Detection and activity of MMP-2 and MMP-9 in Leishmania amazonensis and Leishmania braziliensis promastigotes.

Metalloproteinases (MMPs) are remarkable zinc-dependent endopeptidases, critical for degrading components of the extracellular matrix, thus actively influencing cell migration. Their impact on intracellular parasites, such as the enigmatic protozoan Leishmania, elicits intriguing queries. This study explores into the untapped territory of MMP-2 and MMP-9 within Leishmania spp. promastigotes. Notably, we successfully detected and quantified these MMPs, while also evaluating their activity in two distinct Leishmania species-L. amazonensis (La) and L. braziliensis (Lb)-at various growth stages and isolated from distinct clinical tegumentar disease forms. The results unveiled the presence of MMP-2 and MMP-9 in both species, albeit with distinct localization patterns. Specifically, MMP-9 exhibited significantly higher gelatinolytic activity in La when compared to Lb. Moreover, our data cleverly illustrated the presence and release of MMP-2 and MMP-9 by La and Lb promastigotes, exposing their ability to invade and migrate within a collagen matrix. This pioneering study establishes a compelling correlation between MMP-2 and MMP-9 and their potential role in the dynamics of La and Lb infection. Suggesting their potential as prognostic markers for severe leishmaniasis and promising target molecules for therapeutic interventions, this research opens new avenues for combatting this debilitating parasitic disease.

Management of oral leukoplakia with an 808-nm high-power diode laser: a single-center experience.

PURPOSE: High-power diode laser emerges as a promising approach to the treatment of oral leukoplakia (OL); however, its short- and long-term effects have been barely explored. This study evaluated the postoperative endpoints and the recurrence rate of high-power diode laser treatment in a well-defined series of patients with OL. METHODS: A prospective analysis was performed on 22 individuals comprising 31 OL. The lesions were irradiated using the following protocol: Indium-Gallium-Arsenide diode laser, 808 nm, continuous-wave mode, 1.5-2.0 W, 780.0 ± 225.1 J, and 477.1 ± 131.8 s. Postoperative pain was assessed with a visual analog scale at three endpoints. Clinical follow-up was performed on all patients and the Kaplan-Meier test was used to analyze the probability of recurrence. RESULTS: The series consisted mostly of women (72.7%) with a mean age of 62.8 years. A single laser session was performed in 77.4% of cases. The median score on the scale that assessed pain on the 1st, 14th and 42nd postoperative day was 4, 1, and 0, respectively. The mean follow-up period per lesion was 28.6 months (range: 2-53 months). A complete response was observed in 93.5% of OL cases, while 6.5% had recurrence. The probability of recurrence at 39 months was 6.7%. No patient experienced malignant transformation. CONCLUSION: High-power diode laser for the treatment of OL is safe and effective during the trans- and postoperative period. These findings represent an alternative approach to the management of OL, mainly because a low recurrence rate was observed.

Downregulation of metallothionein 2A reduces migration, invasion and proliferation activities in human squamous cell carcinoma cells.

BACKGROUND: The invasive behaviour of squamous cell carcinoma (SCC), a common malignant tumour of the mouth, is a process mediated by cell proliferation, extracellular matrix proteolysis and other factors. Studies have shown a potential relationship between growth factors, metallothionein 2A (MT2A) and matrix metalloproteinase (MMP) activation in malignant tumours. The aim of this study was to downregulate MT2A in cells (Cal27) derived from human squamous cell carcinoma. METHODS: Cal27 cells with reduced MT2A were subjected to proliferation, migration and invasion assays. Immunofluorescence and western blot confirmed MT2A depletion by siRNA. Growth curve assays assessed cell proliferation. Indirect immunofluorescence analysed the expression of MT2A, MMP-2, MMP-9, epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), tumour necrosis factor alpha (TNF-α) and Ki67. Zymography evaluated the effects of MT2A silencing on MMP-2 and -9 expression. Migration and invasion activities were evaluated using migration and invasion assays. RESULTS: CAL27 cells displayed MT2A, MMP-2, MMP-9, EGF, TGF-α, TNF-α and Ki67. MT2A depletion decreased MMP-9, EGF, TGF-α and Ki67 protein levels, while increasing TNF-α. CONCLUSIONS: MT2A downregulation reduced cell proliferation, migration and invasion activities. Therefore, MT2A has an important role in cell proliferation, migration and invasion in human oral SCC cells.

