Intermittent Fasting Primes the Tumor Microenvironment and Improves Nanomedicine Delivery in Hepatocellular Carcinoma

Fasting has many health benefits, including reduced chemotherapy toxicity and improved efficacy. It is unclear how fasting affects the tumor microenvironment (TME) and tumor-targeted drug delivery. Here the effects of intermittent (IF) and short-term (STF) fasting are investigated on tumor growth, TME composition, and liposome delivery in allogeneic hepatocellular carcinoma (HCC) mouse models. To this end, mice are inoculated either subcutaneously or intrahepatically with Hep-55.1C cells and subjected to IF for 24 d or to STF for 1 d. IF but not STF significantly slows down tumor growth. IF increases tumor vascularization and decreases collagen density, resulting in improved liposome delivery. In vitro, fasting furthermore promotes the tumor cell uptake of liposomes. These results demonstrate that IF shapes the TME in HCC towards enhanced drug delivery. Finally, when combining IF with liposomal doxorubicin treatment, the antitumor efficacy of nanochemotherapy is found to be increased, while systemic side effects are reduced. Altogether, these findings exemplify that the beneficial effects of fasting on anticancer therapy outcomes go beyond modulating metabolism at the molecular level.     

Web accessibility implementation in private sector organizations: motivations and business impact

Despite the prominence of the World Wide Web in people’s everyday lives, most Web presences in private sector organizations still fail to comply with contemporary accessibility standards. As a consequence, a large group of users—i.e., people with impairments—are excluded from accessing these Web presences. In order to explain the managerial rationale, an exploratory case study was conducted in three industry sectors. The results of the analysis shed light on organizations’ motivations to implement or reject Web accessibility standards, reveal positive and negative consequences of implementation, and provide in-depth insights into the determinants for successful and unsuccessful Web accessibility implementation. This study supports organizations in making better decisions on the implementation of Web accessibility.     

Dye and polymer based light sensor for tag integration

In this work we present a light sensor for tag integration based on the principle of a dye sensitized solar cell, using a flexible substrate and a polymer electrolyte. These features make an integration of the light sensor into current smart label fabrication processes possible. A printable light sensor combined with novel conductive polymers could solve reliability issues resulting from bonding processes. The components of the light sensor were chosen in a way to enable screen print production. The dye Ruthenium 535-bis-TBA has been used as active dye and Iodolyte AN-50 by Solaronix and PEDOT/PSS by H.C. Starck have been used as liquid and polymer electrolyte respectively. In order to prepare the liquid electrolyte for tag integration it has been gelatinized by addition of silica gel. Depending on the amount of silica gel different stiffness levels have been achieved. The functional layers have been deposited first on glass substrate and then on KAPTON foil by Du Pont. The polymer has been used as flexible substrate. Special care has been taken regarding the preparation of the transparent electrode. The transparent conductive oxide (TCO) indium tin oxide (ITO), which has been used as transparent electrode, has to be cured at elevated temperatures on the polymer substrate. A complete process flow for an integrated light sensor is being described in this work.     

Towards a comprehensive proteome of normal and malignant human colon tissue by 2-D-LC-ESI-MS and 2-DE proteomics and identification of S100A12 as potential cancer biomarker

The aim of this study was to characterize the proteome of normal and malignant colonic tissue. We previously studied the colon proteome using 2‐DE and MALDI‐MS and identified 734 proteins (Roeßler, M., Rollinger, W., Palme S., Hagmann, M.‐L., et al.., Clin. Cancer Res. 2005, 11, 6550–6557). Here we report the identification of additional colon proteins from the same set of tissue samples using a complementary nano‐flow 2‐D‐LC‐ESI‐MS. In total, 484 proteins were identified in colon. Of these, 252 had also been identified by the 2‐DE/MALDI‐MS approach, whereas 232 proteins were unique to the 2‐D‐LC‐ESI‐MS analysis. Comparing protein expression in neoplastic and normal colon tissue indicated elevated expression of several proteins in colorectal cancer, among them the well established tumor marker carcinoembryonic antigen, as well as calnexin, 40S ribosomal protein S15a, serpin H1, and S100A12. Overexpression of these proteins was confirmed by immunoblotting. Serum levels of S100A12 were determined by ELISA and were found to be strongly elevated in colorectal cancer patients compared to healthy individuals. We conclude, that 2‐D‐LC‐ESI‐MS is a powerful approach to identify and compare protein profiles of tissue samples, that it is complementary to 2‐DE/MALDI‐MS approaches and has the potential to identify novel biomarkers.     

