Exploring natural anthraquinones as potential MMP2 inhibitors: A computational study.

OBJECTIVE: Matrix metalloproteinase-2 (MMP2) plays a significant role in cleaving extracellular matrix components, leading to many cancer cells' progression and invasion behavior. Therefore, MMP2 inhibition may hold promise for cancer treatment. Anthraquinones have shown antineoplastic effects, some of which have been used in clinical practice as anticancer drugs. This study used a computational drug discovery approach to assess the possible inhibitory effects of selected anthraquinones on MMP2. The results were then compared with that of Captopril, which was considered a standard drug. METHODS: This study used the AutoDock 4.0 tool to evaluate the binding affinity of 21 anthraquinones to the MMP2 catalytic domain. The most favorable scores based on the Gibbs free binding energy scores were given to the highest-ranked ligands. The Discovery Studio Visualizer tool illustrated interactions between MMP2 residues and top-ranked anthraquinones. RESULTS: A total of 12 anthraquinones were identified with ΔGbinding scores less than - 10 kcal/mol. Pulmatin (Chrysophanol-8-glucoside) was the most potent MMP2 inhibitor, with a ΔGbinding score of - 12.91 kcal/mol. This anthraquinone was able to restrict MMP2 activity within a picomolar range. CONCLUSION: MMP2 inhibition by anthraquinones, notably Pulmatin, may be a useful therapeutic approach for cancer treatment.

MicroRNA-Based Markers of Oral Tongue Squamous Cell Carcinoma and Buccal Squamous Cell Carcinoma: A Systems Biology Approach.

Objective: Oral tongue squamous cell carcinoma (OTSCC) and buccal squamous cell carcinoma (BSCC) are the first and second leading causes of oral cancer, respectively. OTSCC and BSCC are associated with poor prognosis in patients with oral cancer. Thus, we aimed to indicate signaling pathways, Gene Ontology terms, and prognostic markers mediating the malignant transformation of the normal oral tissue to OTSCC and BSCC. Methods: The dataset GSE168227 was downloaded and reanalyzed from the GEO database. Orthogonal partial least square (OPLS) analysis identified common differentially expressed miRNAs (DEMs) in OTSCC and BSCC compared to their adjacent normal mucosa. Next, validated targets of DEMs were identified using the TarBase web server. With the use of the STRING database, a protein interaction map (PIM) was created. Using the Cytoscape program, hub genes and clusters within the PIM were shown. Next, gene-set enrichment analysis was carried out using the g:Profiler tool. Using the GEPIA2 web tool, analyses of gene expression and survival analysis were also performed. Results: Two DEMs, including has-miR-136 and has-miR-377, were common in OTSCC and BSCC (p value <0.01; |Log2 FC| > 1). A total of 976 targets were indicated for common DEMs. PIM included 96 hubs, and the upregulation of EIF2S1, CAV1, RAN, ANXA5, CYCS, CFL1, MYC, HSP90AA1, PKM, and HSPA5 was significantly associated with a poor prognosis in the head and neck squamous cell carcinoma (HNSCC), while NTRK2, HNRNPH1, DDX17, and WDR82 overexpression was significantly linked to favorable prognosis in the patients with HNSCC. "Clathrin-mediated endocytosis" was considerably dysregulated in OTSCC and BSCC. Conclusion: The present study suggests that has-miR-136 and has-miR-377 are underexpressed in OTSCC and BSCC than in normal oral mucosa. Moreover, EIF2S1, CAV1, RAN, ANXA5, CYCS, CFL1, MYC, HSP90AA1, PKM, HSPA5, NTRK2, HNRNPH1, DDX17, and WDR82 demonstrated prognostic markers in HNSCC. These findings may benefit the prognosis and management of individuals with OTSCC/BSCC. However, additional experimental verification is required.

3D-Printed Soft Membrane for Periodontal Guided Tissue Regeneration.

