Nonsurgical bleeding occurs in a significant proportion of patients implanted with continuous-flow ventricular assist devices (CF-VADs) and is associated with nonphysiologic flow with diminished pulsatility. An in vitro vascular pulse perfusion model seeded with adult human aortic endothelial cells (HAECs) was used to identify biomarkers sensitive to changes in pulsatility. Diminished pulsatility resulted in an ~45% decrease in von Willebrand factor (vWF) levels from 9.80 to 5.32 ng/ml (n = 5, p < 0.05) and a threefold increase in angiopoietin-2 (ANGPT-2) levels from 775.29 to 2471.93 pg/ml (n = 5, p < 0.05) in cultured HAECs. These changes are in agreement with evaluation of patient blood samples obtained pre-CF-VAD implant and 30-day postimplant: a decrease in plasma vWF level by 50% from ~45.59 to ~22.49 μg/ml (n = 15, p < 0.01) and a 64% increase in plasma ANGPT-2 level from 7,073 to 11,615 pg/ml (n = 8, p < 0.05). This study identified vWF and ANGPT-2 as highly sensitive to changes in pulsatility, in addition to interleukin-6 (IL-6), IL-8, and tumor necrosis-α (TNF-α). These biomarkers may help determine the optimal level of pulsatility and help identify patients at high risk of nonsurgical bleeding. 
                        more » 
                        « less   
                    
                            
                            A Facile Graphene Conductive Polymer Paper Based Biosensor for Dopamine, TNF-α, and IL-6 Detection
                        
                    
    
            Paper-based biosensors are a potential paradigm of sensitivity achieved via microporous spreading/microfluidics, simplicity, and affordability. In this paper, we develop decorated paper with graphene and conductive polymer (herein referred to as graphene conductive polymer paper-based sensor or GCPPS) for sensitive detection of biomolecules. Planetary mixing resulted in uniformly dispersed graphene and conductive polymer ink, which was applied to laser-cut Whatman filter paper substrates. Scanning electron microscopy and Raman spectroscopy showed strong attachment of conductive polymer-functionalized graphene to cellulose fibers. The GCPPS detected dopamine and cytokines, such as tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) in the ranges of 12.5–400 µM, 0.005–50 ng/mL, and 2 pg/mL–2 µg/mL, respectively, using a minute sample volume of 2 µL. The electrodes showed lower detection limits (LODs) of 3.4 µM, 5.97 pg/mL, and 9.55 pg/mL for dopamine, TNF-α, and IL-6 respectively, which are promising for rapid and easy analysis for biomarkers detection. Additionally, these paper-based biosensors were highly selective (no serpin A1 detection with IL-6 antibody) and were able to detect IL-6 antigen in human serum with high sensitivity and hence, the portable, adaptable, point-of-care, quick, minute sample requirement offered by our fabricated biosensor is advantageous to healthcare applications. 
        more » 
        « less   
        
    
    
                            - PAR ID:
- 10484617
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Sensors
- Volume:
- 23
- Issue:
- 19
- ISSN:
- 1424-8220
- Page Range / eLocation ID:
- 8115
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
- 
            
