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Prelabor rupture of the membranes
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Roberto Romero, Lami Yeo, Francesca Gotsch, Eleazar Soto, Sonia S. Hassan, Juan Pedro Kusanovic, Ray Bahado-Singh
Finally, there is evidence that genetic factors predispose to preterm PROM. Polymorphisms for genes coding for MMP-1 (30), MMP-9 (31), MMP-8 (32), and SERPINH1 (33) in the fetus have been associated with spontaneous rupture of membranes in case-control studies. Environmental factors, such as BV (25,34) or a pro-inflammatory vaginal milieu (35), have also been associated with PROM. Evidence for a gene–environment interaction for preterm birth has been demonstrated between BV and a polymorphism for the pro-inflammatory cytokine, TNF-α (36,37). It is also possible that gene–gene interactions are operative. The genetic predisposition for preterm PROM is likely to result from the effect of multiple alleles, which individually confer a small risk for preterm PROM. Epigenetic changes in MMP-1 have been found to be associated with preterm PROM (38). Collectively, the evidence reviewed above supports the concept that preterm PROM is not a single condition, but one of the “great obstetrical syndromes.”
Orthogenomics
Published in Kohlstadt Ingrid, Cintron Kenneth, Metabolic Therapies in Orthopedics, Second Edition, 2018
Joseph R. Veltmann, Roberta L. Kline
Candidate gene studies have discovered more than 38 inherited single gene mutations linked to osteoporosis (58). Some of the genes are related to collagen 1 biosynthesis (BMP2, COL1A1, COL1A2, CREB3L1, CRTAP, FDBP10, PLOD2, PPIB, SERPINH1), whereas others are related to osteoclast function (CA2, CCLNCN7, CTSK, OSTM1, PLEKHM1, SNX10, TC1RG1), osteoclast differentiation via NF-ƙB signaling (IKBKG, SQSTM1, TNFRSF 11A, TNFRSF11B, TNFSF11, VCP), and Wnt-regulated endochondral ossification (LRP4, LRP5, LRPS, SOST, WNT1, WTX). An inherited genetic mutation in one of these key genes can lead to severe bone diseases linked to either excessive bone formation or bone reabsorption such as osteogenesis imperfecta, osteopetrosis, sclerosis and autosomal recessive osteoporosis.
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Genetics: OI types 1–5 are inherited in an autosomal dominant manner and most are caused by mutations in the genes COL1A1 or COL1A2. Almost 60% of individuals with mild OI have de novo mutations (mutation detection rate in this group is 100%); virtually 100% of individuals with lethal (type 2) OI or with severe (type 3) OI have a de novo mutation (mutation detection rate in this group 60%–98%). Penetrance of COL1A1 or COL1A2 mutations is complete; expression can be variable. OI types 6–9 are inherited in an autosomal recessive manner, and caused by mutations in CRTAP (OI 7, and a small proportion of cases of OI 2/3), LEPRE (OI 8) and PPIB (OI 9). Mutations within these genes cause decreased collagen 3-prolyl hydroxylation. Recently, mutations in the genes FKBP10 and SERPINH1 have also been found as causing severe recessive forms of OI: both these genes encode for chaperone proteins whose deficiency causes impairment of type 1 procollagen folding and secretion. Recessive mutations in SERPINF1 have been associated with both OI type 3 and 6. SERPINF1 encodes for PEDF (pigment epithelium derived factor), the absence of which disturbs bone homeostasis independent of alterations in type I collagen synthesis or intracellular processing. BMP1 is a further gene resulting in autosomal recessive OI. OI types 6–9 may be grouped together as autosomal recessive OI.
