The interactive effect of seven weeks aerobic exercise training and piperine against paraquat-induced lung damage in male Wistar rats: Investigating role of oxidative and inflammatory indices.

We aimed to evaluate the effects of seven weeks of aerobic exercise training and piperine on paraquat-induced lung damage. Forty-eight male Wistar rats (230 g, six-eight weeks old) were randomly divided into six groups (n = 8): sham, paraquat (5 mg/kg three times a week; intraperitoneally), paraquat + piperine (10 mg/kg/day; orally), paraquat + aerobic exercise training, paraquat + piperine + aerobic exercise training; and paraquat + vitamin E (20 mg/kg/day; orally) as a positive control. Rats were sacrificed on day 50, and both lung tissues were isolated to measure oxidative (MDA), anti-oxidative (GSH), inflammatory (TNF-α), anti-inflammatory (IL-10) markers, and histological evaluations (hematoxylin-eosin staining). The results of the present study revealed that paraquat significantly decreased body weight, GSH, GSH/MDA ratio, IL-10, and IL-10/TNF-α ratio while increasing MDA, TNF-α, and histopathological damage in lung tissue (P < 0.01 to 0.001). In contrast, treatment with all four interventions meaningfully diminished oxidative, inflammatory markers, and histopathological damage while propagating body weight, anti-oxidative and anti-inflammatory markers following the paraquat-induced lung damage (P < 0.05 to P < 0.001). Interestingly, piperine and piperine + exercise training possessed stronger protective effects against paraquat-induced lung damage than exercise training alone (P < 0.01 to 0.001). Treatment with piperine, exercise training, piperine + exercise training, and vitamin E significantly ameliorated paraquat-induced lung damage. Interestingly, the piperine and piperine + exercise training had more protective effects than other groups. Therefore, piperine and the combination of piperine and exercise training may be valuable candidates for preventing lung injuries.

Identification of Circular RNAs as Biomarker Candidates in Lung Cancer Treatment.

OBJECTIVE: Lung cancer is the most common malignancy and among the leading cause of cancer death worldwide. Therefore, there is an important need for biomarkers that can be used in the early diagnosis of the disease and in the follow-up of treatment. Circular RNAs (circRNAs) have a covalently closed circular structure that lacks 3' and 5' polar ends and is resistant to RNAase enzymes. Due to these properties, they can be stably found in body fluids. Therefore, they can serve as potential biomarkers in the diagnosis, monitoring of therapeutic response and prognosis of cancer. In our study, we aimed to investigate the expression levels of circRNA molecules in the treatment of lung cancer and to determine those that have the potential to be biomarkers. METHODS: In this in vitro study, expression levels of 163 circRNAs were investigated in A549 cells, a non-small cell lung cancer cell line, before and after treatment with carboplatin and pemetrexed. Total RNA isolation and cDNA synthesis were performed after treatments. Expression levels of circRNA genes were determined by RT-qPCR method with the designed divergent primer sequences. RESULTS: The study revealed the characterisation of differentially expressed circRNAs by treatment in lung cancer cells. Of them, hsa_circ_0001320 is not expressed in cancer cells, is expressed only after treatment, and increased the level of its expression in response to combination therapy. CONCLUSION: As a result, while carboplatin, pemetrexed, and combined drug applications changed the expression levels of some circRNAs in lung cancer cells, some circRNAs were expressed only after treatment. In treatment follow-up and management, hsa_circ_0001320 has been identified as potential biomarker candidate.

Docosahexaenoic acid (DHA) impairs hypoxia-induced cellular and exosomal overexpression of immune-checkpoints and immunomodulatory molecules in different subtypes of breast cancer cells.

