Blood Cell Fractions Research Articles

Surface-active microrobots can propel through blood faster than inert microrobots

Abstract Microrobots that can move through a network of blood vessels have promising medical applications. Blood contains a high volume fraction of blood cells, so in order for a microrobot to move through the blood, it must propel itself by rearranging the surrounding blood cells. However, swimming form effective for propulsion in blood is unknown. This study shows numerically that a surface-active microrobot, such as a squirmer, is more efficient in moving through blood than an inert microrobot. This is because the surface velocity of the microrobot steers the blood cells laterally, allowing them to propel themselves into the hole they are digging. When the microrobot size is comparable to a red blood cell or when the microrobot operates under a low Capillary number, the puller microrobot swims faster than the pusher microrobot. The trend reverses under considerably smaller microrobot sizes or high Capillary number scenarios. Additionally, the swimming speed is strongly dependent on the hematocrit and magnetic torque used to control the microrobot orientation. A comparative analysis between the squirmer and Janus squirmer models underscores the extensive applicability of the squirmer model. The obtained results provide new insight into the design of microrobots propelled efficiently through blood, paving the way for innovative medical applications.

Deposit of Red Blood Cells at low concentrations in evaporating droplets is dominated by a central edge growth

Evaporation of blood droplets and diluted blood samples is a topic of intensive research, as it is considered a potential low-cost diagnostic tool. So far, samples with a volume fraction down to a few percent of red blood cells have been studied, and these were reportedly dominated by a “coffee-ring” deposit. In this study, samples with lower volume fractions were used to investigate the growth of the evaporative deposit from sessile droplets in more detail. We observed that blood samples and salt solutions with less than 1% volume fraction of red blood cells are dominated by a central deposit. We characterized the growth process of this central deposit by evaporating elongated drops and determined that it is consistent with the Kardar-Parisi-Zhang process in the presence of quenched disorder. Our results showed a sensitivity of the deposit size to fibrinogen concentration and the shape of red blood cells, suggesting that this parameter could be developed into a new and cost-effective clinical marker for inflammation and red blood cell deformation.

Blood cell counts and nonalcoholic fatty liver disease: Evidence from Mendelian randomization analysis.

Previous research has highlighted correlations between blood cell counts and chronic liver disease. Nonetheless, the causal relationships remain unknown. To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease (NAFLD) risk. Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study (GWAS) conducted by the Blood Cell Consortium. Summary-level data for liver enzymes were obtained from the United Kingdom Biobank. NAFLD data were obtained from a GWAS meta-analysis (8434 cases and 770180 controls, discovery dataset) and the Fingen GWAS (2275 cases and 372727 controls, replication dataset). This analysis was conducted using the inverse-variance weighted method, followed by various sensitivity analyses. One SD increase in the genetically predicted haemoglobin concentration (HGB) was associated with a β of 0.0078 (95%CI: 0.0059-0.0096), 0.0108 (95%CI: 0.0080-0.0136), 0.0361 (95%CI: 0.0156-0.0567), and 0.0083 (95%CI: 00046-0.0121) for alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transferase, respectively. Genetically predicted haematocrit was associated with ALP (β = 0.0078, 95%CI: 0.0052-0.0104) and ALT (β = 0.0057, 95%CI: 0.0039-0.0075). Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD [odds ratio (OR) = 1.199, 95%CI: 1.087-1.322] and (OR = 1.157, 95%CI: 1.071-1.250). The results of the sensitivity analyses remained significant. Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis, which may facilitate the diagnosis and prevention of NAFLD.

Additive genotoxic effects in cord blood cells upon indirect exposure to chemotherapeutic compounds crossing an in vitro placental barrier

Prenatal exposure to toxins can adversely affect long-term health outcomes of the offspring. Though chemotherapeutics are now standard of care for treating cancer patients during pregnancy, certain compounds are known to cross the placenta and harm placental tissue. The consequences for the fetus are largely unexplored. Here we examined the responses of newborn cord blood mononuclear cells in tissue culture to two chemotherapeutic drugs, cyclophosphamide and epirubicin, when either directly exposed to these drugs, or indirectly after crossing a placenta trophoblast bilayer barrier. Cord blood mononuclear cells exposed to the conditioned media obtained from cyclophosphamide-exposed trophoblast barriers showed a significant 2.4-fold increase of nuclear ROS levels compared to direct exposure to cyclophosphamide. Indirect exposure to epirubicine-exposed trophoblast barriers not only enhanced nuclear ROS levels but also significantly increased the fraction of cord blood cells with double strand breaks, relative to directly exposed cells. Neither apoptosis nor proliferation markers were affected in cord mononuclear blood cells upon direct or indirect exposure to cyclophosphamide or epirubicin. Our data suggests that trophoblast cells exposed to cyclophosphamide or epirubicine may induce an indirect ‘bystander’ effect and can aggravate genotoxicity in the fetal compartment.

