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estradiol (E2III)

✓ Approved

Johnson & Johnson Services, Inc. · ESR1 · 小分子

什么是 estradiol？

estradiol 是一种小分子，由Johnson & Johnson Services, Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Transdermal。

药物档案

商品名E2III
公司Johnson & Johnson Services, Inc.
药物类别小分子
分子靶点ESR1
给药途径Transdermal
状态Approved
来源： ClinicalTrials.gov, Johnson & Johnson Services, Inc.

作用机制

分子靶点

estradiol 作用于 1 个分子靶点：

ESR1estrogen receptor 1 (ER, ESR)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

estradiol 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Surgical and medical proceduresHormone replacement therapy✓ Approved

相关研究文献

PubMedApplied and environmental microbiology2026-08-05

Characterization of successive ortho-methyl oxidation of the priority pollutant 2,4-xylenol by a Rieske oxygenase system in Pseudomonas putida NCIMB 9866.

Meng Haiqin H, Pan Shun S, Chai Zening Z, Zhou Lixiang L et al.

The catabolism of the priority environmental pollutant 2,4-xylenol requires bacteria to oxidize its ortho-methyl group. Its exact biochemical mechanism is uncharacterized until now. In this study, we resolve key metabolic bottlenecks in Pseudomonas putida NCIMB 9866. We demonstrate that functionally redundant Rieske oxygenase systems ensure the robust ortho-methyl oxidation of 2,4-xylenol. On the para-methyl oxidation branch, PchA2 acts as the main aldehyde dehydrogenase. It shows significantly higher catalytic efficiency than the previously reported PchA. Additionally, we characterized PmmA1B1, a newly identified three-component Rieske oxygenase system responsible for ortho-methyl oxidation, which is supported by two redundant isoenzymes (PmmA2B2 and PmmA3B3), by recruiting the shared endogenous ferredoxin Orf05169. The PmmA1B1-Orf05169 system catalyzes the successive oxidation of the ortho-methyl group of 4-hydroxy-3-methylbenzoate to a carboxyl group, yielding the high-value pharmaceutical precursor 4-hydroxyisophthalate. Structural and kinetic data revealed that the active site architecture of PmmA1 enables efficient successive oxidation, distinguishing it from isoenzymes PmmA2B2 and PmmA3B3 that, when coupled with Orf05169, catalyze only incomplete oxidation. Overall, these results complete the 2,4-xylenol catabolic pathway by defining the enzymes required for both para- and ortho-methyl oxidation. They also reveal functional redundancy as an adaptive feature of microbial aromatic degradation and establish Rieske oxygenases as biocatalysts for converting methylated aromatic pollutants into value-added chemicals.IMPORTANCEMethylated aromatics like 2,4-xylenol pose ongoing environmental risks and are primary targets for bioremediation. We know how bacteria break down many simple aromatics, but the precise ways that enzymes bypass the steric and electronic hurdles of hindered methyl groups remain unclear. In this study, we characterized a novel three-component Rieske oxygenase, PmmA1B1-Orf05169, capable of a rare successive oxidation that turns an ortho-methyl group directly into a carboxyl group. We also found parallel, redundant oxygenase pathways that protect the bacterium's ability to degrade 2,4-xylenol during environmental stress or genetic loss. This discovery not only completes the metabolic map of 2,4-xylenol but also provides a robust biocatalytic tool for the green synthesis of 4-hydroxyisophthalate, a high-value pharmaceutical precursor.

PMID 42554493
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PubMedMolecular psychiatry2026-08-05

Psychedelics and women's mental health: the effects of female sex hormones on psychedelics' efficacy and tolerability.

Kuypers Kim P C KPC, Mason Natasha L NL, Carlier Aurelie A, Totomanova Iva I et al.

Women experience a disproportionate burden of affective and stress-related disorders, with symptom variability shaped by endocrine transitions across the menstrual cycle, pregnancy, postpartum, and menopause. Although psychedelic-assisted therapies are increasingly investigated for these conditions, hormonal state represents a largely unaccounted determinant of variability in exposure, response, and tolerability. This narrative review synthesizes clinical, preclinical, and neuroimaging literature to examine how estradiol and progesterone modulate psychedelic pharmacokinetics, pharmacodynamics, and large-scale brain network dynamics implicated in psychiatric disorders. At the pharmacokinetic level, sex hormones influence gastrointestinal physiology (including gastric pH and transit time), tissue distribution via body composition and fluid balance, and hepatic metabolism through modulation of CYP450 enzymes, particularly CYP3A4 and CYP2D6, which are key pathways for LSD and psilocin biotransformation. Renal elimination plays a comparatively minor role. These processes may collectively alter onset, peak concentration, and systemic exposure across hormonal states, although direct human data for psychedelics remain absent. At the pharmacodynamic level, estradiol and progesterone regulate serotonergic signaling, including dynamic modulation of 5-HT2A receptor density and binding across the menstrual cycle and reproductive lifespan. Platelet, PET, and SPECT studies indicate higher 5-HT2A availability in low-progesterone states and reduced availability in progesterone-dominant or hypoestrogenic states. Beyond 5-HT2A, psychedelics engage broader serotonergic, glutamatergic, and GABAergic systems that converge on prefrontal-limbic, default mode, and salience networks, circuits that are also dysregulated across depression, anxiety, and trauma-related disorders. Hormonal fluctuations may further influence subjective intensity and tolerability, with potential sensitivity peaks in the early-mid follicular and early luteal phases, although direct evidence remains limited. Together, these findings suggest sex hormones as a mechanistically plausible, clinically relevant but under-characterized source of variability in psychedelic treatment response.

