Boron clusters as a platform for new materials: composites of nucleic acids and oligofunctionalized carboranes (C2B10H12) and their assembly into functional nanoparticles

Nanoscale ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 103-114 ◽  
Author(s):  
Damian Kaniowski ◽  
Katarzyna Ebenryter-Olbinska ◽  
Katarzyna Kulik ◽  
Slawomir Janczak ◽  
Anna Maciaszek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nucleic Acids ◽  
Gene Expression Regulation ◽  
Therapeutic Potential ◽  
Building Blocks ◽  
New Materials ◽  
Boron Cluster ◽  
Boron Clusters ◽  
Functional Nanoparticles ◽  
Dual Action

The building blocks based on boron cluster spanning two short DNA adapters assemble into functional nanoparticles due to the formation of DNA helices. They offer dual-action therapeutic potential, e.g., in the BNCT and gene expression regulation.

scholarly journals DNA Modified with Boron–Metal Cluster Complexes [M(C2B9H11)2]—Synthesis, Properties, and Applications

2018 ◽  
Vol 19 (11) ◽  
pp. 3501 ◽  
Author(s):  
Agnieszka Olejniczak ◽  
Barbara Nawrot ◽  
Zbigniew Leśnikowski
Keyword(s):  
Nucleic Acids ◽  
Metal Cluster ◽  
Building Blocks ◽  
Molecular Wires ◽  
Molecular Structures ◽  
Metal Centers ◽  
Cluster Complexes ◽  
Boron Cluster ◽  
Nucleic Acid Therapeutics ◽  
Synthesis Properties

Together with tremendous progress in biotechnology, nucleic acids, while retaining their status as “molecules of life”, are becoming “molecular wires”, materials for the construction of molecular structures at the junction between the biological and abiotic worlds. Herein, we present an overview of the approaches for incorporating metal centers into nucleic acids based on metal–boron cluster complexes (metallacarboranes) as the metal carriers. The methods are modular and versatile, allowing practical access to innovative metal-containing DNA for various applications, such as nucleic acid therapeutics, electrochemical biosensors, infrared-sensitive probes, and building blocks for nanoconstruction.

Nucleoside bearing boron clusters and their phosphoramidites – building blocks for modified oligonucleotide synthesis

2015 ◽  
Vol 39 (2) ◽  
pp. 1202-1221 ◽  
Author(s):  
Michał Matuszewski ◽  
Agnieszka Kiliszek ◽  
Wojciech Rypniewski ◽  
Zbigniew J. Lesnikowski ◽  
Agnieszka B. Olejniczak
Keyword(s):  
Building Blocks ◽  
Electrochemical Characteristics ◽  
Oligonucleotide Synthesis ◽  
X Ray ◽  
Boron Cluster ◽  
Boron Clusters ◽  
Modified Oligonucleotide

Synthesis of four canonical nucleoside-closo-/nido-carborane conjugates, their phosphoramidites, their electrochemical characteristics and the first example of the X-ray structure of a nucleoside-boron cluster conjugate.

scholarly journals No Need to Stick Together to Be Connected: Multiple Types of Enhancers’ Networking

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5201
Author(s):  
Emanuele Vitale ◽  
Mila Gugnoni ◽  
Alessia Ciarrocchi
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Building Blocks ◽  
Regulatory Elements ◽  
Transcriptional Level ◽  
Independent Manner ◽  
Control Of Gene Expression ◽  
Cis Acting ◽  
Regulatory Circuits ◽  
Dna Elements

The control of gene expression at a transcriptional level requires a widespread landscape of regulatory elements. Central to these regulatory circuits are enhancers (ENHs), which are defined as cis-acting DNA elements able to increase the transcription of a target gene in a distance- and orientation-independent manner. ENHs are not independent functional elements but work in a complex and dynamic cooperative network, constituting the building blocks of multimodular domains of gene expression regulation. The information from each of these elements converges on the target promoter, contributing to improving the precision and sharpness of gene modulation. ENHs’ interplay varies in its nature and extent, ranging from an additive to redundant effect depending on contexts. Moving from super-enhancers that drive the high expression levels of identity genes, to shadow-enhancers, whose redundant functions contribute to buffering the variation in gene expression, this review aims to describe the different modalities of ENHs’ interaction and their role in the regulation of complex biological processes like cancer development.

scholarly journals Evolutionary stability of topologically associating domains is associated with conserved gene regulation

