The Philippines stingless bee propolis promotes hair growth through activation of Wnt/ß-catenin signaling pathway.

Although hair loss is not a horrible disease, it sometimes reduces the patients' quality of life (QOL) and increases their mental stress. Currently, there is no effective treatment for hair loss. It is known that honeybee propolis has various biological activities, including stimulating the proliferation of hair matrix keratinocytes. However, little is known with the hair promoting activity of stingless bee propolis. Hence, this study investigates the hair growth-promoting activity of Philippines stingless bee propolis extract and the underlying a molecular mechanism of promoting hair growth. For the evaluation of hair growth stimulating activity, 99.5% ethanolic extract of Philippines stingless bee propolis is examined using the simple shaving model in C57BL/6N mice. Melaninization of dorsal skin and histological analysis of hair follicles (HFs) revealed that propolis promotes hair growth by stimulating HFs development. The expression of mRNA (Wnt3a, Ctnnb1/ß-catenin, Lef1, and Bmp2) and protein (WNT3A and ß-catenin) of selected Wnt/ß-catenin associated genes explains Philippines stingless bee propolis promoting HFs development by activating Wnt/ß-catenin signaling pathway. These results suggest that the treatment of propolis strongly promotes hair growth by stimulating the development of HFs via activation of Wnt/ß-catenin signaling pathway. This further indicates the potential of Philippines stingless bee propolis as a novel promising agricultural product for hair growth.

Feline Niemann-Pick Disease With a Novel Mutation of SMPD1 Gene.

A 4-month-old female mixed-breed cat showed gait disturbance and eventual dysstasia with intention tremor and died at 14 months of age. Postmortem histological analysis revealed degeneration of neuronal cells, alveolar epithelial cells, hepatocytes, and renal tubular epithelial cells. Infiltration of macrophages was observed in the nervous system and visceral organs. The cytoplasm of neuronal cells was filled with Luxol fast blue (LFB)-negative and periodic acid-Schiff (PAS)-negative granules, and the cytoplasm of macrophages was LFB-positive and PAS-negative. Ultrastructurally, concentric deposits were observed in the brain and visceral organs. Genetic and biochemical analysis revealed a nonsense mutation (c.1017G>A) in the SMPD1 gene, a decrease of SMPD1 mRNA expression, and reduced acid sphingomyelinase immunoreactivity. Therefore, this cat was diagnosed as having Niemann-Pick disease with a mutation in the SMPD1 gene, a syndrome analogous to human Niemann-Pick disease type A.

A retrospective survey on canine intracranial tumors between 2007 and 2017.

To clarify the prevalence of canine intracranial tumors in Japan, a retrospective study was performed using data on 186 canine intracranial tumors. Of 186 cases, 159 cases (85.5%) were primary and 27 cases (14.5%) were secondary intracranial tumors. Among primary intracranial tumors, meningioma (50.9%) was the most common, followed by glial tumors (21.4%) and primary intracranial histiocytic sarcoma (12.6%). These 3 tumors were most frequently found in middle-aged to elderly dogs without any sex predilection. Regarding glial tumors, the incidence of oligodendroglial tumors (79.4%) was higher than that of astrocytic tumors (17.6%). A significant breed predisposition (P<0.05) was observed for meningioma in Rough Collie, Golden Retriever, Miniature Schnauzer, and Scottish Terrier; for glial tumors in Bouvier de Flandres, French Bulldog, Newfoundland, Bulldog, and Boxer; for primary intracranial histiocytic sarcoma in Pembroke Welsh Corgi, Siberian Husky, and Miniature Schnauzer. The high incidence of oligodendroglial tumors in dogs and the breed predisposition for primary intracranial histiocytic sarcoma in Pembroke Welsh Corgi have not been reported in previous epidemiological studies on canine tumors. Since the incidence of intracranial tumors was vary among dog breeds, the present results demonstrate the uniqueness of the canine breed population in Japan.

YM155 enhances the cytotoxic activity of etoposide against canine osteosarcoma cells.

Canine osteosarcoma (OSA) is an aggressive and highly malignant primary bone tumor. Its poor survival outcome remains problematic despite recent advances in anti-cancer therapy, therefore highlighting the need for alternative treatment options or drug repositioning. The aim of this study was to determine if YM155, a small-molecule survivin inhibitor, potentiates the chemotherapeutic efficacy of etoposide against canine OSA in vitro and in vivo. In cell culture, YM155 enhanced the cytotoxic effect of etoposide against canine OSA cell lines; however, the molecular mechanism behind this effect was heterogeneous, as only one cell line had an elevated apoptotic level. In addition, this effect was not associated with survivin suppression in two of the cell lines. These results suggest that the molecular target of YM155 is not restricted to survivin alone. When tested on a murine xenograft model, the average tumor volume of the combination treatment group (YM155, 5 mg/kg, intraperitoneally, 5 consecutive days/week; and etoposide, 20 mg/kg, intraperitoneally, every 5 days) was 66% smaller than the control group, although this difference was not statistically significant (P=0.17). Further studies to improve the treatment protocol are necessary to confirm the findings of this study.

Retrospective study of canine cutaneous tumors in Japan, 2008-2017.

