Pub Date : 2022-11-13eCollection Date: 2022-01-01DOI: 10.1177/11772719221137608
Kannan Sridharan, Mona Al Jufairi, Aamal AbdulGhani Mahdi Hejab, Abdulraoof Al Madhoob, Reem Al Marzooq, Safa Taha, Muna Jaber Mulla Aljishi, Ameera Abdulhadi, Eman Al Ansari, Masooma Abdulla Ali, Maryam Ali Ahmed Naser, Ola Al Segai, Kevin Dunne
Background: Preterm neonates, particularly extremely preterm, are susceptible to respiratory distress syndrome (RDS) due to surfactant deficiency. Single nucleotide polymorphisms (SNPs) in the antioxidant enzymes influence the balance between antioxidant and oxidative stress molecules.
Objectives: To ascertain the role of SNPs of antioxidant enzymes and oxidative stress biomarkers in preterm neonates with RDS.
Design: Observational, cross-sectional study.
Methods: Preterm neonates diagnosed with RDS receiving external surfactant within 24 hours were considered as the cases and those without RDS were the control group. Umbilical cord blood and peripheral blood samples before administering surfactant (day 1), and on days 2 and 3 were collected. Plasma malondialdehyde, 8-hydroxy-2-deoxy guanosine (8-OH-dG), advanced oxidation protein products (AOPP), total antioxidant capacity (TAC), visfatin, reduced glutathione, and chaperonin 60 were evaluated using enzyme-linked immunosorbent assay. SNPs in manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPX1 and GPX3), catalase (CAT), glutathione S-transferase (GSTP1) were evaluated using real-time polymerase-chain-reaction. The receiver-operating characteristics curve was used for predicting the accuracy of biomarkers using the area under the curve (AUC) and 95% confidence intervals (95% CI).
Results: GSTP1, MnSOD, and eNOS (rs1799983) SNPs were observed to significantly influence the oxidative biomarker concentrations in the entire study population. SNPs in GSTP1, MnSOD, and eNOS (rs1799983) were significantly associated with differences in oxidative stress biomarkers. MnSOD (rs4880) significantly increased the risk of pulmonary complications in neonates with RDS. DNA damage product (8-OH-dG) concentrations before surfactant administration has the best predictive accuracy (AUC: 0.8; 95% CI: 0.7-1; P = .001) for pulmonary complications with a cut-off value of 5008.8 pg/mL. TAC concentrations are significantly greater on day 2 and day 3 amongst neonates receiving surfactant compared to the control group. AOPP in the umbilical cord blood was observed to significantly predict the severity of RDS (AUC: 0.8; 95% CI: 0.6-1; P = .01) with an optimal cut-off value of 88.78 µmol/L.
Conclusion: We observed that SNPs in eNOS and MnSOD significantly influence the production of oxidative stress biomarkers in preterm neonates. Baseline 8-OH-dG concentrations best predict the risk of pulmonary complications and AOPP concentrations in the umbilical cord blood predict the risk of RDS severity.
{"title":"Evaluation of Genetic Polymorphisms of the Antioxidant Enzymes and Biomarkers of Oxidative Stress in Preterm Neonates With Respiratory Distress Syndrome Receiving External Surfactant.","authors":"Kannan Sridharan, Mona Al Jufairi, Aamal AbdulGhani Mahdi Hejab, Abdulraoof Al Madhoob, Reem Al Marzooq, Safa Taha, Muna Jaber Mulla Aljishi, Ameera Abdulhadi, Eman Al Ansari, Masooma Abdulla Ali, Maryam Ali Ahmed Naser, Ola Al Segai, Kevin Dunne","doi":"10.1177/11772719221137608","DOIUrl":"https://doi.org/10.1177/11772719221137608","url":null,"abstract":"<p><strong>Background: </strong>Preterm neonates, particularly extremely preterm, are susceptible to respiratory distress syndrome (RDS) due to surfactant deficiency. Single nucleotide polymorphisms (SNPs) in the antioxidant enzymes influence the balance between antioxidant and oxidative stress molecules.</p><p><strong>Objectives: </strong>To ascertain the role of SNPs of antioxidant enzymes and oxidative stress biomarkers in preterm neonates with RDS.</p><p><strong>Design: </strong>Observational, cross-sectional study.</p><p><strong>Methods: </strong>Preterm neonates diagnosed with RDS receiving external surfactant within 24 hours were considered as the cases and those without RDS were the control group. Umbilical cord blood and peripheral blood samples before administering surfactant (day 1), and on days 2 and 3 were collected. Plasma malondialdehyde, 8-hydroxy-2-deoxy guanosine (8-OH-dG), advanced oxidation protein products (AOPP), total antioxidant capacity (TAC), visfatin, reduced glutathione, and chaperonin 60 were evaluated using enzyme-linked immunosorbent assay. SNPs in manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPX1 and GPX3), catalase (CAT), glutathione S-transferase (GSTP1) were evaluated using real-time polymerase-chain-reaction. The receiver-operating characteristics curve was used for predicting the accuracy of biomarkers using the area under the curve (AUC) and 95% confidence intervals (95% CI).</p><p><strong>Results: </strong>GSTP1, MnSOD, and eNOS (rs1799983) SNPs were observed to significantly influence the oxidative biomarker concentrations in the entire study population. SNPs in <i>GSTP1</i>, <i>MnSOD</i>, and <i>eNOS</i> (rs1799983) were significantly associated with differences in oxidative stress biomarkers. <i>MnSOD</i> (rs4880) significantly increased the risk of pulmonary complications in neonates with RDS. DNA damage product (8-OH-dG) concentrations before surfactant administration has the best predictive accuracy (AUC: 0.8; 95% CI: 0.7-1; <i>P</i> = .001) for pulmonary complications with a cut-off value of 5008.8 pg/mL. TAC concentrations are significantly greater on day 2 and day 3 amongst neonates receiving surfactant compared to the control group. AOPP in the umbilical cord blood was observed to significantly predict the severity of RDS (AUC: 0.8; 95% CI: 0.6-1; <i>P</i> = .01) with an optimal cut-off value of 88.78 µmol/L.</p><p><strong>Conclusion: </strong>We observed that SNPs in <i>eNOS</i> and <i>MnSOD</i> significantly influence the production of oxidative stress biomarkers in preterm neonates. Baseline 8-OH-dG concentrations best predict the risk of pulmonary complications and AOPP concentrations in the umbilical cord blood predict the risk of RDS severity.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ab/52/10.1177_11772719221137608.PMC9663612.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40689826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-β1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19.
