Animal Inhalation Models to Investigate Modulation of Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs) comprise primarily two disease manifestations, ulcerative colitis (UC) and Crohn’s disease (CD), each with distinctive clinical and pathological features. Environmental and clinical factors strongly affect the development and clinical outcomes of IBDs. Among environmental factors, cigarette smoke (CS) is considered the most important risk factor for CD, while it attenuates the disease course of UC. Various animal models have been used to assess the impact of CS on intestinal pathophysiology. This chapter examines the suitability of animal inhalation/smoke exposure models for assessing the contrary effects of CS on UC and CD. It presents an updated literature review of IBD mouse models and a description of possible mechanisms relevant to relationships between IBD and smoking. In addition, it summarises various technical inhalation approaches, in the context of mouse disease models of IBD

Klotho and vitamin D in multiple sclerosis: an Italian study

Introduction Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D3 levels, and multiple sclerosis (both risk and disease progression). Material and methods 107 patients with MS and 133 healthy controls were enrolled in this study. Serum 25(OH)D3 levels and genotyping of Klotho SNPs were evaluated in all participants by high-performance liquid chromatography and real-time polymerase chain reaction, respectively. Results Allelic and genotypic frequencies did not differ between patients and controls. Concerning rs1207568, we found a trend toward lower serum 25(OH)D3 levels in MS patients with A allele (mutant), both in heterozygosis (AG) and in homozygosis (AA), in comparison to MS patients with G allele in homozygosis (GG) (AG + AA 20.5 ±6.3 µg/l; GG 22.5 ±7.5 µg/l, p = 0.07). Conclusions Our findings did not identify a role of Klotho in the genetic susceptibility to MS

Down-regulation of the LXR transcriptome provides the requisite cholesterol levels to proliferating hepatocytes

n/

Clinical usefulness of presepsin and monocyte distribution width (MDW) kinetic for predicting mortality in critically ill patients in intensive care unit

Background In this study, we explored the accuracy of two new sepsis biomarkers, monocyte distribution width (MDW) and presepsin (PSP), compared to traditional ones, C-reactive protein (CRP) and Procalcitonin (PCT), to identify sepsis and predict intra-hospital mortality by analyzing their kinetic at different time points during hospitalization stay.Methods We enrolled 104 patients admitted to the intensive care unit (ICU) of University Hospital "Paolo Giaccone", Palermo. Among these, 30 (29%) had a clinical diagnosis of sepsis. MDW, PCT, CRP, and PSP were evaluated at admission (T0), after 24 h (T24), 48 h (T48), 72 h (T72), at day 5 (T5), and at discharge (TD).Results Patients with sepsis displayed higher levels of PCT and PSP than patients without sepsis at each timepoint; differently, CRP displayed statistically significant differences only at T0, while MDW only at T0 and T24. Patients with increasing levels of PSP displayed lower median survival time than patients with decreasing levels; differences reached statistical significance only at 48 h (20 vs. 29 days, log rank test, p = 0.046). Interestingly, PSP was an independent predictor of ICU mortality at 48 and 72 h after hospital admission. Also, the kinetic of PSP had prognostic value, with increased values at 48 h after admission being associated with reduced survival.Conclusion Our findings support the role of PSP and its kinetic as a predictor of ICU mortality

Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer

Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Here, we report a role for the NAD+-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1int-/-) have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view, the effects on mouse intestinal cell maturation are mediated by SIRT1-dependent changes in the acetylation status of SPDEF, a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC

Micellar lipid composition profoundly affects LXR‐dependent cholesterol transport across CaCo2 cells

Intraluminal phospholipids affect micellar solubilization and absorption of cholesterol. We here study cholesterol transport from taurocholate–phospholipid–cholesterol micelles to CaCo2 cells, and associated effects on ABC‐A1 mediated cholesterol efflux. Micellar incorporation of egg‐yolk‐phosphatidylcholine markedly increased apical retention of the sterol with decreased expression of ABC‐A1, an effect that is prevented by synthetic liver X receptor (LXR) or retinoid X receptor (RXR) agonists. On the other hand, incorporation of lyso‐phosphatidylcholine (LysoPC) increased ABC‐A1–HDL‐dependent basolateral cholesterol efflux, an effect that is abated when LXR is silenced. Thus, the modulation of cholesterol metabolism via intraluminal phospholipids is related to the activity of the oxysterol nuclear receptor LXR

Providing a nurse-led complex nursing INtervention FOcused on quality of life assessment on advanced cancer patients: The INFO-QoL pilot trial.

