Effect of postmolding heat treatment on in vitro properties of a polyanhydride implant containing gentamicin sulfate

A polyanhydride implant containing gentamicin sulfate was fabricated using a laboratory-scale injection-molding machine. After injection molding, the implants were subject to heat treatment at 60°C for various time periods with or without nitrogen protection. The impact of this heat treatment on the in vitro properties of the implants including copolymer molecular weights, mechanical properties, and in vitro drug-release profiles was investigated. This heat treatment caused a drastic drop in the molecular weight of the copolymer. Heating without nitrogen protection resulted in the hardening of the implant, but heating in the presence of nitrogen rendered the implant less rigid. It was also found that a faster in vitro drug release profile was shown by implants heated without nitrogen protection and a pronounced slowing down in drug release was exhibited by implants heated with nitrogen protection.     

Elevation of Tear MMP-9 Concentration as a Biomarker of Inflammation in Ocular Pathology by Antibody Microarray Immunodetection Assays

Matrix metalloproteinases are a family of enzymes fundamental in inflammatory processes. Between them, MMP-9 is up-regulated during inflammation; thus, its quantification in non-invasive fluids is a promising approach for inflammation identification. To this goal, a biomarker quantification test was developed for ocular inflammation detection using anti-MMP-9 antibody microarrays (AbMAs). After validation with eight healthy control tear samples characterized by ELISA, 20 samples were tested from individuals diagnosed with ocular inflammation due to: cataracts, glaucoma, meibomian gland dysfunction, allergy, or dry eye. Concentration values of tear MMP-9 were obtained for each sample, and 12 patients surpassed the pathological threshold (30 ng/mL). A significant elevation of MMP-9 concentration in the tears of glaucoma patients compared with healthy controls was observed. In order to evaluate the diagnostic ability, an ROC curve analysis was performed using our data, determining the optimal threshold for the test at 33.6 ng/mL of tear MMP-9. In addition, a confusion matrix was applied, estimating sensitivity at 60%, specificity at 88%, and accuracy at 68%. In conclusion, we demonstrated that the AbMAs system allows the quantification of MMP-9 in pathologies that involve inflammation of the ocular surface.     

In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression

Cellular senescence is recognized as a dynamic process in which cells evolve and adapt in a context dependent manner; consequently, senescent cells can exert both beneficial and deleterious effects on their surroundings. Specifically, senescent mesenchymal stromal cells (MSC) in the bone marrow (BM) have been linked to the generation of a supporting microenvironment that enhances malignant cell survival. However, the study of MSC’s senescence role in leukemia development has been straitened not only by the availability of suitable models that faithfully reflect the structural complexity and biological diversity of the events triggered in the BM, but also by the lack of a universal, standardized method to measure senescence. Despite these constraints, two- and three dimensional in vitro models have been continuously improved in terms of cell culture techniques, support materials and analysis methods; in addition, research on animal models tends to focus on the development of techniques that allow tracking leukemic and senescent cells in the living organism, as well as to modify the available mice strains to generate individuals that mimic human BM characteristics. Here, we present the main advances in leukemic niche modeling, discussing advantages and limitations of the different systems, focusing on the contribution of senescent MSC to leukemia progression.     

Serum-Free Cultures: Could They Be a Future Direction to Improve Neuronal Differentiation of Mesenchymal Stromal Cells?

Mesenchymal stem/stromal cells (MSCs) are undifferentiated cells with multilinear potential, known for their immunomodulatory and regenerative properties. Although the scientific community is working to improve their application, concerns limit their use to repair tissues following neurological damage. One of these obstacles is represented by the use of culture media supplemented with fetal bovine serum (FBS), which, due to its xenogenic nature and the risk of contamination, has increased scientific, ethical and safety problems. Therefore, the use of serum-free media could improve MSC culture methods, avoiding infectious and immunogenic transmission problems as well as MSC bioprocesses, without the use of animal components. The purpose of our review is to provide an overview of experimental studies that demonstrate that serum-free cultures, along with the supplementation of growth factors or chemicals, can lead to a more defined and controlled environment, enhancing the proliferation and neuronal differentiation of MSCs.     

