Co-distribution of cysteine cathepsins and matrix metalloproteases in human dentin

It has been hypothesized that cysteine cathepsin's (CTs) along with matrix metalloproteases (MMPs) may work in conjunction in the proteolysis of mature dentin matrix. The aim of this study was to verify simultaneously the distribution and presence of cathepsins B (CT-B) and K (CT-K) in partially demineralized dentin; and further to evaluate the activity of CTs and MMPs in the same tissue. The distribution of CT-B and CT-K in sound human dentin was assessed by immunohistochemistry. A double-immunolabeling technique was used to identify, at once, the occurrence of those enzymes in dentin. Activities of CTs and MMPs in dentin extracts were evaluated spectrofluorometrically. In addition, in situ gelatinolytic activity of dentin was assayed by zymography. The results revealed the distribution of CT-B and CT-K along the dentin organic matrix and also indicated co-occurrence of MMPs and CTs in that tissue. The enzyme kinetics studies showed proteolytic activity in dentin extracts for both classes of proteases. Furthermore, it was observed that, at least for sound human dentin matrices, the activity of MMPs seems to be predominant over the CTs one. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Co-distribution Of Cysteine Cathepsins And Matrix Metalloproteases In Human Dentin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)It has been hypothesized that cysteine cathepsin's (CTs) along with matrix metalloproteases (MMPs) may work in conjunction in the proteolysis of mature dentin matrix. The aim of this study was to verify simultaneously the distribution and presence of cathepsins B (CT-B) and K (CT-K) in partially demineralized dentin; and further to evaluate the activity of CTs and MMPs in the same tissue. The distribution of CT-B and CT-K in sound human dentin was assessed by immunohistochemistry. A double-immunolabeling technique was used to identify, at once, the occurrence of those enzymes in dentin. Activities of CTs and MMPs in dentin extracts were evaluated spectrofluorometrically. In addition, in situ gelatinolytic activity of dentin was assayed by zymography. The results revealed the distribution of CT-B and CT-K along the dentin organic matrix and also indicated co-occurrence of MMPs and CTs in that tissue. The enzyme kinetics studies showed proteolytic activity in dentin extracts for both classes of proteases. Furthermore, it was observed that, at least for sound human dentin matrices, the activity of MMPs seems to be predominant over the CTs one. (C) 2016 Elsevier Ltd. All rights reserved.74101107FAPESP, Brazil [2007/54618-4, 2009/14005-9]CNPq, Brazil [312768/2013-3]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Focus on Extracellular Vesicles: New Frontiers of Cell-to-Cell Communication in Cancer

Extracellular Vesicles (EVs) have received considerable attention in recent years, both as mediators of intercellular communication pathways that lead to tumor progression, and as potential sources for discovery of novel cancer biomarkers. For many years, research on EVs has mainly investigated either the mechanism of biogenesis and cargo selection and incorporation, or the methods of EV isolation from available body fluids for biomarker discovery. Recent studies have highlighted the existence of different populations of cancer-derived EVs, with distinct molecular cargo, thus pointing to the possibility that the various EV populations might play diverse roles in cancer and that this does not happen randomly. However, data attributing cancer specific intercellular functions to given populations of EVs are still limited. A deeper functional, biochemical and molecular characterization of the various EV classes might identify more selective clinical markers, and significantly advance our knowledge of the pathogenesis and disease progression of many cancer types

Assessment of pericallosal artery at 11–14 weeks of gestation: Cohort study and meta‐analysis

Objectives To report the rate of visualization of the pericallosal artery (PCA) in the first trimester of pregnancy (11-14 weeks). Methods Prospective observational study of consecutive fetuses undergoing first trimester risk assessment for chromosomal anomalies. The presence of PCA was assessed in a midsagittal view of fetal brain using high-definition power Color Doppler. A normal course of the PCA was defined as the visualization of an artery emerging from the anterior cerebral artery running parallel the corpus callosum (CC). The reference standard was the visualization of CC and PCA between the 20 and 22 weeks of gestation. We also performed a systematic review and meta-analysis of the published literature. Multivariate logistic regression and random-effect meta-analyses of proportion were used to analyze the data. Results Cohort study: Five-hundred women were included. PCA was identified trans-abdominally or transvaginally at 11-14 weeks of gestation in 98.8% (95% CI 97.4-99.6: 494/500); of the four cases of PCA not identified one had a diagnosis of complete agenesis of the corpus callosum during the anomaly scan which was confirmed at birth. Systematic review of the published literature: Six studies (1093 fetuses, including the present series) were included. The PCA was detected at the 11-14 weeks scan and confirmed to co-exist with a normal CC at time of the anomaly scan in 96.9% (95% CI 93.8-99.0); 20.6% (95% CI 5.7-41.7) of fetuses with no clear identification of the PCA at the 11-14 weeks scan had a normal appearance of the CC at the time of anomaly scan. Conclusion Prenatal ultrasonography has a high diagnostic accuracy in detecting PCA in the first trimester. Visualization of the PCA at the time of 11-14 scan is highly specific for the presence of a normal CC later in pregnancy