Mitochondrial liver

Shwachman-Diamond syndrome (SDS) is a genetic disorder caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. The syndrome is characterized by multiorgan dysfunction primarily involving the bone marrow and exocrine pancreas. Frequently overlooked is the hepatic dysfunction seen in early childhood which tends to improve by adulthood. Here, we report a child who initially presented with failure to thrive and elevated transaminases, and was ultimately diagnosed with SDS. A liver biopsy electron micrograph revealed hepatocytes crowded with numerous small mitochondria, resembling the hepatic architecture from patients with inborn errors of metabolism, including mitochondrial diseases...

BACKGROUND: Luteolin (3,4,5,7-tetrahydroxy flavone) is reported to strongly protect from acute carbon tetrachloride (CCl4 ) -induced liver injury or fibrosis. Ferroptosis can be induced by hepatic injury, and contributes to liver fibrosis development. The exact functional mechanism underlying luteolin inhibition of hepatic injury and whether ferroptosis is involved are unclear. METHODS: Mice model and cell model of liver injury were constructed or induced to explore the effect and molecular mechanisms of Luteolin in the treatment of hepatic injury using CCl4...

Nitrocatechols are the standard pharmacophore to develop potent tight-binding inhibitors of catechol O -methyltransferase (COMT), which can be used as coadjuvant drugs to manage Parkinson's disease. Tolcapone is the most potent drug of this class, but it has raised safety concerns due to its potential to induce liver damage. Tolcapone-induced hepatotoxicity has been attributed to the nitrocatechol moiety; however, other nitrocatechol-based COMT inhibitors, such as entacapone, are safe and do not damage the liver...

BACKGROUND: The global organ shortage is the biggest obstacle to expand urgently needed liver transplantation activities. In addition to donation after brain death (DBD), donation after primary circulatory death (DCD) has also been introduced in many European countries to increase the number of donated organs. OBJECTIVE: This article summarizes the legal and ethical aspects of DCD, the practical donation process of DCD, the clinical results of DCD liver transplantation with a special focus on organ assessment before a planned DCD liver transplantation...

AIMS: With a focus on the discrepancy between preclinical and clinical findings, this review will gather comprehensive information about the effects of calcineurin inhibitors (CNI) on cognitive function and related brain pathology from in vitro, in vivo, and clinical studies. We also summarize the potential mechanisms that underlie the pathways related to CNI-induced cognitive impairment. METHODS: We systematically searched articles in PubMed using keywords 'calcineurin inhibitor*' and 'cognition' to identify related articles, which the final list pertaining to underlying mechanisms of CNI on cognition...

We previously demonstrated in baboons that maternal undernutrition (MUN), achieved by 70 % of control nutrition, impairs fetal liver function, but long-term changes associated with aging in this model remain unexplored. Here, we assessed clinical phenotypes of liver function, mitochondrial bioenergetics, and protein abundance in adult male and female baboons exposed to MUN during pregnancy and lactation and their control counterparts. Plasma liver enzymes were assessed enzymatically. Liver glycogen, choline, and lipid concentrations were quantified by magnetic resonance spectroscopy...

Understanding the relationship between dietary fat and physiological responses is crucial in species adapted to arid environments where water scarcity is common. In this study, we present a comprehensive exploration of gene expression across five tissues (kidney, liver, lung, gastrointestinal tract, and hypothalamus) and 19 phenotypic measurements, investigating the effects of dietary fat in the desert-adapted cactus mouse ( Peromyscus eremicus ). We show impacts on immune function, circadian gene regulation, and mitochondrial function for mice fed a lower-fat diet compared to mice fed a higher-fat diet...

SLC25A26 is the only known human mitochondrial S-adenosylmethionine carrier encoding gene. Recent studies have shown that SLC25A26 is abnormally expressed in some cancers, such as cervical cancer, low-grade glioma, non-small cell lung cancer, and liver cancer, which suggests SLC25A26 can affect the occurrence and development of some cancers. This article in brief briefly reviewed mitochondrial S-adenosylmethionine carrier in different species and its encoding gene, focused on the association of SLC25A26 aberrant expression and some cancers as well as potential mechanisms, summarized its potential for cancer prognosis, and characteristics of mitochondrial diseases caused by SLC25A26 mutation...

Plants provide a wide array of compounds that can be explored for potential anticancer properties. Siphonochilone, a furanoterpene that represents one of the main components of the African plant Siphonochilus aethiopicus, shows numerous health benefits. However, to date, its antiproliferative properties have not been tested. The aim of this study was to analyze the cytotoxic effects of siphonochilone on a panel of cancer cell lines and its underlying mechanism of action. Our results demonstrated that siphonochilone exhibited significant cytotoxic effects on pancreatic, breast, lung, colon, and liver cancer cell lines showing a IC50 ranging from 22 to 124 μM at 72 h of treatment and highlighting its cytotoxic effect against MCF7 and PANC1 breast and pancreas cancer cell lines (22...

BACKGROUND: Retinal ischemia/reperfusion (RIR) is implicated in various forms of optic neuropathies, yet effective treatments are lacking. RIR leads to the death of retinal ganglion cells (RGCs) and subsequent vision loss, posing detrimental effects on both physical and mental health. Apigenin (API), derived from a wide range of sources, has been reported to exert protective effects against ischemia/reperfusion injuries in various organs, such as the brain, kidney, myocardium, and liver...