Cutaneous tumors are commonly found in dogs. To date, few studies have investigated the epidemiology of canine cutaneous tumors in Asian countries. The present study aims to report the prevalence of canine cutaneous tumors in Japan, and assess the association of breed, age, sex, and anatomical locations with the development of common tumor types. A total of 1,435 cases of cutaneous tumors were examined, of which 813 (56.66%) cases were malignant, and 622 (43.34%) were benign. Soft tissue sarcomas (18.40%), mast cell tumor (16.24%), lipoma (9.69%), hair follicle tumors (9.34%), and benign sebaceous tumors (8.50%) outnumbered the other tumor types. Tumors were commonly found on the head (13.87%), hindlimb (10.52%), forelimb (8.01%), chest (5.78%), and neck (5.57%). The risk of developing cutaneous tumors increased significantly in dogs aged 11-year and above (P<0.001). Mixed-breed dogs (14.63%), Miniature Dachshund (9.90%), and Labrador Retriever (8.01%) were the three most presented breeds; while Boxer, Bernese Mountain Dog, and Golden Retriever had an increased risk of cutaneous tumor development in comparison to mixed-breed dogs (P<0.05). Epidemiological information from the present study will serve as a useful reference for regional veterinarians to establish a preliminary diagnosis of canine cutaneous tumors.

Identification of bovine papillomavirus type 1 and 2 from bovine anogenital fibropapillomas.

Papillomavirus (PV) is a well-known pathogen associated with epithelial and mucosal neoplastic diseases. In contrast to human PVs, characterization of animal PVs from the aspect of anogenital neoplasm is still on a learning curve. In the present study, two vulval and one anal warts, histologically diagnosed as fibropapillomas, excised from dairy cattle were analyzed. PCR and sequencing revealed that bovine papillomavirus type 1 (BPV-1) and BPV-2 were detected from anal and vulval fibropapillomas, respectively. Immunohistochemistry detected PV antigen in a few differentiated keratinocytes of one vulval case. Reverse-transcriptase PCR detected the early region, but not the late region of BPV mRNA in all three cases. The present study will provide new insight into the relationship between BPV and anogenital papilloma in cattle.

Pathologic characterization of Felis catus papillomavirus type 5 (FcaPV-5)-associated viral plaques and Bowenoid in situ carcinoma in a Domestic Shorthair cat.

The present paper describes Felis catus papillomavirus (FcaPV) type 5-associated cutaneous mass in a Domestic Shorthair cat. Histological examination revealed multicentric epidermal acanthosis with papillomavirus-associated cytopathic changes, which progressed to a tumor lobule with intact basement membrane. An association between FcaPV-5 and the cutaneous lesions was confirmed by detection of virus antigen and genes using immunohistochemistry, polymerase chain reaction (PCR), sequencing analysis, and in situ hybridization. Based on these findings, the lesions were diagnosed as FcaPV-5-associated viral plaques and Bowenoid in situ carcinoma (BISC). To date, this is the first reported case of FcaPV-5 infection in a cat in Japan, and the second case reported worldwide. For the first time this papillomavirus type is associated with BISC development.

Hierarchical Cluster Analysis of Cytokeratins and Stem Cell Expression Profiles of Canine Cutaneous Epithelial Tumors.

The diagnosis of cutaneous epithelial tumors (CETs) in dogs is based on predominant histological differentiation patterns. However, the expression of a broad panel of antigens has not been comprehensively examined with immunohistochemistry. The present study aims to establish a comprehensive expression profile and identify useful diagnostic markers for each CET type. Cytokeratin (CK), stem cell, and other associated markers were immunohistochemically examined in 110 canine CETs. Among these, CK16 was useful for differentiating between basal and squamous cell carcinomas. Acantholytic squamous cell carcinomas were positive for CK8, CK18, and CK19, suggesting their close association with the apocrine duct. Unlike their benign counterparts, sebaceous carcinomas coexpressed CK5/6 and adipophilin. Smooth muscle actin (SMA) and p63 immunostaining were useful for accurately distinguishing between glandular and ductal differentiation in apocrine tumors. A case of apocrine carcinoma and malignant myoepithelioma was identified using anti-SMA antibodies. Stem cell expression profiles (CK8, CK15, CK19, and CD34) of hair follicle tumors were discrete and indicative of their anatomic origins. The effectiveness of immunohistochemistry for tumor diagnosis was further confirmed by hierarchical cluster analysis, through which selected markers were able to sort CETs into specific groups: CK5/6, CK8, CK14, CK16, CK18, CK19, p63, adipophilin, and SMA sorted tumors of epidermal, apocrine, or sebaceous origin; while CK8, CK14, CK15, CK16, CK19, CD34, and p63 sorted hair follicle tumors in agreement with their histological differentiation. In conclusion, the present study provides comprehensive immunohistochemical information, which could complement histomorphological features for the future classification of canine CETs.

Neuromastoma of the hard palate mucosa in an Australian green tree frog (Litoria caerulea).

A hard palate mass was surgically removed from an Australian green tree frog (Litoria caerulea) and examined pathologically. The tumor consisted of sheets of small cells arranged in a tubular structure and cords or rosettes with fibrovascular stroma. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin and neuron-specific enolase and partially positive for S-100 and doublecortin. These findings indicate that the tumor originated from the neuroectodermal tissue. Based on these findings, the tumor was classified as a neuromastoma (neuroepithelioma). Sensory cells located in the hard palate of the frog were considered to be the origin of the tumor. The frog died after going through 3 surgeries and experiencing difficulties closing its mouth.

Desmoplastic tricholemmoma in a dog.

A 10-year-old mixed breed dog was presented with a 0.8 cm diameter mass below the left eye region. The mass was surgically removed and processed for histopathological examination. Microscopically, tumor cells proliferated in small lobules, nests and cords, and the tumor parenchyma was separated by desmoplastic stroma. Majority of the tumor cells were periodic acid-Schiff (PAS)-positive, and the desmoplastic stroma was densely collagenous and mucinous. Immunohistochemical results showed that the tumor cells were diffusely positive for cytokeratin 15, cytokeratin 19 and CD 34, while cytokeratin 8 reactivity was limited to the tumor cells proliferating in cords. Few tumor cells were positive for nestin. Based on the histopathological findings, the tumor was diagnosed as desmoplastic tricholemmoma.