Publications by authors named "Angelo Santino"

Article Synopsis
  • Misfolded glycoproteins in the endoplasmic reticulum (ER) are retained by the enzyme UGGT, which recognizes and marks them for retention by re-glucosylating their N-linked glycans.
  • In the context of certain congenital mutations in the Trop-2 glycoprotein, which is associated with gelatinous drop-like corneal dystrophy (GDLD), these misfolded versions of Trop-2 are unable to reach the plasma membrane and remain trapped in the ER.
  • The study found that inhibiting UGGT1 in mammalian cells can restore membrane localization of these mutants, suggesting that targeting UGGT1 may offer a new treatment approach for diseases caused by similar misfolded glycoproteins that still
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Misfolded glycoprotein recognition and endoplasmic reticulum (ER) retention are mediated by the ER glycoprotein folding quality control (ERQC) checkpoint enzyme, UDP-glucose glycoprotein glucosyltransferase (UGGT). UGGT modulation is a promising strategy for broad-spectrum antivirals, rescue-of-secretion therapy in rare disease caused by responsive mutations in glycoprotein genes, and many cancers, but to date no selective UGGT inhibitors are known. The small molecule 5-[(morpholin-4-yl)methyl]quinolin-8-ol (5M-8OH-Q) binds a UGGT "WY" conserved surface motif conserved across UGGTs but not present in other GT24 family glycosyltransferases.

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Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ERlocalised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant").

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In the past decades, many studies have widely examined the effects of dietary polyphenols on human health. Polyphenols are well known for their antioxidant properties and for their chelating abilities, by which they can be potentially employed in cases of pathological conditions, such as iron overload. In this review, we have highlighted the chelating abilities of polyphenols, which are due to their structural specific sites, and the differences for each class of polyphenols.

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We report about the response of Arabidopsis thaliana to chronic and temporary Cd stress, and the Cd induced activation of ER stress and unfolded protein response (UPR). Cd-induced UPR proceeds mainly through the bZIP60 arm, which in turn activates relevant ER stress marker genes such as BiP3, CNX, PDI5 and ERdj3B in a concentration- (chronic stress) or time- (temporary stress) dependent manner. A more severe Cd-stress triggers programmed cell death (PCD) through the activation of the NAC089 transcription factor.

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The metabolic engineered Bronze tomato line is characterized by the constitutive over-expression of the gene encoding a structural protein responsible for the stilbenoids biosynthesis and the fruit-specific over-expression of / and genes encoding transcription factors that activate the polyphenol biosynthetic pathway. This tomato line is known for the increased levels of polyphenols in ripe fruits and for beneficial health promoting antioxidant and anti-inflammatory effects. In this study we analyzed the transcriptional and metabolic profiling in mature green, breaker, orange and ripe fruits compared to the normal tomato counterparts during ripening, to unravel the effect of regulatory and structural transgenes on metabolic fluxes of primary and secondary metabolisms.

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Poor vitamin D status is a global health problem; insufficiency underpins higher risk of cancer, neurocognitive decline and all-cause mortality. Most foods contain little vitamin D and plants are very poor sources. We have engineered the accumulation of provitamin D in tomato by genome editing, modifying a duplicated section of phytosterol biosynthesis in Solanaceous plants, to provide a biofortified food with the added possibility of supplement production from waste material.

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Article Synopsis
  • Antioxidants could enhance the effectiveness of treatments for chronic inflammatory diseases, especially in IBD by acting as adjuvants.
  • A study explored the effects of a purple corn supplement on patients with Crohn's disease and ulcerative colitis receiving Infliximab infusions.
  • Results indicated that the purple corn supplement improved treatment responses among Crohn's disease patients but not ulcerative colitis, suggesting the potential for further larger-scale studies.
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Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory bowel diseases (IBDs) are characterized by a leaky intestinal barrier and the consequent translocation of bacterial lipopolysaccharide (LPS) to the basolateral side.

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We aimed to develop an innovative synbiotic formulation for use in reducing dysbiosis, uremic toxins (e.g., -cresol and indoxyl sulfate), and, consequently, the pathognomonic features of patients with chronic kidney disease (CKD).

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Neonatal colonization of the gastrointestinal tract depends on mother microbiome, thus mother microbiota dysbiosis is transmitted to the offspring during the delivery and shaped by breastmilk characteristics. Here we used a murine model of UC predisposition (Winnie) to evaluate the effects of maternal diet during pregnancy and lactation. Using heterozygous breeders, we obtained both Winnie and C57BL/6 littermates from the same mother and compared their microbiota at weaning and adult age, using a diet enriched with 1% tomato fruit of a line - named Bronze - highly enriched in bioactive polyphenols, or Control tomato.

