Targeting an Old Foe for Cancer: A Molecular Dynamics Perspective to Unravel the Specific Binding Nature of 2-Methoxy Estradiol to Human ß-Tubulin Isotypes.

Microtubules, composed of α- and ß-tubulin subunits are crucial for cell division with their dynamic tissue-specificity which is dictated by expression of isotypes. These isotypes differ in carboxy-terminal tails (CTTs), rich in negatively charged acidic residues in addition to the differences in the composition of active site residues. 2-Methoxy estradiol (2-ME) is the first antimicrotubule agent that showed less affinity toward hemopoietic-specific ß1 isotype consequently preventing myelosuppression toxicity. The present study focuses on the MD-directed conformational analysis of 2-ME and estimation of its binding affinity in the colchicine binding pocket of various ß-tubulin isotypes combined with the α-tubulin isotype, α1B. AlphaFold 2.0 was used to predict the 3D structure of phylogenetically divergent human ß-tubulin isotypes in dimer form with α1B. The dimeric complexes were subjected to induced-fit docking with 2-ME. The statistical analysis of docking showed differences in the binding characteristics of 2-ME with different isotypes. The replicas of atom-based molecular dynamic simulations of the best conformation of 2-ME provided insights into the molecular-level details of its binding pattern across the isotypes. Furthermore, the MM/GBSA analyses revealed the specific binding energy profile of 2-ME in ß-tubulin isotypes. It also highlighed, 2-ME exhibits the lowest binding affinity toward the ß1 isotype as supported by experimental study. The present study may offer useful information for designing next-generation antimicrotubule agents that are more specific and less toxic.

A critical and comprehensive review of the current status of 17ß-estradiol hormone remediation through adsorption technology.

Even at low concentrations, steroid hormones pose a significant threat to ecosystem health and are classified as micropollutants. Among these, 17ß-estradiol (molecular formula: C18H24O2; pKa = 10.46; Log Kow = 4.01; solubility in water = 3.90 mg L-1 at 27 °C; molecular weight: 272.4 g mol-1) is extensively studied as an endocrine disruptor due to its release through natural pathways and widespread use in conventional medicine. 17ß-estradiol (E2) is emitted by various sources, such as animal and human excretions, hospital and veterinary clinic effluents, and treatment plants. In aquatic biota, it can cause issues ranging from the feminization of males to inhibiting plant growth. This review aims to identify technologies for remediating E2 in water, revealing that materials like graphene oxides, nanocomposites, and carbonaceous materials are commonly used for adsorption. The pH of the medium, especially in acidic to neutral conditions, affects efficiency, and ambient temperature (298 K) supports the process. The Langmuir and Freundlich models aptly describe isothermal studies, with interactions being of a low-energy, physical nature. Adsorption faces limitations when other ions coexist in the solution. Hybrid treatments exhibit high removal efficiency. To mitigate global E2 pollution, establishing national and international standards with detailed guidelines for advanced treatment systems is crucial. Despite significant advancements in optimizing technologies by the scientific community, there remains a considerable gap in their societal application, primarily due to economic and sustainable factors. Therefore, further studies are necessary, including conducting batch experiments with these adsorbents for large-scale treatment along with economic analyses of the production process.

Rational evolution for altering the ligand preference of estrogen receptor alpha.

Estrogen receptor α is commonly used in synthetic biology to control the activity of genome editing tools. The activating ligands, estrogens, however, interfere with various cellular processes, thereby limiting the applicability of this receptor. Altering its ligand preference to chemicals of choice solves this hurdle but requires adaptation of unspecified ligand-interacting residues. Here, we provide a solution by combining rational protein design with multi-site-directed mutagenesis and directed evolution of stably integrated variants in Saccharomyces cerevisiae. This method yielded an estrogen receptor variant, named TERRA, that lost its estrogen responsiveness and became activated by tamoxifen, an anti-estrogenic drug used for breast cancer treatment. This tamoxifen preference of TERRA was maintained in mammalian cells and mice, even when fused to Cre recombinase, expanding the mammalian synthetic biology toolbox. Not only is our platform transferable to engineer ligand preference of any steroid receptor, it can also profile drug-resistance landscapes for steroid receptor-targeted therapies.

