Cathepsin D Content in Colorectal Cancer

Cathepsin D content and activity were determined in matched paired sets of colorectal tumor tissue and normal mucosa and correlated with a number of biological and clinical parameters. Significantly higher cathepsin D activity was measured in tumor cytosol compared to paired normal mucosa (p < 0.02), in Dukes’ stage A tumors compared to Dukes’ B and C (p < 0.05), in tumors < 5 cm compared to those > 5 cm, or in tumors with a low proliferation rate compared to those with a high proliferation rate (p < 0.05). Moreover, significant differences in enzyme activity between tumor tissue and paired normal mucosa were observed in node-positive and G2 tumors (p < 0.05). No significa…

Difficoltà di identificazione della sindrome MEN2B ad esordio infantile: iter diagnostico.

Functional and molecular charecterizzation of cancer stam cells in anaplastic thyroid carcinoma

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease

Aliment Pharmacol Ther 2012; 35: 238–247 Summary Background  Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). Aims  To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. Methods  One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and H…

Resistin, visfatin, leptin and omentin are differently related to hormonal and metabolic parameters in growth hormone-deficient children

PURPOSE: The effect of growth hormone (GH) on adipose tissue and the role of adipokines in modulating metabolism are documented, but with discordant data. Our aim was to evaluate the impact of GH treatment on a series of selected adipokines known to have a metabolic role and poorly investigated in this setting. METHODS: This is a prospective study. Thirty-one prepubertal children (25 M, 6 F; aged 8.5 ± 1.6 years) with isolated GH deficiency treated with GH for at least 12 months and 30 matched controls were evaluated. Auxological and metabolic parameters, insulin sensitivity indexes, leptin, soluble leptin receptor, adiponectin, visfatin, resistin, omentin, adipocyte fatty acid-binding prot…

Ultrasound Parameters Can Accurately Predict the Risk of Malignancy in Patients with “Indeterminate TIR3b” Cytology Nodules: A Prospective Study

The increase in the incidence of thyroid nodules with cytological findings of TIR3b requires the identification of predictive factors of malignancy. We prospectively evaluated 2160 patients from January 2018 to June 2022 and enrolled 103 patients with indeterminate cytology TIR3b nodules who underwent total (73 patients) and hemi-thyroidectomy (30 patients). Among them, 61 had a histological diagnosis of malignancy (30 classic papillary thyroid carcinoma, 19 had follicular papillary thyroid carcinoma variant, 3 had Hurtle cell carcinoma and 9 had follicular thyroid carcinoma), while 42 had a benign histology. Clinical, ultrasonographic and cytological characteristics were recorded. In addit…

Levothyroxine and insulin requirement in autoimmune polyglandular type 3 syndrome: a real-life study

Abstract Purpose To evaluate factors influencing the insulin and levothyroxine requirement in patients with autoimmune polyglandular syndrome type 3 (APS-3) vs. patients with type 1 diabetes mellitus (T1DM) and autoimmune hypothyroidism (AH) alone, respectively. Methods Fifty patients with APS-3, 60 patients with T1DM and 40 patients with AH were included. Anthropometric, clinical and biochemical parameters were evaluated in all patients. Insulin requirement was calculated in patients with APS-3 and T1DM, while levothyroxine requirement was calculated in APS-3 and AH. Results Patients with APS-3 showed higher age (p = 0.001), age of onset of diabetes (p = 0.006) and TSH (p = 0.004) and lowe…

Serum visfatin levels in acromegaly: Correlation with disease activity and metabolic alterations

Objective: The studies that have extensively evaluated the relation between adipokines and metabolic parameters in acromegaly treatment are quite discordant. We aimed to evaluate and correlate a set of selected adipokines, known to have a metabolic role, with the disease activity, metabolic status and treatment modalities. Design: Data of 56 consecutive acromegalic patients (31 M and 25 F; aged 54 ± 12 years), admitted to the section of Endocrinology of the University of Palermo during the years 2005-2014, including 16 newly diagnosed untreated (ND), 21 during therapy with somatostatin analogues (SA), 12 with pegvisomant (PE) and 7 after surgical treatment (SU), grouped into uncontrolled (g…

Analisi dei meccanismi di controllo dell’apoptosi in una linea cellulare β-pancreatica resistente all’effetto delle citochine.

Th1 and Th2 cell phenotypes in AITD: role of allergy in Graves' disease

Thyrocytes--not innocent bystanders in autoimmune disease.

Distinct subsets of intrathyroidal regulatory CD4+CD25+ and CD8+CD25+ T cells in Hashimoto's thyroiditis: Potential role in the neoplastic cell growth.

Bioactive Scaffolds Based on Amine-Functionalized Gellan Gum for the Osteogenic Differentiation of Gingival Mesenchymal Stem Cells

With the aim to produce a cellularized construct for the guided bone regeneration of dento-alveolar defects, here we produce a porous scaffold using an amine derivative of gellan gum to host gingival mesenchymal stem cells (GMSCs) and allow their osteochondral differentiation. Three derivatives were produced by using the same synthetic procedure, and the viscoelastic properties of their aqueous dispersions were investigated and compared to those of the native polysaccharide to choose the derivative with suitable properties for the scaffold production. Freeze-drying was used to obtain a porous sponge that can be rehydrated with the cells’ suspension to produce an implantable cell containing …

Dual drug-loaded halloysite hybrid-based glycocluster for sustained release of hydrophobic molecules

A dual drug-loaded HNT–CD glycocluster delivery system based on halloysite nanotubes and carbohydrate functionalized cyclodextrin was developed by a green protocol using solvent-free microwave irradiation. The nanohybrid was employed for concurrent load and release of silibinin and curcumin. The new delivery system was characterized by means of TGA, FT-IR spectroscopy, SEM and DLS. These techniques confirm the successful loading of the two drugs in the system. SEM and DLS measurements highlighted that the nanomaterial preserves a tubular structure with an average hydrodynamic radius of ca. 200 nm. The release of the drugs from the HNT glycocluster was investigated by means of UV-vis spectro…

CeRNA and interactome bioinformatic analyses on human telomerase

We present a classic interactome bioinformatic analysis and a study on competing endogenous (ce) RNAs for hTERT. The hTERT gene codes for the catalytic subunit and limiting component of the human telomerase complex. Human telomerase reverse transcriptase (hTERT) is essential for the integrity of telomeres. Telomere dysfunctions have been widely reported to be involved in aging, cancer, and cellular senescence. The hTERT gene network has been analyzed using the BioGRID interaction database (http://thebiogrid.org/) and related analysis tools such as Osprey (http://biodata.mshri.on.ca/osprey/servlet/Index) and GeneMANIA (http://genemania.org/). The network of interaction of hTERT transcripts h…

L’espressione di citochine TH1 e TH2 nei pazienti affetti da tireopatia autoimmune (AITD) e diabete di tipo 1

PFN1 and integrin‐β1/mTOR axis involvement in cornea differentiation of fibroblast limbal stem cells

Abstract Ex vivo limbal stem cell transplantation is the main therapeutic approach to address a complete and functional re‐epithelialization in corneal blindness, the second most common eye disorder. Although important key points were defined, the molecular mechanisms involved in the epithelial phenotype determination are unclear. Our previous studies have demonstrated the pluripotency and immune‐modulatory of fibroblast limbal stem cells (f‐LSCs), isolated from the corneal limbus. We defined a proteomic profile especially enriched in wound healing and cytoskeleton‐remodelling proteins, including Profilin‐1 (PFN1). In this study we postulate that pfn‐1 knock down promotes epithelial lineage…

CeRNA bioinformatic analysis on human telomerase

Messenger RNA (mRNA) translation efficiency is regulated by microRNAs. Each microRNA is able to regulate the translation of multiple mRNAs and each mRNA is regulated by multiple microRNAs. Thus, cellular mRNAs pool competed for microRNAs pool and viceversa. The regulatory network between mRNAs and microRNAs can be studied in the perspective of Competing Endogenous RNAs or ceRNAs. Here it is presented a bioinformatic study on ceRNAs for human telomerase (hTERT). Several genes potentially involved in the regulatory network of hTERT have been harvested by this study. hTERT is essential for the telomeres integrity. Telomere dysfunctions have been widely reported to be involved in Ageing, Cancer…

Search for the mutation of B-RAFV600E in FNA of thyroid nodules

High expression of peroxisome proliferator-activated receptor gamma (PPRgamma) in infiltrating lymphocytes from glands with Hashimoto's thyroiditis.

