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Advances in Genome Editing
Published in Yashwant Pathak, Gene Delivery, 2022
Schuh and co-workers studied targeting of CRISPR/Cas9 and a donor oligonucleotide aiming at Mucopolysaccharidosis type I gene editing in vitro. The DNA were complexed with nanoemulsions, which showed effective introduction into MPS I p.Trp402∗ patient’s fibroblasts (Schuh et al. 2018a). CRISPR/Cas9 plasmids were delivered effectively into a triple-negative breast malignancy, using an antibody-conjugated tumor-targeted nanolipogel. The Lipocalin 2 gene knocking efficiency of 81 percent resulted in a 77 percent reduction in cancer growth. These investigations showed that tumor-targeted nanolipogel are a secure, precise, and efficient delivery vehicle for CRISPR-mediated genome editing with target specificity (Guo et al., 2019).
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
This molecule belongs to the lipocalin family of small lipid (and other hydrophobic molecule) binding proteins, which are as ancient as gram-negative bacteria and have only structural conservation but very little sequence homology; thus, it was difficult to discover by genomic searches. The myriad names of lipocalin 2 testify to its multitude of actions. It was called a siderocalin, as it sequesters bacterial siderophores, thus restricting iron supply to bacteria. In the neutrophil granule, it binds to MPO, MMP9 β-galactosidase, and so forth, and is an important component of neutrophil intracellular traps. NGAL might protect proMMP9 from premature activation. Extracellular NGAL is internalized through several receptors, which also triggers several signaling pathways that are not yet fully elucidated. It may act as an intracellular iron metabolism regulator and also has an effect on subcellular localization of transmembrane proteins, such as cadherins and catenins. Several other lipocalins, for example, retinol binding proteins, are also potentially important for angiogenesis in psoriasis. The mother family “calycin,” to which lipocalins belong, also includes fatty acid binding proteins (FABPs), some of which, for example, FABP4 and FABP5, are important in endothelial cell function and psoriasis.
Genitourinary tract
Published in Brian J Pollard, Gareth Kitchen, Handbook of Clinical Anaesthesia, 2017
Brian J Pollard, Gareth Kitchen
The diagnosis of AKI has to date depended on detection of a decrease in kidney function by an increase in serum creatinine concentration which only occurs after a significant decrease in renal function. Earlier detection of AKI would be beneficial. A number of early biomarkers of AKI are currently being investigated. Neutrophil gelatinase-associated lipocalin (NGAL), a 25 kDa protein that is bound to neutrophils and expressed in injured epithelial cells in organs including the kidney has emerged as an accurate early biomarker of acute kidney injury. Plasma and urine NGAL have proved sensitive, specific and predictive early biomarkers of AKI after cardiac surgery. Other promising biomarkers are cystatin C, interleukin-18 and kidney injury molecule-1 (KIM-1). Further studies are required to validate the sensitivity and specificity of these biomarkers in clinical samples from large cohorts and from multiple clinical situations. Clinically relevant urinary biomarkers are summarized in Box 5.5.
The role of serial cardiac biomarkers in prognostication and risk prediction of chronic heart failure: additional scientific insights with hemodynamic feedback
Published in Expert Review of Cardiovascular Therapy, 2023
Youssra Allach, Jasper J. Brugts
According to literature, individuals with acute kidney injury (AKI), inflammation, and ischemic or nephrotoxic damage had significantly higher levels of the promising renal biomarker NGAL, also known as lipocalin-2. Furthermore, it has been discovered that increased NGAL expression is associated with CV disorders, including HF. That increased NGAL levels are linked to renal impairment in patients with CHF has been demonstrated by the study of Damman, K and colleagues. The median urine NGAL levels in CHF patients were significantly higher than controls, at 175 vs. 37 μg/gCr, respectively (P < 0.0001) [71]. Many research have examined the predictive usefulness of NGAL in CHF patients, including the study by Villacorta, H et al., who discovered that NGAL was a potent predictor of clinical outcomes including CV mortality and HF hospitalizations (HR (95% CI) 1.0035 (1.0019 to 1.0052), P < 0.0001). Interestingly, NGAL appeared even to outperform several clinical measures of renal function, including creatinine and eGFR, as well as the conventional HF biomarker BNP [72]. This was further strengthened by Bolignano, D et al., who found that elderly CHF patients with baseline NGAL concentrations >783 ng/mL had a substantially increased risk of mortality (p = 0.001; log-rank test), with an HR (95%) of 4.08 (1.29 to 12.96) for death [73]. The promising NGAL, a biomarker of kidney injury, has the potential to be a reliable predictive predictor of prognosis in CHF patients.
Anticalin® proteins: from bench to bedside
Published in Expert Opinion on Biological Therapy, 2021
Friedrich-Christian Deuschle, Elena Ilyukhina, Arne Skerra
Natural lipocalin proteins are found in diverse phyla of life and convey essential functions such as the storage, transport and/or excretion of chemically sensitive, hydrophobic, or noxious substances – for example vitamins, pheromones and steroids, or microbial siderophores [9]. As secretory proteins they are involved in essential biological processes within the blood or tissue fluids, including the regulation of cell growth and metabolism or the innate immune response. With a size of merely 160–180 amino acid residues, lipocalins exhibit pronounced homology in their tertiary structures despite surprisingly low amino acid sequence similarity [7,10]. Their highly conserved cup-shaped fold is dominated by a β-barrel, formed by eight circularly arranged antiparallel β-strands, as well as an adjacent α-helix (Figure 1(b)) [8].
Dietary cellulose induces anti-inflammatory immunity and transcriptional programs via maturation of the intestinal microbiota
Published in Gut Microbes, 2020
Florence Fischer, Rossana Romero, Anne Hellhund, Uwe Linne, Wilhelm Bertrams, Olaf Pinkenburg, Hosam Shams Eldin, Kai Binder, Ralf Jacob, Alesia Walker, Bärbel Stecher, Marijana Basic, Maik Luu, Rouzbeh Mahdavi, Anna Heintz-Buschart, Alexander Visekruna, Ulrich Steinhoff
Recent studies have shown that the commensal microbiota is able to influence the transcriptional profile of intestinal epithelial and immune cells.24–26 The possibility that the presence of A. finegoldii within the Oligo-MM12 microbiota alters gene expression and favors intestinal homeostasis was therefore examined. Analogous to SPF mice, immunological markers and expression of genes essentially involved in gut barrier function were measured. A. finegoldii enhanced the frequency of IL17-producing T cells in the intestine and peripheral lymphoid organs (Figure 7a; Fig. S7a-f) and induced a strong and specific upregulation of Reg3γ in the colon (Figure 7b). Colon cultures further revealed selective upregulation of IL-22 in A. finegoldii-associated Oligo-MM12 mice. The inflammation marker lipocalin-2 was not affected under these conditions (Figure 7c, Fig. S7g). Together, IL-22 and Reg3γ, are two factors known to maintain the barrier via segregating the microbiota from the intestinal epithelium.27,28