scholarly journals Aptamers: An Emerging Tool for Diagnosis and Therapeutics in Tuberculosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Shruti Srivastava ◽  
Philip Raj Abraham ◽  
Sangita Mukhopadhyay
Keyword(s):  
Drug Targets ◽  
Rna Aptamers ◽  
Secretory Proteins ◽  
Dna And Rna ◽  
Different Types ◽  
Development Processes ◽  
Therapeutic Measures ◽  
Tb Diagnostics ◽  
Pathogenic Agents ◽  
Global Population

Tuberculosis (TB) has been plaguing human civilization for centuries, and currently around one-third of the global population is affected with TB. Development of novel intervention tools for early diagnosis and therapeutics against Mycobacterium tuberculosis (M.tb) is the main thrust area in today’s scenario. In this direction global efforts were made to use aptamers, the chemical antibodies as tool for TB diagnostics and therapeutics. This review describes the various aptamers introduced for targeting M.tb and highlights the need for development of novel aptamers to selectively target virulent proteins of M.tb for vaccine and anti-TB drugs. The objective of this review is to highlight the diagnostic and therapeutic application of aptamers used for tuberculosis. The discovery of aptamers, SELEX technology, different types of SELEX development processes, DNA and RNA aptamers reported for diseases and pathogenic agents as well have also been described in detail. But the emphasis of this review is on the development of aptamers which can block the function of virulent mycobacterial components for developing newer TB vaccine candidates and/or drug targets. Aptamers designed to target M.tb cell wall proteins, virulent factors, secretory proteins, or combination could orchestrate advanced diagnosis and therapeutic measures for tuberculosis.

Carbazole Derivatives as Kinase-Targeting Inhibitors for Cancer Treatment

2020 ◽  
Vol 20 (6) ◽  
pp. 444-465 ◽  
Author(s):  
Jessica Ceramella ◽  
Domenico Iacopetta ◽  
Alexia Barbarossa ◽  
Anna Caruso ◽  
Fedora Grande ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Drug Targets ◽  
Mechanisms Of Action ◽  
Biological Pathways ◽  
G Protein Coupled Receptors ◽  
Ability To Act ◽  
Different Types ◽  
Activity Of Enzymes ◽  
Intercalating Agents ◽  
G Protein Coupled

Protein Kinases (PKs) are a heterogeneous family of enzymes that modulate several biological pathways, including cell division, cytoskeletal rearrangement, differentiation and apoptosis. In particular, due to their crucial role during human tumorigenesis and cancer progression, PKs are ideal targets for the design and development of effective and low toxic chemotherapeutics and represent the second group of drug targets after G-protein-coupled receptors. Nowadays, several compounds have been claimed to be PKs inhibitors, and some of them, such as imatinib, erlotinib and gefitinib, have already been approved for clinical use, whereas more than 30 others are in various phases of clinical trials. Among them, some natural or synthetic carbazole-based molecules represent promising PKs inhibitors due to their capability to interfere with PK activity by different mechanisms of action including the ability to act as DNA intercalating agents, interfere with the activity of enzymes involved in DNA duplication, such as topoisomerases and telomerases, and inhibit other proteins such as cyclindependent kinases or antagonize estrogen receptors. Thus, carbazoles can be considered a promising this class of compounds to be adopted in targeted therapy of different types of cancer.

