F. R. Pulido, Nayra Caballero Estebaranz, Dácil Oramas Pérez, C. Palacín
Ordinary employment, from the vulnerability-stress model, is believed to trigger relapses in people with long-term mental disorders when subjected to demanding work environments. To test the accuracy of this hypothesis, different databases between 1998 and 2019 (May) were consulted, using various key words. Randomized Clinical Trials (RCTs) that analyzed non-vocational outcomes related to symptomatology and hospitalizations in the Individual Placement and Support (IPS) strategy with severe mental disorders were specifically reviewed. A total of 383 references were reviewed, 26 were selected and 18 were included. Of the selected studies the follow-up period is between 12 months and 24 months for the most part. Samples usually range from 100-200 participants but there are studies with larger samples, one study with over 2059 participants. The most commonly used outcome is admissions and relapses, the most commonly used being days of hospitalization. The most widely used scales were on overall functioning, GAF and to measure relapse, PANNS and BPRS. Competitive employment was found not to cause relapses or hospitalisations, and long-term employment seemed to contribute to a favourable clinical evolution, although the degree of impact on the health status has yet to be proven.
{"title":"Review of individual placement and support (IPS) studies and results on health status of people with long-term mental disorder and competitive employment","authors":"F. R. Pulido, Nayra Caballero Estebaranz, Dácil Oramas Pérez, C. Palacín","doi":"10.15761/JTS.1000398","DOIUrl":"https://doi.org/10.15761/JTS.1000398","url":null,"abstract":"Ordinary employment, from the vulnerability-stress model, is believed to trigger relapses in people with long-term mental disorders when subjected to demanding work environments. To test the accuracy of this hypothesis, different databases between 1998 and 2019 (May) were consulted, using various key words. Randomized Clinical Trials (RCTs) that analyzed non-vocational outcomes related to symptomatology and hospitalizations in the Individual Placement and Support (IPS) strategy with severe mental disorders were specifically reviewed. A total of 383 references were reviewed, 26 were selected and 18 were included. Of the selected studies the follow-up period is between 12 months and 24 months for the most part. Samples usually range from 100-200 participants but there are studies with larger samples, one study with over 2059 participants. The most commonly used outcome is admissions and relapses, the most commonly used being days of hospitalization. The most widely used scales were on overall functioning, GAF and to measure relapse, PANNS and BPRS. Competitive employment was found not to cause relapses or hospitalisations, and long-term employment seemed to contribute to a favourable clinical evolution, although the degree of impact on the health status has yet to be proven.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67492046","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}
A. Jindal, Vaseem A Palejwala, M. Ciomei, A. Degrassi, G. Texidó, K. Shailubhai
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of cancer-related deaths worldwide [1,2]. Chronic liver inflammation resulting from prolonged viral hepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and other metabolic disorders such as excessive alcohol consumption and exposure to aflatoxins represent major etiological factors for HCC [1-3]. These multitude of underlying mechanisms that affect disease course and patient prognosis underscores the importance of a broad-spectrum approach to target multiple mechanisms underlying HCC development and promotion [4]. Current therapies for HCC include specific tyrosine kinase inhibitors (TKIs) such as sorafenib (Nexavar®), regorafenib (Stivarga®), lenvatinib (Lenvima®) and cabozantinib (Cabometyx®) [5-9]. In addition, immunotherapies with nivolumab (Opdivo®) and pembrolizumab (Keytruda®) both inhibiting programmed cell death receptor PD-1, have also been approved as second line treatment for advanced HCC [10,11]. Although these therapies have shown significant clinical benefits for HCC patients, but the clinical response rate is still low. Thus, there is an immediate need for drugs, preferentially with different mechanisms, which could be used in suitable combinations to complement existing therapies and to improve clinical outcome without compromising safety.
