Human Serum Levels Research Articles

The effects of light on vitamin D level in human serum during laboratory processing

This study aimed to analyze the impact of light on the amount of 25- hydroxyvitamin D [25-(OH) D] in the processed serums of the participants that have been referred to the diagnostic lab (King Diagnostic Laboratory) which process tests for around 150 collection sites around ErbiL, Iraq. Scientists and researchers have declared a strong association between vitamin D status and various health issues. Many studies have now shifted to the interaction among/between genes and environment that impact different illnesses correlated with vitamin D. During the periods between 01/April/2020 till 01/April/2021, the total number of cases (N = 5800) of vitamin D content detection in serum have been performed. However, this investigation found that there was a high deficiency (%) in vitamin D levels (nearly 80 %) among the participants contributed to our study and data analysis revealed that they had 25-(OH) D levels very less at 20 μg/L concentration. The amount of vitamin D levels did not vary about with respect to gender and no statistical significance between female and male participants were observed (P > 0.05), moreover, the variation in the group that was subjected to light differed significiantly (P > 0.05). The present research work reveals that there is a significant variation in the use of dark and light collection and testing tube in the process of detecting serum vitamin D levels.

Rapid colorimetric detection of H2O2 in living cells and its upstream series of molecules based on oxidase-like activity of CoMnO3 nanofibers

Most studies on nanozymes in recent years have focused on enhancing their catalytic activity and synthesizing directly, although this task is still complicated. Bimetallic oxides are particularly desirable due to their mixed valence and structural properties. In this study, bimetallic oxide nanofibers (CoMnO3 NFs) were prepared using a quick and effective hydrothermal synthesis technique, and exhibited outstanding oxidase-like activity. The catalytic activity of CoMnO3 NFs displayed an inhibitory response on exposure to H2O2, which was applied in detecting H2O2 and its upstream molecules (glucose and uric acid). Based on this, a straightforward, affordable, and accurate colorimetric approach was developed by combining with 3,3′,5,5′-tetramethylbenzidine. Employing the oxidase activity rather than the traditional peroxidase activity to detect H2O2 drastically reduces the detection time. This method was also successfully used for in situ quantitative monitoring of intracellular H2O2, as well as detecting uric acid and glucose levels in human serum. Moreover, a smartphone-assisted colorimetric sensing system built on self-developed software was developed, enabling the on-site detection of H2O2 without laboratory instruments. This study established theoretical support for the valid design of bimetallic oxide nanozyme activity and might guide the development of detection systems for accurately analyzing biomarkers in foods and biochemical products.

HIF2α-induced upregulation of RNASET2 promotes triglyceride synthesis and enhances cell migration in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC), the most common malignant subtype of renal cell carcinoma, is characterized by the accumulation of lipid droplets in the cytoplasm. RNASET2 is a protein coding gene with a low expression level in ovarian cancers, but it is overexpressed in poorly differentiated neuroendocrine carcinomas. There is a correlation between RNASET2 upregulation and triglyceride expression levels in human serum but is unknown whether such an association is a factor contributing to lipid accumulation in ccRCC. Herein, we show that RNASET2 expression levels in ccRCC tissues and cell lines are significantly higher than those in both normal adjacent tissues and renal tubular epithelial cells. Furthermore, its upregulation is associated with increases in ccRCC malignancy and declines in patient survival. We also show that an association exists between increases in both cytoplasmic lipid accumulation and HIF-2α transcription factor upregulation, and increases in both RNASET2 and triglyceride expression levels in ccRCC tissues. In addition, DGAT1 and DGAT2, two key enzymes involved in triglyceride synthesis, are highly expressed in ccRCC tissues. By contrast, RNASET2 knockdown inhibited their expression levels and lowered lipid droplet accumulation, as well as suppressing in vitro cell proliferation, cell invasion, and migration. In conclusion, our data suggest HIF2α upregulates RNASET2 transcription in ccRCC cells, which promotes both the synthesis of triglycerides and ccRCC migration. As such, RNASET2 may have the potential as a biomarker or target for the diagnosis and treatment of ccRCC.

New approach methodologies: A quantitative in vitro to in vivo extrapolation case study with PFASs.

