Journal of International Translational Medicine最新文献

Exploring the Prognostic and Predictive Roles of Ki-67 in Endometrial Cancer 探讨Ki-67在子宫内膜癌中的预后和预测作用

Journal of International Translational Medicine Pub Date : 2023-11-01 DOI: 10.3390/ijtm3040033

Laura Paleari, Mariangela Rutigliani, Oriana D’Ecclesiis, Sara Gandini, Irene Maria Briata, Tania Buttiron Webber, Nicoletta Provinciali, Andrea DeCensi

{"title":"Exploring the Prognostic and Predictive Roles of Ki-67 in Endometrial Cancer","authors":"Laura Paleari, Mariangela Rutigliani, Oriana D’Ecclesiis, Sara Gandini, Irene Maria Briata, Tania Buttiron Webber, Nicoletta Provinciali, Andrea DeCensi","doi":"10.3390/ijtm3040033","DOIUrl":"https://doi.org/10.3390/ijtm3040033","url":null,"abstract":"Background: Up to now, endometrial cancer (EC) treatments are mainly represented by surgery followed by adjuvant chemotherapy or radiotherapy. The updated guidelines give a 2A recommendation for the use of hormone therapy only in advanced low-grade ECs, underlying the need for more data on the role of hormone therapy in the adjuvant setting. Methods: The clinicopathological data of 158 early-stage EC patients was retrospectively collected. A Ki-67 cut-off value of 40% was established based on literature data. Disease-free survival (DFS) and Overall survival (OS) were evaluated. Results: Results: Multivariate analysis of DFS and OS showed a significantly increased risk of progression in patients with >40% Ki-67 [HR = 3.13 (95% CI; 1.35–7.14); p = 0.007] and a significantly higher relative risk of death [HR = 3.70 (95% CI; 1.69–8.33); p = 0.001]. The predictive role of the Ki-67 index was highlighted by the clinical benefit of adjuvant hormone in patients with high Ki-67. Conclusions: Our results suggest a positive role of the Ki-67 index as a prognostic and potentially predictive marker in EC, although further studies are warranted to reach a definitive conclusion.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135370813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Review Concerning the Use of Etravirine and Darunavir in Translational Medicine 曲曲维林和达那韦在转化医学中的应用综述

Journal of International Translational Medicine Pub Date : 2023-10-27 DOI: 10.3390/ijtm3040032

Mariana Pereira, Nuno Vale

{"title":"A Review Concerning the Use of Etravirine and Darunavir in Translational Medicine","authors":"Mariana Pereira, Nuno Vale","doi":"10.3390/ijtm3040032","DOIUrl":"https://doi.org/10.3390/ijtm3040032","url":null,"abstract":"This comprehensive review explores two antiretroviral drugs, Etravirine (ETV) and Darunavir (DRV), a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor, that are commonly used in human immunodeficiency virus (HIV) infection treatment, often in combination with each other. The pharmacokinetic properties of these drugs are covered as well as the clinical trials of these two drugs combined. This paper also delves into the possible repurposing of these two drugs for other diseases, with drug repurposing being a significant factor in addressing global health challenges. DRV was extensively studied for treating COVID-19, as well as other infections, such as candidiasis and cryptococcosis, while ETV proved to be efficient in hampering Zika virus brain infection. The focus on cancer repurposing is also explored, with the results revealing that ETV has a particular inhibitory effect on ovarian cancer in vitro and on cancer molecules, such as anterior gradient protein 2 homolog (AGR2) and casein kinase 1 (CK1ε), and that DRV has an in silico inhibitory effect on human lactate dehydrogenase A (LDHA) and induces the in vitro and in vivo inhibition of pepsin, consequent laryngopharyngeal reflux, and possible laryngeal and hypopharyngeal carcinomas. The significance of fresh methods of drug development is emphasized in this work, as is the enormous potential for new therapeutic uses of the antiretroviral drugs ETV and DRV in viral and non-viral disorders.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136263949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis 常见的可变免疫缺陷和选择性IgA缺乏:关注自身免疫表现及其发病机制

Journal of International Translational Medicine Pub Date : 2023-10-16 DOI: 10.3390/ijtm3040031

Marta Chiara Sircana, Gianpaolo Vidili, Antonio Gidaro, Alessandro Palmerio Delitala, Fabiana Filigheddu, Roberto Castelli, Roberto Manetti

