Vitamin E is a fat-soluble antioxidant that can protect the polyunsaturated fatty acids (PUFAs) in the membrane from oxidation, regulate the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), and modulate signal transduction. Immunomodulatory effects of vitamin E have been observed in animal and human models under normal and disease conditions. With advances in understating of the development, function, and regulation of dendritic cells (DCs), macrophages, natural killer (NK) cells, T cells, and B cells, recent studies have focused on vitamin E’s effects on specific immune cells. This review will summarize the immunological changes observed with vitamin E intervention in animals and humans, and then describe the cell-specific effects of vitamin E in order to understand the mechanisms of immunomodulation and implications of vitamin E for immunological diseases.

Feeding behavior is influenced primarily by two factors: nutritional needs and food palatability. However, the role of food deprivation and metabolic needs in the selection of appropriate food is poorly understood. Here, we show that the fruit fly, Drosophila melanogaster, selects calorie-rich foods following prolonged food deprivation in the absence of taste-receptor signaling. Flies mutant for the sugar receptors Gr5a and Gr64a cannot detect the taste of sugar, but still consumed sugar over plain agar after 15 h of starvation. Similarly, pox-neuro mutants that are insensitive to the taste of sugar preferentially consumed sugar over plain agar upon starvation. Moreover, when given a choice between metabolizable sugar (sucrose or D-glucose) and nonmetabolizable (zero-calorie) sugar (sucralose or L-glucose), starved Gr5a; Gr64a double mutants preferred metabolizable sugars. These findings suggest the existence of a taste-independent metabolic sensor that functions in food selection. The preference for calorie-rich food correlates with a decrease in the two main hemolymph sugars, trehalose and glucose, and in glycogen stores, indicating that this sensor is triggered when the internal energy sources are depleted. Thus, the need to replenish depleted energy stores during periods of starvation may be met through the activity of a taste-independent metabolic sensing pathway.F ood quantity and quality can vary greatly in natural habitats. To survive such variations, animals must be able to search for and detect appropriate food sources under all conditions, especially during times of food scarcity. Peripheral chemosensory neurons, such as sugar taste neurons, allow animals to detect palatable foods (1-5). Additional mechanisms may be necessary for the detection of foods to meet acute nutritional needs. Indeed, animals learn to positively associate a flavor paired with intragastric sugar infusion (6). Recently, studies of Trpm5 −/− mice, which are insensitive to the taste of sugar, also have revealed that these animals develop a preference for a sugar solution on the basis of its caloric content even in the absence of gustatory input (7). Unfortunately, the nature of such mechanisms is currently unknown. It is also not clear whether they function under starvation conditions. To search for mechanisms by which animals can respond to the caloric content of food independently of orosensory cues, we studied the effect of starvation on food choice in Drosophila mutants that are unable to taste sugar. Specifically, we sought to determine whether food-deprived flies carrying mutations in Gr5a and Gr64a (3-5), the sugar receptor genes, and in poxneuro (poxn) (8-10), a gene that specifies chemosensory neurons, develop a preference for the caloric content of sugars in the absence of taste perception. We found that these mutant flies demonstrated a preference for caloric food upon starvation and that this preference correlated with the energy needs of the fly. Furthermore, wild-type (WT) flies showed a shift in preference to metab...

