The epithelial–mesenchymal transition (EMT) is an essential event during cell development, in which epithelial cells acquire mesenchymal fibroblast-like features including reduced intercellular adhesion and increased motility. EMT also plays a key role in wound healing processes, which are mediated by inflammatory cells and fibroblasts. These cells secrete specific factors that interact with molecules of the extracellular matrix (ECM) such as collagens, laminins, elastin and tenascins. Wound healing follows four distinct and successive phases characterized by haemostasis, inflammation, cell proliferation and finally tissue remodeling. EMT is classified into three diverse subtypes: type-1 EMT, type-2 EMT and type-3 EMT. Type-1 EMT is involved in embryogenesis and organ development. Type-2 EMT is associated with wound healing, tissue regeneration and organ fibrosis. During organ fibrosis, type-2 EMT occurs as a reparative-associated process in response to ongoing inflammation and eventually leads to organ destruction. Type-3 EMT is implicated in cancer progression, which is linked to the occurrence of genetic and epigenetic alterations, in detail the ones promoting clonal outgrowth and the formation of localized tumors. The current review aimed at exploring the role of EMT process with particular focus on type-2 EMT in wound healing, fibrosis and tissue regeneration, as well as some recent progresses in the EMT and tissue regeneration field, including the modulation of EMT by biomaterials.

The prognostic relevance of masked uncontrolled hypertension (MUCH) is incompletely clear, and its global impact on cardiovascular outcomes and mortality has not been assessed. The aim of this study was to perform a meta-analysis on the prognostic value of MUCH. We searched for articles assessing outcome in patients with MUCH compared with those with controlled hypertension (CH) and reporting adjusted hazard ratio and 95% CI. We identified 6 studies using ambulatory blood pressure monitoring (12 610 patients with 933 events) and 5 using home blood pressure measurement (17 742 patients with 394 events). The global population included 30 352 patients who experienced 1327 events. Selected studies had cardiovascular outcomes and all-cause mortality as primary outcome, and the main result is a composite of these events. The overall adjusted hazard ratio was 1.80 (95% CI, 1.57–2.06) for MUCH versus CH. Subgroup meta-analysis showed that adjusted hazard ratio was 1.83 (95% CI, 1.52–2.21) in studies using ambulatory blood pressure monitoring and 1.75 (95% CI, 1.38–2.20) in those using home blood pressure measurement. Risk was significantly higher in MUCH than in CH independently of follow-up length and types of studied events. MUCH was at significantly higher risk than CH in all ethnic groups, but the highest hazard ratio was found in studies, including black patients. Risk of cardiovascular events and all-cause mortality is significantly higher in patients with MUCH than in those with CH. MUCH detected by ambulatory or home blood pressure measurement seems to convey similar prognostic information.

Tissue engineering and/or regenerative medicine are fields of life science exploiting both engineering and biological fundamentals to originate new tissues and organs and to induce the regeneration of damaged or diseased tissues and organs. In particular, de novo bone tissue regeneration requires a mechanically competent osteo-conductive/inductive 3D biomaterial scaffold that guarantees the cell adhesion, proliferation, angiogenesis and differentiation into osteogenic lineage. Cellular components represent a key factor in tissue engineering and bone growth strategies take advantage from employment of mesenchymal stem cells (MSCs), an ideal cell source for tissue repair. Recently, the application of extracellular vesicles (EVs), isolated from stem cells, as cell-free therapy has emerged as a promising therapeutic strategy. This review aims at summarizing the recent and representative research on the bone tissue engineering field using a 3D scaffold enriched with human oral stem cells and their derivatives, EVs, as a promising therapeutic potential in the reconstructing of bone tissue defects.

