Role of chronic exsposure to cigarette smoke on endoglin/CD105 expression in airway epithelium.

Dysregulation of airway epithelial cell function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD and is associated to tissue damage and disease severity. CD105 is a component of the receptor complex of TGF-β, a pleiotropic cytokine involved in cellular proliferation, differentiation and migration. CD105 regulates the expression of different components of the extracellular matrix suggesting a role of CD105 in cellular transmigration and remodeling processes. The aim of the present study was to investigate the expression of endoglin/CD105 in airway epithelium of COPD patients and its involvement in tissue remodeling and progression of COPD. We evaluated the immunoreactivity for CD105 expression in bronchial biopsies isolated from COPD patients and healthy controls (HC). The analysis of metaplastic epithelium was performed in bronchial biopsies by Image Analysis software (Leica Quantimet system). Finally, we investigated the expression of CD105 protein receptor in human bronchial epithelial cells (16HBE cells) exposed to 5% Cigarette Smoke Extract (CSE) for 12 days by western blot. We found that the CD105 immunoreactivity was significantly higher in bronchial epithelium of COPD than HC. Morphometric analysis of bioptic samples of COPD showed an increase of the immunoreactivity for CD105 in the area of metaplastic than in not metaplastic epithelium. Long term exposure to CSE significantly up-regulated CD105 expression in 16HBE. Chronic inflammation due to cigarette smoke might play a critic role on the alteration of CD105 protein expression in COPD, promoting tissue remodeling, angiogenesis and dysregulation of physiological reparative mechanisms, leading to squamous metaplasia

Bladder Epicheck Test: A Novel Tool to Support Urothelial Carcinoma Diagnosis in Urine Samples

Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, cystoscopy, and radiological evaluation of the upper urinary tract are recommended during follow-up in the international urological guidelines. Cystoscopy is the standard examination for the first assessment and follow-up of NMIBC, and urine cytology is a widely used urinary test with high sensitivity for high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). In recent years, various urinary assays, including DNA methylation markers, have been used to detect bladder tumors. Among these, the Bladder EpiCheck test is one of the most widely used and is based on analysis of the methylation profile of urothelial cells to detect bladder neoplasms. This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences

THE ROLE OF BUTYRIC ACID AS A PROTECTIVE AGENT AGAINST INFLAMMATORY BOWEL DISEASES

Inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, are pathologies characterized by a chronic inflammation of the gastrointestinal tract. Their etiopathogenesis is not yet fully understood. Immune system and heat shock proteins (Hsps) dysfunctions are considered to be among the most likely causes of these diseases. Butyrate is a short-chain fatty acid mainly produced by intestinal microflora. It has a trophic, beneficial and protective role in the colonic mucosa, and it also induces changes in Hsp levels and localization. It may therefore be a valuable complementary therapeutic agent when used alongside traditional drugs (mesalazine and corticosteroids) to treat such conditions. The administration of specific probiotic formulations in order to increase the production of butyrate in the endoluminal environment may promote clinical remission in IBD patients. Due to these characteristics, there has been keen interest in the use of butyrate as a novel therapeutic supplement in the recent years. The current findings need to be validated through further clinical trials to better define the biomolecular dynamics of butyrate in the colonocytes of IBD patients

Fourier transform infrared analysis of urinary calculi and metabolic studies in a group of Sicilian children

Introduction. Prevalence of urinary calculi in children has been increasing in the past years. We performed an analysis of the chemical composition of stones formers of the pediatric population in our geographical area over the years 2005 to 2013. Materials and Methods. Fourier transform infrared spectroscopy was employed for the determination of the calculus composition of a group of Sicilian children, and metabolic studies were performed to formulate the correct diagnosis and establish therapy. Results. The prevalence of stone formation was much higher for boys than for girls, with a sex ratio of 1.9:1. The single most frequent component was found to be calcium oxalate monohydrate, and calcium oxalates (pure or mixed calculi) were the overall most frequent components. Calcium phosphates ranked 2nd for frequency, most often in mixed calculi, while urates ranked 3rd. The metabolic disorder most often associated with pure calcium oxalate monohydrate calculi was hypocitraturia, while hyperoxaluria was predominantly associated with calcium oxalate dihydrate calculi. Conclusions. Mixed calculi had the highest prevalence in our pediatric population. Our data showed that Fourier transform infrared spectroscopy was a useful tool for the determination of the calculi composition

