Integrated plasma and urine metabolomics coupled with HPLC/QTOF-MS and chemometric analysis on potential biomarkers in liver injury and hepatoprotective effects of Er-Zhi-Wan

Metabolomics techniques are the comprehensive assessment of endogenous metabolites in a biological system and may provide additional insight into the molecular mechanisms. Er-Zhi-Wan (EZW) is a traditional Chinese medicine formula, which contains Fructus Ligustri Lucidi (FLL) and Herba Ecliptae (HE). EZW is widely used to prevent and treat various liver injuries through the nourishment of the liver. However, the precise molecular mechanism of hepatoprotective effects has not been comprehensively explored. Here, an integrated metabolomics strategy was designed to assess the effects and possible mechanisms of EZW against carbon tetrachloride-induced liver injury, a commonly used model of both acute and chronic liver intoxication. High-performance chromatography/quadrupole time-of-flight mass spectrometry (HPLC/QTOF-MS) combined with chemometric approaches including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to discover differentiating metabolites in metabolomics data of rat plasma and urine. Results indicate six differentiating metabolites, tryptophan, sphinganine, tetrahydrocorticosterone, pipecolic acid, l-2-amino-3-oxobutanoic acid and phosphoribosyl pyrophosphate, in the positive mode. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan metabolism, sphingolipid metabolism, steroid hormone biosynthesis, lysine degradation, glycine, serine and threonine metabolism, and pentose phosphate pathway. Of note, EZW has a potential pharmacological effect, which might be through regulating multiple perturbed pathways to the normal state. Our findings also showed that the robust integrated metabolomics techniques are promising for identifying more biomarkers and pathways and helping to clarify the function mechanisms of traditional Chinese medicine. Graphical Abstract

Overview of the integrated metabolomics strategy     

Multiparametric diagnostics of cardiomyopathies by microRNA signatures

The diagnosis of cardiomyopathies by endomyocardial biopsy analysis is the gold standard for confirmation of causative reasons but is failing if a sample does not contain the area of interest due to focal pathology. Biopsies are revealing an extract of the current situation of the heart muscle only, and the need for global organ-specific or systemic markers is obvious in order to minimize sampling errors. Global markers like specific gene expression signatures in myocardial tissue may therefore reflect the focal situation or condition of the whole myocardium. Besides gene expression profiles, microRNAs (miRNAs) represent a new group of stable biomarkers that are detectable both in tissue and body fluids. Such miRNAs may serve as cardiological biomarkers to characterize inflammatory processes, to confirm viral infections, and to differentiate various forms of infection. The predictive power of single miRNAs for diagnosis of complex diseases may be further increased if several distinctly deregulated candidates are combined to form a specific miRNA signature. Diagnostic systems that generate disease-related miRNA profiles are based on microarrays, bead-based oligo sorbent assays, or on assays based on real-time polymerase chain reactions and placed on microfluidic cards or nanowell plates. Multiparametric diagnostic systems that can measure differentially expressed miRNAs may become the diagnostic tool of the future due to their predictive value with respect to clinical course, therapeutic decisions, and therapy monitoring. We discuss here specific merits, limitations and the potential of currently available analytical platforms for diagnostics of heart muscle diseases based on miRNA profiling. Contains 34 references. Figure

Modern diagnostics of cardiomyopathies will include multiparametric analysis of microRNA profiles in endomyocardial biopsies by real-time PCR or bead-based OLISA techniques. In contrast to high-throughput screening technologies diagnostic systems are realized by down-scaling sample volumes and simultaneous measurement of a limited number of stable disease related parameters.     

Prostate Cancer Review: Genetics,Diagnosis, Treatment Options,and Alternative Approaches

