênicas c-sis/genética , Animais , Diferenciação Celular/genética , Proliferação de Células/genética , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células Cultivadas , Complicações do Diabetes/genética , Complicações do Diabetes/patologia , Complicações do Diabetes/terapia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Diabetes Mellitus/terapia , Humanos , Inflamação/patologia , Inflamação/terapia , Camundongos , Camundongos SCID , Osteogênese/genética , Fenótipo , Proteínas Proto-Oncogênicas c-sis/uso terapêutico , Transdução de Sinais , Cicatrização/genética
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