Rifampicin exerts anti-mucoviscous activity against hypervirulent Klebsiella pneumoniae via binding to the RNA polymerase β subunit.

Objectives: In hypervirulent Klebsiella pneumoniae (hvKP), the hypermucoviscous capsule is known to be a major virulence determinant. We previously discovered that rifampicin (RFP), a bactericidal drug that binds to and inhibits the β subunit of RNA polymerase (RpoB), elicits anti-mucoviscous activity against hvKP by suppressing rmpA, a regulator of capsule production. Here, we aimed to determine whether RFP exerts this effect at sub-growth-inhibitory concentrations via its binding to RpoB.

Muscle Biopsy-proven Drug-induced Microscopic Polyangiitis in a Patient with Tuberculosis.

We herein report a case of muscle biopsy-proven microscopic polyangiitis (MPA) in a patient with tuberculosis. The patient had developed a persistent fever after the initiation of treatment for tuberculosis and was positive for myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA). However, because conventional symptoms were lacking, determination of the biopsy site was difficult.

The Fermented Soy Product ImmuBalance Suppresses Airway Inflammation in a Murine Model of Asthma.

The fermented soy product ImmuBalance contains many active ingredients and its beneficial effects on some allergic diseases have been reported. We hypothesized that ImmuBalance could have potential effects on airway inflammation in a murine model of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation.

Clarifying the pharmacological mechanisms of action of Shenfu Decoction on cardiovascular diseases using a network pharmacology approach.

Since the molecular mechanisms underlying in the pathogenesis of cardiovascular diseases (CVD) are extremely complex and have not yet been elucidated in detail, CVD remain the leading cause of death worldwide. Traditional Chinese medicine involves the treatment of disease from an overall perspective, and its therapeutic effects on CVD have been demonstrated. However, the mechanisms contributing to the multiscale treatment of cardiovascular diseases at the systematic level remain unclear.

Use of an electrophysiological technique for stepwise detection of trace agonist constituents of Hochuekkito in Xenopus oocytes injected with serotonin 2C receptor mRNA.

An electrophysiological bioassay was used to isolate the active compound from Hochuekkito (HET), which the current authors previously described as having potent agonist action against serotonin 2C receptors (5-HT2CR). Synthetic 5-HT2CR mRNA was injected into Xenopus oocytes to specifically express these receptors. Crude extracts and purified products were subjected to an electrophysiological bioassay using the voltage clamp method.

The Wakan-yaku Universe: A Useful Authorized Traditional Concept for Developing Novel Therapeutic Categories and Medicinal Drugs.

This review article mentions about the following points, and proposes its importance and positive thinking. 1) Wakan-yaku (Japanese oriental medicines) is covered by the national health insurance system in Japan as therapeutic drugs to be actively used in medical practice to treat illness. 2) Applications of Wakan-yaku is accomplished based on the reliable own theories which are established with long histories.

Extracellular cathepsin L stimulates axonal growth in neurons.

Objective: Cathepsin L, a lysosomal endopeptidase expressed in most eukaryotic cells, is a member of the papain-like family of cysteine proteases. Although commonly recognized as a lysosomal protease, cathepsin L is also secreted and involved in the degradation of extracellular matrix proteins. Previous studies demonstrated that the secretion of cathepsin L was stimulated by basic fibroblast growth factor (bFGF) and bFGF-enhanced axonal terminal sprouting of motor neurons.

Serotonin 2C receptor as a superhero: diversities and talents in the RNA universe for editing, variant, small RNA and other expected functional RNAs.

The serotonin 2C receptor subtype (5-HT2C) has a unique profession and continues to provide exciting and critical new information. The 5-HT2C is modulated at the RNA level by several mechanisms, including editing, short variant generation, and small RNAs. Recently, these phenomena, which had been demonstrated individually, were shown to be associated with each other.

Comparing the effects of kamikihito in Japan and kami-guibi-tang in Korea on memory enhancement: working towards the development of a global study.

Traditional medicine is widely used in East Asia, and studies that demonstrate its usefulness have recently become more common. However, formulation-based studies are not globally understood because these studies are country-specific. There are many types of formulations that have been introduced to Japan and Korea from China.

Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease.

New tacrine-carbazole hybrids were developed as potential multifunctional anti-Alzheimer agents for their cholinesterase inhibitory and radical scavenging activities. The developed compounds showed high inhibitory activity on acetylcholinesterase (AChE) with IC50 values ranging from 0.48 to 1.

