Biochemistry and Biophysics Reports最新文献_第8页

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

Innate immune overactivation hinders nuclear reprogramming through IFN-IFNAR1 axis 先天免疫过度激活通过IFN-IFNAR1轴阻碍核重编程

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-03 DOI: 10.1016/j.bbrep.2025.102395

Zhimin Song , Yaofeng Wang , Yun Zhang , Jingjing Chen , Tinghong Zhang , Shu Meng

Nuclear reprogramming to pluripotency holds great promise for regenerative medicine. However, innate immune overactivation may impair nuclear reprogramming efficiency but the underlying mechanism is not fully understood. Here we used mouse embryonic fibroblasts isolated from doxycycline-inducible OSKM transgenic mice as the nuclear reprogramming system and administered a high dosage of Polyinosinic polycytidylic acid (PIC) to stimulate TLR3 as the innate immune overactivation. PIC treatment reduced nuclear reprogramming efficiency. We identified that PIC treatment upregulated type I interferon transcription and secretion, IFNAR1 cell surface expression, and nuclear Stat1 level. Importantly, the introduction of Ifnar1 blocking antibody completely reversed this impaired nuclear reprogramming efficiency. Similarly, Ifn-β neutralizing antibody substantially ameliorated the impaired nuclear reprogramming efficiency caused by PIC treatment. Our data suggest that innate immune overactivation impairs nuclear reprogramming through the IFN-IFNAR1 axis. Blocking this signaling pathway can be used as a general strategy to enhance nuclear reprogramming efficiency.

核重编程为多能性为再生医学带来了巨大的希望。然而，先天免疫过度激活可能会损害核重编程效率，但其潜在机制尚不完全清楚。本研究以强西环素诱导的OSKM转基因小鼠胚胎成纤维细胞作为核重编程系统，并给予高剂量多肌苷多胞酸（PIC）刺激TLR3作为先天免疫过度激活。PIC处理降低了核重编程效率。我们发现PIC处理上调I型干扰素的转录和分泌、IFNAR1细胞表面表达和核Stat1水平。重要的是，Ifnar1阻断抗体的引入完全逆转了这种受损的核重编程效率。同样，Ifn-β中和抗体显著改善了PIC处理导致的核重编程效率受损。我们的数据表明先天免疫过度激活通过IFN-IFNAR1轴损害核重编程。阻断该信号通路可作为提高核重编程效率的一般策略。

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引用次数: 0

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

Biochemistry and Biophysics Reports

Pub 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。

{"title":"Curcumin reprograms metabolic pathways and MAPK signaling to exert antidepressant effects","authors":"Sijin Kong , Lijin Wang , ZiXuan Ren","doi":"10.1016/j.bbrep.2025.102399","DOIUrl":"10.1016/j.bbrep.2025.102399","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods and results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102399"},"PeriodicalIF":2.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691633","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

Accumulation of prosaposin and progranulin around the subfornical organ induces polydipsia in SAP-D-deficient mice 磷酸腺苷和颗粒前蛋白在皮质下器官周围的积累引起了sap -d缺乏小鼠的烦渴

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-02 DOI: 10.1016/j.bbrep.2025.102388

Harumi Hisaki , Takao Susa , Noriyuki Okudaira , Miho Akimoto , Masayoshi Iizuka , Junko Matsuda , Shunya Uchida , Hiroko Okinaga , Tomoki Okazaki , Mimi Tamamori-Adachi

Prosaposin (PSAP), a precursor of saposins, is essential for lysosomal hydrolysis of sphingolipids. It binds with progranulin (PGRN) and transports from the Golgi to lysosomes, where it is processed into saposins. PSAP is also secreted and functions on various cells, including neurons. We found that PSAP is highly expressed in the subfornical organ (SFO), a thirst center, in SAP-D-deficient (SAP-D^−/−) mice, which develop primary polydipsia. As polyuria progresses, CD68-positive active microglia infiltrate the SFO and strongly express PSAP and PGRN. Lysosomal marker LAMP1 analysis in the SFO of mice with advanced polydipsia showed increased LAMP1 expression and decreased co-localization of PSAP and LAMP1 in microglia and neurons. This suggests that SAP-D-deficient PSAP struggles to reach lysosomes, causing intracellular accumulation. c-Fos-positive cell counts in the SFO remained significantly higher in SAP-D^−/− mice, reflecting altered drinking behavior. These findings imply that PSAP may drive polydipsia progression.

