Gender Differences in the Impact of a High-Fat, High-Sugar Diet in Skeletal Muscles of Young Female and Male Mice.

In the context of the increasing number of obese individuals, a major problem is represented by obesity and malnutrition in children. This condition is mainly ascribable to unbalanced diets characterized by high intakes of fat and sugar. Childhood obesity and malnutrition are not only associated with concurrent pathologies but potentially compromise adult life.

Molecular events in brain bilirubin toxicity revisited.

The mechanisms involved in bilirubin neurotoxicity are still far from being fully elucidated. Several different events concur to damage mainly the neurons among which inflammation and alteration of the redox state play a major role. An imbalance of cellular calcium homeostasis has been recently described to be associated with toxic concentrations of bilirubin, and this disequilibrium may in turn elicit an inflammatory reaction.

Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications.

Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron.

Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases.

The crucial physiological process of heme breakdown yields biliverdin (BV) and bilirubin (BR) as byproducts. BV, BR, and the enzymes involved in their production (the "yellow players-YP") are increasingly documented as endogenous modulators of human health. Mildly elevated serum bilirubin concentration has been correlated with a reduced risk of multiple chronic pro-oxidant and pro-inflammatory diseases, especially in the elderly.

The potential role of omentin-1 in obesity-related metabolic dysfunction-associated steatotic liver disease: evidence from translational studies.

Background: Obesity, characterized by visceral adipose tissue (VAT) expansion, is closely associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Recent research has highlighted the crucial role of the adipose tissue-liver axis in the development of MASLD. In this study, we investigated the potential role of omentin-1, a novel adipokine expressed by VAT, in obesity-related MASLD pathogenesis.

Bilirubin and Redox Stress in Age-Related Brain Diseases.

Cellular redox status has a crucial role in brain physiology, as well as in pathologic conditions. Physiologic senescence, by dysregulating cellular redox homeostasis and decreasing antioxidant defenses, enhances the central nervous system's susceptibility to diseases. The reduction of free radical accumulation through lifestyle changes, and the supplementation of antioxidants as a prophylactic and therapeutic approach to increase brain health, are strongly suggested.

Inflammation, Dopaminergic Brain and Bilirubin.

Dopamine is a well-known neurotransmitter due to its involvement in Parkinson's disease (PD). Dopamine is not only involved in PD but also controls multiple mental and physical activities, such as the pleasure of food, friends and loved ones, music, art, mood, cognition, motivation, fear, affective disorders, addiction, attention deficit disorder, depression, and schizophrenia. Dopaminergic neurons (DOPAn) are susceptible to stressors, and inflammation is a recognized risk for neuronal malfunctioning and cell death in major neurodegenerative diseases.

Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia.

Recent findings indicated aberrant epigenetic control of the central nervous system (CNS) development in hyperbilirubinemic Gunn rats as an additional cause of cerebellar hypoplasia, the landmark of bilirubin neurotoxicity in rodents. Because the symptoms in severely hyperbilirubinemic human neonates suggest other regions as privileged targets of bilirubin neurotoxicity, we expanded the study of the potential impact of bilirubin on the control of postnatal brain development to regions correlating with human symptoms. Histology, transcriptomic, gene correlation, and behavioral studies were performed.

Celiac Disease and Neurological Manifestations: From Gluten to Neuroinflammation.

Celiac disease (CD) is a complex multi-organ disease with a high prevalence of extra-intestinal involvement, including neurological and psychiatric manifestations, such as cerebellar ataxia, peripheral neuropathy, epilepsy, headache, cognitive impairment, and depression. However, the mechanisms behind the neurological involvement in CD remain controversial. Recent evidence shows these can be related to gluten-mediated pathogenesis, including antibody cross-reaction, deposition of immune-complex, direct neurotoxicity, and in severe cases, vitamins or nutrients deficiency.

Bilirubin Prevents the TH Dopaminergic Neuron Loss in a Parkinson's Disease Model by Acting on TNF-α.

Parkinson's disease (PD), the fastest-growing movement disorder, is still challenged by the unavailability of disease-modifying therapy. Mildly elevated levels of unconjugated bilirubin (UCB, PubChem CID 5280352) have been shown to be protective against several extra-CNS diseases, and the effect is attributed to its well-known anti-oxidant and anti-inflammatory capability. We explored the neuroprotective effect of low concentrations of UCB (from 0.

Models of bilirubin neurological damage: lessons learned and new challenges.

Objective: Jaundice (icterus) is the visible manifestation of the accumulation of bilirubin in the tissue and is indicative of potential toxicity to the brain. Since its very first description more than 2000 years ago, many efforts have been undertaken to understand the molecular determinants of bilirubin toxicity to neuronal cells to reduce the risk of neurological sequelae through the use of available chemicals and in vitro, ex vivo, in vivo, and clinical models. Although several studies have been performed, important questions remain unanswered, such as the reasons for regional sensitivity and the interplay with brain development.

Nonalcoholic Fatty Liver Disease and Altered Neuropsychological Functions in Patients with Subcortical Vascular Dementia.

NAFLD is the most common cause of abnormality in liver function tests. NAFLD is considered a potential cardiovascular risk factor and is linked to cardiovascular risk factors such as obesity, hypertension, type 2 diabetes, and dyslipidemia. Few previous studies have investigated whether NAFLD could be independently associated with cognitive impairment.

Vascular network expansion, integrity of blood-brain interfaces, and cerebrospinal fluid cytokine concentration during postnatal development in the normal and jaundiced rat.

