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Correction: Huynh et al. Spike Protein Impairs Mitochondrial Function in Human Cardiomyocytes: Mechanisms Underlying Cardiac Injury in COVID-19. Cells 2023, 12, 877. 更正:Huynh 等人,《尖峰蛋白损害人类心肌细胞的线粒体功能:COVID-19中心脏损伤的机制。细胞2023,12,877。
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-11 DOI: 10.3390/cells13221865
Tin Van Huynh, Lekha Rethi, Ting-Wei Lee, Satoshi Higa, Yu-Hsun Kao, Yi-Jen Chen

There was an error in the original publication [...].

最初的出版物有一处错误 [......] 。
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引用次数: 0
In Vitro Models of Diabetes: Focus on Diabetic Retinopathy. 糖尿病体外模型:聚焦糖尿病视网膜病变。
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-11 DOI: 10.3390/cells13221864
Giulia Galgani, Giorgia Bray, Alma Martelli, Vincenzo Calderone, Valentina Citi

Diabetic retinopathy is a major eye complication in patients with diabetes mellitus, and it is the leading cause of blindness and visual impairment in the world. Chronic hyperglycemia induces endothelial damage with consequent vascular lesions, resulting in global vasculitis, which affects the small vessels of the retina. These vascular lesions cause ischemic conditions in certain areas of the retina, with a consequent increase in the release of pro-angiogenic mediators. In addition to pharmacological interventions for controlling the blood glycaemic level, the main strategies for treating diabetic retinopathy are the intravitreal injections of drugs, surgical treatments, and vitrectomies. The complexity of diabetic retinopathy is due to its close interactions with different cell types (endothelial cells, astrocytes, and Müller cells). The evaluation of the efficacy of novel pharmacological strategies is mainly performed through in vivo models. However, the use of different animal species leads to heterogenic results and ethical concerns. For these reasons, the development of new and reliable in vitro models, such as cell co-cultures and eye organoids, represents an urgent need in this area of research. This review features an overview of the in vitro models used to date and highlights the advances in technology used to study this pathology.

糖尿病视网膜病变是糖尿病患者眼部的主要并发症,也是全球失明和视力受损的主要原因。长期高血糖会诱发血管内皮损伤,进而导致血管病变,形成影响视网膜小血管的整体性血管炎。这些血管病变会导致视网膜某些区域缺血,从而增加促血管生成介质的释放。除了控制血糖水平的药物干预外,治疗糖尿病视网膜病变的主要策略还有玻璃体内注射药物、手术治疗和玻璃体切除术。糖尿病视网膜病变的复杂性在于它与不同类型细胞(内皮细胞、星形胶质细胞和 Müller 细胞)的密切相互作用。新型药理策略的疗效评估主要通过体内模型进行。然而,使用不同的动物物种会导致不同的结果和伦理问题。因此,开发新的、可靠的体外模型,如细胞共培养和眼有机体,是这一研究领域的迫切需要。本综述概述了迄今为止使用的体外模型,并重点介绍了用于研究该病理学的技术进展。
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引用次数: 0
Oxidative Stress and Antioxidant Strategies: Relationships and Cellular Pathways for Human Health. 氧化应激和抗氧化策略:人类健康的关系和细胞途径》。
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-11 DOI: 10.3390/cells13221871
Alessia Remigante, Rossana Morabito

Chronic diseases and aging have increased significantly in recent decades [...].

近几十年来,慢性疾病和老龄化问题显著增加 [...] 。
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引用次数: 0
Immunohistochemical Characterization of Spermatogenesis in the Ascidian Ciona robusta. 罗氏拟尾柱虫精子发生的免疫组织化学特征
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-11 DOI: 10.3390/cells13221863
Haruka Sakurai, Kogiku Shiba, Katsumi Takamura, Kazuo Inaba

Animals show diverse processes of gametogenesis in the evolutionary pathway. Here, we characterized the spermatogenic cells in the testis of the marine invertebrate Ciona robusta. Ciona sperm differentiate in a non-cystic type of testis, comprising many follicles with various sizes and stages of spermatogenic cells. In the space among follicles, we observed free cells that were recognized by antibody against Müllerian inhibiting substance, a marker for vertebrate Sertoli cells. We further categorized the spermatogenic cells into four round stages (RI to RIV) and three elongated stages (EI to EIII) by morphological and immunohistochemical criteria. An antibody against a vertebrate Vasa homolog recognized a few large spermatogonium-like cells (RI) near the basal wall of a follicle. Consistent with the period of meiosis, a synaptonemal complex protein SYCP3 was recognized from early spermatocytes (RII) to early spermatids (E1). Acetylated tubulins were detected in spermatids before flagellar elongation at the RIV stage and became distributed along the flagella. Electron microscopy showed that the free cells outside the testicular follicle possessed a characteristic of vertebrate Sertoli cells. These results would provide a basis for basic and comparative studies on the mechanism of spermatogenesis.

