Human serum proteomics reveals a molecular signature after one night of sleep deprivation.

Study Objectives: Sleep deprivation is highly prevalent and caused by conditions such as night shift work or illnesses like obstructive sleep apnea. Compromised sleep affects cardiovascular-, immune-, and neuronal systems. Recently, we published human serum proteome changes after a simulated night shift. This pilot proteomic study aimed to further explore changes in human blood serum after 6 hours of sleep deprivation at night. Methods: Human blood serum samples from eight self-declared healthy females were analyzed using Orbitrap Eclipse mass spectrometry (MS-MS) and high-pressure liquid chromatography. We used a within-participant design, in which the samples were taken after 6 hours of sleep at night and after 6 hours of sleep deprivation the following night. Systems biological databases and bioinformatic software were used to analyze the data and comparative analysis were done with other published sleep-related proteomic datasets. Results: Out of 494 proteins, 66 were found to be differentially expressed proteins (DEPs) after 6 hours of sleep deprivation. Functional enrichment analysis revealed the associations of these DEPs with several biological functions related to the altered regulation of cellular processes such as platelet degranulation and blood coagulation, as well as associations with different curated gene sets. Conclusions: This study presents serum proteomic changes after 6 hours of sleep deprivation, supports previous findings showing that short sleep deprivation affects several biological processes, and reveals a molecular signature of proteins related to pathological conditions such as altered coagulation and platelet function, impaired lipid and immune function, and cell proliferation. Data are available via ProteomeXchange with identifier PXD045729. This paper is part of the Genetic and other molecular underpinnings of sleep, sleep disorders, and circadian rhythms including translational approaches Collection.

Enhancing the wound healing process through local injection of exosomes derived from blood serum: An in vitro and in vivo assessment.

Introduction: The skin plays a crucial role as a protective barrier against external factors, but disruptions to its integrity can lead to wound formation and hinder the natural healing process. Scar formation and delayed wound healing present significant challenges in skin injury treatment. While alternative approaches such as skin substitutes and tissue engineering exist, they are often limited in accessibility and cost. Exosomes have emerged as a potential solution for wound healing due to their regenerative properties. Methods: In this study, exosomes were isolated from human blood serum using a kit. The exosomes were characterized, and their effects on cell migration were assessed in vitro. Additionally, the wound healing capacity of exosomes was evaluated in vivo using a rat full-thickness wound model. Results: Our in vitro findings revealed that exosomes significantly promoted cell migration. In vivo experiments demonstrated that the injection of exosomes at different areas of the wound accelerated the wound healing process, resulting in wound closure, collagen synthesis, vessel formation, and angiogenesis in the wound area. These results suggest that exosomes have a promising therapeutic potential for expediting wound healing and minimizing scar formation. Conclusions: The findings of this study highlight the potential of exosomes as a novel approach for enhancing wound healing. Exosomes showed positive effects on both cell migration and wound closure in in vitro and in vivo studies, suggesting their potential use as a regenerative therapy for skin injuries. Further research is needed to fully understand the mechanisms underlying the beneficial effects of exosomes on wound healing and to optimize their application in clinical settings.

CeO2·ZnO@biomass-derived carbon nanocomposite-based electrochemical sensor for efficient detection of ascorbic acid.

Ascorbic acid (AA), a prominent antioxidant commonly found in human blood serum, serves as a biomarker for assessing oxidative stress levels. Therefore, precise detection of AA is crucial for swiftly diagnosing conditions arising from abnormal AA levels. Consequently, the primary aim of this research is to develop a sensitive and selective electrochemical sensor for accurate AA determination. To accomplish this aim, we used a novel nanocomposite comprised of CeO2-doped ZnO adorned on biomass-derived carbon (CeO2·ZnO@BC) as the active nanomaterial, effectively fabricating a glassy carbon electrode (GCE). Various analytical techniques were employed to scrutinize the structure and morphology features of the CeO2·ZnO@BC nanocomposite, ensuring its suitability as the sensing nanomaterial. This innovative sensor is capable of quantifying a wide range of AA concentrations, spanning from 0.5 to 1925 µM in a neutral phosphate buffer solution. It exhibits a remarkable sensitivity of 0.2267 µA µM-1cm-2 and a practical detection limit of 0.022 µM. Thanks to its exceptional sensitivity and selectivity, this sensor enables highly accurate determination of AA concentrations in real samples. Moreover, its superior reproducibility, repeatability, and stability underscore its reliability and robustness for AA quantification.

