{"title":"A mouse model of food allergy permitting skin and nasal symptoms","authors":"Takafumi Morinaga, Takuya Yamamoto, Yukio Sugimoto","doi":"10.1016/j.advms.2023.09.012","DOIUrl":"10.1016/j.advms.2023.09.012","url":null,"abstract":"<div><h3>Purpose</h3><p>Developing experimental animal models<span><span> that show clinical symptoms and methods for quantitative and objective evaluation are important for understanding food allergies. Therefore, this study aimed to develop an </span>ovalbumin (OVA)-induced mouse model of food allergy and a useful method to evaluate the symptoms of food allergy.</span></p></div><div><h3>Material/methods</h3><p><span><span>Mice were sensitized via intraperitoneal injection of OVA. Subsequently, local sensitization was performed once weekly by </span>oral administration of OVA. Itching and nasal symptoms were observed after oral administration of the antigen. First, we examined the dose-dependency of the antigen. Symptoms were checked weekly. In order to confirm food allergy symptoms, the effect of histamine H</span><sub>1</sub><span> receptor antagonist was examined. Finally, we measured antigen-specific IgE antibody levels in the serum.</span></p></div><div><h3>Results</h3><p><span><span>Scratching behavior, sneezing and nasal rubbing were increased. Both itching and </span>rhinitis symptoms increased steadily, after which, the number of symptoms remained almost constant. No difference was observed between the results of 3- and 5-week-old mice. </span>Cetirizine inhibited these symptoms in a dose-dependent manner. In addition, antigen-specific IgE antibodies were produced in both 3- and 5-week-old mice.</p></div><div><h3>Conclusions</h3><p>This method may be useful for evaluating the symptoms of skin and rhinitis that could not be assessed in the conventional food allergy model and could be induced with a low dose of antigen. In particular, the developed method, which measures the number of itching and nasal symptoms, may enable quantitative, objective, and noninvasive evaluation of food allergy severity.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 372-378"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127489","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}
Amira Mohamed Taha , Sara Adel Abdelkader Saed , Mostafa Hossam-Eldin Moawad , Wesam Abd El-Tawab Moawad , Tala Al-hejazi , Yosra Mousa , Ramaswamy Sharma , Russel J. Reiter
{"title":"Safety and efficacy of melatonin as an adjuvant therapy in COVID-19 patients: Systematic review and meta-analysis","authors":"Amira Mohamed Taha , Sara Adel Abdelkader Saed , Mostafa Hossam-Eldin Moawad , Wesam Abd El-Tawab Moawad , Tala Al-hejazi , Yosra Mousa , Ramaswamy Sharma , Russel J. Reiter","doi":"10.1016/j.advms.2023.09.007","DOIUrl":"10.1016/j.advms.2023.09.007","url":null,"abstract":"<div><h3>Background</h3><p><span>Melatonin might be beneficial to </span>coronavirus<span> disease 2019 (COVID-19) patients in terms of both prevention and treatment. We investigated how melatonin affected various clinical and laboratory results in COVID-19 patients.</span></p></div><div><h3>Methods</h3><p><span>PubMed, Scopus, </span>Cochrane Library and Web of Science databases were utilized for searching eligible articles fulfilling our inclusion criteria up to December 2022. We used random effect model in case of significant heterogeneity; in other cases, a fixed model was applied. RevMan was used for meta-analysis.</p></div><div><h3>Results</h3><p><span>We included 11 studies in our review. Clinical improvement rate was found to be statistically significantly higher in patients taking melatonin than in the control group (OR: 5.09; 95% CI: 2.60−9.96, p < 0.001). Patients receiving melatonin showed a non-significant difference in mortality rate compared to the control group (OR: 0.37; 95% CI: 0.07−1.81, p = 0.22). However, in the </span>randomized controlled trials<span> subgroup, melatonin-treated patients showed significantly lower mortality than did the controls (OR: 0.17; 95% CI: 0.08−0.38, p < 0.001). CRP level was statistically significantly lower due to melatonin treatment (weighted mean difference [WMD] = −9.85; 95% CI: −18.54 to −1.16, p = 0.03). Length of hospital stay was statistically significantly shorter in patients taking melatonin compared to controls (WMD = −4.05; 95% CI: −5.39 to −2.7, p < 0.001).