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1.
Anal Chim Acta ; 1306: 342586, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38692787

ABSTRACT

BACKGROUND: Early prostatic cancer (PCa) diagnosis significantly improves the chances of successful treatment and enhances patient survival rates. Traditional enzyme cascade-based early cancer detection methods offer efficiency and signal amplification but are limited by cost, complexity, and enzyme dependency, affecting stability and practicality. Meanwhile, sarcosine (Sar) is commonly considered a biomarker for PCa development. It is essential to develop a Sar detection method based on cascade reactions, which should be efficient, low skill requirement, and suitable for on-site testing. RESULTS: To address this, our study introduces the synthesis of organic-inorganic self-assembled nanoflowers to optimize existing detection methods. The Sar oxidase (SOX)-inorganic hybrid nanoflowers (Cu3(PO4)2:Ce@SOX) possess inherent fluorescent properties and excellent peroxidase activity, coupled with efficient enzyme loading. Based on this, we have developed a dual-mode multi-enzyme cascade nanoplatform combining fluorescence and colorimetric methods for the detection of Sar. The encapsulation yield of Cu3(PO4)2:Ce@SOX reaches 84.5 %, exhibiting a remarkable enhancement in catalytic activity by 1.26-1.29 fold compared to free SOX. The present study employing a dual-signal mechanism encompasses 'turn-off' fluorescence signals ranging from 0.5 µM to 60 µM, with a detection limit of 0.226 µM, and 'turn-on' colorimetric signals ranging from 0.18 µM to 60 µM, with a detection limit of 0.120 µM. SIGNIFICANCE: Furthermore, our study developed an intelligent smartphone sensor system utilizing cotton swabs for real-time analysis of Sar without additional instruments. The nano-platform exhibits exceptional repeatability and stability, rendering it well-suited for detecting Sar in authentic human urine samples. This innovation allows for immediate analysis, offering valuable insights for portable and efficient biosensors applicable to Sar and other analytes.


Subject(s)
Colorimetry , Oxidation-Reduction , Sarcosine , Smartphone , Sarcosine/urine , Sarcosine/analysis , Sarcosine/chemistry , Humans , Nanostructures/chemistry , Limit of Detection , Spectrometry, Fluorescence , Prostatic Neoplasms/diagnosis , Fluorescence , Biosensing Techniques , Sarcosine Oxidase/chemistry
2.
J Agric Food Chem ; 68(17): 4966-4972, 2020 Apr 29.
Article in English | MEDLINE | ID: mdl-32233480

ABSTRACT

In the course of the Maillard reaction in vivo or in food, creatine reacts with the 1,2-dicarbonyl compound methylglyoxal to N-(4-methyl-5-oxo-1-imidazolin-2-yl)sarcosine (MG-HCr). We studied whether the urinary excretion of MG-HCr is affected by its intake with meat or by the intake of creatine and subsequent in vivo formation of MG-HCr. Therefore, 24 h urine of 30 subjects with different dietary habits was analyzed with HPLC-MS/MS. The daily MG-HCr excretion via urine varied between omnivores (0.39-9.67 µmol/day, n = 24), vegetarians (0.18-0.97 µmol/day, n = 19), and vegans (0.10-0.27 µmol/day, n = 8). An intervention study with 18 subjects demonstrated the bioavailability of MG-HCr (ca. 54%) from 200 g of heated meat and its quick excretion with urine. A creatine intervention of 0.44 g did not increase MG-HCr excretion. Thus, the differences in MG-HCr excretion between different diets are mainly caused by the dietary uptake of MG-HCr. We additionally found MG-HCr in milk and egg products, where it is formed during heat treatment. This partly explains differences in MG-HCr excretion of vegetarians and vegans. Hence, MG-HCr in urine is a short-term marker for the intake of heat-processed animal source food.


