Polyurethane/Polylactide-Based Electrospun Nonwovens as Carriers for Human Adipose-Derived Stromal Stem Cells and Chondrogenic Progenitor Cells

Articular cartilage dysfunctions are major cause of pain and disability and lead to serious health complications. Cell-based therapies are proposed as treatment methods for cartilage regeneration. In this study, we proposed polyurethane/poly(L-lactide-co-D, L-lactide)-based electrospun nonwovens as carriers for the delivery of human adipose-derived stromal stem cells. We found that 6:4 and 8:2 polyurethane/poly(L-lactide-co-D, L-lactide) initially enhance proliferative rate of human adipose-derived stromal stem cells, shorten their population doubling time, promote creation of functional chondrogenic nodules during chondrogenic differentiation, improve the collagen-2-to-collagen-1 protein ratio, and upregulate the expression of collagen-2 and aggrecan genes.     

Effect of ALDH1A1 Gene Knockout on Drug Resistance in Paclitaxel and Topotecan Resistant Human Ovarian Cancer Cell Lines in 2D and 3D Model

Ovarian cancer is the most common cause of gynecological cancer death. Cancer Stem Cells (CSCs) characterized by drug transporters and extracellular matrix (ECM) molecules expression are responsible for drug resistance development. The goal of our study was to examine the role of aldehyde dehydrogenase 1A1 (ALDH1A1) expression in paclitaxel (PAC) and topotecan (TOP) resistant ovarian cancer cell lines. In both cell lines, we knocked out the ALDH1A1 gene using the CRISPR/Cas9 technique. Additionally, we derived an ALDH1A1 positive TOP-resistant cell line with ALDH1A1 expression in all cells via clonal selection. The effect of ALDH1A1 gene knockout or clonal selection on the expression of ALDH1A1, drug transporters (P-gp and BCRP), and ECM (COL3A1) was determined by Q-PCR, Western blot and immunofluorescence. Using MTT assay, we compared drug resistance in two-dimensional (2D) and three-dimensional (3D) cell culture conditions. We did not observe any effect of ALDH1A1 gene knockout on MDR1/P-gp expression and drug resistance in the PAC-resistant cell line. The knockout of ALDH1A1 in the TOP-resistant cell line resulted in a moderate decrease of BCRP and COL3A1 expression and weakened TOP resistance. The clonal selection of ALDH1A1 cells resulted in very strong downregulation of BCPR and COL3A1 expression and overexpression of MDR1/P-gp. This finally resulted in decreased resistance to TOP but increased resistance to PAC. All spheroids were more resistant than cells growing as monolayers, but the resistance mechanism differs. The spheroids’ resistance may result from the presence of cell zones with different proliferation paces, the density of the spheroid, ECM expression, and drug capacity to diffuse into the spheroid.     

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.     

Kinetic studies of dyes sorption from aqueous solutions onto the strongly basic anion-exchanger Lewatit MonoPlus M-600

The sorption of Tartrazine, Allura Red, Sunset Yellow and Indigo Carmine from aqueous solutions onto the strongly basic anion-exchanger (Lewatit MonoPlus M-600) of dimethylethanolamine functional groups and styrene–divinylbenzene matrix was investigated. The experimental data obtained at 50, 100, 200, 300 and 500 mg/dm³ initial concentrations at 20 °C were applied to the pseudo-first order, pseudo-second order and Weber–Morris kinetic models. The calculated sorption capacities (q_1,cal) and the rate constant of the first-order adsorption (k₁) were determined. The pseudo-second order kinetic constants (k₂) and capacities (q_2,cal) were calculated from the plots of t/q_t vs. t, 1/q_t vs. 1/t, 1/t vs. 1/q_t, q_t/t vs. q_t and 1/q₂ − q_t vs. t for type 1, type 2, type 3, type 4 and type 5 of the pseudo-second order expression, respectively.     

Application of Structure-Based Models of Mechanical and Thermal Properties on Plasma Sprayed Coatings

Mechanical and thermal properties of thermal sprayed coatings, especially ceramics, are strongly influenced by cracks and pores that are present in the coating microstructure. In the recent past, there have been efforts to find an analytical model describing the coating properties based on the microstructural characteristics. Various analytical models were developed and published in the literature. In this study, several major models were applied to ceramic and metal coatings to describe their elastic modulus and thermal conductivity. The sensitivity of the models to the variations in the microstructure and relevancy of their use in specific cases were examined. The results were compared with those obtained by FEM modeling and experimentally measured values.     

Carbon coating with combined super-hydrophobic and self-lubricating properties on titanium silicon carbide

Carbon coating on Ti₃SiC₂ with combined super-hydrophobic and self-lubricating properties was synthesized by chlorination at 1000 °C followed by modification of the CF₃(CF₂)₅CH₂CH₂SiCl₃ film. Raman spectroscopy confirmed the conversion from Ti₃SiC₂ to highly graphitized carbon coating. Scanning electron microscopy observation showed a highly porous microstructure of graphite flakes on the coating surface. The porous structure as well as organic film on carbon coating endowed the surface with super-hydrophobic property. Because of chemical inertia of the carbon coating and the modifier, the super-hydrophobic surface was very stable under various environments. Carbon coating was a good solid lubricant and greatly reduced friction coefficient of Ti₃SiC₂ sliding against Si₃N₄, which was important for Ti₃SiC₂ used as engineering material.     

Increasing recyclability of PC,ABS and PMMA: Morphology and fracture behavior of binary and ternary blends

Binary and ternary blends of PC, ABS, and PMMA were studied. The blends were produced from original and recycled materials by melt mixing in a wide range of compositions. Instrumented Charpy impact testing, tensile testing, rheology investigations, and electron microscopy were carried out to determine the relationship between the deformation and fracture behavior, blend composition, morphology, and processing parameters. Resistance against unstable crack propagation was evaluated using the concepts of J‐integral and crack‐tip‐opening displacement (CTOD). The transition from ductile elastic‐plastic to brittle‐linear elastic fracture behavior was observed in the case of PC/ABS/PMMA blend at 10% of PMMA. Reprocessing had only a slight influence on the deformation and fracture behavior of the recycled blends. The blends produced from recycled materials proved to be competitive with the original pure materials. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci 2008     

Tracking of Glycans Structure and Metallomics Profiles in BRAF Mutated Melanoma Cells Treated with Vemurafenib

Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) BRAF mutations. The studies were performed using α1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring BRAF mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas.     

Role of HMOX1 Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia

Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene (HMOX1) expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(−413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility. We found that the short alleles are significantly more frequent in ALL patients in comparison to the control group, and that their presence may be associated with a higher risk of treatment failure, reflecting the role of HO-1 in chemoresistance. We also observed that the presence of short alleles may predispose to develop chemotherapy-induced neutropenia. In case of SNP, the 413-T variant co-segregated with short or long alleles, while 413-A almost selectively co-segregated with long alleles, hence it is not possible to determine if SNPs are actually of phenotypic significance. Our results suggest that HO-1 can be a potential target to overcome the treatment failure in ALL patients.