Polyphenols represent the largest and most diverse class of dietary antioxidants. Epidemiological evidence linking specific (poly)phenol classes, such as flavonoids and lignans, to breast cancer (BC) risk remains limited and largely inconclusive in prospective studies. The aim of this study is to examine the association between the intake of total (poly)phenols—and its classes and subclasses—and BC risk—overall and by subtypes (estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2))—in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The EPIC cohort includes 257,960 adult women from seven European countries. During a mean follow-up of 14 years, there were 10,722 incident overall BC cases. Associations were computed using Cox regression models adjusted for potential confounders. No significant associations were found between total (poly)phenol intake and overall BC risk (HRQ5 vs. Q1 = 1.02; 95% CI: 0.95–1.11). In addition, null associations were mostly found between classes and subclasses of (poly)phenols and BC subtypes. After stratifying by menopausal status, no significant associations were observed. In conclusion, this study found no evidence of associations between the intake of any class or subclass of (poly)phenols and BC risk in the European population.

Effects of bisphenol A and bisphenol S on human fallopian tube contractions: An in vitro and in silico study.

An environmentally relevant phthalate mixture impairs ovulatory prostaglandin and progesterone receptor pathways in human granulosa cells in vitro.

Accurate protein recognition is crucial for early disease diagnosis and biomarker screening. Progesterone receptor membrane component-1 (PGRMC1) is a promising cancer biomarker, yet its sensitive and selective detection in complex biological samples remains challenging. Here, a molecularly programmable multichannel fluorescence sensor array was constructed by employing three chemically distinct carbon dots (CDs), synthesized from Congo red coupled with ascorbic acid, citric acid, and glutathione, as parallel sensing units to generate multiple fluorescence response channels. This precursor-engineering strategy enabled the precise modulation of surface functional groups, redox properties, and protein-interaction behaviors, offering a novel route to tailor CDs for specific sensing targets. The resulting CDs functioned as complementary fluorescent sensing units, collectively forming a cross-reactive array capable of 100% accurate discrimination of 11 proteins in both buffer and whole blood samples. For the clinically relevant biomarker PGRMC1, the array displayed a broad linear response (0.010-1.000 ng/mL) and an ultralow limit of detection of 0.013 ng/mL (95% confidence interval from 0.004 to 0.021 ng/mL). More importantly, the analysis of 64 blinded clinical blood samples achieved robust differentiation between breast cancer patients and healthy individuals, demonstrating its translational potential for early cancer diagnosis. Fluorescence lifetime analysis combined with density functional theory calculations elucidated the underlying mechanism of interaction between the CDs and proteins, highlighting the contribution of precursor-dependent surface states. This study introduces a new design paradigm for CD-based fluorescent arrays and showcases their strong promise for complex biological analysis, precision biomarker detection, and clinical diagnostics.

Endometriomsis (EMs) is a complex and chronic gynecological disease characterized by distressing symptoms. Its pathogenesis remains unknown, and there is no effective treatment. Therefore, establishing patient-derived models is crucial for elucidating disease mechanisms and identifying potential therapeutic agents. We developed a coculture system combining epithelial organoids and stromal cells, enabling the study of their dynamic interactions. Using this model, we assessed the therapeutic efficacy of dienogest, a drug clinically used for treating endometriomas. The epithelial gland-like organoids and stromal cells derived from patients with endometriomas were isolated and cultured, respectively. Both of them were cocultured in matrix for partially mimicking invivo pathological features. Immunohistochemical (IHC) assay was used to identify their biomarkers. Cell viability was quantitatively assessed using the CellTiter-Glo® assay following drug treatment. We successfully cultured patient-derived epithelial gland-like organoids and stromal cells derived from patients with endometriomas, a form of endometriosis characterized by ovarian cysts. Morphological and immunohistochemical analyses confirmed high consistency with native endometriotic lesions. These models exhibited comparable expression profiles for key biological markers, including estrogen receptors (ERs), progesterone receptors (PRs), E-cadherin, CD44, Intercellular Adhesion Molecule-1 (ICAM1), Integrin Beta 3 (ITGB3), Cytokeratin 7 (CK7), Matrix Metalloproteinase 2/9 (MMP2/9), Tissue Inhibitor of Metalloproteinases 1 (TIMP1), and TIMP2. Notably, drug responsiveness varied among the patient-derived models by coculturing two types of cells, indicating potential interpatient heterogeneity in treatment outcomes. We propose that this patient-specific endometriomas model serves as a valuable platform for investigating disease mechanisms and screening drug in endometriomas. We established a novel coculture system integrating epithelial organoids and stromal cells to recapitulate the intricate cellular interactions within the endometriotic microenvironment, providing a more relevant invitro representation of the disease. Upon evaluation with dienogest, a clinically used therapeutic agent for endometriomas, the patient-derived models exhibited heterogeneous drug responses.

