Autophagy in cancers including brain tumors: role of MicroRNAs

Autophagy has a crucial role in many cancers, including brain tumors. Several types of endogenous molecules (e.g. microRNAs, AKT, PTEN, p53, EGFR, and NF1) can modulate the process of autophagy. Recently miRNAs (small non-coding RNAs) have been found to play a vital role in the regulation of different cellular and molecular processes, such as autophagy. Deregulation of these molecules is associated with the development and progression of different pathological conditions, including brain tumors. It was found that miRNAs are epigenetic regulators, which influence the level of proteins coded by the targeted mRNAs with any modification of the genetic sequences. It has been revealed that various miRNAs (e.g., miR-7-1-3p, miR-340, miR-17, miR-30a, miR-224-3p, and miR-93), as epigenetic regulators, can modulate autophagy pathways within brain tumors. A deeper understanding of the underlying molecular targets of miRNAs, and their function in autophagy pathways could contribute to the development of new treatment methods for patients with brain tumors. In this review, we summarize the various miRNAs, which are involved in regulating autophagy in brain tumors. Moreover, we highlight the role of miRNAs in autophagy-related pathways in different cancers. Video abstract

Circular RNAs and gastrointestinal cancers: Epigenetic regulators with a prognostic and therapeutic role

Both environmental and genetic factors are involved in the initiation and development of gastrointestinal cancer. Covalent closed circular RNAs (circRNAs) are produced by a mechanism called �back-splicing� from mRNAs. They are highly stable and show cell and tissue specific expression patterns. Although some functions such as �microRNA sponge� and �RNA binding protein sponge� have been reported for a small number of circRNAs, the function of thousands of other circRNAs is still unknown. Dysregulation of circRNAs has been reported in many GI cancers and are involved in metastasis and invasion. CircRNAs have been reported to be useful as prognostic markers and targets for developing new treatments. We first describe the properties and biogenesis of circRNAs. We then summarize recent reports about circRNA functions, expression status, and their potential to be used as biomarkers in GI cancers including, gastric cancer, colorectal cancer, esophageal cancer, hepatocellular carcinoma, gallbladder cancer and pancreatic cancer. © 2019 Elsevier B.V

Mesenchymal stem cell-derived exosomes: A new therapeutic approach to osteoarthritis?

Degenerative disorders of joints, especially osteoarthritis (OA), result in persistent pain and disability and high costs to society. Nevertheless, the molecular mechanisms of OA have not yet been fully explained. OA is characterized by destruction of cartilage and loss of extracellular matrix (ECM). It is generally agreed that there is an association between pro-inflammatory cytokines and the development of OA. There is increased expression of matrix metalloproteinase (MMP) and "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS). Mesenchymal stem cells (MSCs) have been explored as a new treatment for OA during the last decade. It has been suggested that paracrine secretion of trophic factors, in which exosomes have a crucial role, contributes to the mechanism of MSC-based treatment of OA. The paracrine secretion of exosomes may play a role in the repair of joint tissue as well as MSC-based treatments for other disorders. Exosomes isolated from various stem cells may contribute to tissue regeneration in the heart, limbs, skin, and other tissues. Recent studies have indicated that exosomes (or similar particles) derived from MSCs may suppress OA development. Herein, for first time, we summarize the recent findings of studies on various exosomes derived from MSCs and their effectiveness in the treatment of OA. Moreover, we highlight the likely mechanisms of actions of exosomes in OA. © 2019 The Author(s)

Non-coding RNAs and Exosomes: Their Role in the Pathogenesis of Sepsis

Non-coding RNAs and exosomes present an opportunity for early diagnosis as well as an ability to interact with key points of the biological mechanisms, suggesting that measurement of non-coding RNAs and exosomes are a promising approach for intensive care patients. © 2020 The Author(s) Sepsis is characterized as an uncontrolled host response to infection, and it represents a serious health challenge, causing excess mortality and morbidity worldwide. The discovery of sepsis-related epigenetic and molecular mechanisms could result in improved diagnostic and therapeutic approaches, leading to a reduced overall risk for affected patients. Accumulating data show that microRNAs, non-coding RNAs, and exosomes could all be considered as novel diagnostic markers for sepsis patients. These biomarkers have been demonstrated to be involved in regulation of sepsis pathophysiology. However, epigenetic modifications have not yet been widely reported in actual clinical settings, and further investigation is required to determine their importance in intensive care patients. Further studies should be carried out to explore tissue-specific or organ-specific epigenetic RNA-based biomarkers and their therapeutic potential in sepsis patients. © 2020 The Author(s

Exosomal miRNAs: Novel players in viral infection

Exosomes are secreted nanovesicles that are able to transfer their cargo (such as miRNAs) between cells. To determine to what extent exosomes and exosomal miRNAs are involved in the pathogenesis, progression and diagnosis of viral infections. The scientific literature (PubMed and Google Scholar) was searched from 1970 to 2019. The complex biogenesis of exosomes and miRNAs was reviewed. Exosomes contain both viral and host miRNAs that can be used as diagnostic biomarkers for viral diseases. Viral proteins can alter miRNAs, and conversely miRNAs can alter the host response to viral infections in a positive or negative manner. It is expected that exosomal miRNAs will be increasingly used for diagnosis, monitoring and even treatment of viral infections. © 2020 Future Medicine Ltd

Bacterial biofilm in colorectal cancer: What is the real mechanism of action?

