Treatment Of Blood Diseases Research Articles

The essential roles of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis.

Hematopoietic stem cells (HSCs) developing from mesoderm during embryogenesis are important for the blood circulatory system and immune system. Many factors such as genetic factors, chemical exposure, physical radiation, and viral infection, can lead to the dysfunction of HSCs. Hematological malignancies (involving leukemia, lymphoma, and myeloma) were diagnosed in more than 1.3 million people globally in 2021, taking up 7% of total newly-diagnosed cancer patients. Although many treatments like chemotherapy, bone marrow transplantation, and stem cell transplantation have been applied in clinical therapeutics, the average 5-year survival rate for leukemia, lymphoma, and myeloma is about 65%, 72%, and 54% respectively. Small non-coding RNAs play key roles in a variety of biological processes, including cell division and proliferation, immunological response and cell death. With the development of technologies in high-throughput sequencing and bioinformatic analysis, there is emerging research about modifications on small non-coding RNAs, as well as their functions in hematopoiesis and related diseases. In this study, we summarize the updated information of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis, which sheds lights into the future application of HSCs into the treatment of blood diseases.

Activity and function studies of the promoter cis-acting elements of the key enzymes in saponins biosynthesis of DS from Panax notoginseng.

Panax notoginseng is a traditional Chinese medicine for the treatment of blood diseases, in which saponins were the main active components. Dammarenediol synthase (DS) is a key enzyme in the saponin synthesis pathway of P. notoginseng. The promoter is an important region to regulate gene expression, and the study of the promoter sequence provides important evidence for revealing the mechanism of gene expression regulation. However, there was still little research on the promoter function of P. notoginseng. In this study, the 1382bp promoter upstream of DS from P. notoginseng was cloned and sequenced. The promoter sequence was analyzed by online databases. The plant expression vector fused with the β-glucuronidase gene was constructed and transferred into Agrobacterium tumefaciens. Then tobacco was injected, and its response to exogenous hormones (gibberellin and abscisic acid) was studied by transient expression to verify its unique action elements. The results showed that the tobacco leaves transferred with DS promoter had significantly increased GUS protease activity after spraying GA and ABA, indicating that both DS promoter can specifically and significantly respond to exogenous GA and ABA signal. These findings will help us to better understand the regulatory mechanisms of the upstream region of the DS gene and provide a basis for future research on the interaction of cis-acting elements of promoters with related transcription factors.

Regulatory signaling pathways in hematopoietic stem cell development.

The blood system provides the body with oxygen and nutrients, maintains the homeostasis of the internal environment through material exchange, and keeps the body with immune defense and protection. Hematopoietic stem cells (HSCs), which are pluripotent adult stem cells with self-renewal and differentiation potential, are the origin of mature blood cells in the body. The production, development and maturation processes of HSCs and their derivatives are the so-called 'hematopoiesis', which begins in the early embryonic development and throughout the life course; any abnormality during these processes can cause the occurrence of hematological diseases. Therefore, a deeper understanding of hematopoietic development and its regulation is important to the diagnosis and treatment of blood diseases. In recent years, a series of advances have been made in studying hematopoietic development using mice and zebrafish as animal models. It has been shown that BMP, Notch and Wnt signaling pathways play an important role in the fate determination and generation of HSCs. In this review, we systematically summarize the regulatory roles of these signaling pathways in the hematopoietic process of mice and zebrafish embryos, to improve our understanding on the underlying regulatory network of hematopoietic development and provide guidance for clinical application.

When Glycosylation Meets Blood Cells: A Glance of the Aberrant Glycosylation in Hematological Malignancies.

