THP-1 Monocytic Cells Are Polarized to More Antitumorigenic Macrophages by Serial Treatment with Phorbol-12-Myristate-13-Acetate and PD98059.

Background and Objectives: As modulators of the tumor microenvironment, macrophages have been extensively studied for their potential in developing anticancer strategies, particularly in regulating macrophage polarization towards an antitumorigenic (M1) phenotype rather than a protumorigenic (M2) one in various experimental models. Here, we evaluated the effect of PD98059, a mitogen-activated protein kinase kinase MAPKK MEK1-linked pathway inhibitor, on the differentiation and polarization of THP-1 monocytes in response to phorbol-12-myristate-13-acetate (PMA) under various culture conditions for tumor microenvironmental application. Materials and Methods: Differentiation and polarization of THP-1 were analyzed by flow cytometry and RT-PCR. Polarized THP-1 subsets with different treatment were compared by motility, phagocytosis, and so on. Results: Clearly, PMA induced THP-1 differentiation occurs in adherent culture conditions more than nonadherent culture conditions by increasing CD11b expression up to 90%, which was not affected by PD98059 when cells were exposed to PMA first (post-PD) but inhibited when PD98059 was treated prior to PMA treatment (pre-PD). CD11bhigh THP-1 cells treated with PMA and PMA-post-PD were categorized into M0 (HLA-DRlow and CD206low), M1 (HLA-DRhigh and CD206low), and M2 (HLA-DRlow and CD206high), resulting in an increased population of M1 macrophages. The transcription levels of markers of macrophage differentiation and polarization confirmed the increased M1 polarization of THP-1 cells with post-PD treatment rather than with PMA-only treatment. The motility and cytotoxicity of THP-1 cells with post-PD treatment were higher than THP-1 cells with PMA, suggesting that post-PD treatment enhanced the anti-tumorigenicity of THP-1 cells. Confocal microscopy and flow cytometry showed the effect of post-PD treatment on phagocytosis by THP-1 cells. Conclusions: We have developed an experimental model of macrophage polarization with THP-1 cells which will be useful for further studies related to the tumor microenvironment.

Application of machine learning and multivariate approaches for assessing microplastic pollution and its associated risks in the urban outdoor environment of Bangladesh.

Microplastics (MPs) are an emerging global concern due to severe toxicological risks for ecosystems and public health. Therefore, this is the first study in Bangladesh to assess MP pollution and its associated risks for ecosystems and human health in the outdoor urban environment using machine learning and multivariate approaches. The occurrences of MPs in the urban road dust were 52.76 ± 20.24 particles/g with high diversity, where fiber shape (77%), 0.1-0.5 mm size MPs (75%), blue color (26%), and low-density polyethylene (24%) polymer was the dominating MPs category. Pollution load index value (1.28-4.42), showed severe pollution by MPs. Additionally, the contamination factor (1.00-5.02), and Nemerow pollution index (1.38-5.02), indicate moderate to severe MP pollution. The identified polymers based on calculated potential ecological risk (2248.52 ± 1792.79) and polymer hazard index (814.04 ± 346.15) showed very high and high risks, respectively. The occurrences of MPs could effectively be predicted by random forest, and support random vector machine, where EC, salinity, pH, OC, and texture classes were the influencing parameters. Considering the human health aspect, children and adults could be acutely exposed to 19259.68 and 5777.90 MP particles/ year via oral ingestion. Monte-Carlo-based polymers associated cancer risk assessment results indicate moderate risk and high risk for adults and children, respectively, where children were more vulnerable than adults for MP pollution risks. Overall assessment mentioned that Dhaka was the most polluted division among the other divisions.

New established cell lines from undifferentiated pleomorphic sarcoma for in vivo study.

