Biomedical Journal最新文献_第2页

An Ex vivo cultivation model for circulating tumor cells: The success rate and correlations with cancer response to therapy 循环肿瘤细胞的离体培养模型：成功率及其与肿瘤治疗反应的相关性。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2024.100819

I-Hsuan Chiang , Hsuan-Chih Kuo , Chun-Ta Liao , Yung-Chia Kuo , Shao-Ming Yu , Hung-Ming Wang , Yi-Hui Huang , Kim Anh Nguyen Thi , Min-Hsien Wu , Jason Chia-Hsun Hsieh

Background

Cancer mortality is closely linked to recurrence and distant metastasis, posing challenges in real-time tracking due to the invasiveness of current methods. Circulating tumor cells (CTCs) show promise as potential tools; however, their scarcity remains a significant obstacle.

Method

In this prospective study, we validated a simple culture protocol and investigated the correlation between clinical response and CTC growth status. Following negative selection, the isolated cells were subjected to ex vivo cultivation in a two-dimensional environment supplemented with cytokines for up to 21 days, followed by immunofluorescence staining for analysis.

Results

Among 37 participants with solid tumors and distant metastasis (34.8% head and neck cancer), 47 samples were collected, from which CTCs were detected. The percentages of CTCs, atypical CTCs, and white blood cells during cultivation from days 7–21 were significantly different (p < 0.001, p < 0.001, and p = 0.330, respectively). Patients were further categorized into progressive disease (PD) and non-PD groups based on disease status, revealing significant differences in CTC growth rates, which increases from Days 7–21 between groups (5.5x vs. 2.8x growth, respectively; p < 0.001).

Conclusion

With the proposed protocols, we cultured CTCs from patients with various cancers for 21 days and identified a tool for predicting cancer response. The actual cancer status (PD or non-PD) at CTC isolation correlates to CTC growth rate, guiding the required observation time and parameters for culture.

背景：癌症死亡率与复发和远处转移密切相关，由于现有方法的侵入性，对实时跟踪提出了挑战。循环肿瘤细胞（ctc）有望成为潜在的工具；然而，它们的稀缺性仍然是一个重大障碍。方法：在这项前瞻性研究中，我们验证了一种简单的培养方案，并研究了临床反应与CTC生长状态的相关性。阴性选择后，分离的细胞在补充细胞因子的二维环境中体外培养21天，然后进行免疫荧光染色分析。结果：37例实体瘤及远处转移患者（头颈癌34.8%）共采集47例样本，检出ctc。培养第7 ~ 21天CTCs、非典型CTCs和白细胞的百分比差异有统计学意义（p < 0.001, p < 0.001, p = 0.330）。根据病情进一步将患者分为进展性疾病（PD）组和非PD组，发现两组之间CTC生长速率和从第7天到第21天的增长显著差异（分别增长5.5倍和2.8倍）；P < 0.001)。结论：我们的方案培养了来自各种癌症患者的ctc 21天，并确定了预测癌症反应的工具。CTC分离时的实际癌症状态（PD或非PD）与CTC生长速度相关，指导所需的观察时间和培养参数。

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引用次数: 0

High-throughput proteomics-guided biomarker discovery of hepatocellular carcinoma 高通量蛋白质组学引导下的肝细胞癌生物标志物发现。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2024.100752

Dongyoon Shin , Yeongshin Kim , Junho Park , Youngsoo Kim

Liver cancer stands as the fifth leading cause of cancer-related deaths globally. Hepatocellular carcinoma (HCC) comprises approximately 85%–90% of all primary liver malignancies. However, only 20–30% of HCC patients qualify for curative therapy, primarily due to the absence of reliable tools for early detection and prognosis of HCC. This underscores the critical need for molecular biomarkers for HCC management. Since proteins reflect disease status directly, proteomics has been utilized in biomarker developments for HCC. In particular, proteomics coupled with liquid chromatography-mass spectrometer (LC-MS) methods facilitate the process of discovering biomarker candidates for diagnosis, prognosis, and therapeutic strategies.

In this work, we investigated LC-MS-based proteomics methods through recent reference reviews, with a particular focus on sample preparation and LC-MS methods appropriate for the discovery of HCC biomarkers and their clinical applications.

