A standardized protocol for assessing immunodeficiency in mouse models.

Immunodeficient mouse strains are widely used in several fields of biomedical research. Despite that, no standardized system for evaluating immunodeficiency in mice currently exists, and an unbiased comparison of various immunodeficient mouse strains is difficult. The aim of our study was to develop a standardized multi-disciplinary protocol for the morpho-phenotypical assessment of immunodeficient mouse models.

Immunohistochemical characterization of cells of the mononuclear phagocyte system in the mouse.

The mononuclear phagocyte system (MPS) is an ensemble of heterogeneous cells comprising circulating monocytes, macrophages, and dendritic cells. Immunohistochemistry is a valuable technique to detect, quantify, and localize MPS cells in tissues, but a comprehensive characterization of MPS cells in normal tissues of mice is lacking to date. The aim of this study was to immunohistochemically characterize MPS cells in a set of murine healthy tissues and in a subset of representative disease states.

Specific effects on liver relevant for performing a dietary cumulative risk assessment of pesticide residues.

According to the 'EFSA-SANTE Action Plan on Cumulative Risk Assessment for pesticides residues', EFSA initiated a retrospective cumulative risk assessment (CRA) of the effects of pesticide residues on the liver. For this CRA, EFSA identified the following liver-specific effects in accordance with the International Harmonisation of Nomenclature and Diagnostic Criteria (INHAND): (1) hypertrophy due to enzymatic induction, liver; (2) fatty change and/or phospholipidosis, hepatocellular; (3) degeneration/cell death, hepatocellular; (4) porphyria, hepatocellular, biliary duct; (5) cholestasis, hepatocellular, biliary duct; (6) preneoplastic and neoplastic changes, hepatocellular; (7) neoplastic changes, biliary duct. In addition, as gallbladder is part of the extrahepatic biliary system and can be affected by hepatic toxicity, the following specific effects in the gallbladder were defined: (1) erosion/ulceration, gallbladder (2) calculi, gallbladder and (3) neoplastic changes, gallbladder.

Specific effects on kidneys relevant for performing a dietary cumulative risk assessment of pesticide residues.

In consistency with the 'EFSA-SANTE Action Plan on Cumulative Risk Assessment for pesticides residues' EFSA initiated a retrospective cumulative risk assessment (CRA) of the effects of pesticide residues on the kidneys. EFSA identified the following specific effects on kidneys of relevance for cumulative risk assessment: glomerular injury, tubular injury, tubular crystals, papillary necrosis, interstitial nephritis, pelvis erosion/ulceration, pelvis calculi/crystals, renal preneoplastic and neoplastic lesions, and pelvis preneoplastic and neoplastic lesions. A list of histological indicators was defined and will be used to collect information on these specific effects, as reported in the assessment reports of the different active substances used as plant protections products.

Impact of adipose-derived mesenchymal stem cells and their secretome on osteoarthritis in a rat model.

Background: Osteoarthritis is a common degenerative joint disease marked by cartilage degeneration and inflammation. This study investigates the therapeutic potential of adipose-derived stromal cells (ASCs) and their secretome in a rat model of osteoarthritis.

Methods: ASCs were extracted from human adipose tissue, cultured, and primed with human platelet lysate.

Malignant mesothelioma-associated inflammatory microenvironment promotes tumor progression via GPNMB.

Background: Tumor-Associated Macrophages (TAMs) are the main immune component of the tumor stroma with heterogeneous functional activities, predominantly suppressing the immune response and promoting tumor progression, also via secretion of different factors. Among these, GPNMB (Glycoprotein non-metastatic B) is usually associated with disease progression in several tumor types. Malignant pleural mesothelioma (MPM) a severe neoplasia with poor prognosis, is characterized by an abundancy of TAMs, testifying the presence of a long-lasting inflammation which is pathogenetic of the disease.

Sex-dependent modulation of caerulein-induced acute pancreatitis in C57BL/6J mice.

Acute pancreatitis (AP) is a life-threatening condition, with a higher mortality rate in men than women and in which estrogens might play a protective role. This study aimed to investigate sex-dependent differences in a mouse model of caerulein-induced AP. Thirty-six C57BL/6J mice (19 females and 17 males) were treated intraperitoneally with phosphate-buffered saline or caerulein, and sacrificed 12 hours, 2 days, or 7 days after the last injection.

