The clinical utility of miR-215 as a potential biomarker in colon cancer was investigated. The levels of miR-215 were quantified by real-time qRT-PCR in 34 paired normal and tumor specimens. The expression levels of miR-215 were decreased in colon tumors, and were associated with patient survival. Thus, miR-215 is a potential prognostic biomarker in colon cancer. Background We have previously shown that miR-215 suppressed the expression of key targets such as thymidylate synthase (TS), dihydrofolate reductase, and denticleless protein homolog (DTL) in colon cancer. miR-215 is a tumor suppressor candidate due to the upregulation of p53 and p21 by targeting DTL. However, high levels of miR-215 conferred chemoresistance due to cell cycle arrest and reduced cell proliferation by suppressing DTL. In this study, the clinical significance of miR-215 was further investigated as a potential prognostic biomarker in colon cancer patients. Methods Total RNAs were extracted from 34 paired normal and colon (stage II and III) tumor specimens using the Trizol-based approach. The levels of miR-215 and a closely related miR-192 were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) expression analysis. The expression of DTL mRNA and protein were quantified by real time qRT-PCR and immunohistochemistry. Results The expression levels of miR-192 (P = .0008) and miR-215 (P < .0001) were significantly decreased in colon tumors compared with normal tissues. DTL was significantly over-expressed and was inversely correlated with miR-215, further suggesting an in vivo physiologic relevance of miR-215 mediated DTL suppression. Kaplan-Meier survival analysis by Cox regression revealed that high levels of miR-215 expression (hazard ratio, 3.516; 95% confidence interval, 1.007–12.28, P = .025) are closely associated with poor patient’s overall survival. Furthermore, an elevated expression of a miR-215 target protein DTL was detected in colon cancer tissues whereas no expression was present in normal tissues. Conclusion miR-215 has a unique potential as a prognostic biomarker in stage II and III colon cancer.

PurposemicroRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Experimental DesignTotal RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.ResultsThe expression levels of miR-200c (P<0.0001) and miR-205 (P<0.0001) were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028). Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.ConclusionmiR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

Sharks and skates represent the earliest vertebrates with an adaptive immune system based on lymphocyte antigen receptors generated by V(D)J recombination. Shark B cells express two classical immunoglobulins (Ig), IgM and IgW, encoded by an early, alternative gene organization consisting of numerous autonomous miniloci, where the individual gene cluster carries a few rearranging gene segments and one constant region, μ or ω. We have characterized eight distinct Ig miniloci encoding the nurse shark omega heavy (H) chain. Each cluster consists of VH, D and JH segments and six to eight constant (C) domain exons. Two interspersed secretory exons, in addition to the 3’-most C exon with tailpiece, provide the gene cluster with the ability to generate at least six secreted isoforms that differ as to polypeptide length and C domain combination. All clusters appear to be functional, as judged by the capability for rearrangement and absence of defects in the deduced amino acid sequence. We previously showed that IgW VDJ can perform isotype switching to μ C regions; in this study we found that switching also occurs between ω clusters. Thus C region diversification for any IgW VDJ can take place at the DNA level, by switching to other ω or μ C regions, as well as by RNA processing to generate different C isoforms. The wide array of pathogens recognized by antibodies require different disposal pathways, and our findings demonstrate complex and unique pathways for C effector function diversity that evolved independently in cartilaginous fishes.

Background Until today, assessment of renal function has remained a challenge for modern medicine. In many cases, kidney diseases accompanied by a decrease in renal function remain undetected and unsolved, since neither laboratory tests nor imaging diagnostics provide adequate information on kidney status. In recent years, developments in the field of functional magnetic resonance imaging with application to abdominal organs have opened new possibilities combining anatomic imaging with multiparametric functional information. The multiparametric approach enables the measurement of perfusion, diffusion, oxygenation, and tissue characterization in one examination, thus providing more comprehensive insight into pathophysiological processes of diseases as well as effects of therapeutic interventions. However, application of multiparametric fMRI in the kidneys is still restricted mainly to research areas and transfer to the clinical routine is still outstanding. One of the major challenges is the lack of a standardized protocol for acquisition and postprocessing including efficient strategies for data analysis. This article provides an overview of the most common fMRI techniques with application to the kidney together with new approaches regarding data analysis with deep learning. Methods This article implies a selective literature review using the literature database PubMed in May 2021 supplemented by our own experiences in this field. Results and Conclusion Functional multiparametric MRI is a promising technique for assessing renal function in a more comprehensive approach by combining multiple parameters such as perfusion, diffusion, and BOLD imaging. New approaches with the application of deep learning techniques could substantially contribute to overcoming the challenge of handling the quantity of data and developing more efficient data postprocessing and analysis protocols. Thus, it can be hoped that multiparametric fMRI protocols can be sufficiently optimized to be used for routine renal examination and to assist clinicians in the diagnostics, monitoring, and treatment of kidney diseases in the future. Key Points:  Citation Format

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