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  • 1
    Online Resource
    Online Resource
    The Impact of Iron Overload and Ferroptosis on Reproductive Disorders in Humans: Implications for Preeclampsia
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 13 ( 2019-07-04), p. 3283-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 13 ( 2019-07-04), p. 3283-
    Abstract: Iron is an essential element for the survival of most organisms, including humans. Demand for iron increases significantly during pregnancy to support growth and development of the fetus. Paradoxically, epidemiologic studies have shown that excessive iron intake and/or high iron status can be detrimental to pregnancy and is associated with reproductive disorders ranging from endometriosis to preeclampsia. Reproductive complications resulting from iron deficiency have been reviewed elsewhere. Here, we focus on reproductive disorders associated with iron overload and the contribution of ferroptosis—programmed cell death mediated by iron-dependent lipid peroxidation within cell membranes—using preeclampsia as a model system. We propose that the clinical expressions of many reproductive disorders and pregnancy complications may be due to an underlying ferroptopathy (elemental iron-associated disease), characterized by a dysregulation in iron homeostasis leading to excessive ferroptosis.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms20133283
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Endometriosis-Associated Ovarian Cancer: A Review of Pathogenesis
    MDPI AG ; 2013
    In:  International Journal of Molecular Sciences Vol. 14, No. 3 ( 2013-03-06), p. 5367-5379
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 14, No. 3 ( 2013-03-06), p. 5367-5379
    Abstract: Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%–10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion, endometriosis shares several characteristics with invasive cancer, has been shown to undergo malignant transformation, and has been associated with an increased risk of epithelial ovarian carcinoma (EOC). Numerous epidemiologic studies have shown an increased risk of EOC among women with endometriosis. This is particularly true for women with endometrioid and clear cell ovarian carcinoma. However, the carcinogenic pathways by which endometriosis associated ovarian carcinoma (EAOC) develops remain poorly understood. Current molecular studies have sought to link endometriosis with EAOC through pathways related to oxidative stress, inflammation and hyperestrogenism. In addition, numerous studies have sought to identify an intermediary lesion between endometriosis and EAOC that may allow for the identification of endometriosis at greatest risk for malignant transformation or for the prevention of malignant transformation of this common gynecologic disorder. The objective of the current article is to review the current data regarding the molecular events associated with EAOC development from endometriosis, with a primary focus on malignancies of the endometrioid and clear cell histologic sub-types.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms14035367
    Language: English
    Publisher: MDPI AG
    Publication Date: 2013
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Endometrial Decidualization: The Primary Driver of Pregnancy Health
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 11 ( 2020-06-08), p. 4092-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 11 ( 2020-06-08), p. 4092-
    Abstract: Interventions to prevent pregnancy complications have been largely unsuccessful. We suggest this is because the foundation for a healthy pregnancy is laid prior to the establishment of the pregnancy at the time of endometrial decidualization. Humans are one of only a few mammalian viviparous species in which decidualization begins during the latter half of each menstrual cycle and is therefore independent of the conceptus. Failure to adequately prepare (decidualize) the endometrium hormonally, biochemically, and immunologically in anticipation of the approaching blastocyst—including the downregulation of genes involved in the pro- inflammatory response and resisting tissue invasion along with the increased expression of genes that promote angiogenesis, foster immune tolerance, and facilitate tissue invasion—leads to abnormal implantation/placentation and ultimately to adverse pregnancy outcome. We hypothesize, therefore, that the primary driver of pregnancy health is the quality of the soil, not the seed.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21114092
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    The Functions of MicroRNA-200 Family in Ovarian Cancer: Beyond Epithelial-Mesenchymal Transition
    MDPI AG ; 2017
    In:  International Journal of Molecular Sciences Vol. 18, No. 6 ( 2017-06-06), p. 1207-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 18, No. 6 ( 2017-06-06), p. 1207-
    Abstract: The majority of studies on microRNA-200 family members (miR-200s) in human cancers are based on the premise that miR-200s maintain epithelial cell integrity by suppressing epithelial-mesenchymal transition (EMT) through direct inhibition of mesenchymal transcription factors zinc finger E-box-binding homeobox 1/2 (ZEB1/ZEB2) and transforming growth factor-β (TGF-β), a potent inducer of EMT. Hence, downregulation of miR-200 in cancer cells promotes EMT and cancer metastasis. Yet, miR-200s are highly expressed in ovarian cancer, and ovarian cancer metastasizes primarily by dissemination within the pelvic cavity. In this review, we will refocus the epithelial property of ovarian cancer cells and the role of miR-200s in safeguarding this property, as well as the diverse roles of miR-200s in inclusion cyst formation, cancer cell growth, collective movement, angiogenesis, exosome-mediated cell communication, and chemoresponse. Taken together, miR-200s play a significant role in the initiation, progression and metastasis of ovarian cancer and may serve as diagnostic biomarkers and a target in therapeutic development.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms18061207