Among neoplasia-associated epigenetic alterations, changes in cellular glycosylation have recently received attention as a key component of hematological malignancy progression. Alterations in glycosylation appear to not only directly impact cell growth and survival, but also alter the adhesion of tumor cells and their interactions with the microenvironment, facilitating cancer-induced immunomodulation and eventual metastasis. Changes in glycosylation arise from altered expression of glycosyltransferases, enzymes that catalyze the transfer of saccharide moieties to a wide range of acceptor substrates, such as proteins, lipids, and other saccharides in the endoplasmic reticulum (ER) and Golgi apparatus. Novel glycan structures in hematological malignancies represent new targets for the diagnosis and treatment of blood diseases. This review summarizes studies of the aberrant expression of glycans commonly found in hematological malignancies and their potential mechanisms and defines the specific roles of glycans as drivers or passengers in the development of hematological malignancies.

Insights into the mechanism of Arnebia euchroma on leukemia via network pharmacology approach

BackgroundArnebia euchroma (A. euchroma) is a traditional Chinese medicine (TCM) used for the treatment of blood diseases including leukemia. In recent years, many studies have been conducted on the anti-tumor effect of shikonin and its derivatives, the major active components of A. euchroma. However, the underlying mechanism of action (MoA) for all the components of A. euchroma on leukemia has not been explored systematically.MethodsIn this study, we analyzed the MoA of A. euchroma on leukemia via network pharmacology approach. Firstly, the chemical components and their concentrations in A. euchroma as well as leukemia-related targets were collected. Next, we predicted compound-target interactions (CTIs) with our balanced substructure-drug-target network-based inference (bSDTNBI) method. The known and predicted targets of A. euchroma and leukemia-related targets were merged together to construct A. euchroma-leukemia protein-protein interactions (PPIs) network. Then, weighted compound-target bipartite network was constructed according to combination of eight central attributes with concentration information through Cytoscape. Additionally, molecular docking simulation was performed to calculate whether the components and predicted targets have interactions or not.ResultsA total of 65 components of A. euchroma were obtained and 27 of them with concentration information, which were involved in 157 targets and 779 compound-target interactions (CTIs). Following the calculation of eight central attributes of targets in A. euchroma-leukemia PPI network, 37 targets with all central attributes greater than the median values were selected to construct the weighted compound-target bipartite network and do the KEGG pathway analysis. We found that A. euchroma candidate targets were significantly associated with several apoptosis and inflammation-related biological pathways, such as MAPK signaling, PI3K-Akt signaling, IL-17 signaling, and T cell receptor signaling pathways. Moreover, molecular docking simulation demonstrated that there were eight pairs of predicted CTIs had the strong binding free energy.ConclusionsThis study deciphered that the efficacy of A. euchroma in the treatment of leukemia might be attributed to 10 targets and 14 components, which were associated with inhibiting leukemia cell survival and inducing apoptosis, relieving inflammatory environment and inhibiting angiogenesis.

Retinal vessel optical coherence tomography images for anemia screening.

Anemia is a disease that leads to low oxygen carrying capacity in the blood. Early detection of anemia is critical for the diagnosis and treatment of blood diseases. We find that retinal vessel optical coherence tomography (OCT) images of patients with anemia have abnormal performance because the internal material of the vessel absorbs light. In this study, an automatic anemia screening method based on retinal vessel OCT images is proposed. The method consists of seven steps, namely, denoising, region of interest (ROI) extraction, layer segmentation, vessel segmentation, feature extraction, feature dimensionality reduction, and classification. We propose gradient and threshold algorithm for ROI extraction and improve region growing algorithm based on adaptive seed point for vessel segmentation. We also conduct a statistical analysis of the correlation between hemoglobin concentration and intravascular brightness and vascular shadow in OCT images before feature extraction. Eighteen statistical features and 118 texture features are extracted for classification. This study is the first to use retinal vessel OCT images for anemia screening. Experimental results demonstrate the accuracy of the proposed method is 0.8358, which indicates that the method has clinical potential for anemia screening. Graphical abstract.

