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Curcumin reprograms metabolic pathways and MAPK signaling to exert antidepressant effects 姜黄素重编程代谢途径和MAPK信号发挥抗抑郁作用
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-03 DOI: 10.1016/j.bbrep.2025.102399
Sijin Kong , Lijin Wang , ZiXuan Ren

Background

Depression is a prevalent and debilitating mental disorder with limited treatment options. Curcumin, a natural compound with neuroprotective and anti-inflammatory properties, has shown potential antidepressant effects, though the underlying mechanisms remain incompletely understood.

Methods and results

In this study, we investigated the therapeutic effects and molecular mechanisms of curcumin in a chronic unpredictable mild stress (CUMS)-induced rat model of depression. Behavioral assessments, including the sucrose preference test, forced swim test, and open field test, demonstrated that curcumin (50 and 100 mg/kg, orally administered for 21 days) alleviated CUMS-induced anhedonia, behavioral despair, and anxiety-like behaviors, in a dose-dependent manner, with the 100 mg/kg dose exhibiting superior efficacy. Metabolomic profiling of the prefrontal cortex revealed significant metabolic disturbances in CUMS rats, particularly in starch and sucrose metabolism, which were progressively restored by curcumin. Functional enrichment analysis highlighted modulation of neuroinflammation, bioenergetic homeostasis, and signal transduction pathways as key biological processes associated with curcumin's effects. Integrated multi-omics and machine learning approaches identified the MAPK signaling pathway as a central regulatory node. qPCR validation confirmed that curcumin normalized the expression of key MAPK-related genes, including BDNF, EGFR, ERK2, JUN, RAF1, and TNF, with high-dose curcumin consistently showing the most pronounced therapeutic effects.

Conclusion

Our findings demonstrate that curcumin exerts potent antidepressant effects through multi-target mechanisms involving metabolic reprogramming and coordinated regulation of the MAPK signaling pathway. This study provides novel mechanistic insights into curcumin's polypharmacological actions, supporting its potential as a multi-modal therapeutic agent for depression by simultaneously modulating neurotrophic support, inflammatory responses, and intracellular signaling cascades.
抑郁症是一种普遍存在且使人衰弱的精神障碍,治疗方法有限。姜黄素是一种具有神经保护和抗炎特性的天然化合物,已显示出潜在的抗抑郁作用,尽管其潜在机制尚不完全清楚。方法与结果研究姜黄素对慢性不可预测轻度应激(CUMS)大鼠抑郁症模型的治疗作用及其分子机制。行为评估,包括蔗糖偏好试验、强迫游泳试验和开阔场地试验,表明姜黄素(50和100 mg/kg,口服21天)以剂量依赖的方式缓解了cums诱导的快感缺乏、行为绝望和焦虑样行为,其中100 mg/kg剂量表现出更佳的效果。前额叶皮层的代谢组学分析显示,CUMS大鼠的代谢紊乱,尤其是淀粉和蔗糖代谢紊乱,姜黄素逐渐恢复了这些紊乱。功能富集分析强调了神经炎症、生物能量稳态和信号转导途径的调节是与姜黄素作用相关的关键生物学过程。综合多组学和机器学习方法确定了MAPK信号通路是一个中心调控节点。qPCR验证证实姜黄素使mapk相关关键基因BDNF、EGFR、ERK2、JUN、RAF1、TNF的表达正常化,且高剂量姜黄素一贯表现出最显著的治疗效果。结论姜黄素通过代谢重编程和MAPK信号通路的协同调节等多靶点机制发挥有效的抗抑郁作用。这项研究为姜黄素的多药理作用提供了新的机制见解,支持其作为一种多模式的抑郁症治疗药物的潜力,同时调节神经营养支持、炎症反应和细胞内信号级联反应。
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引用次数: 0
Alterations of the tumor microenvironment (TME) by exploratory gene expression analysis in recurrent glioblastoma following apatinib in combination with temozolomide 阿帕替尼联合替莫唑胺治疗复发性胶质母细胞瘤后肿瘤微环境(TME)的探索性基因表达分析
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-01 DOI: 10.1016/j.bbrep.2025.102364
Jingjing Ge , Cheng Li , Fengjun Xue , Chi Zhao , Chenchen Kong , Shaopei Qi , Qianqian Duan , Qin Zhang , Junping Zhang
Apatinib in combination with temozolomide (TMZ) has achieved reasonable clinical efficacy in the treatment of recurrent glioblastoma (rGBM), however, there are currently no clear biomarkers related to clinical efficacy or prognosis. Our retrospective study was to investigate tumor microenvironment (TME) features at the gene expression level that are associated with response and long survival benefit of rGBM treated with apatinib and TMZ. We enrolled 22 rGBMs treated with apatinib in combination with TMZ and collected their tissue samples for RNA transcriptome analysis by the Nanostring nCounter platform. The response group had 40 differentially expressed genes compared to the non-response group, with significantly up-regulated expression of genes related to endothelial cells and apoptosis. Enrichment analysis revealed that signaling pathways related to cell proliferation were down-regulated in the response group. In terms of prognosis, there were 16 differential expressed genes in the long-survival benefit group compared with the short-survival benefit group, and four tumor progression-associated genes were also down-regulated in response group expression. Hypoxia related-genes was significantly up-regulated in the long survival benefit group. Enrichment analysis showed that genes related to cell proliferation were also down-regulated in the long-survival benefit group, while the expression of signaling pathway genes related to cell activation, and immune response was significantly up-regulated. Our study suggests that the combination of apatinib and TMZ may potentially provide clinical benefits in treating rGBM by modulating genes associated with cell proliferation, promoting apoptosis, regulating hypoxia, and enhancing immune response within the tumor microenvironment.
