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.     

Production of in situ aluminum-titanium diboride master alloy formed by slag-metal reaction

Al-TiB₂ master alloys have received much attention in recent years owing to their potential as efficient grain refiners for aluminum foundry alloys. In this study, the process of production of master alloys was investigated to develop a low cost method, namely, slag-metal reaction. This method can be used to fabricate Al-TiB₂ master alloy in situ from the TiO₂-H₃BO₃-Na₃AlF₆ and Al system. Since the price of the raw materials is low and the technology is simple, the processing technique appears to reduce the cost of the master alloy. Because of exothermic reactions, not much energy is needed to melt materials. In this process, Titanium diboride particles were formed in situ through the reactions of TiO₂, H₃BO₃ and Na₃AlF₆. Results showed that when the aluminum melted, the condensed TiB₂ particles that formed in situ were spherical with an average diameter of 1 μm. Furthermore, these TiB₂ particles were distributed uniformly through the master alloy.     

Improved cytotoxicity testing of magnesium materials

Metallic magnesium (Mg) and its alloys are highly suitable for medical applications as biocompatible and biodegradable implant materials. Magnesium has mechanical properties similar to bone, stimulates bone regeneration, is an essential non-toxic element for the human body and degrades completely within the body environment. In consequence, magnesium is a promising candidate as implant material for orthopaedic applications. Protocols using the guideline of current ISO standards should be carefully evaluated when applying them for the characterization of the cytotoxic potential of degradable magnesium materials. For as-cast material we recommend using 10 times more extraction medium than recommended by the ISO standards to obtain reasonable results for reliable cytotoxicity rankings of degradable materials in vitro. In addition primary isolated human osteoblasts or mesenchymal stem cells should be used to test magnesium materials.     

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.     

传统建筑意趣的现代诠释

文章结合杭州西溪新天地的设计分析,从空间序列的建构、文化氛围的建构以及其中人员活动的建构等方面,讨论了现代开发方式与传统街坊理念之间的平衡之道。     

An in-vitro method for prediction of the digestible crude protein content in pig feeds

An in-vitro method using commercially available enzymes for the prediction of the in-vivo digestible crude protein content was developed and tested on seven feedstuffs and 16 diets for pigs. Fat-extracted feed samples were consecutively incubated with pepsin at pH 1 and pancreatin at pH 6.8. From the nitrogen content of the feed sample and of the residue after incubation the in-vitro digestibility of the crude protein was calculated. Using the linear regression of in-vitro on in-vivo digestible crude protein of samples obtained in feeding trials, the in-vivo digestible crude protein content (DXP_p) in g kg^?1 dry matter could be predicted. For feedstuffs and diets the correlation was 0.99 and 0.95 and the residual standard deviation 17 and 6 g kg^?1 dry matter, respectively. In a similar procedure the nitrogen solubilised during incubation with enzymes was analysed. The regression value was similar to that of the original procedure. However, this procedure was abandoned because it was more laborious.     

Non-starch polysaccharides of canola meal: Quantification,digestibility in poultry and potential benefit of dietary enzyme supplementation

The non-starch polysaccharide (NSP) content as determined by gas chromatography (component neutral sugars) and colorimetry (uronic acids) was shown to be 16–22% in ten different samples of defatted canola (low glucosinolate rapeseed) seed. The non-cellulosic components of NSP accounted for 13–16% of the meal and on average consisted of arabinose (33%), xylose (13%), galactose (13%), glucose (5%), mannose (3%), rhamnose (2%), fucose (2%) and uronic acids (30%). Yellow-seeded and brown-seeded samples of canola contained similar contents of total dietary fibre although the composition of the fibre components tended to differ with the former showing a low content of lignin and associated polyphenols and a high content of NSP as compared with the latter type. NDF values tended to be lower for yellow-seeded than for brown-seeded canola due to the relatively high content of NSP in neutral detergent solubles of yellow-seeded canola. An initial balance study with laying hens showed low (<3%) digestibility of the polysaccharide components, and further studies were conducted with a commercial enzyme preparation (SP249, Novo Laboratories Ltd, Lachine, Quebec) to enhance the in-vivo hydrolysis of the NSP fraction of the meal. Laying hens were fed a semipurified diet containing 40% commercial canola meal with and without enzyme (1%). NSP digestibility was increased to 37% by the enzyme supplementation.