Glandular odontogenic cysts: A collaborative investigation of 22 cases and proteins related to invasiveness.

BACKGROUND: A glandular odontogenic cyst (GOC) has an intriguing, aggressive behaviour whose mechanisms have not yet been clarified. OBJECTIVE: To conduct a collaborative cross-sectional study on the clinical, demographic, microscopic and immunohistochemical characteristics of GOCs, emphasizing the histopathological characteristics and expression of proteins related to invasiveness. METHODS: Twenty-two cases of GOC from three oral and maxillofacial pathology services in Brazil were selected from 1988 to 2018. Clinical and demographic data were collected. Histopathological features were evaluated in detail. Sixteen cases of GOC were also submitted to immunohistochemistry to detect MT1-MMP, TKS4, TKS5 and cortactin, the key regulators of invadopodia formation. RESULTS: Glandular odontogenic cysts were primarily seen in men over 40 years of age, in the posterior mandible and the anterior maxilla as a unilocular, radiolucent lesion. All cases presented hobnail cells, clear cells and variable thickness of the lining epithelium, 3 of the 10 key histopathological parameters to be evaluated in GOCs. Immunohistochemistry revealed a greater expression of the studied proteins in the GOCs than in the controls (p < 0.0001). CONCLUSION: Overexpression of proteins that regulate cell invasiveness was identified, and the present study's findings suggest that invadopodia activity is a possible mechanism used by GOCs to promote local invasion, which could partly explain its intriguing biological behaviour.

Gene expression in cell lines from human ameloblastoma immortalized using hTERT and HPV16-E6/E7.

OBJECTIVE: The aim of this study was to evaluate and compare alterations in gene expression using two distinct immortalization methods (hTERT and HPV16-E6/E7) in ameloblastoma cell lines. MATERIALS AND METHODS: A primary cell culture derived from human ameloblastoma (AME-1) was established and immortalized by two different methods using a transfection processes to hTERT and HPV-E6/E7. The RNA-seq was used to verify which immortalization method had less influence on gene expression. It was performed in four steps: extraction and collection of mRNA, PCR amplification, comparison with the human reference genome, and analysis of differential expression. The genes with differentiated expression were identified and mapped. RESULTS: RNA-seq revealed genetic alterations in ameloblastoma cell lines after the immortalization process, including increased expression of tumor genes like MYC, E2F1, BRAF, HRAS, and HTERT, and a decrease in tumor suppressor genes like P53, P21, and Rb. CONCLUSIONS: It is possible to affirm that cell immortalization is not an inert method regarding gene regulation mechanisms and the hTERT method (AME-TERT) presented fewer changes in gene expression levels.

Development of an IEEE 1451 Plug-and-Play Module for Smart Transducers in Industrial Environments.

The use of Sensors and Actuators is ubiquitous in an industrial environment. The advent of the Industrial Internet-of-Things (IIoT) and the 4th industrial revolution demands new, more intelligent and more efficient ways to be able to connect, read and control transducers at the plant floor level. Newer control and data science techniques also largely benefit from structured information endpoints available at the edge of the network. The IEEE 1451 standard presents architecture and methodology to solve these problems with the usage of smart transducers, introducing into edge devices concepts such as self-identification and standardization of data communication. In this work, a transducer interface module is developed using the IEEE 1451 standard focused on flexibility, ease of integration and plug-and-play features. Furthermore, a system architecture, based on IEEE 1451.0 is presented, and development and implementation features are explained. This system is then released as an open-source platform to help and motivate the usage of smart transducer systems. At last, the system is tested, results are collected, and a methodology and metrics are defined for comparison between different smart transducer systems.

A Plug-and-Play Solution for Smart Transducers in Industrial Applications Based on IEEE 1451 and IEC 61499 Standards.