阿帕替尼联合替莫唑胺(TMZ)治疗复发性胶质母细胞瘤(rGBM)取得了合理的临床疗效,但目前尚无明确的与临床疗效或预后相关的生物标志物。我们的回顾性研究旨在探讨肿瘤微环境(TME)在基因表达水平上的特征,这些特征与阿帕替尼和TMZ治疗rGBM的疗效和长期生存获益相关。我们招募了22例接受阿帕替尼联合TMZ治疗的rGBMs,并收集了他们的组织样本,通过Nanostring nCounter平台进行RNA转录组分析。与无反应组相比,反应组有40个差异表达基因,内皮细胞和凋亡相关基因的表达显著上调。富集分析显示,反应组与细胞增殖相关的信号通路下调。在预后方面,与短期生存获益组相比,长生存获益组有16个差异表达基因,反应组也有4个肿瘤进展相关基因表达下调。低氧相关基因在长期生存获益组显著上调。富集分析显示,与细胞增殖相关的基因在长生存获益组中也下调,而与细胞活化和免疫应答相关的信号通路基因的表达则显著上调。我们的研究表明,阿帕替尼和TMZ联合治疗rGBM可能通过调节与细胞增殖相关的基因、促进细胞凋亡、调节缺氧和增强肿瘤微环境内的免疫反应,为治疗rGBM提供潜在的临床益处。
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引用次数: 0
TMEM207-mediated the impairment of skin regeneration through YAP sequestration in an allergic contact dermatitis model 在过敏性接触性皮炎模型中,tmem207通过YAP隔离介导皮肤再生损伤
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-11 DOI: 10.1016/j.bbrep.2025.102409
Shusuke Nomura, Yusuke Kito, Chiemi Saigo, Tamotsu Takeuchi

Aim

The Yes-associated protein (YAP) family of transcriptional coactivators has emerged as a potent promoter of cell proliferation in many types of stem/progenitor cells and cancers. Skin is a squamous epithelium that is continuously regenerated by stem/progenitor cells in the basal layer and is capable of wound healing, and YAP also plays an important role in maintaining skin homeostasis and cellular proliferation. Therefore, we focused on YAP and investigated the importance of YAP regulation in allergic contact dermatitis from the perspective of wound healing and regeneration.

Methods

We investigated the expression and pathological characteristics of Transmembrane protein 207 (TMEM207), focusing on YAP-mediated regulation in atopic models, as abnormal TMEM207 expression may cause various functional abnormalities or regulate the function of YAP.

Results

TMEM207 was detected not only in the stomach and large intestine but also in the bulge region of the sebaceous glands and hair roots in mice expressing TMEM207. In addition, ATP binding cassette subfamily B member 1 (ABCB1) expression decreased in the sebaceous glands, and MIB E3 Ubiquitin Protein Ligase 1 (MIB-1) expression diminished in the epidermis. Furthermore, although we were unable to confirm the binding of TMEM207 to NEDD4, we confirmed the binding of TMEM207 to the Yes1-associated transcription factor (YAP) by immunoprecipitation, and a decrease in the nuclear localization of YAP was observed by immunohistochemical staining.