Previous studies have evaluated the utility of estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry (IHC) in differentiating uterine versus extrauterine leiomyosarcomas (LMS). At best, these studies have shown only modest sensitivity and specificity for these markers in this context. In our own practice, we have noticed that retroperitoneal LMS, such as those arising in the wall of the inferior vena cava, frequently exhibit a remarkable resemblance not to uterine LMS, but rather to uterine leiomyomas (LM) with bizarre nuclei, formerly known as symplastic LM. This includes areas with bland nuclear cytology, punctuated by the presence of cells with large bizarre nuclei but a paradoxically low mitotic index. We refer to these areas in retroperitoneal LMS as "symplastic-like." It has been our experience that these "symplastic-like" areas are frequently the predominant or exclusive component in small core biopsies of retroperitoneal LMS, even when the resection of these tumors reveals the presence of more conventional high-grade LMS morphology. In female patients, symplastic-like morphology in a smooth muscle tumor at an intra-abdominal site raises the possibility of iatrogenic dissemination of a uterine LM with bizarre nuclei from a prior myomectomy or morcellation procedure. We hypothesized that negative staining for ER and PR by IHC could effectively exclude a uterine origin, given the high sensitivity of these markers for all variants of uterine LM. After successfully using ER and PR IHC in our clinical practice on a few index cases, we decided to study a larger cohort of carefully selected cases to systematically determine the sensitivity and specificity of these markers in this very specific context. Confining our search to include only female patients, we identified 8 cases of retroperitoneal LMS that had been confirmed radiologically, intraoperatively and/or histologically to originate from a retroperitoneal source and 6 cases of uterine-based LM with bizarre nuclei, all diagnosed at our institution over an 8-year period. We tested only whole slides for ER and PR IHC. ER and PR were both completely negative in all 8 cases of retroperitoneal LMS and were both strongly expressed in all 6 cases of LM with bizarre nuclei. In conclusion, despite conflicting data in the literature regarding the utility of ER and PR in distinguishing uterine versus extrauterine smooth muscle tumors, we endorse the use of these markers for the specific distinction of retroperitoneal LMS with symplastic-like features from disseminated uterine LM with bizarre nuclei in female patients.

Targeted biologics for TNBC: Advances in nanobodies, antibodies, peptides, and aptamers.

Apocrine carcinoma (AC) is a rare and distinct subtype of invasive breast carcinoma, typically characterized by androgen receptor (AR) positivity and negative expression of oestrogen and progesterone receptors. This study aimed to clarify the metabolic and molecular characteristics of AC, with a particular focus on protein expression related to lipid metabolism and the frequency and nature of PIK3CA mutations. We analysed tissue specimens from 40 cases with AC and 59 cases with other breast cancer subtypes (ER+/HER2-, ER+/HER2+, ER-/HER2+ and triple-negative breast cancer [TNBC]). Immunohistochemistry was performed for a panel of lipid metabolism-related proteins including FASN, AMACR, ACOX1, ACSL1 and catalase. mRNA Expression of ACSL1 was assessed by RT-qPCR and PIK3CA mutations were analysed via targeted sequencing. AC showed significantly higher expression of enzymes involved in fatty acid synthesis and peroxisomal β-oxidation compared to other subtypes. Notably, ACSL1 was upregulated at both protein and mRNA levels, and catalase was upregulated at the protein level, indicating an increase in peroxisomes. PIK3CA Mutations, particularly the hotspot p.H1047R variant, were detected at a significantly higher frequency in AC (68.4%) compared to the other subtypes: ER+/HER2- (52.6%), ER+/HER2+ (27.3%), ER-/HER2+ (50.0%) and TNBC (33.3%) (P < 0.05). AC is characterized by distinct metabolic reprogramming, with preferential upregulation of peroxisomal β-oxidation rather than mitochondrial pathways. These metabolic features are accompanied by a high prevalence of activating PIK3CA mutations, suggesting a link between genomic alterations and metabolic phenotype. These findings provide new insights into the pathobiology of AC and may assist in its histopathological differentiation from other breast cancer subtypes.

