Identification of proteins' expression pathway and the effective miRNAs for the treatment of human papillomavirus-induced cervical cancer: in-silico analyses-experimental research.

Introduction: Cervical cancer is the fourth most common cancer in women. The risk factors for cervical cancer include human papillomavirus (HPV) infection, age, smoking, number of pregnancies, use of oral contraceptives, and diet. However, long-term HPV infection appears to be the main risk factor for developing cervical cancer. This in-silico analysis aims to identify the expression network of proteins and the miRNAs that play a role in the development of HPV-induced cervical cancer. Methods: The critical proteins and miRNAs were extracted using the DisGeNET and miRBase databases. String and Gephi were applied to the network analysis. The GTEx web tool was utilized to Identify tissue expression levels. The Enrichr website was used to explore the molecular function and pathways of found genes. Results: Ten proteins, TP53, MYC, AKT1, TNF, IL6, EGFR, STAT3, CTNNB1, ESR1, and JUN, were identified as the most critical shared gene network among cervical cancer and HPV. Seven miRNAs were found, including hsa-mir-146a, hsa-mir-27, hsa-mir-203, hsa-mir-126, hsa-mir-145, hsa-mir-944, and hsa-mir-93, which have a common expression in cervical cancer and HPV. Conclusion: Overall, the gene network, including TP53, MYC, AKT1, TNF, IL6, EGFR, STAT3, CTNNB1, ESR1, and JUN, and Also, hsa-mir-145, hsa-mir-93, hsa-mir-203, and hsa-mir-126 can be regarded as a gene expression pathway in HPV-induced cervical cancer.

Esophageal chemical burns as a risk factor for esophageal malignancies: in-silico analyses - experimental research.

Introduction: Esophageal chemical burns often occur through accidental or intentional oral consumption of chemical agents and lead to severe complications such as esophageal stricture, acute perforation, and even death. Esophageal squamous cell carcinoma is a squamous epithelium tumor that lines the normal esophagus. Additionally, adenocarcinomas are tumors located at the interface between the distal esophagus and the proximal gastric and divided into esophageal adenocarcinoma and gastric-cardia adenocarcinoma. Various conditions, such as chemical burns, are considered risk factors in the disease's pathogenesis. In the in-silico study, the authors aim to present the relationship between chemical burns and esophageal cancer by analyzing bioinformatics genetic data. Methods: The proper gene set was extracted using the 'GEO' database. The string web tool was utilized to form the gene-interaction network. Gephi and Cytoscape software were applied to achieve network analysis. Results: According to in-silico data, 26 genes, including NCAPH, DLGAP5, CCNB1, KIF11, KIAA0101, CDCA5, BIRC5, NUF2, BUB1B, RRM2, TTK, CDC20, NUSAP1, CCNB2, CCNA2, MELK, TPX2, PRC1, KIF4A, CENPF, TOP2A, CDK1, ASPM, CEP55, BUB1, KIF20A were extracted that can be regarded as the most critical shared genes between chemical burns and esophageal cancer. Conclusion: In sum, esophageal chemical burns can be related to the occurrence of esophageal cancer. Moreover, esophageal chemical burn is an external factor that upregulates present genes and can be regarded as a worsening prognosis or risk factor for esophageal cancer.

Transplantation of bioengineered dermal derived matrix-scaffold in combination with hyperbaric oxygen therapy improves wound healing in diabetic rats.

Successful treatment of diabetic wounds requires multifactorial approaches. Herein we investigated the effects of a bioengineered three-dimensional dermal derived matrix-scaffold (DMS) in combination with hyperbaric oxygen (HBO) in repairing of wound model in diabetic rats. Thirty days after induction of diabetes, a circular wound was created and treatments were performed for 21 days. Animals were randomly allocated into the untreated group, DMS group, HBO group, and DMS+HBO group. On days 7, 14, and 21, tissue samples were obtained for stereological, molecular, and tensiometrical assessments. Our results showed that the wound closure rate, volume of new dermis and epidermis, numerical density fibroblasts and blood vessels, collagen density, and biomechanical characterize were significantly higher in the treatment groups than in the untreated group, and these changes were more obvious in the DMS+HBO ones. Moreover, the expression of TGF-ß, bFGF, miRNA-21, miRNA-146a, and VEGF genes were meaningfully upregulated in treatment groups compared to the untreated group and were greater in the DMS+HBO group. This is while expression of TNF-α and IL-1ß, as well as the numerical density of neutrophil and macrophage decreased more considerably in the DMS+HBO group than in the other groups. Overall, using both DMS engraftment and HBO treatment has more effects on diabetic wound healing.

