The Effects of Morinda citrifolia (Noni) Fruit Juice on the Prevention of Stroke by Promoting Production of Nitric Oxide through the Brain of the Spontaneously Hypertensive Stroke Prone (SHRSP) Rats

Morinda citrifolia (Noni) is a traditional folk medicinal plant and has a long history of use as a food and medicine. In order to reveal the effects of Noni fruit juice (NFJ) on stroke prevention, we performed experiments using spontaneously hypertensive stroke prone (SHRSP) rats. NFJ did not change rat body weight, food intake, and water intake. However, both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly decreased after NFJ treatment in SHRSP rats. Furthermore, NFJ significantly increased the survival rate, urinary nitric oxide (NO) concentration was significantly higher in the NFJ group, and endothelial NO synthase (eNOS) phosphorylation levels increased in the brain after NFJ treatment. Two pathways regulate eNOS phosphorylation: the insulin-dependent pathway and the insulin-independent pathway. For the insulin-dependent pathway, phosphorylation of insulin receptor substrate 1 (IRS1) and protein kinase B (Akt) did not change in the NFJ group. For the insulin-independent pathway, expression of adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, liver kinase B 1 (LKB1), and silent information regulator 1 (Sirt1) significantly increased in the brain of SHRSP rats after NFJ treatment. These data suggested that NFJ prevented stroke by improved blood circulation, increased NO production, and elevated eNOS phosphorylation by stimulating the insulin-independent pathway (Sirt1-LKB1-AMPK-eNOS)

Steroid degradation genes in Comamonas testosteroni TA441: Isolation of genes encoding a Delta4(5)-isomerase and 3alpha- and 3beta-dehydrogenases and evidence for a 100kb steroid degradation gene hot spot.

In previous studies, we identified two major Comamonas testosteroni TA441 gene clusters involved in steroid degradation. Because most of the genes included in these clusters were revealed to be involved in degradation of basic steroidal structures and a few were suggested to be involved in the degradation of modified steroid compounds, we investigated the spectrum of steroid compounds degradable for TA441 to better identify the genes involved in steroid degradation. TA441 degraded testosterone, progesterone, epiandrosterone, dehydroepiandrosterone, cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid. The results suggested TA441 having 3alpha-dehydrogenase and Delta4(5)-isomerase, and 3beta-,17beta-dehydrogenase gene, we isolated these genes, all of which had high homology to the corresponding genes of C. testosteroni ATCC11996. Results of gene-disruption experiments indicated that 3beta,17beta-dehydrogenase is a unique 3beta-dehydrogenase which also acts as a 17beta-dehydrogenase in TA441, and there will be at least one more enzyme with 17beta-dehydrogenating activity. The 3alpha-dehydrogenase and Delta4(5)-isomerase genes were found adjacent in the DNA region between the two main steroid degradation gene clusters together with a number of other genes that may be involved in steroid degradation, suggesting the presence of a steroid degradation gene hot spot over 100kb in size in TA441

Effect of Suplatast Tosilate on Antileukotriene Non-Responders with Mild-to-Moderate Persistent Asthma

ABSTRACTBackgroundImmunomodulatory therapy has been recently introduced for the management of asthma. Suplatast tosilate (ST), a new immune-modifying drug, is known to improve the airway function by inhibiting the release of Th-2 cytokines. However, its efficacy as a controller listed in the guideline, Global Initiative for Asthma 2005 has not been established. In this study we investigated the role of ST in leukotriene receptor antagonist (LTRA) non-responders with mild-to-moderate persistent asthma before initiating corticosteroids inhalation therapy.MethodsThis was a prospective open-level clinical trial. LTRAs was given to 41 patients with asthma for 4 weeks and clinical efficacy was assessed using daily symptom scores. The 10 patients, aged 2.5-8.5 years, who failed to show clinical improvement, were defined as LTRA non-responders. After a 1-week washout period, the efficacy of ST was investigated and compared with LTRA non-responders for the following 4 weeks.ResultsLTRA non-responders showed a significant improvement in the average symptom score, peak expiratory flow, use of rescue medication and the proportion of symptom-free days with ST therapy.ConclusionsST is a good choice for patients who have failed to respond to LTRAs. ST should therefore be added to the list of treatment options for such patients

Bacterial Genes in the Aphid Genome: Absence of Functional Gene Transfer from Buchnera to Its Host

