Showing papers on "Blood serum published in 2020"

Field-resolved infrared spectroscopy of biological systems

Abstract: The proper functioning of living systems and physiological phenotypes depends on molecular composition. Yet simultaneous quantitative detection of a wide variety of molecules remains a challenge1–8. Here we show how broadband optical coherence opens up opportunities for fingerprinting complex molecular ensembles in their natural environment. Vibrationally excited molecules emit a coherent electric field following few-cycle infrared laser excitation9–12, and this field is specific to the sample’s molecular composition. Employing electro-optic sampling10,12–15, we directly measure this global molecular fingerprint down to field strengths 107 times weaker than that of the excitation. This enables transillumination of intact living systems with thicknesses of the order of 0.1 millimetres, permitting broadband infrared spectroscopic probing of human cells and plant leaves. In a proof-of-concept analysis of human blood serum, temporal isolation of the infrared electric-field fingerprint from its excitation along with its sampling with attosecond timing precision results in detection sensitivity of submicrograms per millilitre of blood serum and a detectable dynamic range of molecular concentration exceeding 105. This technique promises improved molecular sensitivity and molecular coverage for probing complex, real-world biological and medical settings. A vibrational spectroscopy technique that measures the electric field emitted from organic molecules following infrared illumination allows their molecular fingerprints to be separated from the excitation background, even in complex biological samples.

The role of high cholesterol in age-related COVID19 lethality

Abstract: Coronavirus disease 2019 (COVID19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originating in Wuhan China in 2019. The disease is notably severe in elderly and those with underlying chronic conditions. A molecular mechanism that explains why the elderly are vulnerable and why children are resistant is largely unknown. Understanding these differences is critical for safeguarding the vulnerable and guiding effective policy and treatments. Here we show loading cells with cholesterol from blood serum using the cholesterol transport protein apolipoprotein E (apoE) enhances the endocytic entry of pseudotyped SARS-CoV-2. Super resolution imaging of the SARS-CoV-2 entry point with high cholesterol showed almost twice the total number of viral entry points. The cholesterol concomitantly traffics angiotensinogen converting enzyme (ACE2) to the viral entry site where SARS-CoV-2 docks to properly exploit entry into the cell. Cholesterol also increased binding of SARS-CoV-2 receptor binding domains. In mouse lung we found age and high fat diet induced cholesterol loading into lung tissue by up to 40%. Based on these findings, we propose a cholesterol dependent model for COVID19 lethality in elderly and the chronically ill. As cholesterol increases with age and inflammation (e.g. obesity, smoking, and diabetes), the cell surface is coated with viral entry points, optimally assembled viral entry proteins, and optimal furin priming. Importantly our model suggests problems arise when cholesterol levels are high in the tissue, not the blood. In fact, rapidly dropping cholesterol in the blood may indicate severe loading of cholesterol in peripheral tissue and a dangerous situation for escalated SARS-CoV-2 infectivity. Molecules that remove cholesterol from tissue or disrupt ACE2 localization with viral entry points or furin localization for priming in the producer cells, likely reduce the severity of COVID19 in critically ill patients.

The Influence of Nanoparticle Shape on Protein Corona Formation

Abstract: Nanoparticles have become an important utility in many areas of medical treatment such as targeted drug and treatment delivery as well as imaging and diagnostics. These advances require a complete understanding of nanoparticles' fate once placed in the body. Upon exposure to blood, proteins adsorb onto the nanoparticles surface and form a protein corona, which determines the particles' biological fate. This study reports on the protein corona formation from blood serum and plasma on spherical and rod-shaped nanoparticles. These two types of mesoporous silica nanoparticles have identical chemistry, porosity, surface potential, and size in the y-dimension, one being a sphere and the other a rod shape. The results show a significantly larger amount of protein attaching from both plasma and serum on the rod-like particles compared to the spheres. Interrogation of the protein corona by liquid chromatography-mass spectrometry reveals shape-dependent differences in the adsorption of immunoglobulins and albumin proteins from both plasma and serum. This study points to the need for taking nanoparticle shape into consideration because it can have a significant impact on the fate and therapeutic potential of nanoparticles when placed in the body.

In Vivo Screening and Antidiabetic Potential of Polyphenol Extracts from Guava Pulp, Seeds and Leaves.

