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Key Message: We demonstrate potential for improved multi-environment genomic prediction accuracy using structural variant markers. However, the degree of observed improvement is highly dependent on the genetic architecture of the trait. Breeders commonly use genetic markers to predict the performance of untested individuals as a way to improve the efficiency of breeding programs. These genomic prediction models have almost exclusively used single nucleotide polymorphisms (SNPs) as their source of genetic information, even though other types of markers exist, such as structural variants (SVs). Given that SVs are associated with environmental adaptation and not all of them are in linkage disequilibrium to SNPs, SVs have the potential to bring additional information to multi-environment prediction models that are not captured by SNPs alone. Here, we evaluated different marker types (SNPs and/or SVs) on prediction accuracy across a range of genetic architectures for simulated traits across multiple environments. Our results show that SVs can improve prediction accuracy, but it is highly dependent on the genetic architecture of the trait and the relative gain in accuracy is minimal. When SVs are the only causative variant type, 70% of the time SV predictors outperform SNP predictors. However, the improvement in accuracy in these instances is only 1.5% on average. Further simulations with predictors in varying degrees of LD with causative variants of different types (e.g., SNPs, SVs, SNPs and SVs) showed that prediction accuracy increased as linkage disequilibrium between causative variants and predictors increased regardless of the marker type. This study demonstrates that knowing the genetic architecture of a trait in deciding what markers to use in large-scale genomic prediction modeling in a breeding program is more important than what types of markers to use., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Understanding how plants adapt to specific environmental changes and identifying genetic markers associated with phenotypic plasticity can help breeders develop plant varieties adapted to a rapidly changing climate. Here, we propose the use of marker effect networks as a novel method to identify markers associated with environmental adaptability. These marker effect networks are built by adapting commonly used software for building gene coexpression networks with marker effects across growth environments as the input data into the networks. To demonstrate the utility of these networks, we built networks from the marker effects of ∼2,000 nonredundant markers from 400 maize hybrids across 9 environments. We demonstrate that networks can be generated using this approach, and that the markers that are covarying are rarely in linkage disequilibrium, thus representing higher biological relevance. Multiple covarying marker modules associated with different weather factors throughout the growing season were identified within the marker effect networks. Finally, a factorial test of analysis parameters demonstrated that marker effect networks are relatively robust to these options, with high overlap in modules associated with the same weather factors across analysis parameters. This novel application of network analysis provides unique insights into phenotypic plasticity and specific environmental factors that modulate the genome., Competing Interests: Conflicts of interest The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This study evaluated if genetic variations in the WNT family members and RUNX2 are associated with craniofacial maturation, investigating dental and skeletal maturity in children and teenagers., Methods: Radiographs from pre-orthodontic treatment of Brazilian patients (7 to 17 years-old) were used to assess dental (panoramic radiographs) and skeletal maturity (cephalometric radiographs). The chronological age (CA) was calculated based on the date of birth and the time the radiographs were performed. For the dental maturity analysis, the Demirjian (1973) method was used and a delta [dental age - chronological age (DA-CA)] was calculated. For the skeletal maturity analysis, the Baccetti et al. (2005) method was used and the patients were classified as "delayed skeletal maturation", "advanced skeletal maturation" or "normal skeletal maturation". DNA isolated from buccal cells was used for genotyping of two genetic variations in WNT family genes: rs708111 (G > A) in WNT3A and rs1533767 (G > A) in WNT11; and two genetic variations in RUNX2: rs1200425 (G > A) and rs59983488 (G > T). A statistical analysis was performed and values of p < 0.05 indicated a significant difference., Results: There were no associations between dental maturity and genotypes (p > 0.05). In the skeletal maturity analysis, the allele A in the rs708111 (WNT3A) was statistically more frequent in patients with delayed skeletal maturation (Prevalence Ratio = 1.6; 95% Confidence Interval = 1.00 to 2.54; p-value = 0.042)., Conclusions: The rs708111 in the WNT3A gene impacts on skeletal maturation., (© 2023. The Author(s).)

