Receptor Alpha Expression Research Articles

Amelioration and Immuno-modulation by Ashwagandha on Wi-fi Induced Oxidative Stress in Regulating Reproduction Via Estrogen Receptor Alpha in Male Japanese Quail.

As global change threatens avian biodiversity, understanding species responses to environmental perturbations due to radiation emitted by enormous increase in the application of wireless communication is very urgent. The study investigates the effect of MW radiation on redox balance, stress level, male fertility and the efficacy of Withania somnifera (WS) root extract (100mg/kg body weight) orally administered in 8weeks old mature male Japanese quail exposed to 2.4GHzMW radiation for 2h/day for 30days with power density = 0.1264 mw/cm2 and SAR = 0.9978 W/Kg. Wi-fi exposure induces a decrease in testicular weight, volume, density and gonado-somatic index (GSI) while Ashwagandha increases them. Oxidative stress parameters increased and activity of SOD, catalase, GSH was reduced in testes of exposed quail while Ashwagandha treatment reinstates the redox balance. Exposure to Wi-fi alters quail reproduction by increase in corticosterone and decreased testosterone with reduced expression of estrogen receptor alpha (ERα) in testis. Wi-fi exposure increases IL1β and reduces IL10 in testis. IL-1β inhibits testicular cell function and promotes apoptosis by increasing NF-κB and decreasing sperm count in exposed quails. Ashwagandha increases expression of ERα, sperm count and immunity in quail testis. Further, decrease in IL1β, NF-κB and increase in IL-10 after administration of Ashwagandha in Wi-fi exposed quail prevents inflammatory damages and enhances gonadal function. Thus, exposure to Wi-fi increases oxidative stress, activates apoptosis, modulates immunity in testis while Ashwagandha reverses them via enhanced ERα expression, increase in sperm count thereby enhancing fertility in male Japanese quail.

Analysis of Estrogen Receptor Alpha (ERα) Expression and Epidermal Growth Factor Receptor (EGFR) Mutation and Their Relationship with Hormonal and Menstrual Factors in Women with Lung Adenocarcinoma

Lung cancer is the second most common cancer worldwide. The proportion of non-smoking women with lung cancer is higher than non-smoking men. Studies have found gender differences in estrogen receptor alpha expression and mutation in the human epidermal growth factor receptor in tumour tissue. The aim of the study is to analyze the expression of estrogen receptor alpha (ERα) and epidermal growth factor receptor (EGFR) in women with lung adenocarcinoma. The study is retrospective and includes 41 non-smoking women with lung adenocarcinoma. We studied the expression of ERα and EGFR mutations in tumour tissue and their relationship with the hormonal and menstrual factors. The positive expression of ERα in tumour tissue is 9.8%, and in these patients, the estradiol levels were many times higher. EGFR mutation expression is found in 26.8%. There is a correlation between the expression of the EGFR mutation and the time of menopause. The expression of ERα and EGFR in non-smoking women with lung adenocarcinoma is most likely related to the influence of sex hormones and menstrual factors.

Genes Associated with the Immune System Affected by Ionizing Radiation and Estrogen in an Experimental Breast Cancer Model.

Breast cancer is a global health issue that, when in the metastasis stage, is characterized by the lack of estrogen receptor-α, the progesterone receptor, and human epidermal growth receptor expressions. The present study analyzed the differential gene expression related to the immune system affected by ionizing radiation and estrogen in cell lines derived from an experimental breast cancer model that was previously developed; where the immortalized human breast epithelial cell line MCF-10F, a triple-negative breast cancer cell line, was exposed to low doses of high linear energy transfer α particle radiation (150 keV/μm), it subsequently grew in the presence or absence of 17β-estradiol. Results indicated that interferon-related developmental regulator 1 gene expression was affected in the estrogen-treated cell line; this interferon, as well as the Interferon-Induced Transmembrane protein 2, and the TNF alpha-induced Protein 6 gene expression levels were higher than the control in the Alpha3 cell line. Furthermore, the interferon-related developmental regulator 1, the Interferon-Induced Transmembrane protein 2, the TNF alpha-induced Protein 6, the Nuclear Factor Interleukin 3-regulated, and the Interferon-Gamma Receptor 1 showed high expression levels in the Alpha5 cell line, and the Interferon Regulatory Factor 6 was high in the Tumor2 cell line. Additionally, to further strengthen these data, publicly available datasets were analyzed. This analysis was conducted to assess the correlation between estrogen receptor alpha expression and the genes mentioned above in breast cancer patients, the differential gene expression between tumor and normal tissues, the immune infiltration level, the ER status, and the survival outcome adjusted by the clinical stage factor. It can be concluded that the genes of the interferon family and Tumor Necrosis factors can be potential therapeutic targets for breast cancer, since they are active before tumor formation as a defense of the body under radiation or estrogen effects.