Rational identification of a Cdc42 inhibitor presents a new regimen for long-term hematopoietic stem cell mobilization

Mobilization of hematopoietic stem cells (HSCs) from bone marrow (BM) to peripheral blood (PB) by cytokine granulocyte colony-stimulating factor (G-CSF) or the chemical antagonist of CXCR4, AMD3100, is important in the treatment of blood diseases. Due to clinical conditions of each application, there is a need for continued improvement of HSC mobilization regimens. Previous studies have shown that genetic ablation of the Rho GTPase Cdc42 in HSCs results in their mobilization without affecting survival. Here we rationally identified a Cdc42 activity-specific inhibitor (CASIN) that can bind to Cdc42 with submicromolar affinity and competitively interfere with guanine nucleotide exchange activity. CASIN inhibits intracellular Cdc42 activity specifically and transiently to induce murine hematopoietic stem/progenitor cell egress from the BM by suppressing actin polymerization, adhesion, and directional migration of stem/progenitor cells, conferring Cdc42 knockout phenotypes. We further show that, although, CASIN administration to mice mobilizes similar number of phenotypic HSCs as AMD3100, it produces HSCs with better long-term reconstitution potential than that by AMD3100. Our work validates a specific small molecule inhibitor for Cdc42, and demonstrates that signaling molecules downstream of cytokines and chemokines, such as Cdc42, constitute a useful target for long-term stem cell mobilization.

Research Progress and Application Prospect of IPS Cells

Differentiated somatic cells can be reprogrammed into induced pluripotent stem cells (iPS cells) by introducingspecific transcription factors. This technique avoids immune rejection and ethical problems in stem cell research.A great revolution in the fi eld of science. As with embryonic stem cells (ES cells), iPS cells are able to self-renewand maintain undiff erentiated state. In vitro, iPS cells can be induced to diff erentiate into a variety of mature cells,therefore, iPS cells in theoretical research and clinical applications are extremely valuable. IPS cell diff erentiationand transplantation in the treatment of blood diseases have a great use, iPS cells can treat nervous system diseases,to provide in vitro disease model, to study the mechanism of disease formation, screening new drugs and thedevelopment of new to provide a new treatment The The use of iPS cells as a nuclear donor cell, with the appropriatereceptor cells after fusion can be directly obtained transgenic animals. Not only can improve the genetic nature ofanimals, but also can break the boundaries of species and get the new animal traits that cannot achieve by usingtraditional mating methods. The research of iPS cells has been widely concerned, and it is the research hotspot in cellbiology and molecular biology. In this paper, the defi nition of iPS cells, the acquisition of iPS cells, the history ofdevelopment, the signifi cance of research, the progress of research, the application of iPS cells, and the problems ofiPS cells were reviewed.

Activation of the Arterial Program Drives Development of Definitive Hemogenic Endothelium with Lymphoid Potential

Understanding the pathways guiding the development of definitive hematopoiesis with lymphoid potential is essential for advancing human pluripotent stem cell (hPSC) technologies for the treatment ofblood diseases and immunotherapies. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs) arise from hemogenic endothelium (HE) lining arteries but not veins. Here, we show that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhanced the formation of arterial-type HE expressing DLL4 and CXCR4. Blood cells generated from arterial HE were more than 100-fold enriched in Tcell precursor frequency and possessed the capacity to produce B lymphocytes and red blood cells expressing high levels of BCL11a and β-globin. Together, these findings provide an innovative strategy to aid in the generation of definitive lymphomyeloid progenitors and lymphoid cells from hPSCs for immunotherapy through enhancing arterial programming of HE.