PER: and polyfluoroalkyl substances (PFASs) have been associated with increased blood lipids in humans. Perfluorooctanoic acid (PFOA) has been also linked with elevated alanine transferase (ALT) serum levels in humans, and in rodents the liver is a main target organ for many PFASs. With the focus on New Approach Methodologies, the chronic oral equivalent effect doses were calculated for PFOA, PFNA (perfluorononanoic acid), PFHxS (perfluorohexanesulfonic acid) and PFOS (perfluorooctane sulfonic acid) based on in vitro effects measured in the HepaRG cell line. Selected in vitro readouts were considered biomarkers for lipid disturbances and hepatotoxicity. Concentration-response data obtained from HepaRG cells on triglyceride (TG) accumulation and expression changes of 12 selected genes (some involved in cholesterol homeostasis) were converted into corresponding human dose-response data, using physiologically based kinetic (PBK) model-facilitated reverse dosimetry. Next to this, the biokinetics of the chemicals were studied in the cell system. The current European dietary PFASs exposure overlaps with the calculated oral equivalent effect doses, indicating that the latter may lead to interference with hepatic gene expression and lipid metabolism. These findings illustrate an in vitro-in silico methodology, which can be applied for more PFASs, to select those that should be prioritized for further hazard characterization.

Sb-doped FeOCl nanozyme-based biosensor for highly sensitive colorimetric detection of glutathione.

Nanozymes have been emerging as substitutes for natural enzymes to construct biosensors towards biomolecular detection. However, the detection of glutathione (GSH) by nanozyme-based biosensors still remains agreat challenge for research on catalytic activity enhancement and thedetection mechanism. In this work, Sb-doped iron oxychloride (Sb-FeOCl) with awell-defined nanorod-like structure is prepared by high-temperature calcination. Sb-FeOCl nanorods have high peroxidase-like activity, which can catalyze the decomposition of H2O2 into ·OH and then oxidize 3,3',5,5'-tetramethylbenzidine (TMB). In view of these intriguing observations, a reliable colorimetric method with a simple mixing and detection strategy is developed for the detection of GSH. The linear range of GSH detection is 1-36μM. The detection limit of GSH reaches a low level of 0.495μM (3σ/slope). The GSH sensing system also exhibits excellent specificity and anti-interference. Taking advantage of the advantages of theSb-FeOCl nanorod-based biosensor, it can be used to quantitatively detect GSH levels in human serum. It can be anticipated that the Sb-FeOCl nanorods have broad prospects in the field of enzymatic biochemical reactions.

Cytochrome c in cancer therapy and prognosis.

Cytochrome c (cyt c) is an electron transporter of the mitochondrial respiratory chain. Upon permeabilization of the mitochondrial outer membrane, cyt c is released into the cytoplasm, where it triggers the intrinsic pathway of apoptosis. Cytoplasmic cyt c can further reach the bloodstream. Apoptosis inhibition is one of the hallmarks of cancer and its induction in tumors is a widely used therapeutic approach. Apoptosis inhibition and induction correlate with decreased and increased serum levels of cyt c, respectively. The quantification of cyt c in the serum is useful in the monitoring of patient response to chemotherapy, with potential prognosis value. Several highly sensitive biosensors have been developed for the quantification of cyt c levels in human serum. Moreover, the delivery of exogenous cyt c to the cytoplasm of cancer cells is an effective approach for inducing their apoptosis. Similarly, several protein-based and nanoparticle-based systems have been developed for the therapeutic delivery of cyt c to cancer cells. As such, cyt c is a human protein with promising value in cancer prognosis and therapy. In addition, its thermal stability can be extended through PEGylation and ionic liquid storage. These processes could contribute to enhancing its therapeutic exploitation in clinical facilities with limited refrigeration conditions. Here, I discuss these research lines and how their timely conjunction can advance cancer therapy and prognosis.

Platinum nanoparticles confined in metal-organic frameworks as excellent peroxidase-like nanozymes for detection of uric acid.

