Biomedical Journal最新文献_第10页

Antrodia cinnamomea extract alleviates bleomycin-induced pulmonary fibrosis in mice by inhibiting the mTOR pathway 蚂蚁肉桂提取物通过抑制mTOR途径减轻博莱霉素诱导的小鼠肺纤维化。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-26 DOI: 10.1016/j.bj.2024.100720

Background

Pulmonary fibrosis is a progressive diffuse parenchymal lung disorder with a high mortality rate. Studies have indicated that injured lung tissues release various pro-inflammatory factors, and produce a large amount of nitric oxide. There is also accumulation of collagen and oxidative stress-induced injury, collectively leading to pulmonary fibrosis. Antrodia cinnamomea is an endemic fungal growth in Taiwan, and its fermented extracts exert anti-inflammatory effects to alleviate liver damages. Hence, we hypothesized and tested the feasibility of using A. cinnamomea extracts for treatment of pulmonary fibrosis.

Methods

The TGF-β1-induced human lung fibroblast cells (MRC-5) in vitro cell assay were used to evaluate the effects of A. cinnamomea extracts on the collagen production in MRC-5. Eight-week-old ICR mice were intratracheally administered bleomycin and then fed with an A. cinnamomea extract on day 3 post-administration of bleomycin. At day 21 post-bleomycin administration, the pulmonary functional test, the expression level of inflammation- and fibrosis-related genes in the lung tissue, and the histopathological change were examined.

Results

The A. cinnamomea extract significantly attenuated the expression level of collagen in the TGF-β1-induced MRC-5 cells. In the A. cinnamome-treated bleomycin-induced lung fibrotic mice, the bodyweight increased, pulmonary functions improved, the lung tissues expression level of inflammatory factor and the fibrotic indicator were decreased, and the histopathological results showed the reduction of thickening of the inter-alveolar septa.

Conclusions

The Antrodia cinnamomea extract significant protects mice against bleomycin-induced lung injuries through improvement of body weight gain and lung functions, and attenuation of expression of inflammatory and fibrotic indicators.

背景：肺纤维化是一种进行性弥漫性肺实质疾病，死亡率很高。研究表明，损伤的肺组织会释放各种促炎因子，并产生大量一氧化氮。此外，胶原蛋白的积累和氧化应激引起的损伤共同导致了肺纤维化。肉桂蕨是台湾特有的真菌，其发酵提取物具有抗炎作用，可减轻肝损伤。因此，我们假设并测试了使用肉桂提取物治疗肺纤维化的可行性：方法：采用TGF-β1诱导的人肺成纤维细胞（MRC-5）体外细胞试验，评估肉桂提取物对MRC-5胶原蛋白生成的影响。对 8 周大的 ICR 小鼠气管内注射博莱霉素，然后在注射博莱霉素后的第 3 天喂食肉桂萃取物。在使用博莱霉素后第 21 天，检测肺功能测试、肺组织中炎症和纤维化相关基因的表达水平以及组织病理学变化：结果：肉桂提取物能显著降低TGF-β1诱导的MRC-5细胞中胶原蛋白的表达水平。肉桂提取物治疗博莱霉素诱导的肺纤维化小鼠体重增加，肺功能改善，肺组织炎症因子和纤维化指标表达水平降低，组织病理学结果显示肺泡间质增厚减轻：结论：肉桂酸蚂蚁提取物能显著保护小鼠免受博莱霉素诱导的肺损伤，改善小鼠的体重增加和肺功能，减少炎症和纤维化指标的表达。

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引用次数: 0

Pharmaceutical cost savings from the treatment of oncology patients in clinical trials. 临床试验中治疗肿瘤患者节省的医药成本。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-26 DOI: 10.1016/j.bj.2024.100742

Borja Gómez Mediavilla, Paloma Lanza León, Virginia Martínez Callejo, David Cantarero Prieto, María Lanza Postigo, Matilde Salcedo Lambea, Yolanda Blanco Mesonero, María Ochagavia Sufrategui, Ignacio Durán, Carmen María Sarabia Cobo

Objective: The aim of this study was twofold: to assess the annual pharmaceutical savings associated with the treatment of cancer patients at Marqués de Valdecilla University Hospital and to estimate the cost of innovative antineoplastic therapies that patients receive as experimental treatment, both during clinical trials throughout 2020.

