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Background The treatment of ovarian cancer has significantly improved since the introduction of PARP inhibitors (PARPi), small molecules designed to directly target and kill cancer cells with deficiencies in homologous recombination (HR) pathway. However, nearly half of patients present with HR-proficient tumors, rendering them not eligible for PARPi-based therapies and underscoring the urgent need for alternative treatment strategies. Methods Oxidative metabolism has been altered either by silencing the mitochondria regulator PGC-1β or by using the OXPHOS inhibitor IACS-010759. The metabolic alterations were characterized by seahorse analysis and metabolomic profiling. DNA damage and repair were evaluated by immunofluorescence and confocal analysis. Efficacy and tolerability of the combination of PARP and OXPHOS inhibitors were investigated in preclinical trials employing patient-derived ovarian cancer xenografts. Results Our findings reveal that PGC-1β silencing sensitizes ovarian cancer cells to PARPi by impairing oxidative metabolism, reducing succinate levels and decreasing Fen1 succinylation and SUMOylation. The impairment of these post-translational modifications hinders Fen1 activation and prevents the recruitment of Rad51, resulting in a HR-deficient-like phenotype. The translational relevance of the findings has been validated using the OXPHOS inhibitor IACS-010759, which synergizes with PARPi to inhibit cancer cell proliferation, while sparing normal cells. Furthermore, the combination therapy delays tumor progression in ovarian cancer xenografts not responsive to PARPi, independently from their HR status. Conclusions Targeting mitochondrial metabolism depicts a novel mechanism to modulate DNA repair and enhance PARPi sensitivity. This approach broadens the therapeutic applicability of PARP inhibitors beyond HR-deficient tumors and offers promising avenues to overcome resistance in ovarian cancer treatment.

Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

For improving aquafeed sustainability, insect meal is currently considered the most promising alternative to fishmeal. However, in this regard, more data are still necessary to avoid possible negative impacts on fish growth performance, metabolism, and welfare. The present study investigated the effects of increasing the inclusion of Hermetia illucens meal (0%, 17%, 33% and 50% of the feed, equating to 0%, 34%, 66% and 100% fishmeal replacement) on fish mortality, growth performance, intestine morphology, and gene expression of intestinal carriers. The results showed no adverse effects on fish mortality, feed intake and body weight and a positive effect on feed conversion ratio. Body weight gain was higher when 17% and 50% of Black soldier fly meals’ feed included (34% and 100% fishmeal replacement, respectively). Gut morphology was not affected by the dietary treatments except for the area of PAS-positive goblet cells that was higher in the treatment fed 33% of insect meal. The mRNA expression of intestinal epithelium functionality-specific marker genes, such as slc15a1 (alias pept1, alias slc15a1b), gata4 and nfkb1b, confirmed that the insect meal-based diets might replace fishmeal-based diets without negative effects. Overall, the results of the present study suggest that using Hermetia illucens larvae meal as a replacement for fishmeal in aquafeeds might help to enhance sustainability while assuring favorable fish growth performance and gut health.

Abstract Background Although the influence of copper ([Cu]) on chronic hepatitis (CH) has been widely studied in dogs, little information is available about the accumulation of other metals. Hypothesis/Objectives We assessed the concentration of lead ([Pb]) in the livers of dogs with CH with or without abnormal hepatic [Cu] to establish if any association existed between [Pb] and either hematologic or biochemical variables, fibrosis, necrosis and inflammation of the liver on histology. Animals Thirty-four dogs with CH that had hepatic [Cu] and [Pb] determined. Methods Retrospective review of medical records of dogs with CH and hepatic [Cu] and [Pb]. Chronic hepatitis was defined using current American College of Veterinary Internal Medicine consensus statement guidelines. Hepatic [Cu] and [Pb] were determined using square wave anodic stripping voltammetry. Dogs were divided into 2 groups based on [Cu]: <400 ppm (LoCu) and ≥400 ppm (HiCu). Results The median [Cu] and [Pb] were 357 ppm (range, 100-7743 ppm) and 58.7 (range, 6.89-224.4 ppm), respectively. Nineteen dogs had LoCu and 15 dogs had HiCu. Median [Pb] was significantly higher in HiCu compared to LoCu dogs (P < .001). Hepatic [Pb] and [Cu] were significantly correlated (rho = 0.7; P < .001). Dogs with microcytosis had higher [Pb] than did dogs with normal red cell volume (P = .02). Hepatic [Pb] was not correlated with either necroinflammatory or fibrosis scores. Conclusions and Clinical Importance Although additional studies are needed to better understand the clinical role of hepatic [Pb], dogs with abnormal hepatic [Cu] may also have higher hepatic [Pb]. In addition, in dogs with high hepatic [Pb], microcytosis may be present.

