Publications by authors named "Yiru C Zhao"

Bud-break is an economically and environmentally important process in trees and shrubs from boreal and temperate latitudes, but its molecular mechanisms are poorly understood. Here, we show that two previously reported transcription factors, EARLY BUD BREAK 1 (EBB1) and SHORT VEGETATIVE PHASE-Like (SVL) directly interact to control bud-break. EBB1 is a positive regulator of bud-break, whereas SVL is a negative regulator of bud-break.

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A majority of breast cancer specific deaths in women with ERα (+) tumors occur due to metastases that are resistant to endocrine therapy. There is a critical need for novel therapeutic approaches to resensitize recurrent ERα (+) tumors to endocrine therapies. The objective of this study was to elucidate mechanisms of improved effectiveness of combined targeting of ERα and the nuclear transport protein XPO1 in overcoming endocrine resistance.

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Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women.

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Article Synopsis
  • The combination of Conjugated Estrogens (CE) and Bazedoxifene (BZA) aims to relieve menopause symptoms in women but its effects on gut microbiome and enzyme activity have not been previously studied.
  • A mouse study revealed that while CE+BZA didn't significantly alter the overall gut microbiome, it did reduce the abundance of Akkermansia, associated with weight gain, and lowered fecal GUS activity linked to Lactobacillaceae abundance.
  • This research suggests that long-term estrogen supplementation can directly influence gut microbial activity and composition, potentially optimizing the metabolism of estrogens for better health outcomes in postmenopausal women or breast cancer patients.
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The bazedoxifene and conjugated estrogens (CE+BZA) combination has been shown to prevent visceral adiposity and weight gain after ovariectomy. However, its impact on the liver transcriptomes associated with prevention of hepatosteatosis is yet to be determined. In the present study, we use liver transcriptomics and plasma metabolomics analysis to characterize the effects of various estrogens on liver.

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Article Synopsis
  • Many breast cancer deaths come from women with recurrent, estrogen receptor-positive tumors, highlighting the need for new treatment methods to make these tumors more sensitive to endocrine therapies.
  • This study focused on validating certain nuclear transport genes, particularly XPO1, as potential indicators of endocrine therapy failure and explored how inhibiting XPO1 could enhance endocrine treatments.
  • Results indicated that high levels of XPO1 were linked to poor survival rates and tamoxifen resistance, but combining XPO1 inhibition with tamoxifen restored sensitivity and reduced recurrence in resistant cancer models.
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There is great medical need for estrogens with favorable pharmacological profiles that support desirable activities for menopausal women, such as metabolic and vascular protection, but that lack stimulatory activities on the breast and uterus. We report the development of structurally novel estrogens that preferentially activate a subset of estrogen receptor (ER) signaling pathways and result in favorable target tissue-selective activity. Through a process of structural alteration of estrogenic ligands that was designed to preserve their essential chemical and physical features but greatly reduced their binding affinity for ERs, we obtained "pathway preferential estrogens" (PaPEs), which interacted with ERs to activate the extranuclear-initiated signaling pathway preferentially over the nuclear-initiated pathway.

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With the advent of the -omics approaches our understanding of the chronic diseases like cancer and metabolic syndrome has improved. However, effective mining of the information in the large-scale datasets that are obtained from gene expression microarrays, deep sequencing experiments or metabolic profiling is essential to uncover and then effectively target the critical regulators of diseased cell phenotypes. Estrogen Receptor α (ERα) is one of the master transcription factors regulating the gene programs that are important for estrogen responsive breast cancers.

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Scope: We studied the impact of dietary supplementation with licorice root components on diet-induced obesity, fat accumulation, and hepatic steatosis in ovariectomized C57BL/6 mice as a menopause model.

Materials And Methods: We evaluated the molecular and physiological effects of dietary licorice root administered to ovariectomized C57BL/6 mice as root powder (LRP), extracts (LRE), or isolated isoliquiritigenin (ILQ) on reproductive (uterus and mammary gland) and nonreproductive tissues important in regulating metabolism (liver, perigonadal, perirenal, mesenteric, and subcutaneous fat). Quantitative outcome measures including body weight, fat distribution (magnetic resonance imaging), food consumption, bone density and weight (Dual-energy X-ray absorptiometry), and gene expression were assessed by the degree of restoration to the preovariectomized health state.

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