Structural and functional dysbiosis of gut microbiota in Tibetan subjects with coronary heart disease.

The gut microbiota plays a crucial role in coronary heart disease (CHD). However, only a few studies focusing on the relationship between gut microbiota and CHD in ethnic populations are available. Here, we employed shotgun sequencing of the gut metagenome to analyze the taxonomic composition and functional annotation of the gut microbiota of 14 CHD patients, 13 patients with non-stenosis coronary heart disease (NCHD), and 18 healthy controls (HT) in Tibetan subjects. We found that the α-diversity of the gut microbiota was not significantly different among the three groups., whereas ß-diversity was significantly altered in the CHD group compared with HT. Based on the receiver operating characteristic curve (ROC) analysis, the relative abundance of Proteobacteria species effectively distinguished patients with CHD from the control group. Most of the enriched species belonged to Proteobacteria. The pathways that contributed the most to the differences between groups were amino acid metabolism-related pathways, especially lysine biosynthesis. The enzymes of the lysine biosynthesis pathway, including K01714 and K00821, were significantly decreased in the CHD group. Our findings increase the understanding of the association between CHD pathogenesis and gut microbiota in the Tibetan population, thus paving the way for the development of improved diagnostic methods and treatments for Tibetan patients with CHD.

Challenges in the Development of Therapy for Dry Age-Related Macular Degeneration.

Dry age-related macular degeneration (AMD), a multifactorial progressive degenerative disease of the retinal photoreceptors, pigmented epithelium and Bruch's membrane/choroid in central retina, causes visual impairment in millions of elderly people worldwide. The only available therapy for this disease is the over-the-counter (OTC) multi-vitamins plus macular xanthophyll (lutein/zeaxanthin) which attempts to block the damages of oxidative stress and ionizing blue light. Therefore development of dry AMD prescribed treatment is a pressing unmet medical need. However, this effort is currently hindered by many challenges, including an incomplete understanding of the mechanism of pathogenesis that leads to uncertain targets, confounded by not yet validated preclinical models and the difficulty to deliver the drugs to the posterior segment of the eye. Additionally, with slow disease progression and a less than ideal endpoint measurement method, clinical trials are necessarily large, lengthy and expensive. Increased commitment to research and development is an essential foundation for dealing with these problems. Innovations in clinical trials with novel endpoints, nontraditional study designs and the use of surrogate diseases might shorten the study time, reduce the patient sample size and consequently lower the budget for the development of the new therapies for the dry AMD.