{"title":"Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis","authors":"Marta Chiara Sircana, Gianpaolo Vidili, Antonio Gidaro, Alessandro Palmerio Delitala, Fabiana Filigheddu, Roberto Castelli, Roberto Manetti","doi":"10.3390/ijtm3040031","DOIUrl":"https://doi.org/10.3390/ijtm3040031","url":null,"abstract":"Inborn errors of immunity (IEI) are multifaced diseases which can present with a variety of phenotypes, ranging from infections to autoimmunity, lymphoproliferation, and neoplasms. In recent decades, research has investigated the relationship between autoimmunity and IEI. Autoimmunity is more prevalent in primary humoral immunodeficiencies than in most other IEI and it can even be their first manifestation. Among these, the two most common primary immunodeficiencies are selective IgA deficiency and common variable immunodeficiency. More than half of the patients with these conditions develop non-infectious complications due to immune dysregulation: autoimmune, autoinflammatory, allergic disorders, and malignancies. Around 30% of these patients present with autoimmune phenomena, such as cytopenia, gastrointestinal and respiratory complications, and endocrine and dermatologic features. Complex alterations of the central and peripheral mechanisms of tolerance are involved, affecting mainly B lymphocytes but also T cells and cytokines. Not only the immunophenotype but also advances in genetics allow us to diagnose monogenic variants of these diseases and to investigate the pathogenetic basis of the immune dysregulation. The diagnosis and therapy of the primary humoral immunodeficiencies has been mostly focused on the infectious complications, while patients with predominant features of immune dysregulation and autoimmunity still present a challenge for the clinician and an opportunity for pathogenetic and therapeutic research.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136112683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Parotid Gland in 32-Year-Old Male, a Case Report 32岁男性原发性腮腺黏膜相关淋巴组织淋巴瘤1例报告

Journal of International Translational Medicine Pub Date : 2023-10-11 DOI: 10.3390/ijtm3040030

Bianca M. Glass, Mira Al Jaberi, John H. Irlam, Samir M. Dalia

引用次数: 0

Mentha longifolia L. Inhibits Colorectal Cancer Cell Proliferation and Induces Apoptosis via Caspase Regulation 长叶薄荷通过Caspase调控抑制结直肠癌细胞增殖和诱导凋亡

Journal of International Translational Medicine Pub Date : 2023-10-07 DOI: 10.3390/ijtm3040029

Nazanin Beheshtian, Ehsan Karimi, Javad Asili, Nadia Beheshtin, Hieu Huu Le, Majid Shakeri

{"title":"Mentha longifolia L. Inhibits Colorectal Cancer Cell Proliferation and Induces Apoptosis via Caspase Regulation","authors":"Nazanin Beheshtian, Ehsan Karimi, Javad Asili, Nadia Beheshtin, Hieu Huu Le, Majid Shakeri","doi":"10.3390/ijtm3040029","DOIUrl":"https://doi.org/10.3390/ijtm3040029","url":null,"abstract":"Naturopathy or herbal medicine has been widely used as an alternative treatment for several illnesses, such as cancer, as they are generally acknowledged as a treatment with lesser side effects. This research evaluated the bioactive compounds profiling, antioxidant, and anticancer potential in Mentha longifolia L. (essential oil and extract), using different solvent polarities (hexane, methanol, and diethyl ether). Meanwhile, the caspase 3 gene expression and cell cycle status of methanolic extract were determined in colorectal cancer cells (Caco-2 and SW48). The overall findings showed that methanolic extraction exhibited the highest total phenolic and flavonoid with respective values of 59.25 mg GAE (Gallic acid) eq./g DW (dry weight) and 20.02 mg RE (Rutin) eq./g DW, respectively, compared to hexane and diethyl ether. Furthermore, piperitenone oxid and piperitonone were found to be the dominant volatile compounds in methanolic extracts and essential oils. Additionally, the methanolic extract possesses higher antioxidant and anticancer activities. The molecular analysis indicated that methanolic extract up-regulated the expression of caspase 3 and increased the SubG1 (method to detecting cell death) peaks in treated Caco-2 and SW48 cell lines. To conclude, M. longifolia L. could serve as an effective therapeutic agent and a remedy for several illnesses, such as cancer caused by oxidative stress.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135301314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A New HRCT Score for Diagnosing SARS-CoV-2 Pneumonia: A Single-Center Study with 1153 Suspected COVID-19 Patients in the Emergency Department 诊断SARS-CoV-2肺炎的新HRCT评分:急诊1153例疑似COVID-19患者的单中心研究

Journal of International Translational Medicine Pub Date : 2023-09-30 DOI: 10.3390/ijtm3040028

Soccorsa Sofia, Giacomo Filonzi, Leonardo Catalano, Roberta Mattioli, Laura Marinelli, Elena Siopis, Laura Colì, Violante Mulas, Davide Allegri, Carlotta Rotini, Beatrice Scala, Alessio Bertini, Michele Imbriani, Michele Domenico Spampinato, Paolo Orlandi