The EPH/Ephrin System in Bone and Soft Tissue Sarcomas’ Pathogenesis and Therapy: New Advancements and a Literature Review

Musculoskeletal sarcomas represent rare heterogenous malignancies of mesenchymal origin that can be divided in two distinct subtypes, bone and soft tissue sarcomas. Current treatment options combine the surgical excision of local tumors and multidrug chemotherapy to prevent metastatic widespread disease. Due to the grim prognosis that usually accompanies such tumors, researchers have attempted to shed light on the molecular pathways implicated in their pathogenesis in order to develop novel, innovative, personalized therapeutic strategies. Erythropoietin-producing human hepatocellular receptors (EPHs) are tyrosine-kinase transmembrane receptors that, along with their ligands, ephrins, participate in both tumor-suppressive or tumor-promoting signaling pathways in bone and soft tissue sarcomas. The EPH/ephrin axis orchestrates cancerous processes such as cell–cell and cell–substrate adhesion and enhances the remodeling of the intracellular cytoskeleton to stimulate the motility and invasiveness of sarcoma cells. The purpose of our study was to review published PubMed literature to extract results from in vitro, in vivo and clinical trials indicative of the role of EPH/ephrin signaling in bone and soft tissue sarcomas. Based on these reports, significant interactions between the EPH/ephrin signaling pathway and a plethora of normal and abnormal cascades contribute to molecular mechanisms enhancing malignancy during sarcoma progression. In addition, EPHs and ephrins are prospective candidates for diagnostic, monitoring and therapeutic purposes in the clinical setting against bone and soft tissue sarcomas.     

In Vivo and In Vitro Degradation Behavior of Magnesium Alloys as Biomaterials

The corrosion behavior of pure Mg,AZ31,and AZ91D were evaluated in various in vitro and in vivo environments to investigate the potential application of these metals as biodegradable implant materials.DC polarization tests and immersion tests were performed in different simulated body solutions,such as distilled(DI) water,simulated body fluid(SBF) and phosphate buffered solution(PBS).Mg/Mg alloys were also implanted in different places in a mouse for in vivo weight loss and biocompatibility investigations.The in vivo subcutis bio-corrosion rate was lower than the corrosion rate for all of the in vitro simulated corrosive environments.The Mg/Mg alloys were biocompatible based on histology results for the liver,heart,kidney,skin and lung of the mouse during the two months implantation.Optical microscopy and scanning electron microscopy were carried out to investigate the morphology and topography of Mg/Mg alloys after immersion testing and implantation to understand the corrosion mechanisms.     

In vitro and in vivo determinations of sun protection factors of sunscreen lotions with octylmethoxycinnamate

The aim of this work was to evaluate the correlation between in vitro and in vivo determinations of sun protection factors (SPF) of sunscreen lotions containing the synthetic sunscreen octyl methoxycinnamate. Three sunscreen lotions containing either 2, 4.5 or 7.5% octyl methoxycinnamate were prepared. The in vitro SPFs of these sunscreen lotions were determined according to the spectrophotometric method of Mansur et al. The in vivo SPF values were determined according to the Food and Drug Administration (FDA) method. The results indicate that there was a good correlation between the in vitro and in vivo determinations for the sunscreen lotions examined.     

一种基于DCT系数重组的降参考3D视频质量评价方法

针对3D视频质量评价,提出了一种基于离散余弦变 换(DCT)系数重组的降参考质量评价方法。方法主要 包括4D数据集构造、DCT变换与重组和降参考(RR)质量评价3个阶段。在4D数据集构造阶段 ,通过联合视 频的空间域、视点域和时间域信息构造包含3D视频全部信息的4D数据集;在DCT变换与重 组阶段,首 先对数据集进行DCT变换,然后筛选复杂度较高的DCT系数进行重组,得到能够表征3D视 频质量的重 组系数集;在RR质量评价阶段,首先采用广义高斯分布(GGD)函数对重组后DCT系数集的每 个子带进行建模, 然后利用系数距离函数和频率比距离函数评估3D视频质量。实验结果表明,本文提出的方 法与主观评价结果有较好的相关性,符合人类视觉系统(HVS)。