Integrated metabolomics, transcriptomics and network pharmacology analysis to reveal the mechanisms of Danggui Buxue tang in treating Alzheimer's disease

Article

作者: Xia, Chunli ; Chen, Baixiong ; Li, Shun ; Chen, Daoyuan ; Li, Xinrui ; Li, Shuanglong ; Tong, Peipei

BACKGROUND:

Alzheimer's disease (AD) is a prevalent, multifactorial, and multisystem chronic neurodegenerative disorder. Existing pharmacotherapeutic interventions for AD present significant limitations. Prior studies have indicated that Danggui Buxue Tang (DBT) reduces Aβ deposition and improves cognitive function. Nevertheless, the therapeutic mechanisms of DBT are not yet fully elucidated.

PURPOSE:

The objective of this study is to clarify the underlying mechanisms by which DBT alleviates AD. This will be accomplished through an integrated approach that encompasses network pharmacology, transcriptomics, metabolomics analyses, and experimental validation.

METHODS:

The chemical composition of DBT was elucidated using HPLC. The neuroprotective efficacy of DBT was assessed through behavioral evaluations and pathological tissue examination. Network pharmacology was leveraged to identify potential therapeutic targets for DBT in AD. Transcriptomic analysis was conducted on SH-SY5Y cells using Illumina sequencing to pinpoint differentially expressed genes. Additionally, an untargeted metabolomic assessment of cerebral tissue was performed using UPLC-MS/MS to ascertain differentially accumulated metabolites. The impact and underlying mechanisms of DBT on AD were explored by integrating network pharmacology, transcriptomics, and metabolomics, and subsequently confirmed through qPCR and WB.

RESULTS:

Behavioral assessments and histopathological analyses have shown that DBT significantly alleviates AD-related symptoms. In APP/PS1 mice, DBT markedly improved cognitive impairment and anxiety-like behavior, and reduced neuronal damage. Further integrative analyses suggest that these effects are mediated, at least in part, by the suppression of neuroinflammation-driven neuronal apoptosis through the modulation of the TNF/NF-κB and MAPK signaling cascades. Additionally, DBT seems to reestablish cerebral metabolic equilibrium by regulating the metabolism of glycerophospholipids, sphingolipids, and terpenoids in the brain tissue affected by Alzheimer's disease.

CONCLUSIONS:

These results highlight the therapeutic potential of DBT for alleviating AD pathology. Our study provides new mechanistic understandings of DBT, suggesting that its therapeutic effects result from the synergistic regulation of multiple pathways to simultaneously inhibit neuroinflammation and neuronal apoptosis, thereby effectively opposing the pathological features of AD.

2025-12-01·AMERICAN JOURNAL OF PSYCHIATRY

Dialectical Behavior Therapy Versus Serotonin Reuptake Inhibitor Treatment for Suicidal Behavior in Borderline Personality Disorder: A Randomized Controlled Trial

Article

作者: Galfalvy, Hanga ; Stanley, Barbara ; Grunebaum, Michael F. ; Brodsky, Beth S. ; Mann, J. John

OBJECTIVE:

The authors compared the efficacy of 6 months of dialectical behavior therapy (DBT) to 6 months of selective serotonin reuptake inhibitors with clinical management (SSRI/M) in reducing suicide-related events (SREs), suicide attempts, nonsuicidal self-injury (NSSI), and related clinical outcomes in individuals diagnosed with borderline personality disorder.

METHODS:

The study sample comprised 84 individuals with borderline personality disorder; more than one suicide attempt, SRE, or NSSI episode in the past 6 months; and another of these behaviors in the past year. Two-thirds had comorbid major depressive disorder. Participants were randomly assigned to receive DBT or SSRI/M. Poisson models were used to analyze numbers of suicide attempts and SREs, and a zero-inflated Poisson model was used for NSSI behaviors. Survival analysis was performed with the log-rank test for time to first suicide attempt or SRE. Follow-up assessments at 12 months were analyzed in a separate model. Mixed-effects regression was used to compare quantitative outcomes.

RESULTS:

Significantly fewer SREs occurred in the DBT arm compared with the SSRI/M arm during the 6-month treatment phase. Significantly fewer suicide attempts occurred in the DBT arm compared with the SSRI/M arm. Survival analysis indicated significantly lower risk for having any SRE in the DBT arm compared with the SSRI/M arm, but no difference in risk of suicide attempt. DBT participants had significantly lower NSSI counts than SSRI/M participants. Severity of depression and suicidal ideation decreased comparably in both treatment groups. After 6 months of treatment, the rate of major depressive disorder was significantly lower in the SSRI/M arm compared with the DBT arm. At 12-month follow-up (6 months after completion of the treatment phase), outcomes were comparable between the two groups.

