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Researchers employed the Infliximab ELISA Assay Kit in a new study aimed at uncovering the connection between infliximab concentrations in tissue and plasma and their impact on ulcerative colitis (UC) disease activity. Explore the full abstract and access the detailed research below.

Abstract

Background: We aimed to determine the correlation between tissue and plasma infliximab concentrations in an outpatient ulcerative colitis (UC) cohort based on histologic disease activity in addition to their relationship with long-term clinical outcomes. We assessed intraparticipant variability in infliximab concentrations between adjacent intestinal samples and the correlation between disease activity and tumor necrosis factor-α (TNF-α).

Methods: A prospective cohort study was conducted in participants with UC receiving infliximab. Blood and 2 sigmoid colon biopsies were obtained at the index colonoscopy for infliximab and TNF-α quantification. Histological disease activity was assessed. Participants were followed for 2 years for the occurrence of hospitalization, surgery, disease relapse, and infliximab discontinuation.

Results: A positive correlation was observed between mean plasma and uninflamed tissue infliximab concentrations only (Rs = 0.75, P = .0071). Lower mean tissue infliximab concentrations correlated with a shorter time to disease relapse vs those with higher mean tissue concentrations (Rs = 0.77, P = .032). This was not seen when using plasma infliximab concentrations. Additionally, no significant intraparticipant variability of infliximab concentrations was observed for all participants independent of disease activity. Neither plasma nor tissue TNF-α correlated with disease activity.

Conclusions: These findings support data generated in patients with Crohn’s disease: plasma infliximab concentrations are reflective of infliximab exposure in tissue in the UC patient in remission, but not for those with active disease. Increasing tissue concentrations in the noninflamed tissues may improve durability of infliximab. Neither plasma nor tissue TNF-α appear to correlate with UC disease activity. Larger follow-up studies would be of benefit.

John Choi, Qian Wang, Melanie Beaton, Richard B Kim, Reena Khanna, Aze Wilson, Infliximab Tissue Concentrations in Patients With Stable Ulcerative Colitis Are Correlated With More Durable Infliximab-associated Disease Remission, Inflammatory Bowel Diseases, 2024;, izae097, https://doi.org/10.1093/ibd/izae097

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A new study has featured the Noradrenaline (Norepinephrine) HS ELISA from DLD Diagnostika! Researchers provide mechanistic insights into C. difficile-associated pathogenesis and help illuminate a target for intervention to limit recurrent disease. Check out the summary and full text below.

Summary

Recurrent Clostridioides difficile infection (CDI) results in significant morbidity and mortality. We previously established that CDI in mice does not protect against reinfection and is associated with poor pathogen-specific B cell memory (Bmem), recapitulating our observations with human Bmem. Here, we demonstrate that the secreted toxin TcdB2 is responsible for subversion of Bmem responses. TcdB2 from an endemic C. difficile strain delayed immunoglobulin G (IgG) class switch following vaccination, attenuated IgG recall to a vaccine booster, and prevented germinal center formation. The mechanism of TcdB2 action included increased B cell CXCR4 expression and responsiveness to its ligand CXCL12, accounting for altered cell migration and a failure of germinal center-dependent Bmem. These results were reproduced in a C. difficile infection model, and a US Food and Drug Administration (FDA)-approved CXCR4-blocking drug rescued germinal center formation. We therefore provide mechanistic insights into C. difficile-associated pathogenesis and illuminate a target for clinical intervention to limit recurrent disease.

Norman KM, et al. Clostridioides difficile toxin B subverts germinal center and antibody recall responses by stimulating a drug-treatable CXCR4-dependent mechanism. Cell Reports. 2024. https://doi.org/10.1016/j.celrep.2024.114245.

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

Our Mouse/Rat 25-OH Vitamin D ELISA Assay Kit was featured in a recent study! Researchers used our kit to explore the impact of standard chow diets on animal model experiments and how diet-related variability can influence experimental outcomes. Check out the abstract and access to the full text below.

Abstract

Standard chow diet contributes to reproducibility in animal model experiments since chows differ in nutrient composition, which can independently influence phenotypes. However, there is little evidence of the role of timing in the extent of variability caused by chow exposure. Here, we measured the impact of diet (5V5M, 5V0G, 2920X, and 5058) and timing of exposure (adult exposure (AE), lifetime exposure (LE), and developmental exposure (DE)) on growth & development, metabolic health indicators, and gut bacterial microbiota profiles across genetically identical C57BL6/J mice. Diet drove differences in macro- and micronutrient intake for all exposure models. AE had no effect on measured outcomes. However, LE mice exhibited significant sex-dependent diet effects on growth, body weight, and body composition. LE effects were mostly absent in the DE model, where mice were exposed to chow differences from conception to weaning. Both AE and LE models exhibited similar diet-driven beta diversity profiles for the gut bacterial microbiota, with 5058 diet driving the most distinct profile. Diet-induced beta diversity profiles were sex-dependent for LE mice. Compared to AE, LE drove 9X more diet-driven differentially abundant genera, majority of which were the result of inverse effects of 2920X and 5058. Our findings demonstrate that lifetime exposure to different chow diets has the greatest impact on reproducibility of experimental measures that are common components of preclinical mouse model studies. Importantly, weaning DE mice onto a uniform diet is likely an effective way to reduce unwanted phenotypic variability among experimental models.

