12 research outputs found

    INO80 function is required for mouse mammary gland development, but mutation alone may be insufficient for breast cancer

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    The aberrant function of ATP-dependent chromatin remodeler INO80 has been implicated in multiple types of cancers by altering chromatin architecture and gene expression; however, the underlying mechanism of the functional involvement of INO80 mutation in cancer etiology, especially in breast cancer, remains unclear. In the present study, we have performed a weighted gene co-expression network analysis (WCGNA) to investigate links between INO80 expression and breast cancer sub-classification and progression. Our analysis revealed that INO80 repression is associated with differential responsiveness of estrogen receptors (ERs) depending upon breast cancer subtype, ER networks, and increased risk of breast carcinogenesis. To determine whether INO80 loss induces breast tumors, a conditional INO80-knockout (INO80 cKO) mouse model was generated using the Cre-loxP system. Phenotypic characterization revealed that INO80 cKO led to reduced branching and length of the mammary ducts at all stages. However, the INO80 cKO mouse model had unaltered lumen morphology and failed to spontaneously induce tumorigenesis in mammary gland tissue. Therefore, our study suggests that the aberrant function of INO80 is potentially associated with breast cancer by modulating gene expression. INO80 mutation alone is insufficient for breast tumorigenesis

    Sugar-Sweetened Coffee Intake and Blood Glucose Management in Korean Patients with Diabetes Mellitus

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    One of the most frequently consumed beverages by Korean adults is 3-in-1 coffee (mixed coffee) with sugar and creamer. Hence, understanding the effect of sugar-sweetened coffee (SSC) consumption on blood sugar levels in patients with diabetes mellitus (DM) is important. This study was conducted using the Korea National Health and Nutrition Examination Survey data from 2008 to 2020. In total, 5671 patients with DM were included in the analysis. Coffee consumption patterns were assessed using a 24 h recall. Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels were used to evaluate whether patients reached the glycemic control targets defined by the Korean Diabetes Association. In total, 46.57% of patients with DM included in this analysis consumed SSC. Patients who frequently consumed SSC had significantly higher FBG and HbA1c levels than those who did not (both p for trend p for trend = 0.01) and 1.29 (95% CI: 1.05–1.58, p for trend = 0.009), respectively. Frequent consumption of SSC can cause difficulty in FBG and HbA1c management in patients with DM

    Association between Phytochemical Index and Osteoporosis in Women: A Prospective Cohort Study in Korea

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    Osteoporosis is a prevalent issue among postmenopausal women, who have a higher incidence of the condition than men. This study aimed to examine the relationship between phytochemical-rich food intake and osteoporosis incidence in premenopausal and postmenopausal women. The data analyzed included 4600 women aged 40–69 who were free of osteoporosis at baseline, with dietary intake evaluated through a semi-quantitative food frequency questionnaire and osteoporosis prevalence determined using interviewer-administered questionnaires and bone mineral density tests. The phytochemical index (PI) was calculated to reflect the intake levels of phytochemical-rich foods. Postmenopausal women in the highest PI quartile had a 16% lower risk of osteoporosis (95% confidence interval (CI): 0.71 to 0.99, p for trend = 0.02) than those in the lowest quartile, while no significant association was observed among premenopausal women (hazard ratio: 0.98, 95% CI: 0.78 to 1.24, p for trend = 0.8). These findings suggest that consuming phytochemical-rich foods may have a protective effect against osteoporosis in postmenopausal women, offering valuable scientific insights. However, additional research is needed to validate these findings using biochemical data. Overall, this study highlights the potential of dietary interventions to reduce the risk of osteoporosis in postmenopausal women

    Epigenetic Factors as Etiological Agents, Diagnostic Markers, and Therapeutic Targets for Luminal Breast Cancer

