Ninjin-yoei-to (NYT), a Kampo medicine, has ameliorative effects on cognitive dysfunction via enhancing cholinergic neuron activity. To explore an efficacy of NYT administration for prevention and cure of Alzheimer's disease, here we examined the effect of NYT on amyloid β1-42 (Aβ1-42)-induced neurodegeneration in the dentate gyrus.A diet containing 3% NYT was administered to mice for 2 weeks and human Aβ1-42 was intracerebroventricularly injected. Neurodegeneration in the dentate granule cell layer of the hippocampus, which was determined 2 weeks after the injection, was rescued by administration of the diet for 4 weeks. Aβ staining (uptake) was not modified in the dentate granule cell layer by pre-administration of the diet for 2 weeks, while Aβ1-42induced increase in intracellular Zn 2+ was reduced, suggesting that pre-administration of NYT prior to Aβ injection is effective for reducing Aβ1-42-induced Zn 2+ toxicity in the dentate gyrus. As a matter of fact, Aβ1-42-induced neurodegeneration in the dentate gyrus was rescued by pre-administration of NYT. Interestingly, the level of metallothioneins, intracellular Zn 2+ -binding proteins, which can capture Zn 2+ from Zn-Aβ1-42 complexes, was elevated in the dentate granule cell layer by pre-administration of NYT. The present study suggests that pre-administration of NYT prevents Aβ1-42mediated neurodegeneration in the dentate gyurs by induced synthesis of metallothioneins, which reduces intracellular Zn 2+ toxicity induced by Aβ1-42.
Despite tremendous success of pneumococcal conjugated vaccine and antimicrobial treatment by amoxicillin, acute otitis media (AOM) still remains as a great medical concern. Failure of antimicrobial treatment includes several factors. The middle ear cavity is surrounded by bone tissue, which makes it difficult to maintain sufficient concentration of antibiotics. Tympanic membrane of AOM patients thickens and actually becomes a barrier for topical therapy. This review discusses novel antimicrobial treatment strategies based on drug delivery systems (DDS) for AOM. To deliver drugs enough to kill the pathogenic bacteria without systemic side effects, the development of new antimicrobial treatment strategy applying innovative drug DDS has been expected. The sustained-release DDS can achieve sufficient time for antimicrobial concentrations to exceed minimum inhibitory concentration (MIC) for time-dependent antibiotics as well as enough maximum concentration for dose-dependent antibiotics to eradicate causative pathogens in the middle ear. The development of trans-tympanic membranes of DDS, such as hydrogels with chemical permeation enhancers (CPEs), is another attractive strategy. Phage is a promising strategy for developing DDS-based therapies. The DDS formulations enable antimicrobial treatment of AOM by a single dose and thus, an attractive future antimicrobial treatment for AOM.
SummaryTo understand the molecular basis of glucose concentration-responsive insulin synthesis and secretion from pancreatic islet beta cells, a group of pancreatic islet beta-cell-related cDNAs was cloned. A pair of cDNA libraries was constructed from a mouse pancreatic islet beta-cell line of MIN6, which was cultured in either high glucose or low glucose media. By applying a random cDNA sequencing approach, 503 and 395 independent species were obtained from a total of 1,011 and 762 clones in the high glucose and low glucose library, respectively. The unknown genes comprised the majority of about 70 % independent clones in both libraries. In Northern blot analysis, 311 (69.4%) of 448 independent clones showed positive signals within 72 h of autoradiographic exposure. Surprisingly, 150 (48.2 %) out of 311 positive clones showed positive signals to MIN6 cells, but not to NIH/3T3 fibroblasts. The expression level of three unknown clones were glucose-concentration dependent. Combination of a random cDNA sequencing approach and Northern blot analysis is useful to obtain a large number of novel genes and islet beta-cell-related genes. [Diabetologia (1995) 38: 381-386] Key words Random cDNA sequencing, MIN6, pancreatic islet beta cell.Understanding the molecular basis of pancreatic islet beta cells is essential in order to develop a logical treatment for diabetes. In addition to glucokinase [1][2][3] and mitochondrial genes [4][5], which are known to be aetiological for non-insulin-dependent diabetes or maturity-onset diabetes of the young, there are others which are related to islet beta-cell Received: 12 July 1994 and in revised form: 20 September 1994Corresponding author: Professor M. Itakura, Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, University of Tokushima, Kuromoto, Tokushima-city, Tokushima, 770, Japan Abbreviations: DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; AGPC, acid guanidinium thiocyanatephenol-chloroform; bp, base pair(s); IAPR islet amyloid polypeptide; HUMMHBA 123, human MHC protein homologous to chicken B complex protein; PACAR pituitary adenylate cyclase activating polypeptide precursor. function and diabetes. It is speculated that the highly-differentiated functions of islet beta cells are based on a group of cell-specific genes. Recently, large,scale cDNA analysis has become a valuable way to examine and register expressed genes in various tissues by determining expressed sequence tags [6][7][8][9]. Abundant transcripts, which are frequently encountered in random sequencing, are assumed to play relatively more important roles than rare transcripts with exceptions including transacting factors and rate-limiting enzymes among others. With this in mind we randomly sequenced cDNA to clone unknown genes which are abundantly expressed and are presumably important for islet beta-cell functions. In this study we report the acquisition of a group of islet beta-cell-related genes by combining a random cDNA sequencing of a total of 1,773 clones from a m...
Transient receptor potential (TRP) channels, neuronal stimulations widely known to be associated with thermal responses, pain induction, and osmoregulation, have been shown in recent studies to have underlying mechanisms associated with inflammatory responses. The role of TRP channels on inflammatory milieu during bacterial infections has been widely demonstrated. It may vary among types of channels/pathogens, however, and it is not known how TRP channels function during pneumococcal infections. Streptococcus pneumoniae can cause severe infections such as pneumonia, bacteremia, and meningitis, with systemic inflammatory responses. This study examines the role of TRP channels (TRPV1 and TRPV4) for pneumococcal nasal colonization and subsequent development of invasive pneumococcal disease in a mouse model. Both TRPV1 and TRPV4 channels were shown to be related to regulation of the development of pneumococcal diseases. In particular, the influx of neutrophils (polymorphonuclear cells) in the nasal cavity and the bactericidal activity were significantly suppressed among TRPV4 knockout mice. This may lead to severe pneumococcal pneumonia, resulting in dissemination of the bacteria to various organs and causing high mortality during influenza virus coinfection. Regulating host immune responses by TRP channels could be a novel strategy against pathogenic microorganisms causing strong local/systemic inflammation.
Streptococcus pneumoniae, one of the most common commensal pathogens among children, is spread by close contact in daycare centers or within a family. Host innate immune responses and bacterial virulence factors promote pneumococcal transmission. However, investigations into the effects of environmental factors on transmission have been limited. Passive smoking, a great concern for children’s health, has been reported to exacerbate pneumococcal diseases. Here, we describe the effect of cigarette smoke exposure on an infant mouse model of pneumococcal transmission. Our findings reveal that the effect of cigarette smoke exposure significantly promotes pneumococcal transmission by enhancing bacterial shedding from the colonized host and by increasing susceptibility to pneumococcal colonization in the new host, both of which are critical steps of transmission. Local inflammation, followed by mucosal changes (such as mucus hypersecretion and disruption of the mucosal barrier), are important underlying mechanisms for promotion of transmission by smoke exposure. These effects were attributable to the constituents of cigarette smoke rather than smoke itself. These findings provide the first experimental evidence of the impact of environmental factors on pneumococcal transmission and the mechanism of pathogenesis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.