Category: Publication Spotlight

The Eagle Bioscience’s Noradrenaline (Norepinephrine) Sensitive ELISA was utilized in a recent publication that focused on epinephrine versus vasopressin in an ovine model of perinatal cardiac arrest. Check out the full text and abstract below.

Abstract

Background: Current neonatal resuscitation guidelines recommend the use of epinephrine for bradycardia/arrest not responding to ventilation and chest compressions. Vasopressin is a systemic vasoconstrictor and is more effective than epinephrine in postnatal piglets with cardiac arrest. There are no studies comparing vasopressin with epinephrine in newly born animal models with cardiac arrest induced by umbilical cord occlusion.

Objective: To compare the effect of epinephrine and vasopressin on the incidence and time to return of spontaneous circulation (ROSC), hemodynamics, plasma drug levels, and vasoreactivity in perinatal cardiac arrest.

Design/Methods: Twenty-seven term fetal lambs in cardiac arrest induced by cord occlusion were instrumented and resuscitated following randomization to epinephrine or vasopressin through a low umbilical venous catheter.

Results: Eight lambs achieved ROSC prior to medication. Epinephrine achieved ROSC in 7/10 lambs by 8 ± 2 min. Vasopressin achieved ROSC in 3/9 lambs by 13 ± 6 min. Plasma vasopressin levels in nonresponders were much lower than responders after the first dose. Vasopressin caused in vivo increased pulmonary blood flow and in vitro coronary vasoconstriction.

Conclusions: Vasopressin resulted in lower incidence and longer time to ROSC compared to epinephrine in a perinatal model of cardiac arrest supporting the current recommendations for exclusive use of epinephrine in neonatal resuscitation.

Rawat, Munmun, et al. “Masked Randomized Trial of Epinephrine versus Vasopressin in an Ovine Model of Perinatal Cardiac Arrest.” Children, vol. 10, no. 2, 2023, p. 349.

If you have any questions about the Noradrenaline (Norepinephrine) Sensitive ELISA or our other offerings, please contact us here.

The Eagle Bioscience’s Dopamine ELISA Assay was utilized in a recent publication that focused on the diverging Parkinson’s Disease Pathology. Check out the full text and abstract below.

Abstract

Multiple neurodegenerative disorders, including Parkinson’s disease (PD) and Alzheimer’s disease-associated dementia (ADAD), are linked with dopaminergic (DA) neuron death and a resulting reduction in dopamine levels in the brain. DA neuron degeneration and the risk of developing PD is connected to genetic mutations affiliated with lysosomal function and protein degradation. Accessible human cellular models for PD-relevant genetic mutations are needed to investigate mechanisms of DA cell death and define points of therapeutic intervention. Human induced pluripotent stem cell (iPSC)-derived midbrain DA neurons offer a developmentally and physiologically relevant in vitro model for investigating PD pathogenic mechanisms across genetic backgrounds. In this study, we generated DA neurons using iPSCs from two clinically diagnosed PD patients, one harboring an inherited GBA^N370Smutation and the other a mutation in LRRK2^G2019S and compared pathophysiology against DA neurons from genetically engineered SNCA^A53T iPSCs and its isogenic apparently healthy normal (AHN) iPSCs. Our results present a novel phenotype for GBA^N370S and LRRK2^G2019Sderived DA neurons, showing that they produced and released significantly more dopamine compared to the AHN and SNCA^A53T mutant DA neurons. All mutant DA neurons developed deficient glucocerebrosidase (GCase) activity, increased mitochondrial stress, aberrant neuronal activity patterns, and increased α-synuclein accumulation. Together these data suggest potentially divergent origins of PD pathogenesis in GBA^N370S and LRRK2^G2019S DA neurons. In addition, compound screening confirmed that GCase modulators can rescue enzyme activity and impact neural activity across all DA mutant neurons, to varying degrees. These data demonstrate unique in vitro phenotypes associated with PD and suggest a diversity of underlying mechanisms across different genetic backgrounds. Together, the cell lines used in this study present a valuable tool for new therapeutic discovery.

Fathi, Ali, et al. Diverging Parkinson’s Disease Pathology between Patient-DerivedGBAn370s, LRRK2g2019sand EngineeredSNCAa53tIpsc-Derived Dopaminergic Neurons, 2023, https://doi.org/10.1101/2023.01.06.521264.

If you have any questions about the Dopamine ELISA Assay or our other offerings, please contact us here.

The Eagle Bioscience’s Proteinase 3 ELISA was highlighted in a recent publication that explored how the PRTN3 variant correlates with increased autoantigen levels. Check out the full text and abstract below.