Subject(s)
Creatine/urine , Diet , Meat/analysis , Pyruvaldehyde/urine , Adult , Animals , Biomarkers/urine , Eating , Feeding Behavior , Female , Humans , Imidazoles/urine , Maillard Reaction , Male , Sarcosine/urine , Vegans , Young Adult
3.
Analyst ; 145(1): 268-276, 2019 Dec 16.
Article in English | MEDLINE | ID: mdl-31746832

ABSTRACT

Immobilized enzymes play significant roles in many practical applications. However, the enzymes need to be purified before immobilization by conventional immobilizing methods, and the purification process is expensive, laborious, complicated and results in a decrease of the enzymatic activity. So, we present a novel method by a facile one-step targeted immobilization of an enzyme without a purification process from complex samples. For this purpose, a novel molecularly imprinted polymer was prepared via a silane emulsion self-assembly method using boric acid-modified Fe3O4 nanoparticles as magnetic nuclei, horseradish peroxidase as a template, 3-aminopropyltriethoxysilane as a functional monomer and tetraethyl orthosilicate as a crosslinking agent. The molecularly imprinted polymers were characterized using a scanning electron microscope, X-ray photoelectron spectroscope, vibrating sample magnetometer and X-ray diffractometer. The as-prepared and characterized materials were employed to immobilize horseradish peroxidase from a crude extract of horseradish. Moreover, the immobilized horseradish peroxidase was employed to develop visual sensors for the detection of glucose and sarcosine. This study demonstrated that the molecularly imprinted polymers prepared via the silane emulsion self-assembly method can facilely immobilize horseradish peroxidase from a crude extract of horseradish without any purification process. The developed visual method based on the immobilized horseradish peroxidase shows great potential applications for the visual detection of glucose and sarcosine.


Subject(s)
Blood Glucose/analysis , Colorimetry/methods , Enzymes, Immobilized/chemistry , Horseradish Peroxidase/chemistry , Polymers/chemistry , Sarcosine/urine , Armoracia/enzymology , Benzidines/chemistry , Blood Glucose/chemistry , Coloring Agents/chemistry , Emulsions/chemistry , Glucose Oxidase/chemistry , Humans , Hydrogen Peroxide/chemistry , Magnetite Nanoparticles/chemistry , Molecular Imprinting , Propylamines/chemistry , Sarcosine/chemistry , Sarcosine Oxidase/chemistry , Silanes/chemistry
4.
Eur J Endocrinol ; 181(6): 647-657, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31614337

ABSTRACT

OBJECTIVE: Excess catecholamine release by pheochromocytomas and paragangliomas (PPGL) leads to characteristic clinical features and increased morbidity and mortality. The influence of PPGLs on metabolism is ill described but may impact diagnosis and management. The objective of this study was to systematically and quantitatively study PPGL-induced metabolic changes at a systems level. DESIGN: Targeted metabolomics by liquid chromatography-tandem mass spectrometry of plasma specimens in a clinically well-characterized prospective cohort study. METHODS: Analyses of metabolic profiles of plasma specimens from 56 prospectively enrolled and clinically well-characterized patients (23 males, 33 females) with catecholamine-producing PPGL before and after surgery, as well as measurement of 24-h urinary catecholamine using LC-MS/MS. RESULTS: From 127 analyzed metabolites, 15 were identified with significant changes before and after surgery: five amino acids/biogenic amines (creatinine, histidine, ornithine, sarcosine, tyrosine) and one glycerophospholipid (PCaeC34:2) with increased concentrations and six glycerophospholipids (PCaaC38:1, PCaaC42:0, PCaeC40:2, PCaeC42:5, PCaeC44:5, PCaeC44:6), two sphingomyelins (SMC24:1, SMC26:1) and hexose with decreased levels after surgery. Patients with a noradrenergic tumor phenotype had more pronounced alterations compared to those with an adrenergic tumor phenotype. Weak, but significant correlations for 8 of these 15 metabolites with total urine catecholamine levels were identified. CONCLUSIONS: This first large prospective metabolomics analysis of PPGL patients demonstrates broad metabolic consequences of catecholamine excess. Robust impact on lipid and amino acid metabolism may contribute to increased morbidity of PPGL patients.


Subject(s)
Metabolomics/methods , Paraganglioma/metabolism , Paraganglioma/surgery , Pheochromocytoma/metabolism , Pheochromocytoma/surgery , Adolescent , Adult , Aged , Catecholamines/urine , Chromatography, Liquid , Creatinine/urine , Female , Histidine/urine , Humans , Male , Middle Aged , Ornithine/urine , Paraganglioma/urine , Pheochromocytoma/urine , Prospective Studies , Sarcosine/urine , Tandem Mass Spectrometry , Tyrosine/urine , Young Adult
5.
Biosens Bioelectron ; 141: 111431, 2019 Sep 15.
Article in English | MEDLINE | ID: mdl-31212197

