Skin cancers (SC) collectively represent the most common type of malignancy in white populations. SC includes two main forms: malignant melanoma and non-melanoma skin cancer (NMSC). NMSC includes different subtypes, namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma (MCC), and keratoacanthoma (KA), together with the two pre-neoplastic conditions Bowen disease (BD) and actinic keratosis (AK). Both malignant melanoma and NMSC are showing an increasing incidence rate worldwide, thus representing an important challenge for health care systems, also because, with some exceptions, SC are generally characterized by an aggressive behavior and are often diagnosed late. Thus, identifying new biomarkers suitable for diagnosis, as well as for prognosis and targeted therapy is mandatory. Nicotinamide N-methyltransferase (NNMT) is an enzyme that is emerging as a crucial player in the progression of several malignancies, while its substrate, nicotinamide, is known to exert chemopreventive effects. Since there is increasing evidence regarding the involvement of this enzyme in the malignant behavior of SC, the current review aims to summarize the state of the art as concerns NNMT role in SC and to support future studies focused on exploring the diagnostic and prognostic potential of NNMT in skin malignancies and its suitability for targeted therapy.
The head and neck tumors (HNT) are a heterogeneous group of diseases ranging from benign to malignant lesions, with distinctive molecular and clinical behaviors. Several studies have highlighted the presence of an altered metabolic phenotype in HNT, such as the upregulation of nicotinamide N-methyltransferase (NNMT). However, its biological effects have not been completely disclosed and the role of NNMT in cancer cell metabolism remains unclear. Therefore, this comprehensive review aims to evaluate the available literature regarding the biological, diagnostic, and prognostic role of NNMT in HNT. NNMT was shown to be significantly overexpressed in all of the evaluated HNT types. Moreover, its upregulation has been correlated with cancer cell migration and adverse clinical outcomes, such as high-pathological stage, lymph node metastasis, and locoregional recurrences. However, in oral squamous cell carcinoma (OSCC) these associations are still debated, and several studies have failed to demonstrate the prognostic significance of NNMT. The shRNA-mediated gene silencing efficiently suppressed the NNMT gene expression and exhibited a clear inhibitory effect on cell proliferation, promoting the expression of apoptosis-related proteins and modulating the cell cycle. NNMT could represent a new molecular biomarker and a new target of molecular-based therapy, although further studies on larger patient cohorts are needed to explore its biological role in HNT.
The aim of this study was to compare the epithelial biological response to machined titanium Ti-6Al-4V grade 5 and titanium Ti-6Al-4V grade 5 coated with zirconia (ZrN) by physical vapor deposition (PVD). Human keratinocytes were cultured in six-well plates. Machined titanium TiAl4V4 grade 5 (T1) and ZrN-coated titanium TiAl4V4 grade 5 (T2) discs were placed in two different wells. The remaining two wells served as control (C). Scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) were performed to compare the T1 and T2 surfaces. Subsequent analyses were performed to explore the effect of T1 and T2 contact with human keratinocyte HUKE cell lines. Cell viability was evaluated using a trypan blue exclusion test and MTT assay. Cell lysates from C, T1, and T2 were Western blotted to evaluate E-cadherin and Integrin-α6β4 expression. SEM revealed that T2 was smoother and more homogeneous than T1. EDS showed homogeneous and uniform distribution of ZrN coating on T2. Cell viability analyses did not show significant differences between T1 and T2. Furthermore, E-cadherin and Integrin-α6β4 expressions of the epithelial cells cultured in T1 and T2 were similar. Therefore, titanium Ti-6Al-4V grade 5 surfaces coated with ZrN by PVD seem to be similar substrates to the uncoated surfaces for keratinocyte adhesion and proliferation.
Guided bone regeneration (GBR) has been shown to be an optimal technique to accelerate the bone regeneration process thanks to the action of membrane barriers that promote tissue healing through the process of osteogenesis, inducing the repopulation with osteoprogenitor cells that prevent the invasion of non-osteogenic tissue. However, current membranes, such as expanded polytetrafluoroethylene or rubber dam, have some disadvantages that could potentially reduce the effectiveness of GBR. Recently, some scaffolds with magnetic properties have been tested to promote rapid osteogenesis. The aim of this laboratory study was to evaluate the intensity of the magnetic field generated by a custom-made rubber dam magnetised with neodymium-iron-boron (Nd2F14B) (three layers of latex filled with Nd2F14B powder on the inner surface) and to understand the effects of such a membrane on cell viability. A magnetic field of 750 G, 400 G, and 900 G was generated on the surface and on the long and wide sides of 3 and 2 cm in contact with the rubber dam. At a distance of 1 mm from the magnetic dam, a magnetic field of 300 G, 150 G, and 400 G was measured on the surface and on the long and wide sides of the rubber dam, respectively. After 72 h, the MG-63 osteoblast-like line showed a slight decrease in cell proliferation (85 ± 10) compared with the unmodified dam (95 ± 6) and the cell control population. According to our findings, this magnetic cofferdam is able to generate a static magnetic field and significantly affect cell proliferation in contrast to other nonabsorbable membranes. Further laboratory studies and subsequent clinical trials are needed to evaluate the significant improvements that can be achieved by using this type of magnetic rubber dam in GBR.