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Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.25, p = 0.005), especially tumors with isocitrate dehydrogenase (IDH) mutations (OR = 1.38, p = 0.007) and IDHmut 1p/19q intact (IDHmut-intact OR = 1.53, p = 0.004) tumors. Genetically inferred increased counts of lymphocytes (IDHmut-intact OR = 0.70, p = 0.004) and neutrophils (IDHmut OR = 0.69, p = 0.019; IDHmut-intact OR = 0.60, p = 0.009) show inverse associations with risk, which may reflect enhanced immune-surveillance. Considering survival, we observe higher mortality risk in patients with IDHmut 1p/19q with genetically predicted increased counts of lymphocytes (hazard ratio (HR) = 1.65, 95% CI: 1.24-2.20), neutrophils (HR = 1.49, 1.13-1.97), and eosinophils (HR = 1.59, 1.18-2.14). Polygenic scores for blood cell traits are also differentially associated with 17 tumor immune microenvironment features in a subtype-specific manner, including signatures related to interferon signaling, PD-1 expression, and T-cell/Cytotoxic responses. Our findings highlight immune-mediated susceptibility mechanisms with potential disease management implications.

AbstractThe transcription factor RUNX1 is a master regulator of hematopoiesis and is frequently mutated in myeloid malignancies. Mutations in its runt homology domain (RHD) frequently disrupt DNA binding and result in loss of RUNX1 function. However, it is not clearly understood how other RUNX1 mutations contribute to disease development. Here, we characterized RUNX1 mutations outside of the RHD. Our analysis of the patient data sets revealed that mutations within the C-terminus frequently occur in hematopoietic disorders. Remarkably, most of these mutations were nonsense or frameshift mutations and were predicted to be exempt from nonsense-mediated messenger RNA decay. Therefore, this class of mutation is projected to produce DNA-binding proteins that contribute to the pathogenesis in a distinct manner. To model this, we introduced the RUNX1R320∗ mutation into the endogenous gene locus and demonstrated the production of RUNX1R320∗ protein. Expression of RUNX1R320∗ resulted in the disruption of RUNX1 regulated processes such as megakaryocytic differentiation, through a transcriptional signature different from RUNX1 depletion. To understand the underlying mechanisms, we used Global RNA Interactions with DNA by deep sequencing (GRID-seq) to examine enhancer-promoter connections. We identified widespread alterations in the enhancer-promoter networks within RUNX1 mutant cells. Additionally, we uncovered enrichment of RUNX1R320∗ and FOXK2 binding at the MYC super enhancer locus, significantly upregulating MYC transcription and signaling pathways. Together, our study demonstrated that most RUNX1 mutations outside the DNA-binding domain are not subject to nonsense-mediated decay, producing protein products that act in concert with additional cofactors to dysregulate hematopoiesis through mechanisms distinct from those induced by RUNX1 depletion.

Familiarisation with manual blood examination methods and the morphologies of leukocytes in peripheral blood contributes to routine veterinary practice. It enables veterinarians to verify automated analysis results and to examine blood cell morphology using the microscope. Third-year students therefore participated in an online module including 10 clinical cases of various mammal species with a haematological focus. Each case required the differentiation of 100 leukocytes using digitised cell images (= items) photographed from corresponding blood films. The study aims to provide insights into student difficulties with different leukocyte morphologies by calculating the Difficulty Index (DI) values. Out of 247 participating students, 96% completed the course in full, contributing 2197 differential white blood count (dWBC) responses for evaluation. The mean DI for all items (n = 1033) was 0.95 (± 0.09 SD), indicating overall low difficulty. Nucleated red blood cells (nRBC) (DI 0.98 ± 0.03 SD), segmented neutrophils (0.98 ± 0.07), and lymphocytes (0.97 ± 0.05) obtained high scores, whereas DIs for myelocytes (0.72 ± 0.14) and monocytes (0.82 ± 0.20) posed a greater challenge for the students to recognise these types of cells. Basophils, metamyelocytes, band neutrophils, platelets, and eosinophils ranged between DIs of 0.83 (± 0.12) to 0.94 (± 0.08). In contrast to hands-on microscopy, this digital format provided valuable training to gain routine in leukocyte differentiation and presentation, particularly of uncommon cell types. These should, however, be reliably distinguished by the examiner from the more common cell types, as they usually have a relatively high clinical significance even if they occur in small numbers. Nevertheless, the lack of dynamic manual adjustments during the microscopic examination emphasises the need for hands-on microscopy in combination with a digital format. [ABSTRACT FROM AUTHOR]

Background: The association between inflammatory indices from peripheral blood cell in early pregnancy and the risk of gestational diabetes mellitus (GDM) is unclear. Methods: This was a retrospective study involving the medical data of 15,807 pregnant women who gave birth in 2019. Data were collected from the medical records and analyzed. The pregnant women's age, educational level, pre-pregnancy body weight, height, parity, family history of diabetes, lipid profile, blood pressure were recorded during 11 ~ 13+ 6 pregnancy weeks. We collected and measured several easily accessible systemic inflammatory indices from peripheral blood cell count, including Neutrophils, Lymphocytes, Monocytes, MHR (monocyte count/HDL-C), SII (platelet count ×neutrophil count/lymphocyte count) and SIRI (neutrophil count ×monocyte count/lymphocyte count), and we analyzed their association with the risk of developing GDM. Results: In the present study, a total of 15,807 women were included, including 2,355 (14.9%) women diagnosed with GDM. Women who were diagnosed with GDM showed markedly lower level of monocyte count and higher level of neutrophil and lymphocyte counts. The GDM group showed relatively lower level of SIRI, while no significant differences were found between GDM group and non-GDM group in MHR or SII. After adjusting for potential confounding factors, we observed a significant association between monocyte counts, MHR and the risk of developing GDM, and the risk tended to decrease with increasing levels of monocyte counts and MHR. Conclusion: The present study revealed that in early pregnancy, monocyte count and MHR have great potential as early diagnostic markers of GDM. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate lymphocyte subsets, especially natural killer (NK) cells, in patients with systemic sclerosis (SSc) and evaluate the diagnostic value of NK cells in secondary pulmonary arterial hypertension (PAH). A total of 115 SSc patients and 100 age- and sex-matched health controls (HCs) were enrolled in this study. Flow cytometry was employed to quantify NK cells, while the association between NK cells and disease activity as well as PAH was investigated to further elucidate its diagnostic potential. The absolute count of NK (CD3-CD56+) cells significantly decreased in SSc patients. There was a negative correlation between the mRSS score and the injury index. The levels of cytokine exhibited significant elevation among SSc patients. Conversely, SSc-PAH patients demonstrated significantly elevated levels of CRP, UA, and BNP. Additionally, there was a significant reduction in the absolute level of NK cells. ROC curve analysis revealed that the optimal cut-off point for NK cells was 185 cells/µL, while for BNP it was 70.50 pg/mL and for UA it was 323.00 µmol/L. Our study revealed a significant inverse correlation between peripheral blood NK cell levels and the incidence of complicated PAH in patients with SSc. [ABSTRACT FROM AUTHOR]

Background: Phototherapy is a common treatment for neonatal hyperbilirubinemia, however it generates reactive oxygen species and induces apoptosis, potentially influencing blood cells. Assessing changes in hematological parameters is essential to minimize complications and enhance outcomes. Objective: This study assessed hematological parameters changes and associated factors in neonates with hyperbilirubinemia undergoing phototherapy. Method: A cross-sectional study was conducted at the University of Gondar Comprehensive Specialized Hospital from May 29 to November 8, 2023. About 246 neonates were selected by convenient sampling. Blood samples were collected before and after phototherapy. Data were entered into Epi-data (4.6.0) and analyzed using SPSS (25.0). The normality of the data was checked by Kolmogorov-Smirnov tests. A paired t-test and Wilcoxon Sign Rank test were used to compare mean differences for normally distributed and skewed data, respectively. Pearson correlation and multiple linear regressions were used to measure the association. A significance level of p < 0.05 was used for statistical significance. Result: Among neonates, 141 (57.3%) were males, and the median age was 2 days. Phototherapy treatment led to significant increases in WBC and lymphocyte count, 11.02 ± 2.21 to 11.35 ± 2.60, and 3.93 ± 1.19 to 4.16 ± 1.34, respectively. However, hemoglobin and platelet count significantly decreased from 15.05 ± 3.67 to 14.55 ± 2.62, and 243.23 ± 74.78 to 239.32 ± 73.29, respectively. Other blood cell parameters were unaffected. WBC and lymphocytes showed a positive association with preterm neonates and intensive phototherapy, while WBC count showed a negative association with total bilirubin. Hemoglobin counts are positively associated with total bilirubin but negatively associated with neonate age and treatment duration. Platelet count showed negative associations with low-birth-weight neonates, intensive phototherapy, and treatment duration. After treatment, normocytic normochromic cells increased, microcytic hypochromic decreased, and abnormal RBC shapes were reduced. Conclusion: Phototherapy significantly affected key hematological parameters, notably WBC, lymphocytes, hemoglobin, and platelet count. Treating neonates with intensive phototherapy affects WBC and platelet counts while undergoing phototherapy for a longer duration affects hemoglobin and platelet counts. Therefore, routine monitoring of these parameters is crucial for neonates undergoing intensive or prolonged phototherapy. [ABSTRACT FROM AUTHOR]

