Diethylstilbestrol Research Articles

Primary Clear Cell Adenocarcinoma of the Cervix: A Clinical Analysis of 18 Cases without Exposure to Diethylstilbestrol.

Objectives Cervical clear cell adenocarcinoma (CCAC) is a rare malignant tumor with independent biological behavior in the female reproductive system. In this report, we collect the clinical and histopathological characteristics of 18 CCAC patients without exposure to diethylstilbestrol (DES) and conduct relevant clinical analysis. Methods We retrospectively analyzed the clinical data of 18 patients with CCAC who were diagnosed and treated from January 2009 to August 2017 in the Second Hospital of Jilin University. Results A total of 18 patients were enrolled. The age of patients ranged from 37 to 74 years with the peak incidence between 45 and 55 years. The median age was 53 years. The most common symptom was vaginal bleeding (66.7%, 12/18). The most common type of lesion was the endocervical type (66.7%, 12/18). The negative rate of human papillomavirus (HPV) examination was 88.9% (8/9). Based on the staging criteria of the International Federation of Gynecology and Obstetrics (FIGO) cervical cancer clinical stage in 2018, 55.6% patients were stage I (n=10), 16.7% were stage II (n=3), 22.2% were stage III (n=4), and 5.6% were stage IV (n=1). Seventeen patients underwent surgery; 64.7% (11/17) of cases showed infiltration of the entire layer of the cervix, pelvic lymph node (PLN) metastasis was observed in 4 patients (26.7%, 4/15), endometrium metastasis was observed in 4 patients (25%, 4/16), and 13 patients (72.2%, 13/18) were diagnosed at an early stage (stage IB1-IIA2). Fifteen patients' immunohistochemistry indicated that napsin A, CK7, CK (AE1/AE3), and PAX-8 were positive, and p53, p16, ER, and vimentin were expressed to different degrees. Follow-up data were obtained in 13 patients (72.2%, 13/18). One patient died of recurrence 5 months after surgery, and the other patients' progression-free survival (PFS) ranged from 9 to 59 months. Tumor size (>4 cm), tumor stage (FIGO IIA2-IV), PLN, and endometrium metastasis had negative effects on PFS (P < 0.05). Conclusions CCAC is a highly invasive malignant tumor, whose pathogenesis may not be associated with HPV infection. Radical hysterectomy combined with chemotherapy (paclitaxel + platinum) has the ideal short-term curative effect. In the future, larger samples of clinical data are required to confirm these insights.

Impact of Hydroalcoholic Extract of Humulus Lupulus L. on Sperm Quality, Reproductive Organs and Hormones in Male Rats.

To investigate the impact of Humulus Lupulus L. hydroalcoholic extract on the body weights, reproductive organs, sperm quality and hormone levels in male rats. By simple random sampling method, seventy male Sprague-Dawley rats were randomly assigned to 7 groups including control group [distilled water, 1 mL/(kg•d)], Tween 80 group [25% Tween 80 solution, 1 mL/(kg•d)], olive oil group [olive oil, 1 mL/(kg•d)], diethyl stilbestrol (DES) group [DES, 100 μg/(kg•body weight)], H50, H150 and H450 [50, 150 and 400 mg/(kg•d) of Humulus Lupulus L extract, respectively]. The administration was performed via gavage once daily for 7 weeks. Body and reproductive organs weights including testes, seminal vesicles, epididymis and prostate were weighted and epididymal sperm quality were determined by digital balance. Blood samples were collected and serum free testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrogen (E2) levels were measured by rat specific enzyme-linked immunosorbent assay. The percentage increase in mean body weights of rats in the DES and H50, H150 and H450 groups decreased significantly compared to olive oil and Tween 80 groups (all P<0.05). The weights of seminal vesicle, epididymis and testes in rats receiving H50 were significantly higher than the control group (P<0.05 or P<0.01). The sperm count in the rats receiving H50 was significantly lower than the control group (P<0.05). The sperm motile characteristics of the rats receiving hydroalcoholic extract at and DES were significantly lower than those of the control or rats receiving vehicles (all P<0.05). In H50, H150, H450 and DES groups, T and LH levels were decreased, and E2 was significantly increased compared to the control (P<0.05 or P<0.01). The FSH level did not change in all groups (P>0.05). Humulus Lupulus L. extract significantly increased the seminal vesicle and testes weights and reduced the sperm motility.