We classified proteomics studies of HCC according to sample types, and we examined the coverage of protein biomarker candidates based on LC-MS methods in relation to study scales and goals. Comprehensively, we proposed protein biomarker candidates categorized by sample types and biomarker types for appropriate clinical use.

In this review, we summarized recent LC-MS-based proteomics studies on HCC and proposed potential protein biomarkers. Our findings are expected to expand the understanding of HCC pathogenesis and enhance the efficiency of HCC diagnosis and prognosis, thereby contributing to improved patient outcomes.

肝癌是全球癌症相关死亡的第五大主要原因。肝细胞癌（HCC）约占所有原发性肝脏恶性肿瘤的85%-90%。然而，只有 20%-30% 的 HCC 患者有资格接受根治性治疗，这主要是由于缺乏可靠的 HCC 早期检测和预后工具。这凸显了HCC治疗对分子生物标志物的迫切需要。由于蛋白质能直接反映疾病状态，因此蛋白质组学已被用于 HCC 生物标志物的开发。特别是，蛋白质组学与液相色谱-质谱联用（LC-MS）方法有助于发现用于诊断、预后和治疗策略的候选生物标记物。在这项工作中，我们通过最近的参考文献综述研究了基于液相色谱-质谱的蛋白质组学方法，尤其关注适合发现 HCC 生物标志物及其临床应用的样品制备和液相色谱-质谱方法。我们根据样本类型对 HCC 蛋白质组学研究进行了分类，并结合研究规模和目标考察了基于 LC-MS 方法的候选蛋白质生物标志物的覆盖范围。综上所述，我们提出了按样本类型和生物标记物类型分类的候选蛋白质生物标记物，以供临床使用。在这篇综述中，我们总结了近期基于 LC-MS 的 HCC 蛋白质组学研究，并提出了潜在的蛋白质生物标记物。我们的研究结果有望拓展人们对 HCC 发病机制的认识，提高 HCC 诊断和预后的效率，从而改善患者的预后。

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引用次数: 0

The effect and mechanism of astragalus polysaccharides on T cells and macrophages in inhibiting prostate cancer 黄芪多糖对T细胞和巨噬细胞抑制前列腺癌的作用和机制

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2024.100741

Ching-Yuan Wu , Yao-Hsu Yang , Yu-Shih Lin , Li-Hsin Shu , Hung-Te Liu , Chung-Kuang Lu , Yu-Huei Wu , Yu-Heng Wu

Background

The impact and underlying mechanisms of astragalus polysaccharide (APS) on prostate cancer, particularly its role in immunomodulation, remain inadequately elucidated.

Methods

This study employed the XTT assay for assessing proliferation in prostate cancer cells and macrophages. T cell proliferation was determined using the Carboxyfluorescein diacetate succinimidyl ester labeling assay. APS’s effect on T cells and macrophages was scrutinized via flow cytometry, Western blot analysis, ELISA, quantitative PCR and cytokine membrane arrays. The effect of APS on interaction between PD-L1 and PD-1 was investigated by the PD-L1/PD-1 homogeneous assay. Additionally, the impact of conditioned medium from T cells and macrophages on PC-3 cell migration was explored through migration assays.

Results

It was observed that APS at concentrations of 1 and 5 mg/mL enhanced the proliferation of CD8⁺ T cells. At a concentration of 5 mg/mL, APS activated both CD4⁺ and CD8⁺ T cells, attenuated PD-L1 expression in prostate cancer cells stimulated with interferon gamma (IFN-γ) or oxaliplatin, and moderately decreased the population of PD-1+ CD4⁺ and PD-1+ CD8⁺ T cells. Furthermore, APS at this concentration impeded the interaction between PD-L1 and PD-1, inhibited the promotion of prostate cancer migration mediated by RAW 264.7 cells, THP-1 cells, CD4⁺ T cells, and CD8⁺ T cells, and initiated apoptosis in prostate cancer cells treated with conditioned medium from APS (5 mg/mL)-treated CD8⁺ T cells, RAW 264.7 cells, or THP-1 cells.

Conclusion

The findings indicate a potential role of 5 mg/mL APS in modulating the PD-1/PD-L1 pathway and influencing the immune response, encompassing T cells and macrophages. Consequently, further in vivo research is recommended to assess the efficacy of APS.

