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losartan + HCTZ (Gizaar / Hyzaar / Cozaar plus)

✓ Approved

Merck & Co. · AGTR1 · 小分子

什么是 losartan + HCTZ？

losartan + HCTZ 是一种小分子，由Merck & Co.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Gizaar, Hyzaar, Cozaar plus
公司Merck & Co.
药物类别小分子
分子靶点AGTR1, SLC12A3
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Merck & Co.

作用机制

分子靶点

losartan + HCTZ 作用于 2 个分子靶点：

AGTR1angiotensin II receptor type 1 (HAT1R, AT1)
SLC12A3solute carrier family 12 member 3 (NCCT, NCC)
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

losartan + HCTZ 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 American journal of sports medicine2026-07-27

Platelet-Derived Growth Factor Synergistic Enhancement of Bone Marrow Stimulation for Enhanced Labral Repair and Functional Recovery in a Rat Bankart Model.

Mendiaz Feabie F, Vaish Bhavya B, Rifat Sumaiya S, Gray Nathan N et al.

Bone marrow stimulation (BMS) is used to treat intra-articular defects, such as articular cartilage defects or to facilitate healing of soft tissue repair; however, BMS yields inconsistent clinical outcomes, potentially due to the inefficient delivery of endogenous progenitor cells. Combining BMS with localized placement of platelet-derived growth factor (PDGF) would enhance in situ progenitor cell responses, leading to enhanced labral tissue repair and functional recovery in a rat model. Controlled laboratory study. A Bankart glenoid labral tear was created in the right shoulder of 50 adult rats. The animals were randomly divided into 5 groups: (1) healthy (baseline), (2) suture only (control), (3) suture + PDGF, (4) suture + BMS, and (5) suture + PDGF + BMS. Healing was assessed at 1.5 (n = 3), 3, and 8 weeks (n = 4). Baseline groups were included at 3 (n = 4) and 8 weeks (n = 5). At each timepoint, labral healing was evaluated by quantifying progenitor cell recruitment, tissue differentiation, and general morphology. Functional recovery was assessed weekly via gait analysis. BMS alone failed to elicit cell recruitment to the injured labral region. However, the combined BMS + PDGF treatment resulted in a 7-fold increase in progenitor cell accumulation at the tear site compared with BMS alone (27.46 ± 11.51 vs 3.5 ± 3.26 cells/0.01 mm2, respectively; P < .001). The combined group was characterized by increased chondrogenic differentiation, greater glycosaminoglycan intensity, and significantly lower Pauli score. Furthermore, gait analyses confirmed that the combined treatment yielded the most robust functional recovery. The synergistic application of BMS + PDGF provided a highly effective method for labral repair compared with isolated treatments, significantly enhancing progenitor cell recruitment, tissue regeneration, and functional recovery. This study identifies a novel repair technique that overcomes limitations of standard suture-only repair. This strategy offers a promising translational approach to improve outcomes in shoulder labral reconstruction.

PMID 42503616
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PubMedJournal of oral rehabilitation2026-07-25

Is Capsaicin Effective in Relieving the Symptoms of Burning Mouth Syndrome? A Systematic Review.

de Andrade Silva Ana Paula AP, Dos Santos Ian Wesley Rocha IWR, da Silva Zuleni Alexandre ZA, Frazão Deborah Ribeiro DR et al.

Burning Mouth Syndrome (BMS) is a type of chronic orofacial pain characterised by a burning sensation inside the mouth without an apparent cause. Capsaicin has been used to manage the symptoms of this syndrome, but there is still no consensus on its effectiveness. To assess whether capsaicin, when used topically or systemically, is able to alleviate the symptoms of BMS. An extensive search was carried out in seven databases and grey literature up to November 2025. There were no restrictions regarding the date or language of publication. The search resulted in 782 articles, of which 4 were included. The methodological quality of the studies was assessed using the Risk of Bias in Systematic Reviews (ROBIS) tool and the certainty of evidence was performed according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Regarding capsaicin administration, 3 studies used topical application and 1 used systemic application. Concentrations ranged from 0.000354% to 0.25%, three times a day, for 1-8 weeks. Regardless of the administration method, a reduction in patient-reported pain scores was observed. Risk of bias assessment showed that three randomised studies presented a moderate risk, while the only non-randomised clinical trial presented a critical risk. The overall certainty of the evidence was low or very low for the outcomes assessed. Evidence suggests that capsaicin is effective in relieving BMS symptoms. However, this result should be interpreted with caution due to the low quality of the evidence obtained to support its use.

