Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
1.
Front Plant Sci ; 14: 1286803, 2023.
Article in English | MEDLINE | ID: mdl-37965015

ABSTRACT

The growing interest in plant protein sources, such as pulses, is driven by the necessity for sustainable food production and climate change mitigation strategies. Faba bean (Vicia faba L.) is a promising protein crop for temperate climates, owing to its remarkable yield potential (up to 8 tonnes ha-1 in favourable growing conditions) and high protein content (~29% dry matter basis). Nevertheless, the adoption of faba bean protein in plant-based products that aim to resemble animal-derived counterparts is hindered by its distinctive taste and aroma, regarded as "off-flavors". In this review, we propose to introduce off-flavor as a trait in breeding programs by identifying molecules involved in sensory perception and defining key breeding targets. We discuss the role of lipid oxidation in producing volatile and non-volatile compounds responsible for the beany aroma and bitter taste, respectively. We further investigate the contribution of saponin, tannin, and other polyphenols to bitterness and astringency. To develop faba bean varieties with diminished off-flavors, we suggest targeting genes to reduce lipid oxidation, such as lipoxygenases (lox) and fatty acid desaturases (fad), and genes involved in phenylpropanoid and saponin biosynthesis, such as zero-tannin (zt), chalcone isomerase (chi), chalcone synthase (chs), ß-amyrin (bas1). Additionally, we address potential challenges, including the need for high-throughput phenotyping and possible limitations that could arise during the genetic improvement process. The breeding approach can facilitate the use of faba bean protein in plant-based food such as meat and dairy analogues more extensively, fostering a transition toward more sustainable and climate-resilient diets.

2.
Int J Mol Sci ; 24(4)2023 Feb 16.
Article in English | MEDLINE | ID: mdl-36835367

ABSTRACT

Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and Ulcerative Colitis (UC), are multifactorial disorders characterized by a chronic inflammatory status with the secretion of cytokines and immune mediators. Biologic drugs targeting pro-inflammatory cytokines, such as infliximab, are broadly used in the treatment of IBD patients, but some patients lose responsiveness after an initial success. The research into new biomarkers is crucial for advancing personalized therapies and monitoring the response to biologics. The aim of this single center, observational study is to analyze the relationship between serum levels of 90K/Mac-2 BP and the response to infliximab, in a cohort of 48 IBD patients (30 CD and 18 UC), enrolled from February 2017 to December 2018. In our IBD cohort, high 90K serum levels were found at baseline in patients who then developed anti-infliximab antibodies at the fifth infusion (22 weeks after the first), becoming non-responders (9.76 ± 4.65 µg/mL compared to 6.53 ± 3.29 µg/mL in responder patients, p = 0.005). This difference was significant in the total cohort and in CD, but not significant in UC. We then analyzed the relationship between serum levels of 90K, C-reactive protein (CRP), and Fecal calprotectin. A significant positive correlation was found at baseline between 90K and CRP, the most common serum inflammation marker (R = 0.42, p = 0.0032). We concluded that circulating 90K could be considered a new non-invasive biomarker for monitoring the response to infliximab. Furthermore, 90K serum level determination, before the first infliximab infusion, in association with other inflammatory markers such as CRP, could assist in the choice of biologics for the treatment of IBD patients, thereby obviating the need for a drug switch due to loss of response, and so improving clinical practice and patient care.


Subject(s)
Biological Products , Colitis, Ulcerative , Crohn Disease , Infliximab , Humans , Biological Products/therapeutic use , Biomarkers , C-Reactive Protein/metabolism , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Cytokines/therapeutic use , Infliximab/therapeutic use
3.
Cell Mol Gastroenterol Hepatol ; 14(1): 151-171, 2022.
Article in English | MEDLINE | ID: mdl-35314399