{"title":"Milciclib and sorafenib synergistically downregulate c-Myc to suppress tumor growth in an orthotopic murine model of human hepatocellular carcinoma","authors":"A. Jindal, Vaseem A Palejwala, M. Ciomei, A. Degrassi, G. Texidó, K. Shailubhai","doi":"10.15761/jts.1000416","DOIUrl":"https://doi.org/10.15761/jts.1000416","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of cancer-related deaths worldwide [1,2]. Chronic liver inflammation resulting from prolonged viral hepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and other metabolic disorders such as excessive alcohol consumption and exposure to aflatoxins represent major etiological factors for HCC [1-3]. These multitude of underlying mechanisms that affect disease course and patient prognosis underscores the importance of a broad-spectrum approach to target multiple mechanisms underlying HCC development and promotion [4]. Current therapies for HCC include specific tyrosine kinase inhibitors (TKIs) such as sorafenib (Nexavar®), regorafenib (Stivarga®), lenvatinib (Lenvima®) and cabozantinib (Cabometyx®) [5-9]. In addition, immunotherapies with nivolumab (Opdivo®) and pembrolizumab (Keytruda®) both inhibiting programmed cell death receptor PD-1, have also been approved as second line treatment for advanced HCC [10,11]. Although these therapies have shown significant clinical benefits for HCC patients, but the clinical response rate is still low. Thus, there is an immediate need for drugs, preferentially with different mechanisms, which could be used in suitable combinations to complement existing therapies and to improve clinical outcome without compromising safety.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67492266","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}
M. M, A. G., Sgambato A, C. G., Iannace C, Gridelli C
{"title":"Trastuzumab emtansine (T-DM1) and concurrent radiotherapy for treatment of HER2-positive breast cancer: Review of literature","authors":"M. M, A. G., Sgambato A, C. G., Iannace C, Gridelli C","doi":"10.15761/jts.1000448","DOIUrl":"https://doi.org/10.15761/jts.1000448","url":null,"abstract":"","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67499496","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}
R. Mohan, P. PhillipHo, L. Dalton, F. Chan, Nguyen Hb
Objective : In this study, we demonstrate the derivation of a de-identified research database from the electronic health records (EHR) and then use it in determining the prognostic value of biomarkers lactate, C-reactive protein (CRP), and procalcitonin in hospitalized patients. Methods : The database was created through a series of data export, transform, load, and visualization. A database glossary was completed, including 650 data elements per patient encounter without personal identifiers. Data visualization and statistical analysis tools were provided to those utilizing the database. Results : From July 2012 to August 2019, the database contained 240,759 distinct hospital encounters, with 2,682 patients meeting criteria for analysis, age 54.5±18.6 years, lactate 1.9±1.7 mmol/L, CRP 10.7±10.0 µg/mL, procalcitonin 4.0±17.5 ng/mL, and mortality 8.7%. ROC area under the curve for lactate, CRP, and procalcitonin was 0.670, 0.553, and 0.672, respectively. Lactate, CRP, and procalcitonin had odds ratio for mortality of 1.111 (1.037-1.190), 1.015 (0.991-1.031), and 0.999 (0.991-1.007), respectively. Conclusions : Our efforts provide a framework for creating EHR-derived de-identified patient data for clinical research. Our analysis of the prognostic value of lactate, CRP, and procalcitonin showed these biomarkers to be less accurate than expected, highlighting the challenges of using existing data.
{"title":"Deriving a patient de-identified clinical research database from an electronic health record system: A single center experience in determining the prognostic value of lactate, C-reactive protein, and procalcitonin in hospitalized patients","authors":"R. Mohan, P. PhillipHo, L. Dalton, F. Chan, Nguyen Hb","doi":"10.15761/jts.1000405","DOIUrl":"https://doi.org/10.15761/jts.1000405","url":null,"abstract":"Objective : In this study, we demonstrate the derivation of a de-identified research database from the electronic health records (EHR) and then use it in determining the prognostic value of biomarkers lactate, C-reactive protein (CRP), and procalcitonin in hospitalized patients. Methods : The database was created through a series of data export, transform, load, and visualization. A database glossary was completed, including 650 data elements per patient encounter without personal identifiers. Data visualization