Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 111
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nutrients ; 13(9)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34578843

RESUMO

Heart failure (HF) characterized by cardiac remodeling is a condition in which inflammation and fibrosis play a key role. Dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) seems to produce good results. In fact, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory and antioxidant properties and different cardioprotective mechanisms. In particular, following their interaction with the nuclear factor erythropoietin 2 related factor 2 (NRF2), the free fatty acid receptor 4 (Ffar4) receptor, or the G-protein coupled receptor 120 (GPR120) fibroblast receptors, they inhibit cardiac fibrosis and protect the heart from HF onset. Furthermore, n-3 PUFAs increase the left ventricular ejection fraction (LVEF), reduce global longitudinal deformation, E/e ratio (early ventricular filling and early mitral annulus velocity), soluble interleukin-1 receptor-like 1 (sST2) and high-sensitive C Reactive protein (hsCRP) levels, and increase flow-mediated dilation. Moreover, lower levels of brain natriuretic peptide (BNP) and serum norepinephrine (sNE) are reported and have a positive effect on cardiac hemodynamics. In addition, they reduce cardiac remodeling and inflammation by protecting patients from HF onset after myocardial infarction (MI). The positive effects of PUFA supplementation are associated with treatment duration and a daily dosage of 1-2 g. Therefore, both the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association (ACC/AHA) define dietary supplementation with n-3 PUFAs as an effective therapy for reducing the risk of hospitalization and death in HF patients. In this review, we seek to highlight the most recent studies related to the effect of PUFA supplementation in HF. For that purpose, a PubMed literature survey was conducted with a focus on various in vitro and in vivo studies and clinical trials from 2015 to 2021.

2.
Nutrients ; 13(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34371986

RESUMO

Cardiovascular disease is the leading cause of death and disability in the Western world. In order to safeguard the structure and the functionality of the myocardium, it is extremely important to adequately support the cardiomyocytes. Two cellular organelles of cardiomyocytes are essential for cell survival and to ensure proper functioning of the myocardium: mitochondria and the sarcoplasmic reticulum. Mitochondria are responsible for the energy metabolism of the myocardium, and regulate the processes that can lead to cell death. The sarcoplasmic reticulum preserves the physiological concentration of the calcium ion, and triggers processes to protect the structural and functional integrity of the proteins. The alterations of these organelles can damage myocardial functioning. A proper nutritional balance regarding the intake of macronutrients and micronutrients leads to a significant improvement in the symptoms and consequences of heart disease. In particular, the Mediterranean diet, characterized by a high consumption of plant-based foods, small quantities of red meat, and high quantities of olive oil, reduces and improves the pathological condition of patients with heart failure. In addition, nutritional support and nutraceutical supplementation in patients who develop heart failure can contribute to the protection of the failing myocardium. Since polyphenols have numerous beneficial properties, including anti-inflammatory and antioxidant properties, this review gathers what is known about the beneficial effects of polyphenol-rich bergamot fruit on the cardiovascular system. In particular, the role of bergamot polyphenols in mitochondrial and sarcoplasmic dysfunctions in diabetic cardiomyopathy is reported.


Assuntos
Cardiomiopatias Diabéticas/fisiopatologia , Mitocôndrias/efeitos dos fármacos , Óleos Vegetais/farmacologia , Polifenóis/farmacologia , Retículo Sarcoplasmático/efeitos dos fármacos , Animais , Suplementos Nutricionais , Humanos , Miocárdio/metabolismo , Azeite de Oliva/farmacologia
3.
Int J Mol Sci ; 22(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34360675

