Biochemistry and Biophysics Reports最新文献_第5页

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

Biochemistry and Biophysics Reports

Pub 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

Comparative analysis of activation of macrophages/microglia in diabetic retinopathy and Familial Exudative Vitreoretinopathy 糖尿病视网膜病变与家族性渗出性玻璃体视网膜病变中巨噬细胞/小胶质细胞活化的比较分析

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-09 DOI: 10.1016/j.bbrep.2025.102396

Jiakai Li , Ping Fei , Xiang Zhang , Yuqing Rao , Jing Li , Peiquan Zhao

Familial Exudative Vitreoretinopathy (FEVR) and Diabetic Retinopathy (DR) are two prominent retinal diseases. The role of macrophages/microglia in the vascular dynamics of FEVR and DR is unknown and thus addressed in this study. FZD4 knockout mouse, a model for FEVR in human characterized by genetic mutations affecting angiogenesis, exhibited reduced b-wave amplitudes and decreased vascular density, replicating human FEVR symptoms. Conversely, STZ-treated C57/BL6 mouse developed heightened fasting glucose levels, reduced insulin content, and increased retinal vasculature, aligning with DR features. Further analysis revealed significant differences in macrophage/microglia populations between the two diseases. In DR, a marked increase in both number and M2-like polarization of retinal macrophages/microglia was observed, contrasting with FEVR. Moreover, DR induced substantial proinflammatory differentiation of macrophages/microglia, evidenced by elevated cytokines such as IL-1β, TNF-α, and IFNɣ. Both conditions significantly upregulated Ang-1 and IL-10, with a more pronounced IL-10 increase in DR, suggesting a more active role in tissue and vessel remodeling. Notably, DR induced higher levels of anti-inflammatory factors like bFGF, TIMP-1, TGFβ1, and VEGF-A compared to FEVR, suggesting a balance of inflammation initiation, progression and resolution. These findings highlight the distinct roles of macrophages/microglia in FEVR and DR, providing insights into their contributions to disease pathogenesis and potential therapeutic strategies through reprogramming macrophages/microglia.

家族性渗出性玻璃体视网膜病变（FEVR）和糖尿病性视网膜病变（DR）是两种突出的视网膜疾病。巨噬细胞/小胶质细胞在FEVR和DR的血管动力学中的作用尚不清楚，因此在本研究中进行了研究。FZD4基因敲除小鼠是一种以影响血管生成的基因突变为特征的人类FEVR模型，其表现出b波振幅降低和血管密度降低，复制了人类FEVR症状。相反，stz处理的C57/BL6小鼠空腹血糖水平升高，胰岛素含量降低，视网膜血管增加，与DR特征一致。进一步分析显示，两种疾病之间巨噬细胞/小胶质细胞群存在显著差异。在DR中，与FEVR相比，视网膜巨噬细胞/小胶质细胞的数量和m2样极化均明显增加。此外，DR诱导巨噬细胞/小胶质细胞大量促炎分化，IL-1β、TNF-α和IFN α等细胞因子升高证明了这一点。两种情况下均显著上调Ang-1和IL-10，其中IL-10在DR中升高更为明显，表明其在组织和血管重塑中发挥更积极的作用。值得注意的是，与FEVR相比，DR诱导了更高水平的抗炎因子，如bFGF、TIMP-1、tgf - β1和VEGF-A，这表明炎症的发生、进展和消退是平衡的。这些发现突出了巨噬细胞/小胶质细胞在FEVR和DR中的独特作用，为巨噬细胞/小胶质细胞重编程对疾病发病机制和潜在治疗策略的贡献提供了见解。

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引用次数: 0

Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications 肝细胞癌（HCC）转移和侵袭的信号通路：分子机制和治疗意义

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-09 DOI: 10.1016/j.bbrep.2025.102403

Jayanta Das , Bhupen Barman , Phulen Sarma , Bipul Kumar Das , Rajiv Chetia , Partha Pratim Kalita

