Antwi-Boasiako C, Kusi-Mensah YA, Hayfron-Benjamin C
… +6 more, Aryee R, Dankwah GB, Abla KL, Owusu Darkwa E, Botchway FA, Sampene-Donkor E
Biomark Insights
· 2019 · PMID 31523130
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The activity of Na-K ATPase is altered in sickle cell disease (SCD), which affects serum electrolyte levels. This alteration is associated with several complications in sickle cell patients. This study evaluated the seru...The activity of Na-K ATPase is altered in sickle cell disease (SCD), which affects serum electrolyte levels. This alteration is associated with several complications in sickle cell patients. This study evaluated the serum levels of sodium, potassium, and chloride in patients with SCD. The study was a case-control cross-sectional study involving 120 SCD patients in the steady state and 48 'healthy' controls. The SCD patients were made up of 69 HbSS patients and 41 HbSC patients. Serum electrolyte levels (Na, K, and Cl) were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS; Varian Australia Pty Ltd). Serum sodium levels were significantly lower in the sickle cell patients, compared with their 'healthy' counterparts ( = .0001). Although the study found significantly higher serum levels of potassium in the SCD patients ( = .0001), there was no significant difference in serum chloride levels between patients with SCD and the controls ( = .098). Serum sodium and chloride levels were not significantly different in both HbSS and HbSC patients ( = .197 and = .553, respectively). The level of serum potassium in the HbSS patients was, however, significantly higher compared with those with the HbSC genotype ( = .0001). There is higher efflux of K from the intracellular into the extracellular space in HbSS patients, which may lead to red cell membrane dysfunction and associated complications.
Furukawa H, Oka S, Shimada K
… +5 more, Hashimoto A, Komiya A, Matsui T, Fukui N, Tohma S
Biomark Insights
· 2019 · PMID 31488947
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OBJECTIVE: Acute-onset diffuse interstitial lung disease (AoDILD) includes acute exacerbation of interstitial lung disease (ILD), drug-induced ILD, and pneumonia, and frequently occurs in patients with rheumatoid arthri...OBJECTIVE: Acute-onset diffuse interstitial lung disease (AoDILD) includes acute exacerbation of interstitial lung disease (ILD), drug-induced ILD, and pneumonia, and frequently occurs in patients with rheumatoid arthritis (RA). Since AoDILD causes a poor prognosis in RA, biomarkers for AoDILD were eagerly desired. Metabolomic analyses were extensively performed in cancer patients and successfully generated better diagnostic biomarkers. In the present study, serum metabolomic profiles of AoDILD in RA were investigated to generate better potential metabolomic biomarkers. METHODS: Serum samples of 10 RA patients with AoDILD were collected on admission and in a stable state, more than 3 months before the admission. Serum metabolomic analyses were conducted on the samples from these RA patients with AoDILD. RESULTS: Apparently distinct serum metabolomic profiles in AoDILD were not observed in univariate or hierarchical cluster analyses. Partial least squares-discriminant analysis (PLS-DA) was performed to select candidate metabolites based on variable importance in projection (VIP) scores. The PLS-DA model generated from the four metabolites with VIP scores more than 2.25 (mannosamine, alliin, kynurenine, and 2-hydroxybutyric acid) could successfully discriminate AoDILD from the stable condition (area under the curve: 0.962, 95% confidence interval: 0.778-1.000). CONCLUSION: It was demonstrated that metabolomic profiling was useful to generate better biomarkers in AoDILD.