Material and methods: An observational and financial analysis of the drug cost related to clinical trials was applied. Direct cost savings to the Regional Health System of Cantabria and the cost of innovative therapies used as an experimental treatment in clinical trials were quantified.

Results: This study includes 38 clinical trials with a sample of 101 patients. The clinical trials analyzed provide a total cost savings of €603,350.21 and an average cost saving of €6,630.22 per patient. Furthermore, the total investment amounts to €789,892.67, with an average investment of €15,488.09 per patient.

Conclusions: Clinical trials are essential for the advancement of science. Furthermore, clinical trials can be a significant source of income for both hospitals and Regional Health Systems, contributing to their financial sustainability.

目的：这项研究有两个目的：评估巴尔德西亚侯爵大学医院每年在治疗癌症患者方面节省的药品费用；估算患者在 2020 年临床试验期间作为试验性治疗接受创新抗肿瘤疗法的费用：对与临床试验相关的药物成本进行了观察和财务分析。对坎塔布里亚地区卫生系统直接节省的费用和临床试验中作为试验性治疗的创新疗法的费用进行了量化：这项研究包括38项临床试验，样本为101名患者。所分析的临床试验共节约成本603,350.21欧元，平均每位患者节约成本6,630.22欧元。此外，总投资额为 789,892.67 欧元，每位患者平均投资额为 15,488.09 欧元：临床试验对科学进步至关重要。此外，临床试验还是医院和地区医疗系统的重要收入来源，有助于其财务可持续性。

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引用次数: 0

m⁶A landscape is more pervasive when Trypanosoma brucei exits the cell cycle. 当布氏锥虫退出细胞周期时，m6A 的分布更为普遍。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-17 DOI: 10.1016/j.bj.2024.100728

Lúcia Serra, Sara Silva Pereira, Idálio J Viegas, Henrique Machado, Lara López-Escobar, Luisa M Figueiredo

N6-methyladenosine (m⁶A) is a mRNA modification with important roles in gene expression. In African trypanosomes, this post-transcriptional modification is detected in hundreds of transcripts and it affects the stability of the variant surface glycoprotein (VSG) transcript in the proliferating blood stream form. However, how the m⁶A landscape varies across the life cycle remains poorly defined. Using full-length, non-fragmented RNA, we immunoprecipitated and sequenced m⁶A-modified transcripts across three life cycle stages of Trypanosoma brucei - slender (proliferative), stumpy (quiescent), and procyclic forms (proliferative). We found that 1037 transcripts are methylated in at least one of these three life cycle stages. While 21% of methylated transcripts are common in the three stages of the life cycle, globally each stage has a distinct methylome. Interestingly, 47% of methylated transcripts are detected in the quiescent stumpy form only, suggesting a critical role for m⁶A when parasites exit the cell cycle and prepare for transmission by the Tsetse fly. In this stage, we found that a significant proportion of methylated transcripts encodes for proteins involved in RNA metabolism, which is consistent with their reduced transcription and translation. Moreover, we found that not all major surface proteins are regulated by m⁶A, as procyclins are not methylated, and that, within the VSG repertoire, not all VSG transcripts are demethylated upon parasite differentiation to procyclic form. This study reveals that the m⁶A regulatory landscape is specific to each life cycle stage, becoming more pervasive as T. brucei exits the cell cycle.

