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Journal of Circulating Biomarkers

Bennett Ma, Gregg Wesolowski, Bin Luo, Traci Lifsted, Keith Wessner, Gary Adamson, Helmut Glantschnig, Laura S Lubbers
Cathepsin K (CatK) inhibitors exhibited chondroprotective and pain-reducing effects in animal models, however, improvements were relatively modest at dose levels achieving maximal suppression of CatK biomarkers in urine. In this report, a previously characterized CatK inhibitor (MK-1256) is utilized to explore the potential of reduced target engagement and/or suboptimal exposure (free drug) as limiting factors to the pharmacological potential of CatK inhibitors in the knee joint. Following oral administration of MK-1256 at a dose level achieving maximal inhibition of urinary biomarker (helical peptide) in dogs, full suppression of the biomarker in synovial fluid was observed...
January 2019: Journal of Circulating Biomarkers
A Safwat, D Sabry, A Ragiae, E Amer, R H Mahmoud, R M Shamardan
This study aimed to evaluate the effect of mesenchymal stem cells (MSCs)-derived exosomes in retina regeneration of experimentally induced diabetes mellitus (DM) in a rabbit model. Exosomes are extracellular vesicles that contain many microRNAs (micRNAs), mRNAs, and proteins from their cells of origin. DM was induced by intravenous (IV) injection of streptozotocin in rabbits. MSCs were isolated from adipose tissue of rabbits. Exosomes were extracted from MSCs by ultracentrifugation. Exosomes were injected by different routes (IV, subconjunctival (SC), and intraocular (IO))...
January 2018: Journal of Circulating Biomarkers
Joshua D Chew, Larry Markham, Holly M Smith, Yan Ru Su, Kelsey Tomasek, James C Slaughter, Douglas Sawyer, Jonathan H Soslow
Biomarkers are routinely used for noninvasive identification or monitoring of disease processes in clinical practice, as well as surrogate end points for drug development. There is a significant lack of data regarding biomarkers in children. An understanding of biomarker levels in a healthy pediatric cohort is essential as more studies begin to apply noninvasive biomarkers to pediatric populations. Brain-derived neurotrophic factor (BDNF) functions in neuronal survival and plasticity and is associated with exercise capacity and inflammatory disease processes...
January 2018: Journal of Circulating Biomarkers
Sandra Carrillo-Ibarra, Alejandra Guillermina Miranda-Díaz, Sonia Sifuentes-Franco, Ernesto Germán Cardona-Muñoz, Adolfo Daniel Rodríguez-Carrizalez, Geannyne Villegas-Rivera, Luis Miguel Román-Pintos
Oxidative stress induces nerve damage in type 2 diabetes mellitus and leads to diabetic polyneuropathy (DPN) and can affect the DNA and antioxidant status. Statins have pleiotropic, protective effects on the peripheral nerves of patients with diabetes. The aim of this study was to determine the effects of ezetimibe/simvastatin and rosuvastatin on DNA damage in patients with DPN. This randomized, double-blind, placebo-controlled, clinical trial comprised outpatients from Guadalajara, Mexico. The inclusion criteria were either gender, age 35-80 years, type 2 diabetes, glycated hemoglobin ≤10%, diabetic polyneuropathy stage 1/2, and signed informed consent...
January 2018: Journal of Circulating Biomarkers
Sven-Jean Tan, Melissa M Chu, Nigel D Toussaint, Michael Mx Cai, Tim D Hewitson, Stephen G Holt
The recently discovered klotho proteins have roles in a diverse range of metabolic processes with the oldest protein, α-klotho, implicated in various cellular pathways in energy, glucose, and phosphate metabolism. Circulating soluble klotho (sKl), derived from membrane α-klotho cleavage, not only has effects on ion channels and insulin signaling pathways, but is inversely associated with mortality. Effects of physical exercise on sKl have not been well studied. The effect of a single high-intensity standardized exercise on sKl and serum phosphate (sPi) levels in healthy adults was investigated...
January 2018: Journal of Circulating Biomarkers
Krishna Sumanth Nallagangula, V Lakshmaiah, C Muninarayana, K V Deepa, K N Shashidhar
Alcoholic liver disease (ALD) progresses from steatosis to alcoholic hepatitis to fibrosis and cirrhosis. Liver biopsy is considered as the gold standard method for diagnosis of liver cirrhosis and provides useful information about damaging process which is an invasive procedure with complications. Existing biomarkers in clinical practice have narrow applicability due to lack of specificity and lack of sensitivity. The objective of this article is to identify proteomic biomarker candidates for alcoholic liver cirrhosis by differential expression analysis between alcoholic liver cirrhotic and healthy subjects...