HCC is one of the deadliest malignancies with a rising global occurrence and poor prognosis. Metastasis and invasion are essential processes in the HCC progression, and have a profound bearing on clinical outcome. This review explores the key signalling pathways involved in HCC metastasis and invasion, focusing on their molecular mechanisms, crosstalk, and therapeutic implications. Alongside the discussion of the Wnt/β-catenin, TGF-β, PI3K/AKT/mTOR, MAPK/ERK, HGF/c-MET, Notch and Hippo-YAP/TAZ pathways, are known to contribute to promoting aggressive HCC behaviour. Stromal interactions, extracellular matrix remodelling, hypoxia and angiogenesis as well as the tumour microenvironment are also highlighted. These pathways are subject to current therapeutic treatments in the form of tyrosine kinase inhibitors and monoclonal antibodies, and research prospective of the Wnt/β-catenin blocker, TGF-β inhibitors, etc. The variations in tumours and resistance patterns to treatment and their existing problems in treating HCC are addressed. The review evaluates new therapeutic targets offering a foundation for further research and clinical advancements in this challenging field.

HCC是最致命的恶性肿瘤之一，全球发病率不断上升，预后不良。转移和侵袭是HCC发展的重要过程，对临床预后有着深远的影响。本文综述了参与HCC转移和侵袭的关键信号通路，重点讨论了它们的分子机制、串扰和治疗意义。除了讨论Wnt/β-catenin外，TGF-β、PI3K/AKT/mTOR、MAPK/ERK、HGF/c-MET、Notch和Hippo-YAP/TAZ通路也有助于促进HCC的侵袭性行为。间质相互作用，细胞外基质重塑，缺氧和血管生成以及肿瘤微环境也被强调。这些途径受到当前以酪氨酸激酶抑制剂和单克隆抗体形式的治疗，以及Wnt/β-catenin阻断剂、TGF-β抑制剂等的研究前景。讨论了肝癌治疗中肿瘤和耐药模式的变化及其存在的问题。该综述评估了新的治疗靶点，为这一具有挑战性的领域的进一步研究和临床进展提供了基础。

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引用次数: 0

Heme as activator and target for artemisinin: Towards multiple pharmacological bioactivity 血红素作为青蒿素的激活剂和靶点：走向多重药理生物活性

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-09 DOI: 10.1016/j.bbrep.2025.102398

Pan Zhu , Xinyi Sun , Yuting Fang , Yufei Li , Liang Guo

Artemisinin, a sesquiterpene trioxane derived from the plant Artemisia annua, possesses a distinctive peroxide bridge structure that endows it with remarkable biological activity, primarily through its interaction with heme. Given artemisinin's well-established clinical safety profile, researchers are increasingly investigating its potential applications in antifungal, anticancer, and antiviral treatments. This review employs heme as a foundational element to dissect the mechanisms underlying the diverse pharmacological actions of artemisinin, thereby expanding its application prospects. It also offers valuable insights for the development of novel pharmaceuticals and innovative therapeutic strategies targeting various human diseases.

青蒿素是一种从植物黄花蒿中提取的倍半萜三氧环，具有独特的过氧化物桥结构，主要通过与血红素的相互作用赋予其显著的生物活性。鉴于青蒿素已确立的临床安全性，研究人员正在越来越多地研究其在抗真菌、抗癌和抗病毒治疗方面的潜在应用。本文以血红素为基础元素，剖析青蒿素多种药理作用的机制，从而拓展其应用前景。它还为开发针对各种人类疾病的新型药物和创新治疗策略提供了宝贵的见解。

引用次数: 0

Development of novel anti-CDH1/E-cadherin monoclonal antibodies for versatile applications 新型多功能抗cdh1 / e -钙粘蛋白单克隆抗体的研制

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-08 DOI: 10.1016/j.bbrep.2025.102401

