scholarly journals Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)

2021 ◽  
Vol 11 (11) ◽  
pp. 1232
Author(s):  
Elena Shakhtshneider ◽  
Dinara Ivanoshchuk ◽  
Olga Timoshchenko ◽  
Pavel Orlov ◽  
Sergey Semaev ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Familial Hypercholesterolemia ◽  
High Throughput Sequencing ◽  
Rare Variants ◽  
Clinical Criteria ◽  
Lipid Metabolism Disorders ◽  
Wide Range ◽  
Clinically Significant ◽  
Lipid Metabolism Genes ◽  
Dependent Probe

The aim of this work was to identify genetic variants potentially involved in familial hypercholesterolemia in 43 genes associated with lipid metabolism disorders. Targeted high-throughput sequencing of lipid metabolism genes was performed (80 subjects with a familial-hypercholesterolemia phenotype). For patients without functionally significant substitutions in the above genes, multiplex ligation-dependent probe amplification was conducted to determine bigger mutations (deletions and/or duplications) in the LDLR promoter and exons. A clinically significant variant in some gene associated with familial hypercholesterolemia was identified in 47.5% of the subjects. Clinically significant variants in the LDLR gene were identified in 19 probands (73.1% of all variants identified in probands); in three probands (11.5%), pathogenic variants were found in the APOB gene; and in four probands (15.4%), rare, clinically significant variants were identified in genes LPL, SREBF1, APOC3, and ABCG5. In 12 (85.7%) of 14 children of the probands, clinically significant variants were detectable in genes associated with familial hypercholesterolemia. The use of clinical criteria, targeted sequencing, and multiplex ligation-dependent probe amplification makes it possible to identify carriers of rare clinically significant variants in a wide range of lipid metabolism genes and to investigate their influence on phenotypic manifestations of familial hypercholesterolemia.

The correlation between lipid metabolism disorders and the prostate cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Justyna Dłubek ◽  
Jacek Rysz ◽  
Zbigniew Jabłonowski ◽  
Anna Gluba-Brzózka ◽  
Beata Franczyk
Keyword(s):  
Prostate Cancer ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Cancer Progression ◽  
De Novo ◽  
Prostate Gland ◽  
Hdl Cholesterol ◽  
Atp Citrate Lyase ◽  
Male Population ◽  
Lipid Metabolism Disorders

: Prostate cancer is second most common cancer affecting male population all over the world. The existence of a correlation between lipid metabolism disorders and cancer of the prostate gland has been widely known for a long time. According to hypotheses, cholesterol may contribute to prostate cancer progression as a result of its participation as a signalling molecule in prostate growth and differentiation via numerous biologic mechanisms including Akt signalling and de novo steroidogenesis. The results of some studies suggest that increased cholesterol levels may be associated with higher risk of more aggressive course of disease. The aforementioned alterations in the synthesis of fatty acids are a unique feature of cancer and, therefore, it constitutes an attractive target for therapeutic intervention in the treatment of prostate cancer. Pharmacological or gene therapy aimed to reduce the activity of enzymes involved in de novo synthesis of fatty acids, FASN, ACLY (ATP citrate lyase) or SCD-1 (stearoyl-CoA desaturase) in particular, may result in cells growth arrest. Nevertheless, not all cancers are unequivocally associated with hypocholesterolaemia. It cannot be ruled out that the relationship between prostate cancer and lipid disorders is not a direct quantitative correlation between carcinogenesis and the amount of the circulating cholesterol. Perhaps the correspondence is more sophisticated and connected to the distribution of cholesterol fractions, or even sub-fractions of e.g. HDL cholesterol.

scholarly journals Dysregulated liver lipid metabolism and innate immunity associated with hepatic steatosis in neonatal BBdp rats and NOD mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
D. Serrano ◽  
J. A. Crookshank ◽  
B. S. Morgan ◽  
R. W. Mueller ◽  
M.-F. Paré ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Liver Lipid ◽  
Nod Mice ◽  
Gene Signature ◽  
Enhanced Expression ◽  
Liver Lipid Metabolism ◽  
Hepatic Innate Immunity ◽  
Lipid Metabolism Genes

