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Lack of Nr2e1 expression in hepatocytes impaired cell survival and aggravated palmitate-induced oxidative stress 肝细胞中缺乏 Nr2e1 的表达会损害细胞存活并加剧棕榈酸酯诱导的氧化应激。
IF 2.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-18 DOI: 10.1016/j.advms.2024.06.002

Purpose

Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator in neural stem cells. However, its function is still not clear in hepatocytes. This study aimed to clarify the effects of Nr2e1-deficiency in hepatocytes in lipotoxic conditions.

Materials/methods

Nr2e1-knockdown AML12 ​cells were generated by lentiviral vector transfection. The influences of Nr2e1-deficiency on hepatocyte survival were determined by cell cycle progression and cell apoptosis rate using flow cytometry. Real-time quantitative PCR and Western blot were used to examine the genes and protein expression related to apoptosis, lipid metabolism, and oxidative stress. Meanwhile, RNA sequencing was adopted in liver samples from Nr2e1-knockout (Nr2e1-KO) mice.

Results

Nr2e1 expression was observed with a significant decrease in AML12 ​cells after palmitic acid-stimulation. Knockdown of Nr2e1 in AML12 ​cells resulted in increased sensitivity to lipotoxicity, evidenced by a partial G0/G1 cell-cycle arrest and higher rates of cell apoptosis. Moreover, Nr2e1-knockdown AML12 ​cells presented increased gene expressions relative to lipid synthesis but decreased levels of β-oxidation related genes. Lack of Nr2e1 augmented palmitate-induced oxidative stress in hepatocytes. In vivo, differential genes in Nr2e1-KO mice liver were enriched in pathways associated with liver regeneration and cell proliferation.

Conclusions

This study indicated that hepatocytes lacking Nr2e1 were more susceptible to lipotoxic-mediated damage. Nr2e1 may serve as a potential target for the development of novel therapies for lipotoxicity-induced liver injury.

目的:核受体亚家族 2 E 组成员 1(Nr2e1)一直被认为是神经干细胞的重要调节因子。然而,它在肝细胞中的功能仍不明确。本研究旨在阐明脂肪毒性条件下Nr2e1缺失对肝细胞的影响:材料/方法:通过慢病毒载体转染产生Nr2e1敲除的AML12细胞。使用流式细胞术通过细胞周期进展和细胞凋亡率测定 Nr2e1 缺失对肝细胞存活的影响。利用实时定量 PCR 和 Western 印迹检测与细胞凋亡、脂代谢和氧化应激相关的基因和蛋白表达。同时,对 Nr2e1 基因敲除(Nr2e1-KO)小鼠的肝脏样本进行了 RNA 测序:结果:在棕榈酸刺激下,AML12细胞中的Nr2e1表达量明显下降。在 AML12 细胞中敲除 Nr2e1 会增加细胞对脂肪毒性的敏感性,表现为部分 G0/G1 细胞周期停滞和更高的细胞凋亡率。此外,Nr2e1敲除的AML12细胞中与脂质合成有关的基因表达量增加,但β氧化相关基因的表达量减少。缺乏 Nr2e1 会增加棕榈酸酯诱导的肝细胞氧化应激。在体内,Nr2e1-KO 小鼠肝脏中与肝脏再生和细胞增殖相关的通路中富含不同的基因:本研究表明,缺乏 Nr2e1 的肝细胞更容易受到脂肪毒性介导的损伤。Nr2e1可能是开发脂肪毒性诱导的肝损伤新型疗法的潜在靶点。
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引用次数: 0
Effect of static magnetic field on gene expression of human umbilical cord mesenchymal stem cells by transcriptome analysis 通过转录组分析静态磁场对人脐带间充质干细胞基因表达的影响。
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-04 DOI: 10.1016/j.advms.2024.06.001
Fang Fang , Chunyan Liu , Qi Huang , Chao Dong , Guirong Zhang , Jinhe Jiang , Shi Lu

Purpose

Static magnetic fields (SMFs) induce various biological reactions and have been applied in the biological therapy of diseases, especially in combination with mesenchymal stem cells (MSCs) and tissue engineering. However, the underlying influence of SMFs on MSCs gene expression remains largely unclear. In this study, we aim to investigate the effects of SMFs on gene expression of human MSCs.

Materials and methods

We exposed human MSCs to two different intensities (0.35 ​T and 1.0 ​T) of SMFs and observed the effects of SMFs on cell morphology. Subsequently, RNA-sequencing was performed to explore the gene expression changes.

Results

Compared with control group cells, no significant differences in cell morphology were observed under a phase contrast inverted microscope, but the transcriptome of SMF-exposed MSCs were significantly changed in both 0.35 ​T and 1.0 ​T groups and the differential expressed genes are involved in multiple pathways, such as ubiquitin mediated proteolysis, TNF signaling pathway, NF-kappa B signaling pathway, TGF-beta signaling pathway, metabolic pathways, and apoptosis, which regulate the biological functions of MSCs.

Conclusions

SMFs stimulation could affect the gene expression of human MSCs and the biological effects vary by the different intensities of SMFs. These data offer the molecular foundation for future application of SMFs in stem cell technology as well as tissue engineering medicine.