January 2018: Journal of Circulating Biomarkers
Ranjeeta Gadde, Dayanand Cd, S R Sheela
Placental protein 13 (PP13), a glycan binding protein predominantly expressed in syncytiotrophoblast, dimeric in nature, lacks N-terminal signal peptide, bypasses the endoplasmic reticulum, and secretes into maternal circulation as exosomes or microvesicles. PP13 has jelly roll fold conformation with conserved carbohydrate recognition domain which specifically binds to β-galactosides of the glycan receptors during placentation. PP13 binds to glycosylated receptors on human erythrocytes and brings about hemagglutination by the property of lectin activity; other functions are immunoregulation and vasodilation during placentation and vascularization...
January 2018: Journal of circulating biomarkers
Joseph W Po, Aflah Roohullah, David Lynch, Anna DeFazio, Michelle Harrison, Paul R Harnett, Catherine Kennedy, Paul de Souza, Therese M Becker
Epithelial cell adhesion molecule (EpCAM)-targeted capture remains the most common isolation strategy for circulating tumor cells (CTCs). However, epithelial-to-mesenchymal transition (EMT) leads to decreased epithelial EpCAM expression affecting the optimal CTC capture. In this study, we tested a cohort of ovarian cancer cell lines using flow cytometry to identify N-cadherin as the additional immunomagnetic cell surface target for ovarian cancer cell isolation. Combined immunomagnetic targeting of mesenchymal N-cadherin and epithelial EpCAM enriched CTCs from advanced ovarian cancer patient blood approximately three times more efficiently than targeting of EpCAM alone...
January 2018: Journal of circulating biomarkers
Ram B Jain, Alan Ducatman
Cross-sectional data from National Health and Nutrition Examination Survey for the years 1999-2012 for those aged ≥20 years, fasting for at least 8 h, and classified as smokers and nonsmokers on the basis of observed serum cotinine levels were used to evaluate the impact of smoking on the adjusted and unadjusted concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol (TC), and triglycerides (TG). Adjustments were made for the effects of gender; race/ethnicity; survey year; dietary intake of alcohol; caffeine; cholesterol; saturated, unsaturated, and total fatty acids; fasting time; body mass index; and poverty income ratio...
January 2018: Journal of Circulating Biomarkers
Krishna Sumanth Nallagangula, K N Shashidhar, V Lakshmaiah, Muninarayana
Liver is the vital organ for synthesis of proteins whose concentration in blood reflects liver dysfunction. Variations in protein domain can generate clinically significant biomarkers. Biomarker pipeline includes discovery of candidates, qualification, verification, assay optimization, and validation. Advances in proteomic approach can discover protein biomarker candidates based on "up-or-down" regulation or fold change in expression which is correlated with disease state. Despite numerous biomarker candidates been discovered, only few are useful in clinical practice which indicates the need for well-established validation regimen...
January 2018: Journal of Circulating Biomarkers
Mohammad J Alkhatatbeh, Anoop K Enjeti, Sara Baqar, Elif I Ekinci, Dorothy Liu, Rick F Thorne, Lisa F Lincz
Enumeration of circulating microvesicles (MVs) by conventional flow cytometry is accomplished by the addition of a known amount of counting beads and calculated from the formula: MV/μl = (MV count/bead count) × final bead concentration. We sought to optimize each variable in the equation by determining the best parameters for detecting 'MV count' and examining the effects of different bead preparations and concentrations on the final calculation. Three commercially available bead preparations (TruCount, Flow-Count and CountBright) were tested, and MV detection on a BD FACSCanto was optimized for gating by either forward scatter (FSC) or side scatter (SSC); the results were compared by calculating different subsets of MV on a series of 74 typical patient plasma samples...
January 2018: Journal of Circulating Biomarkers
Jianlu Song, Zhili Yang
Metastatic follicular thyroid carcinoma (FTC), unresectable or resistance to radioactive iodine, is associated with poor survival. It is believed that this kind of FTC is driven by mutated genes. However, what kind of changes of genome and underlying mechanisms are elusive. The aim of this article is to understand whether there are somatic mutations in circulating cell-free tumor DNA (cfDNA) in a FTC patient with lung and bone metastases. A 55-year-old woman was diagnosed with FTC with bone and lung metastases...
January 2018: Journal of Circulating Biomarkers
Nandini Nair, Enrique Gongora
Growth and differentiation factor-15 (GDF-15) has been implicated in fibrosis, inflammation, and ventricular remodeling. The role of GDF-15 in the regulation of cardiac remodeling in idiopathic dilated cardiomyopathy (DCM) remains poorly defined. This study attempts to analyze the molecular interactions between GDF-15 and markers of fibrosis as well as its positive correlations with worsening functional capacity. The study population consisted of 24 DCM patients and 8 control subjects. All DCM patients had normal coronary angiographic studies...