PMID 42499217
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PubMedPrecision radiation oncology2026-07-25

Nomogram integrating MRI radiomics and white matter hyperintensity grading for predicting overall survival in patients with non-small cell lung cancer and brain metastases receiving whole-brain radiotherapy.

Ni Jianan J, Lu Yuefeng Y, Xu Haoli H, Xu Xuni X et al.

To develop and validate a nomogram integrating radiomic features, white matter hyperintensity (WMH) grading, and clinical factors for predicting overall survival (OS) in patients with non-small cell lung cancer (NSCLC) and brain metastases (BMs) receiving whole-brain radiotherapy (WBRT). One hundred and forty-nine patients with BMs were enrolled. A radiomic score (Rad-score) was developed based on features identified by univariate Cox regression and least absolute shrinkage and selection operator Cox modeling. WMH was graded using the Fazekas scale, into mild- and extensive-burden groups. Cox proportional hazard models incorporating different combinations of these features were developed and compared. A nomogram was constructed by integrating the Rad-score, WMH grade, and independent clinical variables, and its performance was evaluated using receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and calibration plots. Twelve radiomic features were identified. Both the Rad-score (hazard ratio (HR) = 1.072; P < 0.001) and WMH grade (HR = 2.420; P < 0.001) independently and significantly predicted OS. Significant improvements in model fit followed the inclusion of these variables (P < 0.01). The integrated nomogram outperformed the single-feature models, yielding area under the curves (AUCs) of 0.820, 0.900, and 0.889 for 1-, 2-, and 3-year OS, respectively, with a concordance index (C-index) of 0.706 (95% CI: 0.598-0.815). Calibration plots and DCA further supported the predictive accuracy and clinical utility. The radiomics- and WMH grading-based nomogram represents a potential prognostic tool for patients with NSCLC and BMs receiving WBRT.

PMID 42500423
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PubMedOncogene2026-07-25

RON receptor tyrosine kinase regulates abiraterone resistance in prostate cancer via the methylation-dependent and independent dual functions of DNMT1.

Wang Ke-Jie KJ, Wang Kai-Yun KY, Chen Si-Xi SX, Ma Yu-Tao YT et al.

Acquired resistance to the CYP17 inhibitor abiraterone is a critical challenge in the clinical treatment of metastatic prostate cancer; however, the mechanisms driving this resistance remain elusive. This study suggests that aberrant RON expression plays an important role in the development of acquired abiraterone resistance in prostate cancer cells. Increased RON expression was observed in most clinical tumor samples with an abiraterone-insensitive phenotype. In established prostate cancer cell lines, aberrant RON expression is associated with increased abiraterone resistance and enhanced migratory activity. These effects are mediated through dual regulatory functions of DNA methyltransferase 1(DNMT1): RON-mediated regulation of the canonical methyltransferase activity of DNMT1, which inhibits receptor-interacting protein kinase 3(RIPK3) expression, leading to increased cellular survival with impaired RIPK3/MLKL-involved cell death signaling. Concurrently, RON-driven non-methyltransferase activity of DNMT1 is associated with altered mitochondrial functions, thereby potentially enhancing cellular migration. The multi-kinase inhibitor BMS-777607, which has activity against RON, in combination with abiraterone suppressed both proliferation and metastasis in abiraterone-resistant xenograft tumors. The discovery of the RON-DNMT1-RIPK3 functional axis and the association between RON-DNMT1 and mitochondrial bioenergetic activity in this work strongly suggest RON as a critical driver of abiraterone resistance and a potential therapeutic target in prostate cancer.

PMID 42498731
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PubMedThe American journal of case reports2026-07-25

A 46-Year-Old Man Presenting With Chest Pain Due to Apical Hypertrophic Cardiomyopathy (Yamaguchi Syndrome) Diagnosed by Multimodal Cardiac Imaging.

Passos Mauro de Deus MD, de Araújo Daniel Lopes Marques DLM, Mariano Lucas de Ávila LÁ, Ferreira Dilson Palhares DP et al.

