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Introduction: MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that post-transcriptionally control the expression of genes by binding and degrading their target mRNAs. miRNAs can function as possible tumor suppressors or oncogenes in various cancers. Lately, miRNAs application as a biomarker (prognosis and diagnosis) for different diseases has gained much attention. miRNAs exist in a stable form in several biological materials, including tissue, plasma, and serum. The noninvasive and easy screening of miRNAs in serum, blood, tissue, and other body fluids and acceptable stability make microRNA a noticeable factor as biomarkers in human malignancies. Material and Methods: In this review, we searched some online databases like Web of Science, Embase, and PubMed to find eligible manuscripts up to the end of 2021. Results: Abnormal expressions of these molecules are associated with the incidence of many illnesses like cancer. Therefore, they are candidates as a molecular tool for noninvasive tumor prognosis and diagnosis. In the current study, we introduce important miRNAs that may be used as prognostic and diagnostic markers in lung cancer patients. Conclusion: We summarized the latest reports about critical miRNAs related to the diagnosis and prognosis in lung patients.

Abstract: Psoriasis is defined as a chronic autoimmune disorder of the skin in which abnormal proliferation and differentiation of keratinocytes are blamed as the central culprit of disease etiopathogenesis. A complex interplay between environmental factors and genetic risk factors has been suggested to trigger the disease. However, epigenetic regulation appears to connect external stimuli and genetic abnormalities in the development of psoriasis. The discordance in the prevalence of psoriasis between monozygotic twins and environmental factors that contribute to its onset have caused a paradigm shift regarding the mechanisms underlying the pathogenesis of this disease. Epigenetic dysregulation may be involved in aberrancies of keratinocyte differentiation, T-cell activation, and other plausible cells, leading to the initiation and perpetuation of psoriasis. Epigenetics is characterized by heritable alterations in the transcription of genes without nucleotide change and is commonly considered at three levels, i.e., DNA methylation, histone modifications, and microRNAs. To date, scientific evidence has indicated abnormal DNA methylation, histone modifications, and non-coding RNA transcription in psoriatic patients. In order to reverse aberrant epigenetic changes in psoriasis patients, several compounds and drugs (epi-drugs) have been developed to affect the major enzymes involved in the methylation of DNA, or the acetylation of histones, which aim to correct the aberrant methylation and acetylation patterns. A number of clinical trials have suggested the therapeutic potential of such drugs in the treatment of psoriasis. In the present review, we attempt to clarify recent findings with respect to epigenetic irregularities in psoriasis and discuss future challenges.

Background Today modern lifestyles and especially disrupted sleep patterns cause circadian clock rhythm impairments that may be linked with the leptin signaling pathway which subsequently alter a wide range of metabolic processes and have significant health burdens on societies. Nevertheless, there is not any systematic review regarding circadian clock genes and proteins, leptin, and the related signaling pathways. Methods Accordingly, we systematically reviewed circadian clock proteins, leptin, and molecular mechanisms between them by searching Pubmed, Scopus, ProQuest, Web of Sciences, and also Google Scholar until September 2022. After considering inclusion and exclusion criteria, twenty animal model studies were selected as there were not any clinical trial articles about the related molecular pathways. Then the risk of bias for each paper was assessed. Results The results clarified the reciprocal interconnected relationship between the circadian clock genes and leptin and more profoundly, revealed engaged molecular mechanisms and factors. Also, the role of these molecular mechanisms was explained in different physiological processes such as metabolism in the hypothalamus and corresponding peripheral organs. Conclusions All this may demonstrate that these signaling pathways and affecting elements should be considered in the prevention and choosing of new therapeutic targets for related disorders especially obesity and metabolic impairments.

Background: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. A number of dysregulated microRNAs (miRNAs) have been linked to CRC progression and treatment response and are thought to be promising prognostic biomarkers for this cancer. microRNA-330 (miR-330-5p) has been reported to inhibit cell proliferation through suppressing thymidylate synthase (TYMS). In the current study, miR-330-5p, TYMS, and their interactions were investigated to evaluate their therapeutic and diagnostic value for CRC treatment. Methods: The expression levels of miR-330-5p and TYMS were evaluated in silico using TCGA datasets for CRC. Data validation was performed on a set of internal samples (100 pairs of CRC tumor specimens and adjacent non-cancerous samples) utilizing real-time PCR assay. The linkage between clinicopathological parameters and expression levels was also investigated. Results: TCGA results indicated that miR-330-5p and TYMS were significantly upregulated and downregulated in the CRC, respectively. Real-time PCR results confirmed that the expression of miR-330-5p was significantly upregulated in tumor tissues relative to marginal tissues (P = 0.0005), whereas TYMS expression was significantly downregulated (P = 0.0001). The transcript level of miR-330-5p was associated with tumor stage and lymph node metastases. Conclusion: The microRNA-330 inhibited cell proliferation by suppressing thymidylate synthase (TYMS) in colorectal cancer. Therefore, suggesting that they are valuable factors for further studies of alternative treatment and diagnostic methods. © 2021, Springer Science+Business Media, LLC, part of Springer Nature., This study was supported by a grant from the research deputy of the Department of Tuberculosis and Lung Diseases Research Center, University Tabriz University of Medical Sciences, Tabriz, Iran.

