Experimental and molecular pathology最新文献_第7页

Evaluation of direct-to-PCR (D2P) method for molecular diagnosis of infectious diseases 直接- pcr （D2P）方法在传染病分子诊断中的应用评价

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-05-26 DOI: 10.1016/j.yexmp.2025.104972

Rahul Sharma , Vaibhav K. Tamrakar , Rob E. Carpenter , Aditya Sharma , Kamalpreet Suri , Salima Karki , Katelyn Kyser , Randy Sronce , Sadia Almas

This study evaluates the performance of the Direct-to-PCR (D2P) method as a streamlined, extraction-independent alternative to conventional nucleic acid extraction techniques for diagnosing urinary tract infections, sexually transmitted infections, and respiratory tract infections. The D2P approach employs proprietary antimicrobial peptide-based lysis buffers tailored for bacterial, fungal, and viral targets, enabling direct amplification from clinical and contrived specimens without column- or bead-based purification. Comparative analyses were conducted against silica column-based (QIAGEN) and magnetic bead-based (KingFisher) extraction methods using both microbial reference isolates and 116 residual clinical samples. Results demonstrate that the D2P method yields comparable sensitivity and specificity to conventional extraction workflows across a diverse panel of pathogens—including Gram-negative and Gram-positive bacteria, Candida species, ssRNA viruses (e.g., CoV-229E, Parainfluenza Virus 1 and 2), and dsDNA viruses (e.g., HSV, HAdV). Notably, D2P outperformed both QIAGEN and KingFisher in extracting nucleic acids from Candida auris, a multidrug-resistant fungal pathogen. Limit of detection and amplification efficiency remained within acceptable ranges across all platforms, with R² values between 0.92 and 0.99, and slopes consistent with MIQE standards. The D2P protocol reduced total sample processing time from ∼120 min to ∼45 min, minimized hands-on steps, and demonstrated effective performance in turbid or hemolyzed samples—making it suitable for high-throughput and resource-limited settings. However, limitations were observed in samples with high PCR-inhibitor content or low target yield, and broader validation across additional matrices is recommended. These findings support D2P as a reliable, efficient, and scalable molecular diagnostic alternative with broad clinical utility. Integration of D2P into diagnostic workflows could enhance access to rapid, cost-effective pathogen detection in both centralized laboratories and decentralized or point-of-care environments.

本研究评估了直接到pcr （D2P）方法作为传统核酸提取技术诊断尿路感染、性传播感染和呼吸道感染的一种简化的、不依赖提取的替代方法的性能。D2P方法采用专为细菌、真菌和病毒靶点定制的抗菌肽裂解缓冲液，无需柱或珠基纯化，即可从临床和人造标本中直接扩增。对比分析了基于二氧化硅柱（QIAGEN）和基于磁珠（KingFisher）的微生物参考分离物和116份剩余临床样品的提取方法。结果表明，D2P方法在多种病原体(包括革兰氏阴性和革兰氏阳性细菌、念珠菌、ssRNA病毒（如CoV-229E、副流感病毒1和2）和dsDNA病毒（如HSV、hav）中具有与传统提取流程相当的敏感性和特异性。值得注意的是，D2P在提取多重耐药真菌假丝酵母（Candida auris）核酸方面优于QIAGEN和KingFisher。所有平台的检测限和扩增效率均在可接受范围内，R2值在0.92 ~ 0.99之间，斜率与MIQE标准一致。D2P方案将总样品处理时间从~ 120分钟减少到~ 45分钟，最大限度地减少了动手步骤，并且在混浊或溶血样品中表现出有效的性能，使其适用于高通量和资源有限的环境。然而，在高pcr抑制剂含量或低目标产率的样品中观察到局限性，建议在其他基质上进行更广泛的验证。这些发现支持D2P作为一种可靠、有效和可扩展的分子诊断替代方法，具有广泛的临床应用。将D2P整合到诊断工作流程中，可在集中式实验室和分散式或医疗点环境中促进获得快速、具有成本效益的病原体检测。

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引用次数: 0

Estrogen induces the alternative activation of macrophages through binding to estrogen receptor-alpha 雌激素通过与雌激素受体结合诱导巨噬细胞的选择性活化

