Comparison of efficacy and safety profiles of epidural analgesia and opioid analgesia in Chinese patients with thoracic trauma: A preliminary report

Purpose: To compare the efficacy and safety profiles of epidural analgesia (EA) and opioid analgesia (OA) in Chinese patients with thoracic trauma (TT). Methods: Patients with confirmed diagnosis of thoracic trauma were given either EA (via a catheter) or slow-release OA. The following efficacy variables were assessed in the two treatment groups: pain score, and changes in cytokine and catecholamine levels from baseline after treatment. Moreover, respiratory parameters were determined before and after treatment. The safety associated with each anesthesia was also evaluated. Quantitative data were analyzed either with Student’s t-test or MannWhitney test, while  categorical data were analyzed using Fisher exact or Chi-square test, based on data size. Results: A total of 200 patients completed the study (100 patients in each group). Pain, as assessed by verbal rating scale (VRS), was slightly lower in patients after treatment with EA, when compared to the patients treated with OA. However, the difference was not statistically significant (p < 0.05). Maximum inspiratory force (cmH2O) and tidal volume (liters) were slightly improved in patients  treated with EA, when compared to OA-treated patients, although the difference was not statistically significant (p < 0.05). Moreover,  the two treatments produced comparable levels of cytokines and catecholamines. Conclusion: The efficacy and safety data for EA and OA in Chinese non-obese patients with TT indicate numerically favorable outcome for EA, when compared to OA. Keywords: Epidural analgesia, Opioid analgesia, Chinese patients, Thoracic traum

In vitro and in vivo double-enhanced suicide gene therapy mediated by generation 5 polyamidoamine dendrimers for PC-3 cell line

<p>Abstract</p> <p>Background</p> <p>One of the most frequently used and efficient suicide gene therapies for prostate cancer is HSV-TK/GCV system, but its application has been limited due to lack of favorable gene vector and the reduction of "bystander effect". We investigated the effect of a novel combination of HSV-TK/GCV fused with Cx43 and gemcitabine using non-viral vector generation 5 polyamidoamine dendrimers (G5-PAMAM-D) on PC-3 cells.</p> <p>Methods</p> <p>RT-PCR and Western blot were used to detect TK and Cx43 expression. Cell viability and proliferation were measured by using MTT assay. Cell apoptosis was detected with double-staining of Annexin V-FITC and propidium iodide (PI) by flow cytometry. Nude mice models were established to evaluate the therapeutic effect in vivo.</p> <p>Results</p> <p>G5-PAMAM-D efficiently delivered recombinant plasmids into PC-3 cells and HSV-TK and Cx43 could be expressed successfully. With gemcitabine, G5-PAMAM-D mediated HSV-TK and Cx43 expression effectively inhibited prostate cancer PC-3 cell proliferation, leading to more cellular apoptosis and inhibiting PC-3 tumor growth in nude mice models.</p> <p>Conclusions</p> <p>This study illustrates that this new suicide gene system mediated by G5-PAMAM-D is effective in decreasing PC-3 cell proliferation and inducing cell apoptosis, and inhibiting tumor growth in vivo. In a word, our study could provide a potential approach for gene therapy of prostate cancer.</p

Novel peptide–dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer

Phage display technology has been demonstrated to be a powerful tool for screening useful ligands that are capable of specifically binding to biomarkers on the surface of tumor cells. The ligands found by this technique, such as peptides, have been successfully applied in the fields of early cancer diagnostics and chemotherapy. In this study, a novel nonsmall cell lung cancer-targeting peptide (LCTP, sequence RCPLSHSLICY) was screened in vivo using a Ph.D.-C7C™ phage display library. In order to develop a universal tumor-targeting drug carrier, the LCTP and fluorescence-labeled molecule (FITC) were conjugated to an acetylated polyamidoamine (PAMAM) dendrimer of generation 4 (G4) to form a PAMAM–Ac–FITC–LCTP conjugate. The performance of the conjugate was first tested in vitro. In vitro results of cell experiments analyzed by flow cytometry and inverted fluorescence microscopy indicated that PAMAM–Ac–FITC–LCTP was enriched more in NCI-H460 cells than in 293T cells, and cellular uptake was both time- and dose-dependent. The tissue distribution of the conjugate in athymic mice with lung cancer xenografts was also investigated to test the targeting efficiency of PAMAM–Ac–FITC–LCTP in vivo. The results showed that LCTP can effectively facilitate the targeting of PAMAM–Ac–FITC–LCTP to nonsmall cell lung cancer cells and tumors. These results suggest that the LCTP-conjugated PAMAM dendrimer might be a promising drug carrier for targeted cancer diagnosis and treatment