Umbilical cord blood stem cells: transplantation prospects in neurological practice

Umbilical cord blood has evolved from being considered a mere cellular/tissue waste product after childbirth to a valuable biological material with a wide regenerative potential. Today, hematopoietic cord blood stem cells are used in the same way as bone marrow and mobilised peripheral blood as part of the standard medical treatment for haemoblastoses and hereditary blood diseases. There is an increasing amount of experimental data showing possibility of umbilical cord blood cell fractions using for treatment of non-hematological diseases and, in particular, diseases of the central nervous system. One of the key challenges in cell therapy for central nervous system diseases is the choice of cellular material for neurotransplantation. This is particularly relevant for ischemic and traumatic injuries, as well as neurodegenerative diseases. Stem or mature somatic cells prepared for neurotransplantation should have predictable and reproducible characteristics thataccording therapeutic purposes, exactly: trophic and/or neuroprotective action to increase neurons viability in damaged area; axon growth stimulation and myelination; cell matrix restoration or predictable differentiation direction to replace amount of lost brain or spinal cord cells. The fact that umbilical cord blood contains not only hematopoietic, but also various non-hematopoietic stem cells with a wide regenerative potential has become the basis for active use of these cells for neurotransplantation. The proposed review provides historical information about umbilical cord blood introduction into practical medicine, its cellular composition and clinical applications of stem cells various types for children central nervous system diseases treatment, such as ischemic encephalopathy, stroke, cerebral hemorrhage, cerebral palsy, autism, and in adults — for stroke treatment, spinal cord injury and neurodegenerative diseases.

Relationship between thrombus composition and prognosis in patients with acute ischemic stroke undergoing mechanical thrombectomy

BackgroundMechanical thrombectomy has emerged as the primary endovascular treatment for acute ischemic stroke. Numerous studies have investigated the relationship between thrombus composition and factors such as pharmacological thrombolysis, stroke etiology, mechanical thrombectomy, and radiological imaging. However, limited research has explored the association between thrombus composition and clinical outcomes. MethodsThis retrospective analysis examined the histopathological examination of thrombi retrieved from 50 patients with acute ischemic stroke between May 2020 and May 2023. The composition of the retrieved thrombi was assessed using HE staining to quantify the proportions of red blood cells, white blood cells, platelets, and fibrin. Based on the predominant composition of the thrombus, the patients were divided into two groups: erythrocyte-rich and fibrin-rich. Demographics, clinical characteristics, and clinical outcomes assessed by the National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) scores were collected retrospectively. ResultOf the 50 patients, 23 were classified in the erythrocyte-rich group, and 27 were classified in the fibrin-rich group. There were no significant differences between the two groups in terms of age, sex, stroke subtype, history of hypertension and diabetes, thrombus location, NIHSS scores, mRS scores on admission, the time interval from symptom onset to hospitalization and reperfusion, or the rate of successful reperfusion. However, erythrocyte-rich thrombi were associated with a shorter time interval from puncture to reperfusion. No significant differences were found in the red blood cell fraction and fibrin/platelet fraction between large artery atherosclerosis and cardioembolism. At the 90-day follow-up, patients with erythrocyte-rich thrombi exhibited lower NIHSS scores and more favorable functional outcomes (mRS scores of 0–2) compared to those with fibrin-rich thrombi. ConclusionErythrocyte-rich thrombi were linked to shorter time intervals from puncture to reperfusion and favorable clinical outcomes in patients with acute ischemic stroke. The composition of the thrombus may influence the thrombectomy strategy for endovascular therapy.