OBJECTIVES: The current study aimed to perform an in vivo examination using a critical-size periodontal canine model to investigate the capability of a 3D-printed soft membrane for guided tissue regeneration (GTR). This membrane is made of a specific composition of gelatin, elastin, and sodium hyaluronate that was fine-tuned and fully characterized in vitro in our previous study. The value of this composition is its potential to be employed as a suitable replacement for collagen, which is the main component of conventional GTR membranes, to overcome the cost issue with collagen. METHODS: Critical-size dehiscence defects were surgically created on the buccal surface of the roots of canine bilateral mandibular teeth. GTR treatment was performed with the 3D-printed membrane and two commercially available collagen membranes (Botiss Jason® and Smartbrane-Regedent membranes) and a group without any membrane placement was considered as the control group. The defects were submerged with tension-free closure of the gingival flaps. Histologic and histometric analyses were employed to assess the periodontal healing over an 8-week experimental period. RESULTS: Histometric evaluations confirmed higher levels of new bone formation in the 3D-printed membrane group. Moreover, in all defects treated with the membranes, the formation of periodontal tissues, bone, periodontal ligaments, and cementum was observed after 8 weeks, while in the control group, only connective tissue was found in the defect sites. There was no clinical sign of inflammation or recession of gingiva in any of the groups. SIGNIFICANCE: The 3D-printed gelatin/elastin/sodium hyaluronate membrane can be safe and effective for use in GTR for periodontal tissue regeneration therapies, with better or comparable results to the commercial collagen membranes.

Pathogenesis and prognosis of primary oral squamous cell carcinoma based on microRNAs target genes: a systems biology approach.

Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck malignancy, with frequent cervical lymph-node metastasis, leading to a poor prognosis in OSCC patients. The present study aimed to identify potential markers, including microRNAs (miRNAs) and genes, significantly involved in the etiology of early-stage OSCC. Additionally, the main OSCC's dysregulated Gene Ontology annotations and significant signaling pathways were identified. The dataset GSE45238 underwent multivariate statistical analysis in order to distinguish primary OSCC tissues from healthy oral epithelium. Differentially expressed miRNAs (DEMs) with the criteria of p-value < 0.001 and |Log2 fold change| > 1.585 were identified in the two groups, and subsequently, validated targets of DEMs were identified. A protein interaction map was constructed, hub genes were identified, significant modules within the network were illustrated, and significant pathways and biological processes associated with the clusters were demonstrated. Using the GEPI2 database, the hub genes' predictive function was assessed. Compared to the healthy controls, main OSCC had a total of 23 DEMs. In patients with head and neck squamous cell carcinoma (HNSCC), upregulation of CALM1, CYCS, THBS1, MYC, GATA6, and SPRED3 was strongly associated with a poor prognosis. In HNSCC patients, overexpression of PIK3R3, GIGYF1, and BCL2L11 was substantially correlated with a good prognosis. Besides, "proteoglycans in cancer" was the most significant pathway enriched in the primary OSCC. The present study results revealed more possible mechanisms mediating primary OSCC and may be useful in the prognosis of the patients with early-stage OSCC.

3D-printed bi-layered polymer/hydrogel construct for interfacial tissue regeneration in a canine model.

OBJECTIVES: There are complications in applying regenerative strategies at the interface of hard and soft tissues due to the limited designs of constructs that can accommodate different cell types in different sites. The problem originates from the challenges in the adhesion of dissimilar materials, such as polymers and hydrogels, that can be suitable for regenerating different tissues such as bone and soft tissues. This paper presents a design of a new hybrid construct in which a polymer (polycaprolactone (PCL)) membrane firmly adheres to a layer of hydrogen (gelatin). METHODS: PCL membranes with defined size and porosity were fabricated using 3D printing. The gelatin layer was attached to the PCL membranes using the aminolysis procedure. We have examined this construct for the application of Guided Bone Regeneration (GBR) as a typical surgical regenerative procedure of the oral cavity at the interface of bone and soft tissue. Complete in vitro and in vivo investigations on canine tibia bone defects have been performed. Histological analyses for fibrosis morphometric and bone morphometric evaluation, as well as bone-fibrosis histological grading and CBCT imaging, were conducted. RESULTS: Chemical and morphological studies of the membrane proved that gelatin was uniformly attached to the aminolyzed PCL membranes. The in vitro and in vivo studies indicated the membrane's biocompatibility, mechanical stability, and barrier function for the GBR application. Furthermore, in vitro study showed that the membranes could improve osteogenesis and the regeneration of bone defects. The results illustrated that the mean bone density in the membrane groups was about three times more than that of the control group. SIGNIFICANCE: The fabricated 3D-printed hybrid Gelatin/PCL bi-layered membrane can be a good candidate for interfacial tissue engineering and a promising membrane for GBR procedure.