Simple SummaryProstate cancer affects men of all racial and ethnic groups and leads to higher rates of mortality in those belonging to a lower socioeconomic status due to late detection of the disease. There is growing evidence that suggests the contribution of an individual’s genetic profile to prostate cancer. Currently used prostate cancer treatments have serious adverse effects; therefore, new research is focusing on alternative treatment options such as the use of genetic biomarkers for targeted gene therapy, nanotechnology for controlled targeted treatment, and further exploring medicinal plants for new anticancer agents. In this review, we describe the recent advances in prostate cancer research.AbstractProstate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate cancer present with either a localized or advanced disease. In this review, we aim to provide a holistic overview of prostate cancer, including the diagnosis of the disease, mutations leading to the onset and progression of the disease, and treatment options. Prostate cancer diagnoses include a digital rectal examination, prostate-specific antigen analysis, and prostate biopsies. Mutations in certain genes are linked to the onset, progression, and metastasis of the cancer. Treatment for localized prostate cancer encompasses active surveillance, ablative radiotherapy, and radical prostatectomy. Men who relapse or present metastatic prostate cancer receive androgen deprivation therapy (ADT), salvage radiotherapy, and chemotherapy. Currently, available treatment options are more effective when used as combination therapy; however, despite available treatment options, prostate cancer remains to be incurable. There has been ongoing research on finding and identifying other treatment approaches such as the use of traditional medicine, the application of nanotechnologies, and gene therapy to combat prostate cancer, drug resistance, as well as to reduce the adverse effects that come with current treatment options. In this article, we summarize the genes involved in prostate cancer, available treatment options, and current research on alternative treatment options.     

Top-Down and Bottom-Up Identification of Proteins by Liquid Extraction Surface Analysis Mass Spectrometry of Healthy and Diseased Human Liver Tissue

Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15–25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies. Graphical Abstract

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In vitro/in vivo screening of oxidative homeostasis and damage to DNA,protein, and lipids using UPLC/MS-MS

Multiple analytical methods are required to comprehensively assess oxidative homeostasis and specific damage to macromolecules. Our aim was to develop a straightforward strategy for the fast assessment of global oxidative status and specific damage to DNA, proteins, and lipids. To this end, an analytical method, based on ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS/MS), was developed and validated for the quantification of 16 oxidative stress (OS) biomarkers. Some of these markers were unstable; thus, an easy sample treatment procedure, including fractionation and derivatization, was set up. The method was validated according to Food and Drug Administration (FDA) guidelines, and it provided good results in terms of intra- and inter-day precision (≤17.2 and 16 %, respectively), accuracy (relative error measurement between ?16.6 and 19.8 %), and linearity (R ²?>?0.994). The approach was applied to determine the oxidative insult provoked to cultured rat hepatocytes by cumene hydroperoxide and to analyze the liver and serum samples from patients diagnosed with nonalcoholic steatohepatitis. In both studies, significant differences were found if compared to the corresponding control groups; interestingly, ophthalmic acid was shown as an OS biomarker in both models for the first time. A key advantage of the novel approach in comparison with former multi-method approaches is that now a single method is applied to assess the 16 OS biomarkers. Its comprehensive capacity to profile oxidative homeostasis and damage in both in vitro and clinical samples has been illustrated, which indicates that the proposed approach is a good choice to evaluate whether OS is involved in physiological signals, diseases, or toxic events and to what extent.     

The Prognostic Value of Histidine-Rich Glycoprotein RNA in Breast Tissue Using Unmodified Gold Nanoparticles Assay

The aim of is this study is to explore the role of tissue histidine-rich glycoprotein (HRG) RNA as a promising clinically useful biomarker for breast cancer patients prognosis using nanogold assay. Expression of the HRG RNA was assessed by gold nanoparticles and conventional RT-PCR after purification by magnetic nanoparticles in breast tissue samples. The study included 120 patients, 60 of which were histologically proven breast carcinoma cases, 30 had benign breast lesions and 30 were healthy individuals who had undergone reductive plastic surgery. ER, PR and HER2 status were also investigated. The prognostic significance of tissue HRG RNA expression in breast cancer was explored. The magnetic nanoparticles coated with specific thiol modified oligonucleotide probe were used successfully in purification of HRG RNA from breast tissue total RNAs with satisfactory yield. The developed HRG AuNPs assay had a sensitivity and a specificity of 90 %, and a detection limit of 1.5 nmol/l. The concordance rate between the HRG AuNPs assay with RT-PCR after RNA purification using magnetic nanoparticles was 93.3 %. The median follow-up period was 60 months. Among traditional prognostic biomarkers, HRG was a significant independent prognostic marker in relapse-free survival (RFS). HRG RNA is an independent prognostic marker for breast cancer and can be detected using gold NPs assay, which is rapid, sensitive, specific, inexpensive to extend the value for breast cancer prognosis.     

