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The cause of leukemia, a common malignancy of the hematological system, is unknown. The structure of long non-coding RNAs (lncRNAs) is similar to mRNA but no ability to encode proteins. Numerous malignancies, including different forms of leukemia, are linked to Lnc-RNAs. It is verified that the carcinogenesis and growth of a variety of human malignancies are significantly influenced by aberrant lncRNA expression. The body of evidence linking various types of lncRNAs to the etiology of leukemia has dramatically increased during the past ten years. Some lncRNAs are therefore anticipated to function as novel therapeutic targets, diagnostic biomarkers, and clinical outcome predictions. Additionally, these lncRNAs may provide new therapeutic options and insight into the pathophysiology of diseases, particularly leukemia. Thus, this review outlines the present comprehension of leukemia-associated lncRNAs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Collagen family genes (CFGs) play a significant role in the pathogenesis of cancers. This study aimed to evaluate changes in the expression levels (Els) of CFGs related to epithelial-mesenchymal transition (EMT) and metastasis in gastric (GC), breast (BC), and colorectal (CRC) cancers to introduce these genes as potential diagnostic biomarkers for these three types of cancer., Methods: The Cancer Genome Atlas (TCGA) examined ELS changes in CFGs associated with EMT and metastasis to determine their diagnostic value for GC, BC, and CRC. InteractiVenn was used to find genes shared by these three cancers. The biomarker role of CFGs was determined using the receiver operating characteristic (ROC) analysis. GC, BC, and CRC samples were analyzed using the RT-qPCR method to verify the bioinformatics results and evaluate the EL of the selected genes as biomarkers for these cancers., Results: The in-silico results showed a significant increase in the EL of several CFGs involved in EMT and metastasis in GC, BC, and CRC samples compared to healthy samples. Six common genes (COL11A1, COL12A1, COL1A1, COL1A2, COL5A1, and COL5A2) showed significantly increased in these three cancers, therebysupporting their oncogenic role. Furthermore, the biomarker-related analyses indicated that COL11A1 and COL1A1 were common diagnostic biomarkers for the three cancers. The RT-qPCR method confirmed that the ELs of COL11A1 and COL1A1 in the GC, BC, and CRC samples increased significantly compared to the adjacent normal samples., Conclusion: CFGs in EMT and metastasis of GC, BC, and CRC are strong common diagnostic biomarkers for these cancers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Long non-coding RNAs (lncRNAs) are an emerging class of non-coding RNAs that do not encode proteins. These RNAs have various essential regulatory functions. Irregular expression of lncRNAs has been related to the pathological process of varied diseases, and are considered promising diagnostic biomarkers. LncRNAs can release into the circulation and be stable in body fluids as circulating lncRNAs. A subset of circulating lncRNAs that exist in exosomes are referred to as exosomal lncRNA molecules. These lncRNAs are highly stable and resist RNases. Exosomes have captured a great deal of attention due to their involvement in regulating communications between cells. In conditions of autoimmune disease, exosomes play critical roles in the pathological processes. In this context, circulating lncRNAs have been shown to modulate the immune response and indicated as prognosis and diagnostic biomarkers for autoimmune diseases. This review highlights the role of circulating lncRNAs (particularly exosomal) as diagnostic biomarkers for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, and Sjögren's syndrome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Although lifelong renewal and additional compensatory growth in response to demand are undeniable facts, so far, no specific stem cells have been found for pancreatic cells. According to the consensus model, the development of pancreas results from the hierarchical differentiation of pluripotent stem cells towards the appearance of the first endocrine and exocrine cells at approximately 7.5 to 8th gestation week (GW) of human embryo. However, the primitive endocrine cells arising from the embryonic phase of development do not appear to be mature or fully functional. Asymmetric localization of cellular components, such as Numb, partition protein complexes (PAR), planar cell polarity components, and