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Measurement of telomere length is crucial for the study of telomere maintenance and its role in molecular pathophysiology of diseases and in aging. Several methods are used to measure telomere length, the choice of which usually depends on the type and size of sample to be assayed, as well as cost and throughput considerations. The goal of this study was to investigate the factors that may influence the reliability of qPCR-based relative telomere length measurements in whole blood. Day to day intra-individual variability, types of blood anticoagulant, sample storage conditions, processing and site of blood draw were investigated. Two qPCR-based methods to measure telomere length (monoplex vs. multiplex) were also investigated and showed a strong correlation between them. Freezing and thawing of the blood and storage of the blood at 4°C for up to 4 days did not affect telomere length values. Telomere lengths in dried blood spots were significantly higher than both whole blood and peripheral mononuclear blood cells, and were highly correlated with both. We found that telomere length measurements were significantly higher in dried blood spots collected directly from fingertip prick compared to dried blood spots prepared with anticoagulated whole blood collected from the finger, and non-blotted whole blood taken from both finger and arm venipuncture. This suggests that DNA from cells blotted on paper is not equivalent to that collected from venipuncture whole blood, and caution should be taken when comparing between blood sample types. [ABSTRACT FROM AUTHOR]

Background/Aim. Measles is a contagious disease with a good prognosis; however, severe complications may sometimes develop. C-reactive protein (CRP) and blood cells count-derived inflammatory indices -- granulocytelymphocyte ratio (GLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), mean platelet volume (MPV)/platelet count ratio (MPR), red blood cell distribution width (RDW), and MPV are the indicators related to the clinical outcome in various inflammatory diseases. The aim of the study was to analyze the values of CRP, blood cell count, GLR, PLR, MLR, MPR, RDW, and MPV in measles-affected children compared to healthy controls and between measles-affected children with complicated and severely complicated measles form. A particular aim of the paper was to assess the suitability of inflammatory-derived markers for predicting the severity of the disease. Methods. The study included 55 measlesaffected children who developed complications (examination group), while the control group included 30 healthy children. The first peripheral blood count, obtained on the first hospitalization day (before treatment), was used for further analyses. Results. The white blood cells, lymphocytes, monocytes, and platelets count were significantly lower, while GLR, PLR, MPR, and CRP were significantly higher in measles-affected children (p < 0.05). In severely complicated measles form, significantly higher values of granulocytes, CRP, GLR, and PLR were documented, including lower lymphocytes (p < 0.05). A linear regression analysis showed that CRP was the only indicator with predictive significance for the severity of the course of measles. Conclusion. The blood cell count-derived inflammatory indices should not be crucial in assessing the severity of measles in children. CRP was the most valuable predictive factor for the development of the severe course of measles in measles-affected children. [ABSTRACT FROM AUTHOR]

Microfluidic chips have been widely used for in vitro diagnostics using pretreatment of biological samples; however, biologists and clinical researchers have difficulties using them in resource-limited settings. Sample injection systems for microfluidic chips are bulky, expensive, electricity-powered, and complex. A coiled spring-powered device, which can be used to isolate variously sized cells with high efficiency continuously and passively, was developed for portable, low-cost, electricity-free, and simple sample injection. The flow driving power was provided by releasing the compression spring in the mechanical syringe driver with a one-click action. In general, a syringe pump generates a stable passive flow rate. However, the syringe pumps are large in size and expensive because they have many functions such as infusion/withdrawal flow injection and the use of syringes of various sizes, allowing them to be applied in a variety of applications performed in the laboratory. In addition, it is not suitable for portable devices because of the considerable amount of electric power required. To overcome these drawbacks, we developed a device prototype that sorts different-sized particles and separates rare tumor cells or blood cells from blood with high efficiency. The performance of the coiled spring-powered device was evaluated and found to be comparable with that of syringe pump-powered devices. In situations where trained personnel cannot handle microfluidic chips for isolating circulating biomarkers (CTCs, WBCs, or plasma) from blood samples, the coiled spring-powered device can provide diagnostic tools, especially in resource-limited countries. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The detection of circulating tumor cells (CTCs) from peripheral blood is considered as great significance for the diagnosis and prognosis of cancer patients. Raman spectroscopy is a highly sensitive optical detection technique that can provide fingerprint molecular identification information. In this paper, the silver film substrate surface-enhanced Raman scattering (SERS) was used to research several tumor cells, immortalized cells, clinical cancer cells isolated from cancer patient's tissue and blood cells. The results display that there is great difference for the nucleic acid characteristic peaks of those cells. The red blood cells have almost none nucleic acid characteristic peak and the SERS signals of white blood cells are only a slight increase. Except for immortalized cells and few tumor cells, the nucleic acid characteristic peaks of some tumor cells have huge enhancement. Nucleic acid characteristic peaks of clinical cancer cells also have greater enhancement. The discriminant model established by the intensity ratio of the nucleic acid characteristic peak 730 cm -1 to the substrate background peak 900 cm -1 shows that some tumor cells and clinical sample cells can be separated from white blood cells, but tumor cells with relatively low-DNA index cannot be differentiated from white blood cells. This study demonstrates that thin-film SERS technology can distinguish between blood cells and some types of tumor cells. This study opens up a new possible method for the detection of CTCs with label-free SERS spectra.

Hematopoietic stem cells (HSCs) provide all types of blood cells during the entire life of the organism. HSCs are mainly quiescent and can eventually enter the cell cycle to differentiate. HSCs are maintained and tightly regulated in a particular environment. The stem cell niche regulates dormancy and awakening. Deregulations of this interplay can lead to hematopoietic failure and diseases. In this paper, we present a Boolean network model that recapitulates HSC regulation in virtue of external signals coming from the niche. This Boolean network integrates and summarizes the current knowledge of HSC regulation and is based on extensive literature research. Furthermore, dynamic simulations suggest a novel systemic regulation of TP53 in homeostasis. Thereby, our model indicates that TP53 activity is balanced depending on external stimulations, engaging a regulatory mechanism involving ROS regulators and RAS activated transcription factors. Finally, we investigated different mouse models and compared them to in silico knockout simulations. Here, the model could recapitulate in vivo observed behaviors and thus sustains our results. [ABSTRACT FROM AUTHOR]

Cancer is one of the most critical disease. In particular, Leukemia is the most common type of cancer which produces an excessive quantity of leucocytes, replacing normal blood cells. Early detection of leucocytes cells can save human life. Recently, researchers have contributed to the development of computer assisted pathology techniques to automatically detect cancer at early stage. Commonly, assisted pathology systems are based on artificial vision techniques to identify cancer cells in the human body. Blood image segmentation techniques for Leukemia have been proposed based on automatic thresholding schemes involving traditional clustering methods. However, traditional clustering methods are sensitive to initial cluster positions, where the incorrect centering values results into false positive cancer diagnosis. On the other hand, Nature-Inspired Optimization Algorithms (NIOA) are stochastic search methods for finding the optimal solution for complex multimodal functions where traditional optimization approaches are not suitable to operate. Since blood image segmentation is considered as a complex computational task, NIOA methods yield an interesting alternative to proper blood cell segmentation. In this paper, the Stochastic Fractal Search (SFS) algorithm is implemented in order to provide non-false positive segmented outcomes for Leukemia identification. In the experimental study, the proposed approach is compared against traditional clustering methods as well as some NIOAs techniques. The numerical results indicate that SFS, provide superior results in terms of accuracy, time complexity, and quality parameters. [ABSTRACT FROM AUTHOR]

