Estrogenic Properties Research Articles

Long-term 4-nonylphenol exposure drives cervical cell malignancy through MAPK-mediated ferroptosis inhibition

4-NP (4-nonylphenol), a prevalent environmental endocrine disruptor with estrogenic properties, is commonly detected in drinking water and food sources. It poses a significant risk of endocrine disruption, thereby influencing the onset and progression of diverse diseases, including tumorigenesis. However, its specific impact on cervical cancer remains to be fully elucidated. Our study focused on the biological effects of sustained exposure to low-dose 4-NP on human normal cervical epithelial cells (HcerEpic). After a continuous 30-week exposure to 4-NP, the treated cells exhibited a significant malignant transformation, whereas the solvent control group showed limited malignant phenotypes. Subsequent analyses of the metabolomic profiles of the transformed cells unveiled marked irregularities in glutathione metabolism and unsaturated fatty acid metabolism. Analyses of transcriptomic profiles revealed significant activation of the MAPK signaling pathway and suppression of ferroptosis processes in these cells. Furthermore, the expression of MT2A was significantly upregulated following 4-NP exposure. Knockdown of MT2A restored the aberrant activation of the MAPK signaling pathway, elevated antioxidant capacity, ferroptosis inhibition, and ultimately the development of malignant phenotypes that induced by 4-NP in the transformed cells. Mechanistically, MT2A increased cellular antioxidant capabilities and facilitated the removal of toxic iron ions by enhancing the phosphorylation of ERK1/2 and JNK MAPK pathways. The administration of activators and inhibitors of the MAPK pathway confirmed that the MAPK pathway mediated the 4-NP-induced suppression of ferroptosis and, ultimately, the malignant transformation of cervical epithelial cells. Overall, our findings elucidated a dynamic molecular transformation induced by prolonged exposure to 4-NP, and delineated comprehensive biological perspectives underlying 4-NP-induced cervical carcinogenesis. This offers novel theoretical underpinnings for the assessment of the carcinogenic risks associated with 4-NP.

Assessment of estrogenic potential from exudates of microcystin-producing and non-microcystin-producing Microcystis by metabolomics, machine learning and E-screen assay

Cyanobacterial blooms, often dominated by Microcystis aeruginosa, are capable of producing estrogenic effects. It is important to identify specific estrogenic compounds produced by cyanobacteria, though this can prove challenging owing to the complexity of exudate mixtures. In this study, we used untargeted metabolomics to compare components of exudates from microcystin-producing and non-microcystin-producing M. aeruginosa strains that differed with respect to their ability to produce microcystins, and across two growth phases. We identified 416 chemicals and found that the two strains produced similar components, mainly organoheterocyclic compounds (20.2%), organic acids and derivatives (17.3%), phenylpropanoids and polyketides (12.7%), benzenoids (12.0%), lipids and lipid-like molecules (11.5%), and organic oxygen compounds (10.1%). We then predicted estrogenic compounds from this group using random forest machine learning. Six compounds (daidzin, biochanin A, phenylethylamine, rhein, o-Cresol, and arbutin) belonging to phenylpropanoids and polyketides (3), benzenoids (2), and organic oxygen compound (1) were tested and exhibited estrogenic potency based upon the E-screen assay. This study confirmed that both Microcystis strains produce exudates that contain compounds with estrogenic properties, a growing concern in cyanobacteria management.

The Estrogenic Effect of Lysiphyllum strychnifolium (Craib) A. Schmitz Leaf Water Extract in MCF-7 Cells

