The purpose of study is to quantify and compare diffusion of propylene glycol, glucose, glycerol in the human skin in vivo noninvasively. Optical coherence tomography (OCT) was utilized in the functional imaging of optical cleaning agents for monitoring and quantifying the permeability coefficients (PCs) of them. Our experiments showed that the permeability coefficient of 40% propylene glycol from different subjects was averaged and found to be (2.52 ± 0.02) × 10−6 cm/s, the permeability coefficient of 40% glucose was (1.94 ± 0.05) × 10−6 cm/s, and the permeability coefficient of 40% glycerol was (1.82 ± 0.04) × 10−6 cm/s. The results indicated that the diffusion of propylene glycol solutions was faster than that of glucose solution, and the diffusion of glucose solutions was faster than that of glycerol solutions. The dependence of the permeability on the different hyperosmotic analytes could potentially be used in various basic science and clinical fields, such as optical clearing of tissues and cells as well as in clinical pharmacology.
To study the therapeutic effects of anti-fibrosis herbs and selenium on hepatic fibrosis induced by carbon tetrachloride (CCl(4)) in rats and the underlining molecular mechanisms.Fifty-three Wistar rats were randomly divided into: normal control group, model control group, colchicine group, anti-fibrosis herbs group (AF group) and anti-fibrosis herbs plus selenium group (AS group). The last four groups were administered with CCl(4) at the beginning of experiment to induce hepatic fibrosis. Then colchicine, anti-fibrosis herbs and selenium were used to treat them. The normal control group and the model control group were given normal saline at the same time. At the end of the 6(th) week, rats in each group were sacrificed. Blood and tissue specimens were taken. Serum indicators (ALT, AST, HA, LN) were determined and histopathological changes were graded. Lymphocyte CD(4) and CD(8) were examined by flow cytometry. Expression of TGF-beta(1) and NF-kappaB was detected by immunohistochemistry and expression of TGF-beta(1) mRNA was detected by semi-quantified RT-PCR.Histological grading showed much a smaller degree of hepatic fibrogenesis in AS group and AF group than that in colchicine group and model control group. The serum content of ALT, AST, HA and LN in AF group and AS group were significantly lower than that in colchicine group (ALT: 65.8+/-26.5, 67.3+/-18.4 and 96.2+/-20.9 in AF, AS and colchicine groups respectively; AST: 150.8+/-34.0, 154.6+/-27.3 and 215.8+/-24.6 respectively; HA: 228+/-83, 216+/-58 and 416+/-135 respectively; LN: 85.9+/-15.0, 80.6+/-18.6 and 106.3+/-14.2 respectively) (P<0.05). The level of CD(4) and CD(4)/CD(8) ratio in AF group and AS group was significantly higher that those in cochicine group (CD(4): 50.8+/-3.8, 52.6+/-3.4 and 40.2+/-2.1 in AF, AS and colchicine groups respectively; CD(4)/CD(8) ratio: 1.45, 1.46 and 1.26, respectively (P<0.05). The expression level of NF-kappaB and TGF-beta(1) in the liver tissues of AF and AS treatment groups was markedly decreased compared with that in cochicine group, and TGF-beta(1) mRNA was also markedly decreased (1.07+/-0.31 and 0.98+/-0.14 vs 2.34+/-0.43, P<0.05).Anti-fibrosis herbs and selenium have beneficial effects on hepatic fibrosis in rats by enhancing immunity and inhibiting NF-kappaB and TGF-beta(1) expressions.
Abstract Intramuscular expression of functional proteins is a promising strategy for therapeutic purposes. Previously, we developed an intramuscular gene delivery method by combining Pluronic L64 and optimized electropulse, which is among the most efficient methods to date. However, plasmid DNAs (pDNAs) in this method were not compressed, making them unstable and inefficient in vivo. We considered that a proper compression of pDNAs by an appropriate material should facilitate gene expression in this L64-electropulse system. Here, we reported our finding of such a material, Epigallocatechin gallate (EGCG), a natural compound in green teas, which could compress and protect pDNAs and significantly increase intramuscular gene expression in the L64-electropulse system. Meanwhile, we found that polyethylenimine (PEI) could also slightly improve exogenous gene expression in the optimal procedure. By analysing the characteristic differences between EGCG and PEI, we concluded that negatively charged materials with strong affinity to nucleic acids and/or other properties suitable for gene delivery, such as EGCG, are better alternatives than cationic materials (like PEI) for muscle-based gene delivery. The results revealed that a critical principle for material/pDNA complex benefitting intramuscular gene delivery/expression is to keep the complex negatively charged. This proof-of-concept study displays the breakthrough in compressing pDNAs and provides a principle and strategy to develop more efficient intramuscular gene delivery systems for therapeutic applications.
