Hematopoietic Function Of Bone Marrow Research Articles

Association of bone mineral density with peripheral blood cell counts and hemoglobin in Chinese postmenopausal women

Osteoporosis (OP) is a metabolic bone disease that can cause structural changes in bone marrow cavity. Bone marrow is the hematopoietic organ of adults. Accumulating evidence has shown a close connection between bone marrow hematopoietic function and bone formation. Some studies have revealed that OP is associated with hematopoiesis. However, the relationship is not definite.This study aimed to evaluate the association between peripheral blood cell counts (white blood cells [WBC], red blood cells [RBC], platelets [PLT]), hemoglobin [HGB], and bone mineral density [BMD]) in a sample of Chinese postmenopausal women. This is a retrospective study involving 673 postmenopausal women cases. The BMD of lumbar spine and left hip joint were measured by dual-energy X-ray absorptiometry. The levels of blood cell counts and HGB were measured and analyzed.The study results showed the WBC, RBC, PLT, and HGB levels of postmenopausal women in the OP group were all higher than those in the non-osteoporosis group. Spearman linear trend analysis and partial correlation analysis demonstrated that BMD was negatively correlated with WBC, RBC, PLT, and HGB in postmenopausal women.Due to the differences between different countries and races, and there are few studies on the association of BMD with peripheral blood cell counts and HGB in Chinese Postmenopausal Women. Therefore, more large sample studies are needed.

Evaluation of bone marrow hemopoiesis and the elemental status of the red bone marrow of chickens under introduction of copper to the organism.

The role of chemical elements in an organism is versatile and multifunctional. However, you should pay attention to the reaction of the organism on the introduction of chemical elements with different biological roles, which is predetermined by the physiological role of organs and body systems. These include the red bone marrow, which primarily responds to endogenous and exogenous factors by its functional significance. Analyzing the myelogram of birds after the various ways of copper NP introduction into the body and the different dosages, we found that, by the end of the experiment, the total numbers of bone marrow cells in all groups were lower than the initial values: in the second group-12.54% lower (p < 0.05), in third-26.32% lower (p < 0.001), for the fourth-14.75% lower (p < 0.05), with exception for the first experimental group where this index was 45.51% higher (р < 0.001). We revealed the following changes in the peripheral blood: the hemoglobin content by the end of the experiment was significantly higher than the initial values: by 18.63% for the first group (p < 0.01); 28.61% higher in the third group (p < 0.001); and 15.76% higher for the fourth (p < 0.01), except the animals of the second group (3.23% lower). The concentration of erythrocytes in all groups was higher than that of the background: by 24.56% (p < 0.001), by 3.37%, by 26.18% (p < 0.001), and by 14.85% (p < 0.01), respectively; the leukocyte concentration in the first group was 39.63% higher (p < 0.001), it remained at the level of the initial values in the other groups. The erythrocyte sedimentation rate in all groups increased by 2.4, 4.0, 2.01, and 1.86 times (p < 0.001), respectively. We revealed that the introduction of copper into an organism in the form of nanopowder both with feed and intramuscularly significantly caused an increase of the content of such elements as arsenic, copper, and silicon and a decrease of calcium, potassium, magnesium, phosphorus, boron, cobalt, iodine, lithium, sodium, zinc, tin, and strontium in the marrowy aspirate. Moreover, compared with the first group (p < 0.01), increasing doses of nanopowders caused a significant rise in the arsenic and tin concentrations and a decline of iodine and strontium. We found that copper nanoparticles ambiguously affect the bone marrow hemopoiesis of poultry; increasing the dose and changing the type of introduction activating the bone marrow hematopoietic function, in particular, granulocyto-, megakaryocyto-, and erythropoiesis.

Iris extramedullary hematopoiesis in choroidal melanoma.

PURPOSE:Extramedullary hematopoiesis (EMH) usually occurs in patients with loss of bone marrow hematopoietic function, and in a vast majority of cases, it involves the liver, the spleen, or the lymph nodes. We report EMH in the iris of patients enucleated for choroidal melanoma (CM).METHODS:We report a series of three patients with CM, two treated with primary enucleation and one with secondary enucleation.RESULTS:Histopathology revealed EMH in the iris of all patients.CONCLUSION:EMH of the iris can be associated with CM in the absence of any hematological or systemic disorders. To the best of our knowledge, our work is the first report of this abnormal histopathological finding.