Platelets, anucleate blood cells essential for hemostasis, are increasingly recognized for their role in cancer, challenging the traditional notion of their sole involvement in blood coagulation. It has been demonstrated that platelets establish bidirectional communication with tumor cells, contributing to tumor progression and metastasis through diverse molecular mechanisms such as modulation of proliferation, angiogenesis, epithelial-mesenchymal transition, resistance to anoikis, immune evasion, extravasation, chemoresistance, among other processes. Reciprocally, cancer significantly alters platelets in their count and composition, including mRNA, non-coding RNA, proteins, and lipids, product of both internal synthesis and the uptake of tumor-derived molecules. This phenomenon gives rise to tumor-educated platelets (TEPs), which are emerging as promising tools for the development of liquid biopsies. In this review, we provide a detailed overview of the dynamic roles of platelets in tumor development and progression as well as their use in diagnosis and prognosis. We also provide our view on current limitations, challenges and future research areas, including the need to design more efficient strategies for their isolation and analysis, as well as the validation of their sensitivity and specificity through large-scale and rigorous clinical trials. This research will not only enable the evaluation of their clinical viability but could also open new opportunities to enhance diagnostic accuracy and develop personalized treatments in oncology. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint blockade (ICB) therapy, including antibodies targeting the programmed cell death protein 1 (PD-1) pathway, has significantly prolonged the overall survival (OS) in patients with advanced cervical cancer (CC). ICB treatment affects both target cells and various components released by immune cells, which can be observed in peripheral blood. However, there has been limited research on the dynamics of peripheral blood immunophenotyping and its association with OS in CC patients receiving ICB therapy. Methods: Patients with persistent, recurrent, or metastatic CC treated with ICB were enrolled between December 2019 and September 2022. The dynamic changes in peripheral blood immune cells, immunoglobulins, and complement components were analyzed at baseline (within 30 days prior to the first ICB cycle) and after the second cycle of ICB treatment (4–6 weeks after the first ICB treatment). Associations of the baseline levels of peripheral blood immune cells, immunoglobulins, complement components with OS were analyzed using multivariable Cox regression analysis. Results: In this retrospective cohort study, 119 patients who received at least two cycles of ICB were included. Data on peripheral blood immune cells, immunoglobulins, and complement components were available for 70 of these patients. The percentages of suppressor T (Ts) cells and natural killer (NK) cells in peripheral blood increased significantly post-ICB treatment, whereas the Th/Ts ratio and IgM levels decreased. The percentages of cytotoxic T (Tc) cells, Ts cells, the Th/Ts ratio, and levels of IgM, IgA, C3, and C4 were significantly associated with the OS of patients. Furthermore, multivariable Cox regression analysis found that a high level of IgA was associated with poor OS of the patients (HR = 2.918; 95% CI, 1.081–7.877, P = 0.035). Conclusion: Our study demonstrated the potential proliferation of peripheral blood anti-tumor T cells in some CC patients undergoing ICB therapy. The observed associations between peripheral blood immunophenotyping and OS suggest that these biomarkers might have potential as prognostic tools. [ABSTRACT FROM AUTHOR]

Poly(lactide- co -glycolide) (PLG) nanoparticles loaded with doxorubicin have reached phase-I clinical trials for treating advanced solid tumors. This study explores cell hitchhiking, where nanoparticles associate with blood cells and investigates the impact on pharmacokinetics and tumor migration. Previous findings highlighted the early post-injection phase dominated by nonspecific nanoparticle-cell interactions and burst release. In contrast, this study examines the subsequent phase of tumor invasion, emphasizing the role of immune cells, mostly neutrophils, in redistributing the carrier to the tumor site via blood cell hitchhiking. We provide a detailed investigation of nanoparticle extravasation kinetics and mechanisms, showing qualitative and quantitative evidence of increased nanoparticle association with immune cells over time. By 30 min post-injection, approximately 15 % of monocytes and 15–19 % of neutrophils tested positive for nanoparticles, with significant differences observed between ex vivo and in vivo experiments, and between healthy and tumor-bearing animals. This study underscores the ambiguous role of immune cell-mediated tumor targeting. While the total accumulation of the carrier rises, this fraction is partially trapped in immune cells without any chance to escape. [Display omitted] [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) triggers profound functional changes in both immune and non-immune cells in the skin and circulation, though the underlying mechanisms remain unclear. In this study, we conduct single-cell transcriptome analysis of lesional and non-lesional skin, as well as blood samples from BP patients. In lesional skin, non-immune cells upregulate pathways related to metabolism, wound healing, immune activation, and cell migration. LAMP3+DCs from cDC2 show stronger pro-inflammatory signatures than those from cDC1, and VEGFA+ mast cells, crucial for BP progression, are predominantly in lesional skin. As BP patients transition from active to remission stages, blood B cell function shifts from differentiation and memory formation to increased type 1 interferon signaling and reduced IL-4 response. Blood CX3CR1+ ZNF683+ and LAG3+ exhausted T cells exhibit the highest TCR expansion among clones shared with skin CD8+T cells, suggesting their role in fueling skin CD8+T cell clonal expansion. Clinical BP severity correlates positively with blood NK cell IFN-γ production and negatively with amphiregulin (AREG) production. NK cell-derived AREG mitigates IFN-γ-induced keratinocyte apoptosis, suggesting a crucial balance between AREG and IFN-γ in BP progression. These findings highlight functional shifts in BP pathology and suggest potential therapeutic targets. Single-cell analysis reveals bullous pemphigoid alters the function of skin non-immune and immune cells as well as blood lymphocytes, links progression to NK cell IFN-γ/AREG balance, and suggests potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Adaptive immune response is at the core of the mechanism of secondary spinal cord injury (SCI). This study aims to explore the molecular mechanism by which classical dendritic cells (cDC1s) influence CD8+ T cell expansion in SCI. Methods: Peripheral blood samples from patients with SCI and spinal cord tissues from SCI mice were collected, and the population of cDC1 subset was analyzed by flow cytometry. In vivo, the fms-like tyrosine kinase 3 (Flt3) inhibitor quizartinib was administered to deplete cDC1s, while intraperitoneal injection of recombinant Flt3L and immunosuppressive drug FTY-720 was used to expand cDC1s and prevent T cell egress from lymph nodes (LNs), respectively. In vitro, the conditioned medium (CM) of isolated LN fibroblastic stromal cells (FSCs) and pre-DCs were co-cultured. Subsequently, FSC CM-induced DCs were stimulated and co-cultured with CD8+ T cells for proliferation assay. Results: The cDC1 subset was increased in the peripheral blood of SCI patients and in the injured spinal cord of SCI mice. Depletion of cDC1s decreased the proportion of infiltrating CD8+ T cells in the injured spinal cord of SCI mice and reduced the inflammatory response. The Basso Mouse Scale score of SCI mice was increased and the proportion of CD8+ T cells in blood and spinal cord tissue was decreased after FTY-720 injection. Both migratory cDC1s (CD103+) and resident cDC1s (CD8α+) were present in the LNs surrounding the injured spinal cord of SCI mice. Among them, CD103+ cells were derived from the migration of cDC1s in spinal cord tissues, and CD8α+ cDC1s were directionally differentiated from pre-DCs after co-culture with LN-FSCs. Interferon-γ promoted the secretion of Flt3L by LN-FSCs through the activation of JAK/STAT signaling pathway and enhanced the differentiation of pre-DCs into CD8α+ cells. Conclusion: Migratory cDC1s and resident cDC1s promote the expansion of CD8+ T cells in LNs around the injured spinal cord and mediate the adaptive immune response to aggravate neuroinflammation in SCI. [ABSTRACT FROM AUTHOR]