Azizieh FY, Shehab D, Jarallah KA
… +2 more, Gupta R, Raghupathy R
Biomark Insights
· 2019 · PMID 31452599
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INTRODUCTION: Receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and oxidative stress markers are suggested to contribute to bone loss in osteoporosis that occurs in menopause. However, the as...INTRODUCTION: Receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and oxidative stress markers are suggested to contribute to bone loss in osteoporosis that occurs in menopause. However, the association between these markers and bone mineral density (BMD) is controversial. The aim of this study was to measure circulatory levels of these parameters in postmenopausal women with normal or low BMD. METHODS: The study population included 71 postmenopausal women, of whom 25 had normal BMD, 31 had osteopenia, and 15 had osteoporosis. Serum levels of RANKL, OPG, and 5 oxidative stress markers (catalase, peroxiredoxin 2 [PRX2], superoxide dismutase 1 [SOD1], superoxide dismutase 2 [SOD2], and thioredoxin [TRx1]) were measured using the Multiplex system. RESULTS: As compared with subjects having normal BMD, subjects with low BMD had significantly lower median serum levels of OPG, catalase, SOD2, and PRX2 ( = .004, .031, .044, and .041 respectively). Although levels of RANKL were not different between the 2 groups, the RANKL/OPG ratio was higher in women with low BMD ( = .027). CONCLUSIONS: These data provide insights into the possible roles of OPG, RANKL, and oxidative stress in the pathogenesis of postmenopausal osteoporosis. However, the lack of association between these markers and BMD indicates that osteoporosis is complex and multivariate.
Biomark Insights
· 2019 · PMID 31384126
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BACKGROUND: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistoch...BACKGROUND: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistochemistry (IHC). In this study, we sought to determine (1) whether DAXX expression pattern is the same across different uterine carcinoma subtypes, and (2) which uterine carcinomas show loss of nuclear DAXX IHC. DESIGN: We studied 65 uterine carcinomas of the following histologic types: 30 endometrioid (12 FIGO [The International Federation of Gynecology and Obstetrics] grade 1, 12 FIGO grade 2, and 6 FIGO grade 3), 8 serous, 14 clear cell, and 13 undifferentiated/dedifferentiated type (UEC/DDEC). Nuclear DAXX IHC was assessed in each tumor and was graded semi-quantitatively as follows: 0% to 50%, 50% to 75%, and greater than 75% of lesional cells react. RESULTS: A total of 61% (25/41) of high-grade carcinomas (FIGO grade 3, serous, clear cell, and UEC/DDEC]) showed retained DAXX nuclear staining in >75% of lesional cells, compared with only 4.2% (1/24) of the low-grade carcinomas (FIGO grades 1 and 2) ( = .0001), where DAXX expression was cytoplasmic. In addition, in the 11 DDEC cases, all the differentiated components showed loss of nuclear DAXX compared with the undifferentiated components which retained nuclear DAXX expression. CONCLUSIONS: We demonstrate that loss of nuclear DAXX is present in low-grade endometrial carcinomas and the differentiated components in UEC/DDEC, but not in high-grade ones, suggesting DAXX's role in tumor progression and its potential as a therapeutic target in high-grade endometrial carcinomas.
Mrozek S, Delamarre L, Capilla F
… +4 more, Al-Saati T, Fourcade O, Constantin JM, Geeraerts T
Biomark Insights
· 2019 · PMID 31210728
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Glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), and matrix metalloproteinase 9 (MMP-9) are potential biomarkers of traumatic brain injury (TBI) but also of secondary insults to t...Glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), and matrix metalloproteinase 9 (MMP-9) are potential biomarkers of traumatic brain injury (TBI) but also of secondary insults to the brain. The aim of this study was to describe the cerebral distribution of GFAP, UCH-L1, and MMP-9 in a rat model of diffuse TBI associated with standardized hypoxia-hypotension (HH). Adult male Sprague-Dawley rats were allocated to Sham (n = 10), TBI (n = 10), HH (n = 10), and TBI+HH (n = 10) groups. After 4 hours, brains were rapidly removed and immunostaining of GFAP, UCH-L1, and MMP-9 was performed. Areas of interest that have been described as particularly sensitive to hypoxic insults were analyzed. For GFAP, in the neocortex, immunostaining revealed a significant decrease in strong staining for HH and TBI+HH groups compared with TBI group ( < .0001). For UCH-L1, the total immunostaining (6 regions of interest) reported a significant increase in strong staining ( < .0001) and decrease in weak staining ( < .0001) for the HH and TBI+HH groups compared with the Sham and TBI groups. For MMP-9, for the HH and TBI+HH groups, a significant increase in moderate ( < .0001) and weak staining ( < .0001) and a decrease in negative staining ( < .0001) compared with the Sham and TBI groups were observed. UCH-L1 and MMP-9 immunostainings increased after HH alone or HH combined with TBI compared with TBI alone. GFAP immunostaining decreased particularly in the neocortex after HH alone or HH combined with TBI compared with TBI alone. These three biomarkers could therefore be considered as potential biomarkers of HH insults independently of TBI.
Ohno R, Kawamoto R, Kanamoto M
… +6 more, Watanabe J, Fujii M, Ohtani H, Harada M, Kumagi T, Kawasaki H
Biomark Insights
· 2019 · PMID 31210727
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Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms with the potential for progression to pancreatic cancer. Accurate prediction of the malignant potential is challenging and a proper treatment strategy...Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms with the potential for progression to pancreatic cancer. Accurate prediction of the malignant potential is challenging and a proper treatment strategy has not been well established. Preoperative neutrophil-to-lymphocyte ratio (NLR) is a biomarker of the malignant potential in patients with several types of malignancy. We explored malignant potential in patients with IPMN. The present study included 56 patients aged of 73 ± 9 years (mean ± standard deviation) who underwent curative resection for IPMN from 1996 to 2017. We analyzed the relationship between the characteristics including NLR and malignant component for predicting pathological results. The nonmalignant IPMN group (N = 21) included patients with low-grade dysplasia (LGD) and intermediate-grade dysplasia (IGD), and the malignant IPMN group (N = 35) included patients with high-grade dysplasia (HGD) and invasive carcinoma. In a univariate analysis, NLR ⩾ 2.2 ( = .001), prognostic nutritional index (PNI) < 45 ( = .016), CA 19-9 > 37 U/mL ( = .039), and cystic diameter ⩾ 30 mm ( = .010), and mural nodule ( = .010) were significantly different between the malignant IPMN and the nonmalignant IPMN groups. Multivariate analysis showed that high NLR (⩾2.2) (odds ratio 9.79; 95% confidence interval: 2.06-45.6), cystic diameter ⩾ 30 mm (4.65; 1.14-18.9), and mural nodule (4.91; 1.20-20.1) were independently predictive of malignant IPMN. These results suggest that preoperative NLR is a useful predictive biomarker for evaluating malignant potential in patients with IPMN.1.
Bermúdez-Mejía C, Torres-Cordón MF, Becerra-Bayona S
… +10 more, Páez CM, Vargas CI, Cárdenas ME, Serrano SE, Baquero I, Martínez-Vega R, Schulz R, Ilarraza R, Pazin Filho A, Torres-Dueñas D
Biomark Insights
· 2019 · PMID 31205414
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INTRODUCTION: Matrix metalloproteinase-9 (MMP-9) plays an important role in the pathophysiology of sepsis. A single-nucleotide polymorphism (SNP) at position -1562 (C/T) in the MMP-9 gene has been associated with differe...INTRODUCTION: Matrix metalloproteinase-9 (MMP-9) plays an important role in the pathophysiology of sepsis. A single-nucleotide polymorphism (SNP) at position -1562 (C/T) in the MMP-9 gene has been associated with differential MMP-9 expression, being higher when the -1562 T allele is present. We evaluated the association of the SNP MMP9 -1562 C/T with severity and mortality in patients with sepsis to establish whether the prognosis of the disease is affected. MATERIALS AND METHODS: A case-control study exploratory was carried out in a cohort of infected patients. 540 individuals were selected in total, 270 patients with sepsis and 270 controls (infected but non-septic), classified according to the 2016 consensus (Sepsis-3). The presence of the single-nucleotide polymorphism (SNP; allele T and/or allele C) was determined through analyses of restriction fragment length polymorphism and plasma levels of MMP-9 were determined through enzyme-linked immunosorbent assay immunoassay. RESULTS: SNP MMP-9 -1562 has two known alleles (T and C), with predominance of the C over the T allele; in the group of patients with sepsis, T allele was found in 7.2% of cases, while C allele in the rest (92.8%); in comparison, in the group of infected but non-septic patients, frequencies were 9.4% for T allele and 90.6% for the C allele ( = .33). Also, the presence of the polymorphic T allele was not related to the levels of MMP-9 in patients with sepsis in comparison with infected but non-septic patients 780 (397-1375) ng/mL vs 646 (172-1249) ng/mL ( = .64). There was also no association between the SNP and sepsis mortality ( = .78). CONCLUSIONS: We concluded that there was no association between the SNP MMP9 -1562 C/T and sepsis or between the SNP MMP9 -1562 C/T and sepsis mortality in the Northeastern Colombian septic patient cohort. Further research is needed to clarify the correlation among sepsis, genetic factors with allele T and MMP-9 plasma concentration.