Abstract PO2-15-09: Immune related cell fraction in peripheral blood and outcomes of advanced breast cancer patients treated with Eribulin

Abstract Background: Eribulin prolongs overall survival (OS) of patients with advanced breast cancer, and an ad-hoc analysis of the EMBRACE trial showed that baseline absolute lymphocyte count (ALC) was a predictor of OS prolongation. It has been suggested that eribulin improves the immune response to the tumor by improving the hypoxic environment through remodeling of local tumor vessels and reducing hypoxic stress, leading to OS prolongation. However, the details of the immune response mediated by eribulin remain to be fully elucidated. CD8+ cells attack cancer cells as cytotoxic T cells, while regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) suppress activated T cells that attack cancer cells. In this study, we focused on CD8+ cytotoxic T cells, Tregs, MDSCs, and CD4-CD25-FoxP3+ cells in peripheral blood, analyzed the changes of those immune cells before and after eribulin treatment, and examined the effects on the outcomes of breast cancer patients. Methods: Nineteen patients with advanced or recurrent breast cancer treated with eribulin from April 2021 to May 2023 at our hospital were included. Peripheral blood was collected before drug administration as the first treatment (pre-treatment) and before drug administration in the second course (post-treatment), and the cell fractions, including CD4+ cells, CD8+ cells, CD4+CD25+FoxP3+ Tregs, CD11b+CD14+CD33+ MDSCs, and CD4-CD25-FoxP3+ cells, were analyzed by flow cytometry. The cutoff value for ALC was set at 1000 and NLR at 3.0, and each cell fraction was set to its respective median. Kaplan-Meier plots and logrank tests for progression-free survival (PFS) or OS were applied. Results: CD4+ cells were significantly lower post-treatment compared to pre-treatment (p=0.0140). Further, Tregs were significantly lower post-treatment compared to pre-treatment (p=0.0258). There were no significant changes in the levels of CD8+ cells, MDSCs, and CD4-CD25-FoxP3+ cells between pre- and post-treatment. We examined the association between each cell fraction and ALC or NLR, and found that CD4-CD25-FoxP3+ cells were significantly higher in cases with high NLR (p=0.0110). Analysis of the association between each cell fraction and prognosis at pre-treatment revealed that the high CD8+ cell group had significantly better PFS and OS than the low CD8+ cell group (p=0.0129 and p=0.0077, respectively). Interestingly, the high CD4-CD25-FoxP3+ cell group had significantly worse PFS than the low CD4-CD25-FoxP3+ cell group (p=0.0026). Conclusion: In the current study, Tregs in the peripheral blood of breast cancer patients significantly decreased after eribulin treatment, suggesting that eribulin may improve the immune microenvironment by suppressing immunosuppressive cells in cancer, including Tregs. In addition, the CD4-CD25-FoxP3+ cell fraction may serve as a biomarker for eribulin therapy, and further studies are needed to elucidate the details, including analysis of the constituent cells within the fraction. Citation Format: Masayuki Nagahashi, Ayako Bun, Mamiko Kuroiwa, Miki Komatsu, Sayaka Urano, Yukie Fujimoto, Aoi Oshiro, Ayumu Mitsuyoshi, Haruka Kanaoka, Akira Hattori, Reiko Fukui, Tomoko Higuchi, Arisa Nishimukai, Keiko Murase, Yuichi Takatsuka, Yasuo Miyoshi. Immune related cell fraction in peripheral blood and outcomes of advanced breast cancer patients treated with Eribulin [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-15-09.

Associations between per- and polyfluoroalkyl chemicals and abdominal aortic calcification in middle-aged and older adults