Hepatic protein synthesis and morphological parameters in blood of rats under oxidative stress and action of feed additive Butaselmevit-plus

The intensive development of animal husbandry at the present stage requires new approaches to organizing the feeding of farm animals and the introduction of modern feed additives, which are not normally used purely as feed, but are deliberately added to feed or water to improve their quality, increase productivity and animal welfare. To prevent the development of oxidative stress in animals, we used the feed additive "Butaselmevit-plus", which in its composition contains the fruits of milk thistle, selenium, methionine and vitamins A, E and D3. The aim of the study was to investigate the effect of feed additive Butaselmevit-plus on blood morphological parameters and protein synthesis of rat liver under tetrachloromethane poisoning. For research, we used Wistar male rats, which were divided into three groups of 20 animals each. Control rats were intact. The first and second experimental group of rats were administered tetrachloromethane. Experimental intoxication in animals was performed by twice (after 48 h) intragastric administration of tetrachloromethane at a dose of 0.1 ml per 100 g of rat body weight in the form of a 50% oil solution. Experimental group R2 was fed a feed additive of Butaselmevit-plus for a dose of 0.1 g per 100 g of body weight together with the feed for experimental toxicosis for 30 days. On the basis of the conducted researches positive effect of feed additive "Butaselmevit-plus" on the organism of rats, which were intoxicated with tetrachloromethane, is shown, which is shown by normalization of hematological parameters and protein synthesis of liver function. Restoration of hematopoietic function of bone marrow of rats by intoxication with tetrachloromethane is due to the fact that the feed additive "Butaselmevit-plus" contains in its composition fruits thistle, which have a high level of vitamins A and K, and trace elements, namely: Ferum, Cuprum and Cobalt that are directly involved in hematopoiesis. When feeding Butaselmevit-plus as feed supplement, the number of red blood cells in the blood of the second experimental group of rats was higher than that of the first experimental group, but the control values reached only on the 30th day of the experiment. When using the feed additive Butaselmevit-plus in rats under conditions of oxidative stress development, the leukocyte count decreased to the optimum level.

A Randomized Phase 2 Study Comparing Acalabrutinib with or without Obinutuzumab in the Treatment of Early Stage High Risk Patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

A Randomized Phase 2 Study Comparing Acalabrutinib with or without Obinutuzumab in the Treatment of Early Stage High Risk Patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Comparative evaluation of osteogenic activity and the effect on hematopoietic function of bone marrow of fractions of Saussurea controversa and Filipendula ulmaria extracts in experimental osteomyelitis

The aim of the work was to study the effect of fractions from Saussurea controversa and Мeadowsweet extracts on hemopoiesis and regeneration of bone tissue, which are the main target indicators in experimental osteomyelitis.Materials and methods. In the experiment we used butanol, water and element-organic fractions from the Saussurea controversa extract as well as ethyl acetate, butanol and water fractions from the Мeadowsweet extract, obtained by liquid extraction of the extracts from corresponding plants with the help of organic solvents. After modeling osteomyelitis of the right femur in rats and course treatment for 28 days, the state of bone marrow hemopoiesis was evaluated and morphological examination of the affected limb was performed.Results. The butanol fraction (at a dose of 10 mg/kg) containing flavonol glycosides, the water fraction (at a dose of 80 mg/kg) containing polysaccharides in its composition and the element-organic fraction (at a dose of 10 mg/kg) represented by organic calcium showed the highest osteogenic activity in the Saussurea controversa extract. The water fraction from the Meadowsweet extract (at a dose of 50 mg/kg) demonstrated pronounced hemopoietic activity due to stimulating erythro-, granulo- and lymphopoiesis in the bone marrow of rats with experimental osteomyelitis.