丙皂苷（PSAP）是皂苷的前体，是溶酶体水解鞘脂所必需的。它与颗粒前蛋白（PGRN）结合，从高尔基体转运到溶酶体，在那里加工成皂苷。PSAP也在包括神经元在内的多种细胞上分泌并起作用。我们发现PSAP在SAP-D缺乏（sap - / -）小鼠的皮层下器官（SFO）中高度表达，这是一个口渴中心，会发生原发性多饮。随着多尿的进展，cd68阳性的活性小胶质细胞浸润SFO并强烈表达PSAP和PGRN。晚期多饮小鼠SFO溶酶体标记物LAMP1分析显示，LAMP1表达增加，PSAP和LAMP1在小胶质细胞和神经元中的共定位减少。这表明缺乏sap -d的PSAP难以到达溶酶体，导致细胞内积聚。在SAP-D - / -小鼠中，SFO中c- fos阳性细胞计数仍显着升高，反映了饮酒行为的改变。这些发现暗示PSAP可能推动烦渴的进展。

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引用次数: 0

Neuroprotective potential of polyherbal formulation: Evidence from preliminary in-vitro and in-vivo studies 多草药配方的神经保护潜力：来自体外和体内初步研究的证据

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-02 DOI: 10.1016/j.bbrep.2025.102381

Kundlik Rathod, Aswar Urmila

The objective of the study is to develop and evaluate a polyherbal formulation (PHF) for Parkinson's disease (PD). The present research provides preliminary studies which includes exhaustive literature survey leading to the selection of seven medicinal plants. Hydroalcoholic extracts of these plants were subsequently evaluated for their efficacy using haloperidol catalepsy and antioxidant assay. Based on results, four potent extracts, Asparagus racemosus, Convolvulus prostratus, Bacopa monnieri, and Nigella sativa, were chosen for further research. A PHF containing the above extracts was prepared and assessed for physicochemical properties, microbial load, and bioactive constituents. HPTLC analysis confirmed the presence of quercetin, kaempferol, rutin, and β-sitosterol. Molecular docking was performed for the promising actives present in the above extracts, such as kaempferol, quercetin, rutin, and β-sitosterol, highlighting their potential interactions with the PD-related targets. Antioxidant activity was evaluated using DPPH, ABTS, and FRAP assays, confirming potent free radical scavenging properties. Anti-inflammatory effects were demonstrated via heat-induced hemolysis, albumin denaturation, and proteinase inhibition assays. Additionally, the MAO-B enzyme inhibition assay indicated significant antiparkinsonian potential. PHF, combined with antioxidant, anti-inflammatory, and MAO-B inhibitory activities, supports its therapeutic application in neuronal protection. Acute oral toxicity was assessed as per OECD 425 guidelines, confirming its safety.

该研究的目的是开发和评估一种治疗帕金森病（PD）的多草药配方（PHF）。本研究提供了初步研究，包括详尽的文献调查，从而选择了七种药用植物。这些植物的水酒精提取物随后用氟哌啶醇麻醉和抗氧化试验评估其功效。在此基础上，选择总状芦笋、旋花、假马齿苋和黑草四种有效提取物进行进一步研究。制备了含有上述提取物的PHF，并对其理化性质、微生物负荷和生物活性成分进行了评估。hplc分析证实含有槲皮素、山奈酚、芦丁和β-谷甾醇。对上述提取物中存在的有希望的活性物质，如山奈酚、槲皮素、芦丁和β-谷甾醇进行了分子对接，突出了它们与pd相关靶点的潜在相互作用。使用DPPH， ABTS和FRAP测定评估抗氧化活性，证实了有效的自由基清除特性。通过热诱导溶血、白蛋白变性和蛋白酶抑制实验证明了抗炎作用。此外，MAO-B酶抑制试验显示了显著的抗帕金森病潜力。PHF具有抗氧化、抗炎和MAO-B抑制活性，支持其在神经元保护方面的治疗应用。急性口服毒性根据OECD 425指南进行评估，确认其安全性。

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引用次数: 0

Identification of PI3K/AKT/mTOR-related genes as diagnostic biomarkers for cutaneous squamous cell carcinoma PI3K/AKT/ mtor相关基因在皮肤鳞状细胞癌诊断中的应用

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-02 DOI: 10.1016/j.bbrep.2025.102355

Bingyan Yang, Hongyang Zhang, Lingdi Dong, Jianjun Wang, Nan Yu

Background

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer. Considering the substantial improvement in prognosis when detected at an early stage, identifying biomarkers for an early diagnosis of cSCC is crucial. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in cSCC progression; This study aimed to identify PI3K/AKT/mTOR-related genes that may serve as diagnostic indicators for cSCC, thereby providing a diagnostic framework for this disease.

Methods/results

A total of 33 PI3K/AKT/mTOR-related differentially expressed genes (DEGs) in cSCC were acquired by intersecting the DEGs from the Gene Expression Omnibus database between normal and cSCC groups and genes reported to be associated with the PI3K/AKT/mTOR pathway in the literature. LASSO regression identified 11 hub genes (AKT1, AKT3, EIF4EBP1, GFRA1, GRSF1, HIF1A, IGF1, IL11, IL24, KRT75, and MMP3), which were used to construct the diagnostic model. Receiver operating curve analysis revealed that these hub genes displayed strong diagnostic capacity. Quantitative polymerase chain reaction validation confirmed significant differences in mRNA expression of HIF1A, MMP3, IL11, GRSF1, and EIF4EBP1 between cSCC and normal cell lines.

