Equine sarcoids are locally invasive, fibroblastic benign skin tumors. Bovine papillomavirus type-1 (BPV-1) and/or Bovine papillomavirus type-2 (BPV-2) are believed to be the causative agent of sarcoids, although the mechanisms by which the virus induce the tumor are still poorly understood. We hypothesized that in genetically predisposed equines latent BPV infection may be reactivated by immunosoppression and/or mechanical injury leading to a form of pathologic wound which may transform into a sarcoid. In this study, we investigated in 25 equine sarcoids and in five normal skin samples the histological features and evaluated the immunohistochemical and molecular expression of type I and type III Collagen, vimentin (VIM), alfa Smooth Muscle Actin (α-SMA), Matrix Metalloproteinase (MMPs) -2, 9, 14 and tissue inhibitor of metalloproteinase 2 (TIMP-2). In 64 % of investigated sarcoids, type I collagen staining was stronger than that of type III collagen. In 80 % of sarcoids, SFs were strongly positive for vimentin and negative for α-SMA; the remaining sarcoid samples (20 %) showed 70–80 % of SFs labeled for vim and approximately 20–30 % labeled for α-SMA. Moreover, all sarcoid specimen showed a variable staining pattern (weak to moderate) for MMP-9 and MMP-14, and a moderate to strong staining for MMP-2 and TIMP-2. Biochemical analysis confirmed immunohistochemical results and showed in sarcoids, for the first time, the cleaved form of MMP9, the 35 KDa active species for MMP-9. This study revealed that in equine sarcoids exhibit an altered turnover of the Extracellular Matrix (ECM) deposition and degradation, as result of an altered expression of MMPs and TIMPs. Therefore, these observations seem to confirm that the basic mechanism for growth of equine sarcoids could be a neoplastic transformation during wound healing.

Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC.

Background: Nosemosis is an infection of ventricular epithelial cells of adult European honey bees (Apis mellifera), caused by Nosema species. Until recently, it was thought to be caused only

Deformed wing virus (DWV) is capable of infecting honeybees at every stage of development causing symptomatic and asymptomatic infections. To date, very little is known about the histopathological lesions caused by the virus. Therefore, 40 honeybee samples were randomly collected from a naturally DWV infected hive and subjected to anatomopathological examination to discriminate between symptomatic (29) and asymptomatic (11) honeybees. Subsequently, 15 honeybee samples were frozen at −80° and analyzed by PCR and RTqPCR to determinate the presence/absence of the virus and the relative viral load, while 25 honeybee samples were analyzed by histopathological techniques. Biomolecular results showed a fragment of the expected size (69bp) of DWV in all samples and the viral load was higher in symptomatic honeybees compared to the asymptomatic group. Histopathological results showed degenerative alterations of the hypopharyngeal glands (19/25) and flight muscles (6/25) in symptomatic samples while 4/25 asymptomatic samples showed an inflammatory response in the midgut and the hemocele. Results suggest a possible pathogenic action of DWV in both symptomatic and asymptomatic honeybees, and a role of the immune response in keeping under control the virus in asymptomatic individuals.

Sarcoids are the mostcommon skin tumors in horses, characterized by rare regression, invasiveness and high recurrence following surgical intervention and Delta Papillomaviruses are widely recognized as the causative agents of the disease. In order to gain new insights into equine sarcoid development, we have evaluated, in 25 equine sarcoids, by immunohistochemistry and western blotting analysis, the expression levels of VEGF, Ki67 and bcl-2. Moreover, we have measured microvessel density and specific vessel parameters. All sarcoid samples showed a strong and finely granular cytoplasmatic staining for VEGF in the majority (90%) of keratinocytes, sarcoid fibroblasts and endothelial cells. Numerous small blood vessels, immunostained with Von Willebrand factor, often appeared irregular in shape and without a distinct lumen, with mean values of microvessel area and perimeter lower than normal. Moreover, in all sarcoid samples, Ki67 immunoreactivity was moderately positive in 5–10% of dermal sarcoid fibroblasts, while Bcl2 immunoreactivity was detected in 52% of the sarcoid samples, with a weak staining in 20–50% of dermal sarcoid fibroblasts. Biochemical analysis was consistent with immunohistochemical results. This study has provided evidence that in equine sarcoid: VEGF was strongly expressed; the increased number of vessels was not associated with their complete maturation, probably leading to a hypoxic condition, which could increase VEGF synthesis; the levels of sarcoid fibroblasts proliferation were very low. Concluding, VEGF may have a role in equine sarcoid development, not only through the increase of angiogenesis, but also through the control of sarcoid fibroblast activity.