Role of Tandem Mass Spectrometry in Diagnosis and Management of Inborn Errors of Metabolism
P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas in Advanced Studies in Experimental and Clinical Medicine, 2021
Metabolomics is more important in the diagnosis of IEM compared to other branches of clinical medicine, since a large number of small metabolites are excreted in IEM [89]. Urinary metabolomics is a useful tool for various disorders neonatal and infancy including IEM [90]. Selicharová et al. usedproteomicsand metabolomics analyses of human hepatocytes in primary cell culture. This technique helped to search the spectrum of proteins and associated metabolites which are affected by the interruption of methyl groupmetabolism. They studied the effect of hyperhomocysteinemia at two concentrations, 0.1 mM and 2.0 mM, and used the inhibitor, BHMT, Betaine Homocysteine N Methyltransferase. The higher concentration produced up-regulation of phosphatidylethanolamine carboxykinase and ornithine aminotransferase, cellular proliferation was affected, secretome composition was altered and signs of apoptosis were seen. In addition, fibrinogen gamma dimers were detected and defective maturation of apolipoprotein A1 was seen [91].
Precision medicine in coronary artery disease
Debmalya Barh in Precision Medicine in Cancers and Non-Communicable Diseases, 2018
A study was conducted to evaluate the modifications in the plasma protein map during unstable angina (UA) and AMI using proteomics. The protein plasma levels were quantified among patients with AMI (n = 11) and UA (n = 9). The control group was comprised of age-matched volunteers. The proteins that were analyzed included alpha-1-antitrypsin (AAT), apolipoprotein A-I, fibrinogen gamma chain, immunoglobulin gamma heavy chain, and albumin. The main finding of this study was that different AAT isoforms change in plasma during an acute coronary syndrome (ACS). Seven different AAT isoforms were seen in the plasma of control samples. However, the AAT isoform 1 was absent in the ACS samples. In the study, there was also a significant reduction of isoforms 5, 6, and 7 in the AMI samples when compared with UA samples. The fibrinogen gamma chain 1 and 2 were increased in AMI patients compared to UA patients. Five apolipoprotein A-I isoforms were also identified, but these were reduced in plasma from AMI patients with respect to UA patients. The γ-immunoglobulin heavy chains were identified and were found to be increased in the plasma among ACS patients. Thus, the proteomic analysis will help in the mapping of the protein isoforms that are expressed in plasma during an ACS (Mateos-Cáceres et al., 2004).
Alcohol
Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss in Nutrition and Cardiometabolic Health, 2017
The protective effects of a low to moderate alcohol intake on cardiovascular disease are partly thought to be attributable to an increase in high-density lipoprotein (HDL) cholesterol levels. HDL acquires cholesterol from peripheral tissue and facilitates its transport to the liver for removal in the bile. HDL cholesterol is secreted as small particles by the liver and the gut and changes composition in the circulation by exchanging lipids with other lipoproteins or by absorption of cholesterol from peripheral cells. HDL particles include multiple apolipoproteins, primarily apolipoprotein A1 (Hannuksela et al. 2002).
Temporal pathway analysis of cerebrospinal fluid proteome in herpes simplex encephalitis
Published in Infectious Diseases, 2023
Anja Nääs, Peng Li, Clas Ahlm, Elisabeth Aurelius, Josef D. Järhult, Silvia Schliamser, Marie Studahl, Wenzhong Xiao, Jonas Bergquist, Gabriel Westman
When comparing the individual proteins between NMDAR seropositive and seronegative patients, six proteins show lower levels in the seropositive group at various time points. Out of these six (procathepsin H, heparin cofactor 2, complement factor I, protein AMBP apolipoprotein A1 and polymeric immunoglobulin receptor) we find apolipoprotein A1 to be of most interest in this biological context. Apolipoprotein A1 is the main component of the high-density lipoproteins (HDL), and aside from its well-known role in cholesterol metabolism it takes part in the immune response as well, having an anti-inflammatory effect [38]. There seems to be a link between apolipoprotein A1 levels and neurodegenerative disease, where a low level of serum apolipoprotein A1 correlates with a higher risk of dementia [39] and the severity of Alzheimer’s disease [40,41]. A study by Liu et al. showed lower levels of serum apolipoprotein A1 in NMDAR encephalitis patients compared to healthy controls [42]. However, it should be noted that apolipoprotein A1 levels in serum compared to CSF does not always correlate, since it can be transported through transcytosis [43]. Our finding of lower levels in the anti-NMDAR seropositive group is in line with the hypothesis that apolipoprotein A1 has a neuroprotective effect; hence it should probably be interpreted as a potentially protective factor against the development of anti-NMDAR antibodies. No other single protein levels were significantly correlated to the level of brain MRI injury, corticosteroid treatment or neurocognitive status.
BET inhibitors: an updated patent review (2018–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Huanhuan Chen, Zhenling Liu, Lili Zheng, Rongrong Wang, Lei Shi
Moreover, BET transcription complexes function similarly to SWI/SNF chromatin remodeling complexes, capable of co-activating one set of genes while co-repressing a different set of genes, thus exerting opposing effects in cell cycle control [88]. For example, BRD2 is highly expressed in pancreatic β-cells and inhibits β-cell mitosis and insulin transcription. In 3T3-L1 pre-adipocytes, BRD2 normally co-represses peroxisome proliferator-activated receptor-γ (PPAR-γ) and inhibits adipogenesis. Depletion of BRD2 causes lifelong severe obesity in mice with pancreatic islet expansion, hyperinsulinaemia, hepatosteatosis, and elevated pro-inflammatory cytokines [89]. Thus, pro-adipogenic transcription programs should be assessed for BET inhibitor evaluation. Apolipoprotein A1 (ApoA1) upregulation is associated with protection from atherosclerosis progression and with anti-inflammatory effects. Nicodeme et al. identified a new class of ApoA1 upregulators [90]. These compounds bind to the acetyl lysine recognition pocket and directly antagonize the interaction between the BET proteins (BRD2, BRD3, and BRD4) and acetylated histone peptides. Therefore, the impact of ApoA1 may also be considered in the development of BET inhibitors.
Serum and follicular fluid irisin levels in women with polycystic ovaries undergoing ovarian stimulation: correlation with insulin resistance and lipoprotein lipid profiles
Published in Gynecological Endocrinology, 2019
Artemis Bousmpoula, Evangelos Benidis, Styliani Demeridou, Rachil Kapeta-Kourkouli, Anthia Chasiakou, Stamatia Chasiakou, Evangelia Kouskouni, Stavroula Baka
Women with polycystic ovaries are more prone to develop lipid profile abnormalities compared to normal controls, which puts them to an increased risk for CVD later in life due to metabolic dysfunction [24]. Our findings are in concordance with previous studies which demonstrated that classic atherogenic dyslipidemia, characterized by higher total cholesterol, LDL-C and triglycerides and lower HDL-C, is common among PCOS women, although another possible active mechanism might link the androgen excess to increased LDL-C levels [6,11,24]. Apolipoprotein B, lipoprotein(a) and homocysteine levels, as risk factors for CVD, were increased while apolipoprotein A1 levels were decreased in PCOS subjects, as previously reported [25–27]. Irisin levels were positively associated with triglycerides levels and negatively with HDL-C, results which are in line with previous findings [11,17,28]. The contradictory results in the published literature regarding irisin relationship to lipid lipoprotein profile could be attributed to the different recruitment criteria and confounding factors in the populations studied, ethnic heterogeneity and genetic background or to the level of physical activity, the difficulty to distinguish between the ovulatory and anovulatory PCOS phenotypes and discrepancies in the laboratory measurements [25,29].
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