Antioxidant and Antidiabetic Properties of a Thinned-Nectarine-Based Nanoformulation in a Pancreatic β-Cell Line.

Pancreatic β-cells play a crucial role in maintaining glucose homeostasis, although they are susceptible to oxidative damage, which can ultimately impair their functionality. Thinned nectarines (TNs) have gained increasing interest due to their high polyphenol and abscisic acid (ABA) content, both of which possess antidiabetic properties. Nevertheless, the efficacy of these bioactive compounds may be compromised by limited stability and bioavailability in vivo.

Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments.

Non-alcoholic fatty liver disease (NAFLD) causes significant global disease burden and is a leading cause of mortality. NAFLD induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of NAFLD is widely recognised, the precise triggers for disease progression are still to be fully elucidated.

Alcoholic liver disease: Current insights into cellular mechanisms.

Alcoholic liver disease (ALD) due to chronic alcohol consumption is a significant global disease burden and a leading cause of mortality. Alcohol abuse induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of ALD is widely recognized, the precise triggers for disease progression are still to be fully elucidated.

Excessive Iron Induces Oxidative Stress Promoting Cellular Perturbations and Insulin Secretory Dysfunction in MIN6 Beta Cells.

Exposure to high levels of glucose and iron are co-related to reactive oxygen species (ROS) generation and dysregulation of insulin synthesis and secretion, although the precise mechanisms are not well clarified. The focus of this study was to examine the consequences of exposure to high iron levels on MIN6 β-cells. MIN6 pseudoislets were exposed to 20 µM (control) or 100 µM (high) iron at predefined glucose levels (5.

High omega arachidonic acid/docosahexaenoic acid ratio induces mitochondrial dysfunction and altered lipid metabolism in human hepatoma cells.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver disease worldwide and is a growing epidemic. A high ratio of omega-6 fatty acids to omega-3 fatty acids in the diet has been implicated in the development of NAFLD. However, the inflicted cellular pathology remains unknown.

Hepcidin secretion was not directly proportional to intracellular iron-loading in recombinant-TfR1 HepG2 cells: short communication.

Hepcidin is the master regulator of systemic iron homeostasis and its dysregulation is observed in several chronic liver diseases. Unlike the extracellular iron-sensing mechanisms, the intracellular iron-sensing mechanisms in the hepatocytes that lead to hepcidin induction and secretion are incompletely understood. Here, we aimed to understand the direct role of intracellular iron-loading on hepcidin mRNA and peptide secretion using our previously characterised recombinant HepG2 cells that over-express the cell-surface iron-importer protein transferrin receptor-1.

Measurement of 4-Hydroxynonenal (4-HNE) Protein Adducts by ELISA.

Enzyme linked immunosorbent assay (ELISA) is a widely used technique for the measurement of antigens and antibodies alike. We describe here procedures, indirect ELISA and sandwich ELISA for the detection of 4-hydroxynonenal protein adducts. These adducts are stable compounds formed within cells and bodily fluids under conditions of oxidative stress.

Iron Enhances Hepatic Fibrogenesis and Activates Transforming Growth Factor-β Signaling in Murine Hepatic Stellate Cells.

Background: Although excess iron induces oxidative stress in the liver, it is unclear whether it directly activates the hepatic stellate cells (HSC).

Materials And Methods: We evaluated the effects of excess iron on fibrogenesis and transforming growth factor beta (TGF-β) signaling in murine HSC. Cells were treated with holotransferrin (0.

Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease.

Background/aims: Intestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown.

Erratum to: HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication.

The original article has been changed to reflect the correct co-author name: Sebastien Farnaud. The original article was corrected.

HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication.

In liver hepatocytes, the HFE gene regulates cellular and systemic iron homeostasis by modulating cellular iron-uptake and producing the iron-hormone hepcidin in response to systemic iron elevation. However, the mechanism of iron-sensing in hepatocytes remain enigmatic. Therefore, to study the effect of iron on HFE and hepcidin (HAMP) expressions under distinct extracellular and intracellular iron-loading, we examined the effect of holotransferrin treatment (1, 2, 5 and 8 g/L for 6 h) on intracellular iron levels, and mRNA expressions of HFE and HAMP in wild-type HepG2 and previously characterized iron-loaded recombinant-TfR1 HepG2 cells.

Characterization of hepcidin response to holotransferrin in novel recombinant TfR1 HepG2 cells.

Hepcidin is the key regulator of systemic iron homeostasis. The iron-sensing mechanisms and the role of intracellular iron in modulating hepatic hepcidin secretion are unclear. Therefore, we created a novel cell line, recombinant-TfR1 HepG2, expressing iron-response-element-independent TFRC mRNA to promote cellular iron-overload and examined the effect of excess holotransferrin (5g/L) on cell-surface TfR1, iron content, hepcidin secretion and mRNA expressions of TFRC, HAMP, SLC40A1, HFE and TFR2.

Repeat-measures longitudinal study evaluating behavioural and gastrointestinal symptoms in children with autism before, during and after visceral osteopathic technique (VOT).

Unlabelled: This study investigated the influence of visceral osteopathic technique (VOT) on the behaviour and gastrointestinal (GI) symptoms of children with autism using a validated questionnaire to measure outcome.

Methods: The 49 recruited autistic children suffered GI symptoms and impaired social interaction and communication, but were otherwise healthy. Thirty minute VOT sessions were applied to the abdomens of the children over a 6 week period whilst their GI and behavioural parameters were recorded.

Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells.

