Biomechanical evaluation of a sheep tracheal scaffold.

Tissue engineering is a set of techniques for producing or reconstructing tissue that primarily aims to restore or improve the function of tissues in the human body. The aim of the present study was to evaluate the mechanical and histological characteristics of decellularized tracheal scaffolds prepared in comparison with fresh trachea for use in tracheal repair. In order to prepare the scaffold, sheep's trachea was prepared and after cleaning the waste tissues, they were decellularized. Then decellularized scaffolds were evaluated histologically and laboratory and numerical study of the nonlinear mechanical behavior of tracheal tissue and scaffold and their comparison. Examining the results of histological evaluations showed that the decellularization of the scaffolds was completely done. These results were confirmed by hematoxylin-eosin staining. Also, the exact hyperelastic properties of tracheal tissue and scaffold were used in biomechanical models, and according to the presented results, the five-term Mooney-Rivlin strain energy density function became a suitable behavioral model for modeling the hyperelastic behavior of trachea and scaffold. In total, the results of this research showed that the scaffolds obtained from decellularization by preserving the main compositions of the desired tissue can be a suitable platform for investigating cell behaviors.

Exploring the role of interleukin 11 in cancer progression, patient survival, and therapeutic insights.

BACKGROUND: The Interleukin (IL)-11 gene, which is one of the members of the cytokine family, has an oncogenic role in some cancers. The main goal of this study is to analyze IL-11 expression level in 14 prevalent cancers and highlights its role in patients' survival, drug resistance, and sensitivities. Also, an association of this gene with metastasis and inflammation pathways has been investigated. METHODS AND RESULTS: Using the cancer genome atlas (TCGA) data, the level of IL-11 expression and its role in prognosis and survival rate were evaluated in 13 common cancers. Then, confirming the obtained in-silico outcomes, the relative expression level of this gene in colorectal cancer (CRC) samples and their adjusted tissues were assayed by the RT-qPCR method. Furthermore, to examine the association between IL-11 expression and drug resistance and sensitivity, PharmacoGX data was applied. The co-expression network was used to recognize the pathways in which IL-11 was involved. The results from the TCGA dataset indicated that the expression level of IL-11 increased significantly in 13 prevalence cancers compared to the control groups. Interestingly, this enhanced expression level is associated with a high rate of mortality in patients with bladder, stomach, colorectal, and endometrial cancers. Also, the co-expression network analysis showed a strong correlation between IL-11 and the genes of metastasis pathway and the genes related to the inflammation process. Finally, regarding drug sensitivity, IL-11 expression level can be introduced as a remarkable biomarker for cancer detection due to area under curve (AUC). CONCLUSION: Altered expression of the IL-11 gene is observed in 13 common cancers and is associated with prognosis and mortality rate in patients. Moreover, this gene can be considered a prognostic biomarker in different types of cancer, such as CRC.

Comparison of SPAG11A gene expression in infertile men with grade 1 and 2 varicocele before and after treatment.

OBJECTIVE: Sperm Associated Antigen 11A (SPAG11A) protein is a family of the epididymis-specific secretory proteins implicated in sperm maturation and function. Varicocele might cause pathophysiological difficulties in the testis and epididymis, with a harmful effect on the environment for spermatogenesis and sperm maturation. The aim of this study was to evaluate the expression level of the SPAG11A gene and sperm parameters in infertile men with grade 1 and 2 varicocele before and after treatment. METHODS: Semen specimens were collected from 20 infertile men with varicocele pre-and post-treatment and 10 healthy volunteers. Semen analysis was conducted according to world health organization guidelines. Real time PCR (qRT-PCR) reaction was applied for determination of SPAG11A mRNA expression. RESULTS: The results showed that there was a significant difference between the concentration and normal morphology between pre- and post-treatment groups and the controls. There were significant differences between pre-treatment and control groups in terms of progressive and non-progressive mobility. SPAG11A mRNA levels were significantly lower in the pre-treatment group than in healthy control subjects (p=0.007). There was no statistically significant difference in the expression of SPAG11A as well as semen parameters in the post-treatment group compared to the pre-treatment group. CONCLUSIONS: SPAG11A gene expression and semen parameters may be affected by varicocele. Whether varicocele treatment is an effective approach to reduce the adverse effect of this disease on SPAG11A expression and semen parameters needs further investigation.

