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Renal Fanconi syndrome (RFS) affects the proximal tubular resorption in the nephrons. This causes excessive loss of key solutes through the urine. In a canine patient, we successfully managed the renal tubular acidosis and proteinuria caused by RFS via transplantation of canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs). cAT-MSCs were administered ten times at intervals of 2-4 weeks. The post-therapy check-up revealed that the cAT-MSC treatment improved the renal tubular acidosis and proteinuria. Hence, a cAT-MSC transplant may be considered as an adjuvant therapy in veterinary medicine to initiate and maintain relief of RFS-induced acidosis and proteinuria.

A miniaturized force measurement device with zero-compliance mechanism is designed and fabricated using MEMS technology. Zero-compliance mechanism consists of two suspensions connected in series through a detection point. When a force is applied to an object suspended by this mechanism, the position of the object can be kept constant by controlling the detection point. Furthermore, the force can be estimated from the displacement of the detection point because the displacement of the detection point is proportional to the force. The measurement method using zero-compliance mechanism is effective for measuring interatomic force, which is usually a function of the gap between objects. This work focuses on the miniaturization of this mechanism by MEMS technology. An experimental device is designed and fabricated. This device consists of comb-drive actuators, capacitance sensors using comb electrodes and leaf springs. It is experimentally confirmed that zero-compliance can be realized in such a miniature device fabricated using MEMS technology. In addition, measurement performances are improved in the device.

In the assembly of micro components, a slight impact during assembly affects product performance. This work focuses on the assembly of parts including magnetized components. In the assembly of such parts, the attractive force acting between the parts causes a difficulty of assembly without collision. For this reason, such a work is conducted by skilled workers. However, the lack of successors has become a problem. Therefore, a bilateral operation system is developed for training such successors. A bilateral control is installed using two devices including a voice coil motor, a leaf spring and a sensor. The slave device is controlled to follow the motion of the master device. The force applied to the slave device is estimated with a full order observer to reflect the force on the master device. It is confirmed experimentally that the slave device can follow the master device and that the force applied by the slave device can be presented to the master device. In addition, assembling experiments are conducted using the bilateral operation system. The displacement of each device and the applied external force to slave device are obtained. It is demonstrated that the assembling technique could be evaluated quantitatively.

Chronic exposure to prenatal stress can impair neurogenesis and lead to irreversible cognitive and neuropsychiatric abnormalities in offspring. The retina is part of the nervous system; however, the impacts of prenatal stress on retinal neurogenesis and visual function remain unclear. This study examined how elevated prenatal glucocorticoid levels differentially affect retinal development in the offspring of pregnant mice exposed to chronic unpredictable mild stress (CUMS). Offspring were classified into control, stress-resilient, and stress-susceptible groups based on behavioral tests assessing spatial memory and depression-like behaviors. The stress-susceptible group exhibited significantly altered synaptogenesis, reduced ganglion cell development, decreased retinal thickness, and visiual impairment. These mice also showed a pervasive transformation of retinal astrocytes into a proinflammatory A1-like reactive state, evidenced by increased GFAP and decreased STAT3 expression levels. This astrocyte phenotype shift coincided with disruptions in neurogenesis and synaptic formation. Furthermore, prenatal exposure to exogenous corticosterone confirmed that the effects of prenatal stress are mediated by glucocorticoid-induced retinal neurodegeneration. Our findings suggest that elevated prenatal glucocorticoid levels trigger a series of neurodevelopmental disturbances leading to retinal neurodegeneration and vision impairment. This research highlights the impact of prenatal stress on retinal development and visual health, suggesting new avenues for understanding and potentially mitigating the negative effects of early-life stress on neurodevelopment., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To analyze crude protein, crude fat, crude ash, crude fiber, amino acids, fatty acids, and minerals in insect-based dog foods and to evaluate their compliance with nutritional guidelines., Methods: Proximate analysis, mineral analysis, amino acid profiling, and fatty acid composition analysis were conducted from November 27, 2023, through February 2024 on 18 commercially available insect-based dog foods formulated for all-life-stage or adult dogs., Results: Proximate analysis results revealed that all 18 pet foods met the Association of American Feed Control Officials guidelines. However, discrepancies were observed between the values listed on the packaging and those measured in 7 foods. Mineral analysis showed that while all foods met the Association of American Feed Control Officials guidelines for magnesium, discrepancies were found in calcium, phosphorus, zinc, iron, and copper content, with several samples failing to meet recommended levels. Additionally, 2 foods exceeded the recommended maximum ratio for certain fatty acids. Black soldier fly larvae-based foods contained higher levels of lauric and myristic acids compared to other insect-based foods., Conclusions: Insect-based dog foods show promise as sustainable protein sources, but discrepancies in mineral content and fatty acid ratios highlight the need for both stricter regulation and better enforcement of existing guidelines to ensure nutritional adequacy for dog health and accurate labeling., Clinical Relevance: This study provides valuable insights into the nutritional composition of insect-based dog foods, revealing inconsistencies in mineral content and fatty acid ratios. These findings can help the pet food industry develop more nutritionally consistent insect-based diets.