N6-甲基腺苷（m6A）是一种在基因表达中起重要作用的 mRNA 修饰。在非洲锥虫中，这种转录后修饰可在数百个转录本中检测到，而且会影响增殖血流形态中变异表面糖蛋白（VSG）转录本的稳定性。然而，m6A 在整个生命周期中的变化情况仍不十分明确。我们使用全长、非碎裂的 RNA，对布氏锥虫三个生命周期阶段--纤细型（增殖型）、粗壮型（静止型）和原环状型（增殖型）--的 m6A 修饰转录本进行了免疫沉淀和测序。我们发现，有 1037 个转录本在这三个生命周期阶段中至少有一个阶段被甲基化。虽然 21% 的甲基化转录本在生命周期的三个阶段中很常见，但总体而言，每个阶段都有一个独特的甲基化组。有趣的是，47%的甲基化转录本仅在静止期的残体中被检测到，这表明当寄生虫退出细胞周期并准备被采采蝇传播时，m6A 起着关键作用。在这一阶段，我们发现相当一部分甲基化转录本编码参与 RNA 代谢的蛋白质，这与它们的转录和翻译减少是一致的。此外，我们还发现并非所有主要的表面蛋白都受 m6A 的调控，因为原环蛋白并没有被甲基化，而且在 VSG 基因库中，并非所有的 VSG 转录本都会在寄生虫分化为原环形态时被去甲基化。这项研究揭示了 m6A 的调控格局是每个生命周期阶段所特有的，随着布氏原虫退出细胞周期而变得更加普遍。

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引用次数: 0

In vivo SPECT imaging of Tc-99m radiolabeled exosomes from human umbilical-cord derived mesenchymal stem cells in small animals 人脐带间充质干细胞Tc-99 m放射性标记外泌体在小动物体内的SPECT成像。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-16 DOI: 10.1016/j.bj.2024.100721

Extracellular vesicles derived from human umbilical cord-derived mesenchymal stem cells (UCMSC-EVs) have been postulated to have therapeutic potential for various diseases. However, the biodistribution and pharmacokinetics of these vesicles are still unclear. For a better understanding of the in vivo properties of UCMSC-EVs, in the present study, these vesicles were first radiolabeled with Technetium-99m (^99mTc-UCMSC-EVs) and evaluated using in vivo single photon emission computed tomography (SPECT) imaging and biodistribution experiments. SPECT images demonstrated that the liver and spleen tissues mainly took up the ^99mTc-UCMSC-EVs. The biodistribution study observed slight uptake in the thyroid and stomach, indicating that ^99mTc-UCMSC-EVs was stable at 24 h in vivo. The pharmacokinetic analyses of the blood half-life demonstrated the quick distribution phase (0.85 ± 0.28 min) and elimination phase (25.22 ± 20.76 min) in mice. This study provides a convenient and efficient method for ^99mTc-UCMSC-EVs preparation without disturbing their properties. In conclusion, the biodistribution, quick elimination, and suitable stability in vivo of ^99mTc-UCMSC-EVs were quantified by the noninvasive imaging and pharmacokinetic analyses, which provides useful information for indication selection, dosage protocol design, and toxicity assessment in future applications.

从人脐带间充质干细胞（UCMSC-EVs）中提取的细胞外囊泡被认为具有治疗各种疾病的潜力。然而，这些囊泡的生物分布和药代动力学尚不清楚。为了更好地了解 UCMSC-EVs 的体内特性，本研究首先用锝-99m（99mTc-UCMSC-EVs）对这些囊泡进行了放射性标记，并使用体内单光子发射计算机断层扫描（SPECT）成像和生物分布实验对其进行了评估。SPECT 图像显示，肝脏和脾脏组织主要吸收了 99m锝-UCMSC-EVs。生物分布研究观察到甲状腺和胃有轻微摄取，表明 99mTc-UCMSC-EVs 在体内 24 小时内是稳定的。血液半衰期的药代动力学分析表明，99mTc-UCMSC-EVs 在小鼠体内的分布期（0.85 ± 0.28 分钟）和消除期（25.22 ± 20.76 分钟）均较快。该研究为制备 99mTc-UCMSC-EVs 提供了一种方便、高效且不会干扰其特性的方法。总之，该研究通过无创成像和药代动力学分析，量化了 99mTc-UCMSC-EVs 在体内的生物分布、快速消除和适宜的稳定性，为未来应用中的适应症选择、剂量方案设计和毒性评估提供了有用信息。