- 
            In this research, a novel electrochemical biosensor is proposed based on inducing graphene formation on polyimide substrate via laser engraving. Graphene polyaniline (G-PANI) conductive ink was synthesized by planetary mixing and applied to the working zone of the developed sensor to effectively enhance the electrical signals. The laser-induced graphene (LIG) sensor was used to detect alpha-fetoprotein (AFP) and 17β-Estradiol (E2) in the phosphate buffer saline (PBS) buffer and human serum. The electrochemical performance of the biosensor in determining these biomarkers was investigated by differential pulse voltammetry (DPV) and chronoamperometry (CA). In a buffer environment, alpha-fetoprotein (AFP) and 17β-Estradiol detection range were 4–400 ng/mL and 20–400 pg/mL respectively. The experimental results showed a limit of detection (LOD) of 1.15 ng/mL and 0.96 pg/mL for AFP and estrogen, respectively, with an excellent linear range (R2 = 0.98 and 0.99). In addition, the designed sensor was able to detect these two types of biomarkers in human serum successfully. The proposed sensor exhibited excellent reproducibility, repeatability, and good stability (relative standard deviation, RSD = 0.96%, 1.12%, 2.92%, respectively). The electrochemical biosensor proposed herein is easy to prepare and can be successfully used for low-cost, rapid detection of AFP and E2. This approach provides a promising platform for clinical detection and is advantageous to healthcare applications.more » « less
- 
            The endocannabinoidome (eCBome) is the expanded endocannabinoid system (ECS) and studies show that there is a link between this system and how it modulates alcohol induced neuroinflammation. Using conditional knockout (cKO) mice with selective deletion of cannabinoid type 2 receptors (CB2Rs) in dopamine neurons (DAT-Cnr2) and in microglia (Cx3Cr1-Cnr2), we investigated how CB2Rs modulate behavioral and neuroinflammation induced by alcohol. Behavioral tests including locomotor and wheel running activity, rotarod performance test, and alcohol preference tests were used to evaluate behavioral changes induced by alcohol. Using ELISA assay, we investigated the level of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1α (IL-1α), and interleukin-1β (IL-1β) in the hippocampus of mice. The findings demonstrated that locomotor activity, wheel running, and rotarod performance activities were significantly affected by cell-type specific deletion of CB2Rs in dopamine neurons and microglia. The non-selective CB2R agonist, WIN 55,212-2, reduced alcohol preference in the wild type and cell-type specific CB2R cKO mice. In addition, the result showed that cell-type specific deletion of CB2Rsper seand administration of alcohol to CB2R cKO mice increased the expression of proinflammatory cytokines in the hippocampus. These findings suggest the involvement of CB2Rs in modulating behavioral and immune alterations induced by alcohol.more » « less
- 
            In this research, a novel interdigitated gear-shaped, graphene-based electrochemical biosensor was developed for the detection of dopamine (DA). The sensor’s innovative design improves the active surface area by 94.52% and 57% compared to commercially available Metrohm DropSens 110 screen-printed sensors and printed circular sensors, respectively. The screen-printed electrode was fabricated using laser processing and modified with graphene polyaniline conductive ink (G-PANI) to enhance its electrochemical properties. Fourier Transform Infrared (FTIR) Spectroscopy and X-ray diffraction (XRD) were employed to characterize the physiochemical properties of the sensor. Dopamine, a neurotransmitter crucial for several body functions, was detected within a linear range of 0.1–100 µM, with a Limit of Detection (LOD) of 0.043 µM (coefficient of determination, R2 = 0.98) in phosphate-buffer saline (PBS) with ferri/ferrocyanide as the redox probe. The performance of the sensor was evaluated using cyclic voltammetry (CV) and Chronoamperometry, demonstrating high sensitivity and selectivity. The interdigitated gear-shaped design exhibited excellent repeatability, with a relative standard deviation (RSD) of 1.2% (n = 4) and reproducibility, with an RSD of 2.3% (n = 4). In addition to detecting dopamine in human serum, the sensor effectively distinguished dopamine in a ternary mixture containing uric acid (UA) and ascorbic acid (AA). Overall, this novel sensor design offers a reliable, disposable, and cost-effective solution for dopamine detection, with potential applications in medical diagnostics and neurological research.more » « less
- 
            null (Ed.)Activation of the CB2 receptor has been shown to have anti-inflammatory and antinociceptive effects without causing psychoactive effects. Previously, we reported that the compound ethyl 2(2-(N-(2,3-dimethylphenyl) phenylsulfonamido)acetamido)benzoate (ABK5) is a CB2 subtype selective agonist with anti-inflammatory and antinociceptive effects. In the present study, we tested four ABK5 derivatives, ABK5-1, ABK5-2, ABK5-5, and ABK5-6, to analyze the structure of ABK5 to obtain CB2-selective agonists with higher affinity and efficacy. Affinity, subtype selectivity, and G-protein coupling were determined by radioligand binding assays. Selected compounds were then subjected to evaluation of anti-inflammatory effects using two different cell lines, Jurkat (ABK5-1 and 5-2) and BV-2 cells (ABK5-1), which are models of T cells and microglia, respectively. ABK5-1, ABK5-2, and ABK5-6 had comparable CB2 binding affinity with ABK5 (and stimulated G-protein coupling), while only ABK5-1 and ABK5-2 maintained CB2-subtype selectivity. ABK5-5 did not bind CB2 in the detectable range. RT-PCR and ELISA analysis showed that the two compounds also inhibit IL-2 and TNF-α production, and they were more efficacious than ABK5 in inhibiting TNF-α production. CXCL-12 mediated chemotaxis was also evaluated by the transwell migration assay, and both ABK5-1 and ABK5-2 inhibited chemotaxis with a stronger effect observed in ABK5-1. In the microglia cell line BV-2, ABK5-1 inhibited IL-1β and IL-6 production, which suggests this compound has anti-inflammatory effects through targeting multiple immune cells, and may be a candidate for treatment of inflammation.more » « less
 An official website of the United States government
An official website of the United States government 
				
			 
					 
					
 
                                    