Endoscopic endonasal anatomy of the ophthalmic artery in the optic canal.

BACKGROUND: The endoscopic endonasal opening of the optic canal has been recently proposed for tumors with medial invasion of this canal, such as tuberculum sellae meningiomas. Injury of the ophthalmic artery represents a dramatic risk during this maneuver. Therefore, the aim of this study was to analyze the endoscopic endonasal anatomy of the precanalicular and canalicular portion of this vessel, discussing its clinical implication. METHODS: The course of the ophthalmic artery was analyzed through five endoscopic endonasal dissections, and 40 nonpathological consecutive MRAs were reviewed. RESULTS: The ophthalmic artery arises from the intradural portion of the supraclinoid internal carotid artery, in 93 % of cases about 1.9 mm (range: 1-3) posterior to the falciform ligament. At the entrance into the optic canal, the ophthalmic artery is located infero-medially to the optic nerve in 13 % of cases. In 50 % of these cases the artery moves infero-laterally along its course, remaining in a medial position in the others. In cases with an non medial entrance of the ophthalmic artery, it runs infero-lateral to the optic nerve for its entire canalicular portion, with just one exception. CONCLUSION: The endoscopic endonasal approach gives a direct, extensive and panoramic view of the course of the precanalicular and canalicular portion of the ophthalmic artery. Dedicated high-field neuroimaging studies are of paramount importance in preoperative planning to evaluate the anatomy of the ophthalmic artery, reducing the risk of jeopardizing the vessel, particularly for those uncommon cases with an infero-medial course of the artery.

Dissecting human anatomy learning process through anatomical education with augmented reality: AEducAR 2.0, an updated interdisciplinary study.

Anatomical education is pivotal for medical students, and innovative technologies like augmented reality (AR) are transforming the field. This study aimed to enhance the interactive features of the AEducAR prototype, an AR tool developed by the University of Bologna, and explore its impact on human anatomy learning process in 130 second-year medical students at the International School of Medicine and Surgery of the University of Bologna. An interdisciplinary team of anatomists, maxillofacial surgeons, biomedical engineers, and educational scientists collaborated to ensure a comprehensive understanding of the study's objectives. Students used the updated version of AEducAR, named AEducAR 2.0, to study three anatomical topics, specifically the orbit zone, facial bones, and mimic muscles. AEducAR 2.0 offered two learning activities: one explorative and one interactive. Following each activity, students took a test to assess learning outcomes. Students also completed an anonymous questionnaire to provide background information and offer their perceptions of the activity. Additionally, 10 students participated in interviews for further insights. The results demonstrated that AEducAR 2.0 effectively facilitated learning and students' engagement. Students totalized high scores in both quizzes and declared to have appreciated the interactive features that were implemented. Moreover, interviews shed light on the interesting topic of blended learning. In particular, the present study suggests that incorporating AR into medical education alongside traditional methods might prove advantageous for students' academic and future professional endeavors. In this light, this study contributes to the growing research emphasizing the potential role of AR in shaping the future of medical education.

Anatomical Study of the Application of a Galeo-Pericranial Flap in Oral Cavity Defects Reconstruction.

Oral cavity defects occur after resection of lesions limited to the mucosa, alveolar gum, or minimally affecting the bone. Aiming at esthetical and functional improvements of intraoral reconstruction, the possibility of harvesting a new galeo-pericranial free flap was explored. The objective of this study was to assess the technical feasibility of flap harvesting through anatomical dissections and surgical procedure simulations. Ten head and neck specimens were dissected to simulate the surgical technique and evaluate the vascular calibers of temporal and cervical vessels. The procedure was therefore reproduced on a revascularized and ventilated donor cadaver. Anatomical dissections demonstrated that the mean cervical vascular calibers are compatible with superficial temporal ones, proving to be adequate for anastomosis. Perforating branches of the superficial temporal vascularization nourishing the pericranium were identified in all specimens. In conclusion, blood flow presence was recorded after anastomosing superficial temporal and facial vessels in the revascularized donor cadaver, demonstrating both this procedure's technical feasibility and the potential revascularization of the flap and therefore encouraging its potential in vivo application.