在进化过程中,动物的配子发生过程多种多样。在这里,我们描述了海洋无脊椎动物 Ciona robusta 睾丸中生精细胞的特征。栉水母的精子在非囊性睾丸中分化,睾丸由许多具有不同大小和阶段生精细胞的滤泡组成。在滤泡之间的空隙中,我们观察到了游离细胞,这些游离细胞能被针对Müllerian抑制物质的抗体识别,而Müllerian抑制物质是脊椎动物Sertoli细胞的标记物。通过形态学和免疫组化标准,我们进一步将精原细胞分为四个圆形阶段(RI至RIV)和三个伸长阶段(EI至EIII)。针对脊椎动物瓦萨同源物的抗体能识别卵泡基底壁附近的几个大的精原细胞(RI)。与减数分裂时期一致,从早期精母细胞(RII)到早期精子(E1)都能识别出突触复合体蛋白SYCP3。在 RIV 阶段鞭毛伸长之前,精子中检测到乙酰化的小管蛋白,并沿着鞭毛分布。电子显微镜显示,睾丸滤泡外的游离细胞具有脊椎动物 Sertoli 细胞的特征。这些结果将为精子发生机制的基础研究和比较研究提供依据。
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引用次数: 0
Unlocking Potential: A Comprehensive Overview of Cell Culture Banks and Their Impact on Biomedical Research. 释放潜能:细胞培养库及其对生物医学研究影响的全面概述》。
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-10 DOI: 10.3390/cells13221861
Sabine Weiskirchen, Antonio M Monteiro, Radovan Borojevic, Ralf Weiskirchen

Cell culture banks play a crucial role in advancing biomedical research by providing standardized, reproducible biological materials essential for various applications, from drug development to regenerative medicine. This opinion article presents a comprehensive overview of cell culture banks, exploring their establishment, maintenance, and characterization processes. The significance of ethical considerations and regulatory frameworks governing the use of cell lines is discussed, emphasizing the importance of quality control and validation in ensuring the integrity of research outcomes. Additionally, the diverse types of cell culture banks-primary cells, immortalized cell lines, and stem cells-and their specific contributions to different fields such as cancer research, virology, and tissue engineering are examined. The impact of technological advancements on cell banking practices is also highlighted, including automation and biobanking software that enhance efficiency and data management. Furthermore, challenges faced by researchers in accessing high-quality cell lines are addressed, along with proposed strategies for improving collaboration between academic institutions and commercial entities. By unlocking the potential of cell culture banks through these discussions, this article aims to underline their indispensable role in driving innovation within biomedical research and fostering future discoveries that could lead to significant therapeutic breakthroughs.

细胞培养库提供从药物开发到再生医学等各种应用所必需的标准化、可重复的生物材料,在推动生物医学研究方面发挥着至关重要的作用。这篇观点文章全面概述了细胞培养库,探讨了细胞培养库的建立、维护和表征过程。文章讨论了使用细胞系的伦理考虑因素和监管框架的意义,强调了质量控制和验证在确保研究成果完整性方面的重要性。此外,还探讨了各种类型的细胞培养库--原始细胞、永生化细胞系和干细胞,以及它们对癌症研究、病毒学和组织工程等不同领域的具体贡献。此外,还重点介绍了技术进步对细胞库实践的影响,包括提高效率和数据管理的自动化和生物库软件。此外,还探讨了研究人员在获取高质量细胞系方面面临的挑战,以及改善学术机构与商业实体之间合作的建议策略。本文通过这些讨论挖掘细胞培养库的潜力,旨在强调细胞培养库在推动生物医学研究创新和促进未来发现方面不可或缺的作用,这些发现可能会带来重大的治疗突破。
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引用次数: 0
CD47 in Osteosarcoma: Correlation with Metastasis and Macrophage-Mediated Phagocytosis. 骨肉瘤中的 CD47:骨肉瘤中的 CD47:与转移和巨噬细胞介导的吞噬作用的相关性
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-10 DOI: 10.3390/cells13221862
Yunmi Ko, Seog-Yun Park, Jong Woong Park, June Hyuk Kim, Hyun Guy Kang, Jun Ah Lee

