Mechanisms Involved in Therapeutic Effects of Scutellaria baicalensis Georgi in Oral Squamous Cell Carcinoma Based on Systems Biology and Structural Bioinformatics Approaches.

Objective: Oral squamous cell carcinoma (OSCC) is the most frequent oral cancer, constituting more than 90% of all oral carcinomas. The 5-year survival rate of OSCC patients is not satisfactory, and therefore, there is an urgent need for new practical therapeutic approaches besides the current therapies to overcome OSCC. Scutellaria baicalensis Georgi (SBG) is a plant of the family Lamiaceae with several pharmaceutical properties such as antioxidant, anti-inflammatory, and anticancer effects. Previous studies have demonstrated the curative effects of SBG in OSCC. Methods: A systems biology approach was conducted to identify differentially expressed miRNAs (DEMs) in OSCC patients with a dismal prognosis compared to OSCC patients with a favorable prognosis. A protein interaction map (PIM) was built based on DEMs targets, and the hub genes within the PIM were indicated. Subsequently, the prognostic role of the hubs was studied using Kaplan-Meier curves. Next, the binding affinity of SBG's main components, including baicalein, wogonin, oroxylin-A, salvigenin, and norwogonin, to the prognostic markers in OSCC was evaluated using molecular docking analysis. Results: Survival analysis showed that overexpression of CAV1, SERPINE1, ACTB, SMAD3, HMGA2, MYC, EIF2S1, HSPA4, HSPA5, and IL6 was significantly related to a poor prognosis in OSCC. Besides, molecular docking analysis demonstrated the ΔGbinding and inhibition constant values between SBG's main components and SERPINE1, ACTB, HMGA2, EIF2S1, HSPA4, and HSPA5 were as <-8.00 kcal/mol and nanomolar concentration, respectively. The most salient binding affinity was observed between wogonin and SERPINE1 with a criterion of ΔGbinding < -10.02 kcal/mol. Conclusion: The present results unraveled potential mechanisms involved in therapeutic effects of SBG in OSCC based on systems biology and structural bioinformatics analyses.

Microbial community response to biostimulation and bioaugmentation in crude oil-polluted sediments of the Persian Gulf.

The Persian Gulf is a transit point for a lot of crude oil at the international level. The purpose of this research is to compare two methods of biostimulation and bioaugmentation for degradation of sediments contaminated with crude oil in the Persian Gulf. In this research, six types of microcosms were designed (Sediments from Khark Island). Some indicators such as: the quantity of marine bacteria, enzyme activity (Catalase, Polyphenol oxidase, Dehydrogenase), biodiversity indices and the percentage of crude oil degradation were analyzed during different days (0, 20, 40, 60, 80, 100 and 120). The results of this research showed that the highest quantity of heterotrophic and crude oil-degrading bacteria was found in the sixth microcosm (SB). This microcosm represents a combination of two methods: bioaugmentation and biostimulation (3.9 × 106 CFU g-1). Following crude oil pollution, the activity of catalase and polyphenol oxidase increased and the dehydrogenase enzyme decreased. The bioaugmentation microcosm exhibited the highest activity of enzymes among all the microcosms studied. Predominant bacteria in each microcosm belonged to: Cellulosimicrobium, Shewanella, Alcanivorax and Cobetia. The highest degradation of crude oil is related to the Stimulation-Bioaugmentation microcosm (SB). The statistical results of this research proved that there is a significant relationship between the type of method chosen for biodegradation with the sampling time and the quantity of marine bacteria. The results of this research confirm that crude oil pollution in the Persian Gulf sediments can be reduced by choosing the proper bioremediation method.

Cinnamic acids as promising bioactive compounds for cancer therapy by targeting MAPK3: a computational simulation study.