The vascular endothelial growth factor (VEGF) signaling pathway has a crucial role in regulating tumor angiogenesis. VEGF-A shows prominent interaction with the VEGF receptor-1 and VEGF receptor-2 on the membrane of the endothelial cells. The current study aimed to design and model an anti-VEGF peptide based on VEGFR2 binding regions. The effective amino acid sequences in the interaction of VEGF-A and VEGFR-2 were investigated using Chimera, SPDBV and PyMOL software. The VEGF binding sites on the receptor were determined and used as the basis for peptide design. This sequence was then subjected to random mutagenesis, and the binding affinity of resultant peptides analyzed by Hex 8.0.0 and ClusPro software. Then, GROMACS v5.0.6 has been used for Molecular Dynamics (MD) simulation and assessing the stability of target-ligand complexes. Finally, the chosen peptide with the highest affinity was grafted into two loops of SFTI-1 (sunflower trypsin inhibitor-1) and MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II) frameworks for improving the peptide stability. Among the 18 peptides from the second library, four peptides were opted, of which NGIDFNRDKFLFL showed the highest affinity with a total energy of − 742 kcal/mol. We found that this peptide can bond to the VEGF and block VEGF binding to VEGFR2. The RMSD, RMSF, and H-bonds analysis verified the docking results. The peptide grafted into loop 1 of SFTI-1 increased the peptide-VEGF binding affinity compared to peptide alone. The results showed that in silico design could be used for the identification of efficient anti-angiogenic peptides for potential application in antiangiogenic therapies.

The escalating prevalence of coronavirus disease 2019 (COVID-19) worldwide, with an increased rate of morbidity and mortality, highlights an urgent need to develop more effective therapeutic interventions. Despite the authorized treatment against COVID-19 by the European Union (EU), the safety and effectiveness of this therapeutic strategy for a wide variety of patients have remained a significant challenge. In this respect, micronutrients such as vitamins and minerals, as essential factors, can be considered for improving the function of the immune system and accelerating the treatment procedure. Dietary supplements can attenuate vascular and inflammatory manifestations related to infectious diseases in large part due to their anti-inflammatory and antioxidant properties. Recently, it has been revealed that poor nutritional status may be one of the notable risk factors in severe COVID-19 infections. In the current review, we focus on the micronutrient therapy of COVID-19 patients and provide a comprehensive insight into the essential vitamins/minerals and their role in controlling the severity of the COVID-19 infection. We also discuss the recent advancements, challenges, negative and positive outcomes in relevance to this approach.

Drug resistance limits the effectiveness of chemotherapy in colorectal cancer (CRC). Consequently, finding appropriate strategies for re-sensitizing chemo-resistant cells is crucial. Our present study aimed at taking advantage of chemotherapy and gene therapy by restoring microRNA-145 expression in oxaliplatin resistant CRC cells. Bioinformatic analysis of clinical colorectal cancer tissue revealed that miR-145 levels were significantly lower than in adjusted tumors. Afterward, pCMV-miR-145 vectors were transfected into the oxaliplatin-resistant SW-480 CRC cells. Using miR-145 and Oxaliplatin together to treat Oxaliplatin-resistant cells, the results showed significant differences in viability, proliferation, apoptosis and migration compared to the individual treatments. Furthermore, miRNA prediction results as well as mRNA and protein expression indicated that miR-145 targeted ABCC1. Also, mRNA expression analysis was performed to evaluate a panel of genes involved in cell viability, apoptosis, motility, and drug resistance. These genes included K-ras, Bcl2, CASP3, -8, -9, MMP13, MDR-1, and ABCC1. These expression changes tended towards apoptosis induction and decreased proliferation and migration. Based on our findings, miR-145 restoration via decreasing the drug resistance biomarkers ABBCC1 and MDR1, along with other oncogenes such as K-Ras and Bcl2, and increasing apoptosis conductores could sensitize oxaliplatin-resistant cells to chemotherapy.

