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.

Background: The efficacy and safety of equine cartilage as a competent xenograft material for rhinoplasty were evaluated and compared to the outcomes of rhinoplasty using silicone implants. Methods: We performed a multicenter, double-blind, non-inferiority, and randomized confirmatory study. Fifty-six patients were randomized 1:1 to the study group (using MegaCartilage-E) and control group (using silicone implants). The Rhinoplasty Outcome Evaluation (ROE) score, photo documentation, Global Aesthetic Improvement Scale (GAIS), and adverse event data were obtained until 12 months after surgery. The primary efficacy, which is the change in ROE score 6 months after surgery, was assessed in the modified intention-to-treat set. The secondary efficacy was evaluated in the per-protocol set by assessing the change in ROE score 6 and 12 months after surgery and nasofrontal angle, the height of the nasion, and GAIS 1, 6, and 12 months after surgery. Results: The change in ROE score of the study group was non-inferior to that of the control group; it increased by 24.26 ± 17.24 in the study group and 18.27 ± 17.60 in the control group (p = 0.213). In both groups, all secondary outcome measures increased, but there was no statistical difference. In the safety set, treatment-emergent adverse events occurred in 10 patients (35.71%) in the study group and six patients (21.43%) in the control group (p = 0.237). There were 13 adverse device events in the study group and six adverse device events in the control group (p = 0.515). Conclusion Processed equine cartilage can be used effectively and safely as xenograft material for rhinoplasty.

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.

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.

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.

Adenocarcinoma ; Adenoma ; Animals ; Communicable Diseases ; Fibroma ; Humans ; Incidence ; Lung ; Male ; Mammals ; Penis ; Rodentia ; Sebaceous Glands ; Uterus

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.

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.

BACKGROUND: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus. METHODS: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24. RESULTS: The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039). CONCLUSION: Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.
Blood Glucose ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Metformin ; Weight Loss

OBJECTIVE: To investigate the expression of androgen receptor (AR) and its correlation with disease status and survival outcome in uterine leiomyosarcoma with other hormone receptors. METHODS: The medical records and paraffin blocks of 42 patients were reviewed. The immunohistochemical expression of AR, estrogen receptor (ER), progesterone receptor (PR), gonadotropin releasing hormone (GnRH), and cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) were assessed using tissue microarray. RESULTS: In total, AR expression was observed in 11 patients (26.2%). International Federation of Gynecology and Obstetrics (FIGO) stage and AR were independent factors for disease-free survival (DFS) in multivariate regression analysis (odds ratio [OR]=5.8; 95% confidence interval [CI]=1.2–28.4 and OR=0.2; 95% CI=0.05–0.90; p=0.029 and 0.032, respectively). There were no deaths in the AR expression group, whereas the 5-year overall survival (OS) was 54.8% in the no expression group (p=0.014). Co-expression of ER and/or PR with AR was associated with significantly better 5-year DFS and OS than those with negative AR (72.7% vs. 28.6% and 100% vs. 64.3%; p=0.020 and 0.036, respectively). AR may be an independent prognostic marker regardless of ER/PR. CONCLUSION: AR can be a potential prognostic biomarker in uterine leiomyosarcoma.
Cytochrome P-450 Enzyme System ; Disease-Free Survival ; Estrogens ; Gonadotropin-Releasing Hormone ; Gynecology ; Humans ; Immunohistochemistry ; Leiomyosarcoma* ; Medical Records ; Obstetrics ; Paraffin ; Receptors, Androgen* ; Receptors, Progesterone