Abstract

A genome-wide association   study (GWAS) of patients with anti-neutrophil cytoplasmic antibodies (ANCAs) found an association between proteinase-3 ANCA (PR3-ANCA) and a single nucleotide polymorphism (rs62132293) upstream of PRTN3, encoding PR3. The variant (G allele) was shown to be an expression quantitative trait locus in healthy controls, but the clinical impact remains unknown. Longitudinally followed patients with ANCA and healthy controls were genotyped. Gene expression was quantified by real-time quantitative PCR from leukocyte RNA. Plasma PR3 was quantified by ELISA. Among patients, variant carriers had elevated leukocyte PRTN3 expression compared with noncarriers (C/G vs. C/C and G/G vs. C/C). Healthy controls had low PRTN3 regardless of genotype. Myeloperoxidase (MPO) expression did not differ by genotype. PRTN3 expression correlated with circulating PR3, and variant carriers had higher plasma PR3 compared with noncarriers. Among variant carriers, there was an increased risk of relapse in patients with PR3-ANCA versus MPO-ANCA. The risk allele marked by rs62132293 is clinically significant as it is associated with increased autoantigen and may, in part, explain increased relapse in PR3-ANCA. Our results underscore the role of autoantigen availability in ANCA vasculitis.

Chen, Dhruti P., et al. “PRTN3 Variant Correlates with Increased Autoantigen Levels and Relapse Risk in PR3-Anca versus MPO-Anca Disease.” JCI Insight, vol. 8, no. 4, 2023, https://doi.org/10.1172/jci.insight.166107.

If you have any questions about the Proteinase 3 ELISA or our other offerings, please contact us here.

The Eagle Bioscience’s Noradrenaline (Norepinephrine) Sensitive ELISA was utilized in two recent publications! On study explored how norepinephrine transporter defects lead to sympathetic hyperactivity in familial dysautonomia models and the other focused on the effects of a caffeine containing pre-workout supplement on β₂-adrenergic and MAPK signaling during resistance exercise. Check out the full text and abstracts below.

Norepinephrine transporter defects lead to sympathetic hyperactivity in Familial Dysautonomia models

Abstract

Familial dysautonomia (FD), a rare neurodevelopmental and neurodegenerative disorder affects the sympathetic and sensory nervous system. Although almost all patients harbor a mutation in ELP1, it remains unresolved exactly how function of sympathetic neurons (symNs) is affected; knowledge critical for understanding debilitating disease hallmarks, including cardiovascular instability or dysautonomic crises, that result from dysregulated sympathetic activity. Here, we employ the human pluripotent stem cell (hPSC) system to understand symN disease mechanisms and test candidate drugs. FD symNs are intrinsically hyperactive in vitro, in cardiomyocyte co-cultures, and in animal models. We report reduced norepinephrine transporter expression, decreased intracellular norepinephrine (NE), decreased NE re-uptake, and excessive extracellular NE in FD symNs. SymN hyperactivity is not a direct ELP1 mutation result, but may connect to NET via RAB proteins. We found that candidate drugs lowered hyperactivity independent of ELP1 modulation. Our findings may have implications for other symN disorders and may allow future drug testing and discovery.

Wu, HF., Yu, W., Saito-Diaz, K. et al. Norepinephrine transporter defects lead to sympathetic hyperactivity in Familial Dysautonomia models. Nat Commun 13, 7032 (2022). https://doi.org/10.1038/s41467-022-34811-7

The effects of a caffeine containing pre-workout supplement on β2-adrenergic and MAPK signaling during resistance exercise

Abstract

Aim: The acute myocellular responses of caffeine supplementation during resistance exercise (RE) have not been investigated. β₂-Adrenergic receptors (β₂AR) may be a target of the stimulatory effects of caffeine and stimulate bioenergetic pathways including protein kinase A (PKA), and mitogen-activated protein kinases (MAPK).
Purpose: Elucidate the effects of pre-workout supplementation on signaling responses to an acute RE bout.
Methods: In a randomized, counter-balanced, double-blind, placebo-controlled, within-subject crossover study, ten resistance-trained males (mean ± SD; age = 22 ± 2.4 years, height = 175 ± 7 cm, body mass = 84.1 ± 11.8 kg) consumed a caffeine containing multi-ingredient pre-workout supplement (SUPP) or color and flavor matched placebo (PL) 60 min prior to an acute RE bout of barbell back squats. Pre- and post-exercise muscle biopsies were analyzed for the phosphorylation (p-) of β₂AR, PKA, and MAPK (ERK, JNK, p38). Epinephrine was determined prior to supplementation (baseline; BL), after supplementation but prior to RE (PRE), and immediately after RE (POST).
Results: Epinephrine increased at PRE in SUPP (mean ± SE: 323 ± 34 vs 457 ± 68 pmol/l; p = 0.028), and was greatest at POST in the SUPP condition compared to PL (5140 ± 852 vs 2862 ± 498 pmol/l; p = 0.006). p-β₂AR and p-MAPK increased post-exercise (p < 0.05) with no differences between conditions (p > 0.05). Pearson correlations indicated there was a relationship between epinephrine and p-β₂AR in PL (r = − 0.810; p = 0.008), and p-β₂AR and ERK in SUPP (r = 0.941; p < 0.001).
Conclusion: Consumption of a caffeine containing pre-workout supplement improves performance, possibly through increases in pre-exercise catecholamines. However, the acute myocellular signaling responses were largely similar post-exercise.