Conclusion

These five PI3K/AKT/mTOR-related genes have the potential to serve as clinical biomarkers for the diagnosis of cSCC and as candidate therapeutic targets. This study offers valuable insights for further research to elucidate the specific pathological mechanisms and establish innovative treatment approaches for cSCC.

皮肤鳞状细胞癌（cSCC）是一种常见的皮肤癌。考虑到早期发现可显著改善预后，确定cSCC早期诊断的生物标志物至关重要。磷酸肌肽3-激酶(PI3K)/蛋白激酶B (AKT)/哺乳动物雷帕霉素靶蛋白（mTOR）通路在cSCC进展中起关键作用；本研究旨在鉴定可作为cSCC诊断指标的PI3K/AKT/ mtor相关基因，从而为cSCC提供诊断框架。方法/结果将基因表达综合数据库中正常组和cSCC组之间的差异表达基因（deg）和文献中报道的与PI3K/AKT/mTOR通路相关的基因相交，获得cSCC中33个PI3K/AKT/mTOR相关的差异表达基因（deg）。LASSO回归鉴定出11个中心基因（AKT1、AKT3、EIF4EBP1、GFRA1、GRSF1、HIF1A、IGF1、IL11、IL24、KRT75和MMP3），用于构建诊断模型。接受者工作曲线分析显示这些枢纽基因具有较强的诊断能力。定量聚合酶链反应验证证实，在cSCC和正常细胞系中，HIF1A、MMP3、IL11、GRSF1和EIF4EBP1 mRNA的表达存在显著差异。结论这5个PI3K/AKT/ mtor相关基因有潜力作为cSCC的临床生物标志物和候选治疗靶点。本研究为进一步阐明cSCC的具体病理机制和建立创新的治疗方法提供了有价值的见解。

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引用次数: 0

Updates on the role of miR-193b in the pathogenesis of human cancers and other diseases miR-193b在人类癌症和其他疾病发病机制中作用的最新进展

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports

Pub Date : 2025-12-02 DOI: 10.1016/j.bbrep.2025.102392

Sheyda Khalilian , Mohadeseh Fathi , Sara Arezi , Soudeh Ghafouri-Fard

MicroRNAs (miRNAs) have emerged as pivotal regulators of gene expression, fundamentally influencing cellular processes such as proliferation, differentiation, and apoptosis. Among these, miR-193b has garnered significant attention as a potent tumor suppressor in some contexts, while functioning as an oncogene in other situations. Its frequent loss in some types of cancers such as gastric and cervical cancers as well as osteosarcoma positions it not only as a valuable prognostic indicator but also as a potential tool for gene therapy. On the other hand, it has been found to be up-regulated in esophageal and bladder cancers. Meanwhile, data regarding its expression pattern in some types of cancers, such as colorectal, lung and pancreatic cancers is conflicting. Moreover, its influence extends beyond oncology, implicating it in a diverse range of human diseases, including systemic sclerosis, aortic dissection, osteoarthritis, diabetes, psoriasis, Parkinson's disease, Alzheimer's disease, sepsis and allergic rhinitis. However, miR-193b does not have a single, unified function; instead, its role is highly context-dependent, acting as either a protective molecule or a pathogenic driver depending on the specific tissue and disease. This review aims to consolidate the current updates on the role of miR-193b, detailing its molecular mechanisms, validated target genes, and its burgeoning potential as a diagnostic biomarker and therapeutic agent in cancer and other pathological conditions.

MicroRNAs （miRNAs）已成为基因表达的关键调控因子，从根本上影响细胞增殖、分化和凋亡等过程。其中，miR-193b在某些情况下作为一种有效的肿瘤抑制因子而引起了极大的关注，而在其他情况下作为致癌基因发挥作用。它在某些类型的癌症如胃癌和宫颈癌以及骨肉瘤中经常丢失，这使得它不仅是一个有价值的预后指标，而且是基因治疗的潜在工具。另一方面，人们发现它在食道癌和膀胱癌中表达上调。同时，关于其在某些类型的癌症，如结肠直肠癌、肺癌和胰腺癌中的表达模式的数据是相互矛盾的。此外，它的影响不仅限于肿瘤学，还涉及多种人类疾病，包括系统性硬化症、主动脉夹层、骨关节炎、糖尿病、牛皮癣、帕金森病、阿尔茨海默病、败血症和过敏性鼻炎。然而，miR-193b并不是单一、统一的功能；相反，它的作用是高度依赖于环境的，根据特定的组织和疾病，它要么是保护分子，要么是致病驱动因素。本综述旨在巩固miR-193b作用的最新进展，详细介绍其分子机制，验证的靶基因，以及其作为癌症和其他病理疾病的诊断生物标志物和治疗剂的新兴潜力。

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引用次数: 0