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Skeletal Mechanobiology
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Alesha B. Castillo, Christopher R. Jacobs
Once recruited to newly resorbed sites, osteoprogenitors differentiate into mature bone-forming osteoblasts (Figure 13.1c) via activation of several osteogenic signaling pathways. Of these, Wnt signaling is critical at all stages of skeletal maintenance.18 Wnts are secreted glycoproteins that bind a receptor complex comprised of a seven-pass transmembrane protein, frizzled (Fz), and a single pass transmembrane protein of the low-density lipoprotein (LDL) receptor-related protein (LRP) family.19 Canonical Wnt signaling involves several proteins, including dishevelled (Dsh), axin, adenomatous polyposis coli (APC), glycogen synthase kinase (GSK)-3β, and β-catenin. β-catenin is a cytoplasmic phosphoprotein, which, in the absence of Wnt signaling, is targeted for degradation through phosphorylation by GSK-3β. However, upon Wnt binding, Dsh is phosphorylated leading to the phosphorylation and inactivation of GSK-3β, allowing β-catenin to accumulate in the cytoplasm. Subsequently, β-catenin translocates to the nucleus where it interacts with the T-cell and lymphoid enhancer (TCF-LEF) transcription factors to affect gene transcription.19 Target genes include Runx220 and Osterix,21 both of which are osteoblast-specific transcription factors critical in osteoblast differentiation, proliferation, activity, and apoptosis.22 Wnt signaling is inhibited by several proteins including sclerostin, which is encoded by the gene sclerosteosis (SOST),23 dickkopf1 (Dkk1),24 secreted frizzled-related protein 1 (sFRP1),25 and Wise.26 Thus, osteoblast differentiation is regulated by the spatial and temporal expression of Wnt-signaling modulators.
Evaluation of the anti-oxidant property and cytotoxic potential of the metabolites extracted from the bacterial isolates from mangrove Forest and saltern regions of South India
Published in Preparative Biochemistry and Biotechnology, 2018
Subramanian Prathiba, Gurunathan Jayaraman
According to World Health Organization, cancer is the prime cause of mortality and morbidity.[1] Incidentally, there should be pronounced emphasis on prevention and cure of cancer. Antioxidants like Vitamins C, B, and E, carotenoids, and flavonoids help cancer prevention. They also act as supplements during chemotherapy which help to overcome the formation of free radicals.[2] In spite of these advancements, there have been reports related to the development of drug-resistant cancer cells. Also drug efficacy and affordability are the issues which need to be addressed. Therefore there is a continuous necessity to tap newer sources to develop new antioxidant and anticancer products.[3,4] Obviously, the quest for such new sources extends to exploration of natural products. It has been consistently proved that marine sources are rich in metabolites with antioxidant properties and therefore they present excellent scope to develop prospective drug molecules against various cancer types.[5] Microorganisms surviving in the mangrove forest and salterns undergo periodic climatic variation and as a result develop adaptability to huge environmental stress and therefore can be considered as promising habitats for new microbial isolates. Cytarabine from Cryptotheca crypt, Trabectedin from Ecteinascidia turbinate, Brentuximab vedotin from Symploca hydnoides and Lyngbya majuscule[6] isolated from marine sources are the Food and Drug Administration (FDA) approved cancer drugs available in the market.[5] Of the numerous metabolites, pigmented secondary metabolites with antioxidant/anticancer activity needs special attention. Manivasagan et al, reported that the secondary metabolites produced by Streptomyces sp. (Albidopyrone, Trioxacarcin, Chloro-dihydroquinones), Micromonosproa sp. (Diazepinomicin) Nocardia dassonvillei (N-(2-hydroxyphenyl)-2-phenazinamine (NHP)), Dermacoccus (Dermacozines A-G) exhibit anticancer activity.[7] Prodigiosin, a bioactive red pigmented metabolite, has been shown to inhibit Wnt/β-catenin pathway by targeting several sites like low-density lipoprotein-receptor-related protein (LRP) 6, Dishevelled (DVL), and glycogen synthase kinase-3β (GSK3β) in breast cancer MDA-MB-231 and MDA-MB-468 cells.[8]β-carotene induces cell cycle arrest and apoptosis in colon cancer by down regulating cyclin A and Bcl-2 family proteins.[9] 4, 4 diaponeurosporene, a C30 carotenoid was reported to assist the activation of dendritic cells which in turn help in T cell proliferation and this could well be used in treating various types of cancer.[10] Therefore, the importance of secondary metabolites produced by several halotolerant bacteria in the formulation of drugs deserves due recognition.