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      SEMA3B but Not CUL1 as Marker for Pre-Eclampsia Progression

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          Abstract

          Background

          An imbalance between pro- and anti-angiogenic factors contributes to impaired trophoblast invasion during pregnancy, leading to failure of uterine spiral artery remodeling, blood vessel ischemia, and pre-eclampsia (PE). Anti-angiogenic semaphorin 3B (SEMA3B) and pro-angiogenic cullin 1 (CUL1) are expressed in both the placenta and maternal blood. The present study investigated correlations between serum and placental SEMA3B as well as CUL1 levels in late-onset PE.

          Methods

          This cross-sectional study included 50 patients with late-onset (≥ 32 weeks gestation) PE. Maternal serum was obtained before delivery, and placentas were obtained immediately after delivery. SEMA3B and CUL1 levels were evaluated by ELISA. Results were statistically analysed by Spearman correlation test, with a P < 0.05 considered statistically significant.

          Results

          While elevated serum SEMA3B levels significantly correlated with increased placental SEMA3B levels in late-onset PE ( R = 0.620, P = 0.000), alteration of serum CUL1 levels did not correlate with alteration of placental CUL1.

          Conclusion

          Alteration of circulating maternal SEMA3B, but not CUL1, levels can potentially be used to monitor PE progression during pregnancy.

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          Most cited references16

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          Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.

          SCF complexes are the largest family of E3 ubiquitin-protein ligases and mediate the ubiquitination of diverse regulatory and signalling proteins. Here we present the crystal structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF complex, which shows that Cul1 is an elongated protein that consists of a long stalk and a globular domain. The globular domain binds the RING finger protein Rbx1 through an intermolecular beta-sheet, forming a two-subunit catalytic core that recruits the ubiquitin-conjugating enzyme. The long stalk, which consists of three repeats of a novel five-helix motif, binds the Skp1-F boxSkp2 protein substrate-recognition complex at its tip. Cul1 serves as a rigid scaffold that organizes the Skp1-F boxSkp2 and Rbx1 subunits, holding them over 100 A apart. The structure suggests that Cul1 may contribute to catalysis through the positioning of the substrate and the ubiquitin-conjugating enzyme, and this model is supported by Cul1 mutations designed to eliminate the rigidity of the scaffold.
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            Placental origins of preeclampsia: challenging the current hypothesis.

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              Preeclampsia: the role of angiogenic factors in its pathogenesis.

              Preeclampsia, a systemic syndrome of pregnancy clinically characterized by new onset of proteinuria and hypertension, is associated with significant morbidity and mortality to both mothers and fetuses. The pathogenesis of preeclampsia has been enigmatic; this review will focus on understanding the origins of this disorder. Preeclampsia originates in the placenta, starting with inadequate cytotrophoblast invasion and ending with widespread maternal endothelial dysfunction. Production of placental anti-angiogenic factors, specifically soluble fms-related tyrosine kinase 1 and soluble endoglin, have been shown to be upregulated in preeclampsia. These placental anti-angiogenic factors are released into the maternal circulation; their actions disrupt the maternal endothelium and result in hypertension, proteinuria, and the other systemic manifestations of preeclampsia. The molecular basis for placental dysregulation of these pathogenic factors remains unknown, remains unknown. Hypoxia is likely an important regulator. Other factors such as alterations in the renin-angiotensin-aldosterone axis, immune maladaption, excessive shedding of trophoblast debris, oxidative stress, and genetic factors likely contribute to the pathogenesis of the abnormal placentation. As of 2009, the only successful treatment for preeclampsia is delivery. No definitive preventive strategies have been identified. However, several of the recent observations related to phenotypic causality provide stimuli for the development of novel therapies.
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                Author and article information

                Journal
                Malays J Med Sci
                Malays J Med Sci
                Malaysian Journal of Medical Sciences
                The Malaysian Journal of Medical Sciences : MJMS
                Penerbit Universiti Sains Malaysia
                1394-195X
                2180-4303
                January 2019
                28 February 2019
                : 26
                : 1
                : 66-72
                Affiliations
                [1 ]Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
                [2 ]Department of Anatomy, Faculty of Medicine, Trisakti University, Jakarta, Indonesia
                [3 ]Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
                [4 ]Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
                [5 ]Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
                Author notes
                Correspondence: Prof Dr Andrijono Abdul Hamid, PhD (Universitas Indonesia), Professor (Universitas Indonesia), Sp.OG (Universitas Indonesia), Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia, Jl. Salemba Raya No. 4 Jakarta 10430, Indonesia., Tel: (021) 3140966, E-mail: andrijono2@ 123456gmail.com
                Article
                06mjms26012019_oa3
                10.21315/mjms2019.26.1.6
                6419870
                ec232c22-2e86-4a23-bc60-c06aee6bf0ee
                © Penerbit Universiti Sains Malaysia, 2019

                This work is licensed under the terms of the Creative Commons Attribution (CC BY) ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 October 2018
                : 08 January 2019
                Categories
                Original Article

                semaphorin 3b,cullin 1,serum,placenta,pre-eclampsia
                semaphorin 3b, cullin 1, serum, placenta, pre-eclampsia

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