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Multi-Omics Profiling in a Symptomatic Cohort Identifies Coordinated Biomarker Signatures in Ovarian Cancer Serum.

Background/Objectives: Ovarian cancer (OC) is a leading cause of cancer-related mortality in women, largely driven by late-stage diagnosis. … metabolism in OC, consistent with altered redox balance, along with changes in fatty acids and acyl-carnitines, suggesting altered lipid metabolism and inflammatory mechanisms. Lower levels of glycolytic and TCA cycle intermediates in OC suggested altered mitochondrial metabolism and energetic reprogramming. Pairwise comparisons revealed a gradient of signi …

ELOVL5 and VLDLR synergistically affect n-3 PUFA deposition in eggs of different chicken breeds.

There was no significant difference in the composition and content of fatty acids in eggs among different breeds initially, but following th … in White Leghorn, while the mRNA levels of peroxisome proliferator-activated receptor alpha (PPAR), carnitine palmitoyl transferase 1 (CPT1), Acyl CoA oxidase 1 (ACOX1), and Acyl-CoA synthetase (ACSL) were significantly lower than those in White Leghorn. The mRNA level of FABP1 in the duodenum of Dwarf Layer was significantly higher than that of White Legho …

Approach to generalized weakness and peripheral neuromuscular disease.

A large number of intellectually engaging and potentially serious neuromuscular diseases have been presented. The emergency medicine physici … c myopathy that was only diagnosed after enzymatic analysis of a muscle biopsy. Her genetic defect, carnitine palmitoyltransferase deficiency, is unusual as it does not present until late in adolescence or slightly later in life. It is a defect in lipid metabolism in which long-chain fatty acids are unable to gain entrance into the mitochondrion for oxidati …

DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts.

BACKGROUND: Type 2 diabetes (T2D) is a heterogeneous disease with well-known genetic and environmental risk factors contributing to its prevalence. Epigenetic mechanisms related to changes in DNA methylation (DNAm), may also contribute to T2D risk, but larger studies are required to discover novel markers, and to confirm existing ones. RESULTS: We performed a large meta-analysis of individual epigenome-wide association studies (EWAS) of prevalent T2D conducted in four European studies using peripheral blood DNAm. Analysis of differentially methylated regions (DMR) was also undertaken, based o

Omega-3 fatty acids improve lipid metabolism by regulating miR-34a.

Lipid metabolism disorders and hepatic lipid deposition are major contributors to the development of metabolic diseases such as non-alcoholic fatty liver disease. Omega-3 fatty acids have been shown to exert beneficial effects on lipid homeostasis and liver function, but their molecular regulatory mechanisms remain incompletely understood. Here, we investigated the effects of omega-3 fatty acids on lipid metabolism and hepatic lipid deposition in addition to the modulatory role of miR-34a using an in vivo high-fat diet (HFD) model and an in vitro palmitic acid (PA)-induced HepG2 cell model. We

xCT knockdown in human breast cancer cells delays onset of cancer-induced bone pain.

Cancers in the bone produce a number of severe symptoms including pain that compromises patient functional status, quality of life, and survival. The source of this pain is multifaceted and includes factors secreted from tumor cells. Malignant cells release the neurotransmitter and cell-signaling molecule glutamate via the oxidative stress-related cystine/glutamate antiporter, system xC-, which reciprocally imports cystine for synthesis of glutathione and the cystine/cysteine redox cycle. Pharmacological inhibition of system xC- has shown success in reducing and delaying the onset of cancer pa

Stimulus specific changes of energy metabolism in hypertrophied heart.

Cardiac energy metabolism is a determinant of the response to hypertrophic stimuli. To investigate how it responds to physiological or pathological stimuli, we compared the energetic status in models of hypertrophy induced by physiological stimuli (pregnancy or treadmill running) and by pathological stimulus (spontaneously hypertensive rats, SHR) in 15 week-old female rats, leading to a 10% cardiac hypertrophy. Late stage of compensated hypertrophy was also studied in 25 week-old SHR (35% of hypertrophy). Markers of cardiac remodelling did not follow a unique pattern of expression: in trained

[Sichuan Dark Tea-Based Medicated Dietary Formula Improves Obesity-Induced Renal Lipid Metabolism Disorder in Mice by Remodeling Gut Microbiota and Short-Chain Fatty Acid Metabolism].