Evidence of Antidepressive Effects of a Wakan-yaku, Hochuekkito, in Depression Model Mice with Learned-Helplessness Behavior.

Wakan-yaku is a type of Japanese and Sino traditional, systematized medical care that has been practiced for hundreds of years. This medicinal system includes many antidepressive prescriptions. One of the candidates is Hochuekkito, although experimental evidence has not yet been established clearly.

γ-Mangostin increases serotonin 2A/2C, muscarinic, histamine and bradykinin receptor mRNA expression.

Aim Of The Study: γ-Mangostin is a xanthone found in the fruit hulls of Garcinia mangostana L., which have long been used in Southeast Asia as a traditional medicine for the treatment of abdominal pain, dysentery, wound infections, fever and convulsions. Recent studies have revealed that γ-mangostin exhibits a variety of pharmacological activities, including serotonin 2 (5-HT(2)) receptor antagonism, anti-inflammatory effects and analgesic effects.

Serotonin 2C receptor (5-HT2CR) mRNA editing-induced down-regulation of 5-HT2CR function in Xenopus oocytes: the significance of site C editing.

Serotonin 2C receptor (5-HT2CR) mRNA receives editing at 5 nucleotide positions (sites A-E) located in the sequence encoding the second intracellular loop of 5-HT2CR. 5-HT2CR mRNA without editing and with editing at sites AB, ABD, ABC, ABCD, and C are translated to 6 isoforms of 5-HT2CR: INI(non-edited), VNI(AB), VNV(ABD), VSI(ABC), VSV(ABCD), and ISI(C), respectively. In this study, we investigated electrophysiologically the ability of these isoforms to couple with the G protein/phospholipase C (PLC) system using Xenopus oocytes injected with edited 5-HT2CR RNAs and muscarinic M(1) receptor (M1R) RNA.

Possible involvement of signal transducers and activators of transcription 3 system on depression in the model mice brain.

The aim of this study was to examine gene expression changes in the frontal cortex and hippocampus of animals with different susceptibility to stressful stimuli. Using a learned helplessness (LH) paradigm, mice received moderate current stimulation to induce different extents of LH behavior. Changes in mRNA expression were investigated by microarray and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).

Influence of an adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride, on 5-HT2CR mRNA editing in primary cultured cortical cells.

Treatment of primary cultured cortical cells with erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA), an inhibitor of adenosine deaminase (ADAR), for 6 d significantly and concentration-dependently reduced the editing efficacy at sites C and D but not at site A or B of 5-HT2CR mRNA. The treatment failed to affect the editing of ADAR-2 pre-mRNA and a subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptor (GluR2) mRNA. These findings suggest that EHNA is useful for clarifying the functional roles of 5-HT2CR mRNA editing at sites C and D.

Enhanced expression of BCL2/adenovirus EIB 19-kDa-interacting protein 3 mRNA, a candidate for intrinsic depression-related factor, and effects of imipramine in the frontal cortex of stressed mice.

We previously reported that long-term treatment with some antidepressants at low concentrations upregulates BCL2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) mRNA expression in NG108-15 cells without causing cell damage, suggesting that BNIP3 is a candidate of intrinsic depressive disorder-related factor(s). In this study, to clarify the physiologic functions of BNIP3, we investigated whether BNIP3 is actually related to the depressive condition in the brain using learned helplessness (LH) mice, an animal model of depression. Based on the score of escape failure, an index of depression degree, stressed animals were divided into groups with LH and without depressive-like symptoms (i.

Developmental changes in serotonin 2C receptor mRNA editing in the rat cerebral cortex and primary cultured cortical neurons.

Serotonin 2C receptor (5-HT2CR) mRNA has been reported to receive editing at 5 nucleotide positions (named sites A-E) which are located inconsecutively on the nucleotide sequence encoding the 2nd intracellular loop of the receptor protein. To clarify the physiological role of 5-HT2CR mRNA editing, we investigated developmental changes in editing frequencies at sites A-E in the rat cerebral cortex and primary cultured cortical neurons. The editing at sites A and B increased in parallel with the rat brain development and reached a plateau of 80-100% frequency at postnatal days 1-3.

BNIP-3: a novel candidate for an intrinsic depression-related factor found in NG108-15 cells treated with Hochu-ekki-to, a traditional oriental medicine, or typical antidepressants.

