Comedones and epidermal cysts on the abdominal skin of a dog occurring after a laparotomy.

An 8-year-old neutered male shih tzu dog underwent laparotomy for cystolithectomy. Ten days later, multiple various-sized cystic nodules were observed on the suture line and surrounding abdominal skin, although the surgical incision had healed well. Microscopically, various-sized cysts lined with thin walls of stratified squamous epithelium in the dermis were dilated and filled with keratin. Adnexal differentiation from the wall was not seen. Thus, the abdominal lesions were diagnosed as comedones and epidermal cysts. Herein, we describe the case of a dog with comedones and epidermal cysts on the abdominal skin after a laparotomy. Key clinical message: Multiple various-sized cystic lesions of the follicles are described. The implantation of epidermal fragments into the dermis by surgery may induce epidermal cysts and comedones in the skin of hyperadrenocorticism-affected dogs.

Comédons et kystes épidermiques sur la peau abdominale d'un chien survenant après une laparotomie. Un chien shih tzu mâle castré de 8 ans a subi une laparotomie pour cystolithectomie. Dix jours plus tard, de multiples nodules kystiques de différentes tailles ont été observés sur la ligne de suture et sur la peau abdominale environnante, bien que l'incision chirurgicale ait bien cicatrisé. Au microscope, des kystes de différentes tailles bordés de fines parois d'épithélium pavimenteux stratifié dans le derme étaient dilatés et remplis de kératine. Aucune différenciation annexielle par rapport à la paroi n'a été observée. Ainsi, les lésions abdominales ont été diagnostiquées comme des comédons et des kystes épidermiques. Nous décrivons ici le cas d'un chien présentant des comédons et des kystes épidermiques sur la peau abdominale après une laparotomie.Message clinique clé:De multiples lésions kystiques des follicules, de différentes tailles, sont décrites. L'implantation chirurgicale de fragments d'épiderme dans le derme peut provoquer des kystes épidermiques et des comédons dans la peau des chiens atteints d'hypercorticisme.(Traduit par Dr Serge Messier).

Early Osteogenic-Induced Adipose-Derived Stem Cells and Canine Bone Regeneration Potential Analyzed Using Biodegradable Scaffolds.

The complex process of bone regeneration is influenced by factors such as inflammatory responses, tissue interactions, and progenitor cells. Currently, multiple traumas can interfere with fracture healing, causing the prolonging or failure of healing. In these cases, bone grafting is the most effective treatment. However, there are several drawbacks, such as morbidity at the donor site and availability of suitable materials. Advantages have been provided in this field by a variety of stem cell types. Adipose-derived stem cells (ASCs) show promise. In the radiological examination of this study, it was confirmed that the C/S group showed faster regeneration than the other groups, and Micro-CT also showed that the degree of bone formation in the defect area was highest in the C/S group. Compared to the control group, the change in cortical bone area in the defect area decreased in the sham group (0.874), while it slightly increased in the C/S group (1.027). An increase in relative vascularity indicates a decrease in overall bone density, but a weak depression filled with fibrous tissue was observed outside the compact bone. It was confirmed that newly formed cortical bone showed a slight difference in bone density compared to surrounding normal bone tissue due to increased distribution of cortical bone. In this study, we investigated the effect of bone regeneration by ADMSCs measured by radiation and pathological effects. These data can ultimately be applied to humans with important clinical applications in various bone diseases, regenerative, and early stages of formative differentiation.

Fibrinous pleuritis associated with Streptococcus canis in a leopard cat (Prionailurus bengalensis euptilurus).

Leopard cat (Prionailurus bengalensis euptilurus) is a small wild cat assessed as an endangered wildlife in Korea. There have been very few reports of their diseases. Herein, we describe fibrinous pleuritis caused by Streptococcus canis infection with excessive pleural effusion, hydropericardium, mild ascites, and liver fibrosis in a leopard cat. S. canis is a commensal microflora in domestic cats and often affects the upper respiratory tract inducing chronic and severe respiratory diseases. However, there is no literature regarding the S. canis in leopard cats. Therefore, we first report fibrinous pleuritis associated with an S. canis infection in a leopard cat.

Nemopilema nomurai jellyfish venom attenuates phenotypic modulation of PDGF BB-induced vascular smooth muscle cells and κ-carrageenan-induced rat tail thrombosis.