IntroductionPer- and polyfluoroalkyl substances (PFAS) have infiltrated countless everyday products, raising concerns about potential effects on human health, specifically on the cardiovascular system and the development of abdominal aortic calcification (AAC). However, our understanding of this relationship is still limited. ObjectivesThis study aims to investigate the effects of PFAS on AAC using machine learning algorithms. MethodsLeveraging the power of machine learning (ML) technique, extreme gradient boosting (XGBoost), we assessed the relationship between PFAS exposure and AAC risk. We focused on three PFAS compounds, perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) through multiple logistic regression, restricted cubic spline (RCS), and quantile g-computation (QGC) models. To get more insight into the underlying mechanisms, mediation analyses are used to investigate the potential mediating role of fatty acids and blood cell fractions in AAC. ResultsOur findings indicate that elevated serum levels of PFHxS and PFDeA are associated with the increased risk of AAC. The QGC analyses underscore the overall positive association between the PFAS mixture and AAC risk, with PFHxS carrying the greatest weight, followed by PFDeA. The RCS analyses reveal a dose-dependent increase between serum PFHxS concentration and AAC risk in an inverted V-shape way. Moreover, age and PFHxS exposure are identified as the primary factors contributing to abdominal aortic calcification risk in SHapley Additive exPlanation (SHAP) summary plot combined with XGBoost technique. Although PFAS significantly change the profile of fatty acids, we do not find any mediating roles of them in AAC. Despite strong associations between PFAS exposure and hematological indicators, our analysis does not find evidence that these indicators mediate the development of AAC. ConclusionsIn summary, our study highlights the detrimental impact of PFAS on abdominal aortic health and emphasizes the need for further research to understand the underlying mechanisms involved.

Conjugated bisphenol S metabolites in human serum and whole blood

Studies have shown that bisphenol S (BPS) is mainly present as its conjugated metabolites in human blood. However, the distribution of conjugated BPS metabolites in different human blood matrices has not been characterized. In this study, paired human serum and whole blood samples (n = 79) were collected from Chinese participants, and were measured for the occurrence of BPS and 4 BPS metabolites. BPS was detectable in 49% of human serum (<LOD–1.7 ng/mL) and 78% of whole blood (<LOD–2.1 ng/mL) samples. In both human serum and whole blood, BPS-sulfate (BPS–S; 74% and 86%, respectively) and BPS-glucuronide (BPS-G; 68% and 84%, respectively) had higher detection frequency than BPS. Consistently, BPS-S was the predominant BPS metabolite in human serum (mean 0.39 ng/mL) and whole blood (0.41 ng/mL), significantly higher than BPS-G (mean 0.13 and 0.13 ng/mL, respectively). This is contrary to the data from controlled oral exposure studies on model animals and humans, in which BPS-G was the dominant BPS metabolite in serum. BPS-S (mean ± SD, 0.99 ± 0.35) had the highest partitioning coefficient between human serum and whole blood, followed by BPS-G (0.89 ± 0.27) and BPS (0.81 ± 0.28), suggesting their preferential accumulation in the red blood cell fraction. These results represent the first human data on conjugated BPS metabolites in paired human serum and whole blood, which help to elucidate of the occurrence of conjugated BPS metabolites in humans.

Side scatter ratio of the CD105-positive and CD105-negative red blood cell fractions is useful for the detection of low-grade myelodysplastic neoplasms by flow cytometry.

We assessed the utility of red blood cell (RBC) CD105 and side scatter (SSC) parameters by flow cytometry for the detection of low-grade myelodysplastic neoplasms (MDS) in bone marrow specimens. Ten RBC parameters incorporating CD105 or SSC combined with the Meyerson-Alayed scoring system (MASS) metrics were retrospectively evaluated by flow cytometry for utility in detecting low-grade MDS (n = 56) compared with cytopenic controls (n = 86). Myelodysplastic neoplasms were associated with 7 of the RBC parameters in univariate analysis. Multivariate analysis using cutoff values based on optimal and 95% specificity levels of the RBC metrics and the MASS parameters revealed the SSC ratio of CD105-positive and CD105-negative RBC fractions (CD105+/- SSC); the percentage and coefficient of variation of the CD105-positive fraction of RBCs (CD105%, CD105+CV) emerged as significant RBC variables. Two simple scoring schemes using these RBC values along with MASS parameters were identified: 1 using CD105+/- SSC, CD105%, and CD105+CV combined with the percentage of CD177-positive granulocytes (CD177%), myeloblast percentage (CD34%), and granulocyte SSC (GranSSC), and the other incorporating CD105+/- SSC, CD105+CV, CD177%, CD34%, GranSSC, and B-cell progenitor percentage. Both demonstrated a sensitivity of approximately 80%, with a specificity of roughly 90% for the detection of MDS compared with cytopenic controls. The red blood cell parameter, CD105+/- SSC, appears to be beneficial in the evaluation of low-grade MDS by flow cytometry.

Analysis of the Suitability of an Effective Viscosity to Represent Interactions Between Red Blood Cells in Shear Flow.