INVESTIGATION OF CYTOSTATIC ACTIVITY OF THE METHENAMINE SILVER IN VITRO AND IN VIVO

Background: Developing of novel pharmaceutic agents is an actual topic for chemotherapy. Heavy metals possess a significant cytotoxic properties and some of them are widly introduced in medical practice, e.g. cisplatin.Aim and Objective of this study was to investigate the cytostatic effects of prospective silver-based preparation on viral bovine leukemia model in vivo and lymphoblast cells in vitro.Material and Methods: Silver salt of methenamine was suggested as prospective substance and tested was tested on black-motley cattle with bovine leukemia to reveal influence on hematological parameters. Preparation was applied in form of 0.5% solution in different doses and was administered as single intravenous injection. Blood parameters were determined by triple hematological monitoring. Investigation of cytostatic activity was conducted on the leukemic cells of HUT-102 line in Vitro in concentration range of 0.03-3.0 mg/ml.Results: The results showed normalization of blood parameters in dose-dependent manner after intravenous injection of methenamine silver salt. It was revealed a pronounced inhibitory effect of silver-based drug on the leukemic cells both in vitro and in vivo. Control blood test one month after experimental therapy confirmed the stability of the achieved results.Conclusion: The tested drug showed a moderate cytostatic effect. Methenamine silver nitrate can be considered as prospective pharmacological agent. Bovine leukemia was shown as a convenient model for the development of new treatment of blood diseases. Continuation of the work is of interest for both veterinary and medical pharmacotherapy.Keywords: methenamine silver nitrate, HUT 102 cells; lymphocytes, leucosis, cytostatic activity, bovine leukemia, silver hexamethylenetetramine.

Progress in long non-coding RNA in hematopoiesis

Long non-coding RNAs (lncRNAs), which are closely related with human critical illness, can regulate gene expression and involve the physiological and pathological processes on epigenetic, transcriptional and post-transcriptional levels through several mechanisms. LncRNAs also play important regulation roles in the maturation and differentiation process of hematopoietic cell. Besides, in-depth exploration of their mechanism will provide new ideas for the diagnosis and treatment of blood diseases. Key words: Long non-coding RNA; Hematopoiesis

STUDY OF NUTRITIONAL CONSTITUENTS AND SENSORY EVALUATION OF BAKERY PRODUCTS PREPARED FROM SEED AND BARK OF PRUNUS PERSICA (PEACH)

Medicinal plants are local heritage with global importance. Prunuspersica Seeds and Bark are used as traditional medicine for treatment of blood diseases, anemia rheumatism jaundice, antioxidant and anti-inflammatory agent. So the present study was planned for analysed the nutritional constituents of Prunuspersica Seeds and Bark such as Moisture, Protein, fat and ash were analyzed using AOAC methods. Carbohydrate content of the sample was estimated by Difference method. The research was designed to investigate proximate composition. The results of proximate analysis indicated that seeds and bark had appreciable amounts of Protein (2.2% and 1.0%), Carbohydrate (50.3% and 58.7%) and fat (36.9% and 29.2%) on dry basis with observed no significant difference (P≤0.05). Acceptability evaluation of prepared recopies was performed by semi trained panel through 9 point Hedonic rating scale test. The result revealed that among the recipes (Biscuits and Baked bite) prepared by adding 2%, 4%, 6% and 8% Powder of Seed and Bark that variant 1, 2 and 3 were acceptable when comparable to standard recipe. There is no significance difference (P≤0.005) when they were tested statistically. Considering the pharmaceutical action of Seeds and Bark for treatment of many diseases and that the reasonably safe to use, its development is important for the pharmaceutical industries. This study generated base line information about the peach Seeds and Bark which will be beneficial to treat various diseases. This study also indicates that both Seeds and Bark can be valuable in generating awareness among people to control various diseases and to improve their nutrition and health status.

Perception and Assessment of Verbal and Written Information on Sex and Relationships after Hematopoietic Stem Cell Transplantation

This study aimed to investigate experiences of verbal and written information about sex and relationships among men and women treated with hematopoietic stem cell transplantation. The study also aimed to investigate the demand for information and assessment of the quality of written patient information material entitled "Sex and relationships in the treatment of blood diseases." Few studies exist that shed any light on the demand for information about sex and relationships on the part of patients with hematological diseases before, during, and after their treatment. A total of 216 patients undergoing treatment for malignant blood diseases between 2000 and 2010 participated in this study. Patients' experiences of information about sex and relationships, and their opinions about the written patient information, were assessed using a questionnaire created specifically for this study. Most patients (81%) had not received information about sex and relationships from a healthcare professional. Almost 90% of men felt that verbal information was important, compared with 82% of women. The majority also held that written information was important. These results indicate that patients, regardless of gender, age, and treatment, consider oral and written information about sex and relationships to be important and that the healthcare system should provide the information. The written patient information was considered to play an important role in creating an opening for a conversation about a sensitive topic such as sexuality, and also as a source of reference and support for the patient and his/her partner.

