Tumor-tropic Trojan horses: Using mesenchymal stem cells as cellular nanotheranostics.

Various classes of nanotheranostics have been developed for enhanced tumor imaging and therapy. However, key limitations for a successful use of nanotheranostics include their targeting specificity with limited off-site tissue accumulation as well as their distribution and prolonged retention throughout the entire tumor. Due to their inherent tumor-tropic properties, the use of mesenchymal stem cells (MSCs) as a "Trojan horse" has recently been proposed to deliver nanotheranostics more effectively. This review discusses the current status of "cellular nanotheranostics" for combined (multimodal) imaging and therapy in preclinical cancer models. Emphasis is placed on the limited knowledge of the signaling pathways and molecular mechanisms of MSC tumor-tropism, and how such information may be exploited to engineer MSCs in order to further improve tumor homing and nanotheranostic delivery using image-guided procedures.

Retention of Phthalates in Wine Using Nanomaterials as Chemically Modified Clays with H20, H30, H40 Boltron Dendrimers.

The presence of phthalic acid esters in wines presents a major risk to human health due to their very toxic metabolism. In this paper, aluminosilicate materials were used, with the aim of retaining various pollutants and unwanted compounds in wine. The pollutants tested were di-butyl and di-ethyl hexyl phthalates. They were tested and detected using the gas chromatography-mass spectrometry (CG-MS) analytical technique. Nanomaterials were prepared using sodium bentonite, and were chemically modified via impregnation using three types of Boltron dendrimers of second, third and fourth generations (NBtH20, NBtH30 and NBtH40). The synthesized nanomaterials were characterized using the Brunauer-Emmett-Teller (BET) method, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis. In this paper, two aspects were addressed: the first related to the retention of phthalate-type pollutants (phthalic acid esters-PAEs) and the second related to the protein and polyphenol levels in the white wine of the Aligoté grape variety. The results obtained in this study have a major impact on PAEs in wine, especially after treatment with NBtH30 and NBtH40 (volumes of 250-500 µL/10 mL wine), with the retention of the pollutants being up to 85%.

An Adaptive Algorithm and Additively Manufactured Punch Used to Form Aluminum Sheet Metal Parts.

Self-adaptive mechanisms are gaining momentum in industrial processes. It is understandable that as the complexity increases, the human work must be augmented. Considering this, the authors have developed one such solution for the punch-forming process, using additive manufacturing, i.e., a 3D-printed punch, to draw into shape 6061-T6 aluminum sheets. This paper aims to highlight the topological study used to optimize the punch form shape, the methodology of the 3D printing process, and the material used. For the adaptive algorithm, a complex Python-to-C++ bridge was created. It was necessary as the script has computer vision (used for calculating stroke and speed), punch force, and hydraulic pressure measurement capabilities. The algorithm uses the input data to control its subsequent actions. Two approaches are used in this experimental paper, a pre-programmed direction and an adaptive one, for comparison purposes. The results, namely the drawing radius and flange angle, were statistically analyzed using the ANOVA methodology for significance. The results indicate significant improvements when using the adaptive algorithm.

Comparative Determination of Cytotoxicity of Sub-10 nm Copper Nanoparticles to Prokaryotic and Eukaryotic Systems.

Copper nanoparticles demonstrate antibacterial activity, but their toxicity to eukaryotic systems is less understood. Here, we carried out a comparative study to determine the biocompatibility and cytotoxicity of sub-10 nm copper nanoparticles to a variety of biological systems, including prokaryotic cells (Escherichia coli), yeast, mammalian cell lines (HEK293T, PC12), and zebrafish embryos. We determined the bearing threshold for the cell-death-inducing concentration of copper nanoparticles by probing cell growth, viability, as well as embryological features. To exclude the partial toxicity effect from the remnant reactants, we developed a purification approach using agarose gel electrophoresis. Purified CuONP solution inhibits bacterial growth and causes eukaryotic cell death at 170 and 122.5 ppm (w/w) during the 18 h of treatment, respectively. CuONP significantly reduces the pigmentation of retina pigmented epithelium of zebrafish embryos at 85 ppm. The cytotoxicity of CuONP in eukaryotic cells could arise from the oxidative stress induced by CuONP. This result suggests that small copper nanoparticles exert cytotoxicity in both prokaryotic and eukaryotic systems, and therefore, caution should be used to avoid direct contact of copper nanoparticles to human tissues considering the potential use of copper nanoparticles in the clinical setting.

