Hematopoietic Process Research Articles

Along the gut-bone marrow signaling pathway: use of longan polysaccharides to regenerate blood cells after chemotherapy-induced myelosuppression.

Although it has been established that polysaccharides have an effect on bone marrow haematopoiesis, it remains unclear how polysaccharides regulate bone marrow haematopoiesis during absorption and metabolism in vivo. In this study, the effect of a longan polysaccharide of large molecular weight (TLPL) on the gut microbiota of mice and its implications for the haematopoietic process in bone marrow was discussed. Here, the results show that after 21 days of TLPL consumption, the respective quantities of white blood cells, platelets, hemoglobin and bone marrow nucleated cells were determined to be 3.18 ± 1.71 (109 L-1), 1238.10 ± 164.41 (109 L-1), 135.10 ± 4.95 (g L-1), and 1.70 × 107, which reached 56.98%, 117.28%, and 47.74%, respectively, of the results for NC. TLPL both increased the thymus and spleen indexes by up to 2.08 ± 0.64 (mg g-1) and 6.49 ± 2.45 (mg g-1), respectively. Additionally, TLPL remodeled the gut microbiota with a significant increase in Lactobacillus in particular, and a significant increase in the level of the potential intestinal metabolite lactate was detected in the serum. Most importantly, a similarly significant up-regulation of the gene expression of the lactate receptor, Gpr81, in the myeloid cells was observed. These changes contributed to the activation of the secretion of various cytokines associated with haematopoiesis, with the levels of G-CSF, EPO, SCF and PF4 increased by 2.44 times, 1.14 times, 1.56 times and 1.13 times, respectively, compared to the MC group, which subsequently accelerated production of bone marrow cells and blood cells. The findings of this study reveal the unique mechanism of dried longan polysaccharides in ameliorating myelosuppression and provide a feasible strategy for the treatment of chemotherapy-induced myelosuppression with bioactive polysaccharides.

Deciphering avian hematopoietic stem cells by surface marker screening and gene expression profiling

BackgroundAvian species have played a pivotal role in developmental hematopoiesis research, leading to numerous critical discoveries. Avian influenza, particularly the H5N1 strain, poses a significant threat to poultry and has zoonotic potential for humans. Infections often result in abnormal hematologic profiles, highlighting the complex interplay between avian diseases and hematopoiesis. Many avian diseases can suppress immune cells in the bone marrow (BM), impacting immune responses. Studying hematopoietic stem cells (HSCs) in avian BM is crucial for understanding these processes and developing effective vaccines and protection strategies for both avian and human health. MethodsThis study adapted methods from mouse studies to isolate avian HSCs as Lineage-negative (Lin-) cells. These isolated cells were further identified as Lin-Sca1+c-Kit+ (LSK) and were found to be more prevalent than in control groups. RT-PCR analyses were conducted, showing that genes like MEIS1 and TSC1 were upregulated, while SIRT1, FOXO1, and AHR were downregulated in these stem cells. Screening for LSK markers revealed ten unique surface antigens in the Sca1+c-Kit+ cell populations, including highly enriched antigens such as CD178, CD227, and CD184. Additionally, studies on quail HSCs demonstrated that similar labeling techniques were effective in quail BM. ResultsThe research demonstrated that the identification of avian HSC-specific surface antigens provides valuable insights into the pathogenesis of avian influenza and other diseases, enhancing our understanding of how these diseases suppress HSC function. Notably, the upregulation of MEIS1 and TSC1 genes in LSK cells underscores their critical roles in regulating hematopoietic processes. Conversely, the downregulation of SIRT1, FOXO1, and AHR genes provides important clues about their roles in differentiation and immune response mechanisms. DiscussionThe findings of this study deepen our understanding of the effects of avian diseases on the immune system by identifying surface markers specific to avian HSCs. The suppression of HSC function by pathogens such as influenza highlights the importance of understanding these cells in developing targeted vaccines. These results represent a significant step towards improving global health security by mitigating risks associated with avian pathogens.

Protein phosphatase 2A regulates blood cell proliferation and differentiation in Drosophila larval lymph glands.

