Phytotoxic compounds from endophytic fungi.

Weeds represent one of the most challenging biotic factors for the agricultural sector, responsible for causing significant losses in important agricultural crops. Traditional herbicides have managed to keep weeds at bay, but overuse has resulted in negative environmental and toxicological impacts, including the increase of herbicide-resistant species. Within this context, the use of biologically derived (bio-)herbicides represents a promising solution because they are able to provide the desired phytotoxic effects while causing less toxic environmental damage. In recent years, bioactive secondary metabolites, in particular those bio-synthesized by endophytic fungi, have been shown to be promising sources of novel compounds that can be exploited in agriculture, including their use in weed control. Endophytic fungi have the ability to produce volatile and nonvolatile compounds with broad phytotoxic activity. In addition, as a result of the beneficial relationships they establish with their host plants, they are part of the colonization mechanism and can provide protection for their hosts. As such, endophytic fungi can be exploited as bioherbicides and as research tools. In this review, we cover 100 nonvolatile secondary metabolites with phytotoxic activity and more than 20 volatile organic compounds in a mixture, produced by 28 isolates of endophytic fungi from 21 host plant families, collected in 8 countries. This information can form the basis for the application of endophytic fungal compounds in weed control. KEY POINTS: • Endophytic fungi produce a wide variety of secondary metabolites with unique and complex structures. • Fungal endophytes produce volatile and nonvolatile compounds with promising phytotoxic activity. • Endophytic fungi are a promising source of useful bioherbicides.

Multicenter Study of Secukinumab Survival and Safety in Spondyloarthritis and Psoriatic Arthritis: SEcukinumab in Cantabria and ASTURias Study.

Objectives: We aimed to evaluate the drug retention rate and safety of secukinumab (SEC) in patients with axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) in a real clinical setting. Methods: This multicenter retrospective observational study included all AxSpA and PsA patients who received at least one dose of SEC. Adverse events (AE) and the drug retention rate were the main study outcomes. Drug survival was analyzed by Kaplan-Meier curves while predictive factors of discontinuation were evaluated using a Cox regression analysis. The weight of these associations was estimated by hazard ratio (HR) values. Results: We included 154 patients (59 PsA and 95 AxSpA). Mean disease duration was 6.5 years (IQR 2-8). Sixty-one percent of patients were treated with two or more biologics prior to SEC. The 1 and 2-year retention rates for SEC were 66 and 43%, respectively. The main causes of discontinuation were inefficacy (59%) and AE (36%). The factors associated with lower risk of discontinuation were male gender (HR 0.54, 95% CI 0.38-0.78 p = 0.001), obesity (HR 0.53, 95% CI 0.30-0.93 p = 0.027), hypertension (HR 0.55, 95% CI 0.30-0.93 p = 0.008), and diabetes (HR 0.42 95% CI 0.18-0.99 p = 0.047) while number of previous biologics and depression were predictors of discontinuation (HR 1.18, 95% CI 1.04-1.34 p = 0.011 and HR 2.53, 95% CI 1.61-3.96 p < 0.001). Conclusions: SEC showed a good retention rate in a population previously exposed to several biological therapies. As a novelty, cardiometabolic comorbidities were associated with better drug survival.