Carcinogenic and Non-carcinogenic Risk Assessment of Heavy Metals in Groundwater Wells in Neyshabur Plain,Iran

The present work reports the As, Cr, Cu, Pb, Zn, and Fe concentrations of drinking water samples in Neyshabur Plain, Iran. This study aimed also to ascertain the potential consumers’ health risk of heavy metal intake. Heavy metal concentrations were analyzed by inductively coupled plasma optical emission spectrometry. The highest and lowest average values in the analyzed water samples were observed for Fe (9.78 ± 5.61 μg/L) and As (1.30 ± 2.99 μg/L), respectively. These values were well below the limits recommended by the World Health Organization and the Iranian national standard. Heavy metal pollution index and heavy metal evaluation index were used to evaluate drinking water quality. The risk index was calculated by chronic daily intake and hazard quotient according to the United States Environmental Protection Agency approach. Heavy metal pollution index in all the samples was less than 100, indicating that it is a low-level heavy metal. The total risk of all heavy metals in the urban environment varied from 40.164 × 10⁻⁷ to 174.8 × 10⁻⁷. In this research, the maximum average of risk belonged to lead and copper with the respective values of 60.10 × 10⁻⁷and 33.99 × 10⁻⁷ from the selected wells. However, considering the toxic effect of some elements, including Pb and As, in the chronic exposure of consumers, we suggest a continuous evaluation and monitoring of drinking water resources.

     

Nicotine Promotes Acquisition of Stem Cell and Epithelial-to-Mesenchymal Properties in Head and Neck Squamous Cell Carcinoma

The ability of nicotine to enhance the malignancy of cancer cells is known; however, the possibility that nicotine could regulate a cancer stem cell phenotype remains to be well-established. In this study we sought to determine whether long-term exposure to nicotine could promote cancer stem cell-like properties in two head and neck squamous cell carcinoma cell lines, UMSCC-10B and HN-1. Nicotine treatment induced epithelial-to-mesenchymal transition (EMT) in both cell lines by repressing E-cadherin expression, and led to the induction of stem cell markers Oct-4, Nanog, CD44 and BMI-1, which was reversed upon ectopic re-expression of E-cadherin. Nicotine-treated cells formed spheres at a higher efficiency than non-treated cells, formed larger tumors when injected into mice, and formed tumors with 4-fold greater efficiency compared to control cells when injected at limiting doses. Consistent with previous literature, nicotine-treated cells demonstrated a greater capacity for survival and also a higher tendency to invade. Comparison of microRNA profiles between nicotine and control cells revealed the upregulation of miR-9, a repressor of E-cadherin, and the downregulation of miR-101, a repressor of EZH2. Taken together, these results suggest that nicotine may play a critical role in the development of tobacco-induced cancers by regulating cancer stem cell characteristics, and that these effects are likely mediated through EMT-promoting, microRNA-mediated pathways. Further characterization of such pathways remains a promising avenue for the understanding and treatment of tobacco-related cancers.     

Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 Tesla MRI and pathology

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI) studies have previously shown hypointense signal in the motor cortex on T(2)-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or definite ALS by El Escorial criteria and 19 healthy controls underwent 3T MRI. A 7T MRI scan was carried out on five ALS patients who had motor cortex hypointensity on the 3T FLAIR sequence and on three healthy controls. Postmortem 7T MRI of the brain was performed in one ALS patient and histological studies of the brains and spinal cords were obtained post-mortem in two patients. The motor cortex hypointensity on 3T FLAIR images was present in greater frequency in ALS patients. Increased hypointensity correlated with greater severity of upper motor neuron impairment. Analysis of 7T T(2)(*)-weighted gradient echo imaging localized the signal alteration to the deeper layers of the motor cortex in both ALS patients. Pathological studies showed increased iron accumulation in microglial cells in areas corresponding to the location of the signal changes on the 3T and 7T MRI of the motor cortex. These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia.     