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-05-20 DOI: 10.1016/j.yexmp.2025.104971

Amina Belboul , Jason Ashworth , Abdulmannan Fadel , Jessica Mcloughlin , Ayman Mahmoud , Mohamed El Mohtadi

Age-related impaired wounds represent a major health burden resulting in considerable morbidity and mortality in the elderly. When injury occurs, monocytes migrate to the damaged site and undergo differentiation into tissue-resident macrophages, which are crucial for wound repair. For proper resolution of the inflammatory response, macrophages differentiate into two distinct phenotypes classified as classically-activatedpro-inflammatory and alternatively-activatedanti-inflammatory macrophages. Pro-inflammatory macrophages are commonly linked with pro-inflammatory events, while anti-inflammatory macrophages are known to be pro-regenerative. The age-related delay in wound repair is often attributed to the age-related decrease in local and systemic estrogen levels in both genders. However, despite its well-documented anti-inflammatory effect in wound healing, the role of estrogen and involvement of Estrogen Receptors (ERs) in macrophage polarization has gained little attention to date. To investigate the impact of estrogen and ERs on the polarization of macrophages, monocyte-derived macrophages were pre-treated with estrogen, ER-alpha agonist/antagonist or ER-beta agonist/antagonist prior to stimulation with LPS/IFN-γ or IL-4/IL-13 to produce pro-inflammatory or anti-inflammatory macrophages. Our findings confirm that estrogen promotes the alternative activation of macrophages via possible ER-α signalling. Selective targeting of ER-α with agents like PPT could potentially lead to the development of novel therapies to treat excessive inflammation in impaired wounds.

与年龄有关的伤口受损是造成老年人相当高发病率和死亡率的主要健康负担。当损伤发生时，单核细胞迁移到受损部位并分化为组织内巨噬细胞，这对伤口修复至关重要。为了适当地解决炎症反应，巨噬细胞分化为两种不同的表型，即经典激活的促炎巨噬细胞和交替激活的抗炎巨噬细胞。促炎巨噬细胞通常与促炎事件有关，而抗炎巨噬细胞被认为是促进再生的。年龄相关的伤口修复延迟通常归因于年龄相关的局部和全身雌激素水平的下降。然而，尽管雌激素在伤口愈合中的抗炎作用得到了充分的证明，但迄今为止，雌激素和雌激素受体（ERs）在巨噬细胞极化中的作用却很少得到关注。为了研究雌激素和内质网对巨噬细胞极化的影响，在LPS/IFN-γ或IL-4/IL-13刺激单核细胞源性巨噬细胞之前，分别用雌激素、er - α激动剂/拮抗剂或er - β激动剂/拮抗剂预处理单核细胞源性巨噬细胞，产生促炎或抗炎巨噬细胞。我们的研究结果证实，雌激素通过可能的ER-α信号传导促进巨噬细胞的选择性激活。用PPT等药物选择性靶向ER-α可能会导致治疗受损伤口过度炎症的新疗法的发展。

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引用次数: 0

From asbestos exposure to carcinogenesis: Transcriptomic signatures in malignant pleural mesothelioma 从石棉暴露到癌变：恶性胸膜间皮瘤的转录组特征

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-05-20 DOI: 10.1016/j.yexmp.2025.104973

Diletta Rosati , Bianca Giulia Maurizi , Viola Bianca Serio , Debora Maffeo , Angela Rina , Francesca Mari , Maria Palmieri , Antonio Giordano , Elisa Frullanti

Background

The incidence of malignant pleural mesothelioma (MPM) has surged due to widespread asbestos exposure, particularly since the mid-20th century. Despite significant advancements in cancer treatment, an effective cure for MPM remains elusive, largely due to a limited understanding of the molecular mechanisms underlying asbestos-related carcinogenesis. This exploratory study aims to uncover gene expression patterns uniquely altered in mesothelioma patients with documented asbestos exposure, providing a solid foundation for future research focused on identifying novel prognostic and predictive biomarkers.