Conventional smear cytology (CSC) is a specific method used for breast tumor diagnosis in patients with nipple discharge. However, CSC tends to miss diagnose or even misdiagnose due to contaminating blood cells and other impurities. Thus, it is critical to develop more accurate and sensitive methods for clinical evaluation. Using nipple discharge collected directly from patients without aspiration, we performed liquid-based cytology (LBC) to analyze 111 collected samples for cytological evaluation for the first time. Following centrifugation to remove blood cells and protein contaminants, the sample of each nipple discharge was analyzed by light microscopy. In parallel, CSC was performed for comparison. Our results showed LBC has better diagnostic sensitivity than CSC (40.00% vs. 22.22%, = 6.636, P = 0.01). The specificity was improved (LBC 100% vs. CSC 95.2%) and area under the curve was also enhanced (AUCLBC=0.700 vs. AUCCSC=0.587). Moreover, LBC images have a cleaner background, clearer field of view, uniform cell arrangement, and improved colour contrast, with an overall image quality significantly better than CSC. Therefore, LBC provides a new and better diagnostic method for early detection of breast tumors with nipple discharge. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformations (CCMs) are hemorrhagic vascular disorders with varied clinical and radiological presentations, occurring sporadically due to MAP3K3 or PIK3CA mutations or through inherited germline mutations of CCM genes. This study aimed to clarify the clinical, genetic, and pathological features of CCMs using a multicenter cohort across three Chinese centers. We analyzed 290 surgical specimens from symptomatic CCM patients, utilizing whole-exome sequencing, droplet digital PCR, and targeted panel sequencing, alongside immunohistology to examine genotypic and phenotypic differences. Among 290 cases, 201 had somatic MAP3K3, PIK3CA, or germline CCM mutations, each associated with distinct clinical parameters: hemorrhage risk (P < 0.001), lesion size (P = 0.019), non-hemorrhagic epilepsy (P < 0.001), Zabramski classifications (P < 0.001), developmental venous anomaly presence (P < 0.001), and MRI-detected edema (P < 0.001). PIK3CA mutations showed a higher hemorrhage risk than MAP3K3 and combined MAP3K3 & PIK3CA mutations (P < 0.001). Within PIK3CA mutations, the p.H1047R variant correlated with higher bleeding risk than p.E545K (P = 0.007). For non-hemorrhagic epilepsy, patients with single MAP3K3 mutations or combined MAP3K3 & PIK3CA mutations were at greater risk than those with PIK3CA mutations alone. Histopathologically, lesions with PIK3CA mutations displayed cyst walls, pS6-positive dilated capillaries, and fresh blood cells, while MAP3K3 and double mutation lesions exhibited classic CCM pathology with SMA-positive and KLF4-positive vessels, collagen, and calcification. PIK3CA lesions had fewer KLF4-positive cells than double mutations lesions (P < 0.001), and EndMT (SMA-positive) cells compared to double mutation lesions (P < 0.05) and MAP3K3 mutations (P < 0.001), with more pS6 compared to MAP3K3 mutations (P < 0.05). This study underscores the diverse clinical, genomic, and histopathological characteristics in CCMs, suggesting potential predictive markers based on mutation subtypes and MRI features. [ABSTRACT FROM AUTHOR]

Atherosclerosis is caused by injury to the blood arteries and progressive oxidative stress. Blood cells play an important role in its development; thus, their protection is important. Naringenin (N) is documented to possess a protective action against atherosclerosis, and we hypothesize that its derivatives, naringin (Nr) and naringin dihydrochalcone (Nd), with slightly different structures, possess similar or better activity. Therefore, this research aimed to find the mechanism of protective action of N, Nr and Nd in relation to erythrocytes, peripheral blood mononuclear cells (PBMCs) and platelets in terms of their potential anti-atherosclerotic effect. Moreover, their physicochemical properties and the interaction of flavonoids with liposomes were studied. All flavonoids protected erythrocytes from AAPH- and H2O2-induced oxidation to varying degrees. None of them had a destructive effect on erythrocyte membrane, and they did not impact the metabolic activity of PBMC and platelets. Nr and Nd inhibited collagen-induced platelet aggregation better in tested concentrations than N. Studied compounds did not induce liposome aggregation, but N and Nd changed their dipole potential. Obtained results show that Nd possesses slightly better activity than N and may have a better potential health effect on blood cells, which is very important in the design of anti-atherosclerotic therapeutics. [ABSTRACT FROM AUTHOR]

Autonomous Fourier Ptychographic Microscopy (FPM) is a technology widely used in the field of pathology. It is compatible with high resolution and large field-of-view imaging and can observe more image details. Red blood cells play an indispensable role in assessing the oxygen-carrying capacity of the human body and in screening for clinical diagnosis and treatment needs. In this paper, the blood cell data set is constructed based on the FPM system experimental platform. Before training, four enhancement strategies are adopted for the blood cell image data to improve the generalization and robustness of the model. A blood cell detection algorithm based on SCD-YOLOv7 is proposed. Firstly, the C-MP (Convolutional Max Pooling) module and DELAN (Deep Efficient Learning Automotive Network) module are used in the feature extraction network to optimize the feature extraction process and improve the extraction ability of overlapping cell features by considering the characteristics of channels and spatial dimensions. Secondly, through the Sim-Head detection head, the global information of the deep feature map (mean average precision) and the local details of the shallow feature map are fully utilized to improve the performance of the algorithm for small target detection. MAP is a comprehensive indicator for evaluating the performance of object detection algorithms, which measures the accuracy and robustness of a model by calculating the average precision (AP) under different categories or thresholds. Finally, the Focal-EIoU (Focal Extended Intersection over Union) loss function is introduced, which not only improves the convergence speed of the model but also significantly improves the accuracy of blood cell detection. Through quantitative and qualitative analysis of ablation experiments and comparative experimental results, the detection accuracy of the SCD-YOLOv7 algorithm on the blood cell data set reached 92.4%, increased by 7.2%, and the calculation amount was reduced by 14.6 G. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is linked to atherosclerosis plaque formation. In pro-inflammatory conditions, human Natural Killer (NK) cell frequencies in blood or plaque decrease; however, NK cells are underexplored in CAD pathogenesis, inflammatory mechanisms, and CAD comorbidities, such as human cytomegalovirus (HCMV) infection and diabetes. Analysis of PBMC CITE-seq data from sixty-one CAD patients revealed higher blood NK cell SPON2 expression in CAD patients with higher stenosis severity. Conversely, NK cell SPON2 expression was lower in pro-inflammatory atherosclerosis plaque tissue with an enriched adaptive NK cell gene signature. In CAD patients with higher stenosis severity, peripheral blood NK cell SPON2 expression was lower in patients with high HCMV-induced adaptive NK cell frequencies and corresponded to lower PBMC TGFβ transcript expression with dependency on diabetes status. These results suggest that high NK cell SPON2 expression is linked to atherosclerosis pro-homeostatic status and may have diagnostic and prognostic implications in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Umbilical cord blood (UCB) is an alternative therapeutic resource for treating both hematological and non-hematological diseases, especially for pediatric patients. However, UCB transplantation faces challenges, including delayed engraftment, increased risk of graft failure, and slower immune recovery. To maximize its clinical potential, it is essential to understand the variability and functionality of its nucleated cells. This study focused on characterizing UCB cellular populations, viability, and functionality at three key processing stages: freshly collected, post-volume reduction, and post-thawing. Using EuroFlow-based flow cytometry, significant changes were observed in granulocyte and T-cell populations during processing. Additionally, integrating EuroFlow data with hematology counts revealed variability that could affect the yield of specific cell populations, potentially influencing therapeutic decisions. An in vitro migration assay, designed to mimic the vascular niche, was employed to study donor variability in cellular migratory patterns. Notably, thawed UCB cells displayed two distinct migration profiles, distinguishing lymphocyte-like cells from monocyte-like cells. These findings underscore the importance of reproducible cellular quality control measures, such as immunophenotypic and functional donor characterization, to ensure the integrity of UCB composition. A better understanding of these parameters could improve the consistency and reliability of UCB as a starting material for the development of advanced therapies. [ABSTRACT FROM AUTHOR]

Cuproptosis is a novel cell death dependent on mitochondrial respiration and regulated by copper. While the study of it is mainly focused on tumor therapy, in the present study, two key cuproptosis-related genes, ferredoxin (FDX1) and dihydrolipoamide S-acetyltransferase (DLAT) homologs (designated as CgFDX1 and CgDLAT), were identified from Crassostrea gigas. CgFDX1 has a Fer2 domain with a 2Fe-2S cluster forming a unique ferredoxin. CgDLAT is composed of a biotin_lipoyl domain, an E3-binding domain, and a 2-oxoacid_dh domain. CgFDX1 and CgDLAT mRNA were expressed in all the examined tissues. After elesclomol treatment, both mRNA and protein expressions of them were reduced in the hemocytes. The mortality rate of the hemocytes increased significantly, and the hemocytes were accompanied with noticeable adhesive abnormalities and heightened secretion after elesclomol treatment. Additionally, the accumulation or depletion of actin was observed in the hemocytes. The integrity of the double membrane structure of the mitochondria was compromised, and the organization of mitochondrial cristae was disrupted. The contents of copper, malondialdehyde (MDA), pyruvic acid and mitoSOX as well as the ratio of cells with low mitochondrial potential increased significantly in the hemocytes upon elesclomol treatment and the content of citric acid decreased significantly. These findings suggest the potential presence of cuproptosis in oysters and its activation mechanism is relatively conserved in evolution. [ABSTRACT FROM AUTHOR]

