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Sertraline as a potential cancer therapeutic approach: Biological relevance of TCTP in breast cancer cell lines and tumors 舍曲林作为潜在的癌症治疗方法:TCTP在乳腺癌细胞系和肿瘤中的生物学相关性
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.06.001
Antonielle B. Baldissera , Marianna Boia-Ferreira , Alana B.C. Basílio , Jean Silva de Souza Resende , Mauro Antônio Alves Castro , Olga M. Chaim , Luiza Helena Gremski , Silvio S. Veiga , Andrea Senff-Ribeiro
{"title":"Sertraline as a potential cancer therapeutic approach: Biological relevance of TCTP in breast cancer cell lines and tumors","authors":"Antonielle B. Baldissera ,&nbsp;Marianna Boia-Ferreira ,&nbsp;Alana B.C. Basílio ,&nbsp;Jean Silva de Souza Resende ,&nbsp;Mauro Antônio Alves Castro ,&nbsp;Olga M. Chaim ,&nbsp;Luiza Helena Gremski ,&nbsp;Silvio S. Veiga ,&nbsp;Andrea Senff-Ribeiro","doi":"10.1016/j.advms.2023.06.001","DOIUrl":"10.1016/j.advms.2023.06.001","url":null,"abstract":"<div><h3>Purpose</h3><p><span>This study aimed to evaluate the role of Translationally Controlled Tumor Protein (TCTP) in breast cancer (BC) and investigate the effects of </span>sertraline<span><span><span>, a serotonin selective reuptake inhibitor (SSRI), on </span>BC cells. The objective was to assess the potential of sertraline as a therapeutic agent in BC </span>treatment by examining its ability to inhibit TCTP expression and exert antitumor effects.</span></p></div><div><h3>Material and Methods</h3><p>We utilized five different BC cell lines representing the molecular heterogeneity and distinct subtypes of BC, including luminal, normal-like, HER2-positive, and triple-negative BC. These subtypes play a crucial role in determining clinical treatment strategies and prognosis.</p></div><div><h3>Results</h3><p><span><span><span>The highest levels of TCTP were observed in triple-negative BC cell lines, known for their aggressive behavior. Sertraline treatment reduced TCTP expression in BC cell lines, significantly impacting </span>cell viability, </span>clonogenicity, and migration. Additionally, sertraline sensitized triple-negative BC cell lines to cytotoxic chemotherapeutic drugs (doxorubicin and cisplatin) suggesting its potential as an adjunctive therapy to enhance the chemotherapeutic response. Bioinformatic analysis of TCTP mRNA levels in TCGA BC data revealed a negative correlation between TCTP levels and patient survival, as well as between TCTP/</span><em>tpt1</em> and Ki67. These findings contradict our data and previous studies indicating a correlation between TCTP protein levels and aggressiveness and poor prognosis in BC.</p></div><div><h3>Conclusions</h3><p>Sertraline shows a promise as a potential therapeutic option for BC, particularly in triple-negative BC. Its ability to inhibit TCTP expression, enhance chemotherapeutic response, highlights its potential clinical utility in BC treatment, specifically in triple-negative BC subtype.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 227-237"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9694693","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
Interleukin-33/sST2: Dynamic assessment in patients with acute coronary syndrome 白介素-33/sST2:急性冠状动脉综合征患者的动态评估
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.05.001
Anna Witkowska, Mateusz Staciwa, Iwona Duraj, Ewelina Wozniak, Marlena Broncel, Paulina Gorzelak-Pabis