Abstract: The present study investigates the antidiabetic potential of polyphenol extracts purified from guava pulp, seeds and leaves using an in vivo experiment on albino rats. The polyphenols from guava pulp, seeds and leaves were extracted using methanol solvent and the sonication method while being evaluated by total phenolic contents and radical scavenging activity assay. The proximate composition of powders revealed that ash, protein and total sugars were significantly (p leaves > seeds. The findings suggest the feasibility of adding 200–250 mg/kg.bw of polyphenol extracts of pulp as an alternative to diabetic drugs.

Biophotonic sensor for the detection of creatinine concentration in blood serum based on 1D photonic crystal

Abstract: A new biophotonic sensor based on photonic crystal (PC) has been designed for the detection of creatinine concentration in blood, and is considered an important small molecule biomarker of renal dysfunction. Based on the transfer matrix method (TMM), we theoretically investigated the transmittance spectra of a one dimensional alternating dielectric photonic crystal (PC) designed as (AB)7/C/(AB)7 made of MgF2 (A), CeO2 (B) and creatinine concentration present in blood (C). The transmission spectra exhibit resonant peaks within the photonic band gap (PBG) indicative of so-called defect modes, which depend on parameters, such as concentration of creatinine in blood, thickness of defect layer and incident angle. The proposed sensor can determine the physiological levels of creatinine in human blood serum samples. The estimated parameters realize an efficient biophotonic sensor wherein sensitivity was tuned from 136.4 nm per RIU to 306.25 nm per RIU and is very useful for the detection of creatinine.

Prognostic biomarkers in men with metastatic castration-resistant prostate cancer receiving [177Lu]-PSMA-617.

Abstract: We analysed quantitative biomarkers derived from both baseline whole-body imaging and blood serum to identify prognostic markers in patients treated within the lutetium-177 prostate-specific membrane antigen (LuPSMA) phase 2 trial. PET image analysis was carried out using whole-body segmentation quantifying molecular tumour volume (SUV > 3 threshold for PSMA, SUV > liver+2sd for fluorodeoxyglucose (FDG) including SUVmax and SUVmean. For baseline bone scans, EXINI bone scan index (BSI) was used to calculate the percentage of involved bone. Baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH), prostate specific antigen (PSA) and PSA doubling time were also used in this analysis. We used univariate cox regression analysis and log-rank comparison with optimised cut-offs to find suitable biomarkers prognostic of overall survival from time of enrolment. This analysis identified FDG-positive tumour volume (FDGvol; HR 2.6; 95% CI, 1.4–4.8), mean intensity of PSMA-avid tumour uptake (PSMAmean; HR 0.89; 95% CI, 0.8–0.98), bone scan index (BSI; HR 2.3; 95% CI, 1.2–4.4), ALP (HR 1.1; 95% CI, 1–1.2) and LDH (HR 1.2; 95% CI, 1–1.5) as biomarkers prognostic of overall survival. In addition to established biomarkers, both FDG and PSMA PET/CT parameters have prognostic significance for survival in men undergoing LuPSMA therapy.

Selenium-Doped Carbon Quantum Dots Act as Broad-Spectrum Antioxidants for Acute Kidney Injury Management.

Abstract: The manifestation of acute kidney injury (AKI) is associated with poor patient outcomes, with treatment options limited to hydration or renal replacement therapies. The onset of AKI is often associated with a surfeit of reactive oxygen species. Here, it is shown that selenium-doped carbon quantum dots (SeCQDs) have broad-spectrum antioxidant properties and prominent renal accumulation in both healthy and AKI mice. Due to these properties, SeCQDs treat or prevent two clinically relevant cases of AKI induced in murine models by either rhabdomyolysis or cisplatin using only 1 or 50 µg per mouse, respectively. The attenuation of AKI in both models is confirmed by blood serum measurements, kidney tissue staining, and relevant biomarkers. The therapeutic efficacy of SeCQDs exceeds amifostine, a drug approved by the Food and Drug Administration that also acts by scavenging free radicals. The findings indicate that SeCQDs show great potential as a treatment option for AKI and possibly other ROS-related diseases.