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引用次数: 0

Genome-wide association study identifies DRAM1 associated with Tourette syndrome in Taiwan 全基因组关联研究发现 DRAM1 与台湾的妥瑞症有关。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-10 DOI: 10.1016/j.bj.2024.100725

Background

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Several susceptibility loci associated with TS have been identified previously in populations of European descent using genome-wide association studies (GWAS). However, the exact pathogenic mechanism underlying TS is unknown; additionally, the results of previous GWAS for TS were based on Western populations, which may not translate to other populations. Therefore, we conducted a GWAS in Taiwanese patients with TS and chronic tic disorders (CTDs), with an aim to elucidate the genetic basis and potential risk factors for TS in this population.

Methods

GWAS was performed on a Taiwanese TS/CTDs cohort with a sample size of 1007 patients with TS and 25,522 ancestry-matched controls. Additionally, polygenic risk score was calculated and assessed.

Results

Genome-wide significant locus, rs12313062 (p = 1.43 × 10⁻⁸) and other 9 single nucleotide polymorphisms, were identified in chromosomes 12q23.2, associated with DRAM1 and was a novel susceptibility locus identified in TS/CTDs group. DRAM1, a lysosomal transmembrane protein regulated by p53, modulates autophagy and apoptosis, with potential implications for neuropsychiatric conditions associated with autophagy disruption.

Conclusions

This study conducted the first GWAS for TS in a Taiwanese population, identifying a significant locus on chromosome 12q23.2 associated with DRAM1. These findings provide novel insights into the neurobiology of TS and potential directions for future research in this area.

背景：图雷特综合征（TS）是一种以运动和发声抽搐为特征的神经发育障碍。此前，通过全基因组关联研究（GWAS），在欧洲后裔人群中发现了几个与 TS 相关的易感基因位点。然而，TS 的确切致病机制尚不清楚；此外，以前针对 TS 的全基因组关联研究的结果是基于西方人群的，可能并不适用于其他人群。因此，我们在台湾的 TS 和慢性抽搐症（CTDs）患者中开展了一项 GWAS 研究，旨在阐明该人群中 TS 的遗传基础和潜在风险因素：对台湾 TS/CTDs 群体进行了 GWAS 分析，样本量为 1,007 名 TS 患者和 25,522 名祖先匹配对照。此外，还计算并评估了多基因风险评分：结果：在染色体12q23.2上发现了与DRAM1相关的全基因组重要位点rs12313062（p=1.43×10-8）和其他9个单核苷酸多态性，这是TS/CTDs群体中发现的一个新的易感位点。DRAM1是一种受p53调控的溶酶体跨膜蛋白，可调节自噬和细胞凋亡，对与自噬破坏相关的神经精神疾病具有潜在影响：本研究首次在台湾人群中开展了TS的GWAS，在染色体12q23.2上发现了一个与DRAM1相关的重要位点。这些发现为TS的神经生物学提供了新的见解，也为这一领域未来的研究提供了潜在的方向。

