Salivary Vascular Endothelial Growth Factor and Epidermal Growth Factor Levels in Patients with Recurrent Aphthous Stomatitis: a Meta-Analysis.

Recurrent aphthous stomatitis (RAS) has been identified as a common oral lesion with an unknown pathogenesis. Various studies have been conducted to show the important role of two factors named epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in RAS, but certain results have not been achieved. The present meta-analysis was conducted to evaluate the salivary levels of EGF and VEGF in patients with RAS. For this purpose, the related articles in the Web of Science, PubMed, Embase, ProQuest and Scopus databases until January 2022 were searched and their abstracts were studied. Google scholar and scientific information database were also searched for articles in Persian. The searches were completed by the medical subject heading terms considering "recurrent aphthous stomatitis" and "saliva" in combination with "EGF" or "VEGF" keywords. All case control studies that evaluated the salivary levels of EGF and VEGF in patients with RAS were included in this study. To evaluate statistical heterogeneity between the studies, Cochrane Q and I2 tests were adopted. The extracted data then were used in the analysis process based on comprehensive meta-analysis software. Originally, 619 articles were considered, of which 7 articles were selected. According to this meta-analysis, salivary EGF and VEGF levels were significantly lower in the active and remission period of RAS than in healthy individuals (pValue< 0.05). In addition, salivary levels of these factors were significantly lower in the active stage of RAS than in the healing phase. This review study suggests that decreasing of salivary EGF and VEGF levels have significant role in the development of RAS.

Association between 5-Hydroxytryptamine Receptor 2A Gene (rs6313 and rs4941573) Polymorphism and Sleep Bruxism: A Meta-analysis.

Genetic factors may influence sleep bruxism's pathogenesis. Even though the association between the, 5-hydroxytryptamine 2A (5-HTR2A) serotonin receptor gene polymorphism and sleep bruxism has been investigated, inconsistent findings have been discovered. As a result, meta-analysis was performed to gather complete results on this topic. PubMed, Web of Science, Embase, and Scopus databases were searched for all papers containing English abstracts until April 2022. Medical Subject Heading (MESH) terms plus unrestricted keywords were used in the searches. The Cochrane test and the I 2 statistic were used to determine the heterogeneity percentage in numerous researches. Comprehensive Meta-analysis v.2.0 software was used to conduct the analyses. Five properly fitting papers were chosen for meta-analysis from the 39 articles acquired during the initial search. The meta-analysis revealed that the 5-HTR2A polymorphism has no link with sleep bruxism susceptibility across the models studied (P-Value > 0.05). The combined odds ratio analysis revealed no statistically significant association between the 5-HTR2A gene polymorphism with sleep bruxism. Nonetheless, these findings require confirmation through researches with large sample sizes. Identifying genetic markers for sleep bruxism may help clarify and expand our current knowledge of bruxism physiopathology.

Clinicopathological and prognostic value of Ki-67 expression in oral malignant melanoma: A systematic review and meta-analysis.

Background. Ki-67 is one of the new biological markers with clinical value in the pathology and prognosis of oral melanoma. It is a nuclear protein involved in regulating cell proliferation. Some studies have suggested an association between Ki-67 and poor survival in patients with oral melanoma. This systematic review was undertaken to clarify this issue. Methods. Databases of PubMed, Scopus, and Web of Science were searched using relevant English keywords from 1988 to April 2022. STATA software version 16 and random models were used for meta-analysis. Results. Eleven articles were included in this systematic review, six of which were selected for meta-analysis. The mean expression of the Ki-67 index in patients with oral melanoma was estimated at 43.81% (28.66‒58.95 with 95% CI, I2=94.2, P<0.001). In addition, the results showed a significant relationship between Ki-67 expression and the prognosis of oral melanoma lesions. Increased expression of this marker weakens the prognosis and decreases the survival rate. Conclusion. High expression of Ki-67 may serve as a predictive biomarker for poor prognosis in patients with malignant oral melanoma. Therefore, classifying this malignancy by Ki-67 expression may be considered for therapy regimen selection and integrated management.