Conclusion

Our findings indicate that abnormal expression of TMEM207 is involved in the decline of skin regeneration capacity through YAP, leading to the aggravation of Allergic contact dermatitis.
yes相关蛋白(YAP)转录共激活因子家族已成为许多类型的干细胞/祖细胞和癌症中细胞增殖的有效促进子。皮肤是一种鳞状上皮,由基底层的干细胞/祖细胞不断再生,具有伤口愈合的能力,YAP在维持皮肤稳态和细胞增殖方面也起着重要作用。因此,我们以YAP为研究对象,从伤口愈合和再生的角度探讨YAP调控在变应性接触性皮炎中的重要性。方法研究跨膜蛋白207 (Transmembrane protein 207, TMEM207)的表达及病理特征,重点研究YAP在特应性模型中的调控作用,因为TMEM207的异常表达可能导致各种功能异常或调控YAP的功能。结果表达TMEM207的小鼠不仅在胃和大肠中检测到stmem207,而且在皮脂腺凸起区和毛根中也检测到stmem207。此外,ATP结合盒B亚家族成员1 (ABCB1)在皮脂腺中的表达降低,MIB E3泛素蛋白连接酶1 (MIB-1)在表皮中的表达降低。此外,虽然我们无法证实TMEM207与NEDD4的结合,但我们通过免疫沉淀证实了TMEM207与yes1相关转录因子(YAP)的结合,并且通过免疫组织化学染色观察到YAP的核定位减少。结论TMEM207的异常表达通过YAP参与皮肤再生能力下降,导致变应性接触性皮炎加重。
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引用次数: 0
Methodological validation of a cryo-TEM-based detection method for empty capsid ratio in recombinant adeno-associated virus 重组腺相关病毒空衣壳比冷冻tem检测方法的方法学验证
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2025-12-10 DOI: 10.1016/j.bbrep.2025.102397
Lingyi Xu , Jinhuan Chen , Wei Zhu , Yaokun Zhao , Fangfang Zheng , Rong Du , Yuwei Jiang , Yidan Yang , Yuanyuan Chen , Yuanshu Dong , Zhengxi Zhang , Yong Tong
Recombinant adeno-associated virus (rAAV) is one of the most promising vectors for gene therapy. It consists of a protein capsid that encapsulates the genetic material. However, during the production process, except for the full particles containing the genome, a variety of types of particles are also produced concomitantly, such as empty particles (no DNA encapsulated in the capsid), viral fragments, damaged viruses, and viral aggregates. Empty particles have been reported to induce unnecessary immune response and reduce transduction efficiency. Therefore, a quantitative method that objectively assesses the content of rAAV particles containing the genome is crucial for quality measurement. In this study, we developed a technique to detect the proportion of empty capsids in rAAV samples by using cryogenic transmission electron microscopy (cryo-TEM). This method not only accurately quantifies the percentage of empty capsids, but also allows for the characterization and analysis of other different particle types within the sample. Our comprehensive evaluation of specificity, precision, accuracy, linearity, and limit of quantitation (LOQ) demonstrates the advantages of cryo-TEM technology for the quantitative analysis of rAAV empty capsid ratio. Moreover, this research offers a thorough, multidimensional approach to enhance the understanding and implementation of quality control for rAAV.