TBX15 and SDHB expression changes in colorectal cancer serve as potential prognostic biomarkers.

Alterations in the expression of certain genes could be associated with both patient mortality rates and drug resistance. This study aimed to identify genes in colorectal cancer (CRC) that potentially serve as hub genes influencing patient survival rates. RNA-Seq data were downloaded from the cancer genome atlas database, and differential expression analysis was performed between tumors and healthy controls. Through the utilization of univariate and multivariate Cox regression analyses, in combination with the MCODE clustering module, the genes whose expression changes were related to survival rate and the hub genes related to them were identified. The mortality risk model was computed using the hub genes. CRC samples and the RT-qPCR method were utilized to confirm the outcomes. PharmacoGx data were employed to link the expression of potential genes to medication resistance and sensitivity. The results revealed the discovery of seven hub genes, which emerged as independent prognostic markers. These included HOXC6, HOXC13, HOXC8, and TBX15, which were associated with poor prognosis and overexpression, as well as SDHB, COX5A, and UQCRC1, linked to favorable prognosis and downregulation. Applying the risk model developed with the mentioned genes revealed a markedly higher incidence of deceased patients in the high-risk group compared to the low-risk group. RT-qPCR results indicated a decrease in SDHB expression and an elevation in TBX15 levels in cancer samples relative to adjacent healthy tissue. Also, PharmacoGx data indicated that the expression level of SDHB was correlated with drug sensitivity to Crizotinib and Dovitinib. Our findings highlight the potential association between alterations in the expression of genes such as HOXC6, HOXC13, HOXC8, TBX15, SDHB, COX5A, and UQCRC1 and increased mortality rates in CRC patients. As revealed by the PPI network, these genes exhibited the most connections with other genes linked to survival.

Carcinogenic roles of MAFG-AS1 in human cancers

The MAF bZIP transcription factor G-antisense RNA 1 (MAFG-AS1) is located on chromosome 17. MAFG-AS1 was upregulated in 15 human cancers. MAFG-AS1 not only suppresses 16 miRNAs but also directly impacts 22 protein-coding genes' expression. Notably, abnormal MAFG-AS1 expression is connected to clinicopathological characteristics and a worse prognosis in a variety of cancers. Moreover, MAFG-AS1 takes its part in the tumorigenesis and progression of various human malignancies by suppressing apoptosis and promoting proliferation, migration, invasion, aerobic glycolysis, ferroptosis, angiogenesis, EMT, and metastasis. Besides, it can predict treatment effectiveness in ER + breast cancer, urothelial bladder carcinoma, and liver cancer by functioning as a trigger of resistance to tamoxifen, sorafenib, and cisplatin. This study systematically presents the functions of MAFG-AS1 in various cancers, as well as the findings of bioinformatics analyses of the MAFG-AS1, which should give clear advice for future research (AU)

An Update on the Application of CRISPR Technology in Clinical Practice.

The CRISPR/Cas system, an innovative gene-editing tool, is emerging as a promising technique for genome modifications. This straightforward technique was created based on the prokaryotic adaptive immune defense mechanism and employed in the studies on human diseases that proved enormous therapeutic potential. A genetically unique patient mutation in the process of gene therapy can be corrected by the CRISPR method to treat diseases that traditional methods were unable to cure. However, introduction of CRISPR/Cas9 into the clinic will be challenging because we still need to improve the technology's effectiveness, precision, and applications. In this review, we first describe the function and applications of the CRISPR-Cas9 system. We next delineate how this technology could be utilized for gene therapy of various human disorders, including cancer and infectious diseases and highlight the promising examples in the field. Finally, we document current challenges and the potential solutions to overcome these obstacles for the effective use of CRISPR-Cas9 in clinical practice.

Carcinogenic roles of MAFG-AS1 in human cancers.