Many methods to computationally predict red blood cell damage have been introduced, and among these are Lagrangian methods that track the cells along their pathlines. Such methods typically do not explicitly include cell-cell interactions. Due to the high volume fraction of red blood cells (RBCs) in blood, these interactions could impact cell mechanics and thus the amount of damage caused by the flow. To investigate this question, cell-resolved simulations of red blood cells in shear flow were performed for multiple interacting cells, as well as for single cells in unbounded flow at an effective viscosity. Simulations run without adjusting the bulk viscosity produced larger errors unilaterally and were not considered further for comparison. We show that a periodic box containing at least 8 cells and a spherical harmonic of degree larger than 10 are necessary to produce converged higher-order statistics. The maximum difference between the single-cell and multiple-cell cases in terms of peak strain was 3.7%. To achieve this, one must use the whole blood viscosity and average over multiple cell orientations when adopting a single-cell simulation approach. The differences between the models in terms of average strain were slightly larger (maximum difference of 6.9%). However, given the accuracy of the single-cell approach in predicting the maximum strain, which is useful in hemolysis prediction, and its computational cost that is orders of magnitude less than the multiple-cell approach, one may use it as an affordable cell-resolved approach for hemolysis prediction.

Early Phase Persistent Changes in the White Blood Cell Fraction in Patients With Advanced Urothelial Carcinoma Treated With Pembrolizumab: A Multicenter Retrospective Study.

The association of clinical outcomes with posttreatment persistent changes in eosinophils and other white blood cell (WBC) subtypes in patients with advanced urothelial cancer (UC) treated with pembrolizumab after the failure of platinum-based chemotherapy is unclear. We retrospectively analyzed 87 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The changes in WBC subtypes from pretreatment were evaluated three and six weeks after pembrolizumab administration. The association between the changes in the WBC subtypes and clinical outcomes was then evaluated using the Kaplan-Meier method and a Cox regression model. Among WBC subtypes, significant changes in the absolute (AEC) and relative eosinophil count (REC) and the neutrophil-to-eosinophil ratio (NER) were observed at three and six weeks compared with pretreatment (p<0.001). Multivariable Cox regression analyses revealed that a persistent decrease in AEC and REC and a persistent increase in NER were associated with poor overall survival. Persistent increase in AEC and REC and decrease in NER in the early phase after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.

Abstract 25 Cord Blood Mononuclear Cells and Cord Blood Plasma Alter Human Cardiac Endothelial Cell Angiogenic Sprouting and Growth In Vitro

Abstract Introduction The mononuclear cell fraction of human placental cord blood (CBMNC) comprises immune cells, hematopoietic, mesenchymal and other stem or progenitor cells. CBMNCs are proposed to afford therapeutic benefit based on their paracrine release of multiple cytokines, growth factors and other proteins that stimulate signalling for wound healing, including attenuation of inflammation and fibrosis. Whether CBMNCs augment angiogenic sprouting and tube formation by endothelial cells in human ventricular myocardium is not well characterised. Objectives The aim of this study was to investigate the in vitro influence of CBMNCs on endothelial cell angiogenic-like growth. Methods A tube formation assay for human donor primary ventricular myocardium microvascular endothelial cells (HMVECs), (3 female donors, age 48-50 yrs, 3 replicates per treatment group) was established using Matrigel-coated 96-well plates (62,500-78,125 cells/cm2). Cells from passage 5-8 were used for all experiments.. Angiogenic processes, as characterized by endothelial sprouting followed by tube extension into honeycomb-like mesh structures, were imaged over 24 hours. HMVECs were treated with CBMNCs at a concentration of 1:10 (MNC:HMVEC) or cord blood plasma (1μg/μL) at 0h, 3h, or 6h after the HMVECs were seeded. The cells were visualized by phase contrast microscope and images (4x magnification) were analysed using the Angiogenesis Analyzer plugin in FIJI ImageJ. Size exclusion chromatography and multiplex ELISAs were performed to determine the presence of analytes in media collected from each well. Results CBMNC-treated HMVECs exhibited greater average total elongated branching length and more tube-like structured meshes, compared to untreated controls. MMP-1, MMP-2, MMP-9, MMP-10, TIMP-1, TIMP-2, angiopoietin-2, EGF, endoglin, endothelin-1, FGF-2, follistatin, HB-EGF, IL-8, PLGF, VEGF-A, and VEGF-C were detected in extracellular media during in vitro tube formation. With CBMNC treatment, only MMP-9 was increased by 475.94%, whereas angiopoietin-2, follistatin, and PLGF levels were decreased by 27.90%, 15.90%, and 26.18% respectively. In contrast, CB plasma-treated HMVECs did not form tube sprouts, instead an intense endothelial cell proliferation was observed which was associated with increased MMP-2, MMP-9, endothelin-1 and IL-8 levels with decreased angiopoietin-2, HB-EGF, PLGF, and endoglin levels. Discussion CBMNC treatment enhanced pro-angiogenic processes in HMVECs in vitro through increased branching and network formation, whereas CB plasma evoked cell proliferation.