Nicoll, J.X., Fry, A.C. & Mosier, E.M. The effects of a caffeine containing pre-workout supplement on β2-adrenergic and MAPK signaling during resistance exercise. Eur J Appl Physiol 123, 585–599 (2023). https://doi.org/10.1007/s00421-022-05085-0

If you have any questions about our Noradrenaline (Norepinephrine) Sensitive ELISA or our other offerings, please contact us here.

The Eagle Bioscience’s High Sensitive CRP ELISA was utilized in a recent publication exploring risk factors for cardiometabolic disease in professional firefighters. Check out the full text and abstract below.

Abstract

Objective: Firefighters are plagued with cardiometabolic disease (CMD). Obesity, poor cardiorespiratory and muscular fitness, and blood lipids (LDL-C, triglycerides, low HDL-C) are risk factors for CMD. However, markers of oxidative stress, inflammation and insulin resistance can provide further insight regarding CMD risk.

Methods: This study investigated the relationships between fitness metrics (cardiorespiratory and muscular fitness, percent body fat, waist circumference), blood lipids, blood pressure, and years of experience as a firefighter to blood markers of insulin resistance: (homeostatic model assessment for insulin resistance, HOMA-IR), oxidative stress: advanced oxidation protein products (AOPP) and inflammation: C-reactive protein (CRP).

Results: Waist circumference and blood concentrations of triglycerides were significantly related to AOPP and HOMA-IR. Cardiorespiratory fitness was inversely related to AOPP, HOMA-IR and CRP.

Conclusion: These findings demonstrate the importance of high cardiorespiratory fitness and low waist circumference to reduce markers of CMD.

McAllister, Matthew J., et al. “Risk Factors for Cardiometabolic Disease in Professional Firefighters.” Journal of Occupational & Environmental Medicine, Publish Ahead of Print, 2022, https://doi.org/10.1097/jom.0000000000002743.

If you have any questions about the High Sensitive CRP ELISA or our other offerings, please contact us here.

The Eagle Bioscience’s Ultra-Sensitive Streptavidin Coated Clear 96 Well Microplate was utilized in a recent publication that explored non-viral precision T cell receptor replacement for personalized cell therapy. Check out the full text and abstract below.

Abstract

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells. Here we developed a clinical-grade approach based on CRISPR–Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRβ). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen–HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumor biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumors of patients are also demonstrated

Foy, Susan P., et al. “Non-Viral Precision T Cell Receptor Replacement for Personalized Cell Therapy.” Nature, 2022, https://doi.org/10.1038/s41586-022-05531-1.

If you have any questions about the Ultra-Sensitive Streptavidin Coated Clear 96 Well Microplate or our other offerings, please contact us here.

The Eagle Bioscience’s Pregnenolone ELISA Assay was utilized in a recent publication that explored the effects of pregnenolone on provoked alcohol cravings, anxiety, HPA axis and autonomic arousal in individuals with alcohol use disorder. Check out the full text and abstract below.

Abstract

If you have any questions about the Pregnenolone ELISA Assay or our other offerings, please contact us here.

The Eagle Bioscience’s Histamine ELISA Assay was highlighted in a recent publication that explored how histamine deficiency deteriorates LPS-induced periodontal diseases in mice. Check out the full text and abstract below.

