Detection of Rabies Virus in a Yellow-throated Marten (Martes flavigula chrysospila) in Taiwan.

In June 2021, a yellow-throated marten (Martes flavigula chrysospila) submitted for postmortem examination was diagnosed as rabid through laboratory testing. The rabies virus detected was closest phylogenetically to viruses of ferret badgers (Melogale moschata subaurantiaca) in Taiwan, indicating spillover infection from the primary reservoir in this area, the ferret badger.

Unusual manifestations of adrenal insufficiency: A case report of hypopituitarism and Well's syndrome after apoplexy of a silent pituitary gonadotropic adenoma.

RATIONALE: Pituitary apoplexy occurs in about 8% of those with nonfunctioning pituitary adenoma. Subsequent hormone deficiency, especially corticotropic deficiency, is the most common finding. We describe the unusual manifestations of adrenal insufficiency that are usually overlooked in such cases, with the aim of raising awareness of this disease. PATIENT CONCERNS: A 53-year-old male with a history of hyponatremia came to our hospital with intermittent fever and generalized pruritic skin rash. He also reported general weakness, abdominal pain, poor appetite, and severe retroorbital headache. DIAGNOSES: Laboratory data revealed hypereosinophilia, hypotonic hyponatremia, and hypopituitarism, including secondary adrenal insufficiency. Sellar magnetic resonance imaging revealed a pituitary macroadenoma, 2 cm in height, with mild displacement of the optic chiasm. Pathologic report and immunohistochemical stains of surgical specimen showed pituitary gonadotropic adenoma with apoplexy. INTERVENTIONS: Transsphenoidal removal of the pituitary adenoma was performed. The patient received intravenous hydrocortisone then oral form cortisone acetate regularly. OUTCOMES: His symptoms and laboratory data recovered after the operation and medical treatment. LESSONS: This case highlights that eosinophilia, pruritic skin rash and fever can be manifestations of adrenal insufficiency, and that they may initially be regarded as cellulitis.

Pulmonary hair embolism in a rescued free-ranging Eurasian otter Lutra lutra in Kinmen, Taiwan.

Eurasian otters Lutra lutra are listed as Near Threatened on the IUCN Red List and are imperiled by habitat loss, water pollution, and poaching. Harassment and attacks by stray animals are also recognized threats to the health of wild Eurasian otters. Pulmonary hair embolism is a possible complication in animals with deep traumatic injury, but to date no cases have been reported in wildlife. A free-ranging, adult male Eurasian otter was rescued due to severe emaciation and multiple bite wounds. The otter died 3 d after rescue and was necropsied. Grossly, a 1.5 × 1.5 × 1.5 cm firm nodule was observed in the left cranial lung lobe. Histologically, a fragment of hair shaft surrounded by multinucleated foreign body giant cells was observed in a medium-sized vein, and extensive eosinophilic infiltration was noted in the adjacent vascular wall and lung parenchyma. Based on the gross and histological findings, the pulmonary lesion was consistent with eosinophilic pneumonia and vasculitis induced by hair embolism. The presence of well-formed multinucleated foreign body giant cells and eosinophils may imply a late stage of foreign body reaction, and thus the presumptive source of hair embolism is an animal bite. This is the first report of pulmonary hair embolism associated with animal bite in a rescued free-ranging Eurasian otter.

Adrenal pheochromocytoma presenting with Takotsubo-pattern cardiomyopathy and acute heart failure: A case report and literature review.

BACKGROUND: Pheochromocytoma is an endocrine tumor that causes hypertension, facial pallor, and headache. Pheochromocytoma patients rarely present with acute heart failure or cardiogenic shock. METHOD: We discuss the case of a female patient with Takotsubo-pattern cardiomyopathy who presented with acute heart failure caused by pheochromocytoma. RESULT: Treatment was adjusted based on the data of the pulse contour cardiac output system. After intensive hydration and medication for heart failure, the condition of the patient stabilized. CONCLUSION: Before confirming the diagnosis, pulse contour cardiac output data could provide a direction for diagnosis and treatment.

Synergy of endothelial and neural progenitor cells from adipose-derived stem cells to preserve neurovascular structures in rat hypoxic-ischemic brain injury.

