Effect of Long-Term Cisplatin Exposure on the Proliferative Potential of Immortalized Renal Progenitor Cells.

Cisplatin (CisPt) is a widely used chemotherapeutic agent. However, its nephrotoxic effects pose significant risks, particularly for the development of acute kidney injury (AKI) and potential progression to chronic kidney disease (CKD). The present study investigates the impact of non-lethal exposure of CisPt to immortalized human renal epithelial precursor TERT cells (HRTPT cells) that co-express PROM1 and CD24, markers characteristic of renal progenitor cells.

Knockdown of Keratin 6 Within Arsenite-Transformed Human Urothelial Cells Decreases Basal/Squamous Expression, Inhibits Growth, and Increases Cisplatin Sensitivity.

Urothelial carcinoma (UC) is prevalent, especially in elderly males. The high rate of recurrence, treatment regime, and follow-up monitoring make UC a global health and economic burden. Arsenic is a ubiquitous toxicant that can be found in drinking water, and it is known that exposure to arsenic is associated with UC development.

Genetics-driven risk predictions leveraging the Mendelian randomization framework.

Accurate predictive models of future disease onset are crucial for effective preventive healthcare, yet longitudinal data sets linking early risk factors to subsequent health outcomes are limited. To overcome this challenge, we introduce a novel framework, redictive sk modeling using ndelian andomization (PRiMeR), which utilizes genetic effects as supervisory signals to learn disease risk predictors without relying on longitudinal data. To do so, PRiMeR leverages risk factors and genetic data from a healthy cohort, along with results from genome-wide association studies of diseases of interest.

Transcriptomics and epigenetic data integration learning module on Google Cloud.

Multi-omics (genomics, transcriptomics, epigenomics, proteomics, metabolomics, etc.) research approaches are vital for understanding the hierarchical complexity of human biology and have proven to be extremely valuable in cancer research and precision medicine. Emerging scientific advances in recent years have made high-throughput genome-wide sequencing a central focus in molecular research by allowing for the collective analysis of various kinds of molecular biological data from different types of specimens in a single tissue or even at the level of a single cell.

Heavy Metal(oid)s Contamination and Potential Ecological Risk Assessment in Agricultural Soils.

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.

Translating genetic findings to epigenetics: identifying the mechanisms associated with aging after high-radiation exposure on earth and in space.

Purpose: Exposure to radiation is a health concern within and beyond the Earth's atmosphere for aircrew and astronauts in their respective austere environments. The biological effects of radiation exposure from a multiomics standpoint are relatively unexplored and stand to shed light on tailored monitoring and treatment for those in these career fields. To establish a reference variable for genetic damage, biological age seems to be closely associated with the effect of radiation.

A Review: Multi-Omics Approach to Studying the Association between Ionizing Radiation Effects on Biological Aging.

Multi-omics studies have emerged as powerful tools for tailoring individualized responses to various conditions, capitalizing on genome sequencing technologies' increasing affordability and efficiency. This paper delves into the potential of multi-omics in deepening our understanding of biological age, examining the techniques available in light of evolving technology and computational models. The primary objective is to review the relationship between ionizing radiation and biological age, exploring a wide array of functional, physiological, and psychological parameters.

Proteasomes Are Critical for Maintenance of CD133+CD24+ Kidney Progenitor Cells.

Kidney progenitor cells, although rare and dispersed, play a key role in the repair of renal tubules after acute kidney damage. However, understanding these cells has been challenging due to the limited access to primary renal tissues and the absence of immortalized cells to model kidney progenitors. Previously, our laboratory utilized the renal proximal tubular epithelial cell line, RPTEC/TERT1, and the flow cytometry technique to sort and establish a kidney progenitor cell model called Human Renal Tubular Precursor TERT (HRTPT) which expresses CD133 and CD24 and exhibits the characteristics of kidney progenitors, such as self-renewal capacity and multi-potential differentiation.

Pevonedistat Inhibits SOX2 Expression and Sphere Formation but Also Drives the Induction of Terminal Differentiation Markers and Apoptosis within Arsenite-Transformed Urothelial Cells.

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.

Establishing a genomic radiation-age association for space exploration supplements lung disease differentiation.

Purpose: One possible way to quantify each individual's response or damage from ionizing radiation is to estimate their accelerated biological age following exposure. Since there is currently no definitive way to know if biological age estimations are accurate, we aim to establish a rad-age association using genomics as its foundation.

Methods: Two datasets were combined and used to empirically find the age cutoff between young and old patients.

Primary and Immortalized Cultures of Human Proximal Tubule Cells Possess Both Progenitor and Non-Progenitor Cells That Can Impact Experimental Results.

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.

Arsenite Exposure to Human RPCs (HRTPT) Produces a Reversible Epithelial Mesenchymal Transition (EMT): In-Vitro and In-Silico Study.

The human kidney is known to possess renal progenitor cells (RPCs) that can assist in the repair of acute tubular injury. The RPCs are sparsely located as single cells throughout the kidney. We recently generated an immortalized human renal progenitor cell line (HRTPT) that co-expresses PROM1/CD24 and expresses features expected on RPCs.

Contamination Assessment and Potential Human Health Risks of Heavy Metals in Urban Soils from Grand Forks, North Dakota, USA.

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 HNO-HCl acid digestion and inductively coupled plasma mass spectrometry (ICP-MS) analysis.

