Mass spectrometry-based untargeted metabolomics study of non-obese individuals with non-alcoholic fatty liver disease.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by the accumulation of excessive fat in the liver, which can lead to fibrosis and has an increasing prevalence. NAFLD requires non-invasive diagnostic biomarkers. While typically observed in overweight individuals, it can also occur in non-obese/non-overweight individuals. Comparative studies on non-obese NAFLD patients are scarce. This study aimed to conduct a using liquid chromatography-high resolution mass spectrometry (LC-MS/MS)-based metabolic profiling of non-obese NAFLD patients and healthy controls. MATERIALS AND METHODS: The patient group consisted of 27 individuals with NAFLD, while the healthy control group included 39 individuals. Both groups were between 18 and 40 years old, had a BMI of less than 25 and had alcohol consumption less than 20 g/week for men and 10 g/week for women. Serum samples were collected and analyzed using LC-MS/MS. The data were analyzed using the TidyMass and MetaboAnalyst. RESULTS: The LC-MS/MS analyses detected significant changes in D-amino acid metabolism, vitamin B6 metabolism, apoptosis, mTOR signaling pathway, lysine degradation, and phenylalanine metabolism pathways in non-obese NAFLD patients. Significant changes were also observed in the metabolites D-pantothenic acid, hypoxanthine, citric acid, citramalic acid, L-phenylalanine, glutamine, and histamine-trifluoromethyl-toluidide, ß-hydroxymyristic acid, DL-Lactic acid, and 3-methyl-2-oxopentanoic. Overall, the study provides valuable insights into the metabolic changes associated with non-obese NAFLD patients and can contribute to the development of non-invasive diagnostic biomarkers for NAFLD. CONCLUSIONS: This study sheds light on the metabolic changes in non-obese NAFLD patients. Further research is needed to better understand the metabolic changes associated with NAFLD and to develop effective treatment options.

Investigation of serum enzyme activities and oxidative stress markers in preeclampsia: a multiparameter analysis.

OBJECTIVES: Preeclampsia, a high cause of fetomaternal morbidity-mortality, remains a significant burden affecting 8% of all pregnancies. Environmental conditions induce disease development leading to endothelial dysfunction in genetically predisposed women. Our aim is to discuss oxidative stress as a well-established contributing factor to disease progression with being the first study to show new evidence about serum dehydrogenase enzyme levels (isocitrate, malate, glutamate dehydrogenase) with oxidative markers (myeloperoxidase, total antioxidant-oxidant status, oxidative stress index). MATERIAL AND METHODS: Serum parameters were analyzed with photometric method (Abbott ARCHITECT c8000). RESULTS: The enzyme levels and oxidative markers were significantly higher in patients, supporting the redox imbalance in preeclampsia. According to ROC analysis, malate dehydrogenase showed an outstanding diagnostic ability with the highest AUC value of 0.9 and the cut-off value of 51.2 IU/L. Discriminant analysis including malate, isocitrate and glutamate dehydrogenase had predicted preeclampsia with an overall 87.9% accuracy. CONCLUSIONS: Considering the above results, we propose that the enzyme levels increase with oxidative stress functioning as antioxidant defense factors. The unique finding of the study is that the serum levels of malate, isocitrate and glutamate dehydrogenase can be used both separately and combined in the early prediction of preeclampsia. As a novel approach, we also offer combining serum isocitrate and glutamate dehydrogenase levels with ALT, AST tests to state liver functions more reliably in patients. Still, larger sample-sized studies investigating enzyme expression levels are required to confirm the recent findings and to reveal underlying mechanisms.

ST2 and galectin-3 as novel biomarkers for the prediction of future cardiovascular disease risk in preeclampsia.

The aim of this study was to investigate known cardiovascular disease (CVD) risk biomarkers galectin-3 (Gal-3) and human stromelysin-2 (ST2) levels in preeclampsia (PE) and normotensive pregnancies. A case-control study was conducted in a teaching and research hospital. We performed data analysis involving 45 pregnant women with PE and gestational week (GW) matched 35 normotensive pregnant women. The Gal-3 and ST2 levels were determined by using ELISA kit. Gal-3 values did not differ statistically between PE and control groups (535.1 ng/mL vs. 615.2 ng/mL) (p> .05). ST2 value in the PE group was statistically significantly lower than the control group (33.3 pg/mL vs. PE, 54.5 pg/mL, p ˂ .05). >34 GW patients (late-onset PE) had statistically significantly lower Gal-3 values than the ≤34 GW patients (early-onset PE) (507.1 ng/mL vs. 769.6 ng/mL, p ˂ .05). Late-onset PE patients had significantly lower ST2 values than early-onset patients (26.4 pg/mL vs. 57.9 pg/mL, p ˂ .05). We assume that low Gal-3 values in early-onset PE show a higher risk of cardiac fibrosis although both early and late-onset PE patients had an increased CVD risk later in life. We found the superiority of ST2 levels to Gal-3 levels in PE pregnancies for CVD risk assessment.Impact StatementWhat is already known about this subject? Preeclampsia (PE) in pregnancy is a known risk factor for future cardiovascular disease (CVD) and is also associated with increased mortality from ischaemic heart disease later in life. Studies that investigate patients with a higher risk for CVD in PE pregnancies are lacking.What do the results of this study add? We found different levels of two novel cardiac markers with PE and normotensive pregnancies, and also with early and late-onset PE pregnancies.What are the implications of these findings for clinical practice and/or further research? Different adaptive responses from patients during PE pregnancies via altered levels of cardiac markers could help clinicians to identify women with a higher risk of CVD.

