Methanolic extract of Teucrium persicum up-regulates and induces the membrane restoration of E-cadherin protein in PC-3 cells.

Teucrium persicum Boiss. an Iranian endemic plant is used in Iranian traditional medicine. E-cadherin transmembrane protein participates in adherens junctions and is the main partner for ß-catenin protein. The GC-MS analysis was used to detect the chemical constituents of the methanolic extract. Its effects on the transcription of the E-cadherin encoding gene, cellular levels, and localization of E-cadherin protein in PC-3 cells were investigated. About 70 chemical constituents were identified. Indirect immunofluorescence microscopy and western blotting results revealed the restoration of E-cadherin protein at cell adhesion contact sites in cells treated with T. persicum extract. Gene expression studies revealed that the extract increased the transcription of the E-cadherin encoding gene in PC-3 cells. These results suggest that T. persicum extract may contain potent compounds that provide further support for the anticancer properties of T. persicum. Surely, detailed molecular investigations are needed to find the mechanism(s) behind these effects.

Exploring the anticancer properties of the gum of Ferula gummosa: impact on cytotoxicity, caspase 3/7 activity and apoptosis, and gene expression in SW-480 cells.

Ferula gummosa Boiss. is a well-known Iranian endemic plant that grows in the north and northeast regions of Iran. In Iranian traditional medicine, its gum is utilized to treat inflammation, pain, and infections of the gastrointestinal system. However, no studies have been conducted to investigate the anticancer potential of its gum against colorectal cancer cells. This study aimed to identify the chemical components of the gum of F. gummosa and investigate its effects on SW-480 cells. The experiments included MTT, clonogenic, micronucleus formation, acridine orange/ethidium bromide stain, DNA degradation, caspase 3/7 activity assay, and in vitro wound-healing experiment and investigating the expression of BAX, BCL2, MTOR, and PTEN genes. Chemical analysis using GC/MS identified 102 compounds. The gum had a significant cytotoxic effect on SW-480 cells, with an IC50 value of 1.8 µg/ml for 48 hours. The gum induced apoptosis. Microscopic observations revealed a decrease in cell proliferation, as evidenced by nuclear condensation, increased micronucleus formation, and inhibition of colony formation. Additionally, the gum suppressed cell migration, induced the expression of PTEN and BAX, and down-regulated MTOR and BCL2 genes. These findings suggest that Ferula gummosa has strong cytotoxic properties and warrants further investigation.

Association between PON1-rs662 Gene Polymorphism and Diabetic Retinopathy in Population of the Qom, Iran.

Background: Diabetic retinopathy is the most severe diabetic microvascular complication that causes changes in the vessel wall. One of the genes involved in this disease is PON1, which encodes paraoxanase1 protein in liver and kidney. It might regulate inflammatory and microvascular responses to the disease. The rs662 T>C is one of the single nucleotide polymorphisms of this gene that changes glutamine to arginine at position 192. Methods: In this study, 300 samples were collected, including 100 healthy and 100 diabetics without retinopathy, and 100 diabetics retinopathies were studied and their age range was from 30 to 80 years. Then 2.5 ml of blood was collected from all relevant individuals in tubes containing EDTANa2. This polymorphism was examined by tetra-ARMS PCR. Results: Results showed that there is no significant correlation between genotypes and alleles related to PON1 and Diabetes (CC genotype: p=0.609; C allele: p=0.228). On the other hand, an association was observed between PON1 and diabetic retinopathy (CT+CC genotype: p<0.001; CT allele: p<0.001). Considering that the Polyphen database examined the changes caused by replacing the amino acid arginine instead of glutamine at position 129 on the protein, it does not consider these changes dangerous and has introduced this polymorphism as benign. Conclusion: Based on the findings of this study, the rs662 locus could be considered as one of the molecular markers in future research.

Global trends of cancer: The role of diet, lifestyle, and environmental factors.