ABSTRACT

Amperometric enzyme biosensors are some of the simplest and cheapest types of medical devices used in the rapid detection of biomarkers that have been developed in the past fifty years. When the concentrations of biomarkers are at micromoles per liter, such as for sarcosine, which was recently discovered as a biomarker for prostate cancer, the response signal of the interferences is huge, and the biosensor is hard to satisfy the requirements of practical applications. In this manuscript, we describe a strategy for synthesizing a surface electronegative organic-inorganic hybrid mesoporous material, which could reduce the interference signal much better than Nafion and Chitosan. We verify that the surface potential of the carrier nanomaterial plays an important role in excluding anionic interferences. We also prepare a sensitive (16.35 µA mM-1), low LOD (0.13 µM) and wide linear range (1-70 µM) amperometric sarcosine biosensor with excellent anti-interference properties. This mesoporous material provides a bio-composite platform for the development of simple amperometric biosensors for detecting micromoles per liter of analytes in serum or urine.


Subject(s)
Biosensing Techniques/methods , Nanocomposites/chemistry , Sarcosine/blood , Sarcosine/urine , Electrochemical Techniques/methods , Humans , Limit of Detection , Nanocomposites/ultrastructure , Porosity , Surface Properties
6.
Mikrochim Acta ; 186(3): 136, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30707309

ABSTRACT

A nonenzymatic electrochemical sensor is described for the prostate cancer biomarker sarcosine (Sar). Riboflavin was employed to mimic the active center of the enzyme sarcosine oxidase for constructing the biomimetic sensor. The use of riboflavon (Rf) avoids the disadvantages of an enzymatic sensor, such as high cost and poor stability. A glassy carbon electrode (GCE) was modified with a graphene-chitosan (GR) composite and further modified with gold-platinum bimetallic nanoparticles in a polypyrrole (PPy) matrix in order to enhance the catalytic activity of the enzyme mimic. Finally, Rf was electrodeposited on the surface of the AuPt-PPy/GR-modified GCE. Under optimized conditions, the GCE provided high sensitivity and selectivity for Sar at around 0.61 V. Response covers the 2.5-600 µM concentration range, and the detection limit is 0.68 µM. The method was successfully applied to the determination of Sar in spiked urine with 98.0%-103.2% recovery. Graphical abstract Schematic presentation of the fabrication of the Rf/AuPt-PPy/GR/GCE surface and the measurement principle by differential pulse voltammetry (DPV).


Subject(s)
Biomarkers, Tumor/urine , Biomimetic Materials , Sarcosine/urine , Biosensing Techniques , Chitosan/chemistry , Electrochemical Techniques , Electrodes , Gold/chemistry , Graphite/chemistry , Humans , Limit of Detection , Male , Metal Nanoparticles/chemistry , Particle Size , Platinum/chemistry , Prostatic Neoplasms/diagnosis , Pyrroles/chemistry , Riboflavin/chemistry , Sarcosine Oxidase , Surface Properties
7.
Int J Mol Sci ; 19(12)2018 Nov 22.
Article in English | MEDLINE | ID: mdl-30467297

ABSTRACT

BACKGROUND: Sarcosine is an amino acid that is formed by methylation of glycine and is present in trace amounts in the body. Increased sarcosine concentrations in blood plasma and urine are manifested in sarcosinemia and in some other diseases such as prostate cancer. For this purpose, sarcosine detection using the nanomedicine approach was proposed. In this study, we have prepared superparamagnetic iron oxide nanoparticles (SPIONs) with different modified surface area. Nanoparticles (NPs) were modified by chitosan (CS), and sarcosine oxidase (SOX). SPIONs without any modification were taken as controls. Methods and Results: The obtained NPs were characterized by physicochemical methods. The size of the NPs determined by the dynamic light scattering method was as follows: SPIONs/Au/NPs (100⁻300 nm), SPIONs/Au/CS/NPs (300⁻700 nm), and SPIONs/Au/CS/SOX/NPs (600⁻1500 nm). The amount of CS deposited on the NP surface was found to be 48 mg/mL for SPIONs/Au/CS/NPs and 39 mg/mL for SPIONs/Au/CS/SOX/NPs, and repeatability varied around 10%. Pseudo-peroxidase activity of NPs was verified using sarcosine, horseradish peroxidase (HRP) and 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate. For TMB, all NPs tested evinced substantial pseudo-peroxidase activity at 650 nm. The concentration of SPIONs/Au/CS/SOX/NPs in the reaction mixture was optimized to 0⁻40 mg/mL. Trinder reaction for sarcosine detection was set up at 510 nm at an optimal reaction temperature of 37 °C and pH 8.0. The course of the reaction was linear for 150 min. The smallest amount of NPs that was able to detect sarcosine was 0.2 mg/well (200 µL of total volume) with the linear dependence y = 0.0011x - 0.0001 and the correlation coefficient r = 0.9992, relative standard deviation (RSD) 6.35%, limit of detection (LOD) 5 µM. The suggested method was further validated for artificial urine analysis (r = 0.99, RSD 21.35%, LOD 18 µM). The calculation between the detected and applied concentrations showed a high correlation coefficient (r = 0.99). NPs were tested for toxicity and no significant growth inhibition was observed in any model system (S. cerevisiae, S. aureus, E. coli). The hemolytic activity of the prepared NPs was similar to that of the phosphate buffered saline (PBS) control. The reaction system was further tested on real urine specimens. Conclusion: The proposed detection system allows the analysis of sarcosine at micromolar concentrations and to monitor changes in its levels as a potential prostate cancer marker. The whole system is suitable for low-cost miniaturization and point-of-care testing technology and diagnostic systems. This system is simple, inexpensive, and convenient for screening tests and telemedicine applications.


