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1.
Nutrients ; 16(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39125298

RESUMO

PURPOSE: This paper aims to present a unique perspective that emphasizes the intricate interplay between energy, dietary proteins, and amino acid composition, underscoring their mutual dependence for health-related considerations. Energy and protein synthesis are fundamental to biological processes, crucial for the sustenance of life and the growth of organisms. METHODS AND RESULTS: We explore the intricate relationship between energy metabolism, protein synthesis, regulatory mechanisms, protein sources, amino acid availability, and autophagy in order to elucidate how these elements collectively maintain cellular homeostasis. We underscore the vital role this dynamic interplay has in preserving cell life. CONCLUSIONS: A deeper understanding of the link between energy and protein synthesis is essential to comprehend fundamental cellular processes. This insight could have a wide-ranging impact in several medical fields, such as nutrition, metabolism, and disease management.


Assuntos
Aminoácidos , Proteínas Alimentares , Metabolismo Energético , Aminoácidos/metabolismo , Proteínas Alimentares/metabolismo , Humanos , Autofagia , Biossíntese de Proteínas , Animais , Ingestão de Energia , Homeostase
2.
Cells ; 13(14)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39056792

RESUMO

Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix and in mice fed with EAA-rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable antiproliferative properties.


Assuntos
Apoptose , Proliferação de Células , Neoplasias do Colo , Animais , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Camundongos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Aminoácidos/farmacologia , Camundongos Endogâmicos BALB C , Aminoácidos Essenciais/farmacologia
3.
Sci Rep ; 13(1): 15855, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37740075

RESUMO

The chemistry and mineralogy of slabs subducted into lower mantle control slab rheology and impact the deep volatile cycle. It is known that the metamorphism of little-altered oceanic crust results in eclogite rocks with subequal proportions of garnet and clinopyroxene. With increasing pressure, these minerals react to stabilize pyrope-rich tetragonal majoritic garnet. However, some eclogites contain higher proportions of omphacitic clinopyroxene, caused by Na- and Si-rich metasomatism on the ocean floor or during subduction. The mineralogy of such eclogites is expected to evolve differently. Here, we discuss the results of the crystallization products of omphacitic glass at ~ 18 and ~ 25 GPa and 1000 °C to simulate P-T regimes of cold subduction. The full characterization of the recovered samples indicates evidence of crystallization of Na-, Si-rich cubic instead of tetragonal majorite. This cubic majorite can incorporate large amounts of ferric iron, promoting redox reactions with surrounding volatile-bearing fluids and, ultimately, diamond formation. In addition, the occurrence of cubic majorite in the slab would affect the local density, favoring the continued buoyancy of the slab as previously proposed by seismic observations. Attention must be paid to omphacitic inclusions in sublithospheric diamonds as these might have experienced back-transformation from the HP isochemical cubic phase.

4.
Nutrients ; 15(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37242170

RESUMO

BACKGROUND: Doxorubicin (Doxo) is a widely prescribed drug against many malignant cancers. Unfortunately, its utility is limited by its toxicity, in particular a progressive induction of congestive heart failure. Doxo acts primarily as a mitochondrial toxin, with consequent increased production of reactive oxygen species (ROS) and attendant oxidative stress, which drives cardiac dysfunction and cell death. A diet containing a special mixture of all essential amino acids (EAAs) has been shown to increase mitochondriogenesis, and reduce oxidative stress both in skeletal muscle and heart. So, we hypothesized that such a diet could play a favorable role in preventing Doxo-induced cardiomyocyte damage. METHODS: Using transmission electron microscopy, we evaluated cells' morphology and mitochondria parameters in adult mice. In addition, by immunohistochemistry, we evaluated the expression of pro-survival marker Klotho, as well as markers of necroptosis (RIP1/3), inflammation (TNFα, IL1, NFkB), and defense against oxidative stress (SOD1, glutathione peroxidase, citrate synthase). RESULTS: Diets with excess essential amino acids (EAAs) increased the expression of Klotho and enhanced anti-oxidative and anti-inflammatory responses, thereby promoting cell survival. CONCLUSION: Our results further extend the current knowledge about the cardioprotective role of EAAs and provide a novel theoretical basis for their preemptive administration to cancer patients undergoing chemotherapy to alleviate the development and severity of Doxo-induced cardiomyopathy.