Preclinical pharmacology of patient-derived extracellular vesicles for the intraoperative imaging of tumors.

Extracellular vesicles (EVs) derived from the plasma of oncological patients exhibit significant tumor-targeting properties, unlike those from healthy individuals. We have previously shown the feasibility of formulating the near-infrared (NIR) fluorescent dye indocyanine green (ICG) with patient-derived extracellular vesicles (PDEVs) for selective delivery to neoplastic tissue. This staining protocol holds promise for clinical application in intraoperative tumor margin imaging, enabling precise neoplastic tissue resection.

WNT Oncogenic Transcription Requires MYC Suppression of Lysosomal Activity and EPCAM Stabilization in Gastric Tumors.

Background & Aims: WNT signaling is central to spatial tissue arrangement and regulating stem cell activity, and it represents the hallmark of gastrointestinal cancers. Although its role in driving intestinal tumors is well characterized, WNT's role in gastric tumorigenesis remains elusive.

Methods: We have developed mouse models to control the specific expression of an oncogenic form of β-catenin (CTNNB1) in combination with MYC activation in Lgr5 cells of the gastric antrum.

lesions in lungs of experimentally infected Cd40l mice.

The mouse is a well-established model of X-linked hyper-immunoglobulin M (IgM) syndrome, an immunodeficiency disorder of human beings characterized by the lack of expression of the CD40 ligand (CD40L) on activated T-cells, predisposing to infections with opportunistic pathogens like . The aim of our study was to describe the pulmonary lesions in mice experimentally infected with , in comparison with naturally infected severe combined immunodeficient (SCID) mice. Formalin-fixed paraffin-embedded lungs from 26 , 11 SCID, and 5 uninfected mice were examined by histology and immunohistochemistry for the presence of the pathogen and for leukocyte populations (CD3, CD4, CD45R/B220, CD8a, Iba-1, Ly-6G, CD206, MHC II, and NKp46/NCR1).

Tumor-associated macrophages and tumor-infiltrating lymphocytes in canine cutaneous and subcutaneous mast cell tumors.

Cutaneous and subcutaneous mast cell tumors (MCTs) are common canine neoplasms characterized by variable biological behavior. Tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) can be effective prognostic markers in numerous human neoplasms and are increasingly investigated in dogs. The aim of this study was to characterize immune cells in canine MCTs and their relationship with histological location (cutaneous, subcutaneous) and histologic nodal metastatic status (HN0-3).

Weishaar's classification system for nodal metastasis in sentinel lymph nodes: Clinical outcome in 94 dogs with mast cell tumor.

Background: The therapeutic role and prognostic relevance of lymphadenectomy in mast cell tumor (MCT) has historically been evaluated on regional rather than sentinel lymph nodes.

Hypothesis/objectives: To update information about the association of histological nodal (HN) classes with clinical outcome in dogs with MCT after tumor excision and extirpation of normal-sized sentinel nodes (SLN) guided by radiopharmaceutical.

Animals: Ninety-four dogs with histologically-confirmed treatment-naïve MCT (71 cutaneous, 22 subcutaneous and 1 conjunctival MCT) were included if without: distant metastases, lymphadenomegaly, concurrent mixed cutaneous, and subcutaneous MCT.

Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells.

Neutrophils are the most abundant leukocytes in human blood and play a primary role in resistance against invading microorganisms and in the acute inflammatory response. However, their role in colitis and colitis-associated colorectal cancer is still under debate. This study aims to dissect the role of neutrophils in these pathologic contexts by using a rigorous genetic approach.

Evaluation of Surgical Aid of Methylene Blue in Addition to Intraoperative Gamma Probe for Sentinel Lymph Node Extirpation in 116 Canine Mast Cell Tumors (2017-2022).