Psychohematology. Attempt to Summarise

Purpose: This article describes studies involving mental and personality disorders in patients with blood diseases - disorders typology, prevalence, risk factors for developing of mental disturbances and their treatment. Methods: The work is done on the basis of scientific literature search in various databases and analysis of the resulting material. Results: There was obtained information on the prevalence, typologies, risk factors and treatment of blood diseases in the available literature. Conclusions: The presented data of literature suggests clinical heterogeneity and a wide range (from asthenic reactions to delirious states) of psychopathological disorders detected in blood diseases patients. The main risk factors are severe underlying disease, chemotherapy management (especially corticosteroids), elderly patients. In most cases of adjustment disorders there was observed a combination of several risk factors (both general and specific). In the context of the tolerability and safety of pharmacotherapy preference was given to atypical antipsychotics and new generations of antidepressants (SSRI, SNRI). It remains to study the mental disorders and personality disorders, which are formed in patients with specific malignant and nonmalignant (hemophilia, thrombocytopathy etc.) diseases and to develop differentiated approaches to pharmacotherapy and psychotherapy in such states.

From fish tank to bedside in cancer therapy: an interview with Leonard Zon.

Leonard Zon, who is based at Harvard Medical School, is internationally recognized for his pioneering work in hematology and stem cell biology. His lab uses zebrafish as a model to understand blood cell development and, in recent years, has made inspiring breakthroughs in the treatment of blood diseases and cancer, helping to establish zebrafish as a powerful model for translational research. In this interview, Leonard speaks to Disease Models & Mechanisms Editor-in-Chief, Ross Cagan, about the evolution of his career from developmental biologist to physician-scientist and the stories behind some of his major research accomplishments. He also discusses challenges and opportunities in zebrafish research and provides advice on translating basic research findings to the clinic.

Covalent immobilization of stem cell factor and stromal derived factor 1α for in vitro culture of hematopoietic progenitor cells

Hematopoietic stem cells (HSCs) are currently utilized in the treatment of blood diseases, but widespread application of HSC therapeutics has been hindered by the limited availability of HSCs. With a better understanding of the HSC microenvironment and the ability to precisely recapitulate its components, we may be able to gain control of HSC behavior. In this work we developed a novel, biomimetic PEG hydrogel material as a substrate for this purpose and tested its potential with an anchorage-independent hematopoietic cell line, 32D clone 3 cells. We immobilized a fibronectin-derived adhesive peptide sequence, RGDS; a cytokine critical in HSC self-renewal, stem cell factor (SCF); and a chemokine important in HSC homing and lodging, stromal derived factor 1α (SDF1α), onto the surfaces of poly(ethylene glycol) (PEG) hydrogels. To evaluate the system’s capabilities, we observed the effects of the biomolecules on 32D cell adhesion and morphology. We demonstrated that the incorporation of RGDS onto the surfaces promotes 32D cell adhesion in a dose-dependent fashion. We also observed an additive response in adhesion on surfaces with RGDS in combination with either SCF or SDF1α. In addition, the average cell area increased and circularity decreased on gel surfaces containing immobilized SCF or SDF1α, indicating enhanced cell spreading. By recapitulating aspects of the HSC microenvironment using a PEG hydrogel scaffold, we have shown the ability to control the adhesion and spreading of the 32D cells and demonstrated the potential of the system for the culture of primary hematopoietic cell populations.