重组腺相关病毒(rAAV)是最有前途的基因治疗载体之一。它由包裹遗传物质的蛋白质衣壳组成。然而,在生产过程中,除了含有基因组的完整颗粒外,还会同时产生各种类型的颗粒,如空颗粒(衣壳中没有封装DNA)、病毒片段、受损病毒和病毒聚集体。据报道,空颗粒可诱导不必要的免疫反应并降低转导效率。因此,一种客观评估含有基因组的rAAV颗粒含量的定量方法对于质量测量至关重要。在这项研究中,我们开发了一种利用低温透射电子显微镜(cro - tem)检测rAAV样品中空衣壳比例的技术。该方法不仅可以准确地定量空衣壳的百分比,还可以对样品中其他不同颗粒类型进行表征和分析。我们对特异度、精密度、准确度、线性度和定量限(LOQ)进行了综合评价,证明了冷冻透射电镜技术在rAAV空衣壳比定量分析中的优势。此外,本研究还提供了一种全面、多维的方法来增强对rAAV质量控制的理解和实施。
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引用次数: 0
Capsaicin responses in Drosophila: Exploring the possibility of establishing a new Non-TRPV1 model 辣椒素在果蝇中的反应:探索建立新的非trpv1模型的可能性。
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-21 DOI: 10.1016/j.bbrep.2026.102515
Gerardo Flores-Iga, Mohankumar Amirthalingam, Carlos Lopez-Ortiz, Padma Nimmakayala, Umesh K. Reddy
Capsaicin, the primary pungent compound in chili peppers, activates the heat-sensitive ion channel transient receptor potential vanilloid 1 (TRPV1) in mammals, eliciting the characteristic burning sensation. On the other hand, Drosophila melanogaster is a powerful invertebrate genetic model for linking gene function to behavior and physiology that lacks an ortholog of TRPV1, providing a unique opportunity to uncover how capsaicin affects organisms that do not possess this canonical receptor. Although Drosophila exhibits measurable responses to capsaicin, it remains unclear whether these effects reflect direct sensory detection or indirect metabolic and stress-related processes, as mechanistic evidence remains inconclusive. Here, we synthesize capsaicin-related studies in Drosophila, with a particular emphasis on reconciling opposing findings. We propose emerging conceptual frameworks based on convergent evidence implicating chemosensory pathways, metabolic processes, and physiological responses, and highlight key directions for future research aimed at clarifying the multifaceted interaction of capsaicin in TRPV1-lacking systems.
辣椒素是辣椒中主要的刺激性化合物,可以激活哺乳动物的热敏离子通道瞬时受体电位香草素1 (TRPV1),引发特有的灼烧感。另一方面,黑腹果蝇是一种强大的无脊椎动物遗传模型,可以将缺乏TRPV1同源物的基因功能与行为和生理联系起来,为揭示辣椒素如何影响不具有这种典型受体的生物体提供了独特的机会。尽管果蝇对辣椒素表现出可测量的反应,但尚不清楚这些影响是反映直接的感官检测还是间接的代谢和应激相关过程,因为机制证据仍不确定。在这里,我们综合辣椒素在果蝇中的相关研究,特别强调调和相反的发现。我们提出了基于趋同证据的新兴概念框架,包括化学感觉途径、代谢过程和生理反应,并强调了未来研究的关键方向,旨在阐明辣椒素在trpv1缺乏系统中的多方面相互作用。
{"title":"Capsaicin responses in Drosophila: Exploring the possibility of establishing a new Non-TRPV1 model","authors":"Gerardo Flores-Iga,&nbsp;Mohankumar Amirthalingam,&nbsp;Carlos Lopez-Ortiz,&nbsp;Padma Nimmakayala,&nbsp;Umesh K. Reddy","doi":"10.1016/j.bbrep.2026.102515","DOIUrl":"10.1016/j.bbrep.2026.102515","url":null,"abstract":"<div><div>Capsaicin, the primary pungent compound in chili peppers, activates the heat-sensitive ion channel transient receptor potential vanilloid 1 (TRPV1) in mammals, eliciting the characteristic burning sensation. On the other hand, <em>Drosophila melanogaster</em> is a powerful invertebrate genetic model for linking gene function to behavior and physiology that lacks an ortholog of TRPV1, providing a unique opportunity to uncover how capsaicin affects organisms that do not possess this canonical receptor. Although Drosophila exhibits measurable responses to capsaicin, it remains unclear whether these effects reflect direct sensory detection or indirect metabolic and stress-related processes, as mechanistic evidence remains inconclusive. Here, we synthesize capsaicin-related studies in Drosophila, with a particular emphasis on reconciling opposing findings. We propose emerging conceptual frameworks based on convergent evidence implicating chemosensory pathways, metabolic processes, and physiological responses, and highlight key directions for future research aimed at clarifying the multifaceted interaction of capsaicin in TRPV1-lacking systems.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102515"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
EWSR1 as a regulatory target in hepatic stellate cell apoptosis and liver fibrosis therapy EWSR1在肝星状细胞凋亡和肝纤维化治疗中的调控作用。
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-27 DOI: 10.1016/j.bbrep.2026.102526
Zhang Shiwan , Luo Guangcheng , Maisarah Abdul Mutalib
Liver fibrosis is a progressive condition driven by hepatic stellate cell (HSC) activation and resistance to apoptosis, culminating in excessive extracellular matrix (ECM) accumulation and organ dysfunction. Current antifibrotic therapies remain limited, as most target broad pathways such as TGF-β signaling or oxidative stress without addressing upstream regulators. Emerging evidence identifies the RNA-binding protein Ewing Sarcoma Breakpoint Region 1 (EWSR1) as a pivotal modulator of HSC fate. Through transcriptional regulation, non-coding RNA networks, and stress-granule dynamics, EWSR1 integrates TGF-β signaling, oxidative stress responses, and apoptosis resistance. Inhibition of EWSR1 has been reported in experimental models to suppress fibrosis-related gene expression and restore apoptotic sensitivity in activated HSCs, highlighting its therapeutic potential. This review critically synthesizes recent insights into EWSR1 biology, its crosstalk with profibrotic pathways, and its regulatory influence on HSC activation. We further compare EWSR1 with conventional antifibrotic approaches, outline research gaps, and propose directions for translational development. By positioning EWSR1 as a novel molecular node in fibrogenesis, this article underscores its promise as a next-generation therapeutic target for halting or reversing liver fibrosis.