AEducaAR, Anatomical Education in Augmented Reality: A Pilot Experience of an Innovative Educational Tool Combining AR Technology and 3D Printing.

Gross anatomy knowledge is an essential element for medical students in their education, and nowadays, cadaver-based instruction represents the main instructional tool able to provide three-dimensional (3D) and topographical comprehensions. The aim of the study was to develop and test a prototype of an innovative tool for medical education in human anatomy based on the combination of augmented reality (AR) technology and a tangible 3D printed model that can be explored and manipulated by trainees, thus favoring a three-dimensional and topographical learning approach. After development of the tool, called AEducaAR (Anatomical Education with Augmented Reality), it was tested and evaluated by 62 second-year degree medical students attending the human anatomy course at the International School of Medicine and Surgery of the University of Bologna. Students were divided into two groups: AEducaAR-based learning ("AEducaAR group") was compared to standard learning using human anatomy atlas ("Control group"). Both groups performed an objective test and an anonymous questionnaire. In the objective test, the results showed no significant difference between the two learning methods; instead, in the questionnaire, students showed enthusiasm and interest for the new tool and highlighted its training potentiality in open-ended comments. Therefore, the presented AEducaAR tool, once implemented, may contribute to enhancing students' motivation for learning, increasing long-term memory retention and 3D comprehension of anatomical structures. Moreover, this new tool might help medical students to approach to innovative medical devices and technologies useful in their future careers.

An Ancient Science to Improve Today's Clinical Practice: Oral Surgery Meets Human Anatomy.

Human body dissection was a ubiquitous practice in the past, to better understand anatomy and to develop medicine. Today, its role could still be important to answer everyday clinical queries and help surgeons. The example of the possible lack of anesthesia during symphysis surgeries can emphasize the usefulness of dissection. The mandibular symphysis usually receives innervation from inferior alveolar nerve terminations, but, in some rare cases, a particular anastomosis involves the lingual nerve and the nerve to the mylohyoid. The anatomical knowledge resulting from body dissections could help oral surgeons to understand the reason why the patient could feel pain during the surgery, and ensure performance of the right lingual nerve block to obtain complete anesthesia. This clinical situation shows the educational role of an ancient, yet still valid, practice, human dissection, and the importance of anatomical studies to improve surgical skills, to provide better treatment for the patient.

Cellular senescence in vascular wall mesenchymal stromal cells, a possible contribution to the development of aortic aneurysm.

Cellular senescence is a hallmark of ageing and it plays a key role in the development of age-related diseases. Abdominal aortic aneurysm (AAA) is an age related degenerative vascular disorder, characterized by a progressive dilatation of the vascular wall and high risk of rupture over time. Nowadays, no pharmacological therapies are available and the understanding of the molecular mechanisms that lead to AAA onset and development are poorly defined. In this study we investigated the cellular features of senescence in vascular mesenchymal stromal cells, isolated from pathological (AAA - MSCs) and healthy (h - MSCs) segments of human abdominal aorta and their implication in impairing the vascular repair ability of MSCs. Cell proliferation, ROS production, cell surface area, the expression of cyclin dependent kinase inhibitors p21CIP1 and p16INK4a, the activation of the DNA damage response and a dysregulated autophagy showed a senescent state in AAA - MSCs compared to h-MSCs. Moreover, a reduced ability to differentiate toward endothelial cells was observed in AAA - MSCs. All these data suggest that the accumulation of senescent vascular MSCs over time impairs their remodeling ability during ageing. This condition could support the onset and development of AAA.

Assessment of the structural and functional characteristics of human mesenchymal stem cells associated with a prolonged exposure of morphine.