Lysiphyllum strychnifolium (Craib) A. Schmitz (LS) has been widely used as traditional medicine in the northeast region of Thailand to stimulate the production of breast milk. There are no known studies on the estrogenic action of LS on the stimulation of breast milk production. Hence, the present study aimed to investigate the estrogenic effect of LS leaf water extract compared with quercetin, one of the compounds in LS, in human breast cancer cells (MCF-7). The effect of LS leaf water extract and quercetin on cell viability of MCF-7 cells was studied by MTT assay at a concentration range of 0 to 500 µg/mL. The expression of estrogen-dependent genes, the pS2, ERα, and ERβ was also examined by real-time RT-PCR, and the expression of ERα protein was detected by Western blotting. The quercetin content in the LS water extract was 285.67 ± 0.11 µg/g of dry extract. MCF-7 cells treated with LS leaf water extract (20 µg/mL) showed an upregulation of pS2 gene expression similar to that of the treatment with E2 (10−9 M) compared with that of the untreated control. The ERα gene expression was found to be upregulated by quercetin (0.16 µg/mL) and E2 (10−5 M) compared with the untreated control. In addition, quercetin (0.16 µg/mL) and LS extract (0.8, 4, and 20 µg/mL) decreased the phosphorylation of ERα at Ser167. LS extract (20 µg/mL) decreased ERα, but there was no significant effect on the ERα at Ser118 protein expression. This study provided scientific evidence for the potential estrogenic activities of LS leaf water extract. This indicates that ER-dependent pathways in MCF-7 cells served as mediators, facilitating the estrogenic properties of LS and its compounds to function effectively. Since LS induced pS2 gene transcription, it was confirmed that this could affect the transcription of estrogen-responsive genes, causing estrogenic effects. HIGHLIGHTSThis is the first study to demonstrate the estrogenic effect of Lysiphyllum strychnifolium leaf water extract. L. strychnifolium leaf water extract induced pS2 gene transcription, and it was confirmed that this could affect the transcription of estrogen-responsive genes which cause estrogenic effects. The results of this study support the mechanism and scientific evaluation on the use of L. strychnifolium for stimulation of breast milk in folk medicine. GRAPHICAL ABSTRACT

Qixian granule inhibits ferroptosis in vascular endothelial cells by modulating TRPML1 in the lysosome to prevent postmenopausal atherosclerosis

Ethnopharmacological relevanceQiXian Granule (QXG) is an integrated traditional Chinese medicine formula used to treat postmenopausal atherosclerotic (AS) cardiovascular diseases. The previous studies have found that QXG inhibited isoproterenol (ISO)-induced myocardial remodeling. And its active ingredient, Icraiin, can inhibit ferroptosis by promoting oxidized low-density lipoprotein (xo-LDL)-induced vascular endothelial cell injury and autophagy in atherosclerotic mice. Another active ingredient, Salvianolic Acid B, can suppress ferroptosis and apoptosis during myocardial ischemia/reperfusion injury by reducing ubiquitin-proteasome degradation of Glutathione Peroxidase 4 (GPX4) and down-regulating the reactive oxygen species (ROS)- c-Jun N-terminal kinases (JNK)/mitogen-activated protein kinase (MAPK) pathway. Aim of the studyThe objective of this research was to assess the possible impact of QXG on atherosclerosis in postmenopausal individuals and investigate its underlying mechanisms. Materials and methodsFemale ApoE−/− mice underwent ovariectomy and were subjected to a high-fat diet (HFD) to establish a postmenopausal atherosclerosis model. The therapeutic effects of QXG were observed in vivo and in vitro through intraperitoneal injection of erastin, G-protein Coupled Estrogen Receptor (GPER) inhibitor (G15), and silent Mucolipin Transient Receptor Potential Channel 1 (TRPML1) adenovirus injection via tail vein. UPLC-MS and molecular docking techniques identified and evaluated major QXG components, contributing to the investigation of QXG's anti-postmenopausal atherosclerotic effects. ResultsQXG increased serum Estradiol levels, decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, which indicated QXG had estrogen-like effects in Ovx/ApoE−/− mice. Furthermore, QXG demonstrated the potential to impede the progression of AS in Ovx/ApoE−/− mice, as evidenced by reductions in serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels. Additionally, QXG inhibited ferroptosis in Ovx/ApoE−/− mice. Notably, UPLC-MS analysis identified a total of 106 active components in QXG. The results of molecular docking analysis demonstrated that Epmedin B, Astragaloside II, and Orientin exhibit strong binding affinity towards TRPML1. QXG alleviates the progression of atherosclerosis by activating TRPML1 through the GPER pathway or directly activating TRPML1, thereby inhibiting GPX4 and ferritin heavy chain (FTH1)-mediated iron pendant disease. In vitro, QXG-treated serum suppressed proliferation, migration, and ox-LDL-induced MMP and ROS elevation in HAECs. ConclusionQXG inhibited GPX4 and FTH1-mediated ferroptosis in vascular endothelial cells through up-regulating GPER/TRPML1 signaling, providing a potential therapeutic option for postmenopausal females seeking a safe and effective medication to prevent atherosclerosis. The study highlights QXG's estrogenic properties and its promising role in combating postmenopausal atherosclerosis.

