Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss

Hypoxia（low oxygen level） is an important feature during infections and affects the host defence mechanisms. The host has evolved specific responses to address hypoxia, which are strongly dependent on the activation of hypoxia-inducible factor 1（HIF-1）.Hypoxia interferes degradation of HIF-1 alpha subunit（HIF-1α）, leading to stabilisation of HIF-1α, heterodimerization with HIF-1 beta subunit（HIF-1β） and subsequent activation of HIF-1 pathway. Apical periodontitis（periapical lesion） is a consequence of endodontic infection and ultimately results in destruction of tooth-supporting tissue, including alveolar bone. Thus far, the role of HIF-1 in periapical lesions has not been systematically examined. In the present study, we determined the role of HIF-1 in a wellcharacterised mouse periapical lesion model using two HIF-1α-activating strategies, dimethyloxalylglycine（DMOG） and adenovirusinduced constitutively active HIF-1α（CA-HIF1 A）. Both DMOG and CA-HIF1 A attenuated periapical inflammation and tissue destruction. The attenuation in vivo was associated with downregulation of nuclear factor-κappa B（NF-κB） and osteoclastic gene expressions. These two agents also suppressed NF-κB activation and subsequent production of proinflammatory cytokines by macrophages. Furthermore, activation of HIF-1α by DMOG specifically suppressed lipopolysaccharide-stimulated macrophage differentiation into M1 cells, increasing the ratio of M2 macrophages against M1 cells. Taken together, our data indicated that activation of HIF-1 plays a protective role in the development of apical periodontitis via downregulation of NF-κB, proinflammatory cytokines, M1 macrophages and osteoclastogenesis.

Scientific Catch-Up in Asian Economies: A Case Study for Solar Cell

A significant structural change in the pattern of economic development in Asian economies has been observed in recent years. We have seen many cases in which the Asian economies became the center of the world-wide production in an extremely short period of time after a new product entered the market. Also in the science, the number of papers written by Asian researchers has been increasing dramatically. In this situation, the existing studies cannot sufficiently explain the driving force and the mechanism of catch-up or economic growth. Therefore, it is now required to model this new type of economic development. In this paper we analyzed their scientific catch-up status using scientific papers on solar cells to clarify the structural change. After mid 1990s, knowledge creation has been accelerated in the field of solar cell. Now more than three thousand papers are published annually. We found as a result that the catch-up process in Asian economies had progressed rapidly, that some economies had a larger share of scientific papers in the frontier field of advanced science than in the matured fields, and that the strategy largely changed from area to area. A “parallel-running-type growth model” has thus been emerging in Asia. Responding to the significant changes in development model, we have to re-design the framework of economic cooperation. There is a need for further horizontal collaboration among major Asian economies and developed economies. We also showed that bibliometrics is an effective method for presuming a detailed national strategy that is not known to the outside.

Consecutive-Day Intake of Whey Protein Upregulates mTOR mRNA and Protein Expression in Resting Skeletal Muscle of Mice

Background: Although the effect of whey protein intake on protein metabolism in exercise-loaded skeletal muscle has been well documented, little has been reported on its effect on resting muscle. The effects of whey protein intake on protein metabolism in resting mouse skeletal muscle were investigated. Methods: Mice were fed AIN-93G composed of either casein or whey protein as the protein source for 3 or 7 consecutive days. The gastrocnemius muscle was excised, and the expression levels of the regulatory factor, mTOR, and its subunits, Raptor and Rictor, were measured by real-time PCR. The protein expression levels of mTOR and its phosphorylated form were measured by immunofluorescent western blotting. The effects of whey protein were compared to those of the case in control. Results: mTOR expression increased in the gastrocnemius muscle of mice fed whey protein for 7 consecutive days. The expression of Raptor significantly increased, whereas that of Rictor did not change, suggesting a dominant formation of mTORC1 relating to the upregulation of protein synthesis. The protein levels of mTOR and its phosphorylated form significantly increased in mice fed whey protein, indicating enhanced protein synthesis. Increased mTOR expression was not seen in the gastrocnemius muscle of mice fed whey protein for 3 consecutive days. Conclusions: These results indicate that the intake of whey protein for 7 consecutive days, but not 3 days, upregulates the mRNA and protein expression of mTOR in the resting gastrocnemius muscle of mice, suggesting its ability to enhance protein synthesis. Consecutive-day intake of whey protein may induce constitutive alteration of the skeletal muscle, including continuous upregulation of muscle protein synthesis.

