Loss of interleukin-10 exacerbates early Type-1 diabetes-induced bone loss

Type-1 diabetes (T1D) increases systemic inflammation, bone loss, and risk for bone fractures. Levels of the anti-inflammatory cytokine interleukin-10 (IL-10) are decreased in T1D, however their role in T1D-induced osteoporosis is unknown. To address this, diabetes was induced in male IL-10 knockout (KO) and wild-type (WT) mice. Analyses of femur and vertebral trabecular bone volume fraction identified bone loss in T1D-WT mice at 4 and 12 weeks, which in T1D-IL-10-KO mice was further reduced at 4 weeks but not 12 weeks. IL-10 deficiency also increased the negative effects of T1D on cortical bone. Osteoblast marker osterix was decreased, while osteoclast markers were unchanged, suggesting that IL-10 promotes anabolic processes. MC3T3-E1 osteoblasts cultured under high glucose conditions displayed a decrease in osterix which was prevented by addition of IL-10. Taken together, our results suggest that IL-10 is important for promoting osteoblast maturation and reducing bone loss during early stages of T1D.     

Comparative evaluation of in vivo osteogenic differentiation of fetal and adult mesenchymal stem cell in rat critical-sized femoral defect model

Mesenchymal stem cells (MSCs) can be obtained from various sources. MSCs from different origins appear to have different preferences for differentiation. In this study, we have compared the in vivo osteogenic potential of adult MSCs from adipose tissue (AT) and bone marrow (BM) with fetal MSCs from umbilical cord (UC) and umbilical cord blood (UCB) by using a rat critical-sized femoral defect model. We have also sought to determine whether pretreatment with an osteogenic medium promotes osteogenesis in MSCs. Study groups were divided as follows: (1) defect only, (2) scaffold only, (3) AT MSCs in scaffolds, (4) BM MSCs in scaffolds, (5) UC MSCs in scaffolds and (6) UCB MSCs in scaffolds. Groups with MSCs were further divided with respect to their pretreatment. At 12 weeks after surgery, in vivo osteogenesis was measured radiographically and by micro-computed tomography (CT). Based on quantitative assessment by micro-CT, no significant difference of the mean bone volume fraction value (BV/TV) was seen between adult MSCs (AT and BM MSCs) and fetal MSCs (UC and UCB MSCs). The mean BV/TVs were significantly higher in non-pretreated BM MSC (14.2±1.4%) and UCB MSC (14.0±1.2%) and pretreated UC MSC (14.8±2.0%) than in those with the scaffold only (11.3±1.3%; P<0.05). In addition, AT (from 10.4±1.2% to 13.1±2.2%) and UC (from 10.3±0.7% to 14.8±2.0%) MSCs from solid tissues showed a significant increase in the mean BV/TV with pretreatment (P<0.05). In contrast, BM MSC (from 14.2±1.4% to 10.9±1.2%) and UCB MSC (from 14.0±1.2% to 11.6±1.0%) from non-solid tissues showed a significant decrease with pretreatment (P<0.05).     

Algivirga pacifica gen. nov., sp. nov., a Novel Agar-Degrading Marine Bacterium of the Family Flammeovirgaceae Isolated from Micronesia

An aerobic, Gram-negative, coccoid to short rod-shaped and non-flagellated marine bacterial strain S354^T was isolated from seawater of Micronesia. The strain was capable to degrade agar-forming slight depression into agar plate. Growth occurred at a temperature range of 12–44 °C, a pH range of 5–9, and a salinity range of 1–7 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences suggested that S354^T belongs to the family Flammeovirgaceae. The novel strain was most closely related to Limibacter armeniacum YM 11-185^T with similarity of 92.5 %. The DNA G+C content was 43.8 mol%. The major fatty acids (>10 %) were iso-C_15:0 and C_16:1 ω5c. The predominant isoprenoid quinone was determined to be MK-7. Polar lipid profile of S354^T consisted of phosphatidylethanolamine, unknown polar lipid, and unknown glycolipids. Based on the phenotypic, phylogenetic, biochemical, and physiological tests conducted in this study, S354^T is proposed to represent a type strain of a novel genus and species. The 16S rRNA gene sequence of S354^T is registered in GenBank under the accession number JQ639084. The type of strain Algivirga pacifica gen. nov., sp. nov. is S354^T (=KCCM 90107^T=JCM 18326^T).     