Methods: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-β1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed.
Results: Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, P = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis.
Conclusions: Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-β1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.
背景:肺损伤和间质纤维化的生物标志物有助于了解众所周知的间质性肺疾病(ILD)的受累程度和预后。血清Krebs von den Lungen-6 (KL-6)反映肺泡直接损伤,转化生长因子-β1 (TGF-β1)和成纤维细胞生长因子-2 (FGF-2)是ILD和几乎所有纤维化疾病纤维化的主要介质。从这个意义上说,我们旨在评估这些生物标志物与传统炎症标志物和COVID-19临床病程的相关性。方法:纳入经SARS-CoV-2核酸RT-PCR确诊的COVID-19患者,在确诊后1个月采用标准化方法进行前瞻性随访。根据美国国立卫生研究院的标准,将患者分为重症组和非重症组。结果评估重症监护病房(ICU)入院需求、长期呼吸支持和死亡。入组时采集血样,ELISA法检测血清中KL-6、TGF-β1、FGF-2水平。分析这些指标与其他预后指标及预后的关系。结果:共纳入31例重症和28例非重症COVID-19患者,并与健康对照组(n = 30)进行比较。COVID-19患者血清KL-6水平显著升高(中位数[IQR];11.54 [4.86] vs 8.54 [3.98] ng/mL, P = .001], FGF-2水平较低(中位数[IQR];76.84 [98.2] vs 101.62 [210.6] pg/mL)。KL-6值与CRP、纤维蛋白原、d-二聚体和淋巴细胞计数有显著相关性。然而,我们没有发现这些标志物与随后的COVID-19严重程度、死亡率和长期预后之间的关联。结论:血清KL-6水平在COVID-19诊断时显著升高,并与其他传统预后炎症指标有良好的相关性。血清主要纤维化介质TGF-β1、FGF-2在COVID-19诊断时未升高,因此无助于预测长期预后。
{"title":"The Prognostic Value of Lung Injury and Fibrosis Markers, KL-6, TGF-β1, FGF-2 in COVID-19 Patients.","authors":"Hazan Karadeniz, Aslıhan Avanoğlu Güler, Hasan Selçuk Özger, Pınar Aysert Yıldız, Gonca Erbaş, Gülendam Bozdayı, Tuba Deveci Bulut, Özlem Gülbahar, Dilek Yapar, Hamit Küçük, Mehmet Akif Öztürk, Abdurrahman Tufan","doi":"10.1177/11772719221135443","DOIUrl":"https://doi.org/10.1177/11772719221135443","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers of lung injury and interstitial fibrosis give insight about the extent of involvement and prognosis in well-known interstitial lung diseases (ILD). Serum Krebs von den Lungen-6 (KL-6) reflects direct alveolar injury and, transforming growth factor-beta1 (TGF-β1) and fibroblast growth factor-2 (FGF-2) are principal mediators of fibrosis in ILD and in almost all fibrotic diseases. In this sense, we aimed to assess associations of these biomarkers with traditional inflammatory markers and clinical course of COVID-19.</p><p><strong>Methods: </strong>Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled and followed up prospectively with a standardized approach one month after diagnosis. Patients were divided into severe and non-severe groups according to National Institutes of Health criteria. Outcome was assessed for the requirement of intensive care unit (ICU) admission, long term respiratory support and death. Blood samples were collected at enrollment and serum levels of KL-6, TGF-β1, FGF-2 were determined by ELISA. Association between these markers with other prognostic markers and prognosis were analyzed.</p><p><strong>Results: </strong>Overall 31 severe and 28 non-severe COVID-19 patients were enrolled and were compared with healthy control subjects (n = 30). Serum KL-6 levels in COVID-19 patients were significantly higher (median [IQR]; 11.54 [4.86] vs 8.54 [3.98] ng/mL, <i>P</i> = .001] and FGF-2 levels were lower (median [IQR]; 76.84 [98.2] vs 101.62 [210.6] pg/mL) compared to healthy control group. A significant correlation was found between KL-6 values and CRP, fibrinogen, d-dimer and lymphocyte counts. However, we did not find an association between these markers and subsequent severity of COVID-19, mortality and long-term prognosis.</p><p><strong>Conclusions: </strong>Serum KL-6 levels were significantly elevated at the diagnosis of COVID-19 and correlated well with the other traditional prognostic inflammatory markers. Serum levels of principal fibrosis mediators, TGF-β1, FGF-2, were not elevated at diagnosis of COVID-19, therefore did not help to anticipate long term prognosis.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/6c/10.1177_11772719221135443.PMC9643117.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40687245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-31eCollection Date: 2022-01-01DOI: 10.1177/11772719221132693
Jennifer Crow, Glenson Samuel, Emily Farrow, Margaret Gibson, Jefferey Johnston, Erin Guest, Neil Miller, Dong Pei, Devin Koestler, Harsh Pathak, Xiaobo Liang, Cooper Mangels, Andrew K Godwin