Assuntos
Aminoácidos Essenciais , Miócitos Cardíacos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Aminoácidos Essenciais/metabolismo , Doxorrubicina/toxicidade , Estresse Oxidativo , Dieta , Cardiotoxicidade/prevenção & controle
6.
Cancer ; 129(1): 107-117, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36321594

RESUMO

BACKGROUND: The correlation between thalassemia and malignancies other than hepatocellular carcinoma (HCC) and the possible relationship between other hemoglobinopathies and tumor risk have been poorly evaluated. METHODS: Eight Italian specialized centers evaluated the incidence of malignant neoplasms in hemoglobinopathies as well as their sites and features. The study cohort included 4631 patients followed between 1970 and 2021 (transfusion-dependent ß-thalassemia, 55.6%; non-transfusion-dependent thalassemia, 17.7%; sickle cell disease, 17.6%; hemoglobin H disease, 8.3%). RESULTS: A total of 197 diagnoses of cancer were reported (incidence rate, 442 cases per 100,000 person-years). The liver was the most frequent site of tumors in both sexes, with a higher incidence (190 cases per 100,000 person-years) in comparison with the general population found in all types of hemoglobinopathies (except hemoglobin H disease). In recent years, tumors have become the second cause of death in patients with transfusion-dependent thalassemia. A lower risk of breast and prostate cancer was observed in the whole group of patients with hemoglobinopathies. The first cancer diagnoses dated back to the 1980s, and the incidence rate sharply increased after the 2000s. However, although the incidence rate of cancers of all sites but the liver continued to show an increasing trend, the incidence of HCC showed stability. CONCLUSIONS: These findings provide novel insights into the relationship between cancer and hemoglobinopathies and suggest that the overall risk is not increased in these patients. HCC has been confirmed as the most frequent tumor, but advances in chelation and the drugs that have led to the eradication of hepatitis C may explain the recent steadiness in the number of diagnoses that is reported here.


Assuntos
Carcinoma Hepatocelular , Hemoglobinopatias , Neoplasias Hepáticas , Talassemia alfa , Masculino , Feminino , Humanos , Incidência , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/diagnóstico
7.
Nutrients ; 14(14)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35889872

RESUMO

BACKGROUND: Excess body adipose tissue accumulation is a common and growing health problem caused by an unbalanced diet and/or junk food. Although the effects of dietary fat and glucose on lipid metabolism regulation are well known, those of essential amino acids (EAAs) have been poorly investigated. Our aim was to study the influence of a special diet containing all EAAs on retroperitoneal white adipose tissue (rpWAT) and interscapular brown adipose tissue (BAT) of mice. METHODS: Two groups of male Balb/C mice were used. The first was fed with a standard diet. The second was fed with an EAAs-rich diet (EAARD). After 3 weeks, rpWAT and BAT were removed and prepared for subsequent immunohistochemical analysis. RESULTS: EAARD, although consumed significantly less, moderately reduced body weight and BAT, but caused a massive reduction in rpWAT. Conversely, the triceps muscle increased in mass. In rpWAT, the size of adipocytes was very small, with increases in leptin, adiponectin and IL-6 immunostaining. In BAT, there was a reduction in lipid droplet size and a simultaneous increase in UCP-1 and SIRT-3. CONCLUSIONS: A diet containing a balanced mixture of free EAA may modulate body adiposity in mice, promoting increased thermogenesis.