Elucidating Sex-Specific Immune Profiles in a Breast Cancer Model.

Breast cancer is commonly thought of as a "women's disease". However, men are increasingly diagnosed with the disease, and their mortality rates are disparately higher than those of female patients. The abundance and composition of the immune microenvironment are determinants of breast cancer progression and survival. It is well documented that there are sex-specific differences in the immune response to several diseases, including various cancers. However, the effects of these differences in the context of breast cancer remain to be explored. This study demonstrates sex differences in the hormonal and immune landscape of the MMTV-PyMT transgenic murine model of female and male ER+ breast cancer using single-cell RNA sequencing (scRNA-Seq), whole-slide immunohistochemistry, and flow cytometry. Mammary tumors of transgenic male mice had increased estrogen receptor alpha expression and enriched nuclear binding signatures compared to female tumors. In the tumor immune compartment, male mice had lower intratumoral leukocyte infiltration. Yet, scRNA-Seq analysis reveals a more immunostimulatory microenvironment and increased antitumor immune populations in the primary and metastatic lungs as compared to transgenic females. Despite a more favorable innate immune profile, the metastatic burden was increased in male mice. Our data support a sex-dependent immune response in mammary carcinoma associated with the tumor, and likely host, hormonal environment. With emerging therapeutics targeting the tumor immune microenvironment, characterizing immune profiles is critical for optimizing their use in all breast cancer patients.

The mRNA expression profile of glycine receptor subunits alpha 1, alpha 2, alpha 4 and beta in female and male mice

Glycine receptors are ligand-gated chloride-selective channels that control excitability in the central nervous system (CNS). Herein, we have investigated the mRNA expression of the glycine receptor alpha 1 (Glra1), alpha 2 (Glra2), alpha 4 (Glra4) and beta (Glrb) subunits, in adult female and male mice.Single-cell RNA sequencing data re-analysis of the Zeisel et al. (2018) dataset indicated widespread expression of Glra1, Glra2 and Glrb in the CNS, while only a few cells in the cortex, striatum, thalamus, midbrain and spinal cord expressed Glra4. Highest occurrence of Glra1, Glra2 and Glrb were found in the brainstem. Moreover, Glra1 and Glrb were revealed to have the highest occurrences in the spinal cord of the investigated subunits. However, both Glra2 and Glrb had a more widespread expression in the CNS compared with Glra1 and Glra4. Bulk quantitative real-time-PCR (qRT-PCR) analysis revealed Glra1 expression in the hypothalamus, thalamus, brainstem and the spinal cord, and widespread, but low, Glra2 and Glrb expression in the CNS. Moreover, Glrb could be detected in a few visceral organs. Additionally, females and males were found to express Glra1, Glra2 and Glrb differently in certain brain areas such as the brainstem. Expression levels of Glra4 were too low to be detected using qRT-PCR. Lastly, RNAscope spatially validated the expression of Glra1, Glra2 and Glrb in the areas indicated by the single-cell and bulk analyses, and further revealed that Glra4 can be detected in the cortex, amygdala, hypothalamus, thalamus, brainstem, especially the cochlear nucleus, and in the spinal cord.