The MAF bZIP transcription factor G-antisense RNA 1 (MAFG-AS1) is located on chromosome 17. MAFG-AS1 was upregulated in 15 human cancers. MAFG-AS1 not only suppresses 16 miRNAs but also directly impacts 22 protein-coding genes' expression. Notably, abnormal MAFG-AS1 expression is connected to clinicopathological characteristics and a worse prognosis in a variety of cancers. Moreover, MAFG-AS1 takes its part in the tumorigenesis and progression of various human malignancies by suppressing apoptosis and promoting proliferation, migration, invasion, aerobic glycolysis, ferroptosis, angiogenesis, EMT, and metastasis. Besides, it can predict treatment effectiveness in ER + breast cancer, urothelial bladder carcinoma, and liver cancer by functioning as a trigger of resistance to tamoxifen, sorafenib, and cisplatin. This study systematically presents the functions of MAFG-AS1 in various cancers, as well as the findings of bioinformatics analyses of the MAFG-AS1, which should give clear advice for future research.

Association of fatty acid binding protein-4 (FABP-4) T87C and rs8192688 gene polymorphisms and FABP-4 level with cardiovascular disease susceptibility in type 2 diabetic patients.

Type 2 Diabetes Mellitus (T2DM) is known to cause dyslipidemia and increase the risk of cardiovascular disease (CVD). Fatty acid binding protein (FABP)-4 plays a significant role in various stages of T2DM and CVD. Although it has been demonstrated that genetic variations of the FABP-4 gene can affect insulin sensitivity, the results obtained so far are controversial. The aim of this study was to investigate the possible association between T87C and rs8192688 polymorphisms and serum levels of FABP-4 with CVD susceptibility in T2DM patients. The study included 70 healthy controls, 70 individuals with T2DM, and 70 T2DM patients with CVD. Genomic DNA was extracted, and FABP-4 T87C and rs8192688 gene polymorphic sites were amplified using the ARMS-PCR method. Lipid profile and FABP-4 serum levels were significantly higher in T2DM patients with CVD compared to those with only T2DM (p < 0.05). Additionally, FABP-4 T87C gene polymorphism (TC genotypes) and dominant model (TT vs. TC + CC) were significantly associated with a decreased risk of both T2DM and T2DM with CVD patients (p < 0.05). Patients carrying TC + CC genotypes had significantly lower levels of triglyceride and FABP-4 compared to those carrying the TT genotype (p < 0.05). There was no significant association between FABP-4 rs8192688 polymorphism and either T2DM or CVD disease. It appears that FABP-4 T87C polymorphism decreases FABP-4 levels leading to decreased serum TG levels. Since both T2DM and CVD have inflammatory backgrounds, reducing inflammation can improve insulin sensitivity and lower TG levels in these patients.

Pathological roles of miRNAs and pseudogene-derived lncRNAs in human cancers, and their comparison as prognosis/diagnosis biomarkers.

This review examines and compares the diagnostic and prognostic capabilities of miRNAs and lncRNAs derived from pseudogenes in cancer patients. Additionally, it delves into their roles in cancer pathogenesis. Both miRNAs and pseudogene-derived lncRNAs have undergone thorough investigation as remarkably sensitive and specific cancer biomarkers, offering significant potential for cancer detection and monitoring. . Extensive research is essential to gain a complete understanding of the precise roles these non-coding RNAs play in cancer, allowing the development of novel targeted therapies and biomarkers for improved cancer detection and treatment approaches.

Unveiling the regulatory of miR-101-3p on ZNF746 in a Parkinson's disease cell model: Implications for therapeutic targeting.

In this study, we explored the regulatory role of microRNA miR-101-3p on the zinc finger protein 746 (ZNF746), also known as PARIS, which is implicated in both sporadic and familial forms of Parkinson's disease. In a Parkinson's disease cell model, utilizing SH-SY5Y cells treated with 1-methyl-4-phenylpyridine (MPP+), we observed that miR-101-3p was downregulated, while ZNF746 was upregulated. To investigate the direct impact of miR-101-3p on ZNF746, our team conducted overexpression experiments, successfully reversing ZNF746's expression at both the mRNA and protein levels, as confirmed through quantitative PCR and western blotting. We also performed luciferase assays, providing compelling evidence that ZNF746 is a direct target of miR-101-3p. Additionally, we noted that miR-101-3p overexpression resulted in increased expression of PGC1α, a gene targeted by ZNF746. Functionally, we assessed the implications of miR-101-3p overexpression through MTS assays and flow cytometry, revealing significant promotion of cell viability, inhibition of ROS production, and reduced apoptosis in the Parkinson's disease cell model. In conclusion, this study highlights the role of miR-101-3p in regulating ZNF746 expression and suggests its potential as a therapeutic target for Parkinson's disease. These findings provide valuable molecular insights that could pave the way for innovative treatment strategies in combating this debilitating neurodegenerative disorder.

