Ultraviolet enhances the sensitivity of pancreatic cancer cells to gemcitabine by activation of 5' AMP-activated protein kinase

Although gemcitabine is recognized as the standard drug for the treatment of advanced pancreatic cancer, the clinical outcome is not satisfactory. We recently reported that relatively high dose ultraviolet-C (UV-C; 200 J) inhibits cell growth by desensitization of epidermal growth factor receptor (EGFR) in human pancreatic cancer cells. In the present study, we investigated the combination effects of low dose UV-C (10 J) and gemcitabine on apoptosis and cell growth in these cells. UV-C enhanced gemcitabine-induced suppression of cell viability. In addition, the combination use clearly induced apoptosis, while neither UV-C nor gemcitabine alone did. Concurrently, combination use caused the decrease in the EGFR protein level and reduced EGF-induced activation of Akt pathway, subsequently resulting in accumulation of β-catenin. The order of the treatment with UV-C and gemcitabine did not affect their synergistic effects on apoptosis and cell growth. Interestingly, combination use synergistically induced phosphorylation of 5′ AMP-activated protein kinase (AMPK) alpha at Thr172 and acetyl-CoA carboxylase at Ser79 as a downstream molecular target of AMPK. AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-riboside, induced apoptosis and suppressed cell growth in these cells, thus suggesting that combination effects of UV-C and gemcitabine is due to the activation of AMPK. Together, our findings could provide a new aspect of pancreatic cancer therapy.     

Factors Affecting Unhappiness at School among Japanese Adolescents: An Epidemiological Study

Background

Unhappiness at school is one of the main reasons for truancy among adolescents. In order to assess this problem more thoroughly in the context of Japanese adolescents, the present study examined the associations between feelings of unhappiness at school and lifestyle habits, school life realities, and mental health status.

Method

This study was designed as a cross-sectional survey. A self-administered questionnaire was provided to students enrolled in randomly selected junior and senior high schools throughout Japan. We calculated the percentages of both junior and senior high school students who felt unhappy at school based on factors related to school life, lifestyle habits, and mental health status. Multiple logistic regression analyses were performed in order to examine the associations between those factors and students'' feelings of unhappiness at school.

Results

A total of 98,867 valid responses were analysed, 7.9% (Boys: 8.4%, Girls: 7.4%) of which came from students who responded that they felt unhappy at school. For both junior and senior high school students, the percentages of those who felt unhappy at school were significantly higher among those who had not yet decided on their future life course, who did not participate in extracurricular activities, did not eat breakfast every day, went to bed late, had used tobacco or alcohol in the previous 30 days, and had poor mental health compared with others. The results of multiple logistic regression analyses indicated that the adjusted odds ratios for feeling unhappy at school with regard to the above-mentioned factors were significantly high for both junior and senior high school students.

Conclusions

The present results suggest that school employees and administrators must provide health guidance to students, considering that irregular lifestyle habits, lower school engagement, smoking, drinking alcohol, and poor mental health status are all associated with maladaptation to school among adolescents.     

Neuroproteomics and microRNAs studies in multiple sclerosis: transforming research and clinical knowledge in biomarker research

Multiple sclerosis (MS) is a complex disease characterized by extensive phenotypic variability. Biomarkers to capture the different aspects of MS heterogeneity, and to help make a diagnosis and monitor disease progression, while providing insights into etiopathogenesis and response to treatment, are urgently needed. Omics technologies and research efforts with microRNAs have provide unparalleled opportunities for exploring altered protein profiles associated with molecular mechanisms of disease, substantially expanding the list of candidate biomarkers for MS. This review presents evidence from proteomic studies that have focused on identification of biomarkers released in biofluids as a result of the different pathophysiological processes of MS. Also discussed is the emerging role of miRNAs as complementary biomarkers related to cellular processes occurring in MS patients. Also provided is an overview of candidate biomarkers that have been proposed for elucidating pathophysiological processes and disease activity and for guiding clinical diagnosis and/or therapeutic interventions in MS.     

Pregnancy success of lactating Holstein cows after a single administration of a sustained-release formulation of recombinant bovine somatotropin

Background

Results regarding the use of bovine somatotropin for enhancing fertility in dairy cattle are variable. Here, the hypothesis was tested that a single injection of a sustained-release preparation of bovine somatotropin (bST) during the preovulatory period would improve pregnancy success of lactating dairy cows at first service.

