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metoprolol ER + hydrochlorothiazide (Selopress Zok / Dutoprol)

✓ Approved

AstraZeneca UK Limited · ADRB1 · 小分子

什么是 metoprolol ER + hydrochlorothiazide？

metoprolol ER + hydrochlorothiazide 是一种小分子，由AstraZeneca UK Limited研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Selopress Zok, Dutoprol
公司AstraZeneca UK Limited
药物类别小分子
分子靶点ADRB1
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, AstraZeneca UK Limited

作用机制

分子靶点

metoprolol ER + hydrochlorothiazide 作用于 1 个分子靶点：

ADRB1adrenoceptor beta 1 (B1AR, RHR)
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

metoprolol ER + hydrochlorothiazide 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
Vascular disordersHypertension✓ Approved

相关研究文献

PubMedThe Journal of dairy research2026-07-27

Impact of farm- and cow-related factors on milk coagulation properties in Estonian Native and Estonian Red breeds.

Henno Merike M, Sats Andres A, Kaart Tanel T, Jõudu Ivi I et al.

This study evaluated the relative importance of farm- and cow-related factors affecting milk coagulation properties in commercial and native cattle breeds exposed to different housing and management systems. The study included 86 Estonian Red (ER) and 132 Estonian Native (EN) cows from 12 single-breed and 3 dual-breed dairy farms; farm characteristics and management practices were assessed through on-site visits and manager interviews. Individual milk samples were collected every second month during the morning test-day milking from November 2020 to January 2022 and analysed for composition, coagulation properties, casein micelle size distribution, fat globule size distribution and κ-CN genetic variants. The results showed no significant differences in milk coagulation properties between the two breeds. Among cow-related factors, curd firmness in both breeds was most strongly associated with milk protein content (ER: r = 0.23; EN: r = 0.19), casein content (ER: r = 0.30; EN: r = 0.27) and the casein-to-protein ratio (ER: r = 0.17; EN: r = 0.28). The κ-casein genotype affected both the rennet coagulation time and curd firmness in both breeds. The genetic effect of the sire was greater in the ER breed. Separate breed-specific models showed that the proportion of variance in milk coagulation traits explained by farm effects was approximately three to four times higher in EN cows compared to ER cows. These findings suggest that strategies for improving milk coagulation should be tailored to the production context.

PMID 42504716
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PubMedLasers in medical science2026-07-27

Comparison of Laser and Conventional Root Canal Disinfection Protocols in an dual-biofilm in-vitro model.

Wang Jingyi J, Li Wenxu W, Lan Wanxin W, Ye Ling L et al.

To compare the effect of laser and other four traditional root canal disinfection methods on the removal of microorganisms in the root canal of refractory periapical periodontitis. 155 single-canal premolars were made into 13 mm long standard roots, infected with E. faecalis and C. albicans, randomly divided into five groups, and treated with A: lateral syringe irrigation group; B: ultrasonic irrigation group; C: sonic irrigation group; D: Er∶ YAG laser in SWEEPS mode group; E: photodynamic therapy group for root canal irrigation. Root canal samples were collected with 25# K files before and after irrigation. The irrigation effectiveness was quantitatively analyzed by flat colony counting method and observed by scanning electron microscope and confocal laser scanning electron microscope. The Er∶ YAG laser group had the highest clearance efficiency for E. faecalis (P < 0.05), and the ultrasonic irrigation effect was lower than that of Er∶ YAG laser (P < 0.05), while there was no difference between that of sonic irrigation group, photodynamic therapy group and lateral syringe irrigation group (P > 0.05). These five methods were all able to clear C. albicans well without significant difference (P > 0.05). SEM and confocal laser SEM showed that Er∶ YAG laser groups were more effective at removing smear layers and total bacteria. The performance of Er∶ YAG laser eliminating E. faecalis and C. albicans and the smear layer was found superior in the root canal of refractory apical periodontitis. It is recommended to employ Er∶ YAG laser for subsequent root canal decontamination following root canal preparation. Clinical trial number: Not applicable.

PMID 42507243
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PubMedDentistry journal2026-07-27

The Impact of Limited Access to Dental Care on Emergency Room Service Utilization: A Study of Primary Healthcare in a Rural Inland Region of Portugal.

Prada Alexandra A, Galvão Ana A, Monteiro-Soares Matilde M, Dias Cláudia Camila CC

Background/Objectives: This cross-sectional observational study investigated factors associated with emergency room (ER) utilization for dental pain in a rural inland region of Portugal. The main objective was to examine the relationship between access to dental care, sociodemographic characteristics, oral health behaviors, and clinical outcomes with the use of emergency room services for dental problems. Methods: The study sample comprised 423 participants from the districts of Bragança and Vinhais, in Trás-os-Montes, aged 4 to 90 years, who attended their first dental medicine consultation. Participants completed a structured questionnaire addressing sociodemographic characteristics, general health, oral health behaviors, and dental prosthetic use, and underwent oral examination for assessment of the Decayed, Missing, and Filled Teeth (DMFT) index. Associations with reported ER utilization due to toothache were analyzed using Fisher's exact test and the Mann-Whitney U test. Results: Overall, 28.4% of participants reported having visited the ER due to dental pain, and most cases were managed with medication followed by discharge. ER utilization was significantly associated with behavioral risk factors such as smoking, as well as poorer oral hygiene practices, including less frequent tooth brushing. In addition, participants who sought ER care presented higher DMFT scores, indicating a greater burden of untreated dental decay and tooth loss. Conclusions: These findings suggest that limited preventive dental care and unfavorable oral health behaviors are associated with to avoidable ER visits for dental pain in rural settings. This study reinforces the need to strengthen access to preventive oral health services and to advance the integration of dental care into Portugal's National Health Service (SNS), particularly in underserved inland regions.