{"title":"Interleukin-33/sST2: Dynamic assessment in patients with acute coronary syndrome","authors":"Anna Witkowska,&nbsp;Mateusz Staciwa,&nbsp;Iwona Duraj,&nbsp;Ewelina Wozniak,&nbsp;Marlena Broncel,&nbsp;Paulina Gorzelak-Pabis","doi":"10.1016/j.advms.2023.05.001","DOIUrl":"10.1016/j.advms.2023.05.001","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span>Interleukin (IL)-33 and its soluble receptor ST2 (sST2) play a crucial role in the immune response. sST2 has been approved by the Food and Drug Administration as a prognostic biomarker of mortality in chronic heart failure patients, however, the role of IL-33 and sST2 in atherosclerotic cardiovascular disease remains unclear. The aim of this study was to measure serum level of IL-33 and sST2 of patients at the onset of </span>acute coronary syndrome (ACS) and 3 months after primary percutaneous </span>revascularization.</p></div><div><h3>Patients and methods</h3><p><span><span><span>Forty patients were divided into ST segment elevation </span>myocardial infarction<span> (STEMI) group, non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA) group. IL-33 and sST2 level were measured with </span></span>ELISA. Additionally, IL-33 expression in </span>peripheral blood mononuclear cells (PBMCs), was evaluated.</p></div><div><h3>Results</h3><p>All ACS patients had a significantly lower level of sST2 3 months after ACS as compared to the baseline (p ​&lt; ​0.039). The STEMI patients had higher serum levels of IL-33 at the moment of ACS as compared to 3 months after the event, with an average decrease of 17.87 ​pg/ml (p ​&lt; ​0.007). Conversely, sST2 serum levels were still high after 3 months following an ACS in STEMI patients. ROC curve demonstrated that increased IL-33 serum level could be STEMI predictor.</p></div><div><h3>Conclusions</h3><p>The assessment of the baseline and dynamics of changes in IL-33 and sST2 concentrations in patients with ACS may be important for the diagnostic process and may help in understanding of how the immune mechanisms work at the moment of an ACS event.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 195-201"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9498015","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
Monocyte-to-lymphocyte ratio correlates with parathyroid hormone concentration in patients with severe symptomatic aortic stenosis 在症状严重的主动脉狭窄患者中,单核细胞与淋巴细胞的比例与甲状旁腺激素浓度相关。
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.09.011
Anna Olasińska-Wiśniewska , Tomasz Urbanowicz , Kajetan Grodecki , Piotr Kübler , Bartłomiej Perek , Marek Grygier , Marcin Misterski , Maciej Walczak , Mateusz Szot , Marek Jemielity
{"title":"Monocyte-to-lymphocyte ratio correlates with parathyroid hormone concentration in patients with severe symptomatic aortic stenosis","authors":"Anna Olasińska-Wiśniewska ,&nbsp;Tomasz Urbanowicz ,&nbsp;Kajetan Grodecki ,&nbsp;Piotr Kübler ,&nbsp;Bartłomiej Perek ,&nbsp;Marek Grygier ,&nbsp;Marcin Misterski ,&nbsp;Maciej Walczak ,&nbsp;Mateusz Szot ,&nbsp;Marek Jemielity","doi":"10.1016/j.advms.2023.09.011","DOIUrl":"10.1016/j.advms.2023.09.011","url":null,"abstract":"<div><h3>Purpose</h3><p>The normal healthy valve is devoid of inflammatory cells, however background of aortic stenosis (AS) may include inflammatory processes. Moreover, the link between hyperparathyroidism and heart failure is postulated. Simple whole blood analysis with indices is a beneficial tool in cardiovascular diseases’ assessment. The purpose of the study was to evaluate correlation between parathyroid hormone (PTH) and simple blood parameters in severe AS.</p></div><div><h3>Material and methods</h3><p>The study included 62 patients with severe AS. Patients with inflammatory or autoimmune co-morbidities were excluded. Blood samples were collected, and clinical and demographic data were analyzed.</p></div><div><h3>Results</h3><p>The final study group comprised 55 patients (31 females, 56.4%; mean age 77.13 (SD 6.76)). In 23 patients (41.8%), PTH concentration was markedly increased. The study group was divided into two subgroups according to the PTH concentration. Patients from both groups did not differ significantly in terms of age and co-morbidities. PTH concentration correlated positively with monocyte-lymphocyte ratio (MLR) (p ​= ​0.008, Spearman rho 0.356) and platelet-lymphocyte ratio (PLR) (p ​= ​0.047, Spearman rho 0.269), creatinine level (p ​= ​0.001, Spearman rho 0.425) and glomerular filtration rate (GFR-MDRD) (p ​= ​0.009, Spearman rho −0.349).