9-Phenanthrol,a TRPM4 Inhibitor,Protects Isolated Rat Hearts from Ischemia–Reperfusion Injury

Despite efforts to elucidate its pathophysiology, ischemia–reperfusion injury lacks an effective preventative intervention. Because transient receptor potential cation channel subfamily M member 4 (TRPM4) is functionally expressed by many cell types in the cardiovascular system and is involved in the pathogenesis of various cardiovascular diseases, we decided to assess its suitability as a target of therapy. Thus, the aim of this study was to examine the possible cardioprotective effect of 9-phenanthrol, a specific inhibitor of TRPM4. Isolated Langendorff-perfused rat hearts were pretreated with Krebs–Henseleit (K–H) solution (control), 9-phenanthrol, or 5-hydroxydecanoate (5-HD, a blocker of the ATP-sensitive potassium channel) and then subjected to global ischemia followed by reperfusion with the K–H solution. To evaluate the extent of heart damage, lactate dehydrogenase (LDH) activity in the effluent solution was measured, and the size of infarcted area of the heart was measured by 2,3,5-triphenyltetrazolium chloride staining. In controls, cardiac contractility decreased, and LDH activity and the infarcted area size increased. In contrast, in hearts pretreated with 9-phenanthrol, contractile function recovered dramatically, and the infarcted area size significantly decreased. The cardioprotective effects of 9-phenanthrol was not completely blocked by 5-HD. These findings show that 9-phenanthrol exerts a cardioprotective effect against ischemia in the isolated rat heart and suggest that its mechanism of action is largely independent of ATP-sensitive potassium channels.     

Distribution Dynamics of Recombinant Lactobacillus in the Gastrointestinal Tract of Neonatal Rats

One approach to deliver therapeutic agents, especially proteins, to the gastro-intestinal (GI) tract is to use commensal bacteria as a carrier. Genus Lactobacillus is an attractive candidate for use in this approach. However, a system for expressing exogenous proteins at a high level has been lacking in Lactobacillus. Moreover, it will be necessary to introduce the recombinant Lactobacillus into the GI tract, ideally by oral administration. Whether orally administered Lactobacillus can reach and reside in the GI tract has not been explored in neonates. In this study, we have examined these issues in neonatal rats. To achieve a high level of protein expression in Lactobacillus, we tested the impact of three promoters and two backbones on protein expression levels using mRFP1, a red fluorescent protein, as a reporter. We found that a combination of an L-lactate dehydrogenase (ldhL) promoter of Lactobacillus sakei with a backbone from pLEM415 yielded the highest level of reporter expression. When this construct was used to transform Lactobacillus casei, Lactobacillus delbrueckii and Lactobacillus acidophilus, high levels of mRFP1 were detected in all these species and colonies of transformed Lactobacillus appeared pink under visible light. To test whether orally administered Lactobacillus can be retained in the GI tract of neonates, we fed the recombinant Lactobacillus casei to neonatal rats. We found that about 3% of the bacteria were retained in the GI tract of the rats at 24 h after oral feeding with more recombinant Lactobacillus in the stomach and small intestine than in the cecum and colon. No mortality was observed throughout this study with Lactobacillus. In contrast, all neonatal rats died within 24 hours after fed with transformed E. coli. Taken together, our results indicate that Lactobacillus has the potential to be used as a vehicle for the delivery of therapeutic agents to neonates.     

Comparative Analysis of Protocadherin-11 X-Linked Expression among Postnatal Rodents,Non-Human Primates,and Songbirds Suggests Its Possible Involvement in Brain Evolution

Background

Protocadherin-11 is a cell adhesion molecule of the cadherin superfamily. Since, only in humans, its paralog is found on the Y chromosome, it is expected that protocadherin-11X/Y plays some role in human brain evolution or sex differences. Recently, a genetic mutation of protocadherin-11X/Y was reported to be associated with a language development disorder. Here, we compared the expression of protocadherin-11 X-linked in developing postnatal brains of mouse (rodent) and common marmoset (non-human primate) to explore its possible involvement in mammalian brain evolution. We also investigated its expression in the Bengalese finch (songbird) to explore a possible function in animal vocalization and human language faculties.

Methodology/Principal Findings

Protocadherin-11 X-linked was strongly expressed in the cerebral cortex, hippocampus, amygdala and brainstem. Comparative analysis between mice and marmosets revealed that in certain areas of marmoset brain, the expression was clearly enriched. In Bengalese finches, protocadherin-11 X-linked was expressed not only in nuclei of regions of the vocal production pathway and the tracheosyringeal hypoglossal nucleus, but also in areas homologous to the mammalian amygdala and hippocampus. In both marmosets and Bengalese finches, its expression in pallial vocal control areas was developmentally regulated, and no clear expression was seen in the dorsal striatum, indicating a similarity between songbirds and non-human primates.

Conclusions/Significance

Our results suggest that the enriched expression of protocadherin-11 X-linked is involved in primate brain evolution and that some similarity exists between songbirds and primates regarding the neural basis for vocalization.     

Metabolic Syndrome Components Are Associated with Intervertebral Disc Degeneration: The Wakayama Spine Study

Objective

The objective of the present study was to examine the associations between metabolic syndrome (MS) components, such as overweight (OW), hypertension (HT), dyslipidemia (DL), and impaired glucose tolerance (IGT), and intervertebral disc degeneration (DD).

Design

The present study included 928 participants (308 men, 620 women) of the 1,011 participants in the Wakayama Spine Study. DD on magnetic resonance imaging was classified according to the Pfirrmann system. OW, HT, DL, and IGT were assessed using the criteria of the Examination Committee of Criteria for MS in Japan.

Results

Multivariable logistic regression analysis revealed that OW was significantly associated with cervical, thoracic, and lumbar DD (cervical: odds ratio [OR], 1.28; 95% confidence interval [CI], 0.92–1.78; thoracic: OR, 1.75; 95% CI, 1.24–2.51; lumbar: OR, 1.87; 95% CI, 1.06–3.48). HT and IGT were significantly associated with thoracic DD (HT: OR, 1.54; 95% CI, 1.09–2.18; IGT: OR, 1.65; 95% CI, 1.12–2.48). Furthermore, subjects with 1 or more MS components had a higher OR for thoracic DD compared with those without MS components (vs. no component; 1 component: OR, 1.58; 95% CI, 1.03–2.42; 2 components: OR, 2.60; 95% CI, 1.62–4.20; ≥3 components: OR, 2.62; 95% CI, 1.42–5.00).

Conclusion

MS components were significantly associated with thoracic DD. Furthermore, accumulation of MS components significantly increased the OR for thoracic DD. These findings support the need for further studies of the effects of metabolic abnormality on DD.     

Reduced dispersal and survival in the sweet potato weevil (Euscepes postfasciatus) after irradiation

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A neural-specific F-box protein Fbs1 functions as a chaperone suppressing glycoprotein aggregation

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