The discovery of the expression of opioid receptors in the skin and their role in orchestrating the process of tissue repair gave rise to questions regarding the potential effects of clinical morphine treatment in wound healing. Although short term treatment was reported to improve tissue regeneration, in vivo chronic administration was associated to an impairment of the physiological healing process and systemic fibrosis. Human mesenchymal stem cells (hMSCs) play a fundamental role in tissue regeneration. In this regard, acute morphine exposition was recently reported to impact negatively on the functional characteristics of hMSCs, but little is currently known about its long-term effects. To determine how a prolonged treatment could impair their functional characteristics, we exposed hMSCs to increasing morphine concentrations respectively for nine and eighteen days, evaluating in particular the fibrogenic potential exerted by the long-term exposition. Our results showed a time dependent cell viability decline, and conditions compatible with a cellular senescent state. Ultrastructural and protein expression analysis were indicative of increased autophagy, suggesting a relation to a detoxification activity. In addition, the enhanced transcription observed for the genes involved in the synthesis and regulation of type I collagen suggested the possibility that a prolonged morphine treatment might exert its fibrotic potential risk, even involving the hMSCs.

Augmented Reality-Assisted Periosteum Pedicled Flap Harvesting for Head and Neck Reconstruction: An Anatomical and Clinical Viability Study of a Galeo-Pericranial Flap.

Head and neck reconstructive surgeons have recently explored new perspectives in bone restoration using periosteum carrier flaps. Following this idea, we explored the possibility of harvesting a galeo-pericranial flap. The present work studies the vascular supply of the pericranial temporo-parietal region in order to assess the possibility of harvesting a galeo-pericranial flap based on the superficial temporalis vascularization. Anatomical dissections were performed at the Anatomical Institute of the University of Bologna on eight donor cadavers. Then we performed the harvesting of the flap in vivo on eight patients. We introduced augmented reality (AR) to facilitate anatomical visualisation during free flap harvesting. Augmented reality merges virtual and actual objects, allowing direct observation of patient anatomy and the surgical field. No post-operative major or minor complications occurred. We encountered no post-operative functional issues on the donor or recipient sites, and good clinical healing was observed in all patients. In conclusion, we believe that the galea-pericranium flap could represent a new donor site for the harvesting of a periosteum carrier flap.

ElectroBond improves immediate dentin microtensile bond strength of two etch-and-rinse adhesives.

PURPOSE: The aim of this study was to investigate whether an electrical device for dental adhesive application (ElectroBond) influences bonding of two-step etch-and-rinse adhesives. MATERIALS AND METHODS: Human teeth were selected and cut perpendicularly to their long axis to expose middle/ deep dentin. Specimens were then longitudinally sectioned into halves (experimental and control halves) to create two similar bonding substrates. Experimental halves were bonded using an ElectroBond-assisted application, while control halves were bonded with disposable sponges. The adhesives tested were Adper Scotchbond 1XT and XP-BOND. Bonded specimens were submitted to the microtensile bond strength test. Additional adhesive interfaces were prepared and processed for nanoleakage investigation involving TEM examination. RESULTS: The microtensile bond test revealed higher values (p < 0.05) for both adhesives if ElectroBond was used during layering (55.5 +/- 7.9 MPa for Adper Scotchbond 1XT and 54.7 +/- 7.1 MPa for XP-BOND) compared to the conventional mechanical adhesive application technique (41.1 +/- 6.1 MPa for Adper Scotchbond 1XT and 38.0 +/- 7.8 MPa for XP-BOND). No difference between the two adhesives was found under the same application conditions. With electricity-assisted application, TEM micrographs revealed a significant decrease in nanoleakage expression compared to the controls. CONCLUSION: The use of an electric current produced by ElectroBond during the application of two-step etch-and-rinse adhesives may enhance resin impregnation, thus improving dentin hybridization. Further studies should be done to confirm that this device can similarly improve adhesive application in vivo.

Expression of procollagen alpha1 type I and tenascin proteins induced by HEMA in human pulp fibroblasts.