<p>Circulating Irisin Levels as a Marker of Osteosarcopenic-Obesity in Cushing’s Disease</p>

Purpose To evaluate circulating irisin levels in patients with active and controlled Cushing's disease (CD). Design Forty-four patients with CD evaluated during the active phase and after 12 months of biochemical remission and 40 controls were recruited. Methods Phenotypic, anthropometric, hormonal and metabolic parameters, including insulin sensitivity estimation by homeostatic model of insulin resistance, Matsuda index and oral disposition index and circulating irisin levels were evaluated. Results Patients with active CD showed lower irisin levels compared to controls (p<0.001) and controlled CD (p<0.001). The independent variables significantly associated with irisin were waist circumf…

Multicavity halloysite-amphiphilic cyclodextrin hybrids for co-delivery of natural drugs into thyroid cancer cells

Multicavity halloysite nanotube materials were employed as simultaneous carriers for two different natural drugs, silibinin and quercetin, at 6.1% and 2.2% drug loadings, respectively. The materials were obtained by grafting functionalized amphiphilic cyclodextrin onto the HNT external surface. The new materials were characterized by FT-IR spectroscopy, SEM, thermogravimetry, turbidimetry, dynamic light scattering and ζ-potential techniques. The interaction of the two molecules with the carrier was studied by HPLC measurements and fluorescence spectroscopy, respectively. The release of the drugs from HNT-amphiphilic cyclodextrin, at two different pH values, was also investigated by means of…

Identification of Novel Wsf1 Mutations in a Sicilian Child with Wolfram Syndrome

Wolfram Syndrome (WS) is a rare hereditary disease with autosomal recessive inheritance with incomplete penetrance. It is characterized by diabetes mellitus associated with progressive optic atrophy. The diagnosis is essentially clinical and mutation analysis is used to confirm the diagnosis. In the present study we describe the clinical and molecular features of a diabetic child carrying two novel WFS1 mutations. The Sicilian proband and his non-affected family were studied. Ophthalmologic examination included: visual acuity determination and funduscopy, optical coherent tomography, retinal fluorangiography, perimetry and electroretinogram. Molecular methods: automatic sequencing of PCR am…

TRANSPORTAN 10 INTERACTION WITH GIANT VESICLES: INSERTION EFFECTS AND PORE FORMATION

Transportan 10 (TP10) is a 21 residues peptide that belongs to the family of the antimicrobial and cytolytic or cytotoxic amphipathic peptides. It contains a high proportion of positively charged amino acids (four lysines), no negative charges and the N-terminus that impart it a formal +5 charge at neutral pH.1 This large number of positive charges is an essential feature for the electrostatic interaction of TP10 with microbial and tumoral membranes, which are characherized by a net negative charge and also by a higher fluidity if compared with mammalin ones.2 Here, combining spectroscopic and fluorescence lifetime imaging techniques, we analyse the fate of the multifunctional3-4 TP10 and i…

3D polymeric supports promote the growth and progression of anaplastic thyroid carcinoma.

Abstract Anaplastic thyroid carcinoma (ATC) is a rare and aggressive malignancy that accounts for the majority of deaths from all thyroid cancers. ATC exhibits invasiveness and highly resistance to conventional therapies which include cytotoxic chemotherapy, the combination of BRAF and MEK inhibition and, more recently, immunotherapies, that have shown promising but still limited results. A growing knowledge on ATC tumor biology is needed for developing more effective therapies with significant better survival. Researchers have begun to utilize 3D models to culture cancer cells for in vitro studies. In this work, C643 ATC cell line was cultured on polymeric scaffolds with high-interconnecte…

Cathepsin D, B and L circulating levels as prognostic markers of malignant progression

Growing evidence indicates that lysosomal Cathepsins D (CD), B (CB) and L (CL) may promote carcinogenesis and tumor progression. Therefore, we evaluated their potential value as biochemical parameters of malignant progression in patients with benign diseases which may undergo malignant transformation, such as liver cirrhosis (LC) and chronic pancreatitis (CHP) as well as in hepatocellular carcinoma (HCC) and pancreatic cancer (DPC). CD, CB and CL serum levels were determined by immunoenzymatic assays in LC, CHP, HCC or DPC patients and correlated with a number of biochemical and clinical parameters of these diseases. CD serum levels were increased in LC, CHP and HCC, but not in the DPC grou…

Pasireotide versus pituitary surgery: a retrospective analysis of 12 months of treatment in patients with Cushing’s disease

Pituitary surgery represents the first-line treatment for most patients with Cushing’s disease (CD). In the case of surgery failure, additional treatment options are required. Pasireotide has shown favourable results in the first-line treatment of patients with CD, who are not candidates for surgery or in the second-line when surgery has failed. The aim of the current study is to compare the effects of surgery and pasireotide treatment in a cohort of patients with CD, and to evaluate the differences in response rate in terms of hormonal and clinical control, and improvement of metabolic complications

NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self-renewal potential and differentiation capacity. Our aim was to study the different expression of the embryonic stem cell markers NANOG (homeobox protein NANOG), SOX2 (SRY (sex determining region Y)-box 2) and OCT4 (octamer-binding transcription factor 4) and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting pat…

Additional file 4: of Human limbal fibroblast-like stem cells induce immune-tolerance in autoreactive T lymphocytes from female patients with Hashimoto’s thyroiditis

Jurkat cells as a positive control for apoptosis detection. (A) Untreated Jurkat cells (first row) or treated with activating anti-Fas for 4 or 24 h (second and third row, respectively) after AO/EB staining. The arrows indicate many apoptotic body formations, bright green dots in the nuclei as a consequence of chromatin condensation and nuclear fragmentation. Late apoptotic cells were observed with condensed and fragmented nuclei especially after 24 h of anti-Fas treatment. Original magnification: 40×. All pictures are representative of five independent experiments. (PDF 240 kb)

A PUTATIVE PROTEOMIC SIGNATURE FOR STROMAL FIBROBLAST-LIKE STEM CELLS

Additional file 2: Table S1. of Mesenchymal stem cells derived from inflamed dental pulpal and gingival tissue: a potential application for bone formation

The expression values of putative mesenchymal surface stem cells markers. (DOC 31 kb)

Circulating Irisin Levels in Children With GH Deficiency Before and After 1 Year of GH Treatment.

Abstract Purpose To evaluate circulating irisin levels in children with GH deficiency (GHD) and any relation with clinical and metabolic parameters. Patients Fifty-four prepubertal children (mean age, 7.4 ± 0.8 years) with idiopathic GHD treated with GH for at least 12 months and 31 healthy short children as control subjects. Methods Body height, body mass index (BMI), waist circumference (WC), IGF-I, HbA1c, lipid profile, fasting and after–oral glucose tolerance test glucose and insulin, insulin sensitivity indices, and irisin levels were evaluated at baseline and after 12 months of GH replacement (GHR). Results At baseline, children with GHD, in addition to having lower growth velocity (P…

Glycated albumin is correlated to insulin resistance and β-cell secretory function in subjects at risk for developing diabetes

Insulin resistance and β-cell secretory function represent two main issues in the pathogenesis of type 2 diabetes mellitus (T2DM). Conflicting results have been obtained about the association between glycated albumin (GA) and body mass index (BMI), insulin resistance and β-cell function in diabetic patients. Actually, the relationship (if any) between GA and the markers of glucose homeostasis and insulin resistance in subjects at risk of developing diabetes, has not been completely elucidated yet. Two hundred and one patients undergoing to oral glucose tolerance test (OGTT) were enrolled in the study. Routine laboratory tests, including fasting insulin, were performed at enrollment. GA was …

Detection of BRAFv600E mutation in papillary thyroid carcinoma using real time allele-specific amplification on fine needle aspiration biopsy specimens.

BIOINFORMATICS CERNA ANALYSIS FOR THE STUDY OF STEM FACTOR SOX2 IN ANAPLASTIC THYROID CANCER.