Let-7f has essential impacts on biological processes; however, its biological and molecular functions in lung cancer pathogenesis have yet been remained unclear. We aimed to investigate the expression level of let-7f and its candidate target genes both in lung cancer tissues and A549 cell line.Bioinformatics databases were first used to select candidate target genes of let-7f. Then the relative gene and protein expressions of let-7f and its target genes, including HMGA2, ARID3B, SMARCAD1, and FZD3, were measured in lung tissues of NSCLC patients and A549 cell line using qRT-PCR and Western blotting. The electroporation method was used to transfect A549 cells with let-7f mimic and microRNA inhibitor. The impact of let-7f transfection on the viability of A549 cells was assessed using MTT assay. The expression data of studied genes were analyzed statistically.Results indicated significant downregulated expression level of let-7f-5p (p = 0.0013) and upregulated level of the HMGA2 and FZD3 in NSCLC cases (p0.05). In A549 cells, after transfection with let-7f mimic, the expression of both mRNA and protein levels of HMGA2, ARID3B, SMARCAD1, and FZD3 decreased. Also, the overexpression of let-7f significantly inhibited the A549 cell proliferation and viability (p = 0.017).Our findings exhibited the high value of let-7f and HMGA2 as biomarkers for NSCLC. The let-7f, as a major tumor suppressor regulatory factor via direct targeting genes (e.g. HMGA2), inhibits lung cancer cell viability and proliferation and could serve as a marker for the early diagnostic of NSCLC.

Purpose: In this study, we aimed to evaluate the relative level of methylation of this gene in stool samples of colorectal cancer patients.Methods: In present study, stool samples were collected from 40 colorectal cancer patients and 40 healthy controls. After collecting the DNA of the samples, the extracts were treated by sulfite method and the methylation of the target site was evaluated by met-HRM method. Differences in methylation level of the two groups were evaluated by appropriate statistical tests. P value Results: The relative methylation rate of the studied genes (IGFBP3 and TWIST1) in the stool samples was lower than that of the healthy groups and this difference was significant in the confidence interval (P< 0.0001 and P< 0.0025, respectively). Meanwhile, this genes has no significant association with clinical findings Conclusion: Our findings suggest that the IGFBP3 and TWIST1 methylation could be used as a diagnostic biomarker in colorectal cancer. However, it is better to do more studies on the level of protein.

Long non-coding RNAs (lncRNA) have been emerged as a novel class of molecular regulators in cancer. They are dysregulated in many types of cancer; however, there is not enough knowledge available on their expression and functional profiles. Lung cancer is the leading cause of the cancer deaths worldwide. Generally, lncRNAs may be associated with lung tumor pathogenesis and they may act as biomarkers for the cancer prognosis and diagnosis. Compared to other invasive prognostic and diagnostic methods, detection of lncRNAs might be a user-friendly and noninvasive method. In this review article, we selected 27 tumor-associated lncRNAs by literature reviewing to further discussing in detail for using as diagnostic and prognostic biomarkers in lung cancer. Also, in an in silico target analysis, the "Experimentally supported functional regulation" approach of the LncTarD web tool was used to identifying the target genes and regulatory mechanisms of the selected lncRNAs. The reports on diagnostic and prognostic potential of all selected lncRNAs were discussed. However, the target genes and regulatory mechanisms of the 22 lncRNAs were identified by in silico analysis and we found the pathways that are controlled by each target group of lncRNAs. They use epigenetic mechanisms, ceRNA mechanisms, protein interaction and sponge mechanism. Also, 10, 23, 5, and 28 target genes for each of these mechanisms were identified, respectively. Finally, each group of target genes controls 50, 12, 7, and 2 molecular pathways, respectively. In conclusion, LncRNAs could be used as biomarkers in lung cancer due to their roles in control of several signaling pathways related to lung tumors. Also, it seems that lncRNAs, which use epigenetic mechanisms for modulating a large number of pathways, could be considered as important subjects for lung cancer-related diagnostic and prognostic biomarkers.

Purpose Colorectal cancer (CRC) is one of the most prevalence malignancies in a different society with a high rate of death. The KRAS and p38 alpha axes have critical roles in the development, migration, and growth of numerous tumors, such as colorectal malignancy. KRAS mutation acts as an oncogene in various cancers and is correlated with the poor prognosis in colorectal tumors. Also, p38 alpha plays different roles and exhibits tissue-dependent activity. In some tissues act as an oncogene while in others act as a tumor suppressor. In this research, we try to understand the effect of the P38 alpha and KRAS genes suppression by specific siRNAs on the SW480 cell line progression. Methods We evaluate the impact of the P38 alpha and KRAS gene knockdown by special siRNA on the growth and development of the SW480 cell line. SW480 cell line was treated with KRAS and P38 alpha siRNAs, and the cell viability, gene expression, migration ability, and rate of apoptosis were evaluated with MTT assay, real-time PCR, scratch test, and flow cytometry. Results After treatment of the cancer cell with KRAs and P38 alpha siRNAs, cell viability reduced to 29.16%. Also, the expression levels of the KRAS and P38 alpha genes reduced to 26.34% and 16.06%, respectively. Apoptosis rate after combination therapy with KRAS and P38 alpha siRNAs increased to 72.1. Also, we found that these siRNAs suppress cell migration in SW480 cell lines. Conclusion The current study showed that combination therapy with p38 alpha and KRAS siRNA may be considered a novel therapy for colorectal tumor in future., Tuberculosis and Lung Disease Research Center, Tabriz University, of Medical Science, Tabriz, Iran, This study was supported by a grant from the Tuberculosis and Lung Disease Research Center, Tabriz University, of Medical Science, Tabriz, Iran.