Atrazine and diazinon inhibit oocyte maturation and ovulation in zebrafish.

Desmoid tumors are benign mesenchymal neoplasms that originate from muscular fasciae and aponeuroses. Breast involvement is exceptionally rare, accounting for less than 0.2% of all breast tumors. A 41-year-old woman with a history of right-sided invasive ductal carcinoma (IDC) diagnosed in 2022 underwent breast-conserving surgery (BCS) and axillary lymph node dissection (ALND), followed by adjuvant chemotherapy, radiotherapy, and daily tamoxifen (20 mg). The tumor measured 3.5 cm at its greatest dimension, was grade 2, estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, HER2 negative, and had a Ki-67 proliferation index of 25%. Histologic examination revealed a cribriform growth pattern without associated ductal carcinoma insitu (DCIS) or lymphovascular invasion (LVI), and one of nine axillary lymph nodes was positive for metastasis. In 2023, a total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed for ovarian suppression. During routine surveillance in 2024, a new mass was detected at the 2 o'clock position in the right breast. Two core needle biopsies performed over 6 months confirmed fibromatosis. Ongoing tumor enlargement and severe pain, despite radiotherapy, led to a wide local excision. Breast fibromatosis can closely mimic carcinoma both clinically and radiologically, and histologic analysis remains essential for definitive diagnosis. Complete surgical excision with negative margins remains the treatment of choice.

The Value of Internal Positive Controls and Synthetic Calibrators for Performance Assessment of Breast Carcinoma Estrogen Receptor Immunohistochemistry Assay.

Magnetic hyperthermia's potential in triple-negative breast cancer treatment.

Integrating multi-omics approaches to elucidate the mechanism of XiaoPi Decoction in treating hyperplasia of mammary glands via AMPK signaling pathway activation.

Cytotoxicity, antioxidant activity, and gene expression effects of gossypol in primary smooth muscle of myometrium from Ovis aries (PSMo24) cells.

Proteomic signatures in triple-negative breast cancer.

Dominant follicle blood flow at the onset of proestrus does not affect steroid hormones, endometrial receptors, or follicular perfusion in beef cows under FTAI treatment regimens.

Endometriosis is a chronic, estrogen-dependent inflammatory condition that affects approximately 10% of reproductive-age women and is frequently associated with infertility and pelvic pain. Unlike many estrogen-dependent disorders, epidemiologic studies have reported inconsistent associations between obesity, measured by BMI, and endometriosis. Caloric restriction diet (CRD), a dietary regimen that reduces energy intake without malnutrition, has demonstrated anti-inflammatory and anti-proliferative effects in various chronic diseases but remains underexplored in endometriosis. Here, we investigated the effects of CRD on endometriosis using a mouse model with a GFP reporter. Endometriosis was surgically induced by inoculating endometrial fragments, and mice were randomized to receive either adlibitum feeding (regular diet, RD) or CRD. After 90 days, CRD mice exhibited a 24.5% reduction in body weight compared to RD mice, without impairment of female fertility. Notably, both the number and weight of ectopic lesions were significantly reduced in the CRD group compared to the RD group. Immunohistochemical analysis revealed decreased epithelial and stromal cell proliferation, increased apoptosis, and elevated stromal progesterone receptor expression in ectopic lesions from CRD mice. Furthermore, phosphorylation of STAT3 and ERK1/2, key inflammatory and proliferative signaling molecules, was significantly reduced in ectopic lesions from CRD mice. These findings suggest that CRD, without compromising fertility, exerts beneficial effects on endometriosis by targeting cell proliferation, survival, and inflammation. Our results support lifestyle-based dietary interventions as a promising non-hormonal strategy for endometriosis management.