目的:静态磁场(SMF)可诱导各种生物反应,已被应用于疾病的生物治疗,尤其是与间充质干细胞(MSCs)和组织工程相结合。然而,SMF 对间充质干细胞基因表达的潜在影响在很大程度上仍不清楚。在本研究中,我们旨在研究 SMFs 对人间质干细胞基因表达的影响:我们将人间叶干细胞暴露于两种不同强度(0.35 特斯拉和 1.0 特斯拉)的 SMFs,观察 SMFs 对细胞形态的影响。随后,进行 RNA 测序以探讨基因表达的变化:与对照组细胞相比,在相差倒置显微镜下未观察到细胞形态的显著差异,但在 0.35 特斯拉和 1.0 特斯拉组中,差异表达的基因涉及多种途径,如泛素介导的蛋白酶解、TNF 信号通路、NF-kappa B 信号通路、TGF-beta 信号通路、代谢途径和细胞凋亡,这些途径调控间充质干细胞的生物学功能:结论:SMFs刺激可影响人间叶干细胞的基因表达,且不同强度的SMFs可产生不同的生物效应。这些数据为 SMFs 未来在干细胞技术和组织工程医学中的应用提供了分子基础。
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引用次数: 0
Dexmedetomidine improves mitophagy and pyroptosis through the ALKBH5/FUNDC1 axis during epidural-related maternal fever 右美托咪定可通过 ALKBH5/FUNDC1 轴改善硬膜外麻醉相关产妇发热时的有丝分裂和嗜热症。
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-05-28 DOI: 10.1016/j.advms.2024.05.002
Fei Xiao , Hanqing Yao , Jing Qian , Jiayue Huang , Guangfa Xia

Purpose

Epidural analgesia has emerged as a commonly used method for relieving labor pain. However, epidural-related maternal fever (ERMF) is characterized by a high occurrence rate and can have detrimental consequences for the well-being of both the mother and the fetus. This study aimed to investigate the functional role and underlying mechanism of dexmedetomidine (DEX) in ERMF.

Materials and methods

Ropivacaine (ROP)-induced human umbilical vein endothelial cells (HUVECs) were treated with DEX and/or transfected with ALKBH5 or FUNDC1 overexpression plasmid. qPCR and Western blot were adopted for mitophagy and pyroptosis marker protein detection. Autophagosomes were observed through electron microscopy, Caspase-1/PI double-positive cells were determined using flow cytometry. Inflammation-related factors were quantified using ELISA. The N6-methyladenosine (m6A) modification of FUNDC1 mRNA was examined using methylated RNA immunoprecipitation (MeRIP) and the binding between ALKBH5 and FUNDC1 mRNA was confirmed by RNA immunoprecipitation (RIP).

Results

In ROP-induced HUVECs, there was a significant upregulation in ALKBH5 and FUNDC1, resulting in a notable increase in inflammation, pyroptosis, and mitophagy. The administration of DEX demonstrated the ability to alleviate ROP-induced pyroptosis and promote protective mitophagy. Interestingly, DEX treatment significantly reduced the interaction between ALKBH5 and FUNDC1 mRNA, while simultaneously increasing the m6A level of FUNDC1 mRNA in ROP-treated cells. Moreover, the overexpression of FUNDC1 partially reversed the effects of ALKBH5 overexpression on mitophagy and pyroptosis in HUVECs.

Conclusions

DEX can promote mitophagy and inhibit pyroptosis through the ALKBH5/FUNDC1 axis in ERMF, indicating its potential as a therapeutic strategy for clinical ERMF treatment.

目的:硬膜外镇痛已成为缓解分娩疼痛的常用方法。然而,硬膜外相关产妇发热(ERMF)的发生率很高,可能对产妇和胎儿的健康造成不利影响。本研究旨在探讨右美托咪定(DEX)在ERMF中的功能作用和潜在机制:采用qPCR和Western blot技术检测有丝分裂和裂解标志蛋白。电子显微镜观察自噬体,流式细胞仪测定 Caspase-1/PI 双阳性细胞。用酶联免疫吸附法对炎症相关因子进行量化。用甲基化 RNA 免疫沉淀(MeRIP)检测了 FUNDC1 mRNA 的 N6-甲基腺苷(m6A)修饰,用 RNA 免疫沉淀(RIP)证实了 ALKBH5 与 FUNDC1 mRNA 的结合:结果:在ROP诱导的HUVECs中,ALKBH5和FUNDC1明显上调,导致炎症、热噬和有丝分裂显著增加。服用DEX能缓解ROP诱导的热蛋白沉积,促进保护性有丝分裂。有趣的是,在ROP处理的细胞中,DEX处理明显减少了ALKBH5和FUNDC1 mRNA之间的相互作用,同时提高了FUNDC1 mRNA的m6A水平。此外,FUNDC1的过表达部分逆转了ALKBH5过表达对HUVECs中有丝分裂和嗜热的影响:结论:DEX可通过ALKBH5/FUNDC1轴促进ERMF的有丝分裂和抑制脓毒症,有望成为临床治疗ERMF的一种治疗策略。
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引用次数: 0
Cefiderocol – An effective antimicrobial for MDR infections but a challenge for routine antimicrobial susceptibility testing 头孢羟氨苄--治疗耐药菌感染的有效抗菌药,但对常规抗菌药敏感性检测是一项挑战。
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-05-21 DOI: 10.1016/j.advms.2024.05.001
Małgorzata Brauncajs , Filip Bielec , Anna Macieja , Dorota Pastuszak-Lewandoska