certain mRNAs on the apical and basal sides of epithelial cells, causes cellular polarization. According to our model, the equal distribution of cellular components during symmetric cell division yields similar daughter cells that are associated with duct expansion. In contrast, asymmetric cell division is associated with uneven distribution of cellular components among daughter cells, resulting in different fates. Asymmetric cell division leads to duct branching and the development of acinar and stellate cells by a daughter cell, as well as the development of islet progenitor cells through partial epithelial-to-mesenchymal transition (EMT) and delamination of another daughter cell. Recently, we have developed an efficient method to obtain insulin-secreting cells from the transdifferentiation of hESC-derived ductal cells inducing a partial EMT by treatment with Wnt3A and activin A in a hypoxic environment. Similar models can be offered for other tissues and organs such as mammary glands, lungs, prostate, liver, etc. This model may open a new horizon in the field of regenerative medicine and be useful in explaining the cause of certain abnormalities, such as the occurrence of certain cysts and tumors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) is one of the most common types of cancer which affects the colon and the rectum. Approximately one third of annual CRC mortality occurs due to the late detection of this type of cancer. Therefore, there is an urgent need for more powerful diagnostic and prognostic tools for identification and treatment of colorectal tumorigenesis. Non-coding RNAs (ncRNAs) have been implicated in the pathology of CRC and also linked to metastasis, proliferation, differentiation, migration, angiogenesis and apoptosis in numerous cancers. Recently, attention has turned towards ncRNAs as specific targets for diagnosis, prognosis and treatment of various types of cancers, including CRC. In this review, we have tried to outline the roles of ncRNAs, and their involvement in signaling pathways responsible for the progression of CRC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Breast cancer is caused by the interaction of inherited and environmental risk factors. Also, gastric cancer is the second fatal carcinoma. B-cell leukemia/lymphoma 2 gene family plays a crucial role in carcinogenesis by inhibiting the apoptosis process., Materials and Methods: In this study, 129 patients with breast cancer and 132 controls as well as 136 patients with gastric cancer and 50 controls were enrolled. We used Real time PCR to determine the genotype of the samples. Finally, we analyzed the diagram based on high temperature melting curve diagram using the MICPCR software, followed by bioinformatics prediction of rs1016860 functions., Results: rs1016860 of BCL2 gene with CC, CT, and TT genotypes were observed in this region. The association of Estrogen receptor and Progesterone receptor, cancer stage and grade of cancer in the patients with genotypes was significant in breast cancer. The association of the status of primary tumor in the patients with genotypes is significant in gastric cancer (Chi-Square p < 0.05 and p = 0.000 did not follow the Hardy-Weinberg equilibrium)., Discussion: It was predicted that the TT genotype could be dangerous in breast cancer and gastric cancer; it is expected via bioinformatics that this SNP could lead to signaling pathways of cancer progression, by altering the binding potential of miR-629-5p to BCL2 3'UTR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of the current study was to evaluate the effects of conjugated linoleic acid (CLA) on the expression of the genes involved in the reduction of inflammatory conditions induced by tumor necrosis factor alpha (TNF-α). To fulfill this, the C2C12 murine myoblast cell line was used. The experimental treatments consisted of 50 and 100 µM of CLA with 10, 15 and 20 ng/mL of TNF-α. Our results indicated that the concentrations of 50, 100 and 150 µM of CLA at 24 and 48 h increased the cell survival rate (p < 0.05), as compared with the control group. The effect of pre-treating CLA before the inflammation induced by TNF-α showed that the amount of cell death caused by TNF-α was inhibited in both 50 and 100 µM concentrations of CLA (p < 0.05). Modulatory effects of CLA on PGC1-α and Fndc5 transcript levels showed that the PGC1-α and Fndc5 expression levels were significantly increased 48 h after treating with 50 and 100 µM of CLA (p < 0.05). Overall, these findings indicate that using CLA could considerably