</span></p></div><div><h3>Conclusion</h3><p><span>Melatonin was found to have substantial effects on COVID-19 patients when used as adjuvant therapy, enhancing clinical improvement and decreasing time to recovery with a shorter length of hospital stay and a shorter duration of </span>mechanical ventilation.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 341-352"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107168","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}
Ning Li , Yuanxiong Cheng , Shiyong Wang , Hua Liao , Shengming Liu
{"title":"Inhibition of airway smooth muscle contraction and proliferation by LIM kinase inhibitor, LIMKi3","authors":"Ning Li , Yuanxiong Cheng , Shiyong Wang , Hua Liao , Shengming Liu","doi":"10.1016/j.advms.2023.04.002","DOIUrl":"10.1016/j.advms.2023.04.002","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Current medical treatment<span> for asthma aims to inhibit airway smooth muscle (ASM) contraction and proliferation, however, the efficacy of available treatment options is unsatisfactory. Therefore, we explored the effect of LIM domain kinase (LIMK) inhibitor - LIMKi3, on </span></span>ASM to improve the understanding of ASM contraction and proliferation mechanisms, and to investigate new therapeutic targets.</p></div><div><h3>Materials and methods</h3><p><span><span><span>Asthma model was induced in rats by intraperitoneal injection of </span>ovalbumin. Using phospho-specific antibodies, we examined LIMK, phosphorylated LIMK, </span>cofilin and phosphorylated cofilin. ASM contraction was studied in organ bath experiments. </span>ASM cells proliferation was studied with cell counting kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays.</p></div><div><h3>Results</h3><p><span><span>Immunofluorescence indicated that LIMKs are expressed in ASM tissues. </span>Western blot revealed that </span>LIMK1<span> and phospho-cofilin were significantly elevated in asthma ASM tissues. The LIMK inhibitor, LIMKi3 (1 μM) could reduce cofilin phosphorylation and therefore inhibit contraction of ASM tissues, and induce actin filament<span> breakdown as well as cell proliferation reduction in cultured human ASM cells.</span></span></p></div><div><h3>Conclusions</h3><p>ASM contraction and proliferation in asthma may underlie the effects of LIMKs. Small molecule LIMK inhibitor, LIMKi3, might be a potential therapeutic strategy for asthma.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 186-194"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9784698","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}
Aleksandra Oraczewska , Szczepan Cofta , Adam Warcholiński , Ewa Trejnowska , Grzegorz Brożek , Andrzej Swinarew , Daiana Stolz , Raffaele Scala , Adam Barczyk , Szymon Skoczyński
{"title":"The use of non-invasive respiratory assistance to facilitate bronchofiberoscopy performance in patients with hypoxemic (type one) respiratory failure - Study protocol","authors":"Aleksandra Oraczewska , Szczepan Cofta , Adam Warcholiński , Ewa Trejnowska , Grzegorz Brożek , Andrzej Swinarew , Daiana Stolz , Raffaele Scala , Adam Barczyk , Szymon Skoczyński","doi":"10.1016/j.advms.2023.10.011","DOIUrl":"10.1016/j.advms.2023.10.011","url":null,"abstract":"<div><h3>Purpose</h3><p>Bronchofiberoscopy (FOB) is a procedure routinely performed for: lung cancer, obstruction, interstitial diseases, foreign bodies’ removal, airway clearance, and hemoptysis. It causes acute airway narrowing leading to respiratory and cardiovascular stress. Due to increasing number of ill patients with respiratory failure (RF), conventional oxygen therapy (COT) is frequently insufficient to assure accurate oxygenation and prevent RF in patients requiring FOB. In this clinical scenario, patients may be intubated and supported with invasive mechanical ventilation (IMV) with the specific aim of allowing a safe FOB. However, this invasive strategy is associated with an increased risk of IMV-associated complications.