TiO2 Nanoparticles and Their Effects on Eukaryotic Cells: A Double-Edged Sword.

Nanoparticulate TiO2 (TiO2 NPs) is a widely used material, whose potential toxicity towards eukaryotic cells has been addressed by multiple studies. TiO2 NPs are considered toxic due to their production of reactive oxygen species (ROS), which can, among others, lead to cellular damage, inflammatory responses, and differences in gene expression. TiO2 NPs exhibited toxicity in multiple organs in animals, generating potential health risks also in humans, such as developing tumors or progress of preexisting cancer processes. On the other hand, the capability of TiO2 NPs to induce cell death has found application in photodynamic therapy of cancers. In aquatic environments, much has been done in understanding the impact of TiO2 on bivalves, in which an effect on hemocytes, among others, is reported. Adversities are also reported from other aquatic organisms, including primary producers. These are affected also on land and though some potential benefit might exist when it comes to agricultural plants, TiO2 can also lead to cellular damage and should be considered when it comes to transfer along the food chain towards human consumers. In general, much work still needs to be done to unravel the delicate balance between beneficial and detrimental effects of TiO2 NPs on eukaryotic cells.

Correction: Scientific quality of COVID-19 and SARS CoV-2 publications in the highest impact medical journals during the early phase of the pandemic: A case control study.

[This corrects the article DOI: 10.1371/journal.pone.0241826.].

Scientific quality of COVID-19 and SARS CoV-2 publications in the highest impact medical journals during the early phase of the pandemic: A case control study.

BACKGROUND: A debate about the scientific quality of COVID-19 themed research has emerged. We explored whether the quality of evidence of COVID-19 publications is lower when compared to nonCOVID-19 publications in the three highest ranked scientific medical journals. METHODS: We searched the PubMed Database from March 12 to April 12, 2020 and identified 559 publications in the New England Journal of Medicine, the Journal of the American Medical Association, and The Lancet which were divided into COVID-19 (cases, n = 204) and nonCOVID-19 (controls, n = 355) associated content. After exclusion of secondary, unauthored, response letters and non-matching article types, 155 COVID-19 publications (including 13 original articles) and 130 nonCOVID-19 publications (including 52 original articles) were included in the comparative analysis. The hierarchical level of evidence was determined for each publication included and compared between cases and controls as the main outcome. A quantitative scoring of quality was carried out for the subgroup of original articles. The numbers of authors and citation rates were also compared between groups. RESULTS: The 130 nonCOVID-19 publications were associated with higher levels of evidence on the level of evidence pyramid, with a strong association measure (Cramer's V: 0.452, P <0.001). The 155 COVID-19 publications were 186-fold more likely to be of lower evidence (95% confidence interval [CI] for odds ratio, 7.0-47; P <0.001). The quantitative quality score (maximum possible score, 28) was significantly different in favor of nonCOVID-19 (mean difference, 11.1; 95% CI, 8.5-13.7; P <0.001). There was a significant difference in the early citation rate of the original articles that favored the COVID-19 original articles (median [interquartile range], 45 [30-244] vs. 2 [1-4] citations; P <0.001). CONCLUSIONS: We conclude that the quality of COVID-19 publications in the three highest ranked scientific medical journals is below the quality average of these journals. These findings need to be verified at a later stage of the pandemic.

The influence of nano-TiO2 on metabolic activity, cytotoxicity and ABCB5 mRNA expression in WM-266-4 human metastatic melanoma cell line.