ABSTRACT

BACKGROUND & AIMS: Inflammatory bowel diseases are multifactorial diseases commonly treated with either immunomodulatory drugs or anti-tumor necrosis factor (TNF). Currently, failure to respond to anti-TNF therapy (assessed no earlier than 8-12 weeks after starting treatment) occurs in 20%-40% of patients enrolled in clinical trials and in 10%-20% in clinical practice. Murine models of inflammatory bowel disease provide important tools to better understand disease mechanism(s). In this context and among the numerous models available, Winnie-TNF-knockout (KO) mice recently were reported to show characteristics of ulcerative colitis (UC) that are independent of TNF, and with increased interleukin (IL)1ß production. METHODS: Herein, the efficacy of recombinant IL1-receptor antagonist (anakinra) administration was evaluated in Winnie-TNF-KO mice, used as a UC model of primary anti-TNF nonresponders. RESULTS: We analyzed gut mucosal biopsy specimens and circulating cytokine profiles of a cohort of 30 UC patients; approximately 75% of primary nonresponders were characterized by abundant IL1ß in both the serum and local intestinal tissues. In Winnie-TNF-KO mice, administration of anakinra efficiently reduced the histologic score of the distal colon, which represents the most common site of inflammation in Winnie mice. Furthermore, among lamina propria and mesenteric lymph node-derived T cells, interferon γ-expressing CD8+ T cells were reduced significantly after anakinra administration. CONCLUSIONS: Our study provides new insight and alternative approaches to treat UC patients, and points to anti-IL1 strategies (ie, anakinra) that may be a more effective therapeutic option for primary nonresponders to anti-TNF therapy.


Subject(s)
Colitis, Ulcerative , Inflammatory Bowel Diseases , Animals , CD8-Positive T-Lymphocytes , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Disease Models, Animal , Humans , Inflammation/pathology , Inflammatory Bowel Diseases/pathology , Interleukin 1 Receptor Antagonist Protein/pharmacology , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-1beta , Intestinal Mucosa/pathology , Mice , Mice, Knockout , Tumor Necrosis Factor Inhibitors , Tumor Necrosis Factor-alpha
4.
Antioxidants (Basel) ; 11(1)2022 Jan 08.
Article in English | MEDLINE | ID: mdl-35052642

ABSTRACT

Antioxidants are privileged candidates for the development of adjuvants able to improve the efficiency of pharmacological therapies, particularly for chronic inflammatory syndromes. During the last 20 years, anti-TNFα (tumor necrosis factor alpha) monoclonal antibodies infusion has been the biological therapy most frequently administered but there is still large space for improvement in disease remission rates and maintenance. In this context, nutritional bioactive compounds contained in dietary patterns or included as supplements, may act as adjuvants for the induction and maintenance of IBD (inflammatory bowel diseases) remission. To verify this possibility, a single-center preliminary study (SI-CURA, Soluzioni Innovative per la gestione del paziente e il follow up terapeutico della Colite UlceRosA) was designed and carried out to evaluate whether a daily administration of purple corn supplement could improve the response to Infliximab (IFX) infusion of IBD patients with both Crohn's disease (CD) and ulcerative colitis (UC). A cohort of 47 patients was enrolled in the study. Biological samples were collected before the first and the third IFX infusion. All patients received nutritional guidelines, 27 of them received commercial red fruit tea with low anthocyanins content, while 20 received a purple corn supplement with a high anthocyanin content. Results show that the administration of an antioxidant-enriched purple corn supplement could improve IFX-mediated disease remission in terms of circulating inflammatory markers. Comparison between CD and UC patients revealed that, at this anthocyanin dosage, the purple corn extract administration improved the IFX response in CD but not in UC patients. Our results may pave the way for a new metacentric study of CD patients, recruiting a wider cohort and followed-up over a longer observational time.

5.
Front Plant Sci ; 13: 1099293, 2022.
Article in English | MEDLINE | ID: mdl-36684793

ABSTRACT

Establishing Lupinus mutabilis as a protein and oil crop requires improved varieties adapted to EU climates. The genetic regulation of strategic breeding traits, including plant architecture, growing cycle length and yield, is unknown. This study aimed to identify associations between 16 669 single nucleotide polymorphisms (SNPs) and 9 agronomic traits on a panel of 223 L. mutabilis accessions, grown in four environments, by applying a genome wide association study (GWAS). Seven environment-specific QTLs linked to vegetative yield, plant height, pods number and flowering time, were identified as major effect QTLs, being able to capture 6 to 20% of the phenotypic variation observed in these traits. Furthermore, two QTLs across environments were identified for flowering time on chromosome 8. The genes FAF, GAMYB and LNK, regulating major pathways involved in flowering and growth habit, as well as GA30X1, BIM1, Dr1, HDA15, HAT3, interacting with these pathways in response to hormonal and environmental cues, were prosed as candidate genes. These results are pivotal to accelerate the development of L. mutabilis varieties adapted to European cropping conditions by using marker-assisted selection (MAS), as well as to provide a framework for further functional studies on plant development and phenology in this species.