High levels of uric acid (UA) in humans can cause a range of diseases, and traditional assays that rely on uric acid enzymes to break down uric acid are limited by the inherent deficiencies of natural enzymes. Fortunately, the rapid development of nanozymes in recent years is expected to solve the above-mentioned problems. Hence, we used a host-guest strategy to synthesize a platinum nanoparticle confined in a metal-organic framework (Pt NPs@ZIF) that can sensitively detect UA levels in human serum. Unlike previously reported free radical-catalyzed oxidation systems, its unique electron transfer mechanism confers excellent peroxidase-like activity to Pt NPs@ZIF. In addition, UA can selectively inhibit the chromogenic reaction of TMB, thus reducing the absorbance of the system. Therefore, using the peroxidase-like activity of Pt NPs@ZIF and using TMB as a chromogenic substrate, UA can be detected directly without relying on natural enzymes. The results showed a relatively wide detection range (10-1000μM) and a low detection limit (0.2μM). Satisfactory results were also obtained for UA in human serum. This study with simple operation and rapid detection offers a promising method for efficiently detecting UA in serum.

Rapid simultaneous SERS detection of dual myocardial biomarkers on single-track finger-pump microfluidic chip

Acute myocardial infarction (AMI) is a serious disease with high mortality that afflicts many people around the world. The main cause of death from AMI was the inaccurate early diagnosis, which resulted from the medical treatment might be a delay. Therefore, it is crucial to achieve the rapid detection of AMI. The cardiac troponin I (cTnI) level in human serum may significantly increase as the myocardial membrane ruptured, and the creatine kinase-MB (CK-MB) was also associated with the AMI recurrence and the infarct size of myocardial infarction. Both of them are regarded as important cardiac biomarkers for the early diagnosis of AMI. Therefore, we chose these two cardiac biomarkers as indicators for simultaneous detection. We proposed a single-track finger-pump microfluidic chip for simultaneous surface-enhanced Raman scattering (SERS) detection of cTnI and CK-MB. The entire detection process takes only 5 min without the cumbersome syringe pump. Meanwhile, it enables multiple reagent additions and removals of the unbonded reactants. This microfluidic sensor employed "sandwich" immunoassays based on SERS nanoprobes, AMI biomarkers, and magnetic beads. It is possible to detect two cardiac biomarkers simultaneously in a single measurement, greatly simplifying the detection process and reducing the detection time. Magnetic beads with SERS nanoprobes were separated and captured in the microchamber by a round magnet integrated into the chip. Our results showed that the detection limits of cTnI and CK-MB could reach to 0.01 ng mL−1, respectively. The limit of detections (LODs) match with the clinical threshold values for AMI biomarkers. It is believed that the proposed single-track finger-pump microfluidic chip can be used as an effective tool for determining early AMI.

Reduced graphene oxide supported MXene based metal oxide ternary composite electrodes for non-enzymatic glucose sensor applications

Diagnosis and monitoring of glucose level in human blood has become a prime necessity to avoid health risk and to cater this, a sensor’s performance with wide linearity range and high sensitivity is required. This work reports the use of ternary composite viz. MG–Cu2O (rGO supported MXene sheet with Cu2O) for non-enzymatic sensing of glucose. It has been prepared by co-precipitation method and characterized with X-ray powder diffraction, Ultraviolet–visible absorption spectroscopy (UV–Vis), Raman spectroscopy, Field emission scanning electron microscopy, High resolution transmission electron microscopy and Selected area diffraction. These analyses show a cubic structure with spherical shaped Cu2O grown on the MG sheet. Further, the electrocatalytic activity was carried out with MG–Cu2O sensing element by cyclic voltammetry and chronoamperometry technique and compared with M–Cu2O (MXene with Cu2O) composite without graphene oxide. Of these, MG–Cu2O composite was having the high defect density with lower crystalline size of Cu2O, which might enhance the conductivity thereby increasing the electrocatalytic activity towards the oxidation of glucose as compared to M–Cu2O. The prepared MG–Cu2O composite shows a sensitivity of 126.6 µAmM−1 cm−2 with a wide linear range of 0.01to 30 mM, good selectivity, good stability over 30 days and shows a low Relative Standard Deviation (RSD) of 1.7% value towards the sensing of glucose level in human serum. Thus, the aforementioned finding indicates that the prepared sensing electrode is a well suitable candidate for the sensing of glucose level for real time applications.