Lymphoma is one of the most common malignant tumors in dogs. Combination chemotherapy with vincristine, cyclophosphamide, doxorubicin, and prednisolone (CHOP) is the most effective treatment for multicentric lymphoma. Previous studies have evaluated the response of large dogs to CHOP treatment and identified prognostic factors; however, studies on small dogs are lacking. In this study, we investigated the outcomes and prognostic factors for small dogs with multicentric lymphoma treated with CHOP. The responses of patients to CHOP treatment were assessed, and 54.3% were evaluated as being in complete remission (CR), 31.4% in partial remission (PR), and 14.3% in no remission (NR). The overall response rate was 85.7%. The median survival times for CR, PR, and NR patients were 683 days (85-1496 days), 241 days (15-777 days), and 119 days (61-308 days), respectively. Among the CR patients, survival was longer under the following conditions: age under 10 years ( p = 0.011), no cardiovascular heart disease ( p = 0.046), and no history of hospitalization due to side effects from chemotherapy ( p = 0.002). These results might help clinicians build treatment plans for multicentric lymphoma in small breed dogs.

Importance: This is the first reported case of fragrance products-induced recurrent oxidative hemolytic anemia in a dog, detailing the successful therapeutic approach employed., Case Presentation: A 4-year-old intact female Pomeranian dog presented with brown tongue, pigmenturia, peripheral edema, and vomiting. Blood smears revealed a high count of eccentrocytes and Heinz bodies, along with a precipitous decline in packed cell volume and an increase in blood methemoglobin levels, suggesting an oxidative hemolytic crisis. This clinicopathological pattern recurred several times after the patient returned home. Antioxidants, methylene blue, hyperbaric oxygen (HBO) therapy, and blood transfusion were successfully employed to address recurrent hemolytic anemia; however, oxidative hemolytic crises recurred. After the owner removed exposure to various home remedies and fragrances, the clinical signs and hemolytic crises did not recur., Conclusions and Relevance: Recurring oxidative hemolytic crises should raise suspicions of environmental toxicity, which, although harmless in small quantities to humans, can be devastating to small-breed dogs. In addition to removing the causative agents, methylene blue and other antioxidants, along with HBO, may be beneficial in the acute management of oxidative hemolytic anemia., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Background/aim: The soluble interleukin-2 receptor (sIL-2R) serve as a valuable biomarker for tumors in human patients, as its levels increase during the activation of T lymphocytes in clinical states such as inflammation, infection, and tumor. This study aimed to demonstrate that sIL-2R levels can be also elevated in dogs with tumors and evaluate its applicability as a diagnostic and prognostic factor in canine cancer patients., Patients and Methods: Serum was collected from 6 healthy dogs and 34 dogs with solid tumors. The concentration of sIL-2R was measured using a commercial enzyme-linked immunosorbent assay kit., Results: The median sIL-2R concentration was significantly higher in dogs with solid masses than in healthy dogs (117.3 vs 68.33 pg/ml, p = 0.016). The highest median sIL-2R concentration was found in dogs with malignant tumors, followed by those with benign tumors, and healthy dogs (119.6 vs 93.74 vs 68.33 pg/ml, respectively). In dogs with malignant tumors, the mortality rate was significantly higher in the group with high sIL-2R levels than in the group with low sIL-2R levels. Dogs with solid tumors, particularly those with malignant tumors, had higher concentrations of sIL-2R than healthy dogs. Among dogs with malignant tumors, a correlation between sIL-2R concentration and mortality rate was confirmed., Conclusion: Serum sIL-2R levels may be used to detect malignant tumors and serve as a prognostic factor in dogs with malignant tumors., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