To examine the effect of celecoxib on tumor growth and angiogenesis in an orthotopic implantation tumor model of colon cancer.Human colorectal adenocarcinoma HT-29 cells were implanted subcutaneously in nude mice. Four groups of animals received different doses of celecoxib after tumor implantation. After 42 days, all animals were evaluated for changes in body weight, the volume and weight of colorectal tumors, and tumor growth inhibition. The content of prostaglandin E(2) (PGE(2)) in the tumor tissue homogenate was estimated by radioimmunoassay (RIA). Cyclooxygenase-2 (COX-2) and CD34 expression in tumor tissue was assessed by immunohistochemistry, and the microvessel density (MVD) of tumor tissue was determined. Apoptosis of the tumor cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). The expression of vascular endothelial growth factor (VEGF) mRNA and matrix metalloproteinase-2 (MMP-2) mRNA extracted from the tumor tissue was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR).There was no statistically significant change in the animals' body weight between the treatment groups. However, with increasing doses of celecoxib, the volume and weight of the tumor decreased. The rates of tumor growth inhibition for the L (low), M (medium) and H (high) groups were 25.30%, 38.80%, and 76.92%, respectively, which were significant compared to the C (control) group. There were significant differences in COX-2 expression in the tumor tissue between all groups, except between the L and M groups. Celecoxib exposure also reduced PGE2 levels in the tumor tissue homogenates. The level of PGE(2) correlated to the weight of tumor (r=0.8814, P < 0.05) and to COX-2 expression (r=0.8249, Puse < 0.05). Compared to the control group, the tumor cells from celecoxib-treated mice had a significantly higher apoptotic index. Celecoxib also decreased CD34(+) expression in tumors from treated mice. There were significant differences in the MVD between all groups except between groups H and M. Celecoxib significantly reduced the expression of VEGF and MMP-2 mRNA in the group H but not in L and M groups. The MVD in tumor tissue was closely related to the PGE2 levels, as well as the expression of VEGF and MMP-2 mRNA (r = 0.9006, r = 0.8573 and r = 0.6427, respectively; P < 0.05).By inhibiting COX-2, PGE(2) synthesis, and VEGF and MMP-2 mRNA expression in tumor tissue, celecoxib enhances tumor cell apoptosis, thereby inhibiting the growth and angiogenesis of orthotopically implanted tumors in a mouse model of human colorectal cancer.
Asthma is a disease characterized by airway hyperresponsiveness and airway inflammation. Icaritin (ICT) is a plant hormone with various pharmacological activities such as anti-inflammatory, immune regulation, and anti-tumor. This study mainly explored the effects of nebulized inhalation of ICT on airway inflammation and airway remodeling in asthmatic mice.
Abstract Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and uncertain outcomes pose obstacles. microRNAs regulate genes involved in apoptosis, angiogenesis, and myocardial contraction, making them valuable for long-term repair. In this study, we find downregulated miR-199a-5p expression in MI. Intramyocardial injection of miR-199a-5p into the infarcted region of male rats revealed its dual protective effects on the heart. Specifically, miR-199a-5p targets AGTR1, diminishing early oxidative damage post-myocardial infarction, and MARK4, which influences long-term myocardial contractility and enhances cardiac function. To deliver miR-199a-5p efficiently and specifically to ischemic myocardial tissue, we use CSTSMLKAC peptide to construct P-MSN/miR199a-5p nanoparticles. Intravenous administration of these nanoparticles reduces myocardial injury and protects cardiac function. Our findings demonstrate the effectiveness of P-MSN/miR199a-5p nanoparticles in repairing MI through enhanced contraction and anti-apoptosis. miR199a-5p holds significant therapeutic potential for long-term repair of myocardial infarction.
Flame-retardant rigid polyurethane foam was prepared using a one-step method of all-water foaming in this paper. Following an experimental investigation, the optimum water consumption was determined to be 1.4 g, the optimum addition of tin laurate catalyst was found to be 1 g, and the optimum value of isocyanate index was identified to be 1.1. The rigid polyurethane foam, which had been compounded with MEG, exhibited an oxygen index of 31% at a concentration of 25 wt% and a carbon residue of 34.9% at 570°C. In contrast, the rigid polyurethane foam compounded with MEG' exhibited a residual carbon of 39.3% at 570°C. Both methods demonstrated a notable enhancement in flame retardancy, although this was accompanied by a certain degree of reduction in compression properties. In comparison to the aforementioned methods, the rigid polyurethane foam compounded with MEG' has a less pronounced reduction in compression performance and a superior flame retardant effect.
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