RESUMO
We read with great interest the recent article by Meneghini et al. on the assessment of the effects of different alimentary regimens, included Mediterranean diet (MD), on polycystic ovary syndrome (PCOS) patients prior to in vitro fertilization cycles [...].
Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia , Sobrepeso/complicações , Sobrepeso/terapia , Transferência Embrionária , Fertilização in vitro , Obesidade/complicações , Obesidade/terapia , NutrientesRESUMO
Background and Objectives: Hepatocellular carcinoma (HCC) is the leading cause of liver cancer worldwide and has a high mortality rate. Its incidence has increased due to metabolic-associated liver disease (MAFLD) epidemics. Liver transplantation and surgery remain the most resolute measures. Despite the optimistic use of multi-kinase inhibitors, namely sorafenib, the co-existence of chronic liver disease made the response rate low in these patients. Immune checkpoint inhibitors (ICIs) have become a promising hope for certain advanced solid tumors and, also, for advanced HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. Materials and Methods: We conducted a narrative search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: hepatocellular carcinoma, immunotherapy, checkpoint inhibitors, gut microbiota, and fecal microbiota transplantation. Results: ICIs are a promising and sufficiently safe treatment option for HCC. In detail, they have significantly improved survival and prognosis in these patients vs. sorafenib. Although there are several highlighted mechanisms of resistance, the gut microbiota signature can be used both as a response biomarker and as an effect enhancer. Practically, probiotic dose-finding and fecal microbiota transplantation are the weapons that can be used to increase ICI's treatment-response-reducing resistance mechanisms. Conclusion: Immunotherapy has been a significant step-up in HCC treatment, and gut microbiota modulation is an effective liaison to increase its efficacy.
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Carcinoma Hepatocelular , Microbioma Gastrointestinal , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Sorafenibe , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.01 vs. untreated animals), accompanied by a reduction in plasma inflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and C reactive protein, and myeloperoxidase expression in liver tissue. Furthermore, a modulation of the molecular pathways involved in lipid metabolism and storage was demonstrated, since we observed the significant reduction of the mRNA levels of fatty acid synthase, diacylglycerol acyltransferases, the sterol-binding protein SREBP-1, and the lipid transporter perilipin-2, in both treated NAFLD and NASH rats in comparison to untreated ones. In conclusion, this nutraceutical product was effective in reducing liver steatosis and showed further beneficial effects on hepatic inflammation and glycemic control, which were particularly evident in rats characterized by a more severe condition, thus representing a therapeutic option for the treatment of NAFLD and NASH patients.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Phaeophyceae , Alga Marinha , Animais , Proteína C-Reativa/metabolismo , Suplementos Nutricionais , Diglicerídeos/metabolismo , Ácido Graxo Sintases , Inflamação/metabolismo , Interleucina-6/metabolismo , Metabolismo dos Lipídeos , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Modelos Teóricos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Perilipina-2/metabolismo , Peroxidase/metabolismo , Phaeophyceae/metabolismo , RNA Mensageiro/metabolismo , Ratos , Alga Marinha/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Esteróis/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND AND AIM: Coffee intake exerts protective effects against non-alcoholic fatty liver disease (NAFLD), although without fully cleared mechanisms. In this study we aimed to assess whether coffee consumption may influence the expression of long non-coding RNAs (lncRNAs) in the liver. METHODS: C57BL/6J mice were fed a 12-week standard diet (SD), high-fat diet (HFD) or HFD plus decaffeinated coffee solution (HFD + coffee). Expression of specific lncRNAs involved in NAFLD was analyzed by real-time PCR. For the most differentially expressed lncRNAs, the analysis was also extended to their mRNA targets. RESULTS: Decaffeinated coffee intake reduced body weight gain, prevented NAFLD, lowered hyperglycemia and hypercholesterolemia. NAFLD was associated with lower hepatic expression of Gm16551, a lncRNA inhibiting de novo lipogenesis, and higher expression of H19, a lncRNA promoting fibrogenesis. Coffee intake restored Gm16551 to levels observed in lean mice and downregulated gene expression of its targets acetyl coenzyme A carboxylase 1 and stearoyl coenzyme A desaturase 1. Furthermore, coffee consumption markedly decreased hepatic expression of H19 and of its target gene collagen alpha-1(I) chain; consistently, in mice fed HFD + coffee liver expression of αSMA protein returned to levels of mice fed SD. Expression of lncRNA involved in circadian clock such as fatty liver-related lncRNA 1 (FLRL1) and fatty liver-related lncRNA 2 (FLRL2) were upregulated by HFD and were also modulated by coffee intake. CONCLUSION: Hepatoprotective effects of coffee may be depending on the modulation of lncRNAs involved in key pathways of NAFLD onset and progression.
