Innate immunity, oxidative stress and body indices of Eurasian perch Perca fluviatilis after two weeks of exposure to artificial light at night

Artificial light at night (ALAN) can disrupt biological rhythms of fish and other vertebrates by changing the light information of the nocturnal environment. Disrupted biorhythms can impair the immune system of vertebrates as it has been shown for conditions with continuous illumination or long-day photoperiod in many vertebrates, including fish. Nonetheless, this has not been shown so far for typical ALAN scenarios with high light intensities during day and low light intensities at night. Therefore, in this study, proxies for the innate immune system and oxidative stress as well as body indices of Eurasian perch Perca fluviatilis were measured under a wide range of intensities of nocturnal illumination. The authors found no changes in parameters of the innate immune system and no significant changes in proxies for oxidative stress after 2-week exposures to nocturnal illuminance ranging from 0.01 lx to 1 lx in one experiment or from 1 lx to 100 lx in a second experiment. A decrease in the hepato-somatic index at the highest tested light intensity of 100 lx compared to the dark control was the only significant difference in all parameters among treatments. After 2 weeks of exposure, ALAN does not seem to seriously challenge the innate immune system and seems to cause less oxidative stress than expected. The results of this study contradict the findings from other studies applying continuous illumination or long-day photoperiod and highlight the importance of further research in this field. Because ALAN represents a sustained modulation of the environment that may have cumulative effects over time, long-term studies are required for a better understanding of how ALAN modulates the health of fish.Leibniz Association http://dx.doi.org/10.13039/501100001664Peer Reviewe

Glucocorticoid effects in the regenerating fin reflect tissue homeostasis disturbances in zebrafish by affecting Wnt signaling

As a treatment for various immune-mediated diseases, the use of glucocorticoids as anti-inflammatory and immunosuppressive agents is common practice. However, their use is severely hampered by the risk of the development of adverse effects such as secondary osteoporosis, skin atrophy, and peptic ulcer formation. The exact molecular and cellular mechanisms underlying those adverse effects, which involve most major organ systems, are not yet fully understood. Therefore, their investigation is of great importance to improve treatment regimens for patients. Here, we investigated the effects of the glucocorticoid prednisolone on cell proliferation and Wnt signaling in homeostatic skin and intestinal tissue and compared them to the anti-regenerative effects in zebrafish fin regeneration. We also investigated a potential recovery from the glucocorticoid treatment and the impact of short-term treatment with prednisolone. We identified a dampening effect of prednisolone on Wnt signaling and proliferation in highly proliferative tissues, namely the skin and intestine, as well as reduced fin regenerate length and Wnt reporter activity in the fin. The presence of the Wnt inhibitor Dickkopf1 was enhanced in prednisolone treated skin tissue. A decreased number of mucous producing goblet cells was observed in the intestine of prednisolone treated zebrafish. Unexpectedly, proliferation in bone forming osteoblasts of the skull, homeostatic scales, as well as the brain was not decreased, opposite to the observed effects in the skin, fin, and intestine. Short-term treatment with prednisolone for a few days did not significantly alter fin regenerate length, skin cell proliferation, intestinal leukocyte number and proliferation of intestinal crypt cells. However, it affected the number of mucous-producing goblet cells in the gut. Likewise, discontinuation of prednisolone treatment for a few days saved the skin and intestine from a significant reduction of skin and intestinal cell proliferation, intestinal leukocyte number and regenerate length, but did not rescue goblet cell number. The suppressive effects of glucocorticoids in highly proliferative tissues may be relevant in the context of their therapeutic applications in patients with inflammatory diseases

Preclinical assessment of CAR-NK cell-mediated killing efficacy and pharmacokinetics in a rapid zebrafish xenograft model of metastatic breast cancer

Natural killer (NK) cells are attractive effectors for adoptive immunotherapy of cancer. Results from first-in-human studies using chimeric antigen receptor (CAR)-engineered primary NK cells and NK-92 cells are encouraging in terms of efficacy and safety. In order to further improve treatment strategies and to test the efficacy of CAR-NK cells in a personalized manner, preclinical screening assays using patient-derived tumor samples are needed. Zebrafish (Danio rerio) embryos and larvae represent an attractive xenograft model to study growth and dissemination of patient-derived tumor cells because of their superb live cell imaging properties. Injection into the organism’s circulation allows investigation of metastasis, cancer cell-to-immune cell-interactions and studies of the tumor cell response to anti-cancer drugs. Here, we established a zebrafish larval xenograft model to test the efficacy of CAR-NK cells against metastatic breast cancer in vivo by injecting metastatic breast cancer cells followed by CAR-NK cell injection into the Duct of Cuvier (DoC). We validated the functionality of the system with two different CAR-NK cell lines specific for PD-L1 and ErbB2 (PD-L1.CAR NK-92 and ErbB2.CAR NK-92 cells) against the PD-L1-expressing MDA-MB-231 and ErbB2-expressing MDA-MB-453 breast cancer cell lines. Injected cancer cells were viable and populated peripheral regions of the larvae, including the caudal hematopoietic tissue (CHT), simulating homing of cancer cells to blood forming sites. CAR-NK cells injected 2.5 hours later migrated to the CHT and rapidly eliminated individual cancer cells throughout the organism. Unmodified NK-92 also demonstrated minor in vivo cytotoxicity. Confocal live-cell imaging demonstrated intravascular migration and real-time interaction of CAR-NK cells with MDA-MB-231 cells, explaining the rapid and effective in vivo cytotoxicity. Thus, our data suggest that zebrafish larvae can be used for rapid and cost-effective in vivo assessment of CAR-NK cell potency and to predict patient response to therapy