Background: Pistacia atlantica (P. atlantica) has been associated with beneficial medical effects on gastrointestinal complications. Objective: It was intended to assess the effects of P. atlantica in elimination of Helicobacter pylori (H. pylori) infection and amelioration of gastric reflux and chronic cough. Methods: In this clinical trial study, 100 subjects with H. pylori infection who had the symptoms of gastric reflux and chronic cough were recruited and classified into two intervention and placebo groups, continuing 50 subjects each. The intervention group was administered two 500 mg doses of P. atlantica extract each day. The H. pylori antigen load in stool samples was evaluated using ELISA. The severity of cough and gastric re flux was also determined. Results: The subjects in two groups were age and sex matched and the baseline measurements were similar on the day 0. Nonetheless, it was observed that on the day 14, there was a significant reduction of H. pylori antigen load in the intervention group compared with the placebo group (P = 0.00021). Furthermore, the intensity of chronic cough was reduced significantly in the intervention group (P = 0.0014). The gastric reflux was improved in the intervention group at the end of the study. Conclusion: P. atlantica extract was beneficial in controlling H. pylori infection. It also improved the complications of the infection, like gastric reflux and chronic cough. Hence, it is highly recommended to value natural products, along with traditional antibiotics, in ameliorating H. pylori infection.

The health effects of ambient air particulate matter with a diameter of ≤2.5 μm (PM

Colorectal cancer (CRC) is one of the most prevalence malignancies in a different society with a high rate of death. The KRAS and p38α axes have critical roles in the development, migration, and growth of numerous tumors, such as colorectal malignancy. KRAS mutation acts as an oncogene in various cancers and is correlated with the poor prognosis in colorectal tumors. Also, p38α plays different roles and exhibits tissue-dependent activity. In some tissues act as an oncogene while in others act as a tumor suppressor. In this research, we try to understand the effect of the P38α and KRAS genes suppression by specific siRNAs on the SW480 cell line progression.We evaluate the impact of the P38α and KRAS gene knockdown by special siRNA on the growth and development of the SW480 cell line. SW480 cell line was treated with KRAS and P38α siRNAs, and the cell viability, gene expression, migration ability, and rate of apoptosis were evaluated with MTT assay, real-time PCR, scratch test, and flow cytometry.After treatment of the cancer cell with KRAs and P38α siRNAs, cell viability reduced to 29.16%. Also, the expression levels of the KRAS and P38α genes reduced to 26.34% and 16.06%, respectively. Apoptosis rate after combination therapy with KRAS and P38α siRNAs increased to 72.1. Also, we found that these siRNAs suppress cell migration in SW480 cell lines.The current study showed that combination therapy with p38α and KRAS siRNA may be considered a novel therapy for colorectal tumor in future.

Colorectal cancer (CRC) is one of the most lethal and prevalent cancers throughout the world. Despite the remarkable advance in the field, drug resistance still remains as an unresolved problem in cancer. Hence, finding effective compounds with minimal side effects to fight cancer is of central priority. Herbal products have been traditionally used to prevent and treat a variety of diseases. In the present study, the antitumor effect of Terminalia catappa plant ethanolic extract (TCE) was assessed on SW480 CRC model cell line. In this regard, effects of TCE were evaluated on the proliferation, apoptosis, and migration of SW480 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V/PI flow cytometry, and scratch tests, respectively. Furthermore, changes in the expression of genes involved in these events including Bax, Bcl-2, Caspase 3, Caspase 8, Caspase 9, MMP-13, miR-21, and miR-34a were measured by quantitative real-time PCR (qRT-PCR). According to the MTT results, TCE reduced the proliferation of SW480 cells significantly. The flow cytometry test also revealed a notable rate of apoptosis induction after TCE treatment. An inhibitory effect on cell migration was also evident in scratch test. Expression patterns of the assessed genes also changed subsequent to TCE treatment. The results of this study indicated that T. catappa could be considered as a potential source of anticancer compounds and a candidate for further investigations.

Genome engineering technology is of great interest for biomedical research that enables scientists to make specific manipulation in the DNA sequence. Early methods for introducing double-stranded DNA breaks relies on protein-based systems. These platforms have enabled fascinating advances, but all are costly and time-consuming to engineer, preventing these from gaining high-throughput applications. The CRISPR-Cas9 system, co-opted from bacteria, has generated considerable excitement in gene targeting. In this review, we describe gene targeting techniques with an emphasis on recent strategies to improve the specificities of CRISPR-Cas systems for nuclease and non-nuclease applications.