背景：黄芪多糖（APS）对前列腺癌的影响及其内在机制，尤其是其在免疫调节中的作用，仍未得到充分阐明：本研究采用 XTT 法评估前列腺癌细胞和巨噬细胞的增殖情况。T细胞增殖采用羧基荧光素二乙酸琥珀酰亚胺酯标记法进行测定。通过流式细胞术、Western 印迹分析、酶联免疫吸附试验、定量 PCR 和细胞因子膜阵列，仔细研究了 APS 对 T 细胞和巨噬细胞的影响。通过 PD-L1/PD-1 均匀试验研究了 APS 对 PD-L1 和 PD-1 之间相互作用的影响。此外，还通过迁移试验探讨了 T 细胞和巨噬细胞的条件培养基对 PC-3 细胞迁移的影响：结果：观察发现，浓度为 1 毫克/毫升和 5 毫克/毫升的 APS 可增强 CD8+ T 细胞的增殖。浓度为 5 毫克/毫升时，APS 可激活 CD4+ 和 CD8+ T 细胞，减轻受γ干扰素（IFN-γ）或奥沙利铂刺激的前列腺癌细胞中 PD-L1 的表达，并适度减少 PD-1+ CD4+ 和 PD-1+ CD8+ T 细胞的数量。此外，该浓度的APS还阻碍了PD-L1和PD-1之间的相互作用，抑制了由RAW 264.7细胞、THP-1细胞、CD4+ T细胞和CD8+ T细胞介导的前列腺癌迁移的促进作用，并启动了经APS（5 mg/mL）处理的CD8+ T细胞、RAW 264.7细胞或THP-1细胞的条件培养基处理的前列腺癌细胞的凋亡：研究结果表明，5 mg/mL APS 在调节 PD-1/PD-L1 通路和影响免疫反应（包括 T 细胞和巨噬细胞）方面具有潜在作用。因此，建议进一步开展体内研究，以评估 APS 的疗效。

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引用次数: 0

Hepatocyte nuclear factor 4 located in different developmental stages of Schistosoma japonicum and involved in important metabolic pathways 肝细胞核因子 4 位于日本血吸虫的不同发育阶段，参与重要的代谢途径。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2024.100726

Kaijuan Wu , Shuaiqin Huang , Yiming Zhao , Abdulrahim Umar , Hao Chen , Zheng Yu , Jing Huang

Background

Nuclear receptors (NRs) are vital for regulating gene expression in organisms. Hepatocyte nuclear factor 4 (HNF4), a class of NRs, participates in blood feeding and intestinal maintenance in schistosomes. However, there are limited researches on the molecular and functional characterization of HNF4 in Schistosoma japonicum (S. japonicum).

Methods

Highly specific polyclonal antibodies were generated to analyze the expression and tissue localization of S. japonicum HNF4 (SjHNF4). The potential biological functions of SjHNF4 were characterized by transcriptome and pull-down analyses. Subsequently, enrichment analysis was performed to identify the specific signaling pathways linked to SjHNF4.

Results

The SjHNF4 protein was expressed heterologously and purified successfully. High purity and high potency polyclonal antibodies were further prepared. The expression of SjHNF4 was higher in female compared to male worms at both transcriptional and protein levels. Female worms expressed SjHNF4 in their perithecium, reproductive system, and certain parts of the intestinal tissues. SjHNF4 was also detected in the perithecium of male worms, as well as in the head, body of cercariae, and eggs. Furthermore, our findings highlighted the potential role of SjHNF4 in blood feeding and its interaction with crucial pathways such as glucose metabolism, lipid metabolism, and nucleotide metabolism.

Conclusions

This study shed light on the localization of SjHNF4 in different life stages of S. japonicum, particularly associated with the female schistosomes. A strong correlation was observed between SjHNF4 and essential metabolic pathways. These findings laid a solid groundwork for the research on the relationship between NRs and schistosomes.

