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  1. Article ; Online: OLFML3 suppresses trophoblast apoptosis via the PI3K/AKT pathway: A possible therapeutic target in preeclampsia.

    Chen, Haiying / Li, Ruiping / Bian, Jiangyujing / Li, Xiaoqing / Su, Cunjing / Wang, Yang / Zhang, Hongping / Zheng, Jianqiong / Wang, Yeping / Zhang, Hong

    Placenta

    2024  Volume 147, Page(s) 1–11

    Abstract: Introduction: Preeclampsia (PE) is a pregnancy complication that encompasses various pathogenic mechanisms. Shallow implantation of the placenta due to abnormal trophoblast behavior is considered an important mechanism underlying PE; however, its exact ... ...

    Abstract Introduction: Preeclampsia (PE) is a pregnancy complication that encompasses various pathogenic mechanisms. Shallow implantation of the placenta due to abnormal trophoblast behavior is considered an important mechanism underlying PE; however, its exact etiology remains unclear.
    Methods: The expression of OLFML3 in the placenta and important clinical indicators were performed, followed by a correlation analysis. The effect of OLFML3 on the behavior of HTR-8/SVneo cells was examined, and the downstream molecular mechanisms of OLFML3 were investigated in HTR-8/SVneo cells. Additionally, a rat model of PE was generated by adenovirus injection via the tail vein to verify the role of OLFML3.
    Results: OLFML3 is highly expressed in both syncytiotrophoblasts and cytotrophoblasts and deregulated in preeclamptic placentas. OLFML3 overexpression in HTR-8/SVneo cells promoted cell proliferation, migration, invasion, and impeded apoptosis, and triggered phosphorylation on ser473 of AKT. Conversely, OLFML3 knockdown exerted opposite effects. Furthermore, OLFML3 overexpression ameliorates CoCl
    Discussion: OLFML3 may alleviate PE development by inhibiting extravillous trophoblast cell apoptosis through the PI3K/AKT pathway. Our findings indicated that OLFML3 may provide a possible therapeutic target for PE.
    MeSH term(s) Animals ; Female ; Humans ; Pregnancy ; Rats ; Apoptosis ; Cell Movement ; Glycoproteins/metabolism ; Intercellular Signaling Peptides and Proteins/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Placenta/metabolism ; Pre-Eclampsia/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Trophoblasts/metabolism
    Chemical Substances Glycoproteins ; Intercellular Signaling Peptides and Proteins ; OLFML3 protein, human ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
    Language English
    Publishing date 2024-01-19
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 603951-0
    ISSN 1532-3102 ; 0143-4004
    ISSN (online) 1532-3102
    ISSN 0143-4004
    DOI 10.1016/j.placenta.2024.01.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The impact of ABCB1 and CES1 polymorphisms on the safety of dabigatran in patients with non-valvular atrial fibrillation.

    Zhu, Zhu / Qian, Chenyue / Su, Cunjing / Tao, Hong / Mao, Jiaojiao / Guo, Zhening / Zhu, Xinyi / Pan, Jie

    BMC cardiovascular disorders

    2022  Volume 22, Issue 1, Page(s) 481

    Abstract: Background: This study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes in dabigatran in patients with non-valvular atrial fibrillation (NVAF).: Methods: We conducted a prospective study ... ...

    Abstract Background: This study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes in dabigatran in patients with non-valvular atrial fibrillation (NVAF).
    Methods: We conducted a prospective study and enrolled NVAF patients treated with dabigatran in the real world. A total of 86 patients treated with 110 mg DE twice daily were recruited for this study. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration. All bleeding and thromboembolic complications were recorded during the 1.5 years of follow-up.
    Results: Eighty-three patients provided samples at the trough plasma level of dabigatran, and 58 patients provided samples at the peak plasma level of dabigatran. There was a significant association between the CES1 SNP rs8192935 and trough plasma concentrations of dabigatran (P = 0.013). Our results showed that the CES1 SNP rs8192935 significantly influenced dabigatran trough concentrations in the Chinese population, and carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 SNP c.2482-2236G > A (rs4148738) was associated with major bleeding events in the addictive model (P = 0.046, OR = 3.29) and dominant model (P = 0.040, OR = 8.17). Additionally, the ABCB1 SNP c.3435 C > T (rs1045642) was associated with the incidence of major bleeding events in the addictive model (P = 0.043, OR = 3.34) and dominant model (P = 0.046, OR = 7.77). However, no significant associations were found between all the SNPs and the incidence of minor bleeding events.
    Conclusion: Our results indicated that the CES1 polymorphism rs8192935 was associated with trough plasma concentrations of dabigatran. Carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 polymorphisms rs4148738 and rs1045642 were associated with an increased risk for major bleeding events for the first time in a Chinese population.
    MeSH term(s) Humans ; Dabigatran ; Atrial Fibrillation/diagnosis ; Atrial Fibrillation/drug therapy ; Atrial Fibrillation/genetics ; Antithrombins ; Prospective Studies ; Hemorrhage/epidemiology ; Polymorphism, Single Nucleotide ; Anticoagulants/therapeutic use ; Carboxylic Ester Hydrolases/genetics ; Carboxylic Ester Hydrolases/metabolism ; Carboxylic Ester Hydrolases/therapeutic use ; ATP Binding Cassette Transporter, Subfamily B/genetics ; ATP Binding Cassette Transporter, Subfamily B/therapeutic use
    Chemical Substances Dabigatran (I0VM4M70GC) ; Antithrombins ; Anticoagulants ; CES1 protein, human (EC 3.1.1.1) ; Carboxylic Ester Hydrolases (EC 3.1.1.-) ; ABCB1 protein, human ; ATP Binding Cassette Transporter, Subfamily B
    Language English
    Publishing date 2022-11-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2059859-2
    ISSN 1471-2261 ; 1471-2261
    ISSN (online) 1471-2261
    ISSN 1471-2261
    DOI 10.1186/s12872-022-02910-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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