2017 ◽  
Author(s):  
Jan Krefting ◽  
Miguel A. Andrade-Navarro ◽  
Jonas Ibn-Salem
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Target Genes ◽  
Gene Expression Regulation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Building Blocks ◽  
Regulatory Sequences ◽  
Topologically Associating Domains

AbstractBackgroundThe human genome is highly organized in the three-dimensional nucleus. Chromosomes fold locally into topologically associating domains (TADs) defined by increased intra-domain chromatin contacts. TADs contribute to gene regulation by restricting chromatin interactions of regulatory sequences, such as enhancers, with their target genes. Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression.ResultsHere, we hypothesize that TADs represent essential functional units of genomes, which are selected against rearrangements during evolution. We investigate this using whole-genome alignments to identify evolutionary rearrangement breakpoints of different vertebrate species. Rearrangement breakpoints are strongly enriched at TAD boundaries and depleted within TADs across species. Furthermore, using gene expression data across many tissues in mouse and human, we show that genes within TADs have more conserved expression patterns. Disruption of TADs by evolutionary rearrangements is associated with changes in gene expression profiles, consistent with a functional role of TADs in gene expression regulation.ConclusionsTogether, these results indicate that TADs are conserved building blocks of genomes with regulatory functions that are often reshuffled as a whole instead of being disrupted by rearrangements.

scholarly journals The Biomarker and Therapeutic Potential of Circular Rnas in Schizophrenia

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2238
Author(s):  
Artem Nedoluzhko ◽  
Natalia Gruzdeva ◽  
Fedor Sharko ◽  
Sergey Rastorguev ◽  
Natalia Zakharova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Circular Rna ◽  
Circular Rnas ◽  
Cellular Processes ◽  
Non Coding Rna

Circular RNAs (circRNAs) are endogenous, single-stranded, most frequently non-coding RNA (ncRNA) molecules that play a significant role in gene expression regulation. Circular RNAs can affect microRNA functionality, interact with RNA-binding proteins (RBPs), translate proteins by themselves, and directly or indirectly modulate gene expression during different cellular processes. The affected expression of circRNAs, as well as their targets, can trigger a cascade of events in the genetic regulatory network causing pathological conditions. Recent studies have shown that altered circular RNA expression patterns could be used as biomarkers in psychiatric diseases, including schizophrenia (SZ); moreover, circular RNAs together with other cell molecules could provide new insight into mechanisms of this disorder. In this review, we focus on the role of circular RNAs in the pathogenesis of SZ and analyze their biomarker and therapeutic potential in this disorder.

scholarly journals A standardized polyherbal preparation POL-6 diminishes alcohol withdrawal anxiety by regulating Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lalit Sharma ◽  
Aditi Sharma ◽  
Ashutosh Kumar Dash ◽  
Gopal Singh Bisht ◽  
Girdhari Lal Gupta
Keyword(s):  
Gene Expression ◽  
Alcohol Withdrawal ◽  
Therapeutic Potential ◽  
Centella Asiatica ◽  
Ethanol Withdrawal ◽  
In Vivo Studies ◽  
Ocimum Sanctum ◽  
Behavioral Parameters ◽  
Gene Expression Studies

Abstract Background Alcohol abuse is a major problem worldwide and it affects people’s health and economy. There is a relapse in alcohol intake due to alcohol withdrawal. Alcohol withdrawal anxiety-like behavior is a symptom that appears 6–24 h after the last alcohol ingestion. Methods The present study was designed to explore the protective effect of a standardized polyherbal preparation POL-6 in ethanol withdrawal anxiety in Wistar rats. POL-6 was prepared by mixing the dried extracts of six plants Bacopa monnieri, Hypericum perforatum, Centella asiatica, Withania somnifera, Camellia sinesis, and Ocimum sanctum in the proportion 2:1:2:2:1:2 respectively. POL-6 was subjected to phytochemical profiling through LC-MS, HPLC, and HPTLC. The effect of POL-6 on alcohol withdrawal anxiety was tested using a two-bottle choice drinking paradigm model giving animals’ free choice between alcohol and water for 15 days. Alcohol was withdrawn on the 16th day and POL-6 (20, 50, and 100 mg/kg, oral), diazepam (2 mg/kg) treatment was given on the withdrawal days. Behavioral parameters were tested using EPM and LDT. On the 18th day blood was collected from the retro-orbital sinus of the rats and alcohol markers ALT, AST, ALP, and GGT were studied. At end of the study, animals were sacrificed and the brain was isolated for exploring the influences of POL-6 on the mRNA expression of GABAA receptor subunits in the amygdala and hippocampus. Results Phytochemical profiling showed that POL-6 contains major phytoconstituents like withaferin A, quercetin, catechin, rutin, caeffic acid, and β-sitosterol. In-vivo studies showed that POL-6 possesses an antianxiety effect in alcohol withdrawal. Gene expression studies on the isolated brain tissues showed that POL-6 normalizes the GABAergic transmission in the amygdala and hippocampus of the rats. Conclusion The study concludes that POL-6 may have therapeutic potential for treating ethanol-type dependence.