肝纤维化是一种由肝星状细胞(HSC)活化和对凋亡的抵抗驱动的进行性疾病,最终导致细胞外基质(ECM)过度积累和器官功能障碍。目前的抗纤维化疗法仍然有限,因为大多数靶向广泛的途径,如TGF-β信号或氧化应激,而不涉及上游调节因子。新出现的证据表明,rna结合蛋白Ewing肉瘤断点区1 (EWSR1)是HSC命运的关键调节剂。通过转录调控、非编码RNA网络和应激颗粒动力学,EWSR1整合TGF-β信号、氧化应激反应和细胞凋亡抵抗。在实验模型中,抑制EWSR1可以抑制纤维化相关基因的表达,恢复活化的hsc的凋亡敏感性,这突出了其治疗潜力。这篇综述批判性地综合了最近对EWSR1生物学、它与纤维化途径的串扰以及它对HSC激活的调节作用的见解。我们进一步比较了EWSR1与传统抗纤维化方法,概述了研究差距,并提出了转化发展方向。通过将EWSR1定位为纤维化发生中的一个新的分子节点,这篇文章强调了它作为下一代治疗靶点停止或逆转肝纤维化的前景。
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引用次数: 0
Bioanalytical methods for quantification of Bevacizumab in human serum: ELISA versus MSD 人血清中贝伐单抗定量的生物分析方法:ELISA与MSD
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-29 DOI: 10.1016/j.bbrep.2026.102465
Vikas Chandnani , Sanjay Tiwari , Manoj Bob , S.G. Vasantharaju , Gundawar Ravi , A. Supraja , Amol Pawar , Suhas Khandave , Sandeep Jagtap , Muddukrishna Badamane Sathyanarayana
Bevacizumab (BVZ) is an anti-vascular Endothelial Growth Factor-A monoclonal antibody (mAb) widely used in oncology and ophthalmology indications globally. Accurate quantification of mAbs in biological fluids is an essential prerequisite for determining pharmacokinetic (PK) parameters to assess the relationship between drug exposure and response. We developed and evaluated PK assays for BVZ in human serum using enzyme-linked immunosorbent assays (ELISA) and Meso Scale Discovery (MSD) immunoassay platforms to assess sensitivity and performance. The ELISA method, employing a Streptavidin-Biotin detection system with anti-idiotypic antibodies, demonstrated five times greater sensitivity than the conventional horseradish peroxidase-based ELISA format. The validated PK bridging ELISA achieved a quantification range of 10–220 ng/mL, extendable to 5000 ng/mL via dilution. In contrast, the MSD assay utilized electrochemiluminescence detection with Sulfo Tag labeling, offering a 20-fold higher sensitivity and detecting BVZ at concentrations as low as 500 pg/mL. This parallel evaluation concluded that ELISA is suitable for routine PK analysis due to its robustness and cost-efficiency. At the same time, MSD is advantageous for detecting BVZ at low concentrations in early-phase clinical trials and ophthalmic applications where serum levels are minimal.