Effective treatment of cancer requires understanding the nature of the disease and accurately addressing the main root causes. General risk factors for cancer include poor nutrition, an acidogenic diet, an unhealthy lifestyle, and exposure to carcinogens such as toxins, chemicals, and radiation. The risk of developing cancers may be reduced by sufficient oxygenation and maintaining optimal alkalinity and nutritional balance at the cell level. The review paper summarizes some diet and lifestyle modifications that may potentially be considered for preventing and controlling some cancers. Moreover, worldwide statistical data for cancer incidence rates published by International Agency for Research on Cancer are analyzed for certain cancers regionally, concerning the effect of dietary habits and environmental factors that meaningfully correlate with the global trends of cancer. The study of cancer root causes integrated with analyzing the statistics related to cancer incidence rates suggests that the risk of developing cancer may be reduced by modifying dietary habits and lifestyle factors, as well as reducing exposure to carcinogens. Those with healthy balanced dietary habits may have a lower cancer risk than those who frequently have unhealthy diets; hence, considering a balanced natural diet and healthy lifestyle may be suggested as a complementary or alternative solution in cancer treatments.

Antioxidant, cytotoxic, and genotoxic potentials of the gum of Ferula gummosa Boiss on PC-3 cells.

Objective: Ferula gummosa Boiss is a well-known Iranian endemic plant that has been used in Iranian traditional medicine against various diseases. This study aimed to evaluate the antioxidant and cytotoxic capacity of F. gummosa gum on prostate cancer PC-3 cells. Materials and Methods: In this study, we evaluated the total phenolic and flavonoid contents, and antioxidant potentials of the gum. The MTT experiment was conducted to assess the cytotoxic potential of the gum on PC-3 cells. The clonogenic, micronucleus formation, and acridine orange/ethidium bromide staining methods were used to evaluate the survival and proliferation of PC-3 cells. DNA degradation and caspase 3/7 activity evaluations were used to assess apoptosis. The inhibitory effect on the migration of PC-3 cells was examined by in vitro wound-healing experiment. Results: Total phenolic and flavonoid contents, and antioxidant potential of the gum were 9.22 mg of gallic acid equivalent (GAE)/g, 3.6 mg of quercetin equivalents (QE) /g of the extract, and 13 µg/ml, respectively (compared to gallic acid and quercetin, respectively) (p<0.05). The IC50 value was 9.14 µg/ml for 48 hours (compared to non-treated cells) (p<0.01). The pattern of DNA degradation, and caspase 3/7 activity levels (compared to non-treated cells) (p<0.05) proposed decreased cell viability that may be due to apoptosis induction. Microscopic observations revealed nuclear condensation, a significant increase in the formation of micronuclei, and inhibition of forming colonies (compared to non-treated cells) (p<0.01) in PC-3 cells treated with 8 and 10 µg/ml of the gum. Wound-healing assessment showed the migration suppression potentials of the gum (compared to non-treated cells) (p<0.05). Conclusion: These results indicate that F. gummosa has considerable antioxidant and cytotoxic properties that can make it a good nominee for subsequent investigations.

Antioxidant and cytotoxic potentials of the methanolic extract of Teucrium persicum Boiss. in A-375 melanoma cells.

Objective: Teucrium persicum is an Iranian endemic plant used in Iranian traditional medicine. Materials and Methods: The total phenolic and total flavonoid contents, and antioxidant potential of the methanolic extract of T. persicum were determined. The MTT test was used to evaluate the inhibitory effect of the extract on the viability of A-375 cells. The clonogenic, micronucleus formation, and acridine orange/ethidium bromide staining methods were used to evaluate the survival and proliferation of A-375 cells. Apoptosis was evaluated by using DNA fragmentation assay and measuring the activity of caspase 3/7. To study the effect of the extract on the migration of A-375 cells, the in vitro wound-healing (scratch) assay was employed. Results: The average total phenolic and flavonoid contents and antioxidant properties of the extract were 6.97±0.011 mg Ellagic acid (EGA)/g, 46.83±0.0019 mg of the ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline; EQ)/g of dried extract, and 10±0.002 µg/ml, respectively. The IC50 value of the T. persicum methanolic extract was 13 µg/ml for 48 hr. The DNA fragmentation pattern and the activity of caspase3/7 suggested that the reduction of the cell viability may be due to apoptosis induction. Microscopic observations showed nuclear condensation, a considerable increase in micronuclei formation, and inhibition of the colony formation in A-375 cells treated with 7 µg/ml to 15 µg/ml of the extract. Wound-healing assay supported the anti-migration activity of the extract. Conclusion: T. persicum has significant antioxidant and cytotoxic properties. Surely, more detailed molecular and biochemical studies are needed to find the mechanism(s) behind these effects.