Effects of organochlorine pesticides on human and rat 17ß-hydroxysteroid dehydrogenase 1 activity: Structure-activity relationship and in silico docking analysis.

The objective of this study was to examine the effect of 11 organochlorine pesticides on human and rat 17ß-Hydroxysteroid dehydrogenase 1 (17ß-HSD1) in human placental and rat ovarian microsome and on estradiol production in BeWo cells. The results showed that the IC50 values for endosulfan, fenhexamid, chlordecone, and rhothane on human 17ß-HSD1 were 21.37, 73.25, 92.80, and 117.69 µM. Kinetic analysis revealed that endosulfan acts as a competitive inhibitor, fenhexamid as a mixed/competitive inhibitor, chlordecone and rhothane as a mixed/uncompetitive inhibitor. In BeWo cells, all insecticides except endosulfan significantly decreased estradiol production at 100 µM. For rats, the IC50 values for dimethomorph, fenhexamid, and chlordecone were 11.98, 36.92, and 109.14 µM. Dimethomorph acts as a mixed inhibitor, while fenhexamid acts as a mixed/competitive inhibitor. Docking analysis revealed that endosulfan and fenhexamid bind to the steroid-binding site of human 17ß-HSD1. On the other hand, chlordecone and rhothane binds to a different site other than the steroid and NADPH-binding site. Dimethomorph binds to the steroid/NADPH binding site, and fenhexamid binds to the steroid binding site of rat 17ß-HSD1. Bivariate correlation analysis showed a positive correlation between IC50 values and LogP for human 17ß-HSD1, while a slight negative correlation was observed between IC50 values and the number of HBA. ADMET analysis provided insights into the toxicokinetics and toxicity of organochlorine pesticides. In conclusion, this study identified the inhibitory effects of 3-4 organochlorine pesticides and binding mechanisms on human and rat 17ß-HSD1, as well as their impact on hormone production.

A self-powered electrochemical aptasensor for the detection of 17ß-estradiol based on carbon nanocages/gold nanoparticles and DNA bioconjugate mediated biofuel cells.

17ß-Estradiol (E2) is an important endogenous estrogen, which disturbs the endocrine system and poses a threat to human health because of its accumulation in the human body. Herein, a biofuel cell (BFC)-based self-powered electrochemical aptasensor was developed for E2 detection. Porous carbon nanocage/gold nanoparticle composite modified indium tin oxide (CNC/AuNP/ITO) and glucose oxidase modified CNC/AuNP/ITO were used as the biocathode and bioanode of BFCs, respectively. [Fe(CN)6]3- was selected as an electroactive probe, which was entrapped in the pores of positively charged magnetic Fe3O4 nanoparticles (PMNPs) and then capped with a negatively charged E2 aptamer to form a DNA bioconjugate. The presence of the target E2 triggered the entrapped [Fe(CN)6]3- probe release due to the removal of the aptamer via specific recognition, which resulted in the transfer of electrons produced by glucose oxidation at the bioanode to the biocathode and produced a high open-circuit voltage (EOCV). Consequently, a "signal-on" homogeneous self-powered aptasensor for E2 assay was realized. Promisingly, the BFC-based self-powered aptasensor has particularly high sensitivity for E2 detection in the concentration range of 0.5 pg mL-1 to 15 ng mL-1 with a detection limit of 0.16 pg mL-1 (S/N = 3). Therefore, the proposed BFC-based self-powered electrochemical aptasensor has great promise to be applied as a successful prototype of a portable and on-site bioassay in the field of environment monitoring and food safety.

A 4-year study of bovine reproductive hormones that are induced by pharmaceuticals and appear as steroid estrogenic pollutants in the resulting slurry, using in vitro and instrumental analytical methods.