Wakan-yaku is a type of Japanese and Sino traditional, systematized medical care that has been practiced for hundreds of years. To search for novel intrinsic factors related to the action of antidepressants, we used Hochu-ekki-to (HET), a Wakan-yaku medicine with antidepressive effects. First, we verified the quality of the HET by three-dimensional high-performance liquid chromatography and a cytotoxicity check in NG108-15 cells.

Developmental changes in expression and self-editing of adenosine deaminase type 2 pre-mRNA and mRNA in rat brain and cultured cortical neurons.

Adenosine deaminase-1 and -2 (ADAR-1 and -2) are double-stranded RNA-specific enzymes involved in the editing of genes including serotonin 2C receptor (5-HT2CR) mRNA and ADAR-2 pre-mRNA. We reported that the editing efficacy of 5-HT2CR mRNA altered during brain development in rats. The present study aimed to clarify if changes in the expression of ADAR genes and the editing of ADAR-2 pre-mRNA occur during development.

Chotosan enhances macrophage colony-stimulating factor mRNA expression in the ischemic rat brain and C6Bu-1 glioma cells.

Macrophage colony stimulating factor (M-CSF) is a cytokine which has been recently reported to have a neuroprotective effect on ischemic rat brain. In this study, we investigated the effect of chotosan, an oriental medicine, which has been clinically demonstrated to be effective for the treatment of vascular dementia, on M-CSF gene expression in rats with permanent occlusion of bilateral common carotid arteries (P2VO) in vivo and in a C6Bu-1 glioma cell line in vitro. The expression level of M-CSF mRNA in the cerebral cortices of P2VO rats was significantly higher than that in the cerebral cortices of sham-operated animals.

Effects of manganese complexes of curcumin and diacetylcurcumin on kainic acid-induced neurotoxic responses in the rat hippocampus.

This study aimed to investigate the mechanism underlying the protective effects of manganese complexes of curcumin (Cp-Mn) and diacetylcurcumin (DiAc-Cp-Mn) on kainic acid (KA)-induced excitotoxicity in the rat hippocampus. Systemic injection of KA (10 mg/kg, i.p.

Chotosan, a kampo formula, ameliorates chronic cerebral hypoperfusion-induced deficits in object recognition behaviors and central cholinergic systems in mice.

We previously demonstrated that the Kampo formula chotosan (CTS) ameliorated spatial cognitive impairment via central cholinergic systems in a chronic cerebral hypoperfusion (P2VO) mouse model. In this study, the object discrimination tasks were used to determine if the ameliorative effects of CTS on P2VO-induced cognitive deficits are a characteristic pharmacological profile of this formula, with the aim of clarifying the mechanisms by which CTS enhances central cholinergic function in P2VO mice. The cholinesterase inhibitor tacrine (THA) and Kampo formula saikokeishito (SKT) were used as controls.

A novel neuroprotective agent with antioxidant and nitric oxide synthase inhibitory action.

N(alpha)-vanillyl-N(omega)-nitroarginine (N - 1) that combines the active functions of natural antioxidant and nitric oxide synthase inhibitor was developed for its neuroprotective properties. N - 1 exhibited protective effects against hydrogen peroxide-induced cell damage and the inhibitory effect on nitric oxide 'NO' production induced by calcium ionophore in NG 108-15 cells. N - 1 inhibited the constitutive NOS isolated from rat cerebellar in a greater extent than constitutive NOS from human endothelial cells.

Molecular pathopharmacology of 5-HT2C receptors and the RNA editing in the brain.

Among the 14 kinds of serotonin (5-hydroxytryptamine, 5-HT) receptor subtypes (5-HTR), 5-HT(2C) receptor (5-HT2CR) has been intensively investigated because of its physiologically and pathophysiologically important role in the brain. 5-HT2CR has been suggested to be involved in depressive disorders based on findings from pharmacological/neurochemical/behavioral studies using autopsy preparations of humans suffering from depression, animal models of depression, and animals treated with antidepressant drugs. Recently the editing of 5-HT2CR mRNA has been reported to participate in the pathogenesis of depressive disease.

Prevention of kainic acid-induced changes in nitric oxide level and neuronal cell damage in the rat hippocampus by manganese complexes of curcumin and diacetylcurcumin.

Curcumin is a natural antioxidant isolated from the medicinal plant Curcuma longa Linn. We previously reported that manganese complexes of curcumin (Cp-Mn) and diacetylcurcumin (DiAc-Cp-Mn) exhibited potent superoxide dismutase (SOD)-like activity in an in vitro assay. Nitric oxide (NO) is a free radial playing a multifaceted role in the brain and its excessive production is known to induce neurotoxicity.