using-low-cost-dyes-to-visualize-glycogen-accumulation-gut-integrity

Using Low-Cost Dyes to Visualize Glycogen Accumulation and Gut Integrity in <i>Caenorhabditis elegans</i>

Caenorhabditis elegans (C. elegans) is a transparent, non-parasitic nematode with a simple biology, which makes it a great tool for biological sciences ...

Federal University of Pampa

Manganese (Mn) is a metal ubiquitously present in nature and essential for many living organisms. As a trace element, it is required in small amounts for the proper functioning of several important enzymes, and reports of Mn deficiency are indeed rare.

The impact of manganese on neurotransmitter systems.

Bladder cancer is the fourth most common malignancy in men. It can present along the entire continuum of severity, from mild to well-differentiated disease to extremely malignant tumors with low survival rates. Human RAS genes are the most frequently mutated oncogenes in human cancers, and the critical role of aberrant Ras protein function in carcinogenesis is well established. Therefore, considerable efforts have been devoted to the development of anti-Ras inhibitors for cancer treatment. This study presents the biphenyl dihydropyrimidinone LaSOM 335 with high activity against T24 bladder cancer cells (IC  = 10.73 ± 0.53 μM) and selectivity of cytotoxicity for this cancer cell line compared to two non-cancer cell lines investigated. Furthermore, we also show that this compound reduced vulvar development in the mutant let-60 gene of Caenorhabditis elegans. Let-60 is a homolog of the mammalian Ras gene. In addition, we observed that LaSOM 335 inhibits the enzymatic activity of CD73 and decreases CD73 expression. Possibly, this expression decrease is due to downstream EGFR signaling via the Ras-Raf-ERK pathway, that directly regulates CD73 expression via ERK1/2. Evidence suggests that non-immunomodulating functions of CD73 play an equally important role for cancer cell survival, progression, and migration. Regarding we also notice that LaSOM 335 was safe in the in vivo model of C. elegans. The set of these findings makes this biphenyl dihydropyrimidinone a promising candidate for further investigations in the bladder cancer field.

LaSOM 335, active against bladder cancer cells, interferes with Let-60 (hRas) and reduces CD73 expression/activity.

Neurotoxicology of metals and metallic nanoparticles in .

Iron oxide nanoparticles present superparamagnetic properties that enable their application in various areas, including drug delivery at specific locations in the organism. Silver nanoparticles have potent antimicrobial effects. Although the combination of FeO-NPs and Ag-NPs in one hybrid nanostructure (FeO@Ag-NPs) demonstrated promising targeted biomedical applications, their toxicological effects are unknown and need to be assessed. Caenorhabditis elegans is a promising model for nanotoxicological analysis, as it allows an initial screening of new substances. After exposure to FeO-NPs, Ag-NPs and FeO@Ag-NPs, we observed that hybrid NPs reduced the C. elegans survival and reproduction. Higher concentrations of FeO@Ag-NPs caused an increase in cell apoptosis in the germline and a decrease in egg laying, which was associated with a decrease in worm swimming movements and abnormalities in the cholinergic neurons. FeO@Ag-NPs caused an increase in reactive oxygen species, along with activation of DAF-16 transcription factor. A higher expression of the target genes GST-4::GFP and SOD-3::GFP were evidenced, which suggests the activation of the antioxidant system. Our results indicate the reprotoxicity caused by high levels of FeO@Ag-NPs, as well as cholinergic neurotoxicity and activation of the antioxidant system in C. elegans, suggesting that high concentrations of these nanomaterials can be harmful to living organisms.

Article	Year
The impact of manganese on neurotransmitter systems. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)\| PubMed ID: 32480053	2020
LaSOM 335, active against bladder cancer cells, interferes with Let-60 (hRas) and reduces CD73 expression/activity. Chemical biology & drug design\| PubMed ID: 37272688	2023
Neurotoxicology of metals and metallic nanoparticles in . Advances in neurotoxicology\| PubMed ID: 37384197	2023
Iron oxide/silver hybrid nanoparticles impair the cholinergic system and cause reprotoxicity in Caenorhabditis elegans. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association\| PubMed ID: 37451599	2023

Aline Castro Silva

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