BACKGROUND: Tumor cells express immune-checkpoint molecules to suppress anti-tumor immune responses. In part, immune evasion takes place by secreting exosomes bearing immune-checkpoint and immunomodulatory molecules and their inducing and/or regulating agents e.g., microRNAs (miRs). This study aimed to evaluate the effects of omega-3 fatty acid, docosahexaenoic acid (DHA), on the expression of some selected immune-checkpoint and immunomodulatory molecules and their regulating miRs under both normoxic and hypoxic conditions in triple negative (TNBC) invasive and triple positive non-invasive breast cancer cell lines. METHODS: MDA-MB-231 and BT-474 cells were treated with 100 µM DHA under hypoxic and normoxic conditions for 24 h. Exosomes were isolated by ultracentrifuge and confirmed by electron microscope and anti-CD9, -CD63, -CD81 immunoblotting. Total RNA from cells and exosomes were extracted and expression of CD39, CD73, CD47, CD80, PD-L1, B7-H3, B7-H4 genes and their related miRs were evaluated by quantitative Real-time PCR. RESULTS: This study showed significant over-expression of immune-checkpoint and immunomodulatory molecules under hypoxic condition. Treatment with DHA resulted in a significant decrease in immune-checkpoint and immunomodulatory molecule expression as well as an upregulation of their regulatory miRNA expression. CONCLUSION: DHA supplementation may be utilized in breast cancer therapy for down-regulation of cellular and exosomal immune escape-related molecules.

SIGNIFICANCE OF THE STUDY: This study showed anti-immunosuppressive effect of DHA on BC cell lines in normoxic and hypoxic conditions.

Durvalumab and taxane family combination therapy enhances the antitumoral effects for NSCLC: An in vitro study.

Immunotherapy has lately become the most preferred cancer treatment method, and for non-small cell lung cancer (NSCLC) first-line treatment, there are many immunotherapy options. This study aimed to assess the effectiveness and toxicity of paclitaxel (PTX), docetaxel (DTX) chemotherapy, immune checkpoint inhibitor treatment (durvalumab; DVL), and their combination in NSCLC. A-549 cells were treated with DVL in combination with PTX and DTX (a quarter of the IC50 ) to investigate their anticancer effects on these cells. The MTT assay, wound healing tests, and double-staining with Annexin V/PI were used to assess the cell viability, apoptosis, and migration. The results showed that a combination of 0.35 mg/mL DVL with 6.5 µg/mL PTX and 1.75 µg/mL DTX produced a synergistic effect with CI values of 0.88, 0.37, and 0.81, respectively. Moreover, the PTX + DTX + DVL combination led to a significantly increased apoptotic rate up to 88.70 ± 3.39% in the A549 cell line compared to monotherapy (p < .001). In addition, we found that the combination therapy with these agents increased the expression level of Bax, Cas-3, p53, and Bax/Bcl-2 ratio in all experimental groups. In conclusion, the results suggest that combining anti-PD-L1 antibody therapy with chemotherapy may provide a promising approach to enhance treatment outcomes and be a potentially efficacious strategy for treating NSCLC patients. Further research and clinical investigations are needed to elucidate the underlying molecular mechanisms and validate the therapeutic potential of these compounds in vivo.

Immune Features of Tumor Microenvironment: A Genetic Spotlight.

A tumor represents a highly intricate tissue entity, characterized by an exceptionally complex microenvironment that starkly contrasts with the typical physiological surroundings of healthy tissues. Within this tumor microenvironment (TME), every component and factor assume paramount importance in the progression of malignancy and exerts a pivotal influence on a patient's clinical outcome. One of the remarkable aspects of the TME is its remarkable heterogeneity, not only across different types of cancers but even within the same histological category of tumors. In-depth research has illuminated the intricate interplay between specific immune cells and molecules and the dynamic characteristics of the TME. Recent investigations have yielded compelling evidence that several mutations harbored by tumor cells possess the capacity to instigate substantial alterations in the TME. These mutations, often acting as drivers of tumorigenesis, can orchestrate a cascade of events that remodel the TME, thereby influencing crucial aspects of cancer behavior, including its invasiveness, immune evasion, and response to therapies. It is within this nuanced context that the present study endeavors to provide a concise yet comprehensive summary of how specific mutations, within the genetic landscape of cancer cells, can instigate profound changes in TME features. By elucidating the intricate relationship between genetic mutations and the TME, this research aims to contribute to a deeper understanding of cancer biology. Ultimately, the knowledge gained from this study holds the potential to inform the development of more targeted and effective treatments, thereby offering new hope to patients grappling with the complexities of cancer.

microRNAs Regulate Survivin in Colorectal Cancer Patients.

