Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many ...pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.
Background: Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy. One of the neuropsychological tests that detects MHE is the Stroop test (via EncephalApp). The aim was ...to evaluate the Stroop test for the screening and diagnosis of MHE. Methods: This prospective case–control study was performed at the Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, and included patients with cirrhosis and MHE and healthy controls. In all patients, the presence of MHE was confirmed using the animal naming test. The Stroop test was performed on each participant, and the results were compared between the two groups. The test has two components, the “OFF” and “ON” states. Results: A total of 111 participants were included. The median OFF time did not differ between the two groups, 106.3 and 91.4, p > 0.05. However, in patients with MHE, the median values of ON time and total time were significantly higher, with 122.3 vs. 105.3 and 228.0 vs. 195.6, respectively, p < 0.05. Statistical significance between patients and controls in examined parameters was detected in younger participants and the group with higher educational levels. Conclusions: The Stroop test displayed limited sensitivity in Serbian patients. Age and education affect time measurements and test performance.
The coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), includes a clinical spectrum of diseases from mild to severe progressive ...pneumonia, which has affected and still affects the human population worldwide. Most commonly, it is presented by respiratory symptoms, but studies have shown that about 50% of patients with SARS-CoV-2 infection have at least one gastrointestinal symptom (GI), predominantly nausea, diarrhea, vomiting, or loss of appetite. In addition, abnormal liver functional tests are commonly present in the SARS-CoV-2 virus. The aim of our study was to examine the GI and hepatic manifestations of COVID-19 in patients hospitalized due to COVID-19 pneumonia in "COVID hospital Batajnica", University Clinical Center of Serbia in Belgrade. The study included 498 consecutive patients, and the data was obtained from the patient's electronic medical history. GI symptoms included nausea, vomiting, diarrhea, and anorexia. Collected laboratory values included baseline and peak values of blood count, inflammatory parameters, liver function tests, renal function tests, and cardiac enzyme tests. The results have shown that GI symptoms occurred in 26% of cases at diagnosis, which indicates the great susceptibility of the GI system to SARS-CoV-2. There was a high risk of liver injury in patients with COVID-19 pneumonia (>60%). The level of AST is more often increased compared to ALT, which is different from other virus-induced liver lesions and may be a useful indicator of SARS-CoV-2 infection. Further research should focus on the causes of liver damage in SARS-CoV-2 virus and the impact on treatment and outcome of COVID-19 disease.
Although previous studies indicated that chronic alcohol abuse (CAA) and alcoholic liver cirrhosis (ALC) are associated with increased bone fragility, understanding bone fragility determinants is ...still modest in these individuals. We used a comprehensive individualized clinical fracture risk assessment approach (vertebral osteodensitometry, femoral osteodensitometry and geometry, and serum bone turnover biomarkers) to compare adult male patients with ALC who have not previously had femoral or vertebral fractures (
= 39), patients with CAA (without liver cirrhosis,
= 78) who have not previously had femoral or vertebral fractures and healthy age- and sex-matched controls (
= 43). Our data suggested that intertrochanteric bone mineral density was significantly lower in ALC and CAA patients than in controls. Also, the trabecular bone score was considerably lower in ALC patients compared with CAA and control individuals. The most significant inter-group differences in femoral geometry were noted on the femoral shaft. Patients with ALC and CAA have a higher 10-year risk of major osteoporotic fractures compared to the controls. Analysis of bone turnover biomarkers showed increased osteoprotegerin and beta-C-terminal telopeptide serum concentrations and decreased insulin growth factor-1 concentrations in patients with ALC compared to CAA and control groups. Our data revealed that bone alterations are present in patients with ALC and CAA even if they did not sustain a nontraumatic bone fracture, but it is also indicative that current bone-assessing clinical methods are not entirely reliable. Thus, future studies should focus on developing a reliable integrative clinical tool that can be used to accurately predict and prevent bone fracture occurrences in patients with ALC and CAA.
Metabolic dysfunction-associated steatotic liver disease (MASLD) was previously known as nonalcoholic fatty liver disease (NAFLD). The main characteristic of the disease is the process of long-term ...liver inflammation, which leads to hepatocyte damage followed by liver fibrosis and eventually cirrhosis. Additionally, these patients are at a greater risk for developing cardiovascular diseases (CVD). They have several pathophysiological mechanisms in common, primarily lipid metabolism disorders and lipotoxicity. Lipotoxicity is a factor that leads to the occurrence of heart disease and the occurrence and progression of atherosclerosis. Atherosclerosis, as a multifactorial disease, is one of the predominant risk factors for the development of ischemic heart disease. Therefore, CVD are one of the most significant carriers of mortality in patients with metabolic syndrome. So far, no pharmacotherapy has been established for the treatment of MASLD, but patients are advised to reduce their body weight and change their lifestyle. In recent years, several trials of different drugs, whose basic therapeutic indications include other diseases, have been conducted. Because it has been concluded that they can have beneficial effects in the treatment of these conditions as well, in this paper, the most significant results of these studies will be presented.
Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the ...gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA's effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice.
Structural modifications of 1,3-pdta ligand (1,3-propanediamine-N,N,N’,N’-tetraacetate) by introducing two geminal methyl substituents on the middle carbon atom of diamine chain and nature of counter ...cation have significant influence on the nuclearity of manganese(II) and cadmium(II) complexes.
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•Manganese(II) and cadmium(II) complexes with 2,2-diMe-1,3-pdta were synthesized.•Polynuclear structure of complexes was confirmed by X-ray analysis.•Counter cation had influence on the complex nuclearity.•Manganese(II) and cadmium(II) complexes showed selective anti-Candida activity.
New polynuclear manganese(II) and cadmium(II) complexes with 2,2-dimethyl-1,3-propanediamine-N,N,N’,N’-tetraacetato ligand (2,2-diMe-1,3-pdta), {BaM(2,2-diMe-1,3-pdta).3H2O}n (M = Mn (1) or Cd (2)) were synthesized and characterized by IR spectroscopy and single-crystal X-ray diffraction analysis. In addition, complex 2 was characterized by solution 1H and 13C NMR spectroscopy. Crystallographic analysis showed that 2,2-diMe-1,3-pdta ligand is hexadentately coordinated to each M(II) ion through the two nitrogen and four carboxylate oxygen atoms, whereas the one of these oxygen atoms is also involved in coordination to the second M(II) ion of the dinuclear M2(2,2-diMe-1,3-pdta)24− unit in polymeric structures. Moreover, three of four carboxylic groups of 2,2-diMe-1,3-pdta ligand are additionally bonded to four Ba(II) ions, in three distinctive bridging coordination modes. Each Ba(II) ion is surrounded by ten oxygen atoms, seven belonging to carboxylate groups of 2,2-diMe-1,3-pdta, and three belonging to water molecules. The coordination environment around Mn(II) and Cd(II) ions could be assigned as a face capped octahedron, while coordination polyhedron around Ba(II) ion in these two complexes was described as a distorted sphenocorona. The antimicrobial potential of complexes 1 and 2 and corresponding metal salts used for their synthesis was evaluated against different bacterial and Candida spp. Both complexes showed selective antifungal activity against the tested Candida spp. compared to the bacterial strains, with the minimal inhibitory concentration (MIC) values in the range 3.12 – 12.50 µM. Moreover, complex 1 caused the slightly decrease of hyphae length, while no significant influence on hyphal length of complex 2 was observed. With aim to assess the therapeutic profile of the complexes, their cytotoxicity was evaluated against the normal human lung fibroblast cell line (MRC-5).
Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we ...studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes, and whether putative changes in hepatic thyroid hormone availability may be associated with this effect. Serum and hepatic total cholesterol (TChol), bile acid and cholesterol precursors, as well as serum TSH and T4 concentrations, hepatic deiodinase (Dio) 1 enzyme activity and MCT8 protein expression were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered G or D (35mg/kg) to MA rats were evaluated versus vehicle-treated MA females. MA IC females were characterized by: higher (p<0.05) serum TChol, lower (p<0.05) hepatic TChol and its biosynthetic precursors, lower (p<0.05) hepatic 7α-hydroxycholesterol but elevated (p<0.05) 27- and 24-hydroxycholesterol in comparison to YA IC. Both isoflavone treatments decreased (p<0.05) hepatic 27-hydroxycholesterol, G being more effective than D, without affecting any other parameter of Chol metabolism. Only G elevated hepatic Dio1 activity (p<0.05). In conclusion, age-related hypercholesteremia was associated with lower hepatic Chol synthesis and shift from main neutral (lower 7α-hydroxycholesterol) to alternative acidic pathway (higher 27-hydroxycholesterol) of Chol degradation to bile acid. Both isoflavones lowered hepatic 27-hydroxycholesterol, which may be considered beneficial. Only G treatment increased hepatic Dio1 activity, thus indicating local increase in thyroid hormones, obviously insufficient to induce prominent cholesterol-lowering effect.
•Age-related hypercholesteremia in middle-aged acyclic female rats (13-month-old) is associated with:(i) lower hepatic cholesterol biosynthesis and(ii) shift from neutral to acydic pathway of cholesterol degradation to bile acid in the liver.(iii) unchanged TSH and total T4 in serum, as well as Dio1 enzyme activity and MCT8 protein expression in the liver•Soy isoflavones reversed only hepatic 27-hydroxycholesterol to the level of young adults.•Only genistein elevated hepatic Dio1 activity, thus indicating local increase in thyroid hormones.
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