{"title":"A New HRCT Score for Diagnosing SARS-CoV-2 Pneumonia: A Single-Center Study with 1153 Suspected COVID-19 Patients in the Emergency Department","authors":"Soccorsa Sofia, Giacomo Filonzi, Leonardo Catalano, Roberta Mattioli, Laura Marinelli, Elena Siopis, Laura Colì, Violante Mulas, Davide Allegri, Carlotta Rotini, Beatrice Scala, Alessio Bertini, Michele Imbriani, Michele Domenico Spampinato, Paolo Orlandi","doi":"10.3390/ijtm3040028","DOIUrl":"https://doi.org/10.3390/ijtm3040028","url":null,"abstract":"The 2019 coronavirus disease (COVID-19) pandemic is affecting millions of people worldwide. Chest high-resolution computed tomography (HRCT) is commonly used as a diagnostic test for suspected COVID-19; however, despite numerous attempts, there is no single scoring system that is widely accepted and used in clinical practice to estimate the probability of SARS-CoV-2 pneumonia. The aim of this single-center retrospective study is to develop a radiological score to predict the probability of COVID-19 with HRCT. Patients admitted to the emergency department with symptoms suggestive of COVID-19 who underwent both HRCT and RT-PCR on nasopharyngeal swab to detect SARS-CoV-2 infection between 1 March and 30 April 2020 were included. A multivariable regression analysis was conducted to identify all HRCT signs independently associated with a positive RT-PCR assay for SARS-CoV-2 and build the HRCT score. A total of 1153 patients were enrolled in this study. The number of segments with ground glass opacities (OR 1.18, 95% CI 1.11–1.26), number of segments with linear opacities (OR 1.21, 95% CI 1.05–1.42), crazy paving patterns (OR 6, 95% CI 3.79–9.76), and vascular ectasia in each segment (OR 2.46, 95% CI 1.1.5–5.8) were included in the score. The HRCT score showed high discriminatory power (area under the ROC curve of 0.8267 [95% CI 0.8–0.85]) with 72.2% sensitivity, 86.6% specificity, 78% PPV, and 83% NPV for its best cut-off. In summary, the HRCT score has good diagnostic and discriminatory accuracy for COVID-19 and is easy and quick to perform.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136344693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An HSP90 Inhibitor Overcomes FLT3 Inhibitor Resistance in FLT3/ITD-Positive Leukemia Cells with an N676K Mutation HSP90抑制剂克服FLT3/ itd阳性白血病细胞N676K突变的FLT3抑制剂耐药性

Journal of International Translational Medicine Pub Date : 2023-09-07 DOI: 10.3390/ijtm3030027

Hiraku Ogata, Yosuke Minami

{"title":"An HSP90 Inhibitor Overcomes FLT3 Inhibitor Resistance in FLT3/ITD-Positive Leukemia Cells with an N676K Mutation","authors":"Hiraku Ogata, Yosuke Minami","doi":"10.3390/ijtm3030027","DOIUrl":"https://doi.org/10.3390/ijtm3030027","url":null,"abstract":"FLT3 mutations are frequently identified in acute myeloid leukemia (AML). In particular, FLT3-ITD is known to be an indicator of a poor prognosis. FLT3 inhibitors have improved the treatment outcomes of AML patients with mutated FLT3. However, several drug-resistance mechanisms have been reported, and new clinical strategies to overcome drug resistance are needed. Heat shock protein (HSP) 90 is a molecular chaperone that mediates the correct folding and functionality of its client proteins, including FLT3. In the present study, we investigated the effects of an HSP90 inhibitor on FLT3 inhibitor-resistant AML cells. Using MOLM-13 (an AML cell line harboring FLT3-ITD), we established FLT3-selective inhibitor (FI-700)-resistant cell lines with an FLT3 N676K mutation. An HSP90 inhibitor (17-AAG) inhibited the growth of the cell lines, and combination treatment with FI-700 and 17-AAG showed synergistic inhibition. The underlying mechanism is thought to be as follows: HSP90 inhibits the association between HSP90 and FLT3, and thus reduces the phosphorylation of FLT3 and its downstream signaling proteins, which induces the consequent degradation of FLT3. In summary, we demonstrated that the HSP90 inhibitor could inhibit the cell growth of FLT3 inhibitor-resistant AML cells. Our results suggest that HSP90 is a promising molecular target in relapsed/refractory AML.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90384396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptomic Analysis of Insulin-Secreting Murine Hepatocytes Transduced with an Integrating Adeno-Associated Viral Vector 整合腺相关病毒载体转导胰岛素分泌小鼠肝细胞的转录组学分析