Electro-immunosensor for ultra-sensitive determination of cardiac troponin I based on reduced graphene oxide and polytyramine.

This work reports the construction of a novel nanostructured immunosensor for detection of the troponin I biomarker (cTnI). Anti-troponin I antibody was anchored on the modified graphite electrode with reduced graphene oxide and polytyramine for detection of troponin I in serum samples. The performance of the electro-immunosensor was evaluated by differential pulse voltammetry. The immunosensor presented a wide work range, from 4ng mL-1 to 4pg mL-1 , whose detection limit (4pg mL-1 ) is significantly lower than the basal level in human serum, and maintained 100% of response after 30 days of storage. Moreover, the immunosensor showed good selectivity for detection of cTnI in real sample containing interfering substances and specificity of response to cTnI in the serum of healthy and sick patients, and demonstrated the possibility of reuse for two consecutive analyses, in addition to using a simplified and inexpensive platform when compared to other devices, demonstrating them excellent potential for application in diagnosis in the early stages of acute myocardial infarction.

Coaxial electrospinning synthesis of size-tunable CuO/NiO hollow heterostructured nanofibers: Towards detection of glucose level in human serum

Nanofibers (NFs) have found wide applications by virtue of their particular morphology and high specific surface area. In this study, size-tunable hollow CuO/NiO NFs were synthesized by coaxial electrospinning and subsequent calcination. The synthesized hollow CuO/NiO NFs owned large specific surface area for catalytic active sites. In addition, the formation of heterostructure interface between CuO and NiO was beneficial to improve the electrocatalytic performance. As non-enzymatic electrode material, the synthesized CuO/NiO NFs exhibited superior electrocatalytic capability for glucose oxidation. When the molar ratio of CuO to NiO is 0.4, the composite NFs achieved the optimal electrocatalytic ability for glucose oxidation, performing high sensitivity of 1324.17 μA mM−1 cm−2 and wide liner range from 1 to 10,000 μM. The constructed electrode has been utilized to detect glucose concentration in real serum with excellent recovery, indicating that CuO/NiO hollow heterostructured NFs are promising materials for biomedical applications.

An electrochemical paper-based hydrogel immunosensor to monitor serum cytokine for predicting the severity of COVID-19 patients

Analysis of cytokines levels in human serum is critical as it can be a “symptom diagnostic biomarker” in COVID-19, giving real-time information about human health status. Here, we present the construction and performance of a low-price immunosensor (∼US$0.428 per test) based on microfluidic paper-based system to detect cytokine for predicting the health status of COVID-19 patients. Interleukin-6 (IL-6) was selected as the detection model for the close relationship between IL-6 and COVID-19. The assay, which we integrated into foldable paper system, leverages the magnetic immunoassay, the streptavidin-horseradish peroxidase (HRP) associated with tetramethyl benzidine/hydrogen peroxide (TMB/H2O2) to amplify the signal for electrochemical readout. To improve the sensitivity of cytokine detection, a hybrid of gold nanoparticles (AuNPs) and polypyrrole (PPy) hydrogel was modified on the working electrode to increase the conductivity and improve the electron transfer rate. With our prototypic origami paper-based immunosensor operated in differential pulse voltammetry (DPV) mode, we achieved excellent results with a dynamic range from 5 to 1000 pg/mL and a lower detection limit (LOD) of 0.654 pg/mL. Furthermore, we evaluated the capability of the clinical application of the proposed immunosensor using human serum samples from a hospital. The results indicate that our proposed immunosensor has great potential in early diagnosing high-risk COVID-19 patients.

Knock-out of N-glycolylneuraminic acid attenuates antibody-mediated rejection in xenogenically perfused porcine lungs.