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    Luminal breast cancer, an etiologically heterogeneous disease, is characterized by high steroid hormone receptor activity and aberrant gene expression profiles. Endocrine therapy and chemotherapy are promising therapeutic approaches to mitigate breast cancer proliferation and recurrence. However, the treatment of therapy-resistant breast cancer is a major challenge. Recent studies on breast cancer etiology have revealed the critical roles of epigenetic factors in luminal breast cancer tumorigenesis and drug resistance. Tumorigenic epigenetic factor-induced aberrant chromatin dynamics dysregulate the onset of gene expression and consequently promote tumorigenesis and metastasis. Epigenetic dysregulation, a type of somatic mutation, is a high-risk factor for breast cancer progression and therapy resistance. Therefore, epigenetic modulators alone or in combination with other therapies are potential therapeutic agents for breast cancer. Several clinical trials have analyzed the therapeutic efficacy of potential epi-drugs for breast cancer and reported beneficial clinical outcomes, including inhibition of tumor cell adhesion and invasiveness and mitigation of endocrine therapy resistance. This review focuses on recent findings on the mechanisms of epigenetic factors in the progression of luminal breast cancer. Additionally, recent findings on the potential of epigenetic factors as diagnostic biomarkers and therapeutic targets for breast cancer are discussed

    Role of Transcriptional and Epigenetic Regulation in Lymphatic Endothelial Cell Development

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    The lymphatic system is critical for maintaining the homeostasis of lipids and interstitial fluid and regulating the immune cell development and functions. Developmental anomaly-induced lymphatic dysfunction is associated with various pathological conditions, including lymphedema, inflammation, and cancer. Most lymphatic endothelial cells (LECs) are derived from a subset of endothelial cells in the cardinal vein. However, recent studies have reported that the developmental origin of LECs is heterogeneous. Multiple regulatory mechanisms, including those mediated by signaling pathways, transcription factors, and epigenetic pathways, are involved in lymphatic development and functions. Recent studies have demonstrated that the epigenetic regulation of transcription is critical for embryonic LEC development and functions. In addition to the chromatin structures, epigenetic modifications may modulate transcriptional signatures during the development or differentiation of LECs. Therefore, the understanding of the epigenetic mechanisms involved in the development and function of the lymphatic system can aid in the management of various congenital or acquired lymphatic disorders. Future studies must determine the role of other epigenetic factors and changes in mammalian lymphatic development and function. Here, the recent findings on key factors involved in the development of the lymphatic system and their epigenetic regulation, LEC origins from different organs, and lymphatic diseases are reviewed

    Probiotic Properties and Safety Evaluation of <i>Lactobacillus plantarum</i> HY7718 with Superior Storage Stability Isolated from Fermented Squid

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    The aim of this study was to identify new potential probiotics with improved storage stability and to evaluate their efficacy and safety. Sixty lactic acid bacteria strains were isolated from Korean traditional fermented foods, and their survival was tested under extreme conditions. Lactobacillus plantarum HY7718 (HY7718) showed the greatest stability during storage. HY7718 also showed a stable growth curve under industrial conditions. Whole genome sequencing revealed that the HY7718 genome comprises 3.26 Mbp, with 44.5% G + C content, and 3056 annotated Protein-coding DNA sequences (CDSs). HY7718 adhered to intestinal epithelial cells and was tolerant to gastric fluids. Additionally, HY7718 exhibited no hemolytic activity and was not resistant to antibiotics, confirming that it has probiotic properties and is safe for consumption. Additionally, we evaluated its effects on intestinal health using TNF-induced Caco-2 cells. HY7718 restored the expression of tight junction proteins such as zonular occludens (ZO-1, ZO-2), occludin (OCLN), and claudins (CLDN1, CLDN4), and regulated the expression of myosin light-chain kinase (MLCK), Elk-1, and nuclear factor kappa B subunit 1 (NFKB1). Moreover, HY7718 reduced the secretion of proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8, as well as reducing the levels of peroxide-induced reactive oxygen species. In conclusion, HY7718 has probiotic properties, is safe, is stable under extreme storage conditions, and exerts positive effects on intestinal cells. These results suggest that L. plantarum HY7718 is a potential probiotic for use as a functional supplement in the food industry
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