Development of an enhanced chemiluminescence immunoassay (CLIA) for detecting urinary albumin

In the present study, a sensitive and competitive chemiluminescence immunoassay (CLIA) was developed in order to detect human serum albumin (HSA) in urine specimen. The method utilizes a home-made monoclonal anti-albumin antibody conjugated to horseradish peroxidase enzyme (mAb-HRP). Sensitivity, specificity and linearity of the assay were evaluated. According to the results, the proper concentration of HSA and mAb-HRP conjugates was 800?ng/100?μl and 1:200 respectively. In optimal conditions, this method could detect HSA in a high linear range of 10–200?μg?ml^?1 with the low detection limit of 0.025?μg?ml^?1. No evidence of interference with presence of probable substances in the urine samples indicated its high specificity and selectivity. Moreover, high reproducibility as well as high sensitivity and specificity of the test were confirmed using diabetic and non-diabetic samples. Significant concordance was observed between CLIA and immunoturbidimetry assay regarding detection of HSA. The results of the present study can be considered in accordance with the current demands such as reliability, accuracy, convenience and high speed of performance for a precise protein detection method. Furthermore, it may be regarded as a more rapid, simpler and cheaper alternative compared to other sophisticated assays.     

Inhibitor of PI3K/Akt Signaling Pathway Small Molecule Promotes Motor Neuron Differentiation of Human Endometrial Stem Cells Cultured on Electrospun Biocomposite Polycaprolactone/Collagen Scaffolds

Small molecules as useful chemical tools can affect cell differentiation and even change cell fate. It is demonstrated that LY294002, a small molecule inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway, can inhibit proliferation and promote neuronal differentiation of mesenchymal stem cells (MSCs). The purpose of this study was to investigate the differentiation effect of Ly294002 small molecule on the human endometrial stem cells (hEnSCs) into motor neuron-like cells on polycaprolactone (PCL)/collagen scaffolds. hEnSCs were cultured in a neurogenic inductive medium containing 1 μM LY294002 on the surface of PCL/collagen electrospun fibrous scaffolds. Cell attachment and viability of cells on scaffolds were characterized by scanning electron microscope (SEM) and 3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. The expression of neuron-specific markers was assayed by real-time PCR and immunocytochemistry analysis after 15 days post induction. Results showed that attachment and differentiation of hEnSCs into motor neuron-like cells on the scaffolds with Ly294002 small molecule were higher than that of the cells on tissue culture plates as control group. In conclusion, PCL/collagen electrospun scaffolds with Ly294002 have potential for being used in neural tissue engineering because of its bioactive and three-dimensional structure which enhances viability and differentiation of hEnSCs into neurons through inhibition of the PI3K/Akt pathway. Thus, manipulation of this pathway by small molecules can enhance neural differentiation.     

Towards sustainable management of Indonesian tropical peatlands

Large areas of Indonesian peatlands have been converted for agricultural and plantation forest purposes. This requires draining with associated CO₂ emissions and fire risks. In order to identify alternative management regimes for peatlands, it is important to understand the sustainability of different peatland uses as well as the economic benefits peatlands supply under different land uses. This study explores the key sustainability issues in Indonesian peatlands, the ecosystem services supplied by peatlands, and potential responses to promote more sustainable peatland use. A literature review and spatial analysis were conducted. Based on predominantly government data, we estimate the amount of Indonesian peatlands that has been converted between 2000 and 2014. We quantify increases in oil palm and plantation forest crop production in this period, and we analyse key sustainability issues, i.e. peat fires and smoke-haze, soil subsidence and flood risk, CO₂ emissions, loss of habitat (in protected areas), and social conflicts that influence sustainability of Indonesian peatlands management. Among others we show that CO₂ emissions from peatlands in Indonesia can be estimated at between 350 and 400 million ton CO₂ per year, and that encroachment of oil palm and plantation forestry (acacia, rubber) has taken place on 28% of protected areas. However, as we examine, the uncertainties involved are substantial. Based on our findings, we distil several implications for the management of the peatlands.