BBA clinical最新文献

{"title":"Plasma protein-bound di-tyrosines as biomarkers of oxidative stress in end stage renal disease patients on maintenance haemodialysis","authors":"Graziano Colombo ,&nbsp;Francesco Reggiani ,&nbsp;David Cucchiari ,&nbsp;Nicola M. Portinaro ,&nbsp;Daniela Giustarini ,&nbsp;Ranieri Rossi ,&nbsp;Maria Lisa Garavaglia ,&nbsp;Nicola Saino ,&nbsp;Aldo Milzani ,&nbsp;Salvatore Badalamenti ,&nbsp;Isabella Dalle-Donne","doi":"10.1016/j.bbacli.2016.12.004","DOIUrl":"10.1016/j.bbacli.2016.12.004","url":null,"abstract":"<div><h3>Background</h3><p>Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) experience enhanced oxidative stress and systemic inflammation, which are risk factors for cardiovascular disease, the most common cause of excess morbidity and mortality for these patients. Different pathways producing different types of oxidative stress occur in ESRD. The purpose of our study was to determine the effect of HD on plasma levels of protein-bound dityrosine (di-Tyr), a biomarker of protein oxidation.</p></div><div><h3>Methods</h3><p>Protein-bound di-Tyr formation was measured by size exclusion HPLC coupled to fluorescence detector. Clinical laboratory parameters were measured by standardized methods.</p></div><div><h3>Results</h3><p>In most ESRD patients, a single HD session decreased significantly the plasma protein-bound di-Tyr level, although the mean post-HD level remained significantly greater than the one in healthy people. Furthermore, pre-HD plasma protein-bound di-Tyr level was positively correlated with pre-HD serum creatinine and albumin concentrations. No significant correlation was found between plasma protein-bound di-Tyr level and serum concentration of C-reactive protein, a biomarker of systemic inflammation.</p></div><div><h3>Conclusions</h3><p>This study demonstrates that a single HD session does not increase, rather partially decreases, oxidative pathways producing di-Tyr in the haemodialyzed patient.</p></div><div><h3>General significance</h3><p>The choice of the most pertinent biomarkers of oxidative stress is critical for the development of novel treatments for ESRD. However, the relative importance of oxidative stress and inflammation in ESRD remains largely undetermined, and several questions concerning oxidative stress and inflammation remain poorly defined. These results could stimulate further studies on the use of plasma protein-bound di-Tyr as a long-lasting oxidative stress biomarker in ESRD.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 55-63"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.12.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42954440","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}