The use of nanoparticles is becoming increasingly apparent in a growing number of medical fields. To exploit the full potential of these particles, it is essential to examine their behavior in the blood and their possible interactions with blood cells. Dendritic core multi-shell DendroSol™ nanoparticles (DS-NPs) are able to penetrate into viable layers of human skin, but nothing is known about their interaction with blood cells. In the present study, we analyze the effect of DS-NPs on red blood cells (RBCs) using confocal laser scanning microscopy (CLSM), flow cytometry, sedimentation rate analysis, spectrophotometry, and hemolysis assays. DS-NPs labeled with Nile red (NR) were added to RBC suspensions and their accumulation in the area of the RBC membranes was demonstrated by CLSM as well as by flow cytometry. In the presence of DS-NPs, the RBCs show an increased sedimentation rate, which also confirms the binding of the NPs to the cells. Interestingly, in the presence of DS-NPs, the RBCs are stabilized against hypotonic hemolysis as well as against the hemolytic action of Triton X-100. This proven anti-hemolytic effect could be utilized to enhance the circulation time of RBCs loaded with drugs for prolonged sustained release and drug delivery with enhanced bioavailability. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Extensively hydrolyzed protein products not only provide sufficient nutrition but also effectively reduce the allergenicity of milk proteins. However, there was limited information about the sensitization of extensive hydrolysate of milk protein concentrate (EMPH). In this study, the mechanism by which EMPH reduce sensitization was studied by constructing a milk protein concentrate (MPC) sensitization evaluation animal model. The results demonstrated that the serum levels of the specific IgE, IgG, and IgG1 antibodies in the EMPH group (one-step alcalase-protamex [O-AX] and two-step alcalase-protamex [T-AX]) were significantly decreased (P < 0.01). In addition, compared with the MPC group (19.29%), the expression of CD3+CD4+ T cells in the O-AX (16.61%) and T-AX groups (15.94%) was significantly reduced (P < 0.05). This indicated an imbalance of Th1/Th2 in the MPC group, which was confirmed by the results of cytokines and transcription factors in the spleen. The mice in the control MPC group highly expressed FcεRI+CD117+ mast cells (22.25%), peripheral blood B cells (2.91%), and CD3+CD8+ T cells (8.65%). The results indicated that EMPH did not cause an imbalance of Th1/Th2 cells and Treg/Th17 cells in mice and had lower sensitization. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Follicular helper T (Tfh) cells form a distinct population of T-helper cells with different polarizations (type 1, type 2 and type 17) that regulates humoral responses and may participate in the pathophysiology of B-cell-mediated autoimmune diseases such as bullous pemphigoid (BP), a dermatosis mediated by autoantibodies specific for hemi-desmosomal proteins. Objectives To evaluate the impact on circulating Tfh cells of super potent topical corticosteroid (TCS) treatment, which is more effective and safer than high doses of oral corticosteroids, and is the recommended first-line treatment of BP. Methods Using flow cytometry, we compared the frequency, polarization and activation of Tfh cells in the blood of patients with BP with age- and sex-matched control participants without BP at baseline and longitudinally, after the initiation of TCS treatment. Results We found that, at baseline, circulating Tfh cells were more frequent in patients with BP than in participants without BP and exhibited an activated phenotype. We further showed a decrease in type 1 and an increase in type 17 Tfh cells in the blood of patients with BP, which resulted in a higher type 2 + type 17 to type 1 Tfh cell ratio. This ratio correlated positively with disease severity, as measured by the Bullous Pemphigoid Disease Area Index. Remarkably, with TCS treatment, although the frequency of Tfh cells in patients with BP returned to a level similar to that of control participants, the activated phenotype persisted. Interestingly, serum interleukin-21 levels and the Tfh cell subset ratio, similarly to disease activity and serum anti-BP180 and anti-BP230 autoantibodies, decreased with TCS treatment. Conclusions Overall, our findings suggest the involvement Tfh cell polarization in the pathophysiology of BP and open the door to modulation of Tfh cell activity for treatment purposes. [ABSTRACT FROM AUTHOR]

Background Malignant clones of primary cutaneous T-cell lymphomas (CTCL) can show a CD4+, CD8+ or T-cell receptor (TCR)-γδ+ phenotype, but their individual impact on tumour biology and skin lesion formation remains ill defined. Objectives To perform a comprehensive molecular characterization of CD4+ vs. CD8+ and TCR-γδ+ CTCL lesions. Methods We performed single-cell RNA sequencing (scRNAseq) of 18 CTCL skin biopsies to compare classic CD4+ advanced-stage mycosis fungoides (MF) with TCR-γ/δ+ MF and primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (Berti lymphoma). Results Malignant clones of TCR-γ/δ+ MF and Bertilymphoma showed similar clustering patterns distinct from CD4+ MF, along with increased expression of cytotoxic markers such as NKG7 , CTSW , GZMA and GZMM. Only advanced-stage CD4+ MF clones expressed central memory T-cell markers (SELL , CCR7 , LEF1), alongside B1/B2 blood involvement, whereas TCR-γδ+ MF and Berti lymphoma harboured a more tissue-resident phenotype (CD69 , CXCR4 , NR4A1) without detectable cells in the blood. CD4+ MF and TCR-γδ+ MF skin lesions harboured strong type 2 immune activation across myeloid cells, while Berti lymphoma was more skewed toward type 1 immune responses. Both CD4+ MF and TCR-γδ+ MF lesions showed upregulation of keratinocyte hyperactivation markers such as S100A genes and KRT16. This increase was entirely absent in Berti lymphoma, possibly reflecting an aberrant keratinocyte response to invading tumour cells, which could contribute to the formation of the typical ulceronecrotic lesions within this entity. Conclusions Our scRNAseq profiling study reveals specific molecular patterns associated with distinct CTCL subtypes. [ABSTRACT FROM AUTHOR]

Blood cells are crucial components of the human body, closely linked to the aging process. This study aims to explore the causal relationship between 91 blood cell phenotypes and aging through Mendelian randomization (MR) analysis. Exposure data from genome-wide association studies (GWAS) was extracted from the GWAS of blood cell perturbation phenotypes in 2,600 European individuals. Initial analysis utilized GWAS data related to aging from the GWAS Catalog database GCST90014288, with inverse-variance weighting as the primary method for causal analysis. Sensitivity analyses included Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. For significant associations, replication and meta-analysis were conducted using independent aging GWAS data from GCST90014300. Initial analysis revealed that environmental peroxide-impacted red blood cells and ciprofloxacin-impacted reticulocytes accelerated aging. Additionally, elevated neutrophil levels were found to accelerate aging, while LiCl-impacted neutrophils reduced aging risk. Replication and meta-analysis showed consistent results: ciprofloxacin-impacted reticulocytes and elevated neutrophil levels increased the risk of aging, while LiCl-impacted neutrophils reduced the risk. RBCs showed no significant impact on aging progression. Sensitivity analyses confirmed the robustness and reliability of these positive findings. Our study provides evidence of a causal relationship between three blood cell disturbance phenotypes and human aging. [ABSTRACT FROM AUTHOR]

Platelet-rich fibrin (PRF) and Enamel Matrix Derivatives (EMD) can support the local regenerative events in periodontal defects. There is reason to suggest that PRF and EMD exert part of their activity by targeting the blood-derived cells accumulating in the early wound healing blastema. However, the impact of PRF and EMD on blood cell response remains to be discovered. To this aim, we have exposed human peripheral blood mononucleated cells (PBMCs) to PRF lysates prepared by a swing-out rotor and EMD, followed by bulk RNA sequencing. A total of 111 and 8 genes are up- and down-regulated by PRF under the premise of an at least log2 two-fold change and a minus log10 significance level of two, respectively. Representative is a characteristic IFN response indicated by various human leukocyte antigens (HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, HLA-DRB5), gamma Fc receptors (FCGR1A, FCGR1B, FCGR3B), chemokines (CXCL9-11), and calprotectin (S100A8/9 and S100A12), complement (C1QA/B, C2) and interferon-induced guanylate-binding proteins (GBP1, GBP5). With EMD, 67 and 29 genes are up- and down-regulated, respectively. Characteristic of the upregulated genes are tensins (TNS1 and TNS3). Among the genes downregulated by EMD were epsilon Fc receptors (FCER1A; FCER2), Fc receptor-like proteins (FCRL1, FCRL3) and CX3CR1. Genes commonly upregulated by PRF and EMD were most noticeably NXPH4 and MN1, as well as FN1, MMP14, MERTK, and AXL. Our findings suggest that PRF provokes an inflammatory response, while EMD dampens IgE signaling in peripheral mononucleated blood cells. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian cancer (OC) is the sixth most common malignancy in women and the poor 5-year survival emphasises the need for novel therapies. NK cells play an important role in the control of malignant disease but the nature of tumour-infiltrating and peripheral NK cells in OC remains unclear. Methods: Using flow cytometric analysis, we studied the phenotype and function of NK cells in blood, primary tumour and metastatic tissue in 80 women with OC. The cell type contexture of metastatic OC tissue was explored utilising scRNAseq analysis, with a focus on portraying an immunogenic tumour microenvironment and determining the characteristics of a dysfunctional NK cell population. Results: The proportion of peripheral NK cells was markedly elevated with a highly activated profile and increased cytotoxicity. In contrast, NK cell numbers in primary tumour and metastasis were substantially reduced, with downregulation of activatory receptors together with elevated PD-1 expression. scRNA-Seq identified 5 NK cell subpopulations along with increased exhausted and immature NK cells within tumour tissue compared to normal tissue. These features were attenuated following chemotherapy where higher levels of activated and cytotoxic NK cells associated with improved disease-free survival. Correlation of NK cell phenotype with clinical outcomes revealed high levels of DNAM-1 expression on tissue-localised and peripheral NK cells to be associated with reduced survival. Expression of PVR, the DNAM-1 ligand, was significantly increased on tumours and DNAM-1 mediated NK cell lysis of primary tumour tissue was observed in vitro. Discussion: These findings reveal profound modulation of the tumour tissue and systemic profile of NK cells which likely contributes to the high rates of local progression and metastasis seen with OC. Immunotherapeutic approaches that overcome local immune suppression and enhance DNAM-1-targeted lysis of OC offer the potential to improve disease control. [ABSTRACT FROM AUTHOR]