Rena Ubukata, Hiroyuki Suzuki, Mika K. Kaneko, Yukinari Kato

Cadherin (CDH)-mediated extracellular homophilic binding is crucial for maintaining tissue homeostasis. The epithelial cell-cell adhesion molecule cadherin 1 (CDH1/E‐cadherin) forms the adherens junctions in epithelial cells, and the loss of CDH1 facilitates the migration and invasion of carcinoma cells. Although several anti-CDH1 monoclonal antibodies (mAbs) are available for western blotting and immunohistochemistry (IHC), a highly sensitive anti-CDH1 mAb suitable for flow cytometry has not been developed. We developed anti-CDH1 mAbs through a flow cytometry-based high-throughput screening. Two anti-CDH1 mAb clones, Ca₁Mab-3 (IgG₁, κ) and Ca₁Mab-5 (IgG₁, κ), reacted with human CDH1-overexpressed Chinese hamster ovary-K1 (CHO/CDH1) cells in flow cytometry. Furthermore, Ca₁Mab-3 and Ca₁Mab-5 recognized endogenous CDH1-expressing human luminal-type breast cancer cells, such as MCF-7, but not triple-negative breast cancer cells, like MDA-MB-231. The dissociation constant values of Ca₁Mab-3 and Ca₁Mab-5 for CHO/CDH1 were determined as 5.9 × 10⁻¹⁰ M and 1.8 × 10⁻⁹ M, respectively. Ca₁Mab-3 and Ca₁Mab-5 can detect endogenous CDH1 in western blotting and IHC using a cell block. Furthermore, Ca₁Mab-5 is available for IHC in formalin-fixed paraffin-embedded tumor tissues. These results indicate that Ca₁Mab-3 and Ca₁Mab-5 are versatile for basic research and are expected to contribute to clinical applications, such as tumor diagnosis and therapy.

钙粘蛋白（CDH）介导的细胞外亲同性结合对维持组织稳态至关重要。上皮细胞-细胞粘附分子cadherin 1 （CDH1/E‐cadherin）在上皮细胞中形成粘附连接，CDH1的缺失促进了癌细胞的迁移和侵袭。虽然有几种抗cdh1单克隆抗体（mAb）可用于western blotting和免疫组织化学（IHC），但尚未开发出适合流式细胞术的高灵敏度抗cdh1 mAb。我们通过基于流式细胞术的高通量筛选开发了抗cdh1单克隆抗体。两种抗CDH1单抗克隆Ca1Mab-3 （IgG1, κ）和Ca1Mab-5 （IgG1, κ）在流式细胞术中与人CDH1过表达的中国仓鼠卵巢k1 （CHO/CDH1）细胞发生反应。此外，Ca1Mab-3和Ca1Mab-5可以识别内源性表达cdh1的人发光型乳腺癌细胞，如MCF-7，但不能识别三阴性乳腺癌细胞，如MDA-MB-231。测定Ca1Mab-3和Ca1Mab-5对CHO/CDH1的解离常数分别为5.9 × 10−10 M和1.8 × 10−9 M。Ca1Mab-3和Ca1Mab-5可以在western blotting和细胞块免疫组化中检测内源性CDH1。此外，Ca1Mab-5可用于福尔马林固定石蜡包埋肿瘤组织的免疫组化。这些结果表明，Ca1Mab-3和Ca1Mab-5可用于基础研究，并有望在肿瘤诊断和治疗等临床应用中发挥作用。

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引用次数: 0

Influence of PLIN5 and lipid composition on lipid droplet contact sites with other organelles PLIN5和脂质组成对脂滴与其他细胞器接触部位的影响

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-08 DOI: 10.1016/j.bbrep.2025.102402