As a high-grade soft-tissue sarcoma (STS), undifferentiated pleomorphic sarcoma (UPS) is highly recurrent and malignant. UPS is categorized as a tumor of uncertain differentiation and has few options for treatment due to its lack of targetable genetic alterations. There are also few cell lines that provide a representative model for UPS, leading to a dearth of experimental research. Here, we established and characterized new cell lines derived from two recurrent UPS tissues. Cells were obtained from UPS tissues by mincing, followed by extraction or dissociation using enzymes and culture in a standard culture environment. Cells were maintained for several months without artificial treatment, and some cell clones were found to be tumorigenic in an immunodeficient mouse model. Interestingly, some cells formed tumors in vivo when injected after aggregation in a non-adherent culture system for 24 h. The tissues from in vivo study and tissues from patients shared common histological characteristics. Pathways related to the cell cycle, such as DNA replication, were enriched in both cell clones. Pathways related to cell-cell adhesion and cell-cell signaling were also enriched, suggesting a role of the mesenchymal-to-epithelial transition for tumorigenicity in vivo. These new UPS cell lines may facilitate research to identify therapeutic strategies for UPS. [BMB Reports 2023; 56(4): 258-264].

Remedial role of exercise training to deep-fried oil-induced metabolic and histological changes in Wistar rats.

Exercise training is a well-known lifestyle to maintain good health. The present study was conducted to explore the effect of regular exercise training (for 15 min) on biochemical, physiological, and histological changes in fried oil intake (5 g/kg body weight, for 5 weeks) with or without raw oil supplementation. Liver disease and heart muscle injury were accounted for by significant (p < .05) increase in liver and heart biomarker enzymes in serum. Creatinine and urea level were also significantly increased in the fried oil-fed group as a sign of kidney injury. But all the biological markers including triglycerides, low-density lipoprotein cholesterol (LDL-C) was decreased significantly (p < .05) in the exercise-trained rat group. These metabolic changes were substantiated by the histological study of respective organs. Therefore, people should avoid repeatedly deep-fried oil consumption rather than fresh ones though regular exercise training has been found to resolve these metabolic abnormalities. PRACTICAL APPLICATIONS: Exercise training is a common practice to reduce the onset of some metabolic abnormalities for example cardiovascular disease, non-alcoholic fatty liver disease, chronic kidney disease, and also prevents various cell and tissue damages. Repeated frying of vegetable oil not only reduces its nutritional value but also produce free fatty acids and other toxic compounds. The present study revealed that repeatedly heated vegetable oil consumption causes injuries in the heart, liver, kidney, and small intestine by the oxidative products. As a result, the level of biomarkers of these responsive organs was found to be elevated. But regular exercise training ameliorated these detrimental effects. So, in terms of public health concern, regular exercise is one of the best ways to keep the body fit especially those who are consuming deep-fried oil.

Effect of raw and repeatedly fried mustard oil intake on metabolic and organ histological changes in Wistar rat.

Fried dietary oils often cause adverse health effects due to altered chemical and nutritional properties. In the present study with mustard oil, the effect of repeated frying (180°C for 10 min, three times) on chemical characteristics and oral intake of raw and fried mustard oil (5 g/kg for 5 weeks) in Wistar rats were investigated. Repeated frying caused oxidation reactions and free fatty acid content in mustard oil. This fried oil feeding to rats increased serum LDL cholesterol and triglycerides and decreased HDL leading to nonalcoholic fatty liver disease accounted by significant increment of liver enzymes (ALT, AST, ALP) compared with raw oil-fed group. Higher level of serum CK-MB and creatinine in fried oil-fed rats indicate disrupted kidney function. Histological findings of the respective organs ascertained metabolic abnormalities due to fried oil intake. Thus, the study suggests avoidance of using repeatedly fried oils in food products for better consumer health. PRACTICAL APPLICATIONS: Vegetable oil is a common ingredient of food products. Mustard oil is used in many countries both as raw and fried forms for various food preparations. When it is being fried at elevated temperatures in the presence of air, both thermal and oxidative decomposition take place which alter the nutritional and functional bioactive properties of the oil. The findings of the current study revealed the repeatedly fried mustard oil-induced detrimental effects on various organs of Wistar rats. Human beings consuming repeatedly fried mustard oil regularly might also face these acute problems. Thus in context to the public health issue, it is a message to avoid in taking repeated fried oils at household cooking or food industry to maintain better health.