Ehsanul Haque

Studies on populations exposed to inorganic arsenic (iAs) have shown an association with the development of chronic kidney disease (CKD) and renal cell carcinoma (RCC). However, there are few studies addressing how acute exposure of the human kidney to iAs might lead to the long-term alterations that might lead to CKD or RCC. This laboratory’s hypothesis is that renal exposure to iAs might alter the renal cells responsible for the repair and regeneration of nephrons damaged by iAs exposure or other renal toxicants. The kidney possesses a minority epithelial cell population that co-expresses PROM1 and CD24, which are believed to be involved in renal epithelial cell repair. The purpose of this work is to understand the pathogenesis of CKD in renal cortical epithelial cells. Our model consists of acute and chronic exposure of i-As (III) to “Human Renal Tubular Precursor TERT” (HRTPT). The microarray and gene validation study demonstrated a sudden induction of microfibril associated protein 5 (MFAP5) and carcinoembryonic antigen related cell adhesion molecule 5 and 6 (CEACAM 5 and 6) in chronic i-As (III)-exposed cells. Chronically exposed cells also exhibited an induction of the pAKT/AKT pathway and SOX9 transcription factor. The targeting of MFAP5 and CEACAM 5/6 could, therefore, provide a potential therapeutic approach to CKD.

Arsenic, in the form of inorganic arsenite, is toxic to the kidney and can cause acute kidney injury, manifesting as destruction of proximal tubule cells. Nephron repair is possible through the proliferation of resident tubular progenitor cells expressing CD133 and CD24 surface markers. We simulated regenerative repair in the continued presence of i-As (III) using a cell culture model of a renal progenitor cell line expressing CD133 (PROM1) and CD24. Continued exposure and subculturing of progenitor cells to i-As (III) led to a reduction in the expression of PROM1 and CD24, as well as a decrease in the ability to differentiate into tubule-like structures. Cessation of i-As (III) and recovery for up to three passages resulted in continued repression of PROM1 and reduced ability to differentiate. Chronically exposed cells exhibited an ability to form colonies in soft agar, suggesting neoplastic transformation. Chronically exposed cells also exhibited an induction of CD44, a cell surface marker commonly found in renal cell carcinoma, as well as in tubular repair in chronic renal injury such as chronic kidney disease. These results demonstrate potential adverse outcomes of renal progenitor cells chronically exposed to a nephrotoxicant, as well as in environmental exposure to arsenic.

Studies on populations exposed to inorganic arsenic (iAs) have shown an association with the development of chronic kidney disease (CKD) and renal cell carcinoma (RCC). However, there are few studies addressing how acute exposure of the human kidney to iAs might lead to the long-term alterations that might lead to CKD or RCC. This laboratory’s hypothesis is that renal exposure to iAs might alter the renal cells responsible for the repair and regeneration of nephrons damaged by iAs exposure or other renal toxicants. The kidney possesses a minority epithelial cell population that co-express PROM1 and CD24 that are believed to be involved in renal epithelial cell repair. The purpose of this work is to understand the pathogenesis of CKD in renal cortical epithelial cells. Our model consists with acute and chronic exposure of i-As (III) to “Human Renal Tubular Precursor TERT” (HRTPT). The microarray and gene validation study demonstrated a sudden induction of microfibril associated protein 5 (MFAP5) and carcinoembryonic antigen related cell adhesion molecule 5 & 6 (CEACAM 5& 6) in chronic i-As (III) exposed cells. Chronically exposed cells also exhibited an induction of pAKT/AKT pathway, and SOX9 transcription factor. The targeting of MFAP5 & CEACAM5/6 could therefore provide a potential therapeutic approach to CKD.