Nonlinear guided waves in multilayer systems

A nonlinear matrix formalism that allows the calculation of the optical field within a nonlinear multilayer system is presented. Taking advantage of this technique, the field profiles are calculated and the dispersion relation of nonlinear guided waves in such configurations is derived. The numerical results reveal that several field profiles occur, each attached to a certain unit cell of the multilayer system. The various field profiles apply to the corresponding branches of rich structured nonlinear dispersion curves. A comparison of the results of those yielded by an effective medium model is carried out. Appreciable differences are found and are discussed in detail     

Plant-to-Plant Variability in Root Metabolite Profiles of 19 Arabidopsis thaliana Accessions Is Substance-Class-Dependent

Natural variation of secondary metabolism between different accessions of Arabidopsis thaliana (A. thaliana) has been studied extensively. In this study, we extended the natural variation approach by including biological variability (plant-to-plant variability) and analysed root metabolic patterns as well as their variability between plants and naturally occurring accessions. To screen 19 accessions of A. thaliana, comprehensive non-targeted metabolite profiling of single plant root extracts was performed using ultra performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) and gas chromatography/electron ionization quadrupole mass spectrometry (GC/EI-QMS). Linear mixed models were applied to dissect the total observed variance. All metabolic profiles pointed towards a larger plant-to-plant variability than natural variation between accessions and variance of experimental batches. Ratios of plant-to-plant to total variability were high and distinct for certain secondary metabolites. None of the investigated accessions displayed a specifically high or low biological variability for these substance classes. This study provides recommendations for future natural variation analyses of glucosinolates, flavonoids, and phenylpropanoids and also reference data for additional substance classes.     

Electrochemical conversion of 4-alkyloxytoluenes to cyclic and non-cyclic 4-alkyloxybenzaldehyde acetals. A new approach to liquid-crystalline 1,3-dioxanes

4-Ethoxytoluenes bearing substituents in the -position such as a hydroxy group, a halogen atom, or an ester group were anodically oxidized to give the corresponding benzaldehydes or their derivatives (dimethyl acetals, hydrogen sulphite addition products). The electrochemical oxidation of 4-alkyloxytoluenes in alcoholic solutions in the presence of alkanediols led to cyclic acetals, e.g. 1,3-dioxolanes and 1,3-dioxanes. Various 2,5-disubstituted 1,3-dioxanes were thus prepared, the trans isomers exhibiting liquid-crystalline properties. The ratio of cis and trans isomers formed during the electrolysis was found to be in correspondence with the thermodynamic equilibrium.This paper is dedicated to Professor Dr Fritz Beck on the occasion of his 60th birthday.     

The aflatoxin situation in Africa: Systematic literature review

Contamination of African staple foods is a major issue for human and animal health, nutrition, and trade. This review aimed to collect and synthesize the available evidence on geographical spread, scale of contamination, disease burden, economic impact, and mitigation measures for aflatoxins in Africa by way of a systematic literature review. This knowledge can enhance management strategies for the major challenges to combat aflatoxins. The search was conducted by applying a predefined search strategy, using bibliographic databases and websites, covering the period 2010 to 2018. Results showed that maize, peanuts, and animal feeds were the most studied commodities. For maize, all studies indicated mean AFB₁ to exceed the European Union legal limit. From studies on contamination levels and biomarkers, it is clear that overall exposure is high, leading to a substantial increase in long-term disease burden. In addition, concentrations in food occasionally can reach very high levels, causing acute aflatoxicoses. The trade-related impact of aflatoxin contamination was mainly evaluated from the standpoint of aflatoxin regulation affecting products imported from Africa. There was a limited number of studies on health-related economic impacts, pointing out a gap in peer-reviewed literature. A number of mitigation measures have been developed, but proof of cost-effectiveness or even costs alone of the practices is often lacking. We recommend more emphasis to be put in peer-reviewed studies on evidence-based cost-effective mitigation strategies for aflatoxins, on the scale and spread of the problem and its impacts on public health and economics for use in evidence-based policies.     

Chemokine CXCL10 Modulates the Tumor Microenvironment of Fibrosis-Associated Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) constitutes a devastating health burden. Recently, tumor microenvironment-directed interventions have profoundly changed the landscape of HCC therapy. In the present study, the function of the chemokine CXCL10 during fibrosis-associated hepatocarcinogenesis was analyzed with specific focus on its impact in shaping the tumor microenvironment. C57BL/6J wild type (WT) and Cxcl10 knockout mice (Cxcl10^−/−) were treated with diethylnitrosamine (DEN) and tetrachloromethane (CCl₄) to induce fibrosis-associated HCCs. Cxcl10 deficiency attenuated hepatocarcinogenesis by decreasing tumor cell proliferation as well as tumor vascularization and modulated tumor-associated extracellular matrix composition. Furthermore, the genetic inactivation of Cxcl10 mediated an alteration of the tumor-associated immune response and modified chemokine/chemokine receptor networks. The DEN/CCl₄-treated Cxcl10^−/− mice presented with a pro-inflammatory tumor microenvironment and an accumulation of anti-tumoral immune cells in the tissue. The most striking alteration in the Cxcl10^−/− tumor immune microenvironment was a vast accumulation of anti-tumoral T cells in the invasive tumor margin. In summary, our results demonstrate that CXCL10 exerts a non-redundant impact on several hallmarks of the tumor microenvironment and especially modulates the infiltration of anti-tumorigenic immune cells in HCC. In the era of microenvironment-targeted HCC therapies, interfering with CXCL10 defines a novel asset for further improvement of therapeutic strategies.