Background: Impaired levels of surviving are associate with increased survival of tumor cells. In this study, we intended to profile the microRNAs (miRNAs) targeting survivin in the tumoral and marginal tissues obtained from Iranian patients with colorectal cancer (CRC). Materials and Methods: Fifty CRC patients of Iranian Azari ethnicity were recruited. The RNA content of the tumoral and marginal tissues was isolated and the transcript levels of miR-34a, miR-16, miR-150, and miR-203a and survivin were determined through quantitative Real-time PCR. Results: The mRNA expression of survivin was significantly increased (fold change = 3.21, P = 0.0029) in the tumoral tissues in comparison to the marginal tissues. There was significant downregulation of miR-16 (fold change = 0.28, P = 0.003) and miR-203a (fold change = 0.36, P = 0.014) in the tumoral samples in comparison to marginal samples. There was an inverse significant correlation (rho = -0.81; P < 0.001) between the expression of miR-203a and mRNA expression of survivin in the tumoral tissues of CRC patients. The mRNA expression of survivin was higher significantly in the tumoral tissues of CRC patients with lymph node metastasis in comparison to those without lymph node metastasis (P = 0.020). In addition, there was a significantly higher miR-203 expression level in the tumoral tissues of CRC patients with lymph node metastasis in comparison to those without lymph node metastasis (P = 0.011). Conclusion: It is suggested that miR-203 plays an oncogenic role in CRC cancer by regulating survivin and lymph node metastasis.

Expression and promoter methylation of mitogen-activated protein kinase 1 in tumor and marginal cells of breast cancer.

AIM: In the present study, we sought to explore potential differences in the expression and promoter methylation of mitogen-activated protein kinase 1 (MAPK1) between tumor and marginal cells of breast cancer lesions. METHODS: A total of 50 randomly selected patients with breast cancer (BCa) undergoing needle biopsy were enrolled. Clinical specimens containing both tumor and marginal cells were collected and preserved. After DNA extraction using specific primers, MAPK1 mRNA and promoter methylation were measured with spectrophotometry at 260/280 nm absorption wavelengths. To deliver a comparative analysis, data from The Cancer Genome Atlas (TCGA) program regarding breast cancer (BRCA), were downloaded from Xena Functional Genomics Explorer and separately analyzed. The suitability of MAPK1 expression and promoter methylation as biomarkers for BCa was analyzed with receiver operating characteristic (ROC) curves. RESULTS: We found a positive correlation between tumor stage and MAPK1 expression (P-value: 0.029) in BCa. Likewise, MAPK1 expression was significantly associated with lymph node metastasis (P-value: 0.018). There was a significant difference in the expression of MAPK1 mRNA between tumor and marginal cells of BCa and BRCA (P-value < 0.001). However, we did not find any statistically significant difference in MAPK1 promoter methylation between tumor and marginal cells of both BCa and BRCA. With an area under the curve (AUC) of 0.71, the diagnostic accuracy of MAPK1 expression in BCa and BRCA was validated. However, MAPK1 promoter methylation was not found to be a suitable biomarker. CONCLUSION: Our findings suggest that while MAPK1 expression, might be a promising biomarker for evaluating oncogenic activity in patients suspected of BCa. We were not able to detect a prognostic/diagnostic role for MAPK1 promoter methylation.

Association of Promoter Methylation Patterns with Expression of MAPK14 in Tissue of Papillary Thyroid Cancer Patients.