Novel Per- and Polyfluoroalkyl Substances Discovered in Cattle Exposed to AFFF-Impacted Groundwater.

The leaching of per- and polyfluoroalkyl substances (PFASs) from Australian firefighting training grounds has resulted in extensive contamination of groundwater and nearby farmlands. Humans, farm animals, and wildlife in these areas may have been exposed to complex mixtures of PFASs from aqueous film-forming foams (AFFFs). This study aimed to identify PFAS classes in pooled whole blood (n = 4) and serum (n = 4) from cattle exposed to AFFF-impacted groundwater and potentially discover new PFASs in blood. Thirty PFASs were identified at various levels of confidence (levels 1a-5a), including three novel compounds: (i) perfluorohexanesulfonamido 2-hydroxypropanoic acid (FHxSA-HOPrA), (ii) methyl((perfluorohexyl)sulfonyl)sulfuramidous acid, and (iii) methyl((perfluorooctyl)sulfonyl)sulfuramidous acid, belonging to two different classes. Biotransformation intermediate, perfluorohexanesulfonamido propanoic acid (FHxSA-PrA), hitherto unreported in biological samples, was detected in both whole blood and serum. Furthermore, perfluoroalkyl sulfonamides, including perfluoropropane sulfonamide (FPrSA), perfluorobutane sulfonamide (FBSA), and perfluorohexane sulfonamide (FHxSA) were predominantly detected in whole blood, suggesting that these accumulate in the cell fraction of blood. The suspect screening revealed several fluoroalkyl chain-substituted PFAS. The results suggest that targeting only the major PFASs in the plasma or serum of AFFF-exposed mammals likely underestimates the toxicological risks associated with exposure. Future studies of AFFF-exposed populations should include whole-blood analysis with high-resolution mass spectrometry to understand the true extent of PFAS exposure.

Components of the Glutathione Cycle as Markers of Biological Age: An Approach to Clinical Application in Aging.

The oxidative-inflammatory theory of aging states that aging is the result of the establishment of a chronic oxidative-inflammatory stress situation in which the immune system is implicated. Among the redox parameters, those involved in the glutathione cycle have been suggested as essential in aging. Thus, the first objective of this study was to determine if several components of the glutathione cycle (glutathione reductase (GR) and glutathione peroxidase (GPx) activities, and concentrations of oxidized glutathione (GSSG) and reduced glutathione (GSH)) in leukocytes) are associated with the biological age (ImmunolAge) estimated using the Immunity Clock in 190 men and women. The second objective was to identify the best blood fraction (whole blood, blood cells, erythrocytes, or plasma) to quantify these components and correlate them with the estimated ImmunolAge. The results show that the oxidative state of peripheral leukocytes correlates with their functionality, supporting the idea that this is the basis of immunosenescence. In blood, the correlations are more significant in the fraction of blood cells with respect to ImmunolAge (positive correlations with GSSG concentration and the GSSG/GSH ratio, and negative correlations with GPx and GR activities). Therefore, blood cells are proposed as the most effective sample to estimate the biological age of individuals in clinical settings.

Digestive α-L-fucosidase activity in Rhodnius prolixus after blood feeding: effect of secretagogue and nutritional stimuli.

