The retinoids are a group of compounds including vitamin A and its active metabolite all-trans-retinoic acid (ATRA). Retinoids regulate a variety of physiological functions in multiple organ systems, are essential for normal immune competence, and are involved in the regulation of cell growth and differentiation. Vitamin A derivatives have held promise in cancer treatment and ATRA is used in differentiation therapy of acute promyelocytic leukemia (APL). ATRA and other retinoids have also been successfully applied in a variety of dermatological conditions such as skin cancer, psoriasis, acne, and ichthyosis. Moreover, modulation of retinoic acid receptors and retinoid X (or rexinoid) receptors function may affect dermal cells. The studies using complex genetic models with various combinations of retinoic acid receptors (RARs) and retinoid X (or rexinoid) receptors (RXRs) indicate that retinoic acid and its derivatives have therapeutic potential for a variety of serious dermatological disorders including some malignant conditions. Here, we provide a synopsis of the main advances in understanding the role of ATRA and its receptors in dermatology.
Immortalized cell lines are widely used in vitro tools in oncology and hematology research. While these cell lines represent artificial systems and may accumulate genetic aberrations with each passage, they are still considered valuable models for pilot, preliminary, and screening studies. Despite their limitations, cell lines are cost-effective and provide repeatable and comparable results. Choosing the appropriate cell line for acute myeloid leukemia (AML) research is crucial for obtaining reliable and relevant results. Several factors should be considered when selecting a cell line for AML research, such as specific markers and genetic abnormalities associated with different subtypes of AML. It is also essential to evaluate the karyotype and mutational profile of the cell line, as these can influence the behavior and response to the treatment of the cells. In this review, we evaluate immortalized AML cell lines and discuss the issues surrounding them concerning the revised World Health Organization and the French–American–British classifications.
Animal research undoubtedly provides scientists with virtually unlimited data but inflicts pain and suffering on animals. Currently, legislators and scientists alike are promoting alternative in vitro approaches allowing for an accurate evaluation of processes occurring in the body without animal sacrifice. Historically, one of the most infamous animal tests is the Draize test, mainly performed on rabbits. Even though this test was considered the gold standard for around 50 years, the Draize test fails to mimic human response mainly due to human and rabbit eye physiological differences. Therefore, many alternative assays were developed to evaluate ocular toxicity and drug effectiveness accurately. Here we review recent achievements in tissue engineering of in vitro 2D, 2.5D, 3D, organoid and organ-on-chip ocular models, as well as in vivo and ex vivo models in terms of their advantages and limitations.
Summary: Aberrant activity of the phosphatidylinositol‐3 kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR [PAM]) pathway, as well as suppressed retinoic acid signalling, contribute to enhanced proliferation and the differentiation blockade of immature myeloid cells in acute myeloid leukaemia (AML). Inhibition of the PAM pathway was shown to affect especially mixed‐lineage leukaemia‐rearranged AML. Here, we sought to test a combined strategy using small molecule inhibitors against members of the PAM signalling pathway in conjunction with all‐trans retinoic acid (ATRA) to target a larger group of different AML subtypes. We find that ATRA treatment in combination with inhibition of PI3K (ZSTK474), mTOR (WYE132) or PI3K/mTOR (BEZ235, dactolisib) drastically reduces protein levels of the proto‐oncogene MYC. In combination with BEZ235, ATRA treatment led to almost complete eradication of cellular MYC, G1 arrest, loss of clonal capacity and terminal granulocytic differentiation. We demonstrate that PAM inhibitor/ATRA treatment targets MYC via independent mechanisms. While inhibition of the PAM pathway causes MYC phosphorylation at threonine 58 via glycogen synthase kinase 3 beta and subsequent degradation, ATRA reduces its expression. Here, we present an approach using a combination of known drugs to synergistically reduce aberrant MYC levels, thereby effectively blocking proliferation and enabling differentiation in various AML subtypes.
1 August 2020 in International Journal for Parasitology: Parasites and Wildlife
Trichinella nematodes occur in many carnivorous and omnivorous animal species in the sylvatic cycle. Due to their widespread occurrence throughout Poland and diet, free-living Mustelids can act as a potential reservoir for nematodes of the genus Trichinella and play a role in their circulation. The study was designed to determine the presence and predilection sites for Trichinella nematodes in martens (Martes spp.) from the Gleboki Brod Forest District, Poland. Trichinella britovi larvae were detected by molecular methods in 17.54% examined martens (prevalence: 41.67% among pine martens and 13.88% among Martes spp.). The intensity of infection varied from 0.17 to 37.29 larvae per gram (LPG) (mean 5.43; median 3.4). The highest larval burdens were detected in the tongue in pine martens (Martes martes) and the diaphragm in Martes spp., respectively; the lowest levels were found in the masseter in pine martens and the tongue in Martes spp. No statistically significant difference in the intensity of infection was observed between males and females in either group. Our findings indicate that T. britovi is present in martens from the Gleboki Brod Forest District, and the predilection sites for the nematode may differ between males and females. However, due to the low number of examined animals, further studies are necessary to confirm whether they are an important element in the maintenance of Trichinella nematodes in the examined area.