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Obesity is an important risk factor for the development of pregnancy complications. We investigated the effects of pregestational overweight and obesity on maternal lipidome during pregnancy and on newborns' characteristics. The study encompassed 131 pregnant women, 99 with pre-pregnancy body mass index (BMI) < 25 kg/m2 and 32 with BMI ≥ 25 kg/m2. Maternal lipid status parameters, plasma markers of cholesterol synthesis and absorption and sphingolipids were determined in each trimester. Data on neonatal height, weight and APGAR scores were assessed. The results showed a higher prevalence (p < 0.05) of pregnancy and childbirth complications among the participants with elevated pregestational BMI. Levels of total cholesterol, HDL-cholesterol (p < 0.05) and LDL-cholesterol (p < 0.01) were significantly lower, and concentrations of triglycerides were higher (p < 0.05) in women with increased pre-gestational BMI. Lower concentrations of the cholesterol synthesis marker, desmosterol, in the 2nd trimester (p < 0.01) and the cholesterol absorption marker, campesterol, in each trimester (p < 0.01, p < 0.05, p < 0.01, respectively) were also found in this group. Markers of maternal cholesterol synthesis were in positive correlation with neonatal APGAR scores in the group of mothers with healthy pre-pregnancy weight but in negative correlation in the overweight/obese group. Our results indicate that gestational adaptations of maternal lipidome depend on her pregestational nutritional status and that such changes may affect neonatal outcomes.
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Índice de Massa Corporal , Lipidômica , Obesidade , Sobrepeso , Complicações na Gravidez , Humanos , Feminino , Gravidez , Recém-Nascido , Adulto , Obesidade/metabolismo , Obesidade/sangue , Lipidômica/métodos , Sobrepeso/metabolismo , Complicações na Gravidez/metabolismo , Complicações na Gravidez/sangue , Lipídeos/sangue , Colesterol/sangueRESUMO
A specific feature of dyslipidemia in pregnancy is increased high-density lipoprotein (HDL) cholesterol concentration, which is probably associated with maternal endothelium protection. However, preeclampsia is most often associated with low HDL cholesterol, and the mechanisms behind this change are scarcely explored. We aimed to investigate changes in HDL metabolism in risky pregnancies and those complicated by late-onset preeclampsia. We analyze cholesterol synthesis (cholesterol precursors: desmosterol, 7-dehydrocholesterol, and lathosterol) and absorption markers (phytosterols: campesterol and ß-sitosterol) within HDL particles (NCSHDL), the activities of principal modulators of HDL cholesterol's content, and major HDL functional proteins levels in mid and late pregnancy. On the basis of the pregnancy outcome, participants were classified into the risk group (RG) (70 women) and the preeclampsia group (PG) (20 women). HDL cholesterol was lower in PG in the second trimester compared to RG (p < 0.05) and followed by lower levels of cholesterol absorption markers (p < 0.001 for campesterolHDL and p < 0.05 for ß-sitosterolHDL). Lowering of HDL cholesterol between trimesters in RG (p < 0.05) was accompanied by a decrease in HDL phytosterol content (p < 0.001), apolipoprotein A-I (apoA-I) concentration (p < 0.05), and paraoxonase 1 (PON1) (p < 0.001), lecithin-cholesterol acyltransferase (LCAT) (p < 0.05), and cholesterol ester transfer protein (CETP) activities (p < 0.05). These longitudinal changes were absent in PG. Development of late-onset preeclampsia is preceded by the appearance of lower HDL cholesterol and NCSHDL in the second trimester. We propose that reduced capacity for intestinal HDL synthesis, decreased LCAT activity, and impaired capacity for HDL-mediated cholesterol efflux could be the contributing mechanisms resulting in lower HDL cholesterol.