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. Additionally no new neoplasms were observed during this period., Conclusions: To our knowledge, this study is the first to evaluate the safety aspects (≥ 6 months) associated with intravenous allogeneic AT-MSC infusion. These results suggest that allogenic AT-MSC infusion could be a useful and relatively safe therapeutic approach in canines., (© 2024. The Author(s).)

Background: The grade of tracheal collapse (TC) is assessed by the diameter of the narrowed lumen. However, studies on the relationship between TC grade and clinical symptom severity are lacking., Objectives: To investigate the clinical characteristics of small-breed dogs diagnosed with TC and determine if fluoroscopic grading correlates with cough severity., Methods: We retrospectively reviewed medical records from 2022 to 2024. TC diagnosis was confirmed using fluoroscopic examination. Multiple linear regression was employed to investigate factors influencing cough severity, with a significance level set at p  < 0.05., Results: A total of 132 dogs with TC were identified, of which 22 were excluded. The final cohort consisted of 110 dogs, aged between 2-19 years, with no significant sex differences. The majority (97.2%) of dogs had a BCS of ≥4. Among the top four breeds (Maltese, Pomeranian, Poodle, and Chihuahua), the most severe collapse was observed in the carinal region. The grade of collapse on fluoroscopy was mostly related to high BCS ( p  < 0.007) and low body weight ( p  < 0.001). However, interestingly, fluoroscopic findings of collapse location and grade did not correlate with cough severity ( p  = 0.350). Notably, clinical symptoms improved in 86.6% of cases following interventions such as weight reduction, environmental changes, and pharmacotherapy., Conclusions and Clinical Relevance: In small-breed dogs, the severity of cough was not associated with the region or grade of TC diagnosed by fluoroscopy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Kim, Ryu, Youn, Choi and Seo.)

The liver has a unique ability to regenerate in response to injury or disease with hepatocytes and biliary epithelial cells (BECs) driving the regenerative response. Liver progenitor cells (LPCs) also play role in regeneration with the ability to differentiate into either hepatocytes or BECs. However, during chronic liver disease, the regenerative capacity of the liver is impaired. The use of LPCs is a promising therapeutic strategy for patients with chronic liver diseases. LPCs can be expanded in vitro as self-renewing organoids, however, most approaches to LPC organoids do not include critical cells from the LPC niche in 3D organoid cultures. In this study, we highlight the role of liver endothelial cells (LiECs), as a part of LPC niche, in supporting the hepatobiliary organoids in long-term culture even in the absence of defined growth supplements, such as Wnt agonists. Furthermore, LiECs alter the gene expression profile of hepatobiliary organoids involved in inflammation, migration, extracellular matrix organization, and receptor signaling pathway through paracrine manner. Our findings expand the role of LiECs for regulating stemness of LPCs and elucidate a role for niche cells in a LPC organoid co-culture model with a reduction in growth supplements., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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., Methods: Retrospective, multi-institutional analysis to evaluate the outcomes of romiplostim treatment in dogs., Results: Among the dogs treated with romiplostim, 27 experienced an increase in platelet count and 26 maintained a platelet count within the reference range. Platelet count improvement was observed in various conditions: primary ITP (90%, n = 18/20), pancytopenia of unknown etiology (42.9%, n = 3/7), chemotherapy-induced thrombocytopenia (50%, n = 3/6), babesiosis (100%, n = 1/1), radiotherapy-induced thrombocytopenia (0%, n = 0/1), and disseminated intravascular coagulopathy (33.3%, n = 2/6). The median time for platelet recovery (>50 000/μL) after romiplostim administration was 4 days, and the median time for platelet count normalization was 7 days. Median hospitalization time for the improvement group (I) was 5 days. The survival-to-discharge rates were 85%, 40%, and 28.6% for dogs with primary ITP, secondary thrombocytopenia, and thrombocytopenia of unknown etiology, respectively., Conclusions and Clinical Importance: Romiplostim is a well-tolerated and promising treatment for primary ITP in dogs, suggesting its potential as a valuable therapeutic option for dogs with thrombocytopenia caused by various underlying conditions. These findings emphasize the need for further research to optimize romiplostim dosing and understand its role in treating secondary thrombocytopenia and pancytopenia of unknown etiology., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

