Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells.

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM. METHODS: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines. After large-scale production of MSCs in a bioreactor, their efficacy was also evaluated on a human MPM xenograft in mice. RESULTS: MSCs, their lysate and secretome inhibited MPM cell proliferation in vitro with S or G0/G1 arrest of the cell cycle, respectively. MSC lysate induced cell death by apoptosis. The efficacy of MSC was confirmed in vivo by a significant inhibition of tumor growth, similar to that produced by systemic administration of paclitaxel. Interestingly, no tumor progression was observed after the last MSC treatment, while tumors started to grow again after stopping chemotherapeutic treatment. CONCLUSIONS: These data demonstrated for the first time that MSCs, both through paracrine and cell-to-cell interaction mechanisms, induced a significant inhibition of human mesothelioma growth. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy.

Paclitaxel Priming of TRAIL Expressing Mesenchymal Stromal Cells (MSCs-TRAIL) Increases Antitumor Efficacy of Their Secretome.

BACKGROUND: Adipose tissue derived MSCs engineered with the tumor necrosis factor-related apoptosis-inducing ligand protein (MSCs-TRAIL) have a significant anticancer activity. MSCs, without any genetic modifications, exposed to high doses of chemotherapeutic agents are able to uptake the drug and release it in amount affecting tumor proliferation. The purpose of this study was to verify the ability of MSCs-TRAIL to uptake and release paclitaxel (PTX) by providing an increased antitumor efficacy. METHODS: MSCs and MSCs-TRAIL were tested for their sensitivity to Paclitaxel (PTX) by MTT assay and the cells were loaded with PTX according to a standardized procedure. The secretome was analysed by HPLC for the presence of PTX, microarray assay for soluble TRAIL (s-TRAIL) and tested for in vitro anticancer activity. RESULTS: MSCs-TRAIL were resistant to PTX and able to incorporate and then release the drug. The secretion of s-TRAIL by PTX loaded MSCs-TRAIL was not inhibited and the PTX delivery together with s-TRAIL secretion resulted into an increased antitumor efficacy of cell secretoma as tested in vitro on human pancreatic carcinoma (CFPAC-1) and glioblastoma (U87-MG). CONCLUSIONS: Our result is the first demonstration of the possible merging of two new MSCs therapy approaches based on genetic manipulation and drug delivery. If confirmed in vivo, this could potentiate the efficacy of MSCs-TRAIL and strongly contribute to reduce the toxicity due to the systemic treatment of PTX.

Oculofacial alterations in NBAS-SOPH like mutations: Case report.

PURPOSE: To describe the clinical features of a rare case of NBAS-SOPH-like mutations; to emphasize special aspects of the ocular and oro-facial regions. METHODS: Case report. CASE DESCRIPTION: We present a 5-year-old girl initially examined for her dysmorphic features, mental delay, strabismus, and high myopia. During the funduscopic examination, we observed optic atrophy with narrow thinned arterioles with the light brown reflex of the central retina. A genetic assessment revealed NBAS-SOPH like mutation. An assessment by a team of orthodontists defined typical characteristics. CONCLUSIONS: NBAS mutations can also cause complex disease with a broad clinical spectrum ranging from isolated recurrent acute liver failure (RALF) to a multisystemic phenotype. Due to the heterogeneity of the expressions, a multispeciality approach to this situation is recommended.

In Vitro Anticancer Activity of Extracellular Vesicles (EVs) Secreted by Gingival Mesenchymal Stromal Cells Primed with Paclitaxel.

Interdental papilla are an interesting source of mesenchymal stromal cells (GinPaMSCs), which are easy to isolate and expand in vitro. In our laboratory, GinPaMSCs were isolated, expanded, and characterized by studying their secretome before and after priming with paclitaxel (PTX). The secretome of GinPaMSCs did not affect the growth of cancer cell lines tested in vitro, whereas the secretome of GinPaMSCs primed with paclitaxel (GinPaMSCs/PTX) exerted a significant anticancer effect. GinPaMSCs were able to uptake and then release paclitaxel in amounts pharmacologically effective against cancer cells, as demonstrated in vitro by the direct activity of GinPaMSCs/PTX and their secretome against both human pancreatic carcinoma and squamous carcinoma cells. PTX was associated with extracellular vesicles (EVs) secreted by cells (EVs/PTX), suggesting that PTX is incorporated into exosomes during their biogenesis. The isolation of mesenchymal stromal cells (MSCs) from gingiva is less invasive than that from other tissues (such as bone marrow and fat), and GinPaMSCs provide an optimal substrate for drug-priming to obtain EVs/PTX having anticancer activity. This research may contribute to develop new strategies of cell-mediated drug delivery by EVs that are easy to store without losing function, and could have a superior safety profile in therapy.