Biomark Insights
· 2019 · PMID 31105426
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Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylati...Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hypomethylating agents (azacitidine and decitabine) in AML patients are presented. Novel hypomethylating agent (guadecitabine) and experimental DNMT inhibitors in AML are also discussed. In summary, hypermethylation of tumour suppressors mediated by DNMT1 or DNMT3B contributes to the progression and severity of AML (except and inv(16)(p13;q22) AML for DNMT3B), while mutation affecting represents an early genetic lesion in the pathogenesis of AML. In clinical trials of AML patients, expression of DNMTs is downregulated by hypomethylating agents while the clinical response predictive roles of DNMT biomarkers remain unresolved. Finally, nucleoside hypomethylating agents have continued to show enhanced responses in clinical trials of AML patients, and novel non-nucleoside DNMT inhibitors have demonstrated cytotoxicity against AML cells in pre-clinical settings.
Biomark Insights
· 2019 · PMID 31037027
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Damage to hair follicles following exposure to toxic chemotherapeutics can cause substantial hair loss, commonly known as chemotherapy-induced alopecia (CIA). Preventive therapies remain limited; however, recent advances...Damage to hair follicles following exposure to toxic chemotherapeutics can cause substantial hair loss, commonly known as chemotherapy-induced alopecia (CIA). Preventive therapies remain limited; however, recent advances in the use of scalp cooling technologies have proved successful in preventing or reducing hair loss in some patients. Further improvements in scalp cooling efficacy and/or development of novel treatments to prevent chemotherapy-induced hair loss are required. To achieve this, post-chemotherapy assessment of hair follicle damage markers, with and without scalp cooling, would provide invaluable mechanistic and prognostic information. At present, the availability of such data is extremely limited. This article describes the potential utility of a combination of biomarkers in assessing drug-induced alopecia and the protective potential of existing or new treatments. A greater understanding of the precise mechanisms of anti-CIA therapies through biomarker analysis would enhance the rationale, use, and development of such treatments.
Forster CS, Haffey WD, Bennett M
… +2 more, Greis KD, Devarajan P
Biomark Insights
· 2019 · PMID 30906192
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PURPOSE: Distinguishing urinary tract infection (UTI) from urinary tract colonization (UTC) in children with neurogenic bladders who require clean intermittent catheterization (CIC) is challenging. Our objective was to i...PURPOSE: Distinguishing urinary tract infection (UTI) from urinary tract colonization (UTC) in children with neurogenic bladders who require clean intermittent catheterization (CIC) is challenging. Our objective was to identify urinary proteins to distinguish UTI from UTC in CIC-dependent children that have potential to serve as objective markers of UTI. EXPERIMENTAL DESIGN: A total of 10 CIC-dependent children were included in the mass spectrometry analysis (UTI = 5, UTC = 5). Quantitative profiling of urine proteins with isobaric protein labeling was performed using tandem mass spectrometry. Candidate markers were normalized using a collective mixture of proteins from all samples. Relative quantitative abundance of proteins across all samples were compared. Proteins with >50% change in the average abundance were identified as proteins of interest, which were then measured using enzyme-linked immunosorbent assay (ELISA) in an additional 40 samples (no growth = 10, UTC = 15, UTI = 15). RESULTS: Mass spectrometry revealed 8 differentially expressed proteins. Of these, apolipoprotein D, alpha-amylase 2B, non-secretory ribonuclease, CD44 antigen, and prosaposin were measurable by ELISA. Concentrations of both CD44 and prosaposin were significantly higher in UTI, with area under the curves (AUCs) of 0.72 and 0.78, respectively. CONCLUSION: Urinary CD44 and prosaposin are candidate markers that may assist with the diagnosis of UTI in CIC-dependent children.
