BMP9-Induced Survival Effect in Liver Tumor Cells Requires p38MAPK Activation

The study of bone morphogenetic proteins (BMPs) role in tumorigenic processes, and specifically in the liver, has gathered importance in the last few years. Previous studies have shown that BMP9 is overexpressed in about 40% of hepatocellular carcinoma (HCC) patients. In vitro data have also shown evidence that BMP9 has a pro-tumorigenic action, not only by inducing epithelial to mesenchymal transition (EMT) and migration, but also by promoting proliferation and survival in liver cancer cells. However, the precise mechanisms driving these effects have not yet been established. In the present work, we deepened our studies into the intracellular mechanisms implicated in the BMP9 proliferative and pro-survival effect on liver tumor cells. In HepG2 cells, BMP9 induces both Smad and non-Smad signaling cascades, specifically PI3K/AKT and p38MAPK. However, only the p38MAPK pathway contributes to the BMP9 growth-promoting effect on these cells. Using genetic and pharmacological approaches, we demonstrate that p38MAPK activation, although dispensable for the BMP9 proliferative activity, is required for the BMP9 protective effect on serum withdrawal-induced apoptosis. These findings contribute to a better understanding of the signaling pathways involved in the BMP9 pro-tumorigenic role in liver tumor cells.     

Addressing Nanomaterial Immunosafety by Evaluating Innate Immunity across Living Species

The interaction of a living organism with external foreign agents is a central issue for its survival and adaptation to the environment. Nanosafety should be considered within this perspective, and it should be examined that how different organisms interact with engineered nanomaterials (NM) by either mounting a defensive response or by physiologically adapting to them. Herein, the interaction of NM with one of the major biological systems deputed to recognition of and response to foreign challenges, i.e., the immune system, is specifically addressed. The main focus is innate immunity, the only type of immunity in plants, invertebrates, and lower vertebrates, and that coexists with adaptive immunity in higher vertebrates. Because of their presence in the majority of eukaryotic living organisms, innate immune responses can be viewed in a comparative context. In the majority of cases, the interaction of NM with living organisms results in innate immune reactions that eliminate the possible danger with mechanisms that do not lead to damage. While in some cases such interaction may lead to pathological consequences, in some other cases beneficial effects can be identified.     

Bacterial lipopolysaccharide increases interleukin-6 and prostaglandin release in rat cortical type I astrocytes by different mechanisms: role of anti-inflammatory agents

LPS stimulated IL-6 release in a concentration-dependent manner from rat cortical type I astrocytes. This stimulatory action was completely abolished by Dexamethasone (DEX), but was not affected by indomethacin (IND), a 5-cyclooxigenase inhibitor. LPS-induced IL-6 release was partially inhibited by BW 4AC, a 5-lipoxygenase inhibitor. LPS concentration-dependently increased the release of PGE2 from type I astrocytes, an effect completely inhibited by IND. To rule out the possibility that DEX was inhibiting LPS-induced IL-6 release by blocking IL-6 gene expression, we tested the effect of DEX on interleukin 1beta(IL-1)-induced IL-6 release. DEX slightly inhibited IL-1-induced IL-6 release, while IL-1 releasing action on IL-6 was significantly reduced by IND. The involvement of nitric oxide (NO) generation on LPS-induced IL-6 release was also studied. We found that L-NO-arginine, an inhibitor of nitric oxide synthase, concentration-dependently reduced LPS-induced IL-6 release in astrocytes. In conclusion, we provide evidence that LPS action on IL-6 and PGE2 release can be ascribed to the activation of different transduction mechanisms, which can be pharmacologically dissected with the aid of anti-inflammatory drugs.     

Excellent Intrinsic Long-Term Thermal Stability of Co-Evaporated MAPbI3 Solar Cells at 85 °C

Thermal stability is a critical criterion for assessing the long-term stability of perovskite solar cells (PSCs). Here, it is shown that un-encapsulated co-evaporated MAPbI₃ (TE_MAPbI₃) PSCs demonstrate remarkable thermal stability even in an n-i-p structure that employs Spiro-OMeTAD as hole transport material (HTM). TE_MAPbI₃ PSCs maintain over ≈95% and ≈80% of their initial power conversion efficiency (PCE) after 1000 and 3600 h respectively under continuous thermal aging at 85 °C. TE_MAPbI₃ PSCs demonstrate remarkable structural robustness, absence of pinholes, or significant variation in grain sizes, and intact interfaces with the HTM, upon prolonged thermal aging. Here, the main factors driving TE_MAPbI₃ stability are assessed. It is demonstrated that the excellent TE_MAPbI₃ thermal stability is related to the perovskite growth process leading to a compact and almost strain-stress-free film. On the other hand, un-encapsulated PSCs with the same architecture, but incorporating solution-processed MAPbI₃ or Cs_0.05(MA_0.17FA_0.83)_0.95Pb(I_0.83Br_0.17)₃ as active layers, show a complete PCE degradation after 500 h under the same thermal aging condition. These results highlight that the control of the perovskite growth process can substantially enhance the PSCs thermal stability, besides the chemical composition. The TE_MAPbI₃ impressive long-term thermal stability features the potential for field-operating conditions.     

Nanowire Assisted Mechanotyping of Cellular Metastatic Potential

Nanotechnology has provided tools for next generation biomedical devices which rely on nanostructure interfaces with living cells. In vitro biomimetic structures have enabled observation of cell response to various mechanical and chemical cues, and there is a growing interest in isolating and harnessing the specific cues that 3D microenvironments can provide without the requirement for such culture and the experimental drawbacks associated with it. Here, a randomly oriented gold coated Si nanowire substrate with patterned hydrophobic–hydrophilic areas for the differentiation of isogenic breast cancer cells of varying metastatic potential is reported. When considering synthetic surfaces for the study of cell-nanotopography interfaces, randomly oriented nanowires more closely resemble the isotropic architecture of a natural extracellular matrix. In the study reported here, the authors show that primary cancer cells preferably attach to the hydrophilic region of randomly oriented nanowire substrate while secondary cancer cells do not adhere. Using machine learning analysis of fluorescence images, cells are found to spread and elongate on the nanowire substrates as compared to a flat substrate, where they mostly remain round. Such platforms can not only be used for developing bioassays but also as stepping stones for tissue printing technologies where cells can be selectively patterned at desired locations.     

The dimerization domain of LFB1/HNF1 related transcription factors: a hidden four helix bundle?

LFB1/HNF1 and LFB3/HNF1ß bind DNA as dimers and formheterodimers together in vivo and in vitro. The dimerizationdomain has been located in both proteins in the 32 N-terminalresidues. In previous papers we have described the conformationalstability as determined by CD and the secondary structure byNMR studies of a peptide with the amino acid sequence of thedimerization domain of LFB1/ HNF1. This study presents a morecomplete characterization of similar synthetic peptides spanningthe LFB3/HNF1ß dimerization domain and the /ßheterodimer. The HNF1 peptides represent an example of structureswhich cannot be determined by NOE data alone because they arenot sufficient to define one unique solution. An approach ispresented which combines NMR data, the protein structure databaseand structural analyses according to known principles of proteinstructure. On this basis we are able to determine possible solutionsand to identify a four helix bundle as the structure most consistentwith the experimental evidence.