CONCLUSIONS:

Six months of DBT showed greater efficacy than 6 months of SSRI/M in reducing SRE and NSSI behaviors in patients with borderline personality disorder.

2025-12-01·AMERICAN JOURNAL OF GASTROENTEROLOGY

Quantifying Patient Preferences for Risk Tolerance With Novel Dual Biologic Therapies for Inflammatory Bowel Disease

Article

作者: Marko, Melissa ; Yang, Jui-Chen ; Bozzi, Laura M. ; Johnson, F. Reed ; Sheahan, Anna ; Lynch, John ; Wallace, Matthew J. ; Bewtra, Meenakshi ; Janssen, Ellen M.

INTRODUCTION::

Many patients with inflammatory bowel disease (IBD) experience treatment failures despite availability of effective advanced biologic and small-molecule therapies with differing mechanisms of action. Dual biologic therapy (DBT) is being explored to improve efficacy outcomes and address unmet needs in this difficult-to-treat population. This study aimed to understand patient preferences for DBT efficacy and risk tolerance.

METHODS::

Built on evidence from existing treatment-preference studies, a focused discrete-choice experiment (DCE) was developed to measure preferences for treatment type, chance of remission, and risk of serious infection. Individuals with a physician-verified diagnosis of Crohn's disease or ulcerative colitis who had failed or were taking advanced therapy were recruited through an IBD registry. DCE responses were analyzed using a fully correlated random parameters logit model.

RESULTS::

The DCE survey was completed by 280 respondents. The majority of respondents were White, female; had been previously hospitalized for IBD; and were receiving biologic monotherapy for their IBD disease. There was no meaningful difference in preference for DBT or monotherapy ( P = 0.25), while there was strong preference to avoid corticosteroids ( P < 0.001). To improve from a 50% to 70% in chance of remission, respondents would accept up to a 17.5% (95% confidence interval 17.0%–18.0%) risk of serious infection.

DISCUSSION::

The findings suggest that patients prefer safe and efficacious treatments and DBT may be an acceptable option for those who have failed an advanced therapy for IBD. We demonstrate the value of building on existing evidence and designing efficient DCE studies to address knowledge gaps to improve IBD care.