Superchiral near fields detect virus structure

Abstract: Optical spectroscopy can be used to quickly characterise the structural properties of individual molecules. However, it cannot be applied to biological assemblies because light is generally blind to the spatial distribution of the component molecules. This insensitivity arises from the mismatch in length scales between the assemblies (a few tens of nm) and the wavelength of light required to excite chromophores (≥150 nm). Consequently, with conventional spectroscopy, ordered assemblies, such as the icosahedral capsids of viruses, appear to be indistinguishable isotropic spherical objects. This limits potential routes to rapid high-throughput portable detection appropriate for point-of-care diagnostics. Here, we demonstrate that chiral electromagnetic (EM) near fields, which have both enhanced chiral asymmetry (referred to as superchirality) and subwavelength spatial localisation (∼10 nm), can detect the icosahedral structure of virus capsids. Thus, they can detect both the presence and relative orientation of a bound virus capsid. To illustrate the potential uses of the exquisite structural sensitivity of subwavelength superchiral fields, we have used them to successfully detect virus particles in the complex milieu of blood serum. A technique that uses twisted light fields to detect biomolecular structures could find application as a low-cost clinical tool for screening viruses. The protein coatings around many viruses, such as the turnip yellow mosaic virus (TYMV), have complex polyhedral shapes that are difficult to resolve with conventional optical microscopes. Malcolm Kadodwala from the University of Glasgow and other colleagues in the United Kingdom now report that ‘superchiral’ light — localized fields generated by metal nanostructures that spiral as they travel — are sensitive to the asymmetric polyhedral of TYMV. By spectroscopic measurements of particle rotations in superchiral light at different frequencies, the team identified specific asymmetric signals that correlated to virus alignment on gold photonic substrates. This approach was then used to determine TYMV levels in human blood serum spiked with the virus.

Cholesterol and COVID19 lethality in elderly

Abstract: Coronavirus disease 2019 (COVID19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originating in Wuhan China in 2019. The disease in notably severe in elderly and those with underlying chronic conditions. The molecular mechanism as to why the elderly are vulnerable and why children are resistant is largely unknown. Understanding these differences is critical for safeguarding the vulnerable and guiding effective policy and treatments. Here we show loading cells with cholesterol from blood serum using the cholesterol transport protein apolipoprotein E (apoE) enhances the endocytic entry of pseudotyped SARS-CoV-2. Super resolution imaging of the SARS-CoV-2 entry point with high cholesterol showed markedly increased apparent diameter (~10% to 100 nm) and almost twice the total number of viral entry points. The cholesterol concomitantly traffics angiotensinogen converting enzyme (ACE2) to the viral entry site where SARS-CoV-2 docks to properly exploit entry into the cell. Furthermore, we show cholesterol enhances binding of SARS-CoV-2 to the cell surface which increases association with the endocytic pathway. Decreasing cellular cholesterol has the opposite effect. Based on these findings and known loading of cholesterol into peripheral tissue cholesterol during aging and inflammation, we build a cholesterol dependent model for COVID19 lethality in elderly and the chronically ill. As cholesterol increases with age and inflammation (e.g. smoking and diabetes), the cell surface is coated with viral entry points and optimally assembled viral entry proteins. Importantly our model suggests high levels of cholesterol is most alarming in the tissue, not the blood. In fact, rapidly dropping cholesterol in the blood may indicate severe loading of cholesterol in peripheral tissue and a dangerous situation for escalated SARS-CoV-2 infectivity. Polyunsaturated fatty acids (PUFAs) oppose the effects of cholesterol and provide a molecular basis for eating healthy diets to avoid severe cases of COVID19.

A 3D POMOF based on a {AsW12} cluster and a Ag-MOF with interpenetrating channels for large-capacity aqueous asymmetric supercapacitors and highly selective biosensors for the detection of hydrogen peroxide