{"title":"Microparticle subpopulations are potential markers of disease progression and vascular dysfunction across a spectrum of connective tissue disease","authors":"E.M. McCarthy ,&nbsp;D. Moreno-Martinez ,&nbsp;F.L. Wilkinson ,&nbsp;N.J. McHugh ,&nbsp;I.N. Bruce ,&nbsp;J.D. Pauling ,&nbsp;M.Y. Alexander ,&nbsp;B. Parker","doi":"10.1016/j.bbacli.2016.11.003","DOIUrl":"10.1016/j.bbacli.2016.11.003","url":null,"abstract":"<div><h3>Objective</h3><p>Microparticles (MPs) are membrane-bound vesicles derived from vascular and intravascular cells such as endothelial cells (EMPs) and platelets (PMPs). We investigated EMP and PMP numbers across a spectrum of autoimmune rheumatic diseases (AIRDs) with the aim of comparing the levels of, and relationship between, EMPs and PMPs.</p></div><div><h3>Methods</h3><p>Patients with Systemic Lupus Erythematosus (SLE) (<em>n</em> <!-->=<!--> <!-->24), Systemic Sclerosis (SSc) (<em>n</em> <!-->=<!--> <!-->24), Primary Raynauds Phenomenon (RP) (<em>n</em> <!-->=<!--> <!-->17) and “other CTD” (<em>n</em> <!-->=<!--> <!-->15) (Primary Sjogrens Syndrome, UCTD or MCTD) as well as 15 healthy controls were recruited. EMPs and PMPs were quantified using flow cytometry. Associations between MP levels and objective functional vascular assessments were evaluated.</p></div><div><h3>Results</h3><p>SLE patients had significantly higher EMPs compared with healthy controls and SSc patients. Higher PMP levels were noted in SSc and primary RP when compared to healthy controls and ‘other CTD’ patients. A modest correlation was noted between EMP and PMP levels in healthy controls (Spearman <em>r</em> <!-->=<!--> <!-->0.6, <em>p</em> <!-->=<!--> <!-->0.017). This relationship appeared stronger in SLE (<em>r</em> <!-->=<!--> <!-->0.72, <em>p</em> <!-->&lt;<!--> <!-->0.0001) and other CTD patients (<em>r</em> <!-->=<!--> <!-->0.75, <em>p</em> <!-->&lt;<!--> <!-->0.0001). The association between EMPs and PMPs was notably less strong in SSc (<em>r</em> <!-->=<!--> <!-->0.45, <em>p</em> <!-->=<!--> <!-->0.014) and RP (<em>r</em> <!-->=<!--> <!-->0.37, <em>p</em> <!-->=<!--> <!-->0.15). A significantly lower EMP/PMP ratio was detected in SSc/RP patients in comparison to both healthy controls and SLE/other CTD patients. Higher EMP and PMP levels were associated with higher digital perfusion following cold challenge in SSc. In contrast, higher PMP (but not EMP) levels were associated with lower digital perfusion at both baseline and following cold challenge in primary RP. Higher PMP levels were associated with greater endothelial-independent dilation in patients with SLE.</p></div><div><h3>Conclusion</h3><p>MP populations differ across the spectrum of AIRDS, possibly reflecting differences in vascular cell injury and activation. MP levels are associated with functional assessments of vascular function and might have a role as novel vascular biomarkers in AIRDs.</p></div><div><h3>Significance and innovations</h3><p>Levels of circulating endothelial and platelet microparticles differ between SSc/primary RP compared with SLE and other CTDs (UCTD, MCTD and Primary Sjogrens). MP release may occur within different vascular sites across these disease groups (macrovascular and microvascular).</p><p>The association between circulating MP levels and objective assessment of macro- and microvascular dysfunction within these disease areas suggests that MPs might have a useful","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 16-22"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.11.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181852","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}

{"title":"Hemophagocytic lymphohistiocytosis in adults: An under recognized entity","authors":"Abdul Rashid Shah ,&nbsp;Tariq Muzzafar ,&nbsp;Rita Assi ,&nbsp;Dawid Schellingerhout ,&nbsp;Zeev Estrov ,&nbsp;Gevorg Tamamyan ,&nbsp;Hagop Kantarjian ,&nbsp;Naval Daver","doi":"10.1016/j.bbacli.2016.12.002","DOIUrl":"10.1016/j.bbacli.2016.12.002","url":null,"abstract":"<div><p>Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe immune activation with macrophage and T-cell infiltration resulting in, multi organ damage. HLH may be primary or secondary in etiology. A high index of suspicion is essential for early diagnosis and treatment. Diagnostic criteria need to be refined and newer treatment options to be explored in order to improve survival especially in adult HLH and malignancy-associated HLH (M-HLH).</p><p>We report a case of malignancy associated HLH (M-HLH) in adult treated on one of the only FDA-approved protocols for adult HLH to highlight the diagnostic and therapeutic challenges of this disease entity.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 36-40"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.12.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181968","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}