RESUMO

In recent decades, interest in natural compounds has increased exponentially due to their numerous beneficial properties in the treatment of various acute and chronic diseases. A group of plant derivatives with great scientific interest is terpenic compounds. Among the plants richest in terpenes, the genus Ferula L. is one of the most representative, and ferutinin, the most common sesquiterpene, is extracted from the leaves, rhizome, and roots of this plant. As reported in the scientific literature, ferutinin possesses antioxidant and anti-inflammatory properties, as well as valuable estrogenic properties. Neurodegenerative and demyelinating diseases are devastating conditions for which a definite cure has not yet been established. The mechanisms involved in these diseases are still poorly understood, and oxidative stress is considered to be both a key modulator and a common denominator. In the proposed experimental system, co-cultured human neurons (SH-SY5Y) and human oligodendrocytes (MO3.13) were treated with the pro-inflammatory agent lipopolysaccharide at a concentration of 1 µg/mL for 24 h or pretreated with ferutinin (33 nM) for 24 h and subsequently exposed to lipopolysaccharide 1 µg/mL for 24 h. Further studies would, however, be needed to establish whether this natural compound can be used as a support strategy in pathologies characterized by progressive inflammation and oxidative stress phenomena.


Assuntos
Benzoatos/farmacologia , Cicloeptanos/farmacologia , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Neurônios/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Estresse Oxidativo , Sesquiterpenos/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Linhagem Celular , Técnicas de Cocultura , Escherichia coli , Humanos , Inflamação/induzido quimicamente , Neurônios/metabolismo , Neurônios/patologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Substâncias Protetoras/farmacologia
4.
Nutrients ; 13(7)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201904

RESUMO

Doxorubicin is an anthracycline that is commonly used as a chemotherapy drug due to its cytotoxic effects. The clinical use of doxorubicin is limited due to its known cardiotoxic effects. Treatment with anthracyclines causes heart failure in 15-17% of patients, resulting in mitochondrial dysfunction, the accumulation of reactive oxygen species, intracellular calcium dysregulation, the deterioration of the cardiomyocyte structure, and apoptotic cell death. Polyphenols have a wide range of beneficial properties, and particular importance is given to Bergamot Polyphenolic Fraction; Oleuropein, one of the main polyphenolic compounds of olive oil; and Cynara cardunculus extract. These natural compounds have particular beneficial characteristics, owing to their high polyphenol contents. Among these, their antioxidant and antoproliferative properties are the most important. The aim of this paper was to investigate the effects of these three plant derivatives using an in vitro model of cardiotoxicity induced by the treatment of rat embryonic cardiomyoblasts (H9c2) with doxorubicin. The biological mechanisms involved and the crosstalk existing between the mitochondria and the endoplasmic reticulum were examined. Bergamot Polyphenolic Fraction, Oleuropein, and Cynara cardunculus extract were able to decrease the damage induced by exposure to doxorubicin. In particular, these natural compounds were found to reduce cell mortality and oxidative damage, increase the lipid content, and decrease the concentration of calcium ions that escaped from the endoplasmic reticulum. In addition, the direct involvement of this cellular organelle was demonstrated by silencing the ATF6 arm of the Unfolded Protein Response, which was activated after treatment with doxorubicin.


Assuntos
Cardiotoxicidade/tratamento farmacológico , Cynara/química , Doxorrubicina/efeitos adversos , Olea/química , Extratos Vegetais/farmacologia , Animais , Antraciclinas , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Suplementos Nutricionais , Glucosídeos Iridoides , Mitocôndrias , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo , Polifenóis/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo
5.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805912

RESUMO

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Suplementos Nutricionais , Inflamação/metabolismo , Obesidade/metabolismo , Termogênese , Adipogenia , Tecido Adiposo/metabolismo , Animais , Curcumina/química , Dieta , Retículo Endoplasmático/metabolismo , Ácidos Graxos Insaturados/metabolismo , Humanos , Resistência à Insulina , Intestinos/química , Lipídeos/química , Macrófagos/metabolismo , Polifenóis/química , Resveratrol/farmacologia , Transdução de Sinais
6.
Oxid Med Cell Longev ; 2021: 8841911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815663

RESUMO

Despite the international scientific community's commitment to improve clinical knowledge about coronavirus disease 2019 (COVID-19), knowledge regarding molecular details remains limited. In this review, we discuss hypoxia's potential role in the pathogenesis of the maladaptive immune reaction against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The state of infection, with serious respiratory dysfunction, causes tissues to become hypoxic due to a discrepancy between cellular O2 uptake and consumption similar to that seen within tumor tissue during the progression of numerous solid cancers. In this context, the heterogeneous clinical behavior and the multiorgan deterioration of COVID-19 are discussed as a function of the upregulated expression of the hypoxia-inducible factor-1 (HIF-1) and of the metabolic reprogramming associated with HIF-1 and with a proinflammatory innate immune response activation, independent of the increase in the viral load of SARS-CoV-2. Possible pharmacological strategies targeting O2 aimed to improve prognosis are suggested.