Perinatal cerebral hypoxic-ischemic (HI) injury damages the architecture of neurovascular units (NVUs) and results in neurological disorders. Here, we differentiated adipose-derived stem cells (ASCs) toward the progenitor of endothelial progenitor cells (EPCs) and neural precursor cells (NPCs) via microenvironmental induction and investigated the protective effect by transplanting ASCs, EPCs, NPCs, or a combination of EPCs and NPCs (E+N) into neonatal HI injured rat pups. The E+N combination produced significant reduction in brain damage and cell apoptosis and the most comprehensive restoration in NVUs regarding neuron number, normal astrocytes, and vessel density. Improvements in cognitive and motor functions were also achieved in injured rats with E+N therapy. Synergistic interactions to facilitate transmigration under in vitro hypoxic microenvironment were discovered with involvement of the neuropilin-1 (NRP1) signal in EPCs and the C-X-C chemokine receptor 4 (CXCR4) and fibroblast growth factor receptor 1 (FGFR1) signals in NPCs. Therefore, ASCs exhibit great potential for cell sources in endothelial and neural lineages to prevent brain from HI damage.

IL-6 restores dendritic cell maturation inhibited by tumor-derived TGF-ß through interfering Smad 2/3 nuclear translocation.

We previously found, in a canine transferable tumor model, that high concentration of IL-6 produced by tumor-infiltrating lymphocytes effectively restores the MHC expression of the tumor cells and T-cell activation inhibited by tumor-derived TGF-ß. This tumor also significantly suppresses monocyte-derived dendritic cells (DCs) differentiation and the functions of differentiated DCs with unknown mechanisms. In this study, we have demonstrated that a strong reaction of IL-6 was present to neutralize TGF-ß-down-regulated surface marker expression on DCs (MHC II, CD1a, CD40, CD80, CD83, CD86), TGF-ß-hampered DC functions and DC-associated T-cell activation. Western blotting and confocal microscopy results indicated that the presence of IL-6 markedly decreased the nuclear concentration of a TGF-ß signaling transducer, Smad 2/3. In addition, while Smad 7 is a potent molecule inhibiting Smad 2/3 nuclear translocation, no significant increase in Smad 7 gene expression upon addition of IL-6 in TGF-ß-pretreated DCs was detected, which suggested that the blockage of Smad 2/3 nuclear translocation by IL-6 did not occur through a Smad 7-inhibitory mechanism. In conclusion, IL-6 inhibited TGF-ß signaling and concomitantly antagonized the suppression activities of TGF-ß on DC maturation and activity. This study enables further understandings of host/cancer interactions an also provide hints facilitating improvements of DC-based cancer immunotherapy.

Human umbilical vein endothelial cells protect against hypoxic-ischemic damage in neonatal brain via stromal cell-derived factor 1/C-X-C chemokine receptor type 4.

BACKGROUND AND PURPOSE: Agents that protect against neurovascular damage provide a powerful neuroprotective strategy. Human umbilical vein endothelial cells (HUVECs) may be used to treat neonates with hypoxic-ischemia (HI) because of its autologous capability. We hypothesized that peripherally injected HUVECs entered the brain after HI, protected against neurovascular damage, and provided protection via stromal cell-derived factor 1/C-X-C chemokine receptor type 4 pathway in neonatal brain. METHODS: Postpartum day 7 rat pups received intraperitoneal injections of low-passage HUVEC-P4, high-passage HUVEC-P8, or conditioned medium before and immediately after HI. HUVECs were transfected with adenovirus-green fluorescent protein for cell tracing. Oxygen-glucose deprivation was established by coculturing HUVEC-P4 with mouse neuroblastoma neuronal cells (Neuro-2a) and with mouse immortalized cerebral vascular endothelial cells (b.End3). RESULTS: HUVEC-P4-treated group had more blood levels of green fluorescent protein-positive cells than HUVEC-P8-treated group 3 hours postinjection. Intraperitoneally injected HUVEC-P4, but not HUVEC-P8, entered the cortex after HI and positioned closed to the neurons and microvessels. Compared with the condition medium-treated group, the HUVEC-P4-treated but not the HUVEC-P8-treated group showed significantly less neuronal apoptosis and blood-brain barrier damage and more preservation of microvessels in the cortex 24 hours after HI. On postpartum day 14, the HUVEC-P4-treated group showed significant neuroprotection compared with the condition medium-treated group. Stromal cell-derived factor 1 was upregulated in the ipsilateral cortex 3 hours after HI, and inhibiting the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 reduced the protective effect of HUVEC-P4. In vitro transwell coculturing of HUVEC-P4 also significantly protected against oxygen-glucose deprivation cell death in neurons and endothelial cells. CONCLUSIONS: Cell therapy using HUVECs may provide a powerful therapeutic strategy in treating neonates with HI.