Methods

Publicly available RNA sequencing data were analyzed through a bioinformatics pipeline to perform differential gene expression analysis. Additionally, functional enrichment analysis was applied to highlight significantly enriched Gene Ontology (GO) terms related to biological processes, molecular functions, and cellular components, offering insights into the molecular pathways involved in MPM development.

Results

The analysis uncovered a set of differentially expressed genes (DEGs) in MPM patients with documented asbestos exposure, as well as key GO terms. These enriched biological terms reflect processes such as ion homeostasis and oxidative stress response, providing crucial information on the cellular alterations driven by asbestos exposure.

Conclusion

This study's findings deepen our understanding of the molecular landscape underlying asbestos-induced carcinogenesis in MPM. The identification of specific DEGs and enriched GO terms lays the foundation for future investigations, including the development of biomarkers, with potential implications for the diagnostic and prognostic assessment of MPM.

背景：恶性胸膜间皮瘤（MPM）的发病率由于广泛接触石棉而激增，特别是自20世纪中期以来。尽管癌症治疗取得了重大进展，但MPM的有效治疗仍然难以捉摸，这主要是由于对石棉相关致癌的分子机制的了解有限。本探索性研究旨在揭示记录石棉暴露的间皮瘤患者的基因表达模式的独特改变，为未来的研究提供坚实的基础，重点是确定新的预后和预测性生物标志物。方法通过生物信息学管道分析公开的RNA测序数据，进行差异基因表达分析。此外，功能富集分析应用于突出与生物过程、分子功能和细胞成分相关的显著富集的基因本体（GO）术语，为MPM发展中涉及的分子途径提供了见解。结果该分析揭示了记录石棉暴露的MPM患者的一组差异表达基因（DEGs），以及关键的GO术语。这些丰富的生物学术语反映了离子稳态和氧化应激反应等过程，为石棉暴露导致的细胞改变提供了重要信息。结论本研究的发现加深了我们对石棉诱发MPM癌变的分子格局的理解。特异性deg和富集氧化石墨烯的鉴定为未来的研究奠定了基础，包括生物标志物的开发，对MPM的诊断和预后评估具有潜在的意义。

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引用次数: 0

m6A demethylase FTO/ALKBH5 promotes diabetes-induced endothelial cell dysfunction by negatively regulating lncRNA H19 m6A去甲基化酶FTO/ALKBH5通过负调控lncRNA H19促进糖尿病诱导的内皮细胞功能障碍

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-05-16 DOI: 10.1016/j.yexmp.2025.104970

Yanli Luo , Wanjun Luo , Yanan Cao , Zhanpeng Wang

Endothelial cell dysfunction induced by glucose is the most important cause of diabetic vascular complications, which are the leading causes of blindness, disability, renal failure, heart failure, stroke, and even death in diabetic patients. RNA m6A modification is involved in the pathogenesis of human disease. However, the role and underlying mechanism of RNA m6A modification in high glucose-induced endothelial cell dysfunction is not well understood. Herein, this study first demonstrated that m6A levels were decreased and that the demethylases FTO and ALKBH5 were upregulated in diabetic patients and an STZ-induced diabetic mouse model. This study revealed that high glucose induced decreased m6A levels and increased expression of FTO and ALKBH5, and silencing of FTO and ALKBH5 restored high glucose-induced decreases in m6A levels and dysfunction of HUVECs. Next, this study systematically screened differentially expressed lncRNAs, including H19, in HUVECs under high glucose conditions. This study revealed that FTO-ALKBH5 inhibited H19 expression by decreasing m6A modification in H19 transcripts. In addition, this study demonstrated the role of the FTO/ALKBH5/H19 pathway in high glucose-induced cellular dysfunction of HUVECs. Ultimately, this study uncovered that silencing of H19 promoted the expression of cell cycle-related genes, including PTEN, p21 and p27 via interacting with EZH2 and affecting the H3K27me3 histone modification. Overall, this study is the first to dissect the regulation of lncRNA by m6A modification in hyperglycaemia, identifying a new regulatory pathway in high glucose-induced cellular dysfunction and providing biomarkers with the potential to serve as therapeutic targets for high glucose-induced cellular dysfunction.