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Pré-Eclâmpsia , Humanos , Feminino , Gravidez , HDL-Colesterol/metabolismo , Colesterol/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Transporte Biológico , Apolipoproteína A-I/metabolismo , Arildialquilfosfatase/metabolismoRESUMO
Background and Objectives: Diabetic foot (DF) development is driven by complex interactions of hyperglycemia, inflammation, and oxidative stress (OS). We aimed to investigate OS and inflammatory biomarkers in patients with DF and their potential to improve early diagnosis and management of DF. Materials and Methods: The prooxidant−antioxidant balance (PAB), superoxide dismutase (SOD), total oxidative status (TOS), total sulfhydryl groups (SHG), routine biochemical parameters, and complete blood count were determined in 42 patients with type-2 DM, of which 23 patients had DF, while 19 patients were without DF complications. The neutrophils-to-lymphocyte ratio (NLR) was evaluated as a biomarker of inflammation. Results: Patients with DF had significantly higher (p < 0.05) PAB levels (170 ± 33.9 U/L) compared to those without DF complications (142 ± 31.3 U/L). In addition, patients with DF had significantly reduced SOD activities (p < 0.01). NLR values were significantly higher in the DF group (median: 2.8; interquartile range: 2.0−4.3) than in the group without DF (median: 1.4; interquartile range: 1.4−2.1; p < 0.01). A positive correlation was found between the PAB and NLR index (r = 0.449; p < 0.05). The diagnostic accuracy of both PAB (AUC = 0.741; p < 0.01) and NLR (AUC = 0.760; p < 0.01) was estimated as acceptable. Conclusions: In conclusion, the development of DF is associated with enhanced OS and inflammation processes. PAB and NLR could be useful non-invasive biomarkers of DF development.
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Diabetes Mellitus , Pé Diabético , Humanos , Estresse Oxidativo , Antioxidantes/metabolismo , Biomarcadores , Espécies Reativas de Oxigênio , Inflamação/complicações , Neutrófilos/metabolismo , Superóxido DismutaseRESUMO
Resistin might be involved with general inflammation and endothelial dysfunction observed in preeclampsia. We aimed to investigate longitudinal changes in resistin concentrations during high-risk pregnancies and evaluate their significance in preeclampsia development. Ninety-one patients were recruited at 11-14 weeks of gestation. They were followed towards the end of each trimester and before their deliveries. Of the 91 pregnant women, 21 developed preeclampsia, while 70 women did not develop preeclampsia despite being at risk. Compared to the 1st trimester, resistin concentration significantly increased during the 2nd trimester (p<.001). When women were divided into groups of those who developed preeclampsia and those who did not develop preeclampsia, we noticed a significant difference only in women who did not develop preeclampsia (p<.001). Moreover, resistin concentration in the 1st trimester was statistically higher in women who developed preeclampsia when compared to those who did not develop preeclampsia (p<.001). The analysis of the Receiver Operating Characteristics (ROC) curves indicated that inclusion of triglycerides (TG), high-sensitivity C-reactive protein (CRP), and resistin (AUC = 0.870) improved diagnostic accuracy of the basic model including demographic and clinical parameters (AUC = 0.777) for preeclampsia prediction (p<.05). If the concentration of resistin is high in the 1st trimester, such pregnancy at risk is likely to develop preeclampsia as a complication, indicating that resistin concentration in the 1st trimester might contribute to existing predictive and prognostic models for preeclampsia. A multi-marker model, possibly including also resistin and other clinical, metabolic, and inflammatory parameters, seems to be the best approach in late-onset preeclampsia prediction.
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Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Resistina/sangue , Adulto , Feminino , Humanos , Modelos Logísticos , Gravidez , Curva ROC , Fatores de RiscoRESUMO
Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality worldwide. Defects in trophoblast invasion, differentiation of extravillous trophoblasts and spiral artery remodeling are key factors in PE development. Currently there are no predictive biomarkers clinically available for PE. Recent technological advancements empowered transcriptome exploration and led to the discovery of numerous non-coding RNA species of which microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the most investigated. They are implicated in the regulation of numerous cellular functions, and as such are being extensively explored as potential biomarkers for various diseases. Altered expression of numerous lncRNAs and miRNAs in placenta has been related to pathophysiological processes that occur in preeclampsia. In the following text we offer summary of the latest knowledge of the molecular mechanism by which lnRNAs and miRNAs (focusing on the chromosome 19 miRNA cluster (C19MC)) contribute to pathophysiology of PE development and their potential utility as biomarkers of PE, with special focus on sample selection and techniques for the quantification of lncRNAs and miRNAs in maternal circulation.
