Isoliquiritigenin Decreases Bone Resorption and Osteoclast Differentiation.

Scope: A dose-ranging study is performed using young estrogen-depleted rats to determine whether dietary isoliquiritigenin (ILQ) alters bone metabolism and if the effects are associated with estrogen receptor signaling.

Methods And Results: Six-week-old rats (ovariectomized at 4 weeks of age) are fed diets containing 0, 100, 250, or 750 ppm ILQ (n = 5/treatment) for 7 days. Gene expression in femur and uterus, blood markers of bone turnover, body composition, and uterine weight and epithelial cell height are determined.

Genistein Reduces the Risk of Local Mammary Cancer Recurrence and Ameliorates Alterations in the Gut Microbiota in the Offspring of Obese Dams.

The risk of recurrence of estrogen receptor-positive breast cancer remains constant, even 20 years after diagnosis. Recurrence may be more likely in patients pre-programmed for it already in the womb, such as in the daughters born to obese mothers. Maternal obesity persistently alters offspring's gut microbiota and impairs tumor immune responses.

Disruption of global hypothalamic microRNA (miR) profiles and associated behavioral changes in California mice (Peromyscus californicus) developmentally exposed to endocrine disrupting chemicals.

Developmental exposure to endocrine disrupting chemicals (EDCs), e.g., bisphenol A (BPA) or genistein (GEN), causes longstanding epigenome effects.

Author Correction: Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood.

Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment.

(±)-Equol does not interact with genistein on estrogen-dependent breast tumor growth.

Equol (EQ) is a prominent microbial metabolite of the soy isoflavone, daidzein, with estrogen-like properties. The major soy isoflavone, genistein (GEN), stimulated growth of estrogen-dependent breast cancer (EDBC) cells in vitro and tumor growth in vivo but EQ did not. To understand possible interactions of EQ and GEN on EDBC, EQ was used with GEN in combination in vitro and in vivo.

Early genistein exposure of California mice and effects on the gut microbiota-brain axis.

Human offspring encounter high amounts of phytoestrogens, such as genistein (GEN), through maternal diet and soy-based formulas. Such chemicals can exert estrogenic activity and thereby disrupt neurobehavioral programming. Besides inducing direct host effects, GEN might cause gut dysbiosis and alter gut metabolites.

Thermally Abused Frying Oil Potentiates Metastasis to Lung in a Murine Model of Late-Stage Breast Cancer.

Deep-frying is a popular form of food preparation used globally and throughout in the United States. Each time dietary oils are heated to deep-frying temperatures, they undergo chemical alterations that result in a new matrix of lipid structures. These lipid products include triglyceride dimers, polymers, oxidized triglycerides, and cyclic monomers, which raises nutritional concerns about associations between these lipid products and heightened health risks.

Estrogen-independent Myc overexpression confers endocrine therapy resistance on breast cancer cells expressing ERαY537S and ERαD538G mutations.

Approximately 30% of metastatic breast cancers harbor estrogen receptor α (ERα) mutations associated with resistance to endocrine therapy and reduced survival. Consistent with their constitutive proliferation, T47D and MCF7 cells in which wild-type ERα is replaced by the most common mutations, ERαY537S and ERαD538G, exhibit partially estrogen-independent gene expression. A novel invasion/dissociation/rebinding assay demonstrated that the mutant cells have a higher tendency to dissociate from invasion sites and rebind to a second site.

Iron Fortification of Spiced Vinegar in the Philippines.

Unlabelled: Despite existent fortification initiatives in the Philippines, approximately 50% of the population still suffers from iron deficiency anemia (IDA), mainly in rural areas. Fortification of staple foods has been proved successful in China and Vietnam. Coconut spiced vinegar (SV) is an inexpensive, widely available, and culturally acceptable condiment in Filipino households; however, no technical evidence exists on its potential as fortification vehicle.

The effects of dietary levels of genistein on ovarian follicle number and gene expression.

Genistein is a phytoestrogen found in soy. We previously found that adult exposure to dietary levels of genistein affected gestation time, parturition time, litter size, pup weight, and pup mortality in CD-1 mice. The present study investigated the effects of adult genistein exposure on follicle number and gene expression in the ovaries of CD-1 mice.

Licorice root components mimic estrogens in an object location task but not an object recognition task.

This study investigated the efficacy of components of licorice root to alter performance on two different recognition tasks, a hippocampus-sensitive metric change in object location (MCOL) task and a striatum-sensitive double object recognition (DOR) task. Isoliquiritigenin (ISL), licorice root extract (LRE), and whole licorice root powder (LRP) were assessed. Young adult female rats were ovariectomized (OVX) and exposed to ISL, LRE or LRP at 0.

Albumin as a "Trojan Horse" for polymeric nanoconjugate transendothelial transport across tumor vasculatures for improved cancer targeting.

Although polymeric nanoconjugates (NCs) hold great promise for the treatment of cancer patients, their clinical utility has been hindered by the lack of efficient delivery of therapeutics to targeted tumor sites. Here, we describe an albumin-functionalized polymeric NC (Alb-NC) capable of crossing the endothelium barrier through a caveolae-mediated transcytosis pathway to better target cancer. The Alb-NC is prepared by nanoprecipitation of doxorubicin (Doxo) conjugates of poly(phenyl O-carboxyanhydrides) bearing aromatic albumin-binding domains followed by subsequent surface decoration of albumin.

The effects of the botanical estrogen, isoliquiritigenin on delayed spatial alternation.