Methylene Blue (MB) is combined with radiopharmaceutical for intraoperative sentinel lymph node (SLN) mapping, but its role during SLN extirpation has not been investigated yet in veterinary medicine. The aim of this study was to assess whether MB increased surgical detection of SLN beyond the use of intraoperative gamma-probe (IGP) alone in clinically node-negative dogs with mast cell tumors (MCTs) following the detection of sentinel lymphocentrums (SLCs) via preoperative planar lymphoscintigraphy. Dogs enrolled underwent MCT excision and SLC exploration guided by both MB and IGP.

Ferritin nanoconjugates guide trastuzumab brain delivery to promote an antitumor response in murine HER2 + breast cancer brain metastasis.

Brain metastasis (BM) represents a clinical challenge for patients with advanced HER2 + breast cancer (BC). The monoclonal anti-HER2 antibody trastuzumab (TZ) improves survival of BC patients, but it has low central nervous system penetrance, being ineffective in treating BM. Previous studies showed that ferritin nanoparticles (HFn) may cross the blood brain barrier (BBB) through binding to the transferrin receptor 1 (TfR1).

Cytological Quantification of Nodal Mast Cells in Dogs Affected by Non-Neoplastic Condition and Mast Cell Tumor Using Different Sample Preparation Techniques: An Explorative Study.

Cytological evaluation of lymph nodes (LN) in canine cutaneous mast cell tumors (MCT) has a key role in MCT staging. However, cytological discrimination between metastatic and reactive LNs is debated and diagnostic criteria inconsistent. The aim of this study was to retrospectively quantify nodal mast cells (MCs) in non-oncological (NOD) and MCT-bearing dogs (MCTBD), using different sample preparation techniques, to evaluate the significance of the MCT number.

Important functional role of the protein osteopontin in the progression of malignant pleural mesothelioma.

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer of the mesothelial lining associated with exposure to airborne non-degradable asbestos fibers. Its poor response to currently available treatments prompted us to explore the biological mechanisms involved in its progression. MPM is characterized by chronic non-resolving inflammation; in this study we investigated which inflammatory mediators are mostly expressed in biological tumor samples from MPM patients, with a focus on inflammatory cytokines, chemokines and matrix components.

Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3.

is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection.

Swine intestinal segment perfusion model for the evaluation of nutrients bioaccessibility.

Nutrition science requires more science-based evidences for the development of effective functional diets. To reduce animals for experimental purposes innovative reliable and informative models, simulating the complex intestinal physiology, are needed. The aim of this study was to develop a swine duodenum segment perfusion model for the evaluation of nutrient bioaccessibility and functionality across time.

The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease.

Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin is a chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, a chemotactic receptor expressed by leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice.

Development of adverse outcome pathways relevant for the identification of substances having endocrine disruption properties Uterine adenocarcinoma as adverse outcome.

Development of adverse outcome pathways (AOPs) for uterine adenocarcinoma can provide a practical tool to implement the EFSA-ECHA Guidance (2018) for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009. AOPs can give indications about the strength of the relationship between an adverse outcome (intended as a human health outcome) and chemicals (pesticides but not only) affecting the pathways. In this scientific opinion, the PPR Panel explored the development of AOPs for uterine adenocarcinoma.

Live or Heat-Killed Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model.

An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead ()-aerosolized, and tumor development was evaluated.

Efficacy of mucosal vaccination using a protozoan parasite as a vehicle for antigen delivery: IgG and neutralizing response after rectal administration of LeCoVax-2, a candidate vaccine against COVID-19.

Mucosal vaccination is regarded as a promising alternative to classical, intramuscular vaccine delivery. However, only a limited number of vaccines have been licensed for mucosal administration in humans. Here we propose Leishmania tarentolae, a protozoan parasite, as a potential antigen vehicle for mucosal vaccination, for administration via the rectal or oral routes.

Surgical complications following sentinel lymph node biopsy guided by γ-probe and methylene blue in 113 tumour-bearing dogs.

Sentinel lymph node biopsy (SLNB) is an accepted veterinary surgical procedure given the impact of early detection of nodal metastases on staging of several canine malignancies. This study aims at reporting the incidence and risk factors for surgical complications of SLNB in tumour-bearing dogs. A total of 113 client-owned dogs that underwent tumour excision and SLNB guided by γ-probing and blue dye were retrospectively enrolled.