Abstract: {AsW12O40} clusters were grafted onto Ag-MOF to yield two 3D polyoxometallate-based metal organic frameworks (POMOFs), (imi)2[{Ag3(tpb)2}2(H2O){AsW12O40}2]·6H2O (1) and [(Ag7bpy7Cl2){AsWV2WVI10O40}]·H2O (2) (imi = imidazole; tpb = 1,2,4,5-tetrakis(4-pyridyl)benzene; bpy = 4,4′-bipyridyl). These compounds are complicated 3D networks with intersecting channels and novel topologies. They exhibit larger capacitances (929.7 and 986.1 F g−1 at a current density of 3 A g−1), superior rate capabilities, higher capacity retention rates, boosting conductivities and electrocatalytic activities compared to those of their maternal POM, and this can be ascribed to the introduction of Ag-MOF, interpenetrating channels, and the unique stability of the POMOF. An aqueous asymmetric supercapacitor equipment, assembled with 2-CPE, displays remarkable energy density (16.1 W h kg−1) with a power density of 1748.9 W kg−1 and durable cyclic stability. The practical application capability as a power supply device can be confirmed by lighting a red light-emitting diode. Moreover, 2-GCE as a H2O2 biosensor reveals a lower detecting limit (0.48 μM), a wider linear range (1.43 μM to 1.89 mM), high selectivity and high reproducibility, and this was further demonstrated by detecting H2O2 in real blood serum samples.

Surface modified cellulose nanomaterials: a source of non-spherical nanoparticles for drug delivery

Abstract: Cellulose nanomaterials, often called nanocellulose, have created a lot of buzz as a renewable building block for new materials such as nanocomposites, aerogels and hydrogels to be used in many different areas such as packaging, batteries, environmental applications, sensors and food supplements. In the biomedical field, cellulose-based nanomaterials have widely been employed in tissue engineering, diagnostics, drug delivery and wound healing. The area of drug delivery has already been reviewed earlier focusing on cellulose-based formulations including nanoparticles, tablets, hydrogels, and aerogels. In this review, we discuss the use of soluble cellulose nanomaterials that can be used for intravenous (i.v.) administration. Cellulose nanomaterials are attractive carriers for this field as they naturally have a non-spherical shape. This review summarizes the recent advancements in the use of individual cellulose nanomaterials that can be modified with therapeutic agents or targeting ligands as drug delivery systems. To achieve this aim, surface modification is a quintessential step to generate water-soluble individual cellulose nanoparticles to ensure high solubility in blood serum and good protein repellency. The main focus of this review is to provide a summary of surface modification techniques ranging from the covalent attachment of small molecules to the grafting of polymers. We then introduce techniques to immobilize drug molecules onto the surface of cellulose nanomaterials before concluding with a future outlook.

Hypoxic Cancer-Secreted Exosomal miR-182-5p Promotes Glioblastoma Angiogenesis by Targeting Kruppel-like Factor 2 and 4

Abstract: Glioblastoma (GBM) is the most lethal primary brain tumor and has a complex molecular profile. Hypoxia plays a critical role during tumor progression and in the tumor microenvironment (TME). Exosomes released by tumor cells contain informative nucleic acids, proteins, and lipids involved in the interaction between cancer and stromal cells, thus leading to TME remodeling. Accumulating evidence indicates that exosomes play a pivotal role in cell-to-cell communication. However, the mechanism by which hypoxia affects tumor angiogenesis via exosomes derived from tumor cells remains largely unknown. In our study, we found that, compared with the parental cells under normoxic conditions, the GBM cells produced more exosomes, and miR-182-5p was significantly upregulated in the exosomes from GBM cells under hypoxic conditions. Exosomal miR-182-5p directly suppressed its targets Kruppel-like factor 2 and 4, leading to the accumulation of VEGFR, thus promoting tumor angiogenesis. Furthermore, exosome-mediated miR-182-5p also inhibited tight junction-related proteins (such as ZO-1, occludin, and claudin-5), thus enhancing vascular permeability and tumor transendothelial migration. Knockdown of miR-182-5p reduced angiogenesis and tumor proliferation. Interestingly, we found elevated levels circulating miR-182-5p in patient blood serum and cerebrospinal fluid samples, and its expression level was inversely related to the prognosis. IMPLICATIONS: Overall, our data clarify the diagnostic and prognostic value of tumor-derived exosome-mediated miR-182-5p and reveal the distinctive cross-talk between tumor cells and human umbilical vein endothelial cells mediated by tumor-derived exosomes that modulate tumor vasculature.

Rapid and Digital Detection of Inflammatory Biomarkers Enabled by a Novel Portable Nanoplasmonic Imager.