Persistent Basophilia May Suggest an "Accelerated Phase" in the Evolution of CALR-Positive Primary Myelofibrosis Toward Acute Myeloid Leukemia.

Basophils are white blood cells that play an important role in the human immune system. These cells physiologically increase in number in immune response to certain allergies, chronic inflammation, and parasitic infections. Basophils are also a significant indicator for the presence of certain malignancies such as chronic myeloproliferative neoplasms and acute myeloid leukemia. In the current manuscript we present a statistically significant correlation between persistent basophilia in primary myelofibrosis (PMF) and the risk for the subsequent development of acute myeloid leukemia. We have retrospectively identified in the files of the Department of Hematology, Ion Chiricuta Clinical Cancer Center in Cluj Napoca, Romania 623 consecutive patients diagnosed with AML over a period spanning from 2008 to 2018. We afterwards identified 32 patients with AML diagnosis following a previous diagnosis of myelofibrosis (either post-PV, post-ET, or post-PMF). All the patients were diagnosed according to the WHO criteria. We subsequently established a control group consisting of 32 patients with underlying BCR-ABL-negative MPN who did not develop AML (AML-negative group). Following this, we assessed whether the AML-negative patients from our control group also had a persistent (>3 months) absolute basophilia. When comparing both groups of patients with myelofibrosis, the group with subsequent AML development and the one without AML, the follow-up did not present statistically significant differences between the two groups. In the univariate analysis, patients who progressed to AML had more frequently basophilia, longer basophilia duration, higher pre-therapy absolute, and relative basophil count and presented more frequently calreticulin (CALR) mutations. In the current study, we emphasize the need for a closer clinical monitoring for chronic MPNs with marked basophilia, with an important potential clinical impact.

Fibroblast dynamics as an in vitro screening platform for anti-fibrotic drugs in primary myelofibrosis.

Although the cause for bone marrow fibrosis in patients with myelofibrosis remains controversial, it has been hypothesized that it is caused by extensive fibroblast proliferation under the influence of cytokines generated by the malignant megakaryocytes. Moreover, there is no known drug therapy which could reverse the process. We studied the fibroblasts in a novel system using the hanging drop method, evaluated whether the fibroblasts obtain from patients are part of the malignant clone of not and, using this system, we screen a large library of FDA-approved drugs to identify potential drugs candidates that might be useful in the treatment of this disease, specifically which would inhibit fibroblast proliferation and the development of bone marrow fibrosis. We have found that the BM fibroblasts are not part of the malignant clone, as previously suspected and two immunosuppressive medications-cyclosporine and mycophenolate mophetil, as most potent suppressors of the fibroblast collagen production thus potentially inhibitors of bone marrow fibrosis production in myelofibrosis.

Adult acute megakaryoblastic leukemia: rare association with cytopenias of undetermined significance and p210 and p190 BCR-ABL transcripts.

Acute megakaryocytic leukemia (M7-AML) is a rare form of acute myeloid leukemia (AML), which is associated with poor prognosis. The case presented in the current report is a statement for the difficult diagnosis and clinical management of M7-AML in the context of a previous hematologic disorder of undetermined significance and associated genetic abnormalities. Probably, following the complete hematologic remission and further with induction chemotherapy plus tyrosine kinase inhibitor therapy, the clinical management of this case will be followed by a allogeneic bone marrow transplantation, the only proven therapy to improve overall survival.

Synthesis of alkylated potato starch derivatives and their potential in the aqueous solubilization of benzo[a]pyrene.

For the development of renewable bioproducts able to solubilize organic persistent pollutant such as benzo[a]pyrene (BaP), modified potato starch was synthesized by alkylation. The addition of alkyl chains was performed with three different alkylation agents: epoxyalkane, alkenyl succinic anhydride and 1,4-butane sultone. Twelve alkylated starches were obtained with different molar substitutions (MS) and various alkyl chain lengths (to three carbons up to sixteen). The chemical structural characteristics were investigated by methods of (1)H NMR and FTIR. In comparison with the native starch, the ether modified starches showed in general an enhancement of their aqueous solubility whereas the ester modified starches stimulated the BaP aqueous solubilization. Indeed, the compounds P6 and P12, which increased 40-fold the BaP aqueous concentration, present high surfactant properties.