Growth factors are endogenous signaling molecules that regulate cellular responses required for wound healing processes such as migration, proliferation, and differentiation. However, exogenous application of growth factors has limited effectiveness in clinical settings due to their low in vivo stability, restricted absorption through skin around wound lesions, elimination by exudation prior to reaching the wound area, and other unwanted side effects. Sophisticated systems to control the spatio-temporal delivery of growth factors are required for the effective and safe use of growth factors as regenerative treatments in clinical practice, such as biomaterial-based drug delivery systems (DDSs). The current review describes the roles of growth factors in wound healing, their clinical applications for the treatment of chronic wounds, and advances in growth factor-loaded DDSs for enhanced wound healing, focusing on micro- and nano-particulate systems, scaffolds, hydrogels, and other miscellaneous systems.

A better understanding of the molecular mechanisms that govern human adipose tissue-derived mesenchymal stem cells (hASCs) differentiation could improve hASCs-based cell therapy and provide new insights into a number of diseases, including obesity. In this study, we examined the roles of microRNA-21 (miR-21) in adipogenic differentiation of hASCs. We found that miR-21 expression was transiently increased after induction of adipogenic differentiation, peaked at 3 days, and returned to the baseline level 8 days. Lentiviral overexpression of miR-21 enhanced adipogenic differentiation. Overexpression of miR-21 decreased both protein and mRNA levels of TGFBR2. The expression of TGFBR2 was decreased during adipogenic differentiation of hASCs in concordance with an increase in the level of miR-21. In contrast, inhibiting miR-21 with 2 0 -O-methylantisense microRNA increased TGFBR2 protein levels in hASCs, accompanied by decreased adipogenic differentiation. The activity of a luciferase construct containing the miR-21 target site from the TGFBR2 3 0 UTR was lower in LV-miR21-infected hASCs than in LV-miLacZ infected cells. TGF-b-induced inhibition of adipogenic differentiation was significantly decreased in miR-21 overexpressing cells compared with control lentivirus-transduced cells. RNA interference-mediated downregulation of SMAD3, but not of SMAD2, increased adipogenic differentiation. Overexpression and inhibition of miR-21 altered SMAD3 phosphorylation without affecting total levels of SMAD3 protein. Our data are the first to demonstrate that the role of miR-21 in the adipogenic differentiation of hASCs is mediated through the modulation of TGF-b signaling. This study improves our knowledge of the molecular mechanisms governing hASCs differentiation, which may underlie the development of obesity or other metabolic diseases.

Objectives: Few parameters are available to predict neurologic outcome of post-cardiac arrest patients in the early stage of treatment. Optic nerve sheath diameter (ONSD) has been used to indirectly assess intracranial pressure. This study evaluated whether ONSD, an additional parameter in initial brain computed tomography (CT) scans, can be an early predictor of neurologic outcome in post-cardiac arrest patients.Methods: A total of 112 cardiac arrest patients between November 2012 and October 2013 were identified. Ninety-eight comatose cardiac arrest patients were evaluated with brain CT. Of these patients, after exclusion of patients whose brain CT scans were done too late or with poor baseline neurology (Cerebral Performance Category [CPC] ≥ 3), 91 patients were included for this study. The parameters of initial brain CT, i.e., gray matter-to-white matter ratio (GWR) and ONSD, were measured after clinical care as part of a retrospective reanalysis of images. ONSD on brain CT was bilaterally measured 3 mm behind the eyeball at fixed window width and level and averaged to yield the mean value. The performance of ONSD to predict poor neurologic outcome (CPC = 3 to 5) was analyzed using multiple logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and cross-tabulations.Results: Twenty-three patients showed good neurologic outcomes at hospital discharge. Mean (AESD) ONSD was 5.6 (AE0.3) mm in the good outcome group versus 6.3 (AE0.5) mm in the poor outcome group (p < 0.001). After basic clinical covariates were controlled for, i.e., age, Glasgow Coma Scale (GCS) score (3 vs. 4-15), and time from collapse to return of spontaneous circulation (ROSC), ONSD (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.1 to 3.9) and GWR (OR = 0.6; 95% CI = 0.4 to 0.9) were found to be significant factors for predicting poor neurologic outcome. ROC curve analysis showed that ONSD and GWR had areas under the ROC curve of 0.931 (95% CI = 0.87 to 0.98) and 0.922 (95% CI = 0.86 to 0.97), respectively. Combining the cutoff values of ONSD (6.21 mm, sensitivity = 56%; 95% CI = 43% to 68%) and GWR (1.23, sensitivity = 84%; 95% CI = 73% to 92%) to have 100% specificities, the sensitivity was improved to 92% (95% CI = 84% to 98%). Intrarater and interrater intraclass correlation coefficients between the investigators measuring ONSD were 0.888 and 0.833, respectively.Conclusions: Optic nerve sheath diameter on initial brain CT correlated closely with the neurologic outcome of hypoxic ischemic encephalopathy and had good reliability. Additional prospective work may be justified evaluating the standardization and diagnostic performance in real time use as a predictive tool for neurologic outcome following cardiac arrest.