Cancer stem cells (CSC) are believed to play a central role in oncogenesis, but until today their isolation and characterization is still particularly complex. Anaplastic thyroid cancer (ATC) presents several characteristics suggestive of a tumour highly enriched in CSC (high mitotic rate, poor prognosis, high aggressiveness, resistance to treatments, etc). For these reasons ATC represents a good candidate to study CSCs. SOX2 is a key stem transcriptional factor, usually only transiently expressed, that plays a fundamental role in stem cell identity. SOX2 proved to be constitutively expressed in SW1736 cell line, a well established and recognized ATC cell line. The bioinformatics ceRNA anal…

Growth and Osteogenic Differentiation of Discarded Gingiva-Derived Mesenchymal Stem Cells on a Commercial Scaffold

Background In periodontal patients with jawbone resorption, the autologous bone graft is considered a "gold standard" procedure for the placing of dental prosthesis; however, this procedure is a costly intervention and poses the risk of clinical complications. Thanks to the use of adult mesenchymal stem cells, smart biomaterials, and active biomolecules, regenerative medicine and bone tissue engineering represent a valid alternative to the traditional procedures. Aims In the past, mesenchymal stem cells isolated from periodontally compromised gingiva were considered a biological waste and discarded during surgical procedures. This study aims to test the osteoconductive activity of FISIOGRAF…

Visceral adiposity index is associated with insulin sensitivity and adipocytokine levels in newly diagnosed acromegalic patients.

Context: The visceral adiposity index (VAI) has proved to be a marker of visceral adipose dysfunction, strongly associated with insulin sensitivity in both the general and specific populations of patients at metabolic risk. Objective: The objective of the study was to test VAI as a useful tool to assess early metabolic risk in acromegaly. Patients: Twenty-four newly diagnosed acromegalic patients (11 women and 13 men, aged 54.9 ± 13.6 yr) were grouped into those with normal (group A, n = 13, 54.2%) and those with high VAI (group B, n = 11, 45.8%). Outcome Measures: Glucose, hemoglobin A1c, nadir and area under the curve (AUC) of GH (AUCGH) during the oral glucose tolerance test, AUCCpeptide…

Binge-like alcohol exposure in adolescence: behavioural, neuroendocrine and molecular evidence of abnormal neuroplasticity … and return

Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the response to natural positive stimuli and inescapable stress

BRAFV600E mutation and timp-1 hyper-expression in classical variants of papillary thyroid carcinoma (PTC).

Anticancer activity of biogenerated silver nanoparticles: an integrated proteomic investigation

Silver nanoparticles (AgNPs), embedded into a specific polysaccharide (EPS), were biogenerated by Klebsiella oxytoca DSM 29614 under aerobic (AgNPs-EPSaer) and anaerobic conditions (AgNPs-EPSanaer). Both AgNPs-EPS matrices were tested by MTT assay for cytotoxic activity against human breast (SKBR3 and 8701-BC) and colon (HT-29, HCT 116 and Caco-2) cancer cell lines, revealing AgNPs-EPSaer as the most active, in terms of IC50, with a more pronounced efficacy against breast cancer cell lines. Therefore, colony forming capability, morphological changes, generation of reactive oxygen species (ROS), induction of apoptosis and autophagy, inhibition of migratory and invasive capabilities and prote…

Boosting the properties of a fluorescent dye by encapsulation into halloysite nanotubes

Abstract The synthesis of a new biocompatible bichromophoric system (CURBO) was developed, by connecting the skeleton of the naturally occurring curcumin to a BODIPY derivative. The system exhibited an intense fluorescence band with maximum at about 510 nm in organic solvent, while its emission spectra in aqueous solution were more complicated and slightly red-shifted, due to the effect of aggregation for the poor solubility of the dyad. To overcome these problems, the bichomophoric system has been loaded into the halloysite nanotubes (HNT). The HNT/CURBO nanocomposite, suspended in aqueous solution, showed an intensity of emission in the red region of the spectrum higher than the one exhib…

Co-presence of BRAFv600E mutation and ret/ptc3 rearrangement in a patient affected by hyperthyroidism and histologic diagnosis of papillary thyroid microcarcinoma.

Circulating Irisin Levels as a Marker of Osteosarcopenic-Obesity in Cushing’s Disease

Purpose: To evaluate circulating irisin levels in patients with active and controlled Cushing’s disease (CD). Design: Forty-four patients with CD evaluated during the active phase and after 12 months of biochemical remission and 40 controls were recruited. Methods: Phenotypic, anthropometric, hormonal and metabolic parameters, including insulin sensitivity estimation by homeostatic model of insulin resistance, Matsuda index and oral disposition index and circulating irisin levels were evaluated. Results: Patients with active CD showed lower irisin levels compared to controls (p&lt;0.001) and controlled CD (p&lt;0.001). The independent variables significantly associated with irisin were wais…

A ceRNA analysis on LMNA gene focusing on the Hutchinson-Gilford progeria syndrome

Background: Hutchinson-Gilford progeria syndrome is a rare dominant human disease of genetic origin. The average life expectancy is about 20 years, patients’ life quality is still very poor and no efficient therapy has yet been developed. It is caused by mutation of the LMNA gene, which results in accumulation in the nuclear membrane of a particular splicing form of Lamin-A called progerin. The mechanism by which progerin perturbs cellular homeostasis and leads to the symptoms is still under debate. Micro-RNAs are able to negatively regulate transcription by coupling with the 3’ UnTranslated Region of messenger RNAs. Several Micro-RNAs recognize the same 3’ UnTranslated Region and each Micr…

Visfatin as a marker of adipose dysfunction and metabolic impairment in active acromegaly and its possible use during the follow-up

Background Visfatin is an adipokine with insulin-mimetic and adipogenic effect related to insulin resistance (IR) and visceral adipose mass. Although acromegaly is characterized by both adipose dysfunction and IR, data on visfatin levels in acromegaly are very scarce and in the few existing studies no difference was reported between acromegalic patients and controls. Aim To evaluate the visfatin levels in acromegaly in relation to disease activity and type of treatment. Subjects and Methods Data of 56 patients (31 M, age 59 ± 12 yrs) were analyzed. Sixteen patients were newly diagnosed (ND), while the remaining were in therapy with somatostatin analogues (SA, 21), pegvisomant (PE, 12) and a…

Identification and enrichment of thyroid stem cells in anaplastic cell lines

Multiple Pluripotent Stem Cell Markers in Human Anaplastic Thyroid Cancer: The Putative Upstream Role of SOX2

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive endocrine tumor with highly undifferentiated morphology. It has been suggested that cancer stem cells (CSCs) might play a central role in ATC. The objectives of this study were (i) to characterize CSCs from ex vivo ATC specimens by investigating the expression of several pluripotent stem cell markers, and (ii) to evaluate in vitro drug resistance modifications after specific CSC transcription factor switch-off.In ex vivo experiments, eight formalin-fixed, paraffin-embedded ATC specimens were analyzed by reverse-transcription and real-time quantitative PCR and immunohistochemistry. In in vitro experiments using ATC SW1736 cells, the…

ANTITUMOR EFFECTS OF SULPHORAPHANE ON THYROID CARCINOMA CELL LINES

Thyroid cancer is the most frequent endocrine malignancy with a global increasing incidence. Many evidences show that sulphoraphane (SF), a natural isothiocyante found in cruciferous vegetables has a wide range of chemopreventive as well as apoptosis inducing properties. The ability of SF in inducing apoptosis and cell cycle arrest is associated with the regulation of many proteins including Bcl-2 family proteins, caspases, p21, and cyclin dependent kinases. In the present work, we investigated in vitro the activity of SF in three human thyroid cancer cell lines. For this purpose we studied SW1736 (ATC), BC-PAP (PTC) and TT (MTC) cell line by MTT assay, after addition of SF ranging from 0 t…

Are hepatitis G virus and TT virus involved in cryptogenic chronic liver disease?