Membrane Localization of ß-Catenin in Prostate Cancer PC3 Cells Treated with Teucrium persicum Boiss. Extract.

Teucrium persicum Boiss. is an Iranian endemic plant which belongs to the Lamiaceae family and has been used to relieve pains in traditional Iranian medicine. We have previously found that treatment of prostate cancer PC3 cells with Teucrium persicum extract leads to the formation of small populations of epithelial cells. ß-Catenin is a component of cell adherens junctions in epithelial cells and therefore, in this study, we have investigated the effect of Teucrium persicum extract on expression, cellular localization, and transcriptional activity of ß-Catenin protein in PC-3 cells. Indirect immunofluorescence microscopy results showed that the cells treated with T. persicum extract had higher levels of ß-Catenin protein at the cell membrane. Western blotting experiments produced consistent results. Gene expression studies by using a few ß-Catenin-target genes including c-MYC, CYCLIN D1, and a reporter Luciferase gene under the control of several ß-Catenin/TCF binding elements showed that treatment of PC3 cells with the methanolic extract of T. persicum decreases the transcriptional activities of ß-Catenin. The results of this study provide further support for the anticancer properties of T. persicum. Definitely, more detailed molecular investigations are needed to find the mechanism(s) behind these effects. Highlightsß-Catenin protein is a main component of Wnt signaling pathway and adherens junction.Activation of Wnt signaling pathway affects translocation of ß-Catenin.Teucrium persicum extract induces ß-Catenin localization at cell membrane.Teucrium persicum affects the transcriptional activity of ß-Catenin.It stabilizes E-cadherin/ß-Catenin protein complex and adherens junction.

The biological and therapeutic potentials of Cyclotrichium genus: a systematic review.

The genus Cyclotrichium includes nine species that are mainly distributed in Turkey, Lebanon, Iraq, and Iran, and are used in the kitchen, and also in complementary medicine to treat various diseases. During recent years, considerable progress has been made in analyzing their phytochemical composition in parallel with their antimicrobial properties and their therapeutic potentials. This study reviews the present knowledge about investigations on antimicrobial, insecticidal, and anticancer properties of the essential oils and any other purified chemical compounds of the Cyclotrichium species. Various phytochemicals have been isolated from the extracts of the plants of this genus having significant biological and therapeutic potentials. In conclusion, these gathered data strongly support the viewpoint that the species belonging to the genus Cyclotrichium have various biological and pharmaceutical activities to treat various diseases including cancer in addition to the remarkable antimicrobial and insecticidal potential with no or minimal health and environmental hazards.

Antibacterial effect of cerium oxide nanoparticle against Pseudomonas aeruginosa.

BACKGROUND: Antibiotics have been widely used for the treatment of bacterial infections for decades. However, the rapid emergence of antibiotic-resistant bacteria has created many problems with a heavy burden for the medical community. Therefore, the use of nanoparticles as an alternative for antibacterial activity has been explored. In this context, metal nanoparticles have demonstrated broad-spectrum antimicrobial activity. This study investigated the antimicrobial activity of naked cerium oxide nanoparticles dispersed in aqueous solution (CNPs) and surface-stabilized using Pseudomonas aeruginosa as a bacterial model. METHODS: Gelatin-polycaprolactone nanofibers containing CNPs (Scaffold@CNPs) were synthesized, and their effect on P. aeruginosa was investigated. The minimum inhibitory and bactericidal concentrations of the nanoparticls were determined in an ATCC reference strain and a clinical isolate strain. To determine whether the exposure to the nanocomposites might change the expression of antibiotic resistance, the expression of the genes shv, kpc, and imp was also investigated. Moreover, the cytotoxicity of the CNPs was assessed on fibroblast using flow cytometry. RESULTS: Minimum bactericidal concentrations for the ATCC and the clinical isolate of 50 µg/mL and 200 µg/mL were measured, respectively, when the CNPs were used. In the case of the Scaffold@CNPs, the bactericidal effect was 50 µg/mL and 100 µg/mL for the ATCC and clinical isolate, respectively. Interestingly, the exposure to the Scaffold@CNPs significantly decreased the expression of the genes shv, kpc, and imp. CONCLUSIONS: A concentration of CNPs and scaffold@CNPs higher than 50 µg/mL can be used to inhibit the growth of P. aeruginosa. The fact that the scaffold@CNPs significantly reduced the expression of resistance genes, it has the potential to be used for medical applications such as wound dressings.