Human Blood Serum Counteracts EGFR/HER2-Targeted Drug Lapatinib Impact on Squamous Carcinoma SK-BR-3 Cell Growth and Gene Expression.

Lapatinib is a targeted therapeutic inhibiting HER2 and EGFR proteins. It is used for the therapy of HER2-positive breast cancer, although not all the patients respond to it. Using human blood serum samples from 14 female donors (separately taken or combined), we found that human blood serum dramatically abolishes the lapatinib-mediated inhibition of growth of the human breast squamous carcinoma SK-BR-3 cell line. This antagonism between lapatinib and human serum was associated with cancelation of the drug induced G1/S cell cycle transition arrest. RNA sequencing revealed 308 differentially expressed genes in the presence of lapatinib. Remarkably, when combined with lapatinib, human blood serum showed the capacity of restoring both the rate of cell growth, and the expression of 96.1% of the genes expression of which were altered by the lapatinib treatment alone. Co-administration of EGF with lapatinib also restores the cell growth and cancels alteration of expression of 95.8% of the genes specific to lapatinib treatment of SK-BR-3 cells. Differential gene expression analysis also showed that in the presence of human serum or EGF, lapatinib was unable to inhibit the Toll-Like Receptor signaling pathway and alter expression of genes linked to the Gene Ontology term of Focal adhesion.

Serum Induces the Subunit-Specific Activation of NF-κB in Proliferating Human Cardiac Stem Cells.

Cardiovascular diseases (CVDs) are often linked to ageing and are the major cause of death worldwide. The declined proliferation of adult stem cells in the heart often impedes its regenerative potential. Thus, an investigation of the proliferative potential of adult human cardiac stem cells (hCSCs) might be of great interest for improving cell-based treatments of cardiovascular diseases. The application of human blood serum was already shown to enhance hCSC proliferation and reduce senescence. Here, the underlying signalling pathways of serum-mediated hCSC proliferation were studied. We are the first to demonstrate the involvement of the transcription factor NF-κB in the serum-mediated proliferative response of hCSCs by utilizing the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). RNA-Sequencing (RNA-Seq) revealed ATF6B, COX5B, and TNFRSF14 as potential targets of NF-κB that are involved in serum-induced hCSC proliferation.

Serum-Induced Proliferation of Human Cardiac Stem Cells Is Modulated via TGFßRI/II and SMAD2/3.

The ageing phenotype is strongly driven by the exhaustion of adult stem cells (ASCs) and the accumulation of senescent cells. Cardiovascular diseases (CVDs) and heart failure (HF) are strongly linked to the ageing phenotype and are the leading cause of death. As the human heart is considered as an organ with low regenerative capacity, treatments targeting the rejuvenation of human cardiac stem cells (hCSCs) are of great interest. In this study, the beneficial effects of human blood serum on proliferation and senescence of hCSCs have been investigated at the molecular level. We show the induction of a proliferation-related gene expression response by human blood serum at the mRNA level. The concurrent differential expression of the TGFß target and inhibitor genes indicates the participation of TGFß signalling in this context. Surprisingly, the application of TGFß1 as well as the inhibition of TGFß type I and type II receptor (TGFßRI/II) signalling strongly increased the proliferation of hCSCs. Likewise, both human blood serum and TGFß1 reduced the senescence in hCSCs. The protective effect of serum on senescence in hCSCs was enhanced by simultaneous TGFßRI/II inhibition. These results strongly indicate a dual role of TGFß signalling in terms of the serum-mediated effects on hCSCs. Further analysis via RNA sequencing (RNA-Seq) revealed the participation of Ras-inactivating genes wherefore a prevention of hyperproliferation upon serum-treatment in hCSCs via TGFß signalling and Ras-induced senescence is suggested. These insights may improve treatments of heart failure in the future.

Human Blood Serum Can Diminish EGFR-Targeted Inhibition of Squamous Carcinoma Cell Growth through Reactivation of MAPK and EGFR Pathways.