improve the inflammatory condition induced by TNF-α., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Insulin is a peptide hormone responsible for stable glycemia, is entirely secreting from pancreatic β cells at the core of glucose homeostatic regulation. Upon synthesis as preproinsulin on rough endoplasmic reticulum (rER), proinsulin is directed to trans Golgi apparatus. Subsequently, proinsulin packaging into secretory granules occurs in a dynamic and highly efficient process. During maturation stage of secretory granules, proinsulin undergoes cleavage and produces insulin and C-peptide upon acidification of the granules due to the activation of ATP-deriven proton pump. Fusion of the insulin containing secretory granules with the plasma membranes takes place after an increase in intracellular Ca 2+ . Finally, insulin is co-secreting with other components that are present in the secretory granules, including C-peptide, ATP, γ-aminobutyric acid (GABA), ghrelin and amylin. The other accompanying components of the insulin vesicles play important roles in the insulin secretion, insulin receptor activation and other homeostatic effects.. Responding to the glucose stimulation or increases in cytoplasmic Ca 2+ levels, insulin secretion is immediately starts. Whereas, the second phase of insulin secretion is slow and continued, which reaches a plateau within 1-3 hours and lasts for longer period. In contrast to the first phase, the second phase of insulin secretion is independent of the extracellular glucose level. Finally, sequential or compound exocytosis of insulin is repressed to prevent sugar crash arising from excessive and sudden insulin secretion. In this paper we have reviewed the recent progress of molecular scenarios which are behind insulin biogenesis, intracellular sorting and exocytosis events., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The purpose of this study was to investigate the effect of a single bout and 8 weeks of downhill running versus uphill running exercise on expression of PGC1-α, FNDC5 and UCP1 in mice. Forty-eight BALB/c male mice weighing 25-30 g were randomly assigned into 8 groups: 1) acute downhill running (ADR) on a -15° slope; 2) acute uphill running (AUR) on a +15° slope; 3) acute running without inclination (AWI), 4) acute without exercise as control (ACtrl), 5) chronic downhill running (CDR) on a -15° slope; 6) chronic uphill running (CUR) on a +15°slope; 7) chronic running without inclination (CWI), 8) chronic without exercise as control (CCtrl). Twenty four hours after the last training session, the mice were sacrificed and Calf muscles (including soleus and gastrocnemius) and quadriceps muscles (including Rectus femoris and vastus intermedius) were obtained and expression levels of PGC1-α and FNDC5 in crus and quadriceps muscles and UCP1 in visceral and subcutaneous adipose tissues were measured and compared between the groups. PGC-1α and FNDC5 mRNA levels increased after treadmill exercise training in all acute and chronic exercise groups in both skeletal muscle groups. Furthermore mRNA level of UCP1 in subcutaneous adipose tissue but not in visceral adipose tissue increased both after acute and chronic exercise. Collectively, data showed that downhill running exercise to be more effective than other exercises, as downhill running has led to a greater improvement in metabolism may be considered more effective for browning of fat tissue., (Copyright © 2018. Published by Elsevier B.V.)

One of the most importantly involved pathways in cancer development is fatty-acid signaling pathway. Synthesized lipids as energetic sources are consumed by cancer cells for proliferation, growth, survival, invasion and angiogenesis. Fatty acids as signaling compounds regulate metabolic and transcriptional networks, survival pathways and inflammatory responses. Aggregation of fatty acids with fatty acid binding proteins (FABPs) facilitates their transportation to different cell organelles. FABPs, a group of lipid binding proteins modulate fatty acid metabolism, cell growth and proliferation and cancer development. They may be used as tumor marker in some cancers. FABPs are expressed in most malignancies such as prostate, breast, liver, bladder and lung cancer which are associated with the incidence, proliferation, metastasis, invasion of tumors. This review introduces several isoforms of FABPs (FABP1-12) and summarizes their function and their possible roles in cancer development through some proposed mechanisms., (Copyright © 2018. Published by Elsevier B.V.)

