MicroRNA-1 Inhibits the Growth of Breast Cancer Cells MDA-MB-231 and MCF-7 Treated with Hydatid Cyst Fluid.

Antigens in hydatid cyst fluid (HCF) have been discovered to bear a significant resemblance to antigens present in cancer cells. MicroRNA-1 (miR-1) is a well-known member of the tumor inhibitor miRNA family and has been shown to have pro-apoptotic and tumor-inhibitory functions. This study aimed to evaluate the ability of HCF to prevent breast cancer and to explore the underlying mechanisms that affect cancer cells. For this study, MDA-MB-231 and MCF-7 breast cancer cells were cultured and divided into two groups: one group received HCF treatment and the other group was untreated and served as the control group. The cytotoxicity and cell viability of various HCF concentrations on breast cancer cells were evaluated using the MTT assay. In addition, the expression level of miR-1 in HCF-treated and untreated breast cancer cells was analyzed using qRT-PCR. The study found that HCF treatment reduced the growth of MDA-MB-231 and MCF-7 breast cancer cells, indicating that it was cytotoxic to the cells. Specifically, the IC50 concentration of HCF after 24 hours of treatment was 7.32 µg/mL for MDA-MB-231 cells and 13.63 µg/mL for MCF-7 cells. In addition, qRT-PCR analysis revealed that the expression level of miR-1 was significantly increased in HCF-treated MDA-MB-231 (P=0.0203) and MCF-7 (P=0.0394) cell lines compared to untreated controls. Although HCF has been shown to inhibit the growth of breast cancer cells and to upregulate miR-1, a key tumor suppressor in cancer cells, the specific mechanisms responsible for this effect remain unclear. Further studies are needed to fully understand the molecular pathways underlying HCF's antitumor activity and its potential as a therapeutic agent in cancer therapy.

Exploring the dynamic interplay between exosomes and the immune tumor microenvironment: implications for breast cancer progression and therapeutic strategies.

Breast cancer continues to pose a substantial worldwide health concern, demanding a thorough comprehension of the complex interaction between cancerous cells and the immune system. Recent studies have shown the significant function of exosomes in facilitating intercellular communication and their participation in the advancement of cancer. Tumor-derived exosomes have been identified as significant regulators in the context of breast cancer, playing a crucial role in modulating immune cell activity and contributing to the advancement of the illness. This study aims to investigate the many effects of tumor-derived exosomes on immune cells in the setting of breast cancer. Specifically, we will examine their role in influencing immune cell polarization, facilitating immunological evasion, and modifying the tumor microenvironment. Furthermore, we explore the nascent domain of exosomes produced from immune cells and their prospective involvement in the prevention of breast cancer. This paper focuses on new research that emphasizes the immunomodulatory characteristics of exosomes produced from immune cells. It also explores the possibility of these exosomes as therapeutic agents or biomarkers for the early identification and prevention of breast cancer. The exploration of the reciprocal connections between exosomes formed from tumors and immune cells, together with the rising significance of exosomes derived from immune cells, presents a potential avenue for the advancement of novel approaches in the field of breast cancer therapy and prevention.

siRNA-mediated downregulation of BATF3 diminished proliferation and induced apoptosis through downregulating c-Myc expression in chronic myelogenous leukemia cells.

OBJECTIVE: Despite considerable improvement in therapeutic approaches to chronic myeloid leukemia (CML) treatment, this malignancy is considered incurable due to resistance. However, investigating the molecular mechanism of CML may give rise to the development of extremely efficient targeted therapies that improve the prognosis of patients. Basic leucine zipper transcription factor ATF-like3 (BATF3), as transcription factor, is considered a key regulator of cellular activities and its function has been evaluated in tumor development and growth in several cancer types. This study aimed to evaluate the potential of the cellular impact of siRNA-mediated downregulation of BATF3 on CML cancer cells through cell proliferation, induction of apoptosis, and cell cycle distribution. MATERIALS AND METHODS: The transfection of BATF3 siRNA to K562 CML cells was performed by electroporation device. To measure cellular viability and apoptosis, MTT assay and Annexin V/PI staining were carried out, respectively. Also, cell cycle assay and flow cytometry instrument were applied to assess cell cycle distribution of K562 cells. For more validation, mRNA expression of correlated genes was relatively evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The data indicated that siRNA-mediated BATF3 inactivating severely promoted the cell apoptosis. Also, the targeted therapy led to high expression of Caspase-3 gene and Bax/Bcl-2 ratio. Silenced BATF3 also induced cell cycle arrest in phase sub-G1 compared to control. Finally, a noticeable decrement was obtained in c-Myc gene expression through suppression of BATF3 in CML cells. CONCLUSION: The findings of this research illustrated the suppression of BATF3 as an effective targeted therapy strategy for CML.

