Effective delivery of therapeutic agents is the most challenging hurdle in the use of RNA interference for research and in the clinic. Here, we assessed whether a short synthetic peptide, ACSSSPSKHCG (TD-1), could be transported through rat footpad (follicle-free) skin and efficiently deliver small interfering RNA (siRNA) to knock down a target gene. Fluorescence microscopy revealed that topical co-administration of FITC-labeled TD-1 and FAM-labeled siRNA distributed uniformly from the epidermis to the subcutaneous tissue of rat footpad skin. Transmission electron microscopy revealed the absence of cell-cell junctions and enlarged spaces between epithelial cells in the TD-1-treated footpad skin. TD-1 delivery of anti-GAPDH siRNA significantly reduced the level of GAPDH in 72 h. TD-1 can create a transient opening in non-follicle rat skin for delivery of siRNA and reveal a novel mechanism of transdermal delivery of TD-1 and siRNA into the epidermis for gene knockdown. The system might have potential for siRNA delivery in skin for drug therapy.
Estrogen receptors (ERs) are frequently expressed in human tumor tissues. There have been several studies concerning ER expression in esophageal cancers, yet the results are inconsistent, and the prognostic value of the receptors remains unclear. In the present study, we investigated the expression of ER protein and its correlation with clinical features of esophageal squamous cell carcinoma (ESCC) patients. Immunohistochemical staining for the ERs was carried out on paraffin-embedded primary tumor tissue sections from 89 patients with ESCC. Quantitative analyses were performed to determine the prognostic value of the expression of ERs, and Pearson's correlation was used to examine the relationship between ERα and ERβ expression levels. Our results showed that ERα immunoreactivity was significantly lower in ESCC than that in the non-neoplastic epithelium (P=0.0445), whereas the ERβ status was much stronger in ESCC than that in the non-neoplastic epithelium (P=0.0243). A significant inverse correlation was observed between ERα expression and depth of tumor invasion (P=0.0426). Correlation analysis revealed a statistically significant inverse correlation between the expression of ERα and ERβ in ESCC (r=-0.2902, P=0.0058). Kaplan-Meier survival analysis showed that the patients with ERα expression (21/89) had a better outcome than patients without ERα expression (P=0.0280), whereas patients with high ERβ immunoreactivity (44/89) were significantly associated with worse survival (P=0.0366). In conclusion, ERα and ERβ levels were inversely correlated, and the downregulation of ERα and upregulation of ERβ may indicate unfavorable prognosis of ESCC.
A micro-channel heat sink is a promising cooling method for high power integrated circuits (IC). However, the understanding of such a micro-channel device is not sufficient, because the tools for studying it are very limited. The details inside the micro-channels are not readily available. In this letter, a micro-channel heat sink is comprehensively studied using the integrated temperature sensors. The highly sensitive thin film temperature sensors can accurately monitor the temperature change in the micro-channel in real time. The outstanding heat dissipation performance of the micro-channel heat sink is proven in terms of maximum temperature, cooling speed and heat resistance. The temperature profile along the micro-channel is extracted, and even small temperature perturbations can be detected. The heat source formed temperature peak shifts towards the flow direction with the increasing flow rate. However, the temperature non-uniformity is independent of flow rate, but solely dependent on the heating power. Specific designs for minimizing the temperature non-uniformity are necessary. In addition, the experimental results from the integrated temperature sensors match the simulation results well. This can be used to directly verify the modeling results, helping to build a convincing simulation model. The integrated sensor could be a powerful tool for studying the micro-channel based heat sink.
Severe traumatic brain injury (TBI) is a catastrophic event that often has destructive familial, economic, and societal consequences. It contributes to many deaths and cases of permanent disability, especially among patients 15-30 years old. 8,10 The average mortality rate for patients with severe TBI is 39%, and 60% of these patients have an unfavorable outcome on the Glasgow Outcome Scale. 24,26 Furthermore, those who survive tend to have significant disabilities, which also can cause a major socioeconomic burden.Patients with severe TBI have reduced immune function and higher risks of nosocomial infections as a result of decreased energy and increased protein catabolism. 4,7 By providing additional daily calories, nutrition support abbreviatioNs APACHE II = Acute Physiology and Chronic Health Evaluation II; GCS = Glasgow Coma Scale; ICU = intensive care unit; ISS = Injury Severity Score; MV = mechanical ventilation; RCT = randomized controlled trial; RR = risk ratio; TBI = traumatic brain injury; VAP = ventilator-associated pneumonia; WMD = weighted mean difference. obJect Nutritional support is highly recommended for reducing the risk of nosocomial infections, such as pneumonitis, in patients with severe traumatic brain injury (TBI). Currently, there is no consensus for the preferred route of feeding. The authors compared the risks of pneumonitis and other important outcomes associated with small intestinal and gastric feeding in patients with severe TBI. methods This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant randomized controlled trials (up to December 16, 2013) that compared small bowel to gastric feeding in patients with severe TBI were identified from searches in the PubMed and Embase databases. The primary outcome was risk of pneumonia. Secondary outcomes included ventilatorassociated pneumonia, mortality, length of intensive care unit stay, length of hospital stay, duration of mechanical ventilation, total number of complications, aspiration, diarrhea, distention, Glasgow Coma Scale score, Injury Severity Score, and Acute Physiology and Chronic Health Evaluation II score. results Five randomized controlled trials with 325 participants in total were included in the meta-analysis. Compared with gastric feeding, small bowel feeding was associated with a significant reduction in the incidence of pneumonitis (risk ratio [RR] 0.67; 95% CI 0.52-0.87; p = 0.002; I 2 = 0.0%) and ventilator-associated pneumonia (RR 0.52; 95% CI 0.34-0.81; p = 0.003; I 2 = 0.0%). Small intestinal feeding was also associated with a decrease in the total number of complications (RR 0.43; 95% CI 0.20-0.93; p = 0.03; I 2 = 68%). However, small intestinal feeding did not seem to significantly convert any of the other end points in the meta-analysis. coNclusioNs The limited evidence suggests that small bowel feeding in patients with severe TBI is associated with a risk of pneumonia that is lower than that with gast...
Although mammals are notoriously poor at regeneration compared with many lower-order species, the hair follicle, particular to mammals, is capable of regeneration following partial amputation. The detailed internal mechanism of this phenomenon is still unclear. Development and regrowth of the hair follicle depends on dermal-epidermal interaction within the hair follicle. Previous studies have shown that Wnt/β-catenin, Shh, Bmp, PDGF, TGF and Notch signals all take part in the development and growth of the hair follicle, and the Wnt/β-catenin signaling additionally plays an indispensable role in hair follicle morphogenesis and regrowth. In this study, we investigated the localization, as well as, protein levels of Wnt/β-catenin signaling molecules during amputated whisker follicle regeneration.
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