Abstract 3171: The effect of estrogen and phytoestrogens in Inflammatory breast cancer

Abstract Inflammatory breast cancer is an aggressive and lethal type of breast cancer. Frequently, this cancer is diagnosed in an advanced stage with metastasis. IBC diagnosis is associated with a worse survival rate than other types of breast cancer. The presence of dermal and stromal tumor emboli blocking the lymphatic vessels under the skin is considered a hallmark of IBC and assumed to be responsible for the high metastatic behavior and aggressiveness of IBC disease. To this date, there are no effective targeted therapeutics, especially for those patients that account for approximately 20-40% of IBC cases with triple-negative breast cancer (TNBC) classification. Several studies have shown that estrogen can exert non-genomic effects in IBC and non-IBC TNBC, mediated by the expression of alternate estrogen receptors including estrogen receptor alpha-36, and GPR30. In this context, estrogen can activate non-genomic signaling pathways involved in the acquisition of oncogenic phenotypes such as increased motility and invasion in IBC cells. Phytoestrogens, naturally derived structural analogs to 17β-estradiol (E2), were evaluated as an alternative treatment option using in vitro IBC cell models (SUM149 and SUM190). Given the estrogenic properties of phytoestrogens, the drugs were hypothesized to interact with targets in pathways similar to E2 in non-genomic signaling. Several phytoestrogens including coumestrol (Cou) can induce a cytotoxic effect in TNBC. We hypothesize (1) that estrogen non-genomic signaling has an active role in the aggressive metastatic phenotype of IBC, and (2) that Cou has anticancer activity by inhibiting estrogen non-genomic signaling in IBC. To test these hypotheses, IBC cells were treated with E2 or Cou to determine their effects on the activation of downstream kinases by western blot and phospho-kinase array assays. In addition, transcriptional effects upon treatment with Cou were identified using RNA-seq. A dose-response curve in 2D and 3D models was generated to determine the half-maximal inhibitory concentration (IC50) of Cou. Finally, treatment using the IC50 of Cou caused a decrease in cell viability in the TNBC cell line. Also, in comparison to E2, Cou decreases migration, proliferation, and tumor emboli formation in IBC cell lines. In addition, IBC cells were treated using monotherapy and combination therapy with phytoestrogens including Cou, genistein (GN), and/or 8-prenylnaringenin (8-PN). Observed reductions of cell viability in IBC cell lines treated with the different phytoestrogens and combinations make them worthy of further characterization as anti-cancer therapies in in vitro and in vivo models. In summary, IBC cells are responsive to E2 making this signaling pathway attractive for the development of innovative therapeutic strategies with phytoestrogens as potential candidates for treatment. Citation Format: Esther A. Peterson-Peguero, Keishla Rodriguez-Martir, Madeline Ganshert, Dalissa Negron-Figueroa, Ayeisha N. Colon-Ortiz. The effect of estrogen and phytoestrogens in Inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3171.

Alleviative Effect of Rutin on Zearalenone-Induced Reproductive Toxicity in Male Mice by Preventing Spermatogenic Cell Apoptosis and Modulating Gene Expression in the Hypothalamic-Pituitary-Gonadal Axis.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin found in many agricultural products and can cause reproductive disorders, mainly affecting spermatogenesis in male animals. Rutin (RUT) is a natural flavonoid compound recognized for its significant antioxidant, anti-inflammatory and estrogenic properties. The present study aimed to determine the protective role of RUT against ZEN-induced reproductive toxicity in male mice. Twenty-four adult Kunming male mice were divided into four groups: control, RUT (500 mg/kg RUT), ZEN (10 mg/kg ZEN), ZEN + RUT (500 mg/kg RUT + 10 mg/kg ZEN), with six replicates per treatment. The results indicated that RUT mitigated ZEN-induced disruption in spermatogenic cell arrangement, decreased spermatozoa count, and increased sperm mortality in the testes. RUT significantly restored ZEN-induced reduction in T, FSH, LH, and E2 serum levels. Moreover, RUT mitigated ZEN-induced apoptosis by increasing the mRNA expression level of bcl-2, decreasing the mRNA expression level of kiss1-r, and decreasing the protein expression level of caspase 8 in reproductive tissues. These findings indicate the protective role of RUT against ZEN-induced reproductive toxicity in male mice by regulating gonadotropin and testosterone secretions to maintain normal spermatogenesis via the HPG axis, which may provide a new application direction for RUT as a therapeutic agent to mitigate ZEN-induced reproductive toxicity.

Effect of Tempeh and Daidzein on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in Ovariectomized Rats.