Assuntos
Tecido Adiposo Marrom , Aminoácidos Essenciais , Tecido Adiposo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Aminoácidos Essenciais/farmacologia , Animais , Dieta , Dieta Hiperlipídica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Termogênese
8.
Sci Data ; 9(1): 247, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35637188

RESUMO

In this work, we present a comprehensive rheological database including most of the existing data relevant for crystal-bearing magmas collected from the scientific literature, covering the entire range of natural volcanic conditions, in terms of crystal content (1-80%), crystal shape (aspect ratio R from 1 to 13), and strain rate (between 10-7 and 102 s-1). Datasets were collected and discerned as a function of the information which we considered necessary for building a general systematic model describing relative viscosity of crystal-bearing magmas, such as the apparent and melt viscosity, the crystal concentration, crystal shape, and the strain rate. The selected dataset was then used for modelling the relative viscosity of a liquid-solid mixture having different concentrations of particles with different R, subjected to different strain rates. The proposed model allows us to quantitatively describe the rheological behaviour of crystal-bearing magmatic systems.

9.
Front Med (Lausanne) ; 8: 714426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368201

RESUMO

Background: Many patients who have been suffering by Covid-19 suffer of long-Covid syndrome, with symptoms of fatigue and muscular weakness that characterize post-acute sequelae SARS-CoV-2 infection (PASC). However, there is limited knowledge about the molecular pathophysiology, and about the serum profile of these patients. Methods: We studied the blood serum profile of 75 selected patients, with previous confirmed Covid-19, 2 months after hospital discharge, who reported new-onset fatigue, muscle weakness and/or dyspnea not present prior to the virus infection and independently from concomitant diseases and/or clinical conditions. Results: All patients had very high serum concentrations of ferritin and D-Dimer. 87 and 72% of patients had clinically significant low levels of hemoglobin and albumin, respectively. Seventy three percentage had elevations in erythrocyte sedimentation rate and CRP. Twenty seven percentage had elevations in LDH. Conclusions: The co-existence of patient symptoms along with blood markers of coagulation, protein disarrangement and inflammation suggests ongoing alterations in the metabolism, promoting an inflammatory/hypercatabolic state which maintains a vicious circles implicated in the persistence of PASC. The persistence of altered D-Dimer levels raises the possibility of long-term risks of thromboembolic disease. All these markers levels should be accurately evaluated in the long-term follow-up, with individualized consideration for prophylactic nutritional, anti-inflammatory and/or anticoagulant therapy if indicated.

10.
Nutrients ; 13(4)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33810512

RESUMO

Amino-acids (AAs) are the exclusive source of nitrogen for cells. AAs result from the breakdown of food proteins and are absorbed by mucosa of the small intestine that act as a barrier to harmful materials. The quality of food proteins may differ, since it reflects content in Essential-AAs (EAAs) and digestibility but, until now, attention was paid mainly to the interaction between indigested proteins as a whole and microbiota. The link between microbiome and quality of proteins has been poorly studied, although these metabolic interactions are becoming more significant in different illnesses. We studied the effects of a special diet containing unbalanced EAAs/Non-EAAs ratio, providing excess of Non-EAAs, on the histopathology of gut epithelium and on the microbiome in adult mice, as model of qualitative malnutrition. Excess in Non-EAAs have unfavorable quick effect on body weight, gut cells, and microbiome, promoting weakening of the intestinal barrier. Re-feeding these animals with standard diet partially reversed the body alterations. The results prove that an unbalanced EAAs/Non-EAAs ratio is primarily responsible for microbiome modifications, not vice-versa. Therefore, treating microbiota independently by treating co-existing qualitative malnutrition does not make sense. This study also provides a reproducible model of sarcopenia-wasting cachexia like the human protein malnutrition.


Assuntos
Microbioma Gastrointestinal , Enteropatias/etiologia , Desnutrição/complicações , Nitrogênio/administração & dosagem , Aminoácidos/administração & dosagem , Aminoácidos/classificação , Ração Animal , Animais , Peso Corporal , Dieta , Proteínas Alimentares/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória
11.
Int J Mol Sci ; 22(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805128

RESUMO

Chronic heart failure (CHF) is a disease with important clinical and socio-economic ramifications. Malnutrition and severe alteration of the protein components of the body (protein disarrangements), common conditions in CHF patients, are independent correlates of heart dysfunction, disease progression, and mortality. Autophagy, a prominent occurrence in the heart of patients with advanced CHF, is a self-digestive process that prolongs myocardial cell lifespan by the removal of cytosolic components, such as aging organelles and proteins, and recycles the constituent elements for new protein synthesis. However, in specific conditions, excessive activation of autophagy can lead to the destruction of molecules and organelles essential to cell survival, ultimately leading to organ failure and patient death. In this review, we aim to describe the experimental and clinical evidence supporting a pathophysiological role of nutrition and autophagy in the progression of CHF. The understanding of the mechanisms underlying the interplay between nutrition and autophagy may have important clinical implications by providing molecular targets for innovative therapeutic strategies in CHF patients.