BACKGROUND: Thyroid cancer is one of the most prevalent malignancies worldwide. Genetic and epigenetic alterations are one of the main causes of thyroid tumor that is responsible to the activation of oncogenes as well as the inactivation of tumor suppressor genes. This research aimed to investigate the relationship of promoter methylation patterns with the expression of P38α in Iranian patients with thyroid cancer. METHODS: We collected 40 thyroid tumor samples and 40 adjacent normal thyroid samples from 40 Iranian patients with papillary thyroid cancer. The promoter methylation pattern of P38α gene was investigated by methylation-sensitive high-resolution melting (MS-HRM) method. Moreover, mRNA expression of P38α was investigated by Real-Time PCR method. Further validation of the obtained results was performed by the Cancer Genome Atlas (TCGA) dataset. RESULTS: The obtained results indicated that the expression of the P38α (MAPK-14) gene in the thyroid cancer sample was considerably higher than tumor margin sample. Also, P38α gene promoter methylation was higher in thyroid margin tissue as compared to tumor tissue. These results were additionally confirmed by TCGA analysis. The receiver operating characteristic (ROC) curve analysis showed a high accuracy of P38α gene expression as a diagnostic biomarker for thyroid malignancy. CONCLUSION: Our study demonstrated that the P38α expression level gene was associated with thyroid cancer pathogenesis among the Iranian population. We suggested that this gene expression might be used as a biomarker for diagnosis of thyroid tumor.

Salivary Lipids of Patients with Non-Small Cell Lung Cancer Show Perturbation with Respect to Plasma.

A comprehensive lipid profile was analyzed in patients with non-small cell lung cancer (NSCLC) using nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. This study investigated 297 and 202 lipids in saliva and plasma samples, respectively, comparing NSCLC patients to healthy controls. Lipids with significant changes (>2-fold, p < 0.05) were further analyzed in each sample type. Both saliva and plasma exhibited similar lipid alteration patterns in NSCLC, but saliva showed more pronounced changes. Total triglycerides (TGs) increased (>2-3-fold) in plasma and saliva samples. Three specific TGs (50:2, 52:5, and 54:6) were significantly increased in NSCLC for both sample types. A common ceramide species (d18:1/24:0) and phosphatidylinositol 38:4 decreased in both plasma and saliva by approximately two-fold. Phosphatidylserine 36:1 was selectively detected in saliva and showed a subsequent decrease, making it a potential biomarker for predicting lung cancer. We identified 27 salivary and 10 plasma lipids as candidate markers for NSCLC through statistical evaluations. Moreover, this study highlights the potential of saliva in understanding changes in lipid metabolism associated with NSCLC.

Evaluation of Expression Levels of NFATc2 and PPARG Genes Two Effector Elements of WNT Pathway in Non-Small Cell Lung Carcinoma.

Background: There is an emergency need in discovering an efficient profile of molecular biomarkers for early diagnosis of Non-small cell lung cancer (NSCLC). Transcription factors as important groups of regulators that are able to adjust the cell cycles have attracted the attention of most researchers recently. NFATc2 and PPARG are two important factors that have been selected for this project to assess their potential for being a biomarker for NSCLC. Materials and Methods: Here in this study, 50 NSCLC patients were included. During bronchoscopy, which was their routine diagnostic approach, we collected tumoral and marginal normal tissues. After the extraction of the total RNA from the tissues, cDNA was synthesized, and the transcriptional level of NFATc2 and PPARG was examined by quantitative real-time PCR. Subsequently, the data were analyzed by proper statistical analyses. Results: The mRNA expression of NFATc2 and PPARG were down-regulated in biopsy tissues of NSCLC patients compared with their pair marginal tissues (Pvalues were 0.0011 and <0.0001 respectively). Moreover, both of them had significant AUC (area under the curve) in the ROC curve analysis (0.65 for NFATc2 and 0.81 for PPARG, Pvalue <0.05). Conclusion: It appears that mRNA expression of NFATc2 and PPARG possesses the potential to be regarded as a diagnostic or prognostic biomarker for NSCLC.