A Clinicopathological Report of Four Cases of Squamous Odontogenic Tumor-Like Proliferations in Odontogenic Cysts: Suggested Opinions regarding This Unusual Nature.

Distinguishing squamous odontogenic tumor-like proliferations (SOTLPs) is important in odontogenic cysts to avoid misinterpretation such as a squamous odontogenic tumor, well-differentiated squamous cell carcinoma, and acanthomatous type of ameloblastoma. This study is aimed at reporting 4 cases of these clinicopathological proliferations in order to shed more light on the importance of distinguishing them from other similar types. 150 odontogenic cysts were studied in which four cases (2.66%) with SOTLPs were identified including 2 radicular cysts, 1 dentigerous cyst, and 1 odontogenic keratocyst. These proliferations were observed in the cysts' wall particularly adjacent to the epithelial lining. All cysts had inflammation while 3 cases showed budding from the epithelial cyst lining. The findings suggested that lining of odontogenic cysts could be a source of SOTLPs, and inflammation probably played an effective role in their development. Its incidence was 2.66% in the present study. Although SOTLPs are not frequent in odontogenic cysts, their identification is important to prevent wrong histopathologic interpretation and treatment.

Jaw Intraosseous Lesions Biopsied Extracted From 1998 to 2010 in an Iranian Population.

BACKGROUND: Jaw bones might be potential locations for different lesions. Differences in prevalence and the type of lesions can help in designing and programming prevention procedures in health care centers. OBJECTIVES: The aim of the present study was to evaluate the prevalence of intraosseous lesions in the jaws of patients referred to diagnostic and therapeutic centers in Hamadan during 1990-2010. PATIENTS AND METHODS: This cross-sectional descriptive analytical study was carried out in Hamadan in 2011. Data sheets of the subjects were used to collect all the data of patients with intraosseous lesions, including their age, gender, location of the lesion, the radiographic view of lesions, and their type and histopathological diagnoses. Data were analyzed with SPSS, using means and frequencies. RESULTS: A total of 284 intraosseous lesions were reported in our study. The mean age of the subjects was 28.8 ± 15.2 years. The lesions were distributed in males and females almost similarly. The most prevalent lesions were cystic lesions (54.58%), manifestations of systemic conditions in jaw bones (18.3%), benign tumors (15.5%), malignant lesions (6.7%), and inflammatory lesions (4.92%), in a descending order. The most common cystic lesion was radicular cyst; the most common manifestation of systemic conditions in jaw bones was central giant cell granuloma; the most common benign tumor was ameloblastoma; the most common malignant lesion was osteosarcoma; and the most common inflammatory lesion was periapical granuloma. CONCLUSIONS: Our data provided information on the prevalence and types of intraosseous lesions among an Iranian population. This study provided baseline information to help in designing and programming procedures in health care centers in every community so that preventive therapeutic measures can be adopted.

Study of P21 Expression in Oral Lichen Planus and Oral Squamous Cell Carcinoma by Immunohistochemical Technique.