Assuntos
Autofagia , Insuficiência Cardíaca/fisiopatologia , Coração/fisiologia , Desnutrição/fisiopatologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Sobrevivência Celular , Doença Crônica , Citosol/metabolismo , Progressão da Doença , Insuficiência Cardíaca/complicações , Humanos , Desnutrição/complicações , Metabolismo , Camundongos , Músculo Esquelético/metabolismo , Contração Miocárdica , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Ratos , Medição de Risco
12.
Nutrients ; 13(1)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467658

RESUMO

Chronic diseases are characterised by altered autophagy and protein metabolism disarrangement, resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia is linked to a worse prognosis independent of the target organ affected by the disease. Currently, the cornerstone of the therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of haematopoiesis. However, treatment strategies should incorporate the promotion of the synthesis of heme, the principal constituent of haemoglobin (Hb) and of many other fundamental enzymes for human metabolism. Heme synthesis is controlled by a complex biochemical pathway. The limiting step of heme synthesis is D-amino-levulinic acid (D-ALA), whose availability and synthesis require glycine and succinil-coenzyme A (CoA) as precursor substrates. Consequently, the treatment of anaemia should not be based only on the sufficiency of iron but, also, on the availability of all precursor molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate a standard iron infusion and a supply of essential amino acids and vitamins involved in heme synthesis. We reported preliminary data in a select population of aged anaemic patients affected by congestive heart failure (CHF) and catabolic disarrangement, who, in addition to the standard iron therapy, were treated by reinforced therapeutic schedules also providing essential animo acids (AAs) and vitamins involved in the maintenance of heme. Notably, such individualised therapy resulted in a significantly faster increase in the blood concentration of haemoglobin after 30 days of treatment when compared to the nonsupplemented standard iron therapy.


Assuntos
Anemia/diagnóstico , Anemia/terapia , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Anemia/metabolismo , Biomarcadores/sangue , Vias Biossintéticas , Doença Crônica , Terapia Combinada , Gerenciamento Clínico , Suscetibilidade a Doenças , Índices de Eritrócitos , Feminino , Heme/química , Heme/metabolismo , Humanos , Ferro/química , Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Nutrients ; 11(6)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216646

RESUMO

An adequate intake of essential (EAA) and non-essential amino acids (NEAA) is crucial to preserve cell integrity and whole-body metabolism. EAA introduced with diet may be insufficient to meet the organismal needs, especially under increased physiological requirements or in pathological conditions, and may condition lifespan. We therefore examined the effects of iso-caloric and providing the same nitrogenous content diets, any diet containing different stoichiometric blends of EAA/NEAA, on mouse lifespan. Three groups of just-weaned male Balb/C mice were fed exclusively with special diets with varying EAA/NEAA ratios, ranging from 100%/0% to 0%/100%. Three additional groups of mice were fed with different diets, two based on casein as alimentary proteins, one providing the said protein, one reproducing the amino acidic composition of casein, and the third one, the control group, was fed by a standard laboratory diet. Mouse lifespan was inversely correlated with the percentage of NEAA introduced with each diet. Either limiting EAA, or exceeding NEAA, induced rapid and permanent structural modifications on muscle and adipose tissue, independently of caloric intake. These changes significantly affected food and water intake, body weight, and lifespan. Dietary intake of varying EAA/NEAA ratios induced changes in several organs and profoundly influenced murine lifespan. The balanced content of EAA provided by dietary proteins should be considered as the preferable means for "optimal" nutrition and the elevated or unbalanced intake of NEAA provided by food proteins may negatively affect the health and lifespan of mice.