The main objective of the research was to study the environmental "price" of the large-scale, milk production from a rarely known perspective, from the mapping of the estrogenic footprint (the amount of oestrus-inducer hormonal products, and the generated endoestrogens) in the resulting slurry in a dairy cow farm. These micropollutants are endocrine-disrupting chemicals (EDCs) and can be dangerous to the normal reproductive functions even at ng/kg concentration. One of them, 17ß-estradiol, has a 20,000 times stronger estrogenic effect than bisphenol-A, a widely known EDC of industrial origin. While most studies on EDCs are short-term and/or laboratory based, this study is longitudinal and field-based. We sampled the slurry pool on a quarterly basis between 2017 and 2020. Our purpose was testing the estrogenic effects using a dual approach. As an effect-based, holistic method, we developed and used the YES (yeast estrogen screen) test employing the genetically modified Saccharomyces cerevisiae BJ3505 strain which contains human estrogenic receptor. For testing exact molecules, UHPLC-FLD was used. Our study points out that slurry contains a growing amount of EDCs with the risk of penetrating into the soil, crops and the food chain. Considering the Green Chemistry concept, the most benign ways to prevent of the pollution of the slurry is choosing appropriate oestrus-inducing veterinary pharmaceuticals (OIVPs) and the separation of the solid and liquid parts with adequate treatment methods. To our knowledge, this is the first paper on the adaptation of the YES test for medicine and slurry samples, extending its applicability. The adapted YES test turned out to be a sensitive, robust and reliable method for testing samples with potential estrogenic effect. Our dual approach was successful in evaluating the estrogenic effect of the slurry samples.

Quantum Dot-Sensitised Estrogen Receptor-α-Based Biosensor for 17ß-Estradiol.

17ß-estradiol (E2) is an important natural female hormone that is also classified as an estrogenic endocrine-disrupting compound (e-EDC). It is, however, known to cause more damaging health effects compared to other e-EDCs. Environmental water systems are commonly contaminated with E2 that originates from domestic effluents. The determination of the level of E2 is thus very crucial in both wastewater treatment and in the aspect of environmental pollution management. In this work, an inherent and strong affinity of the estrogen receptor-α (ER-α) for E2 was used as a basis for the development of a biosensor that was highly selective towards E2 determination. A gold disk electrode (AuE) was functionalised with a 3-mercaptopropionic acid-capped tin selenide (SnSe-3MPA) quantum dot to produce a SnSe-3MPA/AuE electroactive sensor platform. The ER-α-based biosensor (ER-α/SnSe-3MPA/AuE) for E2 was produced by the amide chemistry of carboxyl functional groups of SnSe-3MPA quantum dots and the primary amines of ER-α. The ER-α/SnSe-3MPA/AuE receptor-based biosensor exhibited a formal potential (E0') value of 217 ± 12 mV, assigned as the redox potential for monitoring the E2 response using square-wave voltammetry (SWV). The response parameters of the receptor-based biosensor for E2 include a dynamic linear range (DLR) value of 1.0-8.0 nM (R2 = 0.99), a limit of detection (LOD) value of 1.69 nM (S/N = 3), and a sensitivity of 0.04 µA/nM. The biosensor exhibited high selectivity for E2 and good recoveries for E2 determination in milk samples.

Identification of Biologically Diverse Tetrahydronaphthalen-2-ols through the Synthesis and Phenotypic Profiling of Chemically Diverse, Estradiol-Inspired Compounds.

Combining natural product fragments to design new scaffolds with unprecedented bioactivity is a powerful strategy for the discovery of tool compounds and potential therapeutics. However, the choice of fragments to couple and the biological screens to employ remain open questions in the field. By choosing a primary fragment containing the A/B ring system of estradiol and fusing it to nine different secondary fragments, we were able to identify compounds that modulated four different phenotypes: inhibition of autophagy and osteoblast differentiation, as well as potassium channel and tubulin modulation. The latter two were uncovered by using unbiased morphological profiling with a cell-painting assay. The number of hits and variety in bioactivity discovered validates the use of recombining natural product fragments coupled to phenotypic screening for the rapid identification of biologically diverse compounds.

Development of a competitive ELISA based on estrogen receptor and weak competitive molecule for the screening of potential estrogens in foods.