</p><p>The multivariable logistic regression with backward analysis revealed MLR (p ​= ​0.029) and GFR (p ​= ​0.028) as independent significant predictors of abnormal PTH values.</p><p>The receiver operator characteristics (ROC) curve was performed for the model of MLR and GFR-MDRD (AUC ​= ​0.777), yielding the sensitivity of 60.9% and specificity of 90.6%.</p></div><div><h3>Conclusions</h3><p>PTH concentration correlates with monocyte-to-lymphocyte and platelet-to-lymphocyte ratios in calcified AS.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 396-401"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41187937","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
Mechanism of molecular interaction of sitagliptin with human DPP4 enzyme - New Insights 西格列汀与人DPP4酶分子相互作用机制的新认识
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.10.002
Michelangelo Bauwelz Gonzatti , José Edvar Monteiro Júnior , Antônio José Rocha , Jonathas Sales de Oliveira , Antônio José de Jesus Evangelista , Fátima Morgana Pio Fonseca , Vânia Marilande Ceccatto , Ariclécio Cunha de Oliveira , José Ednésio da Cruz Freire
{"title":"Mechanism of molecular interaction of sitagliptin with human DPP4 enzyme - New Insights","authors":"Michelangelo Bauwelz Gonzatti ,&nbsp;José Edvar Monteiro Júnior ,&nbsp;Antônio José Rocha ,&nbsp;Jonathas Sales de Oliveira ,&nbsp;Antônio José de Jesus Evangelista ,&nbsp;Fátima Morgana Pio Fonseca ,&nbsp;Vânia Marilande Ceccatto ,&nbsp;Ariclécio Cunha de Oliveira ,&nbsp;José Ednésio da Cruz Freire","doi":"10.1016/j.advms.2023.10.002","DOIUrl":"https://doi.org/10.1016/j.advms.2023.10.002","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Dipeptidyl peptidase 4 (DPP</span><sub>4</sub>) inactivates a range of bioactive peptides. The cleavage of insulinotropic peptides and glucagon-like peptide 1 (GLP<sub>1</sub>) by DPP<sub>4</sub><span> directly influences glucose homeostasis<span>. This study aimed to describe the mode of interaction between sitagliptin (an antidiabetic drug) and human DPP</span></span><sub>4</sub> using <span><em>in silico</em></span> approaches.</p></div><div><h3>Materials and methods</h3><p><span>Docking studies were conducted using AutoDock Vina, 2D and 3D schematic drawings were obtained using PoseView and PLIP servers, and the DPP</span><sub>4</sub>-sitagliptin complex was visualized with Pymol software.</p></div><div><h3>Results</h3><p>The best affinity energy to form the DPP<sub>4</sub>-sitagliptin complex was <em>E</em>-value ​= ​- 8.1 ​kcal ​mol<sup>−1</sup><span>, as indicated by docking simulations. This result suggests a strong interaction. According to our observations, hydrophobic interactions involving the amino acids residues Tyr</span><sup>663</sup> and Val<sup>712</sup><span>, hydrogen bonds (Glu</span><sup>203</sup>, Glu<sup>204</sup>, Tyr<sup>663</sup>, and Tyr<sup>667</sup>), π-Stacking interactions (Phe<sup>355</sup> and Tyr<sup>667</sup>), and halogenic bonds (Arg<sup>123</sup>, Glu<sup>204</sup>, and Arg<sup>356</sup>) were prevalent in the DPP<sub>4</sub>-sitagliptin complex. Root Mean Square Deviation prediction also demonstrated that the global structure of the human DPP<sub>4</sub> did not have a significant change in its topology, even after the formation of the DPP<sub>4</sub>-sitagliptin complex.</p></div><div><h3>Conclusion</h3><p>The stable interaction between the sitagliptin ligand and the DPP<sub>4</sub><span><span> enzyme was demonstrated through </span>molecular docking simulations. The findings presented in this work enhance the understanding of the physicochemical properties of the sitagliptin interaction site, supporting the design of more efficient gliptin-like iDPP</span><sub>4</sub> inhibitors.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 402-408"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49708444","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