Journal of International Translational Medicine Pub Date : 2023-09-06 DOI: 10.3390/ijtm3030026

Alexandra L. G. Mahoney, Sergio Joshua, N. Nassif, A. Simpson

{"title":"Transcriptomic Analysis of Insulin-Secreting Murine Hepatocytes Transduced with an Integrating Adeno-Associated Viral Vector","authors":"Alexandra L. G. Mahoney, Sergio Joshua, N. Nassif, A. Simpson","doi":"10.3390/ijtm3030026","DOIUrl":"https://doi.org/10.3390/ijtm3030026","url":null,"abstract":"Type 1 Diabetes (T1D) is a chronic metabolic disorder for which current treatments are unable to prevent the onset of complications. Previously, we used an adeno-associated viral vector (AAV8) to deliver furin-cleavable human insulin (INS-FUR) to the livers of diabetic non-obese diabetic (NOD) mice to reverse T1D. The use of the traditional AAV8-INS-FUR vector could not bring about normoglycemia. However, this vector, coupled with a transposon system in the AAV8/piggyBac-INS-FUR vector, was able to do so. This study aimed to investigate the transcriptomic profiles of the livers of diabetic, AAV8-INS-FUR-transduced, and AAV8/piggyBac-INS-FUR-transduced NOD mice and compare these to the normal liver to identify genetic differences resulting from delivery of the AAV8/piggyBac-INS-FUR vector which produced normoglycemia. Differential gene expression was determined by RNA-Seq analysis and differentially expressed genes from each treatment were mapped onto cellular pathways to determine the treatments’ cell signaling and downstream effects. We observed distinct differences between the piggyBac-transduced and diabetic models, particularly in terms of metabolic function and the upregulation of key pancreatic markers in the liver of piggyBac-transduced animals. The success of the AAV8/piggyBac-INS-FUR vector in achieving normoglycemia through stable transduction was evident. However, further engineering is necessary to achieve complete pancreatic transdifferentiation of liver cells.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76681891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dexamethasone Treatment Preserves the Structure of Adult Cardiac Explants and Supports Their Long-Term Contractility In Vitro 地塞米松治疗保留了成人心脏外植体的结构并支持其在体外的长期收缩性

Journal of International Translational Medicine Pub Date : 2023-09-05 DOI: 10.3390/ijtm3030025

L. Eisenberg, Keerat Kaur, John M. Castillo, John G. Edwards, C. Eisenberg

{"title":"Dexamethasone Treatment Preserves the Structure of Adult Cardiac Explants and Supports Their Long-Term Contractility In Vitro","authors":"L. Eisenberg, Keerat Kaur, John M. Castillo, John G. Edwards, C. Eisenberg","doi":"10.3390/ijtm3030025","DOIUrl":"https://doi.org/10.3390/ijtm3030025","url":null,"abstract":"Normal contractile function of the myocardium is essential for optimal cardiovascular health. Evaluating drug effects on cardiomyocyte function at the cellular level is difficult for long-term studies. Present culture systems rely on isolated, cardiomyocyte preparations or cardiomyocytes derived from pluripotent stem cells (PSCs), all of which have limitations. Isolated, endogenous cardiomyocytes do not remain contractile in culture long term. While PSC-derived cardiomyocytes show contractile activity for longer periods of time, their phenotype is more embryonic than adult. Here we report that dexamethasone (DEX) treatment of adult mouse atrial tissue can extend its functionality in culture. Normally, cardiac explants cease their capacity as a contractile tissue within the first month, as the tissue flattens and spreads out on the culture substrate, while the cells dedifferentiate and lose their myocardial phenotype. However, with DEX treatment, cardiac explants maintain their contractile function, 3D morphology, and myocyte phenotype for up to 6 months. Moreover, DEX also preserved the contractile phenotype of isolated rat cardiomyocytes. These data with DEX suggest that simple modifications in culture conditions can greatly improve the long-term utility of in vitro model systems for screening drugs and agents that could be employed to alleviate human cardiac disease.","PeriodicalId":43005,"journal":{"name":"Journal of International Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80236132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of Indications for Endoscopic Spine Surgery: An Overview 内窥镜脊柱手术指征的发展:综述

Journal of International Translational Medicine Pub Date : 2023-08-29 DOI: 10.3390/ijtm3030023

Fernanda Wirth, Esthael Cristina Querido Avelar Bergamaschi, Fábio da Silva Forti, J. P. Bergamaschi

引用次数: 1