Enzyme labeled competitive molecules are generally homologous with competitors in competitive broad-spectrum enzyme-linked immunosorbent assays (ELISA). It is speculated that the detectability will be improved when the competitiveness of competitive molecule is weak. Herein, common small molecule food hazard-estrogen disrupting chemicals (EDCs) were used as target model for verification. The dual-estrogen receptor (ER) and three estrogen-enzyme conjugates with various responses were used as recognizers and competitive molecules in ELISA. ELISA based on bisphenol (BPA)-horseradish peroxidase (HRP) has the highest detectability and can screen all six EDCs, in which BPA-HRP showed the weakest ER excitatory activity (Ka = 1.39 × 10-2 nmol·L-1) among three conjugates. The proposal showed good practicability with spiked recovery of 80.0-110 % for estrogens (17ß-estradiol, 17α-estradiol, BPA) in foodstuffs, and revealed biomarkers with weak competitiveness may be applied to other competitive procedures to improve detectability, and it provides sensitive pre-screening strategy for follow-up screening tool.

Kinetic Study of 17α-Estradiol Mechanism during Rat Sperm Capacitation.

17α-Estradiol (αE2) is a natural diastereoisomer of 17ß-estradiol (E2). It is well known that αE2 can bind to estrogen receptors. However, its biological activity is less than that of E2 and is species and tissue specific. The goal of our study was to propose the mechanism of αE2 hormonal response in rat sperm during their capacitation in vitro and compare it with a previously studied mouse model. Concentration changes in externally added αE2 during capacitation of rat sperm were monitored by the high-performance liquid chromatographic method with tandem mass spectrometric detection (HPLC-MS/MS). The calculated values of relative concentrations Bt were subjected to kinetic analysis. The findings indicated that αE2 in rat sperm did not trigger autocatalytic reaction, in contrast to the mouse sperm, and that the initiation of the hormone penetration through the sperm plasma membrane was substantially faster in rats.

Split aptamer regulated CRISPR/Cas12a biosensor for 17ß-estradiol through a gap-enhanced Raman tags based lateral flow strategy.

It is significant to exploit the full potential of CRISPR/Cas based biosensor for non-nucleic-acid targets. Here, we developed a split aptamer regulated CRISPR/Cas12a and gap-enhanced Raman tags based lateral flow biosensor for small-molecule target, 17ß-estradiol. In this assay, one split aptamer of 17ß-estradiol was designed to complement with crRNA of Cas12a so that the trans-cleavage ability of CRISPR/Cas12a can be regulated by the competitive binding of 17ß-estradiol and split aptamers. Through integration of the signal amplification ability of CRISPR/Cas12a and the ultra-sensitive gap-enhanced Raman tags based lateral flow assay, a visible-SERS dual mode determination of 17ß-estradiol can be established. 17ß-estradiol can be visibly recognized as low as 10 pM and accurately quantified with a detection limit of 180 fM by SERS signals, which is at least 103-fold lower than that of the previous immunoassay lateral flow strategies. Our assay provides a novel perspective to develop split aptamer regulated CRISPR/Cas12a coupling with SERS lateral flow strips for ultrasensitive and easy-to-use non-nucleic-acid targets detection.

An irreversible inhibitor of 17ß-hydroxysteroid dehydrogenase type 1 inhibits estradiol synthesis in human endometriosis lesions and induces regression of the non-human primate endometriosis.

Endometriosis is a gynecological disorder affecting about 10% of women and can lead to invalidating painful symptoms and infertility. Since there is no current definitive cure for this disease, new therapeutic options are necessary. 17ß-Hydroxysteroid dehydrogenase type 1 (17ß-HSD1) is involved in the production of estradiol (E2), the most potent estrogen in women, and of 5-androstene-3ß,17ß-diol (5-diol), a weaker estrogen than E2, but whose importance increases after menopause. 17ß-HSD1 is therefore a pharmacological target of choice for the treatment of estrogen-dependent diseases such as endometriosis. We developed a targeted-covalent (irreversible) and non-estrogenic inhibitor of 17ß-HSD1, a molecule named PBRM, and herein evaluated its efficiency for the treatment of endometriosis. In a cell-free assay containing estrone (E1), the natural substrate of 17ß-HSD1, PBRM was able to block the formation of E2 in a collection of 50 human endometriosis lesions from a different clinical feature type, location, and phase. When given orally by gavage at 15 mg/kg to baboons, the resulting plasmatic concentration of PBRM was found to be sufficiently high (up to 125 ng/mL) for an efficacy study in a non-human primate (baboon) endometriosis model. After 2 months of treatment, the number of lesions/adhesions decreased in 60% of animals (3/5) in the PBRM-treated group, compared to the placebo group which showed an increase in the number of lesion/adhesions in 60% (3/5) of animals. Indeed, the total number of lesions/adhesions decreased in treated group (-6.5 or -19% when excluding one animal) while it increased in the control group receiving a placebo (+11%). Analysis of specific endometriotic lesions revealed that PBRM decreased the number of red lesions (-67%; 8/12) and white lesions (-35%; 11/31), but not of blue-black lesions. Similarly, PBRM decreased the surface area of dense adhesions and filmy adhesions, as compared to placebo. Also, PBRM treatment did not significantly affect the number of menstrual days. Finally, this targeted covalent inhibitor showed no adverse effects and no apparent toxicity for the duration of the treatment. These data indicate that 17ß-HSD1 inhibitor PBRM is a promising candidate for therapy targeting endometriosis and supports the need of additional efforts toward clinical trials.

