Fistulous withers causing spinal epidural abscess in a Thoroughbred mare.

This case describes a 15-year-old Thoroughbred mare with fistulous withers that progressed to vertebral osteomyelitis and spinal epidural abscess (SEA), a severe complication that has yet to be reported. Initially treated with antibiotics and anti-inflammatory medication, the mare developed acute hindlimb ataxia and spastic paresis, suggesting spinal cord compression at T3-L3. Diagnostic imaging revealed vertebral fractures and abscessation, but vertebral canal involvement could not be confirmed.

Intravenous gene therapy improves lifespan and clinical outcomes in feline Sandhoff Disease.

Sandhoff Disease (SD), a fatal neurodegenerative disorder, is caused by the absence of ß-hexosaminidase (Hex) and subsequent accumulation of GM2 ganglioside in lysosomes. Previous studies have led to adeno-associated virus (AAV) gene therapy for children with GM2 gangliosidosis in both expanded access and Phase I/II clinical trials via intracranial and/or cerebrospinal fluid-based delivery. The current study investigated intravenous (IV) gene therapy of SD cats, treated at one month of age with a bicistronic AAV vector.

Cytokeratin AE1/AE3 immunolabeling in epithelioid hemangiosarcoma.

Epithelioid hemangiosarcoma (EH), a rare histological variant of hemangiosarcoma, is reported in various animal species, including humans, dogs, cows, horses, and cats. Epithelioid hemangiosarcomas are composed of highly pleomorphic epithelioid cells arranged in cords, islands, nests, or solid cellular areas, similar to epithelial neoplasms. Moreover, in humans, approximately 50% of EHs have cytoplasmic immunolabeling for cytokeratin AE1/AE3 (CK AE1/AE3), making it challenging to distinguish them from carcinomas.

The Development and Characterization of a Next-Generation Oncolytic Virus Armed with an Anti-PD-1 sdAb for Osteosarcoma Treatment .

Osteosarcoma (OS) is a primary bone malignancy characterized by an aggressive nature, limited treatment options, low survival rate, and poor patient prognosis. Conditionally replicative adenoviruses (CRAds) armed with immune checkpoint inhibitors hold great potential for enhanced therapeutic efficacy. The present study aims to investigate the anti-tumor efficacy of CAV2-AU-M2, a CAV2-based CRAd armed with an anti-PD-1 single-domain antibody (sdAb), against OS cell lines .

Case report: Intraneural perineurioma in dogs: a case series and brief literature review.

Intraneural perineurioma is an exceptionally rare neoplasm in animals. This case study comprises a series of three cases and a brief literature review focusing on canine intraneural perineurioma. The pathological and immunohistochemical findings are documented, revealing that canine intraneural perineurioma frequently affects adult dogs aged between 3 and 10 years old, with a male predominance.

Single-Nuclei Multiome (ATAC + Gene Expression) Sequencing of a Primary Canine Osteosarcoma Elucidates Intra-Tumoral Heterogeneity and Characterizes the Tumor Microenvironment.

Osteosarcoma (OSA) is a highly aggressive bone tumor primarily affecting pediatric or adolescent humans and large-breed dogs. Canine OSA shares striking similarities with its human counterpart, making it an invaluable translational model for uncovering the disease's complexities and developing novel therapeutic strategies. Tumor heterogeneity, a hallmark of OSA, poses significant challenges to effective treatment due to the evolution of diverse cell populations that influence tumor growth, metastasis, and resistance to therapies.

Validating the anti-lymphoma pharmacodynamic actions of the endocannabinoids on canine non-Hodgkin lymphoma.

Aims: This study established the in vitro anti-lymphoma pharmacodynamic actions of the endocannabinoids (anandamide-AEA and 2-arachidonoylglycerol-2AG) on canine non-Hodgkin lymphoma (NHL) and human NHL cells.

Main Methods: The expression of cannabinoid (CB and CB) receptors in various canine NHL cells {1771, CLBL-1, CLL-1, peripheral blood mononuclear cells (PBMCs)} was studied using Quantitative real-time PCR (RT-qPCR). Anti-lymphoma cell viability assay was performed to assess the effect of endocannabinoids on various canine and human NHL cells (1771, CLBL-1, CLL-1, Ramos cells).