{"title":"Understanding breast cancer – The long and winding road","authors":"Kiven Erique Lukong","doi":"10.1016/j.bbacli.2017.01.001","DOIUrl":"10.1016/j.bbacli.2017.01.001","url":null,"abstract":"<div><h3>Background</h3><p>Despite a remarkable increase in the depth of our understanding and management of breast cancer in the past 50<!--> <!-->years, the disease is still a major public health problem worldwide and poses significant challenges. The palpability of breast tumors has facilitated diagnosis and documentation since ancient times. The earliest descriptions of breast cancer date back to around 3500<!--> <!-->BCE. For centuries to follow, theories by Hippocrates (460<!--> <!-->BCE) and Galen (200<!--> <!-->CE), attributing the cause of breast cancer to an “excess of black bile” and treatment options including the use of opium and castor oil, prevailed. Surgical resection was introduced in the 18th century. The advent of modern medicine led to the development of novel treatment options that include hormonal, targeted and chemo-therapies. There are still several therapeutic challenges including the treatment of triple negative breast cancer (TNBC), and overcoming drug resistance.</p></div><div><h3>Scope of review</h3><p>The increased incidence and awareness of breast cancer has led to significant changes in diagnosis and treatment in recent decades. But, mankind has come a long way. Herein, I have traced how our understanding of breast cancer has evolved from the early description of the disease around 460<!--> <!-->BCE as “black bile-containing crab-like tumors” to the conventional as a heterogeneous disease with high degree of diversity between and within tumors, as well as among breast cancer patients. How is breast cancer treated today and how do risk factors, breast cancer subtype and drug resistance contribute to the therapeutic challenges at the turn of the 21st century?</p></div><div><h3>Major conclusions</h3><p>Breast cancer remains a serious public health issue worldwide. However, appreciable growth in our understanding of breast cancer in the past century has led to remarkable progress in the early detection, treatment and prevention of the disease. The clinical focus is shifting more towards tailored therapy as more targets are characterized and novel highly innovative approaches are developed.</p></div><div><h3>General significance</h3><p>Tracing the history of breast cancer, highlights how increased awareness of the disease, and progress in research and development have enhance our understanding of the disease.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 64-77"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2017.01.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47285340","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}

{"title":"Pathogenicity in POLG syndromes: DNA polymerase gamma pathogenicity prediction server and database","authors":"Anssi Nurminen ,&nbsp;Gregory A. Farnum ,&nbsp;Laurie S. Kaguni","doi":"10.1016/j.bbacli.2017.04.001","DOIUrl":"10.1016/j.bbacli.2017.04.001","url":null,"abstract":"<div><p>DNA polymerase gamma (POLG) is the replicative polymerase responsible for maintaining mitochondrial DNA (mtDNA). Disorders related to its functionality are a major cause of mitochondrial disease. The clinical spectrum of POLG syndromes includes Alpers-Huttenlocher syndrome (AHS), childhood myocerebrohepatopathy spectrum (MCHS), myoclonic epilepsy myopathy sensory ataxia (MEMSA), the ataxia neuropathy spectrum (ANS) and progressive external ophthalmoplegia (PEO). We have collected all publicly available POLG-related patient data and analyzed it using our pathogenic clustering model to provide a new research and clinical tool in the form of an online server. The server evaluates the pathogenicity of both previously reported and novel mutations. There are currently 176 unique point mutations reported and found in mitochondrial patients in the gene encoding the catalytic subunit of POLG, <em>POLG</em>. The mutations are distributed nearly uniformly along the length of the primary amino acid sequence of the gene. Our analysis shows that most of the mutations are recessive, and that the reported dominant mutations cluster within the polymerase active site in the tertiary structure of the POLG enzyme. The POLG Pathogenicity Prediction Server (<span>http://polg.bmb.msu.edu</span><svg><path></path></svg>) is targeted at clinicians and scientists studying POLG disorders, and aims to provide the most current available information regarding the pathogenicity of <em>POLG</em> mutations.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 147-156"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2017.04.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34975117","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}

{"title":"Metabolomic analysis identifies differentially produced oral metabolites, including the oncometabolite 2-hydroxyglutarate, in patients with head and neck squamous cell carcinoma","authors":"Pranab K. Mukherjee ,&nbsp;Pauline Funchain ,&nbsp;Mauricio Retuerto ,&nbsp;Richard J. Jurevic ,&nbsp;Nicole Fowler ,&nbsp;Brian Burkey ,&nbsp;Charis Eng ,&nbsp;Mahmoud A Ghannoum","doi":"10.1016/j.bbacli.2016.12.001","DOIUrl":"10.1016/j.bbacli.2016.12.001","url":null,"abstract":"<div><h3>Background</h3><p>Metabolomics represents a promising approach for discovering novel targets and biomarkers in head and neck squamous cell carcinoma (HNSCC). Here we used metabolomics to identify oral metabolites associated with HNSCC.</p></div><div><h3>Methods</h3><p>Tumor and adjacent normal tissue from surgical resections and presurgical oral washes as well as oral washes were collected from healthy participants. Metabolites extractions of these samples were analyzed by liquid chromatography-mass spectroscopy (LC/MS), LC/MS/MS and gas chromatography-MS (GC/MS).</p></div><div><h3>Results</h3><p>Among 28 samples obtained from 7 HNSCC cases and 7 controls, 422 metabolites were detected (269 identified and 153 unidentified). Oral washes contained 12 and 23 metabolites in healthy controls and HNSCC patients, respectively, with phosphate and lactate being the most abundant. Small molecules related to energy metabolism were significantly elevated in HNSCC patients compared to controls. Levels of beta-alanine, alpha-hydroxyisovalerate, tryptophan, and hexanoylcarnitine were elevated in HNSCC oral washes compared to healthy controls (range 7.8-12.2-fold). Resection tissues contained 22 metabolites, of which eight were overproduced in tumor by 1.9- to 12-fold compared to controls. TCA cycle analogs 2-hydroxyglutarate <strong>(</strong>2-HG) and 3-GMP were detected exclusively in tumor tissues. Targeted quantification of 2-HG in a representative HNSCC patient showed increase in tumor tissue (14.7<!--> <!-->μg/mL), but undetectable in normal tissue. Moreover, high levels of 2-HG were detected in HNSCC cell lines but not in healthy primary oral keratinocyte cultures.</p></div><div><h3>Conclusions</h3><p>Oral metabolites related to energy metabolism were elevated in HNSCC, and acylcarnitine and 2HG may have potential as non-invasive biomarkers. Further validation in clinical studies is warranted.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 8-15"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9193043","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}