6.
Mol Nutr Food Res ; 65(21): e2100428, 2021 11.
Article in English | MEDLINE | ID: mdl-34495579

ABSTRACT

SCOPE: The study aims to investigate the effects of fresh table grape consumption in healthy subjects on circulating levels of the most common human microRNAs (miRNAs). The regulatory network governed by these modulated miRNAs is also investigated. METHODS AND RESULTS: Autumn Royal table grape, used in this study, is chosen for its high polyphenolic content and antioxidant properties. The study is a randomized controlled trial, in which 40 consecutive subjects are recruited on a voluntary basis and randomly assigned to two groups of the study, the control group, receiving only dietary recommendations and a grape group receiving a daily dose of 5 g of fresh table grape per kg of body weight for 21 days. All analyses are performed at baseline and after 21 days of dietary treatment. Circulating miRNAs levels are detected by Real-Time quantitative PCR (RT-qPCR) followed by bioinformatic functional analysis. The study identifies 20 circulating miRNAs differentially expressed in healthy subjects after grape intake, and in particular, 18 of 20 are down-regulated and 2 are up-regulated. CONCLUSION: The dietary intake of table grape affects circulating miRNAs levels in healthy subjects, particularly the miRNAs related to pathways involved in counteracting cancer development, including gastrointestinal cancers.


Subject(s)
Circulating MicroRNA , Gastrointestinal Neoplasms , MicroRNAs , Vitis , Healthy Volunteers , Humans
7.
Front Cell Infect Microbiol ; 11: 622327, 2021.
Article in English | MEDLINE | ID: mdl-34178715

ABSTRACT

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. Females received enriched diets two weeks before the beginning of the breeding and never stopped for the following six months. No significant effect was observed in regard to the percentage of Winnie-/- offspring, as with both diets the percentage was about 25% as expected. Winnie littermates from breeders fed with the Bronze-enriched diet showed reduced dysbiosis at 4 weeks of age if compared with Winnie under the Control tomato diet. This effect was then reduced when mice reached adult age. Conversely, the microbiota of C57BL/6 does not change significantly, indicating that fortified mothers-diet significantly contribute to preventing dysbiosis in genetically predisposed offspring, but has mild effects on healthy littermates and adult mice. An overall tendency towards reduced inflammation was underlined by the colon weight and the percentage of Foxp3+ cells reduction in Winnie mice fed with Bronze diet. Control diet did not show similar tendency.


Subject(s)
Colitis, Ulcerative , Gastrointestinal Microbiome , Animals , Diet , Disease Models, Animal , Dysbiosis/prevention & control , Female , Lactation , Mice , Mice, Inbred C57BL , Polyphenols , Pregnancy
8.
J Cardiol Cases ; 23(4): 145-148, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33841589

ABSTRACT

We report an unusual case of heart failure due to massive myocardial calcification related to a rare combination of idiopathic mitral annular calcification, myocardial calcification of the left ventricular septum and the inferior wall without other predisposing factors, such as previous myocardial infarction, ventricular aneurysms, myocarditis, rheumatic heart disease, tuberculosis, chronic renal failure, or systemic metabolic disease (sarcoidosis or primary hyperoxaluria). The related restrictive pattern of diastolic filling of the left ventricle could explain this unusual case of heart failure with preserved ejection fraction. .

9.
Int J Mol Sci ; 22(8)2021 Apr 09.
Article in English | MEDLINE | ID: mdl-33918878

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome, characterized from pathological changes in lipid and carbohydrate metabolism. Its main characteristics are excessive lipid accumulation and oxidative stress, which create a lipotoxic environment in hepatocytes leading to liver injury. Recently, many studies have focused on the identification of the genetic and epigenetic modifications that also contribute to NAFLD pathogenesis and their prognostic implications. The present review is aimed to discuss on cellular and metabolic alterations associated with NAFLD, which can be helpful to identify new noninvasive biomarkers. The identification of accumulated lipids in the cell membranes, as well as circulating cytokeratins and exosomes, provides new insights in understanding of NAFLD. This review also suggests that lifestyle modifications remain the main prevention and/or treatment for NAFLD.