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Café/metabolismo , Fígado Gorduroso/metabolismo , Expressão Gênica/efeitos dos fármacos , Cirrose Hepática/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , RNA Longo não Codificante/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.
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Disbiose/tratamento farmacológico , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Arecaceae/química , Berberina/administração & dosagem , Berberis/química , Coffea/química , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Disbiose/imunologia , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Resistência à Insulina/imunologia , Fígado/patologia , Masculino , Camundongos , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Extratos Vegetais/química , Tocotrienóis/administração & dosagemRESUMO
The Asian coastal communities have used the brown seaweeds Fucus vesiculosus and Ascophyllum nodosum since ancient times. Recently, some in vitro and in vivo studies have demonstrated their abilities in reducing risk factors for metabolic syndrome. Here, we analyzed the protective effect of a phytocomplex extracted from these seaweeds on the deposition of fat in the liver after the administration of a high-fat diet (HFD) to rats for five weeks. The administration of F. vesiculosus and A. nodosum led to significant reductions in microvescicular steatosis and plasma biochemical and lipid parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total and conjugated bilirubin, and triglycerides. Furthermore, the postprandial glycemic peak was delayed and significantly reduced (p < 0.01) by the algal extract administration. In conclusion, this extract is effective in reducing microvescicular steatosis and improving glycemic control, thereby lowering the risk of nonalcoholic fatty liver disease, obesity, and diabetes, diseases related to the consumption of fat and sugar-enriched diets.
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Ascophyllum/química , Dieta Redutora/efeitos adversos , Fucus/química , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Glicemia/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Período Pós-Prandial/efeitos dos fármacos , Ratos , Ratos Wistar , Alga Marinha/química , Triglicerídeos/metabolismoRESUMO
Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P < 0·01) and serum cholesterol (P < 0·001), alanine aminotransferase and glucose (P < 0·05). Accordingly, liver PPAR- α (P < 0·05) and acyl-CoA oxidase-1 (P < 0·05) as well as duodenal ATP-binding cassette (ABC) subfamily A1 (ABCA1) and subfamily G1 (ABCG1) (P < 0·05) mRNA expressions increased with coffee consumption. Compared with HFD animals, HFD+COFFEE mice had more undigested lipids in the caecal content and higher free fatty acid receptor-1 mRNA expression in the duodenum and colon. Furthermore, they showed an up-regulation of duodenal and colonic zonulin-1 (P < 0·05), duodenal claudin (P < 0·05) and duodenal peptide YY (P < 0·05) mRNA as well as a higher abundance of Alcaligenaceae in the faeces (P < 0·05). HFD+COFFEE mice had an energy intake comparable with HFD-fed mice but starting from the eighth intervention week they gained significantly less weight over time. Data altogether showed that coffee supplementation prevented HFD-induced NAFLD in mice by reducing hepatic fat deposition and metabolic derangement through modification of pathways underpinning liver fat oxidation, intestinal cholesterol efflux, energy metabolism and gut permeability. The hepatic and metabolic benefits induced by coffee were accompanied by changes in the gut microbiota.
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Café/metabolismo , Dieta Hiperlipídica/efeitos adversos , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Acil-CoA Oxidase/metabolismo , Alanina Transaminase/sangue , Alcaligenaceae , Animais , Glicemia , Colesterol/sangue , Claudinas/metabolismo , Suplementos Nutricionais , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Haptoglobinas/metabolismo , Fígado/patologia , Masculino , Síndrome Metabólica , Camundongos , Camundongos Endogâmicos C57BL , PPAR alfa/metabolismo , Polifenóis/farmacologia , Precursores de Proteínas/metabolismo , RNA Mensageiro/metabolismoRESUMO
Hemojuvelin (Hjv) is a membrane protein that controls body iron metabolism by enhancing signaling to hepcidin. Hjv mutations cause juvenile hemochromatosis, a disease of systemic iron overload. Excessive iron accumulation in the liver progressively leads to inflammation and disease, such as fibrosis, cirrhosis, or hepatocellular cancer. Fatty liver (steatosis) may also progress to inflammation (steatohepatitis) and liver disease, and iron is considered as pathogenic cofactor. The aim of this study was to investigate the pathological implications of parenchymal iron overload due to Hjv ablation in the fatty liver. Wild-type (WT) and Hjv(-/-) mice on C57BL/6 background were fed a standard chow, a high-fat diet (HFD), or a HFD supplemented with 2% carbonyl iron (HFD+Fe) for 12 wk. The animals were analyzed for iron and lipid metabolism. As expected, all Hjv(-/-) mice manifested higher serum and hepatic iron and diminished hepcidin levels compared with WT controls. The HFD reduced iron indexes and promoted liver steatosis in both WT and Hjv(-/-) mice. Notably, steatosis was attenuated in Hjv(-/-) mice on the HFD+Fe regimen. Hjv(-/-) animals gained less body weight and exhibited reduced serum glucose and cholesterol levels. Histological and ultrastructural analysis revealed absence of iron-induced inflammation or liver fibrosis despite early signs of liver injury (expression of α-smooth muscle actin). We conclude that parenchymal hepatic iron overload does not suffice to trigger progression of liver steatosis to steatohepatitis or fibrosis in C57BL/6 mice.