Trace analysis of estrogens in milk samples by molecularly imprinted solid phase extraction with genistein as a dummy template molecule and high-performance liquid chromatography–tandem mass spectrometry

Dummy molecularly imprinted polymer microspheres (DMIPMS) towards estrogens were synthesized by Pickering emulsion polymerization employing genistein (GEN) as a dummy template molecule. The FTIR analysis indicated the successful preparation of the imprinted polymers, and the characterization results of scanning electron microscopy and nitrogen adsorption desorption measurement indicated that the obtained DMIPMS are in possess of regular spherical shapes, porous structures and narrow diameter distribution, a BET surface area of 402.74 m2 g−1, a total pore volume of 0.568 cm3 g−1 and a pore diameter of 3.62 nm. The binding capacity and selectivity of DMIPMS were investigated in equilibrium binding experiments and chromatographic evaluation experiments through scatchard analysis and molecular imprinting factor (IF) analysis, respectively. The MIPs showed high binding capacity and excellent selectivity towards seven selected natural and synthetic estrogens, which are Estrone (E1), 17β-estradiol (βE2), estriol (E3), ethinylestradiol (EE2), dienestrol(DS), diethylstilbestrol (DES), and hexestrol (HEX). A method for selective determination of seven estrogens in milk samples via dummy molecularly imprinted solid phase extraction coupled with HPLC-MS/MS was developed, which showed good linearity from 2 to 500 µg L−1 with a correlation coefficient (R2) of more than 0.999. The detection limits were within the range of 0.10–0.35 µg L−1 and the recoveries of the seven estrogens at three spiking levels (10,100,250 µg L−1) ranged from 88.9% to 102.3% with relative standard deviation (RSD, n = 5) for intra-day and inter-day assays varied from 0.8% to 4.5%. The developed method is thus proven to be efficient and reliable for regular monitoring of trace estrogens in complex matrices such as milk samples.

Graphene Quantum Dots Modified Screen‐printed Electrodes as Electroanalytical Sensing Platform for Diethylstilbestrol

AbstractIn present work a simple methodology for electroanalytical sensing of diethylstilbestrol (DES) using graphene quantum dots (GQD) surface modified screen‐printed electrodes (SPE) is reported. GQD was synthesized by simple bottom‐up method based on citric acid pyrolysis at 200 °C and electrodeposited directly at electrode surface under cyclic voltammetric conditions. The obtained GQD presented an average diameter of 7 nm and was characterized by techniques such as transmission and scanning electron microscopy, and electrochemical impedance spectroscopy. The proposed sensor exhibits a linear response from 0.05 to 7.5 μmol L−1, with limit of detection and quantification of 8.8 nmol L−1 and 29.0 nmol L−1, respectively. The repeatability study presented RSD=3.6 % for 6 consecutive measurements using the same electrode surface and the reproducibility study showed RSD=6.6 % for measurements with 6 different electrode surfaces. The proposed sensor was successfully applied for DES determination in synthetic urine and tap water spiked samples and good recoveries were obtained without any sample pre‐treatment, showing its promising analytical performance.

Ioxynil and diethylstilbestrol disrupt vascular and heart development in zebrafish