Knuth M.M. et al. Timing of standard chow exposure determines the variability of mouse phenotypic outcomes and gut microbiota profile. bioRxiv. 2024. doi: 10.1101/2024.03.28.587032

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Exciting news! Three of our gastrointestinal biomarker ELISA kits were integral to a recently published study. Using our Insulin ELISA Assay Kit, Calprotectin ELISA Assay Kit, High Sensitive CRP ELISA Assay Kit, researchers analyzed blood and stool samples from endurance runners. The study aimed to evaluate the effectiveness of probiotics in treating gastrointestinal injury and permeability. Check out the abstract and access to the full text below.

Abstract

Probiotics are increasingly used to treat conditions associated with gastrointestinal injury and permeability, including exercise-induced gastrointestinal discomfort. This study assessed safety and efficacy of a probiotic in altering the intestinal milieu and mitigating gastrointestinal symptoms (GIS) in endurance runners. In a double blind, crossover study, 16 runners were randomized to 4 weeks of daily supplementation with a probiotic cocktail containing Pediococcus acidilactici bacteria and Lactobacillus plantarum or placebo. Fasting blood and stool samples were collected for measurement of gut permeability markers, immune parameters, and microbiome analyses. Treadmill run tests were performed before and after treatment; participants ran at 65%–70% of VO2max at 27 °C for a maximum of 90 min or until fatigue/GIS developed. A blood sample was collected after the treadmill run test. In healthy individuals, 4 weeks of probiotic supplementation did not alter health parameters, although a marginal reduction in aspartate aminotransferase levels was observed with probiotic treatment only (p = 0.05). GIS, gut permeability-associated parameters (intestinal fatty acid binding protein, lipopolysaccharide binding protein, zonulin, and cytokines), and intestinal microbial content were not altered by the probiotic supplementation. Post-run measurements of GIS and gut-associated parameters did not differ between groups; however, the observed lack of differences is confounded by an absence of measurable functional outcome as GIS was not sufficiently induced during the run. Under the current study conditions, the probiotic was safe to use, and did not affect gut- or immune-associated parameters, or intestinal symptoms in a healthy population. The probiotic might reduce tissue damage, but more studies are warranted.

Lennon S., Lackie T., Miltko A., et al. Safety and efficacy of a probiotic cocktail containing P. acidilactici and L. plantarum for gastrointestinal discomfort in endurance runners: randomized double-blinded crossover clinical trial. Appl Physiol Nutr Metab. 2024. 49(7):890-903. DOI: 10.1139/apnm-2023-0449

If you have any questions about these three gastrointestinal biomarker ELISAs or any of our other offerings, contact us here.

We’re excited to share that the Noradrenaline (Norepinephrine) Sensitive ELISA Assay Kit was featured in a recent publication! The study explored the link between Alzheimer’s Disease and osteoporosis using mouse models. Discover the abstract and access the full text below.

Abstract

Alzheimer’s disease (AD) and osteoporosis often coexist in the elderly. Although observational studies suggest an association between these two diseases, the pathophysiologic link between AD and skeletal health has been poorly defined. We examined the skeletal phenotype of 5xFAD mice, an AD model with accelerated neuron-specific amyloid-β accumulation causing full-blown AD phenotype by the age of 8 months. Micro-computed tomography indicated significantly lower trabecular and cortical bone parameters in 8-month-old male, but not female, 5xFAD mice than sex-matched wild-type littermates. Dynamic histomorphometry revealed reduced bone formation and increased bone resorption, and quantitative RT-PCR showed elevated skeletal RANKL gene expression in 5xFAD males. These mice also had diminished body fat percentage with unaltered lean mass, as determined by dual-energy X-ray absorptiometry (DXA), and elevated Ucp1 mRNA levels in brown adipose tissue, consistent with increased sympathetic tone, which may contribute to the osteopenia observed in 5xFAD males. Nevertheless, no significant changes could be detected between male 5xFAD and wild-type littermates regarding the serum and skeletal concentrations of norepinephrine. Thus, brain-specific amyloid-β pathology is associated with osteopenia and appears to affect both bone formation and bone resorption. Our findings shed new light on the pathophysiologic link between Alzheimer’s disease and osteoporosis.

Jung, Ay, Cyr et al. Amyloid-β neuropathology induces bone loss in male mice by suppressing bone formation and enhancing bone resoptioin. Bone Rep. 2024. 21:101771 DOI: 10.1016/j.bonr.2024.101771

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

An innovative study leveraged multiple ELISA kits from our portfolio to investigate the impact of head-out cold water immersion on thyroid hormone concentrations. The researchers used a range of kits, such as the Free Triiodothyronine (fT3) ELISA, Triiodothyronine T3 ELISA Assay Kit, Free Thyroxine (fT4) ELISA Assay Kit, Thyroxine (T4) ELISA Assay Kit, and Thyroid Stimulating Hormone ELISA Assay Kit. Find the abstract and access to the full text below.