The main reason for the weakening of the body of rabbits is a deficiency of nutrients and biologically ac􀆟ve substances in their diet. The search for non-toxic and highly effec􀆟ve preven􀆟ve drugs of complex ac􀆟on that have a posi􀆟ve effect on the metabolism of minerals in rabbits is of keen interest. Here we present the results of the study of morphological and biochemical parameters of the blood as well as the content of chemical elements in blood plasma in New Zealand White rabbits on the farm in Kyiv region. The paper presents the materials for determining the biochemical status of the body in fa􀆩ening rabbits for the preven􀆟on of microelementoses using a new experimental environmentally friendly tool. The content of total protein, albumin, glucose, total calcium, inorganic phosphorus, total bilirubin, urea, crea􀆟nine, TBA-ac􀆟ve products, Fe, Mn, Cu, Zn, Co and the ac􀆟vity of ALT, AST, LF, and HGT in the blood of New Zealand White rabbits in the first and 50th days of the experiment (before and a􀅌er the use of biologically ac􀆟ve addi􀆟ve "Huminorm plus") are presented here for the first 􀆟me. The use of this addi􀆟ve had a posi􀆟ve effect on haematopoiesis, protein and mineral metabolism, and func􀆟onal status of the liver, which indicates its high efficiency for the preven􀆟on of micronutrient deficiency. "Huminorm Plus" s􀆟mulates poten􀆟al body growth in rabbits up to the age of 90 days. [ABSTRACT FROM AUTHOR]

Objective: This paper aims to investigate the dynamic changes of the T-cell receptor (TCR) β complementarity-determining region 3 (CDR3) repertoire during cyclophosphamide or Cytoxan (CTX) damage or inhibition of bone marrow hematopoiesis caused by a reduction of peripheral blood white blood cells (WBCs) in BALB/c mice. Methods: We analyze TCR CDR3 repertoire of BALB/c mice including (1) NS control group (2) CTX damage group (3) CTX damage + GM-CSF recovery group (4) CTX damage + auto-recovery group. Results: The number of WBCs in the CTX group is significantly lower than that in the NS group and after GM-CSF injection, the GM-CSF group is higher than that in the NS group. The diversity of the CTX damage group is the highest and there is a significant difference in high-frequency clonal proliferation between the CTX damage group and CTX damage + GM-CSF recovery group compared with the NS control group. In addition, the numbers of unique productive CDR3 overlapping numbers in the four experimental groups are similar. Conclusions: These data reveal that CTX significantly reduced the number of WBCs and ratio of high-frequency TCR CDR3 sequences, and indirectly increased the diversity of the TCR CDR3 repertoire. GM-CSF quickly restored the number of WBCs, and partially restored changes in the TCR CDR3 repertoire induced by CTX. Results from monitoring the dynamic changes of the TCR CDR3 repertoire can be used to assess the effects of CTX and GM-CSF on the function of peripheral blood T cells and to explore the possible underlying mechanisms. [ABSTRACT FROM AUTHOR]

This paper focuses on the production of a high-affinity monoclonal antibody (mAb) that can efficiently detect and block purinergic ligand-gated ion channel 7 receptor (P2X7R). To achieve this goal, the extracellular domain of human P2X7R, P2X7R-ECD, was used as an immunogen for BALB/c mice, inducing them to produce spleen lymphocytes that were subsequently fused with myeloma cells. Screening of the resultant hybridoma clones resulted in the selection of one stable positive clone that produced a qualified mAb, named 4B3A4. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated that the purity of the purified 4B3A4 mAb was above 85%, with prominent bands corresponding to molecular weights of 55 kDa (heavy chain) and 25 kDa (light chain), and the BCA assay showed that the concentration of the purified 4B3A4 mAb was 0.3 mg/mL. Western blot analysis revealed that the 4B3A4 mAb could specifically recognize and bind both P2X7R-ECD and the full-length P2X7R protein. Laser scanning confocal microscopy (LSCM) revealed that the 4B3A4 mAb specifically bound to P2X7R on the membrane of human peripheral blood mononuclear cells (PBMCs). P2X7R expression was significantly different between healthy individuals and people with certain cancers as determined by flow cytometry (FCM). In addition, the 4B3A4 mAb significantly reduced ATP-stimulated Ca2+ entry and YO-PRO-1 uptake, which indicated that the 4B3A4 mAb effectively blocked P2X7R activity. These data indicate that the 4B3A4 mAb can be further used as not only an antibody to detect cell surface P2X7R but also as a therapeutic antibody to target P2X7R-related signaling pathways. [ABSTRACT FROM AUTHOR]

Negative magnetophoresis is a novel and attractive method for continuous microparticle sorting inside a magnetic medium. In this method, diamagnetic particles are sorted based on their sizes using magnetic buoyancy force and without any labeling process. Although this method provides some attractive features, such as low-cost fabrication and ease of operation, there are some obstacles that adversely affect its performance, especially for biological applications. Most types of magnetic media, such as ferrofluids, are not biocompatible, and the time-consuming process of sample preparation can be threatening to the viability of the cells within the sample. Furthermore, in this method, both the target and non-target particles are affected by the magnetic field, and therefore, a high separation efficiency cannot be achieved. In this paper, to isolate the abnormal cells from the other blood cells, a microfluidic device was designed using numerical simulation. This model utilizes negative magnetophoresis on a rotating disk, and to reduce the exposure time of the cells inside the magnetic medium, a micromixer is embedded in the upstream of the separator which rapidly prepares the sample. In this part, diluted blood sample and ferrofluid are mixed together utilizing magnetic force. Afterward, the separator sorts the cells into multiple outlets using magnetic buoyancy force as well as centrifugal force. The numerical procedure employed in this study shows that the proposed model is able to recover ∼100% of the abnormal cells from a particular outlet for binary and ternary separation of the cells with high throughputs. Although this percentage of separation may be lower in reality, the optimization of the proposed design by the numerical method can avoid trial-and-error during costly and time-consuming experiments. Also, the device proposed in this study reduces the exposure time of the cells inside the ferrofluid to just a few seconds, which can improve cell viability. [ABSTRACT FROM AUTHOR]

