Hypercholesterolemia represents one key pathophysiological factor predisposing to increasing risk of developing cardiovascular disease worldwide. Controlling plasma cholesterol levels and other ...metabolic risk factors is of paramount importance to prevent the overall burden of disease emerging from cardiovascular-disease-related morbidity and mortality. Dietary cholesterol undergoes micellization and absorption in the small intestine, transport via blood, and uptake in the liver. An important amount of cholesterol originates from hepatic synthesis, and is secreted by the liver into bile together with bile acids (BA) and phospholipids, with all forming micelles and vesicles. In clinical medicine, dietary recommendations play a key role together with pharmacological interventions to counteract the adverse effects of chronic hypercholesterolemia. Bioactive compounds may also be part of initial dietary plans. Specifically, soybean contains proteins and peptides with biological activity on plasma cholesterol levels and this property makes soy proteins a functional food. Here, we discuss how soy proteins modulate lipid metabolism and reduce plasma cholesterol concentrations in humans, with potential outcomes in improving metabolic- and dyslipidemia-related conditions.
The circulating concentrations of adiponectin, an antidiabetic adipokine, have been shown to be reduced in obesity, in relation to an increase in inflammation. The aim of the present work was to ...assess the effect of leptin replacement on adiponectin levels and expression as well as on markers of oxidative stress and inflammation in leptin-deficient ob/ob mice. Twelve-week-old male mice (n = 7-10 per group) were treated with either saline (wild type and ob/ob mice) or leptin (ob/ob mice) for 18 days. A third group of ob/ob mice was treated with saline and pair-fed to the amount of food consumed by the leptin-treated group. Leptin replacement restored values of adiponectin (P < 0.001), reduced circulating 8-isoprostane and serum amyloid A (SAA) levels (P < 0.05 for both), and significantly downregulated the increased gene expression of osteopontin (Spp1, P < 0.05), Saa3 (P < 0.05), Cd68 (P < 0.01), Il6 (P < 0.01) and NADPH oxidase (Nox1 and Nox2, P < 0.01) in the perirenal WAT and Spp1 (P < 0.05) in the liver of ob/ob mice. In cultured adipocytes from ob/ob mice, leptin increased (P < 0.05) the mRNA expression and secretion of adiponectin. We concluded that circulating concentrations of adiponectin are positively regulated by leptin and ameliorate obesity-associated oxidative stress and inflammation in mice.
We aim to systematically review the efficacy of prebiotics in reducing anthropometric and biochemical parameters in individuals with non-alcoholic fatty liver disease (NAFLD). A systematic search ...using PubMed/MEDLINE, Embase, clinicaltrials.gov, Cinahl, and Web of Science of articles published up to 20 March 2020 was performed for randomized controlled trials enrolling >20 adult patients. Random-effect meta-analysis for metabolic outcomes in NAFLD patients was performed for anthropometric data in addition to liver enzyme, carbohydrate, and lipid parameters. We found six trials (comprising a total of 242 patients) with NAFLD, with subjects aged 38-52 years. The mean time of fiber administration varied between 10 and 12 weeks. The main fiber types were psyllium (seeds or powder),
(seeds), and high-performance inulin and oligofructose powder at doses of either 10 or 16 g per day. The control group received either maltodextrin (powder or capsules) or crushed wheat (powder). Patients on the diet with added fiber had improvements in body mass index (BMI) (standardized mean difference (SMD) = -0.494, 95% confidence interval (CI): -0.864 to -0.125,
= 0.009); alanine aminotransferase (ALT) (SMD = -0.667, 95% CI: -1.046 to -0.288,
= 0.001); aspartate aminotransferase (AST) (SMD = -0.466, 95% CI: -0.840 to -0.091,
= 0.015); fasting insulin (SMD = -0.705, 95% CI: -1.115 to -0.295,
= 0.001); and homeostasis model assessment for insulin resistance (HOMA-IR) (SMD = -0.619, 95% CI: -1.026 to -0.211,
= 0.003). Hence, the results show that fiber supplements result in favorable changes as reflected in the measurement of anthropometric, metabolic, and liver-related biomarkers, i.e., body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). These effects suggest the potential benefits of fiber consumption for NAFLD populations. More prospective, controlled studies should be conducted to reveal specific details regarding the fiber type, dosage, and duration for optimal intervention.
