Marine Algal Secondary Metabolites Are a Potential Pharmaceutical Resource for Human Society Developments
Se-Kwon Kim in Marine Biochemistry, 2023
Cell proliferation is the process in which the number of cells increases due to cell division and cell growth, which often occurs in tumors or cancers. Evidence suggests that algae may act as an antiproliferative by inducing maturation of dendritic cells, combining with other cytokines, and modulating the human immune system (Lowenthal and Fitton, 2015). Macrophages are activated by membrane receptors specifically TLR4, CD14, CR3 and SR, leading to the production of cytokines such as IL-12 and IFN, which enhance the activation of NK cells, which in turn stimulates the activation of T cells (Kellogg et al., 2015). In addition, secondary metabolites of algae, such as root bark tannins, flavonoids, catechins, carotenoids, quercetin, and myricetin, have been shown to have relative anticancer activity. Epidemiological studies also show that, compared to other parts of the world, eating seaweed can reduce the incidence of ovarian cancer, breast cancer, and endometrial cancer in the Japanese population (Murata and Nakazoe, 2001).
Long-Term Effects of Perinatal Exposure to Hormones and Related Substances on Normal and Neoplastic Growth of Murine Mammary Glands
Takao Mori, Hiroshi Nagasawa in Toxicity of Hormones in Perinatal Life, 2020
Cell responsiveness or susceptibility to hormones is another important factor for cell growth. The effects of perinatal hormones and related substances on mammary gland responsiveness to mammotropic hormones are not conclusive. The responsiveness is generally little changed or increased by perinatal hormone treatments; however, a few experimental results infer the decrease of responsiveness in rats.6 In this respect, Heideman et al.41 found that progesterone-binding activity of DMB A-induced mammary tumors of rats was elevated by prenatal exposure to DES during the third trimester, but not by the exposure during the second trimester and no alteration was observed in estrogen binding capacities between treatments. Mammary tissue of adult (about 75 days of age) male Holtsman rats whose mothers received 10 mg cyproterone acetate, an antiandrogen, daily for 10 days beginning day 11 of pregnancy showed presence of estrogen-binding sites comparable to the levels in the normal females, while it was undetectable in normal males.41 These rats also had the higher mammary gland activity of conversion of 3H-androstenedione to estrogens than did normal males.42 Mammary gland response to growth factors was lower in the neonatally estrogenized mice than in the control.43
Introducing Molecular Biology of Head and Neck Cancer
John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford in Head & Neck Surgery Plastic Surgery, 2018
PIK3CA encodes the enzyme phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit (also called p110α), which is the catalytic subunit of a heterodimeric enzyme that catalyses the addition of phosphate from ATP to phosphoinositol lipids that regulate a number of signalling pathways, specifically converting PIP2 to PIP3 and thus activating AKT (also known as protein kinase B or PKB) which plays an important role in cell survival and also regulates several other pathways including ones that control cell movement and metabolism. (PIP2 is phosphatidylinositol (4,5)-bisphosphate; PIP 3 is phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3).) This conversion of PIP2 to PIP3 is part of the signalling pathway from RTKs that ultimately controls a wide range of cellular signalling programmes including transcriptional programs that activate progression through the cell cycle and non-transcriptional survival programs such as activating the mTOR pathway that promotes protein synthesis needed for cell growth as part of the process of promoting cell proliferation and survival.148, 149 The reverse reaction, converting PIP3 to PIP2, is, interestingly, carried out by the product of the other commonly mutated gene in head and neck cancers, the PTEN gene, which encodes an enzyme: the phosphatase and tensin homolog.151–153
The discovery and development of topical medicines for wound healing
Published in Expert Opinion on Drug Discovery, 2019
E. Öhnstedt, H. Lofton Tomenius, E. Vågesjö, M. Phillipson
Growth factors are polypeptides that have a large array of functions. The same growth factor and receptor can activate different pathways and thereby induce different responses depending on the target cell type as well as the microenvironment [41,42]. Growth factors are involved in cell growth, proliferation, differentiation, and migration. Growth factors are essential for normal wound healing and increased expression of certain growth factors is detected in acute wounds, including epithelial growth factor (EGF), basic fibroblast growth factor (bFGF), TGF-β, PDGF, and VEGF. Additionally, expression of the same growth factors are depressed in nonhealing wounds, and they are therefore interesting drug candidates for promoting wound healing [41]. For instance, levels of PDGF were found to be reduced in human nonhealing wounds compared to what is observed in acute surgical wounds [10,41]. This was also observed in two experimental models of delayed wound healing, the db/db mice [43] as well as in mice treated with glucocorticoids [43,44]. Nonhealing wounds of diabetic patients have been demonstrated to contain lower levels of IGF-1 and TGF-β1, and in model with diabetic mice bFGF and VEGF also are reduced [45].
Proteomes of exosomes from HPV(+) or HPV(-) head and neck cancer cells: differential enrichment in immunoregulatory proteins
Published in OncoImmunology, 2019
Sonja Ludwig, Lukasz Marczak, Priyanka Sharma, Agata Abramowicz, Marta Gawin, Piotr Widlak, Theresa L. Whiteside, Monika Pietrowska
Analysis of gene ontology was performed to identify functional pathways associated with the detected proteins. The majority (approximately 2/3) of the detected proteins in exosomes from both HPV(+) and HPV(-) cells were cytoplasmic proteins. They were associated with six major biological functions: (a) regulation of cell growth; (b) cellular metabolism; (c) protein metabolism; (d) energy pathways; (e) cell communication and (f) signal transduction (Figure 1b). Among the proteins detected in both types of exosomes were the integrin family members involved in cell surface interactions and proteins mediating proteoglycan-syndecan signaling as well as the VEGF/VEGFR signaling networks. In general, the majority of biological pathways and processes were similarly enriched in proteins detected in HPV(+) (SCC-90) and HPV(-) (PCI-30) exosomes, as shown in the Supplementary File (Table S2). Several pathways showed statistically significant enrichment (p-value with Bonferroni correction <0.05) for either HPV(+) or HPV(-) exosomes, as shown in Figure 1c. These functional terms included an adaptive immune system or cell-extracellular matrix interactions, which were significantly overrepresented in HPV(+) exosomes, and metabolism of RNA or structural components of ribosomes, which were significantly overrepresented in HPV(-) exosomes. However, no statistically significant differences were detected between these selected sets of proteins in their contribution to the specific pathway.
Recent and Evolving Therapies in the Management of Endothelial Diseases
Published in Seminars in Ophthalmology, 2023
Shalini Singh, Sunita Chaurasia
Corneal endothelial cells have the capacity to expand in vitro, but ability to do so in vivo is limited. The first reported protocol for in vitro expansion of endothelial cells was in 1965, and ever since there have been a plethora of protocols explaining isolation and in vitro expansion of endothelial cells because it is extremely challenging to isolate and expand endothelial cells in vitro. Culture and expansion of endothelial cells are achieved by collectively tweaking the following steps: selection of suitable donor tissue, peeling of the corneal endothelium and DM from donor corneas, enzymatic digestion to isolate the hCEC, seeding of the resulting cell suspension using a combination of culture media and growth factors, and expansion and proliferation on appropriate substrates that mimic the in vivo conditions.9 Cell growth is also boosted by the loss of cell contact, supplemented culture medium and growth factors.43 Endothelial to mesenchymal transition is induced by the activation of intra-cellular pathways which causes the CEC to acquire a fibroblast-like phenotype, thereby losing their morphological features and function.43–45Hence, a protocol to achieve isolation, expansion and propagation of CEC along with maintaining cell morphology and function needs to be developed.