A Survey on Computational Methods for Essential Proteins and Genes Prediction

2019 ◽  
Vol 14 (3) ◽  
pp. 211-225 ◽  
Author(s):  
Ming Fang ◽  
Xiujuan Lei ◽  
Ling Guo
Keyword(s):  
Computational Methods ◽  
Drug Targets ◽  
Disease Genes ◽  
Essential Proteins ◽  
Experimental Identification ◽  
Cellular Life ◽  
Different Types ◽  
The Stability ◽  
Human Disease Genes ◽  
Biology Research

Background: Essential proteins play important roles in the survival or reproduction of an organism and support the stability of the system. Essential proteins are the minimum set of proteins absolutely required to maintain a living cell. The identification of essential proteins is a very important topic not only for a better comprehension of the minimal requirements for cellular life, but also for a more efficient discovery of the human disease genes and drug targets. Traditionally, as the experimental identification of essential proteins is complex, it usually requires great time and expense. With the cumulation of high-throughput experimental data, many computational methods that make useful complements to experimental methods have been proposed to identify essential proteins. In addition, the ability to rapidly and precisely identify essential proteins is of great significance for discovering disease genes and drug design, and has great potential for applications in basic and synthetic biology research. Objective: The aim of this paper is to provide a review on the identification of essential proteins and genes focusing on the current developments of different types of computational methods, point out some progress and limitations of existing methods, and the challenges and directions for further research are discussed.

scholarly journals A Multi-Pronged Computational Pipeline for Prioritizing Drug Target Strategies for Latent Tuberculosis

2020 ◽  
Vol 8 ◽  
Author(s):  
Ushashi Banerjee ◽  
Santhosh Sankar ◽  
Amit Singh ◽  
Nagasuma Chandra
Keyword(s):  
Drug Targets ◽  
Metabolic Flux ◽  
Latent Tuberculosis ◽  
Interaction Network ◽  
New Drugs ◽  
Prolonged Treatment ◽  
Flux Analysis ◽  
Protein Protein Interaction ◽  
Candidate Drug ◽  
Global Population

Tuberculosis is one of the deadliest infectious diseases worldwide and the prevalence of latent tuberculosis acts as a huge roadblock in the global effort to eradicate tuberculosis. Most of the currently available anti-tubercular drugs act against the actively replicating form of Mycobacterium tuberculosis (Mtb), and are not effective against the non-replicating dormant form present in latent tuberculosis. With about 30% of the global population harboring latent tuberculosis and the requirement for prolonged treatment duration with the available drugs in such cases, the rate of adherence and successful completion of therapy is low. This necessitates the discovery of new drugs effective against latent tuberculosis. In this work, we have employed a combination of bioinformatics and chemoinformatics approaches to identify potential targets and lead candidates against latent tuberculosis. Our pipeline adopts transcriptome-integrated metabolic flux analysis combined with an analysis of a transcriptome-integrated protein-protein interaction network to identify perturbations in dormant Mtb which leads to a shortlist of 6 potential drug targets. We perform a further selection of the candidate targets and identify potential leads for 3 targets using a range of bioinformatics methods including structural modeling, binding site association and ligand fingerprint similarities. Put together, we identify potential new strategies for targeting latent tuberculosis, new candidate drug targets as well as important lead clues for drug design.

DNA and RNA Aptamers: From Tools for Basic Research Towards Therapeutic Applications

2006 ◽  
Vol 9 (8) ◽  
pp. 619-632 ◽  
Author(s):  
Henning Ulrich ◽  
Cleber Trujillo ◽  
Arthur Nery ◽  
Janaina Alves ◽  
Paromita Majumder ◽  
...  
Keyword(s):  
Basic Research ◽  
Rna Aptamers ◽  
Therapeutic Applications ◽  
Dna And Rna

scholarly journals Securing Software Systems - A Survey

2020 ◽  
Author(s):  
Yong Weixiong ◽  
Kohei Dozono ◽  
Robin Lee ◽  
Alvin Kon Soon Seng ◽  
Fatima tuz Zahra
Keyword(s):  
Development Process ◽  
User Behavior ◽  
Development Stage ◽  
Security And Privacy ◽  
Software Systems ◽  
Privacy Concerns ◽  
Policy Awareness ◽  
Secure Software ◽  
Different Types ◽  
Development Processes