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MicroRNA Circulante/sangue , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , RNA Longo não Codificante/sangue , Biomarcadores/sangue , Diferenciação Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 19/metabolismo , MicroRNA Circulante/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Gravidez , RNA Longo não Codificante/genética , Transcriptoma , Trofoblastos/metabolismoRESUMO
Background: The pre-analytical (PA) phase is the most vulnerable phase of the laboratory testing procedure, with critical procedures-collection, handling, sample transport, and time and temperature of sample storage. This study aimed to examine the stability of basic biochemical parameters depending on the samples' storage conditions and the number of freeze-thaw cycles (FTCs). In parallel, the presence of sample bacterial contamination during routine laboratory work was examined. Methods: Two plasma pools (ethylenediaminetetraacetic acid (EDTA), and sodium-fluoride/potassium oxalate plasma (NaF)) were stored at +4 ËC/-20 ËC. Total chole - sterol (TC), glucose, triglycerides (TG), urea, and albumin concentrations were measured using BioSystems reagents (cholesterol oxidase/peroxidase, glucose oxidase/per - oxidase, glycerol phosphate oxidase/peroxidase, urease/ salicylate, and bromcresol green method, respectively) on Ilab 300+. Sample bacterial contamination was determined by 16S rRNA sequence analysis. The expe - riment encompassed a 5 day-period: Day 1-fresh sample, Day 2-1st FTC, Day 3-2nd FTC, Day 4-3rd FTC, Day 5-4th FTC. The appearance of bacteria in two consecutive samples was the experiment's endpoint.
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Background: The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aimed to investigate the relationship between hypertension, oxidative stress, and inflammation in pediatric patients during the acute phase of the disease. Methods: The study included 33 children, aged 2 to 9 years, with nephrotic syndrome. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (-SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflam - matory parameters such as pentraxin 3 (PTX3), leptin, program med cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA). Results: Patients with nephrotic syndrome and hypertension had significantly higher levels of advanced oxidation protein products and total antioxidant status (p=0.029 and p=0.003, respectively). During the acute phase of the disease, lower activity of sulfhydryl groups and paraoxonase 1 was observed compared to remission (p<0.001, for both). Pentraxin 3 levels were higher, while leptin levels were lower during the acute phase (p<0.001, for both). Pentraxin 3 correlated with advanced oxidation protein products and total antioxidant status during the acute phase but not in remission (rs=0.42, p=0.027 and rs=0.43, p=0.025, respectively). A negative correlation between Advanced oxidation protein products and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028). Conclusions: Results of this study show that hypertension influences oxidative stress markers, and decreased antioxidant capacity may contribute to nephrotic syndrome development. Pentraxin 3 appears as a potential disease activity marker, indicating a dynamic connection between inflammation and oxidative stress. Leptin may also play a role in oxidative stress in nephrotic syndrome.
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Colorectal cancer (CRC) is a highly prevalent malignancy. Previous studies suggested that cholesterol might play a signficant role in malignant transformation and proliferation. Non-cholesterol sterols (NCS), which are transported by serum lipoproteins alongside cholesterol, are regarded as cholesterol synthesis and absorption markers. Quantification of NCS in serum and HDL fraction (NCSHDL), could provide a better insight into the cholesterol metabolism. The aim of this study was to examine the status of cholesterol synthesis and cholesterol absorption markers in serum and HDL fraction and explore their interrelation in CRC patients. Current study was designed as observational, case-control study. The study included 73 CRC patients and 95 healthy subjects. NCS and NCSHDL concentrations were determined by HPLC-MS/MS. Based on NCS and NCSHDL concentrations, different cholesterol homeostasis indices were calculated. Patients had significantly lower NCS (P<0.001) and NCSHDL concentrations (P<0.001 for desmosterolHDL; P<0.05 for lathosterolHDL, P=0.001 for campesterolHDL, P<0.001 for ß-sitosterolHDL). NCSHDL/NCS (P<0.005 for desmosterolHDL/desmosterol; P<0.05 for lathosterolHDL/lathosterol; P<0.001 for both ß-sitosterolHDL/ß-sitosterol and campesterolHDL/campesterol) and synthesis to absorption ratio (CSI/CAI) (P<0.005) were increased in CRC patients. Additionally, low serum concentrations of desmosterol (P<0.001; OR=0.329; 95%CI (0.199-0.542)) and campesterol (P<0.001; OR=0.540; 95%CI (0.424-0.687)) were independent predictors of CRC presence. Our data suggest that cholesterol homeostasis in CRC is shifted towards increased synthesis. Relative abundance of NCS in HDL particles is increased, suggesting the possible overproduction of cholesterol precursors in peripheral tissues.