The Effects of Remdesivir and Dexamethasone on Renal Sirtuin-1 Expression and Renal Function in Male Rats.

Remdesivir (REM) and dexamethasone (DEX) both have been used to treat coronavirus disease 2019 (COVID-19). The present study aimed to evaluate the effects of REM and DEX on kidney structure and function with particular focus on the probable renal sirtuin-1 (SIRT1) expression alteration in rats. Twenty-four male Wistar rats were divided into four groups, as follows: group A (control) received normal saline (5 mL/kg/day for 10 days); group B (REM) received REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days); group C (REM + DEX) received both REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days) and DEX (7 mg/kg/day, for 10 days); group D (DEX) received DEX (7 mg/kg/day for 10 days). Renal SIRT1 expression and kidney structure and function-related factors were evaluated by standard methods. The mean levels of urea in the REM + DEX group (60.83 ± 6.77, mg/dL) were significantly higher than in the control (48.33 ± 3.01, mg/dL; p = 0.002) and DEX (51.22 ± 4.99, mg/dL; p = 0.018) groups. The mean levels of creatinine in the REM (0.48 ± 0.08, mg/dL) and REM + DEX (0.50 ± 0.04, mg/dL) groups were higher than in the control group (48.33 ± 3.0 mg/dL) significantly (p = 0.022 and p = 0.010, respectively). The renal SIRT1 expression was significantly (p = 0.018) lower in the REM + DEX group (0.36 ± 0.35) than in the control group (1.34 ± 0.48). Tubulointerstitial damage (TID) scores in REM + DEX-treated rats (2.60 ± 0.24) were significantly higher than in the control (0.17 ± 0.17, p = 0.001) and DEX (0.50 ± 0.29, p = 0.005) groups. The administration of DEX and REM might lead to kidney injury associated with SIRT1 downregulation.

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.

VISTA and its ligands: the next generation of promising therapeutic targets in immunotherapy.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel negative checkpoint receptor (NCR) primarily involved in maintaining immune tolerance. It has a role in the pathogenesis of autoimmune disorders and cancer and has shown promising results as a therapeutic target. However, there is still some ambiguity regarding the ligands of VISTA and their interactions with each other. While V-Set and Immunoglobulin domain containing 3 (VSIG-3) and P-selectin glycoprotein ligand-1(PSGL-1) have been extensively studied as ligands for VISTA, the others have received less attention. It seems that investigating VISTA ligands, reviewing their functions and roles, as well as outcomes related to their interactions, may allow an understanding of their full functionality and effects within the cell or the microenvironment. It could also help discover alternative approaches to target the VISTA pathway without causing related side effects. In this regard, we summarize current evidence about VISTA, its related ligands, their interactions and effects, as well as their preclinical and clinical targeting agents.

Strategies for modifying the chimeric antigen receptor (CAR) to improve safety and reduce toxicity in CAR T cell therapy for cancer.

Immune cell therapy with chimeric antigen receptor (CAR) T cells, which has shown promising efficacy in patients with some hematologic malignancies, has introduced several successfully approved CAR T cell therapy products. Nevertheless, despite significant advances, treatment with these products has major challenges regarding potential toxicity and sometimes fatal adverse effects for patients. These toxicities can result from cytokine release or on-target off-tumor toxicity that targets healthy host tissue following CAR T cell therapy. The present study focuses on the unexpected side effects of targeting normal host tissues with off-target toxicity. Also, recent safety strategies such as replacing or adding different components to CARs and redesigning CAR structures to eliminate the toxic impact of CAR T cells, including T cell antigen coupler (TAC), switch molecules, suicide genes, and humanized monoclonal antibodies in the design of CARs, are discussed in this review.

The cross-talk between leptin and circadian rhythm signaling proteins in physiological processes: a systematic review.