Designing a Strategy for pH Control to Improve CHO Cell Productivity in Bioreactor.

BACKGROUND: Drastic pH drop is a common consequence of scaling up a mammalian cell culture process, where it may affect the final performance of cell culture. Although CO2 sparging and base addition are used as common approaches for pH control, these strategies are not necessarily successful in large scale bioreactors due to their effect on osmolality and cell viability. Accordingly, a series of experiments were conducted using an IgG1 producing Chinese Hamster Ovary (CHO-S) cell culture in 30 L bioreactor to assess the efficiency of an alternative strategy in controlling culture pH. METHODS: Factors inducing partial pressure of CO2 and lactate accumulation (as the main factors altering culture pH) were assessed by Plackett-Burman design to identify the significant ones. As culture pH directly influences process productivity, protein titer was measured as the response variable. Subsequently, Central Composite Design (CCD) was employed to obtain a model for product titer prediction as a function of individual and interaction effects of significant variables. RESULTS: The results indicated that the major factor affecting pH is non-efficient CO2 removal. CO2 accumulation was found to be affected by an interaction between agitation speed and overlay air flow rate. Accordingly, after increasing the agitation speed and headspace aeration, the culture pH was successfully maintained in the range of 6.95-7.1, resulting in 51% increase in final product titer. Similar results were obtained during 250 L scale bioreactor culture, indicating the scalability of the approach. CONCLUSION: The obtained results showed that pH fluctuations could be effectively controlled by optimizing CO2 stripping.

Evaluation of Salivary Level of Heat Shock Protein 70 in Patients with Chronic Periodontitis.

STATEMENT OF THE PROBLEM: Traditional clinical criteria are usually not sufficient for determining the sites of active periodontal disease, monitoring the response to treatment, or measuring the susceptibility to future disease development. Past studies have shown that heat shock protein 70 (HSP70) are involved in the etiology of periodontal disease. PURPOSE: The aim of this study was to evaluate the level of HSP70 in saliva of patients with chronic periodontitis (CP). MATERIALS AND METHOD: In our case-control study, the saliva samples of 45 patients with CP and 45 age- and sex-matched healthy subjects were collected. Salivary HSP70 was measured by enzyme-linked immunosorbent assay method. The results were analyzed by statistical tests using SPSS 16 and the statistically significant difference was set at p< 0.05. RESULTS: In this study, the mean salivary HSP70 level was 2.81±0.61ng/ml in the patient group and 1.96±0.77ng/ml in the healthy group, with a significant difference (p< 0.05). In addition, the results of spearman correlation analysis showed a positive correlation between salivary HSP 70 and clinical periodontal index. CONCLUSION: The results of this study showed that the salivary HSP70 level in patients with CP is higher than that in healthy subjects. As a result, salivary HSP70 might be considered as a marker in the pathogenesis of CP.

Role of Vitamin D and Vitamin D Receptor in Oral Lichen Planus: A Systematic Review.

BACKGROUND: Oral lichen planus (OLP) is known to be a chronic inflammatory disease associated with various other systemic disorders. Studies have shown that vitamin D deficiency can be involved in the pathogenesis of lichen planus. The aim of this study was to investigate the role of vitamin D and vitamin D receptor in OLP. METHODS: In this review study, all English and Persian articles were searched by relevant keywords from the Google scholar, PubMed, science direct, Cochrane, Scopus and Sid databases until January 2020. RESULTS: From the 16 articles obtained after reviewing the abstracts, finally 14 appropriate articles were included in this study. CONCLUSION: According to the results of the studies, vitamin D deficiency may be associated with an increased risk of OLP lesions.