Estradiol affects the expression of essential molecular factors involved in luteinizing hormone secretion in the plains vizcacha

The plains vizcacha is a rodent that shows reactivation of the hypothalamic–pituitary–ovary (HPO) axis activity at mid-gestation. This process is enabled by the secretion of hypothalamic gonadotropin-releasing hormone (GnRH) at mid-gestation, followed by follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. However, a decrease in the pituitary GnRH receptor (GnRHR) expression is concomitantly determined. Moreover, an increment in the pituitary expression of estrogen receptor alpha (ERα) has been determined. This work aimed to study the impact of estradiol (E2) on GnRHR expression, the transcription factors early growth response protein-1 (Egr-1) and steroidogenic factor-1 (Sf-1), as well as on LH secretion. Three experimental approaches were performed: a physiological one with pregnant plains vizcachas, an in vivo approach with ovariectomized (OVX) animals treated with E2 (OVX + E2), and an ex vivo approach using pituitary glands exposed to a combination of GnRH and E2. Significant increased pituitary expression of Sf-1 and Egr-1 was determined at mid-gestation. Ovariectomy significantly increased adenohypophyseal expression levels of GnRHR, Egr-1, and Sf-1, as well as LH secretion. Then, OVX + E2 showed similar levels to SHAM. Adenohypophyses exposed to GnRH showed induced GnRHR, Egr-1, and Sf-1 expression, and LH secretion, while GnRH + E2 reverted these changes. The mid-gestation pituitary GnRHR decrease may result from the combination of increased E2 and GnRH secretion. Nevertheless, the increased expression of Egr-1 and Sf-1 at mid-gestation, together with LH release, suggests the tightly and complex regulatory system that takes place at mid-gestation, enabling a new progesterone surge that successfully carries the pregnancy to term. New & NoteworthyA significant increment of Sf-1 and Egr-1 at the pituitary of mid-gestating plains vizcachas was determined. Moreover, E2 reverted GnRHR, Egr-1, Sf-1, and LH increase in ovariectomized vizcachas’ pituitaries and ex vivo pituitaries exposed to GnRH. The decrease of the pituitary GnRHR at mid-gestation may result from the increased E2 and GnRH levels. A tightly and complex regulatory system may take place at mid-gestation enabling a new surge of progesterone that carries pregnancy to term.

Variability of folate receptor alpha expression by race among recurrent ovarian cancer patients

Variability of folate receptor alpha expression by race among recurrent ovarian cancer patients

(E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone, a Major Homoisoflavonoid, Attenuates Free Fatty Acid-Induced Hepatic Steatosis by Activating AMPK and PPARα Pathways in HepG2 Cells.

(E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone (HMC), a homoisoflavonoid isolated from Portulaca oleracea, has significant anti-adipogenesis potential; it regulates adipogenic transcription factors. However, whether HMC improves hepatic steatosis in hepatocytes remains vague. This study investigated whether HMC ameliorates hepatic steatosis in free fatty acid-treated human hepatocellular carcinoma (HepG2) cells, and if so, its mechanism of action was analyzed. Hepatic steatosis was induced by a free fatty acid mixture in HepG2 cells. Thereafter, different HMC concentrations (10, 30, and 50 µM) or fenofibrate (10 µM, a PPARα agonist, positive control) was treated in HepG2 cells. HMC markedly decreased lipid accumulation and triglyceride content in free fatty acid-treated HepG2 cell; it (10 and 50 μM) markedly upregulated protein expressions of pAMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. HMC (10 and 50 μM) markedly inhibited the expression of sterol regulatory element-binding protein-1c, fatty acid synthase, and stearoyl-coA desaturase 1, which are the enzymes involved in lipid synthesis. Furthermore, HMC (10 and 50 μM) markedly upregulated the protein expression of peroxisome proliferator-activated receptor alpha (PPARα) and enhanced the protein expressions of carnitine palmitoyl transferase 1 and acyl-CoA oxidase 1. HMC inhibits lipid accumulation and promotes fatty acid oxidation by AMPK and PPARα pathways in free fatty acid-treated HepG2 cells, thereby attenuating hepatic steatosis.

Retinoic acid receptor alpha expression in endometrioid heterotopias and the endometrium of patients with endometriosis