Some pleiotropic effects of statins on hepatocellular carcinoma cells: Comparative study on atorvastatin, rosuvastatin and simvastatin 他汀类药物对肝癌细胞的多效作用:阿托伐他汀、瑞舒伐他汀和辛伐他汀的比较研究
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.07.002
Esmeralda Dautović , Monika Rustemović-Čorbić , Nahida Srabović , Adaleta Softić , Aida Smajlović , Maida Šljivić Husejnović , Alen Hatkić , Dalila Halilčević
{"title":"Some pleiotropic effects of statins on hepatocellular carcinoma cells: Comparative study on atorvastatin, rosuvastatin and simvastatin","authors":"Esmeralda Dautović ,&nbsp;Monika Rustemović-Čorbić ,&nbsp;Nahida Srabović ,&nbsp;Adaleta Softić ,&nbsp;Aida Smajlović ,&nbsp;Maida Šljivić Husejnović ,&nbsp;Alen Hatkić ,&nbsp;Dalila Halilčević","doi":"10.1016/j.advms.2023.07.002","DOIUrl":"10.1016/j.advms.2023.07.002","url":null,"abstract":"<div><h3>Purpose</h3><p><span>For many years, statins have been the most commonly used </span>drugs<span><span> in cholesterol-lowering therapy. In addition to these therapeutic effects, statins exhibit other, pleiotropic effects<span> that can be beneficial, but also harmful to cells and tissues. The aim of this research was to determine and compare the pleiotropic effects of structurally different statins: atorvastatin, simvastatin and </span></span>rosuvastatin<span> at different concentrations on hepatocellular carcinoma (HepG2) cells.</span></span></p></div><div><h3>Materials and methods</h3><p><span><span>The MTT assay was used to determine the cytotoxic effects of statins. The influence of statins on the production of </span>reactive oxygen species (ROS) was determined by measuring fluorescent response of 2,7-dichlorofluorescein </span>diacetate<span> (DCFH-DA). The effect of statins on glucose production and excretion was determined with glucose production assay.</span></p></div><div><h3>Results</h3><p>The obtained results confirmed that all tested statins exhibit cytotoxic effects, increase the production of ROS as well as the production and excretion of glucose from HepG2 cells. It was observed that all the mentioned effects are more pronounced with lipophilic statins, atorvastatin and simvastatin compared to hydrophilic rosuvastatin.</p></div><div><h3>Conclusion</h3><p>The less pronounced pleiotropic effects of rosuvastatin on HepG2 cells are probably due to differences in structure and solubility compared to atorvastatin and simvastatin. Transporter-dependent and a slower influx of rosuvastatin into cells compared to the tested lipophilic statins probably lead to a weaker accumulation of rosuvastatin in HepG2 cells, which results in less pronounced pleiotropic effects compared to lipophilic atorvastatin and simvastatin.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 258-264"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9840272","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
Biomarkers of nitrosative stress in exhaled breath condensate and serum among patients with cystic fibrosis 囊性纤维化患者呼出液和血清中亚硝化应激的生物标志物
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.05.002
Sabina Galiniak , Nataliya Rohovyk , Marta Rachel
{"title":"Biomarkers of nitrosative stress in exhaled breath condensate and serum among patients with cystic fibrosis","authors":"Sabina Galiniak ,&nbsp;Nataliya Rohovyk ,&nbsp;Marta Rachel","doi":"10.1016/j.advms.2023.05.002","DOIUrl":"10.1016/j.advms.2023.05.002","url":null,"abstract":"<div><h3>Purpose</h3><p>The measurement of biomarkers in exhaled breath condensate<span><span> (EBC) offers a non-invasive way to assess airway disease and can be easily done in a clinical setting among patients with </span>cystic fibrosis<span> (CF). The role of oxidative and nitrosative stress in the complex pathophysiology of CF is widely accepted and biomarkers of oxidative and nitrosative stress can be measured in the serum and EBC. To our knowledge, this is the first study to assess markers of nitrosative stress in EBC and serum, collected simultaneously from the CF patients.