BackgroundEndocrine disruption is one of the consequences of industrialization and chemicals released into the environment have a profound impact on organisms. Waterborne micromolar concentrations of ioxynil (IOX) and diethylstilbestrol (DES) in fish affect the development of the heart, vasculature and thyroid gland. ObjectivesThe present study aimed to determine how IOX and DES disrupt the crosstalk between the developing thyroid gland and cardio-vascular system in zebrafish. MethodsTwelve hours post fertilization (hpf) wild type, Tg(fli1:GFP) or Tg(cmalc2:GFPCaaX) zebrafish embryos were exposed to 0.1 μM IOX or DES for 36 h (up until 48 hpf) or 60 h (up until 72 hpf). Embryos were used for vascular endothelial cell sorting, whole-mount immunohistochemistry, tissue selective transcriptomics, selected gene expression analysis by quantitative real-time polymerase chain reaction analysis and determination of heart rate by live imaging. ResultsExposure of zebrafish embryos to IOX and DES (0.1 μM) increased heart beat frequency and reduced ventricle volume and aorta diameter. The transcriptome of endothelial cells from blood vessels of hypertrophic, dilated and arrhythmogenic right ventricular cardiomyopathy was significantly changed and compound-specific toxic effects were found in IOX and DES exposed embryos. Both DES and IOX directly affected vascular and heart development and this indirectly impaired thyroid gland development in zebrafish. Even though the toxicity end-point of the two chemicals was similar, their action seemed to be via different gene regulatory pathways and physiological mechanisms. ConclusionIOX and DES directly disrupt cardiovascular development and there is an associated disruption of thyroid tissue that most likely has long term consequences for this endocrine axis.

Improving Compliance and Decreasing Drug Accumulation of Diethylstilbestrol through Cocrystallization

Diethylstilbestrol (DES), a synthetic nonsteroidal estrogen, has been prescribed for advanced breast cancer and prostate cancer. However, its poor compliance, reactive metabolite toxicity and hydro...

Neurodevelopmental disorders in children exposed in utero to synthetic progestins: analysis from the national cohort of the Hhorages Association*

The medical and scientific communities have not yet fully acknowledged the undesirable effects of the synthetic hormones that have been administered to pregnant women for decades. The somatic effects of in utero exposure to diethylstilbestrol (DES), such as genital malformations, infertility, and cancer, have long been recognized but this has not been the case concerning psychiatric disorders. The progestins used in contraception and hormone replacement therapy are known to affect the adult brain, but no data exist on their effects due to in utero exposure of children. The Hhorages Association, a national patient support group, has assembled a cohort of 1200 women who took synthetic hormones during pregnancy. These women had a combined 1934 children. We obtained full questionnaire responses from 46 women treated with progestins only – and not an estrogenic cocktail – who gave birth to 115 children. Three groups were observed: Group 1 (n = 18): firstborn unexposed children, Group 2 (n = 62): children exposed in utero to synthetic progestins, and Group 3 (n = 35): children born after a previous pregnancy treated with progestins. No psychiatric disorders were reported in Group 1 and the incidence of psychiatric disorders was drastically elevated in Group 2. Our work shows a striking increase in psychiatric disorders among children exposed in utero to progestins and strongly suggests that prenatal exposure is associated with a high risk of psychiatric disorders in adolescence and adulthood, whether accompanied or not by disorders of sex development.

Characterization and application of molecularly imprinted polymer-coated quantum dots for sensitive fluorescent determination of diethylstilbestrol in water samples

Molecularly imprinted silica layers coated to quantum dots (MIP-QDs) were successfully fabricated and applied as the fluorescence probe for highly selective and sensitive determination of diethylstilbestrol (DES). Scanning electron microscopy, Transmission electron microscopy, and Fourier transform infrared spectroscopy indicated successful grafting of molecularly imprinted silica layers onto the surface of QDs. Furthermore, the fluorescence assay based on the MIP-QDs showed excellent selectivity and fluorescence quenching capability in optimal conditions and a good linear relationship was obtained in the range of 2.0 × 10−4–10.0 mg/L with a correlation coefficient of 0.9980. The limit of detection of 5.9 × 10−5 mg/L was acquired. Good recoveries ranging from 95.5% to 107.5% were achieved with relative standard deviations (RSD) below 8.4% for seawater and river water samples. The fabricated MIP-QDs were successfully employed as the recognition and response element of an microtitration 96-well fluorescence detection system. Good recoveries ranging from 82.9% to 102.0% with RSDs below 10.0% were obtained for seawater and river water samples. Results demonstrate that simple, rapid, and sensitive DES determination method based on MIP-QDs can be successfully applied to DES residue detection in seawater and river water samples.

Diethylstilbestrol Alters the Expression of Activins in the Neonatal Mouse Ovary In Vitro.