BACKGROUND: Vitamin A is a fat-soluble compound, which is a biologically inactive food form and undergoes transformation by cytosolic alcohol dehydrogenases and microsomal retinol dehydrogenases into retinaldehyde, followed by oxidation by retinaldehyde dehydrogenases 1, 2 and 3 into retinoic acid. All-trans-retinoic acid has been identified as an active metabolite of retinoic acid, indirectly participating in various processes: differentiation, proliferation and apoptosis. Based on a number of studies, the role of retinoic acid and its receptors in various diseases has been proven. For example, the destruction of the RAR-β gene by the integration of the hepatitis B virus into its loci can be a factor in the development of human hepatocellular carcinoma. Subsequently, it was described that the characteristic point of interruption of translocation t(15:17), observed in acute promyelocytic leukemia, was located at the locus encoding retinoic acid receptor-α. As a result, in patients with acute promyelocytic leukemia, complete remission of the disease could often be achieved by treatment with high doses of all-trans-retinoic acid. Existing data on the ability of retinol to influence the processes of differentiation, proliferation, and apoptosis indicate that retinol may be involved in the pathogenesis of endometriosis, but the mechanisms of its effect on the disease are subject to further study. AIM: The aim of this study was to evaluate the retinoic acid receptor alpha expression in endometrioid heterotopias and the endometrium of patients with different endometriosis stages according to the Revised American Society for Reproductive Medicine classification. MATERIALS AND METHODS: This was a prospective study to determine the retinoic acid receptor alpha expression in the endometrium and endometrioid heterotopias of patients with endometriosis (n = 28) and of the control group (n = 10). RESULTS: The retinoic acid receptor alpha expression in endometrioid heterotopias was lower compared to the eutopic endometrium of patients with endometriosis and the endometrium of patients in the control group by 3.4 and two times, respectively (p 0.001; the Kruskal – Wallis method). CONCLUSIONS: The data obtained indicate the involvement of retinol in the pathogenesis of endometriosis. Despite the relative increase in retinol level in the peripheral blood and peritoneal fluid in patients with endometriosis compared to the control group, shown in our previous studies, the reduced retinoic acid receptor alpha expression in endometrioid heterotopias does not allow for full binding of vitamin A to the receptor and is accompanied by its improper metabolism.

COPD-Like Phenotypes in TBC-Treated Mice Can be Effectively Alleviated via Estrogen Supplement.

Tris(2,3-dibromopropyl) isocyanurate (TBC), recognized as an endocrine disruptor, can cause inflammatory injury to the lung tissue of mice. To investigate the specific respiratory effects of TBC, male C57BL/6J mice were administered a daily dose of 20 mg/kg of TBC over 14 days. Postexposure, these mice developed chronic obstructive pulmonary disease (COPD)-like symptoms characterized by inflammatory lung damage and functional impairment. In light of the antiestrogenic properties of TBC, we administrated estradiol (E2) to investigate its potential protective role against TBC-induced damage and found that the coexposure of E2 notably mitigated the COPD-like phenotypes. Immunohistochemical analysis revealed that TBC exposure reduced estrogen receptor alpha (ERα) expression and increased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, while E2 treatment rebalanced the expression levels of ERα and NF-κB to their normative states. Our findings indicate that TBC, as an antiestrogenic agent, may contribute to the pathogenesis of COPD through an ERα-mediated inflammatory pathway, but that E2 treatment could reverse the impairment, providing a potentially promising remedial treatment. Given the lung status as a primary target of air pollution, the presence of antiestrogenic compounds like TBC in atmospheric particulates presents a significant concern, with the potential to exacerbate respiratory conditions such as COPD and pneumonia.

Interleukin-11Rα2 in the hypothalamic arcuate nucleus affects depression-related behaviors and the AKT-BDNF pathway

Depression is a widespread emotional disorder with complex pathogenesis. An essential function of the hypothalamus is to regulate emotional disorders. However, further investigation is required to identify the pathogenic genes and molecular mechanisms that contribute to the onset of depression within the hypothalamus. Through RNA-sequencing analysis, this study identified the upregulated expression of interleukin-11 receptor alpha 2 (IL-11Rα2) in the hypothalamus of mice with chronic unpredictable stress (CUS)-induced depression. This substantial increase in IL-11Rα2, not IL-11Rα1 expression levels in the hypothalamus under the influence of CUS was found to be associated with depression-related behaviors. We further showed that IL-11Rα2 is expressed in the arcuate nucleus (ARC) proopiomelanocortin (POMC) neurons of the hypothalamus. Male and female mice exhibited behaviors association with depression, when IL-11Rα2 or its ligand IL-11 was overexpressed in the ARC POMC neurons through the action of an adeno-associated virus. In addition, reductions in the expression levels of proteins involved in the protein kinase B signaling pathways and brain-derived neurotrophic factor were observed upon overexpression of IL-11Rα2 in the hypothalamic ARC. This study emphasizes the importance of IL-11Rα2 in the hypothalamus ARC in the development of depression, and presents it as a potential novel target for depression treatment.