Abstract: New point-of-care diagnostic devices are urgently needed for rapid and accurate diagnosis, particularly in the management of life-threatening infections and sepsis, where immediate treatment is key. Sepsis is a critical condition caused by systemic response to infection, with chances of survival drastically decreasing every hour. A novel portable biosensor based on nanoparticle-enhanced digital plasmonic imaging is reported for rapid and sensitive detection of two sepsis-related inflammatory biomarkers, procalcitonin (PCT) and C-reactive protein (CRP) directly from blood serum. The device achieves outstanding limit of detection of 21.3 pg mL-1 for PCT and 36 pg mL-1 for CRP, and dynamic range of at least three orders of magnitude. The portable device is deployed at Vall d'Hebron University Hospital in Spain and tested with a wide range of patient samples with sepsis, noninfectious systemic inflammatory response syndrome (SIRS), and healthy subjects. The results are validated against ultimate clinical diagnosis and currently used immunoassays, and show that the device provides accurate and robust performance equivalent to gold-standard laboratory tests. Importantly, the plasmonic imager can enable identification of PCT levels typical of sepsis and SIRS patients in less than 15 min. The compact and low-cost device is a promising solution for assisting rapid and accurate on-site sepsis diagnosis.

An electrochemical sensor for ifosfamide, acetaminophen, domperidone, and sumatriptan based on self-assembled MXene/MWCNT/chitosan nanocomposite thin film.

Abstract: New multi-walled carbon nanotubes supported on Ti3C2–MXene and chitosan (chit) composite film–based electrochemical sensor for ifosfamide (IFO), acetaminophen (ACOP), domperidone (DOM), and sumatriptan (SUM) have been developed Ti3C2–MXene was synthesized by a fluoride method Structural and chemical characterizations suggested the successful preparation of Ti3C2–MXene with clearly seen layered morphology, defined 0 0 2 diffraction peak at 75° and complete absence of 1 0 4 plane at 39° The electrochemical performance of the sensor was investigated by cyclic voltammetry and adsorptive stripping differential pulse voltammetry The Ti3C2/MWCNT/Chit modified glassy carbon electrode exhibits enhanced electrocatalytic activities toward the oxidation of target analytes Excellent conductivity, large surface area, and high catalytic properties of the Ti3C2–MXene showed synergistic effects with MWCNTs and helped in achieving low detection limits of targets with high selectivity and reproducibility The assay allows determination of IFO, ACOP, DOM, and SUM in the concentration ranges 00011–10, 00042–71, 00046–73, and 00033–61 μM with low detection limits of 000031, 000028, 000034, and 000042 μM, respectively The sensor was successfully applied for voltammetric screening of target analytes in urine and blood serum samples with recoveries > 9521% Schematic illustration of the synthesis of self-assembled MXene/MWCNT/chitosan nanocomposite is given and its application to the voltammetric determination of ifosfamide, acetaminophen, domperidone, and sumatriptan described

Association between periodontitis and glycosylated haemoglobin before diabetes onset: a cross-sectional study.

Abstract: The aim of the present cross-sectional study was to investigate the association between serum glycosylated haemoglobin (HbA1c) levels and periodontal status in patients with periodontitis (CP) and periodontally healthy controls. Furthermore, the objectives were to determine if the periodontitis influenced the serum HbA1c levels. A total of 93 patients with CP and 95 periodontally healthy subjects were enrolled in the present study using a cross-sectional design. At baseline, patients were examined and characterized on a regular basis for blood serum parameters and non-fasting blood samples levels. In all patients, a full periodontal examination was performed and clinical attachment loss (CAL) was the primary outcome variable chosen. The spearman correlation, a stepwise multivariable linear regression, and Jonckheere-Terpstra tests were applied in order to assess the relationship between HbA1c levels and periodontitis. Patients in the CP group presented a significantly higher median serum level of HbA1c [40.9 (31.2; 45.6) mmol/mol)] compared to patients in the healthy control group [35.3 (29.6; 38.6) mmol/mol)] (p < 0.001). HbA1c levels were negatively correlated with the number of teeth and positively correlated with C-reactive protein levels and all periodontal parameters (p < 0.001). Moreover, there was a significant decrease in the number of teeth when HbA1c levels increased (P-trend < 0.001), while there was a significant increase in periodontal parameters (CAL, p = 0.002); PD, p = 0.008; BOP, p < 0.001) when levels of HbA1c increased. Patients with CP and undiagnosed diabetes presented significantly higher serum levels of HbA1c compared to periodontally healthy controls. Moreover, the presence of periodontitis was positively correlated with serum HbA1c levels before diabetes onset. HbA1c levels were positively correlated with the severity of periodontitis before diabetes onset.

