Dual Functions of Microglia in Ischemic Stroke / 神经科学通报·英文版

Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However, increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes, and endothelial cells within the brain parenchyma and the neurovascular unit.

Clonal evolution in leukemia / 中国实验血液学杂志

The theory of evolution of tumor cell population has been established for nearly 40 years. It was widely accepted for research and clinical anti-tumor treatment. Recently, it was suggested that cancer stem cells are the unit of evolution. Considering recent advances on genesis of tumor and leukemia with ecological and evolutionary views, this article reviews origin and evolution of leukemia stem cells. Over the last few years, clinical and experimental data suggest there are two paths for the origin of leukemia stem cells: from a transformed hematopoietic stem cell or progenitor. The mechanisms of leukemia stem cell formation and clonal evolution were elucidated. Sub-clonal mutations and clonal architectures in leukemia were studied and a mosaic evolution pattern is described. Random evolution or non-inherited mutations of leukemia cells would accelerate the progression of malignant disease. Finally, the mosaic or network mechanism for leukemogenesis is also discussed.

Membrane-bound cytokine and feedforward regulation / 中国实验血液学杂志

Feedback and feedforward widely exist in life system, both of them are the basic processes of control system. While the concept of feedback has been widely used in life science, feedforward regulation was systematically studied in neurophysiology, awaiting further evidence and mechanism in molecular biology and cell biology. The authors put forward a hypothesis about the feedforward regulation of membrane bound macrophage colony stimulation factor (mM-CSF) on the basis of their previous work. This hypothesis might provide a new direction for the study on the biological effects of mM-CSF on leukemia and solid tumors, and contribute to the study on other membrane bound cytokines.

Co-evolutionary analysis on strategy for therapy of spreading cancer / 中国实验血液学杂志

Evolutionary medicine can give rational explanation for metabolism diseases via ecology and evolutionary theory. Recently, the view of somatic cell macroevolution was used in the study on the genesis and development of tumors, which provided new insight in the research work on tumors. In this article, the well-adopted tumor therapy strategy, "Dancing with Cancer", was analyzed preliminarily from the point of co-evolution game theory, based on the non-classical immunology theory and genome theory. The importance of increasing host fitness by changing host life-style to enhance tolerance was emphasized, which is the basis of the Dancing with Cancer strategy. On the other hand, the spreading tumor cells are not equally malignant and spreading tumors should be treated as other chronic diseases. Finally, basic and clinical research should be strengthened to improve the efficiency of the "Dancing with Cancer" strategy.

Mechanism of leukemia relapse: novel insights on old problem / 中国实验血液学杂志

Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias. The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms. The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health. Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials. The role and significance of in vivo cell fusion have been studied in more detail. On the other hand, donor cell leukemia was reported. All of these approaches provide novel insights for studying the mechanism of leukemia relapse. Based on previous work, the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic materials.

Leukocyte synapse: structure, function and significance / 中国实验血液学杂志

Neuronal synapse is the critical structure of neuronal network. Immune system is mainly consisted of invisible network. Recently, evidence showed that leukocyte synapses between immune cells named as immunological synapses (IS), were formed under some functional conditions to form temporal local network. In fact, they are dynamic structures, which can be classified into synapse and kinase. Different leukocytes have different synapses. Inflammatory and leukemic cells showed special patterns of IS. Similar structure is also observed in some viral infected lymphocytes, which is called virological synapse (VS). This is one of the mechanisms for viral transmission, not only enhancing the transmission efficiency but also mediating the escape from antibody neutralization, leading persistent infection. Recently the flower-like poly synapses was reported by French scientists. This is a multi-tunneling nanotube flower-like structure on cell surface. We had observed this kind of structure in EB virus infected human leukemic cell line J6-2. In this paper, the structure and function of leukocyte synapses are reviewed combined with authors' own work. Their significance is discussed.

Functional multi-polarization of white blood cells and its significance / 中国实验血液学杂志

Immune and hemopoiesis are one of basic project of experimental hematology. Immune function is a essential activity of white blood cells. It was puzzled for the diversity and complexity of immune response. Polarized immune response of immune cells was discovered 30 years ago, which facilitates the study on differentiation of lymphocyte. Recently recognition on multifunctional polarized immune response of lymphocyte and monocyte/macrophage would promote to elucidate the regulatory network of immune cells, diversity and complexity of immune response as well as the study on hemopoiesis. In this paper the approach of multifunctional polarized immune response of lymphocyte, monocyte/macrophage and dendritic cells were reviewed, and their role, especially in cytokine storm and tumor pro-inflammation condition were discussed.

Reprogramming in origin and development of leukemia stem/progenitor cells / 中国实验血液学杂志

The success of yielding induced pluripotent stem (iPS) cells from human somatic cells demonstrates the important role of reprogramming in the formation of stem/progenitor cells and initiates the exploration of the origin of leukemia stem cells. In our previous work, we have found two types of leukemia, bona fide leukemia and non-bona fide leukemia. Different leukemias originate from different leukemia stem/progenitor cells which are critical to the genesis and evolution of leukemia. Bona fide leukemia and non-bona fide leukemia originate from leukemia stem cells and progenitor cells, respectively. Recent research suggests that different types of leukemia are influenced by the reprogramming state of their origin cells.

