Advances in medical sciences最新文献_第2页

Downregulation and inhibition of TRPM2 calcium channel prevent oxidative stress-induced endothelial dysfunction in the EA.hy926 endothelial cells model - Preliminary studies 下调和抑制TRPM2钙通道可预防EA.hy926内皮细胞模型中氧化应激诱导的内皮功能障碍——初步研究

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-06 DOI: 10.1016/j.advms.2025.01.002

Wioletta Arendt , Klaudia Piekarska , Marta Hałas-Wiśniewska , Magdalena Izdebska , Alina Grzanka , Maciej Gagat

Purpose

Proper functioning of the endothelial barrier is crucial for cardiovascular system homeostasis. Oxidative stress can lead to endothelial dysfunction (ED), damaging lipids, proteins, and DNA. Reactive oxygen species also increase cytoplasmic Ca²⁺ levels, activating transient receptor potential melastatin 2 (TRPM2), a membrane non-selective calcium channel. The study aimed to assess TRPM2's significance in vascular endothelial cells' response to oxidative stress and the potential use of TRPM2 direct and indirect inhibitors in the prevention of oxidative stress-induced ED.

Materials and methods

EA.hy926 endothelial cells were exposed to hydrogen peroxide for 24 h to mimic oxidative stress conditions. To assess the significance of TRPM2 in the response of EA.hy926 cells to hydrogen peroxide TRPM2 siRNA as well as direct (N-(p-Amylcinnamoyl)anthranilic acid, flufenamic acid) and indirect (3-aminobenzamide, 3,4-dihydro-5[4-(1-piperidinyl)butyl]-1(2H)-isoquinolinone) TRPM2 inhibitors were tested.

Results

Results showed that hydrogen peroxide-induced ED is alleviated by TRPM2 downregulation. Moreover, preincubation of cells with both direct and indirect TRPM2 inhibitors for 30 min before hydrogen peroxide treatment reduces its negative effects on cell viability, cell migration, and junctional proteins.

Conclusions

The obtained results suggest that TRPM2 channel may be a potential target in therapy and prevention of cardiovascular diseases connected with oxidative stress-induced ED. However, further research is needed for clinical applications of direct and indirect TRPM2 inhibitors.

目的：内皮屏障的正常功能对心血管系统的稳态至关重要。氧化应激可导致内皮功能障碍（ED），损害脂质、蛋白质和DNA。活性氧也增加细胞质Ca2+水平，激活瞬时受体电位美拉抑素2 (TRPM2)，这是一种膜非选择性钙通道。本研究旨在评估TRPM2在血管内皮细胞对氧化应激反应中的意义，以及TRPM2直接和间接抑制剂在预防氧化应激诱导ed中的潜在应用。材料和方法：将EA.hy926内皮细胞暴露在过氧化氢环境中24小时，模拟氧化应激条件。为了评估TRPM2在EA.hy926细胞对过氧化氢TRPM2 siRNA以及直接（N-（对氨基肉桂基）苯甲酸、氟芬那酸）和间接（3-氨基苯甲酰胺、3,4-二氢-5[4-（1-哌替啶基）丁基]-1(2H)-异喹啉酮）TRPM2抑制剂反应中的意义。结果：过氧化氢诱导的ED可通过下调TRPM2得到缓解。此外，在过氧化氢处理前，将细胞与直接和间接TRPM2抑制剂一起预孵养30分钟，可以减少其对细胞活力、细胞迁移和连接蛋白的负面影响。结论：上述结果提示TRPM2通道可能是治疗和预防氧化应激性ED相关心血管疾病的潜在靶点，但TRPM2直接和间接抑制剂的临床应用还需进一步研究。

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引用次数: 0

Clinical value of CEUS with tumour marker monitoring in evaluating the prognosis of HCC after MWA 超声造影联合肿瘤标志物监测对肝癌MWA术后预后评价的临床价值。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2025-01-02 DOI: 10.1016/j.advms.2025.01.001

Qiang Guo , Yang Yu , Ruyun Ye , Zhiliang Huang , Tingting Shi

Purpose

This study aims to evaluate the prognostic value of contrast-enhanced ultrasound (CEUS) combined with tumour markers in patients with hepatocellular carcinoma (HCC) undergoing microwave ablation (MWA).

Methods

MWA patients with HCC were divided into good prognosis (n = 75) and poor prognosis (n = 69) groups. The levels of alpha-fetoprotein (AFP), carbohydrate antigen (CA19-9), and carcinoembryonic antigen (CEA) before and after MWA were analysed using an independent sample t-test. The correlation between prognosis, ablation lesion area, and tumour marker levels were analysed by Pearson's correlation. The diagnostic power of the ablation lesion area combined with tumour marker levels for the prognosis of patients with MWA was analysed using receiver operating characteristic (ROC) curves.

