Advances in medical sciences最新文献_第4页

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

Advances in medical sciences

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

Advances in medical sciences

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

Advances in medical sciences

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。

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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

Advances in medical sciences

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。

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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

Advances in medical sciences

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 & 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

Advances in medical sciences

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

Advances in medical sciences

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。

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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

Advances in medical sciences

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, Yan-Tong Zhang, Bing Han, Lan Xue, Yan Wei, 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

Dendrobium officinale Polysaccharide (DOP) inhibits cell hyperproliferation, inflammation and oxidative stress to improve keratinocyte psoriasis-like state 铁皮石斛多糖（DOP）可抑制细胞过度增殖、炎症和氧化应激，从而改善类似牛皮癣的角质细胞状态。

IF 2.7 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-03-01 DOI: 10.1016/j.advms.2024.03.005

Bijun Zeng , Yining Yan , Yujin Zhang , Chang Wang , Wenting Huang , Xinyi Zhong , Zi Chen , Mengzhou Xie , Zhibo Yang

Purpose

Psoriasis is a skin disease characterized by excessive proliferation, inflammation and oxidative stress in keratinocytes. The present study aimed to investigate the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on keratinocyte psoriasis-like models.

Methods

The HaCaT keratinocyte inflammation models were induced by interleukin (IL)-22 or lipopolysaccharide (LPS), respectively, and oxidative stress damage within cells was elicited by H₂O₂ and treated using DOP. CCK-8 and EdU were carried out to detect cell proliferation. ELISA, qRT-PCR, and Western blot were conducted to measure the expression of pro-inflammatory cytokines IL17A, IL-23, IL1β, tumor necrosis factor alpha (TNF-α), and IL-6. Reactive oxygen species (ROS) level in keratinocytes was detected by flow cytometry. Cell proliferation-associated proteins (PCNA, Ki67, Cyclin D1) and pathway proteins (p-AKT and AKT), and oxidative stress marker proteins (Nrf-2, CAT, SOD1) were detected by Western blot.

Result

DOP did not affect the proliferation of normal keratinocytes, but DOP was able to inhibit the proliferative activity of IL-22-induced overproliferating keratinocytes and suppress the expression of proliferation-related factors PCNA, Ki67, and Cyclin D1 as well as the proliferation pathway p-AKT. In addition, DOP treatment was able to inhibit IL-22 and LPS-induced inflammation and H₂O₂-induced oxidative stress, including the expression of IL17A, IL-23, IL1β, TNF-α, IL-6, and IL1β, as well as the expression levels of intracellular ROS levels and cellular oxidative stress-related indicators SOD, MDA, CAT, Nrf-2 and SOD1.

Conclusion

DOP inhibits keratinocyte hyperproliferation, inflammation and oxidative stress to improve the keratinocyte psoriasis-like state.

目的：银屑病是一种以角质形成细胞过度增殖、炎症和氧化应激为特征的皮肤病。本研究旨在探讨铁皮石斛多糖（DOP）对角质形成细胞银屑病样模型的治疗作用：方法：分别用白细胞介素（IL）-22或脂多糖（LPS）诱导HaCaT角朊细胞炎症模型，用H2O2诱导细胞内氧化应激损伤并用DOP处理。用 CCK-8 和 EdU 检测细胞增殖。采用 ELISA、qRT-PCR 和 Western 印迹法检测促炎细胞因子 IL17A、IL-23、IL1β、肿瘤坏死因子α（TNF-α）和 IL-6 的表达。流式细胞术检测了角质形成细胞中的活性氧（ROS）水平。通过 Western blot 检测细胞增殖相关蛋白（PCNA、Ki67、Cyclin D1）和通路蛋白（p-AKT 和 AKT）以及氧化应激标志蛋白（Nrf-2、CAT、SOD1）：结果：DOP不影响正常角朊细胞的增殖，但能抑制IL-22诱导的过度增殖角朊细胞的增殖活性，抑制增殖相关因子PCNA、Ki67和细胞周期蛋白D1以及增殖通路p-AKT的表达。此外，DOP还能抑制IL-22和LPS诱导的炎症和H2O2诱导的氧化应激，包括IL17A、IL-23、IL1β、TNF-α、IL-6和IL1β的表达，以及细胞内ROS水平和细胞氧化应激相关指标SOD、MDA、CAT、Nrf-2和SOD1的表达水平：结论：DOP能抑制角朊细胞过度增殖、炎症和氧化应激，从而改善角朊细胞银屑病样状态。