Menopause marks a critical life stage characterized by hormonal changes that significantly impact bone health, leading to a heightened susceptibility to bone fractures. This research seeks to elucidate the impact of daidzein and tempeh on calcium status, calcium transporters, and bone metabolism in an ovariectomized rat model. Forty female Wistar rats, aged 3 months, participated in a two-phase experiment. The initial phase involved inducing a calcium deficit, while the second phase comprised dietary interventions across five groups: Sham (S) and Ovariectomy (O) with a standard diet, O with bisphosphonate (OB), O with pure daidzein (OD), and O with tempeh (OT). Multiple parameters, encompassing calcium levels, calcium transporters, bone histopathology, and serum bone metabolism markers, were evaluated. The findings revealed that the OT group showcased heightened levels of bone turnover markers, such as pyridinoline, C-telopeptide of type I collagen, bone alkaline phosphatase, and procollagen type I N-terminal propeptide, in contrast to S and O groups, with statistical significance (p < 0.05). Histopathologically, both the OD and OT groups exhibited effects akin to the OB group, indicating a decrease in the surface area occupied by adipocytes in the femoral bone structure, although statistically non-equivalent, supporting the directionally similar trends. Although TRPV5 and TRPV6 mRNA expression levels in the jejunum and duodenum did not display statistically significant differences (p > 0.05), the OD and OT groups exhibited increased expression compared to the O group. We hypothesized that obtained results may be related to the effect of isoflavones on estrogen pathways because of their structurally similar to endogenous estrogen and weak estrogenic properties. In conclusion, the daily consumption of pure daidzein and tempeh could potentially improve and reinstate calcium status, calcium transport, and bone metabolism in ovariectomized rats. Additionally, isoflavone products demonstrate effects similar to bisphosphonate drugs on these parameters in ovariectomized rats.

Role of Topical Estrogen in Outcomes of Myringoplasty: Does it Really Affect the Results of Graft Success and Hearing Thresholds?

The tympanic membrane forms a barrier between the external auditory canal and the middle ear. In the inactive mucosal type of chronic otitis media, there is a perforation in the tympanic membrane which is surgically managed by Myringoplasty. Estrogen as a growth factor has been shown to have a mitogenic effect on keratinocytes thus hastening the rate of epithelialization following injury. This property of estrogen is being studied in this study for its role in the outcomes of myringoplasty. This study was carried out from January 2021 to December 2022 in the Department of Otorhinolaryngology, of a tertiary teaching hospital in North India. Patients were assessed by history, examination, otoscopy, Audiometry, and oto-endoscopy. A total of 88 patients were taken out of which 44 patients underwent myringoplasty in which topical estrogen (estradiol valerate solution) was used, and the remaining 44 patients were taken as controls. Patients were then assessed post-operatively based on Audiometry results and graft uptake status. In the estrogen group successful Graft uptake was in seen 40 (90.9%) patients and failed in 4 (9.1%), while in the control group, it was successful in 37 (84.1%) patients and failed in 7 (15.9%), statistically there was no significant difference between two groups in terms of graft uptake (p value = 0.334). Post-operatively, in the estrogen group, the mean change in Air Conduction (AC) was 15.5dB, the change in the air-bone gap (ABG) was 11.5dB and for Bone Conduction (BC) it was 3.2dB. However, in the control group mean post-operative changes in Air Conduction, Air-Bone Gap, and Bone Conduction were 12dB, 10.7dB, and 0.8dBrespectively. Statistically, there was a significant difference in postoperative changes in AC (p value = 0.011) and BC (p value = 0.009) between the two groups. There was no significant difference in post-operative changes in Air-Bone Gap (p value = 0.571). Topical Estrogen (Estradiol valerate) solution is cost-effective, with enriched growth factors that accelerate tympanic membrane perforation closure following myringoplasty and resulted in significant improvement in hearing thresholds both for Air Conduction and Bone Conduction.

