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isosorbide dinitrate + hydralazine (hydralazine + ISDN / BiDil / ISDN + hydralazine)

✓ Approved

Arbor Pharmaceuticals, LLC · CACNA1C · 小分子

什么是 isosorbide dinitrate + hydralazine？

isosorbide dinitrate + hydralazine 是一种小分子，由Arbor Pharmaceuticals, LLC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hydralazine + ISDN, BiDil, ISDN + hydralazine
公司Arbor Pharmaceuticals, LLC
药物类别小分子
分子靶点CACNA1C
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Arbor Pharmaceuticals, LLC

作用机制

分子靶点

isosorbide dinitrate + hydralazine 作用于 1 个分子靶点：

CACNA1Ccalcium voltage-gated channel subunit alpha1 C (CACNL1A1, CACNA1C-IT2)
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

isosorbide dinitrate + hydralazine 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
Cardiac disordersCardiac failure✓ Approved

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Nuciferine ameliorates cognitive impairment and insulin resistance in T2DM by targeting the insulin receptor and activating PI3K/AKT signaling.

Zheng Miao M, Wang Can C, Liu Jiayi J, Xia Yi Y et al.

Insulin resistance is a hallmark of type 2 diabetes (T2DM) and can increase the risk of cognitive impairment, including Alzheimer's disease. Nuciferine, an alkaloid derived from lotus leaves, shows neuroprotective effects. This study investigated nuciferine's protective role in T2DM-induced cognitive impairment (T2DM-CI) and its mechanisms. Mouse models were created using high-fat diets and streptozotocin, along with high glucose-induced HT-22 cells. Nuciferine reduced blood glucose, improved cognitive function, and mitigated glial cell activation, neuron and synapse loss in T2DM mice. It enhanced insulin signaling by increasing protein levels of IR, IRS1, and IGF-1R, reversing PI3K and AKT phosphorylation, inhibiting GSK3β activity, and reducing hyperphosphorylated Tau in HT-22 cells and T2DM mice. mRNA levels of these molecules matched their protein levels. Further studies revealed that nuciferine directly interacts with IR, knocking out IR abolished its effects on the PI3K/AKT pathway. Thus, nuciferine activates the PI3K/AKT pathway via IR, improving insulin resistance and slowing T2DM-CI progression.

PMID 42285687
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PubMedBMJ military health2026-06-13

Antimicrobial resistance and insecticide resistance co-occurrence in synanthropic flies and their implications for military health in large-scale combat operations.

Stoops Craig A CA, Smith Hunter Jackson HJ, Pitzer Jimmy B JB, Milan Neil F NF et al.

Disease and non-battle injuries (DNBI) continue to cause more casualties among military personnel than combat-related injuries during armed conflict. Modern US Force Health Protection programmes have successfully reduced DNBI and infectious disease rates through comprehensive preventive measures. However, the anticipated return to large-scale combat operations (LSCO), which are characterised by high troop concentrations, degraded sanitation and intense operational tempo, will create conditions favourable for vector proliferation and subsequent pathogen transmission. Emerging evidence underscores a dual biological threat: antimicrobial-resistant (AMR) pathogens and insecticide-resistant (IR) synanthropic flies capable of harbouring and transmitting these organisms. This manuscript examines the historical context of DNBI control, the rise of AMR and IR as intersecting threats, and case examples from Iraq and Taiwan illustrating operational challenges. We propose an integrated surveillance and response framework to address AMR-IR convergence that will help protect deployed forces in future LSCO environments.

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PubMedGenomics2026-06-13

Evolocumab protects mice from radiation-induced damage by affecting hematopoietic cell lineage.

Gan Yuhan Y, Zhou Jiawei J, Li Bendong B, Huang Daqian D et al.