A 13-year-old neutered male Korean short-hair cat presented with anorexia, lethargy, and a severely distended abdomen, suggestive of ascites. Abdominocentesis yielded serosanguineous fluid. A subsequent diagnostic workup, including blood tests, ascitic fluid analysis, imaging studies [radiography, ultrasound, and computed tomography (CT)], and histopathological examination, was performed to identify the underlying cause. Imaging studies revealed characteristics of encapsulating peritoneal sclerosis (EPS) such as peritoneal thickening, fat stranding, and calcification. During laparotomy, fibrous membranes encapsulating the abdominal organs and ascites were observed, and multiple calcified regions were detected on the abdominal wall. Histopathological analysis confirmed the diagnosis of poorly differentiated invasive malignant neoplasms, which were further classified as carcinomatosis based on positive cytokeratin and negative vimentin immunohistochemistry results. To our knowledge, this is the first report of sclerosing peritoneal carcinomatosis with osseous metaplasia in a cat., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nam, Song, Lee, Jeung, Ah, Lee and Ryu.)

An 11-year-old neutered male Miniature Poodle with a stage 3 apocrine gland adenocarcinoma was started on chemotherapy with toceranib phosphate after surgery. Beginning on day 10 of toceranib, the dog's foot pads became erythematous and hyperkeratinized. The dog complained of pain, inability to walk, depression, and loss of appetite. The symptoms resolved when toceranib was discontinued and reappeared when toceranib was resumed. Grade 3 palmar-plantar erythrodysesthesia was identified as an adverse event of toceranib based on the VCOG-CTCAE and Naranjo scale. Although very rare in veterinary medicine, clinicians should consider that palmar-plantar erythrodysesthesia can occur after toceranib administration., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Korean Society of Veterinary Science.)

Adipose tissue derived mesenchymal stem/stromal cell (ASC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms have not been fully elucidated. We hypothesize that the tumor necrosis factor-α-stimulated gene/protein 6 (TSG-6) in EVs is a key factor influencing the alleviation of colitis symptoms. DSS-induced colitis mice (C57BL/6, male, Naïve = 6, Sham = 8, PBS = 8 EV = 8, CTL-EV = 8, TSG-6 depleted EV = 8) were intraperitoneally administered EVs (100 ug/mice) on day 1, 3, and 5; colon tissues were collected on day 10 for histopathological, RT-qPCR, western blot and immunofluorescence analyses. In mice injected with EV, inflammation was alleviated. Indeed, EVs regulated the levels of pro- and anti-inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, IL-6, and IL-10 in inflamed colons. However, when injected with TSG-6 depleted EV, the degree of inflammatory relief was reduced. Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) and polarizing macrophage from M1 to M2 in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs and macrophage polarization from M1 to M2 in the colon., Competing Interests: Author YCJ is employed by the commercial company the Chaon Corporation. There are no patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials. The authors declare that no other competing interests exist.

