A prediction of the CRNDE role by modulating NF-κB pathway in inflammatory bowel disease (IBD).

Long non-coding RNAs (lncRNAs) regulate multiple pathways and cellular mechanisms. Recent research has emphasized their involvement in the pathogenesis of complex diseases, such as Inflammatory Bowel Disease (IBD) which is characterized by chronic inflammation of the intestines. The two most common types of IBD are ulcerative colitis and Crohn's disease. CRNDE lncRNA was initially detected in colorectal cancer (CRC) and found to be involved in the tumorigenesis pathways. Further studies revealed the role of CRNDE in activating inflammation and promoting the release of inflammatory cytokines. This study utilizes the RNA-seq data analysis and bioinformatics tools to clarify the role of CRNDE in the IBD pathogenesis and confirms its expression in inflamed HT-29 and Caco-2 cell lines and also colonic and blood samples of UC patients and controls ex vivo. Based on our results, CRNDE was significantly upregulated in IBD samples compared to controls in RNA-seq data analysis and Real-time PCR of inflamed HT-29 cell line and colonic biopsies from UC patients. Additionally, predicted that its expression is positively correlated with the pro-inflammatory cytokines production. CRNDE interactions was investigated with several inflammation-related miRNAs and regulatory proteins computationally. Thus, CRNDE upregulation in the colon of IBD patients could be involved in IBD pathogenesis by promoting inflammatory pathways and targeting anti-inflammatory miRNAs.

Meta-analysis of microarray data to determine gene indicators involved in the cisplatin resistance in ovarian cancer.

BACKGROUND: Significant miss-expressed gene indicators contributing to cisplatin resistance in ovarian cancer have not been completely understood. It seems that several regulatory genes and signaling pathways are associated with the emergence of the chemo-resistant phenotype. AIMS: Here, a meta-analysis approach was adopted to assess deregulated genes involved in relapse after the first line of chemotherapy (cisplatin). METHODS AND RESULTS: To do so, six ovarian cancer libraries were gathered from GEO repository. Batch effect removal and quality assessment, and boxplots and PCA were performed using SVA and ggplot2 packages in R, respectively. Cisplatin-resistant and -sensitive ovarian cancer groups were compared with find genes with significant expression changes using linear regression models in the LIMMA R package. The significance threshold for DEGs was taken as adj p-value < .05 and - 1 > logFC > 1. A total of 261 genes were identified to have significant differential expression levels in the cisplatin-resistant versus cisplatin-sensitive group. Among the 10 top up-regulated and down-regulated genes, PITX2, SNCA, and EPHA7 (up), as well as TMEM98 (down) are indirect upstream regulators of PI3K/AKT signaling pathway, contributing greatly to the development of chemo-resistance in cancer via promoting cell proliferation, survival, and cell cycle progression as well as inhibiting apoptosis. Moreover, a comprehensive assessment of DEGs revealed the dysregulation of not only membrane ion channels KCa1.1, Kv4, and CACNB4, affecting cell excitability, proliferation, and apoptosis but also cell adhesion proteins COL4A6, EPHA3, and CD9, affecting the attachment of normal cells to ECM and apoptosis, introducing good options to reverse cisplatin resistance. CONCLUSION: Our results predict and suggest that upstream regulators of PI3K/AKT signaling pathway, ion channels, and cell adhesion proteins play important roles in cisplatin resistance development in ovarian cancer.

Acute Kidney Injury (AKI) in COVID-19: In silico Identification of LncRNA-MiRNA-Gene Networks and Key Transcription Factors.