Objective: Fatty acid synthase levels are associated with aggressiveness, prognosis, and risk of metastasis in oral squamous cell carcinomas. This enzyme contains seven catalytic domains and its inhibition by synthetic or natural drugs has antineoplastic properties such as C75, which is a synthetic inhibitor of the β- ketoacyl synthase domain, the antibiotic triclosan, ligand of the enoyl reductase domain, and the antiobesity drug orlistat, which inhibits the thioesterase domain. Here, we sought to investigate and compare the in vitro effects of C75, triclosan, and orlistat on malignant phenotypes of the cell line SCC-9: proliferation, cell cycle, apoptosis, adhesion, migration, and invasion., Design: Half-maximal inhibitory concentration (IC 50 ) was determined using cell viability assays. Cell death and cell cycle progression were analyzed by Annexin V-PE/7-ADD-PerCP labeling and propidium iodide staining, respectively. Cell migration and invasion were assayed by transwells assays and cell adhesion using collagen and fibronectin., Results: C75 showed the lowest IC 50 and higher inhibition of lipid droplets at low concentrations and reduced cell motility. Triclosan showed the intermediate IC 50 value, excellent reduction of lipid bodies at the IC 50 when compared with C75 and orlistat. Also, triclosan reduced cell cycle progression, adhesion, migration, and invasion of SCC-9 and induced the highest levels of apoptosis. Orlistat promoted cell cycle arrest, but showed the lowest induction of apoptosis and did not affected invasion and adhesion of SCC-9., Conclusion: Altogether, despite the particular effects of the analyzed fatty acid synthase inhibitors, triclosan showed to better interfere in tumorigenic phenotypes of SCC-9 cells., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Plants resist infection by pathogens using both preexisting barriers and inducible defense responses. Inducible responses are governed in a complex manner by various hormone signaling pathways. The relative contribution of hormone signaling pathways to nonhost resistance to pathogens is not well understood. In this study, we examined the molecular basis of disrupted nonhost resistance to the fungal species Puccinia graminis , which causes stem rust of wheat, in an induced mutant of the model grass Brachypodium distachyon . Through bioinformatic analysis, a 1-bp deletion in the mutant genotype was identified that introduces a premature stop codon in the gene Bradi1g24100 , which is a homolog of the Arabidopsis thaliana gene TIME FOR COFFEE ( TIC ). In Arabidopsis , TIC is central to the regulation of the circadian clock and plays a crucial role in jasmonate signaling by attenuating levels of the transcription factor protein MYC2, and its mutational disruption results in enhanced susceptibility to the hemibiotroph Pseudomonas syringae . Our similar finding for an obligate biotroph suggests that the biochemical role of TIC in mediating disease resistance to biotrophs is conserved in grasses, and that the correct modulation of jasmonate signaling during infection by Puccinia graminis may be essential for nonhost resistance to wheat stem rust in B. distachyon .[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Intact transposable elements (TEs) account for 65% of the maize genome and can impact gene function and regulation. Although TEs comprise the majority of the maize genome and affect important phenotypes, genome-wide patterns of TE polymorphisms in maize have only been studied in a handful of maize genotypes, due to the challenging nature of assessing highly repetitive sequences. We implemented a method to use short-read sequencing data from 509 diverse inbred lines to classify the presence/absence of 445,418 nonredundant TEs that were previously annotated in four genome assemblies including B73, Mo17, PH207, and W22. Different orders of TEs (i.e., LTRs, Helitrons, and TIRs) had different frequency distributions within the population. LTRs with lower LTR similarity were generally more frequent in the population than LTRs with higher LTR similarity, though high-frequency insertions with very high LTR similarity were observed. LTR similarity and frequency estimates of nested elements and the outer elements in which they insert revealed that most nesting events occurred very near the timing of the outer element insertion. TEs within genes were at higher frequency than those that were outside of genes and this is particularly true for those not inserted into introns. Many TE insertional polymorphisms observed in this population were tagged by SNP markers. However, there were also 19.9% of the TE polymorphisms that were not well tagged by SNPs (R2 < 0.5) that potentially represent information that has not been well captured in previous SNP-based marker-trait association studies. This study provides a population scale genome-wide assessment of TE variation in maize and provides valuable insight on variation in TEs in maize and factors that contribute to this variation., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

