Soil pollution caused by heavy metal(oid)s has generated great concern worldwide due to their toxicity, persistence, and bio-accumulation properties. To assess the baseline data, the heavy metal(oid)s, including manganese (Mn), iron (Fe), Cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), lead (Pb), mercury (Hg), chromium (Cr), and cadmium (Cd), were evaluated in surface soil samples collected from the farmlands of Grand Forks County, North Dakota. Samples were digested via acid mixture and analyzed via inductively coupled plasma mass spectrometry (ICP MS) analysis to assess the levels, ecological risks, and possible sources. The heavy metal(oid) median levels exhibited the following decreasing trend: Fe > Mn > Zn > Ni > Cr > Cu > Pb > Co > As > Cd > Hg. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) suggested the main lithogenic source for the studied metal(oid)s. Metal(oid) levels in the current investigation, except Mn, are lower than most of the guideline values set by international agencies. The contamination factor (C_f), geo accumulation index (I_geo) and enrichment factor (EF) showed considerable contamination, moderate contamination, and significant enrichment, respectively, for As and Cd on median value basis. Ecological risk factor (E_r) results exhibited low ecological risk for all studied metal(oid)s except Cd, which showed considerable ecological risk. The potential ecological risk index (PERI) levels indicated low ecological risk to considerable risk. Overall, the results indicate the accumulation of As and Cd in the study area. The high nutrients of the soils potentially affect their accumulation in crops and impact on consumers’ health. This drives the impetus for continued environmental monitoring programs.

Heavy metal (HM) pollution of soil is an increasingly serious problem worldwide. The current study assessed the metal levels and ecological and human health risk associated with HMs in Grand Forks urban soils. A total 40 composite surface soil samples were investigated for Mn, Fe, Co, Ni, Cu, Zn, As, Pb, Hg, Cr, Cd and Tl using microwave-assisted HNO₃-HCl acid digestion and inductively coupled plasma mass spectrometry (ICP-MS) analysis. The enrichment factor (EF), contamination factor (CF), geoaccumulation index (Igeo), ecological risk and potential ecological risk index were used for ecological risk assessment. The park soils revealed the following decreasing trend for metal levels: Fe > Mn > Zn > Cr > Ni > Cu > Pb > As > Co > Cd > Tl > Hg. Based on mean levels, all the studied HMs except As and Cr were lower than guideline limits set by international agencies. Principal component analysis (PCA) indicated that Mn, Fe, Co, Ni, Cu, Zn, As, Cd, Pb, Cr and Tl may originate from natural sources, while Hg, Pb, As and Cd may come from anthropogenic/mixed sources. The Igeo results showed that the soil was moderately polluted by As and Cd and, based on EF results, As and Cd exhibited significant enrichment. The contamination factor analysis revealed that Zn and Pb showed moderate contamination, Hg exhibited low to moderate contamination and As and Cd showed high contamination in the soil. Comparatively higher risk was noted for children over adults and, overall, As was the major contributor (>50%), followed by Cr (>13%), in the non-carcinogenic risk assessment. Carcinogenic risk assessment revealed that As and Cr pose significant risks to the populations associated with this urban soil. Lastly, this study showed that the soil was moderately contaminated by As, Cd, Pb and Hg and should be regularly monitored for metal contamination.

Heavy metal contamination in food has become a significant global food safety concern. This study assessed the concentrations of As, Ca, Cd, Co, Cr, Cu, Fe, Hg, Mn, K, Mg, Na, Ni, Se, Pb, and Zn in 13 locally grown vegetables using microwave-assisted acid digestion and ICP-MS. The potential human health risks associated with their consumption were also evaluated. Vegetable samples were collected from the local farmer’s market in Grand Forks, North Dakota. The mean levels (μg/g) of Na, Mg, K, Ca, Fe, Se, Mn, Cu, Zn, Co, Hg, Cr, Ni, As, Cd, and Pb were 1001, 2935, 30474, 686.0, 52.90, 0.171, 37.63, 4.936, 21.33, 0.069, 0.0030, 0.049, 0.736, 0.083, 0.298, and 0.019, respectively, having the following decreasing trend: K > Mg > Na > Ca > Fe > Mn > Zn > Cu > Ni > Cd > Se > As > Co > Cr > Pb > Hg. The highest total metals level was found in spinach, with the following decreasing order: spinach > tomato > sugar beet > white eggplant > cucumber ~ kale > green chili > green bean > dill ~ potato > capsicum > onion > corn. Spinach exhibited the highest concentrations of Cd, Cr, Pb, and Hg, which suggests a higher risk of metal exposure from its consumption. Toxic metals except Cd were found to be lower than the maximum allowable concentrations set by international agencies among the analyzed vegetables, while Cd levels were higher than maximum allowable levels in most of the vegetables. Health risks associated with metal intake by vegetable consumption were evaluated in terms of estimated daily intake (EDI), non-carcinogenic risks were evaluated by the target hazard quotient (THQ) and Hazard Index (HI), and carcinogenic risks were evaluated by target cancer risk (TCR). The EDI values of all the metals were found to be below the maximum tolerable daily intake (MTDI). The highest EDI value for Mn, Zn, Hg, Cr, Cd, and Pb was noted in spinach. THQ values for Cd, Co, and As were higher than 1 in most of the vegetable species analyzed, indicating non-carcinogenic health effects to consumers. HI results also posed a non-carcinogenic health risk associated with the intake of these vegetables. Mean TCR values of Cr, Ni, As, and Cd indicated carcinogenic risk for consumers. This study showed that there are potential health risks with consumption of these vegetables. Lastly, regular monitoring of metal levels in vegetables is suggested/recommended to minimize health risks and support pollution control efforts.