A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats

As a well‐known traditional Chinese medicine formula, Ding‐Zhi‐Xiao‐Wan has long been used for the routine treatment of Alzheimer's disease. However, the mechanism of Ding‐Zhi‐Xiao‐Wan in treating Alzheimer's disease is unclear. Therefore, a nontargeted metabolomics method based on ultrahigh performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry has been established to explore the metabolic variations in the urine of Alzheimer's disease rats and investigate the therapeutic mechanism of Ding‐Zhi‐Xiao‐Wan on Alzheimer's disease. To develop a better rat model of Alzheimer's disease, amyloid β25‐35 was injected into the bilateral hippocampus of Sprague–Dawley rats. Multivariate analysis approaches were applied to differentiate the urine components between the four groups. Thereafter, a targeted metabolomics method was used to verify the identified endogenous metabolites and determine the mechanism of action of Ding‐Zhi‐Xiao‐Wan. Altogether, 26 potential biomarkers were found, of which 15 biomarkers (10 of which are potential biomarkers found in nontargeted metabolomics) were identified. The results show that Ding‐Zhi‐Xiao‐Wan mainly affects the pathways of taurine and hypotaurine metabolism, tryptophan metabolism, and phenylalanine metabolism. Ding‐Zhi‐Xiao‐Wan might play a role in the treatment of Alzheimer's disease by mediating antioxidative stress, regulation of energy metabolism, improvement of intestinal microbes, and protection of nerve cells.     

Identification of biomarkers in the hair of dogs: new diagnostic possibilities in the study and control of visceral leishmaniasis

Visceral leishmaniasis (VL) is a zoonosis whose etiologic agent in the Americas is Leishmania infantum, and dogs are the main host. Research and innovation in diagnostic techniques are essential to improve the surveillance and control of VL in endemic areas. The present study investigates the profile of the volatile organic compounds (VOCs) emitted by healthy dogs and by dogs infected by L. infantum to detect variations in the VOCs that may be used as biomarkers in the diagnosis of VL. In total, 36 dogs were selected from an endemic area and divided into three groups: G1, not infected with L. infantum; G2, infected without clinical signs of VL; and G3, infected with clinical signs of VL. To analyze the profiles of the VOCs emitted by dogs from the three groups, solid-phase microextraction (SPME) combined with gas chromatography-mass spectrometry (GC-MS) was used. Variations were observed between the profiles of the VOCs emitted in the three groups studied, and they also differentiated infected animals with or without clinical signs. Six VOCs were identified as potential biomarkers of infection, with significant variations between healthy dogs (G1) and infected dogs (G2?+?G3). The detection of variations between groups G2 and G3 suggested that the profiles of some VOCs may be related to the type of immune response and the parasite load of the infected dogs. This study demonstrated the possibility of analysis of VOCs as biomarkers of VL in diagnostic, clinical, and epidemiological work.     

Metabolomics: a revolution for novel cancer marker identification

The repertoire of small-molecular-weight substances present in cells, tissue and body fluids are known as the metabolites. The global analysis of metabolites, such as by high-resolution 1H nuclear magnetic resonance spectroscopy and mass spectrometry, is integral to the rapidly expanding field of metabolomics, which is making progress in various diseases. In the area of cancer and metabolic phenotype, the integrated analysis of metabolites may provide a powerful platform for detecting changes related to cancer diagnosis and discovering novel biomarkers. In this review, metabolomics including the technologies in metabolomics research and extracting information from metabolomics datasets are described. Then we discuss the challenges and opportunities in metabolomics for finding metabolic processes in cancer and discovering novel cancer biomarkers. Finally, we assess the clinical applicability of metabolomics.     

Low surface area carbonized silica obtained by the pyrolysis of dichloromethane: A column packing for adsorption and exclusion chromatography

Carbonized silica has been used as column packing for HPLC. Up to now it has been obtained by the pyrolysis of the vapour of benzene as well as aliphatic and aromatic alcohols. This paper reports on the properties of carbonized silica obtained by the pyrolysis of dichloromethane and used as column packing in HPLC.     