In microscopy, laboratory tests make use of cell counters or flow cytometers to perform tests on blood cells, like the complete blood count, rapidly. However, a manual blood smear examination is still needed to verify the counter results and to monitor patients under therapy. Moreover, the manual inspection permits the description of the cells' appearance, as well as any abnormalities. Unfortunately, manual analysis is long and tedious, and its result can be subjective and error-prone. Nevertheless, using image processing techniques, it is possible to automate the entire workflow, both reducing the operators' workload and improving the diagnosis results. In this paper, we propose a novel method for recognizing white blood cells from microscopic blood images and classify them as healthy or affected by leukemia. The presented system is tested on public datasets for leukemia detection, the SMC-IDB, the IUMS-IDB, and the ALL-IDB. The results are promising, achieving 100% accuracy for the first two datasets and 99.7% for the ALL-IDB in white cells detection and 94.1% in leukemia classification, outperforming the state-of-the-art. [ABSTRACT FROM AUTHOR]

Image-processing methods are applied in many environments to solve various practical problems. Recently, considerable research has been conducted on analysing retinal images, which show the blood vessels in the human eye, to detect diseases in patients. Various diseases related to the eyes can be located by detecting changes in the retinal blood cells. This paper proposes two analysis methods, namely the fuzzy c-means and neuro-fuzzy methods, which analyse optical coherence tomography images of retinal blood cells. The system was implemented in a MATLAB experimental setup, while the efficiency was evaluated with respect to time and accuracy. The performance analysis of the fuzzy c-means and neuro-fuzzy systems indicates that the neuro-fuzzy system has a higher accuracy (93.16%) and a lower processing time (2 s) than the k-means clustering, expectation maximisation, fuzzy clustering and neural network methods. [ABSTRACT FROM AUTHOR]

The way cell differentiate from bone marrow to peripheral blood level plays a crucial role in understanding and treating rare diseases and more common tumours. The main goal of this paper is to introduce a flexible statistical framework able to describe the cell differentiation process and to reconstruct a dependence structure along different levels of differentiation. We use next generation sequencing data on haematological diseases (severe combined immunodeficiency) within a gene therapy framework. The proposed statistical approach is based on Bayesian networks (BNs) and aims at finding a probabilistic model to describe the most important features of cell differentiation, without requiring specific detailed assumptions concerning the interactions among genes or the confounding effects of experimental conditions. Bayesian networks enable analyses on gene therapy-treated patients in a data-driven fashion and allow for exploring all relationships among different blood cell types integrating biological information, subject-matter knowledge, and probabilistic principles. [ABSTRACT FROM AUTHOR]

Summary: Background: Interleukin (IL)‐26 is a signature T helper 17 cytokine described as a proinflammatory and antimicrobial mediator. So far, IL‐26 has been reported in several immune‐mediated inflammatory diseases, but its involvement in inflammatory skin disorders is poorly known. Objectives: To investigate the role of IL‐26 in hidradenitis suppurativa (HS), through its involvement in antimicrobial activity. Methods: IL‐26 was assessed in patients with HS through gene expression and protein analysis at skin and circulating levels. Ex vivo HS organ skin cultures, together with IL‐26 antibody treatment, were performed to determine the IL‐26 activity. Peripheral blood mononuclear cells (PBMCs) from patients with HS and healthy controls were either silenced or not with IL‐26 small interfering (si)RNA in order to measure its antimicrobial, cytotoxic and phagocytic activities against Staphylococcus aureus. Results: Firstly, we observed that IL‐26 is able to modulate the proinflammatory response at the immune cell level. IL‐26 was increased in the plasma of patients with HS compared with healthy controls. Subsequently, we explored the bactericidal, cytotoxic and phagocytic activities of PBMCs against S. aureus in patients with HS and healthy controls. These activities were lower in patients with HS than in controls. Remarkably, the killing activities were reduced when healthy control PBMCs were transfected with IL‐26 siRNA. However, the transfection did not affect the killing activity of HS PBMCs, supporting the idea that IL‐26 lacks efficacy in HS. Conclusions: Our findings suggest that infection susceptibility in HS might be related to IL‐26. Although the role of bacteria remains controversial in HS, this paper supports that there is a defect of antimicrobial response in these patients. What's already known about this topic? Interleukin (IL)‐26 is a T helper 17 cytokine described as an antimicrobial and proinflammatory mediator.IL‐26 has been reported in immune‐mediated inflammatory diseases, but its involvement in inflammatory skin disorders remains unclear.Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by deficiency of IL‐20 and IL‐22 (a close homologue of IL‐26), which causes antimicrobial peptide pauperization leading to severe and recurrent skin infections. What does this study add? IL‐26 plasma levels are higher in patients with HS than in healthy control individuals.The antimicrobial activity of IL‐26 might be ineffective in patients with HS. What is the translational message? Cutaneous antimicrobial incompetence in HS could be related to IL‐26. Linked Comment: Giamarellos-Bourboulis. Br J Dermatol 2019; 181:892–893. Respond to this article [ABSTRACT FROM AUTHOR]

Catheterization has an imperative rule in heat transfer investigations, which are frequently applied to analyze and deal with the heart transfer studies. Here, the entering of a catheter adjusts the flow of the blood and it affects the hemodynamic status in the artery region. In practical clinical cases, catheters cannot be precisely concentric with the artery. The impartial of this work is to investigate the behavior of a blood streaming characteristics, in the case of injecting the catheter eccentrically all the way through a stenotic overlapping artery. In this paper, we consider the heat transfer within the presence of blood corpuscle which has been characterized by a macroscopic two-phase model (i.e. a suspension of erythrocytes in plasma). The model here considers the blood fluid as a liquid fluid with adjourned particles in the gap bounded by the eccentric cylinder. The inside cylinder is identically rigid demonstrating the movable thin catheter and kept at constant temperature, where the outer cylinder is a taper cylinder demonstrating the artery that has overlapping stenosis and it is cooled and maintained at zero temperature. The coupled differential equations for both fluid (plasma) and particle (erythrocyte) phases have been solved. The expressions for the flow characteristics, namely, the flow rate, the impedance (resistance to flow), the wall shear stress and the temperature distribution, have been derived. The model is very useful in medicine, where the hemodynamic speed is higher for eccentric case than that of concentric one. Also, the temperature distribution and the entropy generation in the state of eccentric position are higher than in the case of the concentric position. A significant increase in the magnitude of the impedance and the wall shear stress occurs for an increase in the hematocrit, C for diseased blood. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) induces B-cell proliferation with high efficiency through expression of latent proteins and microRNAs. This process takes place in vivo soon after infection, presumably to expand the virus reservoir, but can also induce pathologies, e.g. an infectious mononucleosis (IM) syndrome after primary infection or a B-cell lymphoproliferation in immunosuppressed individuals. In this paper, we investigated the growth characteristics of EBV-infected B-cells isolated from transplant recipients or patients with IM. We found that these cells grew and withstood apoptosis at highly variable rates, suggesting that the expansion rate of the infected B-cells widely varies between individuals, thereby influencing the size of the B-cell reservoir and the ability to form tumors in infected individuals. All viruses investigated were type 1 and genetically close to western strains. EBV-infected B-cells expressed the transforming EBV latent genes and microRNAs (miRNAs) at variable levels. We found that the B-cell growth rates positively correlated with the BHRF1 miRNA levels. Comparative studies showed that infected B-cells derived from transplant recipients with iEBVL on average expressed higher levels of EBV miR-BHRF1 miRNAs and grew more rapidly than B-cells from IM patients, suggesting infection by more transforming viruses. Altogether, these findings suggest that EBV infection has a highly variable impact on the B-cell compartment that probably reflects the genetic diversity of both the virus and the host. It also demonstrates the unexpected finding that B-cells from different individuals can grow at different speed under the influence of the same virus infection. [ABSTRACT FROM AUTHOR]