BACKGROUND Apical hypertrophic cardiomyopathy (ApHCM), also known as Yamaguchi syndrome, is a rare variant of hypertrophic cardiomyopathy characterized by the thickening of the left ventricle apex (>15 mm) and giant negative T-waves on the precordial leads of the electrocardiogram (ECG), which can present symptoms and electrocardiographic changes that mimic acute coronary syndrome (ACS). This report describes the case of a 46-year-old man with chest pain and giant T-wave inversion on ECG, requiring multimodal cardiac imaging to diagnose ApHCM (Yamaguchi syndrome) and exclude the diagnosis of coronary artery occlusion and myocardial infarction. CASE REPORT We report the case of a 46-year-old man who presented to the Emergency Department with typical chest pain. His ECG revealed significant alterations highly suggestive of ACS, including ST-segment depression and giant negative T-waves (>10 mm) in leads V4-V6. Despite this presentation, serial high-sensitivity troponin levels remained consistently within the normal range. Coronary computed tomography angiography (CCTA) revealed non-obstructive coronary arteries but indicated increased apical left ventricular (LV) wall thickness with characteristic trabeculation, raising suspicion for ApHCM. Transthoracic echocardiography (TTE) confirmed pronounced apical LV thickening (20 mm) and a reduced Global Longitudinal Strain (GLS) of -14.3%. Cardiac magnetic resonance (CMR) imaging provided a definitive diagnosis, identifying significant apical hypertrophy with systolic obliteration of the LV cavity and quantifying multifocal myocardial fibrosis at 6% of the LV mass. The patient's symptoms improved significantly with medical therapy, including losartan, metoprolol, and trimetazidine. CONCLUSIONS This case highlights the critical diagnostic challenge of ApHCM masquerading as ACS. It underscores the indispensable role of a multimodal imaging approach-integrating ECG, TTE, CCTA, and CMR-for an accurate diagnosis, particularly for identifying underlying myocardial fibrosis and guiding appropriate patient management.

PMID 42499159
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PubMedPhytomedicine : international journal of phytotherapy and phytopharmacology2026-07-25

Discovery of natural product-derived rosavin as a programmed death-ligand 1 inhibitor for cancer immunotherapy.

Zou Wei W, Li Tianle T, Plewka Jacek J, Song Xiaoxiong X et al.

Given the limitations of the existing monoclonal antibody (mAb)-based therapies, more efficient and safer small-molecule-based checkpoint therapies targeting the programmed cell death-1 (PD-1) / programmed cell death ligand-1 (PD-L1) axis are gaining growing attention and urgently required. To identify a novel PD-L1 small-molecule inhibitor from natural products and systematically evaluate its antitumor activity, mechanism of action, and potential biomarkers. Based on the co-crystal structure of PD-L1 with BMS-202 (PDB ID: 5J89), molecular docking was employed for high-throughput virtual screening of 16,563 natural products. The binding affinity of candidate compounds to PD-L1 protein was validated through microscale thermophoresis (MST), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assays and nuclear magnetic resonance (NMR). The blockade of PD-1/PD-L1 interaction was assessed using homogeneous time-resolved fluorescence (HTRF), NFAT-Luc luciferase reporter gene system, and cell membrane PD-1 binding assays. In vivo antitumor efficacy was systematically assessed in humanized PD-L1 knock-in B16F10 and MC38 tumor-bearing mouse models. The mechanism of action was investigated using RNA-seq transcriptomics, flow cytometry, and immunofluorescence staining. Finally, response mechanisms and potential biomarkers were systematically analyzed by comparing differential responses across distinct tumor models. Through high-throughput virtual screening, we identified rosavin as a small molecule with a novel scaffold that targets PD-L1, exhibiting the unusual small-molecule property of inhibiting PD-L1 without inducing its dimerization. Rosavin demonstrated significant antitumor activity in vivo by promoting antitumor immunity through enhancing CD8+ T cell activation, consistent with the effects of PD-L1/PD-1 blockade. Notably, rosavin was particularly effective for fighting against tumor progression in microsatellite instability-high (MSI-H) solid tumors and robustly strengthened the expression levels of CXCL9 and CXCL10 in tumors, which may serve as potential biomarkers for predicting responsiveness to rosavin-mediated PD-1/PD-L1 blockade. Rosavin serves as a privileged novel and unexpected scaffold for designing potent PD-1/PD-L1 modulators, offering promising candidates for cancer immunotherapy.

PMID 42497523
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