Comparison of 17ß-Estradiol Adsorption on Corn Straw- and Dewatered Sludge-Biochar in Aqueous Solutions.

Removal of steroid hormones from aqueous environment is of prevailing concern because of their adverse impact on organisms. Using biochar derived from biomass as adsorbent to remove pollutants has become more popular due to its low cost, effectiveness, and sustainability. This study evaluated the feasibility of applying corn straw biochar (CSB) and dewatered sludge biochar (DSB) to reduce 17ß-estradiol (E2) from aquatic solutions by adsorption. The experimental results showed that the adsorption kinetics and isotherm behavior of E2 on the two biochars were well described by the pseudo-second-order (R2 > 0.93) and Langmuir models (R2 > 0.97). CSB has higher E2 adsorption capacity than DSB, and the maximum adsorption capacity was 99.8 mg/g obtained from Langmuir model at 298 K, which can be attributed to the higher surface area, porosity, and hydrophobicity of this adsorbent. Higher pH levels (>10.2) decreased the adsorption capacities of biochar for E2, while the ionic strength did not significantly affect the adsorption process. The regeneration ability of CSB was slightly better than that of DSB. The possible adsorption mechanism for E2 on biochar is suggested as π−π interactions, H−bonding, and micropores filling. These results indicated that CSB has more potential and application value than DSB on reducing E2 from aqueous solutions when considering economy and removal performance.

A signal-off photoelectrochemical aptasensor for ultrasensitive 17ß-estradiol detection based on rose-like CdS@C nanostructure and enzymatic amplification.

Carbon-coated cadmium sulfide rose-like nanostructures (CdS@C NRs) were prepared via a facile solvothermal approach and used as the photoelectrochemical (PEC) sensing platform for the integration of functional biomolecules. Based on this, a novel "signal-off" PEC aptasensor mediated by enzymatic amplification was proposed for the sensitive and selective detection of 17ß-estradiol (E2). In the presence of E2, alkaline phosphatase-modified aptamer (ALP-apta) were released from the electrode surface through the specific recognition with E2, which caused the negative effect on PEC response due to the decrease of ascorbic acid (AA) produced by the ALP in situ enzymatic catalysis. The developed PEC aptasensor for detection of E2 exhibited a wide linear range of 1.0-250 nM, with the low detection limit of 0.37 nM. This work provides novel insight into the design of potential phoelectroactive materials and the application of signal amplification strategy in environmental analysis field.

Phenol and 17ß-estradiol removal by Zoogloea sp. MFQ7 and in-situ generated biogenic manganese oxides: Performance, kinetics and mechanism.