Background Colorectal cancer is one of the most common types of cancer worldwide. MiR-330 has been reported as a cell proliferation inhibitor by suppressing thymidylate synthase (TYMS) in FOLFOX, one of the major chemotherapy regimens used to treat colorectal cancers. A number of dysregulated miRNAs have been linked to CRC progression and treatment response and are thought to be promising prognostic biomarkers for this cancer. In the current study, miR-330, TYMS, and their interactions have been investigated in the absence of this chemotherapy to evaluate their therapeutic and diagnostic value for other treatment methods. Material and Methods The expression levels of miR-330 and TYMS were evaluated in-silico using TCGA datasets for colorectal cancer. Data validation was performed on a set of internal samples (100 pairs of CRC tumor specimens and adjacent non-cancerous samples) were determined utilizing RT-qPCR assay. The linkage between clinicopathological parameters and expression levels was also investigated. Results TCGA results illustrated that miR-330 and TYMS are significantly upregulated and downregulated through colorectal tumorigenesis, respectively. QRT-PCR results confirmed that the expression level of miR-330 was significantly higher in tumor tissues relative to margin tissues (p value = 0/0005) whereas TYMS was significantly down-regulated (p value = 0.0001). However, there was no significant association regarding TYMS and patient pathological features while miR-330 expression was associated with tumor stage and lymph node metastases. Conclusion The microRNA-330 inhibited cell proliferation by suppressing thymidylate synthase (TYMS) in colorectal cancer. Therefore, suggesting that they are valuable factors for further studies of alternative treatment and diagnostic methods.

After cardiovascular illness, cancer is the one of the main and second cause of death in the worldwide. Despite significant advances in this field, low survival, drug resistance, and side effects of chemotherapy remain an unsolved problem. Due to the high mortality rate among cancer patients, finding the new substance to treatment with low side effects is important. Previous studies have been informed that positive effects of herbal medicines on cancer patients, which are very efficient in the treatment of cancer. Methods: In this study, the antitumor effect of ethanolic Terminalia catappa leaf extract (TCE) on MCF-7, MDA-231, and A549 cell lines was examined. For this reason, the effects of TCE on cell migration, gene expression, and growth were investigated by scratch, test, real-time PCR (qPCR) qPCR, and MTT tests respectively. Results: As a reported by the MTT outcomes, TCE significantly decreased the viability of A549, MCF-7, and MDA-231 cells (P < 0.05). Moreover, genes expression patterns that are related to proliferation (miR-21, miR-34a), migration (MMP-13, Vimentin), and apoptosis (Cas-3, Cas-8, Cas-9, Bcl-2, Bax) also have changed significantly after treatment with TCE. Also, in the A549 cell line, Bax (p value: 0.029), Cas-9 (p value: 0.00023), miR-34a (p value: 0.031), Bcl-2 (p value: 0.0076), MMP-13 (p value: 0.041), Cas-3 (p value: 0.00051) and in MCF-7 cell line Bax (p value: 0.0004), Cas-3 (p value: 0.0003), Cas-9(p value: 0.037), miR-34a (p value: 0.005), Bcl-2(pvalue:0.0007), mir-21(p value:0.016), MMP-13(p value: 0.011) and in MDA-231 cell line Bax(p value, This study was supported by a grant from research deputy of Department of Tuberculosis and Lung Diseases Research Center, University Tabriz University of Medical Sciences, Tabriz, Iran.

Different bioinformatic methods apply various approaches to predict how much the effect of a SNP could be deleterious and therefore their results may differ significantly. However, variation studies often need to consider an integrated prediction result to analyze the effect of SNPs. To address this problem, we used an algorithm to map ordinal predictions to a numeral space and averaging them, and based on it we developed the ISNPranker web-tool ( http://isnpranker.semilab.ir/ ). It takes heterogonous outputs of different predictors and generates integrated numerical predictions and ranks SNPs based on them. Afterward, we used ISNPranker to identify the most deleterious coding SNPs (cSNPs) of the human aryl hydrocarbon receptor (AHR) gene. AHR is a ligand-activated transcription factor that governs many molecular and cellular mechanisms and cSNPs may affect its structure, interactions, and function. Forty validated cSNPs of AHR were initially analyzed using 16 publicly available SNP analyzers and the results were introduced to the ISNPranker and integrated predictions were obtained. The cSNPs were ranked in 34 levels of danger and rs200257782 in the ARNT dimerization domain (ADD121-289) of AHR was identified as the most deleterious cSNP. The rs148360742, which affect ADD40-79 and Hsp90 binding domain (HBD27-79) was in the second rank and the third and fourth ranks were occupied by ADD121-289-located variations rs571123681 and rs141667112 respectively. In conclusion, we introduced ISNPranker, which is a web-tool for integrative ranking of SNPs, and we showed that AHR structure and function may be highly sensitive to the cSNPs in the ARNT dimerization domain.

Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women. The high mortality rate is due to lack of early symptoms, late diagnosis, limited treatment options, and also emerging of drug resistance. Todays, molecular markers have become promising in tumor-targeted therapy. Several molecular markers have been known in OC immunotherapy. Identification of the specific molecular markers with prognostic significance is interested. CD24 is a small sialoglycoprotein which is localized in lipid rafts through its glycosylphosphatidylinositol (GPI) anchor. It has been reported that CD24 is overexpressed in many cancers including OC. Also, CD24 is identified as a cancer stem cell marker in OC. The CD24 expression is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in cancer cells is not clearly understood. Recently, CD24 has been identified as an independent prognostic marker of survival in patients with OC. In this study, we reviewed the molecular targets in OC immune-targeted therapy and also presented an overview of the new molecular marker CD24 and its association with the OC by reviewing the recent literature.

Colorectal cancer (CRC) is one of the most lethal and prevalent cancers throughout the world. Despite the remarkable advance in the field, drug resistance still remains as an unresolved problem in cancer. Hence, finding effective compounds with minimal side effects to fight cancer is of central priority. Herbal products have been traditionally used to prevent and treat a variety of diseases.In the present study, the antitumor effect of Terminalia catappa plant ethanolic extract (TCE) was assessed on SW480 CRC model cell line. In this regard, effects of TCE were evaluated on the proliferation, apoptosis, and migration of SW480 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V/PI flow cytometry, and scratch tests, respectively. Furthermore, changes in the expression of genes involved in these events including Bax, Bcl-2, Caspase 3, Caspase 8, Caspase 9, MMP-13, miR-21, and miR-34a were measured by quantitative real-time PCR (qRT-PCR).According to the MTT results, TCE reduced the proliferation of SW480 cells significantly. The flow cytometry test also revealed a notable rate of apoptosis induction after TCE treatment. An inhibitory effect on cell migration was also evident in scratch test. Expression patterns of the assessed genes also changed subsequent to TCE treatment.The results of this study indicated that T. catappa could be considered as a potential source of anticancer compounds and a candidate for further investigations.

Background Lung cancer is one of the most common cancers worldwide whose prevalence and mortality have not any remarkable reduction in recent decades, in spite of the progression in screening and diagnostic methods. MiR-103, miR-184, miR-378, miR-497 and miR-506 are microRNAs which recent evidence has implied the possible roles of them in the carcinogenesis process. Hence, in this study we examined whether there are any significant alterations in the expression level of these micro RNAs during carcinogenesis procedure or not, and if we can use these factors as a diagnostic or prognostic biomarker for non-small cell lung cancer (NSCLC). Methods Fifty NSCLC patients participated in our study and tumor and adjacent normal tumor-free tissues were collected during the bronchoscopy. Total RNA was extracted from cells, cDNA was synthesized and then the expression level of target miRNAs was examined by quantitative Real-time PCR. Subsequently, expression levels of these genes and their correlation with clinicopathologic features of patients were analyzed with proper statistical tests. In these tests Pvalue Results The output data of our study showed the statistically significant down-expression of miR-103 (Fold change = 0.83, Pvalue = 0.036), miR-184a (Fold change = 0.52, Pvalue = 0.011), miR-378 (Fold change = 0.84, Pvalue = 0.041), and miR-497 (Fold change = 0.72, Pvalue = 0.021) between these micro-RNAs only mir-497 and miR-184a are potential biomarkers for NSCLC. Also, the expression levels of these miRNAs had significant relations with metastasis, lymph node involvement, and tumor cell differentiation degree and tumor size of NSCLC patients. Deregulated fifth microRNA, miR-506 was not statistically significant (Pvalue > 0.05). Conclusion According to the results of this study, 4 of our studied microRNAs have the potential to be used as diagnostic or prognostic biomarkers in case of confirmation of the future studies.

Background: In many cases of breast cancer, the aberrant methylation of TP53 gene leads to uncontrolled cell proliferation and apoptosis inhibition. Moreover, expression of oncogenes which are under the control of P53 protein could be altered. Survivin as a conspicuous example of this category plays important roles in tumorigenesis, drug resistance and apoptosis inhibition. The present study was done to reveal the effects of Scrophularia atropatana extract on epigenetic situation of TP53 gene promoter and the expression levels of anti-apoptotic gene, survivin and its potential for production of cancer epi-drugs. Methods: Cytotoxic effect of dichloromethane extracts of Scrophularia plant on MCF-7 cell line was assessed in our previous study. Cell death ELISA (enzyme-linked immunosorbent assay) and TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) tests were used to investigate the occurrence of apoptosis in the treated cells. Methylation Specific PCR (MSP) was employed to assess the changes in methylation status of the TP53 gene promoter. Furthermore, quantitative real time PCR was utilized to evaluate the resulting changes in TP53 and survivin genes expression. Results: Cell death ELISA and TUNEL assays confirmed the occurrence of apoptosis. MSP test revealed a significant change in the methylation status of TP53 promoter. QRT-PCR showed an increased TP53 gene expression in the treated cells while a significant decrease in survivin mRNA was evident. Conclusions: According to the outcomes, dichloromethane extract of S. atropatana returned the TP53 gene promoter hypermethylation to normal state. This plant could be a promising source for production of epi-drugs due to its apoptotic effects and reversal of TP53 epigenetic alterations.