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引用次数: 0

The impact of wound-healing assay, phorbol myristate acetate (PMA) stimulation and siRNA-mediated FURIN gene silencing on endogenous retroviral ERVW-1 expression level in U87-MG astrocytoma cells 伤口愈合试验、肉豆蔻酸磷脂（PMA）刺激和 siRNA 介导的 FURIN 基因沉默对 U87-MG 星形细胞瘤细胞内源性逆转录病毒 ERVW-1 表达水平的影响

IF 2.7 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences

Pub Date : 2024-03-01 DOI: 10.1016/j.advms.2024.02.007

Grzegorz Machnik , Łukasz Bułdak , Karolina Zapletal-Pudełko , Beniamin Oskar Grabarek , Rafał Staszkiewicz , Dawid Sobański , Bogusław Okopień

Purpose

Human endogenous retroviruses (HERVs) are ubiquitous genomic sequences. Normally dormant HERVs, undergo reactivation by environmental factors. This deregulation of HERVs’ transcriptional equilibrium correlates with medical conditions such as multiple sclerosis (MS). Here we sought to explore whether exposing the U-87 MG astrocytoma cells to traumatic injury deregulates the expression of HERV-W family member ERVW-1 encoding syncytin-1. We also examined the expression of FURIN gene that is crucial in syncytin-1 synthesis.

Material and methods

Scratch assay was used as a model of cells injury in U-87 MG cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot (WB) and migration assay using Boyden chamber were used. Phorbol 12-myristate 13-acetate (PMA) and small interfering RNA (siRNA) were used for cell stimulation and gene expression inhibition, respectively.

Results

Results revealed reduced ERVW-1 expression in cells exposed to injury (p < 0.05) while GFAP gene - a marker of active astrocytes, was upregulated (p < 0.01). These findings were confirmed by both WB and RT-qPCR. Expression of FURIN gene was not altered after injury, but cell stimulation by PMA strongly increased FURIN expression, simultaneously downregulating ERVW-1 (p < 0.01). SiRNA-mediated expression inhibition of ERVW-1 and FURIN influenced the mRNA level for SLC1A5 (ASCT2) - primary syncytin-1 receptor, that was significantly lower. FURIN inhibition by siRNA caused strong upregulation of ERVW-1 expression (p < 0.01).

Conclusion

Results showed that mechanical impact affects the expression of endogenous retroviruses in U-87 MG astrocytoma cells by scratch assay. Regulation of FURIN, a crucial enzyme in ERVW-1 turnover may support the therapy of some neurological conditions.

目的人类内源性逆转录病毒（HERV）是一种无处不在的基因组序列。通常处于休眠状态的 HERVs 会因环境因素而重新激活。这种 HERVs 转录平衡的失调与多发性硬化症（MS）等疾病相关。在这里，我们试图探讨 U-87 MG 星形细胞瘤细胞受到创伤是否会降低编码 syncytin-1 的 HERV-W 家族成员 ERVW-1 的表达。我们还检测了在 syncytin-1 合成过程中起关键作用的 FURIN 基因的表达。采用逆转录-定量聚合酶链反应（RT-qPCR）、免疫印迹（WB）和波登室迁移试验。结果结果显示，受到损伤的细胞中 ERVW-1 表达减少（p <0.05），而作为活跃星形胶质细胞标记的 GFAP 基因上调（p <0.01）。WB 和 RT-qPCR 均证实了这些发现。损伤后，FURIN 基因的表达没有改变，但 PMA 对细胞的刺激会强烈增加 FURIN 的表达，同时下调 ERVW-1 的表达（p < 0.01）。SiRNA 介导的 ERVW-1 和 FURIN 表达抑制影响了 SLC1A5（ASCT2）--初级 syncytin-1 受体--的 mRNA 水平，后者的水平显著降低。通过 siRNA 抑制 FURIN 会导致 ERVW-1 表达的强烈上调（p < 0.01）。FURIN 是 ERVW-1 转化过程中的一个关键酶，对它的调节可能有助于某些神经系统疾病的治疗。

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引用次数: 0