This paper presents a method for continuous magnetophoretic separation of red and white blood cells from whole blood based on their native magnetic properties. The microsystem separates the blood cells using a high gradient magnetic separation method without the use of additives such as magnetic tagging or inducing agents. A theoretical model of the magnetophoretic microseparator is derived and verified by comparison with finite element simulation. The microseparator is fabricated using microfabrication technology, enabling the integration of microscale magnetic flux concentrators in an aqueous microenvironment, providing strong magnetic forces, and fast separations. Experimental tests are performed using a permanent magnet to create an external magnetic flux of 0.2 T, and measuring the movement of red blood cells within the microchannel of the microseparator. The experimental results correlate well with the theoretical results. [ABSTRACT FROM AUTHOR]

Drug selection and treatment monitoring via minimally invasive liquid biopsy using circulating tumor cells (CTCs) are expected to be realized in the near future. For clinical applications of CTCs, simple, high-throughput, single-step CTC isolation from whole blood without red blood cell (RBC) lysis and centrifugation remains a crucial challenge. In this study, we developed a novel cancer cell separation chip, "hybrid double-spiral chip", that involves the serial combination of two different Dean flow fractionation (DFF) separation modes of half and full Dean cycles, which is the hybrid DFF separation mode for ultra-high-throughput blood processing at high precision and size-resolution separation. The chip allows fast processing of 5 mL whole blood within 30 min without RBC lysis and centrifugation. RBC and white blood cell (WBC) depletion rates of over 99.9% and 99%, respectively, were achieved. The average recovery rate of spiked A549 cancer cells was 87% with as low as 200 cells in 5 mL blood. The device can achieve serial reduction in the number of cells from approximately 1010 cells of whole blood to 108 cells, and subsequently to an order of 106 cells. The developed method can be combined with measurements of all recovered cells using imaging flow cytometry. As proof of concept, CTCs were successfully enriched and enumerated from the blood of metastatic breast cancer patients (N = 10, 1–69 CTCs per 5 mL) and metastatic prostate cancer patients (N = 10, 1–39 CTCs per 5 mL). We believe that the developed method will be beneficial for automated clinical analysis of rare CTCs from whole blood. [ABSTRACT FROM AUTHOR]

Separation of plasma which is full of various biomarkers is critical for clinical diagnosis. However, the point-of-care plasma separation often relies on microfluidic filtration membranes which are usually limited in purity, yield, hemolysis, extraction speed, hematocrit level, and protein recovery. Here, we have developed a high-performance plasma membrane separation technique based on a Janus membrane and red blood cell (RBC) agglutination reaction. The RBC agglutination reaction can form larger RBC aggregates to separate plasma from blood cells. Then, the Janus membrane, serving as a multipore microfilter to block large RBC aggregates, allows the plasma to flow from the hydrophobic side to its hydrophilic side spontaneously. As a result, the separation technique can extract highly-purified plasma (99.99%) from whole blood with an ultra-high plasma yield (∼80%) in ∼80 s. Additionally, the separation technique is independent of the hematocrit level and can avoid hemolysis. [ABSTRACT FROM AUTHOR]

Leukemia is type of cancer in blood which impacts the lymphatic framework and the bone marrow and also impacts white blood cells. Leukemia, in contrast to other types of cancer, does not produce solid tumors; instead, it produces a huge number of aberrant white blood cells that crowd out the healthy blood cells. Machine learning algorithms that are widely utilized in the treatment of leukemia, whether it is to classify the various forms of leukemia or to determine whether a patient has the disease. It is a malignant kind of cancer that results in a number of medical issues. Expert hematologists and pathologists manually examine blood samples under the microscope to make a diagnosis. Techniques like image processing and pattern recognition can be utilized to help these experts. In order to attain excellent performance in the categorization of malignant leukocytes challenge, this paper suggests straightforward modifications to conventional neural network topologies. Consequently, there is considerable interest in the trustworthy and precise recognition of nonmalignant and malignant cells. Leukemia can be automatically detected using computer-aided diagnostic (CAD) models, which can help doctors and be useful for leukemia early identification. In this single-center study, we attempted to develop a deep learning model for classification of leukemic B-lymphoblasts. Data augmentation methods were utilized to manage the little dataset size and an exchange learning technique was utilized to accelerate learning and upgrade the presentation of the recommended network in order to create a trustworthy and accurate deep learner. The outcomes demonstrate that our suggested approach surpassed seperate networks with a test accuracy of 95.59% in the Leukemic B-lymphoblast examination, and was caable to merge characteristics extracted from the top deep learning models. [ABSTRACT FROM AUTHOR]

Label-free image identification of circulating rare cells, such as circulating tumor cells within peripheral blood nucleated cells (PBNCs), the vast majority of which are white blood cells (WBCs), remains challenging. We previously described developing label-free image cytometry for classifying live cells using computer vision technology for pattern recognition, based on the subcellular structure of the quantitative phase microscopy images. We applied our image recognition methods to cells flowing in a flow cytometer microfluidic channel, and differentiated WBCs from cancer cell lines (area under receiver operating characteristic curve = 0.957). We then applied this method to healthy volunteers' and advanced cancer patients' blood samples and found that the non-WBC fraction rates (NWBC-FRs), defined as the percentage of cells classified as non-WBCs of the total PBNCs, were significantly higher in cancer patients than in healthy volunteers. Furthermore, we monitored NWBC-FRs over the therapeutic courses in cancer patients, which revealed the potential ability in monitoring the clinical status during therapy. Our image recognition system has the potential to provide a morphological diagnostic tool for circulating rare cells as non-WBC fractions. [ABSTRACT FROM AUTHOR]

Aim: Paediatric haematopoietic stem cell donors undergo non-therapeutic procedures and endure known and unknown physical and psychosocial risks for the benefit of a family member. One ethical concern is the risk that they may be pressured by parents or health professionals to act as a donor. This paper adds to what is known about this topic by presenting the views of health professionals.Methods: This qualitative study involved semi-structured interviews with 14 health professionals in Australasia experienced in dealing with paediatric donors. Transcripts were analysed using established qualitative methodologies.Results: Health professionals considered that some paediatric donors experience pressure to donate. Situations that were likely to increase the risk of pressure being placed on donors were identified, and views were expressed about the ethical 'appropriateness' of these practices within the family setting.Conclusions: Children may be subject to pressure from family and health professionals to be tested and act as donors, Therefore, our ethical obligation to these children extends to implementing donor-focused processes - including independent health professionals and the appointment of a donor advocate - to assist in detecting and addressing instances of inappropriate pressure being placed on a child. [ABSTRACT FROM AUTHOR]