January 2018: Journal of circulating biomarkers
Winston Patrick Kuo
No abstract text is available yet for this article.
January 2017: Journal of Circulating Biomarkers
Moran S Saghiv, D Ben Sira, E Goldhammer, M Sagiv
Different studies support the notion that chronic aerobic exercises training can influence the circulating levels of soluble-Klotho (s-Klotho) and insulin-like growth factor 1 (IGF-I). The effects of s-Klotho include improving the quality of life, alleviating the negative impact of age on the body's work capacity, and possibly increasing longevity. This review provides an overview of the latest findings in this field of research in humans. The different modes of dynamic exercise and their impact on circulating levels of s-Klotho and IGF-I in young adult athletes, untrained young adults, trained healthy older adults, untrained healthy older adults, and coronary artery disease (CAD) patients are reviewed and discussed...
January 2017: Journal of Circulating Biomarkers
Ryuichi Kawamoto, Daisuke Ninomiya, Kensuke Senzaki, Teru Kumagi
Abnormally high glycated hemoglobin (Hb) (HbA1c) is significantly associated with oxidative stress and an increased risk of cardiovascular disease (CVD). Serum total bilirubin (T-B) may have a beneficial role in preventing oxidative changes and be a negative risk factor of CVD. Limited information is available on whether serum T-B is an independent confounding factor of HbA1c. The study subjects were 633 men aged 70 ± 9 (mean ± standard deviation (SD)) years and 878 women aged 70 ± 8 years who were enrolled consecutively from among patients aged ≥40 years through a community-based annual check-up process...
January 2017: Journal of Circulating Biomarkers
Anatilde Gonzalez Guerrico, David Hillman, Jeffery Karnes, Brian Davis, Steven Gaston, George Klee
Free human kallikrein 2 (free-hK2) and hK2 pro-form (pro-hK2) have been found to be increased in tumor tissues and serum from patients with prostate cancer. We established semiautomatic assays for free-hK2 and pro-hK2 using a research version of the Beckman Coulter ACCESS2 system. Serum samples from a cohort of 189 men undergoing radical prostatectomy for known high-risk disease were assayed for Prostate-Specific Antigen (PSA), free-PSA, free-hK2, and pro-hK2. Univariate Cox regression and multivariate models were used to predict both Gleason scores and progression-free survival (PFS)...
January 2017: Journal of Circulating Biomarkers
Anna Markowska, R Scott Pendergrast, J Stephen Pendergrast, P Shannon Pendergrast
The discovery of urinary extracellular biomarkers has been impeded by the lack of efficient methods for the isolation of extracellular vesicles (EVs: exosomes and microvesicles) and extracellular nucleic acid (RNA and DNA) from urine. Ultracentrifugation (UC), considered the gold standard for vesicle isolation from many biofluids, is efficacious but laborious, and, like most commercially available methods, is unable to isolate enough material from small volumes for protein or RNA-based biomarker discovery. We have developed a novel precipitation method for the isolation of EVs and nucleic acids from urine...
January 2017: Journal of Circulating Biomarkers
Azhub Gaziev, Serazhutdin Abdullaev, Gulchachak Minkabirova, Kristina Kamenskikh
Activation of cell death in mammals can be assessed by an increase of an amount of cell-free DNA (cf-DNA) in urine or plasma. We investigated the excretion of cf nuclear DNA (nDNA) and cf mitochondrial DNA (mtDNA) in the urine of rats 3 and 24 months in age after X-irradiation and metformin administration. Analyses showed that prior to treatment, the amount of cf-nDNA was 40% higher and cf-mtDNA was 50% higher in the urine of aged rats compared to that of young animals. At 12 h after irradiation, the content of cf-nDNA and cf-mtDNA in the urine of young rats was increased by 200% and 460%, respectively, relative to the control, whereas in the urine of aged rats, it was 250% and 720% higher...
January 2016: Journal of Circulating Biomarkers
Alejandro Bustamante, Fernando Mancha, Hada C Macher, Teresa García-Berrocoso, Dolors Giralt, Marc Ribó, Juan M Guerrero, Joan Montaner
Circulating cell-free DNA (cfDNA) has been described as a prognostic marker for several diseases. Its prognostic value for short-term outcome in stroke patients treated with intravenous thrombolysis remains unexplored. cfDNA was measured on admission in 54 tissue plasminogen activator (tPA)-treated patients and 15 healthy controls using a real-time quantitative polymerase chain reaction assay. Neurological outcome was assessed at 48 h. Predictors of neurological improvement were evaluated by logistic regression analysis, and the additional predictive value of cfDNA over clinical variables was determined by integrated discrimination improvement (IDI)...
January 2016: Journal of Circulating Biomarkers
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