Research into angiogenesis has contributed to progress in the fast-moving field of regenerative medicine. Designing coculture systems is deemed a helpful method to understand the dynamic interaction of various cells involved in the angiogenesis process. We investigated the juxtacrine and paracrine interaction between 3 different cells, namely rat marrow-derived mesenchymal stem cells (rMSCs), rat muscle-derived satellite cells (rSCs), and rat neonatal cardiomyocytes (rCMs), and endothelial cells (ECs) during angiogenesis process. In vitro Matrigel angiogenesis assay was performed whereby ECs were monocultured or cocultured with rMSCs, rSCs, and rCMs or their conditioned media (CM). In addition, in vivo Matrigel plug assay for angiogenesis was conducted to assess the angiogenic potential of the rCM-, rMSC-, and rSC-derived CM. Our results demonstrated that the rMSCs, rSCs, and rCMs elongated along the EC tubules, whereas the rMSCs formed tube-like structures with sprouting tip cells, leading to improved angiogenesis in the coculture system. Moreover, the rMSC-and rSC-derived CM significantly improved angiogenesis tube formation on Matrigel, accelerated EC chemotaxis, and increased the arteriolar density, vascularization index, and vascularization flow index in the Matrigel plug in vivo. Western blotting showed that rMSCs secreted a high level of vascular endothelial growth factor, basic fibroblast growth factor, and stromal-derived factor-1-alpha. Tie2 is also shed from rMSCs. This study demonstrated that stem cells interact with ECs in the juxtacrine and paracrine manner during angiogenesis, and marrow MSCs have superior angiogenic properties.

No abstract

On-demand drug actuation is highly desired. Redox-responsive polymeric DDSs have been shown to be able to respond and release their cargo in a selective manner when encountering a significant change in the potential difference, such as that present between cancerous and healthy tissues. This study offers an added advantage to the field of redox-responsive polymers by reporting a new type of shell-sheddable micelle based on an amphiphilic triblock co-polymer, containing diselenide as a redox-sensitive linkage. The linkage was smartly located at the hydrophilic-hydrophilic bridge in the co-polymer offering complete collapse of the micelle when exposed to the right trigger. The system was able to delay tumor growth and reduce toxicity in a breast cancer tumor model following intraperitoneal injection in mice.

One of the major issues in cell therapy of myocardial infarction (MI) is early death of engrafted cells in a harsh oxidative stress environment, which limits the potential therapeutic utility of this strategy in the clinical setting. Increasing evidence implicates beneficial effects of omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) Abbreviations: AA, ascorbic acid; ANOVA, analysis of variance; ARE, antioxidant response element; bFGF, basic fibroblast growth factor; BSA, bovine serum albumin; Col1, Collagen type 1; CX43, connexin 43; DAPI, 4 0 ,6-diamidino-2-phenylindole; DCF, 2 0 ,7 0 -dichlorofluorescein diacetate; DHA, docosahexaenoic acid; ECL, enhanced chemiluminescence; EF, ejection fraction; EPA, eicosapentaenoic acid; ESC, embryonic stem cell; FS, fractional shortening; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HCl, hydrochloric acid; HO-1, heme oxygenase-1; HRP, horseradish peroxidase; IgG, immunoglobulin G; LAD, left anterior descending artery; LDL, low-density lipoprotein; LV, left ventricle; LVD d , LV end-diastolic dimension; LVD s , LV end-systolic dimension; MI, myocardial infarction; mtDNA, mitochondrial DNA; MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazoliuminner salt; MYH6, myosin heavy chain, α isoform; PAGE, polyacrylamide gel electrophoresis; PBS, phosphate buffered saline; PCR, polymerase chain reaction; PVDF, polyvinylidene difluoride; ROS, reactive oxygen species; SDS, sodium dodecyl sulfate; SEM, standard error of the mean; TBST, tris buffered saline with tween; TNNT2, cardiac troponin † Nasser Aghdami and Hossein Baharvand contributed equally to this work. BioFactors 427Research Communication and ascorbic acid (AA) in cardiovascular diseases, in particular their role in ameliorating fibrosis. In the current study, we aim to assess the cytoprotective role of EPA + DHA and AA in protecting embryonic stem cell (ESC)-derived cardiac lineage cells and amelioration of fibrosis. Herein, we have shown that preincubation of the cells with EPA + DHA + AA prior to H 2 O 2 treatment attenuated generation of reactive oxygen species (ROS) and enhanced cell viability. Gene expression analysis revealed that preincubation with EPA + DHA + AA followed by H 2 O 2 treatment, upregulated heme oxygenase-1 (HO-1) along with cardiac markers (GATA4, myosin heavy chain, α isoform [MYH6]), connexin 43 [CX43]) and attenuated oxidative stressinduced upregulation of fibroblast markers (vimentin and collagen type 1 [Col1]). Alterations in gene expression patterns were followed by marked elevation of cardiac troponin (TNNT2) positive cells and reduced numbers of vimentin positive cells. An injection of EPA + DHA + AA-pretreated ESC-derived cardiac lineage cells into the ischemic myocardium of a rat model of MI significantly reduced fibrosis compared to the vehicle group. This study provided evidence that EPA + DHA + AA may be an appropriate preincubation regimen for regenerative purposes.