Results

The first experiment was conducted in a temperate region of Mexico. Cows inseminated following natural estrus or timed artificial insemination were given a single injection of bST or a placebo injection at insemination (n = 100 cows per group). There was no significant difference between bST and control groups in the proportion of inseminated cows diagnosed pregnant (29 vs 31% pregnant). The second experiment was performed during heat stress in Florida. Cows were subjected to an ovulation synchronization regimen for first insemination. Cows treated with bST received a single injection at 3 days before insemination. Controls received no additional treatment. As expected, bST did not increase vaginal temperature. Treatment with bST did not significantly increase the proportion of inseminated cows diagnosed pregnant although it was numerically greater for the bST group (24.2% vs 17.8%, 124–132 cows per group). There was a tendency (p = 0.10) for a smaller percent of control cows to have high plasma progesterone concentrations (≥ 1 ng/ml) at Day 7 after insemination than for bST-treated cows (72.6 vs 81.1%). When only cows that were successfully synchronized were considered, the magnitude of the absolute difference in the percentage of inseminated cows that were diagnosed pregnant between bST and control cows was reduced (24.8 vs 22.4% pregnant for bST and control).

Conclusion

Results failed to indicate a beneficial effect of bST treatment on fertility of lactating dairy cows.

     

Protein kinase C modulates insulin action in human skeletal muscle

There is good evidence from cell lines and rodents that elevated protein kinase C (PKC) overexpression/activity causes insulin resistance. Therefore, the present study determined the effects of PKC activation/inhibition on insulin-mediated glucose transport in incubated human skeletal muscle and primary adipocytes to discern a potential role for PKC in insulin action. Rectus abdominus muscle strips or adipocytes from obese, insulin-resistant, and insulin-sensitive patients were incubated in vitro under basal and insulin (100 nM)-stimulated conditions in the presence of GF 109203X (GF), a PKC inhibitor, or 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), a PKC activator. PKC inhibition had no effect on basal glucose transport. GF increased (P < 0.05) insulin-stimulated 2-deoxyglucose (2-DOG) transport approximately twofold above basal. GF plus insulin also increased (P < 0.05) insulin receptor tyrosine phosphorylation 48% and phosphatidylinositol 3-kinase (PI 3-kinase) activity approximately 50% (P < 0.05) vs. insulin treatment alone. Similar results for GF on glucose uptake were observed in human primary adipocytes. Further support for the hypothesis that elevated PKC activity is related to insulin resistance comes from the finding that PKC activation by dPPA was associated with a 40% decrease (P < 0.05) in insulin-stimulated 2-DOG transport. Incubation of insulin-sensitive muscles with GF also resulted in enhanced insulin action ( approximately 3-fold above basal). These data demonstrate that certain PKC inhibitors augment insulin-mediated glucose uptake and suggest that PKC may modulate insulin action in human skeletal muscle.     

New broad-spectrum parenteral cephalosporins exhibiting potent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Part 3: 7beta-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido] cephalosporins bearing 4-[3-(aminoalkyl)-ureido]-1-pyridinium at C-3'

Among the prepared C-3' substituted-pyridinium cephalosporins, a series of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido] cephalosporins bearing 4-[3-(aminoalkyl)-ureido]-1-pyridinium at C-3' showed highly potent antibacterial activity against MRSA and Pseudomonas aeruginosa.     

Protective effect of colored rice over white rice on Fenton reaction-based renal lipid peroxidation in rats

Rice has been one of the most important grains. While polished white rice is favored, colored strains of rice, red, or black, have been maintained for religious purposes in Japan. We studied whether feeding of unpolished colored rice instead of white rice ameliorates oxidative renal tubular damage in rats induced by ferric nitrilotriacetate. Whereas renal lipid peroxidation was exacerbated in white rice-fed group in comparison with standard chow group, this exacerbation was not observed in red or black rice-fed groups. These changes were dependent on the proportion of colored rice to standard chow in the diet. Cyanidin 3- O - β- d -glucoside was detectable neither in the serum nor kidney after one week of colored rice diet, but serum protocatechuic acid was significantly increased after black rice diet. There was a generalized decrease in the renal glutathione peroxidase activity in rice diet groups. Renal enzymatic activities of superoxide dismutase, glutathione S -transferase and NAD(P)H quinone reductase were not associated with the levels of lipid peroxidation. However, renal catalase activity was significantly increased in black rice-fed groups. These may partly explain the antioxidative effect. Furthermore, colored strains of rice are rich in proteins. Thus, our data warrants further investigation of the antioxidative effect of colored rice.