Objective: Ewing Sarcoma Family of Tumors (ESFT) are a highly aggressive pediatric bone and soft tissue malignancy with poor outcomes in the refractory and recurrent setting. Over 90% of Ewing Sarcoma (ES) tumors are driven by the pathognomonic EWS-ETS chimeric transcripts and their corresponding oncoproteins. It has been suggested that the EWS-ETS oncogenic action can mediate microRNA (miRNA) processing. Importantly, small extracellular vesicles (sEVs), including those frequently referred to as exosomes have been shown to be highly enriched with tumor-derived small RNAs such as miRNAs. We hypothesized that ESFT-specific sEVs are enriched with certain miRNAs which could be utilized toward an exo-miRNA biomarker signature specific to this disease. Methods: We performed miRNAseq to compare both the exo-derived and cell-derived miRNA content from 8 ESFT, 2 osteosarcoma, 2 non-cancerous cell lines, and pediatric plasma samples. Results: We found that sEVs derived from ESFT cells contained nearly 2-fold more number of unique individual miRNAs as compared to non-ESFT samples. Quantitative analysis of the differential enrichment of sEV miRNAs resulted in the identification of 62 sEV-miRNAs (exo-miRNAs) with significant (P < .05) enrichment variation between ESFT and non-ESFT sEV samples. To determine if we could utilize this miRNA signature to diagnose ESFT patients via a liquid biopsy, we analyzed the RNA content of total circulating sEVs isolated from 500 µL plasma from 5 pediatric ESFT patients, 2 pediatric osteosarcoma patients, 2 pediatric rhabdomyosarcoma patients, and 4 non-cancer pediatric controls. Pearson's clustering of 60 of the 62 candidate exo-miRNAs correctly identified 80% (4 of 5) of pathology confirmed ESFT patients. Importantly, RNAseq analysis of tumor tissue from the 1 outlier, revealed a previously uncharacterized EWS-FLI1 translocation.Conclusions: Taken together, these findings support the development and validation of an exo-miRNA-based liquid biopsy to aid in the diagnosis and monitoring of ESFT.
{"title":"MicroRNA Content of Ewing Sarcoma Derived Extracellular Vesicles Leads to Biomarker Potential and Identification of a Previously Undocumented EWS-FLI1 Translocation.","authors":"Jennifer Crow, Glenson Samuel, Emily Farrow, Margaret Gibson, Jefferey Johnston, Erin Guest, Neil Miller, Dong Pei, Devin Koestler, Harsh Pathak, Xiaobo Liang, Cooper Mangels, Andrew K Godwin","doi":"10.1177/11772719221132693","DOIUrl":"10.1177/11772719221132693","url":null,"abstract":"<p><p><b>Objective:</b> Ewing Sarcoma Family of Tumors (ESFT) are a highly aggressive pediatric bone and soft tissue malignancy with poor outcomes in the refractory and recurrent setting. Over 90% of Ewing Sarcoma (ES) tumors are driven by the pathognomonic <i>EWS-ETS</i> chimeric transcripts and their corresponding oncoproteins. It has been suggested that the EWS-ETS oncogenic action can mediate microRNA (miRNA) processing. Importantly, small extracellular vesicles (sEVs), including those frequently referred to as exosomes have been shown to be highly enriched with tumor-derived small RNAs such as miRNAs. We hypothesized that ESFT-specific sEVs are enriched with certain miRNAs which could be utilized toward an exo-miRNA biomarker signature specific to this disease. <b>Methods:</b> We performed miRNAseq to compare both the exo-derived and cell-derived miRNA content from 8 ESFT, 2 osteosarcoma, 2 non-cancerous cell lines, and pediatric plasma samples. <b>Results:</b> We found that sEVs derived from ESFT cells contained nearly 2-fold more number of unique individual miRNAs as compared to non-ESFT samples. Quantitative analysis of the differential enrichment of sEV miRNAs resulted in the identification of 62 sEV-miRNAs (exo-miRNAs) with significant (<i>P</i> < .05) enrichment variation between ESFT and non-ESFT sEV samples. To determine if we could utilize this miRNA signature to diagnose ESFT patients via a liquid biopsy, we analyzed the RNA content of total circulating sEVs isolated from 500 µL plasma from 5 pediatric ESFT patients, 2 pediatric osteosarcoma patients, 2 pediatric rhabdomyosarcoma patients, and 4 non-cancer pediatric controls. Pearson's clustering of 60 of the 62 candidate exo-miRNAs correctly identified 80% (4 of 5) of pathology confirmed ESFT patients. Importantly, RNAseq analysis of tumor tissue from the 1 outlier, revealed a previously uncharacterized <i>EWS-FLI1</i> translocation.<b>Conclusions:</b> Taken together, these findings support the development and validation of an exo-miRNA-based liquid biopsy to aid in the diagnosis and monitoring of ESFT.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/25/c8/10.1177_11772719221132693.PMC9629554.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40449707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Extracellular vesicles (EV) released from neurons into the blood can reflect the state of nervous tissue. Measurement of neuron derived EV (NDE) may serve as an indicator of brain injury.