Genome reduction is typical of obligate symbionts. In cellular organelles, this reduction partly reflects transfer of ancestral bacterial genes to the host genome, but little is known about gene transfer in other obligate symbioses. Aphids harbor anciently acquired obligate mutualists, Buchnera aphidicola (Gammaproteobacteria), which have highly reduced genomes (420–650 kb), raising the possibility of gene transfer from ancestral Buchnera to the aphid genome. In addition, aphids often harbor other bacteria that also are potential sources of transferred genes. Previous limited sampling of genes expressed in bacteriocytes, the specialized cells that harbor Buchnera, revealed that aphids acquired at least two genes from bacteria. The newly sequenced genome of the pea aphid, Acyrthosiphon pisum, presents the first opportunity for a complete inventory of genes transferred from bacteria to the host genome in the context of an ancient obligate symbiosis. Computational screening of the entire A. pisum genome, followed by phylogenetic and experimental analyses, provided strong support for the transfer of 12 genes or gene fragments from bacteria to the aphid genome: three LD–carboxypeptidases (LdcA1, LdcA2,ψLdcA), five rare lipoprotein As (RlpA1-5), N-acetylmuramoyl-L-alanine amidase (AmiD), 1,4-beta-N-acetylmuramidase (bLys), DNA polymerase III alpha chain (ψDnaE), and ATP synthase delta chain (ψAtpH). Buchnera was the apparent source of two highly truncated pseudogenes (ψDnaE and ψAtpH). Most other transferred genes were closely related to genes from relatives of Wolbachia (Alphaproteobacteria). At least eight of the transferred genes (LdcA1, AmiD, RlpA1-5, bLys) appear to be functional, and expression of seven (LdcA1, AmiD, RlpA1-5) are highly upregulated in bacteriocytes. The LdcAs and RlpAs appear to have been duplicated after transfer. Our results excluded the hypothesis that genome reduction in Buchnera has been accompanied by gene transfer to the host nuclear genome, but suggest that aphids utilize a set of duplicated genes acquired from other bacteria in the context of the Buchnera–aphid mutualism

Assessment of Growth Disturbance in Japanese Children with IBD

In Japan, there is as yet no report on growth retardation in children with IBD. We therefore investigated the cause of growth retardation in Japanese children with IBD. We investigated the height, body weight, serum levels of albumin, IGF-I, CRP, and cytokines, and the amount of corticosteroid administered in children with Crohn's disease (CD, n = 15) and ulcerative colitis (UC, n = 18). Our results suggest that growth retardation is already present before the initial visit in children with CD, and chronic inflammation may be responsible this growth disturbance. Moreover, the amount of PSL used may contribute to growth retardation by decreasing the serum levels of IGF-I in children with IBD

Successful Late Management of Esophageal Perforation with T-Tube Drainage

The late management of spontaneous esophageal perforation is the most challenging problem for the surgeon. In this paper, we present a case in whom a spontaneous esophageal perforation was successfully treated by T-tube drainage after unsuccessful conservative treatment. The patient, a 68-year-old male, was admitted to the hospital with sudden upper abdominal pain. After 2 days, esophageal perforation was diagnosed, and conservative management was begun. Thereafter, the subcutaneous emphysema disappeared, and the patient's temperature decreased. However, on day 13, the patient's temperature spiked above 38°C, and computed tomography showed a mediastinal abscess. An emergency left thoracotomy with laparotomy was performed. Since a 2-cm longitudinal perforation with severe inflammatory reactions was observed, the T-tube drainage method was performed. The patient was discharged without postoperative complications and has not experienced any gastrointestinal symptoms, such as gastroesophageal reflux or dysphagia. In conclusion, the T-tube drainage method appears to be a simple and effective method for the late management of esophageal perforation with severe inflammatory reaction

Expression of TLR4/MyD88 in CRC

BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS: The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15–4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31–4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67–5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27–3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64–5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99–3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01–3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17–4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC

Phylogenetic Analysis of Cellulolytic Enzyme Genes from Representative Lineages of Termites and a Related Cockroach

The relationship between xylophagous termites and the protists resident in their hindguts is a textbook example of symbiosis. The essential steps of lignocellulose degradation handled by these protists allow the host termites to thrive on a wood diet. There has never been a comprehensive analysis of lignocellulose degradation by protists, however, as it has proven difficult to establish these symbionts in pure culture. The trends in lignocellulose degradation during the evolution of the host lineage are also largely unknown. To clarify these points without any cultivation technique, we performed meta-expressed sequence tag (EST) analysis of cDNA libraries originating from symbiotic protistan communities in four termite species and a wood-feeding cockroach. Our results reveal the establishment of a degradation system with multiple enzymes at the ancestral stage of termite-protistan symbiosis, especially GHF5 and 7. According to our phylogenetic analyses, the enzymes comprising the protistan lignocellulose degradation system are coded not only by genes innate to the protists, but also genes acquired by the protists via lateral transfer from bacteria. This gives us a fresh perspective from which to understand the evolutionary dynamics of symbiosis