Results

The levels of AFP, CA19-9, and CEA in the good prognosis group were significantly lower than those in the poor prognosis group (all P < 0.001). The levels of all tumour markers were significantly negatively correlated with the prognosis of patients who underwent MWA (all r < 0, P < 0.001) and positively correlated with the area of tumour-ablated lesions (r > 0, P < 0.001). Moreover, the diagnostic efficacy of CEUS combined with tumour markers for the prognosis of patients who underwent MWA was significantly higher than that of either single diagnostic modality.

Conclusions

CEUS combined with tumour marker monitoring can effectively improve the accuracy of prognostic diagnosis in patients with MWA and provide a reference for timely and reasonable treatment and therapeutic evaluation.

目的：本研究旨在评价超声造影（CEUS）联合肿瘤标志物在肝细胞癌（HCC）微波消融（MWA）患者中的预后价值。方法：将MWA合并HCC患者分为预后良好组（n = 75）和预后不良组（n = 69）。采用独立样本t检验分析MWA前后甲胎蛋白（AFP）、碳水化合物抗原（CA19-9）、癌胚抗原（CEA）水平。采用Pearson相关分析预后、消融病灶面积与肿瘤标志物水平的相关性。采用受试者工作特征（ROC）曲线分析消融病灶面积结合肿瘤标志物水平对MWA患者预后的诊断能力。结果：预后良好组患者AFP、CA19-9、CEA水平显著低于预后不良组（P均< 0.001）。所有肿瘤标志物水平与MWA患者预后呈显著负相关（均r < 0, P < 0.001），与肿瘤消融灶面积呈正相关（均r < 0, P < 0.001）。此外，超声造影联合肿瘤标志物对MWA患者预后的诊断效果显著高于任何一种单一诊断方式。结论：超声造影联合肿瘤标志物监测可有效提高MWA患者预后诊断的准确性，为及时合理的治疗和疗效评价提供参考。

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引用次数: 0

To shock or not to shock - The accuracy of cardiac arrest rhythm assessment by paramedics in a simulated environment 电击还是不电击——护理人员在模拟环境中心脏骤停节律评估的准确性。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-12-18 DOI: 10.1016/j.advms.2024.12.002

Jerzy Jaskuła , Katarzyna Stolarz-Skrzypek , Klaudia Jaskuła , Jerzy Wordliczek , Grzegorz Cebula , Wojciech Zaręba , Małgorzata Kloch

Purpose

Defibrillation in shockable rhythm is a well-known key intervention in cardiopulmonary resuscitation (CPR). The aim of this study was to analyze accuracy (the sum of the numbers of true positive results and true negative results, divided by the number of total results) of deciding by paramedics whether the rhythm was shockable or non-shockable.

Methods

In this study 103 paramedics from various regions of Poland participated voluntarily. Study participants were presented with 22 simulated various electrocardiogram (ECG) recordings based on 10-s videos. These rhythms were also assessed using a manual defibrillator with shock-advisory mode known as automated external defibrillator (AED) mode.

Results

Among the 103 participants, the mean of correct answers (correct decision to defibrillate or correct decision not to defibrillate) was 18/22 (83.7 %). The highest possible score was achieved by the participant with 22/22 (100 %) correct answers, while the lowest was 10/22 (45.5 %). The highest score obtained for single rhythm was 97.1 % and the lowest was 32 %. Mean accuracy of shock-advisory mode was 77.3 %.

Conclusions

Improving the quality of paramedic training and continuous quality monitoring (e.g., by analyzing ECG recordings from resuscitations) is essential to improve the accuracy of defibrillation rhythm recognition. The role of the AED mode can be advisory, but is not a substitute for assessment by medical professionals in Emergency Medical Service.

目的：休克心律除颤是众所周知的心肺复苏（CPR）的关键干预措施。本研究的目的是分析护理人员判断心律是震荡还是非震荡的准确性（真阳性结果和真阴性结果的总和，除以总结果的数量）。方法：在本研究中，来自波兰不同地区的103名护理人员自愿参与。研究参与者观看了22个基于10秒视频的模拟心电图（ECG）记录。这些节律也使用具有休克咨询模式的手动除颤器进行评估，称为自动体外除颤器（AED）模式。结果：在103名参与者中，正确答案（正确决定除颤器或正确决定不除颤器）的平均值为18/22（83.7%）。满分为22/22(100%)，最低为10/22（45.5%）。单节律得分最高为97.1%，最低为32%。冲击预警模式的平均准确率为77.3%。结论：提高护理人员的培训质量和持续的质量监测（例如，通过分析复苏的心电图记录）对于提高除颤节律识别的准确性至关重要。AED模式的作用可以是咨询，但不能代替医疗专业人员在紧急医疗服务中的评估。