OBJECTIVE: To investigate the renoprotective effects of a Sichuan dark tea-based medicated dietary formula (alternatively referred to as Qin … expression of proteins related to fatty acid oxidation, including acetyl-CoA carboxylase 1 (ACC1), carnitine acyltransferase 1 (CTP1), peroxisome proliferators-activated receptor γ (PPARγ), peroxisome proliferators-activated receptor-1 α (PPAR1α), sterol-regulatory element binding proteins (SREBP-1), and key proteins related to lipid synthesis, including f …

Candidate's thesis: enhancing intrinsic cochlear stress defenses to reduce noise-induced hearing loss.

OBJECTIVES/HYPOTHESIS: Oxidative stress plays a substantial role in the genesis of noise-induced cochlear injury that causes permanent heari … defects in mitochondrial bioenergetics and biogenesis. Therefore, NICOS can be reduced by acetyl-L carnitine (ALCAR), an endogenous mitochondrial membrane compound that helps maintain mitochondrial bioenergetics and biogenesis in the face of oxidative stress. 2) A contributing factor in NICOS injury is glutamate excitotoxicity, which can be reduced by anta …

Guilu Erxian oral liquid alleviates oligoasthenospermia via the mitochondria-complement-NETs network.

ETHNOPHARMACOLOGICAL RELEVANCE: Guilu Erxian Oral Liquid (GLEX) is a traditional Chinese medicinal formula first recorded in Yi Bian, a medi … , medium (3.86 mL/kg)-, and high (7.72 mL/kg)-dose groups of GLEX, Wu Zi Yan Zong pill group, and L-Carnitine group. Each group received consecutive gavage for 28 days. Semen quality parameters were assessed using a sperm quality analyzer, along with morphological assessment by hematoxylin and eosin (HE) staining. Serum sex hormone levels were measured usin …

Circadian Rhythm Alteration of the Core Clock Genes and the Lipid Metabolism Genes Induced by High-Fat Diet (HFD) in the Liver Tissue of the Chinese Soft-Shelled Turtle (Trionyx sinensis).

Physiology disorders of the liver, as it is an important tissue in lipid metabolism, can cause fatty liver disease. The mechanism might be r … ductase (Hmgcr), Low-density lipoprotein receptor-related protein 1-like (Ldlr1), Lipin 1 (Lipin1), Carnitine palmitoyltransferase 1A (Cpt1a), Peroxisome proliferator activation receptor α, β and γ (Pparα/β/γ), Sirtuin 1 (Sirt1), Apoa (Apoa1), Apolipoprotein B (Apob), Pyruvate Dehydrogenase kinase 4 (Pdk4), Acyl-CoA synthase long-chain1 (Acsl1), Liver X rec …

Treatment for calcium channel blocker poisoning: a systematic review.

CONTEXT: Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. OBJECTIVE: To evaluate the reported effect … h calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. CONCLUSIONS: The treatment for calcium channel blocker poison …

[Bilateral microsurgical varicocelectomy in infertile men].

UNLABELLED: We assessed how bilateral microsurgical varicocelectomy alters semen quality in a large cohort of infertile men with bilateral v … . Complementary investigation included: the hormone status (FSH, LH, testosterone), semen analyses (carnitine, LDHx, fructoze, zinc). On the basis of the total motile sperm count 198 patients were divided into 5 biological groups: 10 azoospermia and oligospermia extreme (0-1) x 10(6)/cc--83 patients (41.9%); 2) oligospermia severe (1.1-5) x 10(6)/cc)--37 pa …

Toxic lipids stored by Kupffer cells correlates with their pro-inflammatory phenotype at an early stage of steatohepatitis.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis associated with liver inflammation. Steatosis causes recruitment of lymphocytes into the liver and this is worsened by lipopolysaccharides (LPS). As macrophages may be involved in the lymphocyte homing, we studied the role of lipids in determining the phenotype of Kupffer cells (KCs) at the stage of steatosis. METHODS: Steatosis was induced in mice by a high fat diet. The turnover and the recruitment of KCs were analyzed in vivo by flow cytometry. KCs phenotype was assessed by optical and electron microscopy

Micronutrients in Oncological Intervention.

