Sonic hedgehog signaling is associated with resistance to zoledronic acid in CD133high/CD44high prostate cancer stem cells

Molecular Biology Reports - Cancer stem cells (CSCs) are a unique population that has been linked to drug resistance and metastasis and recurrence of prostate cancer. The sonic hedgehog (SHH)...     

Rosularia globulariifolia var. pallidiflora comb. et stat. nov. (Crassulaceae)

Rosularia globulariifolia (Fenzl) A. Berger and R. pallidiflora (Holmboe) Meikle were originally described as species in Umbilicus DC. in 1842 and 1914, respectively. In the present study, morphological and palynological features were examined in detail to determine the status of these taxa. The general characteristics, seed structure and micromorphology, pollen measurements and pollen characteristics were established. Morphologically, the two taxa cannot easily be distinguished. Pollen grains of both species are tricolporate, subspheroidal and eutectate, ornamentation is psilate and exine structures are similar. Based on morphological and palynological similarities, and the fact that both taxa are found in the same habitats, we propose that R. pallidiflora should be reduced to the rank of variety as Rosularia globulariifolia (Fenzl) A. Berger var. pallidiflora (Meikle) Minareci & K. Yildiz comb. et stat. nov.     

Formation and persistence of N7-methylguanine DNA adducts in the target pyloric tissue following chronic exposure to N-methyl-N'-nitro-N-nitrosoguanidine

Outbred 7-week old male Wistar rats were exposed for 21 days to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) via the drinking water and N7-methyl deoxyguanosine 3'-monophosphate (N7-MedGp) levels in DNA from the pyloric mucosa (target tissue) and white blood cells (wbc: non-target tissue) were determined by ³²P-postlabelling. Exposure to MNNG resulted in the non-linear, dose-related formation of N7-medGp in both tissues. Adduct levels in the pyloric mucosa were determined to be 1058, 5.4 and 1.1 μmole N7-medGp mole^-1 deoxyguanosine 3'-monophosphate (dGp) after exposure to 4.1, 0.62 and 0.006 mg MNNG kg^-1 day^-1 respectively whereas adduct levels in the wbc DNA were lower at 5.2, 0.52 and 0.68 μmoles N7-medGp mole^-1 dGp after exposure to 4.1, 0.62 and 0.062 mg MNNG kg^-1 day^-1 respectively. In addition, the persistence of N7-medGp was investigated. Loss of adduct occurred rapidly, with a decrease of 87 and 97% respectively in target tissue and wbc DNA by 48 h after cessation of 4.1 mg MNNG kg^-1 day^-1 exposure; 14 days post-MNNG treatment, however, N7-medGp was still detectable (0.46 μmole N7-medGp mole^-1 dGp) in pyloric mucosal DNA. The quantitation of N7-medGp after exposure to low doses of carcinogen, i.e. 0.006 mg MNNG kg^-1 day^-1, approaching environmentally relevant levels has not been previously reported, and indicates that the ³²P-postlabelling assay developed here possesses sufficient sensitivity to quantitate N7- medGp in human DNA arising from environmental exposure to methylating agents.     

Mechanical force prolongs acute inflammation via T-cell-dependent pathways during scar formation

Mechanical force significantly modulates both inflammation and fibrosis, yet the fundamental mechanisms that regulate these interactions remain poorly understood. Here we performed microarray analysis to compare gene expression in mechanically loaded wounds vs. unloaded control wounds in an established murine hypertrophic scar (HTS) model. We identified 853 mechanically regulated genes (false discovery rate <2) at d 14 postinjury, a subset of which were enriched for T-cell-regulated pathways. To substantiate the role of T cells in scar mechanotransduction, we applied the HTS model to T-cell-deficient mice and wild-type mice. We found that scar formation in T-cell-deficient mice was reduced by almost 9-fold (P < 0.001) with attenuated epidermal (by 2.6-fold, P < 0.01) and dermal (3.9-fold, P < 0.05) proliferation. Mechanical stimulation was highly associated with sustained T-cell-dependent Th2 cytokine (IL-4 and IL-13) and chemokine (MCP-1) signaling. Further, T-cell-deficient mice failed to recruit systemic inflammatory cells such as macrophages or monocytic fibroblast precursors in response to mechanical loading. These findings indicate that T-cell-regulated fibrogenic pathways are highly mechanoresponsive and suggest that mechanical forces induce a chronic-like inflammatory state through immune-dependent activation of both local and systemic cell populations.     

Quantification of Trypsin Activity by a New Biosensing System Based on the Enzymatic Degradation and the Destructive Nature of Trypsin

Trypsin is an enzyme that is included in the hydrolysis class of enzymes. Trypsin catalyzes the cleavage of proteins from a serine residue and is found in the digestive system of vertebrates. The cystic fibrosis, which is an autosomal recessive disorder, is associated with the trypsin deficiency. The meconium ileus is caused by this deficiency. Beside the clinical significance of trypsin, it is also used in many industrial applications, such as tissue culture labs, milk industry, proteomics, and different kinds of food production processes. In this study, a glucose oxidase based electrochemical biosensing system was constructed for sensitive and accurate determination of trypsin activity in different samples. A novel working principle was operated in the reported biosensor, which is based on the trypsin degradation ratio in the bioactive layer of the biosensor. Detailed optimization and characterization experiments were carried out to obtain the best electrochemical signals. The system introduced a linear determination range for trypsin activity between 6.65 and 33.25 U/ml. The biosensor was also used in the analysis of the trypsin activities of real samples.