Background: Obesity triggers a variety of severe conditions, therefore deteriorates metabolism rate of adipose tissues and muscles. Uncoupling proteins which are highly stimulated by fatty acids are potential targets for anti-obesity agents through breaking the electron gradient in the mitochondrial matrix and creating imbalances in the electron transport chain, thereby increasing the amount of substrate used to produce energy. Therefore, the aim of present study is assessment of exercise and high fat diet on expression level of Ucp1 subcutaneous white and brown adipose tissues (scWAT & BAT) respectively., Methods: To perform experiments, 48 male C57BL/6 mice were divided to two major groups and fed with high fat diet (HFD) or low fat diet (LFD) during a period of 12 weeks. After the first intervention, each groups was divided into four groups randomly as (HF-EX), (HF-SED), (LF-EX), (LF-SED) [EX: exercise; SED: sedentary] in form of treadmill running for 45 min/day, 5 days/week during 8 weeks. One day after the last practice session, mice were sacrificed and Ucp1 expression was assessed on scWAT & BAT., Results: Data indicated a down-regulation in scWAT Ucp1 in obese mice similar to what observed for the expression of Pgc1α. Both, BAT Ucp1 and Pgc1α mRNA decreased significantly in response to obesity and physical activity. Moreover, exercise caused significant decrease in scWAT mitochondrial proteins contradictory to BAT., Conclusion: Taken together, exercise exerted controversial effects compared with HFD and obesity on expression of Ucp1 and Pgc1α in scWAT dissimilar to BAT tissues, concluding that obesity may cause a resistance to exercise in terms of metabolic demands for scWAT tissue., (Copyright © 2018. Published by Elsevier B.V.)

Previous studies have shown that miR-200a is markedly deregulated in various neurodegenerative disorders including Alzheimer's disease (AD), Multiple Sclerosis (MS) and PD. Furthermore, studies have shown the key role of miR-200a on expression of SIRT1 and apoptosis. Therefore, we hypothesized that miR-200a/SIRT1 axis should have a crucial role in apoptosis of dopaminergic (DA)neurons. In this study, human SH-SY5Y cells were treated with MPP+ and expression of miR-200a, SIRT1 and its target genes were assessed. Our results confirmed that expression of miR-200a significantly up-regulated during treating of human SH-SY5Y cells with MPP + in order to induce oxidative stress and apoptosis. Additionally, transcript level of SIRT1 in these cells showed significant down-regulation confirming that SIRT1 is indeed decreased due to miR-200a up-regulation during apoptosis. Moreover, expression of P53, FOXO1 and BCL2 were modulated. In this study, we indicated that miR-200a/SIRT1 axis directly correlates with apoptosis and P53 signaling pathway. In conclusion, miR-200a and its target gene, SIRT1, may exert a possible role in induction of apoptosis in DA neurons through regulating P53, apoptosis and FOXO signaling pathways., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: Human non-small cell lung cancer (NSCLC) that harbors activating mutations in epidermal growth factor receptor (EGFR) initially responds to treatment with EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib but eventually tumor cells acquire resistance. To date, several gene expression profiles have been reported in TKIs-resistant EGFR-mutant NSCLC. The objective of this study is to identify robust gene expression signatures, biological processes, and promising overcoming targets for TKIs-resistant EGFR-mutant NSCLC., Materials and Methods: Five publicly available microarray datasets were integrated by performing two network-based meta-analyses following by protein-protein interaction (PPI) network and gene set enrichment analysis., Results and Conclusion: According to our meta-analyses, 830 and 1286 genes were differentially expressed in the TKIs-resistant EGFR-mutant NSCLC cell lines compared to TKIs-sensitive EGFR-mutant NSCLC cell lines in the absence and presence of TKIs treatment, respectively. PPI network analysis identified ESR1 and ELAVL1 to be the most highly ranked hub genes involved in the NSCLC acquired TKI-resistance. Moreover, gene set enrichment analyses indicated that up-regulated genes are mainly distributed in hallmarks "Glycolysis", some "E2F targets". Down-regulated genes mainly contribute to hallmarks "interferon alpha response", "interferon gamma response", and also "E2F targets". For the first time, this study has demonstrated several robust candidate genes and pathways of the NSCLC acquired TKI-resistance. Further