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Familial Hyperparathyroidism
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Luigia Cinque, Alfredo Scillitani, Vito Guarnieri
Parafibromin is also implicated in embryonic development directly regulating genes of cell growth and survival, such as the H19 gene, insulin-like growth factors 1 and 2 (IGF1 and IGF2), insulin-like growth factor binding protein 4 (IGFBP4), high mobility AT-hook 1 and 2 (HMGA1 and HMGA2), and 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (HMGCS2) [85]. Parafibromin was shown to have a dual role as a tumor suppressor and oncoprotein depending on the cellular environment. As a tumor suppressor, parafibromin overexpression seems to result in (i) inhibition of NIH3T3 and HEK293 cell proliferation; (ii) increase in G1 arrest and (iii) apoptosis in Hela cells, and (iv) downregulation of the cell cycle regulator cyclin D1.
Fatty liver in fasted FABP4/5 null mice is not followed by liver function deterioration
Published in Robert Hofstra, Noriyuki Koibuchi, Suthat Fucharoen, Advances in Biomolecular Medicine, 2017
M.R.A.A. Syamsunarno, M. Ghozali, G.I. Nugraha, R. Panigoro, T. Iso, M. Putri, M. Kurabayashi
The liver has a capacity to store the excess of fatty acids in triglyceride form. Then, these fatty acids will be oxidized or exported back into the main vascular system in the Low-Density Lipoprotein (LDL) form. There are two main functions of fatty acid oxidation. First, to generate energy that will be used to sustain hepatocyte function and gluconeogenesis. Second, fatty acid will be partially oxidized to produce ketone bodies, where 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) is a key regulator gene.
Impact of Acutely Increased Endogenous- and Exogenous Ketone Bodies on FGF21 Levels in Humans
Published in Endocrine Research, 2021
Esben Stistrup Lauritzen, Mads Vandsted Svart, Thomas Voss, Niels Møller, Mette Bjerre
However, seven days of starvation are required for the circulating FGF21 concentration to increase in humans,11,12 whereas fasting for up to 72 hours does not change FGF21 levels.13,14 In a placebo-controlled study, Gaich et al. reported an increase in 3-hydroxybutyrate (OHB) levels in patients with type 2 diabetes mellitus (T2D) after treatment with an FGF21 analog (LY2405319) for four weeks15 implying that FGF21 somehow may regulate ketogenesis in humans. Mice fed a ketogenic diet express increased FGF21 levels,8 whereas one human study indicates that ketogenic dieting results in decreased FGF21 levels.13 On the other hand, increased FGF21 levels have been reported in patients with T2D and “diabetic ketosis,”16 and activity in hydroxymethylglutaryl CoA synthase 2 (HMGCS2), which is the rate-limiting enzyme of ketogenesis, is associated with increased FGF21 expression in a human liver carcinoma cell line.17 Additionally, OHB is an inhibitor of class 1 histone deacetylases (HDACs),18 and inhibition of certain class 1 HDACs results in increased FGF21 production.19,20 Despite these diverging findings and the difference between animals and humans, the effects of acutely elevated ketone bodies on FGF21 levels have never been investigated.
Prostate cancer proteomics: clinically useful protein biomarkers and future perspectives
Published in Expert Review of Proteomics, 2018
Paula Intasqui, Ricardo P. Bertolla, Marcus Vinicius Sadi
Proteomic studies have also been conducted to understand the mechanism of castration resistance in prostate cancer cell lines. Androgen-deprivation therapy is the treatment of choice for cases of cancer recurrence and metastatic disease, which, in turn, generally induces the disease to evolve to a castration-resistant phenotype [35]. In this case, cancer cells continue to respond to residual androgen levels, or even in complete absence of androgens, and this has been suggested to be related to androgen receptors amplification, overexpression, splicing variants and/or mutation [35]. Therefore, the proteomes of LNCaP and LNCaP androgen-independent derivative (LNCaP-SF) cells were compared, and 88 differentially expressed proteins were identified. Of these, hydroxymethylglutaryl-CoA synthase, mitochondrial (HMGCS2) presented with a ninefold increase in LNCaP-SF cells. Because this protein is involved in the ketogenic pathway, other proteins of this pathway were also observed to be increased in androgen-independent cells, that is, acetyl-CoA acetyltransferase, mitochondrial (ACAT1); D-beta-hydroxybutyrate dehydrogenase, mitochondrial (BDH1); hydroxymethylglutaryl-CoA lyase, mitochondrial (HMGCL); and succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial (OXCT1). This was confirmed by western blotting and in prostate cancer tissues at mRNA and protein levels. ACAT1 was highly increased in metastatic prostate cancer tissues of men with the castration-resistant phenotype [36].
Microbiota, not host origin drives ex vivo intestinal epithelial responses
Published in Gut Microbes, 2022
Kaline Arnauts, Padhmanand Sudhakar, Sare Verstockt, Cynthia Lapierre, Selina Potche, Clara Caenepeel, Bram Verstockt, Jeroen Raes, Séverine Vermeire, João Sabino, Catherine Verfaillie, Marc Ferrante
In the non-inflamed setting, exposure to UC microbiota resulted in the identification of 4 differentially expressed genes (FDR <0.05) between UC and non-IBD epithelial cells (Figure 2c). In inflamed conditions, treatment with UC microbiota caused 16 differentially expressed genes including PARP9, TGFBI and CMPK2 (Figure 2d). Seven of these 16 genes were significantly differentially expressed in unexposed conditions, while nine were specifically related to microbiota exposure. These genes were linked to mitochondrial pathways (HMGCS2, CMPK2) and repair of DNA damage (PARP9). However, aside from this limited number of genes, no clear distinct transcriptomic or barrier integrity response could be identified.