An essential function of the liver is the formation and secretion of bile, a complex aqueous solution of organic and inorganic compounds essential as route for the elimination of body cholesterol as ...unesterified cholesterol or as bile acids. In bile, a considerable amount of otherwise insoluble cholesterol is solubilized by carriers including two other classes of lipids, namely phospholipid and bile acids. Formation of bile and generation of bile flow are driven by the active secretion of bile acids, lipids and electrolytes into the canalicular and bile duct lumens followed by the parallel movement of water. Thus, water has to cross rapidly into and out of the cell interior driven by osmotic forces. Bile as a fluid, results from complicated interplay of hepatocyte and cholangiocyte uptake and secretion, concentration, by involving a number of transporters of lipids, anions, cations, and water. The discovery of the aquaporin water channels, has clarified the mechanisms by which water, the major component of bile (more than 95%), moves across the hepatobiliary epithelia.
This review is focusing on novel acquisitions in liver membrane lipidic and water transport and functional participation of aquaporin water channels in multiple aspects of hepatobiliary fluid balance. Involvement of aquaporins in a series of clinically relevant hepatobiliary disorders are also discussed.
The multifactorial etiology of major depressive disorder (MDD) includes biological, environmental, genetic, and psychological aspects. Recently, there has been an increasing interest in metallomic ...studies in psychiatry, aiming to evaluate the role of chosen trace elements in the MDD etiology as well as the progression of symptoms. This narrative review aims to summarize the available literature on the relationship between the concentration of chosen elements in the serum of patients with MDD and the onset and progression of this psychiatric condition. The authors reviewed PubMed, Web of Science, and Scopus databases searching for elements that had been investigated so far and further evaluated them in this paper. Ultimately, 15 elements were evaluated, namely, zinc, magnesium, selenium, iron, copper, aluminium, cadmium, lead, mercury, arsenic, calcium, manganese, chromium, nickel, and phosphorus. The association between metallomic studies and psychiatry has been developing dynamically recently. According to the results of current research, metallomics might act as a potential screening tool for patients with MDD while at the same time providing an assessment of the severity of symptoms. Either deficiencies or excessive amounts of chosen elements might be associated with the progression of depressive symptoms or even the onset of the disease among people predisposed to MDD.
(
) is one of the most common human pathogens, affecting half of the world's population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. ...An infection also leads to the progression of epithelial-mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of
and its virulence factors in epithelial-mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included:
(cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor
-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer.
The epidemiological burden of liver steatosis associated with metabolic diseases is continuously growing worldwide and in all age classes. This condition generates possible progression of liver ...damage (i.e., inflammation, fibrosis, cirrhosis, hepatocellular carcinoma) but also independently increases the risk of cardio-metabolic diseases and cancer. In recent years, the terminological evolution from “nonalcoholic fatty liver disease” (NAFLD) to “metabolic dysfunction-associated fatty liver disease” (MAFLD) and, finally, “metabolic dysfunction-associated steatotic liver disease” (MASLD) has been paralleled by increased knowledge of mechanisms linking local (i.e., hepatic) and systemic pathogenic pathways. As a consequence, the need for an appropriate classification of individual phenotypes has been oriented to the investigation of innovative therapeutic tools. Besides the well-known role for lifestyle change, a number of pharmacological approaches have been explored, ranging from antidiabetic drugs to agonists acting on the gut–liver axis and at a systemic level (mainly farnesoid X receptor (FXR) agonists, PPAR agonists, thyroid hormone receptor agonists), anti-fibrotic and anti-inflammatory agents. The intrinsically complex pathophysiological history of MASLD makes the selection of a single effective treatment a major challenge, so far. In this evolving scenario, the cooperation between different stakeholders (including subjects at risk, health professionals, and pharmaceutical industries) could significantly improve the management of disease and the implementation of primary and secondary prevention measures. The high healthcare burden associated with MASLD makes the search for new, effective, and safe drugs a major pressing need, together with an accurate characterization of individual phenotypes. Recent and promising advances indicate that we may soon enter the era of precise and personalized therapy for MASLD/MASH.