Whey Protein Intake Modulates Lipid Metabolism by Transcriptionally Affecting PPARs and SREBP1c and Their Downstream Enzymes in Mice

Background: The effects of whey protein intake on the transcriptional expression of genes related to lipid metabolism in mice were investigated herein. Methods: For 4 weeks, mice were fed AIN-93G composed of either casein or whey protein as the protein source. Then the gastrocnemius muscle, liver, and epididymal adipose tissue were excised. Expression levels of the transcription factors, PPARα, PPARγ, and SREBP1c, and those of the enzymes modulated by these factors, HSL, LPL, ACCα, and FAS, were measured by real-time PCR. The effects of whey protein were compared to those of the case in control. Results: The mRNA expression of PPARα was enhanced in the gastrocnemius muscle, while that of PPARγ was increased in the liver and epididymal adipose tissue. The expression of HSL and LPL was increased in the epididymal adipose tissue and gastrocnemius muscle, respectively. The mRNA expression of SREBP1c was suppressed in all of the three tissues. The expression of ACCα was suppressed in the gastrocnemius muscle and liver, while that of FAS was suppressed in all of the three tissues. Conclusions: These results indicate that whey protein intakes transcriptionally modulate PPARs and SREBP1c directing lipid metabolism toward the enhancement of triglyceride breakdown and suppression of fatty acid synthesis.

Improvement in Nutritional Status of Protein-Malnutrition Elderly after Intervention Using a Casein-Based Balanced Liquid Nutrition Formula as Nutritional Support

A nutritional intervention for 8 weeks was conducted in the elderly (>65 y) living in nursing homes in Shanghai, who showed body weight within the normal range but albumin levels of <35 g/L. The intervened took 400 kcal/day of a balanced liquid nutrition formula containing casein as a major protein source (90% of total protein) in addition to their daily diets, while the non-intervened took only daily diets. Daily diet intakes during the trial were 1738 ± 240 kcal/day in the intervened and 1612 ± 187 kcal/day in the non-intervened. The energy intake in the intervened wascompensated for by reducing their daily diets, which resulted in a similar level to that in the non-intervened. This intervention resulted in intakes of protein and carbohydrate being significantly increased: P16.4%, F27.3%, C56.3% in the intervened;P13.0%, F36.3%, C50.7% in the non-intervened. Albumin level of the intervened increased from 32.7 ± 3.1 g/L to 37.3 ± 1.9 g/L, while it did not significantly change in the non-intervened: 30.0 ± 4.2 g/L to 31.3 ± 4.6 g/L. Using GNRI (geriatric nutritional risk index), nutritional risk levels were assessed;GNRI of the intervened significantly improved from 88.7 ± 6.3 (intermediate risk) to 95.7 ± 4.5 (low risk), while its status did not change in the non-intervened: 84.6 ± 7.7 (intermediate risk) to 86.5 ± 7.9 (intermediate risk). The intervention using a casein-based balanced liquid nutrition formula effectively improved protein-malnutrition in the elderly. This result suggests that a casein-based balanced liquid nutrition formula is an effective nutrition source that can be applied to a nutritional program to improve malnutrition of the elderly.

Protective Effect of Ethanolamine on Hepatic Preneoplastic Alterations Induced by the Administration of <i>N</i>-Nitrosodiethylamine in Rats

The effects of exogenously administered ethanolamine (Etn) on the N-nitrosodiethylamine (NDA)-induced formation of hepatic lesions in rats were investigated. Sprague-Dawley rats were intraperitoneally administered NDA (100 mg/kg body weight) at 7-day intervals, and the animals were allowed free access to water containing Etn (15 or 50 mg/L) for 35 days. NDA-induced hepatic lesions were assessed according to the number of nodules detectable on the liver surface, areas of clear cell foci observed on histopathological thin sections, hydroxyproline levels in liver homogenates, and blood biochemical marker levels. Compared with those from control rats that were not administered Etn, livers from Etn-exposed rats had significantly fewer surface nodules and smaller areas of clear cell foci, indicating that Etn prevented or delayed the formation of preneoplastic cell alterations. Hydroxyproline levels in livers were significantly lower in Etn-treated rats, indicating that the chemical prevented the formation of fibrotic alterations. The protective effects of Etn on NDA-induced hepatic lesions were demonstrated by changes in blood biochemical marker levels. These results suggest that Etn can protect against cellular alterations induced by a carcinogenic chemical, possibly by enhancing hepatic phospholipid synthesis.