Latent infection of human herpes virus in hematopoietic system / 中国实验血液学杂志

Up to date, eight types of human herpes viruses have been identified, all of which are ubiquitous, and usually establish latent infection in the host after primary infection. Since most of the herpes viruses are maintained in an asymptomatic form, they are often neglected. However, under some circumstances, these herpes viruses can cause fatal or severe diseases. Furthermore, the association of herpes viruses with hematopoietic malignancies is attracting researchers' attention. With the extensive development of hematopoietic stem cell and organ transplantation, reports regarding transplantation failure and complication caused by infection of human herpes virus has been increasing. Cytokine storm was firstly suggested as the mechanism of graft-versus-host diseases. In recent years, which has also been applied in the pathogenesis research of inflammation, and is supposed to play an important role in severe virus infection. In this paper, through discussing the possible role of latent infection of human herpes virus in the failure or complication of bone marrow or hematopoietic stem cell transplantation, and in refractory leukemia, the function and significance of latent infection of human herpes virus and the cytokine storm it caused were investigated.

Leukemia stem cells and their microenvironment--editorial / 中国实验血液学杂志

As pioneer of tumor stem cell research, leukemia stem cell research has not only important theoretical significance, but also clinical application potential. The survival and development of stem cells are directly impacted by their microenvironment. The research on leukemia stem cells and their microenvironment are now becoming a hot topic. The author presumes that stem cells are a population with heterogenecity and hierarchy; any single cell from the population is difficult to form a clone; the interaction between the leukemia stem cell and its microenvironment can be described by the concept of leukemia stem cell niche. In this article, the leukemia cell population with heterogenecity and hierarchy as well as leukemia stem cell niche were summarized and discussed.

Inhibitory effect of human mda-7/IL-24 on proliferation of lymphoma cell line Namalwa / 中国肿瘤生物治疗杂志

Objective:To investigate the inhibitory effects of melanoma differentiation associated gene-7(mda-7/IL- 24)on lymphoma cell line Namalwa in vitro and in vivo.Methods:Using RT-PCR,the expression of mda-7/IL-24 was examined in 10 malignant hematopoietic cell lines,including Namalwa,Raji,K562,NB4,U937,Ramous,CEM,KG1a, HL60,J6-1,etc.The coding region of mda-7/IL-24 was cloned from LPS-treated human peripheral blood mononuclear cells(PBMC)by RT-PCR,and the eukaryotic expression vector pTarget-IL-24 was constructed.The recombinant vector, after sequenced,was transfected into Namalwa cell line via lipofectamine reagent.The stable expression transfectants were selected by G418.The expression of mda-7/IL-24 mRNA and protein was verified by RT-PCR and Western blotting.MTT assay,colony forming assay,apoptosis detection,and tumorigenesis in nude mice were used to assess the effects of mda- 7/IL-24 on tumor proliferation,growth characteristics,colony forming,apoptosis,and tumorigenesis.Results:Expression of mda-7/IL-24 mRNA was not found in any of the 10 malignant hematopoietic cell lines and the expression of mda-7/IL- 24 mRNA and protein was found in Namalwa cells transfected with recombinant plasmid pTarget-IL-24.Significant de- crease in tumor cell viability was observed in Namalwa cells stably transfected with mda-7/IL-24,compared with control cells transfected with empty plasmid pTarget(P

Apoptosis or necrosis, should which be expected for tumor cells? / 中国实验血液学杂志

Evidence has indicated that low doses of anti-tumor regimens can induce cell apoptosis in vitro, although different regimens induce apoptosis by different mechanism and pathway. In recent years, new tumor treatment strategy has been mainly focused on inducing tumor cell apoptosis. The present review discusses the advantages and disadvantages of inducing tumor cell apoptosis. The benefit of inducing apoptosis is not to cause inflammatory reaction, but as its disadvantage, it inhibits immune responses, and the phagocytosis of apopotic bodies may result in horizontal transfer of genes (including oncogenes and other oncogenic materials), which can be one of the causes of tumor relapse. This paper proposes that the tumor treatment strategy should be turn into promoting tumor cell necrosis and inducing anti-tumor immune responses.

Effects of various inducers on the expression of P2X7 receptor in human peripheral blood mononuclear cells / 生理学报

Regulation of P2X7 receptor expression is of interest because activation of this receptor by extracellular ATP triggers a wide variety of cell functions in leukocytes. However, its expression and modulation in human peripheral blood mononuclear cells (PBMC) and monocytes remain unclear. RT-PCR was used to detect the constitutive level of P2X7 receptor and the levels upon stimulation with bacteria, bacterial product, mitogen and various cytokines in human PBMC and monocytes. P2X7 receptor mRNA was detected in PBMC and monocytes. P2X7 receptor expression in PBMC was up-regulated by interleukin-2, -4, -6 (IL-2, IL-4, IL-6) tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS) and heat-inactivated Staphylococcus aureus Cowan strain I (SAC). However, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and phytohemagglutinin-M (PHA-M) had little effect on the expression of P2X7 receptor. Furthermore, LPS and M-CSF could up-regulate P2X7 receptor expression in monocytes, while IFN-gamma, TNF-alpha and GM-CSF had weak effects, but pretreatment with these inducers could not further enhance LPS-stimulated P2X7 receptor expression in monocytes. The results obtained demonstrate that inflammatory stimuli drive P2X7 expression, thus supporting the hypothesis that P2X7 receptor may play a role in the inflammatory responses against bacteria infection, which need further verification.

Advance in Biofilm Dispersal Strategies / 微生物学通报

Bacterial biofilm is responsible for a wide variety of nosocomial infections.Many chronic infectious diseases are closely correlated with biofilm formation in the clinic.As the biofilm growth,bacterial clusters detachment and dispersal from mature mixed-species biofilms will result in repeated acute infections.Here reviews three distinct biofilm dispersal strategies: swarming dispersal,clumping dispersal and surface dispersal.Many factors,such as heredity and increased fluid shear in the environment,contribute to this complex and dynamic process.Fundamental investigation upon biofilm will benefit clinical therapy of biofilm-associated infections.