CD47 is expressed on cell surfaces and acts as a "don't eat me" signal by interacting with signal-regulatory protein-α on the macrophage surface. Some cancer cells express CD47 protein and can evade macrophage phagocytosis. Herein, we evaluated the feasibility of targeting CD47 for osteosarcoma by analyzing its expression patterns, clinicopathological correlations, and immunotherapeutic potential. We performed a retrospective analysis on 24 biopsy samples from patients with osteosarcoma to investigate correlations between CD47 protein positivity and clinicopathological characteristics. CD47 protein expression was detected in 20.8% of the biopsy samples. CD47 positivity correlated with metastasis at diagnosis. Patients with CD47-positive tumors were older than those with CD47-negative tumors. However, CD47 protein expression was not associated with sex, tumor size, or histologic response to preoperative chemotherapy. In vitro, CD47 antibody (B6H12) did not affect osteosarcoma cell viability or apoptosis. In a wound-healing assay, CD47 inhibited the migration of osteosarcoma cells. Differentiated macrophages exhibited higher phagocytic activity against osteosarcoma cells when pretreated with B6H12 compared with the isotype control. Our preliminary data suggest a possible interaction between CD47 protein and macrophage phagocytosis in osteosarcoma metastasis. A better understanding of the role of CD47 is necessary to develop an innovative immunotherapeutic approach against osteosarcoma.

CD47 表达于细胞表面,通过与巨噬细胞表面的信号调节蛋白-α 相互作用,发出 "别吃我 "的信号。一些癌细胞表达 CD47 蛋白,可以逃避巨噬细胞的吞噬。在此,我们通过分析 CD47 的表达模式、临床病理相关性和免疫治疗潜力,评估了针对骨肉瘤靶向 CD47 的可行性。我们对 24 例骨肉瘤患者的活检样本进行了回顾性分析,研究 CD47 蛋白阳性与临床病理特征之间的相关性。20.8%的活检样本检测到CD47蛋白表达。CD47 阳性与诊断时的转移相关。CD47阳性肿瘤患者的年龄大于CD47阴性肿瘤患者。不过,CD47蛋白的表达与性别、肿瘤大小或术前化疗的组织学反应无关。在体外,CD47抗体(B6H12)不会影响骨肉瘤细胞的活力或凋亡。在伤口愈合试验中,CD47抑制了骨肉瘤细胞的迁移。与同型对照相比,用 B6H12 预处理的分化巨噬细胞对骨肉瘤细胞表现出更高的吞噬活性。我们的初步数据表明,在骨肉瘤转移过程中,CD47 蛋白与巨噬细胞吞噬功能之间可能存在相互作用。要开发一种创新的骨肉瘤免疫治疗方法,就必须更好地了解 CD47 的作用。
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引用次数: 0
Polyphenolic Compounds Activate SERCA1a and Attenuate Methylglyoxal- and Palmitate-Induced Impairment in Pancreatic INS-1E Beta Cells. 多酚类化合物可激活 SERCA1a 并减轻甲基乙二醛和棕榈酸酯对胰腺 INS-1E Beta 细胞的损伤。
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-09 DOI: 10.3390/cells13221860
Vladimir Heger, Barbora Benesova, Magdalena Majekova, Petronela Rezbarikova, Attila Hunyadi, Lubica Horakova, Jana Viskupicova

Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is an important regulatory protein responsible for maintaining calcium homeostasis within cells. Impairment of SERCA associated with activity/expression decrease has been implicated in multiple chronic conditions, including cardiovascular diseases, diabetes, cancer, neurodegenerative diseases, and skeletal muscle pathologies. Natural polyphenols have been recognized to interact with several target proteins involving SERCA. To date, only a limited number of polyphenolic compounds or their derivatives have been described either to increase SERCA activity/expression directly or to affect Ca2+ signaling pathways. In this study, we tested polyphenols for their ability to activate SERCA1a in the absence or presence of methylglyoxal or palmitate and to impact insulin release in pancreatic beta cells. The protective effects of these compounds against methylglyoxal- or palmitate-induced injury were evaluated. Results indicate that 6-gingerol, resveratrol, and ellagic acid activate SERCA1a and protect against activity decrease induced by methylglyoxal and palmitate. Molecular docking analysis revealed the binding of these polyphenols to Glu439 in the SERCA1a P-domain, suggesting a critical role in the stimulation of enzyme activity. Ellagic acid was found to directly stimulate the activity of SERCA1a, marking the first instance of such an observation.