Cognitive effects of early life exposure to PCBs: Sex-specific behavioral, hormonal and neuromolecular mechanisms involving the brain dopamine system.

Endocrine-disrupting chemicals (EDCs) are environmental toxicants that disrupt hormonal and neurodevelopmental processes. Among these chemicals, polychlorinated biphenyls (PCBs) are particularly concerning due to their resistance to biodegradation and tendency to bioaccumulate. PCBs affect neurodevelopmental function and disrupt the brain's dopamine (DA) system, which is crucial for attentional, affective, and reward processing. These disruptions may contribute to the rising prevalence of DA-mediated neuropsychiatric disorders such as ADHD, depression, and substance use disorders. Notably, these behaviors are sexually dimorphic, in part due to differences in sex hormones and their receptors, which are targets of estrogenic PCBs. Therefore, this study determined effects of early life PCB exposure on behaviors and neurochemistry related to potential disruption of dopaminergic signaling. Male and female Sprague Dawley rats were exposed to PCBs or vehicle perinatally and then underwent a series of behavioral tests, including the sucrose preference test to measure affect, conditioned orienting to assess incentive-motivational phenotype, and attentional set-shifting to evaluate cognitive flexibility and response latency. Following these tests, rats were euthanized, and we measured serum estradiol (E2), midbrain DA cells, and gene expression in the midbrain. Female rats exposed perinatally to A1221 exhibited decreased sucrose preference, and both male and female A1221 rats had reduced response latency in the attentional set-shifting task compared to vehicle counterparts. Conditioned orienting, serum estradiol (E2), and midbrain DA cell numbers were not affected in either sex; however, A1221-exposed male rats displayed higher expression of estrogen receptor alpha ( Esr1 ) in the midbrain and non-significant effects on other DA-signaling genes. Additionally, E2 uniquely predicted behavioral outcomes and DAergic cell numbers in A1221-exposed female rats, whereas DA signaling genes were predictive of behavioral outcomes in males. These data highlight sex-specific effects of A1221 on neuromolecular and behavioral phenotypes.

Effects of prenatal cocaine exposure on estrous cycle, and behavior and expression of estrogen receptor alpha and oxytocin during estrus and diestrus in mice offspring.

Increasing evidence indicates that prenatal cocaine exposure may result in many developmental and long-lasting neurological and behavioral effects. The behaviors of female animals are strongly associated with the estrous cycle. Estrogen receptors and oxytocin are important neuroendocrine factors that regulate social behavior and are of special relevance to females. However, whether prenatal cocaine exposure induces estrous cycle changes in offspring and whether neurobehavioral changes in estrus and diestrus offspring differ remains unclear. On gestational day 12, mice were administered cocaine once daily for seven consecutive days, then the estrous cycle was examined in adult female offspring, as well as locomotion, anxiety level, and social behaviors, and the expression of estrogen receptor alpha-immunoreactive and oxytocin-immunoreactive neurons were compared between estrus and diestrus offspring. Prenatal cocaine exposure resulted in the shortening of proestrus and estrus in the offspring. During estrus and diestrus, prenatally cocaine-exposed offspring showed increased anxiety levels and changed partial social behaviors; their motility showed no significant differences in estrus, but declined in diestrus. Prenatal cocaine exposure reduced estrogen receptor alpha-immunoreactive expression in the medial preoptic area, ventromedial hypothalamic nucleus, and arcuate nucleus and oxytocin-immunoreactive expression in the paraventricular nucleus in estrus and diestrus offspring. These results suggest that prenatal cocaine exposure induces changes in the offspring's estrous cycle and expression of estrogen receptor alpha and oxytocin in a brain region-specific manner and that prenatal cocaine exposure and the estrous cycle interactively change motility and partial social behavior. Estrogen receptor alpha and oxytocin signaling are likely to play important concerted roles in mediating the effects of prenatal cocaine exposure on the offspring.

