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Candidate Substances, Research Background, and Biological Roles
Published in Shojiro Inoué, Biology of Sleep Substances, 2020
In the course of investigations on bromine intoxication in human patients, Yanagisawa and Yoshikawa118 found that, in addition to exogenous bromine, a bromine-containing organic substance occurred physiologically in both CSF and blood. This substance was isolated from a large amount of pooled human CSF and finally identified as 1-methyl-heptyl-γ-bromoacetoacetate (γ-Br or MHBAA).119 Subsequent studies revealed that γ-Br (0.1 to 5 mg i.v.) selectively promoted PS in encephale isolé cats.120 This will be described in detail in Chapters 2 and 7.
Pathogenesis: Molecular mechanisms of osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Anastasia E. Markatseli, Theodora E. Markatseli, Alexandros A. Drosos
Many researchers have made efforts to clarify the mechanisms involved in the homeostasis of bone tissue. Bone formation is mainly regulated by osteoblasts, which are derived from mesenchymal stem cells (39). Osteoblasts are small, cuboid, mononuclear cells. The mesenchymal stem cells first proliferate and then differentiate to osteoblast precursors (or preosteoblasts). Subsequently, preosteoblasts become mature osteoblasts that produce the organic substance of bone (proteins of the extracellular matrix). Thereafter, the genes, which are necessary for the mineralization of the extracellular matrix, are expressed in osteoblasts. As a result, the crystals of hydroxyapatite are incorporated in the organic substance and mineralize it. Osteoblasts produce osteoid with which a bone cavity created by the action of osteoclasts will be filled (39).
The Liquid Scintillation Counting Process. The Gamma Counting Process
Published in Howard J. Glenn, Lelio G. Colombetti, Biologic Applications of Radiotracers, 2019
One of the problems associated with the use of aromatic solvents is the small amount of water they are capable of holding. Most samples of interest to pharmacologists contain varying amounts of water, p-Dioxane is a water-miscible organic substance also capable of dissolving various organic solutes and will, therefore, hold much larger quantities of water in homogeneous solution for liquid scintillation counting. Care must be taken to use peroxide-free dioxane because of the great quenching characteristics of peroxides. Table 2 lists the composition of some common liquid scintillation formulations using dioxane.
Non-specific binding of compounds in in vitro metabolism assays: a comparison of microsomal and hepatocyte binding in different species and an assessment of the accuracy of prediction models
Published in Xenobiotica, 2022
Iain Gardner, Mandy Xu, Chunyan Han, Yi Wang, Xingjin Jiao, Masoud Jamei, Hiba Khalidi, Peter Kilford, Sibylle Neuhoff, Roz Southall, David B. Turner, Helen Musther, Barry Jones, Simon Taylor
LogP was determined by chromatographic procedures. Briefly, thiourea (1 mM) in acetonitrile and ultrapure water mixture (1:1 v/v) was prepared as the unretained organic substance sample. A mixture of acetanilide, methyl benzoate, benzophenone, benzyl benzoate, fluoranthene and DDT (all 1 mM) were prepared in acetonitrile and ultrapure water mixture (1:1 v/v) as the reference substances mixture. Stock solutions of test compounds (2 mM) were prepared in DMSO and diluted with one volume of ultrapure water. Any insoluble compounds were filtered using a 0.45 uM nylon membrane. The retention time of all the samples was evaluated by LC-UV. Ten uL of each sample was injected on to a YMC-Triart HPLC® 1.9 µm C18 (2.0 × 30 mm) column (YMC Co. LTD, Kyoto, Japan) using a Shimadzu ultrafast-liquid chromatography system (Kyoto, Japan) coupled to a Shimadzu SPD-20A PDA detector (Kyoto, Japan). An acidic or basic mobile phase appropriate to the nature of the test compound was used operating over a 16-minute gradient using a flow rate of either 0.3 or 0.6 mL/min.
Methamphetamine leads to the alterations of microRNA profiles in the nucleus accumbens of rats
Published in Pharmaceutical Biology, 2020
Jing Yang, Lihua Li, Shijun Hong, Dongxian Zhang, Yiqing Zhou
A total of 40 differentially transcribed miRNAs (p value < 0.01 & |log2 (fold change)| > 1 in comparison with the control group (Figure 3(A)), 17 up-regulated and 23 down-regulated by METH treatment, were found with quantitative information and included in the next bioinformatic analyses (Figure 3(B)). Differential miRNAs were verified using qPCR, and their relative abundance was consistent with the results of the sequencing analysis (Figure 4). The potential targets of the changed miRNAs were annotated according to their biological process, cellular component, and molecular function by BLAST2TO (Figure 5(A)). Biological processes analysis showed that these proteins were mainly involved in cellular component regulation, localization regulation, regulation of transport, intracellular signal transduction, and organic substance transport. We observed that most of the targets of the differential miRNAs were located in the intracellular region and organelles in the cellular component analysis. Molecular function analysis revealed that a large proportion of the targets played a role in protein binding, enzyme binding, kinase binding, and transferase activity.
Identification of the metabolites produced following Iris tectorum Maxim oral administration and a network pharmacology-based analysis of their potential pharmacological properties
Published in Xenobiotica, 2021
To better understand the pharmacological activities of I. tectorum Maxim extract, six candidate bioactive molecules were screened from our above analyses based on studies of their chemical composition and metabolites in vivo. A C-T network was constructed to reveal the potential interactions between these metabolites (pink) and their putative targets (blue), with these networks ultimately being comprised of 90 predicted interactions between these six compounds and their 36 targets (Figure S1A). This analysis revealed that several targets were able to interact with multiple metabolites. For example, CA (carbonic anhydrase) VII and CA XII were targeted by all six compounds, while CA IV was a target of five of these compounds. CAs are metalloenzymes that serve as catalysts for the reversible hydration of CO2 to yield bicarbonate and protons. CA inhibitors, like acetazolamide, have been used as diuretics, to treat open angle glaucoma, epilepsy and altitude sickness. GO analyses were additionally employed to annotate these protein targets, revealing these targets to be associated with key biological processes (Figure S1B), including immunological activity, the regulation of biological quality, organic anion transport, oxidation-reduction processes, organic substance transport, and the regulation of stress responses. This suggested that these six metabolites may be able to modulate all of these processes. A C-D network was additionally constructed incorporating these compound targets and their corresponding diseases (Figure S1C), revealing that I. tectorum may function as a regulator of important proteins associated with cancers, and diseases of the cardiovascular, digestive, and urogenital systems.