Relationship Between Red Blood Cell Indices and Myxomatous Mitral Valve Disease in Small-Breed Dogs: A Retrospective Study.

Background: Red blood cell (RBC) indices provide information on the size and haemoglobin content of erythrocytes. The RBC distribution width (RDW) is an index of size variability of the circulating RBC population. The correlation between various diseases and RDW in dogs has been demonstrated.

Crisdesalazine alleviates inflammation in an experimental autoimmune encephalomyelitis multiple sclerosis mouse model by regulating the immune system.

Microglia/macrophages participate in the development of and recovery from experimental autoimmune encephalomyelitis (EAE), and the macrophage M1 (pro-inflammatory)/M2 (anti-inflammatory) phase transition is involved in EAE disease progression. We evaluated the efficacy of crisdesalazine (a novel microsomal prostaglandin E2 synthase-1 inhibitor) in an EAE model, including its immune-regulating potency in lipopolysaccharide-stimulated macrophages, and its neuroprotective effects in a macrophage-neuronal co-culture system. Crisdesalazine significantly alleviated clinical symptoms, inhibited inflammatory cell infiltration and demyelination in the spinal cord, and altered the phase of microglial/macrophage and regulatory T cells.

Canine Stem Cell-derived Exosomes for Lung Inflammation: Efficacy of Intratracheal Intravenous Administration in an Acute Lung Injury Mouse Model.

Background/aim: Acute lung injury (ALI) is an important pathological process in acute respiratory distress syndrome; however, feasible and effective treatment strategies for ALI are limited. Recent studies have suggested that stem cell-derived exosomes can ameliorate ALI; however, there remains no consensus on the protocols used, including the route of administration. This study aimed to identify the appropriate route of administration of canine stem cell-derived exosomes (cSC-Exos) in ALI.

Intravenous injection of allogenic canine mesenchymal stem cells in 40 client-owned dogs: a safety assessment in veterinary clinical trials.

Background: The aim of this study was to evaluate the adverse effects of allogeneic mesenchymal stem cells (MSCs) transplanted via intravenous infusion in dogs and examine their safety. We performed a retrospective analysis of various clinical assessments, including physical examination, blood tests, and radiographs, and monitored the formation of neoplasms during a 6-month follow-up period in 40 client-owned dogs that received intravenous infusion of adipose tissue-derived MSCs (AT-MSCs) for the treatment of various underlying diseases between 2012 and 2018.

Results: No significant adverse effects of MSC therapy were detected by clinical assessment, blood tests, or radiographic examination in the 6-month follow-up period after the first MSC treatment.

Deferoxamine preconditioning of canine stem cell derived extracellular vesicles alleviates inflammation in an EAE mouse model through STAT3 regulation.

Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs), specifically those preconditioned with deferoxamine (DFO) in canine adipose tissue-derived MSCs (cAT-MSCs), were explored for treating autoimmune diseases. This study assessed the effects of DFO-preconditioned EVs (EV) in an experimental autoimmune encephalomyelitis (EAE) mouse model. cAT-MSCs were treated with DFO for 48 h, after which EVs were isolated.

The Role of Natural Killer Cells in Oncolytic Virotherapy: Friends or Foes?

Oncolytic virotherapy (OVT) has emerged as a promising cancer immunotherapy, and is capable of potentiating other immunotherapies due to its capacity to increase tumor immunogenicity and to boost host antitumor immunity. Natural killer (NK) cells are a critical cellular component for mediating the antitumor response, but hold a mixed reputation for their role in mediating the therapeutic efficacy of OVT. This review will discuss the pros and cons of how NK cells impact OVT, and how to harness this knowledge for the development of effective strategies that could modulate NK cells to improve OVT-based therapeutic outcomes.

Safety of Gonadal Tissue-Derived Mesenchymal Stem Cell Therapy in Geriatric Dogs with Chronic Disease.

Ensuring the safety of mesenchymal stem cell (MSC) therapy is a fundamental requirement in clinical practice. This study aimed to assess the safety of using gonadal tissue-derived MSCs (n = 10) compared to the commonly utilized adipose tissue-derived MSCs (n = 9) in geriatric dogs with chronic diseases. All participants received allogeneic MSC therapy, and no allergic reactions due to allogeneic cell immunogenicity were noted.

Romiplostim for treatment of thrombocytopenia in dogs: A retrospective assessment and clinical outcomes.

Background: Romiplostim, a thrombopoietin analog, is commonly used to treat immune-mediated thrombocytopenia (ITP) in humans, but its use in dogs remains limited.

Objectives: Evaluate the effects and adverse events of romiplostim administration in dogs with thrombocytopenia caused by various underlying diseases.

Animals: Forty-two client-owned dogs with naturally occurring thrombocytopenia at 2 referral animal hospitals.

Analyzing small RNA sequences from canine stem cell-derived extracellular vesicles primed with TNF-α and IFN-γ and exploring their potential in lung repair.

Acute lung injury is an acute inflammation disorder that disrupts the lung endothelial and epithelial barriers. In this study, we investigated the extracellular vesicles (EVs) obtained via priming inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ on canine adipose mesenchymal stem cells in improving their anti-inflammatory and/or immunosuppressive potential, and/or their ability to alleviate lipopolysaccharide-induced lung injury . We also explored the correlation between epithelial-to-mesenchymal transition and the inflammatory repressive effect of primed EVs.

