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Research Planning and Development Perspectives
Published in Gary M. Matoren, The Clinical Research Process in the Pharmaceutical Industry, 2020
Developments in biochemistry have encouraged a greater focus on enzymes as specific drug targets. Efforts to identify, characterize, and develop inhibitors or activators for key enzymes involved in metabolic processes are increasing. The use of radioactive ligands has enabled researchers to achieve better biological characterization of various hormone and neurotransmitter receptors. The study of such receptors is yielding increased understanding of how hormones and neurotransmitters work that will permit the development of specific, potent antagonists (blockers), and agonists (mimics). Conceptual advances are occurring which will lead to novel approaches to inhibition or stimulation of immunological pathways, that is, control of individual cellular events in the generation and expression of immune responses. The study of metabolic pathways will become even more important in the search for new drug leads. As new compounds are isolated which are involved in important physiological processes, the routes of synthesis and degradation and the role of associated enzymes will provide important clues for drug development projects. Neurobiology is another exciting area and the potential therapeutic implications of synthetic peptides will grow substantially as more active peptides are isolated and peptide analogs resistant to proteolysis are synthesized. Molecular biology and gene technology have progressed dramatically and recombinant DNA technology represents one of the most exciting and potentially productive areas of biomedical research and development.
The Energetics of Fish Sperm Motility
Published in Claude Gagnon, Controls of Sperm Motility, 2020
The energetics of sperm motility in fish must take into account both the energy necessary for survival in the genital tract and the energy required for motility. Various metabolic pathways may contribute to generate energy.
Introduction
Published in Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam, Introduction to Computational Health Informatics, 2019
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam
A biochemical reactions pathway is the control flow of the molecular transformation (degradation and formation) within our body. There are two types of pathways: metabolic pathways and signaling pathways. Metabolic pathways are chains of biochemical reactions that degrade the molecules received from outside or intermediate molecules into the chemical and biochemical molecules needed by our body. The reactions in metabolic pathways are catalyzed by enzymes—a class of proteins used to regulate biochemical reactions.
Recent progress in the development of nanomaterials targeting multiple cancer metabolic pathways: a review of mechanistic approaches for cancer treatment
Published in Drug Delivery, 2023
Ling Zhang, Bing-Zhong Zhai, Yue-Jin Wu, Yin Wang
Cancer is reported as the major cause of premature death in China and other developed nations (Bray et al., 2021). GLOBOCAN 2020 reported that there were 19,292,789 cases of cancer and 9,958,133 deaths from cancer worldwide in 2020 (Sung et al., 2021). Since 2000, the prevalence and mortality of cancer in China have risen gradually (Wei et al., 2020). Cancer cells are distinguished by their uncontrolled proliferation, transformation, and migration to other parts of the body, as well as their propensity to harm normal cells (Suresh, 2007). Cancer cells acquire atypical metabolic pathways to get energy and raw materials for achieving the energy requirements for vigorous cell growth and migration. The reason cancer cells acquire energy via atypical metabolic pathways is that their metabolism is more vigorous than that of normal cells (Zanotelli et al., 2021). Multiple carcinogenic signaling pathways regulate three primary metabolic pathways in cancer cells. These metabolic pathways include lipid, amino acid, and glucose metabolism (Dzobo et al., 2020). The distinctive metabolism of cancer cells implies that changes at the metabolic level are essential for the development and genesis of cancer cells.
Repair mechanism of Wuwei Fuzheng Yijing formula in di-2-ethylhexyl phthalate-induced sperm DNA fragmentation in mice
Published in Pharmaceutical Biology, 2022
Chenming Zhang, Shiqi Wang, Zulong Wang, Qi Zhang, Rubing Chen, Hao Zhang, Zhong Hua, Sicheng Ma
Our combined transcriptome and proteome analysis found that the repairing effect of WFY on DEHP-induced sperm DNA damage was related to the metabolic pathway and the PI3K/Akt pathway. The metabolic pathway involves many functional activities, and changes in the metabolic pathway have been found in many diseases. The PI3K/Akt pathway is correlated with oxidative damage and DNA integrity. Activation of the PI3K/Akt signalling pathway leads to a direct interaction between phosphorylated MDM2 and p53 degradation. P53 degradation causes p53-dependent DNA damage checkpoint or repair dysfunction and ultimately results in the accumulation of DNA damage in sperm (Xian et al. 2017). Although no other Chinese herbal formulas have been found to repair sperm DNA damage through the PI3K/Akt pathway, some Chinese herbal formulas were able to improve other sperm parameters (such as sperm concentration and motility) through the PI3K/Akt pathway, possibly by promoting spermatogenic cell proliferation and inhibiting apoptosis (Chen et al. 2021).
Metabolomics in antimicrobial drug discovery
Published in Expert Opinion on Drug Discovery, 2022
Synergistic action of antimicrobials allows to decrease the effective concentration of antimicrobials thus lowering potential side effects, while the combination of antimicrobials may limit the emergence of resistance compared to monotherapy. Metabolomic analysis may help to identify pathways that are affected by antimicrobial combinations and reveal the mechanisms of synergy in such combinations. For example, untargeted metabolomics was used to reveal the synergy between colistin and doripenem in killing multidrug-resistant Acinetobacter baumannii [91]. The authors found that colistin acts earlier and disrupts the outer membrane and cell wall, while the action of doripenem affects metabolites involved in peptidoglycan biosynthesis. The combination of drugs affected more key metabolic pathways than either of the drugs alone, resulting in depletion of metabolites involved in energy, nucleotide, amino sugar and peptide metabolism.