Three-dimensional (3D) ultrasonography has been shown to be an accurate and appropriate tool for measurement of gallbladder volume in humans. Therefore, we applied this novel technique for the first time to study fasting and postprandial gallbladder volume in 10 healthy dogs and compared the results with those of 2-dimensional (2D) ultrasonography. Fasting gallbladder volumes determined by 3D ultrasonography were significantly higher than corresponding volumes determined by 2D ultrasonography (P<0.01). Additionally, gallbladder volumes were significantly decreased in the postprandial state compared with the fasting state using 3D ultrasonography (P<0.001), but 2D ultrasonography showed no significant difference (P=0.189). The Gallbladder contraction index was higher in 3D ultrasonography than 2D ultrasonography; however, it did not reach statistical significance (P=0.25). In conclusion, 3D ultrasonography was able to measure gallbladder volume in healthy dogs in this study. It is suggested that 3D ultrasonography can be used to accurately estimate gallbladder volume and contractility.

Myocardial infarction is one of the leading causes of death all over the world. Mesenchymal stem cells (MSCs) transplantation has shown a promising potential to recovery of ischemic heart disease due to their capability in differentiating into cardiac cells. However, various investigations have been performed to optimize the efficacy of cardiac cell therapy in recent years. Here, we sought to interrogate the effect of autologous transplantation of undifferentiated and predifferentiated adipose and bone marrow-derived MSCs in a rabbit model of myocardial infarction and also to investigate whether cardiac function could be improved by mechanically induced MSCs via equiaxial cyclic strain. The two sources of MSCs were induced toward cardiomyocyte phenotype using mechanical loading and chemical factors and thereafter injected into the infarcted myocardium of 35 rabbits. Echocardiography and histopathology studies were used to evaluate cardiac function after 2 months. The results demonstrated significant scar size reduction and greater recovery of left ventricle ejection fraction after transplantation of predifferentiated cells, though the differences were not significant when comparing mechanically with chemically predifferentiated MSCs. Thus, although there was no significant improvement in infarcted myocardium between chemically and mechanically predifferentiated MSCs, mechanically induced cells are more preferred due to lack of any chemical intervention and cost reasonableness in their preparation method. Outcomes of this study may be useful for developing future therapeutic strategies, however long-term assessments are still required to further examine their effectiveness.

Neoplasia is a rare cause of ataxia in horses. This report describes a 2-year-old colt presented with sudden-onset ataxia in which a cervical vertebral osteosarcoma causing severe compression of the spinal cord was diagnosed. Radiological changes included a large osteolytic lesion in the vertebral body, the vertebral arch, the right cranial articular process and the right transverse process of C4, interrupting the borders of the vertebral foramen and the right transverse foramen. Myelography revealed a marked spinal cord compression. Necropsy confirmed the presence of a welldemarcated, invasive and firm mass protruding from the fourth cervical vertebral body that led to severe compression of the spinal cord. In spite of its strongly pleomorphic nature, the detection of osteoid confirmed the diagnosis of a central osteosarcoma of the combined type. To the best of our knowledge, a primary single vertebral osteosarcoma causing ataxia in a juvenile horse has not previously been reported, and findings of this case report could help in the diagnostic work-up of similar cases.

Background Hepatic disorders are important and diverse disease entities in birds with nonspecific clinical signs. However, paraclinical examinations such as analysis of hepatic enzymes and diagnostic imaging can help evaluation of the liver changes, a definitive diagnosis is possible only with the histopathological evaluation. The aim of the present study was to determine the feasibility and capability of using three-dimensional (3D) Virtual Organ Computer-aided AnaLysis (VOCAL) ultrasonography as a noninvasive method for etiologic diagnosis of hepatomegaly in common mynah (Acridotheres tristis). Result Mean gray level of liver, mean gray level of muscle, and relative proportion of mean gray level of liver and muscle were calculated using VOCAL 3D-ultrasonography. Statistical analysis of mean gray level of liver and muscle, and relative proportion of gray level of liver and muscle in relation to lipidosis, iron storage, fibroplasia and hepatitis revealed that calculated proportion of mean gray levels of liver and muscle was significantly different among groups with different degrees of lipidosis. Further post-hoc analysis revealed that this proportion in the patients with no or slight lipidosis was significantly greater than the birds which suffered from moderate and severe lipidosis. Conclusion Application of VOCAL three-dimensional ultrasonography and evaluation of proportion of mean gray level of liver and muscle can be used as a helpful noninvasive method for diagnosis and monitoring of moderate to severe liver lipidosis in birds, but further validation and comparison with normal livers are needed in patients and normal population.