Huraib GB, Harthi FA, Arfin M
… +3 more, Khlaiwi AA, Rizvi S, Al-Asmari A
Biomark Insights
· 2019 · PMID 30828245
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has been linked with the etiopathogenesis of psoriasis with inconsistent results. C677T polymorphism was evaluated in 106 Saudi psoriasis vulgaris patients and 280 matched healthy controls using PCR-RFLP (restriction fr...has been linked with the etiopathogenesis of psoriasis with inconsistent results. C677T polymorphism was evaluated in 106 Saudi psoriasis vulgaris patients and 280 matched healthy controls using PCR-RFLP (restriction fragment length plymorphism) technique. The cardiovascular risk factors were also compared in cases and controls. Allele T and genotypes CT and TT were found to be increased while allele C and genotype CC significantly decreased in psoriasis patients as compared with controls ( < .001). These results showed that the T-allele and T-containing genotypes (TT, CT) of C677T are significantly linked with psoriasis susceptibility while C-allele and CC genotype are protective for it. Body mass index, fasting glucose, total cholesterol, low-density lipoprotein, triglycerides, and C-reactive protein, known markers for cardiovascular diseases, were found to be significantly elevated in the patient group as compared with the controls. It is concluded that the C677T polymorphism increases psoriasis risk in Saudi patients.
Byrne JA, Grima N, Capes-Davis A
… +1 more, Labbé C
Biomark Insights
· 2019 · PMID 30783377
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A major reason for biomarker failure is the selection of candidate biomarkers based on inaccurate or incorrect published results. Incorrect research results leading to the selection of unproductive biomarker candidates a...A major reason for biomarker failure is the selection of candidate biomarkers based on inaccurate or incorrect published results. Incorrect research results leading to the selection of unproductive biomarker candidates are largely considered to stem from unintentional research errors. The additional possibility that biomarker research may be actively misdirected by research fraud has been given comparatively little consideration. This review discusses what we believe to be a new threat to biomarker research, namely, the possible systematic production of fraudulent gene knockdown studies that target under-studied human genes. We describe how fraudulent papers may be produced in series by paper mills using what we have described as a 'theme and variations' model, which could also be considered a form of salami slicing. We describe features of these single-gene knockdown publications that may allow them to evade detection by journal editors, peer reviewers, and readers. We then propose a number of approaches to facilitate their detection, including improved awareness of the features of publications constructed in series, broader requirements to post submitted manuscripts to preprint servers, and the use of semi-automated literature screening tools. These approaches may collectively improve the detection of fraudulent studies that might otherwise impede future biomarker research.
Sisson BA, Uvalic J, Kelly K
… +7 more, Selvam P, Hesse AN, Ananda G, Chandok H, Bergeron D, Holinka L, Reddi HV
Biomark Insights
· 2019 · PMID 30745794
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The standard of care in oncology has been genomic profiling of tumor tissue biopsies for the treatment and management of disease, which can prove to be quite challenging in terms of cost, invasiveness of procedure, and p...The standard of care in oncology has been genomic profiling of tumor tissue biopsies for the treatment and management of disease, which can prove to be quite challenging in terms of cost, invasiveness of procedure, and potential risk for the patient. As the number of available drugs in oncology continues to increase, so too does the demand for technologies and testing applications that can identify genomic alterations targetable by these new therapies. Liquid biopsies that use a blood draw from the diseased patient may offset the many disadvantages of the invasive procedure. However, as with any new technology or finding in the clinical field, the clinical utility of an analytical test such as that of the liquid biopsy has to be established. Here, we review the clinical testing space for liquid biopsy offerings and elucidate the technical and regulatory considerations to develop such an assay, using our recently validated PlasmaMonitor test.