Protein phosphatase 2A (PP2A), one of the most abundant protein phosphatases, has divergent functions in multiple types of cells. Its inactivation has been closely associated with leukemia diseases. However, the physiological function of PP2A for hematopoiesis has been poorly understood in organisms. Drosophila hematopoiesis parallels the vertebrate counterpart in developmental and functional features but involves a much simpler hematopoietic system. Here, utilizing the Drosophila major larval hematopoietic organ lymph gland, we studied the function of PP2A for hematopoiesis in vivo. By knocking down the expression of Pp2A-29B that encodes the scaffold subunit of the PP2A holoenzyme complex, we found that PP2A silencing in the differentiating hemocytes resulted in their excessive proliferation. Furthermore, this PP2A inhibition downregulated the expression of Smoothened (Smo), a crucial component in the Hedgehog pathway, and smo overexpression was able to rescue the phenotypes of PP2A depletion, indicating that Smo functions as a downstream effector of PP2A to restrict the hemocyte proliferation. PDGF/VEGF-receptor (Pvr) overexpression also restored the Smo expression and lymph gland morphology of PP2A silencing, suggesting a PP2A-Pvr-Smo axis to regulate lymph gland growth and hemocyte proliferation. Moreover, inhibiting PP2A activity in the blood progenitor cells promoted their differentiation, but which was independent with Smo. Together, our data suggested that PP2A plays a dual role in the Drosophila lymph gland by preserving the progenitor population and restraining the hemocyte proliferation, to properly regulate the hematopoietic process.

Mutational analysis and prediction of the potential impact of missense mutations in the HOXA9 gene in B-cell acute lymphoblastic leukemia

Background: The HOXA9 gene is an essential gene during the developmental stages of the embryo, and its mutations can result in different phenotypes in both fetal and adult life. Additionally, this gene encodes a transcription factor that plays a crucial role in hematopoietic processes. Deregulation of these pathways has been reported in some leukemia cases. This in-silico analysis aims to evaluate the pathogenic effect of missense mutations in the HOXA9 gene by utilizing various bioinformatics tools.Methods: From dbSNP NCBI, 288 non-synonymous/missense mutations of the HOXA9 gene have been obtained. These missense mutations' functional impact was analyzed using various bioinformatics tools, including SIFT, Polyphen-2, PROVEAN, I-Mutant, PHD-SNP, and SNP&GO. Additionally, their structural impacts were investigated using Netsurf P-2.0, HOPE, ConSurf, and PyMOL. Furthermore, the analysis of protein hydrophobicity changes was examined using PEPTIDE 2.0 and ExPASy web tools.Results: Out of the 288 non-synonymous mutations, 45 mutations have been identified as functional genetic variants that affect the structure and stability of the HOXA9 protein. According to the analysis, 10 out of the 45 missense mutations were more likely to be involved in changing the characteristics of the protein. These changes include absolute and relative solvent accessibility (ASA, RSA), classification secondary structure, surface accessibility, noncovalent interactions, and protein conformation.Conclusion: Based on the results of this in-silico study, high-risk deleterious missense mutations have been predicted in the HOXA9 gene. These mutations may be potential candidates for future experimental investigations in various hematologic malignancy conditions.

Innovative Rehabilitation Strategies for Chemical Dependency: Integrating Biochemical Insights and Psychosocial Approaches

Background: The increasing prevalence of substance use disorders underscores the need for a deeper understanding of the biochemical mechanisms underlying addiction, especially their impact on blood and genetic health. Chemical dependency not only affects physiological processes but also interacts with genetic predispositions, influencing the course and complications of addiction. Methods: This study investigates the relationship between chemical dependency, biochemical factors, and their implications for blood composition and genetic health. We examined how substance use disorders alter hematological profiles, affect hematopoiesis, and interact with genetic factors. The research involved analyzing changes in blood markers and genetic expressions related to addiction and recovery. Progressive rehabilitation techniques were evaluated for their effectiveness in addressing these issues. Results: Our findings reveal that chemical dependency significantly impacts blood composition, including alterations in hematological markers and disturbances in hematopoietic processes. Genetic factors were found to play a role in exacerbating addiction risks and health complications. Progressive rehabilitation techniques incorporating advancements in genetics and biochemistry were shown to improve outcomes by providing personalized interventions that address both physiological and psychological aspects of recovery. Conclusion: The study highlights the importance of integrating biochemical and genetic assessments into rehabilitation programs to enhance the effectiveness of treatment. Personalized approaches that address the interplay between addiction, blood health, and genetic predispositions promote better psychosocial adaptation and biochemical stabilization. This comprehensive understanding contributes valuable insights into developing more effective rehabilitation practices, ultimately supporting improved mental health and overall well-being.

Extracellular vesicles originating from melanoma cells promote dysregulation in haematopoiesis as a component of cancer immunoediting.