{"title":"Genome-wide association study identifies DRAM1 associated with Tourette syndrome in Taiwan","authors":"","doi":"10.1016/j.bj.2024.100725","DOIUrl":"10.1016/j.bj.2024.100725","url":null,"abstract":"<div><h3>Background</h3><div>Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Several susceptibility loci associated with TS have been identified previously in populations of European descent using genome-wide association studies (GWAS). However, the exact pathogenic mechanism underlying TS is unknown; additionally, the results of previous GWAS for TS were based on Western populations, which may not translate to other populations. Therefore, we conducted a GWAS in Taiwanese patients with TS and chronic tic disorders (CTDs), with an aim to elucidate the genetic basis and potential risk factors for TS in this population.</div></div><div><h3>Methods</h3><div>GWAS was performed on a Taiwanese TS/CTDs cohort with a sample size of 1007 patients with TS and 25,522 ancestry-matched controls. Additionally, polygenic risk score was calculated and assessed.</div></div><div><h3>Results</h3><div>Genome-wide significant locus, rs12313062 (<em>p</em> = 1.43 × 10<sup>−8</sup>) and other 9 single nucleotide polymorphisms, were identified in chromosomes 12q23.2, associated with <em>DRAM1</em> and was a novel susceptibility locus identified in TS/CTDs group. DRAM1, a lysosomal transmembrane protein regulated by p53, modulates autophagy and apoptosis, with potential implications for neuropsychiatric conditions associated with autophagy disruption.</div></div><div><h3>Conclusions</h3><div>This study conducted the first GWAS for TS in a Taiwanese population, identifying a significant locus on chromosome 12q23.2 associated with <em>DRAM1</em>. These findings provide novel insights into the neurobiology of TS and potential directions for future research in this area.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 6","pages":"Article 100725"},"PeriodicalIF":4.1,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blood oxygenation state in COVID-19 patients: Unexplored role of 2,3-bisphosphoglycerate COVID-19 患者的血液氧合状态：尚未探索的 2,3-二磷酸甘油酯的作用

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-06 DOI: 10.1016/j.bj.2024.100723

Background

COVID-19 reduces lung functionality causing a decrease of blood oxygen levels (hypoxemia) often related to a decreased cellular oxygenation (hypoxia). Besides lung injury, other factors are implicated in the regulation of oxygen availability such as pH, partial arterial carbon dioxide tension (PaCO₂), temperature, and erythrocytic 2,3-bisphosphoglycerate (2,3-BPG) levels, all factors affecting hemoglobin saturation curve. However, few data are currently available regarding the 2,3-BPG modulation in SARS-CoV-2 affected patients at the hospital admission.

Material and methods

Sixty-eight COVID-19 patients were enrolled at hospital admission. The lung involvement was quantified using chest-Computer Tomography (CT) analysed with automatic software (CALIPER). Haemoglobin concentrations, glycemia, and routine analysis were evaluated in the whole blood, while partial arterial oxygen tension (PaO₂), PaCO₂, pH, and HCO₃⁻ were assessed by arterial blood gas analysis. 2,3-BPG levels were assessed by specific immunoenzymatic assays in RBCs.

Results

A higher percentage of interstitial lung disease (ILD) and vascular pulmonary-related structure (VRS) volume on chest-CT quantified with CALIPER had been found in COVID-19 patients with a worse disease outcome (R = 0.4342; and R = 0.3641, respectively). Furthermore, patients with lower PaO₂ showed an imbalanced acid-base equilibrium (pH, p = 0.0208; PaCO₂, p = 0.0496) and a higher 2,3-BPG levels (p = 0.0221). The 2,3-BPG levels were also lower in patients with metabolic alkalosis (p = 0.0012 vs. no alkalosis; and p = 0.0383 vs. respiratory alkalosis).

Conclusions

Overall, the data reveal a different pattern of activation of blood oxygenation compensatory mechanisms reflecting a different course of the COVID-19 disease specifically focusing on 2,3-BPG modulation.

背景COVID-19 会降低肺功能，导致血氧水平下降（低氧血症），这通常与细胞氧合下降（缺氧）有关。除肺损伤外，其他因素也与氧气供应的调节有关，如 pH 值、部分动脉二氧化碳张力（PaCO2）、温度和红细胞 2,3-二磷酸甘油酯（2,3-BPG）水平，这些因素都会影响血红蛋白饱和度曲线。然而，目前有关 SARS-CoV-2 患者入院时 2,3-BPG 调节的数据很少。使用胸部计算机断层扫描（CT）和自动软件（CALIPER）对肺部受累情况进行量化分析。对全血中的血红蛋白浓度、血糖和常规分析进行了评估，同时通过动脉血气分析评估了部分动脉血氧张力（PaO2）、PaCO2、pH 值和 HCO3-。结果发现，在 COVID-19 患者中，用 CALIPER 定量的胸部 CT 上间质性肺病（ILD）和血管性肺相关结构（VRS）体积比例较高，疾病预后较差（分别为 R = 0.4342 和 R = 0.3641）。此外，PaO2 较低的患者酸碱平衡失衡（pH，p = 0.0208；PaCO2，p = 0.0496），2,3-BPG 水平较高（p = 0.0221）。总体而言，这些数据揭示了血液氧合代偿机制的不同激活模式，反映了 COVID-19 疾病的不同病程，特别是在 2,3-BPG 调节方面。