Methods: A sandwich immunoassay was established to measure plasma NDE using anti-neuron CD171 and anti-EV CD9 ([CD171 + CD9+]). Plasma samples were obtained from commercial sources, cross-country (n = 9), football (n = 22), soccer (n = 19), and rugby (n = 18) athletes over time. Plasma was also collected from patients undergoing total aortic arch replacement (TAR) with selective cerebral perfusion during cardiopulmonary bypass before and after surgery (n = 36).
Results: The specificity, linearity, and reproducibility of NDE assay (measurement of [CD171 + CD9+]) were confirmed. By scanning electron microscopy and nanoparticle tracking, spherical vesicles ranging in size from 150 to 300 nm were confirmed. Plasma levels of NDE were widely spread over 2 to 3 logs in different individuals with a significant age-dependent decrease. However, NDE were very stable in each individual within a ± 50% change over time (cross-country, football, soccer), whereas rugby players were more variable over 4 years. In patients undergoing TAR, NDE increased rapidly in days post-surgery and were significantly (P = .0004) higher in those developing postoperative delirium (POD) (n = 13) than non-delirium patients (n = 23).
Conclusions: The blood test to determine plasma levels of NDE was established by a sandwich immunoassay using 2 antibodies against neuron (CD171) and exosomes (CD9). NDE levels varied widely in different individuals and decreased with age, indicating that NDE levels should be considered as a normalizer of NDE biomarker studies. However, NDE levels were stable over time in each individual, and increased rapidly after TAR with greater increases associated with patients developing POD. This assay may serve as a surrogate for evaluating and monitoring brain injuries.
{"title":"Monitoring of Post-Brain Injuries By Measuring Plasma Levels of Neuron-Derived Extracellular Vesicles.","authors":"Naoshi Hotta, Takahiro Tadokoro, John Henry, Daisuke Koga, Keisuke Kawata, Hiroyuki Ishida, Yuko Oguma, Akihiro Hirata, Masato Mitsuhashi, Kenji Yoshitani","doi":"10.1177/11772719221128145","DOIUrl":"https://doi.org/10.1177/11772719221128145","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EV) released from neurons into the blood can reflect the state of nervous tissue. Measurement of neuron derived EV (NDE) may serve as an indicator of brain injury.</p><p><strong>Methods: </strong>A sandwich immunoassay was established to measure plasma NDE using anti-neuron CD171 and anti-EV CD9 ([CD171 <sup>+</sup> CD9<sup>+</sup>]). Plasma samples were obtained from commercial sources, cross-country (n = 9), football (n = 22), soccer (n = 19), and rugby (n = 18) athletes over time. Plasma was also collected from patients undergoing total aortic arch replacement (TAR) with selective cerebral perfusion during cardiopulmonary bypass before and after surgery (n = 36).</p><p><strong>Results: </strong>The specificity, linearity, and reproducibility of NDE assay (measurement of [CD171 <sup>+</sup> CD9<sup>+</sup>]) were confirmed. By scanning electron microscopy and nanoparticle tracking, spherical vesicles ranging in size from 150 to 300 nm were confirmed. Plasma levels of NDE were widely spread over 2 to 3 logs in different individuals with a significant age-dependent decrease. However, NDE were very stable in each individual within <i>a</i> ± 50% change over time (cross-country, football, soccer), whereas rugby players were more variable over 4 years. In patients undergoing TAR, NDE increased rapidly in days post-surgery and were significantly (<i>P</i> = .0004) higher in those developing postoperative delirium (POD) (n = 13) than non-delirium patients (n = 23).</p><p><strong>Conclusions: </strong>The blood test to determine plasma levels of NDE was established by a sandwich immunoassay using 2 antibodies against neuron (CD171) and exosomes (CD9). NDE levels varied widely in different individuals and decreased with age, indicating that NDE levels should be considered as a normalizer of NDE biomarker studies. However, NDE levels were stable over time in each individual, and increased rapidly after TAR with greater increases associated with patients developing POD. This assay may serve as a surrogate for evaluating and monitoring brain injuries.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0f/53/10.1177_11772719221128145.PMC9618756.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40662051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-22eCollection Date: 2022-01-01DOI: 10.1177/11772719221131470
Renata Valente Lisboa, Fabiola Reis de Oliveira, Thaise Oliveira Quaresma, Rafael Moura de Almeida, Rene Donizeti Ribeiro Oliveira, Paulo Louzada Junior
Background: Systemic lupus erythematosus (SLE) is a chronic, multi phenotypic, autoimmune inflammatory disease and renal involvement significantly worsens its prognosis. Apoptosis dysregulation plays a key pathogenic role. Survivin, a protein from the apoptosis inhibitors family, has been considered a promising strategy in cancer therapy and evaluated as one of the regulatory pathways in the scenario of immune-mediated disorders.
Objective: This study aims to explore survivin behaviour in SLE patients with lupus nephritis (LN), assessing its potential as a therapeutic and prognostic biomarker.