肌浆/内质网 Ca2+-ATP 酶(SERCA)是一种重要的调节蛋白,负责维持细胞内的钙平衡。SERCA 的活性/表达下降与多种慢性疾病有关,包括心血管疾病、糖尿病、癌症、神经退行性疾病和骨骼肌病变。人们已经认识到天然多酚与涉及 SERCA 的多个靶蛋白相互作用。迄今为止,只有少数多酚类化合物或其衍生物被描述为可直接提高 SERCA 活性/表达或影响 Ca2+ 信号通路。在这项研究中,我们测试了多酚类化合物在没有或有甲基乙二酸或棕榈酸盐的情况下激活 SERCA1a 以及影响胰岛β细胞胰岛素释放的能力。评估了这些化合物对甲基乙二酸或棕榈酸酯诱导的损伤的保护作用。结果表明,6-姜酚、白藜芦醇和鞣花酸能激活 SERCA1a,并防止甲基乙二酸和棕榈酸诱导的活性下降。分子对接分析表明,这些多酚与 SERCA1a P-domain 中的 Glu439 结合,表明它们在刺激酶活性方面起着关键作用。研究发现鞣花酸可直接刺激 SERCA1a 的活性,这是首次观察到这种情况。
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引用次数: 0
18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Large-Vessel Vasculitis During Active and Inactive Disease Stages Is Associated with the Metabolic Profile, but Not the Macrophage-Related Cytokines: A Proof-of-Concept Study. 18F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描在大血管脉管炎活动期和非活动期与代谢特征有关,但与巨噬细胞相关细胞因子无关:概念验证研究
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-08 DOI: 10.3390/cells13221851
Dimitris Anastasios Palamidas, Georgios Kalykakis, Dimitra Benaki, Loukas Chatzis, Ourania D Argyropoulou, Panagiota Palla, Antonia Kollia, Pavlos Kafouris, Marinos Metaxas, Andreas V Goules, Emmanuel Mikros, Konstantinos Kambas, Constantinos D Anagnostopoulos, Athanasios G Tzioufas

Giant cell arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial GCA and large-vessel vasculitis (LV)-GCA, involving the thoracic aorta and its branches. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosing patients with systemic disease. However, its association with soluble inflammatory markers is still elusive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT-positive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The most-diseased-segment target-to-background ratio (TBRMDS) was calculated for 13 LV-GCA patients, while 14 cranial GCA and 14 Polymyalgia Rheumatica patients with negative initial PET/CT scans served as disease controls. Serum macrophage-related cytokines were evaluated by cytometric bead array (CBA). Finally, previously published NMR/metabolomics data acquired from the same blood sampling were analyzed along with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.32 vs. 2.65, p = 0.006). The analysis identified nine serum metabolites as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group but not in the disease controls. Cytokine levels were not associated with PET/CT activity. Combining CRP, ESR, and TBRMDS with choline levels, a composite index was generated to distinguish active and inactive LV-GCA (20.4 vs. 11.62, p = 0.001). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for everyday clinical practice.

