Effects of true-to-life PET nanoplastics using primary human nasal epithelial cells

Altres ajuts: acords transformatius de la UABSince inhalation is a relevant exposure route, studies using appropriate micro/nanoplastic (MNPLs) models, representative targeted cells, and relevant biomarkers of effect are required. We have used lab-made polyethylene terephthalate (PET)NPLs obtained from PET plastic water bottles. Human primary nasal epithelial cells (HNEpCs) were used as a model of the first barrier of the respiratory system. Cell internalization and intracellular reactive oxygen species (iROS) induction, as well as the effects on mitochondria functionality and in the modulation of the autophagy pathway, were evaluated. The data indicated significant cellular uptake and increased levels of iROS. Furthermore, a loss of mitochondrial membrane potential was observed in the exposed cells. Regarding the effects on the autophagy pathway, PETNPLs exposure significantly increases LC3-II protein expression levels. PETNPLs exposure also induced significant increases in the expression of p62. This is the first study showing that true-to-life PETNPLs can alter the autophagy pathway in HNEpCs

Hazard assessment of different-sized polystyrene nanoplastics in hematopoietic human cell lines

Altres ajuts: acords transformatius de la UABThe environmental presence of micro/nanoplastics (MNPLs) is an environmental and human health concern. Such MNPLs can result from the physicochemical/biological degradation of plastic goods (secondary MNPLs) or can result from industrial production at that size, for different commercial purposes (primary MNPLs). Independently of their origin, the toxicological profile of MNPLs can be modulated by their size, as well as by the ability of cells/organisms to internalize them. To get more information on these topics we have determined the ability of three different sizes of polystyrene MNPLs (50, 200, and 500 nm) to produce different biological effects in three different human hematopoietic cell lines (Raji-B, THP-1, and TK6). Results show that none of the three sizes was able to induce toxicity (growth ability) in any of the tested cell types. Although transmission electron microscopy and confocal images showed cell internalization in all the cases, their quantification by flow cytometry demonstrated an important uptake by Raji-B and THP-1 cells, in comparison with TK6 cells. For the first ones, the uptake was negatively associated with the size. Interestingly, when the loss of mitochondrial membrane potential was determined, dose-related effects were observed for Raji-B and THP-1 cells, but not for TK6 cells. These effects were observed for the three different sizes. Finally, when oxidative stress induction was evaluated, no clear effects were observed for the different tested combinations. Our conclusion is that size, biological endpoint, and cell type are aspects modulating the toxicological profile of MNPLs

Expression Patterns of miR181a and miR30d in Patients with Breast Cancer

One of the important molecular pathways in breast cancer is the PTEN-PI3K-AKT pathway. Any change in the activity of the PTEN gene can alter the PI3K-AKT pathway. Moreover, there are subsets of genes and pathways their expression changes by post-transcriptional regulations. For instance, gene regulation alters by non-coding RNAs such as micro-RNAs as post-transcriptional regulators that prevent the expression of the target transcript. Therefore, it is essential to assess the related alterations in micro-RNA expression patterns to find out the possible causes of conversions in related transcripts and pathways such as the PTENPI3K-AKT pathway in breast cancer. To determine the expression level of miR-181a and miR-30d in 30 breast tumor samples and 30 adjacent normal samples, the RNA extraction, and cDNA synthesis was performed by RiboEx (GeneAll, Korea). Finally, the Real-Time PCR method was used for quantitative analysis of the expression levels of these miRNAs. all the experimental part of the project in done at Islamic Azad University in 2017. After analyzing comparisons in the expression level of miR-181a and miR-30d in tumor and normal tissues, there was a significant increase in the expression level of miR-181a in tumor samples compared with normal samples. Moreover, the expression level of miR-30d in tumor samples reported a significant decrease in comparison with normal samples (P <0.05). Upregulation of miR-181a may affect the transcription of the PTEN gene resulting in the cell progress to cancer. The Downregulation of miR-30d may also lead to cancer cell growth, due to a reduction in the affecting on the CREB gene transcript

Nanoliposomes for doxorubicin delivery: Reversing drug resistance, stimuli-responsive carriers and clinical translation

© 2022 Elsevier B.V.Cancer is still a major threat to human life that is characterized by abnormal proliferation and metastasis of cancer cells. Chemotherapy is procedure of using anti-cancer drugs for preventing dissemination and proliferation of tumor cells to kill them in improving survival rate and prognosis of patients. Chemotherapy has been a common conventional therapy for cancer, and it can be used along with surgical resection in cancer patients. However, drug resistance has led to chemotherapy failure in patients, especially in advanced and metastatic stages. Therefore, nano-scale delivery systems have been developed for reversing drug resistance and potentiating efficacy of chemotherapy agents. Liposomes are spherical vesicles with low particle size and high biocompatibility that have been used for drug delivery in cancer suppression. Liposomes can increase internalization of doxorubicin (DOX) as an anti-cancer drug in tumor cells to boost its cytotoxicity. Furthermore, co-delivery of DOX with other anti-tumor drugs or gene therapy can lead to synergistic cancer therapy. pH-, redox-, light- and multi-sensitive liposomes have been designed for precise delivery of DOX in cancer suppression. Modification of liposomes with ligands such as hyaluronic acid that binds to CD44 receptor, enhances selectivity towards cancer cells. Furthermore, DOX-loaded liposomes mainly internalize in cancer cells via endocytosis that is dependent on different factors such as particle size, zeta potential and other physico-chemical properties