Among extant mammals, the presence of osteoderms is limited to armadillos (Xenarthra, Dasypodidae), being one of its distinctive features. The osteoderms are articulated to form a carapace that covers their body dorsally. In this paper we study the integumentary structures of the armadillos Chaetophractus vellerosus, Chaetophractus villosus, Euphractus sexcinctus, and Zaedyus pichiy (Euphractinae), Dasypus hybridus, and Dasypus novemcinctus (Dasypodinae) within a comparative framework, aiming to identify patterns common to the family and to the subfamilies Dasypodinae and Euphractinae, as well as peculiarities of each species. Differences between the two subfamilies were observed in the dorsal integument, related to the production of blood cells and the mobility of the carapace. The Euphractinae present more numerous and larger cavities filled with adipose tissue in the osteoderms, as well as more marginal follicles than the Dasypodinae. These provide thermal insulation that could be related to their distribution in cooler climates. The sebaceous glands associated with surface follicles are also more developed in the Euphractinae and could be related to preventing the desiccation of the cornified scales in arid climates. [ABSTRACT FROM AUTHOR]

Based upon two overlapped, body-unfitted meshes, a type of unified-field monolithic fictitious domain-finite element method (UFMFD-FEM) is developed in this paper for moving interface problems of dynamic fluid-structure interactions (FSI), which is accompanied with high-contrast physical coefficients across the interface and with contacting collisions between the structure and fluidic channel wall in the immersed FSI case. In particular, the proposed novel numerical method consists of a monolithic, stabilized mixed finite element method within the frame of fictitious domain/immersed boundary method (FD/IBM) for generic fluid-structure-contact interaction (FSCI) problems in the Eulerian–updated Lagrangian description, while involving the no-slip type of interface conditions on the fluid-structure interface, and the repulsive contact force/stress on the structural surface when the immersed structure contacts the fluidic channel wall. The developed UFMFD-FEM for FSI/FSCI problems can deal with the structural motion with large rotational and translational displacements and/or large deformation in an accurate and efficient fashion, which is first validated by two benchmark FSI problems and one FSCI model problem, then by experimental results of a realistic FSCI scenario – the microfluidic deterministic lateral displacement (DLD) problem that is applied to isolate circulating tumor cells (CTCs) from blood cells in the blood fluid through a cascaded filter DLD microchip in practice, where a particulate fluid with the pillar obstacles effect in the fluidic channel, i.e., the effects of fluid-structure interaction and structure collision, play significant roles to sort particles (cells) of different sizes with tilted pillar arrays. The developed unified-field, monolithic fictitious domain-based mixed finite element method can be seamlessly extended to more sophisticated, high dimensional FSCI problems with contacting collisions between the moving elastic structure and fluidic channel wall. • A fluid-structure-contact interaction (FSCI) model involving the interaction and collision effects is developed. • A mixed FEM in the monolithic fictitious domain frame is developed with respect to a unified variable pair of velocity and pressure. • Advanced algorithms are designed to handle structural collision, nonlinear system and interpolation between fictitious fluid and structure. • Numerical approaches are validated by benchmark problems, self- and physically designed DLD problems. • Numerical simulations carried out by the developed UFMFD-FEM can help to optimize the design of DLD microchips. [ABSTRACT FROM AUTHOR]

Non-coding RNA expression has shown to have cell type-specificity. The regulatory characteristics of these molecules are impacted by changes in their expression levels. We performed next-generation sequencing and examined small RNA-seq data obtained from 6 different types of blood cells separated by fluorescence-activated cell sorting of severe COVID−19 patients and healthy control donors. In addition to examining the behavior of piRNA in the blood cells of severe SARS-CoV−2 infected patients, our aim was to present a distinct piRNA differential expression portrait for each separate cell type. We observed that depending on the type of cell, different sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, and neutrophils) have altering piRNA expression patterns. After analyzing the expression of piRNAs in each set of sorted cells from patients with severe COVID−19, we observed 3 significantly elevated piRNAs - piR−33,123, piR−34,765, piR−43,768 and 9 downregulated piRNAs in erythrocytes. In lymphocytes, all 19 piRNAs were upregulated. Monocytes were presented with a larger amount of statistically significant piRNA, 5 upregulated (piR−49039 piR−31623, piR−37213, piR−44721, piR−44720) and 35 downregulated. It has been previously shown that piR−31,623 has been associated with respiratory syncytial virus infection, and taking in account the major role of piRNA in transposon silencing, we presume that the differential expression patterns which we observed could be a signal of indirect antiviral activity or a specific antiviral cell state. Additionally, in lymphocytes, all 19 piRNAs were upregulated. [ABSTRACT FROM AUTHOR]

Rationale: Changes in peripheral blood cell populations have been observed, but not detailed, at single-cell resolution in idiopathic pulmonary fibrosis (IPF). Objectives: We sought to provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. Methods: Peripheral blood mononuclear cells (PBMCs) from patients with IPF and control subjects were profiled using 10× chromium 5′ single-cell RNA sequencing. Flow cytometry was used for validation. Protein concentrations of regulatory T cells (Tregs) and monocyte chemoattractants were measured in plasma and lung homogenates from patients with IPF and control subjects. Measurements and Main Results: Thirty-eight PBMC samples from 25 patients with IPF and 13 matched control subjects yielded 149,564 cells that segregated into 23 subpopulations. Classical monocytes were increased in patients with progressive and stable IPF compared with control subjects (32.1%, 25.2%, and 17.9%, respectively; P < 0.05). Total lymphocytes were decreased in patients with IPF versus control subjects and in progressive versus stable IPF (52.6% vs. 62.6%, P = 0.035). Tregs were increased in progressive versus stable IPF (1.8% vs. 1.1% of all PBMCs, P = 0.007), although not different than controls, and may be associated with decreased survival (P = 0.009 in Kaplan-Meier analysis; and P = 0.069 after adjusting for age, sex, and baseline FVC). Flow cytometry analysis confirmed this finding in an independent cohort of patients with IPF. The fraction of Tregs out of all T cells was also increased in two cohorts of lung single-cell RNA sequencing. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. Conclusions: The single-cell atlas of the peripheral immune system in IPF reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung–blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs). [ABSTRACT FROM AUTHOR]

Background: Hematopoiesis in mammal is a complex and highly regulated process in which hematopoietic stem cells (HSCs) give rise to all types of differentiated blood cells. Previous studies have shown that hairy and enhancer of split (HES) repressors are essential regulators of adult HSC development downstream of Notch signaling. Methods: In this study, we investigated the role of HES1, a member of HES family, in fetal hematopoiesis using an embryonic hematopoietic specific Hes1 conditional knockout mouse model by using phenotypic flow cytometry, histopathology analysis, and functional in vitro colony forming unit (CFU) assay and in vivo bone marrow transplant (BMT) assay. Results: We found that loss of Hes1 in early embryonic stage leads to smaller embryos and fetal livers, decreases hematopoietic stem progenitor cell (HSPC) pool, results in defective multi-lineage differentiation. Functionally, fetal hematopoietic cells deficient for Hes1 exhibit reduced in vitro progenitor activity and compromised in vivo repopulation capacity in the transplanted recipients. Further analysis shows that fetal hematopoiesis defects in Hes1fl/flFlt3Cre embryos are resulted from decreased proliferation and elevated apoptosis, associated with de-repressed HES1 targets, p27 and PTEN in Hes1-KO fetal HSPCs. Finally, pharmacological inhibition of p27 or PTEN improves fetal HSPCs function both in vitro and in vivo. Conclusion: Together, our findings reveal a previously unappreciated role for HES1 in regulating fetal hematopoiesis, and provide new insight into the differences between fetal and adult HSC maintenance. [ABSTRACT FROM AUTHOR]

Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3–CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases. [ABSTRACT FROM AUTHOR]

Intron-containing RNA expressed from the HIV-1 provirus activates type 1 interferon in primary human blood cells, including CD4+ T cells, macrophages, and dendritic cells. To identify the innate immune receptor required for detection of intron-containing RNA expressed from the HIV-1 provirus, a loss-of-function screen was performed with short hairpin RNA-expressing lentivectors targeting twenty-one candidate genes in human monocyte-derived dendritic cells. Among the candidate genes tested, only knockdown of XPO1 (CRM1), IFIH1 (MDA5), or MAVS prevented activation of the interferon-stimulated gene ISG15. The importance of IFIH1 protein was demonstrated by rescue of the knockdown with nontargetable IFIH1 coding sequence. Inhibition of HIV-1-induced ISG15 by the IFIH1-specific Nipah virus V protein, and by IFIH1-transdominant 2-CARD domain-deletion or phosphomimetic point mutations, indicates that IFIH1 (MDA5) filament formation, dephosphorylation, and association with MAVS are all required for innate immune activation in response to HIV-1 transduction. Since both IFIH1 (MDA5) and DDX58 (RIG-I) signal via MAVS, the specificity of HIV-1 RNA detection by IFIH1 was demonstrated by the fact that DDX58 knockdown had no effect on activation. RNA-Seq showed that IFIH1 knockdown in dendritic cells globally disrupted the induction of IFN-stimulated genes by HIV-1. Finally, specific enrichment of unspliced HIV-1 RNA by IFIH1 (MDA5), over two orders of magnitude, was revealed by formaldehyde cross-linking immunoprecipitation (f-CLIP). These results demonstrate that IFIH1 is the innate immune receptor for intron-containing RNA from the HIV-1 provirus and that IFIH1 potentially contributes to chronic inflammation in people living with HIV-1, even in the presence of effective antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Platelet transfusions are routine procedures in clinical treatment aimed at preventing bleeding in critically ill patients, including those with cancer, undergoing surgery, or experiencing trauma. However, platelets are susceptible blood cells that require specific storage conditions. The availability of platelet concentrates is limited to five days due to various factors, including the risk of bacterial contamination and the occurrence of physical and functional changes known as platelet storage lesions. In this article, the problems related to platelet storage lesions are categorized into four groups depending on research areas: storage conditions, additive solutions, new testing methods for platelets (proteomic and metabolomic analysis), and extensive data modeling of platelet production (mathematical modeling, statistical analysis, and artificial intelligence). This article provides extensive information on the challenges, potential improvements, and novel perspectives regarding platelet storage. [ABSTRACT FROM AUTHOR]

Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via stem cell transplantation. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs and progenitor populations at the expense of naive LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1α expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1α expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders. The ability to maintain blood stem cells (HSCs) in vitro would allow us to provide better therapies for blood diseases. Here, the authors report that polymer-organised extracellular proteins, coupled to soft environments mimicking bone marrow stiffness, allow stromal cells to maintain HSCs in vitro. [ABSTRACT FROM AUTHOR]

Nanoparticles (NP) play a crucial role in nanomedicine, serving as carriers for localized therapeutics to allow for precise drug delivery to specific disease sites and conditions. When injected systemically, NP can directly interact with various blood cell types, most critically with circulating platelets. Hence, the potential activation/inhibition of platelets following NP exposure must be evaluated a priori due to possible debilitating outcomes. In recent years, various studies have helped resolve the physicochemical parameters that influence platelet‐NP interactions, and either emphasize nanoparticles' therapeutic role such as to augment hemostasis or to inhibit thrombus formation, or conversely map their potential undesired side effects upon injection. In the present review, we discuss some of the main effects of several key NP types including polymeric, ceramic, silica, dendrimers and metallic NPs on platelets, with a focus on the physicochemical parameters that can dictate these effects and modulate the therapeutic potential of the NP. Despite the scientific and clinical significance of understanding Platelet‐NP interactions, there is a significant knowledge gap in the field and a critical need for further investigation. Moreover, improved guidelines and research methodologies need to be developed and implemented. Our outlook includes the use of biomimetic in vitro models to investigate these complex interactions under both healthy physiological and disease conditions. [ABSTRACT FROM AUTHOR]

Background: Guided bone regeneration (GBR) has become a necessary practice in implantology. Absorbable membranes have shown advantages over non-absorbable membranes, such as blood support of bone tissue. This study aimed to evaluate five collagen membranes in rat calvaria critical-size defects through a histomorphometric analysis of the inflammatory profile during the initial phase of bone repair. Materials and methods: A total of 72 Albinus Wistar rats were used for the study, divided into six groups, with 12 animals per group, and two experimental periods, 7 and 15 days. The groups were as follows: the CG (clot), BG (Bio-Gide®), JS (Jason®), CS (Collprotect®), GD (GemDerm®), and GDF (GemDerm Flex®). Results: Data showed that the BG group demonstrated an inflammatory profile with an ideal number of inflammatory cells and blood vessels, indicating a statistically significant difference between the JS and CS groups and the BG group in terms of the number of inflammatory cells and a statistically significant difference between the JS and CS groups and the GD group in terms of angiogenesis (p < 0.05). Conclusions: We conclude that different origins and ways of obtaining them, as well as the thickness of the membrane, can interfere with the biological response of the material. [ABSTRACT FROM AUTHOR]

Nanomaterials have been extensively used in the biomedical field due to their unique physical and chemical properties. They promise wide applications in the diagnosis, prevention, and treatment of diseases. Nanodrugs are generally transported to target tissues or organs by coupling targeting molecules or enhanced permeability and retention effect (EPR) passively. As intravenous injection is the most common means of administration of nanomedicine, the transport process inevitably involves the interactions between nanoparticles (NPs) and blood cells. Platelets are known to not only play a critical role in normal coagulation by performing adhesion, aggregation, release, and contraction functions, but also be associated with pathological thrombosis, tumor metastasis, inflammation, and immune reactions, making it necessary to investigate the effects of NPs on platelet function during transport, particularly the way in which their physical and chemical properties determine their interaction with platelets and the underlying mechanisms by which they activate and induce platelet aggregation. However, such data are lacking. This review is intended to summarize the effects of NPs on platelet activation, aggregation, release, and apoptosis, as well as their effects on membrane proteins and morphology in order to shed light on such key issues as how to reduce their adverse reactions in the blood system, which should be taken into consideration in NP engineering. [ABSTRACT FROM AUTHOR]