The paracrine function of mesenchymal stem cells (MSCs) during transplantation has been recently studied due to its poor differentiation ratio. Dimethyloxalylglycine (DMOG) has been used to promote angiogenesis in experimental animal models, however, comparable approaches for canine MSCs are not sufficient. In the present study, we assessed whether DMOG improves angiogenesis in canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs). cAT-MSCs were treated with DMOG and their effect on angiogenesis was investigated by cell proliferation assay, western blotting, and tube formation assay. Dimethyloxalylglycine preconditioning enhanced the expression of vascular endothelial growth factor (VEGF) among pro-angiogenic factors in cAT-MSCs via hypoxia-inducible factor-1α stabilization. Dimethyloxalylglycine primed-cAT-MSC-conditioned media increased angiogenesis in human umbilical vein endothelial cells. These results suggest that DMOG conditioning of cAT-MSCs augmented the secretion of VEGF, which acted as a prominent pro-angiogenic factor during angiogenesis. DMOG-primed cAT-MSCs may have the potential to induce beneficial effects in ischemic diseases in clinical trials.

Background: Inflammatory bowel disease (IBD) is an intractable autoimmune disease, relatively common in cats, with chronic vomiting and diarrhea. Previous studies have reported that mesenchymal stem cells (MSCs) alleviate inflammation by modulating immune cells. However, there is a lack of research on cross-talk mechanism between feline adipose tissue-derived mesenchymal stem cells (fAT-MSCs) and immune cells in IBD model. Hence, this study aimed to evaluate the therapeutic effects of fAT-MSC on mice model of colitis and to clarify the therapeutic mechanism of fAT-MSCs., Results: Intraperitoneal infusion of fAT-MSC ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea, and inflammation in the colon of Dextran sulfate sodium (DSS)-treated mice (C57BL/6). Since regulatory T cells (Tregs) are pivotal in modulating immune responses and maintaining tolerance in colitis, the relation of Tregs with fAT-MSC-secreted factor was investigated in vitro. PGE 2 secreted from fAT-MSC was demonstrated to induce elevation of FOXP3 mRNA expression and adjust inflammatory cytokines in Con A-induced feline peripheral blood mononuclear cells (PBMCs). Furthermore, in vivo, FOXP3+ cells of the fAT-MSC group were significantly increased in the inflamed colon, relative to that in the PBS group., Conclusion: Our results suggest that PGE 2 secreted from fAT-MSC can reduce inflammation by increasing FOXP3+ Tregs in mice model of colitis. Consequently, these results propose the possibility of administration of fAT-MSC to cats with not only IBD but also other immune-mediated inflammatory diseases.

Background: Through recent studies, the onset of acute pancreatitis in pancreatic acinar cells (PACs) and the regulatory role of PACs in severe acute pancreatitis (SAP) have been revealed. During the early stages of pancreatitis, the endoplasmic reticulum (ER) in PACs undergoes significant changes, including swelling and vacuolization. In response to an increase in the extracellular stress in ER, PACs lose their functions, leading to cell apoptosis and inflammation response. The beneficial effects of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) on SAP have been well documented in previous studies. However, the underlying mechanism of their action remains controversial., Methods: In this study, the therapeutic effects of intraperitoneally administered hAT-MSCs in a caerulein (50 μg/kg)- and lipopolysaccharide (LPS) (10 mg/kg)-co-induced SAP mouse model were evaluated. Inflammatory response and ER stress were measured in pancreatic tissue samples, and the beneficial effects were evaluated through quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence analysis., Results: Inflammatory response and ER stress were ameliorated following hAT-MSC injection, and the beneficial effects were observed in the absence of significant engraftment of hAT-MSCs. hAT-MSCs transfected with siRNA-targeting tumour necrosis factor-α-induced gene/protein 6 (TSG-6) were unable to inhibit ER stress and inflammation. In addition, TSG-6 from hAT-MSCs significantly suppressed ER stress-induced apoptosis and nuclear factor kappa B (NF-κB) activity in SAP model mice., Conclusions: TSG-6 secreted by hAT-MSCs protects PACs in SAP model mice via the inhibition of ER stress, as well as inflammatory responses. This study has revealed a new area for ER stress-targeted therapy in SAP patients.