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UDP-glucose:glycoprotein glucosyltransferase (UGGT) flags misfolded glycoproteins for ER retention. We report crystal structures of full-length Chaetomium thermophilum UGGT (CtUGGT), two CtUGGT double-cysteine mutants, and its TRXL2 domain truncation (CtUGGT-ΔTRXL2). CtUGGT molecular dynamics (MD) simulations capture extended conformations and reveal clamping, bending, and twisting inter-domain movements.

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Plant food biofortification is recently receiving remarkable attention, as it aims to increase the intake of minerals, vitamins, or antioxidants, crucial for their contribution to the general human health status and disease prevention. In this context, the study of the plant's secondary metabolites, such as polyphenols, plays a pivotal role for the development of a new generation of plant crops, compensating, at least in part, the low nutritional quality of Western diets with a higher quality of dietary sources. Due to the prevalent immunomodulatory activity at the intestinal level, polyphenols represent a nutritionally relevant class of plant secondary metabolites.

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: n-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyses the NAD -dependent oxidative phosphorylation of n-glyceraldehyde-3-phosphate to 1,3-diphospho-n-glycerate and its reverse reaction in glycolysis and gluconeogenesis. : Four distinct crystal structures of human n-Glyceraldehyde-3-phosphate dehydrogenase ( GAPDH) have been determined from protein purified from the supernatant of HEK293F human epithelial kidney cells. : X-ray crystallography and mass-spectrometry indicate that the catalytic cysteine of the protein ( GAPDH Cys152) is partially oxidised to cysteine S-sulfonic acid.

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Wine grape pomace, the by-product of wine making, is a source of polyphenols, metals, and organic acids, and may be exploited for the production of functional beverages. Among red wines, Primitivo and Negramaro varieties possess an interesting amount of polyphenolic compounds and other chemicals. Consequently, study of the biological activity of Primitivo and Negramaro vinification by-products is of great interest as well as optimizing the extraction of its bioactive components.

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Article Synopsis
  • * Researchers created a new mouse model (Winnie-) to study how low-grade chronic inflammation contributes to CRC development, by combining Mucin 2 mutated mice with other mice.
  • * This Winnie- model indicates that chronic inflammation significantly raises the risk of tumor development in genetically predisposed individuals, as it shows early signs of inflammation and abnormal growth in the colon.
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Iron overload is an undesired effect of frequent blood transfusions or genetic diseases. Myelodysplastic syndrome (MDS) patients become transfusion dependent, but due to the combination of ineffective haematopoiesis and repeated blood transfusions they are often subject to iron overload. In this study, we demonstrate that iron-overload mimicking condition alters bone marrow progenitor differentiation towards dendritic cells (DCs).

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Article Synopsis
  • Global warming poses a significant threat to plant growth and agricultural production, making it crucial to identify tomato genotypes that perform well in high temperatures for future breeding programs.
  • The study evaluated various tomato landraces under elevated temperatures, revealing differences in yield, fruit quality, and bioactive compounds, with landraces E30, E94, and PDVIT showing superior performance.
  • The findings suggest that new tomato landraces can be identified for their ability to yield well and maintain nutritional quality in hot climates, providing valuable insights for breeding initiatives.
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Background: Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a multifactorial disorder characterized by chronic inflammation and altered gut barrier function. Dysbiosis, a condition defined by dysregulation of the gut microbiome, has been reported in patients with IBD and in experimental models of colitis. Although several factors have been implicated in directly affecting gut microbial composition, the genetic determinants impacting intestinal dysbiosis in IBD remain relatively unknown.

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Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic inflammation. We produced organoids from the ulcerative colitis murine model Winnie to explore if the chronic inflammatory features observed in the parental intestine were preserved by the organoids.

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Endoplasmic reticulum glycoprotein folding quality control (ERQC) and ER-associated degradation (ERAD) preside over cellular glycoprotein secretion and maintain steady glycoproteostasis. When cells turn malignant, cancer cell plasticity is affected and supported either by point mutations, preferential isoform selection, altered expression levels, or shifts to conformational equilibria of a secreted glycoprotein. Such changes are crucial in mediating altered extracellular signalling, metabolic behavior, and adhesion properties of cancer cells.

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Plants offer a simpler and cheaper alternative to mammalian animal models for the study of endoplasmic reticulum glycoprotein folding quality control (ERQC). In particular, the () innate immune response to bacterial peptides provides an easy means of assaying ERQC function in vivo. A number of mutants that are useful to study ERQC have been described in the literature, but only for a subset of these mutants the innate immune response to bacterial elicitors has been measured beyond monitoring plant weight and some physio-pathological parameters related to the plant immune response.

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Several studies have identified a specific metabolic program that is associated with the process of epithelial-mesenchymal transition (EMT). Whereas much is known about the association between glucose metabolism and EMT, the contribution of lipid metabolism is not still completely understood. Here, we studied epithelial and mesenchymal breast cancer cells by proteomic and lipidomic approaches and identified significant differences that characterised these models concerning specific metabolic enzymes and metabolites including fatty acids and phospholipids.

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