Mahsa Mohammadian , Shima Asfia , Ralf Seemann

Lipid droplets (LDs) maintain cellular lipid homeostasis through dynamic interactions with other organelles. Understanding how these contact sites form is crucial for uncovering the mechanisms of lipid exchange and signaling. In this study, we used an in vitro model to investigate how lipid composition and the LD-associated protein perilipin 5 (PLIN5) influence contact formation between an LD monolayer and a bilayer membrane. Artificial LDs consisting of triolein and coated with either a DOPE or DOPC monolayer containing PLIN5 or not were incubated with large unilamellar vesicles (LUVs) that mimic the bilayer membrane of the organelle. Using double fluorescence labeling of the LUV bilayer and the core, we can distinguish between fusion of the LUV bilayer with the LDs and stable attachment of LUVs to the LD’s surface. Our results show that the probability of fusion between LDs and LUVs is greatly increased for DOPE-coated LDs, while PLIN5 promotes the stable attachment of LUVs to the LD’s surface and prevents fusion. These observations illustrate how certain lipid and protein components can modulate contact formation between LDs and membranes in a controlled in vitro system, and provide a basis for future studies on the molecular mechanisms of organelle communication.

脂滴（ld）通过与其他细胞器的动态相互作用维持细胞脂质稳态。了解这些接触位点如何形成对于揭示脂质交换和信号传导机制至关重要。在这项研究中，我们使用了一个体外模型来研究脂质组成和LD相关蛋白perilipin 5 （PLIN5）如何影响LD单层和双层膜之间的接触形成。由三油酸组成的人工ld表面涂有掺杂或不含PLIN5的DOPC单层，与模拟细胞器双层膜的大单层囊泡（LUVs）一起孵育。通过对LUV双层和核心的双重荧光标记，我们可以区分LUV双层与LD的融合和LUV在LD表面的稳定附着。我们的研究结果表明，dope涂层的LD与luv之间的融合概率大大增加，而PLIN5促进luv在LD表面的稳定附着并阻止融合。这些观察结果说明了在受控的体外系统中，某些脂质和蛋白质成分如何调节lld和膜之间的接触形成，并为未来细胞器通讯的分子机制研究提供了基础。

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引用次数: 0

Reconstitution of CFTR ubiquitination identifies lysine-420 as a regulator of cell surface residence and current 重组CFTR泛素化鉴定赖氨酸420作为细胞表面驻留和电流的调节剂

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-08 DOI: 10.1016/j.bbrep.2025.102393

Jennifer L. Goeckeler-Fried , Xuemei Zeng , Jeong S. Hong , Disha Joshi , Zhengrong Yang , Fan Jiang , John C. Kappes , Eric J. Sorscher , Jeffrey L. Brodsky

Background

The most common loss-of-function mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) is F508del. The misfolded F508del-CFTR protein is targeted for endoplasmic reticulum associated degradation (ERAD), a pathway in which non-native proteins are ubiquitinated and degraded by the proteasome. Because the identification of ubiquitinated residues would highlight how F508del-CFTR is selected for premature degradation, ubiquitination profiles in CFTR- and F508del-CFTR-expressing cells have been examined. Several ubiquitin ligases modify CFTR, however, the relative CFTR-directed activity of each ligase is unknown.

Methods

We reconstituted CFTR ubiquitination using purified CFTR and components of the ubiquitination machinery. Since prior work implicated the Carboxyl terminus of Hsp70-Interacting Protein (CHIP) ubiquitin ligase in both ERAD and plasma membrane turnover, CFTR ubiquitination was examined in the presence of CHIP and a companion ubiquitin conjugating enzyme.

Results

Mass spectrometry identified 16 modified lysines, half of which were previously identified after CFTR was isolated from cells. One lysine, K420, which resides in the regulatory insertion, had been implicated in cyclic nucleotide-dependent activation of CFTR. Here, we find that mutation of K420 increases cell surface levels of CFTR, an effect which in turn increases forskolin-dependent short circuit current.

Conclusions

We establish a system in which residue-specific modifications of CFTR by any component of the ubiquitin machinery can now be surveyed.