Abstract TP287: Estrous Cycle Stages and Cerebral Blood Flow: Implications for Ischemic Tolerance in Stroke

Introduction: Previous stroke studies in female rodents have demonstrated that the severity of ischemic damage is differentially impacted by the estrous cycle. Estrogen is considered to be neuroprotective, but it is unclear whether this protection is dependent on the vasodilator properties of estrogen. In this study, we investigated the impact of estrus cycle stage on stroke lesion volume and whether that impact was dependent on cerebral blood flow (CBF) changes during stroke. Methods: Ischemia was induced in adult ( 10 weeks) male and female Sprague-Dawley rats by 30 minutes middle cerebral artery occlusion (MCAO) using the suture model. Prior to the stroke procedure, the phases of the estrous cycle (proestrus(P), estrus(E), metestrus(M) and diestrus (D)) were determined by vaginal smear tests in female rats. Cerebral blood flow (CBF) was measured by laser doppler and infarct volume were measured by TTC staining at d2 post-stroke. Results: Females in proestrus and diestrus (P/D) stages of the estrous cycle, which have reportedly high levels of estrogen, had significantly (p&lt;0.05) smaller CBF decreases during ischemia and a trend for smaller infarcts than those in estrous and metestrus stages, which have lower estrogen levels. This suggests that the protective effects of estrogen may be related to effects on blood flow. However, when compared to male rats, females in P/D stages had significantly (p&lt;0.05) smaller brain infarcts despite having similar CBF decreases. This implies that additional mechanisms are responsible for the neuroprotection observed in females when compared to males. Conclusion: Estrous cycle stage affects CBF decrease during ischemia, but this does not account for the difference in infarct size observed between male and female rats. Our study indicates that multiple mechanisms are responsible for ischemic tolerance in specific stages of the estrous cycle. Keywords: stroke, estrous cycle, CBF, estrogen

Levels, distribution, sources and human exposure pathways of alkylphenol and alkylphenol ethoxylates in indoor dust in Turkiye

Environmental phenolic chemicals, due to their widespread occurrence and potent estrogenic properties, pose a risk to human exposure. The phenolic organic contaminants alkylphenols (APs) and alkylphenol polyethoxylates (APEs) are used in various household applications, and they may enter to the environment during production and use, potentially appearing in indoor dust. However, little is known about the levels of environmental phenolics in indoor environments. In this study, five of these compounds namely octylphenol (OP), 4-Octylphenol Monoethoxylate (4-OPME), 4-tert-octylphenol (4-t-OP), 4-n-nonylphenol (4-n-NP) and nonylphenol diethoxylate (di-NPE) were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in household dust samples (n = 148) collected from Ankara, the capital of Turkiye. OP and 4-OPME was not present in any of the analyzed samples. The median concentrations of the 148 settling dust samples were 35, 520, and 1910 ng g−1 dust for 4-t-OP, 4-n-NP, and di-NPE, respectively. An assessment of the human (children and adults) exposure pathway to APs and APEs, which are recognized as endocrine-disrupting chemicals found in residential dust, revealed that it was approximately 3 times higher for children than for adults at both moderate and heavy exposure levels. The association between chemical exposure, house characteristics, and family lifestyle was investigated using a multivariate logistic regression model. According to the results of this model, while the high concentrations measured for 4-t-OP were not found to be associated with any of the household parameters, high levels of 4-n-NP and di-NPE were associated with the frequency of house cleaning, repairs made during the previous year, residential type, the number of occupants, flooring materials, and the purchase of new household items within the past year. This study provides a basis for prioritizing toxicology and exposure studies for EDCs and mixtures and may offer new tools for exposure assessment in health studies.

An extensive review on phenolic compounds and their potential estrogenic properties on skin physiology.

Polyphenolic compounds constitute a diverse group of natural components commonly occurring in various plant species, known for their potential to exert both beneficial and detrimental effects. Additionally, these polyphenols have also been implicated as endocrine-disrupting (ED) chemicals, raising concerns about their widespread use in the cosmetics industry. In this comprehensive review, we focus on the body of literature pertaining to the estrogenic properties of ED chemicals, with a particular emphasis on the interaction of isoflavones with estrogen receptors. Within this review, we aim to elucidate the multifaceted roles and effects of polyphenols on the skin, exploring their potential benefits as well as their capacity to act as ED agents. By delving into this intricate subject matter, we intend to provoke thoughtful consideration, effectively opening a Pandora's box of questions for the reader to ponder. Ultimately, we invite the reader to contemplate whether polyphenols should be regarded as friends or foes in the realm of skincare and endocrine disruption.

