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In the last decade, zebrafish have accompanied the mouse as a robust animal model for cancer research. The possibility of screening small-molecule inhibitors in a large number of zebrafish embryos makes this model particularly valuable. However, the dynamic visualization of fluorescently labeled tumor cells needs to be complemented by a more sensitive, easy, and rapid mode for evaluating tumor growth in vivo to enable high-throughput screening of clinically relevant drugs. In this study we proposed and validated a pre-clinical screening model for drug discovery by utilizing bioluminescence as our readout for the determination of transplanted cancer cell growth and inhibition in zebrafish embryos. For this purpose, we used NanoLuc luciferase, which ensured rapid cancer cell growth quantification in vivo with high sensitivity and low background when compared to conventional fluorescence measurements. This allowed us large-scale evaluation of in vivo drug responses of 180 kinase inhibitors in zebrafish. Our bioluminescent screening platform could facilitate identification of new small-molecules for targeted cancer therapy as well as for drug repurposing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hason, Jovicic, Vonkova, Bojic, Simon-Vermot, White and Bartunek.)

Macrophage colony-stimulating factor receptor (M-CSFR/CSF1R) signaling is crucial for the differentiation, proliferation, and survival of myeloid cells. The CSF1R pathway is a promising therapeutic target in many human diseases, including neurological disorders and cancer. Zebrafish are commonly used for human disease modeling and preclinical therapeutic screening. Therefore, it is necessary to understand the proper function of cytokine signaling in zebrafish to reliably model human-related diseases. Here, we investigate the roles of zebrafish Csf1rs and their ligands (Csf1a, Csf1b, and Il34) in embryonic and adult myelopoiesis. The proliferative effect of exogenous Csf1a on embryonic macrophages is connected to both receptors, Csf1ra and Csf1rb, however there is no evident effect of Csf1b in zebrafish embryonic myelopoiesis. Furthermore, we uncover an unknown role of Csf1rb in zebrafish granulopoiesis. Deregulation of Csf1rb signaling leads to failure in myeloid differentiation, resulting in neutropenia throughout the whole lifespan. Surprisingly, Il34 signaling through Csf1rb seems to be of high importance as both csf1rbΔ4bp-deficient and il34Δ5bp-deficient zebrafish larvae lack granulocytes. Our single-cell RNA sequencing analysis of adult whole kidney marrow (WKM) hematopoietic cells suggests that csf1rb is expressed mainly by blood and myeloid progenitors, and the expression of csf1ra and csf1rb is nonoverlapping. We point out differentially expressed genes important in hematopoietic cell differentiation and immune response in selected WKM populations. Our findings could improve the understanding of myeloid cell function and lead to the further study of CSF1R pathway deregulation in disease, mostly in cancerogenesis., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

This study compared women with binge eating disorders or bulimia nervosa with and without night eating syndrome regarding childhood maltreatment and psychopathology relative to healthy controls. The 426 participants (aged 18-60) were divided into two groups: eating disorders (n = 158) and healthy controls (n = 268). Eating disorders was divided into bulimia nervosa, binge eating disorder, and night eating syndrome with binge eating. Participants completed questionnaires: childhood trauma, eating disorders, self-esteem, and psychopathology. No significant differences were found for most variables in the eating disorders subgroups except physical neglect, which was more prevalent in night eating syndrome with binge eating. All variables differed significantly between eating disorders and healthy controls. Significant correlations emerged between childhood maltreatment, psychopathology, emotional abuse, and self-esteem in eating disorders. Regression showed that emotional abuse significantly predicted self-esteem in eating disorders, and group significantly moderated the effect of emotional abuse on psychopathology. Results emphasize that in this specific sample and variables, night eating syndrome with binge eating may be a variant of binge eating disorder or bulimia nervosa and not a separate diagnostic entity. The results highlight the importance of early assessment of childhood maltreatment, particularly emotional abuse, in patients with night eating syndrome., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Macrophages derive from multiple sources of hematopoietic progenitors. Most macrophages require colony-stimulating factor 1 receptor (CSF1R), but some macrophages persist in the absence of CSF1R. Here, we analyzed mpeg1 :GFP-expressing macrophages in csf1r -deficient zebrafish and report that embryonic macrophages emerge followed by their developmental arrest. In larvae, mpeg1 + cell numbers then increased showing two distinct types in the skin: branched, putative Langerhans cells, and amoeboid cells. In contrast, although numbers also increased in csf1r -mutants, exclusively amoeboid mpeg1+ cells were present, which we showed by genetic lineage tracing to have a non-hematopoietic origin. They expressed macrophage-associated genes, but also showed decreased phagocytic gene expression and increased epithelial-associated gene expression, characteristic of metaphocytes, recently discovered ectoderm-derived cells. We further demonstrated that juvenile csf1r -deficient zebrafish exhibit systemic macrophage depletion. Thus, csf1r deficiency disrupts embryonic to adult macrophage development. Zebrafish deficient for csf1r are viable and permit analyzing the consequences of macrophage loss throughout life., Competing Interests: LK, NO, GF, TM, MH, JD, MR, Hv, Pv, Ed, GS, EB, VW, Tv No competing interests declared, (© 2020, Kuil et al.)

Objective: This study aimed to compare dietary patterns (timing and frequency of binge episodes, caloric intake and macronutrient composition) of patients with binge eating disorders (BE) with and without night eating syndrome (NES)., Design: The study includes 59 women (18-60) who sought treatment for Eating Disorders (EDs) and were diagnosed with BED or BN (BE) with or without NES. They were divided into two groups: NES-BE and BE-only. The participants kept 7-day, 24-h food diaries and completed demographic and depression questionnaires., Results: NES-BE reported significantly a higher frequency of binge days and binge episodes during the week, and more energy and fat consumption than BE-only., Conclusions: Individuals with NES-BE exhibit higher levels of eating pathology than individuals with BE-only. Thus, NES-BE may not be simply a variant of BED or BN but rather a separate entity that may lead to a more severe disorder and require early assessment and more intensive and suitable treatment., Level of Evidence: Level V, cross-sectional descriptive study.

Zebrafish ( Danio rerio ) is a valuable non-mammalian vertebrate model widely used to study development and disease, including more recently cancer. The evolutionary conservation of cancer-related programs between human and zebrafish is striking and allows extrapolation of research outcomes obtained in fish back to humans. Zebrafish has gained attention as a robust model for cancer research mainly because of its high fecundity, cost-effective maintenance, dynamic visualization of tumor growth in vivo, and the possibility of chemical screening in large numbers of animals at reasonable costs. Novel approaches in modeling tumor growth, such as using transgene electroporation in adult zebrafish, could improve our knowledge about the spatial and temporal control of cancer formation and progression in vivo. Looking at genetic as well as epigenetic alterations could be important to explain the pathogenesis of a disease as complex as cancer. In this review, we highlight classic genetic and transplantation models of cancer in zebrafish as well as provide new insights on advances in cancer modeling. Recent progress in zebrafish xenotransplantation studies and drug screening has shown that zebrafish is a reliable model to study human cancer and could be suitable for evaluating patient-derived xenograft cell invasiveness. Rapid, large-scale evaluation of in vivo drug responses and kinetics in zebrafish could undoubtedly lead to new applications in personalized medicine and combination therapy. For all of the above-mentioned reasons, zebrafish is approaching a future of being a pre-clinical cancer model, alongside the mouse. However, the mouse will continue to be valuable in the last steps of pre-clinical drug screening, mostly because of the highly conserved mammalian genome and biological processes., Competing Interests: No conflicts of interest.