</span></span></p></div><div><h3>Patients and methods</h3><p>Paired EBC and serum samples were collected from 36 stable patients with CF and 14 healthy controls. Markers of nitrosative stress ‒ 3-nitrotyrosine and nitrate/nitrite were measured in the EBC and serum using an enzyme-linked immunosorbent assay.</p></div><div><h3>Results</h3><p>We found no differences in 3-nitrotyrosine and nitrate/nitrite in the EBC of patients with CF as compared to healthy controls (125.37 ​± ​3.29 vs. 126.24 ​± ​2.21 ​nmol/L, p ​= ​0.218; 12.66 ​± ​7.23 vs. 8.79 ​± ​4.83 ​μmol/L, p ​= ​0.133, respectively). Furthermore, 3-nitrotyrosine and nitrate/nitrite were significantly higher in the serum of patients with CF as compared to the healthy controls (0.13 ​± ​0.02 vs. 0.11 ​± ​0.01 ​nmol/mg protein, p ​= ​0.003; 70.78 ​± ​22.55 vs. 53.08 ​± ​8.5 ​μmol/L, p ​= ​0.009, respectively). No correlations were found between the markers determined in the EBC and serum.</p></div><div><h3>Conclusions</h3><p>The results of the EBC nitrosative stress biomarkers should be interpreted with caution, especially in patients with stable disease, as the EBC values may be independent on levels of circulating markers that are elevated in the serum of patients with stable CF.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 202-207"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9917413","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
Sodium accumulation in the skin is associated with higher density of skin lymphatic vessels in patients with arterial hypertension 高血压患者皮肤钠积聚与皮肤淋巴管密度增高有关
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.08.001
Angelika Chachaj , Ivana Stanimirova , Mariusz Chabowski , Agnieszka Gomułkiewicz , Paweł Hodurek , Natalia Glatzel-Plucińska , Mateusz Olbromski , Aleksandra Piotrowska , Aleksandra Kuzan , Jędrzej Grzegrzółka , Katarzyna Ratajczak-Wielgomas , Aleksandra Nowak , Ewa Szahidewicz-Krupska , Jerzy Wiśniewski , Mariusz A. Bromke , Marzenna Podhorska-Okołów , Andrzej Gamian , Dariusz Janczak , Piotr Dzięgiel , Andrzej Szuba
{"title":"Sodium accumulation in the skin is associated with higher density of skin lymphatic vessels in patients with arterial hypertension","authors":"Angelika Chachaj ,&nbsp;Ivana Stanimirova ,&nbsp;Mariusz Chabowski ,&nbsp;Agnieszka Gomułkiewicz ,&nbsp;Paweł Hodurek ,&nbsp;Natalia Glatzel-Plucińska ,&nbsp;Mateusz Olbromski ,&nbsp;Aleksandra Piotrowska ,&nbsp;Aleksandra Kuzan ,&nbsp;Jędrzej Grzegrzółka ,&nbsp;Katarzyna Ratajczak-Wielgomas ,&nbsp;Aleksandra Nowak ,&nbsp;Ewa Szahidewicz-Krupska ,&nbsp;Jerzy Wiśniewski ,&nbsp;Mariusz A. Bromke ,&nbsp;Marzenna Podhorska-Okołów ,&nbsp;Andrzej Gamian ,&nbsp;Dariusz Janczak ,&nbsp;Piotr Dzięgiel ,&nbsp;Andrzej Szuba","doi":"10.1016/j.advms.2023.08.001","DOIUrl":"10.1016/j.advms.2023.08.001","url":null,"abstract":"<div><h3>Purpose</h3><p>Recent studies, conducted mainly on the rodent model, have demonstrated that regulatory pathway in the skin provided by glycosaminoglycans, nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGF-C) and process of lymphangiogenesis may play an important role in extrarenal regulation of sodium (Na<sup>+</sup>) balance, body water volume, and blood pressure. We aimed to investigate the concentrations and relations among the main factors of this pathway in human skin to confirm that this regulatory axis also exists in humans.</p></div><div><h3>Patients and methods</h3><p>Skin specimens from patients diagnosed with arterial hypertension and from control group were histologically and molecularly examined.</p></div><div><h3>Results</h3><p>The primary hypertensive and control groups did not differ in Na<sup>+</sup> ​concentrations in the skin. However, the patients with hypertension and higher skin Na<sup>+</sup> concentration had significantly greater density of skin lymphatic vessels. Higher skin Na<sup>+</sup>concentration was associated with higher skin water content. In turn, skin water content correlated with factors associated with lymphangiogenesis<em>,</em> i.e. NFAT5, VEGF-C, and podoplanin (PDPN) mRNA expression in the skin. The strong mutual pairwise correlations of the expressions of NFAT5, VEGF-C, vascular endothelial growth factor D (VEGF-D) and PDPN mRNA were noted in the skin in all of the studied groups.