PMID 42552418
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PubMedPhysical chemistry chemical physics : PCCP2026-08-05

Positional isomerism-driven solvatochromism and excited-state behavior in ortho- and para-hydroxy bromobenzylidene Schiff bases: a combined experimental and DFT investigation.

Gülseven Sıdır Yadigar Y, Berber Halil H, Sıdır İsa İ

This study presents a comprehensive investigation of how hydroxyl positional isomerism governs the solvatochromic response and excited-state behavior of bromobenzylidene Schiff base derivatives. Two structurally related isomers, SB-oOH and SB-pOH, were synthesized and systematically analyzed using combined spectroscopic and quantum chemical approaches. The results reveal a striking contrast in photophysical behavior arising solely from the substituent position. SB-oOH exhibits weak solvent-dependent spectral shifts, attributed to intramolecular O-H⋯N hydrogen bonding that restricts π-electron delocalization and stabilizes a localized excitation (LE) state. In contrast, SB-pOH displays pronounced positive solvatochromism, large Stokes shifts, and strong solvent sensitivity, consistent with increased polarizability and stronger light-matter interaction, whereas SB-oOH maintains a more rigid and less responsive electronic structure. Quantitative solvatochromic analysis using linear solvation energy relationship (LSER) models demonstrates that SB-oOH is primarily influenced by nonspecific dielectric interactions, while SB-pOH is strongly governed by both solvent polarity and hydrogen-bonding effects. Theoretical calculations based on density functional theory (DFT) and time-dependent DFT (TD-DFT) support these findings, revealing enhanced HOMO-LUMO separation, a reduced energy gap, and increased electronic delocalization in the para-substituted system. Furthermore, optical band gap and refractive index analyses confirm that the enhanced ICT characteristic of SB-pOH, as supported by the combined experimental and theoretical results, is consistent with increased polarizability and stronger light-matter interactions, whereas SB-oOH maintains a more rigid and less responsive electronic structure. Thus, this study demonstrates that subtle structural variation through hydroxyl positional isomerism can induce profound changes in electronic structure and excited-state dynamics. These findings provide a clear structure-property relationship and offer a rational strategy for designing Schiff base-based functional materials with tunable optoelectronic properties. This study highlights positional isomerism as an effective molecular design tool for controlling excited-state processes.

PMID 42554189
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PubMedBiology open2026-08-05

The neurotrophin DNT-2 via the Toll-2 receptor regulates neuronal survival and morphology during visual system development.

Alshamsi Naser N, Rojo-Cortés Francisca F, Fernandes Jervis J, Perrett Callum C et al.

During vertebrate nervous system development, neurons are produced in excess and those receiving neurotrophin ligands are maintained, enabling neural circuit establishment. An apoptotic wave sweeps across the Drosophila pupal visual system, but whether neurotrophins participate in forming adult visual circuits remained unknown. Here, we show that Drosophila Neurotrophin-3 (spz-3) and DNT-2 (spz-5) are expressed in retinal cells and medulla neurons, and Toll receptors across the visual system. Using loss and gain of function conditions for DNT-3 (spz-3) and DNT-2 (spz-5) we show that they both can, and are required to, promote cell survival. Importantly, genetic interaction data show that DNT-2 can function together with Toll-2. DNT-2 neurons were identified as medulla Mi1 neurons that connect to lamina L1 neurons expressing Toll-2. Loss of function for DNT-2 or Toll-2 induced apoptosis, and Toll-2 knock-down prevented the pro-survival function of DNT-2. DNT-2 over-expression resulted in excess Toll-2 neurons, whereas most Toll-2 neurons were lost in DNT-2 mutants. Furthermore, DNT-2 and Toll-2 were required for appropriate L1 axonal columnar organisation and dendritic morphology. Altogether, evolutionarily conserved neurotrophin family ligands control neuronal number through Toll receptors during visual circuit development in Drosophila.

PMID 42552905
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PubMedFrontiers in immunology2026-08-05

Plasma levels of soluble Flt-1 and Tie-2 correlate with neovascularization in human carotid atherosclerotic plaques - a pilot study.