Abstract Background . Hepatitis G virus can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. Little is known about the relation of another newly discovered agent, the TT virus, with chronic liver disease. Aim . To investigate the rate of infection with hepatitis G virus and TT virus in patients with cryptogenic chronic liver disease. Patients . A total of 23 subjects with chronically raised alanine transaminase and a liver biopsy in whom all known causes of liver disease had been excluded, and 4D subjects with hepatitis C virus-related chronic liver disease. Methods . Evaluation of anti-hepatitis G virus by enzyme immunoassay. Hepatiti…

Limbal stem cells as a potential source of pancreatic beta cells

BACKGROUND/RATIONAL Beta cell replacement therapy represents an alternative approach to conventional insulin regimen for the management of type 1 diabetes. Stem cells theoretically represent a suitable and renewable source of surrogate beta cells. Recently, it has been demonstrated that corneal epithelium contains stem cells in the basal layer of the limbus. Our aim was to isolate and characterize limbal stem cells (LSCs) from adult corneal-limbal biopsies, and to assess their capability to differentiate into insulin-producing cells. METHODS 2-3 mm2 biopsies were obtained from limbus and central cornea of four patients undergoing surgery for ocular diseases not involving conjuctive or corne…

Myristic acid is associated to low plasma HDL cholesterol levels in a Mediterranean population and increases HDL catabolism by enhancing HDL particles trapping to cell surface proteoglycans in a liver hepatoma cell model

Background: HDL-C plasma levels are modulated by dietary fatty acid (FA), but studies investigating dietary supplementation in FA gave contrasting results. Saturated FA increased HDL-C levels only in some studies. Mono-unsaturated FA exerted a slight effect while poly-unsaturated FA mostly increased plasma HDL-C. Aims: This study presents two aims: i) to investigate the relationship between HDL-C levels and plasma FA composition in a Sicilian population following a "Mediterranean diet", ii) to investigate if FA that resulted correlated with plasma HDL-C levels in the population study and/or very abundant in the plasma were able to affect HDL catabolism in an "in vitro" model of cultured hep…

In Vitro Generation of Pancreatic Endocrine Cells from Human Adult Fibroblast-Like Limbal Stem Cells

Stem cells might provide unlimited supply of transplantable cells for β-cell replacement therapy in diabetes. The human limbus is a highly specialized region hosting a well-recognized population of epithelial stem cells, which sustain the continuous renewal of the cornea, and the recently identified stromal fibroblast-like stem cells (f-LSCs), with apparent broader plasticity. However, the lack of specific molecular markers for the identification of the multipotent limbal subpopulation has so far limited the investigation of their differentiation potential. In this study we show that the human limbus contains uncommitted cells that could be potentially harnessed for the treatment of diabete…

Anaplastic Thyroid Carcinoma: A ceRNA Analysis Pointed to a Crosstalk between SOX2, TP53, and microRNA Biogenesis.

It has been suggested that cancer stem cells (CSC) may play a central role in oncogenesis, especially in undifferentiated tumours. Anaplastic thyroid carcinoma (ATC) has characteristics suggestive of a tumour enriched in CSC. Previous studies suggested that the stem cell factorSOX2has a preeminent hierarchical role in determining the characteristics of stem cells in SW1736 ATC cell line. In detail, silencing SOX2 in SW1736 is able to suppress the expression of the stem markers analysed, strongly sensitizing the line to treatment with chemotherapeutic agents. Therefore, in order to further investigate the role of SOX2 in ATC, a competing endogenous RNA (ceRNA) analysis was conducted in order…

BRAFV600E mutation, TIMP-1 upregulation, and NF-κB activation: closing the loop on the papillary thyroid cancer trilogy.

BRAFV600E is the most common mutation found in papillary thyroid carcinoma (PTC). Tissue inhibitor of metalloproteinases (TIMP-1) and nuclear factor (NF)-κB have been shown to play an important role in thyroid cancer. In particular, TIMP-1 binds its receptor CD63 on cell surface membrane and activates Akt signaling pathway, which is eventually responsible for its anti-apoptotic activity. The aim of our study was to evaluate whether interplay among these three factors exists and exerts a functional role in PTCs. To this purpose, 56 PTC specimens were analyzed for BRAFV600E mutation, TIMP-1 expression, and NF-κB activation. We found that BRAFV600E mutation occurs selectively in PTC nodules an…

In Vitro Phenotypic, Genomic and Proteomic Characterization of a Cytokine-Resistant Murine β-TC3 Cell Line

Type 1 diabetes mellitus (T1DM) is caused by the selective destruction of insulin-producing β-cells. This process is mediated by cells of the immune system through release of nitric oxide, free radicals and pro-inflammatory cytokines, which induce a complex network of intracellular signalling cascades, eventually affecting the expression of genes involved in β-cell survival. The aim of our study was to investigate possible mechanisms of resistance to cytokine-induced β-cell death. To this purpose, we created a cytokine-resistant β-cell line (β-TC3R) by chronically treating the β-TC3 murine insulinoma cell line with IL-1β + IFN-γ. β-TC3R cells exhibited higher proliferation rate and resistan…

In Vitro Identification and Characterization of CD133pos Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines

BackgroundRecent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown.Methodology/principal findingsATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133(pos) cells only in ARO and KAT-4 (64+/-9% and 57+/-12%, respectively). These …

Insulin sensitivity and secretion and adipokine profile in patients with Cushing’s disease treated with pasireotide

Purpose: To evaluate the effect of pasireotide on β-cell and adipose function in patients with Cushing’s disease (CD). Methods: Clinical and hormonal parameters, insulin secretion evaluated by HOMA-β and by the area under the curve (AUC2h) of C-peptide during a mixed meal tolerance test and insulin sensitivity, evaluated by the euglycaemic hyperinsulinaemic clamp, were evaluated in 12 patients with active CD, before and after 6 and 12 months of pasireotide. In addition, a panel of adipokines including leptin (Ob), leptin/leptin receptor ratio (Ob/Ob-R ratio), adiponectin, resistin, visfatin, adipocyte fatty acid binding protein (AFABP) and non-esterified fatty acids (NEFAs) was evaluated at…

No association between BRAFV660E and metalloproteinase activity in anaplastic thyroid cell lines

Shedding of Membrane Vesicles Mediates Fibroblast Growth Factor-2 Release from Cells

Fibroblast growth factor-2 (FGF-2), a polypeptide with regulatory activity on cell growth and differentiation, lacks a conventional secretory signal sequence, and its mechanism of release from cells remains unclear. We characterized the role of extracellular vesicle shedding in FGF-2 release. Viable cells released membrane vesicles in the presence of serum. However, in serum-free medium vesicle shedding was dramatically down-regulated, and the cells did not release FGF-2 activity into their conditioned medium. Addition of serum to serum-starved cells rapidly induced intracellular FGF-2 clustering under the plasma membrane and into granules that colocalized with patches of the cell membrane …

Knockdown of NANOG Reduces Cell Proliferation and Induces G0/G1 Cell Cycle Arrest in Human Adipose Stem Cells

The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG, SOX2 and OCT4 represent the core regulatory network that suppresses differentiation-associated genes, maintaining the pluripotency of mesenchymal stem cells. The roles of NANOG in maintaining self-renewal and undifferentiated status of adult stem cells are still not perfectly established. In this study we define the effects of downregulation of NANOG in maintaining self-renewal and undifferentiated state in mesenchymal stem cells (MSCs) derived from subcutaneous adipose tissue (hASCs). hASCs were expanded…

Detection of BRAFV600 mutation in papillary thyroid carcinoma using real time allele-specific amplification on fine needle aspiration biopsy specimens

Molecular characterization of cancer stem cells in anaplastic thyroid carcinoma

Human exfoliated deciduous teeth and oral mucosa: promising applications in tissue regeneration

In the last three decades, the constantly increasing need for therapies, efficiently preventing and/or treating human diseases, has raised the interest in Regenerative Medicine (RM). RM is based on employing mesenchymal stem cells (MSCs), that showed to have great proliferation, self-renewal and multilineage differentiation potential, in vitro as well as in vivo. The opportunity of an accessible, painless and low-cost reservoir of MSCs constitutes the first important step of a successful regenerative therapy to include in the current clinical practice. Oral cavity has recently demonstrated to contain different MSCs niches: dental pulp from permanent and deciduous teeth, periodontal ligament…

Additional file 2: of Human limbal fibroblast-like stem cells induce immune-tolerance in autoreactive T lymphocytes from female patients with Hashimoto’s thyroiditis

f-LSCs arrest T-cell division. (A) One-way mixed leukocyte reaction (MLR) was carried out by seeding 2 × 105 of responder healthy PBMCs into 48-well plates (Corning) and adding 1 × 105 mytomycin-C pre-treated stimulator cells for a final volume of 500 μl of lymphocyte medium. Each responder and stimulator cell population was seeded in triplicate. When MLRs were cocultured with f-LSCs the allogenic activation was greatly reduced. Pictures are representative of five independent experiments. (B) Molecular detection of p27Kit and CCND1 mRNA by qRT-PCR. Results are shown as mean ± SD of three independent experiments; *p 

Dental pulp stem cells for bone tissue engineering: a review of the current literature and a look to the future.

The aim of this narrative review is to investigate the implication of mesenchymal stem cells harvested from human dental pulp in in vivo bone tissue regeneration. We focused on studies related to roles of human dental pulp stem cells in in vivo bone regeneration. A total of 1021 studies were identified; after the assessment of eligibility, only 39 studies were included in the review. The evaluated information of the studies regards the experimental strategies (e.g., the isolation method, the scaffold, the in vivo animal models). The overall main evidences highlighted from the analysis are that dental pulp stem cells and human-exfoliated deciduous teeth stem cells supported by a suitable sc…

Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implications.