Subject(s)
Biomarkers, Tumor/urine , Chitosan/chemistry , Magnetite Nanoparticles/chemistry , Prostatic Neoplasms/diagnosis , Sarcosine Oxidase/chemistry , Sarcosine/urine , Escherichia coli/drug effects , Escherichia coli/growth & development , Ferric Compounds/chemistry , Gold/chemistry , Hemolysis/drug effects , Horseradish Peroxidase/chemistry , Humans , Hydrogen-Ion Concentration , Limit of Detection , Magnetite Nanoparticles/ultrastructure , Male , Oxidation-Reduction , Particle Size , Precision Medicine , Prostatic Neoplasms/urine , Reproducibility of Results , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/growth & development , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development
8.
Biosens Bioelectron ; 122: 88-94, 2018 Dec 30.
Article in English | MEDLINE | ID: mdl-30245326

ABSTRACT

Metabolites, the small molecules that underpin life, can act as indicators of the physiological state of the body when their abundance varies, offering routes to diagnosis of many diseases. The ability to assay for multiple metabolites simultaneously will underpin a new generation of precision diagnostic tools. Here, we report the development of a handheld device based on complementary metal oxide semiconductor (CMOS) technology with multiple isolated micro-well reaction zones and integrated optical sensing allowing simultaneous enzyme-based assays of multiple metabolites (choline, xanthine, sarcosine and cholesterol) associated with multiple diseases. These metabolites were measured in clinically relevant concentration range with minimum concentrations measured: 25 µM for choline, 100 µM for xanthine, 1.25 µM for sarcosine and 50 µM for cholesterol. Linking the device to an Android-based user interface allows for quantification of metabolites in serum and urine within 2 min of applying samples to the device. The quantitative performance of the device was validated by comparison to accredited tests for cholesterol and glucose.


Subject(s)
Biosensing Techniques/instrumentation , Lab-On-A-Chip Devices , Point-of-Care Systems , Cholesterol/blood , Cholesterol/urine , Choline/blood , Choline/urine , Equipment Design , Humans , Male , Oxides/chemistry , Sarcosine/blood , Sarcosine/urine , Semiconductors , Xanthine/blood , Xanthine/urine
9.
Cancer Med ; 7(11): 5411-5419, 2018 11.
Article in English | MEDLINE | ID: mdl-30209891

ABSTRACT

To date, there has been no evidence regarding the association between urinary sarcosine content and prostate cancer survival. Our main objective was to investigate whether levels of post-treatment urinary sarcosine are associated with relapse. The inclusion criteria were (in accordance with EAU 2017) as follows: histopathologically verified adenocarcinoma in prostate biopsy cores or specimens from transurethral resection of the prostate (TURP) or prostatectomy for benign prostatic enlargement (BPE) with retained ability to urinate. The median follow-up was 53 months. In the study, we retrospectively evaluated a cohort of 511 patients with prostate cancer with various risk factors and treatment strategies. Post-treatment sarcosine levels were elevated in 266 (52%) patients and highly elevated (≥200 nmol/L) in 71 (13%) patients. Urinary sarcosine content was significantly associated with number of relapses that patients experienced, P = 0.002 for sarcosine ≥200 vs ≤30 nmol/L. Multivariate analysis revealed that sarcosine was an independent predictor of recurrent relapses (≥2 relapses with an intermediate period of remission), HR = 3.89 (95% CI 1.29-11.7) for sarcosine >200 vs <30 nmol/L. This trend was even more pronounced in a subgroup of patients who underwent radical prostatectomy, HR = 3.29 (95% CI 1.06-10.18), where (single) relapse-free survival could also be predicted by sarcosine levels, HR = 1.96 (1.05-3.66). Urinary sarcosine may become a possible predictor for patients' outcomes, because patients with elevated post-treatment sarcosine could be predicted to have recurrent relapses of the disease.