Parenteral nutrition (PN) is typically administered to individuals with gastrointestinal dysfunction, a contraindication for enteral feeding, and a need for nutritional therapy. When PN is the only energy source in patients, it is defined as total parenteral nutrition (TPN). TPN is a life-saving approach for different patient populations, both in infants and adults. However, despite numerous benefits, TPN can cause adverse effects, including metabolic disorders and liver injury. TPN-associated liver injury, known as intestinal failure-associated liver disease (IFALD), represents a significant problem affecting up to 90% of individuals receiving TPN...

Thermal processing of food is likely to form acrylamide (AA) and elaidic acid (EA), which are both mainly metabolized by the liver. The two substances are associated with the pathogenesis of liver disease. In the current study, we investigated the toxic effects of the combined action of AA and EA on HSC-T6 cells, and the mechanism of apoptosis exacerbated by the co-exposure. The results showed a synergistic effect of AA and EA, which exacerbated the damage and oxidative stress (OS) in HSC-T6. Meanwhile, the expression of endoplasmic reticulum stress (ERS) proteins, such as GRP78 and CHOP, was increased, the ERS pathway was activated, and Ca2+ in cells was increased, which exacerbated mitochondrial damage, and opened IP3R-Grp75-VDAC1 channel...

Indirect immunofluorescence on HEp-2 cell line (HEp-2-IIF) remains "gold standard" method for the detection of antinuclear antibodies (ANA). ANA is an operative definition, showing the possibility of autoantibodies (Aab) to bind nuclear, and cytoplasmic antigens. One of the major examples is represented by anti-mitochondrial antibodies (AMAs), which target proteins of the inner and outer mitochondrial membranes, located into the cytoplasm. The standard IIF on rat kidney/stomach/liver tissue sections, with the combined use of other commercial assays, may all be used in ordinary lab life to validate the AC-21 pattern on Hep-2 cells...

This study investigated the mechanism of silver nanoparticle (AgNP) cytotoxicity from a mitochondrial perspective. The effect of AgNP on manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, against oxidative stress has not been studied in detail. We demonstrated that AgNP decreased MnSOD mRNA level, protein expression, and activity in human Chang liver cells in a time-dependent manner. AgNP induced the production of mitochondrial reactive oxygen species (mtROS), particularly superoxide anion...

BACKGROUND: Vitamin C (ascorbate) is a water-soluble antioxidant and an important cofactor for various biosynthetic and regulatory enzymes. Mice can synthesize vitamin C thanks to the key enzyme gulonolactone oxidase (Gulo) unlike humans. In the current investigation, we used Gulo-/- mice, which cannot synthesize their own ascorbate to determine the impact of this vitamin on both the transcriptomics and proteomics profiles in the whole liver. The study included Gulo-/- mouse groups treated with either sub-optimal or optimal ascorbate concentrations in drinking water...

Organophosphates, a widely used group of pesticides, can cause severe toxicity in human beings and other non-target organisms. Liver, being the primary site for xenobiotic metabolism, is extremely vulnerable to xenobiotic-induced toxicity. Considering the numerous vital functions performed by the liver, including xenobiotic detoxification, protecting this organ from the ubiquitous pesticides in our food and environment is essential for maintaining homeostasis. In this study, we have investigated the impact of the organophosphate pesticide, Chlorpyrifos (CPF), on zebrafish liver at a concentration (300μg/L) which is environmentally realistic...

Copper is an essential trace element, and excessive exposure could result in hepatoxicity, however, the underlying molecular mechanisms remain incompletely understood. The present study is aimed to investigate the molecular mechanisms of copper sulfate (CuSO4 ) exposure-induced hepatoxicity both in vivo and in vitro. In vitro, HepG2 and L02 cells were exposed to various doses of CuSO4 for 24 hours. Cell viability, ROS production, oxidative stress biomarkers, mitochondrial functions, ultrastructure, intracellular calcium (Ca2+) concentration, and the expression of proteins related to mitochondrial apoptosis and endoplasmic reticulum (ER) stress were assessed...

Monocytes (Mos) are crucial in the evolution of metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH), and immunometabolism studies have recently suggested targeting leukocyte bioenergetics in inflammatory diseases. Here, we reveal a peculiar bioenergetic phenotype in circulating Mos of patients with MASH, characterized by high levels of glycolysis and mitochondrial (mt) respiration. The enhancement of mt respiratory chain activity, especially complex II (succinate dehydrogenase [SDH]), is unbalanced toward the production of reactive oxygen species (ROS) and is sustained at the transcriptional level with the involvement of the AMPK-mTOR-PGC-1α axis...

Alterations in cellular signaling, chronic inflammation, and tissue remodeling contribute to hepatocellular carcinoma (HCC) development. The release of damage-associated molecular patterns (DAMPs) upon tissue injury and the ensuing sterile inflammation have also been attributed a role in HCC pathogenesis. Cargoes of extracellular vesicles (EVs) and/or EVs themselves have been listed among circulating DAMPs but only partially investigated in HCC. Mitochondria-derived vesicles (MDVs), a subpopulation of EVs, are another missing link in the comprehension of the molecular mechanisms underlying the onset and progression of HCC biology...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of liver disease and poses significant health risks to patients who progress to metabolic dysfunction-associated steatohepatitis (MASH). Fatty acid (FA) overload alters endoplasmic reticulum (ER) calcium stores and induces mitochondrial oxidative stress in hepatocytes, leading to hepatocellular inflammation and apoptosis. Obese mice have impaired liver sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) function, which normally maintains intracellular calcium homeostasis by transporting Ca2+ ions from the cytoplasm to ER...