In a cyberphysical production system, the connectivity between the physical entities of a production system with the digital component that controls and monitors that system takes fundamental importance. This connectivity has been increasing from the transducers' side, through gathering new functionalities and operating increasingly independently, taking the role of smart transducers, and from the applications' side, by being developed in a distributed and decentralized paradigm. This work presents a plug-and-play solution capable of integrating smart transducers compliant with the IEEE 1451 standard in industrial applications based on the IEC 61499 standard. For this, we implemented the NCAP module of the smart transducer defined in IEEE 1451, which, when integrated with 4diac IDE and DINASORE (development and execution tools compliant with IEC 61499), enabled a solution that presented automatically the smart sensors and actuators in the IDE application and embedded their functionalities (access to data and processing functions) in the runtime environment. In this way, a complete plug-and-play solution was presented from the connection of the transducer to the network until its integration into the application.

Maternal Fluoride Exposure Exerts Different Toxicity Patterns in Parotid and Submandibular Glands of Offspring Rats.

There is currently a controversial and heated debate about the safety and ethical aspects of fluoride (F) used for human consumption. Thus, this study assessed the effects of prenatal and postnatal F exposure of rats on the salivary glands of their offspring. Pregnant rats were exposed to 0, 10, or 50 mg F/L from the drinking water, from the first day of gestation until offspring weaning (42 days). The offspring rats were euthanized for the collection of the parotid (PA) and submandibular (SM) glands, to assess the oxidative biochemistry and to perform morphometric and immunohistochemical analyses. F exposure was associated with a decrease in the antioxidant competence of PA in the 10 mg F/L group, contrasting with the increase observed in the 50 mg F/L group. On the other hand, the antioxidant competence of the SM glands was decreased at both concentrations. Moreover, both 10 and 50 mg F/L groups showed lower anti-α-smooth muscle actin immunostaining area in SM, while exposure to 50 mg F/L was associated with changes in gland morphometry by increasing the duct area in both glands. These findings demonstrate a greater susceptibility of the SM glands of the offspring to F at high concentration in comparison to PA, reinforcing the need to adhere to the optimum F levels recommended by the regulatory agencies. Such findings must be interpreted with caution, especially considering their translational meaning.

Quadratus Femoris Tendinopathy as an Underreported Cause of Groin Pain: Case Report.

Groin pain is a cause of mobility impairment, and its diverse presentation can make the diagnosis difficult. Quadratus femoris muscle tendinopathy is a poorly described etiology, but its diagnosis is important for the success of the therapeutic program. The authors present the case of an 18-year-old woman who complained of chronic pain in the left inguinal region due to regular ballet practice. Physical examination revealed restriction in the left hip medial rotation. Ultrasound and radiographic studies were normal. Magnetic resonance imaging showed asymmetry in the signal intensity of the quadratus femoris muscle. The patient improved significantly after a rehabilitation program that included quadratus femoris muscle-specific exercises. Diagnostic accuracy and an understanding of segmental biomechanics ensure greater effectiveness in the therapeutic approach.

Immunohistochemical analysis of ADAMTS-1, versican and pEGFR expressions in periapical granuloma and radicular cyst.

BACKGROUND: ADAMTS expression can be associated with several inflammatory processes, and has been correlated with tumorigenesis of some neoplasms, but its participation in the development of periapical lesions has not been investigated. Therefore, our objective was to verify the expression of ADAMTS-1, versican and pEGFR in Periapical Granuloma (PG) and in the Radicular Cyst (RC) since they are the most common lesions of the periapex. METHODS: 25 samples of RC and 10 of PG were used. As a control, 10 samples of inflammatory fibrous hyperplasia (IFH) and 10 of dental follicle (DF) were used. The expression of these proteins was investigated using immunohistochemistry. RESULTS: In the epithelium of RC, IFH and DF, the expression of ADAMTS-1 was greater in DF than in RC (p < .001). Versicano showed greater expression in IFH than in RC, DF than in RC (p < .001). pEGFR showed greater expression in IFH and RC than in DF (p < .01 and p < .05, respectively). In connective tissue, ADAMTS-1 expression was greater in PG and RC than in IFH and DF (p < .001). Versicano showed greater expression in PG, RC and IFH compared to DF (p < .001). In pEGFR there was a higher expression in PG when compared to RC, IFH and DF (p < .001). Greater immunostaining occurred in the RC than in the DF (p < .001). CONCLUSIONS: Our results suggest that the studied proteins may participate in the pathogenesis of PG and RC, through the interaction of these proteins, in the remodeling of the ECM (versican) by ADAMTS-1, producing bioactive fragments, which could activate EGFR, contributing to the formation, growth and maintenance of injuries.