In the dental pulp extracellular matrix, the main macromolecules are collagenous proteins, non-collagenous proteins and proteoglycans. Regulated synthesis of the interstitial collagens, in particular, type I collagen, is important during development and wound healing but also in a number of pathological conditions. Tenascin is also a matrix protein highly expressed during development while it decreases in mature organs. Under pathological conditions such as infections and inflammation, during tumorigenesis and mechanical stress applied to cells in culture or tissue in vivo, the expression of tenascin is increased. In this study, HEMA, widely used in dentistry, ophthalmology and drug delivery, has been used to study its influence on the expression of procollagen alpha1 type I and tenascin proteins in the primary cultures of human pulp fibroblasts. Different concentrations of the resin monomer and different times of exposition were tested. The influence of HEMA on the cell viability was evaluated by means of an MTT assay while immunofluorescence and western blotting analysis were performed to detect possible interference with the presence and the synthesis of these proteins. We observed a strong reduction in cell viability in specimens treated for 96 h and 168 h, especially at concentrations of 1 and 3 mmol/L HEMA. Both immunofluorescence and western blotting analysis demonstrated a reduction of procollagen alpha1 type I protein and an overexpression of tenascin protein. Our results showed that long-term exposure and low concentrations of HEMA influence normal cell activity, such as the synthesis of some of the dental pulp extracellular matrix proteins.

Dental adhesion review: aging and stability of the bonded interface.

OBJECTIVE: Most of current dental adhesive systems show favorable immediate results in terms of retention and sealing of bonded interface, thereby counteracting polymerization shrinkage that affects resin-based restorative materials. Despite immediate efficacy, there are major concerns when dentin bonded interfaces are tested after aging even for short time period, i.e. 6 months. METHODS: This study critically discusses the latest peer-reviewed reports related to formation, aging and stability of resin bonding, focusing on the micro and nano-phenomena related to adhesive interface degradation. RESULTS: Most simplified one-step adhesives were shown to be the least durable, while three-step etch-and-rinse and two-step self-etch adhesives continue to show the highest performances, as reported in the overwhelming majority of studies. In other words, a simplification of clinical application procedures is done to the detriment of bonding efficacy. Among the different aging phenomena occurring at the dentin bonded interfaces, some are considered pivotal in degrading the hybrid layer, particularly if simplified adhesives are used. Insufficient resin impregnation of dentin, high permeability of the bonded interface, sub-optimal polymerization, phase separation and activation of endogenous collagenolytic enzymes are some of the recently reported factors that reduce the longevity of the bonded interface. SIGNIFICANCE: In order to overcome these problems, recent studies indicated that (1) resin impregnation techniques should be improved, particularly for two-step etch-and-rinse adhesives; (2) the use of conventional multi-step adhesives is recommended, since they involve the use of a hydrophobic coating of nonsolvated resin; (3) extended curing time should be considered to reduce permeability and allow a better polymerization of the adhesive film; (4) proteases inhibitors as additional primer should be used to increase the stability of the collagens fibrils within the hybrid layer inhibiting the intrinsic collagenolytic activity of human dentin.

Effects of citric acid and EDTA conditioning on exposed root dentin: An immunohistochemical analysis of collagen and proteoglycans.

OBJECTIVE: Preservation of structural and biochemical properties of the root dentin matrix is crucial to favor healing and regenerative periodontal processes. Aim of this study was to evaluate the biochemical characteristics of collagen and chondroitin sulphate of root dentin surfaces exposed by periodontal disease after acid conditioning by means of an immunohistochemical technique. DESIGN: Human teeth scheduled for extraction due to periodontal reason were submitted to: (A) scaling and root planning; (B) ultrasonic instrumentation; (C) no instrumentation. Teeth were then exposed to: (1) 10% citric acid; (2) 17% EDTA; (3) no etching. A double immunolabeling technique was performed to identify type-I collagen and proteoglycans and analyzed under FEI-SEM. RESULTS: Use of 10% citric acid revealed intense labeling for collagen fibrils and proteoglycans; lower labeling was found after EDTA conditioning. Unetched specimens showed residual smear layer on the dentin surface resulting in no evident surface labeling. CONCLUSIONS: This study supports the hypothesis that manual or ultrasonic instrumentation alone is not able to expose the sound dentin matrix, whereas a subsequent acidic conditioning exposes collagen fibrils and associated proteoglycans. The immunohistochemical technique revealed that despite their acidity, both citric acid and EDTA were able to preserve the structural and biochemical properties of the exposed dentin matrix.