Jellyfish venoms have long been recognized as a potentially rich source of natural bioactive compounds with pharmacological potential for the creation of innovative drugs. Our previous study demonstrated that Nemopilema nomurai jellyfish venom (NnV) has a chymotrypsin-like serine protease with fibrinolytic activity in vitro. Therefore, the present study aims to investigate the potential effect of NnV on cell migration, proliferation, and differentiation of vascular smooth muscle cells (VSMC; A7r5 cells) involved in the probable mechanism pathways. We also determined its anti-thrombotic effect through κ-carrageenan-induced Sprague-Dawley (SD) rat tail thrombus model. NnV inhibits on Platelet-derived growth factor (PDGF)-BB-stimulated A7r5 cells migration and proliferation by decreasing matrix metalloproteinase 2 (MMP-2) level and phosphorylation of ERK and Akt in a dose-dependent manner, but not p38. Furthermore, NnV regulates the phenotype transition of differentiation in PDGF-BB-stimulated A7r5 cells via ɑ-SMA and calponin in a dose-dependent manner. In an in vivo study, NnV treatment demonstrated clear anti-thrombotic activity in a dose-dependent manner, which was associated with decreased thrombus formation and length in κ-carrageenan-induced SD rat tail. These findings suggested that NnV has a novel fibrinolytic enzyme that can be used to prevent and/or treat thrombosis-related cardiovascular disorders.

Identification of cardiorespiratory toxic components of Nemopilema nomurai jellyfish venom using sequential chromatography methods.

Jellyfish stings pose a significant threat to humans in coastal areas worldwide, with venomous jellyfish species stinging millions of individuals annually. Nemopilema nomurai is one of the largest jellyfish species, with numerous tentacles rich in nematocysts. N. nomurai venom (NnV) is a complex mixture of proteins, peptides, and small molecules that serve as both prey-capture and defense mechanisms. Yet, the molecular identity of its cardiorespiratory and neuronal toxic components of NnV has not been clearly identified yet. Here, we isolated a cardiotoxic fraction, NnTP (Nemopilema nomurai toxic peak), from NnV using chromatographic methods. In the zebrafish model, NnTP exhibited strong cardiorespiratory and moderate neurotoxic effects. LC-MS/MS analysis identified 23 toxin homologs, including toxic proteinases, ion channel toxins, and neurotoxins. The toxins demonstrated a synergistic effect on the zebrafish, leading to altered swimming behavior, hemorrhage in the cardiorespiratory region, and histopathological changes in organs such as the heart, gill, and brain. These findings provide valuable insights into the mechanisms underlying the cardiorespiratory and neurotoxic effects of NnV, which could be useful in developing therapeutic strategies for venomous jellyfish stings.

Exploring the Fibrin(ogen)olytic, Anticoagulant, and Antithrombotic Activities of Natural Cysteine Protease (Ficin) with the κ-Carrageenan-Induced Rat Tail Thrombosis Model.

Although fibrinolytic enzymes and thrombolytic agents help in cardiovascular disease treatment, those currently available have several side effects. This warrants the search for safer alternatives. Several natural cysteine protease preparations are used in traditional medicine to improve platelet aggregation and thrombosis-related diseases. Hence, this study aimed to investigate the effect of ficin, a natural cysteine protease, on fibrin(ogen) and blood coagulation. The optimal pH (pH 7) and temperature (37 °C) for proteolytic activity were determined using the azocasein method. Fibrinogen action and fibrinolytic activity were measured both electrophoretically and by the fibrin plate assay. The effect of ficin on blood coagulation was studied by conventional coagulation tests: prothrombin time (PT), activated partial thromboplastin time (aPTT), blood clot lysis assay, and the κ-carrageenan thrombosis model. The Aα, Bß, and γ bands of fibrinogen are readily cleaved by ficin, and we also observed a significant increase in PT and aPTT. Further, the mean length of the infarcted regions in the tails of Sprague-Dawley rats was shorter in rats administered 10 U/mL of ficin than in control rats. These findings suggest that natural cysteine protease, ficin contains novel fibrin and fibrinogenolytic enzymes and can be used for preventing and/or treating thrombosis-associated cardiovascular disorders.

Long-term treatment of allogeneic adipose-derived stem cells in a dog with rheumatoid arthritis.