The hematopoietic system is extremely sensitive to ionizing radiation(IR) and is easily damaged after exposure. Recent studies [1, 2] have shown that hematopoietic lineage differentiation may play a key role in Ionizing radiation -induced acute injury. C57BL/6 mice matched for age, sex and weight were randomly grouped and intraperitoneal injected with PBS, Evolocumab (80.0 mg/kg) or MMP9-IN (20.0 mg/kg). Survival time, body weight, pathology, hematopoietic cell differentiation changes and organoids of the mice after IR (10.0 Gy) were compared, and the mechanism of action in tissues was verified by transcriptome sequencing. Ionizing radiation can inhibit hematopoietic cell lineage differentiation and affect cholesterol metabolism. The expression of the Pcsk9 gene was significantly upregulated after IR. Treatment with a Pcsk9 monoclonal antibody (Evolocumab) exerted significant radioprotective effects, including improving the survival rate of irradiated mice, reducing body weight loss, preserving the integrity of the bone marrow cavity, and promoting cellular proliferation. Flow cytometric analysis showed that Evolocumab significantly increased hematopoietic precursor cells and hematopoietic stem cells and promoted their differentiation into ST-LSKs and MPPs. In addition, the proportions of CMPs and GMPs were increased, whereas the proportion of MEPs was decreased. RNA sequencing results suggested that the IR-induced downregulation of Cd3e within the hematopoietic cell lineage pathway could be rescued by Evolocumab, which was further validated at the cellular level. CD3e is a T-cell-associated marker, and Evolocumab treatment was associated with an increased proportion of CD3e+ T cells. Analysis of previously reported hematopoiesis-related factors [3-5] indicated that Evolocumab markedly upregulated Mmp9 expression. Correlation analysis revealed that Pcsk9 was negatively correlated with Cd3e, whereas Cd3e was positively correlated with Mmp9. Following ionizing radiation, Mmp9 knockout (Mmp9 KO) mice exhibited reduced survival compared with wild-type mice. Moreover, in wild-type mice, administration of an MMP9 inhibitor (MMP9-IN) attenuated the radioprotective effects of Evolocumab, indicating that Mmp9 contributes to Evolocumab-mediated radioprotection. Evolocumab exerts a positive effect on promoting the proliferation and differentiation of hematopoietic stem cells against IR-induced hematopoietic system injury, with its protective mechanism likely involving the activation of hematopoietic cell lineages to upregulate CD3e+ T cells and Mmp9 expression.

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PubMedCurrent problems in diagnostic radiology2026-06-13

Awareness, discussion, and understanding of interventional radiology Procedures among non-interventional radiology medical providers on X: A social media infodemiology study.

Morar Satya K SK, Makary Mina S MS

To characterize how non-interventional radiology (IR) medical providers discuss IR procedures on X.com (formerly Twitter, Inc; San Francisco, CA), including awareness, referral intent, engagement, and misinformation. This retrospective infodemiology study evaluated public English-language X posts from January 1, 2024, through December 31, 2025. Long-form queries were used to identify posts related to uterine fibroid embolization (UFE), prostatic artery embolization (PAE), Y90 radioembolization (Y90), transarterial chemoembolization (TACE), gastric artery embolization (GAE), tumor ablation, and related procedures. After de-duplication and exclusion of reposts without commentary, IR-authored posts, and likely marketing or spam accounts, the final primary corpus comprised approximately 5,220 posts. Posts were coded for sentiment, awareness level, and thematic content. Statistical analyses included chi-square tests for categorical comparisons, Kruskal-Wallis tests for nonparametric continuous comparisons, Mann-Kendall trend tests for directional volume analysis, and Wilson's method for confidence interval estimation of referral-intent prevalence. Discussion volume increased over the study period, although quarterly trend testing did not reach conventional statistical significance (tau = 0.43; P = .07). PAE and Y90/TACE produced the highest adjusted post volumes (approximately 4,387 and 4,458 posts, respectively), whereas UFE yielded a smaller but more procedure-specific corpus (approximately 466 posts). GAE demonstrated a high raw post volume (n = 13,853) but an estimated on-topic rate of only 12%, reflecting heavy contamination from non-medical acronyms; the adjusted on-topic estimate was approximately 1,662 posts. Urology and radiation oncology providers showed the clearest engagement with PAE-related content, including explicit referral-intent posts. Medical and surgical oncology accounts were active in Y90/TACE discussions, including research and access-barrier themes. No verified obstetrics and gynecology physician accounts were identified in the long-form UFE corpus. Referral-intent posts represented 8.1% of the primary corpus (95% confidence interval, 6.5%-9.8%; approximately 418 posts) and generated greater engagement than routine educational posts. Misinformation represented approximately 7% of posts by volume but achieved disproportionate reach. Awareness of IR procedures on social media was uneven and specialty-dependent, with misinformation achieving disproportionate reach. These findings support targeted outreach to referring specialties and proactive monitoring of promoted information on social media.