Purpose

Cefiderocol is a novel cephalosporin–siderophore conjugate antibiotic that holds promise to thwart infections caused by multi-drug-resistant gram-negative bacilli. Its antibacterial activity against normally susceptible species is not affected by most β-lactamases, including metallo-β-lactamases. Due to the siderophore-mediated entry into the cell, the activity of cefiderocol is less affected by porin loss or active efflux resistance than many other β-lactam antibiotics. The aim of this study was to assess in vitro susceptibility to the cefiderocol of carbapenemase-producing gram-negative bacilli from clinical samples of hospitalized patients.

Materials and methods

We analyzed 102 clinical strains of carbapenemase-producing Enterobacterales and non-fermentives from hospital centers in Łódź, Poland. Antimicrobial susceptibility to cefiderocol was tested by the minimum inhibitory concentration test strips and disc diffusion methods.

Results

The obtained results turned out to be ambiguous, and the area of technical uncertainty made their interpretation very difficult.

Conclusions

The cost of therapy with this antibiotic, and difficulties in interpreting the drug susceptibility are the limitations to the use of cefiderocol. Intensive work should be carried out to finally standardize an easily accessible and reliable method for the determination of susceptibility to cefiderocol.

目的:Cefiderocol 是一种新型头孢菌素-嗜苷酸盐共轭抗生素,有望挫败由多重耐药革兰氏阴性杆菌引起的感染。它对正常易感菌种的抗菌活性不受大多数β-内酰胺酶(包括金属β-内酰胺酶)的影响。与许多其他 β-内酰胺类抗生素相比,头孢羟氨苄通过苷元介导进入细胞,其活性较少受到孔蛋白缺失或主动外流抗性的影响。本研究的目的是评估住院患者临床样本中产碳青霉烯酶革兰阴性杆菌对头孢羟氨苄的体外敏感性:我们分析了波兰罗兹各医院中心的 102 株产碳青霉烯酶肠杆菌和非发酵菌临床菌株。采用最小抑菌浓度试纸法和盘扩散法检测了对头孢菌素的抗菌敏感性:结果:得到的结果并不明确,技术上的不确定性使解释这些结果非常困难:结论:使用这种抗生素治疗的成本和药物敏感性的解释困难是头孢克肟使用的局限性。应开展深入细致的工作,以最终统一一种易于使用且可靠的方法,用于测定对头孢克洛的药敏性。
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引用次数: 0
The intriguing role of IL33/ST2 axis signaling in oral diseases - A systematic review IL33/ST2 轴信号在口腔疾病中的奇妙作用--系统综述。
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-05-03 DOI: 10.1016/j.advms.2024.04.007
Mala Kamboj , R. Keerthika , Anjali Narwal , Ambika Gupta , Anju Devi , Adarsh Kumar , Gitika Sharma

Purpose

Oral diseases act as a silent epidemic, and the pathogenetic role of interleukin-33/suppression of tumorigenicity-2 axis (IL-33/ST2) remains unclear due to a lack of literature. This review has attempted to highlight the importance of this axis in oral diseases, which may be helpful in developing therapeutic modalities required to halt disease progression.

Materials and methods

A thorough search was conducted using various databases. Original research articles that assessed both IL-33 and ST2 levels in oral diseases using different techniques were included in the review. The risk of bias for each study was analyzed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and Review Manager 5.4 was used to output the results.

Results

In the qualitative data synthesis we included 13 published articles. The most commonly used method was serum estimation, while methods with optimistic results were saliva, real-time quantitative polymerase chain reaction and immunohistochemistry. The predominant mechanism of action was nuclear factor kappa B signaling and type 2 immune response. However, salivary gland epithelial cell activation, activation of mast cells, type 1 immune response, and upregulated angiogenesis are crucial in mediating IL-33/ST2 signaling in oral diseases.

Conclusions

Accumulating evidence demonstrates that the IL-33/ST2 axis is a fundamental pathogenetic mechanism of oral diseases of inflammatory, autoimmune, or neoplastic origin.