Dose addition in mixtures of compounds with dissimilar endocrine modes of action in in vitro receptor activation assays and the zebrafish sexual development test

BackgroundHuman exposure to pesticides is being associated with feminisation for which a decrease of the anogenital distance (AGD) is a sensitive endpoint. Dose addition for the cumulative risk assessment of pesticides in food is considered sufficiently conservative for combinations of compounds with both similar and dissimilar modes of action (MoA). ObjectiveThe present study was designed to test the dose addition hypothesis in a binary mixture of endocrine active compounds with a dissimilar mode of action for the endpoint feminisation. MethodsCompounds were selected from a list of chemicals of which exposure is related to a decrease of the AGD in rats and completed with reference compounds. These chemicals were characterised using specific in vitro transcriptional activation (TA) assays for estrogenic and androgenic properties, leading to a final selection of dienestrol as an ER-agonist and flutamide, linuron, and deltamethrin as AR-antagonists. These compounds were then tested in an in vivo model, i.e. in zebrafish (Danio rerio), using sex ratio in the population as an endpoint in order to confirm their feminising effect and MoA. Ultimately, the fish model was used to test a binary mixture of flutamide and dienestrol. ResultsStatistical analysis of the binary mixture of flutamide and dienestrol in the fish sexual development tests (FSDT) with zebrafish supported dose addition.

Anticonvulsant effect of glycitin in pentylenetetrazol induced male Wistar rat model by targeting oxidative stress and Nrf2/HO-1 signaling.

Epilepsy, characterized by recurrent seizures, poses a significant health challenge globally. Despite the availability of anti-seizure medications, their adverse effects and inadequate efficacy in controlling seizures propel the exploration of alternative therapeutic measures. In hypothesis, glycitin is a phytoestrogenic compound found in soybeans and due to its estrogenic properties may have anti-epileptic and neuroprotective effects. This study investigates the potential anti-epileptic properties of glycitin in the context of pentylenetetrazol (PTZ) induced seizures in male Wistar rats. The rats were pretreated with varying doses of glycitin (5, 10, and 20mg/kg) before PTZ (35mg/kg) administration, and assessments included behavioral observations and histological evaluation via hematoxylin and eosin (H&E) staining. Additionally, oxidative stress markers, such as malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels, were quantified to examine glycitin's impact on oxidative stress. Molecular analysis was conducted to assess the activation of the Nuclear factor erythroid 2-related factor (Nrf2)/Heme oxygenase 1 (HO-1) signaling pathway. Results indicated that glycitin pretreatment effectively mitigated PTZ-induced convulsive behaviors, supported by histological findings from H&E staining. Furthermore, glycitin administration led to significant alterations in MDA, GPx, and SOD levels, suggestive of its ability to modulate oxidative stress. Notably, glycitin treatment induced activation of the Nrf2/HO-1 signaling pathway. These findings underscore the potential of glycitin as an anticonvulsant agent, elucidating its mechanism of action through histological protection, modulation of oxidative stress markers, and activation of the Nrf2/HO-1 signaling pathway.

A Review of the Role of Estrogens in Olfaction, Sleep and Glymphatic Functionality in Relation to Sex Disparity in Alzheimer's Disease.

Several risk factors contribute to the development of Alzheimer's disease (AD), including genetics, metabolic health, cardiovascular history, and diet. It has been observed that women appear to face a higher risk of developing AD. Among the various hypotheses surrounding the gender disparity in AD, one pertains to the potential neuroprotective properties of estrogen. Compared to men, women are believed to be more susceptible to neuropathology due to the significant decline in circulating estrogen levels following menopause. Studies have shown, however, that estrogen replacement therapies in post-menopausal women do not consistently reduce the risk of AD. While menopause and estrogen levels are potential factors in the elevated incidence rates of AD among women, this review highlights the possible roles estrogen has in other pathways that may also contribute to the sex disparity observed in AD such as olfaction, sleep, and glymphatic functionality.

Deciphering the synergistic effects of photolysis and biofiltration to actuate elimination of estrogens in natural water matrix

The presence of estrogens in water environments has raised concerns for human health and ecosystems balance. These substances possess potent estrogenic properties, causing severe disruptions in endocrine systems and leading to reproductive and developmental problems. Unfortunately, conventional treatment methods struggle to effectively remove estrogens and mitigate their effects, necessitating technological innovation. This study investigates the effectiveness of a novel sequential photolysis-granular activated carbon (GAC) sandwich biofiltration (GSBF) system in removing estrogens (E1, E2, E3, and EE2) and improving general water quality parameters. The results indicate that combining photolysis pre-treatment with GSBF consistently achieved satisfactory performance in terms of turbidity, dissolved organic carbon (DOC), UV254, and microbial reduction, with over 77.5 %, 80.2 %, 89.7 %, and 92 % reduction, respectively. Furthermore, this approach effectively controlled the growth of microbial biomass under UV irradiation, preventing excessive head loss. To assess estrogen removal, liquid chromatography-tandem mass spectrometry (LC-MS) measured their concentrations, while bioassays determined estrogenicity. The findings demonstrate that GSBF systems, with and without photolysis installation, achieved over 96.2 % removal for estrogens when the spike concentration of each targeted compound was 10 µg L−1, successfully reducing estrogenicity (EA/EA0) to levels below 0.05. Additionally, the study evaluated the impact of different thicknesses of GAC layer filling (8 cm, 16 cm, and 24 cm) and found no significant difference (p>0.05) in estrogen and estrogenicity removal among them.