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引用次数: 0

Systemic immune-inflammation index in the evaluation of Sjogren's syndrome associated with interstitial lung disease, interstitial pneumonia with autoimmune features, and idiopathic pulmonary fibrosis 评估与间质性肺病相关的干燥综合征、具有自身免疫性特征的间质性肺炎和特发性肺纤维化的全身性免疫炎症指数

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-12-14 DOI: 10.1016/j.advms.2024.12.001

Gokhan Sargin , Kursad Baris , Sule Tas Gulen

Purpose

Interstitial lung disease (ILD) damages the lungs and can be caused by environmental exposures and collagen-vascular diseases. The systemic immune-inflammation index (SII) is investigated to diagnose and manage ILDs in different etiological diseases. The study aims to examine the usefulness of SII in diagnosing specific ILDs like Sjogren's syndrome (SjS)-ILD, interstitial pneumonia with autoimmune features (IPAF), and idiopathic pulmonary fibrosis (IPF).

Materials and methods

In this cross-sectional study, we included 109 patients with IPAF, IPF, and SjS-ILD. Demographic characteristics, symptoms, lung patterns, autoantibodies, and SII were assessed. Morphologic, serologic, and clinical factors determined the classification of IPAF. Student's t-test, Mann-Whitney U test, Pearson-Spearman's method, and receiver operating characteristic (ROC) curves were used to analyze data.

Results

Male patients were more common in IPF and IPAF, while SjS-ILD had mostly female patients. Raynaud's phenomenon and dry mouth/eyes were more common in SjS-ILD compared to IPF and IPAF. The groups had significant differences in patterns, antinuclear antibody positivity, and SII levels. SII levels differed significantly between IPAF, SjS-ILD, and IPF patients, and were correlated with CRP in IPAF and SjS-ILD. The cut-off value of the SII between IPAF and IPF in patients with ILD was 576.1 with 76.0 % sensitivity and 76.0 % specificity.

Conclusions

Evaluation of SII provides valuable information for understanding and identifying different disease groups with ILDs.

目的：间质性肺病（ILD）损害肺部，可由环境暴露和胶原血管疾病引起。全身免疫炎症指数（SII）被用来诊断和治疗不同病因的间质性肺病。本研究旨在探讨 SII 在诊断特定 ILD（如 Sjogren's 综合征（SjS）-ILD、具有自身免疫特征的间质性肺炎（IPAF）和特发性肺纤维化（IPF））时的实用性：在这项横断面研究中，我们纳入了 109 名 IPAF、IPF 和 SjS-ILD 患者。对患者的人口统计学特征、症状、肺部形态、自身抗体和 SII 进行了评估。形态学、血清学和临床因素决定了 IPAF 的分类。数据分析采用了学生 t 检验、Mann-Whitney U 检验、Pearson-Spearman 方法和接收器操作特征曲线（ROC）：结果：男性患者在 IPF 和 IPAF 中更为常见，而 SjS-ILD 则以女性患者居多。与 IPF 和 IPAF 相比，SjS-ILD 更常见雷诺现象和口干/眼干。各组在模式、抗核抗体阳性率和 SII 水平方面存在明显差异。SII水平在IPAF、SjS-ILD和IPF患者之间存在明显差异，在IPAF和SjS-ILD中与CRP相关。在 ILD 患者中，IPAF 和 IPF 之间的 SII 临界值为 576.1，灵敏度为 76.0%，特异度为 76.0%：结论：评估 SII 可为了解和识别 ILD 不同疾病组提供有价值的信息。

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引用次数: 0

Caloric restriction mimetics: Pinostilbene versus resveratrol regarding SIRT1 and SIRT6 interaction 热量限制模拟：蒎烯与白藜芦醇对SIRT1和SIRT6相互作用的影响。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-11-29 DOI: 10.1016/j.advms.2024.11.002

Anca Ungurianu , Denisa Margină , Dragoș P. Mihai , Alina C. Nicolae , Cristina M. Drăgoi , Daniela Grădinaru , Anca Zanfirescu

Purpose

Caloric restriction (CR), the permanent or periodic reduction of caloric intake, is a dietary strategy that promotes longevity and healthspan, yielding multiple beneficial effects, such as improved insulin sensitivity and mitochondrial function, decreased body weight, and mitigation of cardiometabolic risk factors. The purpose of our study was the in silico and in vitro assessment of the effects exerted by pinostilbene on SIRT1 and SIRT6 compared to those of resveratrol, a known activator of these enzymes.