Quercus pyrenaica Honeydew Honey With High Phenolic Contents Cause DNA Damage, Apoptosis, and Cell Death Through Generation of Reactive Oxygen Species in Gastric Adenocarcinoma Cells.

Many studies have shown that honey with high phenolic contents prevents cancer formation. Furthermore, recent studies have demonstrated that honey can be used for the treatment of cancer as well as cancer prevention. Antineoplastic effects of honey are often associated with their antioxidant phenolic contents. However, very few studies have dealt with the association of phenolic contents of honeys in terms of antiproliferative effects. The aim of this study was, therefore, to elucidate the cytotoxic, genotoxic, apoptotic, and reactive oxygen species (ROS) generating effects of honey samples on the basis of their phenolic and flavonoid contents. Fourteen different honey varieties were collected from various parts of Turkey, and their characteristics regarding total phenols, flavonoids, and antioxidant contents were determined to test their effects on gastric cancer cells (AGS). For convenience, 2 honey varieties were selected, namely, Ida Mountains Quercus pyrenaica honeydew honey (QPHH-IM) having the highest phenolic and antioxidant content and Canakkale multifloral honey (MFH-C) with the lowest phenolic and antioxidant content. Levels of 11 different phenolic compounds in QPHH-IM and MFH-C samples were determined by LC-MS/MS. AGS cells were incubated with different concentrations of QPHH-IM and MFH-C for 24 hours, then the cell viability, DNA damage, apoptosis, and generation of ROS were determined. We found that QPHH-IM had more cytotoxic, genotoxic, and apoptotic effects than that of MFH-C. We think that these effects are probably related to pro-oxidant activities due to the high phenolic contents present. Therefore, further research on high-phenolic honey may contribute to the future development of cancer therapeutics.

Effect of Camellia sinensis, Hypericum perforatum and Urtica dioica on kidney and liver injury induced by carbon tetrachloride in rats.

This study is aimed to investigate the effects of Camellia sinensis (CS), Hypericum perforatum (HP) and Urtica dioica (UD) in kidney and liver injury induced by carbon tetrachloride (CCl4) in rats. Highly toxic CCl4 which is used as a solvent in industry comprises experimental toxicity in rats and is widely used in hepatotoxicity and other tissue injury models. The purpose of this investigation is to monitor blood and various tissues by biochemical and histopathological analysis for preventive effects of CS, HP and UD on oxidative stress induced by administration of CCl4 and to enlighten the probable mechanism. Fifty eight rats were divided into five groups; sham group (Group 1, untreated animals), control CCl4 treated group (Group 2), HP extract-treated group (Group 3), UD extract-treated group (Group 4), CS extract-treated group (Group 5). All rats were anaesthetized at the end of the experiment and the blood was collected from each rat. Afterwards, tissue specimens were obtained. The tissue specimens were immersed in 10% formaldehyde for 24 hours. After routine tissue processing, the liver, kidney and stomach were sectioned in 5µm thickness, stained in hematoxylin and eosin. The histological study was performed by using light microscope. The serum marker enzymes were found to be significantly increased in CCl4-induced liver and kidney damage when compared with the sham group (p<0.05). However, treatment with CS, HP, and UD extracts resulted in decreased activity of serum enzymes. Malondialdehyde (MDA) levels were decreased by 20.51±0.95, 27.98±1.58, and 32.39±3.1 nmol/g wet weight protein in kidney homogenates and 16.65±1.75, 17.22±0.71 and 18.92±71 nmol/g wet weight protein in liver homogenates in CS, HP and UD treated groups, respectively. Our results have shown that additive antioxidants like CS, HP and UD will aid in diminishing these deviations in cases of liver and kidney dysfunction.

Oxidative stress and phenotype frequencies of paraoxonase-1 in teratozoospermia.

Oxidative stress causes infertility in men by affecting especially sperm morphology. The aim of the study was to examine the frequencies of paraoxonase-1 (PON1) phenotypes and the serum PON1, arylesterase, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index, catalase and thiol levels in teratozoospermic infertile men and normospermic fertile men. The study included 184 teratozoospermic infertile men and 72 normospermic fertile men. The double substrate method was employed to determine the phenotype distribution of PON1. The evaluation of sperm morphology was made in accordance with the Kruger's criteria. TAS, catalase and thiol levels were determined to be significantly lower in teratozoospermic infertile men compared to normospermic fertile men. A significant change was not observed in the levels of TOS, PON1 and arylesterase. There was a positive correlation between catalase and thiol levels and sperm morphology. While there were significantly more teratozoospermic men with AA phenotypes compared to normospermic men, there were significantly more persons with AB and BB phenotypes in normospermic men than in teratozoospermic men. As far as we know, such a study was conducted for the first time and suggests that PON1 phenotypic distribution may play a significant role in sterile males because of impaired sperm morphology.