In the injured central nervous system (CNS), reactive astrocytes form a glial scar and they are considered a physical barrier to prevent axonal regeneration by producing axonal growth inhibitors, such as chondroitin sulfate proteoglycans. However, the physiological role of reactive astrocytes remains to be elucidated. In this review, we showed that reactive astrocytes play a crucial role in wound healing and functional recovery. At the subacute phase of spinal cord injury (SCI), reactive astrocytes eventually migrated to the lesion epicenter and gradually compacted the infiltrated inflammatory cells and contracted the lesion area, and functional recovery was observed only in this repair phase. Selective deletion of the signal transducer and activator of transcription-3 (STAT3) in reactive astrocytes resulted in their limited migration associated with zinc signaling, markedly widespread damaged area and severe motor deficits. These results suggest that STAT3 is a key regulator of reactive astrocytes migration in the healing process after SCI, providing a beneficial aspect of reactive astrocytes after CNS injury.

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Circulating platelets are targeted by autoantibodies in various pathologic conditions, such as immune thrombocytopenic purpura (ITP). Anti-platelet antibodies cause thrombocytopenia through enhanced platelet clearance via Fcγ receptor-mediated platelet destruction by the reticuloendothelial system and impaired platelet production. Moreover, functional blockade of platelet surface receptors by autoantibodies may further promote bleeding tendency. The major targets of these autoantibodies are platelet membrane glycoproteins, including GPIIb/IIIa and GPIb/IX, receptors for fibrinogen and other platelet-activating ligands, but some patients with ITP have antibodies to a receptor for thrombopoietin, which is a growth factor required for megakaryocytogenesis and platelet production. Several antigen-specific assays have been developed to measure anti-glycoprotein antibodies, whereas we have recently established an enzyme-linked immunospot assay for the detection of circulating B cells secreting IgG anti-GPIIb/IIIa antibodies, which is a sensitive, specific, and convenient method for evaluating the presence or absence of ITP. Production of pathogenic anti-platelet antibodies is maintained by a continuous loop, in which B cells produce anti-platelet antibodies, antibody-coated platelets are phagocytosed and GPIIb/IIIa-derived cryptic peptides presented by splenic macrophages, and GPIIb/IIIa-reactive CD4⁺ T cells exert their helper activity. Important discoveries on cellular and molecular mechanisms for anti-platelet autoantibody production contribute to development of diagnostic assays and therapeutic strategies for ITP.

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Humans have used psychoactive mushrooms for medical, recreational, religious and ritual purposes since pre-history. Previous studies have clarified that psychoactive mushrooms produce psychoactive agents such as psilocybin, psilocin, ibotenic acid, and muscimol. However, the status of psychoactive mushrooms in most countries as illegal hallucinogens has prevented full investigation of their biochemical properties. Recent studies have shown that many psychoactive agents pass through the blood-brain barrier and act on neurotransmitter receptors. Psilocybin and psilocin are 5-HT_1A and 5-HT_2A/C receptor agonists, respectively, while ibotenic acid is a glutamic acid receptor agonist and muscimol is a GABA_A receptor agonist. A new psychoactive agent, aeruginascin, has also been isolated from psychoactive mushrooms, and it is expected that more useful compounds will be discovered as the technology of component analysis advances. In addition, it has been shown that psilocybin and psilocin have high therapeutic efficiency for obsessive-compulsive disorder, which is a difficult-to-treat nervous disease. The increase of nervous diseases in modern society has thus given new importance to psychoactive mushrooms. In this review, we summarize the history of the use of psychoactive mushrooms, from pre-history to the modern age, describe their classification and distribution, survey previous studies, and discuss their therapeutic effects for difficult-to-treat nervous disease. The utilization and distribution of psychoactive mushrooms in Japan is given special attention, as there are few articles on this subject.

