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Abstract Lung adenocarcinoma (LUAD) is the predominant type of non-small lung cancer (NSCLC) with strong invasive ability and poor prognosis. The drug resistance related genes are potentially associated with prognosis of LUAD. Our research aimed to identify the drug resistance related genes and explore their potential prognostic value in LUAD patients. The data used in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Firstly, we screened drug resistance related genes in LUAD by differential gene analysis, univariate Cox regression and drug sensitivity analyses. Subsequently, we constructed a risk score model using LASSO Cox regression analysis, and verified whether the risk score can predict the survival of LUAD patients independent of other factors. Moreover, we explored the immune infiltration of 22 immune cells between high-risk and low-risk patients. Totally 10 drug-resistance positively related genes (PLEK2, TFAP2A, KIF20A, S100P, GDF15, HSPB8, SASH1, WASF3, LAMA3 and TCN1) were identified in LUAD. The risk score model of LUAD constructed with these 10 genes could reliably predict the prognosis of LUAD patients. 18 pathways were significantly activated in high-risk group compared with low-risk group. In addition, the infiltration proportion of multiple immune cells was significantly different between high-risk and low-risk groups, and the proportion of M1 phagocytes was significantly higher in the high-risk group compared with the low-risk group. The drug resistance related genes (PLEK2, TFAP2A, KIF20A, S100P, GDF15, HSPB8, SASH1, WASF3, LAMA3 and TCN1) could predict the prognosis of LUAD patients. Clarifying the roles and mechanisms of these 10 genes in regulating drug resistance in LUAD will help to improve individualized clinical treatment protocols and predict patient sensitivity to treatment.

BACKGROUND: Ménière's disease (MD) is defined as an idiopathic disorder of the inner ear characterized by the triad of tinnitus, vertigo, and sensorineural hearing loss. Although many studies have evaluated the association between variants in the KCNE1 or KCNE3 gene and MD risk, debates still exist. OBJECTIVE: Our aim is to evaluate the association between KCNE gene variants, including KCNE1 rs1805127 and KCNE3 rs2270676, and the risk of MD by a systematic review. METHODS:We searched the literature in PubMed, SCOPUS and EMBASE through May 2015. We calculated pooled odds ratios (OR) and 95% confidence intervals (CIs) using a fixed-effects model or a random-effects model for the risk to MD associated with different KCNE gene variants. The heterogeneity assumption decided the effect model. RESULTS: A total of three relevant studies, with 302 MD cases and 515 controls, were included in this meta-analysis. The results indicated that neither the KCNE1 rs1805127 variant (for G vs. A: OR = 0.724, 95%CI 0.320, 1.638, P = 0.438), nor the KCNE3 rs2270676 variant (for T vs. C: OR = 0.714, 95%CI 0.327, 1.559, P = 0.398) was associated with MD risk. CONCLUSIONS: Based on current evidence from published studies, neither of the two variants from KCNE was significantly associated with the risk of MD. Larger studies with mixed ethnicity subjects and stratified by clinical and sub-clinical characteristics are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Aims To investigate functional and macular pigment (MP) changes in patients with early age-related macular degeneration (AMD) after multiple supplementation with lutein and zeaxanthin. Methods 112 patients with early AMD were randomly (1:1:1:1) assigned to receive 10 mg lutein, 20 mg lutein, lutein (10 mg)+zeaxanthin (10 mg), or placebo daily for 2 years. MP optical density (MPOD) was recorded at baseline, 48 weeks and 2 years. Retinal sensitivities were measured by multifocal electroretinogram for peak-totrough amplitude (N1P1) at baseline and at 48 weeks, and in terms of microperimeter-determined mean retinal sensitivity (MRS) at 48 weeks and 2 years. Results Supplementation with lutein and zeaxanthin augmented MPOD significantly in active treatment groups (all p<0.05). N1P1 response densities showed significant increases in ring 1 and ring 2 after 48 weeks of supplementation, while no significant changes were seen in rings 3-6. Significant increases in MRS were detected after supplementation with either 10 or 20 mg lutein, whereas no such increases were seen in the placebo arm. Conclusions Supplementation with lutein and/or zeaxanthin increases MPOD, and supplemental lutein enhances retinal sensitivity, in patients with early AMD. Trial registration number Clinicaltrials.gov NCT10528605 [ABSTRACT FROM AUTHOR]