Electric device improves bonds of simplified etch-and-rinse adhesives.

OBJECTIVES: This study investigated the effects of an electric field produced by a new device for the application of etch-and-rinse adhesives on demineralized dentin surfaces. METHODS: Three simplified etch-and-rinse adhesives (Single Bond, Prime&Bond NT and One-Step) were applied with the electric device and compared with controls prepared with disposable sponges. Specimens were processed for microtensile bond strength test and nanoleakage investigation using high resolution SEM. RESULTS: Microtensile testing revealed higher bond strengths (p<0.05) for all adhesives tested when electricity was used. Adhesive interfaces prepared with electric impulses exhibited very homogenous hybrid layers with minimal nanoleakage compared with the controls. SIGNIFICANCE: The use of electricity produced by a new electronic device during the application of dentin adhesives may increase adhesive adaptation to the dentin substrate and improve dentin hybridization due to the substrate modifications induced by an electric field on the demineralized dentin organic matrix.

Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function.

Calreticulin is a Ca2+-binding chaperone protein, which resides mainly in the endoplasmic reticulum but also found in other cellular compartments including the plasma membrane. In addition to Ca2+, calreticulin binds and regulates almost all proteins and most of the mRNAs deciding their intracellular fate. The potential functions of calreticulin are so numerous that identification of all of them is becoming a nightmare. Still the recent discovery that patients affected by the Philadelphia-negative myeloproliferative disorders essential thrombocytemia or primary myelofibrosis not harboring JAK2 mutations carry instead calreticulin mutations disrupting its C-terminal domain has highlighted the clinical need to gain a deeper understanding of the biological activity of this protein. However, by contrast with other proteins, such as enzymes or transcription factors, the biological functions of which are strictly defined by a stable spatial structure imprinted by their amino acid sequence, calreticulin contains intrinsically disordered regions, the structure of which represents a highly dynamic conformational ensemble characterized by constant changes between several metastable conformations in response to a variety of environmental cues. This article will illustrate the Theory of calreticulin as an intrinsically disordered protein and discuss the Hypothesis that the dynamic conformational changes to which calreticulin may be subjected by environmental cues, by promoting or restricting the exposure of its active sites, may affect its function under normal and pathological conditions.

ADAM10 localization in temporomandibular joint disk with internal derangement: an ex vivo immunohistochemical study.

The purpose of this study was to determine the presence of ADAM10 in temporomandibular joint disk with internal derangement. Twenty-five paraffin blocks of displaced temporomandibular joint (TMJ) disk specimens from earlier investigations were retrieved from the archives of the University of Catania. Of these 16 had been removed from females and 9 from males; 11 with anterior disk displacement with reduction (ADDwR) and 14 with anterior disk displacement without reduction (ADDwoR). The sections were dehydrated, embedded in paraffin and cut. Then they were incubated in 0.3% H2O2/methanol and half of sections from each sample were incubated in diluted rabbit polyclonal anti-ADAM10 antibody. Then biotinylated anti-mouse/anti-rabbit IgG was applied to the sections, followed by avidin-biotin-perioxidase complex. The results were analyzed and the results were that ADAM10 was overexpressed in the posterior band of sections from patients with ADDwR compared to the other bands of both ADDwR and ADDwoR sections. Overexpression correlated with severe histopathological degeneration. We believe these results have the potential to provide insights into the pathogenesis of TMJ disk degeneration and to help design new therapeutic approaches targeting the proteolytic events that lead to tissue degeneration. Early therapeutic block of ADAM10 activity could succeed in limiting aggrecan-rich matrix breakdown without affecting normal physiology.