APC gene is modulated by hsa-miR-135b-5p in both diffuse and intestinal gastric cancer subtypes.

BACKGROUND: Several genetic and epigenetic alterations are related to the development and progression of Gastric Cancer (GC), one of those being the deregulated microRNA (miRNA) expression profile. miRNAs are small noncoding RNAs that negatively regulate the expression of thousands of genes, including oncogenes and tumor suppressor genes. Our group identified, in previous studies, some miRNAs that are differentially expressed in GC when compared to the gastric mucosa without cancer, including hsa-miR-29c and hsa-miR-135b. The aim of the study was to modulate the expression of the miRNAs hsa-miR-29c-5p and hsa-miR-135b-5p and evaluate the expression of their target genes in 2D and 3D cell cultures. METHODS: hsa-miR-29c-5p and hsa-miR-135b-5p expression profiles were modulated by transfecting mimics and antimiRs, respectively, in 2D and 3D cell cultures. The expression of the proteins coded by the genes CDC42, DNMT3A (target genes of hsa-miR-29c-5p) and APC (target gene of hsa-miR-135b-5p) were measured by Western Blot. RESULTS: Results showed that mimics and antimiRs transfection significantly altered the expression of both miRNAs, increasing the expression of hsa-miR-29c-5p and reducing the expression of hsa-miR-135b-5p, especially in the 3D culture of the cell lines. When analyzing the proteins expression, we observed that AGP01 and AGP03 cell lines transfected with mimics had a reduction in the levels of CDC42 and DNMT3A and all three cell lines transfected with antimiRs had an increase in the expression of the protein APC. CONCLUSION: We concluded that three-dimensional culture can be a more representative in vitro model that resembles better the in vivo reality. Our results also showed that hsa-miR-29c-5p is an important regulator of CDC42 and DNMT3A genes in the intestinal subtype gastric cancer and hsa-miR-135b-5p regulates the APC gene in both intestinal and diffuse subtypes of GC. Dysregulation in their expression, and consequently in their respectively signaling pathways, shows how these miRNAs can influence the carcinogenesis of different histological subtypes of gastric cancer.

Mechanisms of human cytomegalovirus infection with a focus on epidermal growth factor receptor interactions.

Human cytomegalovirus (HCMV) is a widespread opportunistic herpesvirus that causes severe diseases in immunocompromised individuals. It has a high prevalence worldwide that is linked with socioeconomic factors. Similar to other herpesviruses, HCMV has the ability to establish lifelong persistence and latent infection following primary exposure. HCMV infects a broad range of cell types. This broad tropism suggests that it may use multiple receptors for host cell entry. The identification of receptors used by HCMV is essential for understanding viral pathogenesis, because these receptors mediate the early events necessary for infection. Many cell surface components have been identified as virus receptors, such as epidermal growth factor receptor (EGFR), which is characterized by tyrosine kinase activity and plays a crucial role in the control of key cellular transduction pathways. EGFR is essential for HCMV binding, signaling, and host cell entry. This review focuses on HCMV infection via EGFR on different cell types and its implications for the cellular environment, viral persistence, and infection.

The laminin-derived peptide C16 regulates GPNMB expression and function in breast cancer.