Role of IL-27 in HSV-1-Induced Herpetic Stromal Keratitis.

Herpetic stromal keratitis (HSK) is a painful and vision-impairing disease caused by recurrent HSV-1 infection of the cornea. The virus replication in the corneal epithelium and associated inflammation play a dominant role in HSK progression. Current HSK treatments targeting inflammation or virus replication are partially effective and promote HSV-1 latency, and long-term use can cause side effects.

Thymic cavernous haemangioma in a dog.

A 12-year-old male neutered Australian Shepherd Dog was presented to Charlotte Animal Referral & Emergency with a history of a thoracic mass. On physical examination, physiological parameters were within the normal ranges, and a complete haemogram and serum biochemistry profile were unremarkable except for mild thrombocytopenia. A computed tomography scan revealed a 21 × 15 × 12.

Characterization of Canine Adenovirus Type 2 Virus Infection Pattern in Canine and Human Cell Lines.

Canine adenovirus type 2 (CAV2) is a nonhuman adenovirus with a known ability to infect human and canine cells. The cell surface receptors involved in CAV2 transduction are still unknown. Identification of these would provide valuable information to develop enhanced gene delivery tools and better understand CAV2 biology.

Development of OX40 agonists for canine cancer immunotherapy.

Recent breakthroughs in cancer immunotherapy have provided unprecedented clinical benefits to human cancer patients. Cancer is also one of the most common causes of death in pet dogs. Thus, canine-specific immune therapies targeting similar signaling pathways can provide better treatment options for canine cancer patients.

Case report: The first description of a Dieulafoy's lesion in the gastric mucosa of a dog.

An approximately 12-year-old, 31 kg, male neutered Labrador Retriever was presented to the referring hospital with an acute onset (less than 1 day) of hematemesis and melena. The dog was treated supportively for a presumptive gastric ulcer for 4 days with intravenous fluids, gastro protectants, such as pantoprazole, misoprostol, sucralfate, and barium, as well as an anti-emetic (maropitant) and analgesics (fentanyl, gabapentin, and tramadol). Throughout medical management, the dog continued to require blood transfusions approximately every 24 h.

Transcriptomic Analysis of Canine Osteosarcoma from a Precision Medicine Perspective Reveals Limitations of Differential Gene Expression Studies.

Despite significant advances in cancer diagnosis and treatment, osteosarcoma (OSA), an aggressive primary bone tumor, has eluded attempts at improving patient survival for many decades. The difficulty in managing OSA lies in its extreme genetic complexity, drug resistance, and heterogeneity, making it improbable that a single-target treatment would be beneficial for the majority of affected individuals. Precision medicine seeks to fill this gap by addressing the intra- and inter-tumoral heterogeneity to improve patient outcome and survival.

High Olfactory Receptor-Rich 11q11 Copy Number in Girls and African American Children.

Copy number variants (CNVs) provide numerous genetic differences between individuals, and they have been linked with multiple human diseases. Obesity is one of the highly heritable complex disorders, which is associated with copy number variance (CNV). A recent report shows that the 11q11 gene, a novel olfactory receptor, and its copy number variants are involved in the early onset of obesity.

A clinically relevant combination treatment with doxorubicin and cyclophosphamide does not induce hepatotoxicity in C57BL/6J mice.

Background And Aim: Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity. A combination chemotherapy regimen of doxorubicin (DOX) and cyclophosphamide (CPS) is employed in treatment of several cancers such as leukemia, lymphoma, and breast cancer. It is not well understood whether a combination therapy of DOX and CPS can induce hepatotoxicity.

Short palate, lung, and nasal epithelial clone 1 (SPLUNC1) level determines steroid-resistant airway inflammation in aging.

Asthma and its heterogeneity change with age. Increased airspace neutrophil numbers contribute to severe steroid-resistant asthma exacerbation in the elderly, which correlates with the changes seen in adults with asthma. However, whether that resembles the same disease mechanism and pathophysiology in aged and adults is poorly understood.