Rheumatoid arthritis (RA), as one of the most disabling autoimmune diseases, is a common health problem that progressively reduces the life quality of patients. Although various biologics have been introduced for RA, attempts to establish an efficient long-term therapies failed due to the heterogeneity of this disease.In the last decade, immunomodulatory approaches such as T cell adoptive therapy have been developed for controlling autoimmunity. Regulatory T cells (Tregs), the major self-tolerance mediator, are crucial for down-regulation of aberrant immune stimulations. Hence, recruiting ex vivo Tregs emerged as a promising therapy for a variety of autoimmune diseases.The major bottleneck of the Treg adoptive therapy is maintaining the in vivo stability and plasticity of these fascinating cells. Recent progress in genome editing technology clustered regularly interspaced short palindromic repeats (CRISPR) in combination with CRISPR-associated (Cas) 9 system provided a new solution for this bottleneck.The present paper discusses RA pathogenesis and the potential application of new developments in CRISPR-mediated Treg genome editing in personalized therapy of RA.

Lung cancer is a leading cause of cancer-related deaths worldwide, with less than a 5-year survival rate for both men and women. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma oncogene (KRAS) signaling pathways play a critical role in the proliferation and progression of various cancers, including lung cancer. Genetic studies have shown that amplification, over-expression, or mutation of EGFR is an early and major molecular event in many human tumors. KRAS mutation is a negative factor in various cancer, including non-small-cell lung cancer, and complicates therapeutic approaches with adjuvant chemotherapy and anti-EGFR directed therapies. This article is dedicated to evaluating the synergistic effect of a novel EGFR inhibitor AZD8931 and KRAS small interfering RNA (siRNA) on the proliferation and apoptosis of lung adenocarcinoma cancer cells. A549 lung cancer cells were treated with KRAS siRNA and the EGFR inhibitor alone or in combination. The cytotoxic effects of KRAS siRNA and te EGFR inhibitor were determined usingMTT assay, and induction of apoptosis was determined by FACS analysis. Suppression of KRAS, Her-2, and EGFR expression by treatments was measured by qRT-PCR and western blotting. KRAS siRNA and the EGFR inhibitor significantly reduced the proliferation of A549 cells as well as KRAS and EGFR mRNA levels 24 hr after treatment. The results also indicated that the silencing of KRAS and EGFR has synergistic effects on the induction of apoptosis on the A549 cells. These results indicated that KRAS and EGFR might play important roles in the progression of lung cancer and could be potential therapeutic targets for treatment of lung cancer.

Background:Lung cancer is the leading cause of cancer-related death with less than 5-year survival rate for both men and women worldwide. EGFR and MAPK signaling pathways have a critical role in proliferation and progression of various cancers, including lung cancer. P38 map kinase plays different role in various tissue hence showing a tissue-dependent behavior. It acts as an oncogene in some tissues while plays as tumor suppressor in some other tissues. The aim of this study was to investigate the combined effect of P38 αspecific siRNA and EGFR inhibitor on apoptosis and proliferation of A549 lung cancer cell line.Objective:This article is dedicated to the synergistic effect of novel EGFR inhibitor AZD8931 and P38 α siRNA in lung adenocarcinoma cancer cells proliferation and apoptosis.Methods and Materials:The A549 lung cancer cells were treated with P38 α- siRNA and EGFR inhibitor alone or in combination. The cytotoxic effects of P38 α- siRNA and EGFR inhibitor were determined using MTT assay. Relative P38 α and EGFR mRNA levels were measured by QRT-PCR. Induction of apoptosis were measured by FACS analysis.Results:The expression of mRNA related to P38 α, EGFR, and Her2 genes was reduced to 23.4%, 52.4%, and 75, respectively, after treatment of their inhibitors. Also, MTT assay showed that the cell viability after treatment with p38 α SiRNA, EGFR inhibitor and their combination was reduced to 51.02%, 48.9%, and 25.11%, respectively. FACS results indicated that p38 α siRNA, EGFR inhibitor and their combination, reduced the population of live cells to 49.5%, 32.2% and 14.3% in comparison to the population of untreated control cells (99.5%).Conclusion:The results of this study indicated that p38 α and EGFR might play an important role in the development and growth of lung cancer and might be a potential therapeutic target for the treatment of lung cancer.