巨细胞动脉炎(GCA)是一种影响大血管的自身免疫/自身炎症性疾病,多发于 50 岁以上的患者。该病表现为急性炎症反应,有两种表型,即头颅型 GCA 和累及胸主动脉及其分支的大血管炎 (LV)-GCA。18F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描(18F-FDG PET-CT)是有助于诊断全身性疾病患者的成像技术之一。然而,它与可溶性炎症标志物之间的关联仍然难以捉摸。这项概念验证研究旨在确定 PET/CT 阳性 LV-GCA 患者的新型可溶性血清生物标记物,并将其与活动性疾病(0 个月)和非活动性疾病(治疗后 6 个月)相联系。计算了13例左心室-GCA患者的最病变节段靶-背景比(TBRMDS),14例头颅GCA患者和14例初始PET/CT扫描阴性的多发性风湿病患者作为疾病对照。血清中与巨噬细胞相关的细胞因子通过细胞计数珠阵列(CBA)进行评估。最后,对之前发表的从同一血液样本中获得的核磁共振/代谢组学数据以及 PET/CT 结果进行了分析。活动期与非活动期相比,TBRMDS明显增加(3.32 vs. 2.65,p = 0.006)。分析发现,九种血清代谢物对从活动状态到非活动状态的变化更为敏感。其中,胆碱水平只在 LV-GCA 组中发生改变,而在疾病对照组中没有发生改变。细胞因子水平与 PET/CT 活性无关。将 CRP、ESR 和 TBRMDS 与胆碱水平相结合,可生成一个综合指数来区分活动性和非活动性 LV-GCA(20.4 vs. 11.62,p = 0.001)。这些初步结果可为更广泛的研究铺平道路,这些研究将血清代谢组学参数与 PET/CT 成像数据相结合,以提取对日常临床实践有用的敏感的复合疾病指数。
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引用次数: 0
Dysregulation of miRNAs in Soft Tissue Sarcomas. 软组织肉瘤中的 miRNA 失调。
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-08 DOI: 10.3390/cells13221853
Stefano Zoroddu, Angela Lucariello, Antonio De Luca, Luigi Bagella

MicroRNAs (miRNAs) are pivotal regulators of gene expression, influencing key cellular processes such as proliferation, differentiation, apoptosis, and metastasis. In the realm of sarcomas-a diverse group of malignant tumors affecting soft tissues and bone sarcomas-miRNAs have emerged as crucial players in tumorigenesis and tumor progression. This review delves into the intricate roles of miRNAs across various soft tissue sarcoma subtypes, including rhabdomyosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and malignant peripheral nerve sheath tumor (MPNST). We explore how dysregulated miRNAs function as oncogenes or tumor suppressors, modulating critical pathways that define the aggressive nature of these cancers. Furthermore, we discuss the diagnostic and prognostic potential of specific miRNAs and highlight their promise as therapeutic targets. By understanding the miRNA-mediated regulatory networks, this review aims to provide a comprehensive overview of current research while pointing towards future directions for miRNA-based therapies. Our findings underscore the potential of miRNAs to transform the landscape of sarcoma treatment, offering hope for more precise, personalized, and effective therapeutic strategies.

微RNA(miRNA)是基因表达的关键调控因子,影响着细胞的增殖、分化、凋亡和转移等关键过程。在肉瘤--影响软组织和骨肉瘤的多种恶性肿瘤--领域中,miRNA 已成为肿瘤发生和肿瘤进展的关键角色。本综述深入探讨了 miRNA 在各种软组织肉瘤亚型中的复杂作用,包括横纹肌肉瘤、脂肪肉瘤、亮肌肉瘤、滑膜肉瘤、纤维肉瘤、血管肉瘤、未分化多形性肉瘤(UPS)和恶性周围神经鞘瘤(MPNST)。我们探讨了失调的 miRNA 如何作为致癌基因或肿瘤抑制因子发挥作用,如何调节决定这些癌症侵袭性的关键通路。此外,我们还讨论了特定 miRNA 的诊断和预后潜力,并强调了它们作为治疗靶点的前景。通过了解 miRNA 介导的调控网络,本综述旨在全面概述当前的研究,同时为基于 miRNA 的疗法指明未来的方向。我们的研究结果强调了 miRNA 改变肉瘤治疗格局的潜力,为更精确、个性化和有效的治疗策略带来了希望。
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引用次数: 0
Semaglutide Ameliorates Diabetic Neuropathic Pain by Inhibiting Neuroinflammation in the Spinal Cord. 塞马鲁肽通过抑制脊髓神经炎症改善糖尿病神经性疼痛
IF 5.1 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-11-08 DOI: 10.3390/cells13221857
Sing-Ong Lee, Yaswanth Kuthati, Wei-Hsiu Huang, Chih-Shung Wong

Glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes and obesity. Despite the development of several drugs for neuropathic pain management, their poor efficacy, tolerance, addiction potential, and side effects limit their usage. Teneligliptin, a DPP-4 inhibitor, has been shown to reduce spinal astrocyte activation and neuropathic pain caused by partial sciatic nerve transection. Additionally, we showed its capacity to improve the analgesic effects of morphine and reduce analgesic tolerance. Recent studies indicate that GLP-1 synthesized in the brain activates GLP-1 receptor signaling pathways, essential for neuroprotection and anti-inflammatory effects. Multiple in vitro and in vivo studies using preclinical models of neurodegenerative disorders have shown the anti-inflammatory properties associated with glucagon-like peptide-1 receptor (GLP-1R) activation. This study aimed to investigate the mechanism of antinociception and the effects of the GLP-1 agonist semaglutide (SEMA) on diabetic neuropathic pain in diabetic rats.