Regardless of the presence or absence of specific diagnostic mutations, many cancer patients fail to respond to EGFR-targeted therapeutics, and a personalized approach is needed to identify putative (non)responders. We found previously that human peripheral blood and EGF can modulate the activities of EGFR-specific drugs on inhibiting clonogenity in model EGFR-positive A431 squamous carcinoma cells. Here, we report that human serum can dramatically abolish the cell growth rate inhibition by EGFR-specific drugs cetuximab and erlotinib. We show that this phenomenon is linked with derepression of drug-induced G1S cell cycle transition arrest. Furthermore, A431 cell growth inhibition by cetuximab, erlotinib, and EGF correlates with a decreased activity of ERK1/2 proteins. In turn, the EGF- and human serum-mediated rescue of drug-treated A431 cells restores ERK1/2 activity in functional tests. RNA sequencing revealed 1271 and 1566 differentially expressed genes (DEGs) in the presence of cetuximab and erlotinib, respectively. Erlotinib- and cetuximab-specific DEGs significantly overlapped. Interestingly, the expression of 100% and 75% of these DEGs restores to the no-drug level when EGF or a mixed human serum sample, respectively, is added along with cetuximab. In the case of erlotinib, EGF and human serum restore the expression of 39% and 83% of DEGs, respectively. We further assessed differential molecular pathway activation levels and propose that EGF/human serum-mediated A431 resistance to EGFR drugs can be largely explained by reactivation of the MAPK signaling cascade.

Facile immobilization of cholesterol oxidase on Pt,Ru-C nanocomposite and ionic liquid-modified carbon paste electrode for an efficient amperometric free cholesterol biosensing.

In present work, the enzyme cholesterol oxidase (ChOx) was immobilized by Nafion® (Naf) on Pt,Ru-C nanocomposite and an ionic liquid (IL)-modified carbon paste electrode (CPE) in order to create cholesterol biosensor (Naf/ChOx/Pt,Ru-C/IL-CPE). The prepared working electrodes were characterized using scanning electron microscopy-energy-dispersive spectrometry, while their electrochemical performance was evaluated using electrochemical impedance spectroscopic, cyclic voltammetric, and amperometric techniques. Excellent synergism between IL 1-allyl-3-methylimidazolium dicyanamide ([AMIM][DCA]), Pt,Ru-C, and ChOx, as modifiers of CPE, offers the most pronounced analytical performance for improved cholesterol amperometric determination in phosphate buffer solution pH 7.50 at a working potential of 0.60 V. Under optimized experimental conditions, a linear relationship between oxidation current and cholesterol concentration was found for the range from 0.31 to 2.46 µM, with an estimated detection limit of 0.13 µM and relative standard deviation (RSD) below 5.5%. The optimized amperometric method in combination with the developed Naf/ChOx/Pt,Ru-C/IL-CPE biosensor showed good repeatability and high selectivity towards cholesterol biosensing. The proposed biosensor was successfully applied to determine free cholesterol in a human blood serum sample via its enzymatic reaction product hydrogen peroxide despite the presence of possible interferences. The percentage recovery ranged from 99.08 to 102.81%, while RSD was below 2.0% for the unspiked as well as the spiked human blood serum sample. The obtained results indicated excellent accuracy and precision of the method, concluding that the developed biosensor can be a promising alternative to existing commercial cholesterol tests used in medical practice.

Low Overpotential Amperometric Sensor Using Yb2O3.CuO@rGO Nanocomposite for Sensitive Detection of Ascorbic Acid in Real Samples.

The ultimate objective of this research work is to design a sensitive and selective electrochemical sensor for the efficient detection of ascorbic acid (AA), a vital antioxidant found in blood serum that may serve as a biomarker for oxidative stress. To achieve this, we utilized a novel Yb2O3.CuO@rGO nanocomposite (NC) as the active material to modify the glassy carbon working electrode (GCE). The structural properties and morphological characteristics of the Yb2O3.CuO@rGO NC were investigated using various techniques to ensure their suitability for the sensor. The resulting sensor electrode was able to detect a broad range of AA concentrations (0.5-1571 µM) in neutral phosphate buffer solution, with a high sensitivity of 0.4341 µAµM-1cm-2 and a reasonable detection limit of 0.062 µM. The sensor's great sensitivity and selectivity allowed it to accurately determine the levels of AA in human blood serum and commercial vitamin C tablets. It demonstrated high levels of reproducibility, repeatability, and stability, making it a reliable and robust sensor for the measurement of AA at low overpotential. Overall, the Yb2O3.CuO@rGO/GCE sensor showed great potential in detecting AA from real samples.