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引用次数: 0

Mitochondrial dysfunction route as a possible biomarker and therapy target for human cancer 线粒体功能障碍途径可能是人类癌症的生物标记物和治疗靶点

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2024.100714

Rawan Al-Faze , Hoda A. Ahmed , Mohamed A. El-Atawy , Hayat Zagloul , Eida M. Alshammari , Mariusz Jaremko , Abdul-Hamid Emwas , Gehan M. Nabil , Demiana H. Hanna

Mitochondria are vital organelles found within living cells and have signalling, biosynthetic, and bioenergetic functions. Mitochondria play a crucial role in metabolic reprogramming, which is a characteristic of cancer cells and allows them to ensure a steady supply of proteins, nucleotides, and lipids to enable rapid proliferation and development. Their dysregulated activities have been associated with the growth and metastasis of different kinds of human cancer, particularly ovarian carcinoma. In this review, we briefly demonstrated the modified mitochondrial function in cancer, including mutations in mitochondrial DNA (mtDNA), reactive oxygen species (ROS) production, dynamics, apoptosis of cells, autophagy, and calcium excess to maintain cancer genesis, progression, and metastasis. Furthermore, the mitochondrial dysfunction pathway for some genomic, proteomic, and metabolomics modifications in ovarian cancer has been studied. Additionally, ovarian cancer has been linked to targeted therapies and biomarkers found through various alteration processes underlying mitochondrial dysfunction, notably targeting (ROS), metabolites, rewind metabolic pathways, and chemo-resistant ovarian carcinoma cells.

线粒体是活细胞内的重要细胞器，具有信号、生物合成和生物能功能。线粒体在新陈代谢重编程中发挥着至关重要的作用，这是癌细胞的一个特征，使它们能够确保蛋白质、核苷酸和脂质的稳定供应，从而实现快速增殖和发展。它们的活动失调与各种人类癌症，尤其是卵巢癌的生长和转移有关。在这篇综述中，我们简要介绍了癌症中线粒体功能的改变，包括 mtDNA 突变、活性氧的产生、动态变化、细胞凋亡、自噬和钙过量，从而维持癌症的发生、发展和转移。此外，还研究了线粒体功能障碍在卵巢癌中导致基因组、蛋白质组和代谢组学改变的途径。此外，通过线粒体功能障碍的各种改变过程，特别是针对活性氧、代谢物、倒退代谢途径和化疗抗性卵巢癌细胞的改变，卵巢癌已与靶向疗法和生物标志物相关联。

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引用次数: 0

Reflecting on the 1998 enterovirus outbreak: A 25-year retrospective and learned lessons 反思 1998 年肠病毒爆发：25 年回顾与经验教训。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2024.100715

Peng-Nien Huang , Shao-Hsuan Hsia , Kuan-Ying Arthur Huang , Chih-Jung Chen , En-Tzu Wang , Shin-Ru Shih , Tzou-Yien Lin

Enterovirus A71 (EV-A71) infections are a major Asia-Pacific health issue. However, this infection can cause serious and potentially fatal neurological issues. We attempt to explain EV-A71's molecular virology, epidemiology, and recombination events in this review. The clinical and neurological signs of EV-A71 infections are well documented. The review discusses EV-A71 central nervous system infections' causes, diagnostic criteria, treatment choices, and prognosis. Some consequences are aseptic meningitis, acute flaccid paralysis, and acute transverse myelitis. These problems' pathophysiology and EV-A71's central nervous system molecular processes are examined in the review. EV-A71 infections must be diagnosed accurately for therapy. No particular antiviral medications exist for EV-A71 infections, thus supportive care is the main treatment. The study emphasises addressing symptoms including temperature, dehydration, and pain to ease suffering. EV-A71 CNS infections have different prognoses depending on severity. The review discusses long-term effects and neurological sequelae of EV-A71 infections. In conclusion, Asia-Pacific public health is threatened by EV-A71 infections. This review helps prevent, diagnose, and treat EV-A71 infections by addressing the mechanisms, diagnostic criteria, treatment choices, and prognosis. This study fully examines the challenges and considerations of managing and treating EV-A71 infections. It also recommends future research and development to generate effective viral infection treatments.