PURPOSE: There is no clear evidence on whether sunscreens and personal care products containing UV-filters like titanium dioxide (TiO2) are protective against or may be a contributing factor in melanoma development. Extensive studies have shown that TiO2 can cause cell toxicity under in vitro and in vivo conditions. The transmembrane protein ABCB5 is closely linked to tumorigenicity, progression and disease recurrence of diverse human malignancies, including melanoma. Accordingly, the aim of the present study was to investigate in vitro any potential influence of nanosized TiO2 (nano-TiO2) on metastatic melanoma cells' metabolic activity, cytotoxicity and ABCB5 mRNA expression. METHODS: The human metastatic melanoma cell line WM-266-4 (ATCC) was used to obtain dose- and time-dependent responses. We used the MTT and LDH assays to measure metabolic activity of selected cells and cytotoxicity. Real-time quantitative PCR (RT-qPCR) was performed and gene expression ratios were calculated for the target (ABCB5) and the reference (LDHA) gene. Standard statistical tests were used for analysis in SPSS and Excell. RESULTS: Our results suggest decreased metastatic melanoma cells' metabolic activity, increased cytotoxicity and increased ABCB5 mRNA expression after 24 and 48 hrs as compared to control (untreated) cells (p<0.05). Thus, we showed that nano-TiO2 might influence cells' invasiveness and aggressiveness. CONCLUSION: We show for the first time that ABCB5 expression in metastatic melanoma cells might be affected by nano-TiO2 exposure. In addition, nano-TiO2 as a sunscreen ingredient might play a role in metastatic melanoma progression.

In-vitro study of the influence of octocrylene on a selected metastatic melanoma cell line.

BACKGROUND: Octocrylene (OCT) is one of the most widespread chemical UV filters used in sunscreens and cosmetic products. Despite the use of sunscreens and personal care products over decades, melanoma as the most serious and aggressive form of skin cancer is still a cause of concern. Hence the aim of this study was to investigate any potential influence of OCT on metabolic activity, cytotoxicity and ABCB5 mRNA expression in melanoma cells. The ABCB5 transmembrane protein was tested due to its well-known role in the initiation, invasion and metastatic spread of various cancers, including melanoma. METHODS: Metastatic melanoma cell line WM-266-4 (ATCC) was incubated with selected concentrations of OCT and for different time intervals. The MTT and LDH assays to measure the cells' metabolic activity and cytotoxicity were used respectively. Target gene (ABCB5) expression was detected by quantitative real-time PCR (qRT-PCR), using TaqMan® chemistry. RESULTS: Our results suggest decreased metastatic melanoma cells' metabolic activity, increased cytotoxicity and increased ABCB5 mRNA expression (P<0.05) with longer time of exposure to OCT as compared to control cells. Accordingly, we suspect that the surviving cells are more invasive and aggressive, which might explain their microscopically observed cannibalistic activity. CONCLUSIONS: With this study, we elucidate a new promising field for further research to contribute to etiology and prevention of melanoma.

The effect of micro-sized titanium dioxide on WM-266-4 metastatic melanoma cell line.

Titanium dioxide (TiO2) is widely used as an inorganic UV-filter in cosmetic products; however, it has been classified as possibly carcinogenic to humans. While numerous studies demonstrated cytotoxic and genotoxic effects of nano-sized TiO2 in different cell lines, including human skin cells, studies investigating the effects of micro-TiO2 on human keratinocytes and melanocytes, in healthy and cancer cells, are scarce. Adenosine triphosphate (ATP) binding cassette subfamily B member 5 (ABCB5) is a plasma membrane protein known for its role in the tumorigenicity, progression, and recurrence of melanoma. Here, we investigated the effect of micro-TiO2 (average particle size ≤5 µm) on the metabolic activity, cytotoxicity and ABCB5 mRNA expression in metastatic melanoma cells. Metastatic melanoma cell line WM-266-4 was treated with different concentrations of micro-TiO2 for different incubation times to obtain dose- and time-dependent responses. Untreated WM-266-4 cells, cultured under the same conditions, were used as control. The cell metabolic activity was determined by MTT assay. Cytotoxicity of micro-TiO2 was analyzed by lactate dehydrogenase (LDH) cytotoxicity assay. The ABCB5 mRNA expression in melanoma cells was analyzed using quantitative reverse transcription polymerase chain reaction (RT-qPCR). After 120 hours of exposure to micro-TiO2 the metabolic activity of melanoma cells decreased, especially at the two highest micro-TiO2 concentrations. Comparably, the cytotoxicity of micro-TiO2 on melanoma cells increased after 48 and 120 hours of exposure, in a time-dependent manner. The ABCB5 mRNA expression in micro-TiO2-treated melanoma cells also decreased significantly after 24 and 48 hours, in a time-dependent manner. Overall, our results suggest inhibitory effects of micro-TiO2 on the metabolic activity and ABCB5 mRNA expression in metastatic melanoma cells, indicating its potential use as an anticancer agent.