The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular inhibitor of these proteolytic enzymes, were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases. Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p &lt; 0.001). However no difference was observed between HCC and LC groups. Interestingly, a significant relationship was evidenced between cathepsin B serum content and the grade of severity of cirrhosis (r = 0.41; p &lt; 0.001). Cathepsin L was significantly elevated only in sera of cancer patients as comp…

Hutchinson Gilford Progeria Syndrome: A Therapeutic Approach via Adenoviral Delivery of CRISPR/cas Genome Editing System

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare human genetic disease caused by mutations in the LMNA gene. LMNA codes for structural components of the nuclear lamina. Alterations of nuclear lamina lead to a very variable class of diseases known as laminopathies. In detail, HGPS manifests a severe premature ageing phenotype due to the accumulation of a dominant negative form of lamin-A called progerin. With current treatments, the life expectancy of HGPS patients does not exceed their second decade. Death is usually due to cardiovascular complications. Recently, a new technology for mammals in vivo gene editing has been developed: the clustered regularly interspaced short palindromic …

SEARCH OF THE MUTATION OF B-RAFV600E IN FNA OF THYROID NODULES

The role of FAS/FASLig and apoptosis in β-cell death in animal models: relevance for human IDDM

Espressione dei fattori di trascrizione di staminalità in cellule stromali (HASC) ottenute da tessuto adiposo viscerale e sottocutaneo

Caratterizzazione proteomica di una linea beta cellulare resistente all'effetto citochinico

Recherche de la mutation B-RAF V600E sur materiel preleve par citopontion de nodule thyroidiens: utilitè diagnostique et valeur prognostique

Phenotyping of type 2 diabetes mellitus at onset on the basis of fasting incretin tone: Results of a two-step cluster analysis.

Aims/Introduction According to some authors, in type 2 diabetes there is a reduced postprandial action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). However, little is known about the role of fasting incretins in glucose homeostasis. Our aim was to evaluate, through a two-step cluster analysis, the possibility of phenotyping patients with type 2 diabetes at onset on the basis of fasting GLP-1, GIP and ghrelin. Materials and Methods A total of 96 patients with type 2 diabetes within 6 months of onset (mean age 62.40 ± 6.36 years) were cross-sectionally studied. Clinical, anthropometric and metabolic parameters were evaluated. At fasting the follow…

Variabili cliniche nella casistica del policlinico di Palermo nell’ambito del registro dei tumori della tiroide in Sicilia: Età, sesso, autoimmunità, tipo, dimensionilesionali e coinvolgimento delle stazioni linfonodali della tiroide

Effects of GLP-1 receptor agonists on myokine levels and pro-inflammatory cytokines in patients with type 2 diabetes mellitus.

Background and aims: To evaluate the change in circulating serum irisin and interleukin-6 (IL-6), in patients with type 2 diabetes mellitus (T2DM) after 6 and 12 months of GLP-1 treatment. Methods and results: Eighty-five patients with T2DM inadequately controlled with insulin or other hypoglycaemic drugs were added to dulaglutide (N° = 44) and liraglutide (N° = 41) treatment. After 6 months of GLP-1 analogues a significant decrease in BMI (p &lt; 0.001), waist circumference (WC) (p &lt; 0.001), fasting blood glucose (p &lt; 0.001), HbA1c (p &lt; 0.001), total cholesterol (p &lt; 0.001), LDL-cholesterol (p = 0.003), triglycerides (p = 0.017), IL-6 (p = 0.045) and a significant increase in s…

Erratum to: Donor age and long-term culture do not negatively influence the stem potential of limbal fibroblast-like stem cells

In regenerative medicine the maintenance of stem cell properties is of crucial importance. Ageing is considered a cause of reduced stemness capability. The limbus is a stem niche of easy access and harbors two stem cell populations: epithelial stem cells and fibroblast-like stem cells. Our aim was to investigate whether donor age and/or long-term culture have any influence on stem cell marker expression and the profiles in the fibroblast-like stem cell population.Fibroblast-like stem cells were isolated and digested from 25 limbus samples of normal human corneo-scleral rings and long-term cultures were obtained. SSEA4 expression and sphere-forming capability were evaluated; cytofluorimetric…

Iter diagnostico "rapido" per un caso di MEN IIb in un giovane adolescente

Heterogeneity of Stem Cells in the Thyroid

Identification of thyroid stem cells in the past few years has made important contributions to our understanding of the cellular and molecular mechanisms that induce tissue regeneration and repair. Embryonic stem (ES) cells and induced-pluripotent stem cells have been used to establish reliable protocols to obtain mature thyrocytes and functional follicles for the treatment of thyroid diseases in mice. In addition, the discovery of resident thyroid progenitor cells, along with other sources of stem cells, has defined in detail the mechanisms responsible for tissue repair upon moderate or severe organ injury.In this chapter, we highlight in detail the current state of research on thyroid ste…

Insulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis C.

Conflicting data exist regarding the relationship between hepatitis C virus genotype 1 and hepatic steatosis as well as the latter's role in the progression of fibrosis and treatment response. We assessed factors associated with hepatic steatosis in genotype 1 chronic hepatitis C and the impact of hepatic fat on fibrosis development and interferon responsiveness. Two hundred ninety-one non-diabetic patients with genotype 1 chronic hepatitis C were examined for the presence of steatosis and its correlation with clinical, virological, and biochemical data, including insulin resistance (IR), evaluated by the homeostasis model assessment (HOMA) score. Steatosis was graded as mild (1%-20% of hep…

Additional file 5: of Human limbal fibroblast-like stem cells induce immune-tolerance in autoreactive T lymphocytes from female patients with Hashimoto’s thyroiditis

Immunomodulation mechanism played from BM-MSCs on healthy activated PBMCs. (A) Acitive-caspase-3 detection by FACS revealed weak induction of the apoptotic cascade in activated healthy PBMCs after 72 h of coculture with BM-MSCs. FACS histogram plots are representative of five experiments of identical design. (B) The expression percentage of the three activation markers (CD28, PD-1, CD69) in activated healthy PBMCs were assessed by flow cytometry and reported in the histogram. Samples were run after 72 h of incubation with or without BM-MSCs. (C) The CD4/CD8 ratio was calculated from data obtained by flow staining in samples of healthy activated PBMCs alone and after coculture with BM-MSCs. …

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Mesenchymal stem cells derived from inflamed dental pulpal and gingival tissue: a potential application for bone formation

Background Chronic periodontal disease is an infectious disease consisting of prolonged inflammation of the supporting tooth tissue and resulting in bone loss. Guided bone regeneration procedures have become common and safe treatments in dentistry, and in this context dental stem cells would represent the ideal solution as autologous cells. In this study, we verified the ability of dental pulp mesenchymal stem cells (DPSCs) and gingival mesenchymal stem cells (GMSCs) harvested from periodontally affected teeth to produce new mineralized bone tissue in vitro, and compared this to cells from healthy teeth. Methods To characterize DPSCs and GMSCs, we assessed colony-forming assay, immunophenot…

Fine-Needle Aspiration (FNAB) Molecular Analysis for the Diagnosis of Papillary Thyroid Carcinoma through BRAFv600E mutation and RET/PTC rearrangement

Objective: To evaluate BRAFV600E mutation on consecutive fine-needle aspiration biopsy (FNAB) specimens in order to assess FNAB’s usefulness in preoperative papillary thyroid carcinoma (PTC) diagnosis with the contemporaneous analysis of RET=PTC1 and RET=PTC3 rearrangements obtained from ex vivo thyroid nodules. Design: Thyroid FNABs from 156 subjects with nodules and 49 corresponding surgical samples were examined for the presence of BRAF mutation by real-time allele-specific polymerase chain reaction, confirmed with the use of a laser pressure catapulting system. Samples were also examined for RET=PTC rearrangements. The results were compared with the cytological diagnosis and histopathol…

INSULIN RESISTANCE, STEATOSIS AND PROGRESSION OF FIBROSIS IN PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C

Background and aim: Insulin resistance (IR) and steatosis have been associated with fibrosis severity in chronic hepatitis C (CHC), but only few studies investigate their role as predictors of disease evolution. We aimed to assess in patients with CHC if IR and steatosis are linked to progression of fibrosis over time. Material and methods: 86 consecutive G1 HCV infected patients with two paired liver biopsies over a period 67±30 months (range, 13-135), were evaluated at baseline by anthropometric and metabolic measurements, including IR (IR= HOMA-IR >2.7). All biopsies were scored by one pathologist for staging and grading (Scheuer). Steatosis was considered significant if =10. Results: At…

The Daily Consumption of Cola Can Determine Hypocalcemia: A Case Report of Postsurgical Hypoparathyroidism-Related Hypocalcemia Refractory to Supplemental Therapy with High Doses of Oral Calcium

The consumption of soft drinks is a crucial factor in determining persistent hypocalcemia. The aim of the study was to evaluate the biochemical mechanisms inducing hypocalcemia in a female patient with usual high consumption of cola drink and persistent hypocalcemia, who failed to respond to high doses of calcium and calcitriol supplementation. At baseline and after pentagastrin injection, gastric and duodenal secretion samples were collected and calcium and total phosphorus concentrations were evaluated. At the same time, blood calcium, total phosphorus, sodium, potassium, chloride, magnesium concentrations and vitamin D were sampled. After intake of cola (1 L) over 180 min, gastric and du…

Visceral adiposity index (VAI) is predictive of an altered adipokine profile in patients with type 2 diabetes.