Decellularized tracheal scaffold as a promising 3D scaffold for tissue engineering applications.

Tissue engineering is a science that uses the combination of scaffolds, cells, and active biomolecules to make tissue in order to restore or maintain its function and improve the damaged tissue or even an organ in the laboratory. The purpose of this research was to study the characteristics and biocompatibility of decellularized sheep tracheal scaffolds and also to investigate the differentiation of Adipose-derived stem cells (AD-MSCs) into tracheal cells. After the decellularization of sheep tracheas through the detergent-enzyme method, histological evaluations, measurement of biochemical factors, measurement of DNA amount, and photographing the ultrastructure of the samples by scanning electron microscopy (SEM), they were also evaluated mechanically. Further, In order to check the viability and adhesion of stem cells to the decellularized scaffolds, adipose mesenchymal stem cells were cultured on the scaffolds, and the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay was performed. The expression analysis of the intended genes for the differentiation of mesenchymal stem cells into tracheal cells was evaluated by the real-time PCR method. These results show that the prepared scaffolds are an ideal model for engineering applications, have high biocompatibility, and that the tracheal scaffold provides a suitable environment for the differentiation of ADMSCs. This review provides a basis for future research on tracheal decellularization scaffolds, serves as a suitable model for organ regeneration, and paves the way for their use in clinical medicine.

Exploring the Therapeutic Potential of Fe3O4@Glu-Oleuropein Nanoparticles in Targeting KRAS Pathway-Regulating lncRNAs in Colorectal Cancer Cells.

Cancer, the leading cause of death worldwide, has witnessed significant advancements in treatment through targeted therapies. Among the proto-oncogenes prevalent in human cancers, KRAS stands out, and recent research has focused on long noncoding RNAs (lncRNAs) as regulators of miRNAs targeting the KRAS oncogene. This study specifically explores lncRNAs involved in the KRAS pathway in colorectal cancer (CRC). To investigate this, researchers employed iron oxide nanoparticles coated with glucose and conjugated with Oleuropein (Fe3O4@Glu-Oleuropein NPs) to evaluate their impact on candidate lncRNAs associated with KRAS pathway deregulation. The study utilized TCGA data to identify genes affected by KRAS mutation and lncRNAs linked to KRAS in CRC. Enrichr and MsigDB databases helped identify relevant pathways. Genes with a correlation coefficient above 0.5 and a P-value less than 0.01 with candidate lncRNAs were selected. MTT and flow cytometry assays determined the anti-proliferative and apoptotic effects of Fe3O4@Glu-Oleuropein NPs on CRC cells (SW480) and normal cells (HEK293). The findings showed that increased expression of FEZF1-AS1, GAS6-AS1, and LINC00920 correlated with mutated KRAS, and co-expressed genes were significantly involved in hypoxia, KRAS signaling, DNA repair, and IL-2/STAT5 signaling pathways. Fe3O4@Glu-Oleuropein NPs exhibited higher toxicity toward cancer cells, with IC50 values of 92 µg/ml for SW480 and 281 µg/ml for HEK293. Flow cytometry analysis revealed a substantial increase in necrotic and apoptotic cells when treated with Fe3O4@Glu-Oleuropein, along with down-regulation of GAS6-AS1, LINC00920, and FEZF1-AS1 lncRNAs in treated cells. In conclusion, this study highlights the therapeutic potential of Fe3O4@Glu-Oleuropein on colon cancer cells in vitro. The identification of lncRNAs involved in the KRAS pathway provides insights into the underlying mechanisms and offers avenues for further research in targeted cancer therapies.

Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene.

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the subtypes of breast cancer (BC) that is associated with poor survival rates and failure to respond to hormonal and targeted therapies. OBJECTIVE: The aim of this study was to identify a specific gene at the expression level for TNBC and targeting of this type of breast cancer based on it. Using TCGA database, genes that are particularly high expression in TNBC subtypes compared to other BC subtypes (in terms of receptor status) and normal samples were identified and their sensitivity and specificity were evaluated. Using PharmacoGX and Drug Bank data, drug sensitivity and drug-appropriate genes were identified, respectively. The effects of the identified drug on triple-negative cell lines (MDA-MB-468) were evaluated in comparison with the cell line of other subtypes (MCF7) by apoptosis and MTS tests. RESULTS: Data analyzes showed that the expression level of KCNG1 gene in the TNBC subgroup was significantly higher compared to other BC subtypes from the KCN gene family and ROC results showed that this gene had highest sensitivity and specificity in TNBC subtype. The results of drug resistance and sensitivity showed that an increase in the expression level of KCNG1 was associated with sensitivity to Cisplatin and Oxaliplatin. Moreover, Drug Bank results showed that Guanidine hydrochloride (GuHCl) was a suitable inhibitor for KCNG1. In vitro results showed that the expression level of KCNG1 was higher in MDA-MB-468 compared to MCF7. In addition, the rate of apoptosis in response to GuHCl treatment in MDA-MB-468 cell line as TNBC cell model was higher than MCF7 in the same concentration. CONCLUSION: This study revealed that GuHCl could be a suitable treatment for TNBC subtype by targeting of KCNG1.

Colon cancer transcriptome.

Over the last four decades, methodological innovations have continuously changed transcriptome profiling. It is now feasible to sequence and quantify the transcriptional outputs of individual cells or thousands of samples using RNA sequencing (RNA-seq). These transcriptomes serve as a connection between cellular behaviors and their underlying molecular mechanisms, such as mutations. This relationship, in the context of cancer, provides a chance to unravel tumor complexity and heterogeneity and uncover novel biomarkers or treatment options. Since colon cancer is one of the most frequent malignancies, its prognosis and diagnosis seem to be critical. The transcriptome technology is developing for an earlier and more accurate diagnosis of cancer which can provide better protectivity and prognostic utility to medical teams and patients. A transcriptome is a whole set of expressed coding and non-coding RNAs in an individual or cell population. The cancer transcriptome includes RNA-based changes. The combined genome and transcriptome of a patient may provide a comprehensive picture of their cancer, and this information is beginning to affect treatment decision-making in real-time. A full assessment of the transcriptome of colon (colorectal) cancer has been assessed in this review paper based on risk factors such as age, obesity, gender, alcohol use, race, and also different stages of cancer, as well as non-coding RNAs like circRNAs, miRNAs, lncRNAs, and siRNAs. Similarly, they have been examined independently in the transcriptome study of colon cancer.

Coordinated modification in expression levels of HSPA1A/B, DGKH, and NOTCH2 in Parkinson's patients' blood and substantia nigra as a diagnostic sign: the transcriptomes' relationship.

BACKGROUND: Diagnosis of Parkinson's disease (PD) is associated with a vast number of challenges. This study aimed to assess the overlap of PD patients' transcriptomes in the substantia nigra (SN) with peripheral blood mononuclear cells (PBMCs) to discover potential biomarkers for diagnosis. METHODS: GEO data were used to select genes with significant changes in expression level in the SN region and eligible studies. Also, transcriptome data related to blood of PD patients with other neurodegenerative diseases (ND) was considered. Differential expression genes between PD and control were evaluated in the SN and blood, and RT-qPCR was applied to validate the findings. RESULTS: At the expression level, no significant similarity in long non-coding RNA was found between the patients' SN and blood. While in silico results revealed 16 common mRNAs in SN and blood with significant expression levels. Among all overexpressed mRNAs, HSPA1A/B expression level had the highest expression difference between control and PD samples. Moreover, DGKH had the highest score of down-regulated genes in both blood and SN. The NOTCH pathway had the highest score pathway among up-regulated pathways, and the expression levels of NOTCH2, H4C8, and H2BC21 associated with this pathway had the most ability to separate the control and PD populations. Furthermore, RT-qPCR results revealed that HSPA1A/B, NOTCH2, and H4C8 were overexpressed in PD PBMCs, while DGKH expression levels were lower compared to controls. CONCLUSION: Our findings indicate that expression levels of HSPA1A/B, DGKH, and NOTCH2 could be applied as candidate biomarkers to diagnose PD patients in the SN region and PBMCs.