Knowledge of diagnosis and management of selected oral mucosal lesions among dentists in The Netherlands

Background: Knowledge of oral mucosal lesions (OMLs) among dentists is relevant in diagnosing potentially malignant diseases and oral cancer at an early stage. The aim of this survey was to explore dentists' knowledge about OMLs. Material and methods: Respondents to a web-based questionnaire, containing 11 clinical vignettes representing patients with various OMLs, provided a (differential) diagnosis and management for each. Information about demographics and clinical experience of the participants was acquired as well. Descriptive statistics were performed and T-tests were used to test for significant (p<0.05) differences in mean scores for correct diagnosis and management between subgroups based on demographic variables. Results: Forty-four of 500 invited dentists completed the questionnaire. For (potentially) malignant OMLs, the number of correct diagnoses ranged from 14 to 93%, whilst the number of correct management decisions ranged from 43 to 86%. For benign OMLs, the number of correct diagnoses and management decisions ranged from 32 to 100% and 9 to 48%, respectively. For 11 clinical vignettes, mean scores for correct diagnosis, correct management and correct diagnosis and management were respectively 7.2 (±1.8), 5.7 (±1.5), and 3.8 (±1.7). Conclusions: The results show that dentists in the Netherlands do not have sufficient knowledge to accurately diagnose some OMLs and to select a correct management. This may result in over-referral of benign OMLs and under-referral for (potentially) malignant OMLs. Clinical guidelines, that include standardized criteria for referral, and continuing education, may improve dentists' ability to correctly diagnose and accurately manage OMLs. (AU)

The Epigenetic Contribution to the Pathogenesis of Psoriasis: Recent Advances.

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.

Down-regulation and Clinic-pathological Correlation of SIK-1 and SIK-1-LNC in Non-small Cell Lung Cancer Patients

BACKGROUND: Non-small-cell lung cancer (NSCLC) is currently the leading cause of mortality cancer. Introducing noninvasive approaches to diagnose NSCLC, especially at an early phase, might improve the disease's prognosis. Long noncoding RNAs (lncRNAs), which are important regulators of the expression genes inside the cells, have been linked to a range of biological processes, such as cancer progression and metastasis, including NSCLC. The present work aims to determine the potential involvement of SIK-1-LNC and SIK-1 in NSCLC pathogenesis and the possible use of these molecules as novel biomarkers or therapeutic targets. METHODS: In this work, the expression levels of SIK-1-LNC and SIK-1 in 50 pairs of NSCLC tumor and tumor marginal tissues were evaluated. So, after total RNA extraction and complementary DNA synthesis, the SIK-1-LNC and SIK-1 expression levels were evaluated by real-time PCR. In the study groups, clinical and pathological characteristics of the NSCLC patients were also examined. RESULTS: Our findings showed that tumor samples had much lower levels of SIK-1 and SIK-1-LNC expression than tumor margin samples. SIK-1-LNC expression was correlated with SIK-1 levels in NSCLC samples. Interestingly, both stage and lymph node metastasis features of the tumor were associated significantly with SIK-1 and SIK-1-LNC expression levels. A ROC curve analysis indicated a biomarker index of 0.69 and 0.74 for SIK-1 and SIK-1-LNC, respectively. CONCLUSION: Collectively, our study emphasized the role of SIK-1-LNC and SIK-1 downregulation in NSCLC oncogenesis. Additionally, SIK-1 and SIK-1-LNC, particularly the latter, have shown remarkable potential to be utilized as new NSCLC biomarkers and therapeutic targets.

Profiling of circRNA expressions in radiation-treated head and neck cancer cells and the potential role of circPVT1.

