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Immunoregulatory Factors Secreted by Human or Murine Placenta or Gestational Tumors
Published in Gérard Chaouat, The Immunology of the Fetus, 2020
Of the many other well-characterized proteins of putatively or well-established placental origin, six are reported to be suppressive in vitro. First, one must quote pregnancy-associated alpha2 glycoprotein (or alpha2 PAG,PAG,PAM,SP3,PZP as acronyms). Stimson found its immunosuppressive properties on MLR,8 Straube et al. described its adverse effects on macrophage activation and mobility,9 and Svendsen found, interestingly, that it could enhance survival of heart transplant in mice. These effects have been reproduced by a variety of groups, and analogues have been reported in the Salamandra, but the physiological role of this product is still unknown.
Capacitation, the Acrosome Reaction, and Motility in Mammalian Sperm
Published in Claude Gagnon, Controls of Sperm Motility, 2020
Susan S. Suarez, John W. Pollard
In 1982, Florman and Storey demonstrated that the zona pellucida induces the acrosome reaction in mouse sperm.55 Since then, the zona has also been demonstrated to have acrosome reaction-inducing activity in hamsters, rabbits, cattle, pigs, and humans.56-61 In the mouse, an 83-kDa glycoprotein component of the zona, named ZP3, has been shown to account for both the sperm binding and acrosome reaction-inducing activities of the zona pellucida (for review, see Reference 2). Both 55-kDa and 90-kDa glycoproteinaceous components of the porcine zona pellucida have acrosome reaction-inducing activity.59
Pregnancy-Related Proteins in Non-Trophoblastic Tumors
Published in Gábor N. Than, Hans Bohn, Dénes G. Szabó, Advances in Pregnancy-Related Protein Research, 2020
Most recent studies have confirmed extensive sequence homology between α2-PAG and α2-macroglobulin.125 The glycoprotein referred to persistently by Jensen et al.126 as PZP has been localized immunohistochemically to the surface of the syncytiotrophoblast of human afterbirth.127 Chorionic villi prepared from normal full-term placentae were approximately half occupied by endogenous α2-macroglobulin or PZP complexes. These mutual receptors have a somewhat lower affinity in binding the PZP-chymotrypsin complex than it does with respect to the complex formed by α2-macroglobulin proteinase (trypsin), although native PZP and α2-macroglobulin do not bind with these receptors. The common receptor for α2-M and PZP-proteinase complexes has previously been described in human fibroblast cells and in monocyte-derived cultured macrophages and in hepatocytes.126,128,129 Even conservative estimates make it likely that α2-M and PZP proteinase complexes in placenta constitute a significant portion of the total receptor population in pregnant women at term.126 These observations, as well as the fact that α2-PAG affects polymorphonuclear leucocyte and monocyte functions which make up the central components of acute-phase response, suggest that the protein may be a modulator in human acute-phase response.130–132 Thus, the hypotheses made by Bohn101 20 years hence appear to have been confirmed from several different directions; to wit, that α2-PAG may be an acute-phase reactant, and that in the human body its biological function is similar to the “symbodies” binding the surfaces of tumors and placentae. Still, its physiological and pathophysiological roles in trophoblast and tumor immunology have not been completely clarified and will require further intensive experimentation, only after which will it be possible to clearly state its tumor-associated role.
Microanatomy of the metabolic associated fatty liver disease (MAFLD) by single-cell transcriptomics
Published in Journal of Drug Targeting, 2023
Lijun Wang, Kebing Zhou, Qing Wu, Lingping Zhu, Yang Hu, Xuefeng Yang, Duo Li
In recent years, MAFLD has been extensively studied. A study by Chutian Wu et al. [5], which included 26 simple steatosis (SS), 34 non-alcoholic steatohepatitis (NASH), and 13 healthy controls (HC) identified 6 up- and 19 downregulated genes in SS and 13 up- and 19 downregulated genes in NASH compared with HC. Moreover, intersected pathways between SS and NASH included the PI3K-Akt signalling pathway and pathways in cancer. High-throughput sequencing of the liver mRNA of Mongolian gerbils with MAFLD and further bioinformatics analysis obtained 8 hub genes Cd44, App, Cdc42, Cd68, Cxcr4, Csf1r, Adgre1 and Fermt3 involved in inflammation, fibrosis and hepatic cell carcinoma (HCC), and qRT-PCR showed that the above genes were upregulated in different periods of modelling process [6]. A comprehensive bioinformatics analysis of 3 comprehensive gene expression datasets in MAFLD tissues showed that CD24, COL1A1, LUM, THBS2 and EPHA3 were upregulated, while PZP was downregulated, and ‘Glycolysis/gluconeogenesis’, ‘p53 signalling pathway’, ‘glycine, serine and threonine metabolism’ were 3 common pathways related to the MAFLD process [7]. However, these bioinformatic studies on MAFLD have not fully elucidated the pathogenesis of MAFLD, and no in silico analysis has hitherto been performed on MAFLD single-cell sequencing datasets.