Nanobody-based CTLA4 inhibitors for immune checkpoint blockade therapy of canine cancer patients.

Cancer is the leading cause of death in the geriatric dog population. Currently, the use of immune checkpoint inhibitors (ICIs) such as anti-CTLA4 antibodies has markedly improved the prognosis of several cancers in their advanced stages. However, ICIs targeting CTLA4 blockade to treat canine cancer patients are yet to define.

Irg1/itaconate metabolic pathway is a crucial determinant of dendritic cells immune-priming function and contributes to resolute allergen-induced airway inflammation.

Itaconate is produced from the mitochondrial TCA cycle enzyme aconitase decarboxylase (encoded by immune responsive gene1; Irg1) that exerts immunomodulatory function in myeloid cells. However, the role of the Irg1/itaconate pathway in dendritic cells (DC)-mediated airway inflammation and adaptive immunity to inhaled allergens, which are the primary antigen-presenting cells in allergic asthma, remains largely unknown. House dust mite (HDM)-challenged Irg1 mice displayed increases in eosinophilic airway inflammation, mucous cell metaplasia, and Th2 cytokine production with a mechanism involving impaired mite antigen presentations by DC.

In vitro functional genetic modification of canine adenovirus type 2 genome by CRISPR/Cas9.

Genetically modified oncolytic adenoviruses have been proposed as a vehicle for cancer therapy. However, several concerns, such as toxicity to normal cells and organs, lack of suitable cell surface receptors to allow viral entry to the desired cell type(s), and activation of both innate and adaptive immune systems in patients, restrict the successful clinical application of adenoviral-mediated cancer gene therapy. Successful virotherapy will require efficient transductional and transcriptional targeting to enhance therapeutic efficacy by ensuring targeted adenoviral infection, replication, and/or therapeutic transgene expression.

extract, at a physiologically relevant dosage, does not induce hepatotoxicity in C57BL/6J mice.

Background: Botanical supplements have been proven to provide beneficial health effects. However, they can induce unintended adverse events such as hepatotoxicity. extract (OIE, Sabroxy®) has several health benefits including anti-inflammatory, anti-arthritic, antifungal, antibacterial, and neuroprotective effects.

IFN-λ Regulates Neutrophil Biology to Suppress Inflammation in Herpes Simplex Virus-1-Induced Corneal Immunopathology.

HSV-1 infection of the cornea causes a severe immunoinflammatory and vision-impairing condition called herpetic stromal keratitis (SK). The virus replication in corneal epithelium followed by neutrophil- and CD4 T cell-mediated inflammation plays a dominant role in SK. Although previous studies demonstrate critical functions of type I IFNs (IFN-α/β) in HSV-1 infection, the role of recently discovered IFN-λ (type III IFN), specifically at the corneal mucosa, is poorly defined.

Evaluation of tumor immunity after administration of conditionally replicative adenoviral vector in canine osteosarcoma patients.

Osteosarcoma is one among the most common neoplasms in dogs. Current treatments show limited efficacy and fail to prevent metastasis. Conditionally replicative adenoviruses (CRAd) replicate exclusively in targeted tumor cells and release new virus particles to infect additional cells.

Analysis of endogenous and exogenous tumor upregulated promoter expression in canine tumors.

Gene therapy is a promising treatment option for cancer. However, its utility may be limited due to expression in off-target cells. Cancer-specific promoters such as telomerase reverse transcriptase (TERT), survivin, and chemokine receptor 4 (CXCR4) have enhanced activity in a variety of human and murine cancers, however, little has been published regarding these promoters in dogs.

Pyruvate kinase M2 in lung APCs regulates Alternaria-induced airway inflammation.

Sensitivity to allergenic fungi (Alternaria alternata) is associated with acute, severe asthma attacks. Antigen presenting cells (APCs) in the lung sense environmental perturbations that induce cellular stress and metabolic changes and are critical for allergic airway inflammation. However, the mechanisms underlying such environmental sensing by APCs in the lung remains unclear.