Effect of Oligo-Fucoidan, Fucoxanthin, and L-Carnitine on Chronic Kidney Disease in Dogs: A Retrospective Study.

Chronic kidney disease (CKD) commonly occurs in old dogs and cats. Oligo-fucoidan, fucoxanthin, and L-carnitine (OFL) compounds have a variety of reno-protective properties, including anti-inflammatory, anti-oxidative, and anti-fibrotic effects. Because their effects have not been investigated in naturally occurring canine CKD, we examined their reno-protective activities in dog patients with CKD.

Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report.

Background: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog.

Effect of the sodium-glucose cotransporter-2 inhibitor, DWP16001, as an add-on therapy to insulin for diabetic dogs: A pilot study.

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of anti-hyperglycaemic agents.

Objective: This study aimed to evaluate the safety and the adjuvant glycaemic control effect of an SGLT2 inhibitor, DWP16001, in diabetic dogs receiving insulin treatment.

Methods: Nineteen diabetic dogs receiving insulin treatment (NPH, porcine lente and glargine insulin) were divided into two groups according to dosing frequency: DWP TOD group (n = 10) and DWP SID group (n = 9).

Blood vessel organoids generated by base editing and harboring single nucleotide variation in Notch3 effectively recapitulate CADASIL-related pathogenesis.

Human blood vessel organoids (hBVOs) offer a promising platform for investigating vascular diseases and identifying therapeutic targets. In this study, we focused on in vitro modeling and therapeutic target finding of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of hereditary stroke disorder caused by mutations in the NOTCH3 gene. Despite the identification of these mutations, the underlying pathological mechanism is elusive, and effective therapeutic approaches are lacking.

evaluation of the antitumor activity of axitinib in canine mammary gland tumor cell lines.

Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs).

Objectives: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines.

Anti-cancer effects of DHP107 on canine mammary gland cancer examined through in-vitro and in-vivo mouse xenograft models.

Background: Canine mammary gland cancer (CMGC) is a common neoplasm in intact bitches. However, the benefit of adjuvant chemotherapy is unclear. The aim of this study was to investigate the anti-proliferative effects of paclitaxel on CMGC in in-vitro and in-vivo settings.

Changes in Urinary Exosomal Nuclear Matrix Protein-22 in Dogs With Urothelial Carcinoma: A Pilot Study.

Background/aim: Nuclear matrix protein-22 (NMP-22) is widely used in human medicine as a prognostic and diagnostic tool for urothelial carcinoma (UC). In addition, the use of urinary exosomes as a liquid biopsy tool is emerging for the diagnosis of certain types of cancer in human medicine. This study aimed to investigate the change in urinary exosomal NMP-22 for the diagnosis of UC in dogs.

Anticancer effect of superoxide dismutase on canine mammary gland tumour in vitro.

Background: Reactive oxygen species (ROS) have been shown to promote tumour growth and metastasis in human cell lines. The superoxide anion (•O ) is produced during ROS formation and is involved in tumour cell signalling.

Objectives: Superoxide dismutase (SOD) has been applied to canine mammary gland tumours to investigate its antitumour effects in vitro.

Amelioration of DSS-induced colitis in mice by TNF-α-stimulated mesenchymal stem cells derived from feline adipose tissue via COX-2/PGE activation.

Background: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals.

Macrophage induces anti-cancer drug resistance in canine mammary gland tumor spheroid.

Tumor-associated macrophages (TAMs) play an important role in the tumor microenvironment by producing cytokines and growth factors. Furthermore, TAMs play multifunctional roles in tumor progression, immune regulation, metastasis, angiogenesis, and chemoresistance. Hypoxia in the tumor microenvironment induces tumor-supporting transformation of TAMs, which enhances tumor malignancy through developing anti-cancer resistance, for example.

Changes in Lactate-related Fecal Microbiome in Hyperlactatemia Diabetic Dogs.

Background/aim: The correlation between the intestinal microbiome and endocrine disorders has recently been drawing attention as an important key for determining their pathology and clinical assessment. In this study, we evaluated the microbiome of dogs with insulin-dependent diabetes mellitus (IDDM) with respect to blood lactate.

Materials And Methods: Fecal samples were obtained from 17 subjects and real-time quantitative polymerase chain reaction determinations were performed to quantify the gene expression levels of lactate-producing and dysbiosis index-related bacteria.

Tumour necrosis factor stimulated gene 6 intrinsically regulates PD-L1 expressions in breast cancer cells, leading to modulation of tumour microenvironment.

Recent studies have shown that tumour cells express tumour necrosis factor-inducible gene 6 (TSG-6) and its protein, which is known to play a key role in regulating excessive immune responses and proliferation and growth of mesenchymal stem cells (MSCs). It has not been confirmed whether the inhibition of TSG-6 for tumour cells can suppress tumour cell growth and regulate the activation of immune cells in the tumour microenvironment (TME). TSG-6-specific small interfering RNA was transfected into canine and human breast cancer cells (CIPp, CIPm and BT-20).

Evaluation of serum interleukin 2 receptor and beta-2-microglobulin as prognostic factors for canine lymphoma: A pilot study.

Interleukin 2 receptor (IL-2R) is released from activated T cell lymphocytes and related to proliferation of B cells and T cells. Beta-2-microglobulin (B2M) is synthesized from all nucleated cells and constitutes a major histocompatibility complex class I antigen. In human medicine, high concentrations of these two factors have been found to be related to prognosis in aggressive non-Hodgkin's lymphoma.