Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous ...complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.
Non-alcoholic fatty liver disease(NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of ...steatosis and fibrosis(laboratory tests and ultrasonography) or cannot be applied as a screening procedure(liver biopsy). Among the non-invasive tests, transient elastography(Fibro Scan?, TE) with controlled attenuation parameter(CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs.
The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary ...hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models.
Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in the world.Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis(NASH).NAFLD is a ...hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components.Up to80%of patients with NAFLD are obese,defined as a body mass index(BMI)>30 kg/m2.However,the distribution of fat tissue plays a greater role in insulin resistance than the BMI.The large amount of visceral adipose tissue(VAT)in morbidly obese(BMI>40 kg/m2)individuals contributes to a high prevalence of NAFLD.Free fatty acids derived from VAT tissue,as well as from dietary sources and de novo lipogenesis,are released to the portal venous system.Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD.In addition,secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways,which are also activated by free fatty acids,and contribute to insulin resistance.Most NAFLD patients are asymptomatic on clinical presentation,even though some may present with fatigue,dyspepsia,dull pain in the liver and hepatosplenomegaly.Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications,anti-obesity medication and bariatric surgery.This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease.The relative contribution of visceral and liver fat to insulin resistance is discussed,and recommendations for clinical evaluation of affected individuals is provided.
Transplantation is a definitive treatment option for patients with end‐stage liver disease, and for some patients with acute liver failure, hepatocellular carcinoma or end‐stage renal disease. ...Long‐term post‐transplantation complications have become an important medical issue, and cardiovascular diseases (CVD) are now the leading cause of mortality in liver or kidney transplant recipients. The increased prevalence of metabolic syndrome (MS) likely plays a role in the high incidence of post‐transplantation CVD. MS and its hepatic manifestation, non‐alcoholic fatty liver disease (NAFLD), are prevalent among the general population and in pre‐ and post‐transplantation settings. MS components are associated with recurrent or de novo NAFLD in transplant recipients, potentially influencing post‐transplantation survival. Moreover, recent data reveal an important association between NAFLD and risk of incident of chronic kidney disease (CKD). Therefore, NAFLD identification could represent an additional clinical feature for improving the stratification of liver and kidney transplant recipients with regards to risks of CVD, CKD and renal allograft dysfunction. All MS components are potentially modifiable; therefore, it is crucial that hepatologists, nephrologists and primary care physicians become more engaged in managing post‐transplantation metabolic complications. The present review discusses the recent clinical evidence regarding the importance of MS and its components after liver and kidney transplantation, as well as the link between MS and NAFLD after liver and kidney transplantation.
In baker's yeast (
), Trk1, a member of the superfamily of K-transporters (SKT), is the main K
uptake system under conditions when its concentration in the environment is low. Structurally, Trk1 is ...made up of four domains, each similar and homologous to a K-channel α subunit. Because most K-channels are proteins containing four channel-building α subunits, Trk1 could be functional as a monomer. However, related SKT proteins TrkH and KtrB were crystallised as dimers, and for Trk1, a tetrameric arrangement has been proposed based on molecular modelling. Here, based on Bimolecular Fluorescence Complementation experiments and single-molecule fluorescence microscopy combined with molecular modelling; we provide evidence that Trk1 can exist in the yeast plasma membrane as a monomer as well as a dimer. The association of monomers to dimers is regulated by the K
concentration.
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•New ligands and corresponding palladium(II) complexes were synthesized.•Characterization was performed by IR, 1H and 13C NMR spectroscopy.•The interactions of new complexes with ...CT-DNA and HSA were investigated.•In vitro cytotoxic activity of these ligands and complexes were evaluated.•Antimicrobial activity of ligands and complexes were investigated.
In this paper, we presented synthesis, characterization, HSA/DNA binding evaluation, in vitro cytotoxic activity and in vitro antimicrobial activity of three new ligands of general formula. R2-S,S-pddmb (L1-L3) and their corresponding palladium(II) complexes of general formula PdCl2(R2-S,S-pddmb) (R = n-propyl, n-butyl, n-pentyl; S,S-pddmb = (S,S)-propylenediamine-N,N'-di-2-(3-methyl)-butanoate). Ligands and complexes were characterized by elemental microanalysis, infrared, 1H and 13C NMR spectroscopy. The interactions of new palladium(II) complexes with human serum albumin (HSA) and calf thymus DNA (CT-DNA) were investigated using UV–Vis absorption and fluorescence spectroscopy. The high values of the binding constant, Kb, and the Stern-Volmer quenching constant, KSV, are the result of good binding of all complexes to HSA and CT-DNA. In vitro cytotoxic activity of these ligands and complexes was evaluated against four tumor cell lines, 4 T1, CT26, MDA-MD-468, HCT116 and mesenchymal stem cells (mMSC). C3 complex showed high cytotoxic activity against MDA-MD-468 cell line. Flow cytometry analysis showed that L3 ligand and the corresponding complex (C3) stimulated apoptosis of tumor cells via inhibition of expression of antiapoptotic Bcl-2 molecule. L3 ligand and C3 complex slowed down cell proliferation and arrested tumor cell in the G0/G1 phase by decreasing Cyclin-D expression and by increasing expression of P21. In vitro antimicrobial activity of ligands and complexes was also investigated. The testing was performed by microdilution method and minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) were determined. The testing was conducted against 12 microorganisms. The tested ligands and palladium(II) complexes showed selective and moderate activity.
Obesity is defined as an excess amount of body fat and represents a significant health problem worldwide. High prevalence of vitamin D (VD) deficiency in obese subjects is a well-documented finding, ...most probably due to volumetric dilution into the greater volumes of fat, serum, liver, and muscle, even though other mechanisms could not completely be excluded, as they may contribute concurrently. Low VD could not yet be excluded as a cause of obesity, due to its still incompletely explored effects through VD receptors found in adipose tissue (AT). VD deficiency in obese people does not seem to have consequences for bone tissue, but may affect other organs, even though studies have shown inconsistent results and VD supplementation has not yet been clearly shown to benefit the dysmetabolic state. Hence, more studies are needed to determine the actual role of VD deficiency in development of those disorders. Thus, targeting lifestyle through healthy diet and exercise should be the first treatment option that will affect both obesity-related dysmetabolic state and vitamin D deficiency, killing two birds with one stone. However, VD supplementation remains a treatment option in individuals with residual VD deficiency after weight loss.
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