The photoinduced etiopathology of actinic keratosis and squamous cell carcinoma in feline species is well known. This etiology has also been reported for non-epithelial cutaneous tumors in other species. To date, no cases of auricular non-epithelial cutaneous neoplasms erased in a contest of actinic keratosis in cats have been reported. The aim of this study was to describe feline auricular non-epithelial cutaneous neoplasms associated with typical UV-induced cutaneous lesions and solar elastosis. The study was conducted on five feline cases diagnosed with auricular non-epithelial cutaneous tumors (two fibrosarcomas, one mixosarcoma, one epithelioid melanoma and one hemangiosarcoma), selected from the Tumor Registry of the Department of Veterinary Sciences of the University of Pisa (1998–2018). Ten and six feline auricular biopsies of normal skin and skin with actinic keratosis, respectively, were used as controls. Orcein stain was used to investigate solar elastosis. Histological changes related to chronic solar irradiation were documented in the skin adjacent to the neoplastic lesions in the five cats. Considering the anatomical localization and the results of histopathology, this study suggests that non-epithelial cutaneous neoplasms may have a UV-induced etiopathogenesis in the feline species.

The Western Honeybee is a key pollinator for natural as well as agricultural ecosystems. In the last decade massive honeybee colony losses have been observed worldwide, the result of a complex syndrome triggered by multiple stress factors, with the RNA virus Deformed Wing Virus (DWV) and the mite Varroa destructor playing crucial roles. The mite supports replication of DWV to high titers, which exert an immunosuppressive action and correlate with the onset of the disease. The aim of this study was to investigate the effect of 1,3-1,6 β-glucan, a natural innate immune system modulator, on honeybee response to low-titer natural and high-titer experimental DWV infection. As the effects exerted by ß-glucans can be remarkably different, depending on the target organism and the dose administered, two parallel experiments were performed, where 1,3-1,6 ß-glucan at a concentration of 0.5% and 2% respectively, was added to the diet of three cohorts of newly emerged honeybees, which were sampled from a Varroa-free apiary and harboured a low endogenous DWV viral titer. Each cohort was subjected to one of the following experimental treatments: no injection, injection of a high-copy number DWV suspension into the haemocel (experimental DWV infection) or injection of PBS into the haemocoel (physical injury). Control bees fed a ß-glucan-free diet were subjected to the same treatments. Viral load, survival rate, haemocyte populations and phenoloxidase activity of each experimental group were measured and compared. The results indicated that oral administration of 0.5% ß-glucan to naturally infected honeybees was associated with a significantly decrease of the number of infected bees and viral load they carried, and with a significant increase of the survival rate, suggesting that this natural immune modulator molecule might contribute to increase honeybee resistance to viral infection.

As with human species, recent studies also suggest a photoinduced etiopathology for non-epithelial cutaneous tumors in feline species. We report a recent case of a ten-year-old male cat with a white-hair coat and mesenchymal neoplasms of both auricles. Cytology, complete blood count (CBC), serum biochemistry and imaging examinations were performed. After surgery, the samples underwent routinary histopathology and were additionally stained with orcein. A routine analysis yielded values within a normal range and the imaging examination showed no abnormalities, suggesting that the bilateral presentation of neoplasms was primary rather than metastatic. The cytology was inconclusive, but, through histopathology, two well-differentiated fibrosarcomas were diagnosed and histopathological changes related to chronic UV exposure (such as epidermal hyperplasia, stratification disorders, keratinocyte dysplasia and an accumulation of elastotic material) were documented in the skin adjacent to the lesions. An orcein stain succeeded in highlighting elastosis. The elastic fibers lost their regular structure and orientation and appeared to be fragmented, wavy to branched and knotted. A morphometric analysis showed that the amount of elastotic material in the dermis close to the tumors was more than double compared with the more distant areas. Elastosis is considered to be a hallmark of photodamage; thus, an involvement of UV rays in the carcinogenic process of the tumors may be suspected.