Background: Severe neonatal jaundice resulting from elevated levels of unconjugated bilirubin in the blood induces dramatic neurological impairment. Central oxidative stress and an inflammatory response have been associated with the pathophysiological mechanism. Cells forming the blood-brain barrier and the choroidal blood-CSF barrier are the first CNS cells exposed to increased plasma levels of unconjugated bilirubin.

Bilirubin: A Promising Therapy for Parkinson's Disease.

Following the increase in life expectancy, the prevalence of Parkinson's disease (PD) as the most common movement disorder is expected to rise. Despite the incredibly huge efforts in research to find the definitive biomarker, to date, the diagnosis of PD still relies mainly upon clinical symptoms. A wide range of treatments is available for PD, mainly alleviating the clinical symptoms.

Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease.

Homocysteine (Hcy) is a sulfur-containing amino acid generated during methionine metabolism, accumulation of which may be caused by genetic defects or the deficit of vitamin B12 and folate. A serum level greater than 15 micro-mols/L is defined as hyperhomocysteinemia (HHcy). Hcy has many roles, the most important being the active participation in the transmethylation reactions, fundamental for the brain.

Curcumin Prevents Cerebellar Hypoplasia and Restores the Behavior in Hyperbilirubinemic Gunn Rat by a Pleiotropic Effect on the Molecular Effectors of Brain Damage.

Bilirubin toxicity to the central nervous system (CNS) is responsible for severe and permanent neurologic damage, resulting in hearing loss, cognitive, and movement impairment. Timely and effective management of severe neonatal hyperbilirubinemia by phototherapy or exchange transfusion is crucial for avoiding permanent neurological consequences, but these therapies are not always possible, particularly in low-income countries. To explore alternative options, we investigated a pharmaceutical approach focused on protecting the CNS from pigment toxicity, independently from serum bilirubin level.

The Role of Bilirubin and the Other "Yellow Players" in Neurodegenerative Diseases.

Bilirubin is a yellow endogenous derivate of the heme catabolism. Since the 1980s, it has been recognized as one of the most potent antioxidants in nature, able to counteract 10,000× higher intracellular concentrations of HO. In the recent years, not only bilirubin, but also its precursor biliverdin, and the enzymes involved in their productions (namely heme oxygenase and biliverdin reductase; altogether the "yellow players"-YPs) have been recognized playing a protective role in diseases characterized by a chronic prooxidant status.

Behavior in subcortical vascular dementia with sight pathologies: visual hallucinations as a consequence of precocious gait imbalance and institutionalization.

Background: Subcortical vascular dementia (sVAD) is considered the most frequent dementia in old population, and it is due to a small vessel disease. It has a very specific nosography, where the dominant factors are dysexecutive functions, depression, and apathy. Very few studies described visual hallucinations in sVAD, apart from in the final stages of it.

Is Parkinson's disease an unique clinical entity? Rigid or tremor dominant PD: Two faces of the same coin.

Parkinson's disease is one of the most described neurodegenerative pathologies; though it is one of the most complex pathologies, is not fully understood, correctly identified, with its different types of presentation, its clinical course and the neural networks involved. We report on a series consisting of 432 de novo PD diagnosed patients, and 457 control cases. We identify a possible independent relationship between two clinical PD presentation, akinetic-rigid and tremor-dominant, and cognitive and behavioral changes.

Non-alcoholic fatty liver disease and neurological defects.

Introduction And Objectives: Nonalcoholic fatty liver disease (NAFLD) can be considered one of the most common causes of liver disease in our days and is regarded as one of the newest vascular risk factors for cerebrovascular and other neurological diseases.

Materials And Methods: We studied a group of neurological outpatients, divided into two homogenous groups based on the presence or absence of NAFLD.

Results And Conclusions: We testified an independent relationship between NAFLD and common vascular risk factors (age, sex, educational level, BMI, cholesterol and lipid assessment, Hb1ac).

Earliest Mechanisms of Dopaminergic Neurons Sufferance in a Novel Slow Progressing Ex Vivo Model of Parkinson Disease in Rat Organotypic Cultures of Substantia Nigra.

The current treatments of Parkinson disease (PD) are ineffective mainly due to the poor understanding of the early events causing the decline of dopaminergic neurons (DOPAn). To overcome this problem, slow progressively degenerating models of PD allowing the study of the pre-clinical phase are crucial. We recreated in a short ex vivo time scale (96 h) all the features of human PD (needing dozens of years) by challenging organotypic culture of rat substantia nigra with low doses of rotenone.

Bilirubin-Induced Oxidative Stress Leads to DNA Damage in the Cerebellum of Hyperbilirubinemic Neonatal Mice and Activates DNA Double-Strand Break Repair Pathways in Human Cells.

Unconjugated bilirubin is considered a potent antioxidant when present at moderate levels. However, at high concentrations, it produces severe neurological damage and death associated with kernicterus due to oxidative stress and other mechanisms. While it is widely recognized that oxidative stress by different toxic insults results in severe damage to cellular macromolecules, especially to DNA, no data are available either on DNA damage in the brain triggered by hyperbilirubinemia during the neonatal period or on the activation of DNA repair mechanisms.

Histone acetylation as a new mechanism for bilirubin-induced encephalopathy in the Gunn rat.

Bilirubin neurotoxicity has been studied for decades and has been shown to affect various mechanisms via significant modulation of gene expression. This suggests that vital regulatory mechanisms of gene expression, such as epigenetic mechanisms, could play a role in bilirubin neurotoxicity. Histone acetylation has recently received attention in the CNS due to its role in gene modulation for numerous biological processes, such as synaptic plasticity, learning, memory, development and differentiation.