The Wonderful Activities of the Genus Mentha: Not Only Antioxidant Properties.

Medicinal plants and their derived compounds have drawn the attention of researchers due to their considerable impact on human health. Among medicinal plants, mint (Mentha species) exhibits multiple health beneficial properties, such as prevention from cancer development and anti-obesity, antimicrobial, anti-inflammatory, anti-diabetic, and cardioprotective effects, as a result of its antioxidant potential, combined with low toxicity and high efficacy. Mentha species are widely used in savory dishes, food, beverages, and confectionary products. Phytochemicals derived from mint also showed anticancer activity against different types of human cancers such as cervix, lung, breast and many others. Mint essential oils show a great cytotoxicity potential, by modulating MAPK and PI3k/Akt pathways; they also induce apoptosis, suppress invasion and migration potential of cancer cells lines along with cell cycle arrest, upregulation of Bax and p53 genes, modulation of TNF, IL-6, IFN-γ, IL-8, and induction of senescence phenotype. Essential oils from mint have also been found to exert antibacterial activities against Bacillus subtilis, Streptococcus aureus, Pseudomonas aeruginosa, and many others. The current review highlights the antimicrobial role of mint-derived compounds and essential oils with a special emphasis on anticancer activities, clinical data and adverse effects displayed by such versatile plants.

Novel SCN5A variants identified in a group of Iranian Brugada syndrome patients.

Brugada syndrome (BrS) is a rare hereditary arrhythmia syndrome that increases an individual's risk for sudden cardiac death (SCD) due to ventricular fibrillation. This disorder is regarded as a notable cause of death in individuals aged less than 40 years, responsible for up to 40% of sudden deaths in cases without structural heart disease, and is reported to be an endemic in Asian countries. Mutations in SCN5A are found in approximately 30% of patients with Brugada syndrome. This study aimed to investigate mutations in the SCN5A gene in a group of Iranian Brugada syndrome patients. Nine probands (n = 9, male, mean age = 39) diagnosed with Brugada syndrome were enrolled in this study. Exon 2 to 29 were amplified by PCR and subjected to direct sequencing. Eight in silico prediction tools were used to anticipate the effects of non-synonymous variants. Seven known polymorphisms and 2 previously reported disease-causing mutations, including H558R and G1406R, were found in the studied cases. Twenty novel variants were identified: 15 missense, 2 frameshift, 2 synonymous, and one nonsense variants. In silico tools predicted 11 non-synonymous variants to have damaging effects, whereas frameshift and nonsense variants were considered inherently pathogenic. The novel variants identified in this study, alongside previously reported mutations, are highly likely to be the cause of the Brugada syndrome phenotype observed in the patient group. Further analysis is required to understand the physiological effects caused by these variants.

MiRNAs: Biology, Biogenesis, their Web-based Tools, and Databases.

INTRODUCTION: MicroRNAs (miRNAs), which are evolutionarily conserved, and endogenous non-coding RNAs, participate in the post-transcriptional regulation of eukaryotic genes. The biogenesis of miRNAs occurs in the nucleus. Then, in the cytoplasm, they are assembled along with some proteins in a ribonucleoprotein complex called RISC. miRNA component of the RISC complex binds to the complementary sequence of mRNA target depending on the degree of complementarity, and leads to mRNA degradation and/or inhibition of protein synthesis. miRNAs have been found in eukaryotes and some viruses play a role in development, metabolism, cell proliferation, growth, differentiation, and death. OBJECTIVE: A large number of miRNAs and their targets were identified by different experimental techniques and computational approaches. The principal aim of this paper is to gather information about some miRNA databases and web-based tools for better and quicker access to relevant data. RESULTS: Accordingly, in this paper, we collected and introduced miRNA databases and some webbased tools that have been developed by various research groups. We have categorized them into different classes including databases for viral miRNAs, and plant miRNAs, miRNAs in human beings, mice and other vertebrates, miRNAs related to human diseases, and target prediction, and miRNA expression. Also, we have presented relevant statistical information about these databases.