Acute kidney injury in a patient with metabolic syndrome

Introduction: The metabolic syndrome (MS) encompasses many metabolic abnormalities and the insulin resistance is considered as one of the most significant denominators. The chronic kidney disease (CKD) is an emerging health problem but only few patients would reach the end stage renal disease. There exists an increasing strong association between MS and CKD, but up until now the link between MS and CKD is unclear and there are few studies regarding the renal histology in MS. Methods: We describe an acute tubulointerstitial nephritis case, due to both infective and pharmacological aetiology, overlapping relevant histological changes (focal segmental glomerulosclerosis [FSG], hyaline arteriosclerosis) in a patient with MS and previously normal renal function. Despite the severe vascular finding (elevated renal arterial resistive index), the patient recovered a normal renal function. Results: We reviewed the kidney pathological studies in MS and analyzed the principal renal histological images of glomerulomegaly, segmental glomerulosclerosis, and obesity-related glomerulopathy. Conclusion: Despite the strong association, the renal involvement in MS has not been proven. A greater knowledge of the combination of histological renal changes in MS can help to understand the pathophysiological mechanism(s) of MS

First-line ICIs in renal cell carcinoma

Treatment of metastatic renal cell carcinoma (mRCC) has radically changed, switching from interferon alfa (IFN-α) and high-dose interleukin−2 (HD IL−2) to new targeted therapies directed against tumoral neoangiogenesis, the mammalian target of the rapamycin (mTOR) pathway and immune checkpoints. Of note, the inhibition of immune checkpoints restores antitumor immune response, therefore promoting immune-mediated elimination of neoplastic cells. The best example of this targeted treatment is represented by PD-1/PD-L1 inhibition that has become the standard of care in mRCC treatment and has improved mRCC patients’ prognoses after failure of other targeted therapies. In this manuscript, we review the main therapeutic protocols adopted for mRCC, based on the use of immune checkpoint inhibitors (ICIs) alone or combined with other drugs

Targeted Therapies for Inflammatory Bowel Disease and Colorectal Cancer: An Increasing Need for Microbiota-Intestine Mutualism

The involvement of intestinal microbiota and dysbiosis in the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC) is a well-established fact to be taken into real consideration when developing tartgeted therapies. This review aimed to depict what advances in our understanding of the role of intestinal flora in the pathogenesis of IBD and CRC is shaping up the therapeutic protocols of their management. It was demonstrated that there is a circadian regulation of colocytes gene expression in response to microbiota. In addition, dysbiosis leading to a decrease in microbiome biodiversity was also described in IBD patients whereby thick layers of adherent mucosa associated bacteria exist both in ulcerative colitis (UC) and Crohn's disease (CD). Probiotics based approaches using lactobacilli and Bibidobacteria improved clinical symptoms of IBD's through the GALT immune modulation. In addition, fecal microbiota transplantation (FMT) has also been used for IBD treatment. It consists of transferring gastrointestinal microbiota from a healthy donor to an IBD patient by duodenal infusion of liquid stool suspension to establish microbial homeostasis. The passage of bacteria in the injured mucosal zone triggers chronic inflammation and eventually CRC development by creating a carcinogenic environment. Actually, high level of Fusobacterium nucleatun and other bacteria are prevalent in CRC patients, thus suggesting a potential role of these organisms in the initiation and progression processes due to the production of genotoxic metabolites causing a direct damage to DNA integrity. Moreover, regular probiotics intake was shown to actively prevent the whole process. In conclusion, the mutualistic relationship between microbiota and colonic mucosa proved useful in depicting some of the dynamics of the initiation and development of IBD and CRC. Therapies oriented towards establishing equilibrium of intestinal microbiota may represent the key strategy to switch off chronic inflammatory processes hitting colonic mucosa, thus preventing the onset of CRC

Forme fruste perimembranous ventricular septal defect: An autopsy report

Undiagnosed interventricular anatomic variants are not usually associated with sudden death or other cardiac conditions. We present images of a sieve-like interventricular fruste septal anatomic variant that was associated with sudden death in an otherwise healthy 48-year-old man

A Novel Morphological Parameter Predicting Fibrotic Evolution in Myeloproliferative Neoplasms: New Evidence and Molecular Insights

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) represent a group of hematological disorders that are traditionally considered as indistinct slow progressing conditions; still, a subset of cases shows a rapid evolution towards myelofibrotic bone marrow failure. Specific abnormalities in the megakaryocyte lineage seem to play a central role in this evolution, especially in the bone marrow fibrosis but also in the induction of myeloproliferation. In this review, we analyze the current knowledge of prognostic factors of MPNs related to their evolution to myelofibrotic bone marrow failure. Moreover, we focused the role of the megakaryocytic lineage in the various stages of MPNs, with updated examples of MPNs in vitro and in vivo models and new therapeutic implications