Overexpression of Motopsin, an Extracellular Serine Protease Related to Intellectual Disability, Promotes Adult Neurogenesis and Neuronal Responsiveness in the Dentate Gyrus.

Motopsin, a serine protease encoded by PRSS12, is secreted by neuronal cells into the synaptic clefts in an activity-dependent manner, where it induces synaptogenesis by modulating Na/K-ATPase activity. In humans, motopsin deficiency leads to severe intellectual disability and, in mice, it disturbs spatial memory and social behavior. In this study, we investigated mice that overexpressed motopsin in the forebrain using the Tet-Off system (DTG-OE mice).

Safety and feasibility of autologous cord blood infusion for improving motor function in young children with cerebral palsy in Japan: A single-center study.

Introduction: Cerebral palsy (CP) is the most prevalent motor disorder of childhood. It typically results from in utero or perinatal brain injury. Recently, it has been reported that autologous cord blood (ACB) infusion for children with CP improved gross motor function and brain connectivity, but unfortunately, it has never been tried in Japan.

NF90-NF45 is essential for β cell compensation under obesity-inducing metabolic stress through suppression of p53 signaling pathway.

The Nuclear Factor 90 (NF90)-NF45 complex has been known to regulate the progression of transcription, mRNA stability, translational inhibition, RNA export and microRNA biogenesis. However, the physiological functions of the NF90-NF45 complex remain unclear. We newly discovered that the NF90-NF45 complex was expressed in primary β cells and established cell lines.

5-Aminolevulinic acid has the potential to prevent bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis.

Objectives: To investigate the effects of pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis in rats.

Methods: Male Wistar rats (340-460 g) were pretreated with vehicle or with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (100/157 or 300/471 mg/kg/day, po) once daily for 7 days before cystometry. Saline or cyclophosphamide (150 mg/kg, ip) was administered 2 days before cystometry.

Sulfatide with ceramide composed of phytosphingosine (t18:0) and 2-hydroxy FAs in renal intercalated cells.

Diverse molecular species of sulfatide with differences in FA lengths, unsaturation degrees, and hydroxylation statuses are expressed in the kidneys. However, the physiological functions of specific sulfatide species in the kidneys are unclear. Here, we evaluated the distribution of specific sulfatide species in the kidneys and their physiological functions.

Tissue-specific regulation of 11β hydroxysteroid dehydrogenase type-1 mRNA expressions in Cushing's syndrome mouse model.

The 11β hydroxysteroid dehydrogenase type-1 (11βHSD-1) is a predominant 11β-reductase regenerating bioactive glucocorticoids (cortisol, corticosterone) from inactive 11-keto forms (cortisone, dehydrocorticosterone), expressed mainly in the brain, liver and adipose tissue. Although the expression levels of 11β HSD-1 mRNA are known to be influenced by glucocorticoids, its tissue-specific regulation is not completely elucidated. In this study, we examined the effect of persistent glucocorticoid excess on the expression of 11β HSD-1 mRNA in the hippocampus, liver, and abdominal adipose tissue in vivo using quantitative real-time PCR.

A case of intracranial vasospasm in a patient with extensive retropharyngeal cellulitis.

Retropharyngeal cellulitis/abscesses are deep neck infections that may become life-threatening if airway compromise occurs. This condition is more common in children than in adults, and associated intracranial vessel narrowing has been reported. We report an adult patient with extensive retropharyngeal cellulitis and intracranial vasospasm.

Non-neuronal cardiac acetylcholine system playing indispensable roles in cardiac homeostasis confers resiliency to the heart.

Background: We previously established that the non-neuronal cardiac cholinergic system (NNCCS) is equipped with cardiomyocytes synthesizes acetylcholine (ACh), which is an indispensable endogenous system, sustaining cardiac homeostasis and regulating an inflammatory status, by transgenic mice overexpressing choline acetyltransferase (ChAT) gene in the heart. However, whole body biological significances of NNCCS remain to be fully elucidated.

Methods And Results: To consolidate the features, we developed heart-specific ChAT knockdown (ChATKD) mice using 3 ChAT-specific siRNAs.

Structure and Stereochemistry of Amphidinolide N Congeners from Marine Dinoflagellate Amphidinium Species.