Quantifying In Situ Structural Stabilities of Human Blood Plasma Proteins Using a Novel Iodination Protein Stability Assay.

Many of the diseases that plague society today are driven by a loss of protein quality. One method to quantify protein quality is to measure the protein folding stability (PFS). Here, we present a novel mass spectrometry (MS)-based approach for PFS measurement, iodination protein stability assay (IPSA). IPSA quantifies the PFS by tracking the surface-accessibility differences of tyrosine, histidine, methionine, and cysteine under denaturing conditions. Relative to current methods, IPSA increases protein coverage and granularity to track the PFS changes of a protein along its sequence. To our knowledge, this study is the first time the PFS of human serum proteins has been measured in the context of the blood serum (in situ). We show that IPSA can quantify the PFS differences between different transferrin iron-binding states in near in vivo conditions. We also show that the direction of the denaturation curve reflects the in vivo surface accessibility of the amino acid residue and reproducibly reports a residue-specific PFS. Along with IPSA, we introduce an analysis tool Chalf that provides a simple workflow to calculate the residue-specific PFS. The introduction of IPSA increases the potential to use protein structural stability as a structural quality metric in understanding the etiology and progression of human disease. Data is openly available at Chorusproject.org (project ID 1771).

Evaluation of trace-element contamination from serum collection tubes used by the California Biobank Program.

BACKGROUND: Serum samples archived by the California Biobank Program (CBP) can be a valuable resource to researchers with multiple benefits: affordability, relatively large sample sizes, and racial and geographical representativeness. However, there has been little attention given to the reliability of CBP samples for trace-element analysis. The objectives of this study are to estimate the contamination levels from the serum separation tubes (SST, BD 367983) utilized by the CBP for 13 trace elements (Cr, Mn, Co, As, Se, Sr, Mo, Cd, Sb, Hg, Tl, Pb and U) and to evaluate the feasibility of the use of CBP serum samples for biomonitoring trace elements in human body. METHODS: Serum separation tubes were tested using deionized (DI) water and whole blood and compared with two alternative sampling devices, plasma separation tubes (PST, BD 365047) and acid-cleaned blood tubes (ABT, BD 367856). RESULTS AND CONCLUSIONS: The leaching tests for SSTs with DI water demonstrated that detectable levels of Cr, Mn, Co, Sr, Sb, Pb and U were measured, while Sb was elevated. Tests of PSTs also revealed contamination of Mn, Co, Sr and Sb, with Co and Sr being much higher than those found from SSTs. As a more direct approach to estimate trace element contamination, a 45-day time series was conducted using human blood. The differences in elemental concentrations leached into serum/plasma was not considerable between the three types of sampling tubes for Cr, As, Se, Mo, Cd, Hg and Tl. However, SSTs had far greater concentrations than the ABTs for Mn, Co, Sr, Sb and U. For Co and Sr, the PSTs had higher concentrations throughout the experiment than both ABTs and SSTs. Pb showed lower concentrations from the PSTs than the other tubes; we speculate this may be due to re-suspension of settled cellular materials that are elevated in Pb, or re-dissolution of Pb from these materials. Trace-element measurements from 200 samples archived by the CBP using SSTs suggest that SST contamination was negligible for Se and Mo. For Mn, As, Sr, Cd and Hg, based on our leaching results, only a fraction of these samples had considerably high concentrations (e.g., > 10×) compared to the contamination from the SST. For Cr, Co, Sb, Tl, Pb and U, analyte levels were too low in most samples compared to the contamination from the SSTs. Our study also demonstrated that the PSTs could be a "cleaner" alternative to SSTs for analytes such as Cr, As, Cd, Hg, Tl, Pb and U.

Multi-Oxyanion Detection by an Organic Field-Effect Transistor with Pattern Recognition Techniques and Its Application to Quantitative Phosphate Sensing in Human Blood Serum.