Brain and Serum Membrane Vesicle (Exosome) Profiles in Experimental Alcohol-Related Brain Degeneration: Forging the Path to Non-Invasive Liquid Biopsy Diagnostics

Background: Alcohol-related brain degeneration (ARBD) is associated with cognitive–motor impairments that can progress to disability and dementia. White matter (WM) is prominently targeted in ARBD due to chronic neurotoxic and degenerative effects on oligodendrocytes and myelin. Early detection and monitoring of WM pathology in ARBD could lead to therapeutic interventions. Objective: This study examines the potential utility of a non-invasive strategy for detecting WM ARBD using exosomes isolated from serum. Comparative analyses were made with paired tissue (Tx) and membrane vesicles (MVs) from the temporal lobe (TL). Methods: Long Evans rats were fed for 8 weeks with isocaloric liquid diets containing 37% or 0% caloric ethanol (n = 8/group). TL-Tx, TL-MVs, and serum exosomes (S-EVs) were used to examine ethanol’s effects on oligodendrocyte glycoprotein, astrocyte, and oxidative stress markers. Results: Ethanol significantly decreased the TL-Tx expression of platelet-derived growth factor receptor alpha (PDGFRA), 2′,3′-cyclic nucleotide 3′ phosphodiesterase (CNPase), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), glial fibrillary acidic protein (GFAP), and 8-OHdG, whereas in the TL-MVs, ethanol increased CNPase, PDGFRA, and 8-OHdG, but decreased MOG and GFAP concordantly with TL-Tx. Ethanol modulated the S-EV expression by reducing PLP, nestin, GFAP, and 4-hydroxynonenal (HNE). Conclusion: Chronic ethanol exposures differentially alter the expression of oligodendrocyte/myelin, astrocyte, and oxidative stress markers in the brain, brain MVs, and S-EVs. However, directionally concordant effects across all three compartments were limited. Future studies should advance these efforts by characterizing the relationship between ABRD and molecular pathological changes in brain WM-specific exosomes in serum.

718MO Mirvetuximab soravtansine (MIRV) in recurrent platinum-sensitive ovarian cancer (PSOC) with high folate receptor-alpha (FRα) expression: Results from the PICCOLO trial

718MO Mirvetuximab soravtansine (MIRV) in recurrent platinum-sensitive ovarian cancer (PSOC) with high folate receptor-alpha (FRα) expression: Results from the PICCOLO trial

746P Phase III MIRASOL trial: Updated overall survival results of mirvetuximab soravtansine (MIRV) vs. investigator’s choice chemotherapy (ICC) in patients (pts) with platinum-resistant ovarian cancer (PROC) and high folate receptor-alpha (FRα) expression

746P Phase III MIRASOL trial: Updated overall survival results of mirvetuximab soravtansine (MIRV) vs. investigator’s choice chemotherapy (ICC) in patients (pts) with platinum-resistant ovarian cancer (PROC) and high folate receptor-alpha (FRα) expression

Promoting effect of sunset yellow on N-methyl N-nitrosourea-induced rat mammary carcinogenesis: Implications of molecular mechanisms

BackgroundNowadays, the use of food additives, such as Sunset Yellow (SY), is growing, which attracted attention to the potential relationship between some diseases and food additives. AimThe study aimed to investigate the role of Sunset Yellow during chemically-induced mammary gland carcinogenesis in Sprague–Dawley rats. Material and methodsThree groups of female rats were intraperitoneally administered with N-methyl-N-nitrosourea (MNU). Group 1 was set on a basal diet. Group 2 was treated with 161.4 mg\\kg\\day Sunset Yellow (SY). Group 3 was given SY at 80.7 mg\\kg\\day. Groups 4–6 were not administered MNU; Group 4 received vehicles only. Groups 5 and 6 were administered SY similarly to groups 2 and 3 respectively. ResultsSunset Yellow at both doses exerted a significant dose-dependent increase in tumor incidences, multiplicities, volumes, and decreased tumor latency as compared with control. Immunolabeling indexes of the proliferating cell nuclear antigen, estrogen receptor alpha, and progesterone receptor were significantly increased after SY treatment. Oxidative stress markers, serum estrogen, progesterone, and prolactin levels were significantly modified by SY treatment. The mRNA expression of estrogen receptor alpha and epidermal growth factor was up-regulated in SY groups versus control. ConclusionCollectively, SY has significantly promoted MNU-induced mammary tumors in rats with underlying mechanisms correlating SY consumption with estrogen disruption and subsequent antioxidative stress discrepancy.