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Biomarcadores Tumorais/sangue , Colesterol/sangue , Neoplasias Colorretais/sangue , Esteróis/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1−T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, ß-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of ß-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum ß-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn's size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM.
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Adiponectin (ADIPOQ) as both a regulator of metabolic homeostasis and a protein involved in immune response might be of particular interest to contemporary laboratory medicine, especially in terms of minimally invasive diagnostics. The diverse roles of ADIPOQ with regard to the immune and metabolic aspects of colorectal carcinogenesis have been proposed. However, the expression of its receptors ADIPOR1 and ADIPOR2 is scarcely explored in peripheral blood mononuclear cells (PBMCs). Moreover, ADIPORs' relationships with the immune response mediator TNF-α have not been previously investigated in the PBMCs of CRC patients. This study used both in silico and observational case-control analyses with the aim of exploring the association of ADIPOR gene expression and ADIPOQ single nucleotide polymorphisms (SNPs) with the inflammatory marker TNF-α and lipid status parameters in patients with CRC. Publicly available transcriptomic datasets (GSE47756, GSE44076) obtained from analyses of monocytes and CRC tissue samples were employed for the in silico evaluation of ADIPORs' specific genetic traits. GSE47756 and GSE44076 datasets were processed with GSEA software to provide a genetic fingertip of different signaling pathways associated with ADIPORs' mRNA levels. The case-control aspect of the study included the PBMC samples of 73 patients diagnosed with CRC and 80 healthy volunteers. The PCR method was carried out for the PBMC gene expression analysis (ADIPOR1, ADIPOR2, TNF-α mRNA levels) and for the subjects' genotyping (ADIPOQ rs266729, ADIPOR1 rs7539542). GSEA showed significant associations of ADIPOR mRNA expression with gene sets related to metabolic and immune homeostasis in both datasets. The case-control study revealed the association of ADIPOR1 rs7539542 with reduced lipid status parameters in CRC. In addition, PBMC ADIPOR1 mRNA levels decreased in CRC (p < 0.001), whereas ADIPOR2 mRNA did not differ between the groups (p = 0.442). A reduction in PBMC TNF-α mRNA levels was noted in CRC (p < 0.05). Our results indicate that ADIPOR1 and ADIPOR2 play a significant role in the alteration of both metabolic and immune homeostasis during the progression of CRC. For the first time, ADIPOR1 is shown to be a specific receptor for mediating ADIPOQ's effects in the PBMCs of CRC patients.
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Neoplasias Colorretais , Receptores de Adiponectina , Humanos , Adiponectina , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Homeostase , Leucócitos Mononucleares/metabolismo , Lipídeos , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genéticaRESUMO
Introduction: The aim of this study was to investigate lipoprotein particle distributions and the likelihood of achieving cholesterol homeostasis in the remission phase of nephrotic syndrome (NS) in paediatric patients. We hypothesized that lipoprotein particle distributions moved toward less atherogenic profile and that cholesterol homeostasis was achieved. Materials and methods: Thirty-three children, 2 to 9 years old with NS were recruited. Blood sampling took place both in the acute phase and during remission. Serum low-density lipoprotein particles (LDL) and high-density lipoprotein particles (HDL) were separated using non-denaturing polyacrylamide gradient gel (3-31%) electrophoresis. Serum non-cholesterols sterols (NCSs), desmosterol, lathosterol, 7-dehydrocholesterol (7-DHC), campesterol and ß-sitosterol were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results: All patients had desirable serum HDL cholesterol concentrations during remission. The dominant lipoprotein diameters and LDL subclass distribution did not change significantly during follow-up. In contrast, HDL lipoprotein particle distribution shifted towards larger particles. The absolute concentration of desmosterol was significantly lower during remission (P = 0.023). ß-sitosterol concentration markedly increased during remission (P = 0.005). Desmosterol/ß-sitosterol (P < 0.001) and 7-DHC/ß-sitosterol (P = 0.005) ratios significantly declined during disease remission. Conclusions: Favourable changes in the serum lipid profiles, HDL particle subclass distribution and cholesterol metabolism in paediatric patients with NS during remission took place. For the first time, we found that cholesterol homeostasis changed in favour of increased cholesterol absorption during disease remission. Nevertheless, complete cholesterol homeostasis was not achieved during disease remission.