Biomark Insights
· 2019 · PMID 30728712
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INTRODUCTION AND OBJECTIVE: The main goal of asthma treatment is to achieve and maintain clinical control of the disease. The exhaled fraction nitric oxide (FeNO) level is a biomarker of T-helper cell type 2 (Th2) inflam...INTRODUCTION AND OBJECTIVE: The main goal of asthma treatment is to achieve and maintain clinical control of the disease. The exhaled fraction nitric oxide (FeNO) level is a biomarker of T-helper cell type 2 (Th2) inflammation of the airways. Our objective was to determine whether the FeNO level can be used to discriminate between patients with controlled, partially controlled, and uncontrolled asthma. MATERIALS AND METHODS: The FeNO level and asthma control were evaluated in a retrospective and analytic cross-sectional study through data collected from asthmatic patients who were assessed by clinical history, asthma control, physical examination, spirometry, and FeNO level. Asthma control was determined by the criteria of the Global Initiative for Asthma and classified as controlled asthma, partially controlled asthma, and uncontrolled asthma. The FeNO values were classified as low (<25 ppb) or intermediate/high (⩾25 ppb) based on the American Thoracic Society recommendations. RESULTS: The symptoms of 81 asthmatic patients were classified as controlled (34 [42%] patients), partially controlled (27 [33.3%] patients), and uncontrolled (20 [24.7%] patients). The FeNO level discriminated between the uncontrolled and controlled groups ( = .01) and between the uncontrolled and partially controlled groups ( = .01), but not between the controlled and partially controlled groups ( = .98). An FeNO level >30 ppb was associated with uncontrolled asthma ( = .0001) with an area under the receiver operating characteristic curve of 0.78 (95% confidence interval = 0.65-0.89). CONCLUSIONS: FeNO level could be helpful in determining asthma control as >30 ppb was associated with uncontrolled asthma.
Biomark Insights
· 2018 · PMID 30546256
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Atherosclerosis is the underlying cause of most myocardial infarction (MI) and ischaemic stroke episodes. An early sign of atherosclerosis is hypertrophy of the arterial wall. It is known that increased intima media thic...Atherosclerosis is the underlying cause of most myocardial infarction (MI) and ischaemic stroke episodes. An early sign of atherosclerosis is hypertrophy of the arterial wall. It is known that increased intima media thickness (IMT) is a non-invasive marker of arterial wall alteration, which can easily be assessed in the carotid arteries by high-resolution B-mode ultrasound. Similarly, the other key element of MI and ischaemic strokes is the N-methyl-D-aspartate (NMDA) receptor which is an ionotropic glutamate receptor that mediates the vast majority of excitatory neurotransmission in the brain. NMDA activation requires the binding of both glutamate and a coagonist like D-serine to its glycine site. A special enzyme, serine racemase (SR), is required for the conversion of L-serine into D-serine, and alterations in SR activities lead to a variety of physiological and pathological conditions ranging from synaptic plasticity to ischemia, MI, and stroke. The amount of D-serine available for the activation of glutamatergic signalling is largely determined by SR and we have developed ways to estimate its levels in human blood samples and correlate it with the IMT. This research based short communication describes our pilot study, which clearly suggests that there is a direct relationship between the SR, D-serine, and IMT. In this article, we will discuss whether the activity of SR can determine the future consequences resulting from vascular pathologies such as MI and stroke.
Biomark Insights
· 2018 · PMID 30397383
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OBJECTIVES: To assemble an algorithm that will describe a "Signature" predictive of an individual's vulnerability to persistent traumatic brain injury (TBI). SUBJECTS AND METHODS: Studies of athletes and warriors who are...OBJECTIVES: To assemble an algorithm that will describe a "Signature" predictive of an individual's vulnerability to persistent traumatic brain injury (TBI). SUBJECTS AND METHODS: Studies of athletes and warriors who are subjected to repeated head impacts with rapid acceleration/deceleration forces are used to assist in the diagnosis and management of TBI-affected individuals. Data from multiple areas, including clinical, anatomical, magnetic resonance imaging, cognitive function, and biochemical analyses, are integrated to provide a Signature of persistent TBI. RESULTS: Studies to date indicate that susceptibility to TBI results from an interaction between host genetic and structural vulnerability factors and force and torque of impact on the head and torso. The host factors include molecular markers affecting immune and inflammatory responses to stress/insult as well as anatomical features such as the degree of transcortical fiber projections and vascular malformations. The host response to forceful impact includes the release of intracellular neural proteins and nucleic acids into the cerebrospinal fluid and vascular compartment as well as mobilization of cytokines and macrophages into the central nervous system with subsequent activation of microglia and inflammatory responses including autoimmune processes. Maximum impact to the base of the sulci via a "water hammer effect" is consistent with the localization of microvascular and inflammatory responses in the affected brain region. CONCLUSIONS: An assessment of an individuals' predisposition to persistent TBI with delayed cognitive deficits and behavioral changes requires an understanding of host vulnerability (genetic factors and brain structure) and external stressors (force and torque of impact as well as repetitive head injury and time interval between impacts). An algorithm that has utility in predicting vulnerability to TBI will include qualitative and quantitative measures of the host factors weighted against post impact markers of neural injury. Implementation of the resulting "Signature" of vulnerability at early stages of injury will help inform athletes and warriors, along with commanders and management, of the risk/benefit approaches that will markedly diminish health care costs to the nation and suffering to this population. This report attempts to define a strategy to create such an algorithm.