SERS Platform for Dengue Diagnosis from Clinical Samples Employing a Hand Held Raman Spectrometer

Abstract: Dengue is a serious global health concern especially in tropical and subtropical countries. About 2.5 billion of the world's population is at risk for dengue infection. Early diagnosis is the key to prevent the deterioration of health of the patient to severe illness. Laboratory diagnosis of dengue is essential for providing appropriate supportive treatment to dengue patients with febrile illness, which is difficult to diagnose clinically. Here, we demonstrate surface enhanced Raman scattering (SERS) based diagnosis of dengue virus in clinical blood samples collected from total of 102 subjects. All of the samples were well characterized by conventional NS1 antigen and IgM antibody ELISA kits. The silver nanorods array fabricated by glancing angle deposition technique were employed as SERS substrates. A small amount of patient blood serum (5 μL) was taken for analysis and the report was prepared within a minute. SERS spectra of pure NS1 protein as well as spiked in serum was also recorded separately. Principal component analysis (PCA) was employed as the statistical tool to differentiate dengue positive, dengue negative, and healthy subjects on the basis of their respective SERS spectra. This method provides a sensitive, rapid, and field deployable diagnosis of dengue at the early stage (within 5 days of the onset of symptoms).

Post-Stroke Cognitive Impairment: A Review Focusing on Molecular Biomarkers

Abstract: Post-stroke cognitive impairment (PSCI), as one of the major complications after stroke, refers to a series of syndromes from mild cognitive impairment to dementia caused by stroke. Stroke has been reported to increase the risk of cognitive impairment by at least five to eight times. The assessment of PSCI usually relies on neuropsychological tests, but the results of these tests are subjective and inaccurate, and can be insufficient for the diagnosis and prognosis of PSCI. In recent years, an increasing number studies have indicated that changes in the expression of biomarkers such as C-reactive protein (CRP), interleukin 6 (IL-6) and IL-10 in blood, urine and other body fluids are associated with cognitive decline after stroke. Therefore, the detection of biomarkers in circulating blood serum, plasma and cerebrospinal fluid (CSF) may improve the accuracy of diagnosis and prognosis in PSCI. This review aims to summarize the studies on potential molecular biomarkers of PSCI.

Serum Amyloid A (SAA) Proteins

Abstract: As normal constituents of blood serum, the Serum Amyloid A (SAA) proteins are small (104 amino acids in humans) and remarkably well-conserved in mammalian evolution. They are synthesized prominently, but not exclusively, in the liver. Fragments of SAA can associate into insoluble fibrils (called “amyloid”) characteristic of “secondary” amyloid disease in which they can interrupt normal physiology and lead to organ failure. SAA proteins comprise a family of molecules, two members of which (SAA1 and SAA2) are (along with C-reactive protein, CRP) the most prominent members of the acute phase response (APR) during which their serum levels rise dramatically after trauma, infection and other stimuli. Biologic function(s) of SAA are unresolved but features are consistent with a prominent role in primordial host defense (including the APR). SAA proteins are lipophilic and contribute to high density lipoproteins (HDL) and cholesterol transport. SAA proteins interact with specific receptors and have been implicated in tissue remodeling through metalloproteinases, local tissue changes in atherosclerosis, cancer metastasis, lung inflammation, maternal–fetal health and intestinal physiology. Molecular details of some of these are emerging.

Palladium supported on polypyrrole/reduced graphene oxide nanoparticles for simultaneous biosensing application of ascorbic acid, dopamine, and uric acid.

Abstract: In this study, we report a facile and effective production process of palladium nanoparticles supported on polypyrrole/reduced graphene oxide (rGO/Pd@PPy NPs). A novel electrochemical sensor was fabricated by incorporation of the prepared NPs onto glassy carbon electrode (GCE) for the simultaneous detection of ascorbic acid (AA), dopamine (DA) and uric acid (UA). The electrodes modified with rGO/Pd@PPy NPs were well decorated on the GCE and exhibited superior catalytic activity and conductivity for the detection of these molecules with higher current and oxidation peak intensities. Simultaneous detection of these molecules was achieved due to the high selectivity and sensitivity of rGO/Pd@PPy NPs. For each biomolecule, well-separated voltammetric peaks were obtained at the modified electrode in cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements. Additionally, the detection of these molecules was performed in blood serum samples with satisfying results. The detection limits and calibration curves for AA, DA, and UA were found to be 4.9 × 10−8, 5.6 × 10−8, 4.7 × 10−8 M (S/N = 3) and ranging from 1 × 10−3 to 1.5 × 10−2 M (in 0.1 M PBS, pH 3.0), respectively. Hereby, the fabricated rGO/Pd@PPy NPs can be used with high reproducibility, selectivity, and catalytic activity for the development of electrochemical applications for the simultaneous detection of these biomolecules.