葡萄糖诱导的内皮细胞功能障碍是糖尿病血管并发症的最重要原因，糖尿病血管并发症是糖尿病患者失明、残疾、肾功能衰竭、心力衰竭、中风甚至死亡的主要原因。RNA m6A修饰参与了人类疾病的发病机制。然而，RNA m6A修饰在高糖诱导的内皮细胞功能障碍中的作用和潜在机制尚不清楚。本研究首先证明糖尿病患者和stz诱导的糖尿病小鼠模型中m6A水平降低，去甲基化酶FTO和ALKBH5上调。本研究发现，高糖诱导m6A水平下降，FTO和ALKBH5表达增加，FTO和ALKBH5沉默可恢复高糖诱导的m6A水平下降和huvec功能障碍。接下来，本研究系统筛选高糖条件下HUVECs中差异表达的lncrna，包括H19。本研究发现FTO-ALKBH5通过降低H19转录本中m6A修饰来抑制H19的表达。此外，本研究还证实了FTO/ALKBH5/H19通路在高糖诱导的HUVECs细胞功能障碍中的作用。最终，本研究发现，沉默H19通过与EZH2相互作用，影响H3K27me3组蛋白修饰，促进PTEN、p21、p27等细胞周期相关基因的表达。总的来说，本研究首次解剖了m6A修饰对lncRNA在高血糖中的调控作用，确定了高糖诱导的细胞功能障碍的新调控途径，并提供了可能作为高糖诱导的细胞功能障碍治疗靶点的生物标志物。

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引用次数: 0

The multifunctional protein CCN1/CYR61: Bridging physiology and disease 多功能蛋白CCN1/CYR61：连接生理和疾病

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-04-25 DOI: 10.1016/j.yexmp.2025.104969

Racha Kerek, Joe Sawma Awad , Mariam Bassam , Carla Hajjar , Fouad Ghantous, Karelle Rizk, Mohamad Rima

The matricellular protein CYR61/CCN1 is a member of the CCN protein family that plays significant roles in a broad range of physiological processes, including development, tissue repair, and inflammation, among others. CCN1 is also implicated in pathological conditions such as cancer and fibrosis. The diverse functions of CCN1 arise from its ability to bind different receptors located on many cell types, thereby activating diverse signaling pathways. The diverse, yet contradictory, functions mediated by CCN1 makes it a compelling target for investigation, as it offers the prospect of understanding fundamental cellular topics and their possible implications in various diseases. Recently, new cellular functions were attributed to CCN1, including senescence, pro-/anti- fibrosis, and rejuvenation. In this review, we discuss all these new findings along with the basic knowledge about CCN1 to provide an overall understanding of its conflicting roles and their potential corresponding mechanisms of action.

基质细胞蛋白CYR61/CCN1是CCN蛋白家族的一员，在广泛的生理过程中发挥重要作用，包括发育、组织修复和炎症等。CCN1也涉及病理状况，如癌症和纤维化。CCN1的多种功能源于它能够结合位于许多细胞类型上的不同受体，从而激活多种信号通路。CCN1介导的多种多样而又相互矛盾的功能使其成为一个引人注目的研究目标，因为它为理解基本的细胞主题及其在各种疾病中的可能含义提供了前景。最近，新的细胞功能归因于CCN1，包括衰老，促/抗纤维化和年轻化。在这篇综述中，我们讨论了所有这些新发现以及CCN1的基本知识，以全面了解其相互冲突的作用及其潜在的相应作用机制。

引用次数: 0

Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu 有益菌和致病菌之间的交叉喂养利用真核宿主细胞衍生的唾液酸和噬菌体形成病原体-宿主界面环境

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-04-25 DOI: 10.1016/j.yexmp.2025.104967

Darab Ghadimi , Regina Fölster-Holst , Sophia Blömer , Michael Ebsen , Christoph Röcken , Jumpei Uchiyama , Shigenobu Matsuzaki , Wilhelm Bockelmann

Under an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria.