DNA-methyltransferase-3B (DNMT3B) plays an important role in the generation of aberrant methylation in carcinogenesis. Polymorphisms and haplotypes of the DNMT3B gene may influence DNMT3B activity on DNA methylation, thereby modulating the susceptibility to lung cancer. To test this hypothesis, we investigated the association of the -283T > C (from exon 1A transcription start site) and -579G > T (from exon 1B transcription start site) polymorphisms in DNMT3B promoter, and their haplotypes with the risk of lung cancer in a Korean population. The DNMT3B genotype was determined in 432 lung cancer patients and 432 healthy controls that were frequency-matched for age and sex. Individuals with at least one -283T allele were at a significantly decreased risk of adenocarcinoma (AC) and small cell carcinoma (SM) [adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.28-0.82, P = 0.007; and adjusted OR = 0.47, 95% CI = 0.24-0.93, P = 0.03, respectively] compared with those harboring a -283CC genotype. Individuals with at least one -579G allele were also at a significantly decreased risk of AC and SM (adjusted OR = 0.47, 95% CI = 0.28-0.81, P = 0.006; and adjusted OR = 0.51, 95% CI = 0.26-0.99, P = 0.048, respectively) compared with those having a -579TT genotype. The -283T allele was linked with the -579G allele, and haplotype -283T/-579G was associated with a significantly decreased risk of AC (adjusted OR = 0.48, 95% CI = 0.29-0.81, P = 0.006) as compared with haplotype -283C/-579T. In a promoter assay, carriage of the -283T allele showed a significantly lower promoter activity ( approximately 50%) compared with the -283C allele (P < 0.001), but the -579G > T polymorphism did not have an affect on the DNMT3B promoter activity. These results suggest that the DNMT3B -283T > C polymorphism influences DNMT3B expression, thus contributing to the genetic susceptibility to lung cancer.

Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. DNA sequence variations in the vascular endothelial growth factor (VEGF) gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. To test this hypothesis, we investigated the potential association between three VEGF polymorphisms (À À460T > C, +405C > G, and 936C > T)/haplotypes and the risk of lung cancer in a Korean population. VEGF genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency matched for age and sex. VEGF haplotypes were predicted using Bayesian algorithm in the phase program. Compared with the combined +405 CC and CG genotype, the +405 GG genotype found associated with a significantly decreased risk of small cell carcinoma [SCC; adjusted odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.17-0.78]. The 936 CT genotype and the combined 936 CT and TT genotype were also associated with a significantly decreased risk of SCC compared with the 936 CC genotype (adjusted OR, 0.47; 95% CI, 0.26-0.85 and adjusted OR, 0.44; 95% CI, 0.24-0.80, respectively). Haplotype CGT was associated with a significantly decreased risk of SCC (adjusted OR, 0.39; 95% CI, 0.18-0.87), whereas haplotype TCC conferred a significantly increased risk of SCC (adjusted OR, 1.63; 95% CI, 1.14-2.33). None of the VEGF polymorphisms studied significantly influenced the susceptibility to lung cancer except SCC. However, haplotypes TCT and TGT were significantly associated with the risk of overall lung cancer, respectively (adjusted OR, 0.38; 95% CI, 0.25-0.60 and adjusted OR, 3.94; 95% CI, 2.00-7.76, respectively). These effects of haplotypes TCT and TGT on lung cancer risk were observed in three major histologic types of lung cancer. These results suggest that the VEGF gene may be contribute to an inherited predisposition to lung cancer.

BackgroundStriae distensae are atrophic dermal scars with overlying epidermal atrophy causing significant cosmetic concern. Although a variety of laser and light sources have been used for the treatment of striae distensae, to date no definite 'gold standard' treatment modality has been determined.ObjectiveTo assess and compare the efficacy and safety of nonablative fractional photothermolysis and ablative CO2 fractional laser resurfacing in the treatment of striae distensae.MethodsTwenty-four ethnic South Korean patients with varying degrees of atrophic striae alba in the abdomen were enrolled in a randomized blind split study. The patients were treated with 1,550 nm fractional Er:Glass laser and ablative fractional CO2 laser resurfacing. Each half of the abdominal lesion was randomly selected and treated three times at intervals of 4-weeks using the same parameters. Digital photography was conducted and skin elasticity and the width of the widest striae in each subject were measured at the baseline and 4 weeks after the final treatment. Clinical improvement was assessed by comparing pre- and post-treatment clinical photographs by two blinded physicians and participant satisfaction rates were evaluated. Skin biopsies were taken from three participants. All adverse effects were reported during the study.ResultsAlthough they do not statistically differ, both treatments with nonablative fractional laser and ablative CO2 fractional laser showed a significant clinical and histopathologic improvement of striae distensae over pretreatment sites.ConclusionThese results support the use of nonablative fractional laser and ablative CO2 fractional laser as effective and safe treatment modalities for striae distensae of Asian skin. However, neither treatment showed any greater clinical improvement than the other treatment.