Abstract In a previous study we reported that prediabetic rats have a unique gene signature that was apparent even in neonates. Several of the changes we observed, including enhanced expression of pro-inflammatory genes and dysregulated UPR and metabolism genes were first observed in the liver followed by the pancreas. In the present study we investigated further early changes in hepatic innate immunity and metabolism in two models of type 1 diabetes (T1D), the BBdp rat and NOD mouse. There was a striking increase in lipid deposits in liver, particularly in neonatal BBdp rats, with a less striking but significant increase in neonatal NOD mice in association with dysregulated expression of lipid metabolism genes. This was associated with a decreased number of extramedullary hematopoietic clusters as well as CD68+ macrophages in the liver of both models. In addition, PPARɣ and phosphorylated AMPKα protein were decreased in neonatal BBdp rats. BBdp rats displayed decreased expression of antimicrobial genes in neonates and decreased M2 genes at 30 days. This suggests hepatic steatosis could be a common early feature in development of T1D that impacts metabolic homeostasis and tolerogenic phenotype in the prediabetic liver.

scholarly journals AB0875-HPR NON-PHARMACOLOGICAL AND PHARMACOLOGICAL APPROACHES TO THE MANAGEMENT OF PATIENTS WITH OSTEOARTHRITIS AND LIPID METABOLISM DISORDERS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1461.1-1461
Author(s):  
T. Rogatkina ◽  
O. Korolik ◽  
V. Polyakov ◽  
G. Kravtsov ◽  
Y. Polyakova
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Lipid Metabolism ◽  
Lipid Profile ◽  
Fat Mass ◽  
Prognostic Significance ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lipid Metabolism Disorders ◽  
Group I

Background:Attention is drawn to the frequent combination of osteoarthritis (OA) with cardiovascular disease. Non-specific inflammation plays a significant role in the pathogenesis of OA and atherosclerosis. Limiting the physical activity of patients with OA is an additional important factor aggravating the course of cardiovascular disease (CVD). Chronic pain syndrome, causing a neuroendocrine response, is often the cause of the development of complications of atherosclerotic disease. Dyslipidemia is the main cause of atherosclerosis and vascular thrombosis.Objectives:To study variants of lipid metabolism disorders in female and male patients of different age groups with osteoarthritis.Methods:Case histories of 90 patients with OA were analyzed. The average age of patients was 63.27 ± 11.31 years. The average body mass index (BMI) is 39.8 ± 3.2. All patients underwent questionnaires, general clinical and biochemical blood tests with lipid profile determination, anthropometry, bioimpedansometry, and the main metabolic rate assessment using indirect calorimetry in dynamics (at the beginning of the study and after 3 months).Results:Burdened heredity for obesity, arterial hypertension (AH), diabetes mellitus (DM) was revealed. AH was diagnosed in 76 patients (84.4%), type II diabetes in 17 (18.9%), dyslipidemia and hypercholesterolemia in 56 (62.2%). Statins were taken by 43 patients (47.8%) - group I patients, which is associated with low adherence to therapy, group II included patients who did not initially take statins or stopped taking them at least 6 months before inclusion in the study.Against the background of diet therapy and physiotherapy exercises, BMI (R0.99; p <0.05), fat mass (R0.95; p <0.05) significantly decreased, lipid profile normalization was noted: total cholesterol (R0.66; p <0 .05), LDL (R0.69; p <0.05), HDL (R0.95; p <0.05), TG (R0.57; p <0.05), AST decreased (R0.64; p <0.05) and ALT (R0.76; p <0.05) in both groups of patients, regardless of lipid-lowering therapy. A decrease in fat mass correlated with TG levels (R0.51; p <0.05), an increase in skeletal muscle mass (R0.60; p <0.05), lean mass (R0.72; p <0.05), and active cell mass (R0.59; p <0.05). The lipid profile in the I group of patients was significantly better before and at the end of the study. Long-term effects have not been investigated due to the short duration of the study.Conclusion:In patients with OA, a high frequency of concomitant diseases of the cardiovascular system, lipid metabolism disorders was found. Non-drug therapy has a positive effect on the lipid profile and the level of transaminases. The decrease in body weight due to loss of fat mass reliably correlates with the level of TG. Timely use of statins contributes to the normalization of the lipid profile, reduces the risk of cardiovascular disease in patients with OA. It is necessary to study lipid profile disorders in patients with OA with recommendations for lifestyle modification (diet, physical activity), and if necessary, prescribe lipid-correcting therapy.References:[1]E. Simakova, B. Zavodovsky, L. Sivordova [et al]. Prognostic significance of lipid disorders markers determination in pathogenesis of osteoarthritis. Vestnik Rossijskoj voenno-medicinskoj akademii. 2013. No. 2 (42). P.29-32.[2]Zavodovsky B.V., Sivordova L.E. Prognostic significance value of definition of leptin level determination in osteoarthritis. Siberian Medical Journal (Irkutsk). 2012; 115(8):069-072.Disclosure of Interests:None declared

scholarly journals Validation and standardization of DNA extraction and library construction methods for metagenomics-based human fecal microbiome measurements