scholarly journals OP0045 NLRP12 INVOLVES IN THE LUPUS WITH POSITIVE INTERFERON SIGNATURE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 23.2-24
Author(s):  
Y. P. Tsao ◽  
F. Y. Tseng ◽  
C. W. Chao ◽  
M. H. Chen ◽  
S. T. Chen
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Animal Models ◽  
Nucleic Acids ◽  
Disease Activity ◽  
Interferon Signature ◽  
Healthy Donors ◽  
Healthy Control ◽  
Lupus Disease Activity

Background:Systemic lupus erythematous (SLE) is a systemic autoimmune disease with diverse etiological factors. It was recognized that interferon (IFN) signature involved in the progress of SLE. NLRP12 (NOD-like receptor family (NLR) pyrin domain containing 12) is a pyrin containing NLR protein that we had linked its new biological function to the cross-regulation of Toll like receptor (TLRs) and Rig-I like receptor (RIG-I) pathways. NLPR12 acts as an innate immune check-point in regulating type I IFNs expression during TLRs and RIG-I activation. The importance of NLRP12 in lupus disease activity remained to be elucidated.Objectives:To clarify the role of NLRP12 in regulating the interferon signature.Methods:Peripheral blood mononuclear cells (PBMCs) were collected from SLE patients and healthy donors for analysis of NLRP12 and IFN-α gene expression by RT-QPCR. PBMCs were applied for Chromatin immuneprecipitation (ChIP) assay and electrical mobility shift assay (EMSA) to determine the putative transcription factor that regulates NLRP12 expression. An involvement of epigenetic regulation of NLRP12 expression in SLE patients was also analyzed. Bone marrow derived dendritic cells (BMDCs) were collected from wild type mouse and Nlrp12 knocked-out mice. Another CD14+ monocytes were isolated from 10 cases of lupus patients and 8 cases of healthy control, following by stimulating different type of nucleic acids, and IFN-α and IL-6 were measured with ELISA assay. CD14+ monocytes in lupus patients were also pre-treated with IFNAR2 antibody for further nucleic acid stimulation. Two mice models were applied for evaluation the role of Nlrp12: intraperitoneal injection of TMPD (2,6,10,14-tetramethylpentadecane, or pristane) in C57BL/6 mice and Faslpr mice. Both models were conducted with and without Nlrp12 knockout.Results:NLRP12 expression was significantly lower in PBMC isolated from SLE patients compared to healthy donors. The inverse correlation was observed in NLRP12 and IFNA gene expression as well as NLRP12 expression and amount of double-stranded DNA autoantibody in SLE patients. NLRP12 expression showed negative correlations with IFN-α treatment, as well as herpes simplex virus-1 (HSV-1) infection. Results from ChIP and EMSA analysis indicated a potential transcription factor 1 (TF-1) regulating NLRP12 promoter activity. TF-1 lead to transcriptional suppression of NLRP12 in SLE PBMC, and it was gradually induced after IFN treatment. Recruitment of TF-1 to NLRP12 promoter in SLE PBMC compared to the healthy PBMC was detected, and increased when treating with IFN. Human CD14+ monocytes collected from lupus and healthy control stimulating with different type of nucleic acids revealing significant increasing level of IFN-α and IL-6 in lupus patients. Among animal models, both pristine induced mice and Faslpr mice revealed increasing autoantibodies production and severity of glomerulonephritis in Nlrp12-/- group in comparison with Nlrp12+/+ ones, indicating the role of NLRP12 in maintaining positive interferon signature as well as disease activity.Conclusion:Expression level of NLRP1.2 has been demonstrated to be a biomarker of disease activity in SLE patients. The NLRP12 was involved in the interferon signature, which was also negatively regulated by TF-1. Both clinical samples and animal models revealed NLRP12 in maintaining the positive interferon signature, indicating the possible role of exacerbating factor for lupus disease activity.Disclosure of Interests:None declared

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