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Nutraceutical’s Role in Proliferation and Prevention of Gynecological Cancers
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Aaishwarya B. Deshmukh, Jayvadan K. Patel, Bharat Mishra
The phenolic compound naringin changes GM3 ganglioside, thereby affecting the signaling of EGFR and resulting in the inhibition of HeLa [71]. Taxifolin from Siberian larch is shown to possess a synergistic effect when used with a diterpenoid lactone, andrographolide, against HeLa cells by diminishing protective autophagy induced by andrographolide, whereas it increases the mitochondrial outer-membrane permeability and also caspase-dependent and -independent cell death. Various studies have shown that Withaferin A, from Withania somnifera, given in vivo to athymic nude mice models (a murine strain bearing spontaneous deletion in the Foxn1 gene that causes deteriorated or absent thymus), reduced CaSki–HPV type 16 and 18 positive cervical tumor cell lines effectively [71].
Genodermatoses affecting the nail
Published in Eckart Haneke, Histopathology of the NailOnychopathology, 2017
When the nude mouse was identified in 1966, it was detected that the hair follicles could not enter the epidermis and that there was an inborn dysgenesis of the thymus making this animal an excellent model for the study of primary immunodeficiency and xenotransplantation.216 Although mentioned in the original publication, the nail changes found little attention and were only investigated late. A mutation in the winged-helix-nude gene Whn encoding a highly conserved transcription factor now called FOXN1 is responsible for the nude phenotype. Although the exact function of FOXN1 remained long unclear, it is now thought to play a key role in the early stages of keratinocyte differentiation. It directly activates keratin 1 synthesis.217 In nude mice, Krt 3 and other keratins are absent in the hair.218 Although nude mice have the same number of hair follicles219 and show an active cyclical growth pattern,220 the hair shafts have no normal cuticle and break.221 It was shown that the FOXN1 mRNA and acidic hair keratin 3 are co-expressed both in the hair follicles and the nails.220 Less than 20 years ago, the human phenotype of severe functional T cell impairment and congenital alopecia with nail dystrophy was observed.222–227 As was shown recently,228 there are considerable analogies between mouse and human nails and the study of the nail in the nude mouse and other mutant and transgenic mice with nail abnormalities229 may help us understand human nail physiology and pathology.230,231 Nail dystrophy occurs both in homozygous and heterozygous FOXN1 mutant humans whereas hair alterations are not seen in the heterozygous carriers.232
Phylogeny of the mucosal immune system
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Robert D. Miller, Irene Salinas
Studies in jawless vertebrates support the evolution of early primary lymphoid tissues from mucosa-associated lymphoid tissues (MALTs). The primary hematopoietic organ in lampreys is the typhlosole, an organ unique to the agnathans. The typhlosole develops as an invagination in the larval intestine and remains associated with the intestinal wall throughout the life of the organism. In addition, the lamprey pharyngeal gill epithelium contains accumulations of lymphocytes that express VLR genes. Furthermore, a thymus candidate has been proposed in lamprey and coined as “thymoid.” The lamprey thymoid is located in the tips of the gill filaments and secondary lamellae within the gill basket. It is worth noting that this hypothesis is consistent with the development of the thymus in jawed vertebrates from the pharyngeal pouches. The discovery of an adaptive immune system in agnathans makes this question all the more interesting, because the generation of highly diverse VLR antigen receptors in lampreys and hagfish should create the need for some mechanism of self-tolerance, presumably via negative selection. The paradigm of the gnathostome thymus suggests the need for a specific organ in which cells undergo selection. Consistent with this idea, the pharyngeal/gill-associated lymphoid tissue (thymoid) in lampreys has the highest percentage of lymphocytes that are VLRA+, those lymphocytes that share the greatest number of characteristics with gnathostome T cells. Throughout the rest of the lamprey tissues, VLRB+ cells are far more prevalent than VLRA+ cells. Furthermore, there is recent evidence that the lamprey Foxn4L gene expressed in developing gill epithelium is the agnathan ortholog of Foxn1, which is expressed in the developing thymus of jawed vertebrates.
Role of thymus in health and disease
Published in International Reviews of Immunology, 2022
Surendra Gulla, Madhava C. Reddy, Vajra C. Reddy, Sriram Chitta, Manjula Bhanoori, Dakshayani Lomada
Thymic involution associated with aging results in decreased T-cell development efficiency and decreased naive T-cell migration to the periphery. There have been some surprising findings, such as the TECs being the most sensitive compartment in this multi-step process [28]. One of the main factors in thymus involution is depletion of TEC, a strategy aimed at maintaining or restoring TEC precursors is expected to improve immunological function. Forkhead box protein n1 (Foxn1) expression, a critical TEC transcription factor, declines with age, resulting in rapid TEC degradation. Prior to or post thymus involution, overexpression of Foxn1 in TECs has been shown to block or reverse this mechanism [29]. Additionally, Foxn1 absence results in athymia, a condition in which TECs cannot develop or engage hematopoietic progenitor cells. TECs may not generate cell surface molecules required to attach hematopoietic progenitor cells to epithelial cells in the nude thymus. Still, they can restore the nude thymus phenotype in transgenic Foxn1 mice [30,31]. Lizhen chen et al. demonstrated that Foxn1 is essential for postnatal thymus maintenance. Also, Foxn1 is highly dose sensitive, and minor changes in Foxn1 levels significantly impact the thymus phenotypes [32]. Garfin et al. showed that in retinoblastoma (RB) family mutant TECs, enhanced E2F transcription factor activity promotes the expression of Foxn1, which is a key regulator of the thymic epithelium, and concluded that through a bone marrow-independent mechanism, the RB family enhances thymic involution and regulates T cell production [33]. Klug et al. elegantly demonstrated that the typical adult thymus has two different cortical TEC populations that can be recognized by their keratin (K) expression patterns: the major K8(+) K5(-) subset and a minor K8(+) K5(+) subset that is significantly expressed at the cortico-medullary junction [34]. Later, the same research group demonstrated that a cyclin D1 transgene expression in K5+ TECs extends this subset and stimulates the growth of both TECs and thymocytes. These studies hypothesized that “improving thymic function may be accomplished by controlling the proliferation and survival of K8 + 5+ TEC precursors” [35]. Thymopoiesis-promoting factors (eg IL-7), decline with age and their absence impairs TECs’ ability to interact with thymocytes and supply growth factors needed for thymocyte development, resulting in reduced thymopoiesis [36–38]. As TECs are less regenerable, a hypostomal structure allows fat cells to accumulate and fill the thymic space in humans [39,40]. Moreover, heterochronic parabiosis experiments demonstrated that circulating factors from the young are insufficient to stimulate thymus regeneration in the aging thymuses [41]. These studies indicate that organization of TEC compartment has significant role and degradation of the same has reduced thymic function during thymus involution