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  1. Integrated Eutopic Endometrium and Non-Depleted Serum Quantitative Proteomic Analysis Identifies Candidate Serological Markers of Endometriosis
    Manousopoulou A, Hamdan M, Fotopoulos M, Garay-Baquero DJ, Teng J, Garbis SD, et al.
    Proteomics Clin Appl, 2019 05;13(3):e1800153.
    PMID: 30488576 DOI: 10.1002/prca.201800153
    BACKGROUND: Endometriosis affects about 4% of women in the reproductive age and is associated with subfertility. The aim of the present study is to examine the integrated quantitative proteomic profile of eutopic endometrium and serum from women with endometriosis compared to controls in order to identify candidate disease-specific serological markers.

    METHODS: Eutopic endometrium and serum from patients with endometriosis (n = 8 for tissue and n = 4 for serum) are, respectively, compared to endometrium and serum from females without endometriosis (n = 8 for tissue and n = 4 for serum) using a shotgun quantitative proteomics method. All study participants are at the proliferative phase of their menstrual cycle.

    RESULTS: At the tissue and serum level, 1214 and 404 proteins are differentially expressed (DEPs) in eutopic endometrium and serum, respectively, of women with endometriosis versus controls. Gene ontology analysis shows that terms related to immune response/inflammation, cell adhesion/migration, and blood coagulation are significantly enriched in the DEPs of eutopic endometrium, as well as serum. Twenty-one DEPs have the same trend of differential expression in both matrices and can be further examined as potential disease- and tissue-specific serological markers of endometriosis.

    CONCLUSIONS: The present integrated proteomic profiling of eutopic endometrium and serum from women with endometriosis identify promising serological markers that can be further validated in larger cohorts for the minimally invasive diagnosis of endometriosis.

  2. Fulltext Impact of pharmacist-managed diabetes medication therapy adherence clinic (DMTAC) in government health clinics
    Lee XY, Selvadurai S, Cheah KY, Noh NB, Gan CB, Teng J, et al.
    Malaysian Journal of Pharmaceutical Science, 2015;13(1):43-51.
    MyJurnal
    Pharmacist-managed DMTAC has been set up in Malaysia government healthcare facilities to assist diabetic patients in improving their medication adherence level and glycaemic control. The aim of this study is to determine the effect of pharmacist involvement in a DMTAC programme on patient glycaemic control in 14 government health clinics in Kuala Lumpur and Putrajaya. This multi-centre retrospective study collected DMTAC patient demographics, medication regimens, glycated haemoglobin (HbA1c) levels, Modified Morisky Medication Adherence Scale (MMMAS) data, and percentages of understanding towards their medications (based on information retrieved and reviewed from their DMTAC booklets). The data were analysed using IBM SPSS Statistics Version 21.0. Fifty six patients were involved in this study. The mean HbA1c reduction (SD) of the pre- and post-intervention groups showed a statistically significant
    improvement of 1.0% (1.70) (p<0.001); decreasing from 10.7% (1.51) pre-intervention to 9.7% (1.75) post-intervention. The mean medication understanding score for the postintervention group was 97.6% (7.32), which was significantly higher than the preintervention group score of 92.2% (13.61) (p = 0.005). The mean MMMAS of the postintervention group was 7.4 (1.19), which was significantly higher than the pre-intervention group mean MMMAS of 6.5 (2.33) (p = 0.001). This study demonstrated an improvement in glycaemic control, medication understanding, and adherence level among T2DM patients who were enrolled in a pharmacist-managed DMTAC programme.
    Keywords: Diabetes, Diabetes Medication Adherence Therapy Clinic (DMTAC), Endocrine, Pharmacist, HbA1c, Medication adherence, Medication understanding
  3. Fulltext Stearoyl CoA Desaturase Is Essential for Regulation of Endoplasmic Reticulum Homeostasis and Tumor Growth in Glioblastoma Cancer Stem Cells
    Pinkham K, Park DJ, Hashemiaghdam A, Kirov AB, Adam I, Rosiak K, et al.
    Stem Cell Reports, 2019 04 09;12(4):712-727.
    PMID: 30930246 DOI: 10.1016/j.stemcr.2019.02.012
    Inherent plasticity and various survival cues allow glioblastoma stem-like cells (GSCs) to survive and proliferate under intrinsic and extrinsic stress conditions. Here, we report that GSCs depend on the adaptive activation of ER stress and subsequent activation of lipogenesis and particularly stearoyl CoA desaturase (SCD1), which promotes ER homeostasis, cytoprotection, and tumor initiation. Pharmacological targeting of SCD1 is particularly toxic due to the accumulation of saturated fatty acids, which exacerbates ER stress, triggers apoptosis, impairs RAD51-mediated DNA repair, and achieves a remarkable therapeutic outcome with 25%-100% cure rate in xenograft mouse models. Mechanistically, divergent cell fates under varying levels of ER stress are primarily controlled by the ER sensor IRE1, which either promotes SCD1 transcriptional activation or converts to apoptotic signaling when SCD1 activity is impaired. Taken together, the dependence of GSCs on fatty acid desaturation presents an exploitable vulnerability to target glioblastoma.
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