BACKGROUND: Today, modern lifestyles and disrupted sleep patterns cause circadian clock rhythm impairments that are associated with altered leptin levels, which subsequently affect a wide range of physiological processes and have significant health burdens on societies. Nevertheless, there has been no systematic review of circadian clock genes and proteins, leptin, and 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 Google Scholar until September 2022. After considering the inclusion and exclusion criteria, 20 animal studies were selected. The risk of bias was assessed in each study. RESULTS: The results clarified the reciprocal interconnected relationship between circadian clock genes and leptin. Circadian clock genes regulate leptin expression and signaling via different mechanisms, such as CLOCK-BMAL1 heterodimers, which increase the expression of PPARs. PPARs induce the expression of C/EBPα, a key factor in upregulating leptin expression. CLOCK-BMAL1 also induces the expression of Per1 and Rev-erb genes. PER1 activates mTORC1 and mTORC1 enhances the expression of C/EBPα. In addition, REV-ERBs activate the leptin signaling pathway. Also, leptin controls the expression of circadian clock genes by triggering the AMPK and ERK/MAPK signaling pathways, which regulate the activity of PPARs. Moreover, the roles of these molecular mechanisms are elucidated in different physiological processes and organs. CONCLUSIONS: Crosstalk between circadian clock genes and leptin and their affecting elements should be considered in the selection of new therapeutic targets for related disorders, especially obesity and metabolic impairments.

Characterization of CAR T Cells Manufactured Using Genetically Engineered Artificial Antigen Presenting Cells.

OBJECTIVE: Chimeric antigen receptor (CAR) T cell therapy has recently emerged as a promising approach for the treatment of different types of cancer. Improving CAR T cell manufacturing in terms of costs and product quality is an important concern for expanding the accessibility of this therapy. One proposed strategy for improving T cell expansion is to use genetically engineered artificial antigen presenting cells (aAPC) expressing a membrane-bound anti-CD3 for T cell activation. The aim of this study was to characterize CAR T cells generated using this aAPC-mediated approach in terms of expansion efficiency, immunophenotype, and cytotoxicity. MATERIALS AND METHODS: In this experimental study, we generated an aAPC line by engineering K562 cells to express a membrane-bound anti-CD3 (mOKT3). T cell activation was performed by co-culturing PBMCs with either mitomycin C-treated aAPCs or surface-immobilized anti-CD3 and anti-CD28 antibodies. Untransduced and CD19-CARtransduced T cells were characterized in terms of expansion, activation markers, interferon gamma (IFN-γ) secretion, CD4/CD8 ratio, memory phenotype, and exhaustion markers. Cytotoxicity of CD19-CAR T cells generated by aAPCs and antibodies were also investigated using a bioluminescence-based co-culture assay. RESULTS: Our findings showed that the engineered aAPC line has the potential to expand CAR T cells similar to that using the antibody-based method. Although activation with aAPCs leads to a higher ratio of CD8+ and effector memory T cells in the final product, we did not observe a significant difference in IFN-γ secretion, cytotoxic activity or exhaustion between CAR T cells generated with aAPC or antibodies. CONCLUSION: Our results show that despite the differences in the immunophenotypes of aAPC and antibody-based CAR T cells, both methods can be used to manufacture potent CAR T cells. These findings are instrumental for the improvement of the CAR T cell manufacturing process and future applications of aAPC-mediated expansion of CAR T cells.

Optimizing ozone dose and contact time for removal of antibiotic-resistant P. aeruginosa, A. baumannii, E. coli, and associated resistant genes in effluent of an activated sludge process in a municipal WWTP.

This study aimed to investigate the impact of ozonation on inactivation of antibiotic-resistant bacteria (ARB) including E. coli, P. aeruginosa, and A. baumannii, as well as on removal of 16S-rRNA gene and their associated antibiotic-resistant genes (ARGs) indigenously present in effluent of municipal wastewater treatment plant. The Chick-Watson model was used to describe bacterial inactivation rates at specific ozone doses. Maximum reduction of total cultivable A. baumannii, E. coli, and P. aeruginosa were found to be 7.6, 7.1, and 4.7 log, respectively, with the highest ozone dose of 0.48 gO3/gCOD at 12 min contact time. According to the study results, complete inactivation of ARB and bacterial regrowth was not observed after 72 h incubation. The culture methods overestimated the performance of disinfection processes and propidium monoazide combined with qPCR, and showed the presence of viable but non-culturable bacteria after ozonation. ARGs were more persistent to ozone than ARB. The results of this study highlighted the significance of specific ozone dose and contact time in ozonation process considering the bacterial species and associated ARGs as well as the wastewater physicochemical characteristics, in order to help diminish the entrance of the biological microcontaminants into the environment.

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.

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.

Dietary glycemic index and glycemic load mediate the effect of CARTPT rs2239670 gene polymorphism on metabolic syndrome and metabolic risk factors among adults with obesity.