experimental verifications are highly recommended to examine our findings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons in substantia nigra. MPP+ as a dopaminergic neurotoxin induces many parkinsonian-like symptoms in cell culture. MicroRNAs are noncoding RNAs which their deregulation participates in neurodegeneration by affecting most of the mechanisms responsible for neurodegenerative diseases. Differentiated PC12 cells impaired by MPP+ were served as an in vitro model of PD. The aim of present research is to evaluate expression of several miRNAs and possible target genes in MPP+-treated differentiated PC12 cells. PC12 cells were differentiated by induction of NGF. Neurite outgrowth was quantified using image analysis software. MTS assay was served to assess cell viability. DCFH-DA assay and Annexin v staining were used to detect reactive oxygen species (ROS) levels and apoptosis, respectively. An in-silico study was performed to make interaction analysis between selected mRNAs and microRNAs. The expression levels of microRNAs and target genes were examined by RT-qPCR. NGF induced differentiation led to a substantial increase in neurite lengths means and percentage of the neurite-bearing cells. NGF-differentiated PC12 cells substantially expressed TH and retained their dopaminergic characteristic after differentiation. NGF treatment enhanced TH gene expression. MPP+ exposure caused loss of cell viability and induced apoptosis and ROS overproduction. SIRT1, BCL2, and BDNF were down-regulated after MPP+-treatment. In contrast, MPP+ toxicity significantly caused up-regulation in miR-34a, miR-141, and miR-9. The present study showed altered levels of selected microRNAs in response to MPP+ for the first time, suggesting that perturbed expression of them may contribute to the PD-related pathogenic processes, probably by affecting the expression of BCL2, BDNF, and SIRT1 as potential targets., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis is an immune-mediated inflammatory disease of central nervous system. MicroRNAs play important roles in autoimmune diseases such as MS., Objectives: The aim was to evaluate the expression pattern of miR-34a, miR-199a, miR-30c and miR-19a in peripheral blood derived CD4+ T lymphocytes of both relapsing and remitting phases of MS., Methods: Blood samples from 40 RRMS patients (20 in relapsing and 20 in remitting phase) and 20 healthy volunteers were taken. CD4+ T cells were isolated. The expression level of miR-34a, miR-199a, miR-30c and miR-19a, and the percentage of Th17 and Treg cells were measured. Expression of master transcription factors of Th17 and Treg cells and several targets of these miRNAs were also evaluated., Results: Data indicated an increased expression of miR-34a, miR-30c and miR-19a in relapsing phase and decreased expression of miR-199a in remitting phase. ROC curve data add other prestigious information of miR-34a, miR-199a, miR-30c and miR-19a by defining relapsing and remitting phase and also healthy cases with high specificity and sensitivity at a proposed optimum cut-off point., Conclusion: Collectively, we showed a correlation between the four miRNAs with different phases of MS and their possible involvement in differentiation pathways of Th17 cells, as the most important players in MS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Peroxisome proliferator-activated receptor γ (PPARγ) belongs to the nuclear receptor superfamily of PPARs (PPARα, PPARβ/δ, PPARγ). Numerous studies have concentrated on the key role of PPARs in inflammation and a variety of cancers which include prostate, breast, glioblastoma, neuroblastoma, pancreatic, hepatic, leukemia, and bladder and thyroid tumors. This review, specifically deals with anti-tumor and tumorigenicity effects of PPARγ and its natural and synthetic agonists including Troglitazone, Cladosporol A, B, 15-Deoxi-Δ 12-14 -Prostaglondin J2 (15-d-PGJ2), Ciglitazon, docosahexaenoic acid, eicosapentaenoic acid Alpha-eleostreac acid, Amorfrutin C, Sphingosine 1-phosphate, Evodiamine, Excavatolide B vs respected antagonists as GW9662, bisphenol-A-diglycidyl-ether. Considering the contradictory role of PPARγ on tumorigenicity, a number of studies demonstrate mechanisms involved in tumorigenicity effects of PPARγ agonists while several studies suggest key roles of PPARγ agonists in anti-proliferation, metastasis, angiogenesis, apoptosis and immunomodulatory through activation of signaling pathways in different cancer cells as well as in cancer stem cells. The aim of this review is summarizing of tumorigenicity