In-depth peptidomic profile and molecular simulation studies on ACE-inhibitory peptides derived from probiotic fermented milk of different farm animals.

Investigations into ACE inhibitory properties of probiotic fermented bovine, camel, goat, and sheep milk were performed and studied for two weeks of refrigerated storage. Results from the degree of proteolysis suggested higher susceptibility of goat milk proteins, followed by sheep and camel milk proteins, to the probiotic-mediated proteolysis. ACE-inhibitory properties displayed continuous decline in ACE-IC50 values for two weeks of refrigerated storage. Overall, goat milk fermented with Pediococcus pentosaceus caused maximum ACE inhibition (IC50: 262.7 µg/mL protein equivalent), followed by camel milk (IC50: 290.9 µg/mL protein equivalent). Studies related to peptide identification and in silico analysis using HPEPDOCK score revealed presence of 11, 13, 9 and 9 peptides in fermented bovine, goat, sheep, and camel milk, respectively, with potent antihypertensive potential. The results obtained suggest that the goat and camel milk proteins demonstrated higher potential for generating antihypertensive peptides via fermentation when compared to bovine and sheep milk.

The ovaries of ivermectin-resistant Rhipicephalus microplus strains display proteomic adaptations involving the induction of xenobiotic detoxification and structural remodeling mechanisms.

Controlling Rhipicephalus microplus is among the most significant challenges for livestock production worldwide. The indiscriminate use of acaricides stimulates the selection of resistant tick populations and is therefore ineffective. Understanding the molecular foundations of resistance could help inform the search for new alternatives for tick control. Although the ovary has been suggested as a relevant target organ for tick control, there are few existing studies that focus on tick ovarian tissue. Therefore, we conducted a comparative proteomic analysis on ovaries of R. microplus strains with differential resistance to ivermectin. In resistant ticks, we observed the over-accumulation of proteins involved in several biological processes, including translation, proteolysis, transport, cellular organization, differentiation, and xenobiotic detoxification. We also observed the accumulation of many structural and extracellular proteins such as papilin-like protein, which glycosylation increase its stability-based molecular modeling. Therefore, we propose that ovaries of ivermectin-resistant ticks overcome the negative impact of ivermectin through the activation of detoxification mechanisms and structural proteins associated with the remodeling of the ovary's extracellular matrix. SIGNIFICANCE: Understanding the molecular foundation of ivermectin resistance in Rhipicephalus microplus represents an essential step in cattle farming, which could provide clues and alternatives for tick control. Excessive use of chemicals like ivermectin allows the generation of resistant tick strains in different countries. However, limited molecular information is available concerning the tick's resistance to ivermectin. Detailed proteomics scrutiny in various tick organs will provide more comprehensive molecular information. Thus, we conducted an ovary comparative proteomic-based TMT-SPS-MS3 approach. We highlight in ivermectin-resistant ticks the over-accumulation of structural proteins and enzymes connected to detoxification mechanisms.

Molecular Dynamics and Virtual Screening Analysis of Lanosterol Derivatives from Ganoderma Medicinal Mushrooms (Agaricomycetes) as Selective Ligands of Human Androgen Receptor.

Male sex hormones such as testosterone and dihydrotestosterone play important roles in several physiological and pathological processes. The biological activities of the aforementioned metabolites are mediated by the multidomain androgen receptor (AR), which is therefore a well-studied drug target. Ganoderma mushroom lanostanoid extracts have previously been shown to exert antiandrogenic activity; therefore, this work aims to identify which lanostane derivatives might act as selective ligands for AR. Because protein flexibility is of paramount importance for ligand binding, different conformations of AR were sampled to account for binding modes within a ligand binding site, then subjected to virtual screening against a metabolite library. Fifteen Ganoderma lanostanoids were selected as AR ligands, according to their calculated binding affinity to this nuclear receptor. The results show the relevance of certain structural and chemical aspects of our ligands, such as the presence of a ketonic group on C-3, which influences the process through which they bind to AR.

In Silico Analysis of Lanostanoids Characterized in Ganoderma Mushrooms (Agaricomycetes) as Potential Ligands of the Vitamin D Receptor.

The metabolism of vitamin D is a very important pathway involved in the regulation of sterols and maintenance of cell health. The physiological activity of the human hormone 1α,25-dihydroxyvitamin D3, or calcitriol, is mediated by the vitamin D receptor (VDR), an endocrine member of the nuclear receptor superfamily that inhibits cell growth and stimulates cell differentiation, suggesting a potential application in cancer chemoprevention. Since nonpolar extracts obtained from Ganoderma mushrooms have also been shown to exert an antiproliferative effect on several cancer cell lines, it was suggested that at least part of its activity might be mediated by VDR. The aim of this work was to identify possible VDR ligands from an extensive library of lanostanoids isolated from several Ganoderma mushrooms. Using an in silico approach, 30 lanostanoids were found to interact with the VDR ligand-binding pocket in the same way as calcitriol. The possible implications of using these compounds are discussed here.