Arsenic, in the form of inorganic arsenite (i-As3+), is toxic to the kidney and can cause acute kidney injury, manifesting as destruction of proximal tubule cells. Nephron repair is possible through the proliferation of resident tubular progenitor cells expressing CD133 and CD24 surface markers. We simulated regenerative repair in the continued presence of i-As3+ using a cell culture model of a renal progenitor cell line expressing CD133 (PROM1) and CD24. Continued exposure and subculturing of progenitor cells to i-As3+ led to a reduction in the expression of PROM1 and CD24 as well as a decrease in the ability to differentiate into tubule-like structures. Cessation of i-As3 and recovery up to 3 passages resulted in continued repression of PROM1 and reduced ability to differentiate. Chronically exposed cells exhibited an ability to form colonies in soft agar suggesting neoplastic transformation. Chronically exposed cells also exhibited an induction of CD44, a cell surface marker commonly found in renal cell carcinoma as well as in tubular repair in chronic renal injury such as in chronic kidney disease. These results demonstrate potential adverse outcomes of renal progenitor cells chronically exposed to a nephrotoxicant as well as in environmental exposure to arsenic.

Studies have reported the presence of renal proximal tubule specific progenitor cells which co-express PROM1 and CD24 markers on the cell surface. The RPTEC/TERT cell line is a telomerase-immortalized proximal tubule cell line that expresses two populations of cells, one co-expressing PROM1 and CD24 and another expressing only CD24, identical to primary cultures of human proximal tubule cells (HPT). The RPTEC/TERT cell line was used by the authors to generate two new cell lines, HRTPT co-expressing PROM1 and CD24 and HREC24T expressing only CD24. The HRTPT cell line has been shown to express properties expected of renal progenitor cells while HREC24T expresses none of these properties. The HPT cells were used in a previous study to determine the effects of elevated glucose concentrations on global gene expression. This study showed the alteration of expression of lysosomal and mTOR associated genes. In the present study, this gene set was used to determine if pure populations of cells expressing both PROM1 and CD24 had different patterns of expression than those expressing only CD24 when exposed to elevated glucose concentrations. In addition, experiments were performed to determine whether cross-talk might occur between the two cell lines based on their expression of PROM1 and CD24. It was shown that the expression of the mTOR and lysosomal genes was altered in expression between the HRTPT and HREC24T cell lines based on their PROM1 and CD24 expression. Using metallothionein (MT) expression as a marker demonstrated that both cell lines produced condition media that could alter the expression of the MT genes. It was also determined that PROM1 and CD24 co-expression was limited in renal cell carcinoma (RCC) cell lines.

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.

Rhizoctonia solani causes damping-off, as well as crown and root rot of sugar beet ( Beta vulgaris L). This pathogen overwinters as sclerotia or melanized mycelia. Traditionally, the resistance of cultivars to R. solani is evaluated by scoring disease reactions of the crowns and roots of older seedlings, instead of evaluating at seed germination. Most studies that have evaluated cultivar resistance to R. solani have used colonized whole barley grains as artificial inocula. Colonized grains are prone to contamination with other pathogens and are often lost to rodents/birds when applied in the field. Considering those limitations, a study was undertaken (1) to develop in vitro methods to generate natural sclerotia of R. solani on a large scale, (2) to compare pathogenic potentials of R. solani sclerotia, mycelia, and colonized barley grains for optimization of damping-off assays, and (3) to evaluate resistance of selected commercial cultivars to R. solani . Of the six-culture media, amended clarified V8 (ACV8) was the most suitable culture medium to grow and produce sclerotia on a large scale and 10% PDA was the least suitable. Three testing sizes of sclerotia were found to be equally effective in causing plant losses. Sclerotia inocula were comparable with mycelial discs and colonized barley grains in causing pre-emergence damping off under aseptic in vitro conditions. Sclerotia also were equally or more effective than mycelia plug or barley grain inocula in reducing seedling emergence, inducing damping off, and increased root rot under greenhouse in vivo conditions. To conclude, sclerotia can be prepared on a feasible scale and used as natural inocula to screen response to R. solani on sugar beet.

Sugar beet (Beta vulgaris L.) is a globally important crop for sugar. In May 2019, sugar beet seedlings were observed with wilting, lodging and a few were dead in Billings (45.7833° N, 108.5007° W)...

Sugar beet (Beta vulgaris L.) is an economically important crop in North Dakota. In July 2019, light brown to black necrotic leaf lesions with greyish centers were observed on commercial sugar beet...

Minnesota is the top sugar beet (Beta vulgaris L.) producing state in the United States. In September 2018, foliar symptoms were first observed on older sugar beet leaves in about 3% of the cultiva...