Two highly potent cytotoxic 26-membered macrolides, isocaribenolide-I (1) and a chlorohydrin 2, together with known amphidinolide N (3), have been isolated from a free-swimming dinoflagellate Amphidinium species (KCA09053 and KCA09056 strains) collected off Iriomote Island, Japan. The structures of 1 and 2 were determined to be a congener of 3 with an isobutyl terminus and the chlorohydrin form of 3, respectively, by detailed analyses of spectroscopic data. The relative stereochemistries of 1 and 2 were elucidated by the conformational analyses based on NMR data.

Iriomoteolides-14a and 14b, New Cytotoxic 15-Membered Macrolides from Marine Dinoflagellate Amphidinium Species.

Two new macrolides, iriomoteolides-14a (1) and 14b (2) have been isolated from the marine dinoflagellate Amphidinium species (strain KCA09057). Compounds 1 and 2 are 15-membered macrolides, which are structural analogs of amphidinolides O (3) and P (4). The structures of 1 and 2 were assigned on the basis of detailed NMR analyses and chemical conversion studies.

Effects of silodosin and tadalafil on bladder dysfunction in spontaneously hypertensive rats: Possible role of bladder blood flow.

Objectives: To investigate the effects of an alpha1-adrenoceptor antagonist, silodosin, or a phosphodiesterase type 5 inhibitor, tadalafil, on bladder overactivity in spontaneously hypertensive rats.

Methods: Twelve-week-old male spontaneously hypertensive rats were perorally administered silodosin (100 µg/kg), tadalafil (2 or 10 mg/kg) or vehicle once daily for 6 weeks. Wistar rats were used as normotensive controls and were treated with the vehicle.

Complexin 2 regulates secretion of immunoglobulin in antibody-secreting cells.

Introduction: Complexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane. Although much is known about CPLX function in neuronal synaptic vesicle exocytosis, their distribution and role in immune cells are still unclear. In this study, we investigated CPLX2 knockout (KO) mice to reveal the role of CPLXs in exocytosis of lymphocytes.

Induction of regional chemokine expression in response to human umbilical cord blood cell infusion in the neonatal mouse ischemia-reperfusion brain injury model.

Regenerative medicine using umbilical cord blood (UCB) cells shows promise for the treatment of cerebral palsy. Although the efficacy of this therapy has been seen in the clinic, the mechanisms by which UCB cells interact and aid in the improvement of symptoms are not clear. We explored the chemokine expression profile in damaged brain tissue in the neonatal mouse ischemia-reperfusion (IR) brain injury model that was infused with human UCB (hUCB) cells.

Potentiating a non-neuronal cardiac cholinergic system reinforces the functional integrity of the blood brain barrier associated with systemic anti-inflammatory responses.

We previously reported that the heart-specific choline acetyltransferase (ChAT) gene overexpressing mice (ChAT tg) show specific phenotypes including ischemic tolerance and the CNS stress tolerance. In the current study, we focused on molecular mechanisms responsible for systemic and localized anti-inflammatory phenotypes of ChAT tg. ChAT tg were resistant to systemic inflammation induced by lipopolysaccharides due to an attenuated cytokine response.

5-Aminolevulinic acid with ferrous iron improves early renal damage and hepatic steatosis in high fat diet-induced obese mice.

5-Aminolevulinic acid, a natural amino acid, activates mitochondrial respiration and induces heme oxygenase-1 expression. Obesity and type 2 diabetes mellitus are associated with age-related mitochondrial respiration defect, oxidative stress and inflammation. The aim of this study is to investigate the effects of 5-aminolevulinic acid with sodium ferrous citrate on early renal damage and hepatic steatosis.

Iriomoteolides-9a and 11a: two new odd-numbered macrolides from the marine dinoflagellate Amphidinium species.

Iriomoteolides-9a (1) and 11a (2), new 15- and 19-membered macrolides, respectively, have been isolated from the marine dinoflagellate Amphidinium species (strain KCA09052). Compounds 1 and 2 were obtained from the extracts of the algal cells inoculated in the PES and TKF seawater medium, respectively. The structures of 1 and 2 were assigned on the basis of detailed NMR analyses.

Influence of extracellular zinc on M1 microglial activation.

Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia.

CCL11 promotes migration and proliferation of mouse neural progenitor cells.

