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.     

The effect of organofunctional nanosilica on the cross-linking process and thermal resistance of UF resin

The paper investigates the effect of surface modification of fumed nanosilica with (3-aminopropyl)triethoxysilane (APTES) on the kinetics and thermal stability of urea-formaldehyde (UF) resin. In the course of the investigation, nanoparticles were modified with APTES in the ratio 1, 2, 3, 4 and 5 part by weight (PBW) per 100 PBW of SiO₂. The parameters of curing kinetics of the resin, the conversion degree and its thermal stability were determined with use of differential scanning calorimetry (DSC) and thermogravimetric analysis (TG). The effect of nanosilica silanization on the curing process of resin was evaluated by determining the gel time at 100 °C and the activation energy (E_a) of the cross-linking process, the initial and final temperature of the reaction (T_onset, T_endset), the maximum value of the exothermic peak (T_p), the amount of emitted heat (ΔH_Tp) and the conversion degree (α_Tp) that responds to T_p. With the maximum level of silica modification, we have noted a decrease in the reactivity of the resin, which is manifested by a slightly longer gel time of the resin as well as an increase in the value of activation energy of the cross-linking process. It is accompanied by a slight decrease of resin conversion degree α_Tp. The modification of silica, regardless of the amount of silane inoculated on its surface, results in the increase in the thermal stability of UF resin.     

Applicability of Field Plate in Double Channel GaN HEMT for Radio-Frequency and Power-Electronic Applications

Silicon - In the present communication, for the first time, applicability of Field Plate (FP) for Double Channel (DC) AlGaN/GaNHEMT is demonstrated. Impact of design space parameters such as field...     

Fire‐retardant hybrid thermosetting resins from unsaturated polyesters and polysilazanes

This introduces an organic–inorganic thermosetting hybrid resin system based on unsaturated polyester and polysilazanes. It shows the chemical modification of unsaturated polyester structures by end capping to enable the combination of both components. In general, halogen‐free unsaturated polyesters are not fire‐retardant and have to be equipped with additives. Fillers and intumescent additives are preponderantly used in today's fire‐retardant formulations. In contrast to these fire‐retardants, polysilazanes act as ceramizing agents. Polysilazanes are suitable fire‐retardants for resin transfer molding due to their low viscosity. Both burning behavior and glass transition temperature (T_g) are investigated as important application properties. In contrast to state‐of‐the‐art fire‐retardant formulations polysilazane‐based thermosetting hybrid resins burn with high intensity and fast extinction. Therefore, total heat and smoke emission is decreased. The formation of ceramic structures during burning results in high residual mechanical properties and a low mass loss. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40375.     

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.     

Role of Obesity,Physical Exercise,Adipose Tissue-Skeletal Muscle Crosstalk and Molecular Advances in Barrett’s Esophagus and Esophageal Adenocarcinoma

Both obesity and esophageal adenocarcinoma (EAC) rates have increased sharply in the United States and Western Europe in recent years. EAC is a classic example of obesity-related cancer where the risk of EAC increases with increasing body mass index. Pathologically altered visceral fat in obesity appears to play a key role in this process. Visceral obesity may promote EAC by directly affecting gastroesophageal reflux disease and Barrett’s esophagus (BE), as well as a less reflux-dependent effect, including the release of pro-inflammatory adipokines and insulin resistance. Deregulation of adipokine production, such as the shift to an increased amount of leptin relative to “protective” adiponectin, has been implicated in the pathogenesis of BE and EAC. This review discusses not only the epidemiology and pathophysiology of obesity in BE and EAC, but also molecular alterations at the level of mRNA and proteins associated with these esophageal pathologies and the potential role of adipokines and myokines in these disorders. Particular attention is given to discussing the possible crosstalk of adipokines and myokines during exercise. It is concluded that lifestyle interventions to increase regular physical activity could be helpful as a promising strategy for preventing the development of BE and EAC.     

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.     

Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia—The State-of-the-Art Knowledge and Future Prospects

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. Despite the enormous progress in ALL therapy, resulting in achieving a 5-year survival rate of up to 90%, the ambitious goal of reaching a 100% survival rate is still being pursued. A typical ALL treatment includes three phases: remission induction and consolidation and maintenance, preceded by a prednisone prephase. Poor prednisone response (PPR) is defined as the presence of ≥1.0 × 10⁹ blasts/L in the peripheral blood on day eight of therapy and results in significantly frequent relapses and worse outcomes. Hence, identifying risk factors of steroid resistance and finding methods of overcoming that resistance may significantly improve patients’ outcomes. A mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK) pathway seems to be a particularly attractive target, as its activation leads to steroid resistance via a phosphorylating Bcl-2-interacting mediator of cell death (BIM), which is crucial in the steroid-induced cell death. Several mutations causing activation of MAPK-ERK were discovered, notably the interleukin-7 receptor (IL-7R) pathway mutations in T-cell ALL and rat sarcoma virus (Ras) pathway mutations in precursor B-cell ALL. MAPK-ERK pathway inhibitors were demonstrated to enhance the results of dexamethasone therapy in preclinical ALL studies. This report summarizes steroids’ mechanism of action, resistance to treatment, and prospects of steroids therapy in pediatric ALL.     

Three Microbial Musketeers of the Seas: Shewanella baltica,Aliivibrio fischeri and Vibrio harveyi,and Their Adaptation to Different Salinity Probed by a Proteomic Approach

Osmotic changes are common challenges for marine microorganisms. Bacteria have developed numerous ways of dealing with this stress, including reprogramming of global cellular processes. However, specific molecular adaptation mechanisms to osmotic stress have mainly been investigated in terrestrial model bacteria. In this work, we aimed to elucidate the basis of adjustment to prolonged salinity challenges at the proteome level in marine bacteria. The objects of our studies were three representatives of bacteria inhabiting various marine environments, Shewanella baltica, Vibrio harveyi and Aliivibrio fischeri. The proteomic studies were performed with bacteria cultivated in increased and decreased salinity, followed by proteolytic digestion of samples which were then subjected to liquid chromatography with tandem mass spectrometry analysis. We show that bacteria adjust at all levels of their biological processes, from DNA topology through gene expression regulation and proteasome assembly, to transport and cellular metabolism. The finding that many similar adaptation strategies were observed for both low- and high-salinity conditions is particularly striking. The results show that adaptation to salinity challenge involves the accumulation of DNA-binding proteins and increased polyamine uptake. We hypothesize that their function is to coat and protect the nucleoid to counteract adverse changes in DNA topology due to ionic shifts.