China
Africa
Explore chapters and articles related to this topic
Altitude, temperature, circadian rhythms and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Henning Wackerhage, Kenneth A. Dyar, Martin Schönfelder
In summary, Tibetans that live permanently at high altitude have experienced a natural selection of DNA variants of hypoxia-sensing genes such as EPAS1 which encodes HIF-2α, and EGLN1 which encodes PHD2. These mutations limit the increased haematocrit and haemoglobin concentrations at high altitude, allowing the carriers to avoid associated health problems. This is the opposite from the EPOR mutation carriers in Finland who have a higher haematocrit but live at sea level (23). In contrast, people that live in the Andean Altiplano have elevated haemoglobin concentrations, but perhaps selection of additional unidentified alleles that limit the negative consequences of high haemoglobin concentrations. Additionally, there is some evidence that high altitude mice and humans may favour carbohydrate oxidation which is associated with a greater production of ATP per oxygen atom (i.e. P/O ratio).
Oxidative stress and pre-eclampsia
Published in Pankaj Desai, Pre-eclampsia, 2020
An oxygen atom can generate a devastating process called “oxidative stress”. Its habit of rendering butter rancid in the kitchen continues inside the body. Lipids seem to be a delicacy relished by oxygen. In the body vasculature, the excited form of oxygen known as ROS feasts on the lipids and can cause profound effects in the human system. We shall this in detail in the pages that follow.
Additional Techniques for Designing and Representing Structures of Large Molecules
Published in Patrick E. McMahon, Rosemary F. McMahon, Bohdan B. Khomtchouk, Survival Guide to General Chemistry, 2019
Patrick E. McMahon, Rosemary F. McMahon, Bohdan B. Khomtchouk
Step (5): Condensation through step (4) often provides the most useful description of the molecule; further condensation is possible. Bond lines from carbon to oxygen can be eliminated. For double bonded oxygens, which are not drawn in the line of the carbon chain atoms, place the oxygen atom symbol on the same line as the carbons, to the right and next to the carbon (or carbon-hydrogen group) to which it is bonded. Note that the format (CH3COCH2Br) cannot mean that the oxygen is part of the carbon chain such as (H3C—C—O—CH2Br). Although the oxygen has two bonds in this incorrect reconstruction, the second carbon has only two bonds and, thus, cannot be correct. The condensed format can only be regenerated to the original molecule; no information is lost.
Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Caolin Wang, Shan Xu, Liang Peng, Bingliang Zhang, Hong Zhang, Yingying Hu, Pengwu Zheng, Wufu Zhu
In our previous study, a series of quinazoline derivatives were designed and synthesised as noncovalent EGFR inhibitors16. The most promising compound BMC201725-9o exhibited inhibitory activity against EGFR (IC50 = 56 nM). Further research shows that BMC201725-9o can induce apoptosis in A549 cells, but shows weak inhibitory activity against EGFRL858R/T790M (IC50 > 1000 nM). In this study, in order to enhance the inhibitory activity of EGFR against L858R/T790M mutation and improve the target compounds properties, further structural modifications were mainly focused on the position C-7 of quinazoline. The goal of structural modification was to increase inhibitory activity against T790M by increasing the interaction of the compound with the ATP binding site and reduce oxidation of phenolic hydroxyl groups. Following this method, we synthesised one novel quinazoline derivatives by three modification strategies: (a) The introduction of a polar flexible chain on the oxygen atom allows the solubilised tail to better reach the solvent zone. (b) According to the principle of bio-electronic isosteres, oxygen atom is replaced by a more stable carbon atom. (c) Adding heteroatoms on benzene rings to increase hydrogen bonding receptors. The design strategy is shown in Figure 2.
Platelet biomechanics, platelet bioenergetics, and applications to clinical practice and translational research
Published in Platelets, 2018
Mitchell J. George, James Bynum, Prajeeda Nair, Andrew P. Cap, Charles E. Wade, Charles S. Cox, Brijesh S. Gill
While the focus of this review is on clinical platelet function devices, platelet function devices used in translational research deserve brief mention. These devices measure an array of platelet bioenergetic or platelet biomechanical function. For example, devices to measure platelet bioenergetics include the Seahorse XF24 Extracellular Flux Analyzer (Seahorse Bioscience, North Billerica, MA) or the Oxygraph-2k (Oroboros Instruments, Innsbruck, Austria) (10,45–47). These devices are useful in determining platelet mitochondrial function and accommodate the use of metabolic inhibitors. Measurements are possible using intact cells rather than mitochondrial isolates. Because they are a plate based assay, they allow higher throughput than classical oxygen electrode assays. However, one limitation of these devices is the requirement for high levels of ADP which precludes calculation of ATP produced per oxygen atom reduced by the respiratory chain, or the P/O ratio (48). Another device specific limitation of the Oxygraph-2k is that it requires stirring of platelets which likely leads to unwanted activation.
Isolation and identification of three new chromones from the leaves of Pimenta dioica with cytotoxic, oestrogenic and anti-oestrogenic effects
Published in Pharmaceutical Biology, 2018
Brian J. Doyle, Temitope O. Lawal, Tracie D. Locklear, Lorraina Hernandez, Alice L. Perez, Udeshi Patel, Shitalben Patel, Gail B. Mahady
The substitution pattern in the A ring was determined based on HMBC correlations (Figure 1(b)) between both methyl groups and C-7 (δ C 159.4 ppm), suggesting that a hydroxy-substituted carbon, C-7, was positioned between the two methylated carbons, C-6 and C-8. The methyl group assigned to C-6 also correlated with C-5, which was assigned based on HMBC correlation with the hydroxyl proton at δ 13.0 ppm. Furthermore, NMR data for this compound are consistent with previously published NMR data for the 6,8-dimethyl-5,7-dihydroxyflavone syzalterin (Youssef et al. 1998). Also important was the observation that the upshifted carbonyl resonance was indicative of a flavone (double bond between C-2 and C-3), but the downshifted resonances of C-2 and C-1′ did not correspond to a simple flavone structure. Furthermore, the molecular formula derived from HRMS data suggested a sixth oxygen atom. HMBC and HSQC correlations clearly indicated a proton at C-3 rather than the –OH substitution typical of flavonols. Positioning the oxygen atom between C-2 and C-1′ creating a 2-phenoxy moiety results in the observed downshift of C-2 and C-1′ resonances. This is supported by previously published NMR data for the 2-phenoxychromone piliostigmin (Ibewuike et al. 1996).