Obese fat pads are frequently undervascularized and hypoxic, leading to increased fibrosis, inflammation, and ultimately insulin resistance. We hypothesized that VEGF-A–induced stimulation of angiogenesis enables sustained and sufficient oxygen and nutrient exchange during fat mass expansion, thereby improving adipose tissue function. Using a doxycycline (Dox)-inducible adipocyte-specific VEGF-A overexpression model, we demonstrate that the local up-regulation of VEGF-A in adipocytes improves vascularization and causes a “browning” of white adipose tissue (AT), with massive up-regulation of UCP1 and PGC1α. This is associated with an increase in energy expenditure and resistance to high fat diet-mediated metabolic insults. Similarly, inhibition of VEGF-A–induced activation of VEGFR2 during the early phase of high fat diet-induced weight gain, causes aggravated systemic insulin resistance. However, the same VEGF-A–VEGFR2 blockade in ob/ob mice leads to a reduced body-weight gain, an improvement in insulin sensitivity, a decrease in inflammatory factors, and increased incidence of adipocyte death. The consequences of modulation of angiogenic activity are therefore context dependent. Proangiogenic activity during adipose tissue expansion is beneficial, associated with potent protective effects on metabolism, whereas antiangiogenic action in the context of preexisting adipose tissue dysfunction leads to improvements in metabolism, an effect likely mediated by the ablation of dysfunctional proinflammatory adipocytes.

We evaluated the side-effects of insecticides, herbicides and fungicides on adults of the egg parasitoid Telenomus remus (Nixon) under laboratory conditions. The protocol was adapted from that proposed by the Pesticides and Beneficial Organisms Working Group of the International Organization for Biological Control (IOBC) for Trichogramma cacoeciae (Marchal). Chlorpyrifos, acephate, beta-cyfluthrin ? imidacloprid, spinosad, and pyrethroids were harmful to the parasitoid, whereas methoxyfenozide, diflubenzuron, and flufenoxuron had no effect. Of the herbicides examined, only glyphosate ? imazethapyr and 2,4-D amine were classified as harmless on the first and second days of parasitism; paraquat was the most harmful. Other herbicides were harmless on the first day of parasitism, but caused various levels of reduction of T. remus parasitism on the second day. The fungicides were harmless or only slightly harmful.

BackgroundTo date, there is no effective therapy for patients with advanced/metastatic adrenocortical cancer (ACC). The activation of the Wnt/beta-catenin signaling is frequent in ACC and this pathway is a promising therapeutic target.AimTo investigate the effects of the inhibition of the Wnt/beta-catenin in ACC cells.MethodsAdrenal (NCI-H295 and Y1) and non-adrenal (HeLa) cell lines were treated with PNU-74654 (5–200 μM) for 24–96 h to assess cell viability (MTS-based assay), apoptosis (Annexin V), expression/localization of beta-catenin (qPCR, immunofluorescence, immunocytochemistry and western blot), expression of beta-catenin target genes (qPCR and western blot), and adrenal steroidogenesis (radioimmunoassay, qPCR and western blot).ResultsIn NCI-H295 cells, PNU-74654 significantly decreased cell proliferation 96 h after treatment, increased early and late apoptosis, decreased nuclear beta-catenin accumulation, impaired CTNNB1/beta-catenin expression and increased beta-catenin target genes 48 h after treatment. No effects were observed on HeLa cells. In NCI-H295 cells, PNU-74654 decreased cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. Additionally, in NCI-H295 cells, PNU-74654 decreased SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase 48 h after treatment. In Y1 cells, PNU-74654 impaired corticosterone secretion 24 h after treatment but did not decrease cell viability.ConclusionsBlocking the Tcf/beta-catenin complex inhibits the Wnt/beta-catenin signaling in adrenocortical tumor cells triggering increased apoptosis, decreased cell viability and impairment of adrenal steroidogenesis. These promising findings pave the way for further experiments inhibiting the Wnt/beta-catenin pathway in pre-clinical models of ACC. The inhibition of this pathway may become a promising adjuvant therapy for patients with ACC.

Increasing global demands for food underline the need for higher crop yields. The relatively low costs of the most commonly used insecticides in combination with increasing soybean market prices led growers and technical advisors to debate the adequacy of recommended economic thresholds (ETs). The adoption of ETs and pest sampling has diminished in Brazil, leading to excessive pesticide use on soybean. The reduced efficacy of natural biological control, faster pest resurgence, and environment contamination are among the side-effects of pesticide abuse. To address these problems and maximize agricultural production, pest control programs must be guided by a proper integrated pest management (IPM) approach, including the ET concept. Therefore, the most appropriate time to initiate insecticide spraying in soybean is indicated by the available ETs which are supported by experiments over the last 40 years in different edapho-climatic conditions and regions with distinct soybean cultivars. Published scientific data indicate that preventive insecticide use is an expensive and harmful use of chemicals that increases the negative impact of pesticides in agroecosystems. However, the established ETs are for a limited number of species (key pests), and they only address the use of chemicals. There is a lack of information regarding secondary pests and other control strategies in addition to insecticides. It is clear then that much progress is still needed to improve ETs for pest management decisions. Nevertheless, using the current ETs provides a basis for reducing the use of chemicals in agriculture without reducing yields and overall production, thereby improving sustainability.