Haematopoiesis dysregulation with the presence of immature myeloid and erythroid immunosuppressive cells are key characteristics of the immune escape phase of tumour development. Here, the role of in vitro generated B16F10 tumour cell-derived extracellular vesicles (tEVs) as indirect cellular communicators, participating in tumour-induced dysregulation of haematopoiesis, was explored. The isolated tEVs displayed features of small EVs with a size range of 100-200nm, expressed the common EV markers CD63, CD9, and Alix, and had a spherical shape with a lipid bilayer membrane. Proteomic profiling revealed significant levels of angiogenic factors, particularly vascular endothelial growth factor (VEGF), osteopontin, and tissue factor, associated with the tEVs. Systemic administration of these tEVs in syngeneic mice induced splenomegaly and disrupted haematopoiesis, leading to extramedullary haematopoiesis, expansion of splenic immature erythroid progenitors, reduced bone marrow cellularity, medullary expansion of granulocytic myeloid suppressor cells, and the development of anaemia. These effects closely mirrored those observed in tumour-bearing mice and were not seen after heat inactivating the tEVs. In vitro studies demonstrated that tEVs independently induced the expansion of bone marrow granulocytic myeloid suppressor cells and B cells while reducing the frequency of cells in the erythropoietic lineage. These effects of tEVs were significantly abrogated by the blockade of VEGF or heat inactivation. Our findings underscore the important role of tEVs in dysregulating haematopoiesis during the immune escape phase of cancer immunoediting, suggesting their potential as targets for addressing immune evasion and reinstating normal hematopoietic processes.

Targeting IGF2BP1 alleviated benzene hematotoxicity by reprogramming BCAA metabolism and fatty acid oxidation

Benzene is the main environmental pollutant and risk factor of childhood leukemia and chronic benzene poisoning. Benzene exposure leads to hematopoietic stem and progenitor cell (HSPC) dysfunction and abnormal blood cell counts. However, the key regulatory targets and mechanisms of benzene hematotoxicity are unclear. In this study, we constructed a benzene-induced hematopoietic damage mouse model to explore the underlying mechanisms. We identified that Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was significantly reduced in benzene-exposed mice. Moreover, targeting IGF2BP1 effectively mitigated damages to hematopoietic function and hematopoietic molecule expression caused by benzene in mice. On the mechanics, by metabolomics and transcriptomics, we discovered that branched-chain amino acid (BCAA) metabolism and fatty acid oxidation were key metabolic pathways, and Branched-chain amino acid transaminase 1 (BCAT1) and Carnitine palmitoyltransferase 1a (CPT1A) were critical metabolic enzymes involved in IGF2BP1-mediated hematopoietic injury process. The expression of the above molecules in the benzene exposure population was also examined and consistent with animal experiments. In conclusion, targeting IGF2BP1 alleviated hematopoietic injury caused by benzene exposure, possibly due to the reprogramming of BCAA metabolism and fatty acid oxidation via BCAT1 and CPT1A metabolic enzymes. IGF2BP1 is a potential regulatory and therapeutic target for benzene hematotoxicity.

The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function

The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing hematological malignancies with poor prognosis. Using Kat6b germline deletion and overexpression in mice, we determined the role of KAT6B in the hematopoietic system. We found that KAT6B sustained the fetal hematopoietic stem cell pool but did not affect viability or differentiation. KAT6B was essential for normal levels of histone H3 lysine 9 (H3K9) acetylation but not for a previously proposed target, H3K23. Compound heterozygosity of Kat6b and the closely related gene, Kat6a, abolished hematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating hematopoiesis, including the Hoxa cluster, Pbx1, Meis1, Gata family, Erg, and Flt3. In conclusion, we identified the hematopoietic processes requiring Kat6b and showed that KAT6B and KAT6A synergistically promoted HSC development, function, and transcription. Our findings are pertinent to current clinical trials testing KAT6A/B inhibitors as cancer therapeutics.

Zinc Supplementation Enhances the Hematopoietic Activity of Erythropoiesis-Stimulating Agents but Not Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitors.

Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing hemodialysis. However, it remains unclear whether hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have similar reduction effects. HIF-PHI stabilizes HIF, which promotes hematopoiesis, although HIF-1α levels are downregulated by zinc. This study aimed to investigate the effect of zinc supplementation on the hematopoietic effect of HIF-PHI in patients undergoing hemodialysis. Thirty patients undergoing maintenance hemodialysis who underwent periods of treatment with roxadustat or darbepoetin alfa during the past 3 years were retrospectively observed. Participants who underwent periods with and without zinc supplementation were selected, with nine treated with darbepoetin alfa and nine treated with roxadustat. Similarly to the ESA responsiveness index (ERI), the hematopoietic effect of zinc supplementation was determined by the HIF-PHI responsiveness index (HRI), which was calculated by dividing the HIF-PHI dose (mg/week) by the patient's dry weight (kg) and hemoglobin level (g/L). Zinc supplementation significantly increased ERI (p < 0.05), but no significant change was observed (p = 0.931) in HRI. Although zinc supplementation did not significantly affect HRI, adequate zinc supplementation is required to alleviate concerns such as vascular calcification and increased serum copper during the use of HIF-PHI.