Abstract

Histamine is a versatile biogenic amine, generated by the unique enzyme histidine decarboxylase (Hdc). Accumulating evidence has proven that histamine plays important roles in numerous biological and pathophysiological processes. However, the role and mechanism of Hdc/Histamine signaling in periodontal diseases remain unclear. In our current study, the concentration of histamine increased in the serum, and Hdc gene expression was upregulated in the gingiva of WT mice with LPS-induced periodontal inflammation. With Hdc–GFP mice, we identified that Hdc/GFP in the periodontium was expressed in CD11b⁺ myeloid cells, rather than in tryptase-positive mast cells. Hdc-expressing CD11b⁺Gr-1⁺ neutrophils significantly increased in the peripheral blood of Hdc–GFP mice one day after LPS injection. Lack of histamine in Hdc^-/- mice not only promoted the activation and infiltration of more CD11b⁺ cells into the peripheral blood but also upregulated mRNA expression levels of IL-1β, IL-6, MCP-1and MMP9 in the gingiva compared to WT mice one day after LPS stimulation. 28 days after LPS treatment, we observed that Hdc^-/- mice exhibited more alveolar bone loss and more osteoclasts than WT mice, which was slightly ameliorated by the administration of exogenous histamine. In vivo and in vitro mechanistic studies revealed that the mRNA expression levels of proinflammatory cytokines and protein levels of NLRP3, Caspase-1, and cleaved-Caspase-1 were upregulated after blocking histamine receptor 1 and 2, especially histamine receptor 1. Taken together, CD11b⁺Gr-1⁺ neutrophils are the predominant Hdc-expressing sites in periodontal inflammation, and deficiency of endogenous histamine in Hdc^-/- mice exacerbates the destruction of the periodontium. Disruption of the histamine/H₁R/H₂R axis aggravates the inflammatory immune response via NLRP3/Casapse-1 pathway.

Song, Fujie., et al. “Histamine Deficiency Deteriorates LPS-Induced Periodontal Diseases in a Murine Model via NLRP3/Caspase-1 Pathway.” International Immunopharmacology, vol. 115, 2023, p. 109630., https://doi.org/10.1016/j.intimp.2022.109630.

If you have any questions about our Histamine ELISA Assay or our other offerings, please contact us here.

The Eagle Bioscience’s 25-OH Vitamin D ELISA Assay Kit has been used in a number of recent publications! These studies range from exploring the effects of vitamin D on cellular responses, molecular immunity, and mycobacterial killing in cattle, to the role of vitamin D, DKK1, hepcidin, and other oxidative stress biomarkers in type 2 diabetes mellitus patients. Check them all out below!

Flores Villalva, Susana. “The Effects of Vitamin D on the Cellular Responses, Molecular Immunity, and Mycobacterial Killing in Cattle.” University College Dublin. School of Agriculture and Food Science, 2022.

Kamel, Amira A., et al. “The Role of Vitamin D, DKK1, Hepcidin and Oxidative Stress Biomarkers in Type 2 Diabetes Mellitus Patients with and without Diabetic Nephropathy.” The Egyptian Journal of Hospital Medicine, vol. 89, no. 2, 2022, pp. 7137–7146.

Blakely, L.P., et al. “Effect of Vitamin D Source and Amount on Vitamin D Status and Response to Endotoxin Challenge.” Journal of Dairy Science, vol. 106, no. 2, 2023, pp. 912–926.

Fernández-Lázaro, Diego, et al. “25-Hydroxyvitamin D Serum Levels Linked to Single Nucleotide Polymorphisms (Snps) (RS2228570, RS2282679, rs10741657) in Skeletal Muscle Aging in Institutionalized Elderly Men Not Supplemented with Vitamin D.” International Journal of Molecular Sciences, vol. 23, no. 19, 2022, p. 11846.

Kumar, Abhai, et al. “Vitamin D and Inflammatory Cytokines Association in Mild Cognitive Impaired Subjects.” Neuroscience Letters, vol. 795, 2023, p. 137044.

Stenhouse, Claire, et al. “Uptake of Phosphate, Calcium, and Vitamin D by the Pregnant Uterus of Sheep in Late Gestation: Regulation by Chorionic Somatomammotropin Hormone.” International Journal of Molecular Sciences, vol. 23, no. 14, 2022, p. 7795.

If you have any questions about our 25-OH Vitamin D ELISA Kit or any of our other offerings, contact us here.

The Eagle Bioscience’s P1NP ELISA Assay was utilized in a recent publication that explored how maternal vitamin D levels correlate with fetal weight and bone metabolism during pregnancy. Check out the full text and abstract below.

Abstract

Luo, Lian-mei, Wu, Nan, Zhang, Jun and Yang, Dong. “Maternal vitamin D levels correlate with fetal weight and bone metabolism during pregnancy: a materno-neonatal analysis of bone metabolism parameters” Journal of Perinatal Medicine, 2022. https://doi.org/10.1515/jpm-2022-0068

If you have any questions about the P1NP ELISA Assay or our other offerings, please contact us here.