Antibody-mediated rejection has long been known to be one of the major organ failure mechanisms in xenotransplantation. In addition to the porcine α1,3-galactose (α1,3Gal) epitope, N-Glycolylneuraminic acid (Neu5Gc), a sialic acid, has been identified as an important porcine antigen against which most humans have pre-formed antibodies. Here we evaluate GalTKO.hCD46 lungs with an additional cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene knock-out (Neu5GcKO) in a xenogeneic ex vivo perfusion model METHODS: Eleven GalTKO.hCD46.Neu5GcKO pig lungs were perfused for up to 6h with fresh heparinized human blood. Six of them were treated with histamine (H) blocker famotidine and 1-thromboxane synthase inhibitor Benzylimidazole (BIA) and five were left untreated. GalTKO.hCD46 lungs without Neu5GcKO (n=18: eight untreated and 10 BIA+H treated) served as a reference. Functional parameters, blood, and tissue samples were collected at pre-defined time points throughout the perfusion RESULTS: All but one Neu5GcKO organs maintained adequate blood oxygenation and "survived" until elective termination at 6h whereas two reference lungs failed before elective termination at 4h. Human anti-Neu5Gc antibody serum levels decreased during the perfusion of GalTKO.hCD46 lungs by flow cytometry (∼40% IgM, 60% IgG), whereas antibody levels in Neu5GcKO lung perfusions did not fall (IgM p=.007; IgG p<.001). Thromboxane elaboration, thrombin generation, and histamine levels were significantly reduced with Neu5GcKO lungs compared to reference in the untreated groups (p=.007, .005, and .037, respectively); treatment with BIA+H masked these changes. Activation of platelets, measured as CD62P expression on circulating platelets, was lower in Neu5GcKO experiments compared to reference lungs (p=.023), whereas complement activation (as C3a rise in plasma) was not altered. MCP-1 and lactotransferin level elevations were blunted in Neu5GcKO lung perfusions (p=.007 and .032, respectively). Pulmonary vascular resistance (PVR) rise was significantly attenuated and delayed in untreated GalTKO.hCD46.Neu5GcKO lungs in comparison to the untreated GalTKO.hCD46 lungs (p=.003) CONCLUSION: Additional Neu5GcKO in GalTKO.hCD46 lungs significantly reduces parameters associated with antibody-mediated inflammation and activation of the coagulation cascade. Knock-out of the Neu5Gc sialic acid should be beneficial to reduce innate immune antigenicity of porcine lungs in future human recipients.

A novel gold-decorated porous silicon-poly(3-hexylthiophene) ternary nanocomposite as a highly sensitive and selective non-enzymatic dopamine electrochemical sensor

As a key biomolecule for neurotransmission, dopamine (DA) is responsible for many neurological syndromes. Hence, effective DA detection is vital for the rapid-diagnosis of diseases caused by irregular DA levels. Therefore, we designed a non-enzymatic DA sensor using the novel gold-decorated porous silicon-poly-3-hexylthiophene (Au@PSi-P3HT) nanocomposite fabricated glassy carbon electrode. We employed a simple stain etching technique followed by ultra-sonication and photo-reduction techniques to synthesize this novel Au@PSi-P3HT nanocomposite. The structural, morphological, and surface characterizations of the Au@PSi-P3HT nanocomposite were performed using various analytical tools. TEM and FESEM images revealed that gold nanoparticles were randomly dispersed onto the PSi-P3HT sheet-like structure. In the electrochemical investigations, the Au@PSi-P3HT/GCE sensor showed excellent sensitivity (0.5112 μAμM−1cm−2), wide linear dynamic range (LDR = 1.0–460 μM), and reasonably low detection limit (LOD ∼0.63 μM). This newly designed DA sensor was also employed to check the potential chemical interference using several common biomolecules and the obtained results confirmed its selectivity during DA detection. The Au@PSi-P3HT/GCE sensor also exhibited satisfactory results in detecting DA levels in human blood serum and dopamine hydrochloride injection samples. Besides, the Au@PSi-P3HT/GCE sensor displayed superb reproducibility, repeatability, and stability. This novel Au@PSi-P3HT nanocomposite-modified GCE may emerge as a successful means for further designing effective non-enzymatic electrochemical sensors.

Potential of Disease-Modifying Anti-Rheumatic Drugs to Limit Abdominal Aortic Aneurysm Growth.