</p></div><div><h3>Materials and methods</h3><p>Our study is a planned prospective multicenter three-arm randomized controlled trial (RCT). The target number of 300 patients was calculated based on the intubation risk in RF patients, which is 0.2–2%. The patients will be assigned to each arm based on Horowitz index. In each arm, the patients will be randomly assigned to one out of two dedicated respiratory support methods in each group i.e. COT/high flow nasal cannula (HFNC), HFNC/non-invasive ventilation (NIV) and NIV/IMV. In the manuscript the current state of art in the area of respiratory support is discussed. We have underlined knowledge gaps in medical evidence which we are planning to reveal with our results.</p></div><div><h3>Results</h3><p>The results of our study are clinically crucial, because they address current gaps concerning COT/HFNC/NIV/IMV.</p></div><div><h3>Conclusion</h3><p>The expected findings of this study would allow for careful selection of respiratory support method to safely perform FOB in patients with hypoxemic RF.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 474-481"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1896112623000512/pdfft?md5=4d912ec83dfc85bc306489805ad0ac98&pid=1-s2.0-S1896112623000512-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72012986","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}
Do Han Kim , Frank J. Lukens , Donghyun Ko , Paul T. Kröner , Miguel Salazar , Massimo Raimondo , Pedro Palacios Argueta
{"title":"Modified Bedside Index for severity in acute pancreatitis (BISAP) score validation in the national inpatient sample database","authors":"Do Han Kim , Frank J. Lukens , Donghyun Ko , Paul T. Kröner , Miguel Salazar , Massimo Raimondo , Pedro Palacios Argueta","doi":"10.1016/j.advms.2023.05.004","DOIUrl":"10.1016/j.advms.2023.05.004","url":null,"abstract":"<div><h3>Purpose</h3><p>The aim of this study was to build and validate modified score to be used in the healthcare cost and utilization project databases for further classification of acute pancreatitis (AP).</p></div><div><h3>Materials and methods</h3><p><span>The National Inpatient Sample database for the years 2016-2019 was queried for all primary adult discharge diagnoses of AP. An mBISAP score system was created utilizing the ICD-10CM codes for pleural effusion, encephalopathy, </span>acute kidney injury, systemic inflammatory response, and age >60. Each was assigned a 1-point score. A multivariable regression analysis was built to test for mortality. Sensitivity and specificity analyses were performed for mortality.</p></div><div><h3>Results</h3><p>A total of 1,160,869 primary discharges for AP were identified between 2016 and 2019. The pooled mortality rate was: 0.1%, 0.5%, 2.9%, 12.7%, 30.9% and 17.8% (P < 0.01), respectively for scores 0 to 5. Multivariable regression analysis showed increasing odds of mortality with each one-point increment: mBISAP score of 1 (adjusted odds ratio [aOR] 6.67; 95% confidence interval [CI] 4.69-9.48), score of 2 (aOR 37.87; 95% CI 26.05- 55.03), score of 3 (aOR 189.38; 95% CI 127.47-281.38), score of 4 (aOR 535.38; 95% CI 331.74-864.02), score of 5 (aOR 184.38; 95% CI 53.91-630.60). Using a cut-off of ≥3, sensitivity and specificity analyses reported 27.0% and 97.7%, respectively, with an area under the curve (AUC) of 0.811.</p></div><div><h3>Conclusion</h3><p>In this 4-year retrospective study of a US representative database, an mBISAP score was constructed showing increasing odds of mortality with each 1-point increase and a specificity of 97.7% for a cut-off of ≥3.