Toxicity Of Low Concentrations Research Articles

Increasing the radiation-induced cytotoxicity by silver nanoparticles and docetaxel in prostate cancer cells.

Radiation therapy is utilized for treatment of localized prostate cancer. Nevertheless, cancerous cells frequently develop radiation resistance. While higher radiation doses have not always been effective, radiosensitizers have been extensively studied for their ability to enhance the cytotoxic effects of radiation.So, this study aims to evaluate the possible radiosensitization effects of docetaxel (DTX) and silver nanoparticles (SNP) in LNCaP cells. The cytotoxic effects of DTX, SNP and2Gy of X-Ray radiation treatments were assessed in human LNCaP cell line using the MTT test after 24 h. Moreover, the effects of DTX, SNP and radiation on Epidermal growth factor (EGF), Caspase 3, inducible nitric oxide synthase and E-cadherin gene expression were analyzed using the Real-time PCR method. The level of Hydrogen peroxide (H2O2), an oxidative stress marker, was also detected 24h after various single and combined treatments. The combinations of SNP (in low toxic concentration) and/or DTX (0.25× IC50 and 0.5 × IC50 concentrations for triple and double combinations respectively) with radiation induced significant cytotoxicity in LNCaP cells in comparison to monotherapies. These cytotoxic effects were associated with the downregulation of EGF mRNA. Additionally, H2O2 levels increased after Radiation + SNP + DTX triple combination and double combinations including Radiation + SNP and Radiation + DTX versus single treatments. The triple combination treatment also increased Caspase 3 and and E-cadherin mRNA levels in compared to single treatments in LNCaP cells. Our results indicate that the combination of SNP and DTX with radiation induces significant anti-cancer effects. Upregulation of Caspase 3 and E-cadherin gene expression, and decreased mRNA expression level of EGF may be exerted specifically by use of this combination versus single treatments.

Green Chemistry on the Ores Leaching Processes Using Organic Acids: A Qualitative Pedagogical Content Analysis Study

Ores leaching projects aimed to recover toxic and valuable metals from industrial residues. Organic acids like acetic acid and methanesulfonic acid were chosen as leaching agents because they have high selectivity on low concentrations of metals and low toxicity. This study aimed to obtain scientists’ conceptions of ores leaching using organic acids presented in concept maps and Teaching Learning Sequence (TLS). The method used in this study was qualitative content analysis consisting of literature collection, descriptive analysis, category selection, and material evaluation from textbooks, review articles and research articles. The result of this study was in the form of a concept map, and TLS illustrate five sequences of learning materials consisting of mineral products in Indonesia, valorization of industrial process residue with green chemistry-oriented, industrial process residue treatment steps, organic acid properties, and examples of the ores leaching process. The leaching process of ores using organic acids in learning is contextual learning that integrates the concepts of acids and bases, redox reactions, and the principles of solubility learned by high school students. This process also applies the principles of green chemistry, preventing waste in the process and using safe solvents. The results of the concept map and Teaching Learning Sequence (TLS) showed the application of green chemistry in learning, which is expected to be used as a design for teaching materials and didactic designs that can support education for sustainable development. Keywords: Green Chemistry, Organic Acids, Pedagogical Content Analysis

New Dual Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 and 2 Based on Deoxycholic Acid: Design, Synthesis, Cytotoxicity, and Molecular Modeling.

Deoxycholic acid derivatives containing various heterocyclic functional groups at C-3 on the steroid scaffold were designed and synthesized as promising dual tyrosyl-DNA phosphodiesterase 1 and 2 (TDP1 and TDP2) inhibitors, which are potential targets to potentiate topoisomerase poison antitumor therapy. The methyl esters of DCA derivatives with benzothiazole or benzimidazole moieties at C-3 demonstrated promising inhibitory activity in vitro against TDP1 with IC50 values in the submicromolar range. Furthermore, methyl esters 4d-e, as well as their acid counterparts 3d-e, inhibited the phosphodiesterase activity of both TDP1 and TDP2. The combinations of compounds 3d-e and 4d-e with low-toxic concentrations of antitumor drugs topotecan and etoposide showed significantly greater cytotoxicity than the compounds alone. The docking of the derivatives into the binding sites of TDP1 and TDP2 predicted plausible binding modes of the DCA derivatives.

Integrated Management of Industrial Wastewater in the Food Sector

In 2019, a staggering 931 million tons of food went to waste, which is equal to about 17% of all the food available in stores. Dealing with this waste and managing wastewater from various industries will be among the world’s top challenges soon. This is because the global population is expected to grow to around 9 billion people by 2050. Food processing effluent is characterized by valuable material in considerable concentrations, including proteins and lipids with low concentrations of heavy metals and toxicants. Developing an integrated management system for food-processing wastewater should focus on recovering abundant resources, improving the economic value of the process, and mitigating the organic contaminant in the food-processing effluent. This state-of-the-art will review the wastewater management processes of the food processing industry. The latest wastewater treatment processes in different food processing sectors will be reviewed. This review will encompass various physicochemical treatment and recovery techniques, such as precipitation, membrane technology, solvent extraction, foam fractionation, adsorption, and aqueous two-phase systems. Additionally, it will delve into bio-treatment processes that leverage microorganisms and/or enzymes to utilize nutrients found in food-processing wastewater as cost-effective substrates for the production of valuable products. This includes a detailed examination of microalga biomass production within wastewater treatment systems. Finally, the review will put forward future research directions aimed at integrating the principles of the circular economy and developing comprehensive food-processing wastewater management systems.