and anti-tumorigenicity activities of PPARγ agonists and antagonists as well as therapeutic activities of these reagents as a coadjutant drug in the treatment of different cancers., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: Albeit single nucleotide polymorphisms related to ESR1 gene have been studied, only a number of them have been reported to be associated with breast cancer risk. rs1062577 is one of the most recent microRNA-related ESR1 SNPs; however, no study has been conducted to investigate the significance this polymorphism in Iranian population. In this study, we aimed to investigate the frequency and also the association between rs1062577 and breast cancer., Materials and Methods: rs1062577 position was genotyped by Tetra-primer ARMS-PCR in totally 182 blood specimens obtained from breast cancer patients (n=86), and healthy blood donors (n=96). The distribution of different genotypes was statistically analyzed in terms of the potential association between rs1062577 different alleles, breast cancer risk and clinicopathological criteria of breast cancer patients., Results: The statistical analyses confidently indicated that rs1062577 A allele is associated with the increased breast cancer risk in both univariate and multivariate regression models (Odds Ratio=8.403 and 32.602 respectively). rs1062577 T allele was statistically associated with stage I of breast cancer patients (p-value=0.025). In silico studies implied that rs1062577 A allele can alter the binding capacity of ESR1 mRNA and miRNAs via either breakage or formation of hydrogen bonds., Conclusion: rs1062577 A allele is significantly and dramatically associated with the elevated risk and greater stages of breast cancer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Th17 cells are a lineage of CD4(+) T helper cells in immune system which differentiate from naïve CD4(+) T cells and have demonstrated to play a critical role in the pathogenesis of different autoimmune disorders. miRNAs are a novel group of non-coding RNAs which participate in post-transcriptional regulation of gene expression mostly by pairing with 3'UTR of their mRNA targets and inhibition of its translation. It has been demonstrated that miRNAs function in various cellular processes such as differentiation, proliferation, and apoptosis. By now, several signaling pathways and their downstream positive and negative regulators involve in Th17 differentiation have been discovered. Several studies have reported the aberrant miRNA expression profile in patients with autoimmune disease called autoimmune-deregulated miRNAs. Here, using integrative miRwalk database which assembles the data gathered from ten different bioinformatics databases designed to predict miRNA-target interaction, we analyzed possible targeting effect of "autoimmune-deregulated miRNAs" on prominent positive and negative regulators of Th17 differentiation. Our resulting mRNA-miRNA network simply nominated several miRNAs with strong possibility which probably may have inducing (miR-27b, miR-27a, miR-30c, miR-1, and miR-141) or inhibitory (miR-20b, miR-93, miR-20a, miR-152, miR-21, and miR-106a) role in Th17 differentiation by targeting negative or positive regulators of Th17 differentiation, respectively., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Availability of human embryonic stem cells (hESCs) has enhanced the capability of basic and clinical research in the context of human neural differentiation. Derivation of neural progenitor (NP) cells from hESCs facilitates the process of human embryonic development through the generation of neuronal subtypes. We have recently indicated that fibronectin type III domain containing 5 protein (FNDC5) expression is required for appropriate neural differentiation of mouse embryonic stem cells (mESCs). Bioinformatics analyses have shown the presence of three isoforms for human FNDC5 mRNA. To differentiate which isoform of FNDC5 is involved in the process of human neural differentiation, we have used hESCs as an in vitro model for neural differentiation by retinoic acid (RA) induction. The hESC line, Royan H5, was differentiated into a neural lineage in defined adherent culture treated by RA and basic fibroblast growth factor (bFGF). We collected all cell types that included hESCs, rosette structures, and neural cells in an attempt to assess the expression of FNDC5 isoforms. There was a contiguous increase in all three FNDC5 isoforms during the neural differentiation process. Furthermore, the highest level of expression of the isoforms was significantly observed in neural