Epigenetic alterations in AML: Deregulated functions leading to new therapeutic options.

Acute myeloid leukemia (AML) results in disruption of the hematopoietic differentiation process. Crucial progress has been made, and new therapeutic strategies for AML have been developed. Induction chemotherapy, however, remains the main option for the majority of AML patients. Epigenetic dysregulation plays a central role in AML pathogenesis, supporting leukemogenesis and maintenance of leukemic stem cells. Here, we provide an overview of the intricate interplay of altered epigenetic mechanisms, including DNA methylation, histone modifications, and chromatin remodeling, in AML development. We explore the role of epigenetic regulators, such as DNMTs, HMTs, KDMs, and HDACs, in mediating gene expression patterns pushing towards leukemic cell transformation. Additionally, we discuss the impact of cytogenetic lesions on epigenomic remodeling and the potential of targeting epigenetic vulnerabilities as a therapeutic strategy. Understanding the epigenetic landscape of AML offers insights into novel therapeutic avenues, including epigenetic modifiers and particularly their use in combination therapies, to improve treatment outcomes and overcome drug resistance.

The crosstalk between lung cancer and the bone marrow niche fuels emergency myelopoiesis.

Modest response rates to immunotherapy observed in advanced lung cancer patients underscore the need to identify reliable biomarkers and targets, enhancing both treatment decision-making and efficacy. Factors such as PD-L1 expression, tumor mutation burden, and a 'hot' tumor microenvironment with heightened effector T cell infiltration have consistently been associated with positive responses. In contrast, the predictive role of the abundantly present tumor-infiltrating myeloid cell (TIMs) fraction remains somewhat uncertain, partly explained by their towering variety in terms of ontogeny, phenotype, location, and function. Nevertheless, numerous preclinical and clinical studies established a clear link between lung cancer progression and alterations in intra- and extramedullary hematopoiesis, leading to emergency myelopoiesis at the expense of megakaryocyte/erythroid and lymphoid differentiation. These observations affirm that a continuous crosstalk between solid cancers such as lung cancer and the bone marrow niche (BMN) must take place. However, the BMN, encompassing hematopoietic stem and progenitor cells, differentiated immune and stromal cells, remains inadequately explored in solid cancer patients. Subsequently, no clear consensus has been reached on the exact breadth of tumor installed hematopoiesis perturbing cues nor their predictive power for immunotherapy. As the current era of single-cell omics is reshaping our understanding of the hematopoietic process and the subcluster landscape of lung TIMs, we aim to present an updated overview of the hierarchical differentiation process of TIMs within the BMN of solid cancer bearing subjects. Our comprehensive overview underscores that lung cancer should be regarded as a systemic disease in which the cues governing the lung tumor-BMN crosstalk might bolster the definition of new biomarkers and druggable targets, potentially mitigating the high attrition rate of leading immunotherapies for NSCLC.

Reparative osteogenesis in mandible in cases of filling a bone defect with hydroxyapatite-containing osteotropic material and injecting the surrounding soft tissues with thymalin: experimental and morphological study.

Aim of the study was to identify the morphological features of reparative osteogenesis in the lower jaw bone of rats in cases of filling a bone defect with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT") and injecting the surrounding soft tissues with thymalin. Materials and Methods: An experiment was conducted on 48 mature rats of the WAG population weighing 160-180 grams which were divided into four groups. Group 1 included 12 rats with a simulated holey defect in the lower jaw. Group 2 included 12 rats with a simulated holey defect in the lower jaw followed by its closure with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT"). Group 3 included 12 rats with a simulated holey defect in the lower jaw with injecting the surrounding soft tissues with thymalin. Group 4 included 12 rats with a simulated holey defect in the lower jaw followed by its closure with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT") and injecting the surrounding soft tissues with thymalin. The material for the morphological study was a fragment of the lower jaw from the area of the simulated holey defect. Histological, morphometric and statistical research methods were used. Results: In this study, it was shown by the authors an activation of reparative osteogenesis in the lower jaw under conditions of simultaneous filling the bone defect with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT") and injection the surrounding bone defect soft tissue with thymalin. Stimulation of reparative osteogenesis in the lower jaw of rats occurred due to rapid cleaning of the bone defect cavity from necrotic tissues and hematoma fragments; a decrease in the number of neutrophil leukocytes, an increase in the number and morphofunctional state of monocytes, macrophages, lymphocytes, cells of fibroblastic differon; balanced change (increase or decrease) in the number and morphofunctional state of bone forming osteoblasts and bone resorbing osteoclasts depending on the stage of reparative osteogenesis; activation of hematopoietic processes in lamellar bone tissue from the regenerate; activation of bone tissue mineralization processes. Conclusions: Thymalin injection in the soft tissues surrounding the bone defect in the lower jaw, filled with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT"), significantly stimulates the process of reparative osteogenesis, which makes it possible to recommend this technique in dentistry for treatment the patients with mandible bone tissue defects.