Assuntos
Aminoácidos/administração & dosagem , Ração Animal/análise , Dieta/métodos , Proteínas Alimentares/administração & dosagem , Longevidade , Animais , Caseínas/administração & dosagem , Ingestão de Energia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
14.
Med Sci Monit Basic Res ; 25: 139-152, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31073117

RESUMO

BACKGROUND Urocortin (Ucn) is a member of the hypothalamic corticotrophin-releasing factor family and has been shown to reduce cell death in the heart caused by ischemia/reperfusion (I/R) injury. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor known to function as a pro-survival and anti-apoptotic factor, whose activation depends on a variety of cytokines, including IL-6. A recent study demonstrated that urocortin induced IL-6 release from cardiomyocytes in a CRF-R2-dependent manner, suggesting a possible link between CRF-R2 stimulation and STAT3 activation. MATERIAL AND METHODS Experimental work was carried out in HL-1 cardiac myocytes exposed to serum starvation for 16-24 h. RESULTS Ucn stimulation led to IL-6 expression and release from mouse atrial HL-1 cardiomyocytes. Ucn treatment led to rapid phosphorylation of JAK2, which was blocked by the protein synthesis inhibitor cycloheximide or the JAK inhibitor AG490. Urocortin treatment induced STAT3 phosphorylation at Y705 and S727 through transactivation of JAK2 in an IL-6-dependent manner, but had no effect on STAT1 activity. Kinase inhibition experiments revealed that urocortin induces STAT3 S727 phosphorylation through ERK1/2 and Y705 phosphorylation through Src tyrosine kinase. In line with this finding, urocortin failed to induce phosphorylation of Y705 residue in SYF cells bearing null mutation of Src, while phosphorylation of S727 residue was unchanged. CONCLUSIONS Here, we have shown that Ucn induces activation of STAT3 through diverging signaling pathways. Full understanding of these signaling pathways will help fully exploit the cardioprotective properties of endogenous and exogenous Ucn.


Assuntos
Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Urocortinas/metabolismo , Animais , Linhagem Celular , DNA/metabolismo , Interleucina-6/metabolismo , Janus Quinase 2/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Fosfosserina/metabolismo , Fosfotirosina/metabolismo , Ligação Proteica/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Urocortinas/farmacologia
15.
Med Sci Monit Basic Res ; 25: 33-44, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30713336

RESUMO

BACKGROUND Although originally described as a survival mechanism, it is unknown whether and to what extent autophagy is implicated in the terminal stages of heart failure. Here, we studied magnitude and evolution of autophagy in patients with intractable heart failure. MATERIAL AND METHODS Myocardial samples were obtained from 22 patients with ischemic cardiomyopathy and idiopathic dilated cardiomyopathy who were undergoing cardiac transplantation. Hearts from 11 patients who died from non-cardiac causes were used as control samples. Autophagy was evaluated by immunostaining with a monoclonal microtubule associated protein light chain 3 (LC3)-II antibody, while the relationship of autophagy with apoptosis and oncosis was assessed by double staining with TUNEL (terminal deoxynucleotidyl transferase - mediated deoxyuridine triphosphate nick end labeling) assay and complement 9 (C9) immunological staining, respectively. In addition, several necroptotic markers, including RIP1 and RIP3 (receptor interacting protein kinase 1 and 3), anti-C3 (cleaved-caspase-3), and anti-NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) were assessed by immunohistochemistry. RESULTS Anti-LC3-II staining was detected in 8.7±1.6% of the heart failure patient heart samples and in 1.2±0.3% of control patient heart samples. Vacuole formation started at one nuclear pole, before becoming bipolar and involving the cytosol. Subsequently, the autophagic process extended also to the nuclei, which underwent a progressive vacuolization and disintegration, assuming a peculiar "strawberry like appearance". Myocytes with extensive vacuole formation exhibited nuclear degeneration, which was associated with TUNEL, C3, C9, RIP1, and RIP3 positive staining. Conversely, myocytes with less extensive vacuole formation showed RIP1 and NF-κB positive staining, though not positivity for other cell death markers. CONCLUSIONS Autophagy was extensively detected in end-stage heart failure and its progression, resulted in secondary cell death, with occurrence of oncosis and necroptosis exceeding that of apoptosis. Conversely, activation of the RIP1/NF-κB pathway was associated with cell survival.