Background: MicroRNAs (miRNAs) play an important role in the regulation of various genes involved in cell growth, development and the maintenance of body homeostasis. They are closely linked to different human diseases, particularly in cancers. Amplification and overexpression of some miRNAs that are called ‘oncomiRs’ or down-regulation of tumor suppressor miRNAs are associated with genetic alterations that are sufficient to drive tumorigenesis in humans. Lung cancer is the leading cause of cancer-related deaths worldwide. The high mortality rate of lung cancer is not changed even with recent advances in cancer treatment. Several studies demonstrated that miRNAs are involved in the pathogenesis of lung cancer that they negatively or positively regulate gene and protein expression by acting as oncogenes or tumor suppressors. Objective: This article reviewed the current knowledge on the role of miRNAs and their target genes in lung cancer and discussed the potential use of some miRNAs as novel therapeutic agents in lung cancer. Method: Firstly, we collected and summarized all research and review and research articles in databases including Scopus and PubMed. Then, we used related keywords that are important to lung cancer target therapy and their diagnostic and prognostic values. Results: Based on collected articles and research, recognizing critical microRNA and controlling the expression of this microRNA by antagonist oligonucleotides like antagomiRs or anti-miRs and microRNA mimicking will have a remarkable role in treating lung cancer. Conclusion: Many research studies have shown that a combination of chemotherapy plus knockdown or mimicking microRNA is effective and useful in the cancers treatment like lung cancer.

Todays, after four decades from the discovery of monoclonal antibodies by Kohler and Milstein in 1975, a dozen of antibodies are used in cancer targeted therapy with different strategies. The success of these antibodies depends on the specificity of antigens expressed on the cancer cells. Epithelial Cell Adhesion Molecule (EpCAM), a homophilic cell-cell adhesion glycoprotein is a well- known tumor antigen, which expresses on epithelial tumors and circulating tumor cells as well as cancer stem cells. The EpCAM signaling pathway is associated with proliferation, differentiation and adhesion of epithelial cancer cells. Here we review EpCAM structure, expression profile and its signaling pathway in cancer cells. In addition, we focused on structure, mechanism of action and success of anti EpCAM antibodies which have been used in different clinical trials. Based on literatures, Edrecolomab showed limited efficacy in the phase III studies. The wholly human monoclonal antibody Adecatumumab is dose- and target-dependent in metastatic breast cancer patients expressing EpCAM. The chimeric antibody, Catumaxomab, has been approved for the treatment of malignant ascites; however, this Mab showed considerable results in intrapleural administration in cancer patients. Anti EpCAM toxin conjugated antibodies like, Oportuzumab Monatox (scFv antibody and Pseudomonas exotoxin A (ETA)), Citatuzumab Bogatox (Fab fragment with bouganin toxin) and immono-conjugate antibody Tucotuzumab (monoclonal antibody with IL2), have shown acceptable results in different clinical trials. Almost, all of the antibodies were well-tolerated; however, still more clinical trials are needed for the approval of antibodies for the treatment of specific tumors.

Despite worldwide vaccination against devastating diseases for decades, millions of children in remote and impoverished regions of the globe die every year from vaccine-preventable infectious diseases. The reasons for incomplete coverage of vaccination programs are based in part on the relatively high costs of conventional vaccinations, including mass production, refrigeration, transportation, and training as well as funding personnel for their administration. Plant-based edible vaccines (PEVs) have been introduced as a revolutionary cost-effective vaccination modality. However, they suffer from major deficiencies that have restricted their application to bench-scale. This article discusses the deficiencies of PEVs and also provides concise overview on the health-promoting, biological and biotechnological features of spirulina (Arthrospira). In short, we envision that spirulina could be considered as a potential alternative biofactory system to the plants toward the production of edible vaccines in high-yield with low-costs that other hosts cannot yet offer.

Traditional dairy products are potential sources of a variety of microorganisms which participate in food poisoning. Staphylococcus aureus is a conspicuous example of toxigenic bacteria causative for food-borne diseases. Moreover, resistance to methicillin is a prominent index in food hygiene studies. In the present study, we have aimed at characterization and identification of enterotoxigenic methicillin resistant S. aureus (MRSA) isolated from traditional cheeses in Azerbaijan region in the northwest of Iran during 2012. A number of phenotypical and molecular assays were utilized for screening of S. aureus. Subsequently, the prevalence of the genes responsible for the five staphylococcal enterotoxins (SEA-SEE) and also methicillin resistance gene was assessed. The outcomes of phenotypical methods were in conformity with those of the molecular procedures. The results indicated that 16% of cheese samples were contaminated by S. aureus. 110 isolates were authenticated by both phenotypical and molecular methods. All of the mentioned isolates were positive for coa, nuc, and 16S rDNA primers. 21% of these isolates were mecA positive and 60.8% of these MRSA were positive for SEs. Regarding the frequent outbreaks of enterotoxigenic MRSA, new hygiene policies and management practices should be considered to increase food safety and avoid extra treatment costs.