Diagnostic and therapeutic potential of LINC01929 as an oncogenic LncRNA in human cancers.

Recent findings have shown the significant role of long non-coding RNAs in the pathogenesis of various cancers. In this regard, the variation in the expression of LINC01929 was explored in various cancers to explore its impact on the development of diverse malignancies and cancers. The data of the cancer genome atlas (TCGA) were utilized to evaluate the changes in the expression of LINC01929 in various cancers, as well as its relationship with the patients' survival rate. The co-expression of the genes and data merging of TCGA were utilized to identify the LINC01929-associated pathways. The samples of colorectal, gastric, and breast cancers were also examined by the RT-qPCR to confirm the results and evaluate the expression of LINC01929 in the mentioned cancers. In silico investigations indicated a remarkable enhancement in the expression of LINC01929 within the tumor tissues compared to normal samples in 10 types of cancer. Based on the survival results, the increase in the LINC01929 expression is linked to poor prognosis of bladder, breast, colorectal, kidney, and liver cancers. The gene co-expression network showed the strong co-expression of LINC01929 with genes involved in the metastatic pathways including COL5A1. RT-qPCR findings showed a remarkable increment in the expression level of LINC01929 in the colorectal, gastric, and breast tumor tissues versus the adjacent normal tissues. A significant and strong relationship was also found between the expression of LINC01929 and COL5A1. This study indicated a significant enhancement in the expression level of LINC01929 in various cancer types, accompanied by the mortality rate. Moreover, LINC01929 exhibited a strong co-expression with the metastatic genes such as COL5A1. As an oncogene and regulator of the metastatic pathways, LINC01929 can be a proper candidate for diagnostic and therapeutic purposes.

Towards dual function of autophagy in breast cancer: A potent regulator of tumor progression and therapy response.

As a devastating disease, breast cancer has been responsible for decrease in life expectancy of females and its morbidity and mortality are high. Breast cancer is the most common tumor in females and its treatment has been based on employment of surgical resection, chemotherapy and radiotherapy. The changes in biological behavior of breast tumor relies on genomic and epigenetic mutations and depletions as well as dysregulation of molecular mechanisms that autophagy is among them. Autophagy function can be oncogenic in increasing tumorigenesis, and when it has pro-death function, it causes reduction in viability of tumor cells. The carcinogenic function of autophagy in breast tumor is an impediment towards effective therapy of patients, as it can cause drug resistance and radio-resistance. The important hallmarks of breast tumor such as glucose metabolism, proliferation, apoptosis and metastasis can be regulated by autophagy. Oncogenic autophagy can inhibit apoptosis, while it promotes stemness of breast tumor. Moreover, autophagy demonstrates interaction with tumor microenvironment components such as macrophages and its level can be regulated by anti-tumor compounds in breast tumor therapy. The reasons of considering autophagy in breast cancer therapy is its pleiotropic function, dual role (pro-survival and pro-death) and crosstalk with important molecular mechanisms such as apoptosis. Moreover, current review provides a pre-clinical and clinical evaluation of autophagy in breast tumor.

The PBX1/miR-141-miR-200a/EGR2/SOCS3 Axis; Integrative Analysis of Interaction Networks to Discover the Possible Mechanism of MiR-141 and MiR-200a-Mediated Th17 Cell Differentiation.