{"title":"The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features","authors":"Thomas Pabst ,&nbsp;Linda Kortz ,&nbsp;Georg M. Fiedler ,&nbsp;Uta Ceglarek ,&nbsp;Jeffrey R. Idle ,&nbsp;Diren Beyoğlu","doi":"10.1016/j.bbacli.2017.03.002","DOIUrl":"10.1016/j.bbacli.2017.03.002","url":null,"abstract":"<div><h3>Background</h3><p>Early studies established that certain lipids were lower in acute myeloid leukemia (AML) cells than normal leukocytes. Because lipids are now known to play an important role in cell signaling and regulation of homeostasis, and are often perturbed in malignancies, we undertook a comprehensive lipidomic survey of plasma from AML patients at time of diagnosis and also healthy blood donors.</p></div><div><h3>Methods</h3><p>Plasma lipid profiles were measured using three mass spectrometry platforms in 20 AML patients and 20 healthy blood donors. Data were collected on total cholesterol and fatty acids, fatty acid amides, glycerolipids, phospholipids, sphingolipids, cholesterol esters, coenzyme Q10 and eicosanoids.</p></div><div><h3>Results</h3><p>We observed a depletion of plasma total fatty acids and cholesterol, but an increase in certain free fatty acids with the observed decline in sphingolipids, phosphocholines, triglycerides and cholesterol esters probably driven by enhanced fatty acid oxidation in AML cells. Arachidonic acid and precursors were elevated in AML, particularly in patients with high bone marrow (BM) or peripheral blasts and unfavorable prognostic risk. PGF2α was also elevated, in patients with low BM or peripheral blasts and with a favorable prognostic risk. A broad panoply of lipid classes is altered in AML plasma, pointing to disturbances of several lipid metabolic interconversions, in particular in relation to blast cell counts and prognostic risk.</p></div><div><h3>Conclusions</h3><p>These data indicate potential roles played by lipids in AML heterogeneity and disease outcome.</p></div><div><h3>General significance</h3><p>Enhanced catabolism of several lipid classes increases prognostic risk while plasma PGF2α may be a marker for reduced prognostic risk in AML.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 105-114"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2017.03.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34845865","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}