目的:口腔疾病是一种无声的流行病,由于缺乏文献,白细胞介素-33/抑制肿瘤生成-2轴(IL-33/ST2)的致病作用仍不清楚。本综述试图强调该轴在口腔疾病中的重要性,这可能有助于开发阻止疾病进展所需的治疗方法:使用各种数据库进行了全面搜索。综述包括使用不同技术评估口腔疾病中 IL-33 和 ST2 水平的原创研究文章。使用诊断准确性研究质量评估2(QUADAS-2)工具分析了每项研究的偏倚风险,并使用Review Manager 5.4输出结果:在定性数据综合中,我们纳入了 13 篇已发表的文章。最常用的方法是血清估计,而结果乐观的方法是唾液、实时定量聚合酶链反应和免疫组化。最主要的作用机制是核因子卡巴 B 信号转导和 2 型免疫反应。然而,唾液腺上皮细胞活化、肥大细胞活化、1型免疫反应和血管生成上调是介导口腔疾病中IL-33/ST2信号转导的关键:越来越多的证据表明,IL-33/ST2 轴是炎症性、自身免疫性或肿瘤性口腔疾病的基本致病机制。
{"title":"The intriguing role of IL33/ST2 axis signaling in oral diseases - A systematic review","authors":"Mala Kamboj ,&nbsp;R. Keerthika ,&nbsp;Anjali Narwal ,&nbsp;Ambika Gupta ,&nbsp;Anju Devi ,&nbsp;Adarsh Kumar ,&nbsp;Gitika Sharma","doi":"10.1016/j.advms.2024.04.007","DOIUrl":"10.1016/j.advms.2024.04.007","url":null,"abstract":"<div><h3>Purpose</h3><p>Oral diseases act as a silent epidemic, and the pathogenetic role of interleukin-33/suppression of tumorigenicity-2 axis (IL-33/ST2) remains unclear due to a lack of literature. This review has attempted to highlight the importance of this axis in oral diseases, which may be helpful in developing therapeutic modalities required to halt disease progression.</p></div><div><h3>Materials and methods</h3><p>A thorough search was conducted using various databases. Original research articles that assessed both IL-33 and ST2 levels in oral diseases using different techniques were included in the review. The risk of bias for each study was analyzed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and Review Manager 5.4 was used to output the results.</p></div><div><h3>Results</h3><p>In the qualitative data synthesis we included 13 published articles. The most commonly used method was serum estimation, while methods with optimistic results were saliva, real-time quantitative polymerase chain reaction and immunohistochemistry. The predominant mechanism of action was nuclear factor kappa B signaling and type 2 immune response. However, salivary gland epithelial cell activation, activation of mast cells, type 1 immune response, and upregulated angiogenesis are crucial in mediating IL-33/ST2 signaling in oral diseases.</p></div><div><h3>Conclusions</h3><p>Accumulating evidence demonstrates that the IL-33/ST2 axis is a fundamental pathogenetic mechanism of oral diseases of inflammatory, autoimmune, or neoplastic origin.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 264-271"},"PeriodicalIF":2.7,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847042","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
The oxidative stress-associated long non-coding RNAs in pancreatic cancer 胰腺癌中与氧化应激相关的长非编码 RNA
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-04-25 DOI: 10.1016/j.advms.2024.04.006
Setayesh Baradaran-Bagherian , Mahdieh Mehrab Mohseni , Roya Sharifi , Roya Amirinejad , Zeinab Shirvani-Farsani

Purpose

A lot of people are dying from pancreatic cancer (PC) annually. The early detection of this cancer is particularly challenging due to the fact that symptoms tend to appear in advanced stages. It has been suggested that oxidative stress may play a role in the development of PC. Several genes regulate this process, including long noncoding RNAs (lncRNAs). There is no comprehensive study on the expression pattern of lncRNAs related to oxidative stress in PC patients. In the present case-control study, we quantified levels of oxidative stress-associated lncRNAs in PC patients versus healthy controls.

Patients and methods

In the present study, we investigated the expression levels of lincRNA-p21, LUCAT, RMST, FOXD3-AS1, and MT1DP lncRNAs in the peripheral blood mononuclear cells (PBMCs) of 53 ​PC patients and 50 healthy controls. The association between lncRNA expression and clinical and pathological characteristics was also evaluated.

Results

The expression of lincRNA-P21 and rhabdomyosarcoma 2-associated transcript (RMST) lncRNAs in PC patients has significantly decreased. Expression of lncRNA RMST was significantly higher in TNM stage III-IV patients in comparison to TNM stage I-II patients. In addition, a significant positive association was recognized between candidate lncRNA expression, and finally, the AUC values of the expression levels of lincRNA-p21 and RMST were 0.60 and 0.61, respectively.

Conclusions

Altogether, our study suggests a possible role of lincRNA-p21 and RMST lncRNAs in the etiology of PC pathobiology, and their biomarker role may be understood in future studies.