Among various proinflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA), tumor necrosis factor (TNF)-α plays a pivotal role in the release of other cytokines and induction of chronic inflammation. Even though siRNA has the therapeutic potential, they have a challenge to be delivered into the target cells because of their poor stability in physiological fluids. Herein, we design a nanocomplex of polymerized siRNA (poly-siRNA) targeting TNF-α with thiolated glycol chitosan (tGC) polymers for the treatment of RA. Poly-siRNA is prepared through self-polymerization of thiol groups at the 5' end of sense and antisense strand of siRNA and encapsulated into tGC polymers, resulting in poly-siRNA-tGC nanoparticles (psi-tGC-NPs) with an average diameter of 370 nm. In the macrophage culture system, psi-tGC-NPs exhibit rapid cellular uptake and excellent in vitro TNF-α gene silencing efficacy. Importantly, psi-tGC-NPs show the high accumulation at the arthritic joint sites in collagen-induced arthritis (CIA) mice. Treatment monitoring data obtained by the matrix metalloproteinase 3-specific nanoprobe and microcomputed tomography show that intravenous injection of psi-tGC-NPs significantly inhibits inflammation and bone erosion in CIA mice, comparable to methotrexate (5 mg/kg). Therefore, the availability of psi-tGC-NP therapy that target specific cytokines may herald new era in the treatment of RA.

This study assessed the ability of the Sequential Organ Failure Assessment (SOFA) and Acute Physiology, Chronic Health Evaluation (APACHE) II scoring systems, as well as the Simplified Acute Physiology Score (SAPS) II method to predict group mortality in intensive care unit (ICU) patients who were poisoned with organophosphate. The medical records of 149 organophosphate poisoned patients admitted to the ICU from September 2006 to December 2012 were retrospectively examined. The SOFA, APACHE II, and SAPS II were calculated based on initial laboratory data in the Emergency Department, and during the first 24 hr of ICU admission. The probability of death was calculated for each patient based on the SOFA score, APACHE II score, and SAPS II equations. The ability to predict group mortality by the SOFA score, APACHE II score, and SAPS II method was assessed using two by two decision matrices and receiver operating characteristic (ROC) curve analysis. A total of 131 patients (mean age, 61 yr) were enrolled. The sensitivities, specificities, and accuracies were 86.2%, 82.4%, and 83.2% for the SOFA score, respectively; 65.5%, 68.6%, and 67.9% for the APACHE II scoring system, respectively; and 86.2%, 77.5%, and 79.4% for the SAPS II, respectively. The areas under the curve in the ROC curve analysis for the SOFA score, APACHE II scoring system, and SAPS II were 0.896, 0.716, and 0.852, respectively. In conclusion, the SOFA, APACHE II, and SAPS II have different capability to discriminate and estimate early in-hospital mortality of organophosphate poisoned patients. The SOFA score is more useful in predicting mortality, and easier and simpler than the APACHE II and SAPS II.

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Despite recent successful efforts to shorten the door-to-balloon time in patients with acute ST-segment elevation myocardial infarction (STEMI), prehospital delay remains unaffected. Nonetheless, the factors associated with prehospital delay have not been clearly identified in Korea. We retrospectively evaluated 423 patients with STEMI. The mean symptom onset-to-door time was 255 ± 285 (median: 150) min. The patients were analyzed in two groups according to symptom onset-to-door time (short delay group: ≤ 180 min vs long delay group: > 180 min). Inhospital mortality was significantly higher in long delay group (6.9% vs 2.8%; P = 0.048). Among sociodemographic and clinical variables, diabetes, low educational level, triage via other hospital, use of private transport and night time onset were more prevalent in long delay group (21% vs 30%; P = 0.038, 47% vs 59%; P = 0.013, 72% vs 82%; P = 0.027, 25% vs 41%; P < 0.001 and 33% vs 48%; P = 0.002, respectively). In multivariate analysis, low educational level (1.66 [1.08-2.56]; P = 0.021), symptom onset during night time (1.97 [1.27-3.04]; P = 0.002), triage via other hospital (1.83 [1.58-5.10]; P = 0.001) and private transport were significantly associated with prehospital delay (3.02 [1.81-5.06]; P < 0.001). In conclusion, prehospital delay is more frequent in patients with low educational level, symptom onset during night time, triage via other hospitals, and private transport, and is associated with higher inhospital mortality.

Metronome sound guidance during DA-COCPR for the untrained bystanders improved the chest compression rates, but was associated more with shallow compressions than the conventional DA-COCPR in a manikin model.