Assuntos
Autofagia/fisiologia , Insuficiência Cardíaca/fisiopatologia , Miócitos Cardíacos/fisiologia , Apoptose/fisiologia , Caspase 3/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/metabolismo , NF-kappa B/fisiologia , Necrose/fisiopatologia , Complexo de Proteínas Formadoras de Poros Nucleares/fisiologia , Proteínas de Ligação a RNA/fisiologia , Transdução de Sinais
16.
Minerva Med ; 110(1): 3-11, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30667205

RESUMO

BACKGROUND: Intestinal dysbiosis has been proposed as a possible contributor of the development of type 2 diabetes (T2D). Indeed, commensal fungi and opportunistic bacteria stimulate the local immune system, altering intestinal permeability with consequent leaky gut, which in turn activates systemic inflammation responsible for insulin resistance. It is also well known that chronic exercise improves glucose control and diabetes-induced damage. The aim of this study was to evaluate the role of chronic exercise on gut flora composition and leaky gut in T2D stable patients. METHODS: Thirty clinically stable patients with T2D were studied before and after a six months program of endurance, resistance and flexibility training. Metabolic and anthropometric evaluations were carried out. Gut flora and intestinal permeability were measured in stools by selective agar culture medium and molecular biology measurements of zonulin, which is the protein that modulates enterocyte tight junctions. RESULTS: Diabetes causes significant intestinal mycetes overgrowth, increased intestinal permeability and systemic low-grade inflammation. However, exercise improved glycemia, functional and anthropometric variables. Moreover, chronic exercise reduced intestinal mycetes overgrowth, leaky gut, and systemic inflammation. Interestingly, these variables are closely correlated. CONCLUSIONS: Exercise controls diabetes by also modifying intestinal microbiota composition and gut barrier function. This data shows an additional mechanism of chronic exercise and suggests that improving gut flora could be an important step in tailored therapies of T2D.


Assuntos
Diabetes Mellitus Tipo 2/microbiologia , Disbiose/complicações , Exercício Físico , Microbioma Gastrointestinal , Idoso , Feminino , Humanos , Masculino
17.
Int J Mol Sci ; 19(11)2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-30453654

RESUMO

Energy production is the main task of the cancer cell metabolism because the costs of duplicating are enormous. Although energy is derived in cells by dismantling the carbon-to-carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as being dependent on glycolysis. Since the end of the last century, the awareness of the dependence of cancer metabolism on amino acids not only for protein synthesis but also to match energy needs has grown. The roles of specific amino acids such as glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, epidemiological evidence has revealed that some amino acids used as a supplement for therapeutic reasons, particularly the branched-chain ones, may reduce the incidence of liver cancer and a specific molecular mechanism has been proposed as functional to their protective action. By contrast and puzzling clinicians, the metabolomic signature of some pathologies connected to an increased risk of cancer, such as prolonged hyperinsulinemia in insulin-resistant patients, is identified by elevated plasma levels of the same branched-chain amino acids. Most recently, certain formulations of amino acids, deeply different from the amino acid compositions normally present in foods, have shown the power to master cancer cells epigenetically, slowing growth or driving cancer cells to apoptotic death, while being both beneficial for normal cell function and the animal's health and lifespan. In this review, we will analyze and try to disentangle some of the many knots dealing with the complexities of amino acid biology and links to cancer metabolism.