目的 每年都有许多人死于胰腺癌(PC)。由于症状往往出现在晚期,因此早期发现这种癌症尤其具有挑战性。有研究表明,氧化应激可能在胰腺癌的发病过程中起作用。有多个基因可调控这一过程,包括长非编码 RNA(lncRNA)。目前还没有关于 PC 患者中与氧化应激相关的 lncRNA 表达模式的全面研究。在本病例对照研究中,我们量化了PC患者与健康对照组中氧化应激相关lncRNAs的表达水平。结果PC患者中lincRNA-P21和横纹肌肉瘤2相关转录本(RMST)lncRNA的表达明显下降。与TNM I-II期患者相比,lncRNA RMST在TNM III-IV期患者中的表达明显升高。此外,候选lncRNA的表达之间存在明显的正相关,最后,lincRNA-p21和RMST表达水平的AUC值分别为0.60和0.61。
{"title":"The oxidative stress-associated long non-coding RNAs in pancreatic cancer","authors":"Setayesh Baradaran-Bagherian ,&nbsp;Mahdieh Mehrab Mohseni ,&nbsp;Roya Sharifi ,&nbsp;Roya Amirinejad ,&nbsp;Zeinab Shirvani-Farsani","doi":"10.1016/j.advms.2024.04.006","DOIUrl":"10.1016/j.advms.2024.04.006","url":null,"abstract":"<div><h3>Purpose</h3><p>A lot of people are dying from pancreatic cancer (PC) annually. The early detection of this cancer is particularly challenging due to the fact that symptoms tend to appear in advanced stages. It has been suggested that oxidative stress may play a role in the development of PC. Several genes regulate this process, including long noncoding RNAs (lncRNAs). There is no comprehensive study on the expression pattern of lncRNAs related to oxidative stress in PC patients. In the present case-control study, we quantified levels of oxidative stress-associated lncRNAs in PC patients versus healthy controls.</p></div><div><h3>Patients and methods</h3><p>In the present study, we investigated the expression levels of lincRNA-p21, LUCAT, RMST, FOXD3-AS1, and MT1DP lncRNAs in the peripheral blood mononuclear cells (PBMCs) of 53 ​PC patients and 50 healthy controls. The association between lncRNA expression and clinical and pathological characteristics was also evaluated.</p></div><div><h3>Results</h3><p>The expression of lincRNA-P21 and rhabdomyosarcoma 2-associated transcript (RMST) lncRNAs in PC patients has significantly decreased. Expression of lncRNA RMST was significantly higher in TNM stage III-IV patients in comparison to TNM stage I-II patients. In addition, a significant positive association was recognized between candidate lncRNA expression, and finally, the AUC values of the expression levels of lincRNA-p21 and RMST were 0.60 and 0.61, respectively.</p></div><div><h3>Conclusions</h3><p>Altogether, our study suggests a possible role of lincRNA-p21 and RMST lncRNAs in the etiology of PC pathobiology, and their biomarker role may be understood in future studies.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 231-237"},"PeriodicalIF":2.7,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140778600","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
Lipidomic approach to identify Escherichia coli and Shigella spp. by matrix-assisted laser desorption/ionization mass spectrometry 利用基质辅助激光解吸电离质谱法鉴定大肠杆菌和志贺氏杆菌的脂质组学方法
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-04-24 DOI: 10.1016/j.advms.2024.04.005
Adrian Arendowski

Purpose

Escherichia coli (E. coli) and Shigella species, being highly similar, present a challenge for differentiation using classical methods such as phenotyping, 16S rRNA sequencing, or protein profiling using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The paper proposes a method for identifying E. coli, S. flexneri, S. sonnei, and S. boydii by augmenting the Bruker Biotyper database with reference spectra of lipid profiles obtained using MALDI MS in the positive mode.

Materials/methods

Lipid extracts were made from cultured E. coli, S. flexneri, S. sonnei and S. boydii using the Bligh & Dyer protocol. MALDI MS spectra in positive ion mode were performed for the extracts. Reference spectra were created from 30 spectra for each bacterium and added to the Bruker Biotyper database.

Results

Identification of bacteria based on lipid profiles in the Biotyper database gave correct results with scores above 2.49. Statistical analysis of the results by Partial Least Squares-Discriminant Analysis (PLS-DA) showed that it is possible to correctly differentiate the microorganisms studied using the lipidomic approach. A panel of six m/z values was proposed for which the value of the area under the ROC curve is 1, thus enabling the identification of E. coli and S. flexneri with 100 ​% accuracy.

Conclusions

Identification of bacteria from lipid fingerprints obtained by the MALDI MS technique is possible and may become a useful tool in the future, especially for microorganisms that are difficult to distinguish by other methods.