Bilateral Hyperplasia of the Coronoid Process in Pediatric Patients: What is the Gold Standard for Treatment?

OBJECTIVES: The aim of this systematic review of the literature is to describe treatment options for bilateral coronoid process hyperplasia in pediatric patients, to describe etiologic and diagnostic correlations with the treatment, and to evaluate long-term follow-up treatment outcomes. METHODS: A systematic revision of the literature was performed in the Medline, PubMed, Cochrane library, and Embase database up to December 5, 2017. Predetermined Medical Subject Heading keywords were used: "bilateral" or "monolateral" and "coronoid" or "coronoid process" and "hyperplasia" and "temporomandibular joint" or "tmj" and "ankylosis" or "trismus" and "treatment." Results were recorded following PRISMA guidelines. RESULTS: The systematic research produced 1459 results excluding duplicates. Two additional studies from "Grey literature" were also considered. After application of inclusion and exclusion criteria, 38 articles were selected for a qualitative synthesis. Data regarding sex and age of presentation were collected and summarized in a study flow diagram. CONCLUSION: It is possible to conclude that early diagnosis is fundamental to restore stomatognathic multifunction. There is lack of longitudinal studies presenting long-term follow-up to determine treatment stability. Coronoidectomy might be considered gold standard treatment for this pathologic condition.

Prevalence and concordance of oral and genital HPV in women positive for cervical HPV infection and in their sexual stable partners: An Italian screening study.

OBJECTIVES: This cross-sectional study aimed to evaluate the prevalence and type of oral HPV-infection in women with a cervical HPV-lesion and in the oral and genital mucosa of their male partners. METHODS: The study group comprised 44 sexually-active women, 20-45 years with abnormal PAP smear, not more than 6 months prior to referral together with the male partners cohabiting in stable partnerships. A detailed questionnaire was administered concerning the HPV-related risk factors. Oral swabs, oral rinses, cervical swabs and urine samples were collected. HPV DNA was detected using two different polymerase chain reactions (PCRs): MY09-11 and FAP59-64. Positive samples were genotyped by Sanger sequencing and the INNO-LiPA HPV Genotyping Extra II probe assay. The association with risk factors was assessed by fitting a generalized model, using the General Linear Model function in the R-software; correlations were calculated between all data. RESULTS: HPV was detected in 84% of Cervical Samples, in 24.3% of oral samples and in one urine sample. Only 27% of the HPV-positive results were identical with both PCR DNA assays. 8 male had oral HPV-positive samples different from women cervical samples. In one couple the urine-male sample had the same HPV present in the female-cervical sample. A significant association resulted between women/oral sex practices and men/n. of partners. CONCLUSIONS: This study reports that women (20.4%) with a diagnosis of cervical-HPV and their male partners (30,7%) are at high risk for subclinical oral HPV infection.

Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in "distant" pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

Three-Dimensional Virtual Treatment Planning: Presurgical Evaluation.

OBJECTIVE: This article describes a virtual protocol designed to optimize surgical orthodontic diagnosis and treatment plan. METHODS: A total of 15 patients undergoing orthodontic-surgical treatment have been analyzed with a presurgical virtual three-dimensional (3D) treatment planning, which involves 9 steps. All the patients have been treated with the use of occlusal splint guides projected on the basis of the surgical and orthodontic visualized treatment objective . RESULTS: In all the analyzed patients, a precise and optimal orthodontic presurgical preparation has been obtained. CONCLUSIONS: The 3D analysis seems more precise to interpret than two-dimensional; it provides information and images of craniofacial structures free from perspective distortion and it reduces the steps of the presurgical diagnosis. The simplicity of the protocol described in this paper makes possible to apply it in everyday practice.The study described here allows high-precision planning of orthodontic-surgical therapy and optimization of each treatment phase, with consequent advantages in clinical practice: a more accurate orthognathic surgery with predictable results.

Orthodontic-surgical treatment: electromyographic and kinesiographic evaluation in follow up period. Experimental study.