BACKGROUND: Although there are growing demands for stem cell-based therapy for companion animals in various diseases, a few clinical trials have been reported. Moreover, most of them are the results from only one or a few times of stem cell injection. OBJECTIVES: The aim of this study is to describe a long-term treatment with allogeneic adipose-derived stem cells (ASCs) in a dog with rheumatoid arthritis (RA), which is a rare canine disease. METHODS: The dog with RA received intravascular injection of allogeneic ASCs derived from two healthy donors once a month for 11 months. To assess therapeutic effects of ASCs, orthopedic examination and clinical evaluation was performed. Cytokines of tumor necrosis factor-α and interleukin-6 in the plasma were measured using ELISA analysis. RESULTS: Despite this repeated and long-term administration of allogeneic ASCs, there were no side effects such as immunorejection responses or cell toxicity. The orthopedic examination score for the dog decreased after ASCs treatment, and the clinical condition of the dog and owner's satisfaction were very good. CONCLUSIONS: Although ASCs has been suggested as one of the options for RA treatment because of its anti-inflammatory and immunosuppressive functions, it has never been used to treat RA in dogs. The present report describes a case of canine RA treated with allogeneic ASCs for long-term in which the dog showed clinical improvement without adverse effects.

Vitamin C Deficiency Inhibits Nonalcoholic Fatty Liver Disease Progression through Impaired de Novo Lipogenesis.

Despite the increasing clinical importance of nonalcoholic fatty liver disease (NAFLD), little is known about its underlying pathogenesis or specific treatment. The senescence marker protein 30 (SMP30), which regulates the biosynthesis of vitamin C (VC) in many mammals, except primates and humans, was recently recognized as a gluconolactonase. However, the precise relation between VC and lipid metabolism in NAFLD is not completely understood. Therefore, this study aimed to clearly reveal the role of VC in NAFLD progression. SMP30 knockout (KO) mice were used as a VC-deficient mouse model. To investigate the precise role of VC on lipid metabolism, 13- to 15-week-old SMP30 KO mice and wild-type mice fed a 60% high-fat diet were exposed to tap water or VC-containing water (1.5 g/L) ad libitum for 11 weeks. Primary mouse hepatocytes isolated from the SMP30 KO and wild-type mice were used to demonstrate the relation between VC and lipid metabolism in hepatocytes. Long-term VC deficiency significantly suppressed the progression of simple steatosis. The high-fat diet-fed VC-deficient SMP30 KO mice exhibited impaired sterol regulatory element-binding protein-1c activation because of excessive cholesterol accumulation in hepatocytes. Long-term VC deficiency inhibits de novo lipogenesis through impaired sterol regulatory element-binding protein-1c activation.

Senescence Marker Protein 30 (SMP30): A Novel Pan-Species Diagnostic Marker for the Histopathological Diagnosis of Breast Cancer in Humans and Animals.

Senescence marker protein 30 (SMP30) is a cell survival factor playing an important role in vitamin C synthesis and antiapoptosis. Moreover, its cytoprotective role suggests a possibility to be related to cancer cell survival. Mammary carcinoma is a common cancer in both humans and animals. Because of its histopathological diversity, especially in the early stage, histopathological diagnosis may be complicated; therefore, a diagnostic marker is helpful for confirmation. The present study analyzed the expression pattern of SMP30 in mammary carcinoma in humans, dogs, and cats. Immunohistochemistry, immunofluorescence, and western blot analysis were used to investigate SMP30 expression patterns. The expression was specifically observed in neoplastic glandular epithelial cells. The expression increased with the malignancy of glandular epithelial cells with a highly proliferative status. However, SMP30 expression was low in normal mammary gland tissues or well-differentiated adenoma tissues. The patterns were consistently reproduced in canine primary mammary carcinoma cells and MCF-7 and MDA-MB-231 human carcinoma cell lines. This study provides useful information to understand SMP30 expression in various stages of mammary carcinoma and to suggest its utility as a pan-species diagnostic marker, thereby helping to establish strategies for diagnosing mammary carcinoma in several species.

Dataset of Swimming behavioral alterations in Danio rerio by Nemopilema nomurai jellyfish venom.