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引用次数: 0

Aging like fine wine: Mischievous microbes and other factors influencing senescence 像美酒一样老去：调皮的微生物和其他影响衰老的因素。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-01 DOI: 10.1016/j.bj.2024.100722

Aila Akosua Kattner

In this issue, a special section is dedicated to the factors affecting senescence. It examines the interplay between immunosenescence and chronic kidney disease, probes into Peto's paradox, and explores how epigenetic switches can potentially mitigate senescence and inflammation. Additionally, insights are offered on understanding a specific Ras mechanism in yeast for potential therapeutic interventions against cancer and for longevity. Furthermore, the remarkable endurance of last year's Nobel Prize winner in Physiology or Medicine is also highlighted. Moreover, the discovery of potential biomarkers for hepatocellular carcinoma, the link between osteoarthritis and the circadian clock, and the multifaceted role of DNAJA3 in B cell lifecycle are discussed. Further, study findings shed light on the influence of extracellular matrix molecules on cleft palate formation, the renal protective effects of combination therapy in diabetic kidney disease, and novel approaches to detect developmental dysplasia of the hip. Finally, a correspondence delves into the role of autonomic regulation in cognitive decline.

本期特刊专门讨论了影响衰老的因素。它探讨了免疫衰老与慢性肾病之间的相互作用，探究了佩托悖论，并探索了表观遗传开关如何有可能缓解衰老和炎症。此外，还就如何理解酵母中一种特殊的 Ras 机制，从而对癌症和长寿进行潜在的治疗干预提出了见解。此外，还重点介绍了去年诺贝尔生理学或医学奖得主的非凡耐力。此外，还讨论了肝细胞癌潜在生物标志物的发现、骨关节炎与昼夜节律时钟之间的联系以及 DNAJA3 在 B 细胞生命周期中的多方面作用。此外，研究结果还揭示了细胞外基质分子对腭裂形成的影响、联合疗法对糖尿病肾病的肾脏保护作用以及检测髋关节发育不良的新方法。最后，一篇通讯深入探讨了自律神经调节在认知能力下降中的作用。

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引用次数: 0

A tale of Science - The Nobel Prize in Physiology or Medicine 2023 科学的故事 - 2023 年诺贝尔生理学或医学奖。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-03-13 DOI: 10.1016/j.bj.2024.100716

Sophia Julia Häfner

引用次数: 0

Clinical significance of incidental common bile duct dilatation in children: A 10-year single medical center experience 儿童偶然性胆总管扩张的临床意义：单个医疗中心的十年经验

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-03-12 DOI: 10.1016/j.bj.2024.100717

Background

With the widespread use of abdominal ultrasonography (US), incidental detection of common bile duct (CBD) dilatation is common in pediatric populations. This study investigated the causes and clinical significance of CBD dilatation in children without biliary symptoms, jaundice, or causative lesions in US.

Methods

We retrospectively reviewed pediatric patients with CBD dilatation from July 2013 to June 2023. All cases were detected via abdominal US. We analyzed the patients’ clinical manifestations, laboratory data, diagnosis, underlying diseases, and clinical course.

Results

In a total of 687 patients enrolled, 338 met inclusion criteria (90 in hepatobiliary, 248 in CBD dilatation group). Of 128 patients with incidental CBD dilatation who underwent regular US examinations, 91 (71.1%) experienced resolution during follow-up. The proportion of patients with intrahepatic duct dilatation was significantly higher in the non-resolution group (p = 0.038). General health examination group had significant smaller CBD diameter compared to the gastrointestinal and infection groups. Correlation analysis found starting point of resolution decline at 3.24 mm (all-inclusive) and 2.51 mm (infant group) CBD diameter.