Characterization of the effects of Chinese peony (Radix paeoniae Alba) and its active ingredients on the hematopoietic function of the Chinese mitten crab (Eriocheir sinensis)

Hematopoietic tissue (HPT) is crucial for the proliferation and release of newly produced hemocytes during infection in crustaceans. Very few studies have reported how herbs affected the hematopoietic function of crustaceans. Radix paeoniae Alba is a candidate immunopotentiator herb with the potential to be a blood-tonifying drug. In this study, the effects of Radix paeoniae Alba and its monomers (paeoniflorin, albiflorin, and paeonol) on HPT and hemocytes of Eriocheir sinensis were evaluated. After feeding them commercial diets containing different ingredients for three weeks, the HPT development was determined via morphological observation and hematopoietic tissue body index (HTBI) calculation. The count and classification of hemocytes were evaluated using the hemocytometer and flow cytometer. The expression of hematopoietic factor astakine, transglutaminase (TGase), and marker genes for different types of hemocytes (KPI and SOD) and undifferentiated HPT cells (PCNA) were detected using real-time quantitative PCR (qRT-PCR) assay. The results indicated that the HTBI in the Radix Paeoniae Alba, paeoniflorin, and albiflorin groups increased by 114.96%, 111.42%, and 112.50%, which were higher than the control group. The Radix Paeoniae Alba, paeoniflorin, albiflorin, and paeonol groups had higher proportions of ovoid lobules than the control group, especially in the Radix Paeoniae Alba group. The total hemocyte count (THC) of the crab in the Radix Paeoniae Alba, paeoniflorin, and paeonol groups were 8.12, 9.69, and 8.57×106 ind/mL, respectively, which were higher than the control group. Furthermore, all experimental groups showed a higher proportion of granulocytes than the control group, with increased astakine protein being simultaneously detected in the HPT. The qRT-PCR results showed a relatively higher KPI expression in all the experimental groups, and also higher SOD mRNA expression in the Radix Paeoniae Alba, paeoniflorin, and paeonol groups, as compared with the control group. Therefore, these results implied the potential effect of Radix Paeoniae Alba and its monomers on the hematopoietic function of E. sinensis. However, due to the complex ingredient composition in Radix Paeoniae Alba and their different activities in the hematopoietic process, further research needs to be conducted in the future.

Early Hematopoietic Reconstitution Status after Haploidentical Transplantation in AML Patients Is Indicative of Early Complications