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 208-212"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9642302","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":"Phenotypic and functional characterization of subpopulation of Imatinib resistant chronic myeloid leukemia cell line","authors":"Yalda Hekmatshoar , Aynur Karadag Gurel , Tulin Ozkan , Yalda Rahbar Saadat , Asli Koc , Arzu Zeynep Karabay , Sureyya Bozkurt , Asuman Sunguroglu","doi":"10.1016/j.advms.2023.06.002","DOIUrl":"10.1016/j.advms.2023.06.002","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span>Chronic myeloid leukemia (CML) is a </span>hematological malignancy characterized by the presence of BCR-ABL protein. </span>Imatinib<span><span> (IMA) is considered as the first line therapy in management of CML which particularly targets the BCR-ABL tyrosine kinase protein. However, emergence of resistance to IMA hinders its clinical efficiency. Hence, identifying novel targets for therapeutic approaches in CML </span>treatment is of great importance. Here, we characterize a new subpopulation of highly adherent IMA-resistant CML cells that express stemness and adhesion markers compared to naive counterparts.</span></p></div><div><h3>Materials and methods</h3><p><span><span>We performed several experimental assays including FISH, flow cytometry, and </span>gene expression assays. Additionally, bioinformatics analysis was performed by normalized web-available microarray data (GSE120932) to revalidate and introduce probable biomarkers. Protein-protein interactions (PPI) network was analyzed by the STRING database employing </span>Cytoscape v3.8.2.</p></div><div><h3>Results</h3><p>Our findings demonstrated that constant exposure to 5 μM IMA led to development of the adherent phenotype (K562R-adh). FISH and BCR-ABL expression analysis indicated that K562R-adh cells were derived from the original cells (K562R). In order to determine the role of various genes involved in epithelial–mesenchymal transition (EMT) and stem cell characterization, up/down-regulation of various genes including cancer stem cell (CSC), adhesion and cell surface markers<span> and integrins were observed which was similar to the findings of the GSE120932 dataset.</span></p></div><div><h3>Conclusion</h3><p>Treating CML patients with tyrosine kinase inhibitors<span> (TKIs) as well as targeting adhesion molecules deemed to be effective approaches in prevention of IMA resistance emergence which in turn may provide promising effects in the clinical management of CML patients.</span></p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 238-248"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751980","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}
Katarzyna Michałek , Patrycja Oberska , Maciej Murawski , Tomasz Schwarz , Ewa Tomaszewska , Siemowit Muszyński , Małgorzata Świątkiewicz , Łukasz Korytkowski , Joanna Bonior , Mateusz Zelent , David Salako-Adeoye Ayomide , Marta Grabowska
{"title":"Kidney morphology and renal expression of aquaporins 2, 3 and 4 during cerulein – Induced chronic pancreatitis in pigs","authors":"Katarzyna Michałek , Patrycja Oberska , Maciej Murawski , Tomasz Schwarz , Ewa Tomaszewska , Siemowit Muszyński , Małgorzata Świątkiewicz , Łukasz Korytkowski , Joanna Bonior , Mateusz Zelent , David Salako-Adeoye Ayomide , Marta Grabowska","doi":"10.1016/j.advms.2023.09.002","DOIUrl":"10.1016/j.advms.2023.09.002","url":null,"abstract":"<div><h3>Purpose</h3><p>Chronic pancreatitis (CP) is associated with serious complications and reduced quality of life. Kidney failure is a frequent complication of acute pancreatitis (AP), however limited information is available regarding the impact of CP on this condition. In the kidney, 9 aquaporins (AQPs) are expressed to maintain body water homeostasis and concentrate urine. The purpose of this study was to morphologically assess and analyze the location and expression of AQP2, AQP3 and AQP4 and determine whether CP affects renal structure and expression of AQPs in collecting duct (CD) principal cells.</p></div><div><h3>Materials/methods</h3><p>CP was induced in domestic pigs through intramuscular injections of cerulein (1 μg/kg bw/day for 6 days; n = 5); pigs without CP (n = 5) were used as a control group. Kidney samples were collected 6 weeks after the last injection and subjected to histological examination. Expression of AQPs was determined by immunohistochemistry and Western blot.