Assuntos
COVID-19/metabolismo , COVID-19/patologia , Polaridade Celular , Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/metabolismo , Microglia/metabolismo , Efeito Warburg em Oncologia , COVID-19/imunologia , COVID-19/virologia , Humanos , SARS-CoV-2/fisiologia
7.
Antioxidants (Basel) ; 10(3)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807637

RESUMO

Atherothrombosis, a multifactorial and multistep artery disorder, represents one of the main causes of morbidity and mortality worldwide. The development and progression of atherothrombosis is closely associated with age, gender and a complex relationship between unhealthy lifestyle habits and several genetic risk factors. The imbalance between oxidative stress and antioxidant defenses is the main biological event leading to the development of a pro-oxidant phenotype, triggering cellular and molecular mechanisms associated with the atherothrombotic process. The pathogenesis of atherosclerosis and its late thrombotic complications involve multiple cellular events such as inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells (SMCs), extracellular matrix (ECM) alterations, and platelet activation, contributing to chronic pathological remodeling of the vascular wall, atheromatous plague formation, vascular stenosis, and eventually, thrombus growth and propagation. Emerging studies suggest that clotting activation and endothelial cell (EC) dysfunction play key roles in the pathogenesis of atherothrombosis. Furthermore, a growing body of evidence indicates that defective autophagy is closely linked to the overproduction of reactive oxygen species (ROS) which, in turn, are involved in the development and progression of atherosclerotic disease. This topic represents a large field of study aimed at identifying new potential therapeutic targets. In this review, we focus on the major role played by the autophagic pathway induced by oxidative stress in the modulation of EC dysfunction as a background to understand its potential role in the development of atherothrombosis.

8.
J Cardiovasc Med (Hagerstown) ; 22(4): 268-278, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33633042

RESUMO

AIMS: Diabetic cardiomyopathy represents the main cause of death among diabetic people. Despite this evidence, the molecular mechanisms triggered by impaired glucose and lipid metabolism inducing heart damage remain unclear. The aim of our study was to investigate the effect of altered metabolism on the early stages of cardiac injury in experimental diabetes. METHODS: For this purpose, rats were fed a normocaloric diet (NPD) or a high fat diet (HFD) for up to 12 weeks. After the fourth week, streptozocin (35 mg/kg) was administered in a subgroup of both NPD and HFD rats to induce diabetes. Cardiac function was analysed by echocardiography. Matrix metalloproteinases (MMPs) activity and intracellular localization were assessed through zymography and immunofluorescence, whereas apoptotic and oxidative markers by immunohistochemistry and western blot. RESULTS: Hyperglycaemia or hyperlipidaemia reduced ejection fraction and fractional shortening as compared with control. Unexpectedly, cardiac dysfunction was less marked in diabetic rats fed a hyperlipidaemic diet, suggesting an adaptive response of the myocardium to hyperglycaemia-induced injury. This response was characterized by the inhibition of N-terminal truncated-MMP-2 translocation from endoplasmic reticulum into mitochondria and by superoxide anion overproduction observed in cardiomyocytes under hyperglycaemia. CONCLUSION: Overall, these findings suggest novel therapeutic targets aimed to counteract mitochondrial dysfunction in the onset of diabetic cardiomyopathy.