The search for the molecular markers of osteoporosis (OP), based on the analysis of differential deoxyribonucleic acid (DNA) methylation in bone cells and peripheral blood cells, is promising for developments in the field of the early diagnosis and targeted therapy of the disease. The Runt-related transcription factor 2 (RUNX2) gene is one of the key genes of bone metabolism, which is of interest in the search for epigenetic signatures and aberrations associated with the risk of developing OP. Based on pyrosequencing, the analysis of the RUNX2 methylation profile from a pool of peripheral blood cells in men and women over 50 years of age of Russian ethnicity from the Volga-Ural region of Russia was carried out. The level of DNA methylation in three CpG sites of the RUNX2 gene was assessed and statistically significant hypomethylation was revealed in all three studied CpG sites in men (U = 746.5, p = 0.004; U = 784, p = 0.01; U = 788.5, p = 0.01, respectively) and in one CpG site in women (U = 537, p = 0.03) with primary OP compared with control. In the general sample, associations were preserved for the first CpG site (U = 2561, p = 0.0001766). The results were obtained for the first time and indicate the existence of potentially new epigenetic signatures of RUNX2 in individuals with OP. [ABSTRACT FROM AUTHOR]

Ex vivo red blood cell (RBC) production generates unsatisfactory erythroid cells. A deep exploration into terminally differentiated cells is required to understand the impairments for RBC generation and the underlying mechanisms. Here, we mapped an atlas of terminally differentiated cells from umbilical cord blood mononuclear cells (UCBMN) and pluripotent stem cells (PSC) and observed their dynamic regulation of erythropoiesis at single‐cell resolution. Interestingly, we detected a few progenitor cells and non‐erythroid cells from both origins. In PSC‐derived erythropoiesis (PSCE), the expression of haemoglobin switch regulators (BCL11A and ZBTB7A) were significantly absent, which could be the restraint for its adult globin expression. We also found that PSCE were less active in stress erythropoiesis than in UCBMN‐derived erythropoiesis (UCBE), and explored an agonist of stress erythropoiesis gene, TRIB3, could enhance the expression of adult globin in PSCE. Compared with UCBE, there was a lower expression of epigenetic‐related proteins (e.g., CASPASE 3 and UBE2O) and transcription factors (e.g., FOXO3 and TAL1) in PSCE, which might restrict PSCE's enucleation. Moreover, we characterized a subpopulation with high proliferation capacity marked by CD99high in colony‐forming unit‐erythroid cells. Inhibition of CD99 reduced the proliferation of PSC‐derived cells and facilitated erythroid maturation. Furthermore, CD99–CD99 mediated the interaction between macrophages and erythroid cells, illustrating a mechanism by which macrophages participate in erythropoiesis. This study provided a reference for improving ex vivo RBC generation. [ABSTRACT FROM AUTHOR]

C-mannosylation is a post-translational modification that occurs intracellularly in the endoplasmic reticulum. In humans, biosynthesis of C-mannosylation in proteins containing thrombospondin type 1 repeat is catalyzed by the DPY19 family; nonetheless, biological functions of protein C-mannosylation are not yet fully understood, especially in tumor progression. Vasculogenic mimicry (VM) is the formation of fluid-conducting channels by highly invasive and genetically deregulated tumor cells, enabling the tumors to form matrix-embedded vasculogenic structures, containing plasma and blood cells to meet the metabolic demands of rapidly growing tumors. In this study, we focused on DPY19L3, a C-mannosyltransferase, and aimed to unravel its role in VM. Knockout of DPY19L3 inhibited the formation of VM in HT1080 human fibrosarcoma cells. Re-expression of wild-type DPY19L3 recovered VM formation; however, DPY19L3 isoform2, an enzymatic activity-defect mutant, did not restore it, suggesting that the C-mannosyltransferase activity of DPY19L3 is crucial to its function. Furthermore, the knockdown of DPY19L3 in MDA-MB-231 breast cancer cells hindered its network formation ability. Altogether, our findings suggest that DPY19L3 is required for VM formation and stipulate the relevance of C-mannosylation in oncogenesis. [ABSTRACT FROM AUTHOR]

Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells that represent the interface between blood cells on one side and hepatocytes on the other side. LSECs not only form a barrier within the hepatic sinus, but also play important physiological functions such as regulating hepatic vascular pressure, anti-inflammatory and anti-fibrotic. Pathologically, pathogenic factors can induce LSECs capillarization, that is, loss of fenestra and dysfunction, which are conducive to early steatosis, lay the foundation for the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), and accelerate metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. The unique localization, phenotype, and function of LSECs make them potential candidates for reducing liver injury, inflammation, and preventing or reversing fibrosis in the future. [ABSTRACT FROM AUTHOR]

Adult neurogenesis, which takes place in both vertebrate and invertebrate species, is the process by which new neurons are born and integrated into existing functional neural circuits, long after embryonic development. Most studies in mammals suggest that self-renewing stem cells are the source of the new neurons, although the extent of self-renewal is a matter of debate. In contrast, research in the crayfish Procambarus clarkii has demonstrated that the neural progenitors producing adult-born neurons are capable of both self-renewing and consuming (non-self-renewing) divisions. However, self-renewing divisions are relatively rare, and therefore the production of adult-born neurons depends heavily on progenitors that are not replenishing themselves. Because the small pool of neural progenitors in the neurogenic niche is never exhausted throughout the long lives of these animals, we hypothesized that there must also be an extrinsic source of these cells. It was subsequently demonstrated that the neural progenitors originate in hemocytes (blood cells) produced by the immune system that travel in the circulation before ultimately integrating into niches where the neural lineage begins. The current study examines the developmental lineage of the three hemocyte types — hyaline (HC), semigranular (SGC) and granular (GC) cells — with the goal of understanding the origins of the progenitor cells that produce adult-born neurons. Longstanding qualitative metrics for hemocyte classification were validated quantitatively. Then, in a longitudinal study, proliferation markers were used to label the hemocytes in vivo, followed by sampling the circulating hemocyte population over the course of two months. Hemolymph samples were taken at intervals to track the frequencies of the different hemocyte types. These data reveal sequential peaks in the relative frequencies of HCs, SGCs and GCs, which were identified using qualitative and quantitative measures. These findings suggest that the three hemocyte types comprise a single cellular lineage that occurs in the circulation, with each type as a sequential progressive stage in hemocyte maturation beginning with HCs and ending with GCs. When combined with previously published data, this timeline provides additional evidence that HCs serve as the primary neural progenitor during adult neurogenesis in P. clarkii. [ABSTRACT FROM AUTHOR]