Once considered nonfunctional, pseudogene transcripts are now known to provide valuable information for cancer susceptibility, including head and neck cancer (HNC), a serious health problem worldwide, with about 50% unimproved overall survival over the last decades. The present review focuses on the role of pseudogene transcripts involved in HNC risk and prognosis. We combined current literature and in silico analyses from The Cancer Genome Atlas (TCGA) database to identify the most deregulated pseudogene transcripts in HNC and their genetic variations. We then built a co-expression network and performed gene ontology enrichment analysis to better understand the pseudogenes' interactions and pathways in HNC. In the literature, few pseudogenes have been studied in HNC. Our in silico analysis identified 370 pseudogene transcripts associated with HNC, where SPATA31D5P , HERC2P3 , SPATA31C2 , MAGEB6P1 , SLC25A51P1 , BAGE2 , DNM1P47 , SPATA31C1 , ZNF733P and OR2W5 were found to be the most deregulated and presented several genetic alterations. NBPF25P , HSP90AB2P , ZNF658B and DPY19L2P3 pseudogenes were predicted to interact with 12 genes known to participate in HNC, DNM1P47 was predicted to interact with the TP53 gene, and HLA-H pseudogene was predicted to interact with HLA-A and HLA-B genes. The identified pseudogenes were associated with cancer biology pathways involving cell communication, response to stress, cell death, regulation of the immune system, regulation of gene expression, and Wnt signaling. Finally, we assessed the prognostic values of the pseudogenes with the Kaplan-Meier Plotter database, and found that expression of SPATA31D5P , SPATA31C2 , BAGE2 , SPATA31C1 , ZNF733P and OR2W5 pseudogenes were associated with patients' survival. Due to pseudogene transcripts' potential for cancer diagnosis, progression, and as therapeutic targets, our study can guide new research to HNC understanding and development of new target therapies.

We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The number of pan-genes in these diverse genomes exceeds 103,000, with approximately a third found across all genotypes. The results demonstrate that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres revealed additional variation in major cytological landmarks. We show that combining structural variation with single-nucleotide polymorphisms can improve the power of quantitative mapping studies. We also document variation at the level of DNA methylation and demonstrate that unmethylated regions are enriched for cis-regulatory elements that contribute to phenotypic variation., (Copyright © 2021, American Association for the Advancement of Science.)

Salivary gland neoplasms represent an important group of cancers in the head and neck and myoepithelial cells play a key role on the development these tumors. This study evaluated the distribution of mast cells and related proteins (PAR-2, TGFβ1, IL-6) to the myofibroblastic differentiation in malignant tumors of salivary glands with and without myoepithelial differentiation. Immunohistochemical assessement for tryptase mast cells, SMA, PAR-2, TGFβ1, IL-6 was performed in 10 cases of polymorphous low-grade adenocarcinoma, 14 cases of mucoepidermoid carcinoma (MEC) and 10 cases of adenoid cystic carcinoma. When the density of mast cells were compared between tumors, their density was significantly higher in MEC (P=0.08). Tumors with high expression of PAR-2 (79.4%) exhibited a high density of mast cells. Myofibroblasts were more frequent in malignant tumors with low expression (<50%) of cell masts. Individual analysis of the tumors showed no significant difference between the expression of PAR-2, IL-6, TGFβ1, and myofibroblasts. When the density of mast cells, myofibroblasts and the expression of PAR-2 protein, IL-6, and TGFβ1 were compared, it was no statistically significant difference between tumors with and without myoepithelial differentiation. The results of present study suggest a possible participation of mast cells and especially of PAR-2 in the development and progression of malignant salivary cancers, regardless of myoepithelial content., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Wheat stem rust disease caused by Puccinia graminis f. sp. tritici ( Pgt ) is a global threat to wheat production. Fast evolving populations of Pgt limit the efficacy of plant genetic resistance and constrain disease management strategies. Understanding molecular mechanisms that lead to rust infection and disease susceptibility could deliver novel strategies to deploy crop resistance through genetic loss of disease susceptibility. We used comparative transcriptome-based and orthology-guided approaches to characterize gene expression changes associated with Pgt infection in susceptible and resistant Triticum aestivum genotypes as well as the non-host Brachypodium distachyon . We targeted our analysis to genes with differential expression in T. aestivum and genes suppressed or not affected in B. distachyon and report several processes potentially linked to susceptibility to Pgt , such as cell death suppression and impairment of photosynthesis. We complemented our approach with a gene co-expression network analysis to identify wheat targets to deliver resistance to Pgt through removal or modification of putative susceptibility genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Henningsen, Omidvar, Della Coletta, Michno, Gilbert, Li, Miller, Myers, Gordon, Vogel, Steffenson, Kianian, Hirsch and Figueroa.)