Absorption spectroscopy of single red blood cells in the presence of mechanical deformations induced by optical traps

The electronic properties of single human red blood cells under mechanical deformations were investigated using a combination of dual beam optical tweezers and UV-vis absorption spectroscopy. The mechanical deformations were induced by two near-infrared optical traps with different trapping powers and trap configurations. The deformations were applied in two ways: locally, due to the mechanical forces around the traps, and by stretching the cell by moving the traps in opposite directions. In the presence of local deformations, the single cell undergoes a transition from an oxygenated state to a partially deoxygenated state. This process was found to be reversible and strongly power-dependent. Stretching the cell caused an opposite effect, indicating that the electronic response of the whole cell is dominated by the local interaction with the trapping beams. Results are discussed considering light-induced local heating, the Stark effect, and biochemical alterations due to mechanical forces, and are compared with reports of previous Raman spectroscopy studies. The information gained by the analysis of a single red blood cell's electronic response facilitates the understanding of fundamental physiological processes and sheds further light on the cell's mechanochemistry. This information may offer new opportunities for the diagnosis and treatment of blood diseases.

Clinical study on viral hepatitis combined with aplastic anemia

To study the clinical features, outcomes and treatments of viral hepatitis combined with aplastic anemia. 25 cases diagnosed as viral hepatits combined with aplastic anemia in Beijing Ditan Hsopital between April 2004 and September 2009 were retrospectively analyzed. In this group of patients aplastic anemia was finally diagnosed by bone marrow aspiration. We collected clinical data of these patients, including a history of liver disease, drug allergies, hospital medication history, laboratory data, and then performed descriptive analysis. 25 patients with viral hepatitis were diagnosed as complicated with aplastic anemia by histopathological data. Among these patients, 17 were male and 8 were women. Viral hepatitis included: chronic hepatitis B (12 cases), chronic hepatitis C (4 cases), acute hepatits E (1 case), hepatitis caused by CMV infection (1 case), and unclassified hepatitis (7 cases). Among these patients, 7 were diagnosed as severe hepatits. Considering previous history, only 3 patients had history of short term interferon therapy before hospitalization, and the remaining patients did not use drug that affects blood system. Treatments were as followings: using colony stimulating factor in 6 patients, gamma globulin in 9 patients, glucocorticoids in 3 patients, erythropoietin in 1 patient, only oral drug to raise erythrocytes in 2 patients, red blood cells transfusion in 6 patients, platelets transfusion in 2 patients. As for clinical outcomes, 20 patients acquired improved condition and were dicharged, 3 patients were discharged voluntarily and 2 patients died of severe hepatits combined with other complications. Main treatments of viral hepatitis combined with aplastic anemia were to treat primary hepatopathy and nucleoside analogue-based antiviral therapy, to provide symptomatic and supportive treatment for blood diseases. Blood diseases would recover simultaneously while liver disease was improved, and the prognosis was good.

Blood cell generation from the hemangioblast

Understanding how blood cells are generated is important from a biological perspective but also has potential implications in the treatment of blood diseases. Such knowledge could potentially lead to defining new conditions to amplify hematopoietic stem cells (HSCs) or could translate into new methods to produce HSCs, or other types of blood cells, from human embryonic stem cells or induced pluripotent stem cells. Additionally, as most key transcription factors regulating early hematopoietic development have also been implicated in various types of leukemia, understanding their function during normal development could result in a better comprehension of their roles during abnormal hematopoiesis in leukemia. In this review, we discuss our current understanding of the molecular and cellular mechanisms of blood development from the earliest hematopoietic precursor, the hemangioblast, a precursor for both endothelial and hematopoietic cell lineages.

Surgical treatment of spleen-related blood diseases

Objective To explore the surgical indexes, therapeutic efficacy and prevention of complications in treatment of some blood diseases by splenectomy (including laparoscopic splenecto- my). Methods The clinical data of 27 patients with blood diseases receiving splenectomy in our hospi-tal were retrospectively analyzed. Results The effective rate of splenectomy was 100% in 4 cases of hereditary spherocytosis, 76.47% in 17 cases of ITP and low in 6 cases of Non-Hodgkin's lymphoma.The postoperative incidence of complications was 7.41% (2/27). Conclusion Splenectomy is of the first choice for treatment of hereditary spherocytosis. Meanwhile, it is effective for most of the patients with ITP. It is an important approach for comprehensive of malignant lymphoma. Proper choice of indications and perioperative management are helpful for decreasing incidence of postoperative complications. Key words: Splenectomy; Blood disease; Indication; Complication