Current editorial challenges

Since its foundation in 2002, Experimental and Clinical Sciences (EXCLI Journal) published more than 760 original articles and reviews, particularly in the field of cancer research (Abbastabar et al., 2018; Nojadeh et al., 2018; Karimian et al., 2018), cell biology (Li et al., 2017; Niknami et al., 2017; Ahmadi et al., 2017), toxicology (Randjelovic et al., 2017; Hassani et al., 2018; Nakhaee and Mehrpour, 2018), neurosciences (Farajdokht et al., 2017; Ebrahimi et al., 2017), drug discovery (Li et al., 2018; Khedher et al., 2017) and immunology (Fahimi et al., 2018; Sarvari et al., 2018). However, the editors are keen to keep a broad view of science and technology and also welcome manuscripts from other fields of life sciences and interdisciplinary studies. Our main criterion during the review process is the scientific quality of the study. Editors and reviewers focus particularly on whether the methods are sufficiently described, results are presented in a transparent way, have been sufficiently reproduced in independent experiments and justify the main conclusions. If this is the case, also confirmatory studies or studies reporting negative results may be published. Each manuscript should include a statement on the aim of the study and convincingly explain why the experiments are relevant. While a high degree of novelty is welcome, it is not our most important criterion in selecting manuscripts for publication

A concept for maximum exposure levels in cars

Emission of volatile organic substances (VOC) from articles inside a car may lead to adverse health effects in exposed drivers. Presently, no general concept to derive maximum exposure levels inside cars has been published. Therefore, we recommend techniques for three types of maximum exposure levels inside cars, namely for (i) chronic exposure to non-genotoxic substances (ELIA, chronic), (ii) short term exposure inside automotive vehicles (STELIA) and (iii) genotoxic substances acting by threshold mechanisms (ELIA, cm). For derivation of the ELIA, chronic, we recommend to start with a Lowest Observed Adverse Effect Level (LOEL) or a Benchmark Dose 10 (BMD10) and use a procedure including four steps: a. estimation of the No Observed Effect Level (NOEL), b. extrapolation from laboratory animal to man, c. extrapolation to the general population due to interindividual differences and d. extrapolation to continuous exposure. To derive STELIAs a three-step-procedure is recommended, starting with a LOEL and a. estimating the NOEL, b. extrapolating from animal to man and c. extrapolating to the general population. Derivation of ELIA, cm, the maximum exposure level for carcinogens acting by a threshold mechanism, is certainly the most problematic procedure. We recommend to start with the lower 95% confidence limit for the most sensitive tumor type known in animals (BMD05) and a. extrapolate from animal to man and b. use a safety factor of 1/50 000 unless specific research succeeded in demonstrating specific levels of thresholds. It must be considered that a general concept for maximum exposure levels can not replace an intelligent toxicological approach considering the mechanism of action of individual substances. However, the strategy suggested here offers a practical technique for identification of individual problematic exposures that require an intensive toxicological evaluation

Natural Killer Cells and Liver Fibrosis

In the 40 years since the discovery of natural killer (NK) cells, it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue-resident NK cells with distinct phenotypical and functional characteristics have been identified. Here, we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects

Review of the First Fraunhofer Life Science Symposium on Cell Therapy and Immunology

This report covers recent advances in Regenerative Medicine with a special focus on (i) imaging of regeneration, (ii) nanotechnology and tissue engineering, (iii) immunological cell tolerance, (iv) cell therapies in cardiovascular, neurodegenerative, and liver diseases and in spinal regeneration

Gender specific expression of tumor suppressor PKCd versus oncogenic PKCn in renal cell carcinoma

Tumor incidence for renal cell carcinoma is two-fold higher in males than in females. Members of the protein kinase C (PKC) gene family have been shown to be relevant for carcinogenesis. However, little is known about a possible gender specific role of PKC in renal cell carcinoma (RCC). In this study, we quantified expression of eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue. A possible association of PKC-isoforms with gender of the patients was examined. Tissue specimens of 27 patients, 14 males and 13 females, with ccRCC and of the corresponding normal renal tissue were examined. Expression of PKC-isoforms were detected by Western blot analysis and quantified by computer-aided integration. In ccRCCs, as well as in the corresponding normal renal tissue, all PKC-isoforms except PKCy and 0 were detectable. Clear associations with gender of the patients were observed: (i) PKCd was reduced in tumor tissue of female patients (p = 0.023), but not of male patients (p = 0.198). (ii) A 3.6-fold enhanced expression of the oncogene PKC? was found in tumor tissue of female compared to male patients (p = 0.049). Gender specific differences in PKCd as well as PKCn expression suggest that different molecular mechanisms are relevant for carcinogenesis of ccRCC in male and female patients. This may become important for classification and treatment of ccRCC

Detoxification Strategy of Epoxide Hydrolase

The human microsomal epoxide hydrolase, a single enzyme, has to detoxify a broad range of structurally diverse, potentially genotoxic epoxides that are formed in the course of xenobiotic metabolism. The enzyme has developed a unique strategy to combine a broad substrate specificity with a high detoxification efficacy, by immediately trapping the reactive compounds as covalent intermediates and by being expressed at high levels for high trapping capacity. Computer simulation and experimental data as well as existing epidemiologic studies reveal this detoxification strategy as the mechanistic basis for a threshold in the tumorigenesis of mutagenic carcinogens