MicroRNAs as Potential Biomarkers in Gynecological Cancers.

MicroRNAs are non-coding transcripts that, thanks to the ability to regulate the mRNA of target genes, can affect the expression of genes encoding tumor suppressors and oncogenes. They can control many important cellular processes, including apoptosis, differentiation, growth, division, and metabolism. Therefore, miRNAs play an important role in the development of many cancers, including gynecological cancers. Ovarian cancer, endometrial cancer, cervical cancer, and vulvar cancer are the most common cancers in women and are a frequent cause of death. The heterogeneity of the pathogenesis of these gynecological diseases makes the diagnostic process a significant obstacle for modern medicine. To date, many studies have been carried out, in which particular attention has been paid to the molecular pathomechanism of these diseases, with particular emphasis on miRNAs. To date, the changed profile of many miRNAs, which influenced the promotion of proliferation, migration, invasion processes and the simultaneous inhibition of programmed cell death, has been proven many times. Detailed understanding of the molecular effects of miRNAs in the above-mentioned gynecological cancers will enable the development of potential predictive and prognostic biomarkers, as well as the optimization of the diagnostic process.

ONQUADRO: a database of experimentally determined quadruplex structures.

ONQUADRO is an advanced database system that supports the study of the structures of canonical and non-canonical quadruplexes. It combines a relational database that collects comprehensive information on tetrads, quadruplexes, and G4-helices; programs to compute structure parameters and visualise the data; scripts for statistical analysis; automatic updates and newsletter modules; and a web application that provides a user interface. The database is a self-updating resource, with new information arriving once a week. The preliminary data are downloaded from the Protein Data Bank, processed, annotated, and completed. As of August 2021, ONQUADRO contains 1,661 tetrads, 518 quadruplexes, and 30 G4-helices found in 467 experimentally determined 3D structures of nucleic acids. Users can view and download their description: sequence, secondary structure (dot-bracket, classical diagram, arc diagram), tertiary structure (ball-and-stick, surface or vdw-ball model, layer diagram), planarity, twist, rise, chi angle (value and type), loop characteristics, strand directionality, metal ions, ONZ, and Webba da Silva classification (the latter by loop topology and tetrad combination), origin structure ID, assembly ID, experimental method, and molecule type. The database is freely available at https://onquadro.cs.put.poznan.pl/. It can be used on both desktop computers and mobile devices.

How bioinformatics resources work with G4 RNAs.

Quadruplexes (G4s) are of interest, which increases with the number of identified G4 structures and knowledge about their biomedical potential. These unique motifs form in many organisms, including humans, where their appearance correlates with various diseases. Scientists store and analyze quadruplexes using recently developed bioinformatic tools-many of them focused on DNA structures. With an expanding collection of G4 RNAs, we check how existing tools deal with them. We review all available bioinformatics resources dedicated to quadruplexes and examine their usefulness in G4 RNA analysis. We distinguish the following subsets of resources: databases, tools to predict putative quadruplex sequences, tools to predict secondary structure with quadruplexes and tools to analyze and visualize quadruplex structures. We share the results obtained from processing specially created RNA datasets with these tools. Contact: mszachniuk@cs.put.poznan.pl Supplementary information: Supplementary data are available at Briefings in Bioinformatics online.

Apoptosis in Autoimmunological Diseases, with Particular Consideration of Molecular Aspects of Psoriasis.

Apoptosis is a natural physiological process involving programmed cell death. Thanks to this process, it is possible to maintain the homeostasis of the body and the immune system. Dysfunctions of this mechanism lead to development of autoimmune diseases such as psoriasis; these diseases are chronic and treatment is extremely difficult. In psoriasis (a skin disease), apoptosis disorders are manifested by keratinocyte proliferation dysfunction. Autoimmune diseases coexisting with psoriasis include multiple sclerosis, autoimmune thyroid disease, and diabetes, but the common pathogenesis of these diseases is not fully understood. Given the heterogenous nature and chronic and recurrent course of psoriasis, the selection of an effective therapeutic strategy is still a problem. This literature review was focused on the process of apoptosis as a factor in the development of autoimmune diseases, with particular emphasis on psoriasis. The work also includes a review of therapeutic methods of psoriasis based on the latest literature.