The pollution of multifarious pollutants such as heavy metal, organic compounds, and nitrate are a hot research topic at present. In this study, the functions of Zoogloea sp. MFQ7 and its biological precipitation formed during bacterial manganese oxidation on the removal of phenol and 17ß-estradiol (E2) were investigated. Strain MFQ7, a manganese-oxidizing bacteria, can remove 98.34% of phenol under pH of 7.1, a temperature of 30 â„ƒ and Mn2+ concentration of 24.34 mg L-1, additionally, the optimum E2 removal by strain MFQ7 was 100.00% at pH of 7.1, temperature of 28 â„ƒ and Mn2+ concentration of 28.45 mg L-1 by using response surface methodology (RSM) based on Box-Behnken design (BBD) model. The maximum adsorption capacity of bio-precipitation for phenol and E2 was 201.15 mg g-1 and 65.90 mg g-1, respectively. Furthermore, adsorption kinetics and isotherms analysis, XPS, FTIR spectra, Mn(III) trapping experiments elucidated chemical adsorption and Mn(III) oxidation contribute to the removal of phenol and E2 by biogenic manganese oxides. These findings indicated that the adsorption and oxidation of manganese are expected to be one of the effective means to remove these typical organic pollutants containing phenol and E2.

Triazole-estradiol analogs: A potential cancer therapeutic targeting ovarian and colorectal cancer.

1,2,3-triazoles have continuously shown effectiveness as biologically active systems towards various cancers, and when used in combination with steroid skeletons as a carrier, which can act as a drug delivery system, allows for a creation of a novel set of analogs that may be useful as a pharmacophore leading to a potential treatment option for cancer. A common molecular target for cancer inhibition is that of the Epidermal Growth Factor Receptor/Mitogen Activated Protein Kinase pathways, as inhibition of these proteins is associated with a decrease in cell viability. Estradiol-Triazole analogs were thus designed using a molecular modeling approach. Thirteen of the high scoring analogs were then synthesized and tested in-vitro on an ovarian cancer cell line (A2780) and colorectal cancer cell line (HT-29). The most active compound, Fz25, shows low micromolar activity in both the ovarian (15.29 ± 2.19 µM) and colorectal lines (15.98 ± 0.39 µM). Mechanism of action studies proved that Fz25 moderately arrests cells in the G1 phase of the cell cycle, specifically inhibiting STAT3 in both cell lines. Additionally, Fz57 shows activity in the colorectal line (24.19 ± 1.37 µM). Inhibition studies in both cell lines show inhibition against various proteins in the EGFR pathway, namely EGFR, STAT3, ERK, and mTOR. To further study their effects as therapeutics, Fz25 and Fz57 were studied against drug efflux proteins, which are associated with drug resistance, and were found to inhibit the ABC transporter P-glycoprotein. We can conclude that these estradiol-triazole analogs provide a key for future studies targeting protein inhibition and drug resistance in cancer.

Partial Agonistic Actions of Sex Hormone Steroids on TRPM3 Function.

Sex hormone steroidal drugs were reported to have modulating actions on the ion channel TRPM3. Pregnenolone sulphate (PS) presents the most potent known endogenous chemical agonist of TRPM3 and affects several gating modes of the channel. These includes a synergistic action of PS and high temperatures on channel opening and the PS-induced opening of a noncanonical pore in the presence of other TRPM3 modulators. Moreover, human TRPM3 variants associated with neurodevelopmental disease exhibit an increased sensitivity for PS. However, other steroidal sex hormones were reported to influence TRPM3 functions with activating or inhibiting capacity. Here, we aimed to answer how DHEAS, estradiol, progesterone and testosterone act on the various modes of TRPM3 function in the wild-type channel and two-channel variants associated with human disease. By means of calcium imaging and whole-cell patch clamp experiments, we revealed that all four drugs are weak TRPM3 agonists that share a common steroidal interaction site. Furthermore, they exhibit increased activity on TRPM3 at physiological temperatures and in channels that carry disease-associated mutations. Finally, all steroids are able to open the noncanonical pore in wild-type and DHEAS also in mutant TRPM3. Collectively, our data provide new valuable insights in TRPM3 gating, structure-function relationships and ligand sensitivity.

Mechanistic Investigation of Drug Supersaturation in the Presence of Polysorbates as Solubilizing Additives by Solution Nuclear Magnetic Resonance Spectroscopy.