Introduction: Rhodnius prolixus (Hemiptera: Reduviidae) is an important vector of Trypanosoma cruzi, the causative agent of Chagas Disease. This insect is a model for the study of insect physiology, especially concerning the digestion of blood. Among the enzymes produced in the midgut of R. prolixus after blood feeding there is a α-L-fucosidase activity. There are very few studies on α-L-fucosidase of insects, and the role of R. prolixus α-L-fucosidase is still not clear. In this work, we tested if the mechanism for production of this enzyme is similar to the observed for proteases, a secretatogue mechanism that respond to the protein contents of the meal. Methods: We tested if specific proteins or sugars elicit this response, which may help to understand the nature of the physiological substrate for this enzyme. Results: In general, our results showed that the Anterior Midgut was the only midgut fraction that responds to the blood meal in terms of α-L-fucosidase production. Besides that, this response was not triggered by midgut distension or by ingestion of the blood cell fraction. Conversely, the enzyme was produced after feeding with the plasma fraction. However, the production of α-L-fucosidase was also triggered by different biochemical stimuli, as protein or fucoidan ingestion. Discussion: This suggested that the production of the enzyme in the anterior midgut was a general physiological response under control of different convergent signals. Besides that, the comparison between different treatments for artificial blood feeding showed that heparinated blood was the choice with minor side effects for the study of the midgut α-L-fucosidase, when compared to defibrinated or citrated blood.

The expression IL1B correlates negatively with the clinical response to adalimumab in Crohn's disease patients: An ex vivo approach using peripheral blood mononuclear cells

AimsUnderstanding of the molecular mechanisms of anti-TNFα therapy non-response and reliable biomarkers are essential for personalized medicine in Crohn's disease (CD) patients. Using RNA-seq data adjusted for deconvoluted fractions of peripheral blood cells, we recently described MMD gene, coding for a monocyte to macrophage differentiation factor, as a biomarker of adalimumab (anti-TNFα) therapy response in CD. The results also suggest that cell subtype-specific biomarkers may be superior to those measured in bulk peripheral blood. Here, we used functional cell model to further investigate the role of the monocyte to macrophage differentiation in adalimumab treatment response and evaluate monocyte/macrophage specific expression of the inflammatory cytokines as potential biomarkers for (non)response to adalimumab in CD patients. Main methodsThe peripheral monocytes of CD patients responsive and non-responsive to adalimumab were isolated, differentiated into macrophages, and exposed to inflammation and concurrent adalimumab therapy in vitro. The results were correlated to the clinical response of the donor patients. Key findingsCorrelation is shown of the expression of two macrophage differentiation related genes- CD68 and MMD, with the expression of the inflammatory cytokines TNF, IL1B, IL6 and CXCL8. Monocytes and in vitro differentiated macrophages of adalimumab non-responders express more inflammatory cytokines than those of responders. The biggest difference was in the IL1B expression. Additionally, IL1B expression in the in vitro differentiated macrophages of CD patients correlates negatively with their clinical response to adalimumab. SignificanceWe propose the IL1B expression in the macrophages as a possible biomarker for adalimumab response in CD patients.

A prediction model to predict in-hospital mortality in patients with acute type B aortic dissection

BackgroundAcute type B aortic dissection (ABAD) is a life-threatening cardiovascular disease. A practicable and effective prediction model to predict and evaluate the risk of in-hospital death for ABAD is required. The present study aimed to construct a prediction model to predict the risk of in-hospital death in ABAD patients.MethodsA total of 715 patients with ABAD were recruited in the first affiliated hospital of Xinjiang medical university from April 2012 to May 2021. The information on the demographic and clinical characteristics of all subjects was collected. The logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and nomogram were applied to screen the appropriate predictors and to establish a prediction model for the risk of in-hospital mortality in ABAD. The receiver operator characteristic curve and calibration plot were applied to validate the performance of the prediction model.ResultsOf 53 (7.41%) subjects occurred in-hospital death in 715 ABAD patients. The variables including diastolic blood pressure (DBP), platelets, heart rate, neutrophil-lymphocyte ratio, D-dimer, C-reactive protein (CRP), white blood cell (WBC), hemoglobin, lactate dehydrogenase (LDH), procalcitonin, and left ventricular ejection fraction (LVEF) were shown a significant difference between the in-hospital death group and the in-hospital survival group (all P < 0.05). Furthermore, all these factors which existed differences, except CRP, were associated with in-hospital deaths in ABAD patients (all P < 0.05). Then, parameters containing LVEF, WBC, hemoglobin, LDH, and procalcitonin were identified as independent risk factors for in-hospital deaths in ABAD patients by adjusting compound variables (all P < 0.05). In addition, these independent factors were qualified as predictors to build a prediction model (AUC > 0.5, P < 0.05). The prediction model was shown a favorable discriminative ability (C index = 0.745) and demonstrated good consistency.ConclusionsThe novel prediction model combined with WBC, hemoglobin, LDH, procalcitonin, and LVEF, was a practicable and valuable tool to predict in-hospital deaths in ABAD patients.