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutDFG, 80750187, SFB 841: Leberentzündungen: Infektion, Immunregulation und KonsequenzenEC/H2020/800924/EU/International Cancer Research Fellowships - 2/iCARE-2DFG, 252623821, Die Rolle von follikulären T-Helferzellen in T-Helferzell-Differenzierung, Funktion und PlastizitätDFG, 390873048, EXC 2151: ImmunoSensation2 - the immune sensory syste

Use of medicines by adults in Germany

The use of medicines is an essential aspect of treating disease. In this field, surveys that map the population’s use of medicines are of particular interest. The GEDA 2014/2015-EHIS study collected data on the use of medically prescribed and self-medicated drugs during the two weeks that preceded the survey. 58.9% of women and 52.0% of men reported that they had taken medically prescribed drugs during this period. 48.5% of women and 35.4% of men stated they had taken medication during this period that had not been prescribed by a doctor. The prevalence of the use of medically prescribed drugs and self-medication was higher among women than among men. Finally, the prevalence of the use of medically prescribed drugs increased significantly with age, whereas the prevalence of self-medication decreased with age

Arzneimittelanwendung von Erwachsenen in Deutschland

Der Einsatz von Arzneimitteln ist ein wesentlicher Bestandteil der Behandlung von Krankheiten. Daher sind Erhebungen, die das Anwendungsverhalten in der Bevölkerung abbilden, von besonderem Interesse. In der Studie GEDA 2014/2015-EHIS wurde die Anwendung von ärztlich verordneten und in Selbstmedikation eingesetzten Medikamenten in den letzten zwei Wochen vor der Befragung erhoben. 58,9 % der Frauen und 52,0 % der Männer gaben an, in den letzten zwei Wochen ärztlich verordnete Medikamente eingenommen zu haben. 48,5 % der Frauen und 35,4 % der Männer gaben an, in den letzten zwei Wochen Medikamente eingenommen zu haben, die nicht ärztlich verordnet waren. Die Anwendungsprävalenzen der Frauen bei ärztlich verordneter und Selbst medikation lagen über denen der Männer. Während die Anwendungsprävalenz ärztlich verordneter Arzneimittel mit dem Alter deutlich anstieg, nahm die Anwendungsprävalenz von Selbstmedikation mit dem Alter eher ab

Prevalence of hysterectomy in women 18 to 79 years old

In many countries, hysterectomy is one of the most frequently performed surgical procedures in gynaecology. The aim of this study is to analyse the prevalence of hysterectomy in Germany by sociodemographic factors and factors of (reproductive) health. Analyses are based on data from the German Health Interview and Examination Survey for Adults (DEGS1), which is part of the health monitoring of the Robert Koch Institute (RKI). The prevalence of hysterectomy among participating women (18–79 years old) was 17.5% (n=689). Most women (49.1%) were 40–49 years old when surgery was performed; 6.1% of hysterectomised women had cancer of the uterus or ovaries, and 19.7% underwent a simultaneous oophorectomy. There were significant differences in the prevalence of hysterectomy regarding social status, place of residence in 1988, number of live births, and body weight. DEGS1 is the first study showing the prevalence of hysterectomy in a representative sample of the German population. More detailed analyses of the DEGS data, among other data sources, are needed to evaluate the importance of the described associations and to assess trends

Laser-mediated osteoblast ablation triggers a pro-osteogenic inflammatory response regulated by reactive oxygen species and glucocorticoid signaling in zebrafish

In zebrafish, transgenic labeling approaches, robust regenerative responses and excellent in vivo imaging conditions enable precise characterization of immune cell behavior in response to injury. Here, we monitored osteoblast-immune cell interactions in bone, a tissue which is particularly difficult to in vivo image in tetrapod species. Ablation of individual osteoblasts leads to recruitment of neutrophils and macrophages in varying numbers, depending on the extent of the initial insult, and initiates generation of cathepsin K+ osteoclasts from macrophages. Osteoblast ablation triggers the production of pro-inflammatory cytokines and reactive oxygen species, which are needed for successful macrophage recruitment. Excess glucocorticoid signaling as it occurs during the stress response inhibits macrophage recruitment, maximum speed and changes the macrophage phenotype. Although osteoblast loss is compensated for within a day by contribution of committed osteoblasts, macrophages continue to populate the region. Their presence is required for osteoblasts to fill the lesion site. Our model enables visualization of bone repair after microlesions at single-cell resolution and demonstrates a pro-osteogenic function of tissue-resident macrophages in non-mammalian vertebrates