Serum metabolomics as a novel diagnostic approach for disease: a systematic review

Metabolomics is a promising "omics" field in systems biology; its objective is comprehensive analysis of low-molecular-weight endogenous metabolites in a biological sample. It could enable mapping of perturbations of early biochemical changes in diseases and hence provide an opportunity to develop predictive biomarkers that could result in earlier intervention and provide valuable insights into the mechanisms of diseases. Because of the possible discovery of clinically relevant biomarkers, metabolomics has potential advantages that routine approaches to clinical diagnosis do not. Monitoring specific metabolite levels in serum, the most commonly used biofluid in metabolomics, has become an important way of detecting the early stages of a disease. Serum is a readily accessible and informative biofluid, making it ideal for early detection of a wide range of diseases, and analysis of serum has several advantages over analysis of other biofluids. Metabolite profiles of serum can be regarded as important indicators of physiological and pathological states and may aid understanding of the mechanism of disease occurrence and progression on the metabolic level, and provide information enabling identification of early and differential metabolic markers of disease. Analysis of these crucial metabolites in serum has become important in monitoring the state of biological organisms and is widely used for diagnosis of disease. Emerging metabolomics will drive serum analysis, facilitate and improve the development of disease treatments, and provide great benefits for public health in the long-term.     

Ellagic Acid Normalizes Mitochondrial Outer Membrane Permeabilization and Attenuates Inflammation-Mediated Cell Proliferation in Experimental Liver Cancer

Despite great advances in our understanding of the molecular causes of liver cancer, significant gaps still remain in our knowledge of the disease pathogenesis and development of effective strategies for early diagnosis and treatment. The present study was conducted to evaluate the chemopreventive activity of ellagic acid (EA) against experimental liver cancer in rats. This is the first report that implies a possible role of EA in controlling liver cancer through activation of mitochondrial outer membrane permeability via activating proteins such as Bax, bcl-2, cyt-C, and caspase-9, which play important roles in apoptosis. Downregulation of NF-κB, cyclin D1, cyclin E1, matrix metalloproteinases (MMP)-2, MMP-9, and proliferating cell nuclear antigen (PCNA) were noted in EA-treated experimental rats and controlled inflammation mediated liver cancer when compared to the diethylnitrosamine (DEN)-induced group. Transmission electron microscopy (TEM) analysis of the livers of experimental rats demonstrated that EA treatment renovated its internal architecture. Overall, these results demonstrate the value of molecular approaches in identifying the potential role of EA as an effective chemopreventive agent.     

Validation of a confirmatory method for lipophilic marine toxins in shellfish using UHPLC-HR-Orbitrap MS

Lipophilic marine toxins are produced by harmful microalgae and can accumulate in edible filter feeders such as shellfish, leading to an introduction of toxins into the human food chain, causing different poisoning effects. During the last years, analytical methods, based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), have been consolidated by interlaboratory validations. However, the main drawback of LC-MS/MS methods remains the limited number of compounds that can be analyzed in a single run. Due to the targeted nature of these methods, only known toxins, previously considered during method optimization, will be detected. Therefore in this study, a method based on ultra-high-performance liquid chromatography coupled to high-resolution Orbitrap mass spectrometry (UHPLC-HR-Orbitrap MS) was developed. Its quantitative performance was evaluated for confirmatory analysis of regulated lipophilic marine toxins in shellfish flesh according to Commission Decision 2002/657/EC. Okadaic acid (OA), dinophysistoxin-1 (DTX-1), pectenotoxin-2 (PTX-2), azaspiracid-1 (AZA-1), yessotoxin (YTX), and 13-desmethyl spirolide C (SPX-1) were quantified using matrix-matched calibration curves (MMS). For all compounds, the reproducibility ranged from 2.9 to 4.9 %, repeatability from 2.9 to 4.9 %, and recoveries from 82.9 to 113 % at the three different spiked levels. In addition, confirmatory identification of the compounds was effectively performed by the presence of a second diagnostic ion (¹³C). In conclusion, UHPLC-HR-Orbitrap MS permitted more accurate and faster detection of the target toxins than previously described LC-MS/MS methods. Furthermore, HRMS allows to retrospectively screen for many analogues and metabolites using its full-scan capabilities but also untargeted screening through the use of metabolomics software. Figure

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Rapid and Sensitive LC–MS/MS Analysis of Fatty Acids in Clinical Samples

