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Molecular sport nutrition
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Mark Hearris, Nathan Hodson, Javier Gonzalez, James P. Morton
The start of this signalling transduction pathway begins with the accumulation of multiple metabolic signals that occur in response to muscle contraction. For example, a rise in calcium concentrations occur in response to contractile activity whilst an increase in AMP and ADP occurs due to increased ATP usage. These ultimately act as primary messengers which activate specific signalling kinases within the signal transduction pathway. Using the example above, the calcium released in response to muscle contraction binds to a protein called calmodulin and activates the calmodulin-activated protein kinase CaMKII. Once activated, these signalling kinases act as secondary messengers and activate transcription factors and co-activators to initiate the transcription of specific DNA sequences. Whilst these molecular signalling events are relatively short-lived, returning to baseline levels within 24 hours, repeated increases in transcriptional activity and protein synthesis, that occur with regular training, eventually lead to a change in the content of specific proteins (82), discussed in detail in the ‘signal transduction hypothesis’ Chapter 7. Although the modality, intensity and duration of exercise dictate the extent to which these molecular signalling pathways are activated (83–86), such signalling pathways are also sensitive to nutrient availability (87, 88). As such, altering the availability of certain nutrients provides an opportunity to up-regulate the adaptive response to training.
The Fight Against Cancer
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Abnormal signalling pathways disrupt normal cell growth and division. The normal signalling pathway involves hormones, known as growth factors, which are extracellular chemical messengers which activate protein kinase receptors in the cell membrane. These receptors trigger a signal transduction pathway which eventually reaches the nucleus and promotes transcription of proteins and enzymes needed for cell growth and division. Defects in this signalling process results in the cell being constantly instructed to multiply; hence ultimately results in cancerous growths. The complexity of this signalling process means that there are several points of the cell cycle that can go wrong.
Disorders of Growth and Differentiation
Published in Jeremy R. Jass, Understanding Pathology, 2020
Cell division must be coordinated with the needs of tissue and indeed the entire organism. This is achieved by means of hormones and growth factors, hormone and growth factor receptors arranged upon the cell membrane, signal transduction pathways (transferring messages from cell membrane to nucleus) and nuclear proteins (to prepare the cell for division). The function of signal transduction pathways is to bring about amplification and integration of the various messages received by the array of receptors upon the cell surface and so relay an unambiguous message to the nucleus. These cascade systems operate through the enzymatic conversion of an inactive precursor to an active enzyme. This is achieved by a surprisingly limited number of mechanisms (Fig. 18). Some of the genes coding for growth factors, receptors, cell signalling molecules or nuclear proteins that drive mitogenesis are called proto-oncogenes. This is because mutated versions (oncogenes; see Chapter 23) have been shown to drive cell proliferation in neoplasms (Table 4).
The pharmacological properties and corresponding mechanisms of farrerol: a comprehensive review
Published in Pharmaceutical Biology, 2022
Xiaojiang Qin, Xinrong Xu, Xiaomin Hou, Ruifeng Liang, Liangjing Chen, Yuxuan Hao, Anqi Gao, Xufeng Du, Liangyuan Zhao, Yiwei Shi, Qingshan Li
In vivo experiments, the anti-inflammatory activity of farrerol was reported by Xin Ran (2018) and Xiong (2013). Ci et al. (2012) found that farrerol markedly alleviated the allergic airway inflammation in an allergic asthma model, and its mechanism of action was related to the activation of phosphorylation of Akt and nuclear factor (NF-κB) subunit p65. Ci et al. (2012) proved that farrerol could exert anti-inflammatory effects in the treatment of asthma by inhibiting the PI3K and NF-κB signalling pathways. Ci et al. (2012) found that farrerol significantly inhibited T cell-mediated delayed-type hypersensitivity in female BALB/c mice. The mechanism of action may be related to the downregulation of NF-κB activation and nuclear factor of activated T cell 2 signal transduction pathways (Taylor et al. 2013). Additionally, in 2018, Ran et al. (2018) reported that farrerol administration significantly improved the weight changes, clinical scores, colonic length and intestinal epithelial barrier damage and markedly decreased inflammatory cytokine production in TNBS-induced mice. This anti-inflammatory effect was mediated by decreasing the production of interlekin (IL)-1β, IL-6, and tumour necrotic factor (TNF)-α and increasing the expression of claudin-1, zonula occludens 1 (ZO-1), and occludin (Ran et al. 2018). Li et al. (2018) reported that farrerol could ameliorate pathological damage in the mammary glands; attenuate myeloperoxidase (MPO) activity; and inhibit the production of pro-inflammatory mediators and phosphorylation of AKT, NF-κB p65, p38, and ERK1/2 in lipopolysaccharide (LPS)-induced mouse mastitis.
There and back again: a dendrimer’s tale
Published in Drug and Chemical Toxicology, 2022
Barbara Ziemba, Maciej Borowiec, Ida Franiak-Pietryga
The signal transduction pathway is a cascade of biochemical reactions involving the transmission of molecular signals from a cell exterior to its interior. Signals received by cells must be transmitted effectively to the target molecules to assure an appropriate response. Signaling pathway dysregulation can influence cell growth, proliferation, division, metabolism, or survival and lead to disease development. Dendrimers, as nanoparticles, may easily disrupt signal transduction by affecting any element of the pathway. Such activity may have adverse effects, but also advantages, e.g., in cancer or metabolic diseases therapy. Therefore, findings on dendrimers’ biological effects in terms of their interactions with key cellular signal transduction pathways may have important clinical implications.
Determination of cytokine profile and associated genes of the signaling pathway in HNSCC
Published in Journal of Receptors and Signal Transduction, 2022
Aysel Kalayci Yigin, Ali Azzawri, Kayhan Ozturk, Tulin Cora, Mehmet Seven
Cytokines, chemokines and growth factors are important immunmodulators and prognostic markers which have a complex regulatory effect in the control of cellular processes. They act over short distances and at very low concentrations and are also coordinate intercellular signal transduction pathways [8]. To trigger these signal transduction pathways, they bind to receptors (receptor tyrosine kinases) on the membranes of responsive target cells and induce gene expression in target cells. Many cellular activities associated with survival, activation, proliferation, and differentiation of cells are under the control of intracellular signal transduction pathways. Aberrant activations of these components in the signal transduction pathways play a major role in the malignant transformation of many cancers [6]. Therefore, determining these activators involved in the etiopathogenesis of the HNSCC can be notable molecular targets for novel therapeutic approaches. The study aims to evaluate the cytokine, chemokine and growth factor profiling of HNSCC patients, and the relationship of genes involved in the pathway related to these cytokines.