</p></div><div><h3>Conclusions</h3><p>Our study confirms that skin interstitium and the lymphatic system may be important players in the pathophysiology of arterial hypertension in humans. Based on the results of our study and existing literature in this field, we propose the hypothetical model which might explain the phenomenon of salt-sensitivity.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 276-289"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10113211","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
Fascin in migration and metastasis of breast cancer cells – A review 束状蛋白在乳腺癌细胞迁移转移中的作用研究进展
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.08.003
Magdalena Izdebska, Wioletta Zielińska, Adrian Krajewski, Alina Grzanka
{"title":"Fascin in migration and metastasis of breast cancer cells – A review","authors":"Magdalena Izdebska,&nbsp;Wioletta Zielińska,&nbsp;Adrian Krajewski,&nbsp;Alina Grzanka","doi":"10.1016/j.advms.2023.08.003","DOIUrl":"10.1016/j.advms.2023.08.003","url":null,"abstract":"<div><p><span><span><span>Cancer cell migration and </span>metastasis<span> are the biggest problems in the treatment of cancer patients. The most aggressive breast cancer (BC) is the triple-negative type. Therefore, effective therapeutic targets that limit cell migration are sought. One such target may be </span></span>fascin<span>, as its overexpression is characteristic to triple-negative breast cancer. The high level of fascin enables the formation of protrusion and thus promotes the invasion of cancer cells. Fascin also shows co-localization or functional relationships with other proteins. These are proteins involved in the epithelial-mesenchymal transition process, vimentin<span>, cadherins<span><span>, β-catenin, and matrix metalloproteinases 2/9 (MMP-2/9). Fascin is also involved in many </span>signaling pathways protein kinase C-δ (PKCδ), Wnt/β-catenin, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and phosphatidylinositol 3-kinase (PI3K)-Akt. Therefore, in this article, we review currently available </span></span></span></span><em>in vitro</em> studies and compare them with The Cancer Genome Atlas (TCGA) data analysis of BC patients to demonstrate the role of fascin in the migration and invasion of cancer cells.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 290-297"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10136755","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 profile of adipokines associated with fibrosis and impaired microcirculation in systemic sclerosis 系统性硬化症中脂肪因子与纤维化和微循环受损的关系
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.09.001
Anna Niemczyk, Anna Waśkiel-Burnat, Michał Zaremba, Joanna Czuwara, Lidia Rudnicka
{"title":"The profile of adipokines associated with fibrosis and impaired microcirculation in systemic sclerosis","authors":"Anna Niemczyk,&nbsp;Anna Waśkiel-Burnat,&nbsp;Michał Zaremba,&nbsp;Joanna Czuwara,&nbsp;Lidia Rudnicka","doi":"10.1016/j.advms.2023.09.001","DOIUrl":"10.1016/j.advms.2023.09.001","url":null,"abstract":"<div><h3>Purpose</h3><p>Adipokines belong to a group of molecules mostly produced by adipose tissue. Abnormalities in the secretion of several adipokines have already implicated to play a pathogenic role in systemic sclerosis (SSc). However, the possible role of numerous molecules still needs to be clarified. The aim of the study was to determine whether the altered level of selected circulating adipokines might correlate with the intensity of fibrosis and vasculopathy in the course of SSc.</p></div><div><h3>Materials and methods</h3><p>Serum concentrations of chemerin, adipsin, retinol-binding protein 4, apelin, visfatin, omentin-1, and vaspin were determined with ELISA in the sera of patients with SSc (n ​= ​55) and healthy controls (n ​= ​25).