Interactions between osteolineage cells and myeloid cells play important roles in maintaining skeletal homeostasis. Herein, we find that osteolineage cells transfer mitochondria to myeloid cells. Impairment of the transfer of mitochondria by deleting MIRO1 in osteolineage cells leads to increased myeloid cell commitment toward osteoclastic lineage cells and promotes bone resorption. In detail, impaired mitochondrial transfer from osteolineage cells alters glutathione metabolism and protects osteoclastic lineage cells from ferroptosis, thus promoting osteoclast activities. Furthermore, mitochondrial transfer from osteolineage cells to myeloid cells is involved in the regulation of glucocorticoid-induced osteoporosis, and glutathione depletion alleviates the progression of glucocorticoid-induced osteoporosis. These findings reveal an unappreciated mechanism underlying the interaction between osteolineage cells and myeloid cells to regulate skeletal metabolic homeostasis and provide insights into glucocorticoid-induced osteoporosis progression. Bone and blood lineage cells communicate with each other to maintain skeletal homeostasis. Here, the authors show that MIRO1-mediated mitochondrial transfer from osteolineage to myeloid lineage cells regulates bone resorption by altering glutathione metabolism. [ABSTRACT FROM AUTHOR]

Human type 1 diabetes (T1D) is caused by autoimmune attack on the insulin-producing pancreatic beta cells by islet antigen-reactive T cells. How human islet antigen-reactive (IAR) CD4+ memory T cells from peripheral blood affect T1D progression in the pancreas is poorly understood. Here, we aim to determine if IAR T cells in blood could be detected in pancreas. We identify paired αβ (TRA/TRB) T cell receptors (TCRs) in IAR T cells from the blood of healthy, at-risk, new-onset, and established T1D donors, and measured sequence overlap with TCRs in pancreata from healthy, at risk and T1D organ donors. We report extensive TRA junction sharing between IAR T cells and pancreas-infiltrating T cells (PIT), with perfect-match or single-mismatch TRA junction amino acid sequences comprising ~29% total unique IAR TRA junctions (942/3,264). PIT-matched TRA junctions were largely public and enriched for TRAV41 usage, showing significant nucleotide sequence convergence, increased use of germline-encoded versus non-templated residues in epitope engagement, and a potential for cross-reactivity. Our findings thus link T cells with distinctive germline-like TRA chains in the peripheral blood with T cells in the pancreas. Most efforts to examine islet antigen-reactive T cells in type-1 diabetes have been limited to peripheral blood. In this study, the authors examine the T cell receptor (TCR) repertoire of insulin antigen-reactive T cells from peripheral blood from patients with type-1 diabetes as well as pancreata from deceased donors. [ABSTRACT FROM AUTHOR]

Background: Immunotherapeutic approaches, including immune checkpoint inhibitor (ICI) therapy, are increasingly recognized for their potential. Despite notable successes, patient responses to these treatments vary significantly. The absence of reliable predictive and prognostic biomarkers hampers the ability to foresee outcomes. This meta-analysis aims to evaluate the predictive significance of circulating myeloid-derived suppressor cells (MDSC) in patients with solid tumors undergoing ICI therapy, focusing on progression-free survival (PFS) and overall survival (OS). Methods: A comprehensive literature search was performed across PubMed and EMBASE from January 2007 to November 2023, utilizing keywords related to MDSC and ICI. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) directly from the publications or calculated them based on the reported data. A hazard ratio greater than 1 indicated a beneficial effect of low MDSC levels. We assessed heterogeneity and effect size through subgroup analyses. Results: Our search yielded 4,023 articles, of which 17 studies involving 1,035 patients were included. The analysis revealed that patients with lower levels of circulating MDSC experienced significantly improved OS (HR=2.13 [95% CI 1.51-2.99]) and PFS (HR=1.87 [95% CI 1.29-2.72]) in response to ICI therapy. Notably, heterogeneity across these outcomes was primarily attributed to differences in polymorphonuclear MDSC (PMN-MDSC) subpopulations and varying cutoff methodologies used in the studies. The monocytic MDSC (M-MDSC) subpopulation emerged as a consistent and significant prognostic marker across various subgroup analyses, including ethnicity, tumor type, ICI target, sample size, and cutoff methodology. Conclusions: Our findings suggest that standardized assessment of MDSC, particularly M-MDSC, should be integral to ICI therapy strategies. These cells hold the promise of identifying patients at risk of poor response to ICI therapy, enabling tailored treatment approaches. Further research focusing on the standardization of markers and validation of cutoff methods is crucial for integrating MDSC into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Kidney cancer is a prevalent malignancy with an increasing incidence worldwide. Blood cell indices and inflammation-related markers have shown huge potential as biomarkers for predicting cancer incidences, but that is not clear in kidney cancer. Our study aims to investigate the correlations of blood cell indices and inflammation-related markers with kidney cancer risk. Methods: We performed a population-based cohort prospective analysis using data from the UK Biobank. A total of 466,994 participants, free of kidney cancer at baseline, were included in the analysis. The hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk were calculated using Cox proportional hazards regression models. Restricted cubic spline models were used to investigate nonlinear longitudinal associations. Stratified analyses were used to identify high-risk populations. The results were validated through sensitivity analyses. Results: During a mean follow-up of 12.4 years, 1,710 of 466,994 participants developed kidney cancer. The Cox regression models showed that 13 blood cell indices and four inflammation-related markers were associated with kidney cancer incidence. The restricted cubic spline models showed non-linear relationships with kidney cancer. Finally, combined with stratified and sensitivity analyses, we found that the mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet distribution width (PDW), systemic immune-inflammation index (SII), and product of platelet count and neutrophil count (PPN) were related to enhanced kidney cancer risk with stable results. Conclusion: Our findings identified that three blood cell indices (MCHC, RDW, and PDW) and two inflammation-related markers (SII and PPN) were independent risk factors for the incidence of kidney cancer. These indexes may serve as potential predictors for kidney cancer and aid in the development of targeted screening strategies for at-risk individuals. [ABSTRACT FROM AUTHOR]

During ontogeny, γδ T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity. However, their functional role in humans has largely been defined from blood. Here, we analyzed the phenotype, transcriptome, function, and repertoire of human γδ T cells in blood and mucosal and lymphoid tissues from 176 donors across the life span, revealing distinct profiles in children compared with adults. In early life, clonally diverse Vδ1 subsets predominate across blood and tissues, comprising naïve and differentiated effector and tissue repair functions, whereas cytolytic Vδ2 subsets populate blood, spleen, and lungs. With age, Vδ1 and Vδ2 subsets exhibit clonal expansions and elevated cytolytic signatures, which are disseminated across sites. In adults, Vδ2 cells predominate in blood, whereas Vδ1 cells are enriched across tissues and express residency profiles. Thus, antigenic exposures over childhood drive the functional evolution and tissue compartmentalization of γδ T cells, leading to age-dependent roles in immunity. Editor's summary: Our understanding of the functional role of human γδ T cells in tissues is very limited and has been primarily informed by peripheral blood studies. Gray et al. used a multiomics strategy to characterize human γδ T cells in the blood and various mucosal and lymphoid tissues from 176 donors whose ages ranged from just a few days to over 80 years. In contrast to the highly differentiated and cytotoxic γδ T cell populations found in adults, γδ T cells during infancy and childhood are clonally diverse, are tissue specific, and exhibit features of adaptive lymphocytes. —Seth Thomas Scanlon [ABSTRACT FROM AUTHOR]