肠道病毒 A71（EV-A71）感染是亚太地区的一个重大公共卫生问题。EV-A71 主要导致儿童手足口病（HFMD）。然而，这种病毒也会导致患者出现严重的、可能致命的神经系统后果。本综述旨在全面介绍与 EV-A71 相关的分子病毒学、流行病学和重组事件。文献广泛涉及 EV-A71 感染的临床表现和神经系统症状。本综述探讨的并发症之一是脑干脑炎，它可能是 EV-A71 感染的结果。脑干脑炎是指脑干的炎症，脑干是负责各种身体功能的重要区域。本综述探讨了涉及 EV-A71 的中枢神经系统感染的基本机制、诊断标准、治疗方案和预后。与 EV-A71 感染相关的神经系统并发症多种多样，并可能造成严重后果。这些并发症可能包括无菌性脑膜炎、急性弛缓性麻痹和急性横贯性脊髓炎。本综述深入探讨了这些并发症的病理生理学，揭示了 EV-A71 影响中枢神经系统的分子机制。EV-A71 感染的准确诊断对于适当的管理和治疗至关重要。EV-A71 感染的治疗方案主要侧重于支持性护理，因为目前还没有针对这种病毒的特效抗病毒药物。综述强调了控制发烧、脱水和止痛等症状以减轻患者负担的重要性。EV-A71 中枢神经系统（CNS）感染患者的预后会因并发症的严重程度而有所不同。本综述深入探讨了与 EV-A71 感染相关的长期预后和潜在的神经系统后遗症。总之，EV-A71 感染已成为亚太地区主要的公共卫生问题。本综述旨在加深我们对与 EV-A71 相关的分子病毒学、流行病学和神经系统并发症的了解。通过研究其潜在机制、诊断标准、治疗方案和预后，本综述有助于制定预防、诊断和管理 EV-A71 感染的有效策略。本文全面分析了与 EV-A71 和手足口病爆发有关的全球数据。随后的论述深入探讨了针对 EV-A71 疫苗的研发进展和战略制定。总之，本研究全面探讨了 EV-A71 感染管理和治疗中的潜在障碍和注意事项。此外，它还为未来的研发工作提出了建议，目的是为这种病毒感染制定有效的治疗方法。

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引用次数: 0

Molecular diagnosis of nasopharyngeal carcinoma: Past and future 鼻咽癌的分子诊断：过去与未来

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2024.100748

Cheng-Lung Hsu , Yu-Sun Chang , Hsin-Pai Li

Nasopharyngeal carcinoma (NPC) is a malignant tumor originated from the nasopharynx epithelial cells and has been linked with Epstein-Barr virus (EBV) infection, dietary habits, environmental and genetic factors. It is a common malignancy in Southeast Asia, especially with gender preference among men. Due to its non-specific symptoms, NPC is often diagnosed at a late stage. Thus, the molecular diagnosis of NPC plays a crucial role in early detection, treatment selection, disease monitoring, and prognosis prediction. This review aims to provide a summary of the current state and the latest emerging molecular diagnostic techniques for NPC, including EBV-related biomarkers, gene mutations, liquid biopsy, and DNA methylation. Challenges and potential future directions of NPC molecular diagnosis will be discussed.

引用次数: 0

Good things come in small packages: The discovery of small RNAs in the smallest animal model

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2025.100832

Chung-Pei Ma , Szecheng J. Lo , Bertrand Chin-Ming Tan

The 2024 Nobel Prize in Physiology or Medicine has been awarded to two pioneering researchers, Victor Ambros and Gary Ruvkun, marking the fourth time research using Caenorhabditis elegans (C. elegans) has received this prestigious recognition. With a rapid life cycle of just 3.5 days and four distinct larval stages, C. elegans serves as an ideal model for exploring complex genetic mechanisms, particularly heterochronic gene regulation. Ambros and Ruvkun's groundbreaking work on lin-4 and lin-14 genes in C. elegans revealed that lin-4 functions as a 22-nucleotide small RNA—now known as a microRNA (miRNA)—that binds complementarily to the 3′ UTR of lin-14 mRNA, effectively inhibiting LIN-14 protein synthesis. This discovery was the first demonstration of miRNA in post-transcriptional gene regulation, a finding that has since reshaped our understanding of genetic regulation across species. Their research on small RNAs in C. elegans not only opened a new paradigm in molecular biology but also highlighted the power of this model organism in uncovering universal biological principles.