Background: Inflammatory bowel disease (IBD) is an intractable autoimmune disorder that markedly deteriorates one's quality of life. Mesenchymal stem cells (MSCs) alleviate inflammation by modulating inflammatory cytokines in inflamed tissues, and have been suggested as a promising alternative for IBD treatment in human and veterinary cases. Furthermore, tumor necrosis factor-α-induced gene/protein 6 (TSG-6) is a key factor influencing MSC immunomodulatory properties; however, the precise mechanism of TSG-6 release from canine MSCs in IBD remains unclear. This study aimed to assess the therapeutic effects of canine adipose tissue-derived (cAT)-MSC-produced TSG-6 in an IBD mouse model and to explore the mechanisms underlying the immunomodulatory properties., Methods: Mice with dextran sulfate sodium-induced colitis were administered cAT-MSCs intraperitoneally; colon tissues were collected on day 10 for histopathological, quantitative real-time polymerase chain reaction, and immunofluorescence analyses., Results: cAT-MSC-secreted TSG-6 ameliorated IBD and regulated colonic expression of pro- and anti-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-10. To investigate the effect of cAT-MSC-secreted TSG-6 on activated macrophages in vitro, a transwell coculture system was used; TSG-6 released by cAT-MSCs induced a macrophage phenotypic switch from M1 to M2. The cAT-MSC-secreted TSG-6 increased M2 macrophages in the inflamed colon in vivo., Conclusions: TSG-6 released from cAT-MSCs can alleviate dextran sulfate sodium-induced colitis by inducing a macrophage phenotypic switch to M2 in mice.

Two dogs presented to the emergency service after accidental ingestion of afloqualone tablets, a muscle relaxant used for back pain in humans. Toxic effects of the drug in these dogs included vomiting, respiratory depression, seizures, ataxia, bradycardia, and hematuria. Treatment consisted of fluid diuresis, furosemide, and propofol. Flumazenil, a gamma-amino butyric acid antagonist, was administered intravenously; however, it was not effective in stopping the seizures in these dogs. Both dogs recovered with supportive treatment. To the authors' knowledge, this is the first documented report of afloqualone intoxication in dogs.

Background/aim: The kidney excretes waste materials and regulates important metabolic functions, and renal disorders constitute a significant medical problem and can result in fatalities. In the present study, mesenchymal stem cells derived from canine umbilical cord blood (cUCB-MSCs) were isolated and evaluated for their ability to improve renal function in a canine model of acute kidney injury (AKI)., Materials and Methods: The canine AKI model was developed by i.v. injection of cisplatin and gentamycin into 14 male beagle dogs. cUCB-MSCs were administered into the renal corticomedullary junction following AKI induction. Survival time, clinical signs, blood analysis and histological parameters were analyzed., Results: The group treated with AKI plus cUCB-MSCs had decreased blood urea nitrogen and creatinine levels, and showed an extended life-span and improved histological manifestations. MSCs were detected around the tubules of these kidneys at the histological level., Conclusion: Taken together, our findings suggest that cUCB-MSCs could be an alternative therapeutic agent for canine AKI., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Previous studies have revealed that mesenchymal stem cells (MSCs) alleviate inflammatory bowel disease (IBD) by modulating inflammatory cytokines in the inflamed intestine. However, the mechanisms underlying these effects are not completely understood. We sought to investigate the therapeutic effects of human adipose tissue-derived (hAT)-MSCs in an IBD mouse model and to explore the mechanisms of the regulation of inflammation. Dextran sulfate sodium-induced colitis mice were infused with hAT-MSCs intraperitoneally and colon tissues were collected on day 10. hAT-MSCs were shown to induce the expression of M2 macrophage markers and to regulate the expression of pro- and anti-inflammatory cytokines in the colon. Quantitative real time-PCR analyses demonstrated that less than 20 hAT-MSCs, 0.001% of all intraperitoneally injected hAT-MSCs, were detected in the inflamed colon. To investigate the effects of hAT-MSC-secreted factors in vitro, transwell co-culture system was used, demonstrating that tumour necrosis factor-α-induced gene/protein 6 (TSG-6) released by hAT-MSCs induces M2 macrophages. In vivo, hAT-MSCs transfected with TSG-6 small interfering RNA, administered intraperitoneally, were not able to induce M2 macrophage phenotype switch in the inflamed colon and had no significant effects on IBD severity. In conclusion, hAT-MSC-produced TSG-6 can ameliorate IBD by inducing M2 macrophage switch in mice.