在编码囊性纤维化跨膜传导调节因子（CFTR）的基因中，最常见的功能缺失突变是F508del。错误折叠的F508del-CFTR蛋白是内质网相关降解（ERAD）的靶标，这是一种非天然蛋白被蛋白酶体泛素化和降解的途径。由于泛素化残基的鉴定将突出F508del-CFTR是如何被选择用于过早降解的，因此我们研究了CFTR-和F508del-CFTR表达细胞中的泛素化谱。几种泛素连接酶修饰CFTR，然而，每种连接酶的相对CFTR定向活性是未知的。方法利用纯化的CFTR和泛素化机制的组成部分重组CFTR泛素化。由于先前的研究表明hsp70相互作用蛋白（CHIP）泛素连接酶的羧基端参与ERAD和质膜转换，因此在CHIP和伴随的泛素结合酶存在的情况下，研究了CFTR泛素化。结果质谱鉴定出16种修饰赖氨酸，其中一半是在CFTR分离后鉴定出来的。一种赖氨酸，K420，位于调控插入中，与环核苷酸依赖性的CFTR激活有关。在这里，我们发现K420的突变增加了细胞表面CFTR的水平，这种效应反过来又增加了福斯克林依赖的短路电流。结论我们建立了一个系统，在这个系统中，任何泛素机制的组成部分对CFTR的残基特异性修饰现在都可以被调查。

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引用次数: 0

In vitro 3D models of neuron-astrocyte interactions 神经元-星形胶质细胞相互作用的体外3D模型

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-05 DOI: 10.1016/j.bbrep.2025.102400

Tong Su, Zhixiang Li, Yujie Yang, Yangfan Dai, Yueqi Li, Huan Zhao

The pathological processes of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis) also include relationships between neuron and glia cells. Conventional two-dimensional (2D) cell cultures have limitations to mimic the microenvironment of cells inside living organisms because of flaws in intercellular relationships investigated using 2D cell cultures. Recent advances have introduced three-dimensional (3D) cell cultures that have the capability to create 3D cellular architecture to mimic advanced platforms for scientific inquiries into neurodegenerative diseases, simulating microenvironments inside living organisms.This review provides a brief overview of the development of in vitro 3D cell culture models of astrocytes and attempts to highlight the role of astrocytes in crucial pathophysiologic events occurring in 3D cultures. Studies have shown the use of in vitro 3D cultures to better represent the dual functions of astrocytes in neurodegenerative disorders. Looking ahead to the future, novel advances in microfluidics and multi-omics analysis promise to further improve 3D cultures and push forward new insights into neurological dysfunction to spark innovative advances for treatment strategies.

神经退行性疾病（如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症）的病理过程也包括神经元和神经胶质细胞之间的关系。传统的二维（2D）细胞培养在模拟生物体内细胞微环境方面存在局限性，因为使用二维细胞培养研究细胞间关系存在缺陷。最近的进展已经引入了三维（3D）细胞培养，它具有创建3D细胞结构的能力，以模拟神经退行性疾病科学研究的先进平台，模拟生物体内的微环境。本文简要介绍了星形胶质细胞体外3D细胞培养模型的发展，并试图强调星形胶质细胞在3D培养中发生的关键病理生理事件中的作用。研究表明，使用体外3D培养可以更好地代表星形胶质细胞在神经退行性疾病中的双重功能。展望未来，微流体和多组学分析的新进展有望进一步改善3D培养，并推动对神经功能障碍的新见解，从而激发治疗策略的创新进展。

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引用次数: 0

Molecular Boolean analyses of chemokine (C–C motif) receptor 1, α1B-adrenoceptor and arginine vasopressin receptor 1A heteromers 趋化因子（C-C基序）受体1、α 1b肾上腺素受体和精氨酸加压素受体1A异构体的分子布尔分析

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-05 DOI: 10.1016/j.bbrep.2025.102404

Xianlong Gao , Matthias Majetschak

We reported previously that many chemokine receptors can form heteromeric complexes with α_1B-adrenoceptor (α_1B-AR) and arginine vasopressin receptor 1 A (AVPR1A). To gain initial insight into the relative proportions of receptors that may participate in the formation of such heteromers, we performed molecular Boolean (MolBoolean) analyses of receptor-receptor interactions in an expression system and in primary human aortic vascular smooth muscle cells (hVSMCs), utilizing chemokine (C–C motif) receptor 1, α_1B-adrenoceptor and AVPR1A as representative receptor partners. In HEK293T cells co-expressing all three receptors, 60–70 % of each recombinant receptor were located proximal enough to permit heteromerization with the other two receptor partners. In primary human vascular smooth muscle cells, 30–50 % of each receptor were located proximal enough to permit heteromerization with the other two receptor partners. The MolBoolean analyses of receptor-receptor interactions provides new insights into the spatial distribution of GPCRs in the plasma membrane. Our finding that large proportions of the receptor partners may be able to participate in heteromerization supports the concept that such hetero-oligomeric complexes composed of CCR1, α_1B-AR and AVPR1A could be of physiological relevance.

