9 research outputs found

    Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth

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    Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth

    Five undescribed plant-derived bisphenols from Artemisia capillaris aerial parts: Structure elucidation, anti-hepatoma activities and plausible biogenetic pathway

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    Yin-Chen, which belongs to the Asteraceae family and the genus Artemisia, is among the most abundantly used traditional medicines in China for the treatment of hepatitis and bilious disorder. Herein, five undescribed plant-derived bisphenols, capillarisenols A–E (13, 15, 25, 29, 31), and one undescribed phenolic compound (32), together with 32 known phenolic compounds (1–12, 14, 16–24, 26–28, 30, 33–38), were isolated and identified based on spectroscopic evidence from aerial parts of Artemisia capillaris Thunb. Capillarisenols A–E are the type of bisphenols firstly isolated from this plant. The plausible biogenetic pathway of new compounds was also proposed. In addition, the potential anti-hepatoma effects on Huh7 and HepG2 cell lines of all isolated compounds were evaluated in vitro. Capillarisenol C (25) showed significant anti-hepatoma activity in Huh7 and HepG 2 cells, with IC50 values of 4.96 and 8.58 μM, better than the positive control drug (Lenvatinib). This study provided phytochemical evidence for further development and utilisation of A. capillaris in health products

    Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression.

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    The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1β), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1β/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis
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