项与猪源纤维蛋白贴（广州市拜特凇医药科技）相关的新闻（医药）

2025-11-11

·生物通

综述：超越单一疗法：探索双生物制剂策略在风湿性疾病中的疗效与安全性

在现代风湿免疫疾病的治疗中，生物制剂和靶向合成疾病修饰抗风湿药物（b/tsDMARDs）已成为重要手段。这些药物通过针对特定的炎症通路，如肿瘤坏死因子（TNF）、白细胞介素（IL）等，显著改善了患者的临床预后。然而，尽管有多种药物可供选择，仍有一部分患者对单一生物制剂治疗反应不足，难以达到治疗目标。因此，双生物制剂治疗（Dual Biologic Therapy, DBT）作为一种可能的策略，被提出以克服治疗抵抗。DBT通过同时抑制多个炎症通路，理论上可以增强治疗效果，但也伴随着更高的感染风险，尤其是在某些特定的药物组合中。在类风湿关节炎（Rheumatoid Arthritis, RA）领域，DBT的研究表明，虽然其在部分难治性病例中显示出一定的疗效提升，但与单药治疗相比，感染率显著增加。例如，一项2004年的研究显示，将阿那白滞素（anakinra）与依那西普（etanercept）联合使用时，尽管有轻微的疗效提升，但严重感染的发生率明显上升。另一项2006年的研究则发现，虽然ACR50/70的响应率有所提高，但严重感染和不良事件的发生率也显著增加。尽管这些早期研究引发了对DBT安全性的担忧，但后续的一些研究探索了不同的药物组合，例如利妥昔单抗（rituximab）与JAK抑制剂的联合使用。然而，即使在这些研究中，DBT的疗效提升并不明显，且感染风险依然存在，尤其是在高剂量组合中。这表明，在RA患者中，DBT可能更适合那些对其他治疗方案无效的难治性病例，但其使用仍需谨慎评估风险与收益。在银屑病关节炎（Psoriatic Arthritis, PsA）方面，DBT的应用更为广泛，尤其是在涉及多领域（如关节炎、皮肤病变、肠病）的复杂病例中。例如，一项研究显示，将阿普斯特（apremilast）与TNF抑制剂或IL-23抑制剂联合使用，能够显著改善患者的皮肤和关节症状，同时感染风险相对较低。此外，一些案例报告指出，使用维多珠单抗（vedolizumab）与TNF抑制剂的联合治疗，在控制肠道和关节炎症方面具有积极作用，且未观察到严重的感染事件。然而，这些研究大多基于回顾性分析或个案报告，缺乏大规模的随机对照试验（RCTs）支持。因此，虽然DBT在PsA中的应用前景较好，但其长期疗效和安全性仍需进一步验证。对于轴性脊柱关节炎（Axial Spondyloarthritis, axSpA），DBT的研究还处于初步阶段。一些小规模的回顾性研究和个案报告显示，联合使用不同机制的生物制剂可能带来一定的临床改善，尤其是在单一药物治疗无效的情况下。例如，一名患者在使用依那西普和英夫利昔单抗的联合治疗后，出现了显著的临床缓解，且未发生严重感染。此外，另一项研究中，维多珠单抗与戈利木单抗（golimumab）的联合治疗也有效控制了患者的肠道和关节症状。尽管这些案例提供了初步的证据，但目前的证据仍有限，且缺乏标准化的评估体系，使得DBT在axSpA中的应用仍需更多高质量的研究支持。DBT的潜在优势在于其能够同时作用于多个炎症通路，从而更全面地控制疾病活动。然而，这一策略的实施也面临诸多挑战。首先，现有的研究数据存在局限性，大多数研究基于小样本量或单中心经验，缺乏广泛的适用性和长期随访结果。其次，不同地区的感染风险、治疗可及性和药物监测能力存在显著差异，这使得DBT在全球范围内的应用受到地理因素的影响。例如，在资源丰富的地区，可能更容易开展多中心研究和长期随访，而在资源有限的地区，DBT的应用可能受限于缺乏足够的医疗资源和专业知识。此外，DBT的疗效并不总是优于单药治疗。在RA和PsA的研究中，尽管部分病例显示了联合治疗的优势，但整体上并没有一致的证据表明DBT在所有情况下都更有效。这可能与患者个体差异、疾病异质性以及药物组合的选择有关。因此，在临床实践中，DBT的使用应当基于对患者具体情况的全面评估，尤其是在那些对现有治疗方案反应不佳的情况下。为了更好地指导DBT的应用，未来的研究方向应包括以下几个方面。首先，开发能够预测治疗反应的生物标志物，这有助于精准选择适合DBT的患者群体，减少不必要的治疗风险。例如，在RA中，代谢组学分析已经发现了一些能够预测特定生物制剂疗效的代谢物标志物，这些标志物的进一步研究和验证可能为个性化治疗提供重要依据。其次，探索诱导免疫耐受的新策略，这可能为解决治疗抵抗问题提供新的思路。例如，通过靶向CD4? T细胞或调节性T细胞（Tregs）的功能，可以尝试在不损害整体免疫系统的情况下，实现对自身免疫反应的控制。此外，随着CAR-T细胞疗法的发展，这一技术在风湿免疫疾病中的应用也引起了广泛关注。CAR-T细胞通过工程改造，能够特异性地攻击致病性免疫细胞，减少对正常组织的损伤，为难治性疾病的治疗提供了新的可能性。总体而言，DBT作为一种潜在的治疗策略，在某些特定的风湿免疫疾病中可能带来一定的临床益处。然而，由于现有的研究证据尚不充分，且感染风险较高，其应用应当谨慎。未来的研究需要更多高质量的临床试验，以明确DBT在不同疾病类型和患者群体中的疗效和安全性。同时，结合生物标志物和个体化治疗策略，可能有助于提高DBT的适用性和成功率。此外，考虑到不同地区的医疗资源差异，还需要推动针对特定环境和条件的DBT研究，以确保其在全球范围内的安全和有效应用。最终，DBT的推广应建立在充分的科学证据和临床经验基础上，确保其在真正需要的患者中发挥最大作用，同时最小化潜在的风险。

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适应症	最高研发状态	国家/地区	公司	日期
术后出血	临床2期	中国	广州市拜特凇医药科技有限公司	2021-12-30
术后出血	临床2期	中国	广州市众为生物科技股份有限公司	2021-12-30