Background: Neonatal hypoxia-ischemia induces massive brain damage during the perinatal period, resulting in long-term consequences to central nervous system structural and functional maturation. Although neural progenitor cells (NPCs) migrate through the parenchyma and home in to injury sites in the rodent brain, the molecular mechanisms are unknown. We examined the role of chemokines in mediating NPC migration after neonatal hypoxic-ischemic brain injury.

5-aminolevulinic acid combined with ferrous ion reduces adiposity and improves glucose tolerance in diet-induced obese mice via enhancing mitochondrial function.

Background: Mitochondrial dysfunction is associated with obesity and various obesity-associated pathological conditions including glucose intolerance. 5-Aminolevulinic acid (ALA), a precursor of heme metabolites, is a natural amino acid synthesized in the mitochondria, and various types of cytochromes containing heme contribute to aerobic energy metabolism. Thus, ALA might have beneficial effects on the reduction of adiposity and improvement of glucose tolerance through its promotion of heme synthesis.

Sulfatide species with various fatty acid chains in oligodendrocytes at different developmental stages determined by imaging mass spectrometry.

HSO3-3-galactosylceramide (Sulfatide) species comprise the major glycosphingolipid components of oligodendrocytes and myelin and play functional roles in the regulation of oligodendrocyte maturation and myelin formation. Although various sulfatide species contain different fatty acids, it is unclear how these sulfatide species affect oligodendrogenesis and myelination. The O4 monoclonal antibody reaction with sulfatide has been widely used as a useful marker for oligodendrocytes and myelin.

Non-neuronal cardiac cholinergic system influences CNS via the vagus nerve to acquire a stress-refractory propensity.

We previously developed cardiac ventricle-specific choline acetyltransferase (ChAT) gene-overexpressing transgenic mice (ChAT tgm), i.e. an in vivo model of the cardiac non-neuronal acetylcholine (NNA) system or non-neuronal cardiac cholinergic system (NNCCS).

Suppression of MicroRNA-7 (miR-7) Biogenesis by Nuclear Factor 90-Nuclear Factor 45 Complex (NF90-NF45) Controls Cell Proliferation in Hepatocellular Carcinoma.

MicroRNA-7 (miR-7)has been characterized as an anti-oncogenic microRNA (miRNA) in several cancers, including hepatocellular carcinoma (HCC). However, the mechanism for the regulation of miR-7 production in tumors remains unclear. Here, we identified nuclear factor 90 (NF90) and NF45 complex (NF90-NF45) as negative regulators of miR-7 processing in HCC.

Iriomoteolides-10a and 12a, Cytotoxic Macrolides from Marine Dinoflagellate Amphidinium Species.

Two new macrolides, iriomoteolides-10a (1) and -12a (2), have been isolated from a marine dinoflagellate Amphidinium sp. (KCA09053 strain), and their structures were elucidated on the basis of a detailed two dimensional (2D)-NMR analysis. Compound 1 is a novel 21-membered Amphidinium macrolide, which contains one tetrahydrofuran ring, two ketone carbonyls, two hydroxyl groups, and six one-carbon branches.

Re-evaluation of hepatocyte replacement by recipient-derived cells after allogenic liver transplantation: Discrepancy between clinical observations and a rat model.

Aim: Reports suggest that hepatocyte replacement by recipient-derived cells is an active phenomenon after allogenic liver transplantation in rats. However, this phenomenon is rarely observed in humans, and further evaluation is necessary to bridge the gap between clinical practice and animal experiment.

Methods: Fifty percent volume of the liver from green fluorescent protein (GFP) transgenic Lewis rats were transplanted into wild-type Dark Agouti (DA) rats, in which GFP negative hepatocytes were considered as host (DA rat)-derived cells.

Patatin-like phospholipase domain-containing protein 3 is involved in hepatic fatty acid and triglyceride metabolism through X-box binding protein 1 and modulation of endoplasmic reticulum stress in mice.

Aim: Non-alcoholic steatohepatitis (NASH) is the major cause of chronic liver disease worldwide. Endoplasmic reticulum (ER) stress is considered to be an important pathological characteristic in NASH. A sequence variation (I148M) in the patatin-like phospholipase domain-containing protein 3/adiponutrin (PNPLA3) gene is known to be associated with the development of NASH.