Effect of GABA Receptor Agonists or Antagonists Injected Spinally on the Blood Glucose Level in Mice

The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABA_B receptor agonist; 1–10 μg/5 μl) or bicuculline (a GABA_A receptor antagonist; 1–10 μg/5 μl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABA_A receptor agonist; 1–5 μg/5 μl) or phaclofen (a GABA_B receptor antagonist; 5–10 μg/5 μl) administered i.t. did not affect the blood glucose level. Baclofen–induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 μg/5 μl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABA_B receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABA_A receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.     

The Role of HSPA12B in Regulating Neuronal Apoptosis

Heat shock protein A12B (HSPA12B) is the newest member of a recently defined subfamily of proteins distantly related to the 70-kDa family of heat shock proteins (HSP70) family. HSP70s play a crucial role in protecting cells, tissues, organs and animals from various noxious conditions. Here we studied the dynamic expression changes and localization of HSPA12B after middle cerebral artery occlusion (MCAO) with reperfusion induced ischemic insult processes in adult rats. Apoptosis, as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, was also increased in the peri-ischemic cortex compared to non-ischemic hemisphere. The expression of HSPA12B was strongly induced in the ischemic hemisphere of MCAO reperfusion rats in vivo. In vitro studies indicated that the up-regulation of HSPA12B may be involved in oxygen-glucose deprivation-induced PC12 cell death. And knockdown of HSPA12B in cultured differentiated PC12 cells by siRNA showed that HSPA12B inhibited the expression of active caspase-3. Collectively, these results suggested that HSPA12B may be required for protecting neurons from ischemic insults.     

Time-course Changes in Immunoreactivities of Glucokinase and Glucokinase Regulatory Protein in the Gerbil Hippocampus Following Transient Cerebral Ischemia

Glucose is a main energy source for normal brain functions. Glucokinase (GK) plays an important role in glucose metabolism as a glucose sensor, and GK activity is modulated by glucokinase regulatory protein (GKRP). In this study, we examined the changes of GK and GKRP immunoreactivities in the gerbil hippocampus after 5 min of transient global cerebral ischemia. In the sham-operated-group, GK and GKRP immunoreactivities were easily detected in the pyramidal neurons of the stratum pyramidale of the hippocampus. GK and GKRP immunoreactivities in the pyramidal neurons were distinctively decreased in the hippocampal CA1 region (CA), not CA2/3, 3 days after ischemia–reperfusion (I–R). Five days after I–R, GK and GKRP immunoreactivities were hardly detected in the CA1, not CA2/3, pyramidal neurons; however, at this point in time, GK and GKRP immunoreactivities were newly expressed in astrocytes, not microglia, in the ischemic CA1. In brief, GK and GKRP immunoreactivities are changed in pyramidal neurons and newly expressed in astrocytes in the ischemic CA1 after transient cerebral ischemia. These indicate that changes of GK and GKRP expression may be related to the ischemia-induced neuronal damage/death.     

