tDCS efficacy and utility of anhedonia and rumination as clinical predictors of response to tDCS in major depressive disorder (MDD).

BACKGROUND: Anhedonia and rumination are mental disorders' transdiagnostic features but remain difficult to treat. Transcranial direct current stimulation (tDCS) is a proven treatment for depression, but its effects on anhedonia and rumination and whether anhedonia and rumination can be used as a predictive biomarker of treatment response is not well known. This study aimed to investigate the tDCS efficacy and identify the predictive role of anhedonia and rumination in response to tDCS in patients with MDD. METHODS: 182 patients received 10 tDCS sessions delivered at 2 mA to left (anode) dorsolateral prefrontal cortex (DLPFC). Hamilton Rating Scale for Depression (HRSD-17), Snaith-Hamilton Pleasure Scale (SHAPS), and the 10-item Ruminative Response Scale (RRS-10) was administered to patients with MDD before treatment, following it, and after two weeks of tDCS. RESULTS: There was an overall significant improvement in anhedonia from pre- to post-treatment. Regression analyses revealed that responders had higher baseline anhedonia and rumination (reflective pondering) scores. We found that the reduction in HRSD scores after tDCS was significantly associated with anhedonia's baseline values while no relation was found between baseline rumination and tDCS treatment response. CONCLUSION: These results provide new evidence that pronounced anhedonia may be a significant clinical predictor of response to tDCS. Patients with severe or low baseline rumination had an equal chance of achieving clinical response. Prospective tDCS studies are necessary to validate the predictive value of the derived model.

Illuminating the role of lncRNAs ROR and MALAT1 in cancer stemness state of anaplastic thyroid cancer: An exploratory study.

Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans that accounts for a considerable rate of cancer-associated mortality. Since conventional therapies are lacking sufficient efficacy, new treatment approaches are required. This goal could be achieved through a better understanding of the molecular pathogenesis of ATC. Thyroid tumorigenesis is initiated by a subpopulation of cells known as cancer stem cells (CSCs) with specific markers such as CD133 that confers to processes such as self-renewal and metastasis. Besides, some long non-coding RNAs (lncRNAs) promote tumorigenesis by mediating the aforementioned processes. Methods: Here, we designed an exploratory study to investigate the role of lncRNAs ROR and MALAT1 and their related genes in CSC stemness. Using magnetic-activated cell sorting (MACS), the CD133- and CD133+ subpopulations were separated in SW1736 and C643 ATC cell lines. Next, the expression profiles of the CD133 marker, MALAT1, and its associated genes (CCND1, NESTIN, MYBL2, MCL1, IQGAP1), as well as ROR and its related genes (POU5F1, SOX2, NANOG), were explored by qRT-PCR. Results: We found significant up-regulation of ROR, POU5F1, SOX2, NANOG, CD133, MALAT1, IQGAP1, and MCL1 in CD133+ SW1736 cells compared to CD133- cells. As for CD133+ C643 cells, CCND1, IQGAP1, POU5F1, SOX2, NANOG, and NESTIN were significantly up-regulated compared to CD133- cells. Conclusions: This study suggests that these lncRNAs in CD133-positive SW1736 and C643 cells might regulate stemness behaviors in ATC.

Improvement of Heart Function After Transplantation of Encapsulated Stem Cells Induced with miR-1/Myocd in Myocardial Infarction Model of Rat.

Cardiovascular disease is one of the most common causes of death worldwide. Mesenchymal stem cells (MSCs) are one of the most common sources in cell-based therapies in heart regeneration. There are several methods to differentiate MSCs into cardiac-like cells, such as gene induction. Moreover, using a three-dimensional (3D) culture, such as hydrogels increases efficiency of differentiation. In the current study, mouse adipose-derived MSCs were co-transduced with lentiviruses containing microRNA-1 (miR-1) and Myocardin (Myocd). Then, expression of cardiac markers, such as NK2 homeobox 5(Nkx2-5), GATA binding protein 4 (Gata4), and troponin T type 2 (Tnnt2) was investigated, at both gene and protein levels in two-dimensional (2D) culture and chitosan/collagen hydrogel (CS/CO) as a 3D culture. Additionally, after induction of myocardial infarction (MI) in rats, a patch containing the encapsulated induced cardiomyocytes (iCM/P) was implanted to MI zone. Subsequently, 30 days after MI induction, echocardiography, immunohistochemistry staining, and histological examination were performed to evaluate cardiac function. The results of quantitative real -time polymerase chain reaction (qRT-PCR) and immunocytochemistry showed that co-induction of miR-1 and Myocd in MSCs followed by 3D culture of transduced cells increased expression of cardiac markers. Besides, results of in vivo study implicated that heart function was improved in MI model of rats in iCM/P-treated group. The results suggested that miR-1/Myocd induction combined with encapsulation of transduced cells in CS/CO hydrogel increased efficiency of MSCs differentiation into iCMs and could improve heart function in MI model of rats after implantation.