Inflammation is strongly implicated in the pathogenesis of abdominal aortic aneurysms (AAA). This review examined the potential role of biologic disease-modifying anti-rheumatic drugs (bDMARDs) as repurposed drugs for treating AAA. Published evidence from clinical and preclinical studies was examined. Findings from animal models suggested that a deficiency or inhibition of tumour necrosis factor-α (TNF-α) (standard mean difference (SMD): −8.37, 95% confidence interval (CI): −9.92, −6.82), interleukin (IL)-6 (SMD: −1.44, 95% CI: −2.85, −0.04) and IL-17 (SMD: −3.36, 95% CI: −4.21, −2.50) led to a significantly smaller AAA diameter compared to controls. Human AAA tissue samples had significantly increased TNF-α (SMD: 1.68, 95% CI: 0.87, 2.49), IL-1β (SMD: 1.93, 95% CI: 1.08, 2.79), IL-6 (SMD: 2.56, 95% CI: 1.79, 3.33) and IL-17 (SMD: 6.28, 95% CI: 3.57, 8.99) levels compared to non-AAA controls. In human serum, TNF-α (SMD: 1.11, 95% CI: 0.25, 1.97) and IL-6 (SMD: 1.42, 95% CI: 0.91, 1.92) levels were significantly elevated compared to non-AAA controls. These findings implicate TNF-α, IL-17 and IL-6 in AAA pathogenesis. Randomised controlled trials testing the value of bDMARDs in limiting AAA growth may be warranted.

Aptamer-conjugated graphene oxide-based surface assisted laser desorption ionization mass spectrometry for selective extraction and detection of Aβ1-42 in an Alzheimer's disease SH-SY5 cell model.

The generation and accumulation of amyloid-beta peptide (Aβ1–42) in amyloid plaques are key characteristics of Alzheimer’s disease (AD); thus, specific detection of Aβ1–42 is essential for the diagnosis and treatment of AD. Herein, an aptamer-conjugated graphene oxide (Apt-GO) sensor was synthesized by π-π and hydrophobic interactions using thiol poly (ethylene glycol) amine (SH-PEG-NH2) as a spacer unit. Then, it was applied to selective capture of Aβ1–42, and the resulting complex was directly analyzed by surface-assisted laser desorption ionization mass spectrometry (SALDI-MS). The results revealed that the Apt-GO could enhance the detection specificity and reduce non-specific adsorption. This method was validated to be sensitive in detecting Aβ1–42 at a low level in human serum (ca. 0.1 μM) within a linear range from 0.1 to 10 μM. The immobilizing amount of aptamer on the GO was calculated to be 36.1 nmol/mg (RSD = 11.5%). In conclusion, this Apt-GO-based SALDI-MS method was sensitive and efficient in selective extraction and detection of Aβ1–42, which proved to be a good option for early AD diagnosis.

Determination of Blood NOTCH3 Extracellular Domain and Jagged-1 Levels in Healthy Subjects.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic disorder among those responsible for hereditary strokes, and it is caused by a mutation in the NOTCH3 gene on chromosome 19. Blood biomarkers related to the Notch signaling pathway have not been investigated extensively in CADASIL. In this study, we measured the serum and plasma levels of NOTCH3 extracellular domain (N3ECD) and its ligand, Jagged-1, in 279 healthy subjects. The levels of N3ECD and Jagged-1 showed significant correlations in both serum (p < 0.0001, r = 0.2681) and plasma (p < 0.0001, r = 0.4065). The N3ECD levels were significantly higher in the serum than in plasma and tend to increase with age. In contrast, there was no significant difference between the serum and plasma levels of Jagged-1 levels. To summarize, we were able to measure N3ECD and Jagged-1 protein levels in healthy human serum and plasma. Taken together, our findings provide the basis for further studies investigating the clinical use of blood N3ECD and Jagged-1 levels for CADASIL and other Notch signaling-related diseases.