Methods: Male Wistar rats, each weighing between 300 and 350 g, were categorized into four groups: one non-diabetic sham group and three diabetic groups. The diabetic group received a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 60 mg/kg to induce diabetic neuropathy. After 4 weeks of STZ injection, one diabetic group was given saline (vehicle), and the other two were treated with either 1× SEMA (1.44 mg/kg, orally) or 2× SEMA (2.88 mg/kg, orally). Following a 4-week course of oral drug treatment, behavioral, biochemical, and immunohistochemical analyses were carried out. The mechanical allodynia, thermal hyperalgesia, blood glucose, advanced glycation end products (AGEs), plasma HbA1C, and spinal inflammatory markers were evaluated.

Results: SEMA treatment significantly reduced both allodynia and hyperalgesia in the diabetic group. SEMA therapy had a limited impact on body weight restoration and blood glucose reduction. In diabetic rats, SEMA lowered the amounts of pro-inflammatory cytokines in the spinal cord and dorsal horn. It also lowered the activation of microglia and astrocytes in the dorsal horn. SEMA significantly reduced HbA1c and AGE levels in diabetic rats compared to the sham control group.

Conclusions: These results indicate SEMA's neuroprotective benefits against diabetic neuropathic pain, most likely by reducing inflammation and oxidative stress by inhibiting astrocyte and microglial activity. Our findings suggest that we can repurpose GLP-1 agonists as potent anti-hyperalgesic and anti-inflammatory drugs to treat neuropathic pain without serious side effects.

胰高血糖素样肽 1(GLP-1)受体激动剂常用于治疗 2 型糖尿病和肥胖症。尽管已开发出多种用于治疗神经病理性疼痛的药物,但其疗效不佳、耐受性、成瘾性和副作用限制了它们的使用。DPP-4抑制剂替尼列汀已被证明可减少坐骨神经部分横断引起的脊髓星形胶质细胞活化和神经病理性疼痛。此外,我们还发现它能改善吗啡的镇痛效果并降低镇痛耐受性。最近的研究表明,大脑中合成的 GLP-1 可激活 GLP-1 受体信号通路,对神经保护和抗炎作用至关重要。使用神经退行性疾病临床前模型进行的多项体外和体内研究表明,胰高血糖素样肽-1 受体(GLP-1R)激活具有抗炎特性。本研究旨在探讨 GLP-1 激动剂塞马鲁肽(SEMA)对糖尿病大鼠神经病理性疼痛的抗痛机制和影响:雄性 Wistar 大鼠(每只体重在 300 至 350 克之间)分为四组:一组为非糖尿病假组,三组为糖尿病组。糖尿病组一次性腹腔注射 60 毫克/千克的链脲佐菌素(STZ)以诱导糖尿病神经病变。注射 STZ 4 周后,给一个糖尿病组注射生理盐水(载体),给另外两个糖尿病组口服 1× SEMA(1.44 毫克/千克)或 2× SEMA(2.88 毫克/千克)。口服药物治疗 4 周后,进行行为、生化和免疫组化分析。对机械异感、热痛、血糖、高级糖化终产物(AGEs)、血浆 HbA1C 和脊髓炎症标志物进行了评估:结果:SEMA治疗明显减轻了糖尿病组的异动和痛觉亢进。SEMA 治疗对体重恢复和血糖降低的影响有限。在糖尿病大鼠中,SEMA 降低了脊髓和背角中促炎细胞因子的数量。它还降低了背角小胶质细胞和星形胶质细胞的活化程度。与假对照组相比,SEMA 能明显降低糖尿病大鼠的 HbA1c 和 AGE 水平:这些结果表明,SEMA 对糖尿病神经病理性疼痛具有神经保护作用,很可能是通过抑制星形胶质细胞和小胶质细胞的活性来减少炎症和氧化应激。我们的研究结果表明,我们可以重新利用 GLP-1 激动剂作为强效的抗过敏和抗炎药物来治疗神经性疼痛,而不会产生严重的副作用。
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引用次数: 0
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Cells
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