9.
Nutrients ; 13(1)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33477916

RESUMO

Cardiovascular diseases (CVDs), which include congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, and many other cardiac disorders, cause about 30% of deaths globally; representing one of the main health problems worldwide. Among CVDs, ischemic heart diseases (IHDs) are one of the major causes of morbidity and mortality in the world. The onset of IHDs is essentially due to an unbalance between the metabolic demands of the myocardium and its supply of oxygen and nutrients, coupled with a low regenerative capacity of the heart, which leads to great cardiomyocyte (CM) loss; promoting heart failure (HF) and myocardial infarction (MI). To date, the first strategy recommended to avoid IHDs is prevention in order to reduce the underlying risk factors. In the management of IHDs, traditional therapeutic options are widely used to improve symptoms, attenuate adverse cardiac remodeling, and reduce early mortality rate. However, there are no available treatments that aim to improve cardiac performance by replacing the irreversible damaged cardiomyocytes (CMs). Currently, heart transplantation is the only treatment being carried out for irreversibly damaged CMs. Hence, the discovery of new therapeutic options seems to be necessary. Interestingly, recent experimental evidence suggests that regenerative stem cell medicine could be a useful therapeutic approach to counteract cardiac damage and promote tissue regeneration. To this end, researchers are tasked with answering one main question: how can myocardial regeneration be stimulated? In this regard, natural compounds from plant extracts seem to play a particularly promising role. The present review will summarize the recent advances in our knowledge of stem cell therapy in the management of CVDs; focusing on the main properties and potential mechanisms of natural compounds in stimulating and activating stem cells for myocardial regeneration.


Assuntos
Doenças Cardiovasculares/terapia , Miócitos Cardíacos/fisiologia , Extratos Vegetais/farmacologia , Transplante de Células-Tronco , Células-Tronco/fisiologia , Animais , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Diferenciação Celular , Suplementos Nutricionais , Humanos , Miócitos Cardíacos/citologia , Regeneração , Células-Tronco/citologia
10.
Biomolecules ; 11(1)2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33435178

RESUMO

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease that affects about 1% of the global population, with a female-male ratio of 3:1. RA preferably affects the joints, with consequent joint swelling and deformities followed by ankylosis. However, evidence has accumulated showing that patients suffering from RA can also develop extra-articular manifestations, including cardiovascular disease states, neuropathies, and multiorgan dysfunction. In particular, peripheral nerve disorders showed a consistent impact in the course of the disease (prevalence about 20%) mostly associated to vasculitis of the nerve vessels leading to vascular ischemia, axonal degeneration, and neuronal demyelination. The pathophysiological basis of this RA-associated microvascular disease, which leads to impairment of assonal functionality, is still to be better clarified. However, endothelial dysfunction and alterations of the so-called brain-nerve barrier (BNB) seem to play a fundamental role. This review aims to assess the potential mechanisms underlying the impairment of endothelial cell functionality in the development of RA and to identify the role of dysfunctional endothelium as a causative mechanism of extra-articular manifestation of RA. On the other hand, the potential impact of lifestyle and nutritional interventions targeting the maintenance of endothelial cell integrity in patients with RA will be discussed as a potential option when approaching therapeutic solutions in the course of the disease.


Assuntos
Artrite Reumatoide/fisiopatologia , Endotélio Vascular/fisiopatologia , Sistema Nervoso/patologia , Animais , Disfunção Cognitiva/complicações , Estresse do Retículo Endoplasmático , Endotélio Vascular/patologia , Humanos , Estilo de Vida
11.
Pharmacol Res ; 165: 105427, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33453372

RESUMO

Skeletal muscles and bone tissue form the musculoskeletal apparatus, a complex system essential for the voluntary movement. The loss of muscle mass and muscle strength is often associated with a loss of bone mass, in a "hazardous duet" which implies the co-existence of sarcopenia-osteoporosis and exposes patients to a deterioration in quality of life and increased mortality. From the mechanostat theory to the recent definition of the osteosarcopenia syndrome, many aspects of muscle-bone interaction have been investigated in recent decades. The mechanical interaction is now accepted, considering the close anatomical relationship between the two tissues, however, much remains to be discovered regarding the biochemical muscle-bone interaction. Skeletal muscle has been defined as an endocrine organ capable of exerting an action on other tissues. Myokines, bioactive polypeptides released by the muscle, could represent the encrypted message in the communication between muscle and bone. These two tissues have a reciprocal influence on their metabolisms and respond in a similar way to the multiple external factors. The aim of this review is to stimulate the understanding of the encrypted language between muscle and bone, highlighting the role of catabolic pathways and oxidative stress in the musculoskeletal apparatus to elucidate the shared mechanisms and the similarity of response to the same stimuli by different tissues. Our understanding of muscle-bone interactions it could be useful to identify and develop new strategies to treat musculoskeletal diseases, together with pharmacological, nutritional and exercise-based approaches, which are already in use for the treatment of these pathologies.