OBJECTIVES: Mitogen-activated protein kinase-3 (MAPK3) is the upstream regulator in the MAPK cascade and is involved in many critical signaling pathways and biological processes, such as cell proliferation, survival, and apoptosis. MAPK3 overexpression is linked to onset, development, metastasis, and drug resistance in several human cancers. Thus, identifying novel and effective MAPK3 inhibitors is highly demanded. Herein, we aimed to discover organic compounds from cinnamic acid derivatives as potential MAPK3 inhibitors. METHODS: The binding affinity of 20 cinnamic acids to the MAPK3 active site was tested using the AutoDock 4.0 software. Top-ranked cinnamic acids were ranked based on the ΔG binding values between the ligands and the receptor's active site. Interaction modes between top-ranked cinnamic acids and MAPK3 catalytic site were indicated using the Discovery Studio Visualizer tool. Molecular dynamics (MD) simulation was carried out to study the stability of the docked pose for the most potent MAPK3 inhibitor in this study. RESULTS: Cynarin, chlorogenic acid, rosmarinic acid, caffeic acid 3-glucoside, and cinnamyl caffeate exhibited a salient binding affinity to the MAPK3 active site with the criteria of ΔG binding <-10 k cal/mol. Further, the inhibition constant value for cynarin was calculated at the picomolar concentration. The docked pose of cynarin within the MAPK3 catalytic domain was stable in 100 ns simulation. CONCLUSIONS: Cynarin, chlorogenic acid, rosmarinic acid, caffeic acid 3-glucoside, and cinnamyl caffeate might be helpful in cancer therapy by inhibiting MAPK3.

Flavonoids as Strong Inhibitors of MAPK3: A Computational Drug Discovery Approach.

Background: Mitogen-activated protein kinase 3 (MAPK3) mediates the onset, progression, metastasis, drug resistance, and poor prognosis in various malignancies, including glioma, liver, ovarian, thyroid, lung, breast, gastric, and oral cancers. Negative regulation of MAPK3 expression using miRNAs has led to therapeutic effects in cancer. Objectives: The present study performed molecular docking and dynamics simulation to identify potential MAPK3 inhibitors from natural flavonoids, possibly leading to drug development in cancer therapy. Methods: A computational drug discovery approach was performed using the AutoDock tool to identify potential MAPK3 inhibitors from 46 plant-based flavonoids. A cross-validation study was executed using the Schrödinger Maestro docking tool. Molecular dynamics (MD) was executed to evaluate the stability of docked poses between the top-ranked compounds and the MAPK3 catalytic domain. Interactions among the most potent MAPK3 inhibitors and residues within the receptor's active site were studied using the BIOVIA Discovery Studio Visualizer before and after 100 ns MD simulations. Results: Kaempferol 3-rutinoside-4'-glucoside, kaempferol 3-rutinoside-7-sophoroside, rutin, and vicenin-2 exhibited a magnificent binding affinity to the receptor's active site. In addition, the stability of the docked poses of these compounds seemed to be stable after ∼45 ns computer simulations. Conclusion: The present study suggests that kaempferol 3-rutinoside-4'-glucoside, kaempferol 3-rutinoside-7-sophoroside, rutin, and vicenin-2 could strongly bind to the MAPK3 catalytic site and could be assigned as a potent inhibitor for MAPK3. These findings may be helpful in the treatment of various cancers. However, further validation experiments are needed.

Potential Biomarkers and Signaling Pathways Associated with the Pathogenesis of Primary Ameloblastoma: A Systems Biology Approach.

Objective: Ameloblastoma is a benign odontogenic tumor that may lead to ameloblastic carcinoma. This study aimed to determine potential signaling pathways and biological processes, critical genes and their regulating transcription factors (TFs), and miRNAs, as well as protein kinases involved in the etiology of primary ameloblastoma. Methods: The dataset GSE132472 was obtained from the GEO database, and multivariate statistical analyses were applied to identify differentially expressed genes (DEGs) in primary ameloblastoma tissues compared to the corresponding normal gingiva samples. A protein-protein interaction (PPI) map was built using the STRING database. The Cytoscape software identified significant modules and the hub genes within the PPI network. Gene Ontology annotation and signaling pathway analyses were executed by employing the DAVID and Reactome databases, respectively. Significant TFs and miRNAs acting on the hub genes were identified using the iRegulon plugin and MiRWalk 2.0 database, respectively. A protein kinase enrichment analysis was conducted using the online Kinase Enrichment Analysis 2 (KEA2) web server. The approved drugs acting on the hub genes were also found. Results: A total of 1,629 genes were differentially expressed in primary ameloblastoma (P value <0.01 and |Log2FC| > 1). HRAS, CDK1, MAPK3, ERBB2, COL1A1, CYCS, and BRCA1 demonstrated high degree and betweenness centralities in the PPI network. E2F4 was the most significant TF acting on the hub genes. BTK was the protein kinase significantly enriched by the TFs. Cholesterol biosynthesis was considerably involved in primary ameloblastoma. Conclusions: This study provides an intuition into the potential mechanisms involved in the etiology of ameloblastoma.