Pseudomonas aeruginosa in bronchiectasis: infection, inflammation, and therapies
Published in Expert Review of Respiratory Medicine, 2021
Celine Vidaillac, Sanjay H. Chotirmall
While significant advances by our group and others have established the importance of patient stratification in bronchiectasis based on infections such as P. aeruginosa and their accompanying high-risk exacerbation endophenotypes, how best to translate these findings into actionable clinical care is now needed [3,21,178,179]. Patient stratification by microbial taxa or as recently described, concentrations of pregnancy zone protein (PZP) may provide important point of care tools to aid clinical management [178,180]. Recently, the influence of P. aeruginosa colonization on the structure of the lung microbiome community has been described and such work provides a strong indication that next-generation sequencing-based stratification approaches may hold promise in bronchiectasis [181,182]. Despite strong recent advances in understanding the pathophysiology, diagnosis and therapies related to nCF bronchiectasis, the role of P. aeruginosa in this disease remains challenging [7,10,40,87,180,183]. Future work needs to better address host-related biology in the context of P. aeruginosa virulence and adaptation in bronchiectasis. One such example is the emerging role of sex steroids which induces both mucoid conversion and membrane stress in P. aeruginosa leading to enhanced virulence potential in CF. Whether this similarly occurs in nCF bronchiectasis remains to be proven, and how potential concomitant therapies, including steroid-mimics and/or hydrophilic compounds can influence disease course remains to be elucidated.
Forecasting most deleterious nsSNPs in human TLR9 gene and their cumulative impact on biophysical features of the protein using in silico approaches
Published in Systems Biology in Reproductive Medicine, 2023
Heena Gautam, Ved Vrat Verma, Syed Akhtar Husain, Mausumi Bharadwaj
The muTarget tool identifies the effect of mutation on gene expression and gives an expression plot. Here, in the current hypothesis we have used two independent analyses i.e., ‘Genotype’ and ‘Target’ for the TLR9 gene to predict the detailed role of the mutant gene on its expression. In this respect, we performed a ‘Genotype’ run for the TLR9 mutant gene. For uterine cancer, the outcomes of the ‘Genotype’ hypothesis revealed the alteration in the expression of MKNK2, MED18, AEN, C19orf25, OSGIN1, and other genes (Figure 8). However, cervical cancer mutation in TLR9 could not alter the expression of neighboring genes. Next, we performed a ‘Target’ run by selecting TLR9 as the target gene for both cervical and uterine cancers. Our results showed gene alteration for cervical cancer (SOS1, NMT2, EPB41L3, and PZP) where a higher expression is observed for the MUC4 gene (Figure 9(A)). Similarly, for uterine cancer the expression of TLR9 can be influenced by a mutation in various genes i.e., TP53, AGO1, GRM8, SCAF4, and MROH8 (Figure 9(B)). Interestingly, we observed that gene TP53 showed a maximum change in gene expression for uterine cancer as compared to other counterparts’ genes. The comparative outcomes of our muTarget analysis suggest that the expression of various genes has been affected by point mutations in the TLR9 gene. In this respect, with regard to the case of uterine cancer, the expression of MKNK2, MED18, AEN, C19orf25, and OSGIN1 genes have been altered along with mutations in the TLR9 gene (detailed about potential genes are incorporated in Supplementary Data S2).