Overexpression of Desmoglein 2 in a mouse model of Gorlin syndrome enhances spontaneous basal cell carcinoma formation through STAT3-mediated Gli1 expression

Activation of the Hedgehog (Hh) pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCC), with loss of function of Patched1 (Ptc1) being the most common genomic lesion. Sporadic BCCs also overexpress desmoglein-2 (Dsg2), a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1+/lacZ mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1+/lacZ) or the superficial epidermis (Inv-Dsg2/Ptc1+/lacZ mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively. The tumors did not show loss of heterozygosity of Ptc1, despite high levels of Gli1 and phosphorylated Stat3. A panel of sporadic human BCCs showed increased staining of both Dsg2 and P-Stat3 in 9/9 samples. Overexpression of Dsg2 in ASZ001 cells, a Ptc1-/- BCC cell line, induced Stat3 phosphorylation and further increased Gli1 levels, both in an autocrine and paracrine manner. Three different Stat3 inhibitors reduced viability and Gli1 expression in ASZ001 cells, but not in HaCaT cells. Conversely, stimulation of Stat3 in ASZ001 cells with IL-6 increased Gli1 expression. Our results indicate that Dsg2 enhances canonical Hh signaling downstream of Ptc1 to promote BCC development through the activation of P-Stat3 and regulation of Gli1 expression

Comparison of the use of blood pressure telemonitoring versus standard medical care in the achievement of short-term therapeutic goals in blood pressure in patients with uncontrolled hypertension: An open-label clinical trial

Background In Mexico less than half of the treated hypertensive patients reach blood pressure (BP) targets. Most hypertensive individuals rely on the standard medical care (SMC) to achieve the BP control goals; however, the efficacy of BP telemonitoring (BPT) to achieve BP targets has been poorly studied. Aim To compare the efficacy of BPT versus SMC to achieve BP goals in patients with uncontrolled hypertension. Methods A two-arm, open-label clinical trial was conducted in patients ≥18 years with uncontrolled hypertension. The participants were randomized to 2 arms (BPT vs SMC) and followed for 12 weeks. For the statistical analysis, the chi-squared test and covariance were used. Results One hundred and seventy-eight participants were included, BPT (n = 94) and SMC (n = 84), after 12 weeks of follow up, we observed a baseline-adjusted reduction in systolic BP with both BPT (−13.5 [1.3] mmHg) and the SMC (−5.9 [1.4] mmHg; p < 0.001) but a greater decrease with BPT (p < 0.001). Likewise, we found a baseline-adjusted reduction of diastolic BP with BPT (−6.9 [0.9] mmHg) and SMC (−2.7 [0.9] mmHg) (p = 0.007) with a more significant percentage change from baseline with BPT (−6.8% [1.0] vs 2.5% [1.1]; p = 0.007). In the BPT arm, a larger proportion of patients achieved the BP target versus SMC (30.5% vs 12.8%; p = 0.005). Conclusion BPT showed a greater proportion of patients achieving office BP control goals (<140/90 mmHg), compared to standard medical care

Comparison of plants used for skin and stomach problems in Trinidad and Tobago with Asian ethnomedicine

RefereedThis paper provides a preliminary evaluation of fifty-eight ethnomedicinal plants used in Trinidad and Tobago for skin problems, stomach problems, pain and internal parasites for safety and possible efficacy. Thirty respondents, ten of whom were male were interviewed from September 1996 to September 2000 on medicinal plant use for health problems. The respondents were obtained by snowball sampling, and were found in thirteen different sites, 12 in Trinidad and one in Tobago. The uses are compared to those current in Asia. Bambusa vulgaris, Bidens alba, Jatropha curcas, Neurolaena lobata, Peperomia rotundifolia and Phyllanthus urinaria are possibly efficacous for stomach problems, pain and internal parasites. Further scientific study of these plants is warranted

Corrosion studies of PPy/Ni organic–inorganic hybrid bilayer coatings on commercial carbon steel

© 2014, Springer-Verlag Berlin Heidelberg. Electrodeposition of polypyrrole (PPy) was achieved on AISI 1018 carbon steel (CS) using a constant potential regime and cyclic voltammetry techniques evaluating different synthesis parameters, in monomer-containing oxalic acid solutions. Thereafter, CS PPy/Ni bilayer films were produced by Ni deposition onto PPy films using a potentiostatic method. The electrochemical performance of PPy/Ni-coated carbon steel systems was investigated in 3.0 wt% NaCl solutions. For this purpose, scanning Kelvin probe (SKP), open-circuit potential (Eocp), polarization curves, and cyclic voltammetry techniques were used. The influence of electro-synthesis method and parameters were analyzed. It was found that the deviation in the Volta potentials is correlated to the interfacial interaction between the PPy/Ni bilayer coating and substrate. Considering both experimental methods to obtain PPy/Ni coatings, a more effective protection against corrosion can be formed when potentiodynamic (cyclic voltammetry) and potentiostatic techniques are combined.Peer Reviewe