Crop genomics has seen dramatic advances in recent years due to improvements in sequencing technology, assembly methods, and computational resources. These advances have led to the development of new tools to facilitate crop improvement. The study of structural variation within species and the characterization of the pan-genome has revealed extensive genome content variation among individuals within a species that is paradigm shifting to crop genomics and improvement. Here, we review advances in crop genomics and how utilization of these tools is shifting in light of pan-genomes that are becoming available for many crop species.

Single-parent expression (SPE) is defined as gene expression in only one of the two parents. SPE can arise from differential expression between parental alleles, termed non-presence/absence (non-PAV) SPE, or from the physical absence of a gene in one parent, termed PAV SPE. We used transcriptome data of diverse Zea mays (maize) inbreds and hybrids, including 401 samples from five different tissues, to test for differences between these types of SPE genes. Although commonly observed, SPE is highly genotype and tissue specific. A positive correlation was observed between the genetic distance of the two inbred parents and the number of SPE genes identified. Regulatory analysis showed that PAV SPE and non-PAV SPE genes are mainly regulated by cis effects, with a small fraction under trans regulation. Polymorphic transposable element insertions in promoter sequences contributed to the high level of cis regulation for PAV SPE and non-PAV SPE genes. PAV SPE genes were more frequently expressed in hybrids than non-PAV SPE genes. The expression of parentally silent alleles in hybrids of non-PAV SPE genes was relatively rare but occurred in most hybrids. Non-PAV SPE genes with expression of the silent allele in hybrids are more likely to exhibit above high parent expression level than hybrids that do not express the silent allele, leading to non-additive expression. This study provides a comprehensive understanding of the nature of non-PAV SPE and PAV SPE genes and their roles in gene expression complementation in maize hybrids., (© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.)

Due to its importance in the pathogenesis of oral squamous cell carcinoma (OSCC), the Hedgehog (HH) pathway is considered a potential therapeutic target. We investigated the effects of GANT61, a GLI inhibitor, on HH gene expression, as well as on metastatic OSCC cell proliferation and death. Following culture in DMEM medium, cytotoxicity of GANT61 against different tumor and non-tumor cell types was assessed by alamarBlue assays. Cytotoxicity analysis revealed that the metastatic HSC3 cell line was the most sensitive (IC 50 : 36 µM) to the tested compound. The compound's effects on the expression of HH pathways components were analyzed by qPCR and Western blot; cell viability was analyzed by trypan blue assay and flow cytometry were used to investigate cell cycle phase, morphology, and death patterns in HSC3 cells. A significant reduction in mRNA levels of the GLI1 transcription factor was found after 12 h of treatment withGANT61. Protein expression levels of other HH pathway components (PTCH1, SHH, and Gli1) and HSC3 cell viability also decreased after 24 h of treatment. Cell cycle analysis and death pattern evaluations revealed significantly increased nuclear fragmentation in sub-G1 phase, as well as cell death due to apoptosis. In conclusion, the significantly reduced GLI1 gene expression seen in response to the GLI inhibitor indicates diminished downstream activation in HH pathway components. GANT61 significantly reduced cell viability in the metastatic cell line of OSCC and promoted a significant increase in nuclear fragmentation and cell death by apoptosis.