Microbial desalination cell treated spent geothermal brine as a nutrient medium in hydroponic lettuce cultivation: Health risk assessment

The scarcity and contamination of freshwater resources are extremely critical issues today, and the expansion of water reuse has been considered as an option to decrease its impact. Therefore, the reuse of microbial desalination (MDC)-treated spent geothermal brine for agricultural purposes arises as a good solution to prevent water contamination and provide sustainable water usage. In this study, the potential of treated spent geothermal water from MDC system as a nutrient solution for the hydroponic cultivation of lettuce was evaluated. The effects of different water samples (Hoagland solution (R1) as a control, MDC-treated water (R2), 1:1, v/v mixture of MDC-treated water and Hoagland solution (R3), 4:1, v/v mixture of MDC-treated water and Hoagland solution (R4), and tap water (R5)) on lettuce growth were considered. The application of R3 and R4 samples for hydroponic lettuce cultivation was promising since the lettuce plants uptake sufficient nutrients for their growth and productivity with low toxic metal concentrations. In addition, the chlorophyll-a, chlorophyll-b, and carotene contents of lettuce were in the range of 1.045–2.391 mg/g, 0.761–1.986 mg/g, and 0.296–0.423 mg/g in different water samples, respectively. The content of chlorophyll-a was highest in R1 (2.391 mg/g), followed by R3 (2.371 mg/g). Furthermore, the health risk assessment of heavy metal accumulations in the lettuce plants cultivated in the various water samples was determined. Results showed that heavy metal exposure via lettuce consumption is unlikely to suffer noticeable adverse health problems with values below the permissible limit value.

Titanium mesh as the anode of electrochemically active biofilm sensor for improved sensitivity in water toxicity real-time early-warning

As serious water ecological pollution caused by toxicant leakage occurs frequently, early-warning for toxicity presented in water environment attracts increasing attentions as it saves time to retain water safety and human health. Electrochemically active biofilm (EAB) sensor is a promising device for in situ real-time water toxicity early-warning. To improve the sensitivity of EAB sensor particularly for low-concentration toxicity warning, this study employed titanium mesh (TiM) as the anode to construct an EAB sensor. Compared to traditional EAB sensor with carbon felt (CF) anode, the sensitivity of the TiM sensor was increased up to 37.4 times. The effects of mesh size (TiM50, TiM100, TiM150) and operation mode (flow-by and flow-through) on the sensitivity of TiM sensors were further investigated. Results showed the sensor with TiM100 anode had the highest inhibition rate (IR) in flow-by mode, attributed to low charge transfer resistance (Rct) and fast mass transfer. Flow-through operation could further enhance TiM100 sensor's sensitivity from flow-by operation and succeeded to signal as low as 0.0025% formaldehyde, the lowest so far tested in EAB sensor with sensing anode. Multiple toxicity shocks on flow-through TiM100 sensor revealed its good recoverability towards all tested formaldehyde concentration from 0.01% to 0.0025%, during which electrochemical activity degradation and biomass accumulation partially impaired the repeatability. This work highlights the great improvement of EAB sensors by utilizing titanium mesh as EAB carrier and provides a reference for the practical application of metallic materials for EAB sensors.

Celastrus orbiculatus Thunb. extract targeting DJ-1 inhibits non-small cell lung cancer invasion and metastasis through mitochondrial-induced ROS accumulation