Subject(s)
Adenocarcinoma/urine , Neoplasm Recurrence, Local/urine , Prostatic Neoplasms/urine , Sarcosine/urine , Adenocarcinoma/surgery , Aged , Aged, 80 and over , Biomarkers/urine , Humans , Male , Postoperative Period , Prostatectomy , Prostatic Hyperplasia/surgery , Prostatic Hyperplasia/urine , Prostatic Neoplasms/surgery , Recurrence , Retrospective Studies , Treatment Outcome
10.
J Sep Sci ; 41(15): 3121-3128, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29878649

ABSTRACT

Sarcosine is a potential prostate cancer marker. In this study, we developed a method of three-phase solvent bar liquid-phase microextraction combined with high-performance liquid chromatography to determine sarcosine after derivatization with 4-dimethylarminoazobenzene-4-sulfonyl chloride from human urine. The effects of different extraction conditions on extraction efficiency were investigated and optimized. Under optimum experimental conditions, a calibration graph exhibited linearity over the range of 0.05-25 µmol/L with a correlation coefficient (r2 ) of 0.9990. The enrichment factor was 168, and the detection limit was 0.02 µmol/L. The method was successfully used to analyze sarcosine in human urine and non-invasive detection, and good spiked recoveries ranging from 90.5 to 93.6% were obtained. The proposed method exhibited high sensitivity, high enrichment factor, good precision, and a simple setup. It may contribute to the early accurate diagnosis and the progression monitoring of prostatic carcinoma.


Subject(s)
Liquid Phase Microextraction , Sarcosine/urine , Calibration , Chromatography, High Pressure Liquid , Humans , Molecular Structure , Sarcosine/chemistry , Solvents/chemistry
11.
Med Sci Monit ; 24: 3034-3041, 2018 May 09.
Article in English | MEDLINE | ID: mdl-29741162

ABSTRACT

BACKGROUND The aim of this study was to evaluate the role of the urinary sarcosine/creatinine ratio in the diagnosis and prognosis of prostate cancer, using a sarcosine oxidase assay. MATERIAL AND METHODS Urine samples were obtained from 203 patients with benign prostate hyperplasia (BPH) and 209 patients with prostate cancer. Levels of urinary sarcosine were measured using the sarcosine oxidase method. The urinary sarcosine/creatinine ratios were compared between the group of patients with BPH and the patients with prostate cancer. In the two patients groups, the urinary sarcosine/creatinine ratio was compared with the measurement of serum prostate-specific antigen (PSA) and the free/total (F/T) PSA ratio. Correlations between of the urinary sarcosine/creatinine ratio and the Gleason grade and stage of prostate cancer were analyzed. RESULTS There was a significant difference between the urinary sarcosine/creatinine ratio in the BPH group and prostate cancer group (P<0.01), which was independent of serum PSA. The receiver-operating characteristic (ROC) curve, and area under the curve (AUC) for the urinary sarcosine/creatinine ratio was significantly higher compared with the serum PSA and the F/T PSA ratio. There was a significant difference in the urinary sarcosine/creatinine ratio in patients with prostate cancer with Gleason score ≤6, 7, and ≥8, and between patients with metastatic and non-metastatic prostate cancer. CONCLUSIONS The urinary sarcosine/creatinine ratio was a diagnostic indicator of prostate cancer, for patients with a serum PSA level <10 ng/ml, and correlated with the Gleason score and with the presence of metastases (stage) of prostate cancer.


Subject(s)
Biomarkers, Tumor/urine , Creatinine/urine , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/urine , Sarcosine/urine , Area Under Curve , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Prognosis , Prostatic Neoplasms/pathology , ROC Curve
12.
Analyst ; 143(10): 2349-2355, 2018 May 15.
Article in English | MEDLINE | ID: mdl-29671424

ABSTRACT

A novel luminescent probe based on a Tb3+/Cu2+ heterometallic metal-organic framework (MOF) was first designed for beamed monitoring of urinary sarcosine, a differential metabolite that can indicate the progression of prostate cancer (PCa). The fluorescent probe presented high selectivity towards sarcosine in urine. It also displayed good sensitivity with a comparatively low detection limit and a fast response to sarcosine within 5 min. Moreover, such high selectivity and sensitivity towards sarcosine is not subject to interference from other coexisting species in urine. At the same time, this fluorescent material also demonstrated the possibility for recycling. The excellent sensing performance of this Ln-MOF (lanthanide MOF) enables it to be further employed as a serviceable tool for PCa diagnosis and monitoring.