The emergence of new races of Puccinia graminis f. sp. tritici, the causal pathogen of wheat stem rust, has spurred interest in developing durable resistance to this disease in wheat. Nonhost resistance holds promise to help control this and other diseases because it is durable against nonadapted pathogens. However, the genetic and molecular basis of nonhost resistance to wheat stem rust is poorly understood. In this study, the model grass Brachypodium distachyon, a nonhost of P. graminis f. sp. tritici, was used to genetically dissect nonhost resistance to wheat stem rust. A recombinant inbred line (RIL) population segregating for response to wheat stem rust was evaluated for resistance. Evaluation of genome-wide cumulative single nucleotide polymorphism allele frequency differences between contrasting pools of resistant and susceptible RILs followed by molecular marker analysis identified six quantitative trait loci (QTL) that cumulatively explained 72.5% of the variation in stem rust resistance. Two of the QTLs explained 31.7% of the variation, and their interaction explained another 4.6%. Thus, nonhost resistance to wheat stem rust in B. distachyon is genetically complex, with both major and minor QTLs acting additively and, in some cases, interacting. These findings will guide future research to identify genes essential to nonhost resistance to wheat stem rust.

Low-level laser therapy (LLLT) has been shown to be effective in promoting cell proliferation. There is speculation that the biostimulatory effect of LLLT causes undesirable enhancement of tumor growth in neoplastic diseases since malignant cells are more susceptible to proliferative stimuli. This study evaluated the effects of LLLT on proliferation, invasion, and expression of cyclin D1, E-cadherin, β-catenin, and MMP-9 in a tongue squamous carcinoma cell line (SCC25). Cells were irradiated with a diode laser (660 nm) using two energy densities (0.5 and 1.0 J/cm(2)). The proliferative potential was assessed by cell growth curves and cell cycle analysis, whereas the invasion of cells was evaluated using a Matrigel cell invasion assay. Expression of cyclin D1, E-cadherin, β-catenin, and MMP-9 was analyzed by immunofluorescence and flow cytometry and associated with the biological activities studied. LLLT induced significantly the proliferation of SCC25 cells at 1.0 J/cm(2), which was accomplished by an increase in the expression of cyclin D1 and nuclear β-catenin. At 1.0 J/cm(2), LLLT significantly reduced E-cadherin and induced MMP-9 expression, promoting SCC25 invasion. The results of this study demonstrated that LLLT exerts a stimulatory effect on proliferation and invasion of SCC25 cells, which was associated with alterations on expression of proteins studied.

Antiresorptive osteonecrosis of the jaws (ARONJ) is a significant and poorly understood oral complication that may affect patients receiving antiresorptive agents, such as intravenous bisphosphonate therapy. There are scarce reports of the coexistence of ARONJ and metastasis at the same jaw site in the English-language literature. In the present case, a 60-year-old white woman was referred for the evaluation of a nonhealing extraction socket. The patient was undergoing treatment with intravenous zoledronic acid to metastatic breast cancer in bone, and her medical history and clinical characteristics led to the diagnosis of ARONJ. Nevertheless, histologic analysis showed a fragment of necrotic bone and bacterial colonies associated with malignant epithelial cells that were confirmed to be metastatic breast adenocarcinoma. This case showed that jaw metastasis can occur at the same time and site of ARONJ, making diagnosis and management challenging., (Copyright © 2014. Published by Mosby, Inc.)