Breast cancer is an important public health problem, and its progression may be related to the extracellular matrix (ECM), which acts as a structural scaffold and instruction source for neoplastic cells. Laminins are ECM proteins regulating tumor biology. The laminin-derived peptide C16 regulates different properties of tumor cells. Here we analyzed C16-induced differential gene expression in MDA-MB-231 breast cancer cells. MCF-10A normal-like breast cells served as control. Among different cancer-related genes, C16 induced overexpression of GPNMB. This gene encodes a transmembrane protein GPNMB (glycoprotein non-metastatic B), involved with malignant phenotype of breast cancer cells. Immunoblot validated microarray results. To correlate gene and protein expression with cellular function, we investigated whether C16 would regulate invasion in breast cancer cells. siRNA experiments strongly suggested that C16 and GPNMB cooperate to regulate invasion of highly aggressive MDA-MB-231 cancer cells. We addressed regulatory mechanisms involved in C16-mediated increase of GPNMB protein levels in MDA-MB-231 cells, and observed that C16 stimulates ß1 integrin and Src phosphorylation. Furthermore, Src inhibition decreases peptide-induced GPNMB expression levels. To contextualize in vivo our results in vitro, we addressed GPNMB immunostaining in breast cancer human tissue microarrays. Quantitative immunohistochemistry showed that GPNMB is significantly more expressed in breast cancer compared to normal tissue. We concluded that laminin-derived peptide C16 regulates gene and protein expression of GPNMB in breast cancer cells. C16 and GPNMB may cooperate to regulate invasion of highly aggressive MDA-MB-231 cells, probably through Src signaling. GPNMB presented increased expression in breast cancer in vivo compared to normal breast tissue.

Abnormal activation of the Akt signaling pathway in adenoid cystic carcinoma.

PURPOSE: Adenoid cystic carcinoma (ACC) is an intriguing lesion because it shows a slow growth in the beginning, but a late poor prognosis due to perineural invasion, metastasis and recurrence. This study aimed to investigate whether Akt signaling would be deregulated in adenoid cystic carcinoma and its consequence in the expression of associated proteins. METHODS: The expression of the Akt, p-Akt, NFκB, ß-catenin, cyclin D1 and COX-2 was assessed by immunohistochemistry in 10 cases of ACC, 17 cases of pleomorphic adenoma (PA), and 7 cases of normal salivary gland (NSG). RESULTS: p-Akt was overexpressed in ACC when compared to NSG. NFκB, ß-catenin, and COX-2 were overexpressed in ACC and PA when compared to NSG. Most proteins were slightly higher expressed in ACC than in PA, but they never reached significance. p-Akt expression positively correlated with NFκB, ß-catenin, cyclin D1 and COX-2 in ACC and PA, while this correlation trended to be negative in for these proteins (except for NFκB) in NSG using Person's correlation analysis, but without reaching significance. CONCLUSIONS: Our results indicate an abnormal activation of Akt signaling pathway, which can be an important regulator of tumor biology in ACC. Activated Akt correlated with the expression of NFκB, ß-catenin and COX-2, which can potentially influence cell survival in ACC.

Role of HIF-1α and CASPASE-3 in cystogenesis of odontogenic cysts and tumors.

OBJECTIVES: Odontogenic cysts and tumors are the most relevant lesions that affect the gnathic bones. These lesions have in common the formation of cystic areas and this common feature may suggest involvement of similar mechanisms. The hypoxia inducible factor 1 alpha (HIF-1α), a responsive protein to hypoxia and caspase-3, an irreversible apoptosis marker, may contribute to cyst formation. Thus, this study aimed to investigate the immunoexpression of these proteins in odontogenic cysts and tumors. MATERIAL AND METHODS: Twenty cases of ameloblastoma, keratocystic odontogenic tumor (KOT) (n = 20), radicular cyst (RC) (n = 18), dentigerous cyst (DC) (n = 11), calcifying cystic odontogenic tumor (n = 8), and dental follicle (DF) (n = 10) were used to investigate HIF-1α and caspase-3 expression in sequential serial cuts by immunohistochemistry. RESULTS: HIF-1α was overexpressed in RC, DC, and ameloblastoma when compared with DF. The basal and sometimes the lower suprabasal layer showed no or very low expression in DC, KOT, and ameloblastoma, the last also showing strong expression in solid epithelial areas and initial cystic formation regions. Caspase-3 was found to be overexpressed in all lesions, with the highest expression in odontogenic cysts compared to tumors. HIF-1α and caspase-3 were localized in similar areas of the same lesions, especially in the epithelium surrounding cystic formations. CONCLUSIONS: This study showed distinct immunoexpression of HIF-1α and caspase-3 in odontogenic cyst and tumors, with higher expression observed in odontogenic cysts. CLINICAL RELEVANCE: These findings suggest a possible correlation between hypoxia, apoptosis, and cystogenesis, leading to understand the mechanisms responsible to cystic formation in odontogenic lesions.