Subject(s)
Biomarkers , Disease Susceptibility , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Animals , Cytokines/metabolism , Diet , Disease Management , Exercise , Exosomes , Fatty Acids/metabolism , Health Behavior , Hepatocytes/metabolism , Humans , Life Style , Lipid Metabolism , Lipidomics , Lipids/blood , Microbiota , Non-alcoholic Fatty Liver Disease/diagnosis
10.
Viruses ; 13(5)2021 04 22.
Article in English | MEDLINE | ID: mdl-33922257

ABSTRACT

In order to provide insights into the evolutionary and epidemiological viral dynamics during the current COVID-19 pandemic in South Eastern Italy, a total of 298 genomes of SARS-CoV-2 strains collected in the Apulia and Basilicata regions, between March 2020 and January 2021, were sequenced. The genomic analysis performed on the draft genomes allowed us to assign the genetic clades and lineages of belonging to each sample and provide an overview of the main circulating viral variants. Our data showed the spread in Apulia and Basilicata of SARS-CoV-2 variants which have emerged during the second wave of infections and are being currently monitored worldwide for their increased transmission rate and their possible impact on vaccines and therapies. These results emphasize the importance of genome sequencing for the epidemiological surveillance of the new SARS-CoV-2 variants' spread.


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , Base Sequence , COVID-19/epidemiology , Genome, Viral , Humans , Italy/epidemiology , Pandemics , Phylogeny , Retrospective Studies , SARS-CoV-2/classification , Whole Genome Sequencing
11.
Foods ; 10(5)2021 Apr 28.
Article in English | MEDLINE | ID: mdl-33925123

ABSTRACT

Current projections estimate that in 2050 about 10 billion people will inhabit the earth and food production will need to increase by more than 60%. Food security will therefore represent a matter of global concern not easily tackled with current agriculture practices and curbed by the increasing scarcity of natural resources and climate change. Disrupting technologies are urgently needed to improve the efficiency of the food production system and to reduce the negative externalities of agriculture (soil erosion, desertification, air pollution, water and soil contamination, biodiversity loss, etc.). Among the most innovative technologies, the production of microbial protein (MP) in controlled and intensive systems called "bioreactors" is receiving increasing attention from research and industry. MP has low arable land requirements, does not directly compete with crop-based food commodities, and uses fertilizers with an almost 100% efficiency. This review considers the potential and limitations of four MP sources currently tested at pilot level or sold as food or feed ingredients: hydrogen oxidizing bacteria (HOB), methanotrophs, fungi, and microalgae (cyanobacteria). The environmental impacts (energy, land, water use, and GHG emissions) of these MP sources are compared with those of plant, animal, insect, and cultured meat-based proteins. Prices are reported to address whether MP may compete with traditional protein sources. Microalgae cultivation under artificial light is discussed as a strategy to ensure independence from weather conditions, continuous operation over the year, as well as high-quality biomass. The main challenges to the spreading of MP use are discussed.

12.
Cancers (Basel) ; 13(2)2021 Jan 14.
Article in English | MEDLINE | ID: mdl-33466665

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (the Winnie-APCMin/+) combining inflammation and genetics. METHODS: Gut microbiota profiling was performed on 8-week-old Winnie-APCMin/+ mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother's genetics in ACF development, the large intestines of APCMin/+ mice born from wild type mice were investigated by histological analysis at 8 weeks. RESULTS: ACF development in 8-week-old Winnie-APCMin/+ mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APCMin/+ hosts leads to an increased rate of ACF development. CONCLUSIONS: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring.