Objective To investigate the early hematopoietic reconstruction process of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-allo-HSCT) in patients with acute myeloid leukemia, and to explore its correlation with the occurrence of early complications after transplantation. Methods A retrospective analysis was performed on the clinical information of 187 AML patients who underwent haploidentical allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from January 2017 to December 2022, and all of these patients achieved complete remission before transplantation. The results of pre-transplantation-7d-after-tranplantation+14d blood routine were analyzed. The occurrence of aGVHD within 100 days after transplantation was the primary outcome event, and CMV infection within 60 days was the secondary outcome event. The diagnosis and grading of aGVHD is described in Glucksberg and MAGIC. R-4.2.0 statistical software was used for statistical analysis. Results A total of 187 AML patients who underwent haploid transplantation after achieving complete remission were included, with a median age of 35 (27-55) years, including 105 male patients (56.31%) and 82 female patients (43.69%). All patients were grouped into aGVHD patients according to different risk levels: (1) There were differences between the I~IV°aGVHD group and the patients without aGHVD (100 versus 87 patients) in the early post-transplantation plt and WBC absolute levels, and the I~IV°aGVHD group showed a lower plt trend in 1d and 2d, and a higher WBC level (0.08×10 9/L vs 0.07×10 9/L, p=0.036) at 10 days. (2) Compared with patients without aGHVD (70 versus 87 cases), the former showed lower plt levels (62.5×10 9/L vs 80×10 9/L, p=0.029) in 1d and higher WBC levels (0.03×10 9/L vs 0.02×10 9/L, p=0.047; 0.11×10 9/L vs 0.07×10 9/L, p=0.033) in 9d~10d), the Hb level was lower at 1d~3d (91g/L vs 99g/L, p=0.047; 91g/L vs 97.5g×109/L, p=0.039; 89.5g/L vs 95.5g/L, p=0.013). (3) Compared with patients without aGHVD (33 versus 87 patients), the III~IV°aGVHD group showed lower plt levels (60×10 9/L vs 74×10 9/L, p=0.006; 48×10 9/L vs 52×10 9/L, p=0.018; 26×10 9/L vs 36.5×10 9/L, p=0.003) in 1~3d, and high WBC level (0.04×10 9/L vs 0.02×10 9/L, p=0.025; 0.14×10 9/L vs 0.07×10 9/L, p=0.008) showed in 10 days, and lower Hb level in 1d~3d (89g/L vs 99g/L, p=0.047; 89g/L vs 97.5g/L, p=0.039; 83g/L vs 95.5g/L, p=0.013). Based on the maintenance of platelets at 20×109/L for 3 days after transplantation, the cumulative incidence of 100 days III~IV°aGVHD in the ≤3d group was higher (63% vs 30%, p=0.015). Univariate analysis showed that the absolute value of 1~3d plt after transplantation was low, and the PLT maintained at 20×10 9/L after HSCT was short, which was a risk factor for the occurrence of aGVHD. Group analysis of CMV occurring within 60 days showed that in the early post-transplantation period, patients in the non-CMV group had higher absolute platelet values (63.50×10 9/L vs 47.00×10 9/L, p=0.03) than patients in the CMV group at 0 days. Age, pretreatment regimen, transplant type, aGVHD prevention regimen, time to first PLT infusion after transplantation, absolute value of 0 d platelets, and platelet transfusion efficiency were included in univariate and multivariate analysis, and multivariate analysis showed that pretreatment regimen (p=0.017, 1.002 [0.606-0.953]) and transplant type (p&amp;lt;0.001, 0.264 [0.147-0.476]) were independent risk factors affecting the occurrence of CMV. No correlation between platelet transfusion efficiency and PLT infusion frequency and CMV was found. Conclusion Early hematopoietic reconstruction after transplantation in AML-CR patients who received haploid transplantation has certain indicative significance for the occurrence of early complications, and its indicative significance becomes more significant with the increase of aGHVD degree.

CCL1 As a Biomarker of Engraftment Syndrome of Hematological Stem Cell Transplantation

BACKGROUND Many complications occur in the practice of hematopoietic stem cell transplantation, especially those presenting with fever, which can be caused by infection as well as engraftment syndrome (ES), which is difficult to distinguish. The mechanism of ES is unknown, and no characteristic biomarkers have been identified. METHODS We attempted to identify cytokines specific to the engraftment syndrome by cytokine array analysis of sera from 7 patients who underwent HSCT at our institution from January 2019 to March 2022 and who developed fever between 1 week before and the day of engraftment. Cases in which pathogens were detected in blood culture at the time of fever were diagnosed as infections, and cases in which blood culture was negative or clinically treated as engraftment syndrome or fever associated with engraftment were diagnosed as engraftment syndrome. Cases that did not present with fever from infusion to engraftment were used as negative controls. RESULTS. Three of the seven patients had fever due to infection and four had fever due to engraftment syndrome. Median age was 41 (21-62) years, 5 males and 2 females. Four patients had acute leukemia, one had chronic myelomonocytic leukemia, and two had nonhematologic tumors. The donors were blood related in 3 cases, unrelated in 3 cases, and cord blood in 2 cases. Pretreatment was myeloablative (MAC) in 2 patients and reduced intensity pretreatment (RIC) in 5 patients. Cytokine arrays identified five cytokines that were elevated in the ES group. Of these, cytokine The cytokine CCL1 (I-309) tended to be elevated in the ES group (p=0.06). The validity of CCL1 with respect to the diagnosis of fever of engraftment was examined using sera from another 16 hematopoietic stem cell transplant cases performed at the same period, and the results showed that CCL1 was only mildly elevated in cases diagnosed with infection, regardless of the elevated values of fever and inflammatory response, but tended to be elevated in fever of engraftment (area under ROC curve: 0.74 (95% confidence interval 0.422-1)). CONCLUSIONS. CCL1 was identified as a cytokine specific for ES, indicating that CCL1 may be useful in differentiating ES from infection. CCL1 is mainly secreted by T lymphocytes and its oversecretion during the hematopoietic recovery process may be involved in immune activation and the engraftment syndrome.