Prognosis of masked and white coat uncontrolled hypertension (MUCH and WCUCH, respectively) detected by ambulatory blood pressure (BP) monitoring is incompletely clear in elderly treated hypertensive patients. We evaluated prognosis of MUCH and WCUCH identified by ambulatory BP monitoring in this setting. The occurrence of a composite endpoint was evaluated in 1,191 elderly treated hypertensive patients. Controlled hypertension (CH) was defined as clinic BP <140/90 mm Hg and 24-hour BP <130/80 mm Hg, MUCH as clinic BP <140/90 mm Hg and 24-hour BP ≥130 and/or ≥80 mm Hg, WCUCH as clinic BP ≥140 and/or ≥90 mm Hg and 24-hour BP <130/80 mm Hg and sustained uncontrolled hypertension (SUCH) as clinic BP ≥140 and/or ≥90 mm Hg and 24-hour BP ≥130 and/or ≥80 mm Hg. MUCH was identified in 142 patients (12% of all the population, 34% of those with normal clinic BP) and WCUCH in 230 patients (19% of all the population, 30% of those with high clinic BP). During the follow-up (9.1 ± 4.9 years, range 0.4–20 years), 392 events occurred. After adjustment for various covariates, patients with MUCH (hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.12–2.29, P = 0.01) and SUCH (HR 1.81, 95% CI, 1.35–2.42, P < 0.001) had significantly higher cardiovascular risk than those with CH, whereas those with WCUCH (HR 1.09, 95% CI, 0.74–1.60, P = 0.66) had not significantly higher risk. In elderly treated hypertensive patients evaluated by ambulatory BP monitoring, compared to individuals with CH, those with MUCH have significantly higher risk and those with WCUCH have slightly and not significantly higher risk.

In restorative dentistry, the main implants characteristic is the ability to promote the osseointegration process as the result of interaction between angiogenesis and osteogenesis events. On the other hand, implants cytocompatibility remains a necessary feature for the success of surgery. The purpose of the current study was to investigate the interaction between human periodontal stem cells and two different types of titanium surfaces, to verify their cytocompatibility and cell adhesion ability, and to detect osteogenic and angiogenic markers, trough cell viability assay (MTT), Confocal Laser Scanning Microscopy (CLSM), scanning electron microscopy (SEM), and gene expression (RT-PCR). The titanium surfaces, machined (CTRL) and dual acid etched (TEST), tested in culture with human periodontal ligament stem cells (hPDLSCs), were previously treated in two different ways, in order to evaluate the effects of CTRL and TEST and define the best implant surface. Furthermore, the average surface roughness (Ra) of both titanium surfaces, CTRL and TEST, has been assessed through atomic force microscopy (AFM). The vascular endothelial growth factor (VEGF) and Runt-related transcription factor 2 (RUNX2) expressions have been analyzed by RT-PCR, WB analysis, and confocal laser scanning microscopy. Data evidenced that the different morphology and topography of the TEST disk increased cell growth, cell adhesion, improved osteogenic and angiogenic events, as well osseointegration process. For this reason, the TEST surface was more biocompatible than the CTRL disk surface.

Ponatinib, a third-generation tyrosine kinase inhibitor (TKI), is the only approved TKI that is effective against T315I mutations in patients with chronic myeloid leukemia (CML). Specific activation of Notch signaling in CML cells by ponatinib can be considered as the “on-target effect” on the tumor and represents a therapeutic approach for CML. Nevertheless, ponatinib-induced vascular toxicity remains a serious concern, with underlying mechanisms being poorly understood. We aimed to determine the mechanisms of ponatinib-induced vascular toxicity, defining associated signaling pathways and identifying potential rescue strategies. We exposed human umbilical endothelial cells (HUVECs) to ponatinib or vehicle in the presence or absence of the neutralizing factor anti-Notch-1 antibody for exposure times of 0–72 h. Label-free proteomics and network analysis showed that protein cargo of HUVECs treated with ponatinib triggered apoptosis and inhibited vasculature development. We validated the proteomic data showing the inhibition of matrigel tube formation, an up-regulation of cleaved caspase-3 and a downregulation of phosphorylated AKT and phosphorylated eNOS. We delineated the signaling of ponatinib-induced vascular toxicity, demonstrating that ponatinib inhibits endothelial survival, reduces angiogenesis and induces endothelial senescence and apoptosis via the Notch-1 pathway. Ponatinib induced endothelial toxicity in vitro. Hyperactivation of Notch-1 in the vessels can lead to abnormal vascular development and vascular dysfunction. By hyperactivating Notch-1 in the vessels, ponatinib exerts an “on-target off tumor effect”, which leads to deleterious effects and may explain the drug’s vasculotoxicity. Selective blockade of Notch-1 prevented ponatinib-induced vascular toxicity.