Perinatal diethylstilbestrol (DES) treatment induces the polyovular follicle containing two or more oocytes in a follicle of mouse ovary through estrogen receptor (ER) β. The aim of the study was to investigate the direct effects of DES on the neonatal mouse ovary and the gene expression of activins. Ovaries from neonatal wild-type (WT) or ERβ- knockout (ERβKO) mice were organ-cultured in a serum-free medium with or without DES, and polyovular follicle induction and expression of activin signaling related genes were examined. The polyovular follicle and cyst incidence in DES-treated organ-cultured ovaries from WT mice, but not from ERβKO mice, was significantly higher than that of control non-treated cultures. DES altered inhibin (Inh) a, Inhba and Inhbb expression in organ-cultured ovaries from C57BL/6J mice, while no change in Inha and an increase of Inhbb were observed by DES, in both WT and ERβKO mice. Alterations in activin signaling are involved in the polyovular follicle induction by DES.

T-shaped Uterus in the 21st Century (Post DES era) - We Need to Know More!

T-Shaped uterus is a rare uterine malformation, and has classically been associated with “in-utero” exposure of DES (diethylstilbestrol). Surprisingly, the prevalence of T shaped uterus is significant even today. Hysteroscopic metroplasty is a simple procedure which can potentially improve outcomes in sub-fertile women, but the data is not robust. There is a need for centralised database for registration of women with T shaped uterine anomalies, which will help in defining clear diagnostic criteria, surgical indication & technique, and follow up of reproductive outcomes after the procedure.

Pro-Apoptotic Effects of Estetrol on Long-Term Estrogen-Deprived Breast Cancer Cells and at Low Doses on Hormone-Sensitive Cells.

Purpose:Postmenopausal women with estrogen receptor-positive breast cancers often respond initially to tamoxifen or aromatase inhibitor therapy. Resistance to these treatments usually develops within 12 to 18 months. Clinical studies have demonstrated that high-dose estrogen can induce regression of these endocrine-resistant tumors. However, side-effects of high-dose estradiol (E2) or diethylstilbestrol (DES) limit their usage. Estetrol (E4) is the most abundant estrogen during pregnancy and has a long half-life and a low potential for side-effects. Estetrol might then provide benefits similar to DES on tumor regression but with lesser toxicity.Methods:In this study, we systematically evaluated the effects of E4 on cell proliferation and apoptosis in wild-type MCF-7 and long-term estrogen-deprived (LTED) MCF-7 cells and compared its effects with E2 and estriol (E3).Results:Estetrol induced apoptosis in LTED cells but stimulated growth of MCF-7 cells at concentrations from 10−11 to 10−8 M. These effects of E4 are similar to those of E2 but require much higher doses. Differing from E2, E4 at 10−12 M induced apoptosis in MCF-7 cells and another pregnancy estrogen, E3, acted similarly. No antagonistic effect of E4 or E3 against E2 occurred when they were combined.Conclusions:The pro-apoptotic effects of E4 and E3 on LTED cells and at low doses on MCF-7 cells indicate that these steroids could be used as therapeutic agents for endocrine-resistant or sensitive breast cancer.

Reproductive and hormone-related outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): A report from the US National Cancer Institute DES Third Generation Study

BackgroundAnimal studies suggest that prenatal exposure to diethylstilbestrol (DES) causes epigenetic alterations in primordial germ cells that affect the next generation, but human studies are sparse. MethodsWe assessed hormonally mediated outcomes in third generation women whose mothers were prenatally DES-exposed and unexposed. ResultsCompared to the unexposed, DES-exposed third generation women had an increased risk of irregular menses and amenorrhea; the respective prevalence ratios and 95% confidence intervals (CI) in follow-up data were 1.32 (95% CI: 1.10, 1.60) and 1.26 (95% CI: 1.06, 1.49); associations were more apparent in third generation women whose prenatally DES-exposed mothers were affected by vaginal epithelial changes. The follow-up data also indicated an association with preterm delivery (relative risk (RR): 1.54; 95% CI: 1.35, 1.75). ConclusionDES third generation women may have an increased risk of irregular menstrual cycles, amenorrhea, and preterm delivery, consistent with inter-generational effects of endocrine disrupting chemical exposure in humans.