Biomark Insights
· 2018 · PMID 30349178
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B-cell lymphomas represent a diverse group of neoplasms classified primarily by histopatholgy and are often challenging to accurately diagnose. Despite having been recognized less than 20 years ago, microRNAs (miRNAs) ha...B-cell lymphomas represent a diverse group of neoplasms classified primarily by histopatholgy and are often challenging to accurately diagnose. Despite having been recognized less than 20 years ago, microRNAs (miRNAs) have emerged as one of the most promising class of cancer molecular biomarkers and are particularly attractive as they can be readily detected in formalin-fixed paraffin-embedded biopsy material and biological fluids such as blood. Many of the identified B-cell lymphoma miRNA biomarkers also play crucial regulatory roles in normal B-cell development. Below we consider the identity, function, and biomarker potential of miRNAs in B-cell lymphoma and most importantly the barriers that remain to be overcome if they are really to become part of routine clinical practice.
Shervington L, Darekar A, Shaikh M
… +2 more, Mathews R, Shervington A
Biomark Insights
· 2018 · PMID 30262983
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INTRODUCTION AND OBJECTIVE: Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to id...INTRODUCTION AND OBJECTIVE: Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to identify more reliable diagnostic biomarkers to detect early stages of RA. In addition, identifying the correct therapeutic biomarker for the treatment of RA using methotrexate (MTX) would greatly increase the benefits experienced by the patients. MATERIALS AND METHODS: Primary normal synoviocytes human fibroblast-like synoviocytes (HFLS) and its phenotype rheumatic HFLS-RA cells were chosen for this study. The HFLS-RA-untreated and MTX-treated cells were subjected to microarray analysis. RESULTS: Microarray data identified 74 differentially expressed genes. These genes were mapped against an RA inflammatory pathway, shortlisting 10 candidate genes. Gene expression profiling of the 10 genes were studied. Fold change (FC) was calculated to determine the differential expression of the samples. DISCUSSION: The transcription profiles of the 10 candidate genes were highly induced in HFLS-RA cells compared with HFLS cells. However, on treating the HFLS-RA cells with MTX, the transcription profiles of these genes were highly downregulated. The most significant expression FC difference between HFLS and HFLS-RA (treated and untreated) was observed with , and genes. CONCLUSIONS: The data from this study suggest the use of , and gene expression profiles as potential diagnostic biomarkers. In addition, these gene profiles can help in predicting the therapeutic efficacy of MTX.
Åström M, Tajeddinn W, Karlsson MG
… +3 more, Linder O, Palmblad J, Lindblad P
Biomark Insights
· 2018 · PMID 30147294
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BACKGROUND: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explai...BACKGROUND: Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells. CASE PRESENTATIONS: A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-γ) and IL-1α, for the 3 renal cell carcinoma cases compared with healthy blood donors. CONCLUSIONS: In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.
Bobillo-Perez S, Rodríguez-Fanjul J, Jordan Garcia I
Biomark Insights
· 2018 · PMID 30093797
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This review examines the use of procalcitonin in different clinical situations in the pediatric patient, with special emphasis on those requiring intensive care. We review the latest articles on its potency as a biomarke...This review examines the use of procalcitonin in different clinical situations in the pediatric patient, with special emphasis on those requiring intensive care. We review the latest articles on its potency as a biomarker in both infectious processes at diagnosis and on the response to treatment.