Human colorectal cancer is the third most common cancer around the world. Colorectal cancer has various risk factors, but current works have bolded a significant activity for the microbiota of the human colon in the development of this disease. Bacterial biofilm has been mediated to non-malignant pathologies like inflammatory bowel disease but has not been fully documented in the setting of colorectal cancer. The investigation has currently found that bacterial biofilm is mediated to colon cancer in the human and linked to the location of human cancer, with almost all right-sided adenomas of colon cancers possessing bacterial biofilm, whilst left-sided cancer is rarely biofilm positive. The profound comprehension of the changes in colorectal cancer can provide interesting novel concepts for anticancer treatments. In this review, we will summarize and examine the new knowledge about the links between colorectal cancer and bacterial biofilm. © 202

Impacts of Forest-Based Activities on Woodland Characteristics in a Forested Watershed of Southern Zagros, Iran

The purpose of this study was to investigate the impacts of forest-based activities on the conditions of the Ganaveh woodland in the southern Zagros, Iran, and to suggest strategies for improving the implementation of forest resource management plans. Woodland inventory data was gathered in 2003, accompanied with data from interviews in 2008, were used in this study. The results show that there is forest degradation in terms of a lack of forest regeneration and a relatively high incidence of bad quality trees. These defects in the woodland attributes reflect the effects of the traditional management on vegetation cover, and are the causes of concern regarding the sustainability and conservation of the woodland. Overgrazing, seed gathering, and drought in some years are probably the main reasons for the poor natural regeneration in the area. Forest activities over the last decades could be the main causes of the relatively high rate of bad quality oak trees and the high rate of oaks in coppice form. Some efforts to gain acceptance from the woodland users for protecting the preserved areas from animal grazing and seed gathering for a period could be a better alternative for woodland rehabilitation than seeding

CFIm25 and alternative polyadenylation: Conflicting roles in cancer

Alternative polyadenylation (APA) is now widely recognized to regulate gene expression. APA is an RNA-processing mechanism that generates distinct 3� termini on mRNAs, producing mRNA isoforms. Different factors influence the initiation and development of this process. CFIm25 (among others) is a cleavage and polyadenylation factor that plays a key role in the regulation of APA. Shortening of the 3�UTRs on mRNAs leads to enhanced cellular proliferation and tumorigenicity. One reason may be the up-regulation of growth promoting factors, such as Cyclin D1. Different studies have reported a dual role of CFIm25 in cancer (both oncogenic and tumor suppressor). microRNAs (miRNAs) may be involved in CFIm25 function as well as competing endogenous RNAs (ceRNAs). The present review focuses on the role of CFIm25 in cancer, cancer treatment, and possible involvement in other human diseases. We highlight the involvement of miRNAs and ceRNAs in the function of CFIm25 to affect gene expression. The lack of understanding of the mechanisms and regulation of CFIm25 and APA has underscored the need for further research regarding their role in cancer and other diseases. © 201

Psychometric properties of the Persian version of the Anesthetic Trainee Theatre Educational Environment Measure (ATEEM)

Background: The quality improvement of medical education programs and the ongoing reform of the curriculum should be done in the light of clinical training fields and identifying the strengths and improving the weaknesses. Therefore, this study was conducted to evaluate the validity and reliability of ATEEM (Anesthetic Trainee Theatre Educational Environment Measure) questionnaire for assessing learning environment of anesthesiology residents in educational centers affiliated to 3 main medical schools in Tehran, Iran. Methods: This study was conducted on first to fourth year anesthesiology residents using a questionnaire. Validity (face, content, construct) and reliability of ATEEM questionnaire was investigated. Construct validity was measured by confirmatory factor analysis, stability of reliability by test-retest, and internal consistency by Cronbach's alpha. Results: A total of 156 questionnaires out of 190 were fully answered, returned by residents of anesthesiology, and analysis were performed (82 response rate; 44.5 male (n=69); 55.5 female (n=86)). The age range of respondents was 26 to 48 years. The mean total ATEEM score was 114.03 out of 160. Face and content validity of the questionnaire was approved. Content validity ratio (CVR) and content validity index (CVI) were 0.63 and 0.88, respectively. Fitness indices in confirmatory factor analysis were greater than 0.9, and RMSEA (root mean square error of approximation) index was less than 0.08 (0.07). This indicator measures the acceptability of fitness and it is an appropriate measurement model. The average reliability coefficient was 0.73 and the overall Cronbach's alpha coefficient was 0.959. Conclusion: The results of this study showed that the Persian version of the ATEEM questionnaire, with appropriate psychometric properties, can be used to evaluate the anesthetic trainee theatre learning environment used in hospitals. © Iran University of Medical Sciences

The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model

Abstract Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis. Keywords: Melanoma Metastasis Human adipose derived mesenchymal stem cells CXCL1