Background: ADAM17 is one of the main sheddases of the cells and it is responsible for the cleavage and the release of ectodomains of important signaling molecules, such as EGFR ligands. Despite the known crosstalk between ADAM17 and EGFR, which has been considered a promising targeted therapy in oral squamous cell carcinoma (OSCC), the role of ADAM17 in OSCC development is not clear., Method: In this study the effect of overexpressing ADAM17 in cell migration, viability, adhesion and proliferation was comprehensively appraised in vitro. In addition, the tumor size, tumor proliferative activity, tumor collagenase activity and MS-based proteomics of tumor tissues have been evaluated by injecting tumorigenic squamous carcinoma cells (SCC-9) overexpressing ADAM17 in immunodeficient mice., Results: The proteomic analysis has effectively identified a total of 2,194 proteins in control and tumor tissues. Among these, 110 proteins have been down-regulated and 90 have been up-regulated in tumor tissues. Biological network analysis has uncovered that overexpression of ADAM17 regulates Erk pathway in OSCC and further indicates proteins regulated by the overexpression of ADAM17 in the respective pathway. These results are also supported by the evidences of higher viability, migration, adhesion and proliferation in SCC-9 or A431 cells in vitro along with the increase of tumor size and proliferative activity and higher tissue collagenase activity as an outcome of ADAM17 overexpression., Conclusion: These findings contribute to understand the role of ADAM17 in oral cancer development and as a potential therapeutic target in oral cancer. In addition, our study also provides the basis for the development of novel and refined OSCC-targeting approaches.

Objective: To determine the most adequate number and size of tissue microarray (TMA) cores for pleomorphic adenoma immunohistochemical studies., Study Design: Eighty-two pleomorphic adenoma cases were distributed in 3 TMA blocks assembled in triplicate containing 1.0-, 2.0-, and 3.0-mm cores. Immunohistochemical analysis against cytokeratin 7, Ki67, p63, and CD34 were performed and subsequently evaluated with PixelCount, nuclear, and microvessel software applications., Results: The 1.0-mm TMA presented lower results than 2.0- and 3.0-mm TMAs versus conventional whole section slides. Possibly because of an increased amount of stromal tissue, 3.0-mm cores presented a higher microvessel density. Comparing the results obtained with one, two, and three 2.0-mm cores, there was no difference between triplicate or duplicate TMAs and a single-core TMA., Conclusions: Considering the possible loss of cylinders during immunohistochemical reactions, 2.0-mm TMAs in duplicate are a more reliable approach for pleomorphic adenoma immunohistochemical study., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Hemangiomas, vascular malformations, and varices are common benign vascular lesions in the head and neck region. They can occur in the mouth and primarily affect the lips, tongue, buccal mucosa, and palate. The main types of treatments are surgery and intralesional injection of sclerosant agents. However, other therapies have been considered, such as systemic corticosteroids, laser therapy, interferon a, and cryotherapy. Currently, sclerotherapy is employed largely because of its efficiency and ability to conserve the surrounded tissues. Surgery can be used exclusively or associated with sclerotherapy in lesions that do not show complete resolution. This article describes the cases of two patients with oral hemangiomas that were submitted to sclerotherapy with ethanolamine oleate. Although an important decrease was detected after seven applications in both cases, surgical resection of the residual lesion was performed to achieve optimal results.

Objective: The objective of this study was to compare the clinicopathological features of oral sebaceous hyperplasia and sebaceous adenoma., Study Design: Clinical data, microscopical characteristics, and ki-67 immunoexpression were comparatively analyzed on 2 intraoral sebaceous adenomas, 6 intraoral sebaceous hyperplasias, and 21 normal intraoral sebaceous glands., Results: Clinically, sebaceous glands presented as multiple separated papules, sebaceous hyperplasias as a single enlarged papule, and sebaceous adenoma as a well-defined nodule. Microscopically, sebaceous adenoma presented an increased number of lobules, smaller lobules, and a greater number of germinative/squamous cells. Sebaceous hyperplasia also had an increased number of lobules and fewer number of germinative/squamous cells, as compared to normal oral sebaceous glands. Ki-67 expression was seen only in germinative cells and counts were higher in sebaceous adenomas followed by hyperplasias and normal glands., Conclusions: Sebaceous hyperplasias and adenomas showed different clinical, microscopic, and proliferative characteristics, suggesting the usefulness of the studied criteria on diagnosis of these uncommon oral lesions.