Methods: 297 SLE patients were classified based on the American College of Rheumatology (ACR) 1997 criteria, from 2000 to 2015. In a cross-sectional study, the serum level of survivin was measured by an ELISA test and compared between 200 SLE individuals and healthy controls. In a longitudinal cohort, 97 patients with active LN had the concentration of survinin measured, before and after treatment with cyclophosphamide pulse therapy.
Results: The serum concentration of survivin was significantly lower in the SLE group than in healthy controls, regardless of concomitant NL or disease activity. The longitudinal evaluation revealed a significant reduction in survivin serum level after treatment. However, survivin rates were not able to discriminate groups that achieved remission from those that maintained nephritis activity.
Conclusion: Our study suggests that survivin levels in SLE patients are lower than in the general population. Even so, its use as a biomarker in SLE seems limited, not reflecting disease activity or response to LN treatment, as in other contexts.
背景:系统性红斑狼疮(SLE)是一种慢性、多表型、自身免疫性炎症性疾病,累及肾脏会显著恶化其预后。细胞凋亡失调在发病中起关键作用。Survivin是细胞凋亡抑制剂家族的一种蛋白,被认为是一种很有前途的癌症治疗策略,并被评估为免疫介导性疾病的调节途径之一。目的:本研究旨在探讨SLE合并狼疮肾炎(LN)患者的生存行为,评估其作为治疗和预后生物标志物的潜力。方法:根据美国风湿病学会(American College of Rheumatology, ACR) 1997标准对2000 - 2015年297例SLE患者进行分类。在一项横断面研究中,通过ELISA测试测定了200例SLE患者和健康对照者的血清survivin水平。在纵向队列中,97例活动性LN患者在环磷酰胺脉冲治疗前后测量了生存素浓度。结果:SLE组血清survivin浓度明显低于健康对照组,无论是否伴有NL或疾病活动。纵向评估显示治疗后血清survivin水平显著降低。然而,生存率不能区分获得缓解的组和维持肾炎活动的组。结论:我们的研究表明SLE患者的survivin水平低于一般人群。即便如此,它作为SLE生物标志物的用途似乎有限,不能像在其他情况下那样反映疾病活动性或对LN治疗的反应。
{"title":"The Behaviour of Serum Survivin in Patients With Lupus Nephritis.","authors":"Renata Valente Lisboa, Fabiola Reis de Oliveira, Thaise Oliveira Quaresma, Rafael Moura de Almeida, Rene Donizeti Ribeiro Oliveira, Paulo Louzada Junior","doi":"10.1177/11772719221131470","DOIUrl":"https://doi.org/10.1177/11772719221131470","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a chronic, multi phenotypic, autoimmune inflammatory disease and renal involvement significantly worsens its prognosis. Apoptosis dysregulation plays a key pathogenic role. Survivin, a protein from the apoptosis inhibitors family, has been considered a promising strategy in cancer therapy and evaluated as one of the regulatory pathways in the scenario of immune-mediated disorders.</p><p><strong>Objective: </strong>This study aims to explore survivin behaviour in SLE patients with lupus nephritis (LN), assessing its potential as a therapeutic and prognostic biomarker.</p><p><strong>Methods: </strong>297 SLE patients were classified based on the American College of Rheumatology (ACR) 1997 criteria, from 2000 to 2015. In a cross-sectional study, the serum level of survivin was measured by an ELISA test and compared between 200 SLE individuals and healthy controls. In a longitudinal cohort, 97 patients with active LN had the concentration of survinin measured, before and after treatment with cyclophosphamide pulse therapy.</p><p><strong>Results: </strong>The serum concentration of survivin was significantly lower in the SLE group than in healthy controls, regardless of concomitant NL or disease activity. The longitudinal evaluation revealed a significant reduction in survivin serum level after treatment. However, survivin rates were not able to discriminate groups that achieved remission from those that maintained nephritis activity.</p><p><strong>Conclusion: </strong>Our study suggests that survivin levels in SLE patients are lower than in the general population. Even so, its use as a biomarker in SLE seems limited, not reflecting disease activity or response to LN treatment, as in other contexts.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/ea/10.1177_11772719221131470.PMC9597205.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40656300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-18eCollection Date: 2022-01-01DOI: 10.1177/11772719221130719
Ekow Mensah, Khalid Ali, Winston Banya, Frances Ann Kirkham, Manuela Mengozzi, Pietro Ghezzi, Chakravarthi Rajkumar
Objective: There is an association between frailty and arterial stiffness. However, arterial stiffness does not uniformly correlate with the spectrum of frailty states. Both oxidative stress and inflammaging contribute to vascular ageing. There are no human studies exploring links between arterial stiffness, oxidative stress, inflammaging and frailty. Our objective is to investigate arterial stiffness and inflammaging as predictors of frailty states.
Methods: An observational longitudinal cohort study will be used to examine the association between arterial stiffness, oxidative stress and inflammation in 50 older adults (⩾70 years) with clinical frailty scores (CFS) ⩽6 over 6 months. All study measurements will be taken at baseline. Frailty assessment will include hand-grip strength, timed-up and go test, mini-mental state examination, geriatric depression scale and sarcopenia using body composition measurements with Tanita®. Arterial stiffness measurements will include carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV) using Complior (Alam Medical, France). CAVI device will measure Cardio-ankle vascular index and ankle brachial index (ABI). Oxidative stress blood markers nitrotyrosine (NT) and 8-hydroxy-2'-deoxyguanosin (8-oxo-dG) and inflammation markers high-sensitive C-reactive protein (hs-CRP) and interlukin-6(IL-6) will be measured at baseline and 6 month along with lipid profile and glycated haemoglobin.