Iron overload coupled with low hepcidin levels are characteristics of hereditary haemochromatosis. To understand the role of transferrin receptor (TFR) and intracellular iron in hepcidin secretion, Chinese hamster ovary transferrin receptor variant (CHO TRVb-1) cells were used that express iron-response-element-depleted human TFRC mRNA (TFRC∆IRE). Results showed that CHO TRVb-1 cells expressed higher basal levels of cell-surface TFR1 than HepG2 cells (2.

New insights into the role of the branched-chain aminotransferase proteins in the human brain.

The human cytosolic branched-chain aminotransferase (hBCATc) enzyme is strategically located in glutamatergic neurons, where it is thought to provide approximately 30% of de novo nitrogen for brain glutamate synthesis. In health, glutamate plays a dominant role in facilitating learning and memory. However, in patients with Alzheimer's disease (AD), synaptic levels of glutamate become toxic, resulting in a direct increase in postsynaptic neuronal calcium, causing a cascade of events that contributes to the destruction of neuronal integrity and cell death, pathological features of AD.

Regional Increase in the Expression of the BCAT Proteins in Alzheimer's Disease Brain: Implications in Glutamate Toxicity.

Background: The human branched chain aminotransferases (hBCATm, mitochondrial and hBCATc, cytosolic) are major contributors to brain glutamate production. This excitatory neurotransmitter is thought to contribute to neurotoxicity in neurodegenerative conditions such as Alzheimer's disease (AD) but the expression of hBCAT in this disease has not previously been investigated.

Objective: The objective of investigating hBCAT expression is to gain insight into potential metabolic pathways that may be dysregulated in AD brain, which would contribute to glutamate toxicity.

The branched-chain aminotransferase proteins: novel redox chaperones for protein disulfide isomerase--implications in Alzheimer's disease.

Aims: The human branched-chain aminotransferase proteins (hBCATm and hBCATc) are regulated through oxidation and S-nitrosation. However, it remains unknown whether they share common redox characteristics to enzymes such as protein disulfide isomerase (PDI) in terms of regulating cellular repair and protein misfolding.

Results: Here, similar to PDI, the hBCAT proteins showed dithiol-disulfide isomerase activity that was mediated through an S-glutathionylated mechanism.

Hepatic mitochondrial dysfunction induced by fatty acids and ethanol.

Understanding the key aspects of the pathogenesis of alcoholic fatty liver disease particularly alterations to mitochondrial function remains to be resolved. The role of fatty acids in this regard requires further investigation due to their involvement in fatty liver disease and obesity. This study aimed to characterize the early effects of saturated and unsaturated fatty acids alone on liver mitochondrial function and during concomitant ethanol exposure using isolated liver mitochondria and VA-13 cells (Hep G2 cells that efficiently express alcohol dehydrogenase).

S-Nitrosoglutathione inactivation of the mitochondrial and cytosolic BCAT proteins: S-nitrosation and S-thiolation.

Specific proteins with reactive thiol(ate) groups are susceptible to nitric oxide (NO) modification, which can result in S-nitrosation, S-thiolation, or disulfide bond formation. In the present study the effect of NO modification on the functionality of human mitochondrial and cytosolic branched-chain aminotransferases (hBCATm and hBCATc, respectively) was investigated. Here, the NO reactive agents, S-nitrosoglutathione (GSNO), S-nitroso-N-acetyl-dl-penacillamine, and sodium nitroprusside, inactivated both isoforms in a dose-dependent manner.

Effects of 4-hydroxynonenal on mitochondrial 3-hydroxy-3-methylglutaryl (HMG-CoA) synthase.

Chronic ethanol consumption causes increased production of reactive oxygen species in hepatic mitochondria accompanied by elevations in products of lipid peroxidation such as 4-hydroxynonenal (4-HNE). In the current study we investigated the effects of chronic ethanol consumption on a prominent protein-4-HNE adduct in liver mitochondria. Male Sprague-Dawley rats were fed a liquid diet for 31 days in which ethanol constituted 36% of total calories.

Protein adduct species in muscle and liver of rats following acute ethanol administration.

Aims: Previous immunohistochemical studies have shown that the post-translational formation of aldehyde-protein adducts may be an important process in the aetiology of alcohol-induced muscle disease. However, other studies have shown that in a variety of tissues, alcohol induces the formation of various other adduct species, including hybrid acetaldehyde-malondialdehyde-protein adducts and adducts with free radicals themselves, e.g.

Liver dysfunction induced by bile duct ligation and galactosamine injection alters cardiac protein synthesis.

Liver disease has been shown to affect the cardiovascular system and may influence cardiac protein metabolism. This hypothesis was tested by measuring rates of cardiac protein synthesis in 2 models of liver disease in rats. The study consisted of 5 groups--group 1: control, injected with saline and fed ad libitum; group 2: acute liver injury, by dosage with 400 mg/kg galactosamine; group 3: injected with saline and pair-fed to group 2; group 4: chronic liver disease, using bile duct ligation; and group 5: sham-operated and pair-fed to group 4.

Emerging techniques in biomedical research and their application to alcohol toxicity.

This article represents the proceedings of a symposium at the 2002 RSA-ISBRA Meeting in San Francisco. The chairs were Vinood B. Patel and Victor R.

Altered hepatic mitochondrial ribosome structure following chronic ethanol consumption.

Chronic ethanol consumption decreases the synthesis of all 13 polypeptides encoded by the hepatic mitochondrial genome. This alteration in mitochondrial protein synthesis is due to modifications in mitochondrial ribosomes. In the current study, the nature of these alterations was investigated by determining some of the hydrodynamic properties, namely sedimentation coefficient, shape, and mass of mitochondrial ribosomes.