目的 大肠埃希氏菌(E. coli)和志贺氏菌(Shigella)物种高度相似,使用传统方法(如表型分析、16S rRNA 测序或使用基质辅助激光解吸电离质谱(MALDI MS)进行蛋白质分析)进行鉴别是一项挑战。本文提出了一种鉴别大肠杆菌、柔性链球菌、宋内氏菌和波氏杆菌的方法,即利用 MALDI MS 在正向模式下获得的脂质图谱的参考光谱来增强布鲁克 Biotyper 数据库。在正离子模式下对提取物进行 MALDI MS 图谱分析。结果根据 Biotyper 数据库中的脂质图谱对细菌进行鉴定,结果正确率在 2.49 以上。通过偏最小二乘判别分析(PLS-DA)对结果进行的统计分析表明,使用脂质体方法可以正确区分所研究的微生物。结论通过 MALDI MS 技术获得的脂质指纹鉴定细菌是可能的,而且将来可能成为一种有用的工具,特别是对于用其他方法难以区分的微生物。
{"title":"Lipidomic approach to identify Escherichia coli and Shigella spp. by matrix-assisted laser desorption/ionization mass spectrometry","authors":"Adrian Arendowski","doi":"10.1016/j.advms.2024.04.005","DOIUrl":"10.1016/j.advms.2024.04.005","url":null,"abstract":"<div><h3>Purpose</h3><p><em>Escherichia coli</em> (<em>E. coli</em>) and <em>Shigella</em> species, being highly similar, present a challenge for differentiation using classical methods such as phenotyping, 16S rRNA sequencing, or protein profiling using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The paper proposes a method for identifying <em>E. coli</em>, <em>S. flexneri</em>, <em>S. sonnei</em>, and <em>S. boydii</em> by augmenting the Bruker Biotyper database with reference spectra of lipid profiles obtained using MALDI MS in the positive mode.</p></div><div><h3>Materials/methods</h3><p>Lipid extracts were made from cultured <em>E. coli, S. flexneri, S. sonnei</em> and <em>S. boydii</em> using the Bligh &amp; Dyer protocol. MALDI MS spectra in positive ion mode were performed for the extracts. Reference spectra were created from 30 spectra for each bacterium and added to the Bruker Biotyper database.</p></div><div><h3>Results</h3><p>Identification of bacteria based on lipid profiles in the Biotyper database gave correct results with scores above 2.49. Statistical analysis of the results by Partial Least Squares-Discriminant Analysis (PLS-DA) showed that it is possible to correctly differentiate the microorganisms studied using the lipidomic approach. A panel of six <em>m/z</em> values was proposed for which the value of the area under the ROC curve is 1, thus enabling the identification of <em>E. coli</em> and <em>S. flexneri</em> with 100 ​% accuracy.</p></div><div><h3>Conclusions</h3><p>Identification of bacteria from lipid fingerprints obtained by the MALDI MS technique is possible and may become a useful tool in the future, especially for microorganisms that are difficult to distinguish by other methods.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 238-247"},"PeriodicalIF":2.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140782268","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
Effectiveness of antazoline versus amiodarone, flecainide and propafenone in restoring sinus rhythm at the emergency department 安他唑啉与胺碘酮、非卡内酯和普罗帕酮在急诊科恢复窦性心律的效果对比。
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-04-20 DOI: 10.1016/j.advms.2024.04.003
Janusz Springer , Michalina Pejska , Wojciech Homenda , Tomasz Zdrojewski , Ludmiła Daniłowicz-Szymanowicz , Dariusz Kozłowski

Purpose

Little is known about the effectiveness of pharmacological cardioversion (PCV) with antazoline in comparison to flecainide. The aim of this study was to compare the effectiveness of antazoline in restoring sinus rhythm (SR) versus amiodarone, flecainide and propafenone in a group of emergency department (ED) patients.

Materials/methods

This was a single-centre retrospective analysis of patient records from an ED in a large hospital in Poland. We analysed a total of 1878 patient records, divided based on the anti-arrhythmic drug (AAD) administered during PCV: antazoline (n ​= ​1080), antazoline ​+ ​β-blocker (n ​= ​479), amiodarone (n ​= ​129), flecainide (n ​= ​102), propafenone (n ​= ​88). Of the patients, 63.5 ​% were female (median 65 years, [19–100]).

Results

The percentage of successful PCV was significantly higher in the antazoline group (84.3 ​%) than in the antazoline ​+ ​β-blocker (75.8 ​%, p ​= ​0.0001), propafenone (75.6 ​%, p ​= ​0.0364) and amiodarone (68.8 ​%, p ​< ​0.0001) groups. Post-hoc analysis revealed that patients who received PCV with antazoline, antazoline ​+ ​β-blocker, flecainide and propafenone had significantly shorter time to SR than those who received amiodarone (p ​< ​0.0001). Univariate regression analysis revealed that patients who underwent PCV with antazoline were almost twice as likely to return to SR compared to the other groups (p ​< ​0.0001, OR 1.81, 95 ​% CI 1.44–2.27).

Conclusions

This is the first study comparing the effectiveness of antazoline in PCV versus flecainide in addition to the previously studied amiodarone and propafenone. Our results indicate that antazoline is more effective in restoring SR than amiodarone, flecainide and propafenone. In addition, antazoline restored SR significantly faster than amiodarone or propafenone.

目的 关于使用安他唑啉进行药理心脏转复(PCV)与使用氟卡尼进行药理心脏转复(PCV)的效果,人们知之甚少。本研究旨在比较安他唑啉与胺碘酮、非卡尼和普罗帕酮在一组急诊科(ED)患者中恢复窦性心律(SR)的效果。我们共分析了 1878 份病历,根据 PCV 期间使用的抗心律失常药物 (AAD) 进行了划分:安他唑啉(1080 例)、安他唑啉 + β-受体阻滞剂(479 例)、胺碘酮(129 例)、非卡内酯(102 例)、普罗帕酮(88 例)。结果安他唑啉组 PCV 成功率(84.3%)显著高于安他唑啉 + β-受体阻滞剂组(75.8%,p = 0.0001)、普罗帕酮组(75.6%,p = 0.0364)和胺碘酮组(68.8%,p < 0.0001)。事后分析显示,接受安他唑啉、安他唑啉+β-受体阻滞剂、非卡奈德和普罗帕酮 PCV 的患者的 SR 时间明显短于接受胺碘酮的患者(p < 0.0001)。单变量回归分析显示,与其他组别相比,使用安他唑啉进行 PCV 的患者返回 SR 的几率几乎是其他组别的两倍(p < 0.0001,OR 1.81,95 % CI 1.44-2.27)。我们的研究结果表明,安他唑啉在恢复 SR 方面比胺碘酮、非卡因和普罗帕酮更有效。此外,安他唑啉恢复 SR 的速度明显快于胺碘酮或普罗帕酮。
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引用次数: 0
The SPRi determination of cathepsin L and S in plasma and peritoneal fluid of women with endometriosis 用 SPRi 测定子宫内膜异位症妇女血浆和腹腔液中的酪蛋白酶 L 和 S
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-04-18 DOI: 10.1016/j.advms.2024.04.004
Julia Załęcka , Zuzanna Zielińska , Łukasz Ołdak , Agata Sakowicz , Grzegorz Mańka , Mariusz Kiecka , Robert Spaczyński , Piotr Piekarski , Beata Banaszewska , Artur Jakimiuk , Tadeusz Issat , Jakub Młodawski , Maria Szubert , Piotr Sieroszewski , Grzegorz Raba , Kamil Szczupak , Tomasz Kluz , Marek Kluza , Piotr Pierzyński , Michał Ciebiera , Piotr Laudański