引用次数: 0

Epigenetic modifications of cfDNA in liquid biopsy for the cancer care continuum 液体活检中 cfDNA 的表观遗传学修饰，促进癌症治疗的连续性。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2024.100718

Jodie Wong , Rohit Muralidhar , Liang Wang , Chiang-Ching Huang

This review provides a comprehensive overview of the latest advancements in the clinical utility of liquid biopsy, with a particular focus on epigenetic approaches aimed at overcoming challenges in cancer diagnosis and treatment. It begins by elucidating key epigenetic terms, including methylomics, fragmentomics, and nucleosomics. The review progresses to discuss methods for analyzing circulating cell-free DNA (cfDNA) and highlights recent studies showcasing the clinical relevance of epigenetic modifications in areas such as diagnosis, drug treatment response, minimal residual disease (MRD) detection, and prognosis prediction. While acknowledging hurdles like the complexity of interpreting epigenetic data and the absence of standardization, the review charts a path forward. It advocates for the integration of multi-omic data through machine learning algorithms to refine predictive models and stresses the importance of collaboration among clinicians, researchers, and data scientists. Such cooperative efforts are essential to fully leverage the potential of epigenetic features in clinical practice.

本综述全面概述了液体活检临床应用的最新进展，尤其关注旨在克服癌症诊断和治疗难题的表观遗传学方法。文章首先阐明了关键的表观遗传学术语，包括甲基组学、片段组学和核糖体学。综述接着讨论了分析循环游离细胞DNA（cfDNA）的方法，并重点介绍了最近的研究，这些研究展示了表观遗传修饰在诊断、药物治疗反应、最小残留病（MRD）检测和预后预测等领域的临床意义。在承认表观遗传学数据解读的复杂性和缺乏标准化等障碍的同时，该综述描绘了一条前进的道路。它提倡通过机器学习算法整合多组学数据，以完善预测模型，并强调临床医生、研究人员和数据科学家之间合作的重要性。这种合作对于在临床实践中充分利用表观遗传特征的潜力至关重要。

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引用次数: 0

Doxycycline cotherapy with albendazole relieves neural function damage in C57BL/6 and BALB/c mice infected with Angiostrongylus cantonensis 多西环素联合阿苯达唑疗法可缓解C57BL/6和BALB/c小鼠感染坎顿氏安氏梭菌后的神经功能损伤。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2025-02-01 DOI: 10.1016/j.bj.2024.100727

Eny Sofiyatun , Kuang-Yao Chen , Chih-Jen Chou , Hsin-Chia Lee , Yi-An Day , Pei-Jui Chiang , Cheng-Hsun Chiu , Wei-June Chen , Kai-Yuan Jhan , Lian-Chen Wang

Background

We investigated the effects of combination therapy albendazole and doxycycline in Angiostrongylus cantonensis-infected mice during early and late treatment.

Materials and methods

C57BL/6 and BALB/c mice were divided into five groups: (i) uninfected, (ii) infected with A. cantonensis, (iii) infected + 10 mg/kg albendazole, (iv) infected + 25 mg/kg doxycycline, and (v) infected + 10 mg/kg albendazole + 25 mg/kg doxycycline. We administered drugs in both early treatments started at 7-day post infections (dpi) and late treatments (14 dpi) to A. cantonensis-infected C57BL/6 and BALB/c mice. To assess the impact of these treatments, we employed the Morris water maze test to evaluate spatial learning and memory abilities, and the rotarod test to measure motor coordination and balance in C57BL/6 mice. Additionally, we monitored the expression of the cytokine IL-33 and GFAP in the brain of these mice using Western blot analysis.

Results

In this study, A. cantonensis infection was observed to cause extensive cerebral angiostrongyliasis in C57BL/6 mice. This condition significantly affected their spatial learning and memory abilities, as assessed by the Morris water maze test, as well as their motor coordination, which was evaluated using the rotarod test. Early treatment with albendazole led to favorable recovery outcomes. Both C57BL/6 and BALB/c mice express IL-33 and GFAP after co-therapy. The differences of levels and patterns of IL-33 and GFAP expression in mice may be influenced by the balance between pro-inflammatory and anti-inflammatory signals within the immune system.

Conclusions

Combination therapy with anthelmintics and antibiotics in the early stage of A. cantonensis infection, in C57BL/6 and BALB/c mice resulted in the death of parasites in the brain and reduced the subsequent neural function damage and slowed brain damage and neurobehavior impairment. This study suggests a more effective and novel treatment, and drug delivery method for brain lesions that can decrease the neurological damage of angiostrongyliasis patients.

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引用次数: 0