Aims Although there is still no clear definition of “adipose tissue dysfunction” or ATD, the identification of a clinical marker of altered fat distribution and function may provide the needed tools for early identification of a condition of cardiometabolic risk. Our aim was to evaluate the correlations among various anthropometric indices [BMI, Waist Circumference (WC), Hip Circumference (HC), Waist/Hip ratio (WHR), Body Adiposity Index (BAI) and Visceral adiposity Index (VAI)] and several adipocytokines [Visfatin, Resistin, Leptin, Soluble leptin receptors (sOB-R), Adiponectin, Ghrelin, Adipsin, PAI-1, vascular endothelial growth factor (VEGF), Hepatocyte growth factor (HGF) TNF-α, hs-CRP…

Donor age and long-term culture do not negatively influence the stem potential of limbal fibroblast-like stem cells

AbstractBackgroundIn regenerative medicine the maintenance of stem cell properties is of crucial importance. Ageing is considered a cause of reduced stemness capability. The limbus is a stem niche of easy access and harbors two stem cell populations: epithelial stem cells and fibroblast-like stem cells. Our aim was to investigate whether donor age and/or long-term culture have any influence on stem cell marker expression and the profiles in the fibroblast-like stem cell population.MethodsFibroblast-like stem cells were isolated and digested from 25 limbus samples of normal human corneo-scleral rings and long-term cultures were obtained. SSEA4 expression and sphere-forming capability were ev…

BRAFV660E mutation and Timp-1 hyper-expression in classical variants of papyllary thyroid carcinoma.

Different Th1/Th2 cytokine expression in Type 1 diabetes mellitus patients (T1DM) alone or associated with autoimmune thyroid disease (AITD)

Decreased regulatory CD4+CD25+ Treg cells in newly diagnosed type 1 diabetes

Additional file 3: of Human limbal fibroblast-like stem cells induce immune-tolerance in autoreactive T lymphocytes from female patients with Hashimoto’s thyroiditis

Inhibitory effect of BM-MSCs on PBMC proliferation. (A) PBMCs from healthy volunteers were stimulated with anti-CD3 for 72 h in the presence or absence of BM-MSCs (1:10 ratio). No activated PBMCs served as negative controls. Original magnification: 40×. Pictures are representative of at least five independent experiments (B). DNA content was assessed using PI staining and analyzed by flow cytometry. Analysis of cell cycle showed the 28 ± 2.7% of PBMCs after 72 h of activation in G2/S phase. The same cells in the presence of BM-MSCs became 15 ± 3.0% confirming the inhibitory action of BM-MSCs on PBMC proliferation. In the transwell system no significant inhibition of PBMC growing was observe…

BrafV600E mutation and hyperexpression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in papillary thyroid carcinoma

Epigenetic involvement in Hutchinson-Gilford progeria syndrome: a mini-review.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare human genetic disease that leads to a severe premature ageing phenotype, caused by mutations in the &lt;i&gt;LMNA&lt;/i&gt; gene. The &lt;i&gt;LMNA&lt;/i&gt; gene codes for lamin-A and lamin-C proteins, which are structural components of the nuclear lamina. HGPS is usually caused by a de novo &lt;i&gt;C1824T&lt;/i&gt; mutation that leads to the accumulation of a dominant negative form of lamin-A called progerin. Progerin also accumulates physiologically in normal ageing cells as a rare splicing form of lamin-A transcripts. From this perspective, HGPS cells seem to be good candidates for the study of the physiological mechanisms of ageing…

Endocrine and pro-inflammatory activity of visceral (VAT) and subcutaneous (SAT) adipose tissue in morbidly obese patients with and without metabolic syndrome.

Higher cardiometabolic risk in idiopathic versus autoimmune type 1 diabetes: A retrospective analysis

Abstract Background Idiopathic type 1 diabetes mellitus (IDM) is characterized by an onset with insulinopenia and ketoacidosis with negative β-cell autoimmunity markers and lack of association with HLA. The aim of the study is to compare the clinical and metabolic parameters, the macro and microvascular complications, the adipose tissue dysfunction and the insulin secretion and sensitivity indexes in patients with IDM and autoimmune type 1 diabetes mellitus (ADM) at clinical onset. Methods Thirty patients with IDM and 30 with ADM, matched for age and gender, were retrospectively analyzed. BMI, waist circumference, lipids, glycemia, HbA1c, insulin requirement, glutamic oxaloacetic and glutam…

Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection.

BACKGROUND AND AIMS: Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. MATERIAL AND METHODS: One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was def…

Visceral Adiposity Index (VAI) as a simple indicator of “adipose tissue dysfunction” in patients with type 2 diabetes.

Although still there is no a clear definition of “adipose tissue dysfunction”, the identification of clinical and biological markers of altered fat distribution and function may provide the needed tools to early identify a condition of cardiometabolic risk. Visceral Adiposity Index (VAI) is a mathematical gender-specific index estimated with the use of simple anthropometric [(BMI and Waist circumference (WC)] and biochemical parameters [HDL cholesterol (HDL) and Triglycerides (Tg)], that in recent studies has shown to reflect accurately the degree of visceral adiposity and insulin resistance. However, although VAI has been indirectly shown to be a marker of impaired fat distribution and fun…

Dual-release hydrocortisone improves hepatic steatosis in patients with secondary adrenal insufficiency: A real-life study

Background:Conventional glucocorticoid treatment has a significant impact on liver in patients with adrenal insufficiency. Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement in anthropometric and metabolic parameters. We aimed to evaluate the effects of 12-month DR-HC treatment on the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, in patients with secondary adrenal insufficiency (SAI).Methods:A total of 45 patients with hypopituitarism, 22 with hypogonadism, hypothyroidism, ACTH, and GH deficiencies, and 23 with hypogonadism, hypothyroidism, and ACTH deficiency, on replacement therapy for all the pituitar…

Alcohol binge drinking in adolescence and psychological profile: Can the preclinical model crack the chicken-or-egg question?

During adolescence, internal and external factors contribute to engaging with alcohol binge drinking (ABD), putting at risk the neurodevelopment of brain regions crucial for emotional control and stress coping. This research assessed the prevalence of ABD in late adolescent students of Southern Italy and characterized their psychological profile and drinking motives. Translational effects of alcohol binge drinking in the animal model were also studied. Seven hundred and fifty-nine high school students of both sexes (aged 18–20) were recruited. Alcohol Use Disorder Identification Test-Consumption (AUDIT-C), Drinking Motives Questionnaire-Revised Short Form, Millon Clinical Multiaxial Invento…

Lysosomal aspartic and cysteine proteinases serum levels in patients with pancreatic cancer or pancreatitis

Lysosomal cathepsins D (CD), B (CB), and L (CL) serum levels were determined by immunoassays in patients with chronic (CHP) or acute (AP) pancreatitis and in patients with ductal pancreatic carcinoma (DPC) and correlated with some biological and clinical parameters of this tumor. CB serum concentrations significantly higher than those measured in healthy subjects (NS) were observed in CHP, AP, and DPC patients (p &lt; 0.01). However, no significant difference was noted among these groups. Increased CL serum levels were evident only in cancer patients compared to NS, AP, or CHP groups (p &lt; 0.05), while no difference was observed among these groups. Elevated CD serum values were observed i…

The Daily Consumption of Cola Can Determine Hypocalcemia: A Case Report of Postsurgical Hypoparathyroidism-Related Hypocalcemia Refractory to Supplemental Therapy with High Doses of Oral Calcium