贝伐珠单抗(BVZ)是一种抗血管内皮生长因子- a单克隆抗体(mAb),在全球广泛用于肿瘤和眼科适应症。准确定量生物体液中的单克隆抗体是确定药代动力学(PK)参数以评估药物暴露与反应之间关系的必要前提。我们利用酶联免疫吸附测定(ELISA)和Meso Scale Discovery (MSD)免疫测定平台开发并评估了人血清中BVZ的PK测定方法,以评估其敏感性和性能。ELISA方法采用带有抗独特型抗体的链亲和素-生物素检测系统,其灵敏度比传统的辣根过氧化物酶ELISA格式高5倍。经验证的PK桥接ELISA定量范围为10-220 ng/mL,稀释后可扩展至5000 ng/mL。相比之下,MSD检测利用电化学发光检测与Sulfo标签标记,提供高20倍的灵敏度,并检测浓度低至500 pg/mL的BVZ。该平行评价结果表明,ELISA具有稳健性和成本效益,适用于常规药代动力学分析。同时,MSD在早期临床试验和眼科应用中检测低浓度的BVZ是有利的,因为血清水平最低。
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引用次数: 0
A systematic review and meta-analysis of the relationship between neuroinflammation and blood-brain barrier based on in vitro models 基于体外模型的神经炎症与血脑屏障关系的系统回顾和荟萃分析。
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-03 DOI: 10.1016/j.bbrep.2026.102479
Junwei Zhao, Anyongqi Wang, Xiang Li
The blood-brain barrier (BBB) plays a crucial role in maintaining homeostasis within the central nervous system (CNS). Neuroinflammation disrupts the integrity of the BBB. However, there is a lack of comprehensive synthesis of in vitro evidence on this topic. This study aims to systematically review in vitro research examining the effects of neuroinflammatory stimuli on the structure and function of the BBB. PubMed, EMBASE, and Web of Science were searched for studies published between November 2014 and November 2024. Included studies employed in vitro BBB models to assess effects of defined neuroinflammatory on structural and functional. Pooled standardized mean differences (SMD) with 95 % confidence intervals (CI) were calculated using random effects models. Meta-analysis was performed using R. Overall, 55 studies were included. Neuroinflammation was found to significantly decrease transendothelial electrical resistance (TEER) (−2.15, 95 % CI [-2.73, −1.56]) while increasing permeability (2.75, 95 % CI [1.71, 3.79]). Subgroup analyses showed that co-culture models exhibited more severe disruptions compared to mono-cultures measured by a significant decrease in TEER (p < 0.05). Human-derived cells displayed heightened decreases in TEER and increased permeability compared to non-human derived cells (p < 0.05). Co-cultures of endothelial cells and pericytes exhibited pronounced effects of decreased TEER compared to endothelial cells alone (p < 0.05). Stimulation periods exceeding 24 h led to significant changes. Lipopolysaccharide (LPS) caused significant disruptions. Experiments conducted with transwell systems were more sensitive to changes in TEER compared to non-transwell systems (p < 0.05). In vitro evidence confirms neuroinflammation disrupts BBB integrity through reduced TEER, increased permeability. Human-derived cells, particularly hiPSC-derived models, endothelial-pericytes co-cultures, and exposure to LPS exceeding 24 h most effectively replicate pathophysiological disruption, potentially offering optimal platforms for exploring neurological disease-related mechanisms and therapeutic strategy in the future.
血脑屏障(BBB)在维持中枢神经系统(CNS)内的稳态中起着至关重要的作用。神经炎症会破坏血脑屏障的完整性。然而,缺乏关于这一主题的体外证据的综合。本研究旨在系统回顾神经炎症刺激对血脑屏障结构和功能影响的体外研究。检索了2014年11月至2024年11月间发表的PubMed、EMBASE和Web of Science。纳入的研究采用体外血脑屏障模型来评估定义的神经炎症对结构和功能的影响。采用随机效应模型计算95 %置信区间(CI)的合并标准化平均差(SMD)。meta分析采用r进行,共纳入55项研究。发现神经炎症显著降低跨内皮电阻(TEER)(-2.15, 95 % CI[-2.73, -1.56]),同时增加通透性(2.75,95 % CI[1.71, 3.79])。亚组分析显示,与TEER显著降低的单一培养相比,共培养模型表现出更严重的破坏(p p p p )。体外证据证实,神经炎症通过降低TEER、增加渗透性来破坏血脑屏障完整性。人类来源的细胞,特别是hipsc来源的模型,内皮-周细胞共培养,以及暴露于超过24 h的LPS最有效地复制病理生理破坏,可能为未来探索神经系统疾病相关机制和治疗策略提供最佳平台。
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引用次数: 0
Enhanced anticancer activity of nanoemulsified cardamom extract via modulation of apoptosis- and lncRNA-associated pathways in colorectal cancer cells 纳米乳化豆蔻提取物通过调节结直肠癌细胞凋亡和lncrna相关通路增强抗癌活性。
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-01 DOI: 10.1016/j.bbrep.2026.102455
Tahoora Soltani , Mohammad Karimian , Hamidreza Vaziri , Merat Karimi , Majid Nejati