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PubMedThe Plant journal : for cell and molecular biology2026-06-13

Losing genes, gaining edits: how relaxed selection and inverted repeat expansion shape RNA editing in Schizaeaceae plastomes.

Fauskee Blake D BD, Kuo Li-Yaung LY, Kwok van der Giezen Farley F, Pryer Kathleen M KM

RNA editing is a post-transcriptional pyrimidine exchange process that alters plastid and mitochondrial transcripts in nearly all land plants. Although confined to organelles, it is directed by nuclear-encoded PLS-type pentatricopeptide repeat (PPR) proteins, each typically recognizing a specific RNA target. While many editing sites are functionally neutral, edits at cryptic start and internal stop codons have been implicated in modulating organellar gene expression. Ferns-and some lycophytes-are unique among vascular plants in exhibiting both C-to-U and U-to-C editing, making them valuable for studying the evolution of both forms. Here, we examine chloroplast RNA editing in four Schizaeales species (Schizaea dichotoma, Actinostachys digitata, Anemia phyllitidis, Lygodium microphyllum). Schizaea and Actinostachys possess non-photosynthetic gametophytes, providing a natural contrast with fully photosynthetic relatives. Despite extensive plastome reduction, including loss of the ndh suite and, in Actinostachys, all chl genes, Schizaea and Actinostachys exhibit dramatically elevated numbers of C-to-U edits. Genes evolving under relaxed selection accumulate more editing sites, and editing abundance per gene correlates with the magnitude of relaxed constraint, suggesting relaxed selection promotes edit proliferation. Schizaea dichotoma and A. digitata also show expansion of the chloroplast inverted repeat (IR), and genes translocated into the IR exhibit reduced substitution rates and higher editing densities, indicating that IR expansion slows the loss of edits. Finally, annotation of PPR proteins revealed few full-length editing factors, consistent with catalytic domains assembling in trans and highlighting the modular nature of the fern editosome.

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PubMedGenome research2026-06-13

Elevated DNA insertion rate in Cyanophora paradoxa reveals unique repair signature.

Krasovec Marc M, Lipzen Anna A, Grimsley Nigel N, Mirambeau Gilles G et al.

Understanding mutation rate evolution is essential for elucidating evolutionary processes. To date, spontaneous mutation rates have been estimated in approximately 200 species, predominantly animals, plants, green algae, and bacteria. However, both mutation rates and spectra vary widely across the tree of life, and studies on new model species have recently provided valuable insights into the evolution of mutation rates. Here, we estimate the spontaneous mutation rate and spectrum in the glaucophyte Cyanophora paradoxa through a mutation accumulation experiment. While it's µ bs of 2×-10 mutations per site per generation is a typical value for a unicellular species, C. paradoxa exhibits highest insertion-deletion rate measured to date (µ id = 2×-9). This high µ id is primarily driven by insertions in intergenic regions located within or adjacent to palindromes, inverted repeats (IR), or direct repeats (DR), sequence features known to promote noncanonical DNA structures and to act as mutation hotspots. Beyond its magnitude, the insertion spectrum displays a unique pattern of DR and double three nucleotides DR and IR repeats centered around CG nucleotides, likely generated by template switching and topoisomerase activity. This creates a positive feedback loop further amplifying the insertion rate of C. paradoxa These results highlight C. paradoxa's unique mutation patterns and position glaucophytes as key models for studying mutation processes.

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