Peculiarities of the bone-marrow hemopoiesis, peripheral blood, and the elemental status of the red bone marrow of poultry resulted from copper introduction

Metals in an electrically neutral form produced with the method of vacuum condensation from metals are finely dispersed powders. The role of chemical elements in an organism is versatile and multifunctional. However, it is necessary to pay attention to the reaction of an organism on the introduction of chemical elements with different biological roles, which is predetermined by the physiological role of organs and body systems. These include the red bone marrow, which primarily responds to endogenous and exogenous factors by its functional significance. In order to study the influence of copper nanopowders on hematopoiesis of birds, we selected 150 10-day-old broiler chickens which formed 5 groups by the method of analogs (n = 30). All said above allows us to conclude that copper nanoparticles ambiguously affect the bone-marrow hemopoiesis of poultry; increasing the dose and changing the type of introduction activate bone marrow hematopoietic function, in particular, granulocyto-, megakaryocyto-, and erythropoiesis. Different dosages and ways of introduction of copper nanoparticles, in our opinion, ambiguously affect the bone-marrow hemopoiesis of poultry when using copper in doses of 1.7 mg/kg of feed, which is 50% of the daily needs of the organism. E A Sizova et al. proved a stimulating effect of copper nanoparticles in the same dosage on liver cells of chicks.

Effect of enteral nutrition and probiotics on inflammatory factors and immune function in aplastic anemia rats

Objective To investigate the effect of enteral nutrition and probiotics on inflammatory factors and immune function in aplastic anemia (AA) rats. Methods AA rats model were established by intraperitoneal injection of fluorouracil and lavage Maryland, and the successful AA rats model were randomly divided into model group, enteral nutrition group, probiotics group and combination group, 10 rats in each group. Another 10 Wistar rats were selected as blank group. Rats in the blank group and model group were given saline lavage (same volume 0.9% NaCl), rats in the enteral nutrition group were given Peptisorb nutrient solution [10 g/(kg·d)] by lavage, rats in the probiotics group were given live Clostridium butyricum [2 g/(kg·d)] by lavage, and rats in the combination group were given Peptisorb nutrient solution [10 g/(kg·d)] and live Clostridium butyricum [2 g/(kg·d)] by lavage for 4 weeks. The pathological structure of the bone marrow were observed by HE staining, the contents of white blood cells (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (Hb) in blood cell were detected by analyzer, the levels of serum tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2) and interleukin-11 (IL-11) were detected by ELISA method, and the contents of CD4+, CD8+ and NKT cells were detected by flow cytometry instrument. Results The contents of WBC, RBC, PLT and Hb in the model group were significantly lower than that in the blank group, the contents of WBC, RBC, PLT and Hb in enteral nutrition group, probiotics group and combination group were significantly higher than that in the model group, and the combination group was better than the enteral nutrition group and probiotics group (P 0.05). The level of TNF-α and IL-2 were significantly higher and the IL-11 level was significantly lower in the model group than in the blank group, the level of TNF-α and IL-2 were significantly lower and IL-11 level were significantly higher in the enteral nutrition group, probiotics group and combination group than in the model group, and the combination group was better than the enteral nutrition group and probiotics group (P 0.05). The contents of CD4+ and NKT cells were significantly lower and the CD8+ cells was significantly higher in the model group than in the blank group, the level of CD4+ and NKT cells were significantly higher and CD8+ cells were significantly lower in enteral nutrition group, probiotics group and combination group than in the model group, and the combination group was better than the enteral nutrition group and probiotics group (P 0.05). Conclusion Compared with normal consumption or oral glucose, the enteral nutrition combined with probiotics can reduce inflammatory response and improve bone marrow hematopoietic function and immune function in AA rats. Key words: Aplastic anemia; Enteral nutrition; Probiotics; Inflammation factors; Immune function

Treatment progress of elderly patients with acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a special subtype of acute myeloid leukemia characterized by an increase of abnormal promyelocytic cells, failure of bone marrow hematopoietic function accompanied by the chromosome translocation t(15;17). APL has become one of the best paradigms of successful molecule targeted therapy with the development of treatments; however, the overall survival (OS) of elderly APL patients was not optimistic. The discovery of all-trans retinoic acid, arsenic and new drugs has provided new therapeutic choices for elderly patients with APL. This article reviews the treatment progress of elderly patients with APL. Key words: Leukemia, promyelocytic, acute; Elderly; Treatment

Compatibility effects of ginseng and Ligustrum lucidum Ait herb pair on hematopoietic recovery in mice with cyclophosphamide-induced myelosuppression and its material basis

BackgroundGinseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines in treating myelosuppression formula. The present study was designed to profile effect of G and LLA herb pair (G-LLA) on myelosuppressed mice. MethodsThe mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitor cell culture and peripheral blood count, and serum hemopoietic factors were tested by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was used to measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg1, Re, Rb1, Rc, Rb2, Rb3, Rd, Rk3, Rh4, 20 (S)-Rg3, 20 (R)-Rg3, Rk1, Rg5, salidroside, and so on. ResultsG, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cells of myelosuppressed mice (P < 0.01). They significantly increased the colony quantity of colony-forming unit–granulocyte macrophage, burst-forming unit−erythroid, colony-forming unit−erythroid, and colony-forming unit−megakaryocyte and amount of G2/M and S phase cells (P < 0.01). They also significantly decreased the amount of hematopoiesis-related cytokines (P < 0.01). The content of chemical components in G-LLA changed, and the change of rare saponin was the most obvious. ConclusionThese results show that G-LLA herb pair might produce synergistic or complementary compatibility effects on bone marrow suppression after chemotherapy. It suggests that the substance basis of G-LLA for treating bone marrow suppression may be effective chemical components.

PO-150 Different gradient altitude training on the impact of RET、 EPO and RBC

Objective This study is based on the regional characteristics of Guizhou Province, athletes living in the subplateau and training in the plateau-plain and the high plateau-plain.The effects of altitude training on hematological indexes of EPO、RBC and RET.To evaluate the two training modes is more beneficial to endurance runners and explore which one is better. To provide scientific reference for sports training practice.&#x0D; Methods Twenty male endurance runners and divided into two groups (all living on subplateau )： plateau-plain group and high plateau-plain。One group reached to the 1900 m plateau and the other one reached to the 2900 m plateau,training 3 weeks ；The two groups then reached to the plain for 3 weeks of training。Finally arrived at the sub-plateau for performance testing.Using multivariate analysis of variance to test significant differences between groups，The data are represented by the standard deviation of the average（）.P＜0.05 is a significant difference，P＜0.01 is a very significant difference.&#x0D; Results 1 EPO&#x0D; There is no significant difference in EPO between 1900m plateau and 2900m plateau athletes.at the end of plain the amplitude of elevation and basic value of high altitude group is more than that of high altitude group.&#x0D; 2 RBC &#x0D; Comparison of RBC between plateau group and high altitude group during the period of plateau, there is significant difference at the end of plateau (P=0. 049 &lt; 0. 05), and there is a significant difference between the two groups at the end of plateau training (P=0. 043 &lt; 0. 05). The change trend of the two groups is the same, but the increasing is more than the high plateau group, and the decreasing is relatively less during the plain period, and it showed an upward trend at the end of the plain period.&#x0D; 3 Ret&#x0D; There is significant difference in RET between the two groups (P=0. 018 &lt; 0. 05) when the endurance runners arrived at the plateau at the first weak. RET at 2900m altitude is significantly higher than that at 1900m altitude, and at the end of the plateau, the increase of RET in the high plateau group is still higher than that in the plateau group. There is no significant difference between the two groups during the plain period.&#x0D; Conclusions The influence of altitude training on the EPO of the SUBPlateau athletes is more profound than that of the plateau group. During the first week of plateau, EPO decreased significantly, but it fluctuated up and down later, and the two groups are on upward trend during the period of plain. However, the percentage of elevation in the plateau is higher in the high altitude group than in the high altitude group.&#x0D; After plateau training, chose 2900m plateau for training, and the hematopoietic function of bone marrow is improve greatly, nutrition supplement should be paid attention to after plateau training. To prevent the effect of RBC reduction.