12.
Nutrients ; 13(1)2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33477388

RESUMO

There is evidence demonstrating that heart failure (HF) occurs in 1-2% of the global population and is often accompanied by comorbidities which contribute to increasing the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non-pharmacological approaches have led to a significant improvement in clinical outcomes in patients affected by HF, residual unmet needs remain, mostly related to the occurrence of poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to possibly contribute to protection of the failing myocardium, although their place in the treatment of HF requires further assessment, in order to find better therapeutic solutions. In this context, the Optimal Nutraceutical Supplementation in Heart Failure (ONUS-HF) working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease, in order to counteract selected pathways that are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring during the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, impaired cardiac stem cell mobilization and an imbalanced regulation of metalloproteinases. Moreover, we reviewed the potential of the nutraceutical supplementation of several natural products, such as coenzyme Q10 (CoQ10), a grape seed extract, Olea Europea L.-related antioxidants, a sodium-glucose cotransporter (SGLT2) inhibitor-rich apple extract and a bergamot polyphenolic fraction, in addition to their support in cardiomyocyte protection, in HF. Such an approach should contribute to optimising the use of nutraceuticals in HF, and the effect needs to be confirmed by means of more targeted clinical trials exploring the efficacy and safety of these compounds.


Assuntos
Suplementos Nutricionais , Insuficiência Cardíaca/terapia , Animais , Antioxidantes/administração & dosagem , Citrus/química , Suplementos Nutricionais/estatística & dados numéricos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Extrato de Sementes de Uva/administração & dosagem , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Malus/química , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/fisiologia , Miocárdio/citologia , Óxido Nítrico/metabolismo , Apoio Nutricional , Olea/química , Extratos Vegetais/administração & dosagem , Células-Tronco/efeitos dos fármacos , Células-Tronco/fisiologia , Ubiquinona/administração & dosagem , Ubiquinona/análogos & derivados
13.
Pharmacol Res ; 163: 105215, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33007421

RESUMO

Cholesterol homeostasis is a highly regulated process in human body because of its several functions underlying the biology of cell membranes, the synthesis of all steroid hormones and bile acids and the need of trafficking lipids destined to cell metabolism. In particular, it has been recognized that peripheral and central nervous system cholesterol metabolism are separated by the blood brain barrier and are regulated independently; indeed, peripherally, it depends on the balance between dietary intake and hepatic synthesis on one hand and its degradation on the other, whereas in central nervous system it is synthetized de novo to ensure brain physiology. In view of this complex metabolism and its relevant functions in mammalian, impaired levels of cholesterol can induce severe cellular dysfunction leading to metabolic, cardiovascular and neurodegenerative diseases. The aim of this review is to clarify the role of cholesterol homeostasis in health and disease highlighting new intriguing aspects of the cross talk between its central and peripheral metabolism.