Background: Overexpression of miR-141 and miR-200a is known to be associated with the differentiation of T helper 17 (Th17) cells, which are key players in the pathophysiology of autoimmune disorders. However, the function and governing mechanism of these two microRNAs (miRNAs) in Th17 cell skewing are poorly defined. Objectives: The aim of the present study was to identify the common upstream transcription factors and downstream target genes of miR-141 and miR-200a to obtain a better insight into the possible dysregulated molecular regulatory networks driving miR-141/miR-200a-mediated Th17 cell development. Materials and Methods: A consensus-based prediction strategy was applied for in-silico identification of potential transcription factors and putative gene targets of miR-141 and miR-200a. Thereafter, we analyzed the expression patterns of candidate transcription factors and target genes during human Th17 cell differentiation by quantitative real-time PCR and examined the direct interaction between both miRNAs and their potential target sequences using dual-luciferase reporter assays. Results: According to our miRNA-based and gene-based interaction network analyses, pre-B cell leukemia homeobox (PBX1) and early growth response 2 (EGR2) were respectively taken into account as the potential upstream transcription factor and downstream target gene of miR-141 and miR-200a. There was a significant overexpression of the PBX1 gene during the Th17 cell induction period. Furthermore, both miRNAs could directly target EGR2 and inhibit its expression. As a downstream gene of EGR2, the suppressor of cytokine signaling 3 (SOCS3) was also downregulated during the differentiation process. Conclusions: These results indicate that activation of the PBX1/miR-141-miR-200a/EGR2/SOCS3 axis may promote Th17 cell development and, therefore, trigger or exacerbate Th17-mediated autoimmunity.

Identification of genes with high heterogeneity of expression as a predictor of different prognosis and therapeutic responses in colorectal cancer: a challenge and a strategy.

BACKGROUND: Molecular heterogeneity is one of the most important concerns in colorectal cancer (CRC), which results in a wide range of therapy responses and patient prognosis. We aimed to identify the genes with high heterogeneity of expression (HHE) and their relation with prognosis and drug resistance. METHODS: Two cohort studies, the cancer genome atlas (TCGA) and the GSE39582, were used to discover oncogenes genes with HHE. The relationship between identified genes with clinical and genomic characteristics was evaluated based on TCGA data. Also, the GDSC and CCLE data were used for drug resistance and sensitivity. Sixty CRC samples were used to validate the obtained data by RT-qPCR. RESULTS: Findings revealed that 132 genes with HHE were found to be up-regulated in both cohorts and were enriched in pathways such as hypoxia, angiogenesis, and metastasis. Forty-nine of selected genes related to clinical and genomic variables, including stage, common mutations, the tumor site, and microsatellite state that were ignored. The expression level of CXCL1, SFTA2, SELE, and SACS as genes with HHE were predicted survival patients, and RT-qPCR results demonstrated that levels of SELE and SACS had HHE in CRC samples. The expression of many identified genes like BGN, MMP7, COL11A1, FAP, KLK10, and TNFRSE11B was associated with resistance to chemotherapy drugs. CONCLUSIONS: Some genes expression, including SELE, SACS, BGN, KLK10, COL11A1, and TNFRSE11B have an oncogenic function with HHE, and their expression can be used as indicators for differing treatment responses and survival rates in CRC.

Pioglitazone Mediates Cardiac Progenitor Formation through Increasing ROS Levels.

In order to achieve a sufficient population of cardiac-committed progenitor cells, it is crucial to know the mechanisms of cardiac progenitor formation. Previous studies suggested ROS effect on cardiac commitment events to play a key role in the cell signaling and activate cardiac differentiation of pluripotent stem cells. We previously reported that PPARγ activity is essential for cardiac progenitor cell commitment. Although several studies have conducted the involvement of PPARγ-related signaling pathways in cardiac differentiation, so far, the regulatory mechanisms of these signaling pathways have not been discussed and cleared. In this study, we focus on the role of PPARγ agonist in ROS generation and its further effects on the differentiation of cardiac cells from mESCs. The results of this study show that the presence of ROS is necessary for heart differentiation in the precursor stage of cardiac cells, and the coenzyme Q10 antioxidant precludes proper cardiac differentiation. In addition, this antioxidant prevents the action of pioglitazone in increasing oxygen radicals as well as beating cardiomyocyte differentiation properties. In this case, it can be concluded that PPARγ is required to modulate ROS levels during cardiac differentiation.