Subject(s)
Fluorescent Dyes/chemistry , Lanthanoid Series Elements/chemistry , Metal-Organic Frameworks/chemistry , Prostatic Neoplasms/diagnosis , Sarcosine/urine , Disease Progression , Humans , Limit of Detection , Luminescence , Male
13.
Sci Rep ; 8(1): 4958, 2018 03 21.
Article in English | MEDLINE | ID: mdl-29563505

ABSTRACT

The hypothesis that dogs can detect malignant tumours through the identification of specific molecules is nearly 30 years old. To date, several reports have described the successful detection of distinct types of cancer. However, is still a lack of data regarding the specific molecules that can be recognized by a dog's olfactory apparatus. Hence, we performed a study with artificially prepared, well-characterized urinary specimens that were enriched with sarcosine, a widely reported urinary biomarker for prostate cancer (PCa). For the purposes of the study, a German shepherd dog was utilized for analyses of 60 positive and 120 negative samples. Our study provides the first evidence that a sniffer dog specially trained for the olfactory detection of PCa can recognize sarcosine in artificial urine with a performance [sensitivity of 90%, specificity of 95%, and precision of 90% for the highest amount of sarcosine (10 µmol/L)] that is comparable to the identification of PCa-diagnosed subjects (sensitivity of 93.5% and specificity of 91.6%). This study casts light on the unrevealed phenomenon of PCa olfactory detection and opens the door for further studies with canine olfactory detection and cancer diagnostics.


Subject(s)
Dogs/physiology , Prostatic Neoplasms/diagnosis , Sarcosine/chemistry , Smell/physiology , Urinalysis/methods , Animals , Feasibility Studies , Humans , Male , Prostatic Neoplasms/urine , Sarcosine/urine , Sensitivity and Specificity
14.
Anal Chem ; 90(5): 3570-3575, 2018 03 06.
Article in English | MEDLINE | ID: mdl-29417820

ABSTRACT

A selective excitation of [Ir(df-ppy)2(pic)] and [Ru(bpy)3]2+ through tuning the electrode potential is reported in this work. Bidirectional color change from blue-green to red could be observed along with increase and decrease of the potential, which was ascribed to the dual-potential excitation property of [Ir(df-ppy)2(pic)]. Similar to the three-electrode system, selective excitation of ECL could be achieved at the anode of the bipolar electrode (BPE). Both increase and decrease of the faradic reactions at the cathode of the BPE could induce ECL reporting color at the other pole switched from blue-green to red. We applied a closed BPE device for the bioanalysis of multicolor ECL since the organic solvent containing electrochemiluminophores could be separated from the bioanalytes. On the basis of BPE arrays coupled with the ECL switch, the detection of three biomarkers of prostate cancer, PSA, microRNA-141, and sarcosine were integrated in a same device. The cutoff values of the biomarkers could be recognized directly by the naked eye. Such a device holds great potential in the early diagnosis of prostate cancer.


Subject(s)
Luminescent Agents/chemistry , Luminescent Measurements/methods , MicroRNAs/blood , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/urine , Sarcosine/urine , 2,2'-Dipyridyl/analogs & derivatives , 2,2'-Dipyridyl/chemistry , Animals , Aptamers, Nucleotide/chemistry , Biomarkers, Tumor/blood , Biomarkers, Tumor/urine , Biosensing Techniques/methods , Colorimetry/methods , Electrodes , Horses , Humans , Iridium/chemistry , Male , Organometallic Compounds/chemistry
15.
Yakugaku Zasshi ; 137(9): 1147-1154, 2017.
Article in Japanese | MEDLINE | ID: mdl-28867701