Results data analysis plan: Descriptive statistics for continuous data using means and standard deviations for normality distributed variables or medians and inter-quartile ranges for skewed variables will be used. Participants will be categorised into CFS 1-3, and CFS 4-6. Categorical data will use frequencies and comparison between groups. Change in frailty between the groups over 6 months will be compared using paired t-test. Simple linear regression will be done between frailty measures, arterial stiffness, inflammation and oxidative stress biomarkers. Significance will be at P < .05.
Conclusion: This study data will inform a larger, multi-centre study exploring further the interplay between frailty, biomarkers and arterial stiffness parameters.
{"title":"FRailty and Arterial stiffness - the role of oXidative stress and Inflammation (FRAXI study).","authors":"Ekow Mensah, Khalid Ali, Winston Banya, Frances Ann Kirkham, Manuela Mengozzi, Pietro Ghezzi, Chakravarthi Rajkumar","doi":"10.1177/11772719221130719","DOIUrl":"https://doi.org/10.1177/11772719221130719","url":null,"abstract":"<p><strong>Objective: </strong>There is an association between frailty and arterial stiffness. However, arterial stiffness does not uniformly correlate with the spectrum of frailty states. Both oxidative stress and inflammaging contribute to vascular ageing. There are no human studies exploring links between arterial stiffness, oxidative stress, inflammaging and frailty. Our objective is to investigate arterial stiffness and inflammaging as predictors of frailty states.</p><p><strong>Methods: </strong>An observational longitudinal cohort study will be used to examine the association between arterial stiffness, oxidative stress and inflammation in 50 older adults (⩾70 years) with clinical frailty scores (CFS) ⩽6 over 6 months. All study measurements will be taken at baseline. Frailty assessment will include hand-grip strength, timed-up and go test, mini-mental state examination, geriatric depression scale and sarcopenia using body composition measurements with Tanita<sup>®</sup>. Arterial stiffness measurements will include carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV) using Complior (Alam Medical, France). CAVI device will measure Cardio-ankle vascular index and ankle brachial index (ABI). Oxidative stress blood markers nitrotyrosine (NT) and 8-hydroxy-2'-deoxyguanosin (8-oxo-dG) and inflammation markers high-sensitive C-reactive protein (hs-CRP) and interlukin-6(IL-6) will be measured at baseline and 6 month along with lipid profile and glycated haemoglobin.</p><p><strong>Results data analysis plan: </strong>Descriptive statistics for continuous data using means and standard deviations for normality distributed variables or medians and inter-quartile ranges for skewed variables will be used. Participants will be categorised into CFS 1-3, and CFS 4-6. Categorical data will use frequencies and comparison between groups. Change in frailty between the groups over 6 months will be compared using paired t-test. Simple linear regression will be done between frailty measures, arterial stiffness, inflammation and oxidative stress biomarkers. Significance will be at <i>P</i> < .05.</p><p><strong>Conclusion: </strong>This study data will inform a larger, multi-centre study exploring further the interplay between frailty, biomarkers and arterial stiffness parameters.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40581454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-21eCollection Date: 2022-01-01DOI: 10.1177/11772719221125123
Amjad Bani Hani, Nafez Abu Tarboush, Mo'ath Bani Ali, Fahad Alabhoul, Fahad Alansari, Ahmad Abuhani, Mustafa Al-Kawak, Badea'a Shamoun, Suzan Albdour, Mahmoud Abu Abeeleh, Mamoun Ahram
Objectives: Angiotensin-converting enzyme 2 (ACE2) represents the primary receptor for SARS-CoV-2 to enter endothelial cells, causing coronavirus disease of 2019 (COVID-19). In this study, we investigate the association between circulating ACE2 levels with the severity of COVID-19.
Methods: Serum ACE2 levels were measured in 144 COVID-19-positive subjects at hospital admission, and 123 COVID-19-negative control subjects. The association between ACE2 and clinical outcomes was analyzed.
Results: About 144 COVID-19 patients and 123 healthy controls data were analyzed, the mean age of patients was 62 years and 50% of them were males. The mean age of the control group was 55 years and 63% were males. ACE-II level was measured and compared between COVID-19 patients and controls and revealed no significant differences (P > .05). ACE-II level was measured in COVID-19 patients and compared between different patient's subgroups, ACE II level was not dependent on gender, smoking, ACE intake, or comorbidities (P > .05), and was significantly correlated with cardiovascular diseases (CVS) (P-value = .046) ICU admission (P-value = .0007) and Death (P-value = .0082).
Conclusion: There was no significant difference between the COVID-19 and Control group, however, ACE2 serum level was significantly higher in patients with COVID-19 who were critically ill or non-survivors, its increased level is also associated with length of stay. Elevated ACE2 level is associated with the severity of COVID-19 disease, and it has the potential to be a predictor of the severity of the disease.