Human hematopoietic stem cells (HSCs) have traditionally been viewed as self-renewing, multipotent cells with enormous potential in sustaining essential steady state blood and immune cell production throughout life. Indeed, around 86% (1011–1012) of new cells generated daily in a healthy young human adult are of hematopoietic origin. Therapeutically, human HSCs have contributed to over 1.5 million hematopoietic cell transplants (HCTs) globally, making this the most successful regenerative therapy to date. We will commence this review by briefly highlighting selected key achievements (from 1868 to the end of the 20th century) that have contributed to this accomplishment. Much of our knowledge of hematopoiesis is based on small animal models that, despite their enormous importance, do not always recapitulate human hematopoiesis. Given this, we will critically review the progress and challenges faced in identifying adult human HSCs and tracing their lineage differentiation trajectories, referring to murine studies as needed. Moving forward and given that human hematopoiesis is dynamic and can readily adjust to a variety of stressors, we will then discuss recent research advances contributing to understanding (i) which HSPCs maintain daily steady state human hematopoiesis, (ii) where these are located, and (iii) which mechanisms come into play when homeostatic hematopoiesis switches to stress-induced or emergency hematopoiesis. [ABSTRACT FROM AUTHOR]

Hemophilia A (HA) is associated with FVIII coagulation insufficiency or inactivity leading to excessive bleeding. Elevated FVIII, on the contrary, is associated with thrombophilia, thrombosis, myocardial infarctions, and stroke. Active FVIII (aFVIII) uses its C2 domain to bind to blood cells' membranes, consequently carrying out its coagulative function. We developed a reliable flow cytometry (FC) method for FVIII detection that can be utilized for assessing surface-bound FVIII on leukocytes in different coagulation/clinical states; we analyzed 49 pediatric subjects, encompassing patients with HA, other coagulopathies, venous thrombosis, and normal coagulation. Interestingly, the total leukocyte surface FVIII showed a declining trend across thrombosis, normal, and hypo-coagulation states. As expected, the leukocytes of HA patients displayed significantly lower levels of cellular-surface FVIII in comparison to patients with thrombosis. However, no significant correlation was observed between circulating levels of FVIII in plasma and the levels of FVIII bound to leukocytes, indicating that the differences in FVIII surface binding are not directly proportional to the availability of FVIII in the circulation and suggesting a specific binding mechanism governing the interaction between FVIII and leukocytes. Intriguingly, when analyzing the distinct blood subpopulations, we observed that surface FVIII levels were significantly elevated in classical monocytes of thrombosis patients compared to HA patients, healthy controls, and patients with other coagulopathies. Our study highlights the reliability of our FC platform in assessing FVIII abundance on leukocytes' membranes across coagulation states. Monocytes, particularly in cases of thrombosis, exhibit active binding of FVIII on their surface, suggesting a potential role in the pathophysiology of thrombosis that requires further investigation. [ABSTRACT FROM AUTHOR]

Early and accurate diagnosis of leukemia is essential to increase the chances of successful treatment. However, manual analysis of bone marrow cells is a time-consuming process prone to errors. With advancements in health technologies, automating the detection of leukemic cells has become indispensable to accelerating and improving diagnostic accuracy. This study proposes the Y-YOLOv10 model, which combines Principal Component Analysis (PCA) to reduce the dimensionality of images and the YOLOv10 model for real-time detection, distinguishing 12 types of white blood cells. To enhance the diversity and robustness of training, six public datasets were combined, resulting in a comprehensive and representative dataset. Additionally, seven advanced data augmentation techniques were applied, including rotation, zoom, blurring, noise addition, contrast adjustment, horizontal and vertical flips, and cropping. These techniques were used alongside the original data, generating realistic variations and improving the model’s ability to handle real-world laboratory scenarios. Furthermore, H.264 compression artifacts were introduced during training to simulate conditions of reduced image quality, making the Y-YOLOv10 robust to variations in acquisition quality. The Y-YOLOv10 achieved average performances of 96.85% accuracy, 95.21% recall, and 96.76% F1-score, outperforming methods such as YOLOv8 and ResNet50. Additionally, H.264 compression allowed for a 30–40% reduction in data size while maintaining high performance and faster processing times. This study highlights the potential of lightweight deep learning models to improve leukemia classification, reduce the workload of specialists, and ensure a robust and adaptable system for various application conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focuses on the hematological and morphological characteristics of blood cells from Baikal seals (Pusa sibirica) housed in two oceanariums over eight years. We described the morphology of various blood cells, including erythrocytes, leukocytes, and platelets. Additionally, we investigated the differences in blood parameters among sexes and individual seals. The data obtained can be used in marine mammal veterinary medicine as well as in scientific research for comparison of blood parameters in pinnipeds. Studying the blood cell morphology of marine mammals provides an opportunity to elucidate the physiological mechanisms of adaptive changes associated with the aquatic habitat that occur at the cellular level, as well as adaptations to changing environmental conditions and under various physiological and pathological processes. The Baikal seal [Pusa sibirica (family Phocidae)] is endemic to the freshwater Lake Baikal, but comprehensive hematology data are not available. We studied the morphological features of blood cells of twelve clinically normal, adult Baikal seals (n = 6 males, n = 6 females) from two oceanariums under professional care for eight years. The morphology of mature and immature erythrocytes and inclusions are described. The blood of Baikal seals is characterized by the presence of erythrocytes with a size of 8.2 ± 0.6 µm; Howell–Jolly bodies were rarely observed, the number of reticulocytes ranged from 4.1 to 93.1 × 109/L, and nucleated erythrocytes were absent. The morphological features of neutrophils, eosinophils, basophils, and platelets were described. Inter-individual and sex differences in the counts of basophils, platelets, red blood cells, and levels of hemoglobin, the mean corpuscular volume, and the mean corpuscular hemoglobin concentration were statistically observed. The results could be useful for Baikal seal veterinary care, immune response research, and comparative studies with other pinnipeds. [ABSTRACT FROM AUTHOR]