and statistical analysis tools were provided to those utilizing the database. Results : From July 2012 to August 2019, the database contained 240,759 distinct hospital encounters, with 2,682 patients meeting criteria for analysis, age 54.5±18.6 years, lactate 1.9±1.7 mmol/L, CRP 10.7±10.0 µg/mL, procalcitonin 4.0±17.5 ng/mL, and mortality 8.7%. ROC area under the curve for lactate, CRP, and procalcitonin was 0.670, 0.553, and 0.672, respectively. Lactate, CRP, and procalcitonin had odds ratio for mortality of 1.111 (1.037-1.190), 1.015 (0.991-1.031), and 0.999 (0.991-1.007), respectively. Conclusions : Our efforts provide a framework for creating EHR-derived de-identified patient data for clinical research. Our analysis of the prognostic value of lactate, CRP, and procalcitonin showed these biomarkers to be less accurate than expected, highlighting the challenges of using existing data.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67491994","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}
Rahman M U A, Prabhu Ks, Raza A, Elmi M, Mahmood N, S. Mh, Abid Fb, Dermime S, Uddin S, A. M, M. Mi
{"title":"Biological and radiological biomarkers in SARS-CoV-2 infected healthcare workers in governmental hospitals in Qatar","authors":"Rahman M U A, Prabhu Ks, Raza A, Elmi M, Mahmood N, S. Mh, Abid Fb, Dermime S, Uddin S, A. M, M. Mi","doi":"10.15761/jts.1000464","DOIUrl":"https://doi.org/10.15761/jts.1000464","url":null,"abstract":"","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67499166","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}
L. Sokolovska, A. Sultanova, M. Cistjakovs, M. Murovska
The novel coronavirus SARS-CoV-2 poses a great public health crisis. As of December 2019, it has spread all over the world with cases reported in more than 100 countries and the number of infected individuals surpassing 1,000,000. On March 11 World Health Organization officially characterized the COVID-19 as a pandemic. Although genetic analysis revealed some similarities between the novel coronavirus and the causative agent of the 2002 SARS epidemic, both viruses have significant differences. Research done on SARS-CoV has greatly aided the understanding of SARS-CoV-2, as it served as a knowledge base and helped to identify the cell entry receptor and some other features of the disease, but not all of them. Several critical questions remain unanswered and specific therapeutics and vaccine candidates are lacking.
{"title":"COVID-19: The third wave of coronavirus infection outbreak","authors":"L. Sokolovska, A. Sultanova, M. Cistjakovs, M. Murovska","doi":"10.15761/JTS.1000389","DOIUrl":"https://doi.org/10.15761/JTS.1000389","url":null,"abstract":"The novel coronavirus SARS-CoV-2 poses a great public health crisis. As of December 2019, it has spread all over the world with cases reported in more than 100 countries and the number of infected individuals surpassing 1,000,000. On March 11 World Health Organization officially characterized the COVID-19 as a pandemic. Although genetic analysis revealed some similarities between the novel coronavirus and the causative agent of the 2002 SARS epidemic, both viruses have significant differences. Research done on SARS-CoV has greatly aided the understanding of SARS-CoV-2, as it served as a knowledge base and helped to identify the cell entry receptor and some other features of the disease, but not all of them. Several critical questions remain unanswered and specific therapeutics and vaccine candidates are lacking.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67491194","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}
SARS-CoV-2: Endoscopy procedures at risk of airborne particles transmission.
SARS-CoV-2:有空气传播颗粒风险的内窥镜检查程序。
{"title":"SARS-CoV-2: Endoscopy procedures at risk of airborne particles transmission","authors":"Frossard Jl, F. Negro","doi":"10.15761/jts.1000400","DOIUrl":"https://doi.org/10.15761/jts.1000400","url":null,"abstract":"SARS-CoV-2: Endoscopy procedures at risk of airborne particles transmission.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67491734","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}
O. Equils, K. Lekaj, Sahar Fattani, Arthur W. Wu, Gene C. Liu
Received: May 19, 2020; Accepted: June 04, 2020; Published: June 08, 2020 The common cold is frequently associated with anosmia. A significant portion of COVID-19 patients has been reported to have anosmia and taste dysfunction [1]. A recent study from Germany found that among confirmed COVID-19 patients 47% had anosmia with a mean duration of anosmia of 8.9 days as well as an association with dysgeusia in 85% of cases [2].
