Higher body mass index raises immature platelet count: evidence from Mendelian randomization analyses

A higher body mass index (BMI) is a recognised risk factor for thrombosis. Platelets are essential for haemostasis but also contribute to thrombosis when activated pathologically. We hypothesised that an increase in BMI may lead to changes in platelet characteristics, thereby contributing to increased thrombotic risk. The effect of BMI on platelet traits measured by Sysmex XN-1000 was explored in 33388 UK blood donors from the INTERVAL study. Linear regression was used for observational analyses between BMI and platelet characteristics. Mendelian randomization (MR) was used to estimate a causal effect with BMI proxied by a genetic risk score. Follow-up analysis explored the relevance of platelet characteristics on whole blood platelet aggregation in a pre-operative cardiac cohort (COPTIC) using linear regression. Observationally, higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC) and side fluorescence (SFL, a measure of mRNA content used to derive IPC). MR provided causal estimates for a positive effect of BMI on both SFL and IPC (IPC 0.06 SDs higher per SD higher BMI, 95% CI 0.006 to 0.12, P=0.03), but there was no strong evidence for a causal effect of BMI on PCT or PLT. The COPTIC study provided observational evidence for a positive association between IPC and whole blood platelet aggregation induced by adrenaline, TRAP-6 and ADP. Our results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation. Higher IPC could therefore contribute to obesity-related thrombosis.

Genuine and Sequestered Natural Products from the Genus Orobanche (Orobanchaceae, Lamiales)

The present review gives an overview about natural products from the holoparasitic genus Orobanche (Orobanchaceae). We cover both genuine natural products as well as compounds sequestered by Orobanche taxa from their host plants. However, the distinction between these two categories is not always easy. In cases where the respective authors had not indicated the opposite, all compounds detected in Orobanche taxa were regarded as genuine Orobanche natural products. From the about 200 species of Orobanche s.l. (i.e., including Phelipanche) known worldwide, only 26 species have so far been investigated phytochemically (22 Orobanche and four Phelipanche species), from 17 Orobanche and three Phelipanche species defined natural products (and not only natural product classes) have been reported. For two species of Orobanche and one of Phelipanche dedicated studies have been performed to analyze the phenomenon of natural product sequestration by parasitic plants from their host plants. In total, 70 presumably genuine natural products and 19 sequestered natural products have been described from Orobanche s.l.; these form the basis of 140 chemosystematic records (natural product reports per taxon). Bioactivities described for Orobanche s.l. extracts and natural products isolated from Orobanche species include in addition to antioxidative and anti-inflammatory effects, e.g., analgesic, antifungal and antibacterial activities, inhibition of amyloid β aggregation, memory enhancing effects as well as anti-hypertensive effects, inhibition of blood platelet aggregation, and diuretic effects. Moreover, muscle relaxant and anti-spasmodic effects as well as anti-photoaging effects have been described.