Detection of Virulence Genes and Growth Potential in Listeria monocytogenes Strains Isolated from Ricotta Salata Cheese.

Ricotta Salata is a traditional ripened and salted whey cheese made in Sardinia (Italy) from sheep's milk. This product is catalogued as ready-to-eat food (RTE) since it is not submitted to any further treatment before consumption. Thus, foodborne pathogens, such as Listeria monocytogenes, can represent a health risk for consumers. In September 2012, the FDA ordered the recall of several batches of Ricotta Salata imported from Italy linked to 22 cases of Listeriosis in the United States. This study was aimed at evaluating the presence and virulence properties of L. monocytogenes in 87 samples of Ricotta Salata produced in Sardinia. The ability of this product to support its growth under foreseen packing and storing conditions was also evaluated in 252 samples. Of the 87 samples 17.2% were positive for the presence of L. monocytogenes with an average concentration of 2.2 log10 cfu/g. All virulence-associated genes (prfA, rrn, hlyA, actA, inlA, inlB, iap, plcA, and plcB) were detected in only one isolated strain. The Ricotta Salata samples were artificially inoculated and growth potential (δ) was assessed over a period of 3 mo. The value of the growth potential was always >0.5 log10 cfu/g under foreseen packing and storing conditions. This study indicates that Ricotta Salata supports the L. monocytogenes growth to levels that may present a serious risk to public health, even while stored at refrigeration temperatures.

IPMK and ß-catenin mediate PLC-ß1-dependent signaling in myogenic differentiation.

In previous studies, we have reported that phospholipase C (PLC)-ß1 plays a crucial role in myogenic differentiation and we determined the importance of its catalytic activity for the initiation of this process. Here we define the effectors that take part to its signaling pathway. We show that the Inositol Polyphosphate Multikinase (IPMK) is able to promote myogenic differentiation since its overexpression determines the up-regulation of several myogenic markers. Moreover, we demonstrate that IPMK activates the same cyclin D3 promoter region targeted by PLC-ß1 and that IPMK-induced promoter activation relies upon c-jun binding to the promoter, as we have shown previously for PLC-ß1. Furthermore, our data shows that IPMK overexpression causes an increase in ß-catenin translocation and accumulation to the nuclei of differentiating myoblasts resulting in higher MyoD activation. Finally, we describe that PLC-ß1 overexpression determines too an increase in ß-catenin translocation and that PLC-ß1, IPMK and ß-catenin are mediators of the same signaling pathway since their overexpression results in cyclin D3 and myosin heavy chain (MYH) induction.

Nanoleakage within the hybrid layer: a correlative FEISEM/TEM investigation.

The aim of this study was to compare the nanoleakage patterns of the resin-dentin interfaces of three dentin bonding systems at both TEM and field emission in lens SEM (FEI-SEM) levels. A standardized smear layer was created with 180-grit silicon carbide paper (SiC) on dentin disks obtained from 18 noncarious human third molars. Specimens were randomly divided into three groups and bonded with a two-step total etching adhesive (Single Bond, SB), a two-step, self-etching adhesive (Clearfil SE BOND, SEB), and a one-step, self-etching adhesive (XENO III, XEIII). Nanoleakage was evaluated by using an ammoniacal silver-nitrate solution. Specimens were processed for TEM and FEI-SEM observation. The TEM of SB revealed silver deposits in adhesive and hybrid layers (HL). High-magnification FEI-SEM micrographs clearly identified these deposits as spherical clusters mainly associated with nonembedded collagen fibrils. TEM and FEI-SEM examination of SEB revealed some clusters of silver deposits within porosities and small channels of the HL. Additional silver deposits were observed between the peritubular dentin walls and the resin tags. XEIII revealed very fine and diffuse silver grains throughout the entire HL. SEM visualization of nanoleakage at a high level of resolution has not been previously described. FEI-SEM technology supported the TEM visualization with three-dimensional morphological data of the relations between the HL constituents and nanoleakage. The results of the present study confirm the hypothesis that both total- and self-etch adhesives are not able to fully infiltrate the dentin substrate.