Potential biomarkers and signaling pathways associated with the pathogenesis of primary salivary gland carcinoma: a bioinformatics study.

Salivary gland carcinoma (SGC) is rare cancer, constituting 6% of neoplasms in the head and neck area. The most responsible genes and pathways involved in the pathology of this disorder have not been fully understood. We aimed to identify differentially expressed genes (DEGs), the most critical hub genes, transcription factors, signaling pathways, and biological processes (BPs) associated with the pathogenesis of primary SGC. The mRNA dataset GSE153283 in the Gene Expression Omnibus database was re-analyzed for determining DEGs in cancer tissue of patients with primary SGC compared to the adjacent normal tissue (adjusted p-value < 0.001; |Log2 fold change| > 1). A protein interaction map (PIM) was built, and the main modules within the network were identified and focused on the different pathways and BP analyses. The hub genes of PIM were discovered, and their associated gene regulatory network was built to determine the master regulators involved in the pathogenesis of primary SGC. A total of 137 genes were found to be differentially expressed in primary SGC. The most significant pathways and BPs that were deregulated in the primary disease condition were associated with the cell cycle and fibroblast proliferation procedures. TP53, EGF, FN1, NOTCH1, EZH2, COL1A1, SPP1, CDKN2A, WNT5A, PDGFRB, CCNB1, and H2AFX were demonstrated to be the most critical genes linked with the primary SGC. SPIB, FOXM1, and POLR2A significantly regulate all the hub genes. This study illustrated several hub genes and their master regulators that might be appropriate targets for the therapeutic aims of primary SGC.

Evaluation of the miRNA-146a and miRNA-155 Expression Levels in Patients with Oral Lichen Planus.

BACKGROUND: Oral Lichen Planus (OLP) is a chronic autoimmune disease that could be considered as a potential premalignant status. OBJECTIVE: To evaluate the miRNA-146a and miRNA-155 expression levels in patients with oral Lichen planus lesions compared to healthy subjects with normal oral mucosa. METHODS: Forty patients with oral lichen planus and 18 healthy age and gender-matched controls were recruited in this case-control study. Oral lichen planus was diagnosed clinically and pathologically. The expression levels of two miRNAs in peripheral blood samples were determined using commercial TaqMan MicroRNA Assays. Relative quantification of gene expression was calculated by the 2-ΔΔct method. RESULTS: The expression levels of miRNA-146a and miRNA-155 in patients with oral Lichen planus were significantly higher than those of healthy controls. Also, a direct but insignificant correlation was found between miRNA-155 and miRNA-146a expression levels among the patient group. CONCLUSION: Our findings indicate that miRNA-146a and miRNA-155 could be potential biomarkers for the immunopathogenesis of oral lichen planus.

Comparison the effects of bioaugmentation versus biostimulation on marine microbial community by PCR-DGGE: A mesocosm scale.