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The investigations from the aspect of “osteoimmunology”provided a recent advance on bone cell biology¹⁾. Various molecules identified to play a crucial role in immune system also play a role in bone system. For example, RANK-RANKL system was originally identified in dendritic cells and T cells²⁾, but these molecules are both essential for osteoclast differentiation and skeletal development^3,4). Nuclear factor of activated T cells (NFATc1) was also originally identified in T cells, but plays an essential role in osteoclast differentiation⁵⁾. Thus bone and immune systems share common molecules. Here we introduce a seven transmembrane receptor protein, dendritic cell specific transmembarne protein (DC-STAMP) as an“osteoimmunology”molecule, which plays a role in both bone and immune systems.

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Long-standing UV exposure causes accumulation of degenerated elastic fibers in the dermis. This phenomenon is termed as solar elastosis and considered to be a histological marker of photoaging. The molecular mechanism by which the degenerated elastic fibers accumulate in the dermis by long-standing UV irradiation remains unknown, but three possible theories have been proposed; suppression of elastic fiber degradation (1)by leukocyte elastase inhibitor (elafin), (2)by advanced glycation end product (AGE) modification of elastin molecule, (3)by racemization of aspartic acid residue of elastin molecule. Leukocyte-derived elastase inhibitor (elafin) was found to (1)colocalize with elastic fiber accumulations in the dermis, (2)bind to elastin molecule via transglutaminase in vitro, (3)be induced by UVA irradiation, and (4)protect elastin molecule from elastolytic degradation. Abnormal accumulation of elastic fibers in solar elastosis therefore may be a secondary response preventing the elastic fibers from leukocyte elastase attack.

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Objectives: Ischemic stroke can cause major disability and a deteriorated quality of life. The purposes of this study were to examine whether neovascularization might be promoted by the intra-arterial transplantation of mononuclear cells (MNCs) in ischemic murine brain and to determine whether the new endothelial cells are derived from the donor or from the recipient.
Methods: Transient middle cerebral artery occlusion was accomplished using the intraluminal filament technique. Immediately after the embolus was withdrawn, MNCs harvested from C57BL/6J mice (wild-MNCs) or transgenic mice ubiquitously expressing green fluorescent protein (EGFP-MNCs) were infused intra-arterially. The brains of the mice were then sectioned and stained with anti-CD31 antibody to detect the endothelial cells.
Results: At 30 minutes after operation, transplanted EGFP-MNCs were found in the lung, spleen, and liver but not in the brain. At 6 weeks after operation, CD31-positive cells were evident in the murine brain transplanted with MNCs. Furthermore, the CD31-positive cells were stained with anti-GFP antibody in EGFP mice transplanted with wild-MNCs but not in wild-type mice transplanted with EGFP-MNCs.
Discussion: This animal model resembles the typical clinical course of acute cerebral infarction followed by thrombolytic therapies in humans and could be used to examine new therapies after intra-arterial thrombolysis. In cerebral ischemia, just as in limb ischemia, transplanted MNCs did not differentiate into endothelial cells but instead promoted the formation of new vessels.
Conclusion: In murine brain reperfused post ischemia, intra-arterial MNC transplantation promotes neovascularization. Furthermore, the new endothelial cells are derived from the recipient cells.

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Adult bone marrow contains endothelial cells, adipocytes, stromal cells, and blood cells, such as erythrocytes, lymphocytes, platelets. Stromal cells are a population of multipotent cells referred to as mesenchymal stem cells (MSCs), which not only support hematopoiesis, but also differentiate into multiple lineages, including fat, bone and cartilage. Because of this multipotency, MSCs are an attractive candidate for clinical application to promote repair or regeneration of damaged tissues of mesenchymal origin. However, the characteristics of bone marrow MSCs are still unclear, because of the lack of suitable markers for their prospective isolation. Here, we report the potential usefulness of CD271 (low-affinity nerve growth factor receptor: LNGFR) and CD133 (prominin1: AC133), as markers of the MSC population, for the prospective isolation of highly purified MSCs. This isolation method may provide hope for improving the starting population of stem cells for transplantation in diseases like spinal cord injury, cartilage repair and myocardial infarction.

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