Myofibroblasts: function, formation, and scope of molecular therapies for skin fibrosis

Myofibroblasts are contractile, α-smooth muscle actin-positive cells with multiple roles in pathophysiological processes. Myofibroblasts mediate wound contractions, but their persistent presence in tissues is central to driving fibrosis, making them attractive cell targets for the development of therapeutic treatments. However, due to shared cellular markers with several other phenotypes, the specific targeting of myofibroblasts has long presented a scientific and clinical challenge. In recent years, myofibroblasts have drawn much attention among scientific research communities from multiple disciplines and specialisations. As further research uncovers the characterisations of myofibroblast formation, function, and regulation, the realisation of novel interventional routes for myofibroblasts within pathologies has emerged. The research community is approaching the means to finally target these cells, to prevent fibrosis, accelerate scarless wound healing, and attenuate associated disease-processes in clinical settings. This comprehensive review article describes the myofibroblast cell phenotype, their origins, and their diverse physiological and pathological functionality. Special attention has been given to mechanisms and molecular pathways governing myofibroblast differentiation, and updates in molecular interventions

Mobilization of Mesenchymal Stem Cells by Granulocyte Colony-stimulating Factor in Rats with Acute Myocardial Infarction

Abstract Purpose Intravenous delivery of mesenchymal stem cells (MSCs), a noninvasive strategy for myocardial repair after acute myocardial infarction (MI), is limited by the low percentage of MSCs migration to the heart. The purpose of this study was to test whether granulocyte colony-stimulating factor (G-CSF) would enhance the colonization of intravenously infused MSCs in damaged heart in a rat model of acute MI. Methods After induction of anterior MI, Sprague-Dawley rats were randomized to receive: (1) saline (n=9); (2) MSCs (n=15); and (3) MSCs plus G-CSF (50 μg/kg/day for 5 consecutive days, n=13). Results Flow cytometry revealed that G-CSF slightly increased surface CXCR4 expression on MSCs in vitro. After completion of G-CSF administration, MSCs showed a significantly lower colonization in bone marrow and a trend toward higher localization in the infarcted myocardium. At 3 months, vessel density in the infarct region of heart was significantly increased in MSCs group and trended to increase in MSCs+G-CSF group. However, echocardiographic and hemodynamic parameters, including left ventricular (LV) end-diastolic diameters, ejection fraction, and ±dP/dt max , were not statistically different. Morphological analysis showed that infarct size and collagen content were similar in the three groups. Immunohistochemistry revealed that the combined therapy accelerated endothelial recovery of the blood vessels in the ischemic myocardium. However, myocardial regeneration resulting from MSCs differentiation was not observed. Conclusions G-CSF enhanced the migration of systemically delivered MSCs from bone marrow to infarcted heart. However, the beneficial effect of this kind of migration is limited, as cardiac function did not improve

PLGA nano/micro particles encapsulated with pertussis toxoid (PTd) enhances Th1/Th17 immune response in a murine model

This document is the Accepted Manuscript version of the following article: Pan Li, Catpagavalli Asokanathan, Fang Liu, Kyi Kyi Khaing, Dorota Kmiec, Xiaoqing Wei, Sing Song, Dorothy Xing, and Deling Kong, ‘PLGA nano/micro particles encapsulated with pertussis toxoid (PTd) enhances Th1/Th17 immune response in a murine model’, International Journal of Pharmaceutics, Vol. 513 (1-2): 183-190, November 2016, available online at: https://doi.org/10.1016/j.ijpharm.2016.08.059. This manuscript version is made available under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives LicenseCC BY NC-ND 4.0 ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Poly(lactic-co-glycolic acid) (PLGA) based nano/micro particles were investigated as a potential vaccine platform for pertussis antigen. Presentation of pertussis toxoid as nano/micro particles (NP/MP) gave similar antigen-specific IgG responses in mice compared to soluble antigen. Notably, in cell line based assays, it was found that PLGA based nano/micro particles enhanced the phagocytosis of fluorescent antigen-nano/micro particles by J774.2 murine monocyte/macrophage cells compared to soluble antigen. More importantly, when mice were immunised with the antigen-nano/micro particles they significantly increased antigen-specific Th1 cytokines INF-γ and IL-17 secretion in splenocytes after in vitro re-stimulation with heat killed Bordetalla pertussis, indicating the induction of a Th1/Th17 response. Also, presentation of pertussis antigen in a NP/MP formulation is able to provide protection against respiratory infection in a murine model. Thus, the NP/MP formulation may provide an alternative to conventional acellular vaccines to achieve a more balanced Th1/Th2 immune response.Peer reviewedFinal Accepted Versio