Histone deacetylase inhibitors suppress transdifferentiation of gonadotrophs to prolactin cells and proliferation of prolactin cells induced by diethylstilbestrol in male mouse pituitary.

Diethylstilbestrol (DES), an estrogen agonist, increases prolactin (PRL) cells through transdifferentiation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells to PRL cells as well as proliferation of PRL cells in adult male mouse pituitary. Since hyperacetylation of histone H3 is implicated in the regulation of activation of various genes, we examined the effect of DES on the state of histone H3 acetylation. DES significantly reduced the immunohistochemical signal for acetylated histone H3 at lysine 9 (H3K9ac) in PRL, LH and FSH cells, but not for H3K18ac or H3K23ac. DES-treated mice were injected intraperitoneally with HDAC inhibitors (HDACi), sodium phenylbutyrate (NaPB) or valproic acid (VPA), to mimic the acetylation level of histone H3. As expected, HDACi treatment restored the level of H3K9ac expression in these cells, and also inhibited DES-induced increase in PRL cells. Furthermore, NaPB and VPA also abrogated the effects of DES on the population density of both LH and FSH cells. Similarly, the numbers of proliferating and apoptotic cells in the pituitary in NaPB- or VPA-treated mice were comparable to those of the control mice. Considered together, these results indicated that the acetylation level of histone H3 plays an important role in DES-induced transdifferentiation of LH to PRL cells as well as proliferation of PRL cells.

Estrogen Metabolism in Postmenopausal Women Exposed In Utero to Diethylstilbestrol.

Background: Prenatal diethylstilbestrol (DES) exposure is associated with adverse reproductive outcomes and cancer of the breast and vagina/cervix in adult women. DES effects on estrogen metabolism have been hypothesized, but reproductive hormone concentrations and metabolic pathways have not been comprehensively described.Methods: Blood samples were provided by 60 postmenopausal women (40 exposed and 20 unexposed) who were participants in the NCI Combined DES Cohort Study, had never used hormone supplements or been diagnosed with cancer, had responded to the most recent cohort study questionnaire, and lived within driving distance of Boston University Medical School (Boston, MA). Parent estrogens and their metabolites were measured by high-performance liquid chromatography-tandem mass spectrometry. Age-adjusted percent changes in geometric means and associated 95% confidence intervals (CIs) between the exposed and unexposed were calculated.Results: Concentrations of total estrogens (15.3%; CI, -4.1-38.5) and parent estrogens (27.1%; CI, -8.2-76.1) were slightly higher in the DES-exposed than unexposed. Ratios of path2:parent estrogens (-36.5%; CI, -53.0 to -14.3) and path2:path16 (-28.8%; CI, -47.3-3.7) were lower in the DES exposed. These associations persisted with adjustment for total estrogen, years since menopause, body mass index, parity, and recent alcohol intake.Conclusions: These preliminary data suggest that postmenopausal women who were prenatally DES exposed may have relatively less 2 than 16 pathway estrogen metabolism compared with unexposed women.Impact: Lower 2 pathway metabolism has been associated with increased postmenopausal breast cancer risk and could potentially offer a partial explanation for the modest increased risk observed for prenatally DES-exposed women. Cancer Epidemiol Biomarkers Prev; 27(10); 1208-13. ©2018 AACR.

