The Trichoderma genus consists of a group of free-living filamentous fungi, including species able to act as biological control agents (BCAs) against pathogenic fungi. It is believed that this ability is due to synergy between several mechanisms, including the production of a wide variety of secondary metabolites by these organisms. Among these, we highlight the production of peptaibols, an antibiotic peptide group characterized by the presence of non-proteinogenic amino acids such as α-aminoisobutyrate (Aib), as well as by N-terminal modifications and amino alcohols in the C-terminal region. This study aimed to outline a profile of peptaibol production and to identify secreted peptaibols from the Trichoderma asperellum TR356 strain, described as an efficient BCA against S. sclerotiorum. The fungus was grown on TLE 0.3% glucose medium for 5 days, with agitation at 120 rpm in the dark. Liquid medium filtrate was used as the metabolite source. These extracts were subjected to high performance liquid chromatography (HPLC) and subsequent analysis by matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF). The results indicate the production of two classes of peptaibols for this T. asperellum strain. Primary structures of two asperelines (A and E) and five trichotoxins (T5D2, T5E, T5F, T5G and 1717A) have been elucidated. Most of these peptaibols had been previously described in T. viride and T. asperellum marine strains. This is the first report of some of these compounds being produced by a T. asperellum strain from soil. Future analyses will be necessary to elucidate the three-dimensional structures and their activities against pathogens.

COVID-19 has accounted for more than 6 million deaths worldwide. Bacillus Calmette–Guérin (BCG), the existing tuberculosis vaccine, is known to induce heterologous effects over other infections due to trained immunity and has been proposed to be a potential strategy against SARS-CoV-2 infection. In this report, we constructed a recombinant BCG (rBCG) expressing domains of the SARS-CoV-2 nucleocapsid and spike proteins (termed rBCG-ChD6), recognized as major candidates for vaccine development. We investigated whether rBCG-ChD6 immunization followed by a boost with the recombinant nucleocapsid and spike chimera (rChimera), together with alum, provided protection against SARS-CoV-2 infection in K18-hACE2 mice. A single dose of rBCG-ChD6 boosted with rChimera associated with alum elicited the highest anti-Chimera total IgG and IgG2c Ab titers with neutralizing activity against SARS-CoV-2 Wuhan strain when compared with control groups. Importantly, following SARS-CoV-2 challenge, this vaccination regimen induced IFN-γ and IL-6 production in spleen cells and reduced viral load in the lungs. In addition, no viable virus was detected in mice immunized with rBCG-ChD6 boosted with rChimera, which was associated with decreased lung pathology when compared with BCG WT-rChimera/alum or rChimera/alum control groups. Overall, our study demonstrates the potential of a prime-boost immunization system based on an rBCG expressing a chimeric protein derived from SARS-CoV-2 to protect mice against viral challenge.

This study describes the synthetic route and molecular computational docking of LQFM 021, as well as examines its biological effects and toxicity. The docking studies revealed strong interaction of LQFM 021 to phosphodiesterase-3 (PDE-3). In isolated arteries, the presence of endothelium potentiates the relaxation for LQFM 021 and the inhibition cyclic nucleotides reduced the relaxation. Pre-contraction with KCl (45 mm), the treatment with tetraethylammonium (TEA) (5 mm) and inhibition of reticular Ca²⁺-ATPase showed an inhibitory effect on relaxation. Moreover, the compound reduced the contraction evoked by the Ca²⁺ influx. Acute toxicity tests revealed that the compound was practically nontoxic. In conclusion, this study showed that a new synthetic derivative of pyrazole is a possible PDE-3 inhibitor and has vasorelaxant activity and low toxicity.

The liver serves as a major energetic reservoir for other tissues and its metabolic function is controlled by humoral and neural factors. The vagus nerve innervating the gastrointestinal tract plays an important role in regulating peripheral metabolism and energy expenditure. Although the liver receives vagus nerve fibers, the impact of this circuitry in the regulation of hepatic metabolism is still poorly understood. Herein, we used a combination of quantitative proteomics and in vivo imaging techniques to investigate the impact of the vagus nerve on liver metabolism in male mice. Liver-brain axis was impaired by vagotomy (VNX) or knocking down of the vesicular acetylcholine transporter (VAChT-KD). Mice were challenged with high carbohydrate or high-fat feeding. The vagus nerve shapes the metabolic framework of the liver, as vagotomy led to a significant alteration of the hepatic proteome landscape. Differential protein expression and pathway enrichment analyses showed that glycolytic and fatty acid biosynthesis were increased following VNX, whereas β-oxidation was decreased. These results were corroborated in VAChT-KD mice. This metabolic shift facilitated lipid accumulation in hepatocytes in mice fed with a standard commercial diet. Furthermore, VNX worsened liver steatosis following high-carbohydrate or high-fat dietary challenges. This study describes the liver-brain axis mediated by the vagus nerve as an important regulator of the hepatic metabolic landscape.