OBJECTIVE: Radiotherapy is an indispensable treatment modality for head and neck cancers (HNCs). Due to their stable structure, circular RNAs (circRNA) have been implicated as potential biomarkers for clinical use in cancers. The purpose of this study was profiling the circRNA in radiation-treated head and neck cancer cells to identify potential differentially expressed circRNAs. DESIGN: The effects of radiation on the expression level of circRNAs were investigated in HNCs cells, compared to healthy cell lines. To predict the potential role of circRNAs in HNC patients, tissue expression levels, survival analyses of circRNAs, and circRNA-miRNA network were evaluated using TCGA/CPTAC datasets. Based on expression level in irradiated cells, circPVT1 (plasmacytoma variant translocation 1) was further investigated by sequence analysis. RESULTS: The study revealed the characterization of differentially expressed circRNAs in cancer cells and that irradiation made significant changes in the expression of circRNAs. These findings suggest that certain circRNAs, especially circPVT1, may be potential biomarkers to monitor radiotherapy effects in patients with HNCs. CONCLUSIONS: CircRNAs may be promising molecules for improving and understanding radiotherapy efficacy in HNCs.

Multiple function of lncRNA MALAT1 in cancer occurrence and progression.

Long non-coding RNAs (lncRNAs) have received particular attention in the last decade due to its engaging in carcinogenesis and tumorigenesis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA that plays physiological and pathological roles in many aspects of genome function as well as biological processes involved in cell development, differentiation, proliferation, invasion, and migration. In this article, we will review the effects of lncRNA MALAT1 on the progression of six prevalent human cancers by focusing on MALAT1 ability to regulate post-transcriptional modification and signaling pathways.

MicroRNA-Based Biomarkers in Lung Cancer: Recent Advances and Potential Applications.

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. MATERIALS 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.

Promoter methylation levels of RASSF1 and ATIC genes are associated with lung cancer in Iranian patients.

OBJECTIVES: Epigenetic alterations like methylation of tumor suppressor genes or oncogenes, in respiratory epithelium have been associated with lung cancer. Hypermethylation of genes promoter is an epigenetic event, and is responsible to tumor suppressor genes inactivation as well as oncogenes activation. This study aimed to assess the role of methylation status in promoter of RASSF1 and ATIC genes their potential implication in the pathogenesis of lung tumor in Iranian patients. METHODS: In this study, we collected 100 tissue samples (50 lung cancer tissues and 50 adjacent non-cancerous lung tissues) from Iranian lung cancer patients. The genomic DNA was extracted, and methylation status of both RASSF1 and ATIC genes was investigated by methylation-sensitive high-resolution melting (MS-HRM) assay technique and Real-Time PCR. Cancer Genome Atlas (TCGA) dataset was also analyzed for further validation of the gene's methylation. RESULTS: Methylation of RASSF1 gene promoter was significantly higher in lung tumor tissues. However, promoter methylation levels of ATIC gene was significantly lower in lung tumor tissues. These results were additionally confirmed by TCGA analysis. Promoter methylation of both RASSF1 and ATIC genes was significantly associated with lymph node metastasis, and clinical stage of lung cancer. The receiver operating characteristic (ROC) curve analysis indicated a high accuracy of promoter methylation in these genes as a diagnostic biomarker for lung cancer. CONCLUSIONS: Methylation levels of both RASSF1 and ATIC genes promoters were associated with lung cancer pathogenesis in Iranian population, and may be a suitable biomarker for diagnosis and prognosis of lung cancer in early stage of tumorigenesis.

MicroRNAs expression in peripheral blood mononuclear cells of patients with multiple sclerosis propose.