Decellularized human amniotic membrane loaded with epigallocatechin-3-gallate accelerated diabetic wound healing.

Diabetic wounds, as one of the most important complications of diabetes, face many challenges in treatment. Herein we investigated whether decellularized human amniotic membrane (dAM) loaded with epigallocatechin-3-gallate (EGCG) could promote healing in diabetic rats. Sixty diabetic rats were randomly planned into the untreated group, dAM group, EGCG group, and dAM + EGCG group. On days 7, 14, and 21, five rats from each group were sampled for stereological, molecular, and tensiometrical assessments. Our finding revealed that the wound closure rate, the total volumes of new epidermis and dermis, the numerical densities of fibroblasts, blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were considerably increased in the treated groups than in the untreated group, and these changes were more obvious in the dAM + EGCG ones. Furthermore, the expression of TGF-ß, bFGF, and VEGF genes were significantly upregulated in all treated groups compared to the untreated group and were greater in the dAM + EGCG group. This is while expression of TNF-α and IL-1ß, as well as cell numerical densities of neutrophils and macrophages decreased more considerably in the dAM + EGCG group in comparison to the other groups. In conclusion, it was found that using both dAM transplantation and EGCG has more effect on diabetic wound healing.

Coenzyme Q10 attenuates neurodegeneration in the cerebellum induced by chronic exposure to tramadol.

BACKGROUND: Chronic use of tramadol can cause neurotoxic effects and subsequently cause neurodegeneration in the cerebellum. The main damage mechanisms identified are oxidative stress and inflammation. Currently, we investigated the effects of coenzyme Q10 (CoQ10) in attenuates of neurodegeneration in the cerebellum induced by chronic exposure to tramadol. MATERIAL AND METHODS: Seventy-two male mature albino rats were allocated into four equal groups, including; non-treated group, CoQ10 group (which received CoQ10 at 200 mg/kg/day orally for three weeks), tramadol group (which received tramadol hydrochloride at 50 mg/kg/day orally for three weeks), and tramadol+CoQ10 group (which received tramadol and CoQ10 at the same doses as the previous groups). Tissue samples were obtained for stereological, immunohistochemical, biochemical, and molecular evaluations. Also, functional tests were performed to evaluate behavioral properties. RESULTS: We found a significant increase in stereological parameters, antioxidant factors (catalase, glutathione, and superoxide dismutase), and behavioral function scores in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). In addition, malondialdehyde levels, the density of apoptotic cells, as well as the expression of pro-inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6) and autophagy (lysosome-associated membrane protein 2, autophagy-related 5, beclin 1, and autophagy-related 12) genes were considerably reduced in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). CONCLUSION: We conclude that the administration of CoQ10 has neuroprotective effects in the cerebellum of rats that have chronic exposure to tramadol.

Effect of root resection on sealing ability of orthograde apical plugs of mineral trioxide aggregate and calcium enriched mixture.

OBJECTIVE: There is some concern that root resection may alter the seal of the previously set orthograde material. The aim of this study was to evaluate the apical sealing ability of orthograde mineral trioxide aggregate (MTA) and calcium enriched mixture (CEM) plugs after resection of the roots. MATERIALS AND METHODS: The fluid filtration method was carried out on a total of 51 roots in three experimental (n=15) and two control (n=3) groups. The root canals were prepared 3 mm shorter than the working length. In groups A and B, 4 mm of MTA and CEM were placed in an orthograde technique, respectively, and after setting, 3 mm of the root end was resected. In group C, the apical 3 mm of each root was resected, root end preparation was carried out to a depth of 3 mm and filled with MTA. Apical microleakage values of each group were measured. Data was analyzed using Kruskal-Wallis test. RESULTS: Means and standard deviations of apical microleakage in groups A (MTA orthograde), B (CEM orthograde) and C (MTA retrograde) were 2.31×10(-4) (0.32×10(-4)), 3.33×10(-4) (0.29×10(-4)) and 4.42×10(-4) (0.40×10(-4)) µl.min(-1).cmH2o(-1), respectively. The mean values were greater in group C; however, statistical analysis revealed no significant differences between these groups (P>0.05). CONCLUSION: Based on the results of this study, when there is an orthograde access to the root canal and surgery is likely to be necessary in the future, MTA and CEM can be placed in an orthograde technique and it just resects the root during surgery.