14.
Minerva Endocrinol (Torino) ; 46(2): 214-225, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32969628

RESUMO

BACKGROUND: Despite the abundance of studies on the beneficial effects of a fiber rich diet as well as polyphenols deriving from Citrus fruits on postprandial serum glucose and insulin, clinical evidence on their synergic effects on healthy subjects have never been published. We aimed to investigate the feasibility of a new dietary approach in controlling glucose and insulin response at breakfast time by testing a brioche enriched with wheat bran and bergamot fiber. METHODS: We enrolled 11 healthy volunteers in a cross-over study. Participants consumed a classic brioche at breakfast and our functional brioche, containing wheat bran and bergamot fiber, on another day. Vital functions, biochemical parameters (including glucose and insulin), anthropometric measurements as well as resting energy expenditure and fat oxidation were evaluated before and after the intake of both meals. RESULTS: The mean age was ~25 years. The mean BMI was 23.5 kg/m2. The consumption of the functional brioche reduced the glucose Cmax(0-120 min) by ~6% and prevented the insulin increase over time by 30%, finally demonstrating insulin Cmax(0-120 min) and iAUC(0-120 min) values significantly lower compared to classic brioche (respectively P value =0.04 and 0.03). The stepwise multivariable analysis confirmed the association between the consumption of the functional brioche containing bran and bergamot fiber and glucose Cmax(0-120 min) (B=-0.45; P=0.034), and insulin iAUC(0-120 min) (B=-764 P=0.036). CONCLUSIONS: The association of wheat bran and bergamot fiber significantly influences glucose metabolism and may exert insulin-like effects on healthy volunteers. If confirmed, berga-brioche would be a useful tool in preventing diabetes and controlling the glycometabolic status of type 2 diabetic patients.

15.
Biomedicines ; 8(12)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33265917

RESUMO

Oligodendrocytes are myelinating cells of the central nervous system which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, insulating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption a large amount of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions, including energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced, the myelination process is impaired. When myelination has finished, oligodendrocyte will have synthesized about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the dysfunction of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review, the induced malfunction of oligodendrocytes by harmful exogenous stimuli has been outlined. In particular, the effects of alcohol consumption and heavy metal intake are discussed. Furthermore, the response of the oligodendrocyte to excessive mitochondrial oxidative stress and to the altered regulation of the functioning of the endoplasmic reticulum will be explored.

16.
Molecules ; 25(23)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297504

RESUMO

The employment studies of natural extracts in the prevention and treatment of several diseases highlighted the role of different species of genus Ferula L., belonging to the Apiaceae family, dicotyledonous plants present in many temperate zones of our planet. Ferula communis L. is the main source of sesquiterpene ferutinin, a bioactive compound studied both in vitro and in vivo, because of different effects, such as phytoestrogenic, antioxidant, anti-inflammatory, but also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. The present review will focus on the molecular mechanisms involved in the different activities of Ferutinin, starting from its antioxidant potential at low doses until its ionophoric property and the subsequent mitochondrial dysfunction induced through administration of high doses, which represent the key point of its anticancer action. Furthermore, we will summarize the data acquired from some experimental studies on different cell types and on several diseases. The results obtained showed an important antioxidant and phytoestrogenic regulation with lack of typical side effects related to estrogenic therapy. The preferential cell death induction for tumor cell lines suggests that ferutinin may have anti-neoplastic properties, and may be used as an antiproliferative and cytotoxic agent in an estrogen dependent and independent manner. Nevertheless, more data are needed to clearly understand the effect of ferutinin in animals before using it as a phytoestrogen or anticancer drug.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Benzoatos/farmacologia , Cicloeptanos/farmacologia , Ferula/química , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antioxidantes/química , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Benzoatos/química , Benzoatos/uso terapêutico , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/farmacologia , Compostos Bicíclicos com Pontes/uso terapêutico , Linhagem Celular Tumoral , Cicloeptanos/química , Cicloeptanos/uso terapêutico , Relação Dose-Resposta a Droga , Transporte de Elétrons/efeitos dos fármacos , Terapia de Reposição Hormonal , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Fitoestrógenos/química , Fitoestrógenos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/química , Sesquiterpenos/uso terapêutico
17.
ACS Omega ; 5(47): 30436-30443, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33283091