Age, dose, and binding to TfR on blood cells influence brain delivery of a TfR-transported antibody

BackgroundTransferrin receptor 1 (TfR1) mediated brain delivery of antibodies could become important for increasing the efficacy of emerging immunotherapies in Alzheimer's disease (AD). However, age, dose, binding to TfR1 on blood cells, and pathology could influence the TfR1-mediated transcytosis of TfR1-binders across the blood–brain barrier (BBB). The aim of the study was, therefore, to investigate the impact of these factors on the brain delivery of a bispecific TfR1-transported Aβ-antibody, mAb3D6-scFv8D3, in comparison with the conventional antibody mAb3D6.MethodsYoung (3–5 months) and aged (17–20 months) WT and tg-ArcSwe mice (AD model) were injected with 125I-labeled mAb3D6-scFv8D3 or mAb3D6. Three different doses were used in the study, 0.05 mg/kg (low dose), 1 mg/kg (high dose), and 10 mg/kg (therapeutic dose), with equimolar doses for mAb3D6. The dose-corrected antibody concentrations in whole blood, blood cells, plasma, spleen, and brain were evaluated at 2 h post-administration. Furthermore, isolated brains were studied by autoradiography, nuclear track emulsion, and capillary depletion to investigate the intrabrain distribution of the antibodies, while binding to blood cells was studied in vitro using blood isolated from young and aged mice.ResultsThe aged WT and tg-ArcSwe mice showed significantly lower brain concentrations of TfR-binding [125I]mAb3D6-scFv8D3 and higher concentrations in the blood cell fraction compared to young mice. For [125I]mAb3D6, no significant differences in blood or brain delivery were observed between young and aged mice or between genotypes. A low dose of [125I]mAb3D6-scFv8D3 was associated with increased relative parenchymal delivery, as well as increased blood cell distribution. Brain concentrations and relative parenchymal distribution of [125I]mAb3D6-scFv8D6 did not differ between tg-ArcSwe and WT mice at this early time point but were considerably increased compared to those observed for [125I]mAb3D6.ConclusionAge-dependent differences in blood and brain concentrations were observed for the bispecific antibody mAb3D6-scFv8D3 but not for the conventional Aβ antibody mAb3D6, indicating an age-related effect on TfR1-mediated brain delivery. The lowest dose of [125I]mAb3D6-scFv8D3 was associated with higher relative BBB penetration but, at the same time, a higher distribution to blood cells. Overall, Aβ-pathology did not influence the early brain distribution of the bispecific antibody. In summary, age and bispecific antibody dose were important factors determining brain delivery, while genotype was not.

The variability of arsenic in blood and urine of humans

BackgroundHumans are exposed to inorganic and organic arsenic. The total arsenic (As) concentration in urine is a commonly used biomarker of exposure. However, little is known about variability of As in biological fluids and the diurnal variation of As excretion. ObjectivesMain objectives were to assess the variability of As in urine, plasma (P-As), whole blood (B-As), and the blood cell fraction (C-As), and to assess diurnal variation of As excretion. MethodsSix urine samples were collected at fixed times during 24 h on two different days around one week apart among 29 men and 31 women. Blood samples were collected when the morning urine samples were delivered. The intra-class correlation coefficient (ICC) was calculated as the ratio of the between-individuals variance to the total observed variance. ResultsGeometric mean (GM) 24 h urinary excretions of As (U-As24 h) were 41 and 39 µg/24 h on the two days of sampling. Concentrations of B-As, P-As and C-As were highly correlated with U-As24 h and As in first void morning urine. No statistically significant differences were observed for the urinary As excretion rate between the different sampling times. A high ICC was observed for As in the cellular blood fraction (0.803), while ICC for first morning urine corrected for creatine was low (0.316). ConclusionsThe study suggests that C-As is the most reliable biomarker for use in exposure assessment of individual exposure. Morning urine samples have low reliability for such use. No apparent diurnal variation was observed in the urinary As excretion rate.