Paper based point of care immunosensor for the impedimetric detection of cardiac troponin I biomarker

Abstract: Advancements in health care monitoring demand a rapid, accurate and reliable early diagnosis of “Heart Attack” (acute myocardial infarction) with an objective to develop a cost-effective, rapid and label-free point of care diagnostic test kit for the detection of cardiac troponin I (cTnI) on paper-based multi-frequency impedimetric transducers. Paper based sensing platforms were developed by integrating carboxyl group functionalized multi-walled carbon nanotubes (MWCNT) with antibodies of cardiac troponin I (anti-cTnI) biomarker and was characterized using Electrochemical Impedance Spectroscopy (EIS). Various concentrations of cTnI with anti cTnI were studied as a function of impedance change. The suitability of the proposed immunosensor is demonstrated by spiking cTnI in blood serum samples. The limit of detection (LoD) and sensitivity of the proposed sensor was determined to be 0.05 ng/mL and 1.85 mΩ/ng/mL respectively, with a response time of ~1 min. The shelf life of the fabricated sensor was nearly 30 days. The rapid response, very low detection limit, and cost effectiveness offer a portable platform to detect cTnI in blood serum samples. The proposed immunosensor, therefore, offers an affordable healthcare diagnostic platform in resource limited areas.

Label-free diagnosis for colorectal cancer through coffee ring-assisted surface-enhanced Raman spectroscopy on blood serum.

Abstract: Surface-enhanced Raman spectroscopy (SERS) is garnering considerable attention for the swift diagnosis of pathogens and abnormal biological status, that is, cancers. In this work, a simple, fast and inexpensive optical sensing platform is developed by the design of SERS sampling and data analysis. The pretreatment of spectral measurement employed gold nanoparticle colloid mixing with the serum from patients with colorectal cancer (CRC). The droplet of particle-serum mixture formed coffee-ring-like region at the rim, providing strong and stable SERS profiles. The obtained spectra from cancer patients and healthy volunteers were analyzed by unsupervised principal component analysis (PCA) and supervised machine learning model, such as support-vector machine (SVM), respectively. The results demonstrate that the SVM model provides the superior performance in the classification of CRC diagnosis compared with PCA. In addition, the values of carcinoembryonic antigen from the blood samples were compiled with the corresponding SERS spectra for SVM calculation, yielding improved prediction results.

Quantitative analysis of human blood serum using vibrational spectroscopy

Abstract: Analysis of bodily fluids using vibrational spectroscopy has attracted increasing attention in recent years. In particular, infrared spectroscopic screening of blood products, particularly blood serum, for disease diagnostics has been advanced considerably, attracting commercial interests. However, analyses requiring quantification of endogenous constituents or exogenous agents in blood are less well advanced. Recent advances towards this end are reviewed, focussing on infrared and Raman spectroscopic analyses of human blood serum. The importance of spectroscopic analysis in the native aqueous environment is highlighted, and the relative merits of infrared absorption versus Raman spectroscopy are considered, in this context. It is argued that Raman spectroscopic analysis is more suitable to quantitative analysis in liquid samples, and superior performance for quantification of high and low molecular weight components, is demonstrated. Applications for quantitation of viral loads, and therapeutic drug monitoring are also discussed.

RNA cargos in extracellular vesicles derived from blood serum in pancreas associated conditions.