RESUMO

Multiple myeloma (MM) is a hematological malignancy characterized by abnormal plasma cell proliferation within the bone marrow which leads to progressive bone marrow failure, skeletal osteolytic lesions, and renal insufficiency, thus severely affecting the quality of life. MM is always preceded by monoclonal gammopathy of uncertain significance (MGUS), which progresses to asymptomatic-MM (aMM) or symptomatic-MM (sMM) at a rate of 1% per year. Despite impressive progress in the therapy of the disease, MM remains incurable. Based on these premises, the identification of biomarkers of MGUS progression to MM is a crucial issue in disease management. In this regard, exosomes (EXs) and their precious biomolecular cargo could play a pivotal role in MM detection, stratification, and follow-up. Raman spectroscopy, a label- and manipulation-free technique, and its enhanced version, surface-enhanced Raman spectroscopy (SERS), have been used for characterizing MGUS, aMM, and sMM patient-derived EXs. Here, we have demonstrated the capability of Raman spectroscopy for discriminating EXs along the progression from MGUS to aMM and sMM, thus providing useful clinical indications for patient care. The used SERS devices, based on random nanostructures, have shown good potential in terms of sensitivity, but further developments are needed for achieving reproducible and quantitative SERS results.

18.
Int J Mol Sci ; 21(23)2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33291346

RESUMO

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells, which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of a SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to a detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with the ACE2 receptor located in the endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function, which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease, leading to irreversible tissue damage and death of people with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated with the interaction of SARS CoV-2 with the ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.


Assuntos
COVID-19/complicações , COVID-19/fisiopatologia , Células Endoteliais/patologia , SARS-CoV-2/fisiologia , Trombose/etiologia , Vasculite/etiologia , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , Células Endoteliais/metabolismo , Humanos , SARS-CoV-2/isolamento & purificação , Trombose/metabolismo , Trombose/fisiopatologia , Vasculite/metabolismo , Vasculite/fisiopatologia
19.
Antioxidants (Basel) ; 9(12)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339104

RESUMO

In clinical practice, inflammatory pain is an important, unresolved health problem, despite the utilization of non-steroidal anti-inflammatory drugs (NSAIDs). In the last decade, different studies have proven that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in the development and maintenance of inflammatory pain and hyperalgesia via the post-translation modification of key proteins, such as manganese superoxide dismutase (MnSOD). It is well-known that inducible cyclooxygenase 2 (COX-2) plays a crucial role at the beginning of the inflammatory response by converting arachidonic acid into proinflammatory prostaglandin PGE2 and then producing other proinflammatory chemokines and cytokines. Here, we investigated the impact of oxidative stress on COX-2 and prostaglandin (PG) pathways in paw exudates, and we studied how this mechanism can be reversed by using antioxidants during hyperalgesia in a well-characterized model of inflammatory pain in rats. Our results reveal that during the inflammatory state, induced by intraplantar administration of carrageenan, the increase of PGE2 levels released in the paw exudates were associated with COX-2 nitration. Moreover, we showed that the inhibition of ROS with Mn (III) tetrakis (4-benzoic acid) porphyrin(MnTBAP) antioxidant prevented COX-2 nitration, restored the PGE2 levels, and blocked the development of thermal hyperalgesia.

20.
Antioxidants (Basel) ; 9(11)2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33182469

RESUMO

Neuropathic pain is a chronic painful disease. Data have shown that reactive oxygen species (ROS) are implicated in chronic pain. Particularly, the enhanced ROS production alters the mitochondrial genome and proteome through the accumulation of lipid peroxidation products, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). Sirtuin 3 (SIRT3) is a mitochondrial protein and its activity can reduce ROS levels by modulating key antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Here, we evaluated the role of SIRT3 in the maintenance of basal levels of ROS in a model of chronic constriction injury (CCI) of the sciatic nerve and the protective effects of a natural antioxidant, the bergamot polyphenolic fraction (BPF). Rats were exposed to CCI of the sciatic nerve in the presence or absence of BPF (25-75 mg/kg). Level of acetylation, post-translational modulation on cysteine residues of proteins by HNE and SIRT3 activation, were detected in the spinal cord through western blotting, WES methodology and enzymatic assays. Our results reported that SIRT3 carbonylation and therefore its inactivation contributes to mitochondrial MnSOD hyperacetylation during CCI induced neuropathic pain in rats. In particular, we have demonstrated a close relation between oxidative stress, hyperalgesia, allodynia and sirtuins inactivation reverted by BPF administration.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...