Background/aim: The transcription factors Oct4 and Sox2 enhance the proliferation and pluripotency of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs); however, the anti-inflammatory effects of Oct4- and Sox2-overexpressing hAT-MSCs (Oct4/Sox2-hAT-MSCs) are unclear. Here, we evaluated the anti-inflammatory effects of Oct4/Sox2-hAT-MSCs in vitro and in vivo., Materials and Methods: Supernatants from green-fluorescent protein (GFP)- and Oct4/Sox2-hAT-MSCs were used to treat lipopolysaccharide (LPS)-stimulated RAW264.7 cells and inflammatory cytokine expression was determined. In LPS-induced mice, GFP- and Oct4/Sox2-hAT-MSCs were injected intraperitoneally and survival rates, as well as sickness scores of mice, were monitored., Results: Decreased expression of pro-inflammatory cytokines was observed in Oct4/Sox2-hAT-MSC supernatant-exposed RAW264.7 cells compared to that in GFP-hAT-MSC supernatant-exposed RAW264.7 cells. The sickness score was reduced to 34.9% and the survival rate was increased by 11.1% in Oct4/Sox2-hAT-MSC-injected mice compared to that in GFP-hAT-MSC-injected mice., Conclusion: Our findings provide important insights into the development of therapies utilizing Oct4/Sox2-hAT-MSCs in inflammatory diseases., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: A high prevalence of cholestatic disease, including gallbladder mucocele (GBM), has been reported in dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH)., Hypothesis/objectives: Differences exist in the clinical features of dogs with PDH and concurrent cholestatic disease, and also is the management of these dogs with trilostane., Animals: Sixty-five client-owned dogs with naturally occurring PDH., Methods: This was a retrospective, observational case series. Each dog was treated with trilostane for at least 3 months before the study, and had a good clinical response, as determined by owners. Statistical comparisons of clinical signs, results of routine blood tests, basal and post-ACTH cortisol concentration, and optimal trilostane dosage were made after dogs were separated into the following 3 groups by ultrasonographic imaging: normal on ultrasound (NOU) group, cholestasis group, and GBM group., Results: The GBM group had more severe clinical signs and significantly different total serum cholesterol concentration and post-ACTH stimulation cortisol concentration at the time of diagnosis. Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than did the other dogs (P = .003). The optimal trilostane dosages for the GBM and cholestasis groups were 2.5 and 1.5 times the dosage of the NOU group, respectively (P < .001)., Conclusions and Clinical Importance: Gallbladder disease associated with cholestatic disease is correlated with PDH in dogs, in both its clinical features and drug management. These findings may be associated with hypercholesterolemia, unidentified genetic factors, and the hydrophobic nature of trilostane., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Severe acute pancreatitis (SAP) is associated with systemic complications and high mortality rate in dogs. Mesenchymal stem cells (MSCs) have been investigated for their therapeutic potential in several inflammation models. In the present study, the effects of canine adipose tissue-derived (cAT)-MSCs in a rat model of SAP induced by retrograde injection of 3% sodium taurocholate solution into the pancreatic duct were investigated. cAT-MSCs labeled with dioctadecyl-3,3,3'-tetramethylindo-carbocyanine perchlorate (1 × 10⁷ cells/kg) were systemically administered to rats and pancreatic tissue was collected three days later for histopathological, quantitative real-time polymerase chain reaction, and immunocytochemical analyses. Greater numbers of infused cAT-MSCs were detected in the pancreas of SAP relative to sham-operated rats. cAT-MSC infusion reduced pancreatic edema, inflammatory cell infiltration, and acinar cell necrosis, and decreased pancreatic expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, -6, -12, -17, and -23 and interferon-γ, while stimulating expression of the anti-inflammatory cytokines IL-4 and IL-10 in SAP rats. Moreover, cAT-MSCs decreased the number of clusters of differentiation 3-positive T cells and increased that of forkhead box P3-positive T cells in the injured pancreas. These results indicate that cAT-MSCs can be effective as a cell-based therapeutic strategy for treatment of SAP in dogs., Competing Interests: There is no conflict of interest.