A microfluidic chip using Au@SiO2 array–based highly SERS-active substrates for ultrasensitive detection of dual cervical cancer–related biomarkers

In this work, a microfluidic chip using Au@SiO2 array-based highly active SERS substrates was developed for quantitative detection of squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) associated with cervical cancer. The chip consisted of six functional units with pump-free design, enabling parallel detection of multiple samples in an automatic manner without external pumps and improving the portability. Ag nanocubes (AgNCs) were labeled with Raman reporters and coupled with antibodies (labeling) to prepare SERS tags, while the Au nanoparticle-modified SiO2 microsphere (Au@SiO2) array was conjugated with antibodies (coating) to generate the highly SERS-active capturing substrate. In the presence of target biomarkers, they were captured by SERS tags and capturing substrate, resulting in the formation of "sandwich" structures which were trapped in the detection chamber. As the immune reaction proceeded, a large number of "hot spots" were generated by the proximity of the Au@SiO2 array substrate and AgNCs, greatly amplifying SERS signals. With this chip, the limits of detection of the SCCA and CEA levels in human serum were estimated to be as low as 0.45pgmL-1 and 0.36pgmL-1, respectively. Furthermore, the good selectivity and reproducibility of this chip were confirmed. Finally, clinical serum samples were analyzed by this chip, and the outcomes were consistent with those of enzyme-linked immunosorbent assay (ELISA). Thus, the proposed microfluidic chip can be potentially applied for the clinical diagnosis of cervical cancer.

Physiologically-based toxicokinetic modeling of human dermal exposure to diethyl phthalate: Application to health risk assessment

Diethyl phthalate (DEP) has been most frequently detected in personal care products (PCPs) as a solvent followed by indoor air as one of the semi-volatile organic compounds (SVOCs). Human exposure to DEP predominantly occurs via dermal uptake. However, the available physiologically based toxicokinetics (PBTK) models are developed in rats for risk assessment of DEP exposure resulting from the oral than dermal pathway. To address this issue, DEP in simulated PCPs was dermally administrated to five adult volunteers at real population levels. Following the construction of a dermal absorption model for DEP, the dermal PBTK modeling of DEP involving PCPs and air-to-skin exposure routes in humans was developed for the first time. The data of monoethyl phthalate (MEP) in serum or urine obtained from published human studies and this study were applied to calibrate and validate the developed dermal PBTK model. Monte Carlo simulation was used to evaluate model uncertainty. The dermal absorption fraction of DEP was obtained to be 56.2% for PCPs exposure and 100% for air-to-skin exposure, respectively. Approximate 24.9% of DEP in exposed skin became absorbed into systemic circulation. Model predictions were generally within 2-fold of the observed MEP levels in human serum or urine. Uncertainty analysis showed 90% of the predicted variability (P95/P5) fell within less than one order of magnitude. Assuming human intake of 5 mg/kg bw per day, the predicted serum area under the curve at steady state of DEP from the dermal route was 1.7 (PCPs) and 2.4 (air) times of those from the peroral route, respectively. It suggested that dermal exposure to DEP would pose greater risk to human health compared with oral exposure. The application of the developed dermal PBTK model provides a valuable insight into health risk assessment of DEP in humans.

Impedimetric Detection of Calreticulin by a Disposable Immunosensor Modified with a Single-Walled Carbon Nanotube-Conducting Polymer Nanocomposite.

A label-free impedimetric immunosensing system was constructed for ultrasensitive determination of the calreticulin (CALR) biological marker in human serum samples utilizing an electrochemical impedance spectroscopy analysis technique for the first time. The new biosensor fabrication procedure consisted of electrodeposition of single-walled carbon nanotubes (SWCNTs) incorporating polymerization of an oxiran-2-yl methyl 3-(1H-pyrrol-1-yl) propanoate monomer (Pepx) onto a low-cost and disposable indium tin oxide (ITO) electrode. The SWCNTs-PPepx nanocomposite layer was prepared onto the ITO after the one-step fabrication procedure. The fabrication procedure of the immunosensor and the characteristic biomolecular interactions between the anti-CALR and CALR were characterized by electrochemical analysis and morphological monitoring techniques. Under optimum conditions, the proposed biosensor was responsive to CALR concentrations over the detection ranges of 0.015-60 pg/mL linearly, and it had a very low detection limit (4.6 fg/mL) and a favorable sensitivity (0.43 kΩ pg-1 mL cm-2). The reliability of the biosensor system in clinical analysis was investigated by successful quantification of CALR levels in human serum. Moreover, the repeatability and reproducibility results of the biosensor were evaluated by using Dixon, Grubbs, T-test, and F-tests. Consequently, the proposed biosensor was a promising method for scientific, rapid, and successful analysis of CALR in human serum samples.