PURPOSE: Acute kidney injury (AKI) accounts for up to 29% of severe COVID-19 cases and increases mortality among these patients. Viral infections participate in the pathogenesis of diseases by changing the expression profile of normal transcriptome. This study attempts to identify LncRNA-miRNA-gene and TF-gene networks as gene expression regulating networks in the kidney tissues of COVID-19 patients. METHODS: In this analysis, four kidney libraries from the GEO repository were considered. To conduct the preprocessing, Deseq2 software in R was used for the purpose of data normalization and log2 transformation. In addition, pre- and post-normalization, PCA and box plots were developed using ggplot2 software in R for quality control. The expression profiles of the kidney samples of COVID-19 patients and control individuals were compared using DEseq2 software in R. The considered significance thresholds for DEGs were Adj P value < 0.05 and |logFC| >2. Then, to predict molecular interactions in lncRNA-miRNA-gene networks, different databases, including DeepBase v3.0, miRNATissueAtlas2, DIANA-LncBase v3, and miRWalk, were used. Furthermore, by employing ChEA databases, interactions at the TF-Gene level were obtained. Finally, the obtained networks were plotted using Stringdb and Cytoscape v8. RESULTS: Results obtained from the comparison of the post-mortem kidney tissue samples of the COVID-19 patients with the healthy kidney tissue samples showed significant changes in the expression of more than 2000 genes. In addition, predictions regarding the miRNA-gene interaction network based on DEGs obtained from this meta-analysis showed that 11 miRNAs targeted the obtained DEGs. Interestingly, in the kidney tissue, these 11 miRNAs interacted with LINC01874, LINC01788, and LINC01320, which have high specificity for this tissue. Moreover, four transcription factors of EGR1, SMAD4, STAT3, and CHD1 were identified as key transcription factors regulating DEGs. Taken together, the current study showed several dysregulated genes in the kidney of patients affected with COVID-19. CONCLUSION: This study suggests lncRNA-miRNA-gene networks and key TFs as new diagnostic and therapeutic targets for experimental and preclinical studies.

The critical role of gut-brain axis microbiome in mental disorders.

The Gut-brain axis is a bidirectional neural and humoral signaling that plays an important role in mental disorders and intestinal health and connects them as well. Over the past decades, the gut microbiota has been explored as an important part of the gastrointestinal tract that plays a crucial role in the regulation of most functions of various human organs. The evidence shows several mediators such as short-chain fatty acids, peptides, and neurotransmitters that are produced by the gut may affect the brain's function directly or indirectly. Thus, dysregulation in this microbiome community can give rise to several diseases such as Parkinson's disease, depression, irritable bowel syndrome, and Alzheimer's disease. So, the interactions between the gut and the brain are significantly considered, and also it provides a prominent subject to investigate the causes of some diseases. In this article, we reviewed and focused on the role of the largest and most repetitive bacterial community and their relevance with some diseases that they have mentioned previously.

Probiotics and probiotic-based vaccines: A novel approach for improving vaccine efficacy.

Vaccination is defined as the stimulation and development of the adaptive immune system by administering specific antigens. Vaccines' efficacy, in inducing immunity, varies in different societies due to economic, social, and biological conditions. One of the influential biological factors is gut microbiota. Cross-talks between gut bacteria and the host immune system are initiated at birth during microbial colonization and directly control the immune responses and protection against pathogen colonization. Imbalances in the gut microbiota composition, termed dysbiosis, can trigger several immune disorders through the activity of the adaptive immune system and impair the adequate response to the vaccination. The bacteria used in probiotics are often members of the gut microbiota, which have health benefits for the host. Probiotics are generally consumed as a component of fermented foods, affect both innate and acquired immune systems, and decrease infections. This review aimed to discuss the gut microbiota's role in regulating immune responses to vaccination and how probiotics can help induce immune responses against pathogens. Finally, probiotic-based oral vaccines and their efficacy have been discussed.

Obesity, a challenge in the management of inflammatory bowel diseases.

