Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

<p>Abstract</p> <p>Background</p> <p>Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN.</p> <p>Methods</p> <p>Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD₅₀) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters.</p> <p>Results</p> <p>After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group.</p> <p>Conclusions</p> <p>The results revealed that the LD₅₀of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity.</p

Optimization of Tensile Shear Strength of Linear Mechanically Welded Outer-to-Inner Flattened Moso Bamboo (Phyllostachys pubescens)

International audienceMechanical welding technology has been widely employed in the making of bonding joints with wood. Moso bamboo, a lignocellulosic biomaterial, can also be bonded using mechanical welding technology. The surface response methodology was used to define welding parameters yielding optimal joint strength. In the range of this experiment, it was found that the vibration amplitude and the welding pressure both had a significant influence on the performance of the joint, while the welding time did not. The quadratic model was able to significantly fit the actual results and could be used to determine and optimize the bonding strength

Prevalence and Clustering of Cardiovascular Risk Factors among Medical Staff in Northeast China

Background: The clustering of cardiovascular disease (CVD) risk factors has become a major public health challenge worldwide. Although many studies have investigated CVD risk factor clusters, little is known about their prevalence and clustering among medical staff in Northeast China. This study aimed to estimate the prevalence and clustering of CVD risk factors and to investigate the association between relevant characteristics and the clustering of CVD risk factors among medical staff in Northeast China. Methods: A cross-sectional survey of 3720 medical staff from 93 public hospitals in Jilin Province was used in this study. Categorical variables were presented as percentages and were compared using the χ2 test. Multiple logistic regression analysis was used to evaluate the association between relevant characteristics and the clustering of CVD risk factors. Results: The prevalence of hypertension, diabetes, dyslipidemia, being overweight, smoking, and drinking were 10.54%, 3.79%, 17.15%, 39.84%, 9.87%, and 21.75%, respectively. Working in a general hospital, male, and age group 18–44 years were more likely to have 1, 2, and ≥3 CVD risk factors, compared with their counterparts. In particular, compared with being a doctor, being a nurse or medical technician was less likely to have 1, 2, and ≥3 CVD risk factors only in general hospitals. Conclusions: The findings suggest that medical staff of general hospitals, males, and older individuals have a high chance associated with CVD risk factor clustering and that more effective interventions should be undertaken to reduce the prevalence and clustering of CVD risk factors, especially among older male doctors who work in general hospitals

Morphological Development of Sub-Grain Cellular/Bands Microstructures in Selective Laser Melting

In this paper, single-layer and bulk 316 L selective laser melting (SLM) experiments were conducted, fine submicron-scale geometric symmetrical cellular (hexagonal, pentagonal and square), elongated cellular and bands solidification morphologies were found in the laser-melt top surface. Meanwhile, morphological developed sub-grain patterns with quasi-hexagonal cellular, elongated cellular and bands structures (size ~1 &#956;m) coexisting inside one single macro-solidified grain were also identified. This demonstrated the transitions from quasi-hexagonal-cells to elongated cells/bands, and transitions reverse, occurred in the whole bulk under some circumstances during SLM. Based on the experimental realities, these morphologies are formed by the local convection and B&#233;nard instabilities in front of the solid/liquid interface (so-called mushy zones) affected by intricate temperature and surface tension gradients. Quasi-hexagonal cellular convective fields are then superimposed on macro-grain solidification to form the sub-grain patterns and micro-segregations. This explanation seems reasonable and is unifying as it can be expanded to other eutectic alloys with face center cubic (FCC) prevenient phase prepared by SLM, e.g., the Al-Si and Co-Cr-Mo systems

Differences in small noncoding RNAs profile between bull X and Y sperm

The differences in small noncoding RNAs (sncRNAs), including miRNAs, piRNAs, and tRNA-derived fragments (tsRNAs), between X and Y sperm of mammals remain unclear. Here, we employed high-throughput sequencing to systematically compare the sncRNA profiles of X and Y sperm from bulls (n = 3), which may have a wider implication for the whole mammalian class. For the comparison of miRNA profiles, we found that the abundance of bta-miR-652 and bta-miR-378 were significantly higher in X sperm, while nine miRNAs, including bta-miR-204 and bta-miR-3432a, had greater abundance in Y sperm (p < 0.05). qPCR was then used to further validate their abundances. Subsequent functional analysis revealed that their targeted genes in sperm were significantly involved in nucleosome binding and nucleosomal DNA binding. In contrast, their targeted genes in mature oocyte were significantly enriched in 11 catabolic processes, indicating that these differentially abundant miRNAs may trigger a series of catabolic processes for the catabolization of different X and Y sperm components during fertilization. Furthermore, we found that X and Y sperm showed differences in piRNA clusters distributed in the genome as well as piRNA and tsRNA abundance, two tsRNAs (tRNA-Ser-AGA and tRNA-Ser-TGA) had lower abundance in X sperm than Y sperm (p < 0.05). Overall, our work describes the different sncRNA profiles of X and Y sperm in cattle and enhances our understanding of their potential roles in the regulation of sex differences in sperm and early embryonic development

Transcriptional regulation of increased CCL2 expression in pulmonary fibrosis involves nuclear factor-kappa B and activator protein-1

National Natural Science Foundation of China [30900661, 81072208]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry; Science Foundation of Shantou University Medical College; Basic Science and Clinical Research Foundation of Shantou University Medical CollegeChemokine (CC motif) ligand-2 (CCL2) is a member of C-C chemokine superfamily that contributes to inflammatory and fibrotic process. Studies in patients and experimental animals provide compelling evidence that increased CCL2 expression plays an important role in the development of fibroproliferative lung disease. The up-regulated CCL2 expression in pulmonary fibrosis is also involved in the potent profibrotic effects that thrombin exerts during lung injury. Here, we investigated the transcriptional mechanism involved in CCL2 production by thrombin in human primary lung fibroblasts and explored the transcriptional mechanism of increased CCL2 expression in pulmonary fibrosis. Thrombin increased CCL2 mRNA levels but not mRNA stability, suggesting it was acting transcriptionally. The increased binding of transcription factors to nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) elements in the CCL2 promoter contributed to active transcription following thrombin stimulation. Primary human lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF) produced significantly higher levels of CCL2 than nonfibrotic lung fibroblasts. Furthermore, chromatin immunoprecipitation assays detected increased binding of NF-kappa B p65 and AP-1 subunit c-Jun to the CCL2 promoter of IPF cells both in the presence and absence of thrombin stimulation. The significantly increased binding of p65 and c-Jun to the CCL2 promoter was also observed in the lung tissue of bleomycin-induced pulmonary fibrosis murine model. Collectively, these findings strongly suggest that the increased binding of transcription factors to NF-kappa B and AP-1 elements in the CCL2 promoter is responsible for the active transcription expression of CCL2 in pulmonary fibrosis. (C) 2013 Elsevier Ltd. All rights reserved