Conclusions

Most children with incidental CBD dilatation did not have abnormal hepatobiliary function or other sonographic abnormalities. They usually remained asymptomatic and experienced uneventful clinical courses.

背景：随着腹部超声波检查（US）的广泛应用，偶然发现胆总管（CBD）扩张在儿科人群中很常见。本研究调查了在 US 检查中没有胆道症状、黄疸或致病病变的儿童中出现总胆管扩张的原因和临床意义：我们回顾性研究了2013年7月至2023年6月期间CBD扩张的儿童患者。所有病例均通过腹部超声检查发现。我们分析了患者的临床表现、实验室数据、诊断、基础疾病和临床过程：在总共 687 例入选患者中，338 例符合纳入标准（90 例为肝胆管扩张组，248 例为 CBD 扩张组）。在接受定期US检查的128例偶然CBD扩张患者中，91例（71.1%）在随访期间症状得到缓解。在未缓解组中，肝内导管扩张患者的比例明显更高（P = 0.038）。与胃肠道组和感染组相比，一般健康检查组的 CBD 直径明显较小。相关性分析发现，CBD直径在3.24毫米（所有组）和2.51毫米（婴儿组）时为缓解下降的起点：结论：大多数偶然CBD扩张的儿童没有肝胆功能异常或其他声像图异常。结论：大多数偶然CBD扩张的患儿没有肝胆功能异常或其他声像图异常，他们通常没有症状，临床过程也很顺利。

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引用次数: 0

Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis 嘌呤能 P2X7 和 A2B 受体信号的改变限制了血吸虫病中巨噬细胞介导的宿主防御。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-03-03 DOI: 10.1016/j.bj.2024.100713

Background

The occurrence of co-infections during schistosomiasis, a neglected tropical disease, with other parasites have been reported suggesting an impaired host immune defense. Macrophage purinergic P2X7 receptor (P2X7R) plays an important role against intracellular pathogens. Therefore, we investigated the P2X7R-mediated phagocytosis and killing capacity of Leishmania amazonensis by macrophages during schistosomiasis in vitro and in vivo.

Methods

Swiss and C57BL/6 (Wild type) and P2X7R^−/− were randomized in two groups: control (uninfected) and Schistosoma mansoni-infected. Alternatively, control Swiss and S. mansoni-infected mice were also infected with L. amazonensis.

Results

The pre-treatment of control macrophages with the P2X7R antagonist (A74003) or TGF-β reduced the phagocytosis index, mimicking the phenotype of cells from S. mansoni-infected mice and P2X7R^−/− mice. Apyrase also reduced the phagocytosis index in the control group corroborating the role of ATP to macrophage activation. Moreover, l-arginine-nitric oxide pathway was compromised during schistosomiasis, which could explain the reduced killing capacity in response to ATP in vitro and in vivo. We found an increased extracellular nucleotide (ATP, ADP and AMP) hydrolysis along with an increased frequency of F4/80⁺ CD39⁺ macrophages from the S. mansoni-infected group. Moreover, the content of adenosine in the cell supernatant was higher in the S. mansoni-infected group in relation to controls. Schistosomiasis also increased the expression of macrophage adenosine A_2BR. In good accordance, both ADA and the selective A_2BR antagonist restored the phagocytosis index of macrophages from S. mansoni-infected group.

Conclusions

Altogether, the altered P2X7R and A_2BR signaling limits the role of macrophages to host defense against L. amazonensis during schistosomiasis, potentially contributing to the pathophysiology and clinically relevant co-infections.