Myofibroma is a benign mesenchymal neoplasm composed of myofibroblasts which has been described with different synonyms since the first report in 1951. It may show clinical and histologic features that may be misinterpreted as a malignancy. We describe 2 cases of oral myofibromas affecting infants; the first one showed a rapid growth with teeth displacement and ulceration; the second one presented a relatively slow growth with an indolent course. Differential diagnosis included benign and malignant mesenchymal neoplasms, salivary gland tumors, and reactive processes. Microscopic analysis of both lesions revealed a spindle cell tumor with immunoreactivity for vimentin, muscle-specific actin, and specific smooth muscle isoform alpha-actin, rendering the diagnoses of myofibroma. The patients were treated with surgical excision, and both are in follow-up without any signs of recurrence. Myofibroma presents a wide range of differential diagnosis, including benign and malignant neoplasms. Therefore, accurate diagnosis may avoid an unnecessary aggressive therapy.

The aim of the present study was to analyze the prevalence of nonsyndromic oral clefts in children receiving treatment at the Center for the Rehabilitation of Craniofacial Anomalies, José do Rosário Vellano University, Alfenas, MG, Brazil. All the data for the epidemiological study was retrieved from the files of 126 pediatric patients with oral clefts without any additional malformation, who came to the center for treatment between 2000 and 2005. A predominance of clefts was observed in Caucasians, and the ratio of male to female was 1.3. Males were 2.57 times more affected by cleft lip and palate (CLP) than females. CLP with a prevalence of 39.68% and isolated cleft lip (CL) with a prevalence of 38.09% were the most common anomalies, followed by isolated cleft palate (CP; 22.23%). Complete and unilateral CLP (26.19%) presented the highest prevalence, followed by incomplete and unilateral CL (23.81%). The present study presents the experience of a reference hospital in the state of Minas Gerais; however, the real prevalence of oral clefts in Brazil is still unknown. Our findings differ from those of a few previous Brazilian reports because they suggest similar prevalences of CLP and CL, and a higher prevalence of CLP in Caucasian males.

Sialolithiasis is one of the most common disorders of particular major salivary glands. It is caused by sialolith within the ducts or parenchyma of particularly major salivary glands. Although sialolithasis is not uncommon, it often is clinically misdiagnosed when minor salivary glands are affected. This article describes the clinical and microscopic findings of nine cases of sialolithiasis of minor salivary glands. The lesions frequently appeared as single and asymptomatic nodules in middle-aged patients. Only three sites were affected: four lesions were found in the upper lip, three in the buccal mucosa, and two in the lower lip. The most common clinical hypotheses for diagnosis were mucocele, sialoadenitis, and benign salivary gland tumor. Sialolithiasis of minor salivary glands was misdiagnosed frequently. It should be considered as a possible diagnosis when swelling of the oral tissues is observed.

The objective of this study was to compare fibroblasts from the periodontal ligament (PLF) and gingival fibroblasts (GF) as to morphology, proliferation rate and protein synthesis. PLF and GF were explanted from tissues of the same patient. To characterize and compare the morphology of cells, PLF and GF were plated and analyzed under phase-contrast and optical microscopies. Proliferation rates were determined by means of automated counts carried out in days 1, 4, 7, 15 and 21, and also by means of the bromodeoxyuridine labelling index (BrdU). Total protein content was analyzed by means of electrophoresis in 10% polyacrylamide gel and zimography containing gelatin as substrate. PLF were bigger and more elongated than GF in subconfluence and confluence conditions. The proliferative rate of PLF was higher than that of GF at 1, 4, and 7 days (p < 0.05). At 15 and 21 days, there was no statistically significant difference as to the number of cells. PLF presented a significantly greater proliferative potential, in relation to GF (p < 0.05). The synthesis of protein in a period of 24 hours was similar for both PLF and GF. Our results demonstrated that PLF and GF are different as to morphology and proliferative capacity, however, they do not differ as to protein synthesis.

