Experimental and molecular pathology最新文献_第7页

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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引用次数: 0

The role of lactate and lactylation in ischemic cardiomyopathy: Mechanisms and gene expression 乳酸和乳酸化在缺血性心肌病中的作用：机制和基因表达

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-03-01 DOI: 10.1016/j.yexmp.2025.104957

Mei Zhang , Xue Kong , Chenlu Wu , Jiuhong Li , Hui Yang , Lingzhi Huang

Ischemic cardiomyopathy (ICM) is a significant global public health issue, with its pathophysiology encompassing atherosclerotic plaque formation, thrombosis, hypoperfusion, ischemic cell death, and left ventricular remodeling. Lactate is not only regarded as an energy metabolite but also acts as a signaling molecule that influences various physiological processes, regulating metabolism and muscle contraction. Lactylation, an emerging epigenetic modification, affects protein functionality and gene expression through the P300 enzyme. In ICM, lactate accumulation leads to pH imbalance and myocardial cell dysfunction, impacting cellular signaling. This paper will analyze the role of lactylation in ICM, focusing on coronary artery disease (ASCVD) and myocardial infarction (MI). It will also explore the differential expression and immunological characteristics of lactylation-related genes in normal and ICM tissues, providing potential targets for future research.

缺血性心肌病（ICM）是一个重要的全球公共卫生问题，其病理生理学包括动脉粥样硬化斑块形成、血栓形成、灌注不足、缺血性细胞死亡和左心室重构。乳酸不仅被认为是一种能量代谢物，而且作为一种影响各种生理过程的信号分子，调节代谢和肌肉收缩。乳酸化是一种新兴的表观遗传修饰，通过P300酶影响蛋白质功能和基因表达。在ICM中，乳酸积累导致pH失衡和心肌细胞功能障碍，影响细胞信号传导。本文将分析乳酸化在ICM中的作用，重点是冠状动脉疾病（ASCVD）和心肌梗死（MI）。探索正常组织和ICM组织中乳酸化相关基因的差异表达和免疫学特征，为今后的研究提供潜在的靶点。

引用次数: 0

Dynamic full-field optical coherence tomography for extemporaneous high-resolution imaging of adrenal glands 动态全视野光学相干断层成像技术用于肾上腺的即时高分辨率成像

IF 2.8 4区医学 Q2 PATHOLOGY

Experimental and molecular pathology

Pub Date : 2025-02-19 DOI: 10.1016/j.yexmp.2025.104958

Irene A. Spiridon , Michel Vix , Didier Mutter , Barbara Seeliger

Background

There is an interindividual variance in postoperative adrenocortical capacity, and the minimal functional remnant size is unknown. New imaging technologies may allow for improved intraoperative assessment of adrenal tissue morphology, cell activity, and surgery-related changes. The aim of this experimental study was to provide a pilot assessment of adrenal gland architecture with dynamic full-field optical coherence tomography (D-FF-OCT) in comparison to standard hematoxylin-eosin (HE) examination.

Methods

D-FF-OCT was performed on freshly resected porcine adrenal glands to simultaneously assess both morphology and metabolic activity in real time, and for comparison with standard histopathology. Left and right adrenal glands were assessed from 8 pigs (1 M, 7 F, mean weight 43.9 ± 8.3 kg).

Results

The evaluation with D-FF-OCT proved fast in terms of acquisition time, averaging 32 min/specimen. The technique required a relatively short learning curve and provided morphological details similar to standard microscopy. In the comparative analysis of both methods, D-FF-OCT scans allowed easy identification of normal adrenal morphology and facilitated differentiation of the structural components of the cortical and medullary areas based on architectural and vascular patterns. Furthermore, it was possible to distinguish more accurately between cell subpopulations based on their metabolic activity.

Conclusion

While HE examination remains the gold standard for morphological evaluation, time weighs heavy on this ancillary technique. In our study, we prove that D-FF-OCT is effective in achieving a comparable level of morphological details, with added metabolic activity of the cells, a combination which can prove useful in the real-time assessment of various diseases requiring adrenal surgery.

背景术后肾上腺皮质容量存在个体间差异，最小功能残余大小尚不清楚。新的成像技术可以改善术中对肾上腺组织形态、细胞活性和手术相关变化的评估。本实验研究的目的是提供动态全场光学相干断层扫描（D-FF-OCT）对肾上腺结构的初步评估，并与标准苏木精-伊红（HE）检查进行比较。方法采用sd - ff - oct对新鲜切除的猪肾上腺进行实时形态学和代谢活性评估，并与标准组织病理学进行比较。对8头猪（1 M, 7 F，平均体重43.9±8.3 kg）的左右肾上腺进行了评估。结果D-FF-OCT评估的采集时间较短，平均为32 min/个标本。该技术需要相对较短的学习曲线，并提供类似于标准显微镜的形态学细节。在两种方法的对比分析中，D-FF-OCT扫描可以很容易地识别正常肾上腺形态，并根据建筑和血管模式促进皮质和髓质区域结构成分的区分。此外，根据细胞的代谢活性更准确地区分细胞亚群是可能的。结论虽然HE检查仍然是形态学评价的金标准，但时间对这种辅助技术的影响很大。在我们的研究中，我们证明了D-FF-OCT在获得相当水平的形态学细节方面是有效的，并且增加了细胞的代谢活性，这一组合可以被证明在实时评估需要肾上腺手术的各种疾病中是有用的。

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引用次数: 0