cells compared to hESCs and the rosette structures known as neural precursor cells (NPCs). High expression levels of FNDC5 in human fetal brain and spinal cord tissues have suggested the involvement of this gene in neural tube development. Additional research is necessary to determine the major function of FDNC5 in this process., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Fibronectin type III domain-containing 5 protein (Fndc5) is an exercise hormone and its transcript profile in mouse showed high degree of expression in heart, skeletal muscle and brain. Our previous studies indicated a significant increase (approximately 10 fold) in mRNA level of Fndc5 when embryonic stem cells were differentiated into beating bodies. As a step closer to identify the involvement of Fndc5 in the process of cardiomyocyte differentiation, we generated a stably inducible transduced mouse embryonic stem cell (mESC) line that overexpressed Fndc5 following Doxycycline induction. Our results indicated that the overexpression of Fndc5 during spontaneous cardiac differentiation significantly increased not only at RNA levels for mesodermal markers but also at the transcriptional levels for cardiac progenitor and cardiac genes. These data suggest that Fndc5 may be involved in cardiomyocyte differentiation. Therefore, a new hope will be arisen for potential application of this myokine for regeneration of damaged cardiac tissues especially in cardiac failure., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Multiple sclerosis is an inflammatory autoimmune disease widely characterized by myelin destruction of CNS. Th-17 cells, have been demonstrated to play a crucial role in pathogenesis of MS. MicroRNAs are a new class of non-coding RNAs that participate in post-transcriptional regulation of gene expression. Previous studies have reported a potential role of various miRNAs in induction of Th-17 differentiation and progress of autoimmune diseases. In recent years, it has been shown that miR-326 and miR-26a involved in progress of Th-17 and MS disease., Objective: To evaluate expression pattern of miR-326 and miR-26a in peripheral blood lymphocytes of relapsing-remitting MS patients during relapsing and remitting phases compared to healthy control subjects., Materials and Methods: Forty RR-MS patients of Isfahan population were diagnosed as relapsing (n=20) or remitting phase (n=20) patients according to clinical manifests and expression level of miR-26a and miR-326 was measured in these groups by quantitative real time PCR method compared to 20 healthy controls. In-silico molecular signaling pathway enrichment analysis was also performed on validated and predicted targets (targetome) of miR-26a by DAVID database to explore possible role of miR-26a in Th17 differentiation., Results: We observed up-regulation of both miR-326 and miR-26a in relapsing phase of multiple sclerosis patients compared with remitting phase (p value=0.0001) and healthy controls (p value=0.0091). ROC curve analysis confirmed valuable and precise potential of miR-326 to discriminate between relapsing and remitting phases of multiple sclerosis with specificity and sensitivity of 100% at a proposed optimum cutoff point. Furthermore, in-silico molecular signaling pathway enrichment analysis detected TGF-β signaling pathway as one of the most statistically relevant pathway with miR-26a targetome., Conclusion: Our results confirmed potential of miR-326 as a diagnostic biomarker to discriminate between relapsing and remitting phases of multiple sclerosis disease. Similar expression pattern to miR-326 and in-silico molecular enrichment analysis altogether suggest an inducing role of miR-26a in differentiation of pathogenic Th17 cells during pathogenesis of multiple sclerosis by targeting major components of the TGF-β signaling pathway (i.e. SMAD4 and SMAD1) and disarrangement of this signaling pathway., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Deficiency in the PTS2 protein import pathway due to mutations in PEX7 gene results in the rhizomelic chondrodysplasia punctata (RCDP) type 1. In the present study, we have reported a novel missense mutation, W75R, in the PEX7 gene in an Iranian patient with the RCDP type 1. The inability of PEX7 protein to transport PTS2 containing proteins including peroxisomal 3-ketoacyl-CoA thiolase and PTS2-EGFP protein to the surface of the peroxisomes showed that the W75R mutation in PEX7 gene severely impaired the function of PEX7 protein and was responsible for RCDP type 1 in this patient., (Copyright © 2013 Elsevier B.V. All rights reserved.)