Simple Summary: Quantification of enzymic activity, metabolites, and hematological responses is useful for determining the physiological, nutritional, metabolic, and clinical status of high-risk beef calves. In the initial days after calves arrive at the feedlot, they regain lost water and body weight, stabilize or improve their immunity, and establish a social structure. The ruminal microorganisms are adapted to grain-based diets; therefore, it is expected that blood and serum parameters change during the initial days after arrival. However, to date, information on changes in health indicators, such as blood and serum parameters, during adaptation in the first 56 d of arrival is scarce. According to the results of this study, the more days at reception, the more blood and serum parameter values related to health and immunity were improved, whereas the concentration of blood parameters related to tissue injury was minimized; this behavior indicates an improvement in the physiological, nutritional, metabolic, and clinical status of high-risk beef calves during their stay. Apparently, at least 42 d is the minimum period after arrival to permit calves to reach more adequate physiological and metabolic conditions before starting the fattening phase. The objective of this study was to evaluate the changes in enzymic activity, metabolites, and hematological responses during the first 56-d of arrival of newly received calves, which were qualified at reception as high-risk but diagnosed as clinically healthy. A total of 320 blood samples were taken from 64 crossbred bull calves (average initial body weight = 148.3 ± 1.3 kg) at different times from arrival (d 0, 14, 28, 42, and 56 of received). Calves included in the study were received in June (n = 20), November (n = 24), and April (n = 20); thus, experimental treatments were arranged in a generalized complete block design (three blocks = month of arrival). The following parameters were determined: total white blood cells (WBC): lymphocytes (LYM), lymphocytes % (LYM%), monocytes (MON), monocytes % (MON%), granulocytes (GRA), granulocytes % (GRA%), platelets (PLT), and mean platelet volume (MPV); red blood cells (RBC): red blood cell distribution width test % (RDW%), hematocrit (HCT), and mean corpuscular volume (MCV); hemoglobin (HGB): mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). The enzymatic activity and metabolites analyzed were alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), globulin (GLO), ALB/GLO ratio, blood urea nitrogen (BUN), creatinine (CRE), total bilirubin (TBIL), total cholesterol (TCHO), triglycerides (TG); (4) calcium (Ca), glucose (GLU), sodium (Na+), potassium (K+), and chlorine (Cl−). It was observed that ALP, ALT, TP, ALB, GLO, ALB/GLO ratio, TCHO, TG, Ca, and GLU increased as days from reception increased (linear effect, p ≤ 0.04), whereas CRE and TBIL were reduced (linear effect, p ≤ 0.02). A quadratic response (p ≤ 0.001) was observed to GGT and AST values being maximal on days 1 and 56 after arrival (p ≤ 0.001). Na+, K+, and Cl− concentrations were not affected by prolonged days after arrival. Finally, blood cells of LYM, LYM%, PLT, RBC, HGB, HCT%, MCV, and MCH increased (linear effect, p ≤ 0.001) as the number of days after arrival increased. Whereas MON% was linearly decreased (p ≤ 0.05). It was concluded that even when all parameters were within the range of reference intervals (RIs) determined for healthy cattle, during the period of monitoring, as the days after arrival lengthened, blood serum parameters related to health and immunity increased, and metabolites related to tissue injury decreased. In contrast, plasmatic electrolytes (Na+, K+, and Cl−) were slightly reduced as the day after arrival increased. Apparently, at least 42 d is the minimum period after arrival to permit calves to reach more adequate physiological and metabolic conditions before starting the fattening phase. [ABSTRACT FROM AUTHOR]

Context • Laparoscopic gastrectomy (LG) provides advantages such as rapid postoperative recovery and little trauma, but postoperative complications are still unavoidable. Detecting serious complications after LG surgery is still a difficult problem for digestive surgeons. Objective • The study intended to evaluate the clinical significance of the C-reactive protein (CRP) ratio in predicting postoperative complications after LG. Design • The research team performed a retrospective analysis. Setting • The study took place at Department of General Surgery, Qingdao Clinical Medical College, Nanjing Medical University, Qingdao, China. Participants •Participants were 128 patients with gastric cancer, confirmed through histopathology, who underwent an LG in the general surgery department of the hospital between January 2015 and January 2020. Groups • Based on the optimal cut-off value of the CRP ratio, the research team divided participants into two groups, with 30 participants with a CRP ratio of >2.0 in the high CRP-value group and 98 with a CRP ratio of ≤2.0 in the low CRP-value group. Also, based on the incidence of complications, the team divided participants into a second set of groups, with 30 participants in a severe complications group and 98 in a nonsevere complications group. Outcome Measures • The research team: (1) determined participants' CRP ratios and compared the clinicopathological characteristics of the high and low CRP-value groups, (2) identified the postoperative complications that participants experienced and compared the clinicopathological characteristics of the severe and nonsevere complications groups, (3) analyzed the predictive value of the CRP levels for early complications after LG using a receiver operating characteristic (ROC) curve, and (4) performed a multivariate regression analysis to determine the risk factors for serious complications. Results • No significant differences existed between the two complication groups in CRP value, white-blood-cell (WBC) count, and WBC count ratio on days 1 and 3 after surgery (P > .05), but the severe complications group had a significantly higher CRP ratio than the nonsevere complications group did (P < .001). The ROC curve showed that the sensitivity, specificity, positive predictive value, and negative predictive value of CRP in predicting severe complications after LG were 67.19%, 84.38%, 73.28%, and 83.27%, respectively. Thank you for your suggestion, we have added tables for these data. Compared to the low CRP-ratio group, the high CRPvalue group had: (1) a significantly higher body mass index (BMI), with p=0.031; (2) was significantly more likely to have preoperative underlying diseases (P = .011); (3) was significantly more likely to have had a total gastrectomy (P = .006); (4) was significantly more likely to be in the T3+T4 stage (P = .034); (5) was significantly more likely to be in the tumor, node, metastasis (TNM) stage II or III (P = .010); and (6) was significantly more likely to have had postoperative severe complications (P < .001). The multivariate analysis found that the independent risk factors for severe complications after LG included: (1) preoperative underlying diseases- OR=3.624, 95% CI: (1.191, 11.206) and P = .023; (2) an advanced TNM stage [OR=9.037, 95% CI: (1.729, 47.226), P = .009; and (3) a CRP ratio >2.2 [OR=20.473, 95% CI: (7.948, 52.737), P < .001. Conclusions • The CRP ratio after LG can effectively predict postoperative complications that need treatment, and when the ratio is more than 2.2, digestive surgeons should pay attention to the possibility of serious complications. [ABSTRACT FROM AUTHOR]

Objective • Our aim was to analyze the risk factors of hypertensive disorders of pregnancy (HDP) and explore its influence on fetal risk factors, infant's blood cells and markers of inflammation. Methods • A total of 123 patients with HDP were in the HDP group, and 121 healthy pregnant women were selected as the control group. The general clinical data of the participants were recorded. Statistics of maternal and infant outcomes, delivery methods, routine blood lab results and coagulation factors of the newborn were recorded. Univariate analysis and multi-factor analysis were used to explore the risk factors for HDP. Results • The overall incidence of poor maternal outcomes in the HDP group was higher than in the control group. The incidence of premature delivery; postpartum hemorrhage; coagulopathy; placental abruption; heart failure and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome was significantly higher in the HDP group than in the control group (P < .05). The cesarean section rate in the HDP group was significantly higher than in the control group (P < .05). The overall incidence of poor outcomes in fetuses and newborns in the HDP group was higher than in the control group. The incidence of infant low birth weight, intraventricular hemorrhage (IVH), neonatal respiratory distress syndrome (NRDS), asphyxia and all-cause neonatal death were higher than in the control group (P < .05). The incidence of small gestational age (SGA), fetal distress and intrauterine death in the HDP group were higher than in the control group (P < .05). In the HDP group, neonatal white blood cells (WBC), neutrophils (NEUT) and platelets (PLT) were significantly lower than in the control group (P < .05), while hemoglobin (Hgb) and hematocrit (Hct) were higher (P < .05). Conclusions • HDP endangers the health of mother and infant; Age, body mass index (BMI) (>24 kg/m2 ), parity, history of hypertension, family history of hypertension and other factors may be involved in the occurrence and development of HDP. [ABSTRACT FROM AUTHOR]

Background: Natural killer (NK) cells are an important part of the immune system and play a central role in cell-mediated immune responses. Recent studies have shown that NK cells promote organ rejuvenation, thus achieving anti-aging effects from the inside to out. Methods: We amplified and cultured human peripheral blood NK cells and the positive rate reached 43.91%. After purification, the positive rate reached 92.65%. The cultured NK showed a good killing effect on tumor cells and the NK cells reached the standard preparation scale. The NK cells cultured by us were co-cultured with the PBMC of aging macaques and the quantitative PCR and WB results showed that the expression of aging gene and aging protein of the PBMC of aging macaques decreased significantly after co-culture, with statistical significance (P<0.01). Result: These results indicate that NK cells prepared with standard preparation have anti-aging effect, which will have extensive significance in preclinical research. [ABSTRACT FROM AUTHOR]

Stem cells are subject to continuous regulation to ensure that the correct balance between stem cell differentiation and self-renewal is maintained. The dynamic and ongoing nature of stem cell regulation, as well as the complex signaling microenvironment in which stem cells are typically found, means that studying them in their endogenous environment in real time has multiple advantages over static fixed-sample approaches. We recently described a method for long-term, ex-vivo , live imaging of the blood progenitors in the Drosophila larval hematopoietic organ, the Lymph Gland (LG). This methodology has allowed us to analyze multiple aspects of fly hematopoiesis, in real time, in a manner that could not be carried out previously. Here, we describe novel insights derived from our quantitative live imaging approach. These insights include: the identification of extensive filopodia in the progenitors and description of their morphology and dynamics; visualization and quantitative analysis of JAK/STAT signaling in progenitors by the simultaneous tracking of thousands of vesicles containing internalized Domeless receptors; quantitative analysis of the location, morphology, and dynamics of mitochondria in blood progenitors; long-term tracking of patterns of cell division and migration of mature blood cell in the LG; long-term tracking of multiple cell behaviors in the distal committed progenitors; analysis of Ca2+ signaling of blood progenitors in the secondary lobes of the LG. Together, these observations illustrate the power of imaging fly hematopoiesis in real time and identify many previously undescribed processes and behaviors in the LG that are likely to play important roles in the regulation of progenitor differentiation and self-renewal. [Display omitted] • Using live imaging, we identify novel features of fly hematopoiesis. • Live imaging is used to study the secondary lobes of the fly lymph gland. • Live imaging reveals subcellular events in live intact lymph glands. • Live imaging shows cell-type specific behavior of different blood cell populations. [ABSTRACT FROM AUTHOR]

