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Surface Engineered Graphene Oxide and Its Derivatives
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Zaira Zaman Chowdhury, Abu Nasser Faisal, Shahjalal Mohammad Shibly, Devarajan Thangadurai, Saher Islam, Jeyabalan Sangeetha
GO and its derivatives have a wide range of surface-functional groups. For instance, pristine Gr is known to exhibit hydrophobic behaviour. Due to presence of –COOH groups, GO is partly hydrophobic (Hasan et al. 2010), and rGO is partially hydrophilic (Bagri et al. 2010). These can alter the structure and function of the protein and cell membrane due to having strong molecular interactions with the cells (Sanchez et al. 2012). rGO can bind with the membrane of the cells, resulting in activation of the mitochondria which stimulate the receptors. Overall, the phenomenon leads to the apoptosis of the cells (Jaworski et al. 2013). Due to existence of oxygen containing functional groups with smooth, hydrophilic surface of GO, it has less hazardous aspect than rGO (Sasidharan et al. 2012). The double-stranded DNA has base pairs where GO can penetrate to disrupt the transfer of genomic component at the cellular scale, which could be the primary reason for mutagenic impact of GO (Liu et al. 2013; Seabra et al. 2014).
The Emerging Role of Exosome Nanoparticles in Regenerative Medicine
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Zahra Sadat Hashemi, Mahlegha Ghavami, Saeed Khalili, Seyed Morteza Naghib
Previously, oncogene amplifications (c-myc), mitochondrial DNA, single-stranded DNA (ssDNA), and retrotransposon RNA transcripts have been discovered in EVs. However, Thakur et al. have indicated the existence of the double-stranded DNA (dsDNA) cargos in the tumour-derived exosomes. These dsDNA cargos can be used as novel biomarkers in cancer detection (Thakur et al. 2014).
Radiopharmaceuticals for Radionuclide Therapy
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Meltem Ocak, Emre Demirci, Jessie R. Nedrow, Rebecca Krimins
Targeted α-therapy (TAT) has emerged as a highly potent treatment modality against a variety of metastatic cancers. The high linear-energy transfer (LET) of α-particles allows them to deposit large amounts of energy over a short range (50-100 µm in tissue), minimizing damage to nearby untreated cells. The high LET results in cell death due to the high prevalence of irreparable double-stranded DNA breaks [82]. The potential of TAT was evident when it was demonstrated that castrate-resistant prostate cancer patients with bone metastases had an increase in overall survival when treated with Xofigo with minimal toxicity and was not just palliative treatment [83].The success of Xofigo and more recently, the remarkable imaging responses seen in patients with metastatic prostate cancer following treatment with an Actinium-225 (225Ac) labelled anti-PSMA small molecule has cemented TAT as a highly potent therapy for metastatic cancer [84]. Subsequently, the success of TAT has highlighted limitations including the supply/availability of α-emitting radioisotopes, the complexities of the decay chains of radioisotopes, the high potency of α-particles within normal tissues, and the possible development of resistant to TAT [85].
Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro, molecular docking, molecular dynamics, and SAR studies
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Faten Farouk, Ayman Abo Elmaaty, Ahmed Elkamhawy, Haytham O. Tawfik, Radwan Alnajjar, Mohammed A. S. Abourehab, Mohamed A. Saleh, Wagdy M. Eldehna, Ahmed A. Al‐Karmalawy
Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. It is a nuclear enzyme that is essential for cell survival. TOP-2 is involved in various stages of DNA replication as well as chromosome assembly and segregation. It acts by breaking the double-stranded DNA and promoting the relaxation of over-coiled strands9,10. Therefore, it is responsible for the topological changes in double-stranded DNA that are required prior to replication and transcription. TOP-2 exerts its function via introducing a protein-bridged cut in DNA strands11. A higher level of TOP-2 expression and a prolonged intracellular half-life is observed in malignant cells over normal ones making the enzyme a potential target for anticancer therapy. Drug candidates that target TOP-2 can be classified as TOP-2 poisons and TOP-2 catalytic inhibitors. The TOP-2 poisons exert their function by increasing the covalent binding between the TOP-2 and DNA. This group includes most of the clinically relevant compounds e.g. doxorubicin (DOX). The TOP-2 catalytic inhibitors act by halting the activity of TOP-2 which is crucial for tumour survival12,13.
Emergence of varicella-zoster virus resistance to acyclovir: epidemiology, prevention, and treatment
Published in Expert Review of Anti-infective Therapy, 2021
Kimiyasu Shiraki, Masaya Takemoto, Tohru Daikoku
Double-stranded DNA needs to be separated into two single strands (replication fork) before DNA synthesis, and complementary strands are synthesized from each DNA strand to produce two new double-stranded DNA molecules during DNA replication (Figure 3). The HP complex is responsible for unwinding viral DNA at the replication fork, separating double-stranded DNA into two single strands, and synthesizing RNA primers (Okazaki fragments) in the lagging strand for DNA synthesis. DNApol initiates complementary DNA synthesis in the two separated DNA strands. The HP complex consists of three proteins: VZVORF55 (helicase), VZVORF6 (primase), and VZVORF52 (cofactor). The helicase unwinds the duplex DNA ahead of the fork and separates the double strand into two single strands. The primase lays down RNA primers that extend the two-subunit DNApol. The HP complex possesses multienzymatic activities, including DNA-dependent ATPase, helicase, and primase activities, all of which are required for the HP complex to function in viral DNA replication.
Analysis of plant-derived phytochemicals as anti-cancer agents targeting cyclin dependent kinase-2, human topoisomerase IIa and vascular endothelial growth factor receptor-2
Published in Journal of Receptors and Signal Transduction, 2021
Bishajit Sarkar, Md. Asad Ullah, Syed Sajidul Islam, MD. Hasanur Rahman, Yusha Araf
Due to the supercoiled structure of the DNA molecules, it is necessary to unwind the double-stranded DNA before replication, transcription, recombination, and other processes. DNA topoisomerases are the enzymes that function in unwinding, cutting, shuffling, and relegating the DNA double helix structure. The human genome encodes six topoisomerases that are grouped into three types: type Iα, type Iβ, and type IIα. DNA topoisomerase IIα is one of the necessary topoisomerases that function in various cellular functions. However, it is a genotoxic enzyme which can lead to cancer development. When DNA topoisomerase II cuts the double-stranded DNA, it may remain covalently attached to the broken end of the DNA. This reaction intermediate is known also as the cleavage complex. If the amount of the cleavage complex in the cell falls too much, then the cells are not able to divide into daughter cells due to mitotic failure, which results in the death of the cells. Moreover, if the amount of the cleavage complex increases too much, the temporary cleavage complex structures can become permanent double-stranded breaks in the DNA. These double-stranded breaks are caused by the faulty DNA tracking system which then initiates the faulty recombination and repair pathways of DNA replication and expression, leading to cancer (Figure 2). For this reason, DNA topoisomerase IIα is a potential target for anti-cancer drug development [77–81].