Materials and methods

Molecular docking was carried out to determine the interactions with SIRT1 and SIRT6 and, further, the effect of pinostilbene on their activity was tested in vitro to evaluate if it parallels resveratrol's effects regarding SIRT activation.

Results

Molecular docking indicates that resveratrol and pinostilbene bind similarly to SIRT6, while pinostilbene may be able to activate SIRT1 more efficiently than resveratrol. In vitro activity assays showed that while both resveratrol and pinostilbene activate SIRT1 and SIRT6, the concentration-dependent effects differ. For resveratrol, a greater effect was observed at the medium concentration (25 μM), whereas pinostilbene showed a more pronounced activation at the lowest concentration (5 μM).

Conclusions

Our results offer a glimpse into the structural features and interactions of pinostilbene and resveratrol with SIRT1 and SIRT6, contributing to understanding their potential roles in various cellular processes regulated by SIRT.

目的：热量限制（CR），即永久或定期减少热量摄入，是一种促进长寿和健康的饮食策略，可产生多种有益效果，如改善胰岛素敏感性和线粒体功能，降低体重，减轻心脏代谢危险因素。我们研究的目的是在体内和体外评估pinostilbene对SIRT1和SIRT6的影响，并与白藜芦醇（一种已知的这些酶的激活剂）进行比较。材料与方法：通过分子对接确定与SIRT1和SIRT6的相互作用，并进一步在体外测试蒎烯对其活性的影响，以评估其是否与白藜芦醇对SIRT激活的作用相似。结果：分子对接表明，白藜芦醇和蒎烯与SIRT6的结合相似，而蒎烯可能比白藜芦醇更有效地激活SIRT1。体外活性分析表明，尽管白藜芦醇和蒎烯都能激活SIRT1和SIRT6，但其浓度依赖性不同。对于白藜芦醇，在中等浓度（25 μM）下的活化效果更明显，而蒎烯在最低浓度（5 μM）下的活化效果更明显。结论：我们的研究结果揭示了蒎烯二苯乙烯和白藜芦醇与SIRT1和SIRT6的结构特征和相互作用，有助于了解它们在SIRT调控的各种细胞过程中的潜在作用。

{"title":"Caloric restriction mimetics: Pinostilbene versus resveratrol regarding SIRT1 and SIRT6 interaction","authors":"Anca Ungurianu , Denisa Margină , Dragoș P. Mihai , Alina C. Nicolae , Cristina M. Drăgoi , Daniela Grădinaru , Anca Zanfirescu","doi":"10.1016/j.advms.2024.11.002","DOIUrl":"10.1016/j.advms.2024.11.002","url":null,"abstract":"<div><h3>Purpose</h3><div>Caloric restriction (CR), the permanent or periodic reduction of caloric intake, is a dietary strategy that promotes longevity and healthspan, yielding multiple beneficial effects, such as improved insulin sensitivity and mitochondrial function, decreased body weight, and mitigation of cardiometabolic risk factors. The purpose of our study was the <em>in silico</em> and <em>in vitro</em> assessment of the effects exerted by pinostilbene on SIRT1 and SIRT6 compared to those of resveratrol, a known activator of these enzymes.</div></div><div><h3>Materials and methods</h3><div>Molecular docking was carried out to determine the interactions with SIRT1 and SIRT6 and, further, the effect of pinostilbene on their activity was tested <em>in vitro</em> to evaluate if it parallels resveratrol's effects regarding SIRT activation.</div></div><div><h3>Results</h3><div>Molecular docking indicates that resveratrol and pinostilbene bind similarly to SIRT6, while pinostilbene may be able to activate SIRT1 more efficiently than resveratrol. <em>In vitro</em> activity assays showed that while both resveratrol and pinostilbene activate SIRT1 and SIRT6, the concentration-dependent effects differ. For resveratrol, a greater effect was observed at the medium concentration (25 μM), whereas pinostilbene showed a more pronounced activation at the lowest concentration (5 μM).</div></div><div><h3>Conclusions</h3><div>Our results offer a glimpse into the structural features and interactions of pinostilbene and resveratrol with SIRT1 and SIRT6, contributing to understanding their potential roles in various cellular processes regulated by SIRT.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 44-50"},"PeriodicalIF":2.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting treatment resistance in cervical cancer: A new avenue for senolytic therapies 针对宫颈癌的耐药性：老年溶解疗法的新途径

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-11-15 DOI: 10.1016/j.advms.2024.11.001

Madré Meyer , Carla Fourie , Haynes van der Merwe , Hennie Botha , Anna-Mart Engelbrecht