{"title":"Proposed mechanism for anosmia during COVID-19: The role of local zinc distribution","authors":"O. Equils, K. Lekaj, Sahar Fattani, Arthur W. Wu, Gene C. Liu","doi":"10.15761/JTS.1000397","DOIUrl":"https://doi.org/10.15761/JTS.1000397","url":null,"abstract":"Received: May 19, 2020; Accepted: June 04, 2020; Published: June 08, 2020 The common cold is frequently associated with anosmia. A significant portion of COVID-19 patients has been reported to have anosmia and taste dysfunction [1]. A recent study from Germany found that among confirmed COVID-19 patients 47% had anosmia with a mean duration of anosmia of 8.9 days as well as an association with dysgeusia in 85% of cases [2].","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67491842","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}
M. Nanayakkara, Ilaria Cimmino, C. Cerchione, V. D'Esposito, F. Oriente, R. Troncone, P. Formisano, M. Barone, R. Valentino
Bisphenol-A (BPA) is an endocrine disruptor found in the majority of plastic components with pro-inflammatory effects on adipose tissue, the immune system and the intestine, the first tissue exposed to the effects of BPA. Humans are chronically exposed to BPA through contaminated food and beverages. The aim of this study was to investigate the effect of a very low dose of BPA (0.1 nM) on intestinal epithelial cells during differentiation, compare it with that of a low dose of BPA (1 nM), and determine the role of probiotics in preventing BPA-induced alterations in intestinal permeability and inflammation. Human colon adenocarcinoma-derived cells (Caco2 cells) were treated with 0.1 nM and 1 nM BPA in the presence of G-1 and G15, a specific GPR30 agonist and antagonist, respectively, and probiotics during differentiation, after which transepithelial electrical resistance (TEER) measurements, confocal fluorescence experiments, real-time RT-PCR and Western blot analysis were carried out. Even at a dose of 0.1 nM, BPA significantly reduced TEER in differentiated Caco2 cells. The increased permeability of the enterocyte monolayer and a reduction in Caco2 cell thickness confirmed the effects of BPA. In addition, BPA induced GPR30 expression and ERK1/2 and NF-κB phosphorylation, especially in the early phase of CaCo2 cell differentiation. However, inhibition of GPR30 by G15 reduced the effect of BPA on ERK1/2 and NF-κB phosphorylation. Interestingly, the supernatant of cells grown with the probiotic LGG could prevent the decrease in TEER, alteration of tight junctions (TJs) and induction of pNF-κB. Very low-dose BPA (0.1 nM) and low-dose BPA (1 nM) induced intestinal inflammation and altered intestinal permeability through a mechanism involving GPR30. Treatment with the probiotic LGG reversed the effects of BPA. *Correspondence to: M. Vittoria Barone, Department of Translational Medicine, Federico II University of Naples & ELFID (European Laboratory for the Investigation of Food Induced Disease), Italy, E-mail: mv.barone@unina.it
{"title":"Inflammation induced by very low-dose bisphenol-a can be prevented by probiotics","authors":"M. Nanayakkara, Ilaria Cimmino, C. Cerchione, V. D'Esposito, F. Oriente, R. Troncone, P. Formisano, M. Barone, R. Valentino","doi":"10.15761/jts.1000403","DOIUrl":"https://doi.org/10.15761/jts.1000403","url":null,"abstract":"Bisphenol-A (BPA) is an endocrine disruptor found in the majority of plastic components with pro-inflammatory effects on adipose tissue, the immune system and the intestine, the first tissue exposed to the effects of BPA. Humans are chronically exposed to BPA through contaminated food and beverages. The aim of this study was to investigate the effect of a very low dose of BPA (0.1 nM) on intestinal epithelial cells during differentiation, compare it with that of a low dose of BPA (1 nM), and determine the role of probiotics in preventing BPA-induced alterations in intestinal permeability and inflammation. Human colon adenocarcinoma-derived cells (Caco2 cells) were treated with 0.1 nM and 1 nM BPA in the presence of G-1 and G15, a specific GPR30 agonist and antagonist, respectively, and probiotics during differentiation, after which transepithelial electrical resistance (TEER) measurements, confocal fluorescence experiments, real-time RT-PCR and Western blot analysis were carried out. Even at a dose of 0.1 nM, BPA significantly reduced TEER in differentiated Caco2 cells. The increased permeability of the enterocyte monolayer and a reduction in Caco2 cell thickness confirmed the effects of BPA. In addition, BPA induced GPR30 expression and ERK1/2 and NF-κB phosphorylation, especially in the early phase of CaCo2 cell differentiation. However, inhibition of GPR30 by G15 reduced the effect of BPA on ERK1/2 and NF-κB phosphorylation. Interestingly, the supernatant of cells grown with the probiotic LGG could prevent the decrease in TEER, alteration of tight junctions (TJs) and induction of pNF-κB. Very low-dose BPA (0.1 nM) and low-dose BPA (1 nM) induced intestinal inflammation and altered intestinal permeability through a mechanism involving GPR30. Treatment with the probiotic LGG reversed the effects of BPA. *Correspondence to: M. Vittoria Barone, Department of Translational Medicine, Federico II University of Naples & ELFID (European Laboratory for the Investigation of Food Induced Disease), Italy, E-mail: mv.barone@unina.it","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67491959","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}