我们之前报道过许多趋化因子受体可以与α 1b -肾上腺素受体（α1B-AR）和精氨酸抗利尿激素受体1 A （AVPR1A）形成异质复合物。为了初步了解可能参与这些异聚体形成的受体的相对比例，我们对表达系统和人主动脉血管平滑肌细胞（hVSMCs）中的受体-受体相互作用进行了分子布尔（MolBoolean）分析，利用趋化因子（C-C基序）受体1、α 1b -肾上腺素受体和AVPR1A作为代表性受体伙伴。在共表达所有三种受体的HEK293T细胞中，每个重组受体的60-70 %位于足够近的位置，从而允许与其他两个受体伙伴异质化。在原代人血管平滑肌细胞中，每种受体的30 - 50% %位于近端，足以与其他两个受体伙伴异质化。受体-受体相互作用的MolBoolean分析为gpcr在质膜中的空间分布提供了新的见解。我们发现大部分受体伴侣可能能够参与异聚，这支持了由CCR1、α1B-AR和AVPR1A组成的异聚物复合物可能具有生理相关性的概念。

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引用次数: 0

CircRNAs: Novel biomarkers and therapeutic targets for diseases of the central nervous system 环状rna：中枢神经系统疾病的新生物标志物和治疗靶点

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-03 DOI: 10.1016/j.bbrep.2025.102394

Jiafang Cui, Ling Shen, Bing Han

Circular RNAs (circRNAs) are a class of covalently closed, non-coding RNA molecules characterized by their exceptional stability and tissue-specific expression. Once considered splicing artifacts, they have emerged as pivotal regulators in cellular pathophysiology, particularly within the central nervous system (CNS), where they are highly abundant. This review synthesizes the current understanding of the biogenesis, molecular functions, and regulatory roles of circRNAs in major CNS disorders, underscores their significant potential as next-generation diagnostic and prognostic biomarkers, as well as promising therapeutic targets. Moving from bench to bedside, the review critically examines the burgeoning landscape of circRNA-based therapeutics. We assess the promise and limitations of current delivery platforms, including exosomes and lipid nanoparticles (LNPs), with special attention to the formidable challenge of traversing the blood-brain barrier (BBB). To conclude, we outline the prevailing challenges and future perspectives, emphasizing that the development of more sensitive detection methods and optimized delivery systems is paramount to translating the immense potential of circRNAs into tangible clinical solutions for CNS diseases.

环状RNA （circRNAs）是一类共价封闭的非编码RNA分子，其特点是具有优异的稳定性和组织特异性表达。它们曾经被认为是剪接的产物，现在已经成为细胞病理生理学的关键调节因子，特别是在它们高度丰富的中枢神经系统（CNS）中。这篇综述综合了目前对环状rna在主要中枢神经系统疾病中的生物发生、分子功能和调控作用的理解，强调了它们作为下一代诊断和预后生物标志物的巨大潜力，以及有希望的治疗靶点。从实验室到临床，这篇综述批判性地审视了基于circrna的治疗方法的新兴前景。我们评估了当前递送平台的前景和局限性，包括外泌体和脂质纳米颗粒（LNPs），特别关注穿越血脑屏障（BBB）的艰巨挑战。最后，我们概述了当前的挑战和未来的前景，强调开发更敏感的检测方法和优化的递送系统对于将circrna的巨大潜力转化为中枢神经系统疾病的切实临床解决方案至关重要。

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引用次数: 0