Assuntos
Aminoácidos/metabolismo , Dieta , Neoplasias/patologia , Animais , Apoptose , Autofagia , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo
18.
Front Med (Lausanne) ; 5: 136, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868589

RESUMO

Objective: Inadequate protein intake can impair protein balance thus leading to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets, with various EAA/NEAA blends, on body composition and the risk of developing tissue wasting in late middle-aged male mice. Methods: Six groups of late middle-aged male mice were fed for 35 days with iso-nutrients, iso-caloric, and iso-nitrogenous special diets containing different EAA/NEAA ratios ranging from 100/0% to 0/100%. One group fed with standard laboratory rodent diet (StD) served as control. Preliminarily, we verified the palatability of the diets by recording the mice preference, and by making accessible all diets simultaneously, in comparison to StD. Body weight, food and water consumption were measured every 3 days. Blood and urine samples, as well as heart, kidneys, liver, spleen, triceps surae, retroperitoneal WAT, and BAT were harvested and weighed. Results: Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, the diet containing a EAA/NEAA-imbalance, with moderate NEAAs prevalence, was able to induce catabolic stimuli, generalized body wasting, and systemic metabolic alterations comparable to those observed with diet containing NEAA alone. In addition, complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-containing diets induced significant decreases in body weight by reducing primarily fat reserves, but at the same time they improved the clinical parameters. On these basis we can deduce that tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Conclusion: Our results indicate that diets containing an optimized balance of AA composition is necessary for preserving overall body energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates, including body wasting.

19.
Nutrients ; 10(4)2018 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-29565819

RESUMO

Proteins are macro-molecules crucial for cell life, which are made up of amino acids (AAs). In healthy people, protein synthesis and degradation are well balanced. However, in the presence of hypercatabolic stimulation (i.e., inflammation), protein breakdown increases as the resulting AAs are consumed for metabolic proposes. Indeed, AAs are biochemical totipotent molecules which, when deaminated, can be transformed into energy, lipids, carbohydrates, and/or biochemical intermediates of fundamental cycles, such as the Krebs' cycle. The biochemical consequence of hyper-catabolism is protein disarrangement, clinically evident with signs such as sarcopenia, hypalbuminemia, anaemia, infection, and altered fluid compartmentation, etc. Hypercatabolic protein disarrangement (HPD) is often underestimated by clinicians, despite correlating with increased mortality, hospitalization, and morbidity quite independent of the primary disease. Simple, cheap, repeatable measurements can be used to identify HPD. Therefore, identification and treatment of proteins' metabolic impairment with appropriate measurements and therapy is a clinical strategy that could improve the prognosis of patients with acute/chronic hypercatabolic inflammatory disease. Here, we describe the metabolism of protein and AAs in hypercatabolic syndrome, illustrating the clinical impact of protein disarrangement. We also illustrate simple, cheap, repeatable, and worldwide available measurements to identify these conditions. Finally, we provide scientific evidence for HPD nutritional treatment.


Assuntos
Envelhecimento/metabolismo , Aminoácidos/metabolismo , Proteínas Alimentares/metabolismo , Metabolismo Energético , Músculo Esquelético/metabolismo , Enteropatias Perdedoras de Proteínas/metabolismo , Sarcopenia/metabolismo , Fatores Etários , Aminoácidos/administração & dosagem , Animais , Proteínas Alimentares/administração & dosagem , Suplementos Nutricionais , Humanos , Músculo Esquelético/fisiopatologia , Estado Nutricional , Enteropatias Perdedoras de Proteínas/dietoterapia , Enteropatias Perdedoras de Proteínas/fisiopatologia , Proteólise , Sarcopenia/dietoterapia , Sarcopenia/fisiopatologia
20.
Oxf Med Case Reports ; 2018(3): omx103, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29527312

RESUMO

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood disorder characterized by intravascular hemolysis, thrombosis and bone marrow failure. Acute kidney injury, including acute renal failure, have been reported in patients with PNH. We report the case of a 36-year-old male patient with PNH who developed acute kidney injury following an infection of undetermined diagnosis. Although hemolysis was initially controlled and renal function stabilized following packed red blood cell transfusion and empirical levofloxacin and prednisone, he later experienced recurrent episodes of hemolysis and hematuria requiring monthly red blood cell support. Given the high risk of thromboembolic events, treatment with standard-dose eculizumab was started. The patient's hematologic values improved, renal function was maintained, and no thromboembolic events occurred.

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