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Desmosterol , Síndrome Nefrótica , Criança , Pré-Escolar , HDL-Colesterol , Humanos , Lipoproteínas , Espectrometria de Massas em TandemRESUMO
Exposure to lead (Pb) is still rising concern worldwide, having in mind that even low-dose exposure can induce various harmful effects. Thus, in-depth knowledge of the targets of Pb toxicity and corresponding mechanisms is essential. In the presented study, the six groups (male Wistar rats, n = 6) received 0.1; 0.5; 1; 3; 7; 15 mg Pb/kg body weight/day for 28 days, each day by oral gavage, while the control group received distilled water only. All animals were sacrificed 24 h after the treatment, and blood was collected for the analysis of hematological, biochemical, oxidative status and essential elements levels. An external and internal dose-response relationship was performed using PROASTweb 70.1 software. The results showed that low doses of Pb affect hematological parameters and lipid profile after 28 days. The possible mechanisms at examined Pb dose levels were a decrease in SOD, O2â¢- and Cu and an increase in Zn levels. The dose-dependent nature of changes in cholesterol, HDL cholesterol, O2.-, SOD, AOPP in serum and hemoglobin, Fe, Zn, Cu in blood were obtained in this study. The most sensitive parameters that were alerted are Cu blood levels (BMDL5: 1.4 ng/kg b.w./day) and SOD activity (BMDL5: 0.5 µg/kg b.w./day). The presented results provide information that may be useful in further assessing the health risks of low-level Pb exposure.
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Benchmarking , Chumbo , Animais , Chumbo/toxicidade , Masculino , Oxirredução , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
INTRODUCTION: The link between preeclampsia and dyslipidemia has been established. Even though lipid profile parameters have been intensively investigated in the pathology of preeclampsia, their accurate molecular mechanisms of action have not been fully decoded. OBJECTIVES: We aimed to identify the specifics of cholesterol metabolism in women affected by late-onset preeclampsia and single out potential biomarkers associated with late-onset syndrome. PATIENTS AND METHODS: A total of 90 pregnant women with a priori risk for preeclampsia were monitored at 4 time points during gestation and, based on the outcome of pregnancy, they were classified into the high-risk group (70 women) and the preeclampsia group (20 women). Cholesterol metabolic profiling was done using liquid chromatography-tandem mass spectrometry. RESULTS: The only significant change in the preeclampsia group was an increase in the lathosterol level (P = 0.001). The first-trimester lathosterol level was higher in the preeclampsia group compared with the high-risk group (P = 0.02). Further, in the preeclampsia group, positive correlations were found between desmosterol and ß-sitosterol (ρ = 0.474; P = 0.03) in the third trimester, desmosterol and campesterol changes between the second and the first (ρ = 0.546; P = 0.02), and the third and first trimesters (ρ = 0.754; P <â 0.001), as well as between the desmosterol and ß-sitosterol differences between the third and first trimesters (ρ = 0.568; P = 0.01). No similar correlations were found in the high-risk group. CONCLUSIONS: Late-onset preeclampsia could be associated with an altered lipid profile. By studying the quantitative metabolic signatures of cholesterol, we might assume that both cholesterol synthesis and absorption are increased, that is, there is an imbalance in the cholesterol homeostasis regulation in women affected by the disease.