An association between − 866G/A polymorphism in the promoter of UCP2 and obesity: A meta-analysis

− 866G/A polymorphism in the promoter of UCP2 gene has been reported to be associated with obesity, but the results remain inconclusive. To assess the relation of UCP2 − 866G/A polymorphism and obesity susceptibility, a meta-analysis was performed. PubMed, ISI, Wanfang database, VIP and CBM were searched to identify relevant studies up to July 31, 2012. Odds ratios (OR) and 95% confidence interval (95% CI) were pooled using fixed or random effect models. Subgroup analysis was performed by ethnicity (categorized as Asian and European). Heterogeneity and publication bias evaluation were performed to validate the credibility. Meta-regression and the ‘leave one out’ sensitive analysis were used to explore the potential sources of between-study heterogeneity. 14 studies were included in this meta-analysis. After exclusion of articles that deviated from the HWE in controls, and were the key contributors to between-study heterogeneity, the meta-analysis showed a significant association of the A allele with reduced risk of obesity in overall analysis and in European in the dominant, codominant and additional models. In Asian, no significant association was found between the − 866G/A in UCP2 gene and obesity susceptibility. The meta-analysis suggested that UCP2 − 866G/A polymorphism was associated with obesity. The A allele may be an important protective factor for obesity in European, but not in Asian. Further studies are needed to elucidate the relationship.     

Microbial diversity and prevalence of foodborne pathogens in cheap and junk foods consumed by primary schoolchildren

Aerobic plate counts (APC), coliforms, Bacillus cereus, Escherichia coli and eight foodborne pathogens were tested in 1008 cheap and junk foods, including candies, dried cakes, chewing gum, chocolate, dried and seasoned seafood, ice cream, and sugary foods. APCs were positive for 342 samples (33·9%), and the majority of the counts were 2–3 log CFU g^?1 or ml^?1 (average: 1·10 log CFU g^?1 or ml^?1). Most samples (97·3%) contained no coliforms (average: 0·07 log CFU g^?1 or ml^?1). Bacillus cereus was detected in 68 samples (average: 0·14 log CFU g^?1 or ml^?1). Escherichia coli and Listeria monocytogenes were detected in 6 and 1 samples, respectively, whereas other foodborne pathogens were not isolated. The highest bacterial counts were associated with dried and seasoned seafood products and dried cakes, suggesting that appropriate regulations of these food types should be considered. Cheap and junk foods were produced mainly in developing countries, but there were no significant differences in the bacterial counts among different countries of origin. The presence of foodborne pathogens may pose a risk for children. These results suggest that there is cause for deeper concern about the safety of these foods and that effective countermeasures should be established to improve their microbiological safety.

Significance and Impact of the Study

Food safety is especially important for children, but only limited information is available about the microbiological quality of cheap and junk foods that are consumed frequently by primary schoolchildren (e.g. dried cakes, candies and chocolates). The present study investigated the microbial quality of cheap and junk foods, and our results indicate that these foods are a potential health risk for children, therefore, deeper concern about the safety of these foods and effective countermeasures should be established to improve their microbiological safety. The present study may contribute to the development of an appropriate child food safety management system.     

The Reverse Roles of Transient Receptor Potential Canonical Channel-3 and -6 in Neuronal Death Following Pilocarpine-Induced Status Epilepticus

Transient receptor potential canonical channel (TRPC) is a nonselective cation channel permeable to Ca²⁺, which is expressed in many cell types, including neurons. However, the alterations in TRPC receptor expressions in response to status epilepticus (SE) have not been explored. Therefore, the present study was designated to elucidate the roles of TRPC3 and TRPC6 in neuronal death following SE. In non-SE animals, TRPC3 and TRPC6 immunoreactivity was abundantly detected in the dendrites of pyramidal cells and the cell bodies of dentate granule cells. Following SE, TRPC3 expression was significantly elevated in CA1-, CA3 pyramidal cells, and dentate granule cells, while TRPC6 expression was reduced in these regions. Pyrazole-3 (a TRPC3 inhibitor) effectively prevented up-regulation of neuronal TRPC3 expression induced by SE. Hyperforin (a TRPC6 activator) effectively prevented down-regulation of neuronal TRPC6 expression induced by SE. In addition, both Pyr3 and hyperforin effectively protected neuronal damages from SE. Therefore, the present study yields novel information regarding the role of TRPC3 and 6 in epileptogenic insults and suggests that TRPC 3 and 6 may be involved in neurodegeneration following SE.