PMID 42505719
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PubMedJournal of cell science2026-07-27

Vimentin intermediate filaments support autophagosome biogenesis at ER-endosome contact sites in response to starvation.

Frenger Quentin Q, Amiri Czajkowski Dobrawa D, Alemany Carla C, Lecoeuche Damiana D et al.

Macroautophagy (autophagy) is a fundamental catabolic process requiring the biogenesis of the autophagosome to support cell survival during stress. Although the roles of F-actin and microtubule cytoskeleton in autophagy are well established, the contribution of intermediate filaments (IFs) remains poorly understood. Here, we investigated the role of the type III IF vimentin in supporting the early steps of starvation-induced autophagy. We demonstrate that starvation triggers a rapid, perinuclear compaction of vimentin IFs, which showed enhanced overlap with the endoplasmic reticulum (ER) and correlated with transient vimentin phosphorylation at serine 56. We reveal that autophagic proteins accumulate at the vimentin-ER interface, physically connecting the autophagosome biogenesis machinery to the vimentin IF network. Knockout or pharmacological perturbation of vimentin-IFs dynamics using withaferin-A significantly impairs starvation-induced autophagic flux. Mechanistically, we reveal that vimentin IFs are essential coordinators for the mobilization of endosome-ER membrane contact sites (EERCS), a crucial hub for autophagosome nucleation. Together, our findings uncover a novel role for vimentin IFs as a dynamic cytoskeletal coordinator that spatially organizes membrane contact sites to promote the efficient initiation of autophagosome biogenesis in response to nutrient stress.

PMID 42504778
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PubMedCombinatorial chemistry & high throughput screening2026-07-27

Pinoresinol Diglucoside Potentiates α-lipoic Acid-mediated Attenuation of ROS-induced Cell Injury by Affecting Oxidative and ER Stress in NIH-3T3 Fibroblasts.

Zhang Yan Y, Yang Lian L, Wang Han H, Cui Ximao X et al.

A Large amount of ROS generated by radiotherapy leads to radiationinduced skin injury (RISI), but drugs that can treat RISI are still limited in the clinic. An oxidative-stress model was established by inducing NIH-3T3 cells with H2O2, and the protective effects of α-lipoic acid (α-LA) combined with pinoresinol diglucoside (PDG) on H2O2-induced cell injury were evaluated. Cell viability was assessed by the CCK-8 assay. Oxidative stress was evaluated by detecting the expressions of oxidative and antioxidant factors. Endoplasmic reticulum (ER) stress was evaluated by detecting ER stress-associated biomarkers. A Western blot was performed to assess the expression of the indicated proteins. Co-administration of α-LA and PDG significantly abolished H2O2-induced cell death and oxidative stress in NIH-3T3 fibroblasts, including changes in cell viability, ROS generation, and the expressions of oxidative and antioxidant factors. Mechanistically, PDG enhanced the ability of α-LA to suppress H2O2-induced JNK activation and PARP cleavage. PDG also potentiated α-LA-mediated upregulation of AKT activation, as well as the expression of Nrf2 in H2O2- treated NIH-3T3 fibroblasts. Moreover, PDG strengthened the inhibitory effect of α-LA on H2O2-induced ER stress in these cells. The present study investigated the protective effects of α-LA and PDG against ROSinduced injury in NIH-3T3 fibroblasts, and further investigations using in vivo models of RISI will be performed in future studies. This study revealed that co-administration of α-LA and PDG exerted the protective effects on H2O2-induced cell injury by reducing oxidative stress and ER stress, suggesting a promising therapeutic strategy for the treatment of RISI in the future.

PMID 42504717
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PubMedJournal of medicinal chemistry2026-07-27

A Structure-guided Active Site Affinity Ligand Unmasks a Stress-Sensitizing Role for BLVRB in the Endoplasmic Reticulum.

Thekke Veedu Rahul Raghavan RR, Sheriff Jawaad J, Nesbitt Natasha M NM, Marchenko Natalia N et al.

Biliverdin IXb reductase (BLVRB) is an NAD(P)H-dependent oxidoreductase that regulates hematopoiesis and cellular stress, although measurement and sequelae of cellular active site engagement remain undefined. Here, we report the development of a nanoBRET platform enabling real-time BLVRB target engagement. Structure-guided design and chemical syntheses of BODIPY-labeled pyrazolopyrimidinone inhibitors generate cell-permeable acceptor ligands retaining high-affinity binding to the BLVRB active site. In vitro and cellular nanoBRET assays demonstrate specific energy transfer and inform equilibrium binding affinities, target engagement, and residence time analyses for diverse panels of BLVRB inhibitors. NanoBRET demonstrates strong concordance with enzymatic inhibition and is validated by crystallographic structures confirming active site binding. Live-cell imaging using affinity ligands reveals predominant endoplasmic reticulum localization and transient suppression of the ER stress chaperone GRP78/BiP without eliciting a canonical unfolded protein response. These studies inform a redox-regulated mechanism whereby spatiotemporal BLVRB active site engagement functions as a stress sensitizer modulating ER proteostasis.

PMID 42505148
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