Chronic Arsenic Exposure Upregulates the Expression of Basal Transcriptional Factors and Increases Invasiveness of the Non-Muscle Invasive Papillary Bladder Cancer Line RT4.

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.

Protein interactions with metallothionein-3 promote vectorial active transport in human proximal tubular cells.

Metallothionein 3 (MT-3) is a small, cysteine-rich protein that binds to essential metals required for homeostasis, as well as to heavy metals that have the potential to exert toxic effects on cells. MT-3 is expressed by epithelial cells of the human kidney, including the cells of the proximal tubule. Our laboratory has previously shown that mortal cultures of human proximal tubular (HPT) cells express MT-3 and form domes in the cell monolayer, a morphological feature indicative of vectorial active transport, an essential function of the proximal tubule.

Association between Arsenic Level, Gene Expression in Asian Population, and In Vitro Carcinogenic Bladder Tumor.

The IARC classified arsenic (As) as "carcinogenic to humans." Despite the health consequences of arsenic exposure, there is no molecular signature available yet that can predict when exposure may lead to the development of disease. To understand the molecular processes underlying arsenic exposure and the risk of disease development, this study investigated the functional relationship between high arsenic exposure and disease risk using gene expression derived from human exposure.

Role of HRTPT in kidney proximal epithelial cell regeneration: Integrative differential expression and pathway analyses using microarray and scRNA-seq.

Damage to proximal tubules due to exposure to toxicants can lead to conditions such as acute kidney injury (AKI), chronic kidney disease (CKD) and ultimately end-stage renal failure (ESRF). Studies have shown that kidney proximal epithelial cells can regenerate particularly after acute injury. In the previous study, we utilized an immortalized in vitro model of human renal proximal tubule epithelial cells, RPTEC/TERT1, to isolate HRTPT cell line that co-expresses stem cell markers CD133 and CD24, and HREC24T cell line that expresses only CD24.

Postbaccalaureate terminal degree and career choices of students who performed undergraduate research.

This study analyzed terminal degree and career choices of students who performed undergraduate research. In one analysis, the study compared terminal degree and career choices between a course-based undergraduate research experience (CURE) and traditional non-course-based undergraduate research experiences at one primarily undergraduate institution (PUI). Students who pursued postbaccalaureate programs chose terminal degrees at levels exceeding 75%, with no significant difference between a CURE experience and a traditional research experience.

Zinc, Zinc Transporters, and Cadmium Cytotoxicity in a Cell Culture Model of Human Urothelium.

We explored the potential role of zinc (Zn) and zinc transporters in protection against cytotoxicity of cadmium (Cd) in a cell culture model of human urothelium, named UROtsa. We used real-time qRT-PCR to quantify transcript levels of 19 Zn transporters of the Zrt-/Irt-like protein (ZIP) and ZnT gene families that were expressed in UROtsa cells and were altered by Cd exposure. Cd as low as 0.

Elevated glucose represses lysosomal and mTOR-related genes in renal epithelial cells composed of progenitor CD133+ cells.

Hyperglycemia is one of the major health concern in many parts of the world. One of the serious complications of high glucose levels is diabetic nephropathy. The preliminary microarray study performed on primary human renal tubular epithelial (hRTE) cells exposed to high glucose levels showed a significant downregulation of mTOR as well as its associated genes as well as lysosomal genes.

Meta-analysis of gene expression profiling reveals novel basal gene signatures in MCF-10A cells transformed with cadmium.

Cadmium (Cd) is an environmental toxicant and a human carcinogen. Several studies show an association of Cd exposure to the development of breast cancer. Previously, we have transformed the immortalized non-tumorigenic cell line MCF-10A with Cd and have demonstrated that the transformed cells have anchorage independent growth.

Activation of PPARγ and inhibition of cell proliferation reduces key proteins associated with the basal subtype of bladder cancer in As3+-transformed UROtsa cells.

Environmental exposure to arsenite (As3+) has a strong association with the development of human urothelial cancer (UC) and is the 5th most common cancer in men and the 12th most common cancer in women. Muscle invasive urothelial cancer (MIUC) are grouped into basal or luminal molecular subtypes based on their gene expression profile. The basal subtype is more aggressive and can be associated with squamous differentiation, characterized by high expression of keratins (KRT1, 5, 6, 14, and 16) and epidermal growth factor receptor (EGFR) within the tumors.

Characterization and determination of cadmium resistance of CD133/CD24 and CD133/CD24 cells isolated from the immortalized human proximal tubule cell line, RPTEC/TERT1.

Stem/progenitor cells are involved in the regeneration of the renal tubules after damage due to a toxic insult. However, the mechanism involved in the regeneration of the tubules by the stem cells is not well understood due to the lack of immortal cell lines that represent the stem/progenitor cells of the kidney. A previous study from our laboratory has shown that the immortalized cell line RPTEC/TERT1 contains two populations of cells, one co-expressing CD24 and CD133, the other expressing CD24 only.

Enrichment of genes associated with squamous differentiation in cancer initiating cells isolated from urothelial cells transformed by the environmental toxicant arsenite.

Arsenic is an environmental toxicant with long-term exposure associated with the development of urothelial carcinomas. Our lab has developed an in-vitro model of urothelial carcinoma by exposing the immortal, but non-tumorigenic bladder cell line, the UROtsa, to arsenite (As). These transformed cells form tumors in immune-compromised mice, which resemble urothelial carcinomas with components of the tumor exhibiting squamous differentiation.