The influence of sodium selenite and the phytopreparation Emelin on indicators of natural resistance, safety and laying hen product quality

Food products produced in Ukraine must meet safety and quality indicators in accordance with regulatory and legal acts and provide ordinary consumers with nutrients. Phytoadditives are widely used in most countries of the world, including Ukraine, of great importance in the technological process of growing agricultural animals, especially poultry. The aim of the work was to study the influence of sodium selenite and the herbal preparation "Emelin" on indicators of natural resistance, safety and quality of products of laying hens. To obtain scientific information, the following methods of observation were used: biological, hematological studies, statistical. 260 laying hens of the "Adler silver" breed at the age of 6–11 months were used for experimental research (tests). Optimum sanitary and hygienic conditions for feeding and keeping the birds were created. It was established that the phytosupplement "Emelin" in combination with sodium selenite stimulates hematopoietic processes, which is confirmed by an increase in the hemoglobin content by 12.1-19.5% (p&lt;0.01) and erythrocytes by 11.5-19.9% (p&lt;0 .01) in the peripheral blood of laying hens compared to the control group. The leukocyte content index and erythrocyte sedimentation rate during the research were within the physiological norm in all experimental groups. In the laying hens of the second experimental group, which were fed sodium selenite and the phytopreparation "Emelin", an increase in the weight of eggs compared to the control group was observed by 2.15- 2.51% (р&lt;0.05. It should be noted that with an increase in the weight of the eggs increases and the weight of its constituent parts increases. The use of feed enriched with sodium selenite in the amount of 0.25 mg/kg of dry matter of compound feed and phytopreparation "Emelin" made it possible to increase by 13.5% the number of carcasses of the 1st commodity category in the first and second experimental groups compared with the control (p&lt;0.05), and with the combined use of sodium selenite and the phytonutrient "Emelin" in the third experimental group - by 19.6% (p&lt;0.05), respectively. In addition, the use of feeds enriched with sodium selenite and the phytopreparation "Emelin" allowed not only to minimize the number of non-standard carcasses, but also the possibility of their appearance, which is confirmed by the results of the absence of non-standard carcasses in the third experimental group. The overall economic efficiency of the comprehensive use of the combination of sodium selenite and the herbal preparation "Emelin" was mainly determined by the increase in productivity (egg production) of laying hens, as well as the cost of the herbal preparation, which was (0.97 UAH/kg) and sodium selenite (3.5 UAH/kg) . Thus, feeding the sodium selenite complex in the form of an organic form, at a dose of 25 μg/kg, and the herbal phytopreparation "Emelin", at a dose of 7.0 ml per experimental group, had a positive effect on the productivity, preservation and quality of the carcasses of laying hens. Key words: laying hens, keeping conditions, conservation, productivity, egg production, morphological indicators of blood, phytopreparation, ecologically harmless, food safety, consumer.

Bioinformatics analysis of primary biliary cholangitis key genes and molecular mechanisms

Objective: To extract the differentially expressed key genes of primary biliary cholangitis (PBC) using bioinformatics methods, so as to provide information for further study into the mechanism. Methods: The GSE119600 dataset was downloaded from the GEO database to obtain differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Protein-protein interaction (PPI) network reconstruction, Cytoscape software visualization, and core gene screening were performed. The area under the receiver operating characteristic curve (ROC AUC) was used to assess the diagnostic effectiveness of genes and plot the pROC software package. The x-Cell software was used to calculate the enrichment score of 34 immune cells in each sample. Finally, four key genes (PSMA4, PSMA1, PSMB1, and PSMA3) were selected. Blood samples were analyzed using the qPCR method. Results:: A total of 373 immune-related differentially expressed genes were identified. Eight genes (PSMC6, PSMB2, PSMB1, PSMA3, PSMA4, PSMA1, PSMD7, and PSMB5) were screened from the 178 nodes and 596 edges as hub genes of the PPI network, which were significantly related to amino acid metabolism, hematopoietic stem cell differentiation, cell cycle, and immune processes. PSMA4, PSMA1, PSMB1, and PSMA3 were defined as immunological biomarkers for PBC with an AUC value of the ROC curve > 0.7. Immunoinfiltrating cell analysis showed that the proportion of eosinophils was significantly higher in PBC patients compared to the control group, whereas the proportion of CD4+ memory T cells, plasma cells, Th2 cells, and cDC cells was significantly lower in PBC patients than the control group. Plasma cells were associated with all four immunological biomarkers. Seven PBC patients and seven healthy subjects were selected for peripheral blood qPCR validation, which demonstrates that PSMB1, PSMA3, PSMA1, and PSMA4 levels were significantly lower in PBC patients than healthy subjects, with a statistically significant difference. Conclusion:: Bioinformatics screened eight key genes, of which four were key immunological markers and may serve as a basis for clinical diagnosis and mechanism exploration.