INTRODUCTION: The aim of this study was to investigate muscular function and mandibular kinesiology of patients undergoing orthodontic-surgical treatment by electromyography and kinesiography. Electromyographic evaluation is essential to estimate masticatory forces in patients undergoing combined surgical-orthodontic treatment. MATERIALS AND METHODS: 60 patients referred for orthodontic surgical treatment were included in the study, 43 patients presented a class III while 17 presented a class II. The patients underwent electromyographic and kinesiographic examinations during all the therapeutic orthodontic-surgical phases. RESULTS: The relationship between fundamental electromyographic values and age, weight, asymmetry and activation was weak. A strong and positive relationship was observed between the relaxation percentage after TENS (transcutaneous electrical neuromuscular stimulation), the steepness of the post-surgery rehabilitation curve, the initial POC (percentage overlapping coefficient), and for the values in microvolts of the right and left temporal and masseters at the beginning of treatment. CONCLUSIONS: Patients with dentofacial deformities corrected by surgical treatment, have a significant positive treatment outcome in respect of masticatory activity and performance electromyographic evaluation on, before, during and follow up period of the analized patients permit to underline that this examination can predict long term stability.

Cytotoxic and Antimicrobial Activities of Cantharellus cibarius Fr. (Cantarellaceae).

Antibacterial and cytotoxic activities of cyclohexane, dichloromethane, methanol, and aqueous extracts of Cantharellus cibarius were tested. Broth microdilution assay was performed against 10 bacterial strains (Staphylococcus aureus, S. epidermidis, Micrococcus luteus, Bacillus subtilis, Enterococcus feacalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella abony), with emphasis on Helicobacter pylori. Methanol extract was the most active against H. pylori strains with minimal inhibitory concentration values between 4 and 32 µg/mL. All extracts were active against antibiotic resistant H. pylori. Methanol and aqueous extracts had no cytotoxicity against tested cell lines, whereas cyclohexane and dichloromethane extracts were active against HeLa and N87 cells, but also against healthy MRC-5 cells (IC50 39.26 ± 1.24-134.79 ± 0.01 µg/mL). The tested aqueous extracts have shown 68% of angiotensin-converting enzyme inhibitory activity in doses of 1.25 mg/mL. Chemical analysis has shown the presence of linoleic, cis-vaccenic, and oleic acids, sterols, ß-glucans, and polyphenolic compounds.

Natural Killer Cells in the Orchestration of Chronic Inflammatory Diseases.

Inflammation, altered immune cell phenotype, and functions are key features shared by diverse chronic diseases, including cardiovascular, neurodegenerative diseases, diabetes, metabolic syndrome, and cancer. Natural killer cells are innate lymphoid cells primarily involved in the immune system response to non-self-components but their plasticity is largely influenced by the pathological microenvironment. Altered NK phenotype and function have been reported in several pathological conditions, basically related to impaired or enhanced toxicity. Here we reviewed and discussed the role of NKs in selected, different, and "distant" chronic diseases, cancer, diabetes, periodontitis, and atherosclerosis, placing NK cells as crucial orchestrator of these pathologic conditions.

Orthodontic--surgical treatment and respiratory function: rhinomanometric assessment.

BACKGROUND: Several correlations between morphological and/or positional alterations of the jaws and respiratory functional impairments have been reported. Nasal airway obstruction represents a critical issue with no clearly defined gold standard as for its measurement. Rhinomanometry was adopted by multiple Authors to evaluate whether patients with malocclusion developed respiratory functional changes after an orthodontic-surgical treatment. However, there are contrasting findings in the literature regarding the possibility of improving the respiratory function by means of surgically-assisted rapid palatal expansion (SARPE) or bimaxillary repositioning of the bony bases. METHODS: Ten patients aged from 18 to 30 years and scheduled for orthodontic-surgical treatment of maxillary constriction volunteered as participants for this study. Orthognathic surgery consisted in: 1) SARPE in 4 patients; 2) Le Fort I down fracture combined with a bilateral sagittal split osteotomy (BSSO) in 6 patients. All patients underwent a computerized rhinomanometric test before treatment (T0) and 40 days after surgery, at the time of the inter-maxillary splint removal (T1). Specifically, all 10 patients received AAR evaluations, while 6 patients received both active anterior (AAR) and active posterior rhinomanometry (APR). RESULTS: Both AAR and APR tests showed a decrease in mean nasal resistance following the intervention. As for the AAR, a difference of 0.19 Pa/s/cm3 was found. The difference found for APR at a reference pressure of 75 Pa was 0.24 Pascal/s/cm3, while for APR at 150 Pa it was 0.20 Pa/s/cm3. CONCLUSIONS: This study helps to confirm respiratory benefits obtainable after mono and bi-maxillary orthognathic surgery.

Cell-mediated drug delivery by gingival interdental papilla mesenchymal stromal cells (GinPa-MSCs) loaded with paclitaxel.