We herein report an organic field-effect transistor (OFET) based chemical sensor for multi-oxyanion detection with pattern recognition techniques. The oxyanions ubiquitously play versatile roles in biological systems, and accessing the chemical information they provide would potentially facilitate fundamental research in diagnosis and pharmacology. In this regard, phosphates in human blood serum would be a promising indicator for early case detection of significant diseases. Thus, the development of an easy-to-use chemical sensor for qualitative and quantitative detection of oxyanions is required in real-world scenarios. To this end, an extended-gate-type OFET has been functionalized with a metal complex consisting of 2,2'-dipicolylamine and a copper(II) ion (CuII-dpa), allowing a compact chemical sensor for oxyanion detection. The OFET combined with a uniform CuII-dpa-based self-assembled monolayer (SAM) on the extended-gate gold electrode shows a cross-reactive response, which suggests a discriminatory power for pattern recognition. Indeed, the qualitative detection of 13 oxyanions (i.e., hydrogen monophosphate, pyrophosphate, adenosine monophosphate, adenosine diphosphate, adenosine triphosphate, terephthalate, phthalate, isophthalate, malonate, oxalate, lactate, benzoate, and acetate) has been demonstrated by only using a single OFET-based sensor with linear discriminant analysis, which has shown 100% correct classification. The OFET has been further applied to the quantification of hydrogen monophosphate in human blood serum using a support vector machine (SVM). The multiple predictions of hydrogen monophosphate at 49 and 89 µM have been successfully realized with low errors, which indicates that the OFET-based sensor with pattern recognition techniques would be a practical sensing platform for medical assays. We believe that a combination of the OFET functionalized with the SAM-based recognition scaffold and powerful pattern recognition methods can achieve multi-analyte detection from just a single sensor.

Dual recognition strategy for selective fluorescent detection of dopamine and antioxidants based on graphite carbon nitride in human blood serum.

In this work, a strong blue-emitting fluorescent biosensor based on graphite carbon nitride nanoparticles (GCNNs) (Ex = 340 nm and Em = 435 nm) was synthesized by a facile one-step hydrothermal method. With the aid of hydrogen peroxide and horseradish peroxidase, pyrocatechol structure of dopamine (DA) was oxidized to o-quinone structure of polydopamine (PDA) by hydroxyl radical. PDA was able to rapidly and significantly quench fluorescence of GCNNs. In the meanwhile, oxidative self-polymerization from DA to PDA would be blocked by antioxidants, such as glutathione (GSH) and ascorbic acid (AA). Thus, the fluorescence of GCNNs@DA sensor would be recovered owing to the decrease of o-quinone. Based on above-mentioned dual recognition strategy of "turn-off" and "turn off-on", a fast, simple and ultrasensitive method was developed to measure DA and antioxidants. Under the optimal experimental conditions, the detection limits of DA, GSH and AA were 0.064 µmol L-1, 0.11 µmol L-1 and 0.16 µmol L-1 with relative standard deviations of 1.7%, 9.3% and 8.0%, respectively. As one of metal-free quantum dots, our GCNNs-based sensors were also successfully applied to the determination of DA as well as GSH and AA in human serum. The recoveries for the spiked samples were in the range of 93.8%-109% and 95.0%-110% of DA and antioxidants, which shows great promise to clinicalapplication.

Blood serum denaturation profile examined by differential scanning calorimetry reflects the effort put into ultramarathon by amateur long-distance runners.

The impact of participation in the ultramarathon on the health and mental and physical condition is very complex. Undoubtedly, exercise brings many benefits but also involves health risks. Especially such an extreme effort as the one associated with finishing the ultramarathon run, can be dangerous to the health of the runner. With the variety of possible biomarkers of excessive fatigue that threaten health and life, a question arises which of them are the best and which should be considered in amateur long-distance runners showing particularly high individual variability. In this study differential scanning calorimetry (DSC) has been applied to show the overall effect of the 12-h run on blood sera of participants. Serum samples were obtained from the blood of ten male amateur long-distance runners, collected before and immediately after the run. Distinct changes in the shape of DSC curves have been observed for serum after finishing the run relative to pre-race serum. Statistically significant differences between stages "before" and "after" ultramarathon running have been found for parameters of the endothermic transition associated with denaturation of serum proteins. An increase in the temperature (from 70.9 ± 0.9 to 75.8 ± 2.9 °C) and excess heat capacity (from 0.859 ± 0.201 to 1.102 ± 0.226 Jg-1 °C-1) at peak maximum, the enthalpy of serum denaturation (from 18.55 ± 6.52 to 22.08 ± 5.61 Jg-1) and the first moment of the thermal transition with respect to the temperature (from the value of 67.0 ± 2.1 to 72.6 ± 2.1 °C) has been observed. These results show a clear impact of running an ultramarathon on the participant's blood serum.