Topology-based classification of tetrads and quadruplex structures.

MOTIVATION: Quadruplexes attract the attention of researchers from many fields of bio-science. Due to a specific structure, these tertiary motifs are involved in various biological processes. They are also promising therapeutic targets in many strategies of drug development, including anticancer and neurological disease treatment. The uniqueness and diversity of their forms cause that quadruplexes show great potential in novel biological applications. The existing approaches for quadruplex analysis are based on sequence or 3D structure features and address canonical motifs only. RESULTS: In our study, we analyzed tetrads and quadruplexes contained in nucleic acid molecules deposited in Protein Data Bank. Focusing on their secondary structure topology, we adjusted its graphical diagram and proposed new dot-bracket and arc representations. We defined the novel classification of these motifs. It can handle both canonical and non-canonical cases. Based on this new taxonomy, we implemented a method that automatically recognizes the types of tetrads and quadruplexes occurring as unimolecular structures. Finally, we conducted a statistical analysis of these motifs found in experimentally determined nucleic acid structures in relation to the new classification. AVAILABILITY AND IMPLEMENTATION: https://github.com/tzok/eltetrado/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Discovering Structural Motifs in miRNA Precursors from the Viridiplantae Kingdom.

A small non-coding molecule of microRNA (19⁻24 nt) controls almost every biological process, including cellular and physiological, of various organisms' lives. The amount of microRNA (miRNA) produced within an organism is highly correlated to the organism's key processes, and determines whether the system works properly or not. A crucial factor in plant biogenesis of miRNA is the Dicer Like 1 (DCL1) enzyme. Its responsibility is to perform the cleavages in the miRNA maturation process. Despite everything we already know about the last phase of plant miRNA creation, recognition of miRNA by DCL1 in pre-miRNA structures of plants remains an enigma. Herein, we present a bioinformatic procedure we have followed to discover structure patterns that could guide DCL1 to perform a cleavage in front of or behind an miRNA:miRNA* duplex. The patterns in the closest vicinity of microRNA are searched, within pre-miRNA sequences, as well as secondary and tertiary structures. The dataset consists of structures of plant pre-miRNA from the Viridiplantae kingdom. The results confirm our previous observations based on Arabidopsis thaliana precursor analysis. Hereby, our hypothesis was tested on pre-miRNAs, collected from the miRBase database to show secondary structure patterns of small symmetric internal loops 1-1 and 2-2 at a 1⁻10 nt distance from the miRNA:miRNA* duplex.

Persisted/recurrent hyperparathyroidism associated with development of multi-drug resistance phenotype and proliferation of parathyroid transplants.

The surgical treatment of secondary hyperparathyroidism (HPTH) requires sub-total excision of parathyroid glands or total excision with their autotransplantation. Although this approach has been considered as a safe method of treatment, in this report we describe persisted/recurrent HPTH after parathyroid transplantation. Due to parathormone (PTH) hypersecretion and uncontrolled proliferation, the parathyroid grafts were removed and used for generation of cell cultures, which further have been subjected to in vitro studies. As a control we used parathyroid tissue, obtained during multiorgan harvesting. We found increased proliferation and up-regulated PTH production by the graft-derived, but not control in vitro cultured cells. Moreover, due to decrease of in vivo radiotracer uptake by parathyroid grafts, the expression of multi-drug resistance-involved factors, including P-glycoprotein (P-gp/mdr1), multi-drug resistance-associated protein (mrp) and bcl-2 have been investigated using RT-PCR. The analysis revealed increased expression of both, mdr1 and mrp in graft-derived cells, in contrast to control cells, which did not express P-gp/mdr1 or mrp. However, we did not observe any difference in expression of bcl-2 between analyzed cells. The up-regulated expression of P-gp/mdr1 on graft-derived cells was further confirmed by immunofluorescence studies. The described case indicates potential risk associated with transplantation of parathyroid tissue. Our results confirm a role of MDR phenomenon in occurrence of false negative results in parathyroid tissue scintigraphy studies. Moreover, they indicate that standard histological examination of transplanted material could not be sensitive enough to exclude any potential danger of abnormal graft progression. Thus, they could support the concept to use encapsulated parathyroid transplants.