Nutritional supplements are widely used among patients with cancer who perceive them to be anticancer and antitoxicity agents. Depending on the type of malignancy and the gender 30%-90% of the cancer patients supplement their diets with antioxidant and immuno-stabilizing micronutrients, such as selenium, vitamin C, and vitamin D, often without the knowledge of the treating physician. From the oncological viewpoint, there are justifiable concerns that dietary supplements decrease the effectiveness of chemotherapy and radiotherapy. Recent studies, however, have provided increasing evidence that

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… In the studies cited, l -carnitine was used in the form of l -carnitine, acetyl- or propionyl- l -carnitine. In the USA, propionyl- l -carnitine is used particularly in cardiovascular disease. … As chloroacetyl carnitine is not as well resorbed in the kidneys as free l -carnitine, the excretion of l -carnitine is increased, leading to a secondary l -carnitine deficiency [ 166 , 169 , 174 ]. …

Pregnancies in Women With Long-Chain Fatty Acid Oxidation Disorders: Results of a European and North American Survey.

Long-chain fatty acid oxidation disorders (lcFAODs) are genetic disorders of energy metabolism that are associated with a risk of metabolic decompensation, especially during catabolic episodes. With improvement in diagnostics and treatment, more women with lcFAODs now reach child-bearing age. So far, little is known about the risk and outcome of pregnancies, particularly in women with more severe forms of lcFAODs. We performed an international web-based survey among health care professionals involved in the care of individuals with lcFAODs and collected data on 89 pregnancies in 39 women (mild

Fibroblast growth factor-21 prevents diabetic cardiomyopathy via AMPK-mediated antioxidation and lipid-lowering effects in the heart.

Our previous studies showed that both exogenous and endogenous FGF21 inhibited cardiac apoptosis at the early stage of type 1 diabetes. Whether FGF21 induces preventive effect on type 2 diabetes-induced cardiomyopathy was investigated in the present study. High-fat-diet/streptozotocin-induced type 2 diabetes was established in both wild-type (WT) and FGF21-knockout (FGF21-KO) mice followed by treating with FGF21 for 4 months. Diabetic cardiomyopathy (DCM) was diagnosed by significant cardiac dysfunction, remodeling, and cardiac lipid accumulation associated with increased apoptosis, inflammati

Alkylthio acetic acids (3-thia fatty acids)--a new group of non-beta-oxidizable peroxisome-inducing fatty acid analogues--II. Dose-response studies on hepatic peroxisomal- and mitochondrial changes and long-chain fatty acid metabolizing enzymes in rats.

The activity of key enzymes involved in oxidation and esterification of long-chain fatty acids was investigated after male Wistar rats were treated with different doses of sulfur substituted fatty acid analogues, 1,10-bis(carboxymethylthiodecane) (BCMTD, non-beta-oxidizable and non-omega-oxidizable), 1-mono(carboxymethylthiotetradecane) (CMTTD, trivial name, alkylthio acetic acid, non-beta-oxidizable) and 1-mono(carboxyethylthiotetradecane) (CETTD trivial name, alkylthio propionic acid, beta-oxidizable). The sulfur substituted dicarboxylic acid and the alkylthio acetic acid induced in a dose-d

Serelaxin (recombinant human relaxin-2) treatment affects the endogenous synthesis of long chain poly-unsaturated fatty acids and induces substantial alterations of lipidome and metabolome profiles in rat cardiac tissue.

BACKGROUND AND PURPOSE: Recombinant human relaxin-2, serelaxin, is being proved as a novel drug with therapeutic efficacy in some cardiovasc … ar metabolites. Identified ion features in the methanol extract platform included fatty acids, acyl carnitines, bile acids, monoacylglycerophospholipids, monoetherglycerophospholipids, free sphingoid bases, and oxidized fatty acids. The chloroform / methanol extract platform provided coverage over glycerolipids, cholesterol esters, sphingolipids, diacylglyc …