INTRODUCTION: The importance of genetic and dietary factors in occurrence and progression of chronic diseases such as metabolic syndrome (MetS) has been established. However, complex interrelationships, including direct and indirect effects of these variables are yet to be clarified. So, our aim was to investigate the mediating role of glycemic indices in the relationship between CARTPT rs2239670 polymorphism, socio-demographic and psychological factors and metabolic risk factors and the presence of MetS in adults with obesity. METHODS: In a cross-sectional study of 288 apparently healthy adults with obesity aged 20-50 years, dietary glycemic index (GI) and glycemic load (GL) were measured using a validated semi-quantitative food frequency questionnaire (FFQ). Biochemical parameters, blood pressure and anthropometric indicators were assayed by standard methods. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Structural equation modeling (SEM) was used in the statistical analysis. RESULTS: CARTPT rs2239670 had a positive direct effect on MetS (B = 0.037 ± 0.022; P = 0.043) and, on the other hand, this variant was found to be indirectly associated with MetS presence through mediation of GI (B = 0.039 ± 0.017; P = 0.009). CARTPT was a significant predictor of both dietary GI and GL (B = 1.647 ± 0.080 and B = 3.339 ± 0.242, respectively). Additionally, glycemic indicators appeared to mediate the association of age and gender with LDL-C (B = 0.917 ± 0.332; P = 0.006) and HDL (B = 1.047 ± 0.484; P = 0.031), respectively. GI showed a positive relationship with LDL-C (P = 0.024) in men and similar relationships were found between GL and LDL-C (P = 0.050) and cholesterol (P = 0.022) levels in women. CONCLUSION: The SEM findings suggest a hypothesis of the mediating effect of glycemic indices in the relationship between genetic susceptibility to obesity and MetS presence. Our findings need to be confirmed with large prospective studies.

The production of the first functional antibody mimetic in higher plants: the chloroplast makes the DARPin G3 for HER2 imaging in oncology.

BACKGROUND: Designed mimetic molecules are attractive tools in biopharmaceuticals and synthetic biology. They require mass and functional production for the assessment of upcoming challenges in the near future. The DARPin family is considered a mimetic pharmaceutical peptide group with high affinity binding to specific targets. DARPin G3 is designed to bind to the HER2 (human epidermal growth factor receptor 2) tyrosine kinase receptor. Overexpression of HER2 is common in some cancers, including breast cancer, and can be used as a prognostic and predictive tool for cancer. The chloroplasts are cost-effective alternatives, equal to, and sometimes better than, bacterial, yeast, or mammalian expression systems. This research examined the possibility of the production of the first antibody mimetic, DARPin G3, in tobacco chloroplasts for HER2 imaging in oncology. RESULTS: The chloroplast specific DARPin G3 expression cassette was constructed and transformed into N. tabacum chloroplasts. PCR and Southern blot analysis confirmed integration of transgenes as well as chloroplastic and cellular homoplasmy. The Western blot analysis and ELISA confirmed the production of DARPin G3 at the commercial scale and high dose with the rate of 20.2% in leaf TSP and 33.7% in chloroplast TSP. The functional analysis by ELISA confirmed the binding of IMAC purified chloroplast-made DARPin G3 to the extracellular domain of the HER2 receptor with highly effective picomolar affinities. The carcinoma cellular studies by flow cytometry and immunofluorescence microscopy confirmed the correct functioning by the specific binding of the chloroplast-made DARPin G3 to the HER2 receptor on the surface of HER2-positive cancer cell lines. CONCLUSION: The efficient functional bioactive production of DARPin G3 in chloroplasts led us to introduce plant chloroplasts as the site of efficient production of the first antibody mimetic molecules. This report, as the first case of the cost-effective production of mimetic molecules, enables researchers in pharmaceuticals, synthetic biology, and bio-molecular engineering to develop tool boxes by producing new molecular substitutes for diverse purposes.

Exosome application in treatment and diagnosis of B-cell disorders: leukemias, multiple sclerosis, and arthritis rheumatoid.

Exosomes, known as a type of extracellular vesicles (EVs), are lipid particles comprising heterogeneous contents such as nucleic acids, proteins, and DNA. These bi-layered particles are naturally released into the extracellular periphery by a variety of cells such as neoplastic cells. Given that exosomes have unique properties, they can be used as vectors and carriers of biological and medicinal particles like drugs for delivering to the desired areas. The proteins and RNAs being encompassed by the circulating exosomes in B-cell malignancies are deemed as the promising sources for diagnostic and prognostic biomarkers, as well as therapeutic agents. Exosomes can also provide a "snapshot" view of the tumor and metastatic landscape at any particular time. Further, clinical research has shown that exosomes are produced by immune cells such as dendritic cells can stimulate the immune system, so these exosomes can be used in antitumor vaccines. Despite the great potential of exosomes in the fields of diagnostic and treatment, further studies are in need for these purposes to reach a convergence notion. This review highlights the applications of exosomes in multiple immune-related diseases, including chronic lymphocytic leukemia, multiple sclerosis, and arthritis rheumatoid, as well as explaining sundry aspects of exosome therapy and the function of exosomes in diagnosing diseases.

Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis.

OBJECTIVES: The aim of this study was to investigate the effects of curcumin on the viability, migration, and apoptosis of A549 lung cancer cells. Furthermore, RECK/MMPs axis as a probable regulator of cancer cell migration was assessed. METHODS: In this study, effect of curcumin on viability changes, cell migration, and percentage of apoptosis of A549 non-small cell lung carcinoma was examined. The methylation status of RECK gene was investigated using MS-HRM technique. Moreover, expression changes of genes involved in apoptosis and migration (including CASP3, CASP8, CASP9, BAX, BCL2, MMP9, MMP2, and RECK) were investigated by quantitative Real-Time PCR. RESULTS: The results of MTT assay showed that the cytotoxic effect of curcumin was in a dose dependent manner. Flow cytometry results demonstrated a significant increase in the percentage of apoptotic cells in curcumin treated group. In addition, curcumin inhibited migration rate in lung cancer cells. qRT-PCR revealed that expression of the candidate genes was in line with suppressed growth and migration. This could be due to, decreased methylation of the RECK gene promoter after curcumin treatment. CONCLUSIONS: Curcumin inhibited lung cancer cells through various molecular pathways. RECK/MMPs axis as a regulator of cancer cell migration was modulated after curcumin treatment and invasion of lung cancer cells was decreased.

Evaluation of a human gut-associated phage and gut dominant microbial phyla in the metabolic syndrome.

BACKGROUND & AIMS: Metabolic syndrome (MetS) is an expanding public health problem worldwide and is reasoned one of the risk factors of cardiovascular disease. Recent evidence suggests that dysbiosis of the gut microbiota may play an essential role in metabolic disorders. The objective of this study was to assess the differences in the two gut dominant phyla and a gut-associated phage between MetS and healthy control subjects. METHODS: The study included 60 subjects among whom 30 were MetS, and 30 were healthy control subjects. The entire studied group was subjected to clinical, laboratory assessment, and anthropometric evaluation. Stool samples were collected from both MetS and healthy control subjects. The Firmicutes, Bacteroidetes, and crAssphage were assessed by quantitative PCR (qPCR). RESULTS: The MetS group had significantly higher body mass index, fasting plasma glucose, triglyceride, and waist circumference were compared with healthy controls (Pv < 0.05). The relative abundance of the Firmicutes phyla and crAssphage were high in the MetS group and only crAssphage were statistically significantly high in the MetS group compared to the healthy controls (Pv < 0.05). The quantity of Bacteroidetes phyla was low in the MetS group compared to the healthy controls, though there were no significant differences between the two groups (Pv > 0.05). CONCLUSION: The results of this study indicate that adults with MetS have a different gut microbial composition in comparison to healthy controls. This could be probably considered when creating approaches to control MetS by modifying the gut microbiota.

Thymoquinone Potentiates Methotrexate Mediated-Apoptosis in Saos-2 Osteosarcoma Cell Line.

INTRODUCTION: Recently, various studies have concentrated on the therapeutic potential of thymoquinone (TQ), a natural polyphenol, in various human malignancies, including osteosarcoma. However, the underlying mechanisms in TQ-mediated anti-cancer effects are not yet fully understood. Therefore, the present study investigated the effect of TQ on methotrexate (MTX)-induced apoptosis in Saos-2 cells. METHODS: Saos-2 cells were treated with MTX, TQ, and a combination of both, and cell viability was assessed by MTT assay. mRNA expression of apoptotic markers, including Bax, Bcl-2, and caspase-3, was assessed using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: MTX resulted in significant inhibition of cell proliferation in a dose-dependent manner. The combination of TQ and MTX inhibited proliferation compared to single treatments (P<0.05). TQ also induced apoptosis by regulating pro-apoptotic markers including Bax and caspase-3 and reducing anti-apoptotic mediators including Bcl-2. In addition, TQ increased MTX-induced apoptosis in Saos-2 cells. CONCLUSION: The findings of the present study highlight new insights into understanding the role of TQ as a potential therapeutic agent in osteosarcoma by increasing MTX-induced apoptosis.