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Online Resource
    Deep Learning-Based Prediction Model for the Cobb Angle in Adolescent Idiopathic Scoliosis Patients
    MDPI AG ; 2024
    In:  Diagnostics Vol. 14, No. 12 ( 2024-06-14), p. 1263-
    Details
    In: Diagnostics, MDPI AG, Vol. 14, No. 12 ( 2024-06-14), p. 1263-
    Abstract: Scoliosis, characterized by spine deformity, is most common in adolescent idiopathic scoliosis (AIS). Manual Cobb angle measurement limitations underscore the need for automated tools. This study employed a vertebral landmark extraction method and Feedforward Neural Network (FNN) to predict scoliosis progression in 79 AIS patients. The novel intervertebral angles matrix format showcased results. The mean absolute error for the intervertebral angle progression was 1.5 degrees, while the Pearson correlation of the predicted Cobb angles was 0.86. The accuracy in classifying Cobb angles ( 〈 15°, 15–25°, 25–35°, 35–45°, 〉 45°) was 0.85, with 0.65 sensitivity and 0.91 specificity. The FNN demonstrated superior accuracy, sensitivity, and specificity, aiding in tailored treatments for potential scoliosis progression. Addressing FNNs’ over-fitting issue through strategies like “dropout” or regularization could further enhance their performance. This study presents a promising step towards automated scoliosis diagnosis and prognosis.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics14121263
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
    detail.hit.zdb_id: 2662336-5
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  • 6
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    Online Resource
    Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 8 ( 2020-07-27), p. 2065-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 8 ( 2020-07-27), p. 2065-
    Abstract: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a subtype of non-small cell lung cancer (NSCLC) characterized by marked lymphocytic infiltration and association with Epstein–Barr virus (EBV). The molecular basis underlying the disease remains unclear. We sought to study the molecular landscape by multiple approaches including whole genomic sequencing, capture-based targeted sequencing, fluorescent in situ hybridization and immunohistochemistry. Tumor cells from 57 EBV-positive pulmonary LELCs were isolated by careful microdissection prior to genomic sequencing. Integrated analysis revealed a distinct genomic landscape of low TP53 mutation rate (11%), low incidence of known drivers in the RTK/RAS/RAF (11%) and PI3K/AKT/mTOR pathways (7%), but enriched for loss-of-function mutations in multiple negative regulators of the NF-κB pathway. High level programmed cell death ligand-1 (PD-L1) expression was shown with 47% and 79% of the cases showing positive PD-L1 immunoreactivity at ≥50% and ≥1% tumor proportion score, respectively. Subsets of the patients with actionable fibroblast growth factor receptor 3 (FGFR3) aberrations (4%) and mismatch repair deficiency (4%) were potentially eligible for precision medicine. Pulmonary LELC showed a distinct genomic landscape, different from major NSCLC subtypes but resembled that of EBV-associated nasopharyngeal carcinoma. Our work facilitated the understanding of molecular basis underlying pulmonary LELC to explore potential therapeutic options.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12082065
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 7
    Online Resource
    Online Resource
    Baveno VII Criteria Is an Accurate Risk Stratification Tool to Predict High-Risk Varices Requiring Intervention and Hepatic Events in Patients with Advanced Hepatocellular Carcinoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 9 ( 2023-04-26), p. 2480-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 9 ( 2023-04-26), p. 2480-
    Abstract: The Baveno VII criteria are used in patients with liver cirrhosis to predict high-risk varices in patients with liver cirrhosis. Yet its use in patients with advanced hepatocellular carcinoma (HCC) has not been validated. HCC alone is accompanied with a higher variceal bleeding risk due to its association with liver cirrhosis and portal vein thrombosis. The use of systemic therapy in advanced HCC has been thought to further augment this risk. Upper endoscopy is commonly used to evaluate for the presence of varices before initiation of treatment with systemic therapy. Yet it is associated with procedural risks, waiting time and limited availability in some localities which may delay the commencement of systemic therapy. Our study successfully validated the Baveno VI criteria with a 3.5% varices needing treatment (VNT) missed rate, also with acceptable 〈 5% VNT missed rates when considering alternative liver stiffness (LSM) and platelet cut-offs. The Baveno VII clinically significant portal hypertension rule-out criteria (LSM 〈 15 kPa and platelet 〉 150 × 109/L) also revealed a low frequency (2%) of hepatic events, whilst the rule-in criteria (LSM 〉 25 kPa) was predictive of a higher proportion of hepatic events (14%). Therefore, our study has successfully validated the Baveno VII criteria as a non-invasive stratification of the risk of variceal bleeding and hepatic decompensation in the HCC population.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15092480
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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