Abstract

This study tested the hypothesis that acute moderate normobaric hypoxia augments circulating thyroid hormone concentrations during and following 1 h of cold head-out water immersion (HOWI), compared with when cold HOWI is completed during normobaric normoxia. In a randomized crossover single-blind design, 12 healthy adults (27 ± 2 yr, 2 women) completed 1 h of cold (22.0 ± 0.1°C) HOWI breathing either normobaric normoxia (F⁢IO2 = 0.21) or normobaric hypoxia (F⁢IO2 = 0.14). Free and total thyroxine (T3) and triiodothyronine (T4), and thyroid-stimulating hormone (TSH) concentrations were measured in venous blood samples obtained before (baseline), during (15-, 30-, and 60 min), and 15 min following HOWI (post-), and were corrected for changes in plasma volume. Arterial oxyhemoglobin saturation and core (rectal) temperature were measured continuously. Arterial oxyhemoglobin saturation was lower during hypoxia (90 ± 3%) compared with normoxia (98 ± 1%, P < 0.001). Core temperature fell from baseline (normoxia: 37.2 ± 0.4°C, hypoxia: 37.2 ± 0.4°C) to post-cold HOWI (normoxia: 36.4 ± 0.5°C, hypoxia: 36.3 ± 0.5°C, P < 0.001) in both conditions but did not change differently between conditions (condition × time: P = 0.552). Circulating TSH, total T3, free T4, total T3, and free T4 concentrations demonstrated significant main effects of time (all P ≤ 0.024), but these changes did not differ between normoxic and hypoxic conditions (condition × time: all P ≥ 0.163). These data indicate that acute moderate normobaric hypoxia does not modify the circulating thyroid hormone response during 1 h of cold HOWI.

Keeler JM, et al. Acute moderate normobaric hypoxia does not modify circulating thyroid hormone concentrations induced by 1 h of head-out cold-water immersion. Journal of Applied Physiology. 2024 136(6):1400-1409. https://doi.org/10.1152/japplphysiol.00061.2024

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In their latest research, scientists utilized the Creatinine Microplate Assay Kit to shed light on why lung cancer is more prevalent among African Americans compared to Whites, even when both groups have similar smoking habits. See the abstract and full text below.

Abstract

Background: After accounting for smoking history, lung cancer incidence is greater in African Americans than Whites. In the multiethnic cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day. Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans.

Methods: In a nested case–control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White; 56% African American). TNE, the trans-3-hydroxycotinine/cotinine ratio, 4-(methylnitrosamino)-1–3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid were quantified in urine. Unconditional logistic regression was used to estimate the ORs and 95% confidence intervals (CI) for each biomarker and lung cancer risk.

Results: TNE, NNAL, and Cd were higher in cases than controls (adjusted for age, race, sex, body mass index, and cigarettes per day). Among cases, these levels were higher in African Americans compared with Whites. After accounting for age, sex, body mass index, and pack-years, a one-SD increase in log-TNE (OR = 1.30; 95% CI, 1.10–1.54) and log-NNAL (OR = 1.27; 95% CI, 1.03–1.58 with TNE adjustment) was associated with lung cancer risk. In this study, in which NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL.

Conclusions: Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years.

Murphy, Guillermo, Thomson et al. Association of urinary biomarkers of tobacco exposure with lung cancer risk in African American and White cigarette smokers in the Southern Community Cohort Study. Cancer Epidemiol Biomarkers Prev. (2024) https://doi.org/10.1158/1055-9965.EPI-23-1362

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In a recent study on fibrous dysplasia (FD), researchers employed the Free Soluble RANKL ELISA from Biomedica! Researchers developed a comprehensive genetic profile of FD bone marrow stromal cells and examined various cytokines connected to disease severity. Check out the abstract and full text below to learn more.

Abstract

Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants of GNAS encoding for Gαs and leading to excessive cyclic adenosine monophosphate signaling in bone-marrow stromal cells (BMSCs). The effect of Gαs activation in the BMSC transcriptome and how it influences FD lesion microenvironment are unclear. We analyzed changes induced by Gαs activation in the BMSC transcriptome and secretome. RNAseq analysis of differential gene expression of cultured BMSCs from patients with FD and healthy volunteers, and from an inducible mouse model of FD, was performed, and the transcriptomic profiles of both models were combined to build a robust FD BMSC genetic signature. Pathways related to Gαs activation, cytokine signaling, and extracellular matrix deposition were identified. To assess the modulation of several key secreted factors in FD pathogenesis, cytokines and other factors were measured in culture media. Cytokines were also screened in a collection of plasma samples from patients with FD, and positive correlations of several cytokines to their disease burden score, as well as to one another and bone turnover markers, were found. These data support the pro-inflammatory, pro-osteoclastic behavior of FD BMSCs and point to several cytokines and other secreted factors as possible therapeutic targets and/or circulating biomarkers for FD.

Michel, Z et al. Transcriptomic Signature and Pro-Osteoclastic Secreted Factors of Abnormal Bone-Marrow Stromal Cells in Fibrous Dysplasia. Cells 2024, 13, 774. https://doi.org/10.3390/cells13090774

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