在肠道发炎的环境下，游离硅酸的增加与某些致病细菌菌株的过度生长有关。最近，肠道噬菌体（噬菌体）的保护性免疫调节活性也得到了强调。然而，迄今为止，噬菌体在致病菌、有益菌及其宿主细胞硅铝酸之间三重相互影响中的作用尚未得到研究。我们利用包含结肠细胞（T84 细胞）、单核细胞（THP-1 细胞）和肝细胞（Huh7 细胞）的人类三重共培养细胞模型，建立了一个硫代硫酸钠酶显式模型，其中有益菌和致病菌通过交叉进食和竞争游离硫代硫酸钠而相互作用。在两种不同的细胞培养基中：1）标准杜氏改良鹰培养基（DMEM）；2）含 2,3-脱氢-2-脱氧-N-乙酰神经氨酸（DANA）的 DMEM。评估了受刺激共培养细胞的生理、功能和结构健康指标的变化。对细胞培养上清液中的丝胶酸和促炎细胞因子的浓度进行了量化。P. a PAO1 引发了白细胞介素 6 和 8（IL-6 和 IL-8）的释放，并伴随着游离硅酸水平的升高，降低了共培养细胞的活力，破坏了细胞单层的完整性。KPP22 噬菌体和双歧杆菌能明显减弱这些破坏作用。除了革兰氏阴性致病菌和双歧杆菌在细菌细胞壁的结构和组成上的差异已得到充分证实外，似乎还有两个不同的因素在调节病原体-宿主界面环境中起着关键作用：(i) 噬菌体的存在和 (ii) 双歧杆菌对宿主细胞分泌的游离硅酸的利用。

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引用次数: 0

Morphological characteristics, extracellular vesicle structure and stem-like specificity of human follicular fluid cell subpopulation during osteodifferentiation 骨分化过程中卵泡液细胞亚群的形态学特征、细胞外囊泡结构和茎样特异性

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-04-19 DOI: 10.1016/j.yexmp.2025.104965

Wiesława Kranc , Mariusz Kaczmarek , Katarzyna Kowalska , Wojciech Pieńkowski , Sylwia Ciesiółka , Aneta Konwerska , Paul Mozdziak , Maciej Brązert , Michal Jeseta , Robert Z. Spaczyński , Leszek Pawelczyk , Bartosz Kempisty

Extracellular vesicles can play an important role in the processes occurring after stem cell transplantation, preventing cell apoptosis, stimulating immunological processes, and promoting the synthesis of extracellular matrix. Human follicular fluid (FF) can be a source of a subpopulation of cells with mesenchymal stem cells (MSCs) properties. Moreover these subpopulations of FF cells can differentiate into osteoblasts. In presented studies flow cytometry of ovarian FF cells confirmed positive expression of MSCs markers such as: CD44, CD90, CD105, CD73 and negative expression of a hematopoietic marker: CD45. The CD90+, CD105+, CD45- cell subpopulation has been obtained during magnetic separation using appropriate antibodies conjugated with microbeads. The extracellular vesicles (EVs) secreted by the cells during osteodifferentiation process differed from those secreted by cells culture in the basal medium. Based on the previous and current electron microscopy research, changes in size, number, and shape would support the notion that released EVs could be crucial to the ovarian FF cell subpopulation differentiation process. Osteogenic differentiation has been confirmed via Alizarin red staining. Therefore, follicular fluid (FF) can be a new source of a cell subpopulation with MSC properties, with the cells capable of differentiating into the osteogenic lineage. EVs could play a key role as mediators in tissue regeneration, especially bone tissue regeneration.

细胞外囊泡在干细胞移植后发生的过程中发挥重要作用，可防止细胞凋亡，刺激免疫过程，促进细胞外基质的合成。人卵泡液（FF）可能是具有间充质干细胞（MSCs）特性的细胞亚群的来源。此外，这些FF细胞亚群可以分化成成骨细胞。在目前的研究中，卵巢FF细胞的流式细胞术证实MSCs标记物如CD44、CD90、CD105、CD73阳性表达，而造血标记物CD45阴性表达。利用适当的抗体结合微珠进行磁分离，获得了CD90+， CD105+， CD45-细胞亚群。细胞在骨分化过程中分泌的细胞外囊泡（EVs）与在基础培养基中培养的细胞分泌的细胞外囊泡不同。根据以往和目前的电镜研究，大小、数量和形状的变化支持了释放的ev可能对卵巢FF细胞亚群分化过程至关重要的观点。茜素红染色证实成骨分化。因此，卵泡液（FF）可以成为具有间充质干细胞特性的细胞亚群的新来源，这些细胞能够分化成成骨谱系。ev可能在组织再生，特别是骨组织再生中发挥重要的介质作用。