背景：血吸虫病是一种被忽视的热带疾病，有报道称血吸虫病与其他寄生虫同时感染，这表明宿主的免疫防御功能受损。巨噬细胞嘌呤能 P2X7 受体（P2X7R）在对抗细胞内病原体方面发挥着重要作用。因此，我们研究了血吸虫病期间巨噬细胞在体外和体内介导的 P2X7R 对亚马逊利什曼原虫的吞噬和杀灭能力：方法：将瑞士和 C57BL/6（野生型）以及 P2X7R-/- 随机分为两组：对照组（未感染）和感染曼氏血吸虫组。另外，对照组瑞士小鼠和感染曼氏血吸虫的小鼠也感染了亚马逊血吸虫：结果：用P2X7R拮抗剂（A74003）或TGF-β预处理巨噬细胞可降低吞噬指数，模拟曼氏血吸虫感染小鼠和P2X7R-/-小鼠细胞的表型。Apyrase也降低了吞噬指数，证实了ATP对巨噬细胞活化的作用。此外，L-精氨酸-一氧化氮通路受损，这可以解释体外和体内对 ATP 的杀伤能力降低的原因。我们发现，曼森氏杆菌感染组细胞外核苷酸（ATP、ADP和AMP）水解增加，F4/80+ CD39+巨噬细胞的频率增加。此外，与对照组相比，曼森氏杆菌感染组细胞上清液中的腺苷含量更高。血吸虫病也增加了巨噬细胞腺苷 A2BR 的表达。ADA和选择性A2BR拮抗剂能很好地恢复曼氏血吸虫病感染组巨噬细胞的吞噬指数：总之，P2X7R 和 A2BR 信号的改变限制了血吸虫病期间巨噬细胞在宿主防御亚马逊嗜血杆菌中的作用，可能会导致病理生理学和临床相关的合并感染。

{"title":"Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis","authors":"","doi":"10.1016/j.bj.2024.100713","DOIUrl":"10.1016/j.bj.2024.100713","url":null,"abstract":"<div><h3>Background</h3><div>The occurrence of co-infections during schistosomiasis, a neglected tropical disease, with other parasites have been reported suggesting an impaired host immune defense. Macrophage purinergic P2X7 receptor (P2X7R) plays an important role against intracellular pathogens. Therefore, we investigated the P2X7R-mediated phagocytosis and killing capacity of <em>Leishmania amazonensis</em> by macrophages during schistosomiasis <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Methods</h3><div>Swiss and C57BL/6 (Wild type) and P2X7R<sup>−/−</sup> were randomized in two groups: control (uninfected) and <em>Schistosoma mansoni</em>-infected. Alternatively, control Swiss and <em>S. mansoni</em>-infected mice were also infected with <em>L. amazonensis</em>.</div></div><div><h3>Results</h3><div>The pre-treatment of control macrophages with the P2X7R antagonist (A74003) or TGF-β reduced the phagocytosis index, mimicking the phenotype of cells from <em>S. mansoni</em>-infected mice and P2X7R<sup>−/−</sup> mice. Apyrase also reduced the phagocytosis index in the control group corroborating the role of ATP to macrophage activation. Moreover, <span>l</span>-arginine-nitric oxide pathway was compromised during schistosomiasis, which could explain the reduced killing capacity in response to ATP <em>in vitro</em> and <em>in vivo</em>. We found an increased extracellular nucleotide (ATP, ADP and AMP) hydrolysis along with an increased frequency of F4/80<sup>+</sup> CD39<sup>+</sup> macrophages from the <em>S. mansoni</em>-infected group. Moreover, the content of adenosine in the cell supernatant was higher in the <em>S. mansoni</em>-infected group in relation to controls. Schistosomiasis also increased the expression of macrophage adenosine A<sub>2B</sub>R. In good accordance, both ADA and the selective A<sub>2B</sub>R antagonist restored the phagocytosis index of macrophages from <em>S. mansoni</em>-infected group.</div></div><div><h3>Conclusions</h3><div>Altogether, the altered P2X7R and A<sub>2B</sub>R signaling limits the role of macrophages to host defense against <em>L. amazonensis</em> during schistosomiasis, potentially contributing to the pathophysiology and clinically relevant co-infections.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 6","pages":"Article 100713"},"PeriodicalIF":4.1,"publicationDate":"2024-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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