Alginate-based microencapsulation of live cells may offer the opportunity to treat chronic and degenerative disorders. So far, a thorough assessment of physical-chemical behavior of alginate-based microbeads remains cloudy. A disputed issue is which divalent cation to choose for a high performing alginate gelling process. Having selected, in our system, high mannuronic (M) enriched alginates, we studied different gelling cations and their combinations to determine their eventual influence on physical-chemical properties of the final microcapsules preparation,in vitroandin vivo. We have shown that used of ultrapure alginate allows for high biocompatibility of the formed microcapsules, regardless of gelation agents, while use of different gelling cations is associated with corresponding variable effects on the capsules’ basic architecture, as originally reported in this work. However, only the final application which the capsules are destined to will ultimately guide the selection of the ideal, specific gelling divalent cations, since in principle there are no capsules that are better than others.
Aryl hydrocarbon receptor (AhR) is expected to promote initiation, progression and invasion of cancer cells regulating proliferation, differentiation, gene expression, inflammation, cell motility and migration. Furthermore, an immunosuppressant function of AhR has been recognized. This study evaluated AhR expression and its role in thyroid cancer progression. AhR expression was assessed by qPCR in 107 thyroid cancer samples (90 PTCs, 11 MTCs, 6 ATCs), and by immunohistochemistry in 41 PTCs. To estimate receptor activation, the expression of target genes CYP1A1 and CYP1B1 was measured. AhR functional effects were evaluated in kynurenine-stimulated FTC-133 and BcPap cell lines by analyzing the expression of genes involved in EMT and cell motility. AhR mRNA expression resulted significantly higher in all the analyzed thyroid cancer samples compared to normal thyroid and a statistically significant correlation with CYP1B1 was detected. Kynurenine-stimulated FTC-133 and BcPap showed the activation of a specific AhR-driven EMT program characterized by E-cadherin decrease and SLUG, N-cadherin and fibronectin increase, resulting in boost of cell motility and invasion. This study confirmed the importance of the IDO1-Kyn-AhR pathway in thyroid cancer tumorigenesis, suggesting an AhR pivotal role in mediating an immunosuppressive microenvironment and favoring the acquisition of a mesenchymal phenotype that could promote invasiveness and metastasis.
Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p < 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p ≤ 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc–CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.
Botulinum neurotoxin A (BoNT/A) appears to be one of the best intravesical treatments for interstitial cystitis/bladder painful syndrome (IC/BPS). We aimed to point out what the evidence is regarding the effects of BoNT/A intravesically injected in patients with IC/BPS. We performed a systematic review of all randomized controlled trials (RCTs) assessing BoNT/A for IC/BPS by using Medline, EMBASE, CINAHL, CENTRAL and MetaRegister of Controlled Trials. Standardized mean differences (SMD) were extracted from the available trials and combined in a meta-analysis applying a random effect model, including heterogeneity of effects. Twelve trials were identified. Significant benefits from BoNT/A injections were detected in: Interstitial Cystitis Symptom Index and Problem Index (ICSI, ICPI) (small to medium effect size: SMD = –0.302; p = 0.007 and –0.430, p = 0.004, respectively); Visual Analog Scale (VAS) for pain and day-time urinary frequency (medium effect size: SMD = –0.576, p < 0.0001 and –0.546, p = 0.013, respectively). A great effect size was detected for post-void residual volume (PVR, SMD = 0.728; p =0.002) although no clinically relevant in most cases. Great heterogeneity was observed in treatments’ methodologies and symptoms assessment. Overall, BoNT/A intravesical injections significantly improve some of the most relevant symptoms affecting IC/BPS patients.
Background: Non-alcoholic fatty liver disease (NAFLD) has an estimated prevalence of 20–30% in the general population and even higher in individuals with metabolic risk factors. The aim of this study was to evaluate the effect of a lifestyle intervention program on surrogate markers of hepatic steatosis in obesity and/or type 2 diabetes patients, enrolled in the C.U.R.I.A.Mo. (Centro Universitario di Ricerca Interdipartimentale Attività Motoria) trial. Methods: 102 subjects (56 females and 46 males, aged between 23 and 78) with type 2 diabetes, obesity or a BMI of at least 25 kg/m2 with comorbidities, participated in the intensive phase of a multidisciplinary lifestyle intervention program at the Healthy Lifestyle Institute of the University of Perugia (C.U.R.I.A.Mo.). Six indices related to NAFLD (Visceral Adiposity Index, Fatty Liver index, Non-Alcoholic Fatty Liver Disease liver fat score and liver fat equation, hepatic steatosis index and TyG index) were calculated before and after a three-month multidisciplinary lifestyle intervention. Results: The intervention improved the anthropometric and clinical parameters in the total population, the obese and/or diabetics. Data showed a significant weight loss, a reduced waist circumference, triglycerides, and an improvement in Mediterranean diet adherence. Hepatic steatosis indices were significantly reduced in the total population and in different subgroups (males, females, obesity and diabetes).