S100ß Protein as a Predictor of Poststroke Functional Outcome: A Prospective Study.

BACKGROUND: Stroke is one of the leading causes of disability worldwide. Early prediction of poststroke disability using clinical models is of great interest, especially in the rehabilitation field. Although some biomarkers and neuroimaging techniques have shown potential predictive value, there are still insufficient data to support their clinical utility in predicting poststroke functional recovery. We aimed to assess the value of serum biomarkers (C-reactive protein [CRP], D-dimer, fibrinogen, and S100ß protein) in predicting medium-term (12 weeks) functional outcome in patients with acute ischemic stroke. METHODS: This is an observational, prospective study in a sample of patients hospitalized for ischemic stroke (N = 131). Peripheral blood levels of biomarkers of interest were determined at admission (CRP, D-dimer, and fibrinogen) or at 48 hours poststroke (S100ß protein). Functional status was accessed at 48 hours and 12 weeks poststroke using the modified Rankin Scale (mRS). RESULTS: S100ß protein levels measured at 48 hours were significantly associated with mRS scores at 12 weeks (odds ratio = 1.005, 95% confidence interval [CI] [1.005-1.007]; P <.001). This association was not seen for the remaining biomarkers of interest. The S100ß cutoff for poor functionality at 12 weeks was 140.5 ng/L or more (sensibility 83.8%; specificity 71.4%; area under the curve = .80, 95% CI [.722, .879]). CONCLUSIONS: S100ß levels in peripheral blood at 48 hours poststroke reflect acute stroke severity and predict functional outcome at 12 weeks with a cutoff value of 140.5 ng/dL. The value of S100ß as predictor of functional recovery after stroke should be emphasized in further clinical research and clinical practice.

Is the femoral lateral condyle's bone morphology the trochlea of the ACL?

PURPOSE: The purpose of this study was to investigate the association of different osteoarticular femoral and tibial morphology and morphometric parameters with the risk of anterior cruciate ligament (ACL) rupture. METHODS: Thirty-six patients (29 male and 7 female) with an ACL rupture (<6 months) and 36 age and sex-matched controls were included. The anatomomorphological parameters and morphometrics of the distal epiphysis of the femur and proximal epiphysis of the tibia were measured through conventional lateral radiography of the knee. RESULTS: It was found statistically significant smaller heights of femur's lateral condyle, AP distances of the tibial plateaus and smaller XY and WX distances, as well as, higher XY/AB and B/AB ratios (p < 0.05). In turn, women had smaller AP distances of the femur's lateral condyle, AP distances of the femur's diaphysis, AP distances of the tibial plateaus and heights of femur's lateral condyle, as well as, higher values of XY/AB (Porto ratio) and B/AB ratios (p < 0.05). CONCLUSIONS: Several femoral and tibial bone morphological parameters were identified as potential risk factors for sustaining an ACL injury. These parameters are clinically relevant to identify individuals with higher risk of ACL injury, decide between conservative or surgical treatment and identify individuals who may benefit from preventive neuromuscular programs. LEVEL OF EVIDENCE: Case-control study, Level III.

Role of hypoxia-related proteins in invasion of ameloblastoma cells: crosstalk between NOTCH1, hypoxia-inducible factor 1α, a disintegrin and metalloproteinase 12, and heparin-binding epidermal growth factor.