E-Cadherin/ß-Catenin Complex: A Target for Anticancer and Antimetastasis Plants/Plant-derived Compounds.

Plants reputed to have cancer-inhibiting potential and putative active components derived from those plants have emerged as an exciting new field in cancer study. Some of these compounds have cancer-inhibiting potential in different clinical staging levels, especially metastasis. A few of them which stabilize cell-cell adhesions are controversial topics. This review article introduces some effective herbal compounds that target E-cadherin/ß-catenin protein complex. In this article, at first, we briefly review the structure and function of E-cadherin and ß-catenin proteins, Wnt signaling pathway, and its target genes. Then, effective compounds of the Teucrium persicum, Teucrium polium, Allium sativum (garlic), Glycine max (soy), and Brassica oleracea (broccoli) plants, which influence stability and cellular localization of E-cadherin/ß-catenin complex, were studied. Based on literature review, there are some compounds in these plants, including genistein of soy, sulforaphane of broccoli, organosulfur compounds of garlic, and the total extract of Teucrium genus that change the expression of variety of Wnt target genes such as MMPs, E-cadherin, p21, p53, c-myc, and cyclin D1. So they may induce cell-cycle arrest, apoptosis and/or inhibition of Epithelial-Mesenchymal Transition (EMT) and metastasis.

Microsatellite (SSR) amplification by PCR usually led to polymorphic bands: Evidence which shows replication slippage occurs in extend or nascent DNA strands.

Microsatellites or simple sequence repeats (SSRs) are very effective molecular markers in population genetics, genome mapping, taxonomic study and other large-scale studies. Variation in number of tandem repeats within microsatellite refers to simple sequence length polymorphism (SSLP); but there are a few studies that are showed SSRs replication slippage may be occurred during in vitro amplification which are produced 'stutter products' differing in length from the main products. The purpose of this study is introducing a reliable method to realize SSRs replication slippage. At first, three unique primers designed to amplify SSRs loci in the great gerbil (Rhombomys opimus) by PCR. Crush and soak method used to isolate interesting DNA bands from polyacrylamide gel. PCR products analyzed using by sequencing methods. Our study has been shown that Taq DNA polymerase slipped during microsatellite in vitro amplification which led to insertion or deletion of repeats in sense or antisense DNA strands. It is produced amplified fragments with various lengths in gel electrophoresis showed as 'stutter bands'. Thus, in population studies by SSRs markers recommend that replication slippage effects and stutter bands have been considered.

Anticancer properties of Teucrium persicum in PC-3 prostate cancer cells.

Crude extracts or phytochemicals obtained from some plants have potential anti-cancer properties. Teucrium persicum is an Iranian endemic plant belonging to the Lamiaceae family which has traditionally been used to relieve abdominal pains. However, the anti-cancer properties of this species of the Teucrium genus have not been investigated previously. In this study, we have used a highly invasive prostate cancer cell line, PC-3, which is an appropriate cell system to study anti-tumor properties of plants. A methanolic extract obtained from T persicum potently inhibited viability of PC-3 cells. The viability of SW480 colon and T47D breast cancer cells was also significantly decreased in the presence of the T persicum extract. Flow cytometry suggested that the reduction of cell viability was due to induction of apoptosis. In addition, the results of wound healing and gelatin zymography experiments supported anti-cell invasion activity of T persicum. Interestingly, sublethal concentrations of T persicum extract induced an epithelial-like morphology in a subpopulation of cells with an increase in E-Cadherin and ß-Catenin protein levels at the cell membrane. These results strongly suggest that T persicum is a plant with very potent anti-tumor activity.