Caffeic acid phenethyl ester (CAPE) is a component of propolis, which is a substance taken from the hives of honeybees, and is known to exhibit an anti-inflammatory activity. Such activity has been thought to be partly based on its potential and specific inhibitory activities toward nuclear factor-κB, a transcription factor. Therefore, in the present study, we evaluated the effect of CAPE on functional locomotor recovery after spinal cord injury (SCI) caused by hemi-transection, because inflammatory responses are a major cause of the secondary injury observed following SCI and play a pivotal role in regulating the pathogenesis of acute and chronic SCI. When CAPE was i.p.-administered at a dosage of 10 μmol/kg, it enhanced the recovery of locomotor function and reduced the lesion size while suppressing the expression of the mRNAs for a pro-inflammatory cytokine interleukin-1β and the inflammatory enzymes, inducible nitric oxide synthase and cyclooxygenase-2. These results suggest CAPE to be a promising therapeutic tool for reducing the secondary neuronal damage following primary physical injury to the spinal cord.
Endothelin (ET)-1 is a potent vasoconstrictor that has been implicated in the pathogenesis of a number of diseases, and some studies suggest that circulating ET-1 is elevated in sepsis. The present study investigated whether ET plays a role in sepsis-mediated acute lung injury and whether its expression could be down regulated by blockade of TNF-α in septic lung. Male Wistar rats at 8 weeks of age were administered with either saline or lipopolysaccharide (LPS) at different time points (1, 3, 6 and 10 h) and various tests were then performed. The features of acute lung injury were observed at 1 h after LPS administration, which gradually became severe with time. Systolic and diastolic pressures were reduced just about one hour after LPS administration, whereas pulmonary TNF-α levels were significantly increased at various time points after LPS administration. LPS induced a time-dependent expression of ET-1 and ETA receptor in the lungs compared to control, peaking and incre sing by 3 fold at 6 h after induction of endotoxemia, whereas levels of ETB receptor, which has vasodilating effects, were remarkably down regulated time-dependently. We conclude that time-dependent increase of ET-1 and ETA receptor with the down regulation of ETB receptor may play a role in the pathogenesis of acute lung injury in endotoxemia. Finally, treatment of LPS-administered rats with TNF-α blocking peptide for three hours significantly suppressed levels of pulmonary ET-1. These data taken together, led us to conclude that differential alteration in ET expression and its receptors may be mediated by TNF-α and may, in part, account for the pathogenesis of acute lung injury in endotoxemia.
The leaves of Laurus noblis L. (laurel) are mainly used as a spice in cooking, and the essential oil obtained by steam distillation of the leaves is used as an additive in foods, drugs and cosmetics. We investigated the effect of the volatiles emitted from the leaves of L. noblis at different doses (low-dose and high-dose groups) on vigilance performance in a visual discrimination task. By inhaling volatiles of the leaves of L. noblis, the decrease of the rate of true hits found in the control group was prevented in the low-dose group. The high-dose group showed higher scores than the low-dose group for subjective effects related to negative emotion. Meanwhile, both groups showed physiological effects suggesting stimulation of circulation. These findings suggest that the volatiles emitted from the leaves of L. noblis at low concentration could be utilized to maintain a high level of vigilance performance, such as the rate of true hits by improving physiological arousal without incurring the detrimental performance effects of negative emotion.
Collagen sponge is one of the medical materials that are frequently used in clinical medicine. However, the problem of prion disease harmfully affected the usage of mammals-derived medical materials. Since there have been no reports about prion disease occurring in marine products, we produced the collagen and elastin sponge (CES) made from salmon, and investigated whether the CES could be a substitute for mammalian collagen sponge. Fibroblasts were seeded in the CES to examine whether the CES could be used as a scaffold for tissue engineering. The results of the WST-1 assay showed that the fibroblasts were viable and were well proliferated in the CES. To examine whether the CES could be used as an artificial dermis, the CES and TERUDERMIS (traditional collagen sponge) were grafted onto the skin defects on the dorsum of rats. The histological findings of these ulcers showed non-significant difference between the CES and TERUDERMIS. Because of the safety, the abundance of the resources, and the possessing same ability as TERUDERMIS, the biomedical materials derived from marine products may be a substitute for those derived from mammals.
The TNF-family molecule, Receptor Activator of Nuclear factor κ B Ligand (RANKL) is known as a key regulator for bone remodeling, and is essential for the development and activation of osteoclasts. In this study, we examined the regulation of RANKL in primary human bone marrow adipocytes and the relationship between bone marrow adipocytes and bone metabolism. RANKL expression and the RANKL/osteoprotegerin (OPG) mRNA ratio in marrow adipocytes increased following dexamethasone treatment. In co-cultures of human osteoclast precursors and bone marrow adipocytes with dexamethasone, osteoclast precursors differentiated to TRAP-positive multinuclear cells. Moreover, the ability of bone resorption was confirmed in co-culture in flasks coated with calcium phosphate film. Osteoclast precursor differentiation and bone resorption were blocked by RANKL antibody pretreatment. TRAP-positive multinuclear cells did not form in coculture without cell-to-cell contact conditions. We conclude that primary human bone marrow adipocytes have the ability to promote osteoclast differentiation and activities, similar to osteoblasts and other RANKL-expressing cells.