PURPOSE Unmet needs for advanced-disease cancer patients are fatigue, pain, and emotional support. Little information is available about the feasibility of interventions focused on patient-reported outcome measurement developed according to the Medical Research Council (MRC) Framework in advanced-disease cancer patients. We aimed to pilot a nurse-led complex intervention focused on QoL assessment in advanced-disease cancer patients. METHODS The INFO-QoL study was based on an exploratory, nonequivalent comparison group, pre-test-post-test design. Study sites received either the INFO-QoL intervention or usual care. Adult advanced-disease cancer patients admitted to hospice inpatient units that gave their informed consent were included in the study. Subjects were 187 patients and their families and 19 healthcare professionals. We evaluated feasibility, acceptability, and patients' outcomes using the Integrated Palliative Care Outcome Scale. RESULTS Nineteen healthcare professionals were included. The mean competence score increased significantly over time (p < 0.001) and the mean usefulness score was high 8.63 (±1.36). In the post-test phase, 54 patients were allocated to the experimental unit and 36 in the comparison unit. Compared to the comparison unit, in the experimental unit anxiety (R2 = 0.07; 95% CI = -0.06; 0.19), family anxiety (R2 = 0.22; 95% CI = -0.03; 0.41), depression (R2 = 0.31; 95% CI = -0.05; 0.56) and sharing feelings (R2 = 0.09; 95% CI = -0.05; 0.23), were improved between pre-test and post-test phase. CONCLUSIONS The INFO-QoL was feasible and potentially improved psychological outcomes. Despite the high attrition rate, the INFO-QoL improved the quality and safety culture for patients in palliative care settings

REV-ERBα Participates in Circadian SREBP Signaling and Bile Acid Homeostasis

The nuclear receptor REV-ERBα shapes the daily activity profile of Sterol Response Element Binding Protein (SREBP) and thereby participates in the circadian control of cholesterol and bile acid synthesis in the liver

Inflammatory Bowel Disease–Associated Changes in the Gut: Focus on Kazan Patients

BACKGROUND: Several studies have highlighted the role of host-microbiome interactions in the pathogenesis of inflammatory bowel disease (IBD), resulting in an increasing amount of data mainly focusing on Western patients. Because of the increasing prevalence of IBD in newly industrialized countries such as those in Asia, the Middle East, and South America, there is mounting interest in elucidating the gut microbiota of these populations. We present a comprehensive analysis of several IBD-related biomarkers and gut microbiota profiles and functions of a unique population of patients with IBD and healthy patients from Kazan (Republic of Tatarstan, Russia). METHODS: Blood and fecal IBD biomarkers, serum cytokines, and fecal short-chain fatty acid (SCFA) content were profiled. Finally, fecal microbiota composition was analyzed by 16S and whole-genome shotgun sequencing. RESULTS: Fecal microbiota whole-genome sequencing confirmed the presence of classic IBD dysbiotic features at the phylum level, with increased abundance of Proteobacteria, Actinobacteria, and Fusobacteria and decreased abundance of Firmicutes, Bacteroidetes, and Verrucomicrobia. At the genus level, the abundance of both fermentative (SCFA-producing and hydrogen (H2)-releasing) and hydrogenotrophic (H2-consuming) microbes was affected in patients with IBD. This imbalance was confirmed by the decreased abundance of SCFA species in the feces of patients with IBD and the change in anaerobic index, which mirrors the redox status of the intestine. CONCLUSIONS: Our analyses highlighted how IBD-related dysbiotic microbiota-which are generally mainly linked to SCFA imbalance-may affect other important metabolic pathways, such as H2 metabolism, that are critical for host physiology and disease development