Synthesis, In Vitro, In Vivo and In Silico Antidiabetic Bioassays of 4-Niztro(thio)phenoxyisobutyric Acids Acting as Unexpected PPARγ Modulators: An In Combo Study

Four isobutyric acids (two nitro and two acetamido derivatives) were prepared in two steps and characterized using spectral analysis. The mRNA concentrations of PPARγ and GLUT-4 (two proteins documented as key diabetes targets) were increased by 3T3-L1 adipocytes treated with compounds 1–4, but an absence of in vitro expression of PPARα was observed. Docking and molecular dynamics studies revealed the plausible interaction between the synthesized compounds and PPARγ. In vivo studies established that compounds 1–4 have antihyperglycemic modes of action associated with insulin sensitization. Nitrocompound 2 was the most promising of the series, being orally active, and one of multiple modes of action could be selective PPARγ modulation due to its extra anchoring with Gln-286. In conclusion, we demonstrated that nitrocompound 2 showed strong in vitro and in vivo effects and can be considered as an experimental antidiabetic candidate.

Inclusion of Direct-Fed Microbials in Lactating Dairy Cow Diets

This report summarizes the information relating to the usage of direct-fed microbials, such as their modes of action and effectiveness in lactating dairy cows. Written by S. L. Bennett and A. P. Faciola, and published by the UF/IFAS Department of Animal Sciences, December 2021.

Biology and Management of Ragweed Parthenium (Parthenium hysterophorous L.) in Tomato, Pepper, Cucurbit, and Strawberry Production

Ragweed parthenium is an herbaceous annual or short-lived perennial weed. It is difficult to manage in many fields due to known resistance to commonly used herbicides. There are a limited number of modes of action that can be used in some vegetable and berry crops. This new 4-page publication of the UF/IFAS Environmental Horticulture Department provides management recommendations. Written by Nathan S. Boyd, Shaun M. Sharpe, Chris Marble, and Shawn Steed.https://edis.ifas.ufl.edu/ep613

Chicken Immune Cell Assay to Model Adaptive Immune Responses In Vitro

Knowledge about the modes of action of immunomodulating compounds such as pathogens, drugs, or feed additives, e.g., probiotics, gained through controlled but animal-related in vitro systems using primary cultured peripheral blood mononuclear cells (PBMCs) will allow the development of targeted nutrition strategies. Moreover, it could contribute to the prevention of infectious diseases and the usage of antimicrobials, and further promote the health of the animals. However, to our knowledge, a protocol for the isolation of PBMCs with reduced thrombocyte count from chicken blood and subsequent cell culture over several days to assess the effects of immunomodulating compounds is not available. Therefore, we established an optimized protocol for blood sampling and immune cell isolation, culture, and phenotyping for chicken PBMCs. For blood sampling commercial Na–citrate tubes revealed the highest count of vital cells compared to commercial Li–heparin (p < 0.01) and K3EDTA (p < 0.05) tubes. Using combined dextran and ficoll density gradient separation, the thrombocyte count was significantly reduced (p < 0.01) compared to slow-speed centrifugation with subsequent ficoll. For cell culture, the supplementation of RPMI-1640 medium with 10% chicken serum resulted in the lowest relative cell count of thrombocytes compared to fetal calf serum (FCS) (p < 0.05). To validate the ability of the cell culture system to respond to stimuli, concanavalin A (conA) was used as a positive control. The optimized protocol allows the isolation and cultivation of vital PBMCs with reduced thrombocyte count from chicken blood for subsequent investigation of the modes of action of immunomodulating compounds.