The mechanisms of sulfated polysaccharide drug of propylene glycol alginate sodium sulfate (PSS) on bleeding side effect

Propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide derivative, has been used as a heparinoid drug to prevent and treat hyperlipidemia and ischemic cardio-cerebrovascular diseases in China for 30 years. But its bleeding risk should not be overlooked. Here we clarified the reasons and mechanism leading to bleeding side effect of PSS. It was found that PSS fractions with low mannuronic acid (M)/guluronic acid (G) ratio and high molecular weight (Mw) can excessively extend activated partial thromboplastin time (APTT) and thrombin time (TT), over-inhibit the thrombin (FIIa) activity mediated by anti-thrombin III (ATIII) to induce bleeding risk. In addition, the fraction of low M/G ratio can suppress platelet aggregation mediated by adenosine diphosphate (ADP) and induce platelet reduction by improving platelet antibody (PA)-IgA/G in serum and by inhibiting or damaging the bone marrow hematopoietic function. And the fraction of high Mw can restrain the reticulated platelet (RP) production, then reduce mean platelet volume (MPV) and platelet-large cell counts or ratio, and finally decrease platelet amount by inhibiting or damaging the bone marrow hematopoietic function. In brief, PSS fractions with low M/G ratio and high Mw were the main reasons to bring about bleeding by excessively suppressing coagulant factors activities and weakening platelet function. Our results suggested that it is very necessary to control the M/G ratio and the range of Mw of PSS to guarantee its safety and effectiveness in clinical.

THE MORPHOLOGY OF CHRONIC POSTSTERNOTOMY OSTEOMYELITIS OF THE STERNUM, WHICH DEVELOPED AFTER CARDIOSURGICAL INTERVENTIONS

Discusses the pathological changes of bone tissue of the sternum in cardiac surgery patients with post-sternotomy chronic osteomyelitis of the sternum. It is established that in the pathological process involved informed of all the vessels and bone marrow of the sternum then the bone tissue. In the examined patients revealed the devastation of the bone marrow, accompanied by inflammatory exudative manifestations. Discovered damage to blood vessels, multiple foci of hemorrhage in the bone and muscle tissue, deposition of hemosiderin, a violation of hematopoietic function of bone marrow. A significant number of sequesters. Sequestered most of trabeculae inside the bone with the transition to the cortical plate. In 3 of 4 examined patients, they are mainly localized in the region of the surgical incision throughout its length. In some cases it was noted the defeat of the periosteum and muscle, which leads to the formation of fistulas. The result is a fistulous form of chronic osteomyelitis. On the basis of pathomorphological picture was revealed that 3 patients had the place exogenous mechanism of infection of the surgical field.

6,7,3′,4′-Tetrahydroxyisoflavone improves the survival of whole-body-irradiated mice via restoration of hematopoietic function

Purpose: 6,7,3′,4′-tetrahydroxyisoflavone (T3) is a novel chemically synthesized compound reported in our previous study. This study was designed to explore the radioprotective effect of T3, and if so, its potential mechanisms.Materials and methods: KunMing mice were exposed to various doses of γ irradiation (60 Co) after being treated with dimethyl sulfoxide (DMSO) or T3. Briefly, survival rate, dose reducing factor (DRF), body weight change (%), spleen index (SI) and thymus index (TI) of irradiated mice with or without different doses of T3 treatment were evaluated routinely. The hematopoietic function of bone marrow was emphatically investigated. In vitro experiments were performed to observe the protective effect of T3 on irradiated human lymphocyte AHH-1 cells by cell viability or flow cytometry (FCM) assays.Results: A single dose of subcutaneous administration of T3 significantly improved the survival rate, and enhanced the restoration of hematopoietic function in irradiated mice. T3 also decreased the apoptosis of irradiated AHH-1 cells in vitro.Conclusions: T3 protected mice against lethal γ irradiation-induced injury probably through the restoration of hematopoietic function. This implied that T3 could be further developed as a radioprotector.

The prognostic value of neutrophil-lymphocyte ratio is superior to derived neutrophil-lymphocyte ratio in advanced gastric cancer treated with preoperative chemotherapy and sequential R0 resection: a 5-year follow-up.