OBJECTIVE: Gingival tissue is composed of cell types that contribute to the body's defense against many agents in oral environment, wound healing and tissue regeneration. Thanks to their easy and scarcely invasive withdrawal procedure, interdental papilla provide a good source of mesenchymal stromal cells (GinPa-MSCs). We isolated GinPa-MSCs and verified their ability to uptake/release the anticancer agent Paclitaxel (PTX). METHODS: In vitro expanded GinPa-MSCs were characterized for CD markers by FACS, tested for differentiation ability and analyzed by TEM. Their ability to uptake/release PTX was assessed according to a standardized procedure. RESULTS: The CD expression and chondro-adipo-osteo differentiation ability confirmed the mesenchymal feature of GinPa-MSCs. Surprisingly, 28% of GinPa-MSCs expressed CD14 marker and had an impressive pinocytotic activity. GinPa-MSCs were able to take up and release a sufficient amount of PTX to demonstrate effective in vitro activity against pancreatic carcinoma cells, suggesting that the drug was not inactivated. CONCLUSIONS: The procedure to obtain MSCs from interdental papilla is less invasive than that used for both bone marrow and adipose tissue, GinPa-MSCs are easy to expand and can be efficiently loaded with PTX. Taken together these qualities suggest that GinPa-MSCs may prove to be a good tool for cell-mediated drug delivery in cancer, particularly if related to stomatognathic system.

Functional evaluation in orthodontic surgical treatment: long-term stability and predictability.

BACKGROUND: The introduction of electromyographic and kinesiographic technology in orthodontics allows to obtain objective data regarding the functional aspects of the mandibular movements and the masticatory muscular activity. It is then important to be able to correlate the data obtained by instrumental activity with the clinical ones. The aim of this study consists to analyse the post ortodontic surgical stability through instrumental evaluation of the masticatory muscles and mandibular movements. METHOD: 30 patients undergo electromyographic and kinesiographic evaluations through all the surgical orthodontic iter and were than followed during other 4 years. JMP software was used to analyze and correlate the electromyographic and knesioographic data during treatment and during the follow up. RESULTS: A linear correlations between some functional objective values collected from the examinations at the beginning and during therapy and the follow up one has been demonstrated. CONCLUSION: It is important to submit patients in surgical ortodontic treatment to instrumental analysis which can evidence how masticatory function and mandibular movements are performed. It is also important to highlight some functional values also from the beginning of the treatment because an alteration of such values can be related to a better or worse postsurgical rehabilitation.

Three-dimensional evaluation of upper airway in patients with obstructive sleep apnea syndrome during oral appliance therapy.

Obstructive sleep apnea syndrome (OSAS) represents a frequent and common respiratory disease characterized by repeated episodes of complete and/or partial obstruction of upper airways during sleep, normally associated with reduction of oxygen saturation in blood. The oral appliances (OAs) are considered to be an effective treatment modality thanks to the upper airway enlargement. Lateral cephalometry has been used for the 2-dimensional evaluation of upper airway form with several limits. We obtained an accurate 3-dimensional (3D) volume analyses with cone beam computed tomography (CBCT) scans to confirm the effects of OA on the upper airway in patients with OSAS. Ten Italian patients with moderate or severe OSA (3 males and 7 females, 53.4 ± 11.3 years of age, and BMI 24.5 ± 2.7), who cannot tolerate continuous positive air pressure therapy and rejected a surgical approach, were treated with non-adjustable customized OAs and evaluated with CBCT and polysomnography. Upper airway form was examined in the presence and absence of OA and the volume was measured and compared in 2 different areas. Specific planes have been considered to match the data and calculate the benefit obtained with therapy. Nine out of ten patients showed an improvement of total upper airway volume and an improvement in apnea-hypopnea index. Volume increased both in the posterior soft palate region and in the posterior tongue region. In the inferior area, we observed greater differences. 3D image reconstruction accurately confirmed morphological changes in the upper airway during OA therapy. The use of this 3D evaluation is expected to improve the results of OA therapy in the future.

Presurgical virtual three-dimensional treatment planning.

AIM: This article describes an experimental protocol designed to optimize surgical orthodontic diagnosis and treatment plan. MATERIALS AND METHODS: In this study, 15 patients undergoing orthodontic-surgical treatment have been analyzed.The superimposition between models and respective presurgical setup for each group was performed. A best-fit algorithm was used to find the position of the arches in space for which the sum of the discrepancies was the shortest.A punctual variation colorimetric map indicating percentages of areas subjected to different discrepancies was used to evaluate the degree of congruence between the 2 models.Furthermore, for each arch the software provided metric values of maximum positive deviation, maximum negative deviation, mean deviation, and standard deviation that characterize the points compared in the superimposition. RESULTS: For all the considered patients, the orthodontic preparation for surgery was obtained according to the splint guides and the orthodontic planning. CONCLUSION: The protocol described here allows high-precision planning of orthodontic-surgical therapy optimization of each treatment phase, with consequent advantages in clinical practice.