Highlights of This Issue

Epidemiologic studies have examined association between human papillomaviruses (HPVs) and esophageal cancer, but results have been inconsistent. Agalliu and colleagues carried out a nested case–control study (125 cases; 372 controls) among 96,650 cancer-free participants in two large cohort studies to investigate associations of alpha, beta, and gamma HPV detection in the oral cavity and risk of esophageal cancer. Oral HPV16 detection was not associated with esophageal cancer (OR = 0.54, 95% confidence interval: 0.1–4.84). Although some oral HPV types were more common in cases than controls, none of the associations were statistically significant. Oral HPVs may not contribute to risk of esophageal cancer.Melanoma incidence has been rising over decades despite public efforts to promote sun protection behaviors. Dietary factors may also affect the development of melanoma; some have emerged as promising candidates for chemoprevention. Yang and colleagues conducted a narrative review of the relationship between dietary factors, including coffee and caffeine, citrus fruits, alcohol, polyunsaturated fatty acid, niacin/nicotinamide, folate, and vitamin D, with melanoma risk from the perspective of epidemiology. Biological mechanisms and some future directions were also discussed and outlined. The associations discussed may have important public health implications in terms of reducing melanoma incidence through dietary modification.In patients with acute lymphoblastic leukemia (ALL), adolescents and young adults (AYA) experience increased risk of relapse as compared with children, while predictors of relapse among AYA vary by time of relapse. Wolfson and colleagues found that among AYA with ALL, aspects of healthcare delivery (clinical trial enrollment, nonwhite race/ethnicity) are associated with relapse during therapy, and aspects of treatment (shorter duration of maintenance and consolidation) are associated with relapse after completing therapy. These findings highlight the importance of clinical trial enrollment and therapy duration (maintenance, consolidation) in ensuring durable remissions in AYA ALL. Future studies encompassing healthcare delivery, treatment, and biology are needed.Prenatal diethylstilbestrol (DES) exposure is associated with adverse reproductive and neoplastic outcomes. In this study by Troisi and colleagues, age-adjusted ratios of serum estrogens metabolized in the 2-pathway compared to the 16-pathway were about 30% lower in postmenopausal women who were prenatally DES exposed [2-pathway:16-pathway = 0.37, 95% confidence interval (CI) = 0.31–0.44; n = 40] than unexposed (2-pathway:16-pathway = 0.51, CI = 0.40–0.66; n = 20), and remained lower with adjustment for total estrogen, years since menopause, body mass index, parity, and alcohol intake. Lower 2-pathway metabolism is associated with increased postmenopausal breast cancer risk and could partially explain the modest increased risk observed in DES exposed women.

A Microextraction Coupled with HPLC-UV for a Sensitive Detection of Estrogens in Water

Environmental concerns over trace levels of estrogens concentrations in water environment have increased because of their adverse effects on humans, animals and aquatic life. In this contribution, we developed a simple and highly sensitive analytical protocol for trace analysis of 3 important estrogens namely 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and diethylstilbestrol (DES) in water, resulting in pg/mL level detection. Microextraction by packed sorbent (MEPS) using a C18 sorbent in combination with HPLC-UV was applied to extract/enrich, separate, identify and quantify the estrogens at pg/mL level in water. Achieved recoveries in spiked water samples ranged from 85.02 to 98.07 % with RSD (%) ranged from 5.11–9.12. Limit of detection (LODs) were as low as 0.09–0.47 pg/mL in spiked samples. To investigate the real world application, the protocol was applied to a total of 9 real water samples including drinking water, private well water, hospital waste water, and river water, and yielded concentrations ranging for two estrogens (EE2 and E2) from 2.21 to 3.75 ng/mL, and DES was not found in any real sample studied.

Diethylstilbestrol (DES) induces autophagy in thymocytes by regulating Beclin-1 expression through epigenetic modulation

Diethylstilbestrol (DES) is an endocrine disruptor that was used to prevent adverse effects of pregnancy in women in late 1940s until early 1970s. Its use was banned following significant toxicity and negative effects not only in the mothers but also transgenerationally. Previous studies from our laboratory showed that DES induces thymic atrophy and immunosuppression in mice. In this study, we investigated the molecular mechanisms through which DES triggers thymic atrophy, specifically autophagy. To that end, we treated C57BL/6 mice with DES, and determined expression of two autophagy-related proteins, microtubule-associated protein-1 light chain 3 (LC3) and Beclin-1 (Becn1). We observed that DES-induced thymic atrophy was associated with increased autophagy in thymocytes and significant upregulation in the expression of both Becn1 and LC3. DES also caused downregulation in the expression of miR-30a in thymocytes, and transfection studies revealed that miR-30a targeted Becn1. Upon examination of methylation status of Becn1, we noted hypomethylation of Becn1 in thymocytes of mice exposed to DES. Together, these data demonstrate for the first time that DES induces autophagy in thymocytes potentially through epigenetic changes involving hypomethylation of Becn1 and down-regulation of miR-30a expression.