This paper aims to discuss the standard guidelines of the development process of secure software and will give justification on different types and ways of the software development processes. Additionally, a survey is conducted, the aim of which is to observe user behavior towards software system usage, user attitude in terms of privacy and policy awareness, security and privacy concerns. This is followed by discussion on how to secure software systems in development stage.

scholarly journals A Combined ELONA-(RT)qPCR Approach for Characterizing DNA and RNA Aptamers Selected against PCBP-2

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1213 ◽  
Author(s):  
Miguel Moreno ◽  
María Fernández-Algar ◽  
Javier Fernández-Chamorro ◽  
Jorge Ramajo ◽  
Encarnación Martínez-Salas ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Rna Aptamers ◽  
Dna Aptamers ◽  
General Strategy ◽  
Label Free ◽  
Mobility Shift ◽  
Real Time Quantitative Pcr ◽  
High Affinity ◽  
Dna And Rna ◽  
Electrophoretic Mobility Shift Assays

Improvements in Systematic Evolution of Ligands by EXponential enrichment (SELEX) technology and DNA sequencing methods have led to the identification of a large number of active nucleic acid molecules after any aptamer selection experiment. As a result, the search for the fittest aptamers has become a laborious and time-consuming task. Herein, we present an optimized approach for the label-free characterization of DNA and RNA aptamers in parallel. The developed method consists in an Enzyme-Linked OligoNucleotide Assay (ELONA) coupled to either real-time quantitative PCR (qPCR, for DNA aptamers) or reverse transcription qPCR (RTqPCR, for RNA aptamers), which allows the detection of aptamer-target interactions in the high femtomolar range. We have applied this methodology to the affinity analysis of DNA and RNA aptamers selected against the poly(C)-binding protein 2 (PCBP-2). In addition, we have used ELONA-(RT)qPCR to quantify the dissociation constant (Kd) and maximum binding capacity (Bmax) of 16 high affinity DNA and RNA aptamers. The Kd values of the high affinity DNA aptamers were compared to those derived from colorimetric ELONA performed in parallel. Additionally, Electrophoretic Mobility Shift Assays (EMSA) were used to confirm the binding of representative PCBP-2-specific RNA aptamers in solution. We propose this ELONA-(RT)qPCR approach as a general strategy for aptamer characterization, with a broad applicability in biotechnology and biomedicine.

Practical application of whole genome and transcriptome tumour analysis to guide chemotherapy decision-making for patients with advanced cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22020-e22020
Author(s):  
Janessa J. Laskin ◽  
Howard John Lim ◽  
Karen A. Gelmon ◽  
Cheryl Ho ◽  
Daniel John Renouf ◽  
...  
Keyword(s):  
Decision Making ◽  
Drug Targets ◽  
Cell Cancer ◽  
Copy Number Variations ◽  
Whole Genome ◽  
Incurable Cancer ◽  
Dna And Rna ◽  
Drug Databases ◽  
Tumour Biopsy ◽  
The Impact

e22020 Background: We propose that applying personal genomic information prospectively, in a clinically realistic timeframe can aid chemotherapy decision-making and result in more effective cancer treatment. We are investigating this approach in a variety of cancers to examine timeliness, deliverability, and rate of actionable targets identified. Methods: Eligible subjects with incurable cancer and limited chemo options have a tumour biopsy and “normal” blood taken for analysis. Archival specimens are concurrently analyzed to look for changes with time and treatment. Samples are subject to both an Ampliseq amplicon panel and in-depth whole genome DNA and RNA sequencing (WGS). Bioinformatics approaches identity genes with somatic and copy number variations, and expression changes. Variants are integrated into a pathway analysis to identify tumour specific processes that may drive the tumour, these are then matched to drug databases, with manual literature reviews, to indentify drugs that may be useful or even contra-indicated. Results: Between July 2012 -Jan 2013, 9 subjects (of 30 planned) are enrolled: 2 cases each of: colorectal and breast and 1 each of: squamous skin, squamous ethmoid sinus, nasopharyngeal, lung, and CLL-peripheral mantle cell cancer. 5 have completed analyses. Cancer panel results correlated well with WGS; although the panel is more rapid, it provides less comprehensive information and has not been as informative for identifying candidate druggable drivers. Extensive pathway mapping uncovered potential drug targets in each case that would not have necessarily been considered without this analyses. To date, 4 subjects have started chemo based on the analyses and 1 patient has had his diagnosis radically changed. There are significant genomic differences between archival and fresh tumour samples. Conclusions: This approach is feasible and yields actionable targets that can inform real-time chemotherapy decision-making. Archival samples do not appear to adequately represent post-treatment cancers. The impact of WGS vs. panel sequencing will require more subjects but it appears a panel may be insufficient for detailed treatment guidance.