Human Blood Serum Induces p38-MAPK- and Hsp27-Dependent Migration Dynamics of Adult Human Cardiac Stem Cells: Single-Cell Analysis via a Microfluidic-Based Cultivation Platform.

Migratory capabilities of adult human stem cells are vital for assuring endogenous tissue regeneration and stem cell-based clinical applications. Although human blood serum has been shown to be beneficial for cell migration and proliferation, little is known about its impact on the migratory behavior of cardiac stem cells and underlying signaling pathways. Within this study, we investigated the effects of human blood serum on primary human cardiac stem cells (hCSCs) from the adult heart auricle. On a technical level, we took advantage of a microfluidic cultivation platform, which allowed us to characterize cell morphologies and track migration of single hCSCs via live cell imaging over a period of up to 48 h. Our findings showed a significantly increased migration distance and speed of hCSCs after treatment with human serum compared to control. Exposure of blood serum-stimulated hCSCs to the p38 mitogen-activated protein kinase (p38-MAPK) inhibitor SB239063 resulted in significantly decreased migration. Moreover, we revealed increased phosphorylation of heat shock protein 27 (Hsp27) upon serum treatment, which was diminished by p38-MAPK-inhibition. In summary, we demonstrate human blood serum as a strong inducer of adult human cardiac stem cell migration dependent on p38-MAPK/Hsp27-signalling. Our findings further emphasize the great potential of microfluidic cultivation devices for assessing spatio-temporal migration dynamics of adult human stem cells on a single-cell level.

Short- and medium-chain chlorinated paraffins in human blood serum of Czech population.

Short- and medium-chain chlorinated paraffins (SCCPs; MCCPs) are widespread environmental pollutants with bioaccumulation potential and adverse effects on human health. The analysis of blood serum is an important strategy to assess the human exposure to various contaminants, including SCCPs and MCCPs. Lately, the information about the exposure of Chinese population has been reported; nevertheless, data on human exposure to SCCPs and MCCPs outside East Asia are still very limited. In this pilot study, SCCPs and MCCPs were determined in 27 serum samples obtained from Czech adults. The samples were extracted by a three-step extraction (repeated with a clean solvent) by a mixture of n-hexane:diethyl ether (9:1, v/v) with subsequent clean-up on Florisil® solid phase extraction column. Gas chromatography coupled with high resolution mass spectrometry operated in negative chemical ionisation was employed for the instrumental analysis. The method recoveries ranged from 71 to 89% with repeatabilities of <20% (expressed as relative standard deviation). In the samples, SCCP concentrations were in the range of <150-2600 ng/g lipid weight, lw (median 370 ng/g lw) and the MCCP concentrations were in the range of <200-2110 ng/g lw (median 360 ng/g lw), respectively. To the best of our knowledge, our reported results are the first data about chlorinated paraffins in human blood serum in Europe, showing exposure to these compounds with yet to be studied effects on human health.

A simple analytical methodology for platinum nanoparticles control in complex clinical matrices via SP-ICP-MS.

A simple method based on the use of inductively coupled plasma mass spectrometry in single particle mode (SP-ICP-MS) has been proposed, for the first time, for the study of platinum nanoparticles (PtNPs) in complex clinical matrices such as human urine and blood serum. Critical parameters for signal acquisition were optimized to achieve a correct and simultaneous sizing and counting (particle-based in particles L-1 and mass-based in ng L-1) of 50 and 70 nm PtNPs. Different reagents, as tetramethylammonium hydroxide (TMAH) and/or Triton X-100, and concentrations have been tested to ensure an adequate stabilization and extraction of PtNPs. Finally, TMAH at 1% is demonstrated to be the best reagent to extract the NPs guaranteeing their integrity. No heating or any additional treatment was required, which allows sample preparation, and the overall process, to be simple and fast. Good precisions for size (2% RSD) and particle number and mass concentrations (<1% RSD), and limits of detection of 21.6 nm and 1.9 × 105 particles L-1 were reported. The influence of matrix on the determination of PtNP sizes and number- and mass-based concentrations was evaluated. Particle sizes were in all cases in accordance with values determined by TEM or SEM, whereas recoveries of PtNPs in terms of concentration ranged between 92 and 101%. The stability of PtNP characteristics after 24 h was specifically studied in human urine spiked with PtNPs. Statistically significant differences were only reported for the particle number concentrations of 50 nm PtNPs in female urine samples. The present work will be relevant to understand the behaviour of PtNPs in body fluids and to take appropriate actions in future (pre)clinical trials.