{"title":"A novel dominant D109A CRYAB mutation in a family with myofibrillar myopathy affects αB-crystallin structure","authors":"Jakub P. Fichna ,&nbsp;Anna Potulska-Chromik ,&nbsp;Przemysław Miszta ,&nbsp;Maria Jolanta Redowicz ,&nbsp;Anna M. Kaminska ,&nbsp;Cezary Zekanowski ,&nbsp;Sławomir Filipek","doi":"10.1016/j.bbacli.2016.11.004","DOIUrl":"10.1016/j.bbacli.2016.11.004","url":null,"abstract":"<div><p>Myofibrillar myopathy (MFM) is a group of inherited muscular disorders characterized by myofibrils dissolution and abnormal accumulation of degradation products. So far causative mutations have been identified in nine genes encoding Z-disk proteins, including αB-crystallin (CRYAB), a small heat shock protein (also called HSPB5).</p><p>Here, we report a case study of a 63-year-old Polish female with a progressive lower limb weakness and muscle biopsy suggesting a myofibrillar myopathy, and extra-muscular multisystemic involvement, including cataract and cardiomiopathy. Five members of the proband's family presented similar symptoms. Whole exome sequencing followed by bioinformatic analysis revealed a novel D109A mutation in <em>CRYAB</em> associated with the disease.</p><p>Molecular modeling in accordance with muscle biopsy microscopic analyses predicted that D109A mutation influence both structure and function of CRYAB due to decreased stability of oligomers leading to aggregate formation. In consequence disrupted sarcomere cytoskeleton organization might lead to muscle pathology. We also suggest that mutated RQDE sequence of CRYAB could impair CRYAB chaperone-like activity and promote aggregation of lens crystallins.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 1-7"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.11.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181930","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}

{"title":"Proteomic analysis of bronchoalveolar lavage fluid (BALF) from lung cancer patients using label-free mass spectrometry","authors":"Abduladim Hmmier ,&nbsp;Michael Emmet O'Brien ,&nbsp;Vincent Lynch ,&nbsp;Martin Clynes ,&nbsp;Ross Morgan ,&nbsp;Paul Dowling","doi":"10.1016/j.bbacli.2017.03.001","DOIUrl":"10.1016/j.bbacli.2017.03.001","url":null,"abstract":"<div><h3>Background</h3><p>Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC).</p></div><div><h3>Methods</h3><p>Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC). Validation of candidate biomarkers identified in BALF was performed in a larger cohort of plasma samples by detection with enzyme-linked immunoassay.</p></div><div><h3>Results</h3><p>Four proteins (Cystatin-C, TIMP-1, Lipocalin-2 and HSP70/HSPA1A) were selected as a representative group from discovery phase mass spectrometry BALF analysis. Plasma levels of TIMP-1, Lipocalin-2 and Cystatin-C were found to be significantly elevated in AD and SqCC compared to control.</p></div><div><h3>Conclusion</h3><p>The results presented in this study indicate that BALF is an important proximal biofluid for the discovery and identification of candidate lung cancer biomarkers.</p></div><div><h3>General significance</h3><p>There is good correlation between the trend of protein abundance levels in BALF and that of plasma which validates this approach to develop a blood biomarker to aid lung cancer diagnosis, particularly in the era of lung cancer screening. The protein signatures identified also provide insight into the molecular mechanisms associated with lung malignancy.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 97-104"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2017.03.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34845864","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}

{"title":"A post-publication analysis of the idealized upper reference value of 2.5 mIU/L for TSH: Time to support the thyroid axis with magnesium and iron especially in the setting of reproduction medicine","authors":"Roy Moncayo,&nbsp;Helga Moncayo","doi":"10.1016/j.bbacli.2017.03.003","DOIUrl":"10.1016/j.bbacli.2017.03.003","url":null,"abstract":"<div><p>Laboratory medicine approaches the evaluation of thyroid function mostly through the single determination of the blood level of thyroid stimulating hormone (TSH). Some authors have suggested an upper reference value for TSH of 2.5<!--> <!-->mIU/L. This suggestion has not been confirmed by recent clinical studies. These studies have delivered a clinically valid reference range going from 0.3 to 3.5<!--> <!-->mIU/L. These values are valid for both for the general population as well as in the setting of fertility and pregnancy.</p><p>Current biochemical evidence about the elements required to maintain thyroid function shows that these not only include dietary iodine but also magnesium, iron, selenium and coenzyme Q10. Iron is important for the synthesis of thyroid peroxidase; magnesium-ATP contributes to the active process of iodine uptake; iodine has to be sufficiently present in the diet; selenium acts through selenoproteins to protect the thyroid cell during hormone synthesis and in deiodination of thyroxine; coenzyme Q10 influences thyroid vascularity. As a consequence, good clinical practice requires additional biochemical information on the blood levels of magnesium, selenium, coenzyme Q10 as well as iron status.</p><p>Since these elements are also important for the maintenance of reproductive function, we postulate that they constitute the connecting link between both endocrine systems.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":"7 ","pages":"Pages 115-119"},"PeriodicalIF":0.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2017.03.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34913538","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}