AimThe role of neutrophil–lymphocyte ratio (NLR) and derived neutrophil–lymphocyte ratio (d-NLR) in outcome prediction is assessed in patients with advanced gastric cancer receiving preoperative chemotherapy in a 5-year follow-up cohort.Patients and methodsPatients undergoing preoperative chemotherapy and sequential R0 resection for advanced gastric cancer were enrolled from July 2004 to November 2011. Wilcoxon matched-pairs signed-rank test was used to evaluate the change of peripheral blood parameters. Receiver operating curve was used to identify the optimal cutoff values of NLR and d-NLR. Survival function was analyzed using Kaplan–Meier curves and Cox proportional hazard model.ResultsSignificant difference was found between baseline and post-chemotherapy blood parameters, including leukocytes, neutrophils, lymphocytes, NLR and d-NLR (all P<0.05). High baseline NLR group (NLR ≥2.230) had a significant shorter recurrence-free survival (RFS) (hazard ratio [HR] =1.814, 95% confidence interval [95% CI]: 1.112–2.960, P=0.015) and shorter overall survival (OS) (HR =1.867, 95% CI: 1.129–3.089, P=0.013) than those of the low baseline NLR group (NLR <2.230). High baseline d-NLR group (d-NLR ≥1.885) also had a shorter RFS (HR =1.805, 95% CI: 1.116–2.919, P=0.014) and shorter OS (HR =1.783, 95% CI: 1.091–2.916, P=0.019) than those of the low baseline d-NLR group (d-NLR <1.885). However, post-chemotherapy NLR and d-NLR showed no prognostic significance on RFS and OS (all P>0.05). Multivariate analysis showed that higher baseline NLR but not d-NLR was identified as an independent factor associated with worse RFS (HR =1.707, 95% CI: 1.042–2.797, P=0.034) and worse OS (HR =1.758, 95% CI: 1.058–2.919, P=0.029).ConclusionBaseline NLR and d-NLR may serve as convenient, easily measured prognostic indicators in advanced gastric cancer treated with preoperative chemotherapy and sequential R0 resection, especially to baseline NLR, which showed independent prognostic significance on RFS and OS, while post-chemotherapy NLR and d-NLR lost their usefulness due to the inhibition of bone marrow hematopoietic function. Patients with high baseline NLR and d-NLR values need multimodal therapy.

Pyruvate dehydrogenase kinase 1 is essential for transplantable mouse bone marrow hematopoietic stem cell and progenitor function.

BackgroundAccumulating evidence suggests that hypoxic areas in the bone marrow are crucial for maintenance of hematopoietic stem cells (HSCs) by supporting a quiescent state of cell cycle and regulating the transplantation capacity of long-term (LT)-HSCs. In addition, HSCs seem to express a metabolic profile of energy production away from mitochondrial oxidative phosphorylation in favor of glycolysis. At oxygen deprivation, hypoxia inducible factor 1α (HIF-1α) is known to induce glycolytic enzymes as well as suppressing mitochondrial energy production by inducing pyruvate dehydrogenase kinase 1 (Pdk1) in most cell types. It has not been established whether PDK1 is essential for HSC function and mediates hypoxia-adapting functions in HSCs. While the Pdk gene family contains four members (Pdk1-4), it was recently shown that Pdk2 and Pdk4 have an important role in regulating LT-HSCs.Principle findingsHere we demonstrate that PDK1 activity is crucial for transplantable HSC function. Whereas Pdkl, Pdk2, and Pdk3 transcripts were expressed at higher levels in different subtypes of HSCs compared to differentiated cells, we could not detect any major differences in expression between LT-HSCs and more short-term HSCs and multipotent progenitors. When studying HIF-1α-mediated regulation of Pdk activity in vitro, Pdk1 was the most robust target regulated by hypoxia, whereas Pdk2, Pdk3, and Pdk4 were not affected. Contrary, genetic ablation in a cre-inducible Hif-1α knockout mouse did not support a link between HIF-1α and Pdk1. Silencing of Pdk1 by shRNA lentiviral gene transfer partially impaired progenitor colony formation in vitro and had a strong negative effect on both long-term and short-term engraftment in mice.ConclusionsOur study demonstrates that PDK1 has broad effects in hematopoiesis and is a critical factor for engraftment of both HSCs and multipotent progenitors upon transplantation to recipient mice. While Pdk1 was a robust hypoxia-inducible gene mediated by HIF-1α in vitro, we could not find evidence of any in vivo links between Pdk1 and HIF-1α.