Accidental aspiration of foreign bodies in dental practice: clinical management and prevention.

OBJECTIVE: Foreign body aspiration is a possible complication of dental treatment that may result in a life-threatening situation. The foreign body is often spontaneously ejected from the airway, but in other cases, surgical intervention is needed. Prevention, diagnostic procedures, treatment and complications are discussed. MATERIALS AND METHODS: Three cases of aspiration of dental instruments are described: the piece was localised in the right main bronchus in two cases and in the left main bronchus in one case. RESULTS: All three cases underwent surgery (resection and bronchoscopy); in one case, the surgical attempt failed, and the foreign body was not located by radiography; it was assumed to have been expelled spontaneously. CONCLUSION: The management of dental materials and instruments requires particular care, especially if the patient is supine or semi-recumbent. The dentist must be able to manage emergency situations in which patients accidentally inspire or swallow dental instruments or materials during treatment. Preventive techniques must be put in place because these incidents are preventable if the correct precautions are taken.

Orthodontic Treatment of Binder Syndrome: A Case Report With 5 Years of Follow-up.

We report here the case of orthodontic nonsurgical treatment in a patient with Binder syndrome. This rare syndrome (<1/10,000) is a deforming alteration of the middle third of the face, also known as maxillonasal dysplasia/dysostosis. The therapeutic approach often undertaken is an orthodontic-surgical protocol, which includes several invasive interventions such as LeFort I or II. In this patient and early diagnosis made it possible to intervene on an orthodontic level only, thus avoiding highly invasive surgical procedures (as of a 5-year follow-up).

Prevalence of sinonasal disease in children with Juvenile idiopathic arthritis.

OBJECTIVES/HYPOTHESIS: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is caused by a multitude of well-studied disorders. However, the association between JIA and/or its treatment and sinonasal inflammatory disease (SNID) has never been studied. We therefore investigated this relationship to gain more insight into burdening pathologies connected to JIA. STUDY DESIGN: Retrospective evaluation. METHODS: A retrospective evaluation according to the Lund-Mackay score of cone-beam computed tomography scans (CBCT) performed in 70 children affected by JIA and compared to CBCT scans of 124 healthy controls was conducted. The prevalence of sinonasal opacification and adenoid hypertrophy in patients affected with JIA was compared with findings obtained in unaffected children. RESULTS: JIA was significantly associated with SNID (P = .030). Of patients with JIA, 18.6% had SNID, whereas in children without JIA, only 8.1% had SNID. The odds ratio values were 5.38 (95% confidence interval [CI]: 1.90-15.26) for treated and 0.92 (95% CI: 0.18-4.83) for untreated JIA. No clear difference was found depending on the duration of JIA. No association was found between adenoid hypertrophy and SNID (P = .816). CONCLUSIONS: Our data suggest that JIA patients, especially when undergoing immunosuppressive therapy, should be subjected to an ear, nose, and throat evaluation. A prospective study including clinical evaluation would be of the utmost importance to provide evidence on which to base comprehensive healthcare for these patients. LEVEL OF EVIDENCE: 3b.

Upper airway obstuction in class II patients. Effects of Andresen activator on the anatomy of pharingeal airway passage. Cone beam evalution.

AIM: The aim of this study is to assess the response and changes on pharyngeal airway passage (PAP) to class II Andresen appliance in class II growing patients with obstructive sleep apnea syndrome (OSAS). METHODS: The sample consisted of forty patients with a class II malocclusion in the age range of 9 to 14 years with mandibular retrusion and OSAS and ten control group subjects. A CBCT was taken before treatment (T0) and a second one after a follow-up period of approximately 16 months (T1). The dimensions of PAP were determined according to the method described by Jena et al. with Mimics program. The following parameters were considered: DOP, DPH, MP-H, PAS, PNS-U, SNA, SNB, ANB. The statistical analysis was carried out with t test. RESULTS: The change in ANB, SNB, MP-H, PNS-U, PAS was significantly more in the patients undergoing treatment as compared to the control group. The improvement of DOP and DPH among the treatment group subjects was significantly more compared to the control group subjects. CONCLUSIONS: Class II correction by functional appliances during childhood might help to eliminate the adaptive changes in the upper airway and predisposing factors to OSAS, thus decreasing the risk of OSAS development in adulthood.