{"title":"Serum ACE2 Level is Associated With Severe SARS-CoV-2 Infection: A Cross-Sectional Observational Study.","authors":"Amjad Bani Hani, Nafez Abu Tarboush, Mo'ath Bani Ali, Fahad Alabhoul, Fahad Alansari, Ahmad Abuhani, Mustafa Al-Kawak, Badea'a Shamoun, Suzan Albdour, Mahmoud Abu Abeeleh, Mamoun Ahram","doi":"10.1177/11772719221125123","DOIUrl":"https://doi.org/10.1177/11772719221125123","url":null,"abstract":"<p><strong>Objectives: </strong>Angiotensin-converting enzyme 2 (ACE2) represents the primary receptor for SARS-CoV-2 to enter endothelial cells, causing coronavirus disease of 2019 (COVID-19). In this study, we investigate the association between circulating ACE2 levels with the severity of COVID-19.</p><p><strong>Methods: </strong>Serum ACE2 levels were measured in 144 COVID-19-positive subjects at hospital admission, and 123 COVID-19-negative control subjects. The association between ACE2 and clinical outcomes was analyzed.</p><p><strong>Results: </strong>About 144 COVID-19 patients and 123 healthy controls data were analyzed, the mean age of patients was 62 years and 50% of them were males. The mean age of the control group was 55 years and 63% were males. ACE-II level was measured and compared between COVID-19 patients and controls and revealed no significant differences (<i>P</i> > .05). ACE-II level was measured in COVID-19 patients and compared between different patient's subgroups, ACE II level was not dependent on gender, smoking, ACE intake, or comorbidities (<i>P</i> > .05), and was significantly correlated with cardiovascular diseases (CVS) (<i>P</i>-value = .046) ICU admission (<i>P</i>-value = .0007) and Death (<i>P</i>-value = .0082).</p><p><strong>Conclusion: </strong>There was no significant difference between the COVID-19 and Control group, however, ACE2 serum level was significantly higher in patients with COVID-19 who were critically ill or non-survivors, its increased level is also associated with length of stay. Elevated ACE2 level is associated with the severity of COVID-19 disease, and it has the potential to be a predictor of the severity of the disease.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/e9/10.1177_11772719221125123.PMC9500304.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33481564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-12eCollection Date: 2022-01-01DOI: 10.1177/11772719221123913
Oula Nasrallah, Samar Alzeer
Objective: Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder whose cause remains unknown. Oxidative stress is one of the possible causes of many disorders, including neurological ones. This study aims to measure some oxidative stress biomarkers (Malondialdehyde "MDA," Advanced Oxidation Protein Product "AOPP," Glutathione "GSH") within Syrian children with ASD.
Methods: MDA, AOPP & GSH were measured in the plasma of a total of 60 children. The ages of the children ranged from 1 to 13 years old. Thirty children had ASD and were compared with 30 controls that don't have ASD. Fifteen of the controls were siblings of an ASD child, while the remaining 15 had no relations with ASD.
Results: MDA and AOPP plasma levels were higher in ASD children compared with non-related controls (P = .0001). However, there were no significant differences between MDA and AOPP plasma levels in ASD children in comparison with related controls (P > .05). Alternatively, GSH plasma levels were lower in ASD children compared with both related and non-related controls (P = .0001).
Conclusion: Further studies are needed to investigate more regarding the diagnostic use of oxidative stress biomarkers, and the therapeutic use of antioxidants in children affected with the autism spectrum disorder.
{"title":"Measuring Some Oxidative Stress Biomarkers in Autistic Syrian Children and Their Siblings: A Case-Control Study.","authors":"Oula Nasrallah, Samar Alzeer","doi":"10.1177/11772719221123913","DOIUrl":"https://doi.org/10.1177/11772719221123913","url":null,"abstract":"<p><strong>Objective: </strong>Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder whose cause remains unknown. Oxidative stress is one of the possible causes of many disorders, including neurological ones. This study aims to measure some oxidative stress biomarkers (Malondialdehyde \"MDA,\" Advanced Oxidation Protein Product \"AOPP,\" Glutathione \"GSH\") within Syrian children with ASD.</p><p><strong>Methods: </strong>MDA, AOPP & GSH were measured in the plasma of a total of 60 children. The ages of the children ranged from 1 to 13 years old. Thirty children had ASD and were compared with 30 controls that don't have ASD. Fifteen of the controls were siblings of an ASD child, while the remaining 15 had no relations with ASD.</p><p><strong>Results: </strong>MDA and AOPP plasma levels were higher in ASD children compared with non-related controls (<i>P</i> = .0001). However, there were no significant differences between MDA and AOPP plasma levels in ASD children in comparison with related controls (<i>P</i> > .05). Alternatively, GSH plasma levels were lower in ASD children compared with both related and non-related controls (<i>P</i> = .0001).</p><p><strong>Conclusion: </strong>Further studies are needed to investigate more regarding the diagnostic use of oxidative stress biomarkers, and the therapeutic use of antioxidants in children affected with the autism spectrum disorder.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/5c/10.1177_11772719221123913.PMC9476242.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40368002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-11eCollection Date: 2022-01-01DOI: 10.1177/11772719221118868
E Melinda Mahabee-Gittens, Georg E Matt, Ashley L Merianos
High levels of NNAL, the tobacco smoke exposure (TSE) biomarker of the carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), indicate future cancer risk. A prior study of smokers' children revealed NNAL levels as high as active smokers. Therefore, we conducted a case series to examine the sociodemographics, TSE and clinical patterns, and other TSE biomarker levels in 9 children with extreme NNAL levels of >200 pg/ml to generate hypotheses and explore potential causes and implications. We identified 0 to 4-year-olds who presented to an emergency setting and lived with ⩾1 smoker who were part of a parental tobacco cessation trial (n = 461). Of these children, 52 had urinary NNAL, cotinine, and N-oxides results (n = 52). Nine children (17.3%) had NNAL levels >200 pg/ml, ranging from 206.4 to 1399.0 pg/ml (Median (Mdn) = 489.2 pg/ml; Interquartile Range (IQR) = 222.7-1289.3 pg/ml). The cotinine Mdn (IQR) was 38.5 (10.3-102.2) ng/ml and the N-oxides Mdn (IQR) = 93.8 (24.7-109.6) pg/ml. While all biomarker levels were alarmingly high, these young children would not have been flagged for very high cancer risk based on urinary cotinine levels alone. This underscores the critical role of comprehensive TSE biomarker measurement in capturing different TSE exposure patterns and assessing children's future risk for cancer and other TSE-related morbidities.