ABSTRACT

Considering the pharmacological effects of chiral drugs, enantiopure drugs may differ from their racemic mixture formulation in efficacy, potency, or adverse effects. Levomethorphan (LVM) and Dextromethorphan (DXM) act on the central nervous system and exhibit different pharmacological features. LVM, the l-stereoisomer of methorphan, shows many similarities to opiates such as heroin, morphine and codeine, including the potential for addiction, while the d-stereoisomer, DXM, does not have the same opioid effect. In the present study, NMR-based metabolomics were performed on the urine of rats treated with these stereoisomers, and showed significant differences in metabolic profiles. In urine within 24 h after treatment of these samples, levels of citrate, 2-oxoglutarate, creatine, and dimethylglycine were higher in LVM-treated rats than in DXM-treated rats. While urinary levels of hippurate and creatinine gradually increased over 72 h in DXM-treated rats, these metabolites were decreased in the urine by 48-72 h after treatment with LVM. The levels of these changed metabolites may provide the first evidence for different cellular responses to the metabolism of stereoisomers.


Subject(s)
Illicit Drugs/metabolism , Illicit Drugs/pharmacology , Magnetic Resonance Spectroscopy , Animals , Citric Acid/urine , Creatine/urine , Creatinine/urine , Dextromethorphan/chemistry , Dextromethorphan/metabolism , Dextromethorphan/pharmacology , Hippurates/urine , Illicit Drugs/chemistry , Ketoglutaric Acids/urine , Male , Metabolomics , Rats , Sarcosine/analogs & derivatives , Sarcosine/urine , Stereoisomerism , Time Factors
16.
Biol Chem ; 398(7): 775-784, 2017 06 27.
Article in English | MEDLINE | ID: mdl-27902449

ABSTRACT

Choline metabolism is by oxidation to betaine, which is demethylated to N,N-dimethylglycine; dimethylglycine is oxidatively demethylated to sarcosine. This pathway is important for osmoregulation and as a source of methyl groups. We asked whether another metabolite was involved. We synthesized the N-oxide of dimethylglycine (DMGO) by oxidizing dimethylglycine with peracetic acid, and measured DMGO in human plasma and urine by HPLC-MS/MS with positive ion detection, using two chromatography procedures, based on ion exchange and HILIC separations. The molecular ion DMGOH+ (m/z=120) yielded four significant fragments (m/z=103, 102, 58 and 42). The suspected DMGO peak in human body fluids showed all these fragments, and co-chromatographed with added standard DMGO in both HPLC systems. Typical plasma concentrations of DMGO are under 1 µmol/l. They may be lower in metabolic syndrome patients. Urine concentrations are higher, and DMGO has a higher fractional clearance than dimethylglycine, betaine and choline. It was present in all of over 80 human urine and plasma samples assayed. Plasma DMGO concentrations correlate with plasma DMG concentrations, with betaine and choline concentrations, with the osmolyte myo-inositol, and strongly with urinary DMGO excretion. We conclude that DMGO is probably a normal human metabolite.


Subject(s)
Betaine/metabolism , Choline/metabolism , Sarcosine/analogs & derivatives , Adult , Humans , Male , Metabolism, Inborn Errors/urine , Methylamines/urine , Sarcosine/blood , Sarcosine/metabolism , Sarcosine/urine , Young Adult
17.
Int J Mol Sci ; 17(3): 377, 2016 Mar 17.
Article in English | MEDLINE | ID: mdl-26999116

ABSTRACT

Herein, we present a study focused on the determination of the influence of long-distance (53 km) bicycle riding on levels of chosen biochemical urinary and serum prostate cancer (PCa) biomarkers total prostate-specific antigen (tPSA), free PSA (fPSA) and sarcosine. Fourteen healthy participants with no evidence of prostate diseases, in the age range from 49-57 years with a median of 52 years, underwent physical exercise (mean race time of 150 ± 20 min, elevation increase of 472 m) and pre- and post-ride blood/urine sampling. It was found that bicycle riding resulted in elevated serum uric acid (p = 0.001, median 271.76 vs. 308.44 µmol/L pre- and post-ride, respectively), lactate (p = 0.01, median 2.98 vs. 4.8 mmol/L) and C-reactive protein (p = 0.01, 0.0-0.01 mg/L). It is noteworthy that our work supports the studies demonstrating an increased PSA after mechanical manipulation of the prostate. The subjects exhibited either significantly higher post-ride tPSA (p = 0.002, median 0.69 vs. 1.1 ng/mL pre- and post-ride, respectively) and fPSA (p = 0.028, median 0.25 vs. 0.35 ng/mL). Contrary to that, sarcosine levels were not significantly affected by physical exercise (p = 0.20, median 1.64 vs. 1.92 µmol/mL for serum sarcosine, and p = 0.15, median 0.02 µmol/mmol of creatinine vs. 0.01 µmol/mmol of creatinine for urinary sarcosine). Taken together, our pilot study provides the first evidence that the potential biomarker of PCa-sarcosine does not have a drawback by means of a bicycle riding-induced false positivity, as was shown in the case of PSA.