Chronic liver diseases (CLDs) in dogs are progressive conditions that often lead to liver failure. Metabolic dysfunctions such as cholestasis, obesity, hyperlipidemia, and endocrine disorders play a key role in human liver diseases like MASLD (Metabolic Dysfunction Associated Steatotic Liver Disease) and MASH (Metabolic Dysfunction Associated Steatohepatitis), but their significance in canine CLDs is poorly understood. This study aims to evaluate the association between hepatic lipid accumulation and inflammation or fibrosis in canine CLDs and its potential association with metabolic dysfunctions. Sixteen client-owned dogs with CLDs were assessed for clinical data, histological features, and liver immunohistochemistry (IHC). Histological and IHC markers of inflammation (Iba-1, iNOS, NF-κB), fibrosis (CD206, α-SMA, Sirius Red), and lipid accumulation (adipophilin) were assessed to identify correlations with clinical conditions. The applied markers showed effectiveness in their use on canine liver tissue. Adipophilin-marked lipid accumulation correlated positively with inflammatory markers, indicating a link between steatosis and inflammation. Metabolic dysfunctions were linked to hepatic lipid accumulation and inflammation. These findings show a potential alignment of canine CLDs with human MASLD/MASH, where lipid-induced inflammation drives disease progression. IHC markers could effectively assess these processes, suggesting potential for guiding diagnostics and therapies, though further research is needed to clarify clinical associations.

The aim of the present study was to compare the effects of two different nitrogen-rich ingredients such as hydrolysed fish protein and autolysed yeast, on gilthead sea bream (Sparus aurata) growth performances and histological gut morphology. Animals were allocated to three experimental groups: the first received a fishmeal-based diet (FM), the second and the third received hydrolysed fish protein (HFP) and autolysed yeast (AY), respectively, to replace an equal amount of fishmeal. The experiment lasted 92 days. No significant differences in body weight and mortality were observed among the different groups. Villus branching, intraepithelial lymphocytes and inflammatory infiltrate of the submucosa were more prominent in AY than HFP and FM. The gut absorbent surface ratio was 5.94, 6.44 and 7.28 for group FM, HFP and AY, respectively, with statistical significant difference between FM and AY and between HFP and AY. A significant increment in the goblet cell density was observed for HFP and AY in comparison to FM. A statistically significant increase in small-sized goblet cells was observed in AY compared to FM. All our findings suggest that it is possible to use either HFP or AY, as partial replacer of FM in the S. aurata diet. Highlights Yeast-derived products as a suitable alternative nitrogen source. Autolyzed yeast as a novel approach in the use of yeast products. Use of autolysed yeast for replacing fishmeal in aqua feed. Use of hydrolysed fish protein for replacing fishmeal in aqua feed.

Case summary Ectopic thyroid tissue is rarely reported in dogs and cats in its prediaphragmatic location and has never been described in the liver. A 15-year-old spayed female domestic shorthair cat was diagnosed by ultrasound with a heterogeneous hypoechoic nodular area in the liver at the periphery of the quadrate lobe. A generic diagnosis of carcinoma was made after ultrasound-guided fine-needle aspiration and cytological examination. The patient underwent staging by CT scan and subsequently underwent hepatic lobectomy. Histologically, a diagnosis of thyroid adenocarcinoma was made, confirmed immunohistochemically using positive thyroglobulin staining; the tumour was suspected to be of metastatic origin. CT scans excluded primary thyroid involvement; in addition, lesions at other sites were not detected. Therefore, a final diagnosis of thyroid adenocarcinoma arising from ectopic thyroid tissue in the liver was made. The cat recovered uneventfully from surgery. Relevance and novel information This report describes an unusual case of an adenocarcinoma originating from presumed thyroid ectopic tissue within the liver of a cat. Ectopic thyroid tissue has been rarely reported in both dogs and cats and, to the authors’ knowledge, it has never been described in the liver of a cat.