</p></div><div><h3>Results</h3><p>The kidneys of animals with CP exhibited moderate changes, including glomerular enlargement, increased collagen percentage, numerous stromal erythrorrhages and inflammatory infiltrations compared to control group. Although the total abundance of AQP2 in the CD decreased in pigs after cerulein administration, the difference was not statistically significant. Expression of AQP3 and AQP4 was limited to the basolateral membrane of the CD cells. AQP4 abundance remained relatively stable in both groups, while AQP3 expression increased nearly three-fold in pigs with CP.</p></div><div><h3>Conclusion</h3><p>This study identified morphological alterations and a statistically significant increase in the expression of renal AQP3 when pigs developed CP.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 306-313"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10242135","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}
Pelin Aydin , Zeynep B. Aksakalli-Magden , Maide S. Civelek , Sevgi Karabulut-Uzuncakmak , Behzad Mokhtare , Mustafa Ozkaraca , Fatih Alper , Zekai Halici
{"title":"The melatonin agonist ramelteon attenuates bleomycin-induced lung fibrosis by suppressing the NLRP3/TGF-Β1/HMGB1 signaling pathway","authors":"Pelin Aydin , Zeynep B. Aksakalli-Magden , Maide S. Civelek , Sevgi Karabulut-Uzuncakmak , Behzad Mokhtare , Mustafa Ozkaraca , Fatih Alper , Zekai Halici","doi":"10.1016/j.advms.2023.09.004","DOIUrl":"10.1016/j.advms.2023.09.004","url":null,"abstract":"<div><h3>Purpose</h3><p><span><span>The possible effects of ramelteon<span>, a melatonin receptor agonist<span> on bleomycin-induced lung fibrosis were analyzed via </span></span></span>transforming growth factor β1 (TGF-β1), the </span>high mobility group box 1 (HMGB1) and Nod-like receptor pyrin domain-containing 3 (NLRP3) which are related to the fibrosis process.</p></div><div><h3>Materials and methods</h3><p><span>Bleomycin (0.1 mL of 5 mg/kg) was administered by intratracheal instillation to induce </span>pulmonary fibrosis<span><span> (PF). Starting 24 h after bleomycin administration, a </span>single dose<span> of ramelteon was administered by oral gavage to the healthy groups, i.e. PF + RM2 (pulmonary fibrosis model with bleomycin + ramelteon at 2 mg/kg) and PF + RM4 (pulmonary fibrosis model with bleomycin + ramelteon at 4 mg/kg) at 2 and 4 mg/kg doses, respectively. Real-time polymerase chain reaction (real-time PCR) analyses, histopathological, and immunohistochemical staining<span> were performed on lung tissues. Lung tomography images of the rats were also examined.</span></span></span></p></div><div><h3>Results</h3><p><span>The levels of TGF-β1, HMGB1<span>, NLRP3, and </span></span>interleukin 1 beta (IL-1β) mRNA expressions increased as a result of PF and subsequently decreased with both ramelteon doses (p < 0.0001). Both doses of ramelteon partially ameliorated the reduction in the peribronchovascular thickening, ground-glass appearances, and reticulations, and the loss of lung volume.</p></div><div><h3>Conclusions</h3><p>The severity of fibrosis decreased with ramelteon application. These effects of ramelteon may be associated with NLRP3 inflammation cascade.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 322-331"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10273418","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}
Zekai Halici , Vedat Bulut , Elif Cadirci , Muhammed Yayla
{"title":"Investigation of the effects of urotensin II receptors in LPS-induced inflammatory response in HUVEC cell line through calcineurin/NFATc/IL-2 pathway","authors":"Zekai Halici , Vedat Bulut , Elif Cadirci , Muhammed Yayla","doi":"10.1016/j.advms.2023.10.008","DOIUrl":"10.1016/j.advms.2023.10.008","url":null,"abstract":"<div><h3>Purpose</h3><p>The effect of urotensin II<span> (U-II), a powerful endogenous vasoconstrictor substance, on the immune system and its mediators is very important.</span></p><p><span>It was herein aimed to demonstrate the possible relationship between the calcineurin/nuclear factor of activated T-cells cytoplasmic 1/interleukin-2 (CaN/NFATc/IL-2) pathway and urotensin receptors (UTRs) in inflammatory response due to </span>lipopolysaccharide (LPS).