Dioscorea alata L. Tubers Ethanol Extract Improves Insulin Resistance and Estrogen Defectively in Type 2 Diabetic Ovariectomized Rats

Dioscorea alata L., commonly known as water yam, has attracted the attention of scientific researchers for its potential anti-diabetic and estrogenic properties. However, the existing literature lacks specific studies on the anti-diabetic and estrogenic effects of D. alata in the context of type 2 diabetic ovariectomized rats. Thus, Our research focuses on investigating the influence of D. alata on the antidiabetic and estrogenic properties in rats. These rats have developed diabetes through a high-fat diet and streptozotocin induction and have also undergone ovariectomy, making them type 2 diabetic ovariectomized rats (T2DM OVX). This comprehensive study both in vitro and in vivo methodologies. We conducted a phytochemical analysis, revealing the presence of key bioactive constituents, including flavonoids, alkaloids, terpenoids, tannins, saponins, cardiac glycosides, and steroids. The results of our phytochemical screening confirm the remarkable antidiabetic properties of the D. alata extract, as it effectively inhibits α-glucosidase activity, leading to a significant reduction in fasting blood glucose levels. Additionally, it enhances body weight, serum insulin levels, and pancreatic islet size. The extract also demonstrates notable estrogenic effects by significantly increasing uterine wet weight, endometrial and myometrium thickness, bone calcium, and overall bone density, while reducing bone porosity in the T2DM OVX rats. It is important to note that while the D. alata extract exhibits slightly less potent α-glucosidase inhibition compared to acarbose, it showcases potent antidiabetic activity at a dose of 1,000 mg/kg body weight, comparable to Metformin (250 mg/kg body weight). In terms of estrogenic activity, it is slightly less potent than 17β-estradiol (1 mg/kg body weight). These findings provide robust evidence supporting the traditional use of D. alata and its efficacy in the context of antidiabetic and estrogenic properties within the T2DM OVX model.

Assessment of alkylphenols migration from packaging to fruit juices: Influential factors and health risks

Migration of plastic components or additives from packaging materials to food poses a potential health risk to humans. Alkylphenols, including 4-Nonylphenol and 4-tert-Octylphenol, are classified among the endocrine disrupting chemicals which exhibit estrogenic properties. One of the predominant pathways of human exposure to Alkylphenols primarily involves the ingestion of food and beverages, which have contaminated to Alkylphenols through leaching from the packaging materials. The objective of this study was to examine the presence of 4-Nonylphenol and 4-tert-Octylphenol compounds in various juice samples packed in Polyethylene terephthalate bottles and multilayer Tetrapack containers. Additionally, an evaluation was conducted regarding the influence of the expiration period and the two flavor of fruit juice (sour cherry and pineapple) on the leakage rate of alkylphenols. Health risk from exposure to alkylphenols through drinking packaged fruit juices was also estimated. 4-Nonylphenol and 4-tert-Octylphenol were detected in 100% of the samples at concentrations from 158.8 ng/L to 7604.2 ng/L and from 4.1 ng/L to 1373.8 ng/L, respectively. The results showed that over time, the concentration of contaminants in packaged fruit juices significantly increased. Fruit juices with a sour flavor, with a more acidic pH, typically tend to have a higher concentration of contaminants. Furthermore, the average concentration for both flavors was higher in polyethylene terephthalate packaging compared to Tetrapack. The risk assessment revealed that the group of children under 18 years of age is at a higher risk of health issues compared to the adult group due to exposure to alkylphenols found in packaged fruit juices.