Cervical cancer poses a significant global health challenge, particularly impacting women in economically developing nations. This disparity stems from a combination of factors, including inadequate screening infrastructure and resource limitations. However, the foremost contributor is the widespread lack of awareness and limited accessibility to Human Papillomavirus (HPV) vaccination, which is a key preventative measure against cervical cancer development. Despite advancements in cervical cancer prevention, treatment resistance remains a major hurdle in achieving improved patient outcomes. Cellular senescence, specifically the senescence-associated secretory phenotype (SASP) and its bidirectional relationship with the immune system, has been implicated in resistance to conventional cervical cancer chemotherapy treatments. The exact mechanisms by which this state of growth arrest and the associated changes in immune regulation contribute to cervical cancer progression and the associated drug resistance are not entirely understood. This underscores the necessity for innovative strategies to address the prevalence of treatment-resistant cervical cancer, with one promising avenue being the utilisation of senolytics. Senolytics are agents that have promising efficacy in clearing senescent cells from tumour tissues, however neither the utilisation of senolytics for addressing senescence-induced treatment resistance nor the potential integration of immunotherapy as senolytic agents in cervical cancer treatment has been explored to date. This review provides a concise overview of the mechanisms underlying senescence induction and the pivotal role of the immune system in this process. Additionally, it explores various senolytic approaches that hold significant potential for advancing cervical cancer research.

宫颈癌对全球健康构成了重大挑战，尤其影响到经济发展中国家的妇女。造成这种差异的因素很多，包括筛查基础设施不足和资源限制。然而，最主要的原因是人们普遍缺乏对人类乳头瘤病毒（HPV）疫苗接种的认识，而且接种机会有限，而接种HPV疫苗是预防宫颈癌发展的关键措施。尽管在宫颈癌预防方面取得了进展，但治疗耐药性仍是改善患者预后的一大障碍。细胞衰老，特别是衰老相关分泌表型（SASP）及其与免疫系统的双向关系，已被认为与传统宫颈癌化疗的耐药性有关。这种生长停滞状态和相关的免疫调节变化导致宫颈癌进展和相关耐药性的确切机制尚不完全清楚。这凸显了采用创新策略来解决宫颈癌耐药问题的必要性，其中一个很有前景的方法就是使用抗衰老剂。衰老剂是一种在清除肿瘤组织中衰老细胞方面具有良好疗效的药物，但迄今为止，还没有人探索过利用衰老剂来解决衰老引起的耐药性问题，也没有人探索过将免疫疗法作为衰老剂整合到宫颈癌治疗中的可能性。本综述简要概述了衰老诱导的基本机制以及免疫系统在这一过程中的关键作用。此外，它还探讨了在推进宫颈癌研究方面具有巨大潜力的各种衰老溶解方法。

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引用次数: 0

Recurrent hepatocellular carcinoma is associated with the enrichment of MYC targets gene sets, elevated high confidence deleterious mutations and alternative splicing of DDB2 and BRCA1 transcripts 复发性肝细胞癌与 MYC 目标基因组的富集、高置信度的有害突变以及 DDB2 和 BRCA1 转录本的替代剪接有关。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-10-30 DOI: 10.1016/j.advms.2024.10.004

Oğuzhan Karaosmanoğlu

Purpose

Recurrence is the main cause of hepatocellular carcinoma (HCC) related deaths. Underlying recurrence biology can be better understood by comparative analysis of the complete set of transcripts between recurrent and non-recurrent HCC. In this study, transcriptomic data (GSE56545) from 21 male patients diagnosed with either recurrent or non-recurrent HCC were reanalyzed to identify deregulated pathways, somatic mutations, fusion transcripts, alternative splicing events, and the immune context in recurrent HCC.

Materials and methods

DESeq2 was used for differential expression analysis, Mutect2 for somatic mutation analysis, Arriba and STAR-Fusion for fusion transcript analysis, and rMATs for alternative splicing analysis.

Results

The results revealed that MYC targets gene sets (Hallmark_MYC_targets_V1 and Hallmark_MYC_targets_V2) were significantly enriched in recurrent HCC. Among the MYC targets, CBX3, NOP56, CDK4, NPM1, MCM5, MCM4 and PA2G4 upregulation was significantly associated with poor survival. Somatic mutation analysis demonstrated that the numbers of high confidence deleterious mutations were significantly increased in recurrent HCC. Alternative splicing-mediated production of non-functional DDB2 and oncogenic BRCA1 D11q were discovered in recurrent HCC. Finally, CD8⁺ T-cells were significantly decreased in recurrent HCC.

Conclusions

These results indicated that the enrichment of MYC targets gene sets is one of the most critical factors that leads to the development of recurrent HCC. In addition, elevated deleterious mutation numbers and alternative spliced DDB2 and BRCA1 isoforms have been identified as prominent contributors to increasing genomic instability in male patients with recurrent HCC.