Cyclosporin A (CyA) is a potent immunosuppressor used in organ transplantation and in the management of various autoimmune diseases. Gingival overgrowth is one of the side-effects of the CyA-treatment, affecting the attached gingiva of 25-81% of treated patients. To investigate the production and activity of matrix metalloproteinases (MMPs) in the CyA-induced gingival overgrowth, 2 well-documented models were utilized: the in vivo CyA-induced rat gingival overgrowth and primary cultures of human gingival fibroblasts treated with CyA. Our results obtained from the Western blot assays demonstrated clearly that the production of MMP-1 and MMP-3 was significantly inhibited by CyA at similar concentrations found in the serum of patients undergoing CyA-treatment. Moreover, the gelatinolytic activity of MMP-2 was also reduced both in cultured fibroblasts and in the rat CyA-induced gingival overgrowth. Taken together, the data presented here suggest that these inhibitory effects may contribute to the extracellular matrix (ECM) components accumulation in the CyA-induced gingival overgrowth.

Hsps expressed on the cell surface have been associated with tumor invasiveness and used as targets for molecular surveillance. The present study utilized four human oral squamous cell carcinoma cells lines, SCC-4, SCC-9, SCC-15, SCC-25, the murine epidermoid carcinoma cell line LL/2, and primary cultures of human gingival fibroblasts to assess the cell surface expression of colligin/Hsp47, a proposed marker for malignancy. Immunoprecipitation studies following protein crosslinking revealed that Hsp47 was associated with a number of membrane proteins including the tetraspanin CD9. Cytometric analyses were performed to determine the distribution of cell surface colligin/Hsp47 during the phases of the cell cycle. These studies showed that colligin/Hsp47 was not limited to any phase of the cell cycle in epidermoid carcinoma cells. Boyden chamber tumor invasion assays and colloidal gold migration assays utilizing a reconstituted basement membrane (Matrigel), collagen type I, and laminin-5 substrates revealed that cell lines expressing constitutive high levels of colligin/Hsp47 manifested the lowest invasion and migration indices. The incorporation of antibodies against Hsps into the migration and invasion assays, likewise, increased the invasion indices and the phagokinetic migration indices. These data indicate that colligin/Hsp47 is anchored to the cell membrane in a complex with CD9 where it moderates tumor cell invasion and motility possibly by acting as a serpin protein inhibitor or as a receptor for collagen.

Rabbit polyclonal antibody against mouse EHS laminin was used to investigate the distribution and composition of laminin in the rat first molar tooth germ. Immunohistochemical analysis showed that laminin is expressed in the inner and outer epithelia of the enamel organ and in small blood vessels in the dental papilla and strellate reticulum. Immunoblots revealed that tooth germ laminin differs from EHS laminin. Tooth germ laminin contains beta chains, while the alpha 1 chain is substituted by a 300-kDa chain. Two-dimensional electrophoresis analysis of tooth germ extract showed that beta chains appeared as four spots with approximate pI values of 6.6, 7.5, 7.8 and 8.5. These results indicate that more than-one type of laminin isoform is present in the first molar tooth germ. Additionally, we have shown that despite the early degradation of tooth germ basement membrane, the laminin molecule is still intact at the time of birth.

Atrophy of salivary glands may occur by ductal obstruction caused by calculus, infection or neoplastic processes, or as consequence of systemic diseases and aging. In the present work, we have used histochemical methods to study the expression of elastic and collagen fibers during experimental atrophy of the submandibular gland of mice. Glandular atrophy was accompanied by a rapid increase in collagen deposition in both septal and intralobular regions. The expression of elastic fibers was not significantly altered during atrophy: a discrete increase of elastic fibers was noted only around ductal structures. The results showed that experimental ductal obstruction is a useful in vivo model to study molecular events that take part in the remodeling of the extracellular matrix during atrophy of salivary glands.