The consumption of soft drinks is a crucial factor in determining persistent hypocalcemia. The aim of the study is to evaluate the biochemical mechanisms inducing hypocalcemia in a female patient with usual high consumption of cola drink and persistent hypocalcemia, who failed to respond to high doses of calcium and calcitriol supplementation. At baseline and after pentagastrin injection, gastric secretion (Gs) and duodenal secretion (Ds) samples were collected and calcium and total phosphorus (Ptot) concentrations were evaluated. At the same time, blood calcium, Ptot, sodium, potassium, chloride, magnesium concentrations, and vitamin D were sampled. After intake of cola (1 L) over 180 min,…

ISOLAMENTO E CARATTERIZZAZIONE DI CELLULE STAMINALI NELLE LINEE CELLULARI DI CARCINOMA TIROIDEO

Flow cytometric DNA analysis and lysosomal cathepsins b and l in locally advanced laryngeal cancer. Relationship with clinicopathologic parameters and prognostic significance

Background. The traditional factors of locally advanced laryngeal squamous cell carcinoma (LSCC) have limited predictive value for the identification of high risk patients. Therefore, it is extremely important to define prognostic factors that identify the more aggressive types. Reliable and reproducible prognostic indicators are being investigated to help clinicians identify high risk groups and address more rational treatment. Methods. Flow cytometric DNA ploidy and S-phase fraction (SPF) measurements were performed on frozen tumor tissues from a consecutive series of 71 patients with Stage III and IV LSCC. Lysosomal cathepsin B and L activity levels were determined biochemically in match…

Decremento delle cellule T regolatorie (Treg) CD4+CD25+FOXP3+ nei linfociti periferici dei pazienti affetti da diabete di tipo 1.

Differential protein expression in cytokine-sensitive and -resistant pancreatic beta cell lines

Erratum: Donor age and long-term culture do not negatively influence the stem potential of limbal fibroblast-like stem cells (Stem Cell Research and Therapy (2016) 7 (8))

Following publication of the original article in Stem Cell Research and Therapy [1], it was brought to our attention that panel 5E in Fig. 5 is a duplicate of panel 5F. Please find below the figure with the correct panel E. We apologize for the inconvenience this may have caused.

HEPATIC STEATOSIS IS ASSOCIATED WITH SEVERE FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B

Background and aim: Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the characteristics of steatosis and IR in CHB patients, compared to CHC subjects, and to evaluate the potential association between these features and fibrosis severity. Material and methods: 170 consecutive patients with CHB (28 HBeAg positive, 128 HBeAg negative, and 14 HBeAg negative/anti-HDV positive), and 170 sex, age and BMI matched genotype 1 CHC patients were evaluated by liver biopsy and metabolic measurements, including IR, by…

Production of a Double-Layer Scaffold for the “On-Demand” Release of Fibroblast-like Limbal Stem Cells

The production and characterization of a double layer scaffold, to be used as a system for the “on demand” release of corneal limbal stem cells are here reported. The devices used in the clinics and proposed so far in the scientific literature, for the release of corneal stem cells in the treatment of limbal stem cell deficiency, cannot control the in vivo space-time release of cells since the biomaterial of which they are composed is devoid of stimuli responsiveness features. Our approach was to produce a scaffold composed of two different polymeric layers that give the device the appropriate mechanical properties to be placed on the ocular surface and the possibility of releasing the stem…

Anti-Inflammatory Action of Heterogeneous Nuclear Ribonucleoprotein A2/B1 in Patients with Autoimmune Endocrine Disorders

Our previous studies documented that human fibroblast-limbal stem cells (f-LSCs) possess immunosuppressive capabilities, playing a role in regulating T-cell activity. This study highlights the molecular activities by which human f-LSCs can attenuate the inflammatory responses of self-reactive peripheral blood mononuclear cells (PBMCs) collected from patients with autoimmune endocrine diseases (AEDs). Anti-CD3 activated PBMCs from twenty healthy donors and fifty-two patients with AEDs were cocultured on f-LSC monolayer. 2D-DIGE proteomic experiments, mass spectrometry sequencing and functional in vitro assays were assessed in cocultured PBMCs. We identified the downmodulation of several huma…

Differential regulation of Fas-mediated apoptosis in both thyrocyte and lymphocyte cellular compartments correlates with opposite phenotypic manifestations of autoimmune thyroid disease.

Several mechanisms are probably involved in determining the evolution of autoimmune thyroid disease (AITD) towards either hypothyroidism and the clinical syndrome known as Hashimoto's thyroiditis (HT) or toward hyperthyroidism and the symptoms of Graves' disease (GD). To gain further insight into such mechanisms we performed an exhaustive comparative analysis of the expression of key molecules regulating cell death (Fas, Fas ligand [FasL], Bcl-2) and apoptosis in both thyrocytes and thyroid infiltrating lymphocytes (TILs) from patients with either GD or HT. GD thyrocytes expressed less Fas/FasL than HT thyrocytes, whereas GD TILs had higher levels of Fas/FasL than HT TILs. GD thyrocytes exp…

Transportan 10 Induces Perturbation and Pores Formation in Giant Plasma Membrane Vesicles Derived from Cancer Liver Cells

Continuous progress has been made in the development of new molecules for therapeutic purposes. This is driven by the need to address several challenges such as molecular instability and biocompatibility, difficulties in crossing the plasma membrane, and the development of host resistance. In this context, cell-penetrating peptides (CPPs) constitute a promising tool for the development of new therapies due to their intrinsic ability to deliver therapeutic molecules to cells and tissues. These short peptides have gained increasing attention for applications in drug delivery as well as for their antimicrobial and anticancer activity but the general rules regulating the events involved in cell…

BRAFV600E Mutation and p27kip1 Expression in Papillary Carcinomas of the Thyroid ≤1 cm and Their Paired Lymph Node Metastases

BACKGROUND. BRAFV600E mutation and p27kip1 expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas. METHODS. Tissue samples from 214 consecutive patients who underwent total or near-total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) ≤1 cm were analyzed for BRAFV600E mutation by a real-time, allele-specific amplification and for p27kip1 expression by immunohistochemistry. RESULTS. The BRAFV600E mutation was detected in 88 of the tumors examined, with significant differences between groups with and without lymph node (LN) metastases; the mean age of patients with BRAFV600E …

Serum miRNAs in women affected by hyperandrogenic polycystic ovary syndrome: the potential role of miR-155 as a biomarker for monitoring the estroprogestinic treatment.

MicroRNAs can be used as very efficient circulating biomarkers. The role of microRNAs in polycystic ovary syndrome (PCOS) and the effects of antiandrogen therapy on microRNA expression is still not fully understood. A panel of serum microRNAs were retrotranscribed via looped reverse primer transcription specific for each miRNA and quantified via probe specific RT-PCR in 16 Caucasian hyperandrogenic PCOS women selected according to the Rotterdam criteria and in a subset of seven patients after four months of sequential reverse antiandrogenic therapy. All women recruited underwent an oral glucose tolerance test (OGTT) and a baseline total cholesterol, high density lipoproteins cholesterol, tr…

HSP90 in ageing progression and ageing related diseases

HSP90 activities decline during ageing. Noteworthy, HSP90 mediated retrotransposon silencing seems to have a key role in the maintenance of genome integrity. Furthermore, inhibition of HSP90 activities lead to cell senescence and apoptosis. Original bioinformatics analyses and literature data will be discussed in the light of the potential involvement of HSP90 in ageing progression and ageing related diseases.

NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells (ASCs)

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 &amp;plusmn; 10; BMI between 25 and 30 range) undergoing elective open-abd…

Additional file 1: of Human limbal fibroblast-like stem cells induce immune-tolerance in autoreactive T lymphocytes from female patients with Hashimoto’s thyroiditis

Immunophenotyping of BM-MSCs. (A) The immunological profile of BM-MSCs was assessed by flow cytometry before (upper panel) and after 48 h of cytokine-treatment (IL-1β, IL-6, and IFNγ, 500 U/ml) (lower panel) using the same Abs for f-LSC immune characterization. All histogram plots include the percentage of expression of each protein as representative value of five independent experiments. (PDF 572 kb)

Amplificazione real-time allele-specifica per l'individuazione della mutazione V600E del B-RAF nel carcinoma papillare su agoaspirato tiroideo.

Effects of pasireotide treatment on coagulative profile: a prospective study in patients with Cushing's disease.