Effects of the antioestrogen tamoxifen on steroid induced morphological and biochemical changes in the castrated dog prostate

1982 ◽  
Vol 100 (3) ◽  
pp. 462-472 ◽  
Author(s):  
P.-J. Funke ◽  
U. W. Tunn ◽  
Th. Senge ◽  
F. Neumann
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Biochemical Analysis ◽  
Squamous Metaplasia ◽  
Combined Treatment ◽  
Prostatic Hyperplasia ◽  
Biochemical Changes ◽  
Weight Increase ◽  
Histochemical Reaction ◽  
Dna And Rna ◽  
Different Types

Abstract. The effect of the antioestrogen tamoxifen (TA) was investigated in different types of steroid-induced benign prostatic hyperplasia (BPH) in the castrated dog by histological, histochemical and biochemical analysis. A 6 months treatment with oestradiol-17β (E2) alone resulted in cystic and stromal hyperplasia and squamous epithelial metaplasia with a striking prostatic weight increase. DNA and RNA content of the total glands increased significantly. The histochemical results and zinc values indicated the loss of normal epithelial function due to metaplatic transformation. The E2 induced cystic and metaplastic hyperplasia was prevented by TA while the stromal proliferation was significantly decreased but not abolished. Biochemical determinations revealed an effect similar to castration. After combined treatment with E2 and 3α-androstanediol (3α-diol) TA completely suppressed squamous metaplasia. A 3α-diol induced glandular proliferation, monitored by a positive histochemical reaction, and significantly elevated zinc, DNA and RNA contents prevailed. A partial stromal stimulation indicates stimulating effects of 3α-diol too on the stroma. The antioestrogenic effects of tamoxifen on experimentally induced BPH mainly manifest at the E2 induced epithelial alterations. The abolishing effects at the stromal level are distinct but not so impressive.

scholarly journals Oligonucleotide-based systems: DNA, microRNAs, DNA/RNA aptamers

2016 ◽  
Vol 60 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Pawan Jolly ◽  
Pedro Estrela ◽  
Michael Ladomery
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Rna Aptamers ◽  
Locked Nucleic Acid ◽  
Synthetic Analogue ◽  
Dna And Rna ◽  
Naturally Occurring ◽  
Wide Range ◽  
Synthetic Oligonucleotides ◽  
Shed Light

There are an increasing number of applications that have been developed for oligonucleotide-based biosensing systems in genetics and biomedicine. Oligonucleotide-based biosensors are those where the probe to capture the analyte is a strand of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or a synthetic analogue of naturally occurring nucleic acids. This review will shed light on various types of nucleic acids such as DNA and RNA (particularly microRNAs), their role and their application in biosensing. It will also cover DNA/RNA aptamers, which can be used as bioreceptors for a wide range of targets such as proteins, small molecules, bacteria and even cells. It will also highlight how the invention of synthetic oligonucleotides such as peptide nucleic acid (PNA) or locked nucleic acid (LNA) has pushed the limits of molecular biology and biosensor development to new perspectives. These technologies are very promising albeit still in need of development in order to bridge the gap between the laboratory-based status and the reality of biomedical applications.

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