Colorectal cancer is a common, deadly disease, highlighting the need for safe and effective treatments. This study compared the anticancer effects of crude and nanoemulsified Elettaria cardamomum (cardamom) extract on HCT-116 colorectal cancer cells. Both the crude extract and nanoemulsion were prepared, and the nanoemulsion was characterized using transmission electron microscopy and dynamic light scattering. In an in vitro study, cell viability was measured by MTT assay, apoptosis by Annexin V/PI staining, and migration by scratch assay. The expression of genes related to apoptosis, migration, and angiogenesis, as well as lncRNAs MALAT1, NEAT1, and GAS5, was analyzed using real-time PCR. Physicochemical analysis showed spherical nanoemulsion particles with two size populations in a multimodal distribution. The IC50 was found to be 279 μg/mL for crude extract and 54.36 μg/mL for the nanoemulsion. Our molecular findings showed that the cardamom nanoemulsion exerted significantly stronger anticancer effects than the crude extract, including a greater decrease in cell viability, increased apoptosis, and more effective migration inhibition. Gene expression analysis showed that the nanoemulsion upregulated BAX and GAS5 while downregulating BCL2, MMP2, MMP9, HIF1A, VEGFA, MALAT1, and NEAT1. These expression changes were particularly pronounced at early time points compared to the crude extract. Bioinformatic analyses identified correlations between these lncRNAs and crucial genes involved in cell survival, migration, and angiogenesis, emphasizing possible lncRNA-miRNA-mRNA regulatory axes. The cardamom nanoemulsion demonstrates enhanced anticancer activity relative to the crude extract and could represent a novel therapeutic approach for colorectal cancer by modulating lncRNAs and related molecular pathways.
结直肠癌是一种常见的致命疾病,因此需要安全有效的治疗方法。本研究比较了粗豆蔻提取物和纳米乳化豆蔻提取物对HCT-116结直肠癌细胞的抗癌作用。制备了粗提物和纳米乳,并利用透射电镜和动态光散射对纳米乳进行了表征。在体外研究中,MTT法测定细胞活力,Annexin V/PI染色测定细胞凋亡,划痕法测定细胞迁移。实时荧光定量PCR分析细胞凋亡、迁移和血管生成相关基因以及lncRNAs MALAT1、NEAT1和GAS5的表达。理化分析表明,球形纳米乳颗粒具有两种大小的种群,呈多模态分布。粗提物的IC50为279 μg/mL,纳米乳的IC50为54.36 μg/mL。我们的分子研究结果表明,小豆蔻纳米乳比粗提取物具有更强的抗癌作用,包括更大程度地降低细胞活力,增加细胞凋亡,更有效地抑制迁移。基因表达分析显示,纳米乳上调BAX和GAS5,下调BCL2、MMP2、MMP9、HIF1A、VEGFA、MALAT1和NEAT1。与粗提物相比,这些表达变化在早期时间点尤为明显。生物信息学分析确定了这些lncrna与参与细胞存活、迁移和血管生成的关键基因之间的相关性,强调了可能的lncRNA-miRNA-mRNA调控轴。与粗提取物相比,小豆蔻纳米乳具有更强的抗癌活性,可能通过调节lncrna和相关分子途径为结直肠癌的治疗提供了一种新的途径。
{"title":"Enhanced anticancer activity of nanoemulsified cardamom extract via modulation of apoptosis- and lncRNA-associated pathways in colorectal cancer cells","authors":"Tahoora Soltani ,&nbsp;Mohammad Karimian ,&nbsp;Hamidreza Vaziri ,&nbsp;Merat Karimi ,&nbsp;Majid Nejati","doi":"10.1016/j.bbrep.2026.102455","DOIUrl":"10.1016/j.bbrep.2026.102455","url":null,"abstract":"<div><div>Colorectal cancer is a common, deadly disease, highlighting the need for safe and effective treatments. This study compared the anticancer effects of crude and nanoemulsified <em>Elettaria cardamomum</em> (cardamom) extract on HCT-116 colorectal cancer cells. Both the crude extract and nanoemulsion were prepared, and the nanoemulsion was characterized using transmission electron microscopy and dynamic light scattering. In an <em>in vitro</em> study, cell viability was measured by MTT assay, apoptosis by Annexin V/PI staining, and migration by scratch assay. The expression of genes related to apoptosis, migration, and angiogenesis, as well as lncRNAs MALAT1, NEAT1, and GAS5, was analyzed using real-time PCR. Physicochemical analysis showed spherical nanoemulsion particles with two size populations in a multimodal distribution. The IC<sub>50</sub> was found to be 279 μg/mL for crude extract and 54.36 μg/mL for the nanoemulsion. Our molecular findings showed that the cardamom nanoemulsion exerted significantly stronger anticancer effects than the crude extract, including a greater decrease in cell viability, increased apoptosis, and more effective migration inhibition. Gene expression analysis