Free fatty acids (FFAs), major cellular metabolites, play an important role during tumor pathogenesis. Enhanced de novo fatty acid synthesis in tissues is a characteristic feature of cancer. Therefore, measurement of FFA concentration in biological samples is beneficial for cancer research and clinical diagnosis. Herein, a rapid, stable, and sensitive detection methodology was established to simultaneously quantify 22 FFAs using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI–MS/MS). The HPLC–MS/MS system was run in negative ion mode for 15 min using multiple reaction monitoring. The lipids were extracted from colon tissues of colon cancer patients and then injected into the HPLC–MS/MS system for analysis. Colon samples were analyzed by inter-day repeatability and intra-day repeatability, with less than 5 % deviation for most fatty acids. This approach is successful to determine low picogram concentrations of each FFA molecule using milligrams of tissue, and provides a promising method for FFA microanalysis in clinical samples.     

Antitumoral and MMP-2 inhibition activity of raloxifene or tamoxifen loaded nanoparticles containing dimethyl-β-cyclodextrin

A new nanoparticle formulation has been developed by using dimethyl-β-cyclodextrin (DM-β-CD) with raloxifene HCl or tamoxifene citrate. Both drugs are insoluble in water and represent as low bioavailibilities when given orally. Tamoxifen has an FDA approval for breast cancer prevention and the treatment. Raloxifene is approved for osteoprosis treatment. Both drugs were selected as a model drug antitumoural activity and MMP-2 inhibition studies were evaluated on breast cancer cell lines MCF-7 and MDA-MB 231. MMP-2 is known to be responsible for tumour invasion and initation the of angiogenesis. DM-β-CD and sodium taurocholate (NaTC) have been used as absorption enhancers to increase penetration effect of raloxifene/tamoxifen on the tumour cells and aimed to provide high antitumoral activity and MMP-2 inhibition results by developed nanoparticle formulations. The effects of two absorption enhancers were compared. The highest antitumoral activity was observed for DM-β-CD—raloxifene HCl nanoparticle formulation and also MMP-2 enzyme inhibit effectively.     

Recent advances in metabolomics in neurological disease, and future perspectives

Discovery of clinically relevant biomarkers for diseases has revealed metabolomics has potential advantages that classical diagnostic approaches do not. The great asset of metabolomics is that it enables assessment of global metabolic profiles of biofluids and discovery of biomarkers distinguishing disease status, with the possibility of enhancing clinical diagnostics. Most current clinical chemistry tests rely on old technology, and are neither sensitive nor specific for a particular disease. Clinical diagnosis of major neurological disorders, for example Alzheimer’s disease and Parkinson’s disease, on the basis of current clinical criteria is unsatisfactory. Emerging metabolomics is a powerful technique for discovering novel biomarkers and biochemical pathways to improve diagnosis, and for determination of prognosis and therapy. Identifying multiple novel biomarkers for neurological diseases has been greatly enhanced with recent advances in metabolomics that are more accurate than routine clinical practice. Cerebrospinal fluid (CSF), which is known to be a rich source of small-molecule biomarkers for neurological and neurodegenerative diseases, and is in close contact with diseased areas in neurological disorders, could potentially be used for disease diagnosis. Metabolomics will drive CSF analysis, facilitate and improve the development of disease treatment, and result in great benefits to public health in the long-term. This review covers different aspects of CSF metabolomics and discusses their significance in the postgenomic era, emphasizing the potential importance of endogenous small-molecule metabolites in this emerging field.     

Characterization of Volatile Organic Metabolites in Lung Cancer Pleural Effusions by SPME–GC/MS Combined with an Untargeted Metabolomic Method

Headspace solid-phase microextraction and gas chromatography/mass spectrometry (HS-SPME–GC/MS) method combined with XCMS Online was tentatively applied to characterize the dysregulated volatile organic metabolites (VOMs) in benign and malignant pleural effusions. A total of 9 dysregulated feature groups were isolated from metabolic features in 35 pleural effusion samples (20 benign effusions and 15 malignant ones from lung cancer patients). Principle component analysis, partial least squares discriminant analysis (PLS-DA) and orthogonal PLS-DA were built to separate benign from malignant pleural effusion groups and to find dysregulated metabolites in significantly different amounts between the two groups. Four dysregulated VOMs such as 2-ethyl-1-hexanol, cyclohexanone, 1,2,4,5-tetramethylbenzene and naphthalene were selected according to the variable influence on the projection value. The concentration of the four dysregulated VOMs in benign and malignant effusions were further determined by external standard method. The median concentrations of 4 VOMs in malignant effusion samples were from 4.7 to 91,121.9 nM, whereas their median levels were only 1.9–318.3 nM in benign ones. The results show that the proposed SPME–GC/MS-based metabolomic approach combined with XCMS Online data processing is a simple, rapid and available method for the characterization of dysregulated VOMs in malignant and benign pleural effusions.     