Milk is a good source of bioavailable calcium compared with other foods. Recent in vitro and in vivo studies have shown that milk whey protein, especially its basic protein fraction (milk basic protein, MBP), contains several components capable of promoting bone formation and inhibiting bone resorption. The objective of this study was to examine the effects of MBP on bone mineral density (BMD) and bone metabolism of healthy young women. Eighty-four healthy young women were randomly assigned to three groups: control group, whole milk group or MBP group treated with milk containing 40 mg MBP for 8 months. The bone mineral density of total body, the lumbar vertebrae L2–L4 and the left forearm of each subject were measured by dual-energy X-ray absorptiometry (DEXA) at 0 and 8 months of treatment. Serum indexes of bone metabolism were measured at 0, 3, 6 and 8 months. Eighty-one subjects who completed the study in accordance with the protocol were included in the analysis. Total BMD in all groups significantly increased compared with baseline values. However, no significant difference on the mean rate of gain of total BMD was observed among the MBP group (2.19%), the whole milk group (2.63%) and the control group (1.61%). Serum cross-linked N-teleopeptides of type-I collagen (NTx) in MBP group at 8 months and in whole milk group at 6 months were significantly decreased from baseline. There were no significant differences between whole milk group and MBP group; however, after combining the milk groups, NTx had significantly decreased from baseline. No significant increase was observed in serum bone-specific alkaline phosphatase (BAP) in both whole milk group and MBP group. No significant effect of MBP on bone mineral density and bone metabolism was observed, but milk supplementation was effective in suppressing bone resorption. [ABSTRACT FROM AUTHOR]

Observational epidemiological studies have shown that a high consumption of lutein-containing foods is associated with decreased risk of chronic diseases. However, results are inconsistent, suggesting the possibility that confounders may impact serum lutein concentration alter consumption. The present study aimed to determine the factors affecting serum lutein status and to characterize dynamic changes of lutein concentration in serum during lutein supplementation in healthy Chinese subjects. After baseline characteristics were determined, thirty-seven healthy participants were randomized to receive 6 mg lutein/d. 12 mg lutein/d, or placebo for 12 weeks, as well as to be observed for 6 additional weeks after the cessation of supplementation. Serum levels of lutein and β-carotene were measured by HPLC at weeks 0. 1, 3. 6, 9. 12 and 18. Dietary intake was estimated by food-frequency questionnaires. No significant sex differences were found in serum concentration of lutein. Serum lutein level positively correlated with dietary lutein, retinol equivalents, vitamin C, vitamin E, β-carotene and fat intake alter adjustment for calorie intake, but not with BMI. After 12-weeks of supplementation, lutein levels increased approximately 1.8-fold and 2.3-fold for the 6-, and 12-mg dose groups respectively, approaching a plateau at week 9, and then decreased to baseline values at week 18. No adverse events or reductions in serum β-carotene were observed throughout the study. Our findings indicate that increasing the consumption of lutein-rich fruit and vegetables can be considered as a long-term, sustainable and salve approach to reach and maintain high serum levels of lutein. [ABSTRACT FROM AUTHOR]

Objective: This randomized controlled trial examined serum and macular (in vivo measured macular pigment optical density [MPOD]) responses to supplemental lutein and zeaxanthin in Chinese subjects with early age-related macular degeneration. Methods: One hundred and eight patients with early age-related macular degeneration older than 50 y were randomized to low lutein (LL; 10 mg/d), high lutein (HL; 20 mg/d), lutein plus zeaxanthin (LZ; each 10 mg/d), or placebo during a 48-wk intervention. Serum concentrations were quantified by C30 high-performance liquid chromatography (at baseline and 4, 12, 24, and 48 wk), and MPOD was measured by analysis of autofluorescence images (at baseline and 24 and 48 wk). Results: Serum lutein levels in the LL, LZ, and HL groups increased significantly in the first 4 wk and then increased 4.24-, 4.66-, and 6.23-fold during the trial, respectively (all P < 0.001). The serum lutein level in the HL group was significantly higher than that in the LL or LZ group at 48 wk (P < 0.05). Similarly, the serum zeaxanthin concentration in the LZ group increased 3.11-fold at 48 wk. MPOD increased smoothly in all treated groups, and the increase from baseline was greatest in the HL group at 24 and 48 wk (both P < 0.05). MPOD and serum lutein levels increased linearly with the dosage and their increasing rates were statistically correlated (all P < 0.05). No notable changes were detected in the placebo group for MPOD and serum concentrations. Conclusion: Xanthophyll supplementation significantly increased serum concentrations and MPOD in patients with early age-related macular degeneration, and a higher lutein supplementation (20 mg/d) might be more effective in increasing these two biochemical markers in Chinese patients without significant side effects. [ABSTRACT FROM AUTHOR]