Ganoderma lucidum, a Potential Revolutionary Macro Fungus in the Field of Medicine

Abstract:: Ganoderma lucidum is a traditional Asian medication used in China, Korea, and Japan. It is a well-known medicinal fungus that is regarded as the elixir of life. Polysaccharides, proteins, enzymes, sterols, fatty acids, vitamins, minerals, and peptides are some of the 400 physiologically active substances. Anti-inflammatory, anti-ulcer, anti-diabetic, antiandrogenic, anti-aging, anti-fibrotic, antioxidant, hepatoprotective, sleep-promoting, anticarcinogenic, chemo and radioprotective, immunomodulation, estrogenic, and antibacterial properties are just a few of the numerous reported pharmacological effects. This review will help us to examine the role that this macro fungus holds in various therapeutic applications and how it can be a significant influence in the field of medicine.

Estrogenic activity of Bryonia dioica Jacq. through in silico and in vitro studies on pS2 gene expression in the breast cancer cell line MCF-7

Bryonia dioica is a member of the Cucurbitaceae that produces bioactive secondary metabolites (PSM), especially steroidal cucurbitacins. Tubers accumulate cucurbitacins, tetrahydrocucurbitacins, bryonioside, and polyphenols such as kaempferol and isovitexin. Through in vitro and simulation studies, this study explores the potential estrogenic and antiestrogenic properties of Bryonia dioica. In silico study was performed by molecular docking simulation to predict the binding affinity of BryoniaPSM in Estrogen Receptor Alpha using Molegro Virtual Docker ver 6.0. The in vitro investigation of a methanolic tuber extract used MCF-7 cells, a breast cancer cell line with estrogen receptor (ER), in a medium with or without estradiol. We also analyzed the effect of the extract on the expression of the estrogen-dependent pS2 gene using real-time polymerase chain reaction (RT-PCR). Molecular docking showed that Cucurbitacin-E exhibited the best binding affinity to the estrogen receptor with binding sites at His 524, Gly 521, Arg 394, Glu 353, and Leu 391. Methanolic extract of Bryonia dioica exhibited cytotoxic activity in MCF-7 cells with IC50 = 185 µg/mL (in medium without E2) and IC50 = 125 µg/mL (in medium with E2). In media with and without estrogen, it can stimulate the expression of the pS2 gene at a concentration of 50 µg/mL, a marker for estrogenic activity. The results suggest that Bryonia dioica contains phytoestrogenic PSM with ER agonistic and cytotoxic activities.

Association Between Urinary Bisphenols and Body Composition Among American Adults: Cross-Sectional National Health and Nutrition Examination Survey Study.

Bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) are widely used in various consumer products. They are environmental contaminants with estrogenic properties that have been linked to various health outcomes. Understanding their impact on body composition is crucial for identifying potential health risks and developing preventive strategies. However, most current studies have only focused on their relationship with BMI. This study aimed to investigate the association between urinary levels of BPA, BPS, and BPF and body composition, including BMI, lean mass, and fat mass, in a large population-based sample. We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey 2003-2016. Body composition data were assessed using dual-energy X-ray absorptiometry, which provided precise measurements of lean mass, fat mass, and other indicators. We used multivariate linear regression models to estimate the associations, adjusting for potential confounders such as age, gender, race, socioeconomic factors, and lifestyle variables. The results revealed significant associations between bisphenol exposure and body composition. After adjusting for covariates, BPS showed a positive association with BMI, with quartiles 3 and 4 having 0.91 (95% CI 0.34-1.48) and 1.15 (95% CI 0.55-1.74) higher BMI, respectively, compared with quartile 1 (P<.001). BPA was negatively associated with total lean mass (TLM) and appendicular lean mass, with quartiles 2, 3, and 4 having -7.85 (95% CI -11.44 to -4.25), -12.33 (95% CI -16.12 to -8.54), and -11.08 (95% CI -15.16 to -7.01) lower TLM, respectively, compared with quartile 1 (P<.001). BPS was negatively associated with TLM, with quartiles 3 (β=-10.53, 95% CI -16.98 to -4.08) and 4 (β=-11.14, 95% CI -17.83 to -4.45) having significantly lower TLM (P=.005). Both BPA and BPS showed a positive dose-response relationship with trunk fat (BPA: P=.002; BPS: P<.001) and total fat (BPA: P<.001; BPS: P=.01). No significant association was found between BPF and any body composition parameter. This large-sample study highlights the associations between urinary levels of BPA and BPS and alterations in body composition, including changes in lean mass, fat mass, and regional fat distribution. These findings underscore the importance of understanding the potential health risks associated with bisphenol exposure and emphasize the need for targeted interventions to mitigate adverse effects on body composition.