Characterization of Stress-Exposed Granulocyte Colony Stimulating Factor Using ELISA and Hydrogen/Deuterium Exchange Mass Spectrometry

Information on the higher-order structure is important in the development of biopharmaceutical drugs. Recently, hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) has been widely used as a tool to evaluate protein conformation, and unique automated systems for HDX-MS are now commercially available. To investigate the potential of this technique for the prediction of the activity of biopharmaceuticals, granulocyte colony stimulating factor (G-CSF), which had been subjected to three different stress types, was analyzed using HDX-MS and through comparison with receptor-binding activity. It was found that HDX-MS, in combination with ion mobility separation, was able to identify conformational changes in G-CSF induced by stress, and a good correlation with the receptor-binding activity was demonstrated, which cannot be completely determined by conventional peptide mapping alone. The direct evaluation of biological activity using bioassay is absolutely imperative in biopharmaceutical development, but HDX-MS can provide the alternative information in a short time on the extent and location of the structural damage caused by stresses. Furthermore, the present study suggests the possibility of this system being a versatile evaluation method for the preservation stability of biopharmaceuticals. Graphical Abstract

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Isolation of Biogenic Amines Using Paramagnetic Microparticles Off-Line Coupled with Ion Exchange Liquid Chromatography

This study aims at the possibility of single structured paramagnetic microparticles (PMPs), composed of maghemite (γ-Fe₂O₃) core modified with chitosan called MAN8, or tetraethyl orthosilicate covered with Dowex called MAN35, to be helpful for isolation of biogenic amines prior to their further analysis. Primarily, we synthesized and characterized PMPs. To obtain the information about bead morphology, scanning electron microscopy was employed. Furthermore, X-ray fluorescence was employed to carry out the elemental composition analyses. To obtain further insight into interaction between PMP surface and biogenic amines, scanning electron microscope was employed. It was shown that binding of biogenic amines causes increase of relative current response of deprotonated microparticles. We tested the specificity of PMPs to bind biogenic amines on histamine, tyramine, spermine, spermidine, putrescine, and cadaverine. We found that two types of our PMPs were able to selectively bind spermidine, cadaverine, and histamine in the case of MAN35; and histamine, tyramine, and putrescine in the case of MAN8. Finally, we carried out the analyses of real samples obtained from patients suffering from prostate carcinoma, where histamine was determined as the most abundant biogenic amine (10.456–13.654 µg mL^?1). The prepared PMPs were able to isolate the biogenic amines from real samples, and thus they may be helpful in construction of biosensors, or Lab-on-a-Chip platforms, enabling less painful, and more rapid diagnosis of prostate cancer.     

An experimental and theoretical study on the structure and photoactivity of XFe2O4 (X = Mn,Fe, Ni,Co, and Zn) structures

XFe₂O₄ magnetic nanoparticles (X = Mn, Fe, Co, Ni, and Zn) were prepared by using two methods: coprecipitation and hydrothermal. The synthesized nanoparticles were compared according to the separation in an external magnetic field and finally, the hydrothermal method was specified as a better synthesis method. The magnetic nanoparticles were characterized by physico-chemical analysis methods such as Vibrating Sample Magnetometer (VSM), X-ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), nitrogen adsorption-adsorption isotherm and Transmission Electron Microscopy (TEM). Magnetic properties of synthesized nanoparticles were studied by ab-initio theoretical methods to confirm and compare with the experimental results. According to the VSM analysis, all of magnetic nanoparticles had good magnetization while CoFe₂O₄ nanoparticles showed the ferromagnetic behavior. The magnetic properties of XFe₂O₄ configurations were studied using Density Functional Theory ab-initio method. The theoretical results were consistent with experimental magnetizations in the absence of external field. Finally, the photocatalytic behavior of prepared samples was investigated in the presence of oxone as an accelerated agent for degradation of an azo dye.