In order to better understand the effects of biostimulation and bioaugmentation processes on a marine microbial community, three different mesocosm experiments were planned. Natural seawater (10.000L) was artificially polluted with crude oil (1L) and (1) inorganic nutrients (Biostimulating Mesocosm, BM), (2) inorganic nutrients and an inoculum of Alcanivorax borkumensis SK2 (Single Bioaugmentation Mesocosm, SBM), (3) inorganic nutrients and inoculums of A. borkumensis SK2 and Thalassolituus oleivorans MIL-1 (Consortium Bioaugmentation Mesocosm, CBM). During the experimental period (20days), samples were taken from each mesocosm and the community structure was analyzed by PCR-DGGE. The 16S rRNA gene DGGE banding patterns and sequence analysis demonstrated that biostimulation had the lowest effect on microbial biodiversity in the mesocosms; however, the biodiversity of the marine microbial community dramatically decreased in the CBM (Shannon index was 0.6 in T3). The community structures among the three mesocosms were also markedly different, and major bacteria derived from DGGE bands were related to uncultured Gamma Proteobacteria. The biodegradation results show that the Single Bioaugmentation Mesocosm (SBM) system had the highest percentage of degradation (95%) in comparison to the BM mesocosm (80%) and CBM (70%).

Study the symbiotic crude oil-degrading bacteria in the mussel Mactra stultorum collected from the Persian Gulf.

Symbiotic associations are complex partnerships that can lead to new metabolic capabilities and the establishment of novel organisms. The diversity of these associations is very broad and there are still many mysteries about the origin and the exact relationship between the organisms that are involved in a symbiosis. The aim of the present study is to find symbiotic crude-oil degrading bacteria in the mussels that collected from the Persian Gulf. Fifteen crude-oil degrading bacteria were isolated from Mactra stultorum mussel that collected from oil contaminated area at Persian Gulf. According to high growth rate on crude oil five strains were selected from 15 isolated strains for more study. Determination of the nucleotide sequence of the gene encoding 16S rRNA show that these isolated strains belong to: Alcanivorax dieselolei strain BHA25, Idiomarina baltica strain BHA28, A. dieselolei strain BHA30, Alcanivorax sp. strain BHA32 and Vibrio azureus strain BHA36. Analysis of remaining of crude oil by Gas Chromatography (GC) confirmed that these strains can degrade: 64%, 63%, 71%, 58% and 75% of crude oil respectively.

Immobilization of Microbes for Bioremediation of Crude Oil Polluted Environments: A Mini Review.

Petroleum hydrocarbons are the most common environmental pollutants in the world and oil spills pose a great hazard to terrestrial and marine ecosystems. Oil pollution may arise either accidentally or operationally whenever oil is produced, transported, stored and processed or used at sea or on land. Oil spills are a major menace to the environment as they severely damage the surrounding ecosystems. To improve the survival and retention of the bioremediation agents in the contaminated sites, bacterial cells must be immobilized. Immobilized cells are widely tested for a variety of applications. There are many types of support and immobilization techniques that can be selected based on the sort of application. In this review article, we have discussed the potential of immobilized microbial cells to degrade petroleum hydrocarbons. In some studies, enhanced degradation with immobilized cells as compared to free living bacterial cells for the treatment of oil contaminated areas have been shown. It was demonstrated that immobilized cell to be effective and is better, faster, and can be occurred for a longer period.

Enrichment and isolation of crude oil degrading bacteria from some mussels collected from the Persian Gulf.

To date, little is known about existing relationships between mussels and bacteria in hydrocarbon-contaminated marine environments. The aim of this study is to find crude oil degrading bacteria in some mussels at the Persian Gulf. Twenty eight crude oil degrading bacteria were isolated from three mussels species collected from oil contaminated area at Persian Gulf. According to high growth and degradation of crude oil four strains were selected between 28 isolated strains for more study. Determination the nucleotide sequence of the gene encoding for 16S rRNA show that these isolated strains belong to: Shewanella algae isolate BHA1, Micrococcus luteus isolate BHA7, Pseudoalteromonas sp. isolate BHA8 and Shewanella haliotis isolate BHA35. The residual crude oil in culture medium was analysis by Gas Chromatography (GC). The results confirmed that these strains can degrade: 47.24%, 66.08%, 27.13% and 69.17% of crude oil respectively. These strains had high emulsification activity and biosurfactant production. Also, the effects of some factors on crude oil degradation by isolated strains were studied. The results show that the optimum concentration of crude oil was 2.5% and the best degradation take place at 12% of salinity. This research is the first reports on characterization of crude oil degrading bacteria from mussels at Persian Gulf and by using of these bacteria in the field the effect of oil pollution can be reduce on this marine environment.