目的：复发是肝细胞癌（HCC）相关死亡的主要原因。通过比较分析复发和非复发 HCC 的全套转录本，可以更好地了解复发的生物学基础。本研究重新分析了21例诊断为复发性或非复发性HCC男性患者的转录组数据（GSE56545），以确定复发性HCC中的失调通路、体细胞突变、融合转录本、替代剪接事件和免疫环境：DESeq2用于差异表达分析，Mutect2用于体细胞突变分析，Arriba和STAR-Fusion用于融合转录本分析，rMATs用于替代剪接分析：结果发现，MYC靶基因集（Hallmark_MYC_targets_V1和Hallmark_MYC_targets_V2）在复发性HCC中明显富集。在MYC靶点中，CBX3、NOP56、CDK4、NPM1、MCM5、MCM4和PA2G4的上调与生存率低明显相关。体细胞突变分析表明，高置信度的有害突变数量在复发性 HCC 中明显增加。在复发性 HCC 中发现了替代剪接介导的无功能 DDB2 和致癌 BRCA1 D11q 的产生。最后，CD8+ T细胞在复发性HCC中明显减少：这些结果表明，MYC 靶基因组的富集是导致复发性 HCC 发生的最关键因素之一。结论：这些结果表明，MYC靶基因集的富集是导致复发性HCC发生的最关键因素之一，此外，有害突变数量的增加以及DDB2和BRCA1同工酶的替代剪接也是导致男性复发性HCC患者基因组不稳定性增加的主要原因。

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引用次数: 0

Knockout of histone deacetylase 8 gene in breast cancer cells may alter the expression pattern of the signaling molecules 在乳腺癌细胞中敲除组蛋白去乙酰化酶 8 基因可能会改变信号分子的表达模式。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-10-20 DOI: 10.1016/j.advms.2024.10.003

Nahid Bahrami , Mohammad Abdi

Purpose

Breast cancer (BC) is the most common cancer diagnosed in the world and it is also the main leading cause of cancer deaths in women. Change in epigenetic mechanisms promotes BC initiation and progression. Histone deacetylase 8 (HDAC8) was found to act as a potential oncogene in different malignancies. For better understanding of the HDAC8 function in BC development, we investigated the effect of HDAC8 deletion on the expression of genes involved in signaling pathways.

Materials and methods

In this study, CRISPR technology was used to knockout the HDAC8 gene in MDA-MB-468, MDA-MB-231 and MCF-7 cell lines. For this purpose, two gRNAs were designed and cloned into the PX459 vector. The gRNA-containing vectors were transfected into the BC cell lines and then the effect of this deletion on the expression of genes involved in signaling pathway was determined using quantitative real-time PCR (qRT-PCR).

Results

Analysis of qRT-PCR results showed a reduction in the expression of studied genes in BC cell lines after deletion of the HDAC8 gene compared to untreated controls. Although this decline was not significant for FGF2 and FGFR1 genes, however the mTOR, IGF1R, INSR, VEGFA and VEGFR2 genes showed statistically significant reduction in the studied BC cell lines. In addition, the down-regulation of PDGFC and PDGFRA genes were only significant in the TNBC cell lines.

Conclusion

Overall, our study showed that HDAC8 can exert its oncogenic effects by altering the expression level of molecules involved in some signaling pathways, and inhibiting HDAC8 can revert these effects.

目的：乳腺癌（BC）是世界上最常见的癌症，也是女性癌症死亡的主要原因。表观遗传机制的变化会促进乳腺癌的发生和发展。组蛋白去乙酰化酶 8（HDAC8）被发现在不同的恶性肿瘤中充当潜在的致癌基因。为了更好地了解HDAC8在BC发病中的功能，我们研究了HDAC8缺失对信号通路相关基因表达的影响：本研究采用CRISPR技术在MDA-MB-468、MDA-MB-231和MCF-7细胞系中敲除HDAC8基因。为此，研究人员设计了两个 gRNA，并将其克隆到 PX459 载体中。将含 gRNA 的载体转染到 BC 细胞系中，然后使用实时定量 PCR（qRT-PCR）测定这种缺失对信号通路相关基因表达的影响：qRT-PCR结果分析表明，与未处理的对照组相比，HDAC8基因缺失后，BC细胞系中研究基因的表达量有所下降。虽然FGF2和FGFR1基因的表达量下降不明显，但在所研究的BC细胞系中，mTOR、IGF1R、INSR、VEGFA和VEGFR2基因的表达量出现了统计学意义上的显著下降。此外，PDGFC 和 PDGFRA 基因的下调仅在 TNBC 细胞系中明显：总之，我们的研究表明，HDAC8可以通过改变参与某些信号通路的分子的表达水平来发挥其致癌作用，而抑制HDAC8可以逆转这些作用。