Background
Social containment measures imposed in Europe during the lockdown to face COVID‐19 pandemic can generate long‐term potential threats for metabolic health.
Methods
A cohort of 494 ...non‐COVID‐19 subjects living in 21 EU countries were interviewed by an anonymous questionnaire exploring anthropometric and lifestyle changes during 1‐month lockdown. A subgroup of 41 overweight/obese Italian subjects with previously diagnosed nonalcoholic fatty liver (NAFLD) joined the study following a 12‐month follow‐up period promoting weight loss by healthy lifestyle.
Results
During the lockdown, body weight increased in 55% of subjects (average 2.4 ± 0.9 kg). Weight change increased with age, but not baseline body mass index. Subjects living in Italy had greater weight gain than those living in other European Countries. Weight gain during the lockdown was highest in subjects reporting no physical activity, and low adherence to Mediterranean diet. In the NAFLD group, weight gain occurred in 70% of cases. Subjects reporting weight loss during lockdown had decreased fatty liver score at 3 months before the lockdown, as compared with 1 year before.
Conclusions
Strict measures of social containment—even short‐term—pave the way to the increased risk of metabolic abnormalities in the medium‐long term. In this context, adherence to Mediterranean diet and regular physical activity play a protective role both in terms of weight gain and fatty liver development/progression, with implication for primary and secondary prevention. When adopting measures imposing social containment, intensive educational campaigns must increase public awareness about beneficial effects of healthy lifestyles.
Thyroid diseases, including congenital hypothyroidism, thyroiditis, and childhood thyrotoxicosis, are progressively increasing. The incidence of thyroid cancer in children and adolescents has also ...increased in recent decades, mirroring the trends observed in adults. These epidemiologic trends develop in parallel with the rising costs associated with diagnosis and treatment of thyroid diseases. Both genetic and environmental factors are involved in these diseases, and a number of widely diffused toxic chemicals of anthropogenic origin can impair thyroid function and make thyroid cancer worse. Synthetic substances persistently contaminate environmental matrices (i.e., air, soil, water) and the food chain and bio-accumulate in humans, starting from in utero life. Environmental toxins such as air pollutants, endocrine disruptors, and high-frequency electromagnetic fields can act on common targets through common pathways, combined mechanisms, and with trans-generational effects, all of which contribute to thyroid damage. Both experimental and epidemiologic observations show that mechanisms of damage include: modulation of synthesis; transportation and metabolism of thyroid hormones; direct interference with hormone receptors: modulation of gene expression; and autoimmunity. We should not underestimate the available evidence linking environmental pollutants with thyroid disease, cancer included, since toxic substances increasingly diffuse and thyroid hormones play a key role in maintaining systemic metabolic homeostasis during body development. Thus, primary prevention measures are urgently needed in particular to protect children, the most exposed and vulnerable subjects.
Chocolate is well known for its fine flavor, and its history began in ancient times, when the Maya considered chocolate (a cocoa drink prepared with hot water) the "Food of the Gods". The food ...industry produces many different types of chocolate: in recent years, dark chocolate, in particular, has gained great popularity. Interest in chocolate has grown, owing to its physiological and potential health effects, such as regulation of blood pressure, insulin levels, vascular functions, oxidation processes, prebiotic effects, glucose homeostasis, and lipid metabolism. However, further translational and epidemiologic studies are needed to confirm available results and to evaluate other possible effects related to the consumption of cocoa and chocolate, verifying in humans the effects hitherto demonstrated only in vitro, and suggesting how best to consume (in terms of dose, mode, and time) chocolate in the daily diet.
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