Purpose

Endometriosis is a common disease with a complex pathomechanism and atypical symptoms, often leading to delayed diagnosis. Currently, the sole method for confirming the presence of the disease is through laparoscopy and histopathological examination of collected tissue. However, this invasive procedure carries potential risk and complications, necessitating the exploration of non-surgical diagnostic methods for endometriosis. This study aims to analyze peritoneal fluid and plasma samples for the expression of cathepsin L and cathepsin S to identify potential biomarkers for non-invasive diagnostic approaches to endometriosis.

Material and methods

In this cross-sectional study, plasma and peritoneal fluid samples were obtained during laparoscopy from 63 patients diagnosed with chronic pelvic pain or infertility. The study group consisted of women with confirmed endometriosis. The concentrations of cathepsins L and S were determined using an SPRi biosensor.

Results

The study did not reveal significant differences in the concentrations of cathepsin L and cathepsin S between the control group and the study group, both in peritoneal fluid and plasma.

Conclusions

Based on the results of this study, it appears that cathepsins L and S are not suitable candidates as biomarkers for endometriosis.

目的 子宫内膜异位症是一种常见疾病,病理机制复杂,症状不典型,往往导致诊断延误。目前,确诊该病的唯一方法是通过腹腔镜检查和对采集的组织进行组织病理学检查。然而,这种侵入性手术存在潜在风险和并发症,因此有必要探索子宫内膜异位症的非手术诊断方法。本研究旨在分析腹腔液和血浆样本中猫胰蛋白酶 L 和猫胰蛋白酶 S 的表达,以确定子宫内膜异位症非侵入性诊断方法的潜在生物标志物。研究组由确诊为子宫内膜异位症的妇女组成。研究结果显示,对照组和研究组腹腔液和血浆中的钙蛋白 L 和钙蛋白 S 的浓度没有明显差异。
{"title":"The SPRi determination of cathepsin L and S in plasma and peritoneal fluid of women with endometriosis","authors":"Julia Załęcka ,&nbsp;Zuzanna Zielińska ,&nbsp;Łukasz Ołdak ,&nbsp;Agata Sakowicz ,&nbsp;Grzegorz Mańka ,&nbsp;Mariusz Kiecka ,&nbsp;Robert Spaczyński ,&nbsp;Piotr Piekarski ,&nbsp;Beata Banaszewska ,&nbsp;Artur Jakimiuk ,&nbsp;Tadeusz Issat ,&nbsp;Jakub Młodawski ,&nbsp;Maria Szubert ,&nbsp;Piotr Sieroszewski ,&nbsp;Grzegorz Raba ,&nbsp;Kamil Szczupak ,&nbsp;Tomasz Kluz ,&nbsp;Marek Kluza ,&nbsp;Piotr Pierzyński ,&nbsp;Michał Ciebiera ,&nbsp;Piotr Laudański","doi":"10.1016/j.advms.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.advms.2024.04.004","url":null,"abstract":"<div><h3>Purpose</h3><p>Endometriosis is a common disease with a complex pathomechanism and atypical symptoms, often leading to delayed diagnosis. Currently, the sole method for confirming the presence of the disease is through laparoscopy and histopathological examination of collected tissue. However, this invasive procedure carries potential risk and complications, necessitating the exploration of non-surgical diagnostic methods for endometriosis. This study aims to analyze peritoneal fluid and plasma samples for the expression of cathepsin L and cathepsin S to identify potential biomarkers for non-invasive diagnostic approaches to endometriosis.</p></div><div><h3>Material and methods</h3><p>In this cross-sectional study, plasma and peritoneal fluid samples were obtained during laparoscopy from 63 patients diagnosed with chronic pelvic pain or infertility. The study group consisted of women with confirmed endometriosis. The concentrations of cathepsins L and S were determined using an SPRi biosensor.</p></div><div><h3>Results</h3><p>The study did not reveal significant differences in the concentrations of cathepsin L and cathepsin S between the control group and the study group, both in peritoneal fluid and plasma.</p></div><div><h3>Conclusions</h3><p>Based on the results of this study, it appears that cathepsins L and S are not suitable candidates as biomarkers for endometriosis.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 224-230"},"PeriodicalIF":2.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650306","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
Single-cell sequencing analysis confirms the association of ANRIL with the increased smooth muscle cell proliferation and migration gene signatures in pulmonary artery hypertension in silico 单细胞测序分析证实 ANRIL 与肺动脉高压中平滑肌细胞增殖和迁移基因特征的相关性
IF 2.7 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-04-16 DOI: 10.1016/j.advms.2024.04.002
Yan Li, Yan-Tong Zhang, Bing Han, Lan Xue, Yan Wei, Ge Li

Purpose

Smooth muscle cell (SMC) dysregulation is part of the pathological basis of pulmonary artery hypertension (PAH). We aimed to explore the heterogeneity of SMCs in PAH.

