Cancer survivors may experience long-term adverse effects of cancer treatments such as premature ovarian failure and infertility. We aimed to investigate the potential effects and toxicity of bortezomib (BTZ) as an effective anticancer drug on ovaries, raise awareness to the negative consequences of the treatment, and help increase the quality of life after treatment. Mice were distributed into bortezomib (BTZ1, BTZ2) and saline-injected control groups (C1, C2) at a dose of 1 mg/kg twice per week for 6 weeks. We sacrificed C1, BTZ1 groups at day 1 and C2, BTZ2 groups at 4 weeks after the last injection. Ovary samples were examined using histopathological and immunohistochemical methods. Ovarian follicle impairment was detected on BTZ-treated mice and was associated with a statistically significant decreased population of primordial and antral follicles compared with control groups. In experimental groups, Caspase-3 and Ki67 expressions were increased, whereas estrogen receptor alpha (ERα) and progesterone receptor (PR) expressions were decreased in various developmental stages of follicles. BTZ specifically targets granulosa cells by inducing granulosa cell apoptosis and may have long-term effects on follicles. Bortezomib treatment may adversely affect ovarian function by accelerating ovarian reserve depletion and changing ERα and PR hormone levels that can cause fertility problems in the long term.

Hepatic progenitor cells are periportally resident cells capable of differentiating into mature hepatocytes or cholangiocytes to ensure hepatic regeneration. This reaction is termed a ductular reaction. In the present study, regenerative response of the feline liver to different hepatic diseases was investigated immunohistochemically. Regeneration of the liver through hepatocellular replication and proliferation of progenitor cell compartment were comparatively evaluated. Histological and immunohistochemical stainings were conducted on feline liver samples (n=40) representing various hepatobiliary diseases. Cytokeratin (CK) 7, CK19, Proliferating cell nuclear antigen (PCNA), Ki67, and Human hepatocyte marker 1 (Hep Par-1) were used. The presence of progenitor cells within feline livers was proved, both as passive cells in normal liver and as active cells (ductular reaction) in hepatic lesions. CK7 was found to be a suitable antibody for immunohistochemically detecting feline progenitor cells. In acute events, regeneration was predominantly shaped by the division of hepatocytes. In chronic events and severe acute events, hepatocytes lost their ability to divide and regeneration mainly occurred through progenitor cells. Location of the ductular reaction varied between different hepatic diseases. Parenchymal ductular reaction was detected in fulminant hepatitis, chronic hepatitis, hepatocellular lipidosis and metastatic lymphoma, whereas septal ductular reaction was detected in chronic hepatitis and metastatic lymphoma. Ductular reaction exhibited positive staining for Hep Par-1 in chronic and severe acute events. This study indicates the major role played by hepatic progenitor cells in regeneration of the feline liver. Moreover, it shows how the activation pattern of ductular reaction varies according to the hepatobiliary disease type.

Adipose-derived mesenchymal stromal cells (ASC) transplant to recover the optimal tissue structure/function relationship is a promising strategy to regenerate tissue lesions. Because filling local tissue defects by injection alone is often challenging, designing adequate cell carriers with suitable characteristics is critical for in situ ASC delivery. The aim of this study was to optimize the generation phase of a platelet–lysate-based fibrin hydrogel (PLFH) as a proper carrier for in situ ASC implantation and (1) to investigate in vitro PLFH biomechanical properties, cell viability, proliferation and migration sustainability, and (2) to comprehensively assess the local in vivo PLFH/ASC safety profile (local tolerance, ASC fate, biodistribution and toxicity). We first defined the experimental conditions to enhance physicochemical properties and microscopic features of PLFH as an adequate ASC vehicle. When ASC were mixed with PLFH, in vitro assays exhibited hydrogel supporting cell migration, viability and proliferation. In vivo local subcutaneous and subgingival PLFH/ASC administration in nude mice allowed us to generate biosafety data, including biodegradability, tolerance, ASC fate and engraftment, and the absence of biodistribution and toxicity to non-target tissues. Our data strongly suggest that this novel combined ATMP for in situ administration is safe with an efficient local ASC engraftment, supporting the further development for human clinical cell therapy.

Dozens of missed recessive loci affecting homozygous carriers' life expectancy were recently reported. This article details the clinical, biological and pathological manifestations of a new bovine genetic disorder caused by the ITGB7 p.G375S point mutation in the French Holstein cattle breed (BLIRD: OMIA:002872-9913). Our thorough study involved database analysis of genotyped cattle and a series of case-control investigations of forty individuals homozygous for the causative variant. These variant homozygotes had a significantly shorter lifespan (fewer than 64% surviving past three years vs. 87% in control), along with reduced body weight, daily weight gain, and dairy performance. The mutation did not affect most biochemical parameters, but a marked lymphocytic leucocytosis, moderate eosinophilia and differences in faecal microbiota were observed. Although non-pathognomonic symptoms may be confused with those of common environmental diseases, the blood profile effectively identified suspected carriers who developed ill-thrift and poor growth as heifers. Our research demonstrates that the bovine ITGB7 p.G375S substitution leads to reduced longevity, poor condition and production in most homozygous carriers. Furthermore, this spontaneous model may help to refine the functions of the integrin β7 (ITGB7) in immune homeostasis and defence.

Fetal anasarca is a congenital condition defined by excessive fluid accumulation throughout the body and subcutaneous edema. A 9-month-old Pekingese bitch with dystocia was presented to the Obstetrics and Gynecology Department of Ankara University, Faculty of Veterinary Medicine. Three stillborn puppies were removed by caesarian section and sent to the Pathology Department of Ankara University, Faculty of Veterinary Medicine for necropsy. Grossly, two of the puppies were larger than normal, had diffuse subcutaneous swelling with visceral effusion and were diagnosed with fetal anasarca. As for the third one, pulmonary hypoplasia was reported. All the fetuses additionally showed palatoschisis, bird tongue and lissencephaly. For histopathological examination, samples from the organs were collected and routinely processed. Severe edematous and degenerative changes were noted in the skin, liver, heart and kidneys of the anasarcous fetuses. Extramedullary hematopoiesis was also observed to different degrees in the livers and the spleens of all fetuses. The current case represents the first histopathologically described case of canine fetal anasarca in Turkey and it highlights the predisposition of brachycephalic dogs to fetal anasarca which is referred to be heritable as a recessive trait.