Understanding blood development and leukemia using sequencing-based technologies and human cell systems.

Our current understanding of human hematopoiesis has undergone significant transformation throughout the years, challenging conventional views. The evolution of high-throughput technologies has enabled the accumulation of diverse data types, offering new avenues for investigating key regulatory processes in blood cell production and disease. In this review, we will explore the opportunities presented by these advancements for unraveling the molecular mechanisms underlying normal and abnormal hematopoiesis. Specifically, we will focus on the importance of enhancer-associated regulatory networks and highlight the crucial role of enhancer-derived transcription regulation. Additionally, we will discuss the unprecedented power of single-cell methods and the progression in using in vitro human blood differentiation system, in particular induced pluripotent stem cell models, in dissecting hematopoietic processes. Furthermore, we will explore the potential of ever more nuanced patient profiling to allow precision medicine approaches. Ultimately, we advocate for a multiparameter, regulatory network-based approach for providing a more holistic understanding of normal hematopoiesis and blood disorders.

Zinc and aging: a narrative review of the effects on hematopoiesis and its link with diseases.

There has been a global increase in the older population in recent decades and, as age advances, complex metabolic and epigenetic changes occur in the organism, and these may trigger some health complications commonly found among this population. Additionally, several changes occur in older people that can reduce the dietary intake or the process of nutrient absorption. In this way, tissues with high nutrient requirements are more affected. Hematopoiesis is the process of formation, development, and maturation of blood cells and is a process with a high turnover. This high demand makes the integrity of the hematopoietic process susceptible to various factors that impair physiological function, such as aging and micronutrient bioavailability. Among these micronutrients, Zinc is considered an important micronutrient, playing diverse roles across various tissues and cell types. Some of the alterations in hematopoiesis that appear as a consequence of aging and due to insufficient micronutrient intake are well described in the literature; however, not much is known about how zinc deficiency contributes towards the development of diseases seen in aging. Considering the importance of zinc to act on several biological processes, this narrative review discusses several studies related to the physiological requirements, deficiency, or excess of zinc, including studies in experimental models and humans, and aimed to shed light on the relationship between zinc and the regulation of hematopoietic tissue, exploring possible links between this mineral with common disorders that appear during aging.

Research on the specific toxicity of the drug “BTF plus” – a means for nor-malizing metabolic processes in animals and poultry

Laboratory studies were conducted to determine the subacute toxicity and tolerance of the veterinary drug “BTF plus” on white rats, dogs, and guinea pigs. The “BTF plus” preparation is a complex vitamin and mineral preparation based on butophosphane, L-carnitine, and cyanocobalamin, which normalizes and corrects metabolic processes in animals and poultry. The drug is used for various types of animals and poultry as a stimulating, tonic and general strengthening agent for obstetric pathologies (difficult births, postpartum complications, paresis, eclampsia, sexual cycle disorders); metabolic disorders caused by irrational feeding, malnutrition, asthenic syndrome, etc.; anemia with helminthiasis; secondary anemias, as an additional means in the treatment of magnesium and calcium deficiency; to increase muscle activity, with significant loads, overstrain and exhaustion in animals; to increase the body's resistance to various pathogens; to stimulate growth, development and live weight gain in young animals and poultry; as an additional means in the treatment of diseases caused by various factors (infectious and non-infectious origin). When administered subcutaneously to rats, the drug “BTF plus” under the conditions of a subacute toxicological experiment in doses (by absolute weight of the drug) of 200.0, 1000.0, and 2000.0 mg/kg of body weight does not cause hemo-, hepato- and nephrotoxic effects on the body of laboratory animals, but on the contrary, stimulates hematopoietic processes and has a positive effect on metabolic processes in their body. Subcutaneous administration of the drug “BTF plus” to dogs in doses (by absolute weight of the drug) of 200.0, 1000.0, and 2000 mg/kg of body weight for ten days does not cause hepatotoxic and nephrotoxic effects on the body under the conditions of a subacute toxicological experiment, but on the contrary, stimulates hematopoietic processes and has a positive effect on metabolic processes in the body of target animals. The tolerance of guinea pigs to the drug “BTF plus” was studied. It was established that the drug does not hurt the body and behavior of ants when administered subcutaneously in doses (based on the absolute weight of the drug) (5000,0–15000,0) mg/kg of body weight. Further studies will be the next stage of pre-registration tests aimed at studying the embryotoxic and carcinogenic effect of “BTF plus”, which is mandatory material of the “Safety and residue studies” section of the dossier for this medicinal product.