Nuciferol C, a new sesquineolignan dimer from Cocos nucifera L.: bioactivity and theoretical investigation.

Nuciferol C (NC), an undescribed dimer of nuciferol B (NB), was isolated from the endocarp of Cocos nucifera L. The planar structure of NC was determined using 1D- and 2D-NMR spectroscopy as well as high resolution MS spectrometry. The absolute configuration was concluded based on analysis of NOESY spectra. NC showed cytotoxic activity against colon cancer cells (CaCo-2) with an IC50 value of 76 μM, and significantly decreased the expression of human epidermal growth factor receptor (EGFR) and tumor necrosis factor alpha (TNF-α) in CaCo-2 as compared with untreated cells by 39% and 33%, respectively (p < 0.05). In addition, NC exhibited anti-herpes simplex virus (HSV-I) activity with an IC50 value of 23 μM. In silico study of NC was implemented at three levels: density functional theory (DFT) was used to study its electronic properties, molecular mechanics was used to estimate the docking results, and finally, molecular dynamic simulation was used to study the behavior and stability of NC inside the active site of the target protein of HSV-1.

Pubertal maternal presence reduces anxiety and increases adult neurogenesis in Kunming mice offspring

Puberty is a critical period of emotional development and neuroplasticity. However, most studies have focused on early development, with limited research on puberty, particularly the parental presence. In this study, four groups were established, and pubertal maternal presence (PMP) was assessed until postnatal days 21 (PD21), 28 (PD28), 35 (PD35), and 42 (PD42), respectively. The social interaction and anxiety behaviors, as well as the expression of oxytocin (OT) in the paraventricular nucleus (PVN) and supraoptic nucleus (SON), and the number of new generated neurons and the expression of estrogen receptor alpha (ERα) in the dentate gyrus (DG) were assessed. The results suggest that there is a lot of physical contact between the mother and offspring from 21 to 42 days of age, which reduces anxiety in both female and male offspring in adulthood; for example, the PMP increased the amount of time mice spent in the center area in the open field experiment and in the bright area in the light-dark box experiment. PMP increased OT expression in the PVN and SON and the number of newly generated neurons in the DG. However, there was a sexual difference in ERα, with ERα increasing in females but decreasing in males. In conclusion, PMP reduces the anxiety of offspring in adulthood, increases OT in the PVN and SON, and adult neurogenesis; ERα in the DG may be involved in this process.

Phaleria macrocarpa Fruit Flavonoid Extract on Estrogen Receptor Alpha Expression in Ovariectomized Mice

Menopause signifies the cessation of ovarian function, presenting significant health challenges for women globally. Hormonal shifts during menopause impact various systems, including cardiovascular and reproductive health. Changes in reproductive organs increase susceptibility to health issues, necessitating effective management strategies. This study used a true experimental method with a randomized post-test-only control group design to investigate the potential of Phaleria macrocarpa fruit extract, which contains flavonoids, to modulate Estrogen Receptor Alpha (ERa) expression in menopausal mice. Following ovariectomy (OVX), mice treated with flavonoid showed increased ERa expression, with the highest expression observed at a dose of P2 (7.5 mg/mice/day), approaching those in non-OVX control (K-) with a percentage difference of 29.82%. Compared to the OVX control group (K+), the percentage increase was 2387.74%. Therefore, the P2 dose is considered the optimum dose. Regression analysis revealed a significant correlation of 43.3% between flavonoid dosage and ERa expression (p &lt; 0.05). These findings suggest flavonoids as promising natural Selective Estrogen Receptor Modulators (SERMs) for managing menopausal symptoms and reducing endometrial disease risk with ERa modulation. Further research is needed to elucidate the mechanisms of flavonoids, including molecular pathways such as ligand binding and transcription, interactions with other hormones like progesterone, long-term effects, and potential clinical applications. To initiate clinical trials, the author established the P1 dose (3.75 mg/mice/day), which demonstrated expression levels approaching the effects produced by P2. Overall, flavonoids offer potential therapeutic benefits in addressing menopausal health concerns, with the identified optimal dosage providing valuable guidance for future studies and clinical interventions.