Blood cells are the most integral part of the body, which are made up of erythrocytes, platelets and white blood cells. The examination of subcellular structures and proteins within blood cells at the nanoscale can provide valuable insights into the health status of an individual, accurate diagnosis, and efficient treatment strategies for diseases. Super-resolution microscopy (SRM) has recently emerged as a cutting-edge tool for the study of blood cells, providing numerous advantages over traditional methods for examining subcellular structures and proteins. In this paper, we focus on outlining the fundamental principles of various SRM techniques and their applications in both normal and diseased states of blood cells. Furthermore, future prospects of SRM techniques in the analysis of blood cells are also discussed. [ABSTRACT FROM AUTHOR]

Miana leaves are known to possess bacterial inhibitory properties comparable to those of antibiotics and can be used to treat vibriosis in shrimp. However, the bioactive compounds in miana leaves and their potential as immunostimulants in feed, particularly their effects on total hemocytes and the phagocytic activity of the tiger prawns, have not yet been fully explored. The experiment used miana leaf extract in feed at concentrations of 0, 10, 20, and 40g/ kg. Bioactive compounds were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS), and statistical analysis of total hemocytes, phagocytic activity, and the tiger prawn survival was performed using the SPSS program. The analysis identified 100 chemical compounds in the ethanol fraction of miana leaf extract. Among these, the three compounds with the highest peak areas were: carbamic acid, methyl ester (CAS methyl carbamate) at 21.13%; 4(5H)-Thiazolone, 2-amino- (CAS pseudothiohydantoin) at 16.16%; and Cyclotrisiloxane, hexamethyl- (CAS 1,1,3,3,5,5-hexamethyl-cyclohexasiloxane) at 20.50%. The experimental results showed that the miana leaf extract significantly affected phagocytic activity and survival but did not influence the total hemocytes of the tiger prawns. The highest values for phagocytic activity, survival, and total hemocytes were observed in the 40g/ kg treatment, with values of 76%, 6.25 x 10^5 CFU/mL, and 86.67%, respectively. In conclusion, miana leaf extract contains active antibacterial, antiviral, and anti-inflammatory compounds, and it enhances total hemocytes, phagocytic activity, and the survival of the tiger prawns. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to describe clinical characteristics—including blood counts and pharmacologic cytoreductive treatment patterns—and outcomes after 6 months of hydroxyurea (HU) treatment among patients with polycythemia vera (PV) in US community practices. Methods: This retrospective observational study included adult patients with a PV diagnosis (1JAN2008–31JAN2020) and ≥2 postdiagnosis visits in the iKnowMed electronic health record database (US Oncology Network and non-Network clinics). Suboptimal HU response required ≥1 criterion after ≥3 months of treatment: white blood cell count (WBC) >10 × 109/L, platelet count >400 × 109/L, and/or hematocrit >45%. Patient characteristics were summarized from structured data using descriptive statistics; overall survival was assessed by Kaplan–Meier method. Results: Among 5871 patients, mean age at diagnosis was 66.1 years (69.8% ≥60 years); 67.2, 59.4, 38.2, and 33.9% of patients had elevated hematocrit, hemoglobin, WBC, and platelets, respectively; 6.1% had a previous thrombotic event. Of 4185 (71.3%) high-risk and 1675 low-risk patients, 55.0 and 32.0% received pharmacologic cytoreductive treatment, most commonly HU (89.8 and 88.9%). After 6 months of pharmacologic cytoreductive treatment, 56.9% had a suboptimal response. Five-year survival probability was 81.5 and 84.3% among patients with suboptimal and optimal responses to HU, respectively, which was not statistically different but suggests potential for survival benefits with longer follow-up. Conclusion: Nearly half of high-risk patients with PV did not receive pharmacologic cytoreductive treatment. Of those who did, over half had suboptimal response, suggesting these patients may need dose adjustments, improved adverse effect management, or alternative treatments. Longer follow-up may be needed to assess an association between HU response and survival. PLAIN LANGUAGE SUMMARY: Polycythemia vera (PV) is a rare blood cancer that causes an overproduction of blood cells. The aim of treatment is to reduce the number of blood cells and prevent blood clots. Hydroxyurea is a drug often used for treatment, but it does not work for all patients and the side effects can lead some patients to discontinue treatment. For this analysis, the authors looked at health records of almost 6000 patients with PV who were treated in community practices in the United States between 2008 and 2020. The study found that after 6 months of receiving hydroxyurea, blood cell numbers remained elevated in over half of the patients, indicating the treatment was inadequate. This finding suggests that patients with PV may need medication dosage adjustments, improved management of their treatment side effects, or alternative treatments sooner than is currently common. [ABSTRACT FROM AUTHOR]

Mammalian blood cells originate from specialized 'hemogenic' endothelial (HE) cells in major arteries. During the endothelial-to-hematopoietic transition (EHT), nascent hematopoietic stem cells (HSCs) bud from the arterial endothelial wall and enter circulation, destined to colonize the fetal liver before ultimately migrating to the bone marrow. Mechanisms and processes that facilitate EHT and the release of nascent HSCs are incompletely understood, but may involve signaling from neighboring vascular endothelial cells, stromal support cells, circulating pre-formed hematopoietic cells, and/or systemic factors secreted by distal organs. We used single cell RNA sequencing analysis from human embryonic cells to identify relevant signaling pathways that support nascent HSC release. In addition to intercellular and secreted signaling modalities that have been previously functionally validated to support EHT and/or developmental hematopoiesis in model systems, we identify several novel modalities with plausible mechanisms to support EHT and HSC release. Our findings paint a portrait of the complex inter-regulated signals from the local niche, circulating hematopoietic/inflammatory cells, and distal fetal liver that support hematopoiesis. [ABSTRACT FROM AUTHOR]

COVID-19 and post-COVID (long COVID) are associated with thromboembolic complications; however, it is still not clear whether platelets play a leading role in this phenomenon. The platelet hyperreactivity could result from the direct interaction between platelets and viral elements or the response to inflammatory and prothrombotic factors released from blood and vessel cells following infection. The existing literature does not provide clear-cut answers, as the results determining platelet status vary according to methodology. Elevated levels of soluble markers of platelet activation (P selectin, PF4), increased platelet aggregates, and platelet-derived microparticles suggest the activation of platelets circulating in the bloodstream of COVID-19 patients. Similarly, platelets isolated from COVID-19 patients demonstrate increased reactivity in response to collagen, thrombin, and ADP. By contrast, an analysis of whole blood from COVID-19 patients indicates the reduced activation of the fibrinogen receptor. Similarly, some in vitro studies report potential targets for SARS-CoV-2 in platelets, whereas others do not indicate any direct effect of the virus on platelets. The aim of this work is to review and evaluate the reliability of the methodology for testing platelet function after contact with SARS-CoV-2. Despite the diversity of methods yielding varying results and the influence of plasma components or blood cells, it can be concluded that platelets play an important role in the development of thrombotic complications after exposure to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this research was to examine the relationship between the hemoglobin-to-red blood cell distribution width ratio (HRR) and cardiovascular disease (CVD)-related mortality in people who have diabetes. METHODS: Data derived from the National Health and Nutrition Examination Survey (NHANES), between the years 1999 to 2018, were meticulously analyzed. Mortality data, encompassing events until December 31, 2019, were systematically collected. A comprehensive group comprising of 8,732 participants were subjected to scrutiny, and subsequently, classified into four distinct groups predicated upon quartiles of baseline HRR levels: Q1 (n = 2,183), Q2 (n = 2,181), Q3 (n = 2,185), and Q4 (n = 2,183). The correlation between HRR and CVD-related mortality was examined through the use of survival curves and Cox proportional hazard regression models, the latter incorporating weights as advised by NHANES. RESULTS: Among the 8,732 participants in the study cohort, CVD-related mortality was identified in 710 cases. The Kaplan-Meier analysis demonstrated a significant association, indicating that a decreased HRR was correlated with a reduction in survival in cases with CVD. Both univariate and multivariable Cox proportional hazard regression analyses consistently indicated that patients exhibiting a lower HRR exhibited a markedly elevated risk of CVD-related mortality in comparison to those with higher HRR. Notably, the correlation between HRR and decreasing CVD-related mortality was discerned to be non-linear. CONCLUSION: In patients with diabetes, a decreased HRR was associated with an increased risk of CVD-related mortality. [ABSTRACT FROM AUTHOR]