SC-1, a sorafenib derivative, shows anti-tumor effects in osteogenic sarcoma cells.

Despite significant advances in the treatment of osteosarcoma (OS), overall survival rate of OS patients has remained relatively constant for over two decades and novel approaches are needed to further improve prognosis. Here, we report the anti-tumor effect of SC-1, a novel sorafenib derivative that closely resembles sorafenib structurally but is devoid of kinase inhibitory activity, on OS cells through mediation of signal transducer and activator of transcription 3 (STAT3). SC-1 showed similar effects to sorafenib on growth inhibition and apoptosis, and downregulated phospho-STAT3 (p-STAT3) at tyrosine 705 in all tested OS cell lines (U2OS, HOS, and 143B). Expression of STAT3-driven genes, including cylcin D1 and c-myc, were also repressed by SC-1. Ectopic expression of STAT3 in 143B cells abolished apoptosis in SC-1-treated cells. Inhibition of SHP-1 decreased SC-1-induced apoptosis. SC-1 upregulated the activity of SHP-1 in tested OS cell lines in a dose-dependent manner. Finally, SC-1 reduced 143B tumor growth significantly in vivo, which was associated with downregulation of p-STAT3 and upregulation of SHP-1 activity. These data demonstrate that SC-1 has clinical potential for the treatment of OS patients.

Spheroid formation and neural induction in human adipose-derived stem cells on a chitosan-coated surface.

The application of stem cells appears to have great therapeutic potential to facilitate nerve regeneration in patients with neurodegenerative disease or spinal cord injury. Human adipose-derived stem cells (hADSCs), a subset of multipotent mesenchymal stem cells, possess the great advantages of an abundant amount of cells, less ethical conflict and minimal invasive surgical procedures to obtain the cells. Chitosan, a naturally derived polysaccharide from chitin, has been widely studied to facilitate and guide the direction of nerve regeneration as a biomaterial for the neural tube. Chitosan also serves as a three-dimensional culture substrate to facilitate cellular sphere formation among various cells but is as yet unexplored in hADSCs. In this study, the ability of hADSCs to transdifferentiate from the mesenchymal into the neural lineage by seeding hADSCs on a chitosan-coated surface to form therapeutic cell spheres was investigated. The optimal seeding density (2 × 10(4) cells/cm(2)) and harvesting time (72 h) to obtain sphere formation were determined by cell viability on a chitosan-coated surface. Expression of neural lineage markers was observed by immunofluorescent staining of nestin, neurofilament heavy chain and glial fibrillary acidic protein. The neural induction potentials were also provoked by replating spheres from primary to tertiary passages. The effect of neural induction in hADSCs on a chitosan-coated surface may help to provide cell sources for facilitating nerve regeneration in future clinical applications.

A comparison between adipose tissue and dental pulp as sources of MSCs for tooth regeneration.

In this study, several in vivo and in vitro comparisons were performed to test the possibility of using adipose-derived stem cells (ADSCs), a more convenient cell source than dental pulp stem cells (DPSCs), in tooth regeneration. Using an efficient, non-engineering implantation method, we first demonstrated that both implants of ADSCs and DPSCs were able to grow self-assembled new teeth in adult rabbit extraction sockets with high success rate. The stem cells were necessary because the implants grew no tooth without them. A stepwise comparison showed that the regenerated teeth from these two types of adult stem cells were living with nerves and vascular system and remarkably similar to a normal tooth in many details. Further strictly controlled, side-by-side comparisons between the two types of stem cells also showed that the expression patterns of gene markers and the broad differentiation potentials induced by specific methods in vitro were very similar. Although a few differences were found, they did not affect the tested tooth regeneration in vivo or differentiation in vitro. Furthermore, rabbit ADSCs had a higher growth rate and a better senescence resistance in culture. All these findings suggest that ADSCs, one of the richest adult stem cells in mammals, are very similar and useful as DPSCs for regenerative dentistry.