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引用次数: 0

The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathways 褪黑素对无病理分化的C2C12肌管的影响：保氧作用和促生存信号通路的增强

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-04-12 DOI: 10.1016/j.yexmp.2025.104966

Garth Wentley , Russel J. Reiter , Yong-Xiao Wang , Gerald Maarman

Previous research has demonstrated that melatonin protects against muscle damage while also improving the performance of injured muscle. However, its impact on healthy skeletal muscle remains largely unexplored. We exposed differentiated C2C12 myotubes to two melatonin concentrations (10 nM or 50 nM). The 10 nM concentration did not affect any of the mitochondrial respiration parameters. Whereas 50 nM concentration reduced mitochondrial complex II-linked oxidative phosphorylation (OXPHOS), electron transfer system (ETS) capacity, the contribution of complex II to ETS, and residual oxygen consumption (ROX). Neither concentration influenced the mitochondrial coupling control ratios, nor the coupling control efficiency ratios. Furthermore, neither concentration affected ATP production but reduced superoxide dismutase activity. The 50 nM increased catalase activity without affecting autophagy or citrate synthase activity. Moreover, 50 nM reduced activated JAK2 and STAT3 protein expression, while 10 nM reduced JAK2 without affecting STAT3. Th 50 nM increased activated AKT and ERK1/2 expression with no effect on p38 or PGC1-α expression. Our data suggests that melatonin (50 nM) triggers an oxygen-sparing effect on mitochondrial respiration, which is mediated via its antioxidant actions and its ability to enhance pro-survival pathways. Therefore, melatonin intake may have ergogenic effects on healthy muscles, in the absence of pathology, e.g., consumption before sporting events or physical exercise may aid in the reduction of oxidative stress often associated with such activities. However, this is an in vitro study, and therefore, the clinical relevance of the data should be considered with caution.

以往的研究表明，褪黑激素能防止肌肉损伤，同时还能提高受伤肌肉的性能。然而，褪黑激素对健康骨骼肌的影响在很大程度上仍未得到研究。我们将分化的 C2C12 肌管暴露于两种浓度（10 nM 或 50 nM）的褪黑激素。浓度为 10 nM 的褪黑激素不影响线粒体呼吸的任何参数。而 50 nM 浓度则降低了线粒体与复合体 II 相关的氧化磷酸化（OXPHOS）、电子传递系统（ETS）能力、复合体 II 对 ETS 的贡献以及剩余耗氧量（ROX）。两种浓度都不会影响线粒体耦合控制比率或耦合控制效率比率。此外，两种浓度都不影响 ATP 的产生，但降低了超氧化物歧化酶的活性。50 nM 会提高过氧化氢酶的活性，但不会影响自噬或柠檬酸合成酶的活性。此外，50 nM 降低了活化的 JAK2 和 STAT3 蛋白表达，而 10 nM 则降低了 JAK2，但不影响 STAT3。Th 50 nM 增加了活化的 AKT 和 ERK1/2 的表达，但对 p38 或 PGC1-α 的表达没有影响。我们的数据表明，褪黑素（50 nM）会对线粒体呼吸产生保氧作用，这种作用是通过其抗氧化作用和增强促生存途径的能力介导的。因此，在没有病变的情况下，摄入褪黑素可能会对健康肌肉产生促进作用，例如，在体育赛事或体育锻炼前摄入褪黑素可能有助于减少与此类活动相关的氧化应激。不过，这是一项体外研究，因此应谨慎考虑数据的临床相关性。

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引用次数: 0

Gut-lung Axis mediates asthma pathogenesis: Roles of dietary patterns and their impact on the gut microbiota 肠肺轴介导哮喘发病机制：饮食模式的作用及其对肠道微生物群的影响

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-04-06 DOI: 10.1016/j.yexmp.2025.104964

