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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
DNA strands consist of nucleotides joined by phosphodiester bonds linking the sugar of one nucleotide to the phosphate group of the next. DNA coils into a double helix of two antiparallel strands (Figure 2.1). Complementary base pairing of adenine with thymine and guanine with cytosine ensures the fidelity of DNA transcription and replication. When DNA is copied, each parental strand acts as a template for replication: incoming nucleotides form hydrogen bonds with an appropriate base on the template strand. Base mispairing, induced by damage or mutation, introduces structural alterations which can be detected and/or removed by DNA repair proteins.
Introduction to Cancer
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The UV band, which is invisible to the human eye, constitutes one component of the spectrum of sunlight and represents approximately 3% of all the solar radiation reaching the Earth’s surface. Three types of UV light have been identified. One of these, UV-C (200 to 290 nm), is generally thought to be the most carcinogenic. UV-B (290 to 320 nm) causes the most sunburn, and UV-A (320 to 400 nm), which can be up to 1,000 times stronger than UV-B, is able to penetrate underlying tissues of the skin leading to “photo-aging” damage. For many years it was thought that UV-A could not cause any lasting damage. However, more recent studies strongly suggest that it may also enhance the development of skin cancers. Fortunately, the ozone layer absorbs most of the more carcinogenic UV-C radiation, although there is presently concern that depletion of the ozone layer through the release of chlorofluorocarbons used in the air conditioner and refrigeration industries and in the production of Styrofoam insulation may increase the intensity of UV-C at the Earth’s surface in the future. UV radiation occurs at a similar wavelength to the region of maximum absorbance by DNA (i.e., 260 nm), and the major damage is intrastrand covalent linkage of adjacent pyrimidines (usually thymines) to form so-called thymine dimers. These thymine dimers create distortions in the DNA helix and can block replication and transcription, thus leading to tumorigenesis.
BRCA Mutation and PARP Inhibitors
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Arjun Mittra, James H. Doroshow, Alice P. Chen
PARP inhibitors also sensitize mismatch repair (MMR) deficient cells that are resistant to the methylating agent temozolomide [74, 132]. Wild-type MMR acts in three ways. First, MMR corrects errors of replication. Second, the wild type causes replication arrest. Third, MMR can result in cell death. If MMR function is abnormal, cells are more likely to survive with abnormal DNA after exposure to the cytotoxic agent [58]. After exposure to temozolomide, the 06-methylguanine that is a consequence of drug exposure incorrectly pairs with thymine. The wild-type MMR complex MutSa (MSH2/MSH6 heterodimer) recognizes the mismatch pair, and ultimately leads to apoptosis. However, if the tumor cell is deficient in MMR, resistance to temozolomide can occur [79].
Cancer targeted drug delivery using active low-density lipoprotein nanoparticles encapsulated pyrimidines heterocyclic anticancer agents as microtubule inhibitors
Published in Drug Delivery, 2022
Laila Jaragh-Alhadad, Haider Behbehani, Sadashiva Karnik
Based on that, previously we synthesized pyrimidine heterocyclic anticancer agents their chemical functional groups mimic amino acids both cytosine and thymine chemical structure, applied structure-activity relationship in different positions with different moieties, and chemically and physically characterized the agents (Behbehani et al., 2012). The pyrimidine heterocyclic anticancer agent particles’ size and morphology were tested and then loaded into nano-LDL particles to ensure the effective cellular uptake by the cancer cell’s LDL-receptor and the bioactivity effect. Using two strategies to target proliferation protein microtubule (α, β tubulin) (Figure 2) which is an attractive strategy because microtubule is an important protein for cell division and mitosis. Its function and expression are elevated in cancer cells (Jaragh-Alhadad et al., 2022a; Laila et al., 2022).
CFTR gene variants as a reason for impaired spermatogenesis: a pilot study and a Meta-analysis of published data
Published in Human Fertility, 2022
Mariya Levkova, Trifon Chervenkov, Mari Hachmeriyan, Lyudmila Angelova
The 5 T variant is located in intron 8 in front of exon 9 of the donor/acceptor splice site of the CFTR gene (Tsui & Dorfman, 2013). This polymorphism is associated with impaired splicing of the mRNA from exon 9 and leads to transcripts which are missing this particular exon (Du et al., 2014). It is a variant of the IVS8-(n)T mutation, where n indicates the number of the thymine (T) residues and has three variants with 5, 7 or 9 thymines, respectively called 5 T, 7 T and 9 T variants (Kiesewetter et al., 1993). The 7Т and 9Т variants are considered normal, but the 5Т variant is the reason for lower levels of mRNA due to the missing exon 9 (Lorenzi et al., 2020). This mistake in the splicing process leads to the lack of the normal CFTR protein and it cannot function properly (Tsui & Dorfman, 2013). That is why the clinical presentation depends on the number of thymine bases (Dequeker et al., 2009).
Thermal, structural, antimicrobial, and physicochemical characterisation of thyme essential oil encapsulated in β- and γ-cyclodextrin
Published in Journal of Microencapsulation, 2022
Jasim Ahmed, Mehrajfatema Z. Mulla, Hassan Al-Attar, Shaikhah AlZuwayed, Mohammed Ejaz, Sarah Al-Jassar, Harsha Jacob, Linu Thomas, Noor Al-Ruwaih, Antony Joseph
Among essential oils, thyme (Thymus vulgaris L.) oil, which is extracted from the leaves of T. vulgaris L. as such or its major compounds (e.g. thymol and carvacrol) has several applications in food (He et al. 2022), agriculture (Barros et al. 2022), packaging (Zhang et al. 2021), and pharmaceuticals (Garg et al. 2021). Most of the desired properties of thyme essential oil (TEO) have been attributed to the dominant presence of phenolic compounds, namely thymol, carvacrol, and paracymene (Purcell et al. 2016). Additionally, it has been reported that thymol and carvacrol in TEO have shown synergistic effects by acting as superior antimicrobial agents over pure thymol (Burt et al. 2005). Direct addition of TEO into the food matrix has shown many limitations, in particular, volatilisation and oxidation of active compounds when applied in the presence of light and oxygen (Carvalho et al. 2016, Yilmaztekin et al. 2019, Yang et al. 2021). In our earlier work on the development of EO-based packaging materials, it has been observed that the direct addition of EO to the polymer solution requires a large volume of oils (Ahmed et al. 2017, Ahmed et al. 2019, Ahmed et al. 2020), which significantly deteriorates the sensory characteristics of a food product. These limitations require a suitable process that can retain the desirable characteristics of EO in a suitable matrix.