13.
Sci Rep ; 10(1): 15942, 2020 09 29.
Article in English | MEDLINE | ID: mdl-32994523

ABSTRACT

Dendritic cells are the most important antigen-presenting cells that link the innate and acquired immune system. In our previous study, we identified that the upregulation of miR-369-3p suppresses the LPS-induced inflammatory response, reducing C/EBP-ß, TNFα and IL-6 production. With the aim of gaining further insight into the biological function of miR-369-3p during acute inflammatory response, in the present study we identified novel gene targets of miR-369-3p and demonstrated the suppressive ability of these genes on the inflammatory dendritic cells. Bioinformatic analyses revealed that iNOS is a potential target of miR-369-3p. We demonstrated that the ectopic induction of miR-369-3p markedly reduced iNOS mRNA and protein as well as NO production. Moreover, we found that the upregulation of miR-369-3p decreased the release of TNFα, IL-6, IL-12, IL-1α, IL-1ß in response to LPS, and increased the production of anti-inflammatory cytokines such as IL-10 and IL-1RA. In addition, LPS-induced nuclear translocation of NF-kB was inhibited by miR-369-3p. Levels of miR-369-3p were decreased in human inflamed regions of human intestine obtained from IBD patients. Our results provide novel additional information on miR-369-3p as a potential core of the signaling regulating the inflammatory response. These findings suggest that miR-369-3p should be considered as a potential target for the future development of new molecular therapeutic approaches.


Subject(s)
Inflammation/genetics , MicroRNAs/genetics , Nitric Oxide Synthase Type II/metabolism , Animals , CCAAT-Enhancer-Binding Protein-beta/metabolism , Cytokines/metabolism , Dendritic Cells/metabolism , Dendritic Cells/physiology , Inflammation/metabolism , Interleukin-12/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Male , Mice , Mice, Inbred C57BL , MicroRNAs/metabolism , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/metabolism
14.
Int J Mol Sci ; 21(8)2020 Apr 23.
Article in English | MEDLINE | ID: mdl-32340123

ABSTRACT

(1) Background: Colorectal cancer (CRC) is among the best examples of the relationship between inflammation and increased cancer risk. (2) Methods: To examine the effects of spontaneous low-grade chronic inflammation on the pathogenesis of CRC, we developed a new murine model of colitis-associated cancer (CAC) by crossing Mucin 2 mutated mice (Winnie) with ApcMin/+ mice. (3) Results: The resulting Winnie-ApcMin/+ model combines an inflammatory background with a genetic predisposition to small intestinal polyposis. Winnie-ApcMin/+ mice show an early occurrence of inflammatory signs and dysplastic lesions in the distal colon with a specific molecular signature. (4) Conclusion: The Winnie-ApcMin/+ model is a perfect model to demonstrate that chronic inflammation represents a crucial risk factor for the onset and progression of tumoral lesions in individuals genetically predisposed to CRC.


Subject(s)
Colitis-Associated Neoplasms/etiology , Disease Susceptibility , Genes, APC , Animals , Apoptosis/genetics , Biopsy , Cell Proliferation , Cytoskeleton , Disease Models, Animal , Disease Progression , Genetic Predisposition to Disease , Immunohistochemistry , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Mice , Neoplasm Grading
15.
Int J Mol Sci ; 21(4)2020 Feb 17.
Article in English | MEDLINE | ID: mdl-32079304

ABSTRACT

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). Cells cultured in iron-enriched culture medium for seven days fail to differentiate into conventional CD11c+MHCIIhi DCs and fail to efficiently respond to LPS (Lipopolysaccharides). Cells appear smaller than control DCs but vital and able to perform FITC-dextran (Fluorescein isothiocyanate-dextran) endocytosis. At molecular level, cells cultured in iron-enriched conditions show increased ARG1 and PU.1, and decreased IRF8 expression.


Subject(s)
Bone Marrow/metabolism , CD11c Antigen/metabolism , Cell Differentiation/physiology , Dendritic Cells/metabolism , Histocompatibility Antigens Class II/metabolism , Iron Overload/metabolism , Animals , Arginase/genetics , Arginase/metabolism , Bone Marrow/drug effects , Bone Marrow Cells/metabolism , Cytokines/metabolism , Dendritic Cells/drug effects , Gene Expression Regulation , Hematopoiesis , Inflammation , Interferon Regulatory Factors/genetics , Interferon Regulatory Factors/metabolism , Lipopolysaccharides/adverse effects , Mice , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Trans-Activators/metabolism
16.
Microb Drug Resist ; 26(8): 909-917, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32101078