This article reports data associated with Prakash et al. [1]. Nemopilema nomurai jellyfish venom (NnV) can lead to neurotoxicity in zebrafish (Danio rerio) model. In the present study, zebrafish were treated with NnV by intraperitoneal injection and the swimming behavior of each fish was evaluated using a score scale. The dose of NnV in each treatment group was based on the protein concentration of NnV. Swimming is the main locomotory movements in the fishes. NnV modulated the swimming behavior of Danio rerio in a dose-dependent manner. In this article provided data are directly related to the previously published research article - "Danio rerio as an alternative vertebrate model for jellyfish venom study: the toxinological aspects of Nemopilema nomurai venom" [1] where the downregulation of acetylcholinesterase activity as well as histopathological alterations were observed from the brain of Danio rerio treated with NnV. Here we provide datasets, including mortality rate table, swimming behavior graph, and videos of zebrafish after NnV envenomation.

Mesenchymal Stem Cell and MicroRNA Therapy of Musculoskeletal Diseases.

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

Danio rerio as an alternative vertebrate model for jellyfish venom study: The toxinological aspects of Nemopilema nomurai venom.

Nemopilema nomurai venom (NnV) is severely toxic to many organisms. However, the mechanism of its poisoning has not been properly understood yet. The present work demonstrates that zebrafish (Danio rerio) is an alternative vertebrate model for studying NnV jellyfish venom for the first time. In this model, NnV appears to cause severe hemorrhage and inflammation in cardiopulmonary regions of zebrafish. NnV also altered the swimming behavior of zebrafish accompanied by a significant downregulation of acetylcholinesterase (AChE) activity in brain tissues. Histopathological changes observed for various organs of D. rerio caused by NnV corresponded to an increase in lactate dehydrogenase (LDH) activity in tissues. NnV also significantly altered glutathione S-transferase (GST) activity in cardiopulmonary and brain tissues of D. rerio. SDS-PAGE revealed many protein bands of NnV of various sizes after silver staining. Taken together, these results indicate that Danio rerio can be a useful alternative animal model for jellyfish venom toxicology studies. Findings of the present study also suggest that Danio rerio could be used to develop an effective treatment strategy and discover the mechanism of action of jellyfish venom envenomation.

Thymic Hematoma Found in a Wild Eurasian Otter (Lutra lutra).

Thymic hematomas are uncommon in animals, and the few reported cases are all in dogs. In May 2019, we necropsied a wild Eurasian otter (Lutra lutra) in Junju, Republic of Korea, and found a thymic hematoma without any signs of trauma or hemorrhage in other organs, except for a hemothorax. This study describes the macroscopic and microscopic examinations of a thymic hematoma in an Eurasian otter.

Preputial gland adenoma in a wild nutria (Myocastor coypus): a case report.

Tumor incidence in wild mammals is reportedly very low. Wild nutria, a large rodent, is known to carry many infectious diseases, but rarely exhibits neoplastic diseases. We necropsied a male wild nutria and found a large nodular mass in the left inguinal region, adjacent to the penis. Histopathologically, the mass was diagnosed as preputial gland adenoma. Spontaneous preputial gland adenomas are extremely rare in all animals. Moreover, reports of tumors in nutrias have been limited to adenocarcinomas of the lungs and uterus, as well as subcutaneous fibromas. Here, we describe preputial gland adenoma in a wild nutria.

Sertoli Cell Tumor (SCT) in a Captive Black Bear (Ursus americanus).

A black bear of 29-year-old (Ursus americanus) died unexpectedly in captivity without any gross lesions or clinical signs. We identified a firm, lobulated, yellowish tan, and well-circumscribed mass embedded inside the testicular tissue at the time of necropsy. The tumor sections exhibited soft necrotic and hemorrhagic areas beneath its capsule. Histologically, the tumor comprised Sertoli cells arranged in tubules and solid sheets supported by prominent fibrous connective tissues. The Sertoli cells were positive for vimentin and ER-ß expression, whereas it showed negative staining for inhibin-α, cytokeratin 19, and S-100. To the best of our knowledge, this is the rare case report of testicular Sertoli cell tumor in black bear.

Protective Effects of Nutria Bile against Thioacetamide-Induced Liver Injury in Mice.