Comparing the Levels of Gingival Crevicular Fluid Prostaglandin E2 in Generalized Chronic Periodontitis Between Healthy and Type 2 Diabetes Patients: A Case-Control Study

Objective: To compare the prostaglandin E2 (PGE2) levels of gingival crevicular fluid in generalized chronic periodontitis between healthy and type 2 diabetic patients. Material and Methods: 56 diabetic and non-diabetic participants with generalized chronic periodontitis were selected randomly. They were divided into two groups (G1: generalized chronic periodontitis patients with normal blood sugar; and G2: generalized chronic periodontitis patients with diabetes). Gingival crevicular fluid samples were obtained from both groups. The average of 2 samples per day were centrifuged in a laboratory at 2500 rpm and temperature of 4°C for 5 minutes and placed in a refrigerator at -20°C. The level of PGE2 was measured using ELISA and Abcam kit. Data were analyzed by Kolmogorov-Smirnov, Mann-Whitney U Test, Pearson and independent T tests. The significant amount was considered 0.05 in this test (α<0.05). Results: The mean level of PGE2 was significantly different in the two groups and the mean level of PGE2 in the control group was lower than the case group. There was no statistically significant relationship between PGE2 with pocket depth, fasting blood sugar (FBS) and HBA1C (p>0.05). Conclusion: PGE2 level of diabetic patient group with chronic generalized periodontitis was significantly more than non-diabetic group with generalized chronic periodontitis.

Therapeutic Fc fusion protein misfolding: A three-phasic cultivation experimental design.

Cell culture process optimization is a critical solution to most of the challenges faced by the pharmaceutical manufacturing. One of the major problems encountered in large-scale production of therapeutic proteins is misfolded protein production. The accumulation of misfolded therapeutic proteins is an immunogenic signal and a risk factor for immunogenicity of the final product. The aim of this study was the statistical optimization of three-phasic temperature shift and timing for enhanced production of correctly folded Fc-fusion protein. The effect of culture temperatures were investigated using the biphasic culture system. Box-Behnken design was then used to compute temperature and time of shifting optimum. Response surface methodology revealed that maximum production with low level of misfolded protein was achieved at two-step temperature shift from 37°C to 30°C during the late logarithmic phase and 30°C to 28°C in the mid-stationary phase. The optimized condition gave the best results of 1860 mg L-1 protein titer with 24.5% misfolding level. The validation experiments were carried out under optimal conditions with three replicates and the protein misfolding level was decreased by two times while productivity increased by ~ 1.3-fold. Large-scale production in 250 L bioreactor under the optimum conditions was also verified the effectiveness and the accuracy of the model. The results showed that by utilizing two-step temperature shift, productivity and the quality of target protein have been improved simultaneously. This model could be successfully applied to other products.

Long Non-Coding RNA SNHG6 as a Potential Biomarker for Hepatocellular Carcinoma.

Long Non-coding RNAs (lncRNAs) refer to all non-protein coding transcripts longer than 200 nucleotides. Their critical roles in different biological pathways have been already well established. Altered expression of lncRNAs can be involved in the cancer initiation and/or progression. Since patients with hepatocellular carcinoma (HCC) are usually diagnosed in late stages, developing diagnostic methods seems to be essential. In this study, the expression levels of different lncRNAs were systematically analysed in different genomic and transcriptome datasets. The analyses showed that SNHG6 is among the lncRNAs with distinctive dysregulation of expression and copy number variation in HCC tumors compared with normal tissues. The results also suggest that the dysregulation of SNHG6 is highly cancer type specific. Through co-occurrence analyses, we found that SNHG6 and its related co-expressed genes on 8q are involved in the structural integrity of ribosome and translation. This comprehensive in silico analysis, provides a resource for investigating SNHG6 in hepatocellular carcinoma and lays the groundwork for design of next researches.

Evaluation effect of low level Helium-Neon laser and Iranian propolis extract on Collagen Type I gene expression by human gingival fibroblasts: an in vitro study.