Transportation of medical samples between laboratories or hospital sites is typically performed by motorized ground transport. Due to the increased traffic congestions in urban environments, drone transportation has become an attractive alternative for fast shipping of samples. In accordance with the CLSI guidelines and the ISO 15189 standard, the impact of this transportation type on sample integrity and performance of laboratory tests must be thoroughly validated. Blood samples from 36 healthy volunteers and bacterial spiked urine samples were subjected to a 20–40 min drone flight before they were analyzed and compared with their counterparts that stayed on the ground. Effects on stability of 30 routine biochemical and hematological parameters, immunohematology tests and flow cytometry and molecular tests were evaluated. No clinically relevant effects on blood group typing, flow cytometry lymphocyte subset testing and on the stability of the multicopy opacity-associated proteins (Opa) genes in bacterial DNA nor on the number of Abelson murine leukemia viral oncogene homolog 1 (abl) housekeeping genes in human peripheral blood cells were seen. For three of the 30 biochemistry and hematology parameters a statistically significant difference was found: gamma-glutamyl transferase (gamma-GT), mean corpuscular hemoglobin (MCH) and thrombocyte count. A clinically relevant effect however was only seen for potassium and lactate dehydrogenase (LDH). Multi-rotor drone transportation can be used for medical sample transportation with no effect on the majority of the tested parameters, including flow cytometry and molecular analyses, with the exception of a limited clinical impact on potassium and LDH. [ABSTRACT FROM AUTHOR]

Objective: Hammada Scoparia (Pomel) as an endemic plant from the Amaranthaceae family, holds a significant position in the Saharan region of southern Algeria's traditional medicine. The aerial parts of Hammada scoparia was used to cure inflammation and wound healing management. The aim of this study was to determine the phytochemical constituents of the aqueous extract obtained from the aerial parts of Hammada scoparia (AEHs)and assess its effectiveness in wound healing. Methods: Formulation of Wound healing cream were prepared from Hammada scoparia aerial parts aqueous extract then the wounds were applied on the skin of the dorsal region of each Wistar albino for 13 days. Hematological, inflammation and histological parameters were evaluated. Different bioactive compounds were identified within AEHs using HPLC analysis. Results: High-Performance Liquid Chromatography (HPLC) analysis identified 21 phenolic compounds, with rutin being the most abundant, followed by naringenin, gallic Acid, valinin, and hydroxy-comarin. The formulated AEHs cream exhibited superior wound healing properties, with a 96.54% healing rate by day 13, outperforming the DOUCE PLUS cream and control groups. Physical analyses indicated the cream's white color, neutral odor, humid texture, pH of 6.8, and excellent stability. Hematological parameters revealed the AEHs cream influenced red blood cells (RBCs), white blood cells (WBCs), and platelet (PLT) levels positively. Inflammation markers, including C-reactive protein (CRP) and sedimentation rate (ESR), were also favorably modulated by the treatment. Histological studies indicated that H. scoparia cream promoted re-epithelialization, fibroblast activity, collagen deposition, and angiogenesis, thus facilitating an effective healing process. Conclusion: The study concludes that Hammada scoparia possess significant wound healing properties, corroborating their traditional medicinal use. [ABSTRACT FROM AUTHOR]

The detection of extremely rare circulating tumor cells (CTCs) in peripheral blood and simultaneously identifying their viabilities are significant for cancer diagnosis and prognosis as well as monitoring the efficacy of personalized treatment. A lens-free imaging system features high-resolution images taken over a large field of view (FOV), which has great potential for CTC detection and viability determination. But current still lens-free systems restrict the application for CTC detection in real samples due to the inherent limitations of lens-free technology: (1) the location of cells in the FOV will affect the imaging; (2) the extremely rare CTCs probably did not exist in one observation. In this paper, we realized the detection of CTCs in whole blood and the simultaneous determination of their viabilities by lens-free imaging cytometry. Our in-flow system plus a large FOV range of lens-free imaging highly increased the detection rate of rare CTCs with a high throughput of 150,000 cells per minute and improved the recognition efficiency for blood cells, living/dead CTCs by using a cell tracing–assisted deep learning algorithm. With this method, the average precision of blood cells, living/dead lung cancer cells A549, and living/dead colon cancer cells SW620 reached 98.80%, 97.88%, 97.93%, 97.72%, and 98.60%, respectively. Our system got a highly consistent result with the manual counting method using fluorescent staining (Pearson's r 99.93% for SW620) and can easily detect as few as 10 dead or living CTCs from 100,000 white blood cells (WBCs). Finally, real clinical samples were detected in our system. Both dead and living CTCs were found in all six advanced-stage cancer patients, and the number of living CTCs per million WBCs ranged from 13 to 39, more than that of the dead CTCs (5 to 25), while none of the CTCs were detected in six healthy control subjects. Moreover, we also found that CTCs died very quickly after leaving the human body, indicating that CTCs should be studied as soon as possible after sampling. Although this method is implemented for CTCs, it can also be used for the detection of other rare cells. [ABSTRACT FROM AUTHOR]

Parasitoid elimination in Drosophila melanogaster involves special hemocytes, called lamellocytes, which encapsulate the eggs or larvae of the parasitoid wasps. The capsules are melanized, and metabolites of the melanization reaction may play a potential role in parasitoid killing. We have observed a variation in the melanization capacity of different, commonly used D. melanogaster strains, such as Canton-S, Oregon-R, and BL5905, BL6326. In this work, we aimed to clarify a possible connection between the effectiveness of capsule melanization and the success of parasitoid elimination following infection with Leptopilina parasitoid wasps. Circulating hemocytes and lamellocyte attachment were visualized by confocal and epifluorescence microscopy using indirect immunofluorescence. Expression profiles of the PPO2 and PPO3 prophenoloxidase genes, which encode key enzymes in the melanization reaction, were detected by qRT-PCR. Parasitization assays were used to analyze fly and wasp eclosion success. Active encapsulation and melanization reactions against Leptopilina boulardi were observed in the BL5905 and the BL6326 strains, though restricted to the dead supernumerary parasitoids, while fly and wasp eclosion rates were essentially the same in the four examined D. melanogaster strains. We conclude that encapsulation and melanization carried out by D. melanogaster following L. boulardi infection have no impact on survival. [ABSTRACT FROM AUTHOR]

Perinatal depression (PND) is a global health concern, affecting millions of childbearing women. Emerging data suggest that inflammation may play a role in the development of PND. Peripheral blood inflammatory biomarkers before pregnancy are widely tested in clinical practice at minimum cost, yet their potential role in PND risk remains unknown. We conducted a prospective cohort study of 4483 birthing women during 2009–2021 within the LifeGene study with linkage to Swedish registers. Peripheral blood inflammatory biomarkers were profiled at baseline. Cases of PND were identified using validated tools or clinical diagnosis from subsequent pregnancies and postpartum periods. Logistic regression models were employed to assess the associations of each inflammatory biomarker (z scored) with PND. We identified 495 (11.0 %) PND cases with an average age of 29.2 years. Pre-pregnancy platelet-to-lymphocyte ratio (PLR) was positively associated [OR, 95 % CI:1.14(1.01,1.27)], while lymphocyte count was inversely associated [OR, 95 % CI: 0.89(0.80,0.98)] with PND. A dose-response relationship was indicated for both PLR and lymphocytes when analyzed in categories based on tertile distribution. These associations appeared more pronounced for postpartum depression than antepartum depression and were independent of psychiatric comorbidities. With implications for future mechanistic research, these findings suggest that blood levels of lymphocytes and PLR before pregnancy are associated with subsequent risk of PND in a dose-response manner. • First study to assess the relationship between inflammatory biomarkers before pregnancy and risk of perinatal depression. • Lower level of lymphocytes associated with elevated risk of perinatal depression • Higher level of platelet-to-lymphocyte ratio associated with elevated risk of perinatal depression • Such associations appeared more pronounced for postpartum depression than antepartum depression. • Inflammation and immune dysregulation may play a role in the mechanism of perinatal depression. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cells (HSCs) possess the capacity for self-renewal and the sustained production of all mature blood cell lineages. It has been well established that a metabolic rewiring controls the switch of HSCs from a self-renewal state to a more differentiated state, but it is only recently that we have appreciated the importance of metabolic pathways in regulating the commitment of progenitors to distinct hematopoietic lineages. In the context of erythroid differentiation, an extensive network of metabolites, including amino acids, sugars, nucleotides, fatty acids, vitamins, and iron, is required for red blood cell (RBC) maturation. In this review, we highlight the multifaceted roles via which metabolites regulate physiological erythropoiesis as well as the effects of metabolic perturbations on erythroid lineage commitment and differentiation. Of note, the erythroid differentiation process is associated with an exceptional breadth of solute carrier (SLC) metabolite transporter upregulation. Finally, we discuss how recent research, revealing the critical impact of metabolic reprogramming in diseases of disordered and ineffective erythropoiesis, has created opportunities for the development of novel metabolic-centered therapeutic strategies. [ABSTRACT FROM AUTHOR]