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Dieta Hiperlipídica , Fígado Gorduroso/complicações , Hemocromatose/congênito , Ferro/metabolismo , Cirrose Hepática/etiologia , Fígado/metabolismo , Proteínas de Membrana/deficiência , Actinas/metabolismo , Animais , Glicemia/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Progressão da Doença , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/prevenção & controle , Proteínas Ligadas por GPI , Genótipo , Hemocromatose/complicações , Hemocromatose/genética , Hemocromatose/metabolismo , Proteína da Hemocromatose , Hepcidinas/metabolismo , Ferro/sangue , Compostos de Ferro/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Fatores de Risco , Fatores de Tempo , Aumento de PesoRESUMO
BACKGROUND: Yoga is a psychophysical, spiritual science of holistic living, aiming towards body and mind development; it can influence well-being, cognitive processes, personality (Gunas), psychophysiological parameters, and human health. Since it has been observed that Morningness-Eveningness disposition is associated with personality, and that personality can characterize people practicing Yoga, in this exploratory study we posited that Morningness-Eveningness might be associated with personality in Yoga trainees. Since Yoga can have influences over cognitive perspectives, and since it has been observed that Morningness-Eveningness disposition can associate with cognitive processes, we investigated a sample of Yoga trainees with reference to relationship with styles of learning and thinking (relevant aspects of cognitive functioning) and also with Morningness-Eveningness disposition. MATERIAL AND METHODS: We tested 184 Yoga trainees using the following questionnaires: Styles of Learning and Thinking (Torrance), Big Five Questionnaire (Caprara, Barbaranelli, Borgogni), and reduced Morningness-Eveningness Questionnaire (Natale). RESULTS: We found that Morning types score significantly higher than Evening types on Conscientiousness, Friendliness, Scrupulousness, Openness to Culture, emotional Stability, emotion Control, they score higher than intermediate types on Conscientiousness, Friendliness, Scrupulousness. Moreover, data showed that the high majority of subjects, also with reference to Morningness-Eveningness disposition, have right-sided styles of learning and thinking, pointing out a tendency towards right-sided cognitive precessing in the whole sample. Personality traits of the Yoga trainees were also investigated. CONCLUSIONS: Data are discussed with reference to existing literature, psychological and neuroscientific perspectives are suggested, previous studies about Yoga published on Medical Science Monitor are also considered.
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Ritmo Circadiano/fisiologia , Cognição/fisiologia , Personalidade , Yoga/psicologia , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Patients with thalassemia major require lifelong chelation therapy to prevent iron-induced organ damage. The orally active chelator deferiprone has been proposed as an alternative for patients unable or unwilling to use deferoxamine. One report has concluded that deferiprone may worsen hepatic fibrosis in patients with thalassemia, whereas others have found no detrimental effect. A panel of 3 pathologists evaluated 112 coded liver biopsies obtained from 56 patients before and after deferiprone therapy. Fibrosis was scored with the Laennec and Ishak systems. The mean interval between liver biopsies was 3.1 years (range, 1.2-4.9 years). In 11 patients seronegative for hepatitis C, fibrosis scores before and after therapy were 1.12 +/- 1.07 and 0.97 +/- 0.84 (P =.42) with the use of the Ishak system, and 0.71 +/- 0.65 and 0.70 +/- 0.53 (P =.91) with the Laennec system. Among 45 patients seropositive for hepatitis C, fibrosis scores before and after therapy were 1.91 +/- 1.13 and 2.04 +/- 1.30 (P =.43) with the use of the Ishak system and 1.26 +/- 0.73 and 1.35 +/- 0.90 (P =.41) with the Laennec system. When the data set was limited to biopsies that each contained 6 or more portal tracts (31 patients), analysis still showed no significant change in fibrosis with time. With the use of the Laennec system, the fibrosis score did not increase by more than one level in any patients without hepatitis C; it increased by more than one level in 1 patient with hepatitis C; and it did not decrease by more than one level in any of the 56 patients. This analysis of the largest collection of liver biopsies reported to date in patients receiving deferiprone demonstrates no evidence of deferiprone-induced progression of hepatic fibrosis during long-term therapy.