Angiopoietin-like Proteins in Colorectal Cancer—A Literature Review

Colorectal cancer (CRC) is one of the most common types of malignancy, with an annual incidence of about 10% of the total number of new cases. Despite well-developed screening tests, mortality from this type of cancer remains unchanged. Therefore, it is important to search for more accurate markers that are useful in the detection of colorectal cancer (especially in its early stages), and treatment. Angiopoietin-like proteins (ANGPTLs) are a family of eight proteins with a diversity of applications, including pro- and anti-angiogenic properties. Consequently, we performed an extensive search of the literature, pertaining to our investigation, via the MEDLINE/PubMed database. Based on the available literature, we summarize that some of those proteins are characterized by increased or decreased concentrations during the course of CRC. We can also assume that some ANGPTLs can inhibit the development of CRC, while others induce its progress. Moreover, some factors are dependent on the stage or histological type of the tumor, the presence of hypoxia, or metastases. Most importantly, some ANGPTLs can be useful in anti-cancer therapy. Therefore, further studies on ANGPTLs as potential markers of CRC should be continued.     

Highly Enantioselective Production of (R)-Halohydrins with Whole Cells of Rhodotorula rubra KCh 82 Culture

Biotransformation of ten α-haloacetophenones in the growing culture of the strain Rhodotorula rubra KCh 82 has been carried out. Nine of the substrates underwent an effective enantioselective reduction to the respective (R)-alcohols according to Prelog’s rule, with the exception of 2-chloro-1,2-diphenylethan-1-one that was not transformed by this strain. The expected reduction proceeded without dehalogenation, leading to the respective (R)-halohydrins in high yields. The use of this biocatalyst yielded (R)-2-bromo-1-phenyl-ethan-1-ol (enantiomeric excess (ee) = 97%) and its derivatives: 4''-Bromo- (ee = 99%); 4''-Chloro- (ee > 99%); 4''-Methoxy- (ee = 96%); 3''-Methoxy- (ee = 93%); 2''-Methoxy- (ee = 98%). There were also obtained and characterized 2,4''-dichloro-, 2,2'',4''-trichloro- and 2-chloro-4''-fluoro-phenyetan-1-ol with >99% of enantiomeric excesses.     

Surface chemistry of SnO2 nanowires on Ag-catalyst-covered Si substrate studied using XPS and TDS methods

In this paper we investigate the surface chemistry, including surface contaminations, of SnO₂ nanowires deposited on Ag-covered Si substrate by vapor phase deposition (VPD), thanks to x-ray photoelectron spectroscopy (XPS) in combination with thermal desorption spectroscopy (TDS). Air-exposed SnO₂ nanowires are slightly non-stoichiometric, and a huge amount of C contaminations is observed at their surface. After the thermal physical desorption (TPD) process, SnO₂ nanowires become almost stoichiometric without any surface C contaminations. This is probably related to the fact that C contaminations, as well as residual gases from air, are weakly bounded to the crystalline SnO₂ nanowires and can be easily removed from their surface. The obtained results gave us insight on the interpretation of the aging effect of SnO₂ nanowires that is of great importance for their potential application in the development of novel chemical nanosensor devices.     

Chrysin,Apigenin and Acacetin Inhibit Tumor Necrosis Factor-Related Apoptosis—Inducing Ligand Receptor-1 (TRAIL-R1) on Activated RAW264.7 Macrophages

Expression level of Tumor Necrosis Factor—related apoptosis—inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4'' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity) of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide)-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages.     

3D printing hybrid organometallic polymer‐based biomaterials via laser two‐photon polymerization

Materials with microscale structures are gaining increasing interest due to their range of technical and medical applications. Additive manufacturing approaches to such objects via laser two‐photon polymerization, also known as multiphoton fabrication, enable the creation of new materials with diverse and tunable properties. Here, we investigate the properties of 3D structures composed of organometallic polymers incorporating aluminium, titanium, vanadium and zirconium. The organometallic polymer‐based materials were analysed using a variety of techniques including SEM, energy‐dispersive X‐ray spectroscopy, X‐ray photoelectron spectroscopy analysis and contact angle measurements and their biocompatibility was tested in vitro. Cell viability and mode of death were determined by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay and acridine orange/ethidium bromide staining. Polymers incorporating Al, Ti and Zr supported cell adhesion and proliferation, and showed low toxicity in vitro, whereas the organometallic polymer incorporating V was shown to be cytotoxic. Inductively coupled plasma optical emission spectrometry suggested that leaching of the V from the organometallic polymer is the likely cause of this. The preparation of the organometallic polymers is straightforward and both simple 2D and complex 3D structures can be fabricated with ease. Resolution tests of the newly developed organometallic polymer incorporating Al show that suspended lines with widths down to 200 nm can be fabricated. We believe that the materials described in this work show promising properties for the development of objects with sub‐micron features for biomedical applications (e.g. biosensors, drug delivery devices, tissue scaffolds etc.). © 2019 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Computer-Aided Search for 5-Arylideneimidazolone Anticancer Agents Able To Overcome ABCB1-Based Multidrug Resistance

ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar.     

Can Developments in Tissue Optical Clearing Aid Super-Resolution Microscopy Imaging?

The rapid development of super-resolution microscopy (SRM) techniques opens new avenues to examine cell and tissue details at a nanometer scale. Due to compatibility with specific labelling approaches, in vivo imaging and the relative ease of sample preparation, SRM appears to be a valuable alternative to laborious electron microscopy techniques. SRM, however, is not free from drawbacks, with the rapid quenching of the fluorescence signal, sensitivity to spherical aberrations and light scattering that typically limits imaging depth up to few micrometers being the most pronounced ones. Recently presented and robustly optimized sets of tissue optical clearing (TOC) techniques turn biological specimens transparent, which greatly increases the tissue thickness that is available for imaging without loss of resolution. Hence, SRM and TOC are naturally synergistic techniques, and a proper combination of these might promptly reveal the three-dimensional structure of entire organs with nanometer resolution. As such, an effort to introduce large-scale volumetric SRM has already started; in this review, we discuss TOC approaches that might be favorable during the preparation of SRM samples. Thus, special emphasis is put on TOC methods that enhance the preservation of fluorescence intensity, offer the homogenous distribution of molecular probes, and vastly decrease spherical aberrations. Finally, we review examples of studies in which both SRM and TOC were successfully applied to study biological systems.     

Molecular Network Approach Reveals Rictor as a Central Target of Cardiac ProtectomiRs

Cardioprotective medications are still unmet clinical needs. We have previously identified several cardioprotective microRNAs (termed ProtectomiRs), the mRNA targets of which may reveal new drug targets for cardioprotection. Here we aimed to identify key molecular targets of ProtectomiRs and confirm their association with cardioprotection in a translational pig model of acute myocardial infarction (AMI). By using a network theoretical approach, we identified 882 potential target genes of 18 previously identified protectomiRs. The Rictor gene was the most central and it was ranked first in the protectomiR-target mRNA molecular network with the highest node degree of 5. Therefore, Rictor and its targeting microRNAs were further validated in heart samples obtained from a translational pig model of AMI and cardioprotection induced by pre- or postconditioning. Three out of five Rictor-targeting pig homologue of rat ProtectomiRs showed significant upregulation in postconditioned but not in preconditioned pig hearts. Rictor was downregulated at the mRNA and protein level in ischemic postconditioning but not in ischemic preconditioning. This is the first demonstration that Rictor is the central molecular target of ProtectomiRs and that decreased Rictor expression may regulate ischemic postconditioning-, but not preconditioning-induced acute cardioprotection. We conclude that Rictor is a potential novel drug target for acute cardioprotection.     

Targeted Therapy in the Treatment of Pediatric Acute Lymphoblastic Leukemia—Therapy and Toxicity Mechanisms

Targeted therapy has revolutionized the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) with specific genetic abnormalities. It is still being described as a new landmark therapeutic approach. The main purpose of the use of molecularly targeted drugs and immunotherapy in the treatment of ALL is to improve the treatment outcomes and reduce the doses of conventional chemotherapy, while maintaining the effectiveness of the therapy. Despite promising treatment results, there is limited clinical research on the effect of target cell therapy on the potential toxic events in children and adolescents. The recent development of highly specific molecular methods has led to an improvement in the identification of numerous unique expression profiles of acute lymphoblastic leukemia. The detection of specific genetic mutations determines patients’ risk groups, which allows for patient stratification and for an adjustment of the directed and personalized target therapies that are focused on particular molecular alteration. This review summarizes the knowledge concerning the toxicity of molecular-targeted drugs and immunotherapies applied in childhood ALL.