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引用次数: 0

Combination therapy of placenta-derived mesenchymal stem cells and artificial dermal scaffold promotes full-thickness skin defects vascularization in rat animal model 胎盘间充质干细胞与人工真皮支架的联合疗法促进了大鼠动物模型全厚皮肤缺损血管的形成。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-10-17 DOI: 10.1016/j.advms.2024.10.002

Kun Zhang , Dongjie Xiao , Fang Li , Guodong Song , Guobao Huang , Yunshan Wang , Hua Liu

Purpose

Recently, placenta-derived mesenchymal stem cells (PMSCs) have garnered considerable attention in tissue repair and regeneration. The present study was conducted to evaluate the effect of PMSCs on artificial dermal scaffold (ADS) angiogenesis and their combination therapy on wound closure.

Material and methods

Herein, the growth and survival of PMSCs in ADS were explored. CCK8, scratch wound, and tubule formation assays were employed to investigate the effects of ADS conditioned medium (CM) and ADS-PMSCs CM on human umbilical vein endothelial cells (HUVECs). The effect of ADS-PMSCs on full-thickness skin defects healing was evaluated based on a rat model. Wound healing progresses was meticulously investigated through hematoxylin and eosin (HE), Masson's trichrome, and immunohistochemical staining analyses.

Results

In vitro cell culture results demonstrated the proliferation of PMSCs in ADS. The ADS-PMSCs CM notably stimulated the proliferation, migration, and tube formation of HUVECs compared to the ADS CM group. In the rat full-thickness skin defect model, the ADS-PMSCs treatment significantly accelerated the vascularization area of ADS after 2 weeks. Besides, HE and Masson's trichrome staining results indicated that ADS-PMSCs treatment significantly enhanced fibroblast proliferation and collagen fiber 2 weeks after surgical procedure. Compared to the ADS group, collagen fiber arrangement was thicker in the ADS-PMSCs group. Immunohistochemical staining reinforced this finding, illustrating a substantial increase in CD31 expression within the ADS-PMSCs group.

Conclusions

The results suggest that the combination of ADS with PMSCs accelerates ADS vascularization by fostering granulation tissue development and boosting the formation of new blood vessels.

目的：最近，胎盘间充质干细胞（PMSCs）在组织修复和再生方面受到广泛关注。本研究旨在评估胎盘间充质干细胞对人工真皮支架（ADS）血管生成的影响及其对伤口闭合的联合治疗作用。采用 CCK8、划痕伤口和小管形成试验研究 ADS 条件培养基（CM）和 ADS-PMSCs CM 对人脐静脉内皮细胞（HUVECs）的影响。以大鼠模型为基础，评估了 ADS-PMSCs 对全厚皮肤缺损愈合的影响。通过苏木精和伊红（HE）、马森三色染色和免疫组化染色分析，对伤口愈合进展进行了细致的研究：体外细胞培养结果表明，PMSCs 在 ADS 中增殖。与 ADS CM 组相比，ADS-PMSCs CM 组明显刺激了 HUVECs 的增殖、迁移和管形成。在大鼠全厚皮肤缺损模型中，ADS-PMSCs 治疗 2 周后明显加快了 ADS 的血管化面积。此外，HE 和 Masson's trichrome 染色结果表明，ADS-PMSCs 治疗能明显促进成纤维细胞的增殖和胶原纤维的形成。与 ADS 组相比，ADS-PMSCs 组的胶原纤维排列更粗。免疫组化染色证实了这一发现，表明 ADS-PMSCs 组 CD31 表达量大幅增加：结论：研究结果表明，ADS 与 PMSCs 的结合可促进肉芽组织的发育和新血管的形成，从而加速 ADS 的血管化。