Research Progress on Pathogenesis of Aplastic Anemia

Aplastic anemia is a disease characterized by low bone marrow hematopoietic function and derease of whole blood cells caused by a variety of reasons. Its pathogenesis includes abnormality of hematopoietic stem cells (seed theory), hematopoietic microenvironment (soil theory) and immune function (such as worms theory). These 3 causes of disease interact each other and facilitate the development of aplastic anemia, thereby increase the complexity of the etiological diagnosis and uncertainty of treatment. On this basis, this review summarizes the latest research progress on the blood supply of bone marrow microcirculation in the hematopoietic microenvironment, stromal cells, cytokins, the immune function of dendritic cells, natural killer cells, T cell subgroup, the secretion of cytokines, cell signal transduction, and hematopoietic stem cell gene abnormality to provides the theoretic basis for the diagnosis and treatment of aplastic anemia.

Blood disorders typically associated with renal transplantation.

Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival.

Echinacoside improves hematopoietic function in 5-FU-induced myelosuppression mice

AimsWe aimed to investigate the effects of echinacoside (ECH) on hematopoietic function in 5-FU-induced bone marrow depression mice. Main methodsIn vitro, after stimulation with ECH, the proliferation ability of bone marrow (BM) cells and bone marrow stromal cells (BMSCs) derived from myelosuppression mice were assessed by CCK8 assay and morphology, respectively. In vivo, 5-FU-induced myelosuppression or control mice were intragastrically administrated with either ECH at 15mg/kg or the equal volume of normal saline daily for 12days before BM cells were isolated for colony-forming cell assay. Meanwhile, BMSCs were cultured for 4weeks before cells were observed for growth pattern, cell culture supernatants were collected for GM-CSF secretion by ELISA, and RNA of the cells were extracted for EPO and GM-CSF RT-PCR. BM cells or BMSCs stimulated with ECH for 24h or 48h were collected for protein extraction and Western blotting. Key findingsECH stimulated the growth of BM cells but not BMSCs derived from 5-FU treated mice. The intragastric administration of ECH in 5-FU treated mice could increase the number of total hematopoietic progenitor cells and GM progenitor cells to healthy control mice level, but not BFU progenitor cells. BMSCs from ECH treated myelosuppression mice grew more vigorously and expressed more GM-CSF, but not EPO. ECH activated the PI3K signaling pathway in 5-FU suppressed BM cells. SignificanceECH could improve the hematopoietic function of bone marrow in 5-FU-induced myelosuppression mice. ECH can be considered as an alternative effective therapy for patients during chemotherapy or HSC transplantation.

Effects and mechanism of iron overload on hematopoiesis in mice with bone marrow injury

To explore effects of iron overload on hematopoiesis in mice with bone marrow injury and its possible mechanism (s). C57BL/6 mice were divided into control, iron, irradiation, irradiation+iron groups. The iron-overloaded model of bone marrow injury was set up after mice were exposed to the dose of 4 Gy total body irradiation and (or) were injected iron dextran intraperitoneally. Iron overload was confirmed by observing iron deposits in mice and bone marrow labile iron pool. Additionally, the number of peripheral blood and bone marrow mononuclear cells and the frequency of erythroid cells and myeloid cells were counted and hematopoietic function was assessed. (1)Iron overload occurred by bone marrow biopsy and flow cytometry analysis. (2)Compared with control group, the number of platelets [(801.9±81.2)×10⁹/L vs (926.0±28.2)×10⁹/L] and BMMNC and the frequency of erythroid cells and myeloid cells decreased. Moreover, hematopoietic colony forming units and single-cell cloning counts decreased significantly in irradiation group (P<0.05). (3)Compared with irradiation group, the number of platelets [(619.0±60.9)×10⁹/L vs (801.9±81.2)×10⁹/L] and the frequency of erythroid cells and myeloid cells decreased; moreover, hematopoietic colony forming units and single-cell cloning counts decreased significantly in irradiation+iron group (P<0.05). (4)Compared with irradiation group, ROS level increased by 1.94 fold in BMMNC, 1.93 fold in erythroid cells and 2.70 fold in myeloid cells, respectively (P<0.05). The dose of 4 Gy total body irradiation caused bone marrow damage and iron overload based on this injury model, which could damage bone marrow hematopoietic function aggravatingly. And further study found that iron overload was closely related to increased ROS level in BMMNC. The findings would be helpful to further study the injury mechanism of iron overload on the hematopoiesis of bone marrow.