Thyroid status affects rat liver regeneration after partial hepatectomy by regulating cell cycle and apoptosis proteins

In rats, various growth factors and hormones, as well as partial hepatectomy (PH) are able to trigger the proliferative response of hepatocytes. Although recent evidence highlights the important role of thyroid hormones and thyroid status in regulating the growth of liver cells in vitro and in vivo models, the mechanism involved in the pro-proliferative effects of thyroid hormones is still unclear. Here we have investigated how in rats made hypo- and hyperthyroid after prolonged treatment respectively with propylthiouracil (PTU) and triiodothyronine (T3), the thyroid status affects liver regeneration after PH by regulating cell cycle and apoptosis proteins. Our results show that both in control and partially hepatectomized animals hyperthyroidism increases the cyclin D1, E and A levels and the activity of cyclin-cdk complexes, and decreases the levels of cdk inhibitors such as p16 and p27. On the contrary hypothyroidism induces a down-regulation of the activity of cyclin cdk complexes decreasing cyclin levels. Thyroid hormones control also p53 and p73, two proteins involved in apoptosis and growth arrest which are induced by PH. In particular, hypothyroidism increases and T3 treatment decreases p73 levels. The analysis of the phosphorylated forms of p42/44 and p38 MAPK revealed that they are induced during hepatic regeneration in euthyroid and hyperthyroid rats whereas they are negatively regulated in hypothyroid rats. In conclusion our data demonstrate that thyroid status can affects liver regeneration, altering the expression and the activity of the proteins involved in the control of cell cycle and growth arrest. Copyright © 2005 S. Karger AG, Basel

Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey

Fibromyalgia (FM) is an unsolved central pain processing disturbance. We aim to provide a unifying model for FM pathogenesis based on a loop network involving thalamocortical regions, i.e., the ventroposterior lateral thalamus (VPL), the somatosensory cortex (SC), and the thalamic reticular nucleus (TRN). The dynamics of the loop have been described by three differential equations having neuron mean firing rates as variables and containing Hill functions to model mutual interactions among the loop elements. A computational analysis conducted with MATLAB has shown a transition from monostability to bistability of the loop behavior for a weakening of GABAergic transmission between TRN and VPL. This involves the appearance of a high-firing-rate steady state, which becomes dominant and is assumed to represent pathogenic pain processing giving rise to chronic pain. Our model is consistent with a bulk of literature evidence, such as neuroimaging and pharmacological data collected on FM patients, and with correlations between FM and immunoendocrine conditions, such as stress, perimenopause, chronic inflammation, obesity, and chronic dizziness. The model suggests that critical targets for FM treatment are to be found among immunoendocrine pathways leading to GABA/glutamate imbalance having an impact on the thalamocortical system

Vestibular disability/handicap in Fibromyalgia : a questionnaire study

Fibromyalgia (FM) is a poorly understood, central pain processing disorder characterized by a broad range of symptoms, such as chronic pain, sleep disruption, chronic fatigue, and psychosomatic symptoms. In addition, recent studies have shown that FM patients also experience dizziness. We aimed to establish a prevalence rate of vestibular symptoms in a population of FM patients through a battery of questionnaires investigating socio-demographic, clinical and psychological characteristics, combined with the Dizziness Handicap Inventory (DHI) and the Situational Vertigo Questionnaire (SVQ). A total of 277 respondents, officially diagnosed with FM, completed the full study, while 80 controls were also included for DHI and SVQ questionnaires. We found that FM participants were significantly affected by vestibular symptoms, which correlated with FM-associated pain and non-pain symptoms. The dizziness reported by FM participants showed peculiar features suggesting an FM-intrinsic mechanism of vestibular dysfunction, possibly linked to migraine and dysautonomia conditions. Correlations between dizziness and depressive mood (or neuroticism), revealed an impact of dizziness on psychological status, leading to depressive reactions and interpersonal difficulties, and possibly involving a noxious, self-sustained stress condition. In conclusion, data showed a manifesting dizziness condition in FM patients that warrants careful clinical attention due to its possible inherent role in the syndrome

use of an in vitro model of hepatic steatosis for studying the anti oxidant and antisteatotic effects of fucoidan polysaccharides

Non Alcoholic Fatty Liver Disease (NAFLD) is characterised by fat accumulation in hepatocytes in the form of triacyglycerols (TAGs) within cytosolic lipid droplets. Fucoidans (FUs) are biologically active polysaccharides usually isolated from brown marine algae, but recently identified also in terrestrial plants. In this study, we aimed to investigate the anti-oxidant and anti-steatotic effects of FUs purified from C. compressa, F. hermonis, and E. globulus. To this aim, we used a validated NAFLD in vitro model consisting of rat hepatoma FaO cells exposed to an oleate/palmitate mixture. Such a model is suitable for rapid investigation of direct effects of natural and artificial compounds, together with satisfying the strategy of 3Rs for laboratory use of animals. Our results indicated that all FUs display anti-oxidant and anti-steatotic activities. Steatotic FaO cells may be employed to further study the biological effects of FUs

Innovative In Vitro Strategy for Assessing Aluminum Bioavailability in Oral Care Cosmetics

