Assessment of Plasma Phospholipid Very-Long-Chain Saturated Fatty Acid Levels and Healthy Aging.

Importance: Identifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism shown to have beneficial associations in cardiovascular disease and total mortality, but whether they are associated with overall healthy aging is unknown. Objective: To examine the association of circulating levels of 3 VLSFAs with unhealthy aging events, including incident chronic disease (cardiovascular disease, cancer, lung disease or severe kidney disease), physical dysfunction, and cognitive decline. Design, Setting, and Participants: This cohort study used 1992 to 2014 data from the Cardiovascular Health Study (CHS). The CHS is a multicenter, population-based study of cardiovascular disease among older adults. Among the 4559 CHS participants with available fatty acid data, 1879 participants who had an age-related event before their first measurement were excluded. Data analysis was performed in 2020. Main Outcomes and Measures: Plasma phospholipid VLSFA levels were measured by thin-layer chromatography followed by gas chromatography. The main outcome was the hazard ratio (HR) of an incident unhealthy aging event associated with serial measures of plasma arachidic acid, behenic acid, and lignoceric acid. Results: Among the 2680 study participants (976 men [36.4%]), the mean (SD) age was 74.7 (4.8) years old at entry. During a median (interquartile range) of 6.4 (2.9-12.9) years of follow-up, 2484 participants experienced an unhealthy event. Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of lignoceric acid were similarly associated with 16% lower risk of an unhealthy event (HR, 0.84; 95% CI, 0.73-0.95; P for trend = .001). Conclusions and Relevance: These findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events. These results highlight the need to explore determinants of circulating VLSFAs for potential novel efforts to promote healthy aging.

A Novel Biomarker Panel for the Early Detection and Risk Assessment of Hepatocellular Carcinoma in Patients with Cirrhosis.

Novel biomarkers for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis are urgently needed. We previously identified osteopontin (OPN) as a promising biomarker for the early detection of HCC. This study is to further validate the performance of OPN and identify fatty acids (FA) that could improve OPN's performance in HCC risk assessment in patients with cirrhosis. To that end, we selected 103 patients with cirrhosis under surveillance. Among them, 40 patients developed HCC during follow-up. We investigated in these 103 patients, the association between HCC incidence and prediagnostic serum levels of AFP, OPN, and 46 FAs. OPN performance was higher than AFP in detecting prediagnosis HCCs and the combination with AFP further improved OPN's performance. For patients with a diagnosis of HCC within 18 months of follow-up (HCC < 18 months), AUC for OPN + AFP was 0.77. Abundance of 11 FAs [four long-chain saturated FAs (SFA), four n-3 poly-unsaturated FAs (PUFA), and three n-6 PUFAs] were statistically different between patients who developed HCC and those who did not. Abundance changes correlated with time to diagnosis for the PUFAs, but not for the SFAs. Adding arachidic acid (20:0) and n-3 docosapentaenoic acid (22:5n3) to OPN and AFP improved the discriminatory performance (AUC = 0.83). AUC for this panel reached 0.87 for HCC < 18 months (82% sensitivity at 81% specificity). In conclusion, we identified a panel of 4 markers with strong performances that could have significant utility in HCC early detection in patients with cirrhosis under surveillance. PREVENTION RELEVANCE: This study identified a panel of 4 biomarkers that identifies with high performance patients with cirrhosis at high risk for HCC. This panel could have utility in HCC early detection in patients with cirrhosis under surveillance.

Fitness Cost of Transgenic cry1Ab/c Rice Under Saline-Alkaline Soil Condition.

The environmental release and biosafety of transgenic Bt crops have attracted global attention. China has a large area of saline-alkali land, which is ideal for large-scale production of Bt transgenic rice. Therefore an understanding of the fitness of Bt transgenic rice in saline-alkaline soils and the ability to predict its long-term environmental effects are important for the future sustainable use of these crops. In the present study, we aimed to evaluate the fitness of cry1Ab/c transgenic rice in both farmland and natural ecosystems. Transgenic cry1Ab/c rice Huahui1, for which a national biosafety certificate was obtained, was grown on normal farmland and saline-alkaline soils in a glass greenhouse. The expression pattern of exogenous Cry1Ab/c protein, and vegetative and reproductive fitness of rice were assessed. The expression of the exogenous Cry1Ab/c protein in the transgenic rice grown on saline-alkaline soil was lower than that in the strain grown on farmland soil. Under both the soil conditions, vegetative growth abilities, as evaluated by tiller number and biomass, and reproductive growth abilities, as measured by filled grain number and filled grain weight per plant, showed a significantly higher fitness cost for Huahui1 than that for the parental rice Minghui63 grown under the same soil conditions. In saline-alkaline soil, the fitness cost of Huahui1was moderately higher than that of Minghui63. Therefore, the ecological risk of cry1Ab/c transgenic rice is not expected to be higher than that of parental rice Minghui63 if the former escapes into natural saline-alkaline soil. The results of the present study provide a scientific basis to improve environmental safety assessment of the insect-resistant transgenic rice strain Huahui1 before commercialization.

Nightshift work and genome-wide DNA methylation.

The negative health effects of shift work, including carcinogenesis, may be mediated by changes in DNA methylation, particularly in the circadian genes. Using the Infinium HumanMethylation450 Bead Array (Illumina, San Diego, CA), we compared genome-wide methylation between 65 actively working dayshift workers and 59 actively working nightshift workers in the healthcare industry. A total of 473 800 loci, including 391 loci across the 12 core circadian genes, were analyzed to identify methylation markers associated with shift work status using linear regression models adjusted for gender, age, body mass index, race, smoking status and leukocyte cell profile as measured by flow cytometry. Analyses at the level of gene, CpG island and gene region were also conducted. To account for multiple comparisons, we controlled the false discovery rate (FDR ≤0.05). Significant differences between nightshift and dayshift workers were found at 16 135 of 473 800 loci, across 3769 of 20 164 genes, across 7173 of 22 721 CpG islands and across 5508 of 51 843 gene regions. For each significant loci, gene, CpG island or gene region, average methylation was consistently found to be decreased among nightshift workers compared to dayshift workers. Twenty-one loci located in the circadian genes were also found to be significantly hypomethylated among nightshift workers. The largest differences were observed for three loci located in the gene body of PER3. A total of nine significant loci were found in the CSNK1E gene, most of which were located in a CpG island and near the transcription start site of the gene. Methylation changes in these circadian genes may lead to altered expression of these genes which has been associated with cancer in previous studies. Gene ontology enrichment analysis revealed that among the significantly hypomethylated genes, processes related to host defense and immunity were represented. Our results indicate that the health effects of shift work may be mediated by hypomethylation of a wide variety of genes, including those related to circadian rhythms. While these findings need to be followed-up among a considerably expanded group of shift workers, the data generated by this study supports the need for future targeted research into the potential impacts of shift work on specific carcinogenic mechanisms.