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Dieter M. Tourlousse ◽  
Koji Narita ◽  
Takamasa Miura ◽  
Mitsuo Sakamoto ◽  
Akiko Ohashi ◽  
...  
Keyword(s):  
Dna Extraction ◽  
High Throughput Sequencing ◽  
Performance Metrics ◽  
Collaborative Study ◽  
Human Microbiome ◽  
Second Phase ◽  
Intermediate Precision ◽  
Fecal Microbiome ◽  
Library Construction ◽  
Wide Range

Abstract Background Validation and standardization of methodologies for microbial community measurements by high-throughput sequencing are needed to support human microbiome research and its industrialization. This study set out to establish standards-based solutions to improve the accuracy and reproducibility of metagenomics-based microbiome profiling of human fecal samples. Results In the first phase, we performed a head-to-head comparison of a wide range of protocols for DNA extraction and sequencing library construction using defined mock communities, to identify performant protocols and pinpoint sources of inaccuracy in quantification. In the second phase, we validated performant protocols with respect to their variability of measurement results within a single laboratory (that is, intermediate precision) as well as interlaboratory transferability and reproducibility through an industry-based collaborative study. We further ascertained the performance of our recommended protocols in the context of a community-wide interlaboratory study (that is, the MOSAIC Standards Challenge). Finally, we defined performance metrics to provide best practice guidance for improving measurement consistency across methods and laboratories. Conclusions The validated protocols and methodological guidance for DNA extraction and library construction provided in this study expand current best practices for metagenomic analyses of human fecal microbiota. Uptake of our protocols and guidelines will improve the accuracy and comparability of metagenomics-based studies of the human microbiome, thereby facilitating development and commercialization of human microbiome-based products.

scholarly journals Quantification of platelet-bound IgG by 125I-Staphylococcal protein A in immune thrombocytopenic purpura and other thrombocytopenic disorders

Blood ◽  
1984 ◽  
Vol 63 (1) ◽  
pp. 154-161 ◽  
Author(s):  
GM Shaw ◽  
J Axelson ◽  
JG Maglott ◽  
AF LoBuglio
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Protein A ◽  
Normal Subjects ◽  
Unknown Etiology ◽  
Staphylococcal Protein A ◽  
Thrombocytopenic Purpura ◽  
Clinical Criteria ◽  
Staphylococcal Protein ◽  
Wide Range ◽  
Immune Hemolytic Anemia

Abstract In this report we describe the use of an 125I-Staphylococcal protein A (SPA) assay to measure platelet-bound IgG in the evaluation of 62 thrombocytopenic patients. Platelets from 150 normal subjects were found to bind 146 +/- 112 molecules of SPA per platelet (mean +/- 2 SD). Nineteen of 20 patients with untreated immune thrombocytopenia had platelet IgG values above this range, with 15 of 20 having values above 1,000 molecules of SPA per platelet. Patients with immune thrombocytopenic purpura by clinical criteria, but who had failed conventional therapy (corticosteroids or splenectomy), had a wide range of platelet IgG levels: 4 of 20 had normal values, 6 of 20 had minimally elevated levels in the range seen with nonimmune thrombocytopenia, and 10 of 20 had much higher values. Fifteen patients with thrombocytopenia of apparent nonimmune origin and 7 others with chronic stable thrombocytopenia of unknown etiology were found to have platelet IgG levels within or only slightly above the normal range. Because of its simplicity, accuracy, and clinical correlation, the 125I- SPA assay provides an important new approach for studying platelet IgG in thrombocytopenic states. The data obtained with this technique are similar to those found in immune hemolytic anemia and suggest that the platelet-bound IgG so measured has pathophysiologic relevance in immune thrombocytopenic purpura.

Effects of VO2 nanoparticles on human liver HepG2 cells: Cytotoxicity, genotoxicity, and glucose and lipid metabolism disorders

NanoImpact ◽  
2021 ◽  
Vol 24 ◽  
pp. 100351
Author(s):  
Jia-Bei Li ◽  
Wen-Song Xi ◽  
Shi-Ying Tan ◽  
Yuan-Yuan Liu ◽  
Hao Wu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders
Sign in / Sign up

Export Citation Format

Share Document