Aluminum is an element found in nature and in cosmetic products. It can interfere with the metabolism of other cations, thus inducing gastrointestinal disorder. In cosmetics, aluminum is used in antiperspirants, lipsticks, and toothpastes. The aim of this work is to investigate aluminum bioavailability after accidental oral ingestion derived from the use of a toothpaste containing a greater amount of aluminum hydroxide than advised by the Scientific Committee on Consumer Safety (SCCS). To simulate in vitro toothpaste accidental ingestion, the INFOGEST model was employed, and the amount of aluminum was measured through the ICP-AES analysis. Tissue barrier integrity was analyzed by measuring transepithelial electric resistance, and the tissue architecture was checked through light microscopy. The margin of safety was also calculated. Overall, our results indicate that the acute exposure to aluminum accidentally ingested from toothpastes is safe for the final user, even in amounts higher than SCCS indications

An extensive review on phenolic compounds and their potential estrogenic properties on skin physiology

Polyphenolic compounds constitute a diverse group of natural components commonly occurring in various plant species, known for their potential to exert both beneficial and detrimental effects. Additionally, these polyphenols have also been implicated as endocrine-disrupting (ED) chemicals, raising concerns about their widespread use in the cosmetics industry. In this comprehensive review, we focus on the body of literature pertaining to the estrogenic properties of ED chemicals, with a particular emphasis on the interaction of isoflavones with estrogen receptors. Within this review, we aim to elucidate the multifaceted roles and effects of polyphenols on the skin, exploring their potential benefits as well as their capacity to act as ED agents. By delving into this intricate subject matter, we intend to provoke thoughtful consideration, effectively opening a Pandora’s box of questions for the reader to ponder. Ultimately, we invite the reader to contemplate whether polyphenols should be regarded as friends or foes in the realm of skincare and endocrine disruption

The Role of the Stress Response in Metabolic Dysfunction-Associated Fatty Liver Disease: A Psychoneuroendocrineimmunology-Based Perspective

The novel term metabolic dysfunction-associated fatty liver disease (MAFLD), which has been proposed to describe the major cause of hepatic disease, pinpoints the coexistence of multiple metabolic disturbances and liver steatosis, giving rise to different phenotypic manifestations. Within the psychoneuroendocrineimmunological (PNEI) network that regulates body–mind interactions, the stress response plays a pervasive role by affecting metabolic, hormonal, immune, and behavioral balance. In this perspective, we focus on chronic psychosocial stress and high levels of cortisol to highlight their role in MAFLD pathogenesis and worsening. From a PNEI perspective, considering the stress response as a therapeutic target in MAFLD allows for simultaneously influencing multiple pathways in the development of MAFLD, including dysmetabolism, inflammation, feeding behaviors, gut–liver axis, and dysbiosis, with the hope of better outcomes

Stress-Related Weight Gain: Mechanisms Involving Feeding Behavior, Metabolism, Gut Microbiota and Inflammation

The body stress response is a highly adaptive phenomenon activated by different types of physical and emotional stressors. Chronic and/or excessive stress is, on the other hand, often maladaptive. In this short review we deal with the influence of the stress response on weight gain and fat accumulation. Chronic stress appears to promote a shift from homeostatic regulation of food intake to hedonic overeating. Hyperactivation of the stress response triggers metabolic changes that might slow down energy expenditure while promoting visceral fat accumulation. Chronically elevated glucocorticoid levels also enhance the inflammatory response and cytokines secreted by visceral fat can in turn increase metabolic abnormalities towards obesity. Changes in the gut microbiota, which is highly sensitive to the stress hormones as well as to the type of food ingested, can also be involved in stress-related weight gain. Given the vicious circles that interlock stress, food, metabolism and inflammation, strategies for stress control and management should be taken into account to prevent weight gain particularly in Western-lifestyle countries

Le potenzialit\ue0 della dieta vegana come prevenzione e cura [The potential of vegan diets as an instrument for prevention and treatment]

Negli ultimi decenni, l'alimentazione del mondo cosiddetto occidentale ha conosciuto un'autentica rivoluzione: un tempo ricca di vegetali e povera di derivati animali, oggi \ue8 caratterizzata dall'onnipresenza di carne e cereali raffinati, mentre verdura e frutta sono diventati marginali. Il risultato \ue8 un aumento del rischio di sviluppare patologie quali diabete, cancro, malattie cardiovascolari, neurodegenerative e autoimmuni. Studi recenti hanno dimostrato che attraverso una dieta vegana \ue8 possibile prevenire, migliorare e arrestare il decorso delle patologie croniche che pi\uf9 affliggono i paesi ricchi, in particolare in virt\uf9 di alcune sue peculiarit\ue0: restrizione proteica e calorica, controllo dell'infiammazione e miglioramento della composizione del microbiota intestinale. L'obiettivo del presente articolo \ue8 quello di riassumere brevemente i meccanismi molecolari in grado di spiegare il potenziale protettivo oggi attribuito a una dieta strettamente vegetale, ricordando che, a patto di provvedere all'integrazione della vitamina B12, si tratta di un regime alimentare completo e salutare in tutte le fasi della vita.Dietary habits in the so-called Western world have undergone a genuine revolution over the last decades: once rich in plant foods and low in animal products and derivatives, our diets are now marked by the ubiquitous presence of meat and refined grains, while fruits and vegetables play a marginal role. As a result, the risk of developing diseases such as diabetes, cancer or cardiovascular, neurodegenerative and autoimmune disorders has increased. Recent studies have shown that the typical features of a vegan diet - protein and calorie restriction, reduction of inflammation and a healthier gut microbiota - allow to prevent, improve and halt the progress of the most common chronic conditions in the developed world. This article describes the molecular mechanisms behind the protective potential that is nowadays associated to a 100% plant based diet, emphasizing that, as long as we supplement it with vitamin B12, a vegan diet is healthy and complete, and satisfies all physiological needs at all life stages