{"title":"Combination therapy of placenta-derived mesenchymal stem cells and artificial dermal scaffold promotes full-thickness skin defects vascularization in rat animal model","authors":"Kun Zhang , Dongjie Xiao , Fang Li , Guodong Song , Guobao Huang , Yunshan Wang , Hua Liu","doi":"10.1016/j.advms.2024.10.002","DOIUrl":"10.1016/j.advms.2024.10.002","url":null,"abstract":"<div><h3>Purpose</h3><div>Recently, placenta-derived mesenchymal stem cells (PMSCs) have garnered considerable attention in tissue repair and regeneration. The present study was conducted to evaluate the effect of PMSCs on artificial dermal scaffold (ADS) angiogenesis and their combination therapy on wound closure.</div></div><div><h3>Material and methods</h3><div>Herein, the growth and survival of PMSCs in ADS were explored. CCK8, scratch wound, and tubule formation assays were employed to investigate the effects of ADS conditioned medium (CM) and ADS-PMSCs CM on human umbilical vein endothelial cells (HUVECs). The effect of ADS-PMSCs on full-thickness skin defects healing was evaluated based on a rat model. Wound healing progresses was meticulously investigated through hematoxylin and eosin (HE), Masson's trichrome, and immunohistochemical staining analyses.</div></div><div><h3>Results</h3><div><em>In vitro</em> cell culture results demonstrated the proliferation of PMSCs in ADS. The ADS-PMSCs CM notably stimulated the proliferation, migration, and tube formation of HUVECs compared to the ADS CM group. In the rat full-thickness skin defect model, the ADS-PMSCs treatment significantly accelerated the vascularization area of ADS after 2 weeks. Besides, HE and Masson's trichrome staining results indicated that ADS-PMSCs treatment significantly enhanced fibroblast proliferation and collagen fiber 2 weeks after surgical procedure. Compared to the ADS group, collagen fiber arrangement was thicker in the ADS-PMSCs group. Immunohistochemical staining reinforced this finding, illustrating a substantial increase in CD31 expression within the ADS-PMSCs group.</div></div><div><h3>Conclusions</h3><div>The results suggest that the combination of ADS with PMSCs accelerates ADS vascularization by fostering granulation tissue development and boosting the formation of new blood vessels.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 8-16"},"PeriodicalIF":2.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing the accuracy and effectiveness of diagnosis of spontaneous bacterial peritonitis in cirrhotic patients: A machine learning approach utilizing clinical and laboratory data 提高肝硬化患者自发性细菌性腹膜炎诊断的准确性和有效性：一种利用临床和实验室数据的机器学习方法。

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-10-16 DOI: 10.1016/j.advms.2024.10.001

Babak Khorsand , Mohsen Rajabnia , Ali Jahanian , Mobin Fathy , Somayye Taghvaei , Hamidreza Houri

Purpose

Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid that develops naturally, without being triggered by any surgical conditions or procedures, and is a common complication of cirrhosis. With a potential mortality rate of 40 %, accurate diagnosis and prompt initiation of appropriate antibiotic therapy are crucial for optimizing patient outcomes and preventing life-threatening complications. This study aimed to expand the use of computational models to improve the diagnostic accuracy of SBP in cirrhotic patients by incorporating a broader range of data, including clinical variables and laboratory values.

Patients and methods

We employed 5 machine learning classification methods - Decision Tree, Support Vector Machine, Naive Bayes, K-Nearest Neighbor, and Random Forest, utilizing a variety of demographic, clinical, and laboratory features and biomarkers.

Results

Ascitic fluid markers, including white blood cell (WBC) count, lactate dehydrogenase (LDH), total protein, and polymorphonuclear cells (PMN), significantly differentiated between SBP and non-SBP patients. The Random Forest model demonstrated the highest overall accuracy at 86 %, while the Naive Bayes model achieved the highest sensitivity at 72 %. Utilizing 10 key features instead of the full feature set improved model performance, notably enhancing specificity and accuracy.

Conclusion

Our analysis highlights the potential of machine learning to enhance the accuracy of SBP diagnosis in cirrhotic patients. Integrating these models into clinical workflows could substantially improve patient outcomes. To achieve this, ongoing multidisciplinary research is crucial. Ensuring model interpretability, continuous monitoring, and rigorous validation will be essential for the successful implementation of real-time clinical decision support systems.

目的：自发性细菌性腹膜炎（SBP）是一种腹腔积液的细菌感染，是肝硬化的常见并发症。腹腔积液的潜在死亡率高达 40%，因此准确诊断和及时启动适当的抗生素治疗对于优化患者预后和预防危及生命的并发症至关重要。本研究旨在扩大计算模型的使用范围，通过纳入更广泛的数据（包括临床变量和实验室值）来提高肝硬化患者SBP的诊断准确性：我们采用了 5 种机器学习分类方法--决策树、支持向量机、Naive Bayes、K-近邻和随机森林，并利用了各种人口统计学、临床和实验室特征及生物标志物：结果：腹水标志物，包括白细胞（WBC）计数、乳酸脱氢酶（LDH）、总蛋白和多形核细胞（PMN），能显著区分SBP和非SBP患者。随机森林模型的总体准确率最高，达 86%，而 Naive Bayes 模型的灵敏度最高，达 72%。利用 10 个关键特征而不是全部特征集提高了模型的性能，尤其是提高了特异性和准确性：我们的分析凸显了机器学习在提高肝硬化患者 SBP 诊断准确性方面的潜力。将这些模型整合到临床工作流程中可以大大改善患者的预后。为此，持续的多学科研究至关重要。确保模型的可解释性、持续监测和严格验证对于实时临床决策支持系统的成功实施至关重要。

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引用次数: 0