Zamani Mahtab M, Skagen Karolina K, Lindberg Beate B, Bjerkeli Vigdis V et al.

To determine whether circulating soluble Flt-1 (sFlt-1) and soluble Tie-2 (sTie-2) are associated with intraplaque neovascularization (IPN) in human carotid atherosclerotic plaques. Forty-four patients with ≥50% carotid stenosis underwent conventional carotid ultrasound and superb microvascular imaging (SMI); 29 had plasma collected and 11 provided carotid endarterectomy specimens for histology. IPN was quantified as neovessel counts in 2-minute SMI cine loops and as microvessel counts in excised plaques. Plasma VEGF-A/B/C/D, Ang-2, sFlt-1, and sTie-2 were measured by immunoassays. Public single-cell RNA-seq data from human carotid plaques were interrogated to map FLT1, TEK, VEGFA, ANGPT1, and ANGPT2 expression to specific plaque cell populations. IPN was detected in 33/44 (75%) patients, with 0-16 neovessels on SMI (median 4). Plasma sFlt-1 correlated with SMI neovessel counts (r=0.42, p=0.030), with a similar trend for sTie-2 (r=0.37, p=0.057), whereas VEGF-A/B/C/D and Ang-2 showed no significant relationships. In the surgical subgroup, histological neovessel counts correlated with sFlt-1 (r=0.65, p=0.030) and SMI neovessel count (r= 0.68, p =0.02) but not sTie-2. sFlt-1 and sTie-2 correlated with BMI (and sTie-2 also with age), yet log-sFlt-1 remained independently associated with SMI-derived neovessel counts after adjustment for age and BMI (B = 13.24, 95% CI 0.17-26.30, p=0.047; R²=0.18), while sTie-2 was not. No significant associations were observed between IPN or sFlt-1/sTie-2 and lipid profile, CRP, leukocyte counts, or other conventional risk factors. Single-cell transcriptomics showed FLT1 and ANGPT2 broadly expressed across endothelial, smooth-muscle, and myeloid clusters, with TEK largely confined to endothelial cells and ANGPT1 to smooth-muscle cells, supporting local activation of VEGF-FLT1 and Ang-TEK/Tie-2 signaling within plaques. In this pilot study, higher plasma sFlt-1, and, to a lesser degree sTie-2, correlated with carotid IPN on SMI and histology, independent of age and BMI. These findings suggest that soluble VEGF- and Ang/Tie-2-receptor pathways may serve as circulating, context-sensitive markers of intraplaque angiogenesis and plaque vulnerability, meriting evaluation in larger longitudinal cohorts.

PMID 42553160
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PubMedDiseases of the colon and rectum2026-08-05

Trends in the Utilization of Two-Stage Versus Three-Stage Ileal Pouch Anal Anastomosis Among Privately Insured Patients With Ulcerative Colitis in the USA, 2007 to 2023.

Taylor Kathryn K KK, Kin Cindy J CJ, Kirilcuk Natalie N NN, Morris Arden M AM et al.

Ileal pouch anal anastomosis can be performed via 2- and 3-stage techniques, with similar short- and long-term clinical outcomes. 2-stage ileal pouch anal anastomosis became the predominant approach in the 2000s; whether this trend has continued remains unknown. To compare trends in the utilization of 3-stage, traditional 2-stage, and modified 2-stage IPAA for ulcerative colitis as well as markers of disease severity over time. Retrospective cohort. Privately insured patients from an administrative database. Non-elderly adults with a diagnosis of ulcerative colitis who underwent ileal pouch anal anastomosis between 2007 and 2023 and remained enrolled in their insurance plan for ≥ 6 months after surgery. Proportion of patients undergoing 3-stage, traditional 2-stage, and modified 2-stage ileal pouch anal anastomosis; annualized change in disease severity at the time of ileal pouch anal anastomosis creation. Four thousand thirty-nine patients underwent IPAA during the study period (2,179 traditional 2-stage; 1,107 3-stage; and 753 modified 2-stage). The proportion of patients undergoing a traditional 2-stage IPAAs decreased steadily (1.3% points per year [95% CI -1.7 to -0.9]) with a commensurate rise in both 3-stage (0.3% points per year [95% CI -0.02-0.7]) and modified 2-stage operations (0.9% points per year [95% CI 0.6-1.2]). Patients undergoing 3-stage or modified 2-stage IPAA had a more rapid increase in exposure to advanced therapies in the year before surgery (+ 2.9 vs + 2.0% points). Limitations: potential misclassification, generalizability. More patients are undergoing 3-stage and modified 2-stage operations than traditional 2-stage ileal pouch anal anastomosis. This shift parallels an increase in multiple markers of disease severity at IPAA creation, especially exposure to advanced therapies. See Video Abstract.

PMID 42554159
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