Age-related declines in cognitive function can impair working memory, reduce speed of processing, and alter attentional resources. In particular, menopausal women may show an acceleration in the rate of cognitive decline as well as an increased vulnerability to brain diseases as estrogens may play a neuroprotective and neurotrophic role in the brain. To treat menopausal symptoms, many women turn to botanical estrogens that are promoted as a safe and natural alternative to traditional hormone replacement therapy.

Extract of Ginkgo biloba exacerbates liver metastasis in a mouse colon cancer Xenograft model.

Background: Metastasis refers to the spread of a primary tumor cell from the primary site to other locations in the body and it is generally associated with the severity of a tumor. Extract of Ginkgo biloba (EGb) contains various bioactive compounds and it exerts beneficial effects including improvements in brain function and reduced risk of cardiovascular diseases. On the other hand, increased risk of thyroid and liver cancers by EGb have been reported in animals.

Preconception exposure to dietary levels of genistein affects female reproductive outcomes.

Genistein is a phytoestrogen found in soy and soy-based products. Previously, we found that genistein adversely affected estradiol levels and follicle growth in vitro. Proper hormone production and follicle growth are key regulators of normal fertility.

Low calcium diet increases 4T1 mammary tumor carcinoma cell burden and bone pathology in mice.

Breast cancer metastasizes to bone in the majority of patients with advanced disease. We investigated the effects of inadequate dietary calcium (Ca) on bone turnover, tumor growth, and bone response to tumor in tibia inoculated with 4T1 mammary carcinoma cells. Nine-month-old female Balb/c mice were placed on an adequate Ca (5 g/kg diet, n = 30) or low Ca (80 mg/kg diet, n = 31) diet for 14 days, then injected intratibially with 1,000 4T1 cells (transfected with luciferase for bioluminescence imaging), and sacrificed at 5, 10, or 21 days post-inoculation (n = 7-10 mice/group).

Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats.

Purpose: Whether it is safe for estrogen receptor-positive (ER+) patients with breast cancer to consume soy isoflavone genistein remains controversial. We compared the effects of genistein intake mimicking either Asian (lifetime) or Caucasian (adulthood) intake patterns to that of starting its intake during tamoxifen therapy using a preclinical model.

Experimental Design: Female Sprague-Dawley rats were fed an AIN93G diet supplemented with 0 (control diet) or 500 ppm genistein from postnatal day 15 onward (lifetime genistein).

Effects of isoliquiritigenin on ovarian antral follicle growth and steroidogenesis.

Isoliquiritigenin is a botanical estrogen used as a dietary supplement. Previous studies show that other botanical estrogens affect ovarian estradiol synthesis, but isoliquiritigenin's effects on the ovary are unknown. Thus, this study tested the hypothesis that isoliquiritigenin inhibits ovarian antral follicle growth and steroidogenesis.

Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer.

The negative impact of chemotherapy on cognitive function in cancer patients has gained increasing attention in the last decade. Whilst the short-term acute effects on cognition are expected following chemotherapy, the persistence of such impairments in the long-term is still in question. This is despite clinical evidence indicating cognitive difficulties may persist well beyond treatment and affect quality of life.

Pamidronate functionalized nanoconjugates for targeted therapy of focal skeletal malignant osteolysis.

Malignant osteolysis associated with inoperable primary bone tumors and multifocal skeletal metastases remains a challenging clinical problem in cancer patients. Nanomedicine that is able to target and deliver therapeutic agents to diseased bone sites could potentially provide an effective treatment option for different types of skeletal cancers. Here, we report the development of polylactide nanoparticles (NPs) loaded with doxorubicin (Doxo) and coated with bone-seeking pamidronate (Pam) for the targeted treatment of malignant skeletal tumors.

Effects of letrozole on breast cancer micro-metastatic tumor growth in bone and lung in mice inoculated with murine 4T1 cells.

Breast cancer (BC) is the leading cancer in women worldwide. Metastasis occurs in stage IV BC with bone and lung being common metastatic sites. Here we evaluate the effects of the aromatase inhibitor letrozole on BC micro-metastatic tumor growth in bone and lung metastasis in intact and ovariectomized (OVX) mice with murine estrogen receptor negative (ER-) BC cells inoculated in tibia.

Pharmacokinetics of isoflavones from soy infant formula in neonatal and adult rhesus monkeys.

Consumption of soy infant formula represents a unique exposure scenario in which developing children ingest a mixture of endocrine-active isoflavones along with a substantial portion of daily nutrition. Genistein and daidzein were administered as glucoside conjugates to neonatal rhesus monkeys in a fortified commercial soy formula at 5, 35, and 70 days after birth. A single gavage dosing with 10 mg/kg bw genistein and 6 mg/kg bw daidzein was chosen to represent the upper range of typical daily consumption and to facilitate complete pharmacokinetic measurements for aglycone and total isoflavones and equol.

Interplay between steroid hormone activation of the unfolded protein response and nuclear receptor action.

To identify new pathways of estrogen action and novel estrogen receptor α (ERα) biomodulators, we performed high throughput screening and used follow on assays and bioinformatics to identify small molecule ERα inhibitors with a novel mode of action. These studies led to identification of rapid extranuclear activation of the endoplasmic reticulum stress sensor, the unfolded protein response (UPR), as a new pathway of estrogen-ERα action. Moreover, increasing evidence indicates that the mechanism underlying anticipatory activation of the UPR is shared among steroid and peptide hormones and is conserved from insects to humans.

Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro.

Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles.