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    • Finally our work showed that

    2021-10-11

    Finally, our work showed that HAART resulted in significant inter-individual variability among DEGs, which reflected the Alrestatin in HIV-affected human gene expressions (Fig. 1, Fig. 2, Fig. 3, Fig. 4). These observations also highlighted the importance of determining common as well as personal specific DEG profiles to develop effective diagnostic markers and treatment targets.
    Conclusions In this study, we use RNA sequencing (RNA-Seq) technology to identify common DEGs and special DEGs for HIV positive and HIV negative person between pre- and post-HAART. We found 11 down-regulate DEGs and 14 up-regulated DEGs in HIV positive patient. Our work showed that HAART resulted in significant inter-individual variability among DEGs, which reflected the diversity in HIV-affected human gene expressions. The newly identified HIV-related genes, ADM (which encodes Adrenomedullin), a peptide hormone in circulation control, may contribute to HIV-associated hypertensions, providing new insights into HIV pathology and novel strategies for developing anti-HIV target. These observations also highlighted the importance of determining common as well as personal specific DEG profiles to develop effective diagnostic markers and treatment targets. The following are the supplementary data related to this article.
    Author contributions statement
    Introduction In recent years, a number of seven transmembrane (7TM) receptors have been cloned and characterized that are highly promiscuous and thus respond to a range of natural agonists. Furthermore, several promiscuous taste receptors have been identified in tissues other than taste buds, such as the gut, suggesting that they have other functions than sensing tastants. Interestingly, these promiscuous receptors respond to organic nutrients or their immediate breakdown products, that is, fatty acids, sugars, amino acids, and proteolytic products, and thus possibly serve as chemosensors for food intake (Conigrave & Brown, 2006, Egan & Margolskee, 2008, Engelstoft et al., 2008). For decades, it has been known that the organic nutrients cause release of hormones from the gut, pancreas, and other organs, but the molecular nature of the chemosensors has been enigmatic. The identification of promiscuous 7TM receptors responding to the organic nutrients located in the relevant tissues has potentially identified the missing links. In that regard, it makes perfect sense that these nutrient-sensing receptors have evolved to be promiscuous in order to respond to the wide range of foods digested by humans, and it opens for the perspective that mixtures of ligands work in a concerted fashion to activate one receptor, as has been shown for the calcium-sensing receptor (CaR) (Conigrave et al., 2000, Conigrave et al., 2004).
    The family C of 7TM receptors is intriguing both from a structural and a functional point of view. They are believed to evolve from the linking of two separate entities (Conklin and Bourne, 1994); a class of bacterial periplasmic-binding proteins (Felder et al., 1999, O'Hara et al., 1993), involved in nutrient uptake (Quiocho and Ledvina, 1996), and the archetypical 7TM structure found in all G protein-coupled receptors (). In fact, most members of family C 7TM receptors have a preserved ability to respond to nutrient-like compounds being it amino acids, ions, or sugars, but they do so by different modes of interaction: The mGlu and γ-aminobutyric acid type B (GABAB) receptors respond exclusively to one agonist (either l-glutamate () or GABA (Wellendorph and Bräuner-Osborne, 2009)), probably reflecting the important roles of these receptors in neurotransmission, whereas the subgroup of receptors formed by the CaR, T1Rs, and GPRC6A, phylogenetically distinct within family C receptors (Bjarnadóttir et al., 2005, Kuang et al., 2006, Wellendorph & Bräuner-Osborne, 2009) are promiscuous by nature and respond to subsets of l-α-amino acids and divalent cations (CaR, GPRC6A, and the heterodimeric receptor T1R1/T1R3) or sugars and d-amino acids (the heterodimeric receptor T1R2/T1R3). Due to the ingenious differential l-amino acid preference for each of these receptors, they potentially cover stimuli from all of the 20 proteinogenic l-amino acids (Conigrave & Hampson, 2006, Wellendorph & Bräuner-Osborne, 2009) (Fig. 5.1) which together with their expression in relevant tissues (Fig. 5.2) allows for a nutrient-sensing capacity of emerging physiological significance (for reviews see (Conigrave & Hampson, 2006, Conigrave & Hampson, 2010, Rozengurt & Sternini, 2007, Sternini et al., 2008)). Thus, this subgroup of receptors are able to sense an impressive range of nutrients already from food enters the mouth, via receptors in the taste buds, to the additional proteolytic breakdown and chemosensing in the stomach and gut (Table 5.1), where the concentration of free l-amino acids may notably rise as high as to approach millimolar concentrations (Adibi and Mercer, 1973).