The introduction of solubilizing additives has historically been an attractive approach to address the ever-growing proportion of poorly water-soluble drug (PWSD) compounds within the modern drug discovery pipeline. Lipid-formulations, and more specifically micelle formulations, have garnered particular interest because of their simplicity, size, scalability, and avoidance of solid-state limitations. Although micelle formulations have been widely utilized, the molecular mechanism of drug solubilization in surfactant micelles is still poorly understood. In this study, a series of modern nuclear magnetic resonance (NMR) methods are utilized to gain a molecular-level understanding of intermolecular interactions and kinetics in a model system. This approach enabled the understanding of how a PWSD, 17ß-Estradiol (E2), solubilizes within a nonionic micelle system composed of polysorbate 80 (PS80). Based on one-dimensional (1D) 1H chemical shift differences of E2 in PS80 solutions, as well as intermolecular correlations established from 1D selective nuclear Overhauser effect (NOE) and two-dimensional NOE spectroscopy experiments, E2 was found to accumulate within the palisade layer of PS80 micelles. A potential hydrogen-bonding interaction between a hydroxyl group of E2 and a carbonyl group of PS80 alkane chains may allow for stabilizing E2-PS80 mixed micelles. Diffusion and relaxation NMR analysis and particle size measurements using dynamic light scattering indicate a slight increase in the micellar size with increasing degrees of supersaturation, resulting in slower mobility of the drug molecule. Based on these structural findings, a theoretical orientation model of E2 molecules with PS80 molecules was developed and validated by computational docking simulations.

Safety and Effectiveness of F-18 Fluoroestradiol Positron Emission Tomography/Computed Tomography: a Systematic Review and Meta-analysis.

BACKGROUND: We conducted a pooled analysis of the diagnostic accuracy of F-18 fluoroestradiol (F-18 FES) positron emission tomography/computed tomography (PET/CT) assessing estrogen receptor expression of patients who have recurrent or metastatic breast cancer. METHODS: Two investigators and seven related experts (from the departments of nuclear medicine, hematological oncology, surgery, and evidence-based medicine) evaluated the effectiveness of F-18 FES PET/CT according to diagnostic accuracy and correlation with immunohistochemistry tests via systematic literature review, and safety according to test-related side effects. The present study was conducted in accordance with the Scottish Intercollegiate Guidelines (SIGN), and the Cochrane, and Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The SIGN tools were used for quality assessment. RESULTS: Of the 512 articles retrieved in the literature search, 8 were deemed to be eligible for inclusion. Results of the evaluation indicated that the F-18 FES PET/CT test was safe because patients who reported pain in the injection site in the analyzed articles are most likely to be caused by mechanical injury from needle injection not by administration of radioactive materials. Assessment of diagnostic accuracy based on data from seven studies revealed a pooled sensitivity and specificity of 0.86 and 0.85, respectively. CONCLUSION: As such, the test was evaluated to be a safe and effective and, considering the anatomical site where only invasive tests are possible, the test was deemed to have high clinical utility.

Electrochemical Microfluidic Paper-Based Aptasensor Platform Based on a Biotin-Streptavidin System for Label-Free Detection of Biomarkers.

Timely and rapid detection of biomarkers is extremely important for the diagnosis and treatment of diseases. However, going to the hospital to test biomarkers is the most common way. People need to spend a lot of money and time on various tests for potential disease detection. To make the detection more convenient and affordable, we propose a paper-based aptasensor platform in this work. This device is based on a cellulose paper, on which a three-electrode system and microfluidic channels are fabricated. Meanwhile, novel nanomaterials consisting of amino redox graphene/thionine/streptavidin-modified gold nanoparticles/chitosan are synthesized and modified on the working electrode of the device. Through the biotin-streptavidin system, the aptamer whose 5'end is modified with biotin can be firmly immobilized on the electrode. The detection principle is that the current generated by the nanomaterials decreases proportionally to the concentration of targets owing to the combination of the biomarker and its aptamer. 17ß-Estradiol (17ß-E2), as one of the widely used diagnostic biomarkers of various clinical conditions, is adopted for verifying the performance of the platform. The experimental results demonstrated that this device enables the determination of 17ß-E2 in a wide linear range of concentrations of 10 pg mL-1 to 100 ng mL-1 and the limit of detection is 10 pg mL-1 (S/N = 3). Moreover, it enables the detection of targets in clinical serum samples, demonstrating its potential to be a disposable and convenient integrated platform for detecting various biomarkers.