ABSTRACT

Objective: Helicobacter pylori antibiotic resistance is a constantly evolving process and local surveillance is warranted to guide clinicians in the choice of therapy. Materials and Methods: Antibiotic susceptibility testing was performed by E-test on 92 H. pylori strains, and resistance to clarithromycin and levofloxacin was also evaluated using a commercially available genotyping method. Results: In naïve patients the resistance to clarithromycin, levofloxacin, and metronidazole was 37.7%, 26.2%, and 16.4%, respectively, significantly lower than the percentage found in treated patients. Concomitant resistance to ≥2 antibiotics was also observed in naïve patients. The A2143G mutation of the 23S-rRNA gene was the most frequently detected, also in naïve patients. The highest minimum inhibitory concentration (MIC)50 value (256 mg/L) was associated with A2142 mutations in all the patients carrying them. For levofloxacin resistance a mutation in codon 87 was detected in 63.9% and in codon 91 in 36.1% of the H. pylori strains, without significant differences in the patients groups. A mutation in codon 87 was associated with the highest MIC50 value (32 mg/L). Conclusions: In our area, a high prevalence of H. pylori primary resistance was detected; these rates were higher in patients who had experienced failure of several courses of therapy. A better knowledge of the local epidemiology of resistance, and the genotypes responsible, will improve the H. pylori eradication rates.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/drug effects , Drug Resistance, Bacterial/genetics , Helicobacter pylori/drug effects , Helicobacter pylori/genetics , Adult , Aged , Clarithromycin/pharmacology , Drug Resistance, Bacterial/physiology , Drug Therapy, Combination , Female , Genes, Bacterial , Genotyping Techniques , Humans , Italy , Levofloxacin/pharmacology , Male , Metronidazole/pharmacology , Microbial Sensitivity Tests , Middle Aged , Phenotype , Point Mutation , RNA, Ribosomal, 23S/genetics , Young Adult
17.
Inflamm Bowel Dis ; 26(4): 546-556, 2020 03 04.
Article in English | MEDLINE | ID: mdl-31748792

ABSTRACT

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. METHODS: We compared the microbiome of normal, uninflamed wild-type (WT) mice with that of a murine model of UC (ie, Winnie strain). Winnie mice possess a missense mutation in Muc2 that manifests in altered mucus production as early as 4 weeks of age, with ensuing colonic inflammation. To better address the potential role of mutant Muc2 in promoting dysbiosis in Winnie mice, we evaluated homozygous mutant mice (Winnie-/-) with their WT littermates that, after weaning from common mothers, were caged separately according to genotype. Histologic and inflammatory status were assessed over time, along with changes in their respective microbiome compositions. RESULTS: Dysbiosis in Winnie mice was already established at 4 weeks of age, before histologic evidence of gut inflammatory changes, in which microbial communities diverged from that derived from their mothers. Furthermore, dysbiosis persisted until 12 weeks of age, with peak differences in microbiome composition observed between Winnie and WT mice at 8 weeks of age. The relative abundance of Bacteroidetes was greater in Winnie compared with WT mice. Verrucomicrobia was detected at the highest relative levels in 4-week-old Winnie mice; in particular, Akkermansia muciniphila was among the most abundant species found at 4 weeks of age. CONCLUSIONS: Our results demonstrate that mutant genetic determinants involved in the complex regulation of intestinal homeostasis, such as that observed in Winnie mice, are able to promote early gut dysbiosis that is independent from maternal microbial transfer, including breastfeeding. Our data provide evidence for intestinal dysbiosis attributed to a Muc2-driven mucus defect that leads to colonic inflammation and may represent an important target for the design of future interventional studies.


Subject(s)
Colitis/genetics , Dysbiosis/genetics , Gastrointestinal Microbiome , Intestinal Mucosa/pathology , Mucin-2/genetics , Age Factors , Animals , Body Weight , Colitis/physiopathology , Colon/physiopathology , Disease Models, Animal , Dysbiosis/physiopathology , Female , Inflammation/genetics , Inflammation/physiopathology , Male , Mice , Mice, Inbred C57BL , Mutation, Missense , RNA, Ribosomal, 16S/genetics , Sex Factors
18.
Int J Mol Sci ; 20(22)2019 Nov 16.
Article in English | MEDLINE | ID: mdl-31744123

ABSTRACT

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. Furthermore, we investigated if quercetin administration to in vitro cultured organoids could suppress LPS-induced inflammation in wild-type organoids (WT-organoids) and spontaneous inflammation in ulcerative colitis organoids (UC-organoids). Our data demonstrate that small intestinal organoids obtained from Winnie mice retain the chronic intestinal inflammatory features characteristic of the parental tissue. Quercetin administration was able to suppress inflammation both in UC-organoids and in LPS-treated WT-organoids. Altogether, our data demonstrate that UC-organoids are a reliable experimental system for investigating chronic intestinal inflammation and pharmacological responses.