Generation of high yield insulin-producing cells (IPCs) from various sources of stem cells.

Type 1 diabetes mellitus occurs when beta cell mass is reduced to less than 20% of the normal level due to immune system destruction of beta cell resulting in an inability to secrete enough insulin. The prevalence of diabetes is expanding according to the American Diabetes Association and the World Health Organization (WHO), foretold to exceed 350 million by 2030. The current treatment does not cure many of the serious complications associated with the disease such as neuropathy, nephropathy, dyslipidemia, retinopathy and cardiovascular disease. Whole pancreas or isolated pancreatic islet transplantation as an alternative therapy can prevent or reduce some of the complications of diabetes. However, the shortage of matched organ or islets cells donor and alloimmune responses limit this therapeutic strategy. Recently, several reports have raised extremely promising results to use different sources of stem cells to differentiate insulin-producing cells and focus on the expansion of these alternative sources. Stem cells, due to their potential for multiple differentiation and self-renewal can differentiate into all cell types, including insulin-producing cells (IPCs). Generation of new beta cells can be achieved from various stem cell sources, including embryonic stem cells (ESCs), adult stem cells, such as mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs). Thus, this chapter discusses on the assistance of cellular reprogramming of various stem cells as candidates for the generation of IPCs using transcription factors/miRNA, cytokines/small molecules and tissue engineering.

A systematic review on thyroid organoid models: time-trend and its achievements.

Current in vitro models have played important roles in improving knowledge and understanding of cellular and molecular biology, but cannot exactly recapitulate the physiology of human tissues such as thyroid. In this article, we conducted a systematic review to present scientific and methodological time-trends of the reconstruction and generation of 3 D functional thyroid follicles and organoids for thyroid research in health and disease. "Web of Science (ISI)", "Scopus", "Embase", "Cochrane Library", and "PubMed" were systematically searched for papers published since 1950 to May 2020 in English language, using the predefined keywords. 212 articles were reviewed and finally 28 papers that met the inclusion and exclusion criteria were selected. Among the evidence for the examination of 3 D cell culture methods in thyroid research, there were only a few studies related to the organoid technology and its potential applications in understanding morphological, histological, and physiological characteristics of the thyroid gland and reconstructing this tissue. Besides, there was no study using organoids to investigate the tumorigenesis process of thyroid. Based on the results of this study, despite all the limitations and controversies, the exciting and promising organoid technology offers researchers a wide range of potential applications for more accurate modeling of thyroid in health and diseases and provides an excellent preclinical in vitro platform. In future, organoid technology can provide a better understanding of the molecular mechanisms of pathogenesis and tumorigenesis of thyroid tissue and more effective treatment for related disorders due to more accurate simulation of the thyroid physiology.

MicroRNAs contribution in tumor microenvironment of esophageal cancer.

BACKGROUND: miRNAs have recently been implicated in tumor's microenvironment remodeling and tumor-stromal cells interactions. We have previously reported a signaling role for miR-21, as a secretory molecule released by cancer associated fibroblasts (CAF) adjacent to esophagus tumor cells. OBJECTIVE: To discover other potential signaling miRNAs, we employed a co-culture system of esophageal cancer cell line and normal fibroblasts to mimic the tumor microenvironment. METHODS: We measured the expression profile of secretory miRNAs in the conditioned media (CM) of our co-culture system using a panel PCR array. We used pathway enrichment analysis to define potential pathways regulated by these miRNAs. Then using ultracentrifugation, we purified exosomes secreted to the CM of co-cultured cell lines and evaluated exosomal secretion of these miRNAs. RESULTS: We found 18 miRNAs which were significantly up/down-regulated in the CM of co-culture system. Pathways related to cell adhesion, endocytosis and cell junctions were among the enriched pathways that might be related to CAF phenotype and tumor progression. Moreover, we detected higher exosomal levels of miR-33a and miR-326 in the purified exosomes both in co-cultured and untreated CM. So, these miRNAs are mainly secreted into the CM by means of exosomes. CONCLUSIONS: Briefly, our data shed more light on the role of CAFs through secretion of miRNAs within tumor microenvironment and propose novel therapeutic targets for esophageal and probably other cancer types.