Obesity, a morbid condition snowballing in the world, may cause many health issues in healthy and ill people. Many disorders are known to be influenced by obesity, mainly in a catastrophic way, including inflammatory bowel disease (IBD). Many studies sought to determine the effects that obesity prompts IBD. Some of them indicate that obesity is associated with poor outcomes. There is no consistency regarding the correlation between obesity and IBDs due to the equivocal nature of obesity and the shortage of extensive and reliable investigations. However, to a worldwide consensus, obesity has a unique disease burden and can cause poor prognosis when it accompanies other ailments. Here, we have reviewed some of the alterations and impacts that obesity may impose on the pathogenesis and clinical management of IBD. Conclusively, inflammatory processes of IBD are reinforced by obesity. Furthermore, as a two-way road, obesity can be caused by IBD. However, autoimmunity in IBD is not found to have a consistent relationship with obesity. Although, medical and surgical treatments of IBD are affected by obesity in terms of their efficacy and outcomes. The most important aspect of obesity that can influence the course of disease management is associated with significant disabilities that obesity may cause rather than a metabolic or molecular rationale.

Overview of Three Proliferation Pathways (Wnt, Notch, and Hippo) in Intestine and Immune System and Their Role in Inflammatory Bowel Diseases (IBDs).

Inflammatory bowel disease (IBD) is a disorder, which involves the gastrointestinal (GI) tract consisting Crohn's disease (CD) and ulcerative colitis (UC). The etiology of this disease is not yet clear and, hence, there are numerous medications and treatments for patients with IBD, although a definite and permanent treatment is still missing. Therefore, finding novel therapeutic approaches are vital for curing patients with IBD. In the GI tract, there are various lineages of cells with different roles that their existence is necessary for the barrier function of intestinal epithelial cells (IECs). Therefore, signaling pathways, which manage the hemostasis of cell lineages in intestine, such as Wnt, Notch, and Hippo, could have crucial roles in regulation of barrier function in the intestine. Additionally, these signaling pathways function as a governor of cell growth, tissue homeostasis, and organ size. In patients with IBD, recent studies have revealed that these signaling pathways are dysregulated that it could result in depletion or excess of a cell lineage in the intestine. Moreover, dysregulation of these signaling pathways in different cell lineages of the immune system could lead to dysregulation of the immune system's responses in IBD. In this article, we summarized the components and signaling of Wnt, Notch, and Hippo pathways and their role in the intestine and immune system. Furthermore, we reviewed latest scientific literature on the crosstalk among these three signaling pathways in IBD. An overview of these three signaling pathways and their interactions in IBD could provide a novel insight for prospective study directions into finding efficient medications or treatments.

Serological response to SARS-CoV-2 is attenuated in patients with inflammatory bowel disease and can affect immunization.

In this study we indicated that impaired serological responses to SARS-CoV-2 infection among patients with IBD, could have significant implications for this group of patients and should be considered in vaccination program.

Circulating tumor DNA applications in monitoring the treatment of metastatic colorectal cancer patients.

Colorectal cancer is the third most common cancer worldwide. New cancer treatment strategies such as monoclonal antibodies against growth factor and angiogenesis receptors have improved the overall survival (OS) and progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients. However, acquired resistance could happen after these therapies. Circulating tumor DNA (ctDNA) is the DNA fraction derived from tumor cells which could be applied as a non-invasive method for detecting tumor mutations before, during, and after therapies. Here, we reviewed most of the studies examining ctDNA as treatment monitoring in mCRC patients who receive different target therapies. Also, we compared ctDNA with other existing cancer-treatment monitoring methods.

Circulating tumor DNA applications in monitoring the treatment of metastatic colorectal cancer patients.

Colorectal cancer is the third most common cancer worldwide. New cancer treatment strategies such as monoclonal antibodies against growth factor and angiogenesis receptors have improved the overall survival (OS) and progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients. However, acquired resistance could happen after these therapies. Circulating tumor DNA (ctDNA) is the DNA fraction derived from tumor cells which could be applied as a non-invasive method for detecting tumor mutations before, during, and after therapies. Here, we reviewed most of the studies examining ctDNA as treatment monitoring in mCRC patients who receive different target therapies. Also, we compared ctDNA with other existing cancer-treatment monitoring methods.