127 research outputs found
Microbiota and LPS-Induced Obesity Inflammation: Therapeutic Implications
No full textObesity and chronic low-grade inflammation are becoming global epidemics. The dysbiosis has a specific role in the metabolism and energy stocks of the host. The discovery that a low-grade of inflammation could be directly connected to the intestinal microbiota metabolic endotoxemia (elevated levels of plasma lipopolysaccharides) has allowed the identification of novel mechanisms involved in the control of the intestinal barrier. In this review, it will analyze the latest news to explain how human symbiotic microorganisms participate in the growth of the fat reserves and promote insulin resistance as a low-grade inflammation. Besides, it will discuss new treatments with probiotics and prebiotics as a promising therapeutic approach to reverse the host's metabolic changes linked to dysbiosis observed in obesity
Genotype-phenotype correlation in Cystic Fibrosis: the role of modifier genes.
No full textMore than 1,000 mutations have been identified in the cystic fibrosis (CF) transmembrane regulator (CFTR) disease gene. The impact of these mutations on the protein and the wide spectrum of CF phenotypes prompted a series of Genotype-Phenotype correlation studies. The CFTR genotype is invariably correlated with pancreatic status-in about 85% of cases with pancreatic insufficiency and in about 15% of cases with pancreatic sufficiency. The correlations between the CFTR genotype and pulmonary, liver, and gastrointestinal expression are debatable. The heterogeneous phenotype in CF patients bearing the same genotype or homozygotes for nonsense mutations implicated environmental and/or genetic factors in the disease. However, the discordant phenotype observed in CF siblings argued against a major role of environmental factors and suggested that genes other than CFTR modulate the CF phenotype. A locus that modulates gastrointestinal expression was identified in mice and subsequently in humans. By analyzing nine CF patients discordant for meconium ileus we were able to show that this locus had a dominant effect. Moreover, in a collaborative study we found a higher rate of polymorphisms in β-defensin genes 1 and 2 in CF patients and in controls. In another multicenter study mutations in α-1 antitrypsin (A1AT) and mannose binding lectin genes were found to be independent risk factors for liver disease in CF patients. The body of evidence available suggests that the variegated CF phenotype results from complex interactions between numerous gene products
Craft Non-Alcoholic and Low-Alcohol Beer (NABLAB): Perceived Role as Functional Foods Among Italian Consumers and a Focus on Benefits for Well-Being and Physical Activity
No full textThis study investigates Italian consumers' perceptions and generational differences regarding craft non-alcoholic/low-alcohol beers (NABLAB) as functional beverages. An online survey reveals growing interest linked to wellness benefits, though product familiarity remains limited. Receptiveness is highest among Baby Boomers and Millennials, while Generation Z shows curiosity.
The findings suggest that enhanced availability and health-focused communication could promote these products and support a cultural shift toward reduced alcohol consumption
Synthetic analogs of human beta-defensin having antimicrobial, antiviral and chemotactic activity
No full textThe invention concerns peptides having sequences corresponding to fragments of human beta defensins 1 and/or 3 having antibacterial and/or antiviral activity, even in the presence of high sodium chloride concentration
Dimerization in tailoring uptake efficacy of the HSV-1 derived membranotropic peptide gH625
No full textgH625 constitutes a promising delivery vehicle for the transport of therapeutic biomacromolecules across membrane barriers. We report an application of multivalency to create a complex nanosystem for delivery and to elucidate the mechanism of peptide-lipid bilayer interactions. Multivalency may offer a route to enhance gH625 cellular uptake as demonstrated by results obtained on dimers of gH625 by fluorescence spectroscopy, circular dichroism, and surface plasmon resonance. Moreover, using both phase contrast and light sheet fluorescence microscopy we were able to characterize and visualize for the first time the fusion of giant unilamellar vesicles caused by a membranotropic peptide
Low expression of human beta-defensin 1 in duodenum of celiac patients is partially restored by a gluten-free diet.
No full textBACKGROUND: Human beta-defensins (hBDs) are small cationic, widely expressed proteins involved in innate immunity that exert strong bactericidal activity toward various pathogens. However, the role of hBDs in various diseases to which bacterial infection add severity, as it is in celiac disease (CD), is not yet clear. We analyzed the expression of the hBD1, hBD2, hBD3 and hBD4 genes in patients with CD during the active phase and after remission following a gluten-free diet to determine their role in development and relapse of CD.
METHODS: We studied 21 unrelated adults with CD (confirmed by anti-thyroglobulin antibodies and intestinal biopsy); 14 were evaluated at diagnosis, before diet modification, and seven after 2 years of a gluten-free diet. Thirty-six unrelated adults served as controls. We analyzed the mRNA expression of hBD1, 2, 3 and 4 on biopsy samples of duodenum obtained from all patients during endoscopy for diagnostic purposes. We used real-time polymerase chain reaction with TaqMan probes and obtained gene expression data using the delta-Ct method.
RESULTS: hBD1 mRNA was significantly lower in patients with active CD compared with patients on diet modification, whereas the mRNA levels of the other three defensins did not differ significantly between the two subgroups. Interestingly, the gluten-free diet restored only partially hBD1 expression as compared to a normal group of celiac-free subjects.
CONCLUSIONS: Our data reinforce the evidence that hBD1 expression is greatly reduced in the duodenum of patients with active CD. It also strengthens the concept that reduced activity of immune peptides may predispose individuals to bacterial proliferation that contributes to the pathogenesis of C
Host defense peptide-derived privileged scaffolds for anti-infective drug discovery
No full text'Privileged scaffolds' are molecular frameworks which have been successfully exploited for small molecule drug discovery. Peptide privileged scaffolds, featuring a strictly conserved multiple-disulfide framework and high variability in the rest of the sequence, display a broad range of biological effects, including antimicrobial and antiviral activity. Unlike small molecules, however, the cost of manufacturing these peptides is high, and their synthesis challenging. We previously described a simplified privileged scaffold corresponding to the γ-core of human β-defensin-3 (HBD3). The γ-core is a common structural signature found in virtually all host defense peptides (HDPs) stabilized by multiple disulfides, and we showed that for HBD3, it represents the evolutionary starting point of the full-length molecule and, thus, is itself a primordial HDP. Accordingly, we showed that the peptide folded rapidly and was stable in human serum, and displayed many of the biological activities of HBD3. We report here that in addition to the previously reported antibacterial activity on planktonic bacteria, the γ-core peptide is active against biofilm formation and maturation. We also show that it is readily cell penetrant, like HBD3, although with a different mechanism, which is independent from CD98. Overall, the potency of the single-disulfide, 23-amino acid γ-core is comparable with the full-length peptide across the whole spectrum of examined properties, and the peptide is not toxic to human cells. The HBD3 γ-core peptide may therefore represent the first example of an economically viable lead peptide derived from a HDP privileged scaffold. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd
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