Sealing Ability of Orthograde MTA and CEM Cement in Apically Resected Roots Using Bacterial Leakage Method.

INTRODUCTION: The aim of this in vitro study was to determine the sealing ability of orthograde ProRoot mineral trioxide aggregate (MTA) and calcium enriched mixture (CEM) cement as root-end filling materials. MATERIALS AND METHODS: Fifty four extracted single-rooted human teeth were used. The samples were randomly divided into 3 experimental groups. In group A and B, 4 mm of WMTA and CEM cement were placed in an orthograde manner and 3 mm of apices were resected after 24 hours. In group C the apical 3 mm of each root was resected and the root-end prepared with ultrasonic tips to a depth of 3 mm and subsequently, then filled with MTA. The apical sealing ability was performed with bacterial leakage method. Statistical analysis was carried out with Chi-square test. RESULTS: There were no significant differences in the extent of bacterial leakage between the three experimental groups (P>0.05). CONCLUSION: Based on the limitations of this in vitro study, we concluded that MTA and CEM cement can be placed in an orthograde manner when there is a potential need for root-end surgery.

Use of fluid filtration method to evaluate the effect of master cone size on the apical seal of severely curved root canals.

The apical third of most root canals shows some degree of curvature, which is important in cleaning/shaping and obturation during root canal treatment. The present study evaluated the effect of master cone size on the apical seal of severely curved root canals. Thirty-eight mesial roots of human mandibular first molars were prepared using the crown-down technique. All samples were mature roots with closed apices, had no carious lesions or resorption, and had a canal curvature of > 45º to 60º. Two samples were used as a negative and positive control to evaluate the fluid filtration equipment, and the remaining 36 samples were equally divided into groups A, B, and C based on master cone size, namely, gutta-percha #20, #25, and #30, respectively. The fluid filtration method was used to evaluate microleakage. No significant difference in microleakage was observed among groups (P = 0.31). In conclusion, an increase in master cone size up to #30 does not significantly influence apical microleakage.

Effect of calcium hydroxide premedication on the marginal adaptation of calcium-enriched mixture cement apical plug.

BACKGROUND: This study was to evaluate the effects of calcium hydroxide premedication on the marginal adaptation of the calcium-enriched mixture (CEM) cement as an apical plug. MATERIALS AND METHODS: In this in vitro study, forty single rooted teeth were prepared and apical portion of the roots were immersed in sulfuric acid to produce open apices. The teeth were divided into 2 experimental groups. In medicated group, calcium hydroxide was placed in all canals for 1 week and in non-medicated group no dressing was used. Then, a 4-mm apical plug of CEM cement was placed in canals; each root was prepared for observation using scanning electron microscope and the maximum distance between CEM cement and surrounding dentin was measured. The data were analyzed by t-test, and significance level was set at α = 0.05. RESULTS: The mean width of gap in medicated and non-medicated groups was 158/1 µm and 147/1 µm, respectively. There was no significant difference between the two groups (P > 0.05). CONCLUSION: Calcium hydroxide premedication had no adverse effect on the marginal adaptation of CEM cement apical plug.

Effect of previous calcium hydroxide dressing on the sealing properties of the new endodontic cement apical barrier.

OBJECTIVES: Using the fluid filtration method, an in vitro study was conducted to evaluate the effects of medication with calcium hydroxide on the sealing ability of the New Endodontic Cement (NEC) apical barrier in the short and long terms. METHODS: Fifty extracted single rooted teeth were prepared and apical resorption produced using acid sulfuric for four days. The teeth were randomly divided into two experimental groups (n=20) and two control groups. In group 1, calcium hydroxide was placed into all canals for one week and in group 2, no medication was used. In both groups, a 4 mm NEC apical plug was placed in the canals and the remaining portion of the canals was filled with gutta-percha. The amount of microleakage of all samples was evaluated after one week and three months. The data were statistically analyzed using two-way ANOVA. RESULTS: There was no significant difference between the two groups in either time period (P>.05). In both group 1 and group 2, microleakage increased after three months but this increase was not statistically significant (P>.05). CONCLUSIONS: According to the result of this study, medication with calcium hydroxide had no adverse effect on the short- and long-term sealing properties of an NEC apical plug.

The Effect of Calcium Hydroxide on the Short and Long-Term Sealing Properties of MTA Apical Barrier.

