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- Spagnuolo, R., et al.
(författare)
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Deregulation of SGK1 in Ulcerative Colitis: A Paradoxical Relationship Between Immune Cells and Colonic Epithelial Cells
- 2018
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998 .- 1536-4844. ; 24:9, s. 1967-1977
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammatory bowel disease (IBD) is due to the interaction of genetic and environmental factors that trigger an unbalanced immune response ultimately resulting in the peculiar inflammatory reaction. Experimental models of IBD point to a role of T-cell-derived cytokines (Th17) and to SGK1 as mediator of the Th17 switch. We hypothesize that SGK1, a salt inducible kinase, directs lymphocytic behavior and tissue damage. Methods: Eleven controls and 32 ulcerative colitis (UC) patients were randomized according to endoscopic Mayo score. Mucosal biopsies from different intestinal tracts were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction to check the expression of disease markers including SGK1. Peripheral blood mononuclear cells (PBMCs) from patients and controls were analyzed by fluorescence-activated cell sorting. Finally, an in vitro cell model was developed to test the hypothesis. Results: SGK1 mRNA and protein expression in lesional areas of UC patients were lower than in normal peri-lesional areas of the same patients and in normal tissues of healthy controls. SGK1 expression was increased in PBMCs from UC patients, particularly in the CD4+ cell population, enriched in Th17 cells. IL17/IL13 was increased in patients and correlated with SGK1 expression. Genetically engineered Jurkat cells confirmed the effect of SGK1 overexpression on viability of RKO cells. Conclusions: These observations suggest a pathogenic mechanism whereby SGK1 overexpression in CD4+ T cells induces the secretion of the inflammatory cytokines IL17 and IL13, which downregulate the expression of SGK1 in target tissues. Our data suggest a novel hypothesis in the pathogenesis of UC, integrating colonic epithelial cells and lymphocytes.
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- Spagnuolo, R., et al.
(författare)
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Satisfaction with Social Roles and Physical Function in Immune-mediated Inflammatory Diseases: A Cross-Sectional Study
- 2022
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Ingår i: Reviews on Recent Clinical Trials. - : Bentham Science Publishers Ltd.. - 1574-8871. ; 17:3, s. 177-186
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although mood disorders have been well characterized by immune-mediated inflammatory diseases, physical function and satisfaction with social roles have not yet been defined as independent domains. Objective: The study aims to assess satisfaction with social roles and physical function alterations in a population with immune-mediated inflammatory diseases and identify associated characteristics. Methods: Physical function and social role satisfaction were evaluated through the Patient-reported Outcomes Measurement System. Besides comparison between groups, univariate and multivariable logistic regression analyses were performed to identify independent predictors. Results: Two hundred sixty-five patients with immune-mediated inflammatory diseases and 206 controls were recruited. Compared to controls, patients with inflammatory bowel diseases had impaired physical function (p<0.001), while patients with inflammatory arthritis reported impairment in both domains (p<0.001, each). In the univariate logistic regression, gender, high school educational level, physical activity, and occupation were positively associated with physical function and social role satisfaction (pp=0.001; pp=0.001 and pp=0.012; p=0.008; p=0.004, respectively). Active disease and steroids were inversely associated with physical function and social roles satisfaction (p=0.033; p=0.022 and p=0.002; p=0.038, respectively). Further associations were found between age and physical function (p=0.002) and biological treatment and ESR with social roles satisfaction (pp=0.043; respectively). In the multivariable regression, gender was found to be associated with physical function (p<0.001) and social roles satisfaction (p=0.003). Negatively associated factors were biological treatment for satisfaction with social roles (p<0.001) and steroids for physical function (p=0.021), and social roles satisfaction (p=0.018). Conclusion: Immune-mediated inflammatory diseases determine alterations in physical function and social life satisfaction. Gender and treatment are independently associated factors. Patient-reported outcomes should be considered in clinical management to define patients' real needs.
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- Carvalho, Andre F., et al.
(författare)
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Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders
- 2020
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Ingår i: Translational Psychiatry. - : NATURE PUBLISHING GROUP. - 2158-3188. ; 10:1
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Forskningsöversikt (refereegranskat)abstract
- The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimers disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.
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- Gupta, Rahul, et al.
(författare)
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Element-resolved evidence of superdiffusive spin current arising from ultrafast demagnetization process
- 2023
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Ingår i: Phys. Rev. B. - : American Physical Society. ; 108:6
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Tidskriftsartikel (refereegranskat)abstract
- Using element-specific measurements of the ultrafast demagnetization of Ru/Fe65Co35 hetero-structures, we show that Ru can exhibit a significant magnetic contrast (3% asymmetry) resulting from ultrafast spin currents emanating from the demagnetization process of the FeCo layer. We use this magnetic contrast to investigate how superdiffusive spin currents are affected by the doping of heavy elements in the FeCo layer. We find that the spin currents are strongly suppressed, and that the recovery process in Ru slows down by Re doping. This is in accordance with a change in interface reflectivity of spin currents as found by the superdiffusive spin transport model.
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- Mancina, Rosellina Margherita, et al.
(författare)
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PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes
- 2016
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998. ; 22:1, s. 134-140
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. Methods: The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. Results: Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). Conclusions: Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.
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- Spagnuolo, R., et al.
(författare)
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Multifaceted pathogenesis of liver steatosis in inflammatory bowel disease: a systematic review
- 2021
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Ingår i: European Review for Medical and Pharmacological Sciences. - 1128-3602. ; 25:18, s. 5818-5825
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Non-Alcoholic Fatty Liver Disease (NAFLD), as a hepatic manifestation of metabolic syndrome (MET)-related obesity, insulin resistance, dyslipidemia, and hypertension, is the main cause of chronic liver disease. Inflammatory Bowel Diseases (IBD). (Crohn's Disease (CD) and Ulcerative Colitis (UC)). are often associated with extraintestinal manifestations. Of these. NAFLD is one of the most frequently reported. To highlight the etiopathogenesis of NAFLD in IBD, we performed a systematic review emphasizing the relationship between NAFLD genetic alterations, metabolic syndrome, and drugs. MATERIALS AND METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria, we performed a systematic literature search on PubMed, Google Scholar, and Web of Science for literature updated from 2010 to 1 March 2021. Inclusion criteria for studies were observational design and Randomized Controlled Trials (RCTs); written in English; primary research only; based on adult patients, and human research only. RESULTS: We identified nine studies on the link between NAFLD and IBD. Among these, two described the genetic predisposition to NAFLD of patients with IBD. Four reported an association between MetS and NAFLD in IBD patients. Regarding medications, none of four studies included. detected a relationship between NAFLD onset and IBD treatment (corticosteroids, immunomodulators, methotrexate, or biologics). However, a retrospective study showed a protective effect of anti-TNF alpha therapies against altered liver enzymes. CONCLUSIONS: In this interplay between genetic, metabolic, drug, and inflammatory factors, the underlying pathogenic mechanisms behind NAFLD in IBD are still far from clear. Further studies are needed to better clarify the role of individual components influencing the development of NAFLD in IBD.
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