Histopathology,Molecular Identification and Antifungal Susceptibility Testing of Nannizziopsis arthrosporioides from a Captive Cuban Rock Iguana (Cyclura nubila)

Mycopathologia - Chrysosporium-related fungi, the cause of superficial and deep mycoses, are an emerging infectious disease affecting not only reptiles but also immunocompromized humans. However,...     

Pleomorphic extra-renal manifestation of the glomerular podocyte marker podocalyxin in tissues of normal beagle dogs

Podocalyxin (PC) was initially identified as a major sialoprotein on the apical surface of glomerular podocytes to perform the filtration barrier function. Later, it was reported to be expressed in endothelial cells, megakaryotes/platelets, and hemangioblasts, the common progenitor cells of the hematopoietic and endothelial cells. Recently, increasing numbers of reports have indicated that PC is not merely a molecule restricted at renal glomerulus, angiogenic or hematopoietic system. To further elucidate the expression pattern and address the possible physiological role of PC in adult mammals, we conducted an extensive study by immunohistochemistry and immunofluorescence staining on various tissues of healthy adult beagle dogs. By combinatory usage of two different anti-podocalyxin antibodies recognizing distinct epitopes in PC, we have demonstrated that (1) PC is expressed in renal tubules, mesothelium, myocardium, striated muscles in tongue, esophagus and extraocular region, myoepithelial cells in esophagus and salivary glands, neurons, and ependyma, etc.; (2) there are at least three forms of PC proteins, depending upon the accessibility of two different PC antibodies, expressed in different organs/systems; and (3) a particular form of PC is distributed in a vesicle-like compartment in certain organs/systems, such as the central nervous system. Electronic Supplementary Material The online version of this article () contains supplementary material, which is available to authorized users.     

Molecular Mechanisms Responsible for Neuron-Derived Conditioned Medium (NCM)-Mediated Protection of Ischemic Brain

The protective value of neuron-derived conditioned medium (NCM) in cerebral ischemia and the underlying mechanism(s) responsible for NCM-mediated brain protection against cerebral ischemia were investigated in the study. NCM was first collected from the neuronal culture growing under the in vitro ischemic condition (glucose-, oxygen- and serum-deprivation or GOSD) for 2, 4 or 6 h. Through the focal cerebral ischemia (bilateral CCAO/unilateral MCAO) animal model, we discovered that ischemia/reperfusion (I/R)-induced brain infarction was significantly reduced by NCM, given directly into the cistern magna at the end of 90 min of CCAO/MCAO. Immunoblocking and chemical blocking strategies were applied in the in vitro ischemic studies to show that NCM supplement could protect microglia, astrocytes and neurons from GOSD-induced cell death, in a growth factor (TGFβ1, NT-3 and GDNF) and p-ERK dependent manner. Brain injection with TGFβ1, NT3, GDNF and ERK agonist (DADS) alone or in combination, therefore also significantly decreased the infarct volume of ischemic brain. Moreover, NCM could inhibit ROS but stimulate IL-1β release from GOSD-treated microglia and limit the infiltration of IL-β-positive microglia into the core area of ischemic brain, revealing the anti-oxidant and anti-inflammatory activities of NCM. In overall, NCM-mediated brain protection against cerebral ischemia has been demonstrated for the first time in S.D. rats, due to its anti-apoptotic, anti-oxidant and potentially anti-glutamate activities (NCM-induced IL-1β can inhibit the glutamate-mediated neurotoxicity) and restriction upon the infiltration of inflammatory microglia into the core area of ischemic brain. The therapeutic potentials of NCM, TGFβ1, GDNF, NT-3 and DADS in the control of cerebral ischemia in human therefore have been suggested and require further investigation.     

Elevated Krüppel-like factor 4 transcription factor in canine mammary carcinoma

Background

Krüppel-like factors (KLFs) are critical regulators of biological and physiological systems and have been extensively studied for their roles in cell proliferation, differentiation and survival in the context of cancer. Among the KLFs, KLF4 is highly expressed in human breast cancers and plays an oncogenic role. The present study examined the expression of KLF4 and assessed its significance in canine mammary carcinoma.

Results

Immunohistochemistry was employed to investigate the expression of KLF4 in 142 cases of canine mammary tumor. 75 of the 142 (52.8%) cases were histologically confirmed as mammary carcinoma. Quantification of immunohistochemistry was carried out using Quick score which multiply the staining intensity by the percentage of positive cells. High KLF4 expression was identified in 44 of the 75 (59%) dogs with mammary carcinoma and none in the benign cases. High KLF4 expression occurred only in the tumor cells and not the adjacent normal cells in mammary carcinoma (P < 0.001). Moreover, the high expression level of KLF4 expression was statistically associated with poor grade, late stage, histological subtypes of simple and complex carcinoma, and shorter 24-month survival. The Kaplan-Meier survival analysis also indicated that dogs with high nuclear KLF4 expression had a significantly shorter survival than those with low/moderate KLF4 expression (P = 0.011).

Conclusions

KLF4 is highly and frequently expressed in canine mammary carcinoma and correlates with a more aggressive phenotype.