showed that the nanoemulsion upregulated BAX and GAS5 while downregulating BCL2, MMP2, MMP9, HIF1A, VEGFA, MALAT1, and NEAT1. These expression changes were particularly pronounced at early time points compared to the crude extract. Bioinformatic analyses identified correlations between these lncRNAs and crucial genes involved in cell survival, migration, and angiogenesis, emphasizing possible lncRNA-miRNA-mRNA regulatory axes. The cardamom nanoemulsion demonstrates enhanced anticancer activity relative to the crude extract and could represent a novel therapeutic approach for colorectal cancer by modulating lncRNAs and related molecular pathways.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102455"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A colorimetric amplification-based method for identification of Moraxella catarrhalis, a human respiratory tract pathogen 基于比色扩增法鉴定人呼吸道病原菌卡他莫拉菌
IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-12 DOI: 10.1016/j.bbrep.2026.102488
Kiana Gholizad Monavari, Hamidreza Mollasalehi
Moraxella catarrhalis is a significant pathogen associated with both upper and lower respiratory tract infections. This study aims to identify M. catarrhalis using the ompCD gene, which encodes a major outer membrane protein. Spectrophotometry was used to evaluate the accuracy of the colorimetric method by measuring the A450/A570. The colorimetric measurements and PCR method specificity were assessed utilizing twenty bacterial samples. The results of M. catarrhalis detection confirmed the presence of a specific band at 273 base pairs and a light red color, with an A450/A570 ratio of 1.5. However, 100% specificity was observed in negative samples with an A450/A570 ratio of 1.15 or less, lacking an amplicon band and showing a deep red color. Furthermore, the selectivity of the techniques was confirmed. The methods revealed a detection limit of 0.05 ng/μL. The colorimetric PCR approach is a suitable point-of-care test for rapidly and accurately identifying M. catarrhalis.
卡他莫拉菌是一种与上呼吸道和下呼吸道感染相关的重要病原体。本研究旨在利用编码一种主要外膜蛋白的compcd基因来鉴定卡他氏分枝杆菌。采用分光光度法测定A450/A570,评价比色法的准确性。利用20个细菌样本评估比色测量和PCR方法的特异性。M. catarrhalis检测结果证实在273个碱基对处存在一个特定的条带,颜色为浅红色,A450/A570比值为1.5。阴性样品中,A450/A570比值小于等于1.15,缺乏扩增带,呈深红色,特异性为100%。此外,还证实了该技术的选择性。方法检出限为0.05 ng/μL。比色PCR方法是一种适用于快速、准确地鉴定卡塔卡分枝杆菌的即时检测方法。
{"title":"A colorimetric amplification-based method for identification of Moraxella catarrhalis, a human respiratory tract pathogen","authors":"Kiana Gholizad Monavari,&nbsp;Hamidreza Mollasalehi","doi":"10.1016/j.bbrep.2026.102488","DOIUrl":"10.1016/j.bbrep.2026.102488","url":null,"abstract":"<div><div><em>Moraxella catarrhalis</em> is a significant pathogen associated with both upper and lower respiratory tract infections. This study aims to identify <em>M. catarrhalis</em> using the <em>ompCD</em> gene, which encodes a major outer membrane protein. Spectrophotometry was used to evaluate the accuracy of the colorimetric method by measuring the A450/A570. The colorimetric measurements and PCR method specificity were assessed utilizing twenty bacterial samples. The results of <em>M. catarrhalis</em> detection confirmed the presence of a specific band at 273 base pairs and a light red color, with an A450/A570 ratio of 1.5. However, 100% specificity was observed in negative samples with an A450/A570 ratio of 1.15 or less, lacking an amplicon band and showing a deep red color. Furthermore, the selectivity of the techniques was confirmed. The methods revealed a detection limit of 0.05 <em>n</em>g/<em>μ</em>L. The colorimetric PCR approach is a suitable point-of-care test for rapidly and accurately identifying <em>M. catarrhalis</em>.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102488"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146185155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Biochemistry and Biophysics Reports
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