</p></div><div><h3>Methods</h3><p><span>An LPS-induced inflammation model was used on the human umbilical vein endothelial cells<span> (HUVEC) cell line and drugs were applied accordingly, forming the following groups: Control Group, LPS Group, Agonist Group (10</span></span><sup>−8</sup> M U-II), Antagonist Group (10<sup>−6</sup><span> M palosuran), Tacrolimus (TAC) Group (10 ng/mL FK-506), Agonist + TAC Group, and Antagonist + TAC Group. Gene expression analyses were performed using real-time polymerase chain reaction (RT-PCR).</span></p></div><div><h3>Results</h3><p><span><span>In the analysis of the cell viability at 48 and 72 h, there was a decrease in the Agonist Group, while in the Agonist + TAC Group, the cell viability increased. In the Antagonist Group, cell viability was maintained when compared to the LPS Group, while in the TAC Group, this effect was reduced. The </span>mRNA expression levels of UTR, CaN, NFATc, IL-2 receptor (IL-2R), IL-6 and </span>nuclear factor kappa B (NF-κB) were higher in the LPS Group than in the Control Group, and even the UTR, CaN, NFATc, IL-2R were higher with agonist administration. This effect of the agonist was shown to be completely mitigated in the presence of the CaN inhibitor.</p></div><div><h3>Conclusion</h3><p>U-II and its receptors can perform key functions regarding the endothelial cell damage via the CaN/NFATc/IL-2 pathway.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 433-440"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419625","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}
Alena Mazurakova , Zuzana Solarova , Lenka Koklesova , Martin Caprnda , Robert Prosecky , Artur Khakymov , Denis Baranenko , Peter Kubatka , Ladislav Mirossay , Peter Kruzliak , Peter Solar
{"title":"Heat shock proteins in cancer – Known but always being rediscovered: Their perspectives in cancer immunotherapy","authors":"Alena Mazurakova , Zuzana Solarova , Lenka Koklesova , Martin Caprnda , Robert Prosecky , Artur Khakymov , Denis Baranenko , Peter Kubatka , Ladislav Mirossay , Peter Kruzliak , Peter Solar","doi":"10.1016/j.advms.2023.10.005","DOIUrl":"10.1016/j.advms.2023.10.005","url":null,"abstract":"<div><p><span><span><span>Heat shock proteins (HSPs) represent cellular chaperones that are classified into several families, including </span>HSP27, HSP40, </span>HSP60<span><span>, HSP70, and HSP90. The role of HSPs in the cell includes the facilitation of protein folding<span><span><span> and maintaining protein structure. Both processes play crucial roles during stress conditions in the cell such as heat shock<span>, degradation, and hypoxia<span>. Moreover, HSPs are important modulators of cellular proliferation and differentiation, and are strongly associated with the molecular orchestration of carcinogenesis. The expression and/or activity of HSPs in </span></span></span>cancer cells<span><span> is generally abnormally high and is associated with increased metastatic potential and activity of </span>cancer stem cells, more pronounced </span></span>angiogenesis, downregulated </span></span>apoptosis<span><span>, and the resistance to anticancer therapy in many patients. Based on the mentioned reasons, HSPs have strong potential as valid diagnostic, prognostic, and therapeutic biomarkers in </span>clinical oncology. In addition, numerous papers describe the role of HSPs as chaperones in the regulation of immune responses inside and outside the cell. Importantly, highly expressed/activated HSPs may be inhibited </span></span></span><em>via</em> immunotherapeutic targets in various types of cancers. The aim of this work is to provide a comprehensive overview of the relationship between HSPs and the tumor cell with the intention of highlighting the potential use of HSPs in personalized cancer management.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 464-473"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476990","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}