A novel interaction between megakaryocytes and activated fibrocytes increases TGF-ß bioavailability in the Gata1(low) mouse model of myelofibrosis.

Despite numerous circumstantial evidences, the pathogenic role of TGF-ß in primary myelofibrosis (PMF), the most severe of the Philadelphia-negative myeloproliferative neoplasms, is still unclear because of the modest (2-fold) increases in its plasma levels observed in PMF patients and in the Gata1(low) mouse model. Whether myelofibrosis is associated with increased bioavailability of TGF-ß bound to fibrotic fibres is unknown. Transmission electron-microscopy (TEM) observations identified that spleen from PMF patients and Gata1(low) mice contained megakaryocytes with abnormally high levels of TGF-ß and collagen fibres embedded in their cytoplasm. Additional immuno-TEM observations of spleen from Gata1(low) mice revealed the presence of numerous activated fibrocytes establishing with their protrusions a novel cellular interaction, defined as peripolesis, with megakaryocytes. These protrusions infiltrated the megakaryocyte cytoplasm releasing collagen that was eventually detected in its mature polymerized form. Megakaryocytes, engulfed with mature collagen fibres, acquired the morphology of para-apoptotic cells and, in the most advanced cases, were recognized as polylobated heterochromatic nuclei surrounded by collagen fibres strictly associated with TGF-ß. These areas contained concentrations of TGF-ß-gold particles ~1000-fold greater than normal and numerous myofibroblasts, an indication that TGF-ß was bioactive. Loss-of-function studies indicated that peripolesis between megakaryocytes and fibrocytes required both TGF-ß, possibly for inducing fibrocyte activation, and P-selectin, possibly for mediating interaction between the two cell types. Loss-of-function of TGF-ß and P-selectin also prevented fibrosis. These observations identify that myelofibrosis is associated with pathological increases of TGF-ß bioavailability and suggest a novel megakaryocyte-mediated mechanism that may increase TGF-ß bioavailability in chronic inflammation.

HEMA but not TEGDMA induces autophagy in human gingival fibroblasts.

Polymerized resin-based materials are successfully used in restorative dentistry. Despite their growing popularity, one drawback is the release of monomers from the polymerized matrix due to an incomplete polymerization or degradation processes. Released monomers are responsible for several adverse effects in the surrounding biological tissues, inducing high levels of oxidative stress. Reactive oxygen species are important signaling molecules that regulate many signal-trasduction pathways and play critical roles in cell survival, death, and immune defenses. Reactive oxygen species were recently shown to activate autophagy as a mechanism of cell survival and cell death. Although the toxicity induced by dental resin monomers is widely studied, the cellular mechanisms underlying these phenomena are still unknown. The aim of the study was to investigate the behavior of human gingival cells exposed to 2-hydroxy-ethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) to better elucidate the mechanisms of cell survival and cell death induced by resin monomers. Primary culture of human gingival cells were exposed to 3 mmol/L of HEMA or 3 mmol/L of TEGDMA for 24, 48, and 72 h. Morphological investigations were performed by transmission electron microscopy to analyze the ultrastructure of cells exposed to the monomers. The expression of protein markers for apoptosis (caspase - 3 and PARP) and autophagy (beclin - 1 and LC3B I/II) were analyzed by western blot to investigate the influence of dental resin monomers on mechanisms underlying cell death. Results showed that HEMA treatment clearly induced autophagy followed by apoptosis while the lack of any sign of autophagy activation is observed in HGFs exposed to TEGDMA. These data indicate that cells respond to monomer-induced stress by the differential induction of adaptive mechanisms to maintain cellular homeostasis.