Introduction: Cushing’s disease (CD) is characterized by procoagulative profile. Treatment with cortisol-reducing medications might normalize the coagulation impairment potentially eliminating the risk of thromboembolic complications. Aim: The aim of this prospective study is to evaluate the effectiveness of 6–12 months of treatment with pasireotide (Signifor®, Novartis) 600 µg twice daily on coagulative factors in 21 patients (16 females, mean age 46 ± 12.2 years) with CD. Biochemical, hormonal (urinary free cortisol, UFC; late night salivary cortisol, LNSC; ACTH) and coagulative parameters as Protrombin time (PT), aPTT, factors VIII, IX and XI, antithrombin III, protein C, protein S, fibr…

IL CONSUMO DI BEVANDE RICCHE DI ACIDO ORTOFOSFORICO COME FATTORE DI RISCHIO PER LO SVILUPPO DI IPOCALCEMIA: IL CASO DI UNA DONNA CON IPOPARATIROIDISMO POST-CHIRURGICO

Differente pattern di espressione di citochine a fenotipo Th1 e Th2 nei pazienti affetti da diabete di tipo 1 (T1DM) e con associata tireopatia autoimmune (AITD)

Human limbal fibroblast-like stem cells induce immune-tolerance in autoreactive T lymphocytes from female patients with Hashimoto’s thyroiditis

Background Due to their “natural immune privilege” and immunoregulatory properties human fibroblast-like limbal stem cells (f-LSCs) have acquired great interest as a potential tool for achieving immunotolerance. Hashimoto’s thyroiditis (HT) is the most common thyroid autoimmune disease and cause of hypothyroidism. To date, conventional hormone replacement therapy and unspecific immunosuppressive regimens cannot provide a definitive cure for HT subjects. We explored the immunosuppressant potential of human f-LSCs on circulating lymphomonocytes (PBMCs) collected from healthy donors and female HT patients. Methods We assessed the immunophenotyping of f-LSCs, both untreated and after 48 h of pr…

Cathepsin D serum mass concentrations in patients with hepatocellular carcinoma and/or liver cirrhosis

Cathepsin D serum mass concentrations were determined by enzyme immunoassay in patients with hepatocellular carcinoma (n = 51) and/or liver cirrhosis (n = 92) or benign steatosis (n = 16) and correlated with some biochemical and clinical properties of these diseases. Increased cathepsin D serum mass concentrations (P &lt; 0.001) were observed in all these groups of patients as compared to normal subjects (n = 98). However, patients with steatosis had serum mass concentrations of this enzyme significantly lower (mean 2—3 fold) than those measured in cancer patients (P &lt; 0.05) or cirrhotic patients (P &lt; 0.001). Interestingly, significantly higher cathepsin D serum mass concentrations (m…

Comparison between euglycemic hyperinsulinemic clamp and surrogate indices of insulin sensitivity in children with growth hormone deficiency

Objective: Data about the impact of growth hormone treatment (GHT) on insulin sensitivity in children are quite controversial, due to the different surrogate indices that have been used. Design: We evaluated insulin sensitivity through the euglycemic hyperinsulinemic clamp, considered the gold standard technique, in 23 children affected by growth hormone deficiency (GHD) at baseline and after 12. months of GHT and in 12 controls with short stature at baseline, and we compared the clamp-derived index (M-value) with the most commonly used surrogate index of insulin sensitivity, as ISI Matsuda, and with circulating plasma markers of insulin sensitivity, as adiponectin and resistin levels. Resu…

L’espressione del “peroxisome proliferator-activated gamma” (PPARgamma) nelle tireopatie croniche autoimmuni

Social stress under binge-like alcohol withdrawal in adolescence: evidence of cannabidiol effect on maladaptive plasticity in rats.

Abstract Background Alcohol binge drinking may compromise the functioning of the nucleus accumbens (NAc), i.e. the neural hub for processing reward and aversive responses. Methods As socially stressful events pose particular challenges at developmental stages, this research applied the resident–intruder paradigm as a model of social stress, to highlight behavioural neuroendocrine and molecular maladaptive plasticity in rats at withdrawal from binge-like alcohol exposure in adolescence. In search of a rescue agent, cannabidiol (CBD) was selected due to its favourable effects on alcohol- and stress-related harms. Results Binge-like alcohol exposed intruder rats displayed a compromised defensi…

Metabolic Profile in a Cohort of Young Sicilian Patients with Klinefelter’s Syndrome: The Role of Irisin

Klinefelter’s syndrome (KS) is the main cause of hypogonadism and infertility in men and is often related to obesity, metabolic syndrome, and diabetes. The purpose of our real-life observational study was to investigate the metabolic and anthropometric parameters in a population of patients with Klinefelter syndrome compared to a group of healthy age-matched subjects. Methods. In our study, 25 consecutive Caucasian adult outpatients (age range 21–52 years, mean age 32.9 ± 12.2) with KS in testosterone replacement therapy and 30 healthy men (age range 25–45 years, mean age 32.4 ± 7.62) were studied. In both groups of subjects, anthropometric indices, lipid profile, glucose metabolic paramete…

RNA mediated trans-activation: its therapeutic potential in anaplastic thyroid cancer

RNA mediated trans-Activation is a proposed mechanism involved in the setting of the epigenetic state of chromatin. It has been studied first in Drosophila melanogaster where it seems that at least some transcribed loci are marked as transcriptionally active by their own transcripts. This effect acts in trans and in some cases could give rise to a transgenerational paramutational-like effect. This work studies RNA mediated trans-activation in the light of one of its possible applications, specifically its use as a therapeutic strategy for the incurable and highly aggressive ATC (anaplastic thyroid cancer). We explore the possibility to reactivate the Thyroid specific NIS (Natrium-Iodine sym…

Competing endogenous RNA and interactome bioinformatic analyses on human telomerase.

We present a classic interactome bioinformatic analysis and a study on competing endogenous (ce) RNAs for hTERT. The hTERT gene codes for the catalytic subunit and limiting component of the human telomerase complex. Human telomerase reverse transcriptase (hTERT) is essential for the integrity of telomeres. Telomere dysfunctions have been widely reported to be involved in aging, cancer, and cellular senescence. The hTERT gene network has been analyzed using the BioGRID interaction database (http://thebiogrid.org/) and related analysis tools such as Osprey (http://biodata.mshri.on.ca/osprey/servlet/Index) and GeneMANIA (http://genemania.org/). The network of interaction of hTERT transcripts h…

Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection

Background and aims: Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. Material and methods: One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was def…

CD4(+)IL-13(+) cells in peripheral blood well correlates with the severity of atopic dermatitis in children.

BACKGROUND In atopic dermatitis (AD) a Th1/Th2 imbalance has been reported, and interleukin (IL)-13 seems to play a pivotal role in the inflammatory network. We tried to assess the correlation between the immunological marker CD4(+)IL-13(+) and the clinical phase of extrinsic AD in children. METHODS Twenty children with AD were studied. Assessed parameters were: clinical severity (SCORAD index), total serum immunoglobulin E (IgE), blood eosinophil count, and percentage of CD4(+)IFNgamma(+), CD4(+)IL-4(+), CD4(+)IL-13(+) T cells. Determinations were carried out in the acute phase and after clinical remission were achieved. Ten nonatopic-matched children served as controls. RESULTS At baselin…

Disfunzione del tessuto adiposo e diabete mellito tipo 2: scarsa utilità diagnostica della quantificazione del grasso tramite RMN.

Antitumor effect of aminobisphosphonates on anaplastic thyroid carcinoma cell lines.

Additional file 1: Figure S1. of Mesenchymal stem cells derived from inflamed dental pulpal and gingival tissue: a potential application for bone formation

A) Bar graph represents the MTT absorbance mean values ± SD of P-DPSCs and P-GMSCs vs. their healthy control. The differences were not significant. B) The histograms represent the comparison of DT. Mean values ± SD are based on three independent experiments. n.s = not significant (p value &gt; 0.05). C) Each field shows a cell cycle analysis representative of each sample investigated. (TIF 11728 kb)

Additional file 3: Figure S2. of Mesenchymal stem cells derived from inflamed dental pulpal and gingival tissue: a potential application for bone formation

A, B) Basal gene expression of IL-1β and TNF-α receptors in P-DPSCs, H-DPSCs, P-GMSCs, and H-GMSCs. C, D) Gene expression of IL-1β and TNF-α receptors under cytokine stimulation at 24, 48, and 72 h (cytokine treatment: 20 ng/ml IL-1β + 40 ng/ml TNF-α). *p value