A. GiaiVia, M. Mccarthy, M. Francke, G. Pipino, F. Oliva, A. Mazzocca, N. Maffulli
Introduction: The physiopathology of calcific tendinopathy is largely unknown, but it could be the result of an active cell-mediated process. Many endocrine and metabolic diseases may impair the homeostasis of the tendon, and recent studies focus on the influence of extracellular matrix on the differentiation pathway of mesenchymal stem cells (MSCs). The present study investigates whether hyperglycemia may influence the differentiation of tendon derived-MSCs (TD-MSCs) into an osteoblast lineage. Methods: MSCs were harvested from discarded human tendon excised during arthroscopic rotator cuff repair. The resulting TD-MSCs were counted, plated and grown to confluence in supplemented medium ( α MEM). TD-MSCs were treated with α MEM containing low (5.0 mM), physiological (10 mM) or high (25 mM) glucose, (+) and (-) 10 -10 mM insulin for 0, and 24 hours, 7, 14 and 30 days. Control cells were treated with α MEM. Only quantitative polymerase chain reaction (qPCR) was used to measure changes in gene expression levels specific for fibrocartilage of TD-MSCs (collagen type I-II-III, aggrecan, osteopontin, fibronectin and alkaline phosphatase). Calcium levels were measured after 30 days in culture. Immunohistochemistry staining was used to determine the amount of the specific proteins present in each group tested. Results: There was an increased gene expression of collagen type I, alkaline phosphatase, aggrecan and osteopontin in TD-MSCs supplemented with high glucose compared to other groups (p<0.05). When insulin was added to the α MEM, a higher increase of collagen type I and III was found in TD-MSCs cultured with high dose glucose. The synthesis of alkaline phosphatase and the expression of aggrecan and osteopontin genes were higher in TD-MSCs cultured with high dose glucose and high dose glucose with insulin. After 30 days, calcium content was increased in the high glucose group and in the high glucose medium and insulin. Conclusions: When cultured in a high glucose medium, TD-MSCs express bone markers, and are able to differentiate toward an osteoblast lineage. These results reinforce the concept that calcific tendinopathy may be caused by erroneous differentiation of MSCs in the presence of high levels of serum glucose.
{"title":"Hyperglycemia induces osteogenic differentiation of tendon derived mesenchymal stem cells","authors":"A. GiaiVia, M. Mccarthy, M. Francke, G. Pipino, F. Oliva, A. Mazzocca, N. Maffulli","doi":"10.15761/jts.1000417","DOIUrl":"https://doi.org/10.15761/jts.1000417","url":null,"abstract":"Introduction: The physiopathology of calcific tendinopathy is largely unknown, but it could be the result of an active cell-mediated process. Many endocrine and metabolic diseases may impair the homeostasis of the tendon, and recent studies focus on the influence of extracellular matrix on the differentiation pathway of mesenchymal stem cells (MSCs). The present study investigates whether hyperglycemia may influence the differentiation of tendon derived-MSCs (TD-MSCs) into an osteoblast lineage. Methods: MSCs were harvested from discarded human tendon excised during arthroscopic rotator cuff repair. The resulting TD-MSCs were counted, plated and grown to confluence in supplemented medium ( α MEM). TD-MSCs were treated with α MEM containing low (5.0 mM), physiological (10 mM) or high (25 mM) glucose, (+) and (-) 10 -10 mM insulin for 0, and 24 hours, 7, 14 and 30 days. Control cells were treated with α MEM. Only quantitative polymerase chain reaction (qPCR) was used to measure changes in gene expression levels specific for fibrocartilage of TD-MSCs (collagen type I-II-III, aggrecan, osteopontin, fibronectin and alkaline phosphatase). Calcium levels were measured after 30 days in culture. Immunohistochemistry staining was used to determine the amount of the specific proteins present in each group tested. Results: There was an increased gene expression of collagen type I, alkaline phosphatase, aggrecan and osteopontin in TD-MSCs supplemented with high glucose compared to other groups (p<0.05). When insulin was added to the α MEM, a higher increase of collagen type I and III was found in TD-MSCs cultured with high dose glucose. The synthesis of alkaline phosphatase and the expression of aggrecan and osteopontin genes were higher in TD-MSCs cultured with high dose glucose and high dose glucose with insulin. After 30 days, calcium content was increased in the high glucose group and in the high glucose medium and insulin. Conclusions: When cultured in a high glucose medium, TD-MSCs express bone markers, and are able to differentiate toward an osteoblast lineage. These results reinforce the concept that calcific tendinopathy may be caused by erroneous differentiation of MSCs in the presence of high levels of serum glucose.","PeriodicalId":74000,"journal":{"name":"Journal of translational science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67492371","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}