Methods

The profile GSE210248 was obtained from NCBI Gene Expression Omnibus, containing the scRNA-seq data of pulmonary arteries (PA) from three patients with PAH and three healthy donors. After quality control, normalization, and dimension reduction, cell clustering analysis was performed. Differential expression analysis and functional enrichment analysis were carried out successively in smooth muscle cells (SMCs). The enrichment scores of cell cycle and cell migration gene sets in SMCs were calculated. Then, the Spearman correlation coefficients between antisense non-coding RNA in the INK4 locus (ANRIL) expression and two gene sets were computed.

Results

Eight cell clusters were identified in PA from samples. The proportion of SMCs was increased in PAH samples. SMCs were divided into five subclusters with diverse biological functions. Muscle contraction-related SMC1 was decreased, while extracellular matrix organization-related SMC2, immune and inflammatory response-related SMC4 and SMC5 were increased in PAH samples compared with healthy donors. The enrichment scores of cell cycle and cell migration gene sets in SMCs were higher in PAH samples than in donors. ANRIL was down-regulated significantly in PAH samples and was negatively related to the scores of two gene sets.

Conclusion

SMCs exhibited significant heterogeneity in PAH. The altered abilities of SMC proliferation and migration in PAH were associated with ANRIL expression.

目的平滑肌细胞(SMC)失调是肺动脉高压(PAH)病理基础的一部分。我们的目的是探索 PAH 中平滑肌细胞的异质性。方法从 NCBI 基因表达总库中获得了 GSE210248 资料,其中包含 3 名 PAH 患者和 3 名健康供体的肺动脉(PA)scRNA-seq 数据。经过质量控制、归一化和降维处理后,进行了细胞聚类分析。先后对平滑肌细胞(SMC)进行了差异表达分析和功能富集分析。计算了平滑肌细胞中细胞周期和细胞迁移基因组的富集得分。然后计算了 INK4 位点反义非编码 RNA(ANRIL)表达与两个基因组之间的 Spearman 相关系数。PAH 样本中 SMC 的比例有所增加。SMC 被分为五个亚群,具有不同的生物学功能。与健康供体相比,PAH样本中与肌肉收缩相关的SMC1减少,而与细胞外基质组织相关的SMC2、与免疫和炎症反应相关的SMC4和SMC5增加。PAH 样本中 SMCs 细胞周期和细胞迁移基因集的富集得分高于供体。ANRIL 在 PAH 样本中明显下调,并与两个基因组的得分呈负相关。PAH中SMC增殖和迁移能力的改变与ANRIL的表达有关。
{"title":"Single-cell sequencing analysis confirms the association of ANRIL with the increased smooth muscle cell proliferation and migration gene signatures in pulmonary artery hypertension in silico","authors":"Yan Li,&nbsp;Yan-Tong Zhang,&nbsp;Bing Han,&nbsp;Lan Xue,&nbsp;Yan Wei,&nbsp;Ge Li","doi":"10.1016/j.advms.2024.04.002","DOIUrl":"https://doi.org/10.1016/j.advms.2024.04.002","url":null,"abstract":"<div><h3>Purpose</h3><p>Smooth muscle cell (SMC) dysregulation is part of the pathological basis of pulmonary artery hypertension (PAH). We aimed to explore the heterogeneity of SMCs in PAH.</p></div><div><h3>Methods</h3><p>The profile GSE210248 was obtained from NCBI Gene Expression Omnibus, containing the scRNA-seq data of pulmonary arteries (PA) from three patients with PAH and three healthy donors. After quality control, normalization, and dimension reduction, cell clustering analysis was performed. Differential expression analysis and functional enrichment analysis were carried out successively in smooth muscle cells (SMCs). The enrichment scores of cell cycle and cell migration gene sets in SMCs were calculated. Then, the Spearman correlation coefficients between antisense non-coding RNA in the INK4 locus (ANRIL) expression and two gene sets were computed.</p></div><div><h3>Results</h3><p>Eight cell clusters were identified in PA from samples. The proportion of SMCs was increased in PAH samples. SMCs were divided into five subclusters with diverse biological functions. Muscle contraction-related SMC1 was decreased, while extracellular matrix organization-related SMC2, immune and inflammatory response-related SMC4 and SMC5 were increased in PAH samples compared with healthy donors. The enrichment scores of cell cycle and cell migration gene sets in SMCs were higher in PAH samples than in donors. ANRIL was down-regulated significantly in PAH samples and was negatively related to the scores of two gene sets.</p></div><div><h3>Conclusion</h3><p>SMCs exhibited significant heterogeneity in PAH. The altered abilities of SMC proliferation and migration in PAH were associated with ANRIL expression.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 217-223"},"PeriodicalIF":2.7,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640958","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
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Advances in medical sciences
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