Polymorphisms in DNA repair genes may be associated with differences in the capacity to repair DNA damage and thereby influence an individual's susceptibility to smoking-related cancer. To test this hypothesis, we investigated the potential association of 7 XPC polymorphisms (-449G?C, -371G?A, -27G?C, Val499-Arg, PAT-/+, IVS11-5C?A and Lys939Gln) and their haplotypes with lung cancer risk in a Korean population. XPC genotypes were determined in 432 lung cancer patients and 432 healthy controls frequency-matched for age and sex. XPC haplotypes were predicted using a Bayesian algorithm in the Phase program. The combined -27CGþCC genotype was associated with a significantly increased risk for overall lung cancer compared to the -27GG genotype (adjusted OR = 1.97, 95% CI 1.22-3.17, p = 0.005). The other 6 polymorphisms were not significantly associated with overall risk of lung cancer. When lung cancer cases were categorized by tumor histology, the -371AA genotype was associated with a significantly increased risk of squamous cell carcinoma compared to the combined -371GG and GA genotype (adjusted OR = 2.08, 95% CI 1.09-4.00, p = 0.03). The PAT-/+, IVS11-5C?A and Lys939Gln polymorphisms were associated with a significantly decreased risk of small cell carcinoma (SM) under a dominant model for the polymorphic allele (adjusted OR = 0.49, 95% CI 0.29-0.82, p = 0.006; adjusted OR = 0.60, 95% CI 0.36-1.00, p = 0.05; and adjusted OR = 0.58, 95% CI 0.35-0.97, p = 0.04, respectively). Consistent with genotyping analyses, haplotype 4 (1112222) containing the PAT+/IVS11-5A/939Gln alleles was associated with a significantly decreased risk of SM (adjusted OR = 0.56, 95% CI 0.37-0.85, p = 0.007 and Bonferroni-corrected p = 0.049), whereas haplotype 5 (1122111) containing the -27C allele was associated with a significantly increased risk of SM (adjusted OR = 2.88, 95% CI 1.41-5.87, p = 0.004 and Bonferronicorrected p = 0.028). These results suggest that XPC polymorphisms/haplotypes may contribute to genetic susceptibility for lung cancer. ' 2005 Wiley-Liss, Inc.

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It has been demonstrated that adipose-derived stem cells (ADSCs) secrete cytokines and exhibit diverse pharmacological actions. The present study examined the unknown pharmacological action of ADSCs regarding whitening effects. A conditioned medium of ADSCs (ADSC-CM) was harvested and the whitening effect of ADSC-CM was studied in melanoma B16 cells. ADSC-CM treatment inhibited the synthesis of melanin and the activity of tyrosinase in a dose dependent manner. To clarify the underlying mechanisms of the whitening action of ADSCs, protein levels of melanogenic proteins were measured by Western blot. Although expressions of microphthalmia-associated transcription factor and tyrosinase-related protein 2 (TRP2) remained unchanged, those of tyrosinase and TRP1 were down-regulated. Transforming growth factor-b b1 (TGF-b b1), a potent regulator of melanogenic proteins, was neutralized by the addition of a blocking antibody to ADSC-CM, and down-regulated expression of tyrosinase and TRP1 was almost reversed. Collectively, these results indicate that secretary factors of ADSC inhibit melanin synthesis by down-regulating the expression of tyrosinase and TRP1, which are mainly mediated by TGF-b b1.Key words adipose-derived stem cell; melanin; tyrosinase; tyrosinase-related protein 1 (TRP1); transforming growth factor-b1 (TGF-b1)