Synthesis of high luminescent Eu3+ doped nanoparticle and its application as highly sensitive and selective detection of Fe3+ in real water and human blood serum.

The present work reports a highly efficient Ca doped Eu: Y2O3 i.e Ca0.05Eu0.01Y1.94O3 (CEY.) nanophosphor material synthesized through a facile combustion method, as a simple and selective turn-off fluorescence probe for the quantitative analysis of iron ions (Fe3+). The proposed sensor allows the quantification of iron in the range of 10 µM-90 µM with a limit of detection (LOD) ∼ 63.2 nM under the natural pH range. Moreover, CEY nanophosphor shows an excellent fluorescence phenomenon with a gradual increase in the Fe3+ ion concentration. It has been observed that the corresponding PL intensity gets completely quenched with 500 µM Fe3+ ion concentration. Furthermore, the applicability of the sensor as an efficient probe has been investigated with real water samples, iron tablets, and human blood serum (HBS). The selectivity of the probe has also been analyzed with various metal ions and biomolecules. Thus, in turn, the as-obtained sensing probe illustrates an excellent accuracy, sensitivity, and selectivity, and offers potential application in clinical diagnosis, biological and real water sample studies, with the detection of Fe3+ ion. Furthermore, it does not require any acidic medium for a level-free, and non-enzymic detection of a real sample with almost not affecting the sample quality and henceforth provides more reliable results.

Human blood serum can donor-specifically antagonize effects of EGFR-targeted drugs on squamous carcinoma cell growth.

Many patients fail to respond to EGFR-targeted therapeutics, and personalized diagnostics is needed to identify putative responders. We investigated 1630 colorectal and lung squamous carcinomas and 1357 normal lung and colon samples and observed huge variation in EGFR pathway activation in both cancerous and healthy tissues, irrespectively on EGFR gene mutation status. We investigated whether human blood serum can affect squamous carcinoma cell growth and EGFR drug response. We demonstrate that human serum antagonizes the effects of EGFR-targeted drugs erlotinib and cetuximab on A431 squamous carcinoma cells by increasing IC50 by about 2- and 20-fold, respectively. The effects on clonogenicity varied significantly across the individual serum samples in every experiment, with up to 100% differences. EGF concentration could explain many effects of blood serum samples, and EGFR ligands-depleted serum showed lesser effect on drug sensitivity.

Metal-organic framework precursors derived Ni-doping porous carbon spheres for sensitive electrochemical detection of acetaminophen.

The sensitive and selective determination of acetaminophen (AP) in the human body is highly desirable to ensure human health. In this work, nickel-doping nanoporous carbon (Ni/C) was fabricated by directly calcining Ni based metal-organic framework (Ni-MOF). The Ni/C based electrochemical sensor was developed for sensitive and selective determination of AP in human blood serum and urine samples. The prepared Ni/C composite possess plentiful catalytic active sites, ordered mesoporous structure and large specific surface area, which endow the constructed Ni/C sensor with a prominent performance for acetaminophen sensing. Under the optimal conditions, the developed method offered good linearity in the range of 0.20-53.75 µM with a low detection limit (S/N = 3) of 4.04 × 10-2 µM. The electrocatalytic performance of the sensor towards AP was further measured by differential pulse voltammetry and cyclic voltammetry. The results demonstrated that the Ni/C sensor can be feasibly employed for the determination of AP in human blood serum and urine samples with excellent anti-interference stability and good reproducibility. The research reveals a great promising of the Ni/C electrochemical sensor for clinical applications and paves a way for the construction of high-performance electrochemical sensors for AP determination.