INTRODUCTION: The aim of this study was to evaluate the effects of remnant root canal medicament, calcium hydroxide on the short and long term sealing ability of mineral trioxide aggregate (MTA) apical barrier. MATERIALS AND METHODS: Fifty single-rooted teeth were prepared and apical resorptions were made using sulfuric acid. The teeth were allocated into two experimental groups and two control groups. In group 1, calcium hydroxide was placed into canals for one week. In group 2, no medication was placed. In both groups, a 4-mm MTA plug was placed in the root canals. The remaining portion of the canal was filled with gutta-percha/sealer. The microleakage was evaluated after 7 days and 3 months using fluid filtration technique. Repeated measurement ANOVA was used for statistical analysis. RESULTS: There was no significant difference in sealing ability between the two groups in either time periods. In both groups, microleakage decreased after three months but this decrease was not statistically significant. CONCLUSION: Medication with calcium hydroxide had no adverse effect on the short and long-term sealing properties of MTA plug.

Medication with calcium hydroxide improved marginal adaptation of mineral trioxide aggregate apical barrier.

INTRODUCTION: The purpose of this study was to evaluate the effect of calcium hydroxide premedication on the marginal adaptation of the mineral trioxide aggregate (MTA) apical barrier. METHODS: Forty single-rooted teeth were prepared and apically resorbed using sulfuric acid for 4 days. Teeth were allocated into two groups according to whether calcium hydroxide was placed in the canals for 1 week (medicated group) or not (nonmedicated group) before placing a 4-mm MTA apical plug in the canals. The roots were mounted on aluminum stubs, the root apex was viewed from the top under scanning electron microscopy, and the maximum distance between MTA and the surrounding dentin was measured. RESULTS: The mean gap widths in the medicated and nonmedicated groups were 70.2 µm and 130.0 µm, respectively (p < 0.05). CONCLUSIONS: Calcium hydroxide treatment improves marginal adaptation of the MTA apical plug.

Cytotoxic effect of a new endodontic cement and mineral trioxide aggregate on L929 line culture.

INTRODUCTION: The aim of this study was to compare the cytotoxicity of Mineral Trioxide Aggregate (MTA) and a New Endodontic Cement (NEC) on L929 mouse fibroblasts. MATERIALS AND METHODS: Different dilutions (Neat, 1/2, 1/10, 1/100) of fresh and set materials placed adjacent flasks of L929 in DMEM medium. Cellular viability was assessed using MTT assay in three time intervals (24, 48, and 72 h after mixing). Differences in mean cell viability values between materials were assessed by using the One-way ANOVA and Bonferoni post-test. Optical microscopic analysis of morphology of the untreated control and the cement-treated cell cultures were carried out in all experimental periods. RESULTS: It was indicated that there was not a significant difference in cytotoxicity among the materials of test and between them and the control group. However, there was a statistically significant difference between different time intervals within each group (P< 0.05) and between different concentration of test materials (P<0.05). In all samples, set materials showed better viability than fresh ones. CONCLUSION: According to results of this study, NEC and MTA have similar cytotoxic effect on L929 cell culture.

Finite element evaluation of stress distribution in mature and immature teeth.

INTRODUCTION: Traumatic injuries may affect the vitality and development of tooth. So divergence or parallelism of canal walls induces an open apex which is very susceptible to fracture. The aim of this study was to determine the stress distribution pattern in immature teeth and compare it with mature teeth. MATERIALS AND METHODS: In order to analyze stress distribution using finite element method, models were first designed according to actual samples by "ANSYS" software. Two models of the maxillary central incisors were designed, one mature and one with open apex. Mature tooth was designed as having undergone root canal therapy with gutta-percha and the immature one with both MTA plug and gutta-percha. Samples were loaded in seven stages and then, the stress distribution in each model was measured, using the "ANSYS" software. RESULTS: During gutta-percha condensation, the immature tooth transfers the stress directly to the external root surface where force is directly applied, whereas during masticatory occlusal forces, the stress is transferred to middle third of buccal and lingual surfaces and to buccal cervix in lunar shape. During traumatic forces, stress concentration was on the cervical region of buccal surface and middle third of buccal and lingual surfaces. MTA plug prevents stress distribution toward apical region and forces concentrate in dentin at the point where stress terminates. CONCLUSION: Within the limitations of this simulated mechanical analysis, it was confirmed that the pattern of stress distribution in mature and immature teeth is different. Cervical area of the buccal surface in immature teeth is one of the stress concentration areas, which contribute to the high rate of fracture in this area.