Antinociceptive Effect of a p-Cymene/ß-Cyclodextrin Inclusion Complex in a Murine Cancer Pain Model: Characterization Aided through a Docking Study.

Pain is one of the most prevalent and difficult to manage symptoms in cancer patients, and conventional drugs present a range of adverse reactions. The development of ß-cyclodextrins (ß-CD) complexes has been used to avoid physicochemical and pharmacological limitations due to the lipophilicity of compounds such as p-Cymene (PC), a monoterpene with antinociceptive effects. Our aim was to obtain, characterize, and measure the effect of the complex of p-cymene and ß-cyclodextrin (PC/ß-CD) in a cancer pain model. Initially, molecular docking was performed to predict the viability of complex formation. Afterward, PC/ß-CD was obtained by slurry complexation, characterized by HPLC and NMR. Finally, PC/ß-CD was tested in a Sarcoma 180 (S180)-induced pain model. Molecular docking indicated that the occurrence of interaction between PC and ß-CD is favorable. PC/ß-CD showed complexation efficiency of 82.61%, and NMR demonstrated PC complexation in the ß-CD cavity. In the S180 cancer pain model, PC/ß-CD significantly reduced the mechanical hyperalgesia, spontaneous nociception, and nociception induced by non-noxious palpation at the doses tested (p < 0.05) when compared to vehicle differently from free PC (p > 0.05). Therefore, the complexation of PC in ß-CD was shown to improve the pharmacological effect of the drug as well as reducing the required dose.

High Genotypic Diversity, Putative New Types and Intra-Genotype Variants of Bovine Papillomavirus in Northeast Brazil.

Bovine papillomavirus (BPV) can cause damage to the epithelial and mucosal tissue and currently presents 28 known types. Not all BPV types are associated with the development of cancer in cattle. Studies have shown that variants of human papillomavirus types can present different pathogenic profiles. However, despite the similarity, it is not yet known whether variants of BPV types can also present varying degrees of pathogenicity. Thus, the aim of this study was to evaluate the genetic variability of BPV types and variants isolated in Northeastern Brazil. Samples were obtained from animals with papillomatous lesions. BPV DNA was detected by the amplification of the L1 gene and genotyping was performed by sequencing. Mutations were analyzed in a phylogenetic, structural and functional context. In total, 52 positive samples were obtained and 11 different BPV types were identified in the samples. Ten putative new BPV types were also identified. In addition, several non-synonymous mutations were identified and predicted to alter protein stability, having an impact on immune evasion. The study demonstrated a high genetic diversity of BPV in the region with a large number of mutations identified, serving as a basis for more efficient control measures to be adopted for bovine papillomatosis.

Molecular characterization of Canis familiaris oral papillomavirus 1 identified in naturally infected dogs from Northeast Brazil.

BACKGROUND: Canine papillomavirus (CPV) has 20 described types associated with papillomas or squamous cell carcinoma (SCC). Knowledge about CPV diversity is scarce. Studies on papillomaviruses that infect other hosts show substantial diversity with some types and variants being associated with cancer. HYPOTHESIS/OBJECTIVES: The aim of this study was to assess the genetic variability of the capsid L1 gene of CPV identified in lesions of naturally infected dogs from Brazil. ANIMALS: Six dogs presenting with oral and cutaneous warts from different veterinary clinics in Sergipe state, Northeast Brazil. METHODS AND MATERIALS: Nine skin biopsy samples were collected for histopathological and molecular analyses. Bioinformatics tools were used for genotyping and diversity analysis. Mutations were characterized based on their impact on the L1 protein structure. RESULTS: Sequences of CPV1 were obtained from exophytic papillomas. These sequences had at least five different mutations showing that all sequences were putative CPV1 variants. One CPV1 sequence, obtained from an oral SCC, had a highly destabilizing substitution in the L1 protein which was likely to be associated with changes in protein function. CONCLUSIONS AND CLINICAL IMPORTANCE: Despite the small number of cases analysed and the partial analysis of L1 nucleotide and amino acid sequences, this study has demonstrated diversity in CPV samples from Northeast Brazil. A putative new CPV1 variant associated with oral SCC, with novel protein structure changing mutations, was identified which may be important for understanding papillomavirus pathogenesis.

Comparative transcriptomic analysis of bovine papillomatosis.

BACKGROUND: Bovine papillomavirus (BPV) belongs to the Papillomaviridae family and infects epithelial cells of bovines and closely related animals, causing hyperproliferative lesions known as warts or papillomas, which may regress or progress to form benign or malignant tumors. The virus enters the host cell and interacts with it by altering the regulation of genes that are responsible for controlling the cell cycle, thus triggering lesion formation. It is not yet known which host genes are regulated by viral infection. Therefore, the objective of this study was to make use of next-generation RNA sequencing methods to identify differentially expressed genes associated with BPV infection, which might elucidate possible marker genes that could be used to control the disease. RESULTS: Transcriptome analysis revealed that 1343 genes were differentially regulated (FDR < 0.05). A comparison of gene expression in infected and noninfected cows indicated that 655 genes were significantly upregulated, and 688 genes were significantly downregulated. Most differentially expressed genes were associated with BPV infection pathways, which supports the hypothesis that viral infection was the mechanism associated with this regulation. CONCLUSIONS: This is the first study that focused on a large-scale evaluation of gene expression associated with BPV infection, which is important to identify possible metabolic pathways regulated by host genes for lesion development. In addition, novel targets could be identified in order to find ligands that interact with BPV, with the aim of interrupting the infection cycle.

Patterns of vector species richness and species composition as drivers of Chagas disease occurrence in Brazil.

Chagas disease represents one of the major health issue in Latin America. Epidemiological control is focused on disease vectors, so studies on the ecology of triatomine vectors constitute a central strategy. Recently, research at large spatial scale has been produced, and authors commonly rely on the assumption that geographical regions presenting good environmental conditions for most vector species are also those with high risk of infection. In the present work, we provide an explicit evaluation for this assumption. Employing species distribution models and epidemiological data for Chagas disease in Brazilian territory, our results show that species richness is a poor predictor for the observed pattern of Chagas disease occurrence. Species composition proved to be a better predictor. We stress that research on macroecology of infectious diseases should go beyond the analysis of biodiversity patterns and consider human infections as a central part of the focal ecological systems.