Yanbo Liu, Ying Zhou, Haoyue Zhang, Kaixuan Zhao, Dong Yang

The gut-lung axis, a vital signaling network linking the gastrointestinal and pulmonary systems, regulates immune responses and the progression of respiratory diseases. Nutritional components can modulate the gut microbiome and regulate the synthesis of critical intestinal microbial metabolites, which are essential for maintaining immune homeostasis and supporting respiratory health. Conversely, poor dietary habits exacerbate asthma and other respiratory conditions through the modulation of systemic inflammation and immune responses. Dietary interventions, such as the Mediterranean diet, are reported to restore microbial balance and improve respiratory health by increasing the production of anti-inflammatory metabolites, potentiating immune responses, and preserving epithelial barrier integrity. In contrast, Western dietary patterns, which are characterized by high fat and low fiber intake, disrupt microbial diversity, resulting in increased levels of pro-inflammatory metabolites that aggravate airway inflammation and asthma severity. This review aimed to elucidate the mechanisms underlying the regulatory effects of gut microbes and their metabolites on asthma. Additionally, previous findings related to the gut-lung axis have been summarized, providing insights into potential therapeutic strategies for asthma management.

肠-肺轴是连接胃肠道和肺系统的重要信号网络，调节免疫反应和呼吸系统疾病的进展。营养成分可以调节肠道微生物群，调节关键肠道微生物代谢物的合成，这对维持免疫稳态和支持呼吸健康至关重要。相反，不良的饮食习惯通过调节全身炎症和免疫反应加重哮喘和其他呼吸系统疾病。据报道，饮食干预，如地中海饮食，可以通过增加抗炎代谢物的产生、增强免疫反应和保持上皮屏障的完整性来恢复微生物平衡和改善呼吸健康。相比之下，西方饮食模式以高脂肪和低纤维摄入为特征，破坏了微生物多样性，导致促炎代谢物水平升高，加重了气道炎症和哮喘的严重程度。本文旨在阐明肠道微生物及其代谢物对哮喘调节作用的机制。此外，总结了先前与肠-肺轴相关的研究结果，为哮喘管理的潜在治疗策略提供了见解。

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引用次数: 0

Advances in sepsis research: Insights into signaling pathways, organ failure, and emerging intervention strategies 败血症研究进展：洞察信号通路、器官衰竭和新兴干预策略

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-03-25 DOI: 10.1016/j.yexmp.2025.104963

Yehua Li , Siying Ren , Shen’ao Zhou

Sepsis is a complex syndrome resulting from an aberrant host response to infection. A hallmark of sepsis is the failure of the immune system to restore balance, characterized by hyperinflammation or immunosuppression. However, the net effect of immune system imbalance and the clinical manifestations are highly heterogeneous among patients. In recent years, research interest has shifted from focusing on the pathogenicity of microorganisms to the molecular mechanisms of host responses which is also associated with biomarkers that can help early diagnose sepsis and guide treatment decisions. Despite significant advancements in medical science, sepsis remains a major challenge in healthcare, contributing to substantial morbidity and mortality worldwide. Further research is needed to improve our understanding of this condition and develop novel therapies to improve outcomes for patients with sepsis. This review explores the related signal pathways of sepsis and underscores recent advancements in understanding its mechanisms. Exploration of diverse biomarkers and the emerging concept of sepsis endotypes offer promising avenues for precision therapy in the future.

脓毒症是一种复杂的综合征，由宿主对感染的异常反应引起。败血症的一个标志是免疫系统恢复平衡的失败，其特征是过度炎症或免疫抑制。然而，免疫系统失衡的净效应和临床表现在患者之间是高度异质性的。近年来，研究兴趣从关注微生物的致病性转向宿主反应的分子机制，这也与生物标志物有关，可以帮助早期诊断败血症并指导治疗决策。尽管医学科学取得了重大进步，但败血症仍然是医疗保健领域的主要挑战，在世界范围内造成了大量的发病率和死亡率。需要进一步的研究来提高我们对这种情况的理解，并开发新的治疗方法来改善脓毒症患者的预后。这篇综述探讨了脓毒症的相关信号通路，并强调了了解其机制的最新进展。多种生物标志物的探索和脓毒症内型概念的出现为未来的精确治疗提供了有希望的途径。

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