Lactiplantibacillus plantarum 299v supplementation modulates β-cell ER stress and antioxidative defense pathways and prevents type 1 diabetes in gluten-free BioBreeding rats
Published in Gut Microbes, 2022
Pinar Sargin, Mark F. Roethle, Shuang Jia, Tarun Pant, Ashley E. Ciecko, Samantha N. Atkinson, Nita H. Salzman, Ru-Jeng Teng, Yi-Guang Chen, Susanne M. Cabrera, Martin J. Hessner
The DRlyp/lyp HCD+Lp299v islet transcriptome exhibited higher abundance of transcripts related to translation initiation, positive regulation of insulin secretion, chaperone binding and protein processing (Figure 3b). This included eukaryotic initiation factors, including Eif4g1 which regulates glucose homeostasis and β-cell function,52 and Eif3f a translational enhancer that improves protein synthesis efficiency.53Eef2 and Eef1d, which encode translation elongation factors, were also most abundant in DRlyp/lyp HCD+Lp299v islets. DRlyp/lyp HCD+Lp299v islets exhibited reduced abundance of translational repressors (Paip2, Eif4g2, Fmr, Cirbp), while showing high abundance of transcripts encoding products required for protein processing within the ER. These included Ssr2 and Sec61a1, necessary for translocating nascent peptides into the ER, and chaperones/co-chaperones (Cdc37, Creld2, Dnajb11, Hsp90b1, Pfdn1, Serpinh1, Sil1) including Dnajc3 which maintains insulin-folding homeostasis.54 Transcripts encoding isomerases (Ppib, Fkbp11, Pdia6) and oxidases necessary for protein maturation within the ER exhibited higher abundance in DRlyp/lyp HCD+Lp299v islets, this included quiescin sulfhydryl oxidase 1 (Qsox1), which also acts to inhibit autophagy.
Effect of Regulating the Expression of HSP47 on Collagen Metabolism in Scleral Fibroblasts
Published in Current Eye Research, 2021
Qingge Guo, Qingshan Tian, Xiang Tian, Taixiang Liu
Heat shock protein 47 (HSP 47) is a collagen-specific molecular chaperone that localizes to the endoplasmic reticulum (ER). It is encoded by the SERPINH1 gene and appears to preferentially identify Gly-Xaa-Arg sequences that bind to collagen. HSP 47 thus helps to assemble procollagen in the ER and to facilitate the trafficking of trimeric molecules to the Golgi apparatus. The fact that collagens produced in HSP 47-/- cells are sensitive to trypsin digestion suggests that HSP 47 is involved in collagen metabolism and is a key factor in regulating changes in collagen levels.7,8 In addition, HSP 47 can promote the transdifferentiation of Tenon’s fibroblasts into myofibroblasts.9 The most reliable marker of myofibroblast phenotype is α-smooth muscle actin (α-SMA), which is expressed in microfilaments and stress fibers and accounts for the highly contractile characteristics of myofibroblasts.10 During the development of myopia, scleral remodeling results in myofibroblasts with decreased contractile force that are unable to maintain matrix stability.11 Previous studies have indicated that the expression of α-SMA in the sclera from myopic guinea pigs, mice, and tree shrews decreases under strain stimulation. Yuan et al. found RhoA/ROCK2 was an important mechanotransduction pathway in the differentiation of fibroblasts to myofibroblasts.12
The power of proteomics to monitor senescence-associated secretory phenotypes and beyond: toward clinical applications
Published in Expert Review of Proteomics, 2020
Nathan Basisty, Abhijit Kale, Sandip Patel, Judith Campisi, Birgit Schilling
Recently, a SILAC study showed that senescent cells secrete bioactive protein factors that alter hemostasis and drive blood clotting [68]. From this unbiased SILAC MS analysis performed in senescent human lung fibroblasts after genotoxic stress (X–irradiation) in culture, dozens of novel SASP factors were identified. Notably, the SASP contained 44 proteins that participated in hemostasis or blood clotting, including SERPINs (SERPINE1 & 2, SERPINF1 & 2, SERPINB2, SERPINH1, SERPING1) and thrombospondins (THBS1 & 2). This study [68] used a transgenic mouse model that enabled the selective elimination of senescent cells (p16-3MR mice [23]) to test if senescent cells alter hemostasis. When senescent cells were increased in mice with a single intraperitoneal dose (10 mg/kg) of the chemotherapeutic agent doxorubicin [34], blood clotting increased; conversely, when senescent cells were selectively removed, the blood clotting response returned to normal. These results suggest that senescent cells secrete factors into plasma at concentrations sufficient to promote clotting, and, presumably, other phenotypes. Since they enter the circulation, SASP factors hold potential as plasma biomarkers for aging and age-related diseases that are driven by senescent cells. In addition, since senescent cells drive the clotting-related side-effects of anti-cancer therapies, understanding the SASP is important for patients exposed to genotoxic chemotherapies. Furthermore, targeting senescent cells or the SASP may be a clinical strategy to mitigate the side effects of certain chemotherapeutic drugs and, presumably, other drugs that drive cells into senescence, such as HIV protease inhibitors [70,71].