Subject(s)
Bicycling , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Sarcosine/blood , Biomarkers, Tumor/blood , Biomarkers, Tumor/urine , C-Reactive Protein/analysis , Humans , Lactic Acid/blood , Male , Middle Aged , Prostatic Neoplasms/diagnosis , Reproducibility of Results , Sarcosine/urine , Uric Acid/blood
18.
Future Oncol ; 12(3): 399-411, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26768791

ABSTRACT

Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer.


Subject(s)
Prostatic Neoplasms/metabolism , DNA Methylation , Early Detection of Cancer , Humans , Male , MicroRNAs/blood , Oncogene Proteins, Fusion/genetics , Prostate/metabolism , Prostate/pathology , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/therapy , Sarcosine/urine , Treatment Outcome
19.
Faraday Discuss ; 185: 299-309, 2015.
Article in English | MEDLINE | ID: mdl-26394608

ABSTRACT

Monitoring Prostate Cancer (PCa) biomarkers is an efficient way to diagnosis this disease early, since it improves the therapeutic success rate and suppresses PCa patient mortality: for this reason a powerful analytical technique such as electrochemiluminescence (ECL) is already used for this application, but its widespread usability is still hampered by the high cost of commercial ECL equipment. We describe an innovative approach for the selective and sensitive detection of the PCa biomarker sarcosine, obtained by a synergistic ECL-supramolecular approach, in which the free base form of sarcosine acts as co-reagent in a Ru(bpy)3(2+)-ECL process. We used magnetic micro-beads decorated with a supramolecular tetraphosphonate cavitand (Tiiii) for the selective capture of sarcosine hydrochloride in a complex matrix like urine. Sarcosine determination was then obtained with ECL measurements thanks to the complexation properties of Tiiii, with a protocol involving simple pH changes - to drive the capture-release process of sarcosine from the receptor - and magnetic micro-bead technology. With this approach we were able to measure sarcosine in the µM to mM window, a concentration range that encompasses the diagnostic urinary value of sarcosine in healthy subjects and PCa patients, respectively. These results indicate how this ECL-supramolecular approach is extremely promising for the detection of sarcosine and for PCa diagnosis and monitoring, and for the development of portable and more affordable devices.


Subject(s)
Early Detection of Cancer/methods , Electrochemical Techniques , Prostatic Neoplasms/diagnosis , Sarcosine/urine , Urinalysis/methods , Early Detection of Cancer/economics , Humans , Limit of Detection , Luminescence , Male , Microspheres
20.
J Chromatogr Sci ; 53(8): 1310-5, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25688037

ABSTRACT

Sarcosine, N-methyl glycine, could be used as a biomarker for the diagnosis of prostate cancer. It exists in biosamples at low levels; therefore, sensitive methods are necessary for its detection. In this study, we developed a sensitive and selective method for the analysis of sarcosine, based on derivatizing sarcosine with a fluorescent reagent levofloxacin acyl chloride. The resulting derivative is highly responsive to a fluorimetric detector (λex = 290 nm, λem = 460 nm). The sarcosine derivative can be separated from its molecular isomers (α-l-alanine, α-d-alanine and ß-alanine) on a hexyl-phenyl column by gradient elution using sodium acetate buffer (pH 3.8; 50 mM) and tetrahydrofuran as the mobile phase. The method showed a determination range of sarcosine in water over 44.5-1780.0 ng/mL (0.5-20.0 µM) and the limit of detection at 8.9 ng/mL (0.1 µM) (S/N = 3 with 20 µL injected). Intra- and inter-day precision (as % relative standard deviation) and accuracy (as % relative error) were all below 4.8%. Application of the method to the analysis of sarcosine in human urine proved feasible.


Subject(s)
Chromatography, High Pressure Liquid/methods , Fluorescent Dyes/chemistry , Levofloxacin/chemistry , Sarcosine/analysis , Sarcosine/chemistry , Adult , Aged , Biomarkers, Tumor , Humans , Levofloxacin/analogs & derivatives , Limit of Detection , Linear Models , Male , Middle Aged , Reproducibility of Results , Sarcosine/urine , Young Adult
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