Nonsteroidal Anti-Inflammatory Drugs for Wounds: Pain Relief or Excessive Scar Formation?

The inflammatory process has direct effects on normal and abnormal wound healing. Hypertrophic scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Two cytokines—transforming growth factor-β (TGF-β) and prostaglandin E2 (PGE2)—are lipid mediators of inflammation involving wound healing. Overproduction of TGF-β and suppression of PGE2 are found in excessive wound scarring compared with normal wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) or their selective cyclooxygenase-2 (COX-2) inhibitors are frequently used as a pain-killer. However, both NSAIDs and COX-2 inhibitors inhibit PGE2 production, which might exacerbate excessive scar formation, especially when used during the later proliferative phase. Therefore, a balance between cytokines and medication in the pathogenesis of wound healing is needed. This report is a literature review pertaining to wound healing and is focused on TGF-β and PGE2

Purification and Characterization of Hemagglutinating Proteins from Poker-Chip Venus (Meretrix lusoria) and Corbicula Clam (Corbicula fluminea)

Hemagglutinating proteins (HAPs) were purified from Poker-chip Venus (Meretrix lusoria) and Corbicula clam (Corbicula fluminea) using gel-filtration chromatography on a Sephacryl S-300 column. The molecular weights of the HAPs obtained from Poker-chip Venus and Corbicula clam were 358 kDa and 380 kDa, respectively. Purified HAP from Poker-chip Venus yielded two subunits with molecular weights of 26 kDa and 29 kDa. However, only one HAP subunit was purified from Corbicula clam, and its molecular weight was 32 kDa. The two Poker-chip Venus HAPs possessed hemagglutinating ability (HAA) for erythrocytes of some vertebrate animal species, especially tilapia. Moreover, HAA of the HAP purified from Poker-chip Venus was higher than that of the HAP of Corbicula clam. Furthermore, Poker-chip Venus HAPs possessed better HAA at a pH higher than 7.0. When the temperature was at 4°C–10°C or the salinity was less than 0.5‰, the two Poker-chip Venus HAPs possessed better HAA compared with that of Corbicula clam

An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010

<p>Abstract</p> <p>Background</p> <p>In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak.</p> <p>Methods</p> <p>Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software.</p> <p>Results</p> <p>Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (<it>p </it>< 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008.</p> <p>Conclusions</p> <p>HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities.</p

Optimal Unit Commitment by Considering High Penetration of Renewable Energy and Ramp Rate of Thermal Units-A case study in Taiwan

When large amounts of wind power and solar photovoltaic (PV) power are integrated into an independent power grid, the intermittent renewable energy destabilizes power output. Therefore, this study explored the unit commitment (UC) optimization problem; the ramp rate was applied to solve problems with 30 and 10 min of power shortage. The data of actual unit parameters were provided by the Taiwan Power Company. The advanced priority list method was used together with a combination of a generalized Lagrangian relaxation algorithm and a random feasible directions algorithm to solve a large-scale nonlinear mixed-integer programming UC problem to avoid local and infeasible solutions. The results showed that the proposed algorithm was superior to improved particle swarm optimization (IPSO) and simulated annealing (SA) in terms of the minimization of computation time and power generation cost. The proposed method and UC results can be effective information for unit dispatch by power companies to reduce the investment costs of power grids and the possibility of renewable energy being disconnected from the power system. Thus, the proposed method can increase the flexibility of unit dispatch and the proportion of renewable energy in power generation

A Critical Dose of Doxorubicin Is Required to Alter the Gene Expression Profiles in MCF-7 Cells Acquiring Multidrug Resistance

<div><p>Cellular mechanisms of multidrug resistance (MDR) are related to ABC transporters, apoptosis, antioxidation, drug metabolism, DNA repair and cell proliferation. It remains unclear whether the process of resistance development is programmable. We aimed to study gene expression profiling circumstances in MCF-7 during MDR development. Eleven MCF-7 sublines with incremental doxorubicin resistance were established as a valued tool to study resistance progression. MDR marker P-gp was overexpressed only in cells termed MCF-7/ADR-1024 under the selection dose approaching 1024 nM. MCF-7/ADR-1024 and authentic MCF-7/ADR shared common features in cell morphology and DNA ploidy status. MCF-7/ADR-1024 and authentic MCF-7/ADR down regulated repair genes BRCA1/2 and wild type p53, apoptosis-related gene Bcl-2 and epithelial-mesenchymal transition (EMT) epithelial marker gene E-cadherin. While detoxifying enzymes glutathione-S transferase-π and protein kinase C-α were up-regulated. The genes involving in EMT mesenchymal formation were also overexpressed, including N-cadherin, vimentin and the E-cadherin transcription reppressors Slug, Twist and ZEB1/2. PI3K/AKT inhibitor wortmannin suppressed expression of Slug, Twist and mdr1. Mutant p53 with a deletion at codons 127-133 markedly appeared in MCF-7/ADR-1024 and authentic MCF-7/ADR as well. In addition, MCF-7/ADR-1024 cells exerted CSC-like cell surface marker CD44 high/CD24 low and form mammospheres. Overall, results suggest that resistance marker P-gp arises owing to turn on/off or mutation of the genes involved in DNA repair, apoptosis, detoxifying enzymes, EMT and ABC transporters at a turning point (1.024 μM doxorubicin challenge). Behind this point, no obvious alterations were found in most tested genes. Selection for CSC-like cells under this dose may importantly attribute to propagation of the population presenting invasive properties and drug resistance. We thereby suggest two models in the induction of drug resistance. Model 1: Selection for CSC-like cells. Model 2: Mutations for gain-of resistance. Either model 1 or model 2 requires doxorubicin dose approaching 1 μM to alter gene regulation.</p></div

Presence of cancer stem cell-like properties upon doxorubicin selection.

<p>(A) Analysis of mammary stem cell markers in selected MCF-7/ADR-n sublines. Cells were sorted for CD44 high/CD24 low cell surface antigens by flow cytometry. Cell population was distributed in the quadrant. (B) Mammospheres formation of MCF-7/ADR-1024 cells in a three-dimensional culture, followed by a limiting dilution assay. A representative phase-contrast microscopic image shows mammosphere formation of MCF-7/ADR-1024 compared to MCF-7/WT from a total of 50 countable  mammospheres on day 21.</p

ABC transports are upregulated in the induction of drug resistance.

<p>(A)MDR-1 mRNA levels in the series of resistant cells. (B) P-gp detected in MCF-7/ADR-1024 and MCF-7/ADR using Western blotting. (C) P-gp function detected by the accumulation of intracellular rhodamine-123 dye followed by FACS analysis. The cells were treated with or without verapamil 4 μM for 2 hours and then were added with rhodamine-123 dye 5 μM for 1 h. Histogram displays the X-axis as fluorescence intensity and the Y-axis as cell counts. (D) Protein levels of MRP-1 measured by Western blotting. (E) MRP-1 protein function detected by the accumulation of fluorescent dye calcein-AM followed by FACS analysis. Cells were treated with or without MK571 10 μM for 2 hours and then were added with calcein-AM 0.3 μM for 1 h.</p