</p></div><div><h3>Results</h3><p>The serum concentration of adipsin (p ​= ​0.03) and visfatin (p ​= ​0.04) was significantly increased and the level of retinol-binding protein 4 (p ​= ​0.03) was decreased in diffuse compared to limited cutaneous SSc. Moreover, serum adipsin level correlated positively with the intensity of skin fibrosis measured with the modified Rodnan skin score (r ​= ​0.31, p ​= ​0.02) and was significantly higher in patients with pulmonary arterial hypertension than in those without the condition (p ​= ​0.03). The concentrations of adipsin (p ​= ​0.01) and visfatin (p ​= ​0.04) were significantly increased and the level of apelin (p ​= ​0.02) was decreased in patients with active digital ulcerations compared to individuals without this complication.</p></div><div><h3>Conclusion</h3><p>Adipsin may be considered a pivotal protein in the development of both fibrosis and impaired microcirculation. Its abnormal concentration reflects the intensity of skin thickening and the presence of pulmonary arterial hypertension. Adipsin, visfatin, and apelin are adipose tissue-derived molecules associated with digital vasculopathy.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 298-305"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211605","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
CRISPR/Cas9-mediated high-mobility group A2 knockout inhibits cell proliferation and invasion in papillary thyroid carcinoma cells CRISPR/Cas9介导的高迁移率A2组敲除抑制甲状腺乳头状癌细胞的细胞增殖和侵袭。
IF 2.7 4区 医学
Advances in medical sciences Pub Date : 2023-09-01 DOI: 10.1016/j.advms.2023.10.001
Shan Jin, Hong Yong, Yousheng Liu, Wuyuntu Bao
{"title":"CRISPR/Cas9-mediated high-mobility group A2 knockout inhibits cell proliferation and invasion in papillary thyroid carcinoma cells","authors":"Shan Jin,&nbsp;Hong Yong,&nbsp;Yousheng Liu,&nbsp;Wuyuntu Bao","doi":"10.1016/j.advms.2023.10.001","DOIUrl":"10.1016/j.advms.2023.10.001","url":null,"abstract":"<div><h3>Purpose</h3><p>Metastasis<span><span> and recurrence are the prognostic risk factor in patients<span> with thyroid carcinoma. High-mobility group A2 (HMGA2) protein plays a crucial role in </span></span>papillary thyroid carcinoma<span> (PTC) metastasis. The aim of this study was to investigate the mechanisms underlying the HMGA2 effect on PTC cell proliferation and invasion.</span></span></p></div><div><h3>Materials and methods</h3><p>We used the CRISPR/Cas9 system to perform knockout of the <em>HMGA2</em><span> gene in the human PTC cell line TPC-1. The knockout monoclonal cells were screened and verified by PCR analysis and genomic sequencing. Cell proliferation was examined after the knockout of the </span><em>HMGA2</em><span> gene using cell counting kit-8 (CCK-8) assays. Furthermore, cell migration and invasion after the knockout were examined by cell scratch tests. Additionally, the changes in cell cycle and apoptosis after the knockout were detected by flow cytometry.</span></p></div><div><h3>Results</h3><p>The results of the PCR analysis and the genomic sequencing confirmed that the human PTC TPC-1 ​cell line with knockout of <em>HMGA2</em> gene was successfully established. The knockout of the <em>HMGA2</em> gene significantly reduced the cell proliferation, growth, and invasion. Meanwhile, the knockout of the <em>HMGA2</em> gene delayed the conversion of the G2/M phase and promoted cell necrosis.</p></div><div><h3>Conclusion</h3><p>The CRISPR/Cas9-mediated <em>HMGA2</em> knockout in the TPC-1 ​cell line inhibited cell proliferation and invasion, which might be due to the blockage of the cell cycle in the G2/M phase and the promotion of cell necrosis.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 409-416"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41187925","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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