STATEMENT OF THE PROBLEM: Lichen planus is a mucocutaneous disease that is relatively common in middle aged individuals. Some studies have shown that oral lichen planus has a potential to progress to squamous cell carcinoma.p21 is a cyclin-dependent kinase inhibitor that regulates the cell cycle, thus it acts as an inhibitor in cell proliferation. PURPOSE: This study was aimed to evaluate and compare the immunostaining of p21 (as a proliferation inhibitory factor) in oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). MATERIALS AND METHOD: In this descriptive cross-sectional study, p21expression was investigated in 24 samples of oral lichen planus (OLP), 24 samples of oral squamous cell carcinoma (OSCC) and 24 samples of oral epithelial hyperplasia (OEH) by employing immunohistochemical staining. RESULTS: The mean percentage of p21-positive cells in OSCC (54.5±6.6) was significantly higher than that in OLP (32.8±6.08) and OEH (9.4±3.8). Moreover, OLP samples expressed p21 significantly higher than the OEH. Kruskal Wallis test revealed a statistically significant difference between the groups regarding the intensity of staining (p< 0.001). CONCLUSION: According to the findings of this study, the expression of p21 might be related to the potential carcinogenic transformation of lichen planus to SCC. Therefore, continuous follow-up periods for OLP are recommended for diagnosis of the malignant transformations in early stages.

Immunohistochemical Expression of Mast Cell in Oral Reactive Lesions.

STATEMENT OF THE PROBLEM: Soft tissue reactive lesions are the most common lesions of the oral cavity. Although many studies have shown the interaction of mast cells with fibroblasts and their participation in fibrosis, the role of mast cells in these lesions is not well understood. PURPOSE: The aim of this study was to evaluate the mast cells (MCs) count in oral soft-tissue reactive lesions including peripheral giant cell granuloma (PGCG), peripheral ossifying fibroma (POF), irritation fibroma (IF) and normal oral mucosa. MATERIALS AND METHOD: In this cross-sectional study, 50 samples including IF, PGCG, POF (14 cases for each group) and 8 cases of normal oral mucosa were stained with tryptase antibody through immunohistochemistry. The number of mast cells was counted in 5HPF containing maximum counts for each section stained with tryptase. Statistical analysis including Chi-square test and Tukey test with a significance level of 0.05 were considered. RESULTS: The number of MCs was found to have increased in reactive lesions compared with normal oral mucosa. MCs count in the POF group was higher than the others. CONCLUSION: These findings suggest a possible role of mast cells in the pathogenesis of reactive oral lesions and induction of fibrous tissues. Chemical mediators released from mast cells might influence other cells, especially fibroblasts, to induce fibrosis.

An Immunohistochemical Survey to Evaluate the Expression of CD105 and CD34 in Ameloblastoma and Odontogenic Keratocyst.

UNLABELLED: Statement of the Problem : Ameloblastoma is the most common odontogenic tumor which is slow-growing, locally invasive and exhibit specific biologic behavior and high recurrence rate. Likewise, odontogenic keratocyst is a developmental odontogenic cyst that has a high recurrence rate and aggressive behavior. There are limited studies considering the relationship between the angiogenesis factors and the biologic behavior of these lesions. PURPOSE: the aim of this study was to evaluate the mean density of vessels in odontogenic keratocysts and ameloblastoma and investigate its possible relationship with biological behavior of these lesions. MATERIALS AND METHOD: In this descriptive-analytic cross-sectional study, 40 cases, comprising 10 odontogenic keratocysts and 30 ameloblastomas (10 plexiform, 10 follicular, and 10 unicystic type) were selected and were stained immuno-histochemically with CD34 and CD105. The micro vessel density was assessed and compared in all groups. T- test for the independent samples' One- way Anova, Wilcoxon test and Tukey tests were adopted for statistical analysis. RESULTS: A statistically significant difference was observed in mean vascular density (MVD) between the odontogenic keratocyst and ameloblastoma groups concerning the CD105 and CD34 markers (p= 0.005, p= 0.000, respectively). The MVD was significantly higher in ameloblastomas than odontogenic keratocyst. MVD with CD34 was significantly higher than MVD with CD105 in ameloblastomas (p= 0.00). CONCLUSION: It can be suggested that angiogenesis might be one of the mechanisms that is more possible to contribute the aggressive biological behaviors in ameloblastoma rather than odontogenic keratocyst.