{"title":"High Levels of the Carcinogenic Tobacco-Specific Nitrosamine NNAL and Associated Findings in Children of Smokers: A Case Series.","authors":"E Melinda Mahabee-Gittens, Georg E Matt, Ashley L Merianos","doi":"10.1177/11772719221118868","DOIUrl":"10.1177/11772719221118868","url":null,"abstract":"<p><p>High levels of NNAL, the tobacco smoke exposure (TSE) biomarker of the carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), indicate future cancer risk. A prior study of smokers' children revealed NNAL levels as high as active smokers. Therefore, we conducted a case series to examine the sociodemographics, TSE and clinical patterns, and other TSE biomarker levels in 9 children with extreme NNAL levels of >200 pg/ml to generate hypotheses and explore potential causes and implications. We identified 0 to 4-year-olds who presented to an emergency setting and lived with ⩾1 smoker who were part of a parental tobacco cessation trial (n = 461). Of these children, 52 had urinary NNAL, cotinine, and N-oxides results (n = 52). Nine children (17.3%) had NNAL levels >200 pg/ml, ranging from 206.4 to 1399.0 pg/ml (Median (Mdn) = 489.2 pg/ml; Interquartile Range (IQR) = 222.7-1289.3 pg/ml). The cotinine Mdn (IQR) was 38.5 (10.3-102.2) ng/ml and the N-oxides Mdn (IQR) = 93.8 (24.7-109.6) pg/ml. While all biomarker levels were alarmingly high, these young children would not have been flagged for very high cancer risk based on urinary cotinine levels alone. This underscores the critical role of comprehensive TSE biomarker measurement in capturing different TSE exposure patterns and assessing children's future risk for cancer and other TSE-related morbidities.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2022-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/e3/10.1177_11772719221118868.PMC9379955.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40707662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-07-14eCollection Date: 2022-01-01DOI: 10.1177/11772719221111882
István Pócsi, Mark E Dockrell, Robert G Price
Environmental and occupational exposure to heavy metals and metalloids is a major global health risk. The kidney is often a site of early damage. Nephrotoxicity is both a major consequence of heavy metal exposure and potentially an early warning of greater damage. A paradigm shift occurred at the beginning of the 21st century in the field of renal medicine. The medical model of kidney failure and treatment began to give way to a social model of risk factors and prevention with important implications for environmental health. This development threw into focus the need for better biomarkers: markers of exposure to known nephrotoxins; markers of early damage for diagnosis and prevention; markers of disease development for intervention and choice of therapy. Constituents of electronic waste, e-waste or e-pollution, such as cadmium (Cd), lead (Pb), mercury (HG), arsenic (As) and silica (SiO2) are all potential nephrotoxins; they target the renal proximal tubules through distinct pathways. Different nephrotoxic biomarkers offer the possibility of identifying exposure to individual pollutants. In this review, a selection of prominent urinary markers of tubule damage is considered as potential tools for identifying environmental exposure to some key metallic pollutants.
{"title":"Nephrotoxic Biomarkers with Specific Indications for Metallic Pollutants: Implications for Environmental Health.","authors":"István Pócsi, Mark E Dockrell, Robert G Price","doi":"10.1177/11772719221111882","DOIUrl":"https://doi.org/10.1177/11772719221111882","url":null,"abstract":"<p><p>Environmental and occupational exposure to heavy metals and metalloids is a major global health risk. The kidney is often a site of early damage. Nephrotoxicity is both a major consequence of heavy metal exposure and potentially an early warning of greater damage. A paradigm shift occurred at the beginning of the 21st century in the field of renal medicine. The medical model of kidney failure and treatment began to give way to a social model of risk factors and prevention with important implications for environmental health. This development threw into focus the need for better biomarkers: markers of exposure to known nephrotoxins; markers of early damage for diagnosis and prevention; markers of disease development for intervention and choice of therapy. Constituents of electronic waste, e-waste or e-pollution, such as cadmium (Cd), lead (Pb), mercury (HG), arsenic (As) and silica (SiO<sub>2</sub>) are all potential nephrotoxins; they target the renal proximal tubules through distinct pathways. Different nephrotoxic biomarkers offer the possibility of identifying exposure to individual pollutants. In this review, a selection of prominent urinary markers of tubule damage is considered as potential tools for identifying environmental exposure to some key metallic pollutants.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/90/10.1177_11772719221111882.PMC9290154.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}