Abstract: Exosomes are extracellular vesicles which are released from healthy and tumor cells into blood circulation. Unique biomolecular cargos such as RNA and protein are loaded in these vesicles. These molecules may have biological functions such as signaling, cell communications and have the potential to be analyzed as biomarkers. In this initial study, we describe the analysis of exosomes in the serum of healthy subjects, intraductal papillary mucosal neoplasms and pancreatic ductal adenocarcinoma including the characterization of their RNA cargos by next generation sequencing (EXO-NGS). Results indicate the presence of a wide variety of RNAs including mRNA, miRNA, lincRNA, tRNA and piRNA in these vesicles. Based on the differential mRNA expression observed upon EXO-NGS analysis, we independently evaluated two protein coding genes, matrix metalloproteinase-8 (MMP-8) and transcription factor T-Box 3 (TBX3) by qRT-PCR for selective expression in the serum samples. Results indicate a variable expression pattern of these genes across serum samples between different study groups. Further, qRT-PCR analysis with the same serum exosomes processed for EXO-NGS, we observed two long non-coding RNAs, malat-1 and CRNDE to be variably expressed. Overall, our observations emphasize the potential value of different exosome components in distinguishing between healthy, premalignant and malignant conditions related to the pancreas.

Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review

Abstract: Background Programmed cell death-1 (PD-1) inhibitor has been indicated for many types of malignancies. However, these inhibitors also cause immune-related adverse events. Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%-4.5% of patients treated with PD-1 inhibitors. Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis (SC); however, the associated clinical and pathological features are unclear. Aim To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature. Methods The review, conducted using electronic databases in PubMed, was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English. We scanned the references of the selected literature to identify any further relevant studies. Six cases previously studied by us, including three that have not yet been published, were included in this review. Results Thirty-one PD-1 inhibitor-related SC cases were evaluated. Median age of patients was 67 years (range, 43-89), with a male to female ratio of 21:10. The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer. Agents that caused PD-1 inhibitor-related SC were nivolumab (19 cases), pembrolizumab (10 cases), avelumab (1 case), and durvalumab (1 case). The median number of cycles until PD-1 inhibitor-related SC onset was 5.5 (range, 1-27). Abdominal pain or discomfort (35.5%, 11/31) was the most frequent symptom. Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes, and a normal level of serum immunoglobulin G4. Biliary dilation without obstruction (76.9%, 20/26), diffuse hypertrophy of the extrahepatic biliary tract (90.5%, 19/21), and multiple strictures of the intrahepatic biliary tract (30.4%, 7/23) were noted. In 11/23 (47.8%) cases, pathological examination indicated that CD8+ T cells were the dominant inflammatory cells in the bile duct or peribiliary tract. Although corticosteroids were mainly used for PD inhibitor-related SC treatment, the response rate was 11.5% (3/26). Conclusion Some clinical and pathological features of PD-1 inhibitor-related SC were revealed. To establish diagnostic criteria for PD-1 inhibitor-related SC, more cases need to be evaluated.

Effect of Dietary Supplementation with Moringa oleifera Leaves and/or Seeds Powder on Production, Egg Characteristics, Hatchability and Blood Chemistry of Laying Japanese Quails

Abstract: The present study aimed to evaluate the effect of dietary Moringa oleifera (M. oleifera) leaves and/or seed powder on laying Japanese quail performance in terms of egg production, egg quality, blood serum characteristics, and reproduction. In total, 168 Japanese quails (120 hens and 48 males) at eight weeks of age in laying period were randomly distributed to four treatment groups, with six replicates per group and seven birds (five hens and two males) per replicate. The first group (G1) served as a control group, while G2, G3 and G4 groups were supplemented with M. oleifera leaves (ML) and M. oleifera seeds (MS) and their combination ((1 g/kg ML; 1 g/kg MS; and 1 ML g/kg + 1 MS g/kg (MSL), respectively). From the results, feed consumption, feed conversion ratio, egg weight, fertility and hatchability from fertile eggs, egg and yolk index, and Haugh unit were not affected by dietary treatments. However, egg production, egg mass, eggshell thickness, and hatchability were significantly increased and blood aspartate transaminase (AST) and urea decreased in the MS treatment. Both triglycerides and total cholesterol were reduced (p < 0.05) in all treatments with ML, MS, and MSL, with no significant differences in alanine aminotransferase (ALT), albumin, total protein, globulin, and A/G ratio among dietary treatment. Our results clearly indicated that the inclusion of M. oleifera seeds in Japanese quail diet significantly increased egg production and improved hatchability, along with some egg quality parameters, and also lowered some blood biochemical components.