Advances in medical sciences最新文献

{"title":"Dexmedetomidine improves mitophagy and pyroptosis through the ALKBH5/FUNDC1 axis during epidural-related maternal fever","authors":"Fei Xiao ,&nbsp;Hanqing Yao ,&nbsp;Jing Qian ,&nbsp;Jiayue Huang ,&nbsp;Guangfa Xia","doi":"10.1016/j.advms.2024.05.002","DOIUrl":"10.1016/j.advms.2024.05.002","url":null,"abstract":"<div><h3>Purpose</h3><p>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.</p></div><div><h3>Materials and methods</h3><p>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).</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 272-280"},"PeriodicalIF":2.7,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178654","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}

{"title":"Cefiderocol – An effective antimicrobial for MDR infections but a challenge for routine antimicrobial susceptibility testing","authors":"Małgorzata Brauncajs ,&nbsp;Filip Bielec ,&nbsp;Anna Macieja ,&nbsp;Dorota Pastuszak-Lewandoska","doi":"10.1016/j.advms.2024.05.001","DOIUrl":"10.1016/j.advms.2024.05.001","url":null,"abstract":"<div><h3>Purpose</h3><p>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 <em>in vitro</em> susceptibility to the cefiderocol of carbapenemase-producing gram-negative bacilli from clinical samples of hospitalized patients.</p></div><div><h3>Materials and methods</h3><p>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.</p></div><div><h3>Results</h3><p>The obtained results turned out to be ambiguous, and the area of technical uncertainty made their interpretation very difficult.</p></div><div><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 256-263"},"PeriodicalIF":2.7,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1896112624000300/pdfft?md5=d3e590e890a4b14b15738e115c75f1e0&pid=1-s2.0-S1896112624000300-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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}

{"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}

{"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}

{"title":"Effectiveness of antazoline versus amiodarone, flecainide and propafenone in restoring sinus rhythm at the emergency department","authors":"Janusz Springer ,&nbsp;Michalina Pejska ,&nbsp;Wojciech Homenda ,&nbsp;Tomasz Zdrojewski ,&nbsp;Ludmiła Daniłowicz-Szymanowicz ,&nbsp;Dariusz Kozłowski","doi":"10.1016/j.advms.2024.04.003","DOIUrl":"10.1016/j.advms.2024.04.003","url":null,"abstract":"<div><h3>Purpose</h3><p>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.</p></div><div><h3>Materials/methods</h3><p>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]).</p></div><div><h3>Results</h3><p>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 ​&lt; ​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 ​&lt; ​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 ​&lt; ​0.0001, OR 1.81, 95 ​% CI 1.44–2.27).</p></div><div><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 248-255"},"PeriodicalIF":2.7,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140793335","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}

{"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}

{"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}

{"title":"Dendrobium officinale Polysaccharide (DOP) inhibits cell hyperproliferation, inflammation and oxidative stress to improve keratinocyte psoriasis-like state","authors":"Bijun Zeng ,&nbsp;Yining Yan ,&nbsp;Yujin Zhang ,&nbsp;Chang Wang ,&nbsp;Wenting Huang ,&nbsp;Xinyi Zhong ,&nbsp;Zi Chen ,&nbsp;Mengzhou Xie ,&nbsp;Zhibo Yang","doi":"10.1016/j.advms.2024.03.005","DOIUrl":"10.1016/j.advms.2024.03.005","url":null,"abstract":"<div><h3>Purpose</h3><p>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 <em>Dendrobium officinale</em> polysaccharide (DOP) on keratinocyte psoriasis-like models.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Result</h3><p>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.</p></div><div><h3>Conclusion</h3><p>DOP inhibits keratinocyte hyperproliferation, inflammation and oxidative stress to improve the keratinocyte psoriasis-like state.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 1","pages":"Pages 167-175"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193084","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}

{"title":"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","authors":"Grzegorz Machnik ,&nbsp;Łukasz Bułdak ,&nbsp;Karolina Zapletal-Pudełko ,&nbsp;Beniamin Oskar Grabarek ,&nbsp;Rafał Staszkiewicz ,&nbsp;Dawid Sobański ,&nbsp;Bogusław Okopień","doi":"10.1016/j.advms.2024.02.007","DOIUrl":"10.1016/j.advms.2024.02.007","url":null,"abstract":"<div><h3>Purpose</h3><p>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 <em>ERVW-1</em> encoding syncytin-1. We also examined the expression of <em>FURIN</em> gene that is crucial in syncytin-1 synthesis.</p></div><div><h3>Material and methods</h3><p>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.</p></div><div><h3>Results</h3><p>Results revealed reduced <em>ERVW-1</em> expression in cells exposed to injury (p ​&lt; ​0.05) while <em>GFAP</em> gene - a marker of active astrocytes, was upregulated (p ​&lt; ​0.01). These findings were confirmed by both WB and RT-qPCR. Expression of <em>FURIN</em> gene was not altered after injury, but cell stimulation by PMA strongly increased <em>FURIN</em> expression, simultaneously downregulating <em>ERVW-1</em> (p ​&lt; ​0.01). SiRNA-mediated expression inhibition of <em>ERVW-1</em> and <em>FURIN</em> influenced the mRNA level for <em>SLC1A5</em> (<em>ASCT2</em>) - primary syncytin-1 receptor, that was significantly lower. <em>FURIN</em> inhibition by siRNA caused strong upregulation of <em>ERVW-1</em> expression (p ​&lt; ​0.01).</p></div><div><h3>Conclusion</h3><p>Results showed that mechanical impact affects the expression of endogenous retroviruses in U-87 MG astrocytoma cells by scratch assay. Regulation of <em>FURIN</em>, a crucial enzyme in <em>ERVW-1</em> turnover may support the therapy of some neurological conditions.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 1","pages":"Pages 113-124"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139951402","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}