Several eradication programs have been developed and executed to curb alien invasive species that tend to damage the ecological environments they colonize; however, only few studies have evaluated the utilization of carcasses of these species after eradication. Nutria (Myocastor coypus) is an invasive rodent species targeted by eradication programs in many countries. We noted that nutria produce large amounts of ursodeoxycholic acid (UDCA) in their bile. UDCA is a unique component responsible for the anti-inflammatory and hepatoprotective effects exerted by bear bile. Therefore, we sought to examine the medicinal utility of nutria carcasses by investigating the hepatoprotective effect of their bile in mice. C57BL/6 mice were injected with thioacetamide (TAA), which induced liver damage by increasing Kupffer cell infiltration. Administration of nutria bile reduced hepatic inflammation, improved hepatic function, and increased the levels of senescence marker protein 30 (an indicator of hepatocyte viability). Our results show that nutria bile exerts protective effects against TAA-induced liver injury in mice, suggesting that nutria carcasses may be used for the treatment of liver injuries.

Therapeutic Effect of Rumex japonicus Houtt. on DNCB-Induced Atopic Dermatitis-Like Skin Lesions in Balb/c Mice and Human Keratinocyte HaCaT Cells.

Rumex japonicus Houtt. (RJ) is traditionally used in folk medicines to treat patients suffering from skin disease in Korea and other parts of East Asia. However, the beneficial effect of RJ extract on atopic dermatitis (AD) has not been thoroughly examined. Therefore, this study aimed to investigate the anti-inflammatory effects of RJ on AD in vitro and in vivo. Treatment with RJ inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) as well as the activation of nuclear factor-kappa B (NF-κB) in tumor necrosis factor-α (TNF-α) stimulated in HaCaT cells. The five-week-old Balb/c mice were used as an AD-like mouse model by treating them with 1-chloro-2, 4-dinitrobenzene (DNCB). Topical administration of RJ to DNCB-treated mice significantly reduced clinical dermatitis severity, epidermal thickness, and decreased mast cell and eosinophil infiltration into skin and ear tissue. These results suggest that RJ inhibits the development of AD-like skin lesions by regulating the skin inflammation responses in HaCaT cells and Balb/c mice. Thus, RJ may be a potential therapeutic agent for AD.

The immunomodulatory effect of antimicrobial peptide HPA3P restricts Brucella abortus 544 infection in BALB/c mice.

The discovery of antimicrobial peptides (AMPs) in recent years has been promising for the treatment of multidrug resistant pathogenic microbes. Brucellosis is still considered one of the most common zoonoses in the world. In this study, we evaluated the effect HPA3P peptide in the bacterial uptake and intracellular growth of Brucella abortus (B. abortus) 544 in murine macrophages RAW 264.7. HPA3P was further utilized in a mouse model for infection and treatment. This peptide did not show cytotoxicity or bactericidal effect to B. abortus. However, it inhibited bacterial internalization at 0, 15 and 30 min incubation at two different doses at 12 and 24 µM as well as reduced intracellular growth after 2, 24 and 48 h incubation. Mice treated with HPA3P demonstrated a significant 1.01-log reduction (P < 0.0001) and spleen weight reduction compared to the nanocarrier control (P < 0.01). Significant increases in key cytokines Interferon-γ (IFN-γ) and Tumor necrosis factor (TNF) at 3, 7 and 14 days post-infection were observed in HPA3P treated mice similar to the antibiotic control group with both compared to the nanocarrier control. Monocyte chemoattractant protein-1 (MCP-1) was also heightened at 14 days post-infection. Histopathological analysis also suggests reduced bacterial granuloma in the liver and spleens of HPA3P treated group compared with the nanocarrier control group. In this study, the modulation of crucial cytokines IFN-γ and TNF might have led to a considerable reduction in the proliferation of B. abortus in a mouse model of brucellosis. Further investigation might be required to maximize the efficacy of HPA3P treatment in murine brucellosis.

A Case of Fascioliasis in A Wild Nutria, Myocastor coypus, in Republic of Korea.

A total of 44 adult or juvenile nutrias were necropsied for disease survey. A large nodule was found in the liver of a nutria. The histopathological specimen of the hepatic nodule was microscopically examined, and sectional worms were found in the bile duct. The worms showed a tegument with spines, highly branches of vitelline glands and intestine. Finally, we histopathologically confirmed fascioliasis in a wild nutria. In the present study, a case of fascioliasis in a wild nutria is first confirmed in Korea.