Among endogenous signaling networks involved in both rewarding and homeostatic mechanisms of obesity, a relevant role is played by the endocannabinoid (ECS) and the opioid (EOS) systems. We here studied the transcriptional regulation of ECS and EOS genes in the hypothalamus of Diet-induced obesity rats, a preclinical model of obesity, as well as in humans with obesity and healthy controls. A significant and selective increase in type 1 cannabinoid receptor gene (Cnr1) expression was observed at the beginning of obesity development (5 weeks on high fat diet) as well as after 21 weeks of high diet exposure. After 5 weeks on high fat diet, selective up-regulation of mu opioid receptor gene (Oprm1) expression was also observed. Consistently, epigenetic studies showed a selective and significant decrease in DNA methylation at specific CpG sites at both gene promoters in overweight rats, but only after 5 weeks on high fat diet. Moreover, significantly lower levels of DNA methylation were observed at selected CpG sites of both receptor gene promoters, analyzed in peripheral blood mononuclear cells from younger (<30 years old) humans with obesity, as well as in those with shorter time length from disease onset. Taken together, we here provide evidence of selective, synergistic and time-dependent transcriptional regulation of CNR1 and OPRM1 genes in overweight rats, as well as in human subjects. These alterations in genes regulation could contribute to the development of the obese phenotype, and we thus suggest CNR1 and OPRM1 epigenetic modulation as possible biomarkers of obesity development. Due to the reversible nature of the epigenetic hallmark, our data might also open new avenue to early environmental strategies of intervention.

Canine osteosarcoma is highly resistant to current chemotherapy; thus, clarifying the mechanisms of tumor cell resistance to treatments is an urgent need. We tested the geldanamycin derivative 17-AAG (17-allylamino-17-demethoxygeldanamycin) prototype of Hsp90 (heat shock protein 90) inhibitors in 2 canine osteosarcoma cell lines, D22 and D17, derived from primary and metastatic tumors, respectively. With the aim to understand the interplay between cell death, autophagy, and mitophagy, in light of the dual effect of autophagy in regulating cancer cell viability and death, D22 and D17 cells were treated with different concentrations of 17-AAG (0.5 μM, 1 μM) for 24 and 48 hours. 17-AAG-induced apoptosis, necrosis, autophagy, and mitophagy were assessed by transmission electron microscopy, flow cytometry, and immunofluorescence. A simultaneous increase in apoptosis, autophagy, and mitophagy was observed only in the D22 cell line, while D17 cells showed low levels of apoptotic cell death. These results reveal differential cell response to drug-induced stress depending on tumor cell type. Therefore, pharmacological treatments based on proapoptotic chemotherapy in association with autophagy regulators would benefit from a predictive in vitro screening of the target cell type.

Nutritional supplements, also known as complementary feeds, are products administered with the aim of furnishing health benefits, regardless of nutritional needs. They have been used since ancient times in veterinary dermatology, and a number of studies have focused on investigating the health benefits of some ingredients found in commercially available complementary feed for dogs. The aim of this paper is to review the literature available on the use of nutritional supplementation for the management of canine skin diseases, critically appraising the clinical efficacy of such interventions and summarizing the current state of knowledge. This review highlights how these feeds can be considered useful in the management of dermatological disorders and outlines their beneficial effects in the prevention of dietary deficiencies and treatment of diseases, alone, or in addition to conventional pharmacological therapy. In recent years, nutritional supplements have found increasing potential application in veterinary medicine, and the scientific proofs of their beneficial effects are described in this review.

Canine atopic dermatitis (AD) is a multifactorial allergic disease associated with immune and abnormal skin barrier dysfunction and it is one of the primary causes of pruritus. Using a novel in vitro model of AD, here we tried to revert the alteration of transcriptional regulation of AD canine key genes testing a nutraceutical mixture containing flavonoids, stilbene, and cannabinoids, which are already well-known for their applications within dermatology diseases. The nutraceutical mixture induced in inflamed cells a significant downregulation (p < 0.05) of the gene expression of ccl2, ccl17, and tslp in keratinocytes and of ccl2, ccl17, and il31ra in monocytes. Consistent with the observed alterations of tslp, ccl2, ccl17, and il31ra messenger RNA (mRNA) levels, a significant increase (p < 0.05) of DNA methylation at specific CpG sites on the gene regulatory regions was found. These results lay the foundation for the use of these natural bioactives in veterinary medicine and provide a model for deeper understanding of their mechanisms of action, with potential translation to human research.

Dead specimens provide valuable data for the conservation of threatened species, allowing investigations of mortality, health conditions, and demographic parameters. The Eurasian otter (Lutra lutra) is a semiaquatic carnivore listed as endangered in Italy. In 2009, we started the first post mortem (PM) study of otters in Italy, through collaborative research between mammal ecologists and veterinary pathologists, using standardized protocols. Twenty-eight otters, mostly collected between 2009 and 2017, were examined. Most otters were males (67%), between 1 and 3 years old (64%), and predominantly in good nutritional condition. Adult males were significantly larger than adult females (p < 0.02), as expected for the species, although both sexes appeared to be smaller than otters examined in Central–northern Europe. The youngest sexually mature female was 3 years old. Road traffic collisions were the major cause of death, especially in young individuals, and mainly occurred in autumn–winter, particularly for females. Investigations of the scene of death contributed to revealing factors forcing otters to travel out of the water and move over the road, suggesting appropriate measures to reduce vehicle collision risk. Other causes of death included blunt chest trauma of uncertain origin, dog and conspecific attacks, or diseases of infectious or non-infectious origin, such as ulcerative gastritis, pleuropneumonia and peritonitis. Other diagnosed diseases included lymphoma. Ecto- and endoparasites were rarely detected, although we report the first documentation of heartworm and Ixodes hexagonus infestation in Italian otters. It is important to continue comprehensive, standardized PM investigations of otters in Italy to define baseline health, biometric and demographic parameters, collect biological samples for comparative analyses, and to reduce road-kill mortality. The present study suggests that the timely collection of carcasses and collaborative and coordinated research efforts are essential for obtaining useful data for the conservation of otters.