The need for population care increases with the age of the population. Pneumonia is the fourth leading cause of death in Japan, yet the risk of pneumonia could be reduced by eliminating opportunistic infection sources such as oral bacteria (e.g. Porphyromonas gingivalis). Previously, we reported removal of P. gingivalis by macrophages during the early stages of cellular immunity, although neither neutrophils nor antibodies participated in the antimicrobial activity. BCG is a live vaccine against tuberculosis, and is thought to maintain cellular immunity as the antigen remains in vivo for longer periods. In this experiment, we attempted to clarify the relationship between aging and the elimination of P. gingivalis by examining the protective capacity of BCG against P. gingivalis infection in mice of various ages. In young mice, the reduction in numbers of P. gingivalis was accompanied by increased IFN-γ and IL-12 levels, and nitric oxide was continuously produced. The augmentation of bactericidal activity, namely the effects of the vaccine, was clear in young mice, but weaker in older mice. Activation of cellular immunity was not observed in older mice, even when boosters were administered.
Previous studies suggest that propofol and sevoflurane anaesthesia in rats may have variable effects on the proteome. Brains from untreated rats and rats anaesthetised with intravenous propofol infusion or inhaled sevoflurane were collected at various time points post-anaesthesia and subjected to global protein expression profiling using two-dimensional gel electrophoresis. Significant changes in protein spot intensity (i.e. expression) between the propofol and sevoflurane groups demonstrated clear similarities and differences in proteomic regulation by these anaesthetics. The proteins regulated were broadly classified into groups involved in cytoskeletal/neuronal growth, cellular metabolism, signalling, and cell stress/death responses. Proteins concerned with cell death and stress responses were down-regulated by both agents, but the anaesthetics had variable effects on proteins in the other groups. Importantly, proteins such as Ulip2 and dihydropyrimidinaselike-2 were regulated in opposite directions by propofol and sevoflurane. Moreover, the timecourse of regulation of proteins varied depending on the agent used. These data suggest different underlying mechanisms of proteomic regulation. We found that sevoflurane anaesthesia had more pronounced effects, on a wider range of proteins, and over an apparently longer duration than propofol. Thus, sevoflurane could be considered a more disruptive anaesthetic agent. Our findings show that protein expression is regulated differentially according to the anaesthetic agent and the method of delivery support and extend our previous observations of differential genomic regulation by anaesthetics in the brain. This study highlights the power of proteomic studies in assessing the effects of certain anaesthetics on the integrity of neuronal structure and function.
The mushroom Hericium erinaceus has been used as a food and herbal medicine since ancient times in East Asia. It has been reported that H. erinaceus promotes nerve growth factor secretion in vitro and in vivo. Nerve growth factor is involved in maintaining and organizing cholinergic neurons in the central nervous system. These findings suggest that H. erinaceus may be appropriate for the prevention or treatment of dementia. In the present study, we examined the effects of H. erinaceus on amyloid β(25-35) peptide-induced learning and memory deficits in mice. Mice were administered 10 μg of amyloid β(25-35) peptide intracerebroventricularly on days 7 and 14, and fed a diet containing H. erinaceus over a 23-d experimental period. Memory and learning function was examined using behavioral pharmacological methods including the Y-maze test and the novelobject recognition test. The results revealed that H. erinaceus prevented impairments of spatial short-term and visual recognition memory induced by amyloid β(25-35) peptide. This finding indicates that H. erinaceus may be useful in the prevention of cognitive dysfunction.
The primary cilium is now considered to function as a fundamental, not rudimentary, structure for mechanical and chemical sensing by individual cells. Primary cilia in neurons express type III adenylyl cyclase (ACIII) and GPCRs for somatostatin (somatostatin receptor 3, SSTR3), serotonin, and melanin-concentrating hormone. The present immunohistochemical and electron microscopic study revealed an abundant occurrence of SSTR3-expressing solitary cilia in insulin- and growth hormone-secreting cells of the mouse. The SSTR3 immunoreactivity was restricted to the plasma membrane of cilia in both cell types, differing from previously reported immunohistochemical localization of SSTRs to cell bodies. The primary cilia in the islet cells were longer than those in the pituitary cells and extended for a long distance in the intercellular canalicules endowed with microvilli. No other endocrine organs were provided with the SSTR3-expressing primary cilia, while the primary cilia in these organs were frequently immunolabeled with ACIII antibody. Since the somatostatin inhibition of both insulin and GH release is regulated mainly by SSTR1 and SSTR5, the primary cilia expressing SSTR3 may be involved in a signaling which differs from that via other SSTR subtypes expressing in cell bodies.