BACK GROUND AND AIM: production of collagen by fibroblast cells is a key component in wound healing. Several studies have shown that low level laser therapy (LLLT) and propolis extract stimulate collagen Type I production. The aim of this study is to evaluation the combined effect of LLL helium neon (632.8 nm) and Iranian propolis extract on collagen Type I gene expression by human gingival fibroblasts (HGF3-PI 53). METHODS AND MATERIALS: Human gingival fibroblasts after culturing divided into six experimental groups: G1-control group, which received no irradiation and propolis extract, G2-irradiated at1.5 J/cm2, G3-irradiated at 0.15 J/cm2, G4-recived extract of propolis, G5- combined extract of propolis and 1.5 J/cm2 laser irradiation and G6- combined extract of propolis and 0.15 J/cm2 laser irradiation. The experiments were conducted in triplicate. After 24 hour, the total RNA was extracted and cDNA synthesis was performed. Type I collagen mRNA expression was determined with real time PCR. RESULTS: The obtained results illustrated a statistically significant difference between G3 (0.15 J/cm2) and G1 (control group) in levels of collagen Type I messenger RNA (mRNA) expression (p<0.05). The irradiated cells showed a 1.4 times increase in mRNA expression of the collagen Type I gene. Expression of this gene decreases in other groups that this difference was statistically significant. CONCLUSION: LLLT in different dosage and propolis extract may result in decreased or increased collagen type I gene expression. However this effect should be investigated in clinical studies.

Generation of stable ARE- driven reporter system for monitoring oxidative stress.

BACKGROUND: NF-E2-related factor2 (Nrf2)-antioxidant response element (ARE) signaling pathway is the major defensive mechanism against oxidative stress and is up regulated by specific antioxidants and oxidants to comprise the chemoptotective response. Detection of ARE-activating compounds helps to develop new drugs and identify/quantify the tension range of the oxidants. Important reasons promoting this work are high throughput, rapid and inexpensive experiments relative to the in vitro studies for ARE-Nrf2 pathway monitoring of chemicals and environmental samples. METHODS: In this study hepatoma Huh7 reporter cell line was generated which contains a luciferase gene under the control of an ARE. This is the first example of ARE construct containing one copy of extended consensus response element. The cells were treated with hydroquinone (HQ) and p-benzoquinone (BQ) (oxidative stress inducers) and the antioxidant, curcumin. RESULTS: The luciferase activity was induced in a concentration-dependent manner in a concentration range of 1-2 µM for BQ and HQ. Curcumin was also validated as an ARE inducer in concentration above 10 µM. In addition, this reporter cell line provides a rapid detection as early as 4 h to respond to the ARE inducers. CONCLUSION: It is a powerful tool for the sensitive and selective screening of chemicals, drugs and environmental samples for their antioxidant and oxidant activities.

Comparison of shear bond strength of calcium-enriched mixture cement and mineral trioxide aggregate to composite resin.

AIM: Adhesion of composite resin and pulp capping biomaterials remarkably influences treatment outcomes. This in vitro study aimed to compare the shear bond strength of composite resin to calcium enriched mixture (CEM) cement, mineral trioxide aggregate (MTA) and resin modified glass ionomer (RMGI) with or without acid etching. MATERIALS AND METHODS: A total of 90 cylindrical acrylic blocks containing a central hole, measuring 4 mm diameter and 2 mm height were prepared. The blocks were randomly divided into three experimental groups based on being filled with CEM, MTA or RMGI. Samples in each group were then randomly divided into two subgroups, i.e. with or without phosphoric acid etching. Placing composite resin cylinders on the samples, shear bond strengths were measured using a universal testing machine. Failure modes of the samples were evaluated under a stereomicroscope. Data were analyzed using two-way ANOVA and Tukey tests. RESULTS: Shear bond strengths in the etched and nonetched samples were not significantly different (p = 0.60). There was a significant difference in shear bond strength values of the three experimental materials (p < 0.001) and RMGI showed the highest strength values (p < 0.001); no significant difference was observed between MTA and CEM (p = 0.51). The interaction of the type of material and surface etching was statistically significant (p < 0.001). All of the samples showed cohesive failure mode. CONCLUSION: Acid etching of MTA, CEM and RMGI do not improve the shear bond strength of these materials to composite resin. Besides, shear bond strength values of MTA and CEM to composite resin, are favorable due to their cohesive mode of failure. CLINICAL SIGNIFICANCE: When MTA and CEM biomaterials are used in vital pulp therapy, it is advisable to cover these materials with RMGI. In addition, if it is not possible to use RMGI, the surface etching of MTA and CEM biomaterials is not necessary prior to composite restoration using total-etch adhesive resin.