BACKGROUND: MicroRNAs (miRs) are involved in the autoimmune and neurological diseases, including multiple sclerosis (MS), through modulating post-transcriptional gene regulation. Accumulating evidence indicates that miR-10, miR-24a, miR-124, and miR-21 play an imperative role in MS pathogenesis. Therefore, the current research aimed to analyze the expression of the selected miRNAs for MS in Iranian population. METHODS AND RESULTS: Blood sample of 75 relapsing-remitting MS (RRMS) patients and 75 healthy individuals suffering no neurodegenerative illness was collected. Subsequently, the isolation of peripheral blood mononuclear cells (PBMCs) was performed by employing Ficoll-Hypaque density gradient method. Afterward, total RNA was extracted and subjected to qRT-PCR analysis. The obtained results evidenced that the relative expression of miR-10 (P = 0.0002), miR-21 (P = 0.0014), and miR-124 (P = 0.0091) significantly decreased in RRMS patients compared to healthy participants. On the contrary, no notable change was observed between the studies groups regarding miR-24a expression levels (P = 0.107). ROC curve analysis estimated an area under the curve (AUC) value equal to 0.75 with P = 0.0006 for miR-10, while it was decreased for miR-21 (AUC = 0.67 and P = 0.0054) and miR-124 (AUC = 0.66 and P = 0.012). CONCLUSION: The change in miR-10, miR-124, and miR-21 expression patterns was implied to participate in MS development. Further large scale observational studies are recommended.

Suppression of the malignancy of mammary tumor in mice model by inactivated preparation of Mycobacterium obuense.

Breast cancer (BC) is a significant cause of global mortality in women. This study was aimed to evaluate the immune-activation of malignant BC via the administration of attenuated Mycobacterium obuense. For this purpose, an in vivo model was developed with BALB/c mice. Mice were injected with 2.00 × 106 4T1 cells with breast tumor cell line. Forty-two mice were equally divided into control as well as low dose (0.20 mg 100 µL-1) and high dose (0.50 mg 100 µL-1) groups of M. obuense to investigate gene expression in the antitumor effects of M. obuense. In one group, paclitaxel was administrated as a choice drug in BC treatment. Antitumor manners were characterized by cytotoxicity against tumor target cells, size of the tumor and the expression of some BC metastatic genes together with pathology. The MTT assay demonstrated that different concentrations of both low and a high dose of bacteria did present no cytotoxicity effect on 4T1 cells. According to our findings, M. obuense significantly repressed tumor growth. M. obuense downregulated the expression of collagen type I alpha 1 (COLIA1), cFos, alkaline phosphatase (ALP), claudin 3 (cldn3), and conversely, activated transcription factor 4 (ATF4) and Twist related protein-1 (Twist1). All these alternations induced a decrease in the migratory and invasive capabilities of BC. The result of pathology was indicative of tumor regression in the paclitaxel and HK- M. obuense -recipient group. Thus, it seems most likely that M. obuense might impinge upon cell growth and metastatic behavior of malignant cells exerting anti-tumor activity in BC.

Association between miRNA-145 and miRNA-155 expression in peripheral blood mononuclear cells of patients with multiple sclerosis: a case-control study.

INTRODUCTION: MicroRNAs (miR or miRNA) are short regulatory RNAs, which modulate post-transcriptional gene expression. Dysregulation of these molecules contributes to pathogenicity of autoimmune disorders, such as multiple sclerosis (MS). AIMS: This study was conducted to investigate changed expression pattern of miRNA-145 and miRNA-155 in MS. METHODS: We collected blood samples of 75 patients with relapsing-remitting MS patients and 75 healthy controls. Ficoll-Hypaque density gradient method was used to isolate peripheral blood mononuclear cells. Also, total RNA was extracted and subjected to RT-PCR analysis. We used the Mann-Whitney U test to evaluate the differences in expression levels of target miRNAs between the groups. RESULTS: We found that expression of miRNA-145 (P = 0.012) and miRNA-155 (P = 0.005) were partly reduced in patients with relapse-remitting MS in comparison with healthy controls. The miRNA-145 had an area under curve (AUC) of 0.621 (P = 0.01) and miRNA-155 levels had an AUC of 0.625 (P = 0.008). CONCLUSION: Decreased expression of miRNA-145 and miRNA-155 contributes to development of relapse-remitting MS, while further large scale observational studies and meta-analyses are required.