Turn-on fluorometric immunosensor for diethylstilbestrol based on the use of air-stable polydopamine-functionalized black phosphorus and upconversion nanoparticles.

The preparation of air-stable black phosphorus (BP) is challenging because atomic layers of BP degrade rapidly on exposure to oxygen. A strategy is presented for the synthesis of BP functionalized with polydopamine (PDA/BP). Dopamine was self-polymerized to yield polydopamine (PDA) which then was used to coat the surface of BP. PDA can be easily reduced and this prevents BP degradation. PDA/BP also is a viable matrix for the adsorption of proteins due to the presence of functional groups. Without any chemical activation, diethylstilbestrol (DES)-specific monoclonal antibody was adsorbed on the PDA/BP surface. PDA/BP quenches the fluorescence antigen-modified NaYF4:Yb,Ho,Nd upconversion nanoparticles (UCNPs; photoexcited at 808 nm) via specific immuno recognition. Exposure to DES causes the dissociation of UCNP from the PDA/BP surface and fluorescence at 475, 525, 545 and 660nm to recover. This is due to the DES competition with antigen for binding to theantibody. Based on thiscompetitive immuno mechanism, a turn-on fluorometric immunoassay was constructed. It has a response that covers the 0.1 to 1000ngmL-1 DES concentration range with a detection limit of 83pgmL-1. This method was successfully applied to the determination of DES in spiked food and human urine samples. Graphical abstract Air-stable polydopamine-functionalized black phosphorus was obtained by modification of black phosphorus with polydopamine and then was coupled with specific monoclonal antibody. Combined with antigen-modified upconversion nanoparticles, a turn-on fluorometric immunoassay was constructed to detect diethylstilbestrol.

Polyacetal-Based Combination Therapy for the Treatment of Prostate Cancer.

The high incidence of prostate carcinogenesis has prompted the search for novel effective treatment approaches. We have employed curcumin (Curc) and diethylstilbestrol (DES) to synthesize a series of polyacetal (PA)-based combination conjugates for prostate cancer (PCa) treatment. Given their bihydroxyl functionalities, Curc and DES molecules were incorporated into a PA mainchain using a one-pot reaction between diols and divinyl ethers. The PA-conjugates released both drugs under acidic conditions, such as those found in the tumor microenvironment, endosomes, or lysosomes, while remaining stable at neutral pH 7.4. The drug ratio was optimized to achieve anticancer drug synergism with elevated cytotoxicity against LNCaP-hormone-dependent human PCa cells conferred via the induction of S phase cell cycle arrest by the upregulation of p53 and CDK inhibitors p21Waf/CIP1 and downregulation of cyclin D1. The application of rationally designed PA-Curc-DES combination conjugates represents a potentially exciting new treatment for prostate cancer.

In situ reduced silver nanoparticles embedded molecularly imprinted reusable sensor for selective and sensitive SERS detection of Bisphenol A

Sensitive and selective detection of target analyte is very important in many fields such as commodity inspection and quality monitoring. In this work, we constructed a MIPs@AgNPs surface-enhanced Raman scattering (SERS) sensor by in-situ preparation of silver nanoparticles (AgNPs) inside molecularly imprinted polymers (MIPs) matrix for bisphenol A (BPA) detection. In-situ formed AgNPs are evenly distributed and closely packed in the matrix, which is beneficial for hot spot formation and analyte-AgNPs affinity. Our MIPs@AgNPs sensor shows good BPA selectivity against structurally related molecules such as bisphenol AF (BPAF) and diethylstilbestrol (DES). Excellent sensitivity of this MIPs@AgNPs sensor is demonstrated with the detection limit of at least 5 × 10−8 mol L−1 for BPA. This sensor is reliable for the quantitative detection of BPA in real samples, validated with results of HPLC. Regeneration of this kind of SERS sensor can be easily realized by solvent rinsing and NaBH4 reduction. Together with the advantages of ease-of-fabrication, selective recognition, sensitivity and reusability, this kind of MIPs@AgNPs SERS sensor will have a promising practical applications.