Subject(s)
Intestinal Mucosa/drug effects , Quercetin/pharmacology , Animals , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , Disease Models, Animal , Gene Expression/drug effects , In Vitro Techniques , Intestinal Mucosa/metabolism , Intestinal Mucosa/ultrastructure , Lipocalin-2/genetics , Lipocalin-2/metabolism , Lipopolysaccharides/toxicity , Mice , Mice, Inbred C57BL , Microscopy, Electron, Transmission , Secretory Leukocyte Peptidase Inhibitor/genetics , Secretory Leukocyte Peptidase Inhibitor/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
19.
J Stroke Cerebrovasc Dis ; 28(11): 104308, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31416760

ABSTRACT

Stroke involving some areas of the cerebral hemisphere, such as insula, amygdala, and lateral hypothalamus, may cause changes in autonomic control of cardiac function. A 58-year-old woman presented to the emergency department for acute onset of left facial-brachial-crural hemiparesis and dysarthria. A brain CT scan showed subacute ischemic lesion with hemorrhagic infarction in right insular-rolandic cortex. Over the next few days ECG showed severe bradycardia with elongation of QTc, significative pauses (5 seconds), runs of nonsustained ventricular tachycardia and torsades de pointes. Drug induced and other several possible causes of elongation of QT and bradycardia such as hypokalemia, a history of heart failure, and structural heart disease were ruled out. The case confirms that insular cortex plays a major role in stroke-induced cardiovascular changes.


Subject(s)
Cerebral Cortex/blood supply , Heart Conduction System/physiopathology , Heart Rate , Long QT Syndrome/etiology , Stroke/complications , Torsades de Pointes/etiology , Action Potentials , Bradycardia/etiology , Bradycardia/physiopathology , Cardiac Pacing, Artificial , Cerebral Cortex/diagnostic imaging , Female , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Long QT Syndrome/therapy , Middle Aged , Pacemaker, Artificial , Stroke/diagnostic imaging , Stroke/physiopathology , Stroke/therapy , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/physiopathology , Torsades de Pointes/diagnosis , Torsades de Pointes/physiopathology , Torsades de Pointes/therapy , Treatment Outcome
20.
J Electrocardiol ; 54: 90-92, 2019.
Article in English | MEDLINE | ID: mdl-30965210

ABSTRACT

Brugada phenocopies are clinical entities characterized by electrocardiographic patterns that are identical to true Brugada syndrome, but are elicited by a number of clinical circumstances. ECG normalizes upon resolution of underlying condition, family history of arrhythmic syncope or ventricular arrhythmias is strictly absent and provocative tests with sodium channel blockers have to be negative. We describe herein the case of type-2 ECG Brugada pattern in a patient with acute pulmonary embolism presenting with recurrent syncope but negative provocative test with sodium channel blockers. Transthoracic echocardiography and transcranial Doppler did not show atrial septal defect. In conclusion, to the best of our knowledge no other cases excluded atrial septal defect and paradoxical embolism as a possible cause of acute pulmonary embolism related Type-2 Brugada ECG pattern. Therefore in our case right ventricle transmural myocardial ischemia due to acute pulmonary embolism, mainly secondary to right ventricle stretch, could explain Brugada ECG pattern.


Subject(s)
Brugada Syndrome/etiology , Electrocardiography , Pulmonary Embolism/complications , Syncope/etiology , Brugada Syndrome/diagnosis , Diagnosis, Differential , Echocardiography , Humans , Male , Middle Aged , Phenotype , Pulmonary Embolism/diagnosis , Syncope/diagnosis
SELECTION OF CITATIONS
SEARCH DETAIL
...