AIMS: Ameloblastoma AME is a benign tumour characterized by local invasiveness, high recurrence rates, and diverse histological patterns. The oxygen concentration is reduced in specific areas of the tumour microenvironment, which leads to intratumoral hypoxia. Crosstalk between NOTCH1, a disintegrin and metalloproteinase 12 (ADAM-12), hypoxia-inducible factor 1α (HIF-1α) and heparin-binding epidermal growth factor (HB-EGF) under hypoxic conditions has been implicated in invadopodia formation, tumour invasiveness, and metastasis development. The aim of this study was to analyse the expression of these proteins, in order to further elucidate the mechanisms underlying AME invasiveness. METHODS AND RESULTS: Twenty cases of AME, eight calcifying cystic odontogenic tumours CCOTs and 10 samples of dental follicle were used to investigate the expression of these proteins by immunohistochemistry with the primary antibodies anti-NOTCH1, anti-ADAM-12, anti-HIF-1α, and anti-HB-EGF. Immunostaining results were expressed as the percentage of stained area in images acquired in an AxioScope microscope equipped with an AxioCamHRc camera and a × 40 objective. The results showed that immunoexpression of all proteins was higher in the AME samples than in the CCOT and dental follicle samples (P < 0.05). CONCLUSIONS: AME showed an increased presence of proteins associated with tumour invasiveness, which indicates a possible role of these proteins in the biological behaviour of this tumour.

Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer.

BACKGROUND: ADAMTS are metalloproteases with disintegrin and thrombospondin motifs. They are secreted proteases playing a role in biological processes such as inflammation, angiogenesis, and urogenital development. ADAMTS have specific substrates, such as the proteoglycans (PG) versican, aggrecan, and brevican. Despite data indicating a role of ADAMTS in tumor invasion and metastases, effects played by these molecules in cancer progression are still controversial. In ovarian cancer, the importance of ADAMTS gene mutations was recently described and related to chemotherapy outcome. OBJECTIVE: To analyze protein levels of ADAMTS-1, -4, and -5, and TIMP-3 in human ovarian cancer classified as benign, borderline, or malignant. We also assessed the expression of the ADAMTS substrates aggrecan, brevican, and versican in these neoplasms. Correlations between overall survival and protein expression were performed. METHODS: Tumors were classified according to the WHO Classification of Tumors of Female Reproductive Organs. Protein and PG expression was studied by immunohistochemistry. Differences in labeling were analyzed by percent measurements of stained areas. RESULTS: ADAMTS-1, ADAMTS-5, and its tissue inhibitor TIMP-3 are increased in borderline and malignant tumors compared to benign neoplasms. Aggrecan and versican levels were increased in malignant subtypes compared to benign ovarian cancer. Higher ADAMTS-1, TIMP-3, and versican expression was associated with a shorter overall survival. CONCLUSIONS: Comparison of protease, TIMP-3, and substrate expression showed that in malignant tumors all ADAMTS and TIMP-3 expression levels were significantly raised compared to the substrates studied.

Facial Fractures: Large Epidemiologic Survey in Northern Brazil Reveals Some Unique Characteristics.

PURPOSE: Facial fractures are an important health problem worldwide that can cause temporary or permanent disability and an economic burden. Identifying the risk factors associated with facial fractures is a valuable tool to create preventive public health strategies. This study evaluated the epidemiologic profile of facial fractures in northern Brazil. PATIENTS AND METHODS: Medical records of 1,969 patients who sustained facial fractures were analyzed for characteristics of the population, types of facial fractures, and treatment performed. RESULTS: The zygomatic complex was the most prevalent fracture site (28.8%). Road traffic accident (RTA) was the most common etiology (52%), followed by interpersonal violence (IPV; 34%). Among IPV cases, gunshot wounds were responsible for 14% of cases and 3% resulted from stab wounds. The third decade of life was the most prevalent age group, with a remarkable change in prevalence and etiology pattern at 15 years of age. Open reduction and internal fixation was the most used treatment, especially when the mandible was involved and at least 2 facial bones were fractured. There were 37 deaths (1.9%), with a higher risk observed for stab wounds (3.1-fold higher) and when at least 3 bones were fractured (4.1-fold higher). CONCLUSIONS: This epidemiologic survey identified RTA and IPV as important risk factors for facial fractures and a high prevalence of fractures caused by gunshot wounds. A unique preponderance of facial fractures caused by stab wounds was found, which was responsible for the highest risk of mortality.