Extremely low-frequency electromagnetic field (ELF-EMF) induced alterations in gene expression and cytokine secretion in clear cell renal carcinoma cells.

BACKGROUND: The study aimed to investigate the influence of extremely low-frequency electromagnetic fields (ELF-EMF) on clear cell renal cell carcinoma (ccRCC) by assessing alterations in gene expression and the secretion of cytokines and chemokines. MATERIAL AND METHODS: Three ccRCC cell lines (786-O, 769-P, and CAKI-1) and a healthy HEK293 cell line were subjected to ELF-EMF exposure (frequency 50 Hz, magnetic field strength 4.5 mT) for 30 min daily for 5 days. The study examined the expression of ADAM28, NCAM1, and VEGFC genes, along with the secretion of 30 cytokines and chemokines. RESULTS: Notably, primary tumor-derived cell lines, but not those from metastatic sites, exhibited ADAM28 gene expression, which increased following ELF-EMF exposure. A statistically significant reduction in VEGFC gene expression was observed in 769-P cells after ELF-EMF exposure. Additionally, NCAM1 gene expression was upregulated in HEK293, 769-P, and 786-O cells, representing normal embryonic kidney cells and primary tumor cells, but not in CAKI-1 cells, which model metastatic sites. After EMF exposure, there was a statistically significant decrease in transforming growth factor ß1 (TGF-ß1) concentration in the cell culture supernatants of HEK293 and CAKI-1 cell lines, with no other significant changes in the secretion of tested cytokines. CONCLUSIONS: Given the study's findings and available research, caution is warranted when drawing conclusions about the potential inhibitory effect of ELF-EMF on ccRCC progression. Standardization of experimental models is imperative when assessing the effects of EMF in a human context. Med Pr Work Health Saf. 2024;75(2):133-141.

Time-dependent cytokines changes in ultra-rush wasp venom immunotherapy.

Venom immunotherapy (VIT) represents a potential therapeutic approach for the management of venom allergies, aiming to modify the immune response to venom allergens and enhance its precision. Previous studies have demonstrated that VIT induces a shift in T helper cell responses from Th2 to Th1, characterized by the production of IL-2 and interferon-gamma by CD4+ and CD8+ cells. In order to explore long-term pathways following VIT treatment and verify potential new outcomes, the serum concentrations of 30 cytokines were assessed in a cohort of 61 patients (18 control, 43 study group) exhibiting hypersensitivity to wasp venom. Cytokine levels were measured at 0, 2, 6, and 24 weeks after the initiation phase of VIT in the study group. The present study found no significant alterations in the levels of IL-2 and IFN-γ in the peripheral blood following VIT. However, a noteworthy finding was the substantial increase in the concentration of IL-12, a cytokine capable of promoting the differentiation of Th0 cells into Th1 cells. This observation supports the involvement of the Th1 pathway in the desensitization process induced by VIT. Additionally, the study revealed a significant rise in the levels of IL-9 and TGF-ß after VIT. These cytokines may play a role in the generation of inducible regulatory T (Treg) cells, indicating their potential importance in the immune response to venom allergens and the desensitization process associated with VIT. Nevertheless, further investigations are required to comprehend the underlying mechanisms driving the VIT process comprehensively.

Differential Effects of Overexpression of Wild Type and Kinase-Dead MELK in Fibroblasts and Keratinocytes, Potential Implications for Skin Wound Healing and Cancer.

Maternal embryonic leucine-zipper kinase (MELK) plays a significant role in cell cycle progression, mitosis, cell migration, cell renewal, gene expression, embryogenesis, proliferation, apoptosis, and spliceosome assembly. In addition, MELK is known to be overexpressed in multiple types of cancer and is associated with cancer proliferation. Tumorigenesis shares many similarities with wound healing, in which the rate of cell proliferation is a critical factor. Therefore, this study aimed to determine the involvement of MELK in the regulation of cell division in two cell types involved in this process, namely fibroblasts and keratinocytes. We examined how temporal overexpression of wild-type and kinase-dead MELK kinase variants affect the rate of proliferation, viability, cell cycle, and phosphorylation state of other kinases involved in these processes, such as ERK1/2, AKT1, MAPK9, p38, and p53. We explored if MELK could be used as a therapeutic stimulator of accelerated wound healing via increased proliferation. We observed that aberrant expression of MELK results in abnormal proliferation, altered cell cycle distribution, and decreased viability of the cells, which challenge the utility of MELK in accelerated wound healing. Our results indicate that, at least in healthy cells, any deviation from precisely controlled MELK expression is harmful to fibroblasts and keratinocytes.

Looking into the Eyes-In Vitro Models for Ocular Research.

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.