The bladder is a target organ for inorganic arsenic, a carcinogen and common environmental contaminant found in soil and water. Urothelial carcinoma (UC) is the most common type of bladder cancer (BC) that develops into papillary or non-papillary tumors. Papillary tumors are mostly non-muscle invasive (NMIUC), easier treated, and have a better prognosis. Urothelial carcinoma can be molecularly sub-typed as luminal or basal, with papillary tumors generally falling into the luminal category and basal tumors exclusively forming muscle invasive urothelial carcinomas (MIUC). It is unclear why some UCs develop more aggressive basal phenotypes. We hypothesized that chronic arsenic exposure of a papillary luminal bladder cancer would lead to the development of basal characteristics and increase in invasiveness. We treated the human papillary bladder cancer cell line RT4 with 1 µM arsenite (As³⁺) for twenty passages. Throughout the study, key luminal and basal gene/protein markers in the exposed cells were evaluated and at passage twenty, the cells were injected into athymic mice to evaluate tumor histology and measure protein markers using immunohistochemistry. Our data indicates that chronic As³⁺- treatment altered cellular morphology and decreased several luminal markers in cell culture. The histology of the tumors generated from the As³⁺-exposed cells was similar to the parent (non-treated) however, they appeared to be more invasive in the liver and displayed elevated levels of some basal markers. Our study demonstrates that chronic As³⁺ exposure is able to convert a non-invasive papillary bladder cancer to an invasive form that acquires some basal characteristics.

Urothelial cancer (UC) is a common malignancy and its development is associated with arsenic exposure. Around 25% of diagnosed UC cases are muscle invasive (MIUC) and are frequently associated with squamous differentiation. These patients commonly develop cisplatin (CIS) resistance and have poor prognosis. SOX2 expression is correlated to reduced overall and disease-free survival in UC. SOX2 drives malignant stemness and proliferation in UC cells and is associated with development of CIS resistance. Using quantitative proteomics, we identified that SOX2 was overexpressed in three arsenite (As³⁺)-transformed UROtsa cell lines. We hypothesized that inhibition of SOX2 would reduce stemness and increase sensitivity to CIS in the As³⁺-transformed cells. Pevonedistat (PVD) is a neddylation inhibitor and is a potent inhibitor of SOX2. We treated non-transformed parent and As³⁺-transformed cells with PVD, CIS, or in combination and monitored cell growth, sphere forming abilities, apoptosis, and gene/protein expression. PVD treatment alone caused morphological changes, reduced cell growth, attenuated sphere formation, induced apoptosis, and elevated the expression of terminal differentiation markers. However, the combined treatment of PVD with CIS significantly elevated the expression of terminal differentiation markers and eventually led to more cell death than either solo treatment. Aside from a reduced proliferation rate, these effects were not seen in the parent. Further research is needed to explore the potential use of PVD with CIS as a differentiation therapy or alternative treatment for MIUC tumors that may have become resistant to CIS.

CD133+CD24+ renal tubular progenitor cells play a crucial role in the repair and regeneration of renal tubules after acute kidney injury. The aim of this study is to investigate the responses of the human renal tubular precursor TERT (HRTPT) CD133+CD24+ cells and human renal epithelial cell 24 TERT (HREC24T) CD133-CD24+ cells to hypoxic stress, as well as their gene expression profiles. Whole transcriptome sequencing and functional network analysis identified distinct molecular characteristics of HRTPT cells as they were enriched with hypoxia-inducible factor-1A (HIF1A), epidermal growth factor (EGF), and endothelin-1 (EDN1). Our in vitro experiments demonstrated that, under hypoxia (2.5% oxygen), HRTPT cells showed minimal cell death and a 100-fold increase in HIF1A protein levels. In contrast, HREC24T cells exhibited significant cell death and only a two-fold increase in HIF1A protein level. These results indicate that CD133+CD24+ renal tubular progenitor cells have enhanced survival mechanisms under hypoxic stress, enabling them to survive and proliferate to replace damaged tubular cells. This study provides novel insights into the protective role of CD133+CD24+ renal tubular progenitor cells in hypoxic renal injury and identifies their potential survival mechanisms.