Progesterone (P4) regulates diverse reproductive processes across vertebrates through nuclear receptors; however, its mechanisms in squamate reptiles—particularly in viviparous species—remain poorly understood. In Squamata, P4 primarily acts through progesterone receptor (PR) isoforms A and B, although relatively few reptilian PR sequences have been characterized to date. Squamate PR exhibits ~50% overall sequence divergence from mammalian homologs yet retains striking conservation in both the ligand and DNA-binding domain across vertebrates. Despite the broadly conserved physiological roles of P4 (folliculogenesis, ovulation, courtship behavior, pregnancy maintenance, and parturition/oviposition), P4 dynamics in viviparous squamates remain unresolved due to heterogeneous circulating hormone concentrations and limited PR phylogeny and structure studies. While mammalian models dominate P4 research due to their biomedical relevance, squamates offer unique evolutionary insights: as the only reptile order exhibiting both oviparity and viviparity within the same clade, squamates represent an ideal model for investigating transitions in parity mode. Elucidating P4 mechanisms in squamates will help bridge this critical evolutionary gap, with important implications for reproductive biology and conservation.

Cervical carcinoma remains one of the most prevalent malignancies affecting women worldwide. While human papillomavirus (HPV) infection is a well-established etiological factor, growing evidence suggests that female sex hormones and their receptors may significantly influence the pathogenesis and progression of cervical cancer. Hormonal imbalances, particularly involving estrogen and progesterone, may impact tumor growth and immune modulation within the tumor microenvironment. This study investigates the functional role of selected female sex hormones and their corresponding receptors in Iraqi women diagnosed with cervical carcinoma. A total of 60 female participants were enrolled from gynecology and oncology departments in Baghdad and Karbala, Iraq. Thirty women with histologically confirmed cervical carcinoma were assigned to the patient group, while thirty age-matched healthy volunteers served as controls. Blood samples were collected under fasting conditions, and serum levels of sex hormone-binding globulin (SHBG), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), progesterone, estrogen receptor alpha (ERα), and progesterone receptor (PR) were quantified using standardized ELISA kits. Statistical comparisons were conducted using SPSS with significance set at p &lt; 0.05. Significant hormonal differences were observed between patient and control groups. Estradiol levels were markedly lower in postmenopausal patients than in premenopausal patients, while DHEAS levels were significantly higher in the same comparison. SHBG and DHEAS levels were also elevated in patients compared to controls. Importantly, ERα levels were significantly decreased, while PR levels were significantly increased in cervical cancer patients relative to controls. A strong association was observed between cervical cancer diagnosis and positive family history (73.3% in patients vs. 13% in controls). Our findings suggest that imbalances in circulating sex hormones and alterations in receptor expression—particularly reduced ERα and elevated PR, may contribute to cervical carcinogenesis. These hormonal and biochemical signatures, alongside potential hereditary patterns, highlight the importance of incorporating hormonal profiling in the clinical evaluation of cervical cancer. Further research is warranted to explore the therapeutic potential of targeting hormone receptor pathways in cervical cancer management.

Objectives: Tumor budding, defined as single cells or small clusters (≤4 cells) at the invasive front of tumors, has emerged as a histopathological marker associated with epithelial-mesenchymal transition and poor prognosis in various cancers. While widely studied in colorectal cancer, its significance in breast carcinoma remains underexplored. This study aimed to evaluate the clinicopathological relevance of tumor budding in invasive breast carcinoma of no special type operated at our institute. Material and Methods: A retrospective observational study was conducted on 25 cases of modified radical mastectomy specimens diagnosed as invasive breast carcinoma, no special type. Tumor budding was assessed on H and E-stained sections by two pathologists. Cases were categorized into low (mean &lt;4/10 high power field (HPF) and high (≥4/10 HPF) budding groups. Correlations with clinicopathological parameters and immunohistochemical profiles estrogen receptor (ER), progesterone receptor (PR), Human Epidermal Growth Factor Receptor 2 (HER-2), Ki-67 were evaluated using the chi-square test. Results: High tumor budding was observed in 68% of cases and was significantly associated with lymphovascular invasion (p = 0.008), tumor necrosis (p = 0.001), advanced nodal stage (p = 0.029), and high Ki-67 index (p = 0.024). No significant correlation was found with age, tumor size, grade, hormone receptor status, or HER2 expression. High tumor budding was prevalent in ER-positive, HER2-negative, and Ki-67-high subtypes. Conclusion: Tumor budding correlated with several adverse histopathological features in this exploratory study. These findings suggest that tumor budding may serve as a potential prognostic histopathological marker in invasive carcinoma, particularly in setups with limited access to molecular testing. However, larger prospective studies are warranted before considering routine incorporation into histopathological reporting.