Ethnopharmacological relevanceCelastrus orbiculatus Thunb. is an ancient traditional Chinese herb with a long history of medicinal use. The ethyl acetate extract of Celastrus orbiculatus Thunb. (COE) has been shown to have anti-tumor effects in various preclinical studies. However, the anti-invasive and metastatic efficacy of COE in non-small cell lung cancer (NSCLC) and the mechanism by which COE regulates cellular oxidation levels are yet to be elucidated. AimTo study the anti-dissemination effect of COE on NSCLC and to elucidate the molecular mechanism of COE in regulating cellular oxidation levels and its effect on lung cancer invasion and metastasis. MethodsCCK-8 assay was used to detect the toxic effects of COE on NSCLC. Transwell assay and high-content imaging was used to detect the Motility of NSCLC. Transmission electron microscopy and three-dimensional (3D) imaging of mitochondrial fluorescence were employed to detect the number and structure of mitochondria. JC-1 probe was used to detect the level of mitochondrial membrane potential. Firefly luciferase assay was used to detect the level of total intracellular ATP. MitoSox probe and DCFH-DA probe were applied to detect the level of reactive oxygen species (ROS) inside the mitochondria and the total intracellular ROS, respectively. Immunohistochemistry was used to detect protein expression in xenograft tumors. ResultsCOE inhibited motility and induced DJ-1 downregulation in NSCLC at low toxic concentrations, and the antiseptic effect of COE was reduced significantly after the overexpression of DJ-1. COE induced structural disruption of mitochondria in NSCLC and accumulation of superoxide compounds, decreased the volume of membrane potential depolarization, and impaired energy production, ultimately leading to a large accumulation of ROS at the cellular level. The antioxidant acetylcysteine (NAC) significantly reversed the antiseptic capacity of COE. In a xenograft tumor model, protein expression of DJ-1, E-cadherin, N-cadherin, and MMP-2 in COE group was significantly changed compared to the model group. ConclusionIn the present study, COE inhibited NSCLC invasion and metastasis and was associated with the downregulation of DJ-1 and elevated ROS. COE-mediated downregulation of DJ-1 may be the primary cause of mitochondrial structural and functional dysfunction in NSCLC, eventually leading to ROS accumulation.

Triptonodiol, a Diterpenoid Extracted from Tripterygium wilfordii, Inhibits the Migration and Invasion of Non-Small-Cell Lung Cancer.

Lung cancer is the most prevalent oncological disease worldwide, with non-small-cell lung cancer accounting for approximately 85% of lung cancer cases. Tripterygium wilfordii is a traditional Chinese herb that is widely used to treat rheumatism, pain, inflammation, tumors, and other diseases. In this study, we found that Triptonodiol extracted from Tripterygium wilfordii inhibited the migration and invasion of non-small-cell lung cancer and inhibited cytoskeletal remodeling, which has not been previously reported. Triptonodiol significantly inhibited the motility activity of NSCLC at low toxic concentrations and suppressed the migration and invasion of NSCLC. These results can be confirmed by wound healing, cell trajectory tracking, and Transwell assays. We found that cytoskeletal remodeling was inhibited in Triptonodiol-treated NSCLC, as evidenced by the reduced aggregation of actin and altered pseudopod morphology. Additionally, this study found that Triptonodiol induced an increase in complete autophagic flux in NSCLC. This study suggests that Triptonodiol reduces the aggressive phenotype of NSCLC by inhibiting cytoskeletal remodeling and is a promising anti-tumor compound.

Investigation on the Toxicity of Nanoparticle Mixture in Rainbow Trout Juveniles

The environmental impacts of nanoparticle mixtures in the aquatic environment is not well understood. The purpose of this study examined the sub-lethal toxicity of low concentrations (ug/L range) of selected nanoparticles alone and in mixtures in juvenile trout. Fish were exposed to to individual and two environmentally relevant mixtures of silver (nAg), copper oxide (nCuO) and cerium oxide (nCeO) nanoparticles for 96 h at 15 °C. After the exposure period, fish were depurated overnight and tissue levels in Ag, Ce, Cu and Zn were determined along with a suite of effects biomarkers such as oxidative stress/inflammation, denatured protein tagging (ubiquitin), DNA strand breaks (genotoxicity) and acetylcholinesterase (AChE) activity. The data showed that these nanoparticles behaved as suspended matter but were nevertheless bioavailable for fish with bioconcentration factors of 6, 8 and 2 for nAg, nCeO and nCuO respectively. Only nCuO alone increased malonaldehyde (lipid peroxidation) contents but all nanoparticles increased DNA damage, protein-ubiquitin labeling, and decreased AChE activity. Globally, the toxicity of nCeO and nCuO was generally stronger than nAg, and antagonist effects were found in the mixtures. The interactions involved in these antagonisms are not well understood but do not involve the liberation of free ions and labile zinc in tissues. In conclusion, the bioavailability and toxicity of these nanoparticles are influenced by mixtures of nanoparticles, which is likely to occur in contaminated environments.

Gene expression study alerted to possible impairment in Daphnia magna individuals as a consequence of exposure to sublethal concentrations of prochloraz

In the present study, Daphnia magna individuals were exposed for 21 days to 87, 130, 170, 230 and 380 μg/L of prochloraz. The expression of genes related to lipid metabolism (fabd), oxidative stress (cat and gst), heat shock proteins synthesis (hsp70 and hsp90), haemoglobin synthesis (hgb1 and hgb2), metallothioneins synthesis (mt-a, mt-b and mt-c), and vitellogenin synthesis (vgt1 y vgt2) were analyzed. Results showed that some gene expression in D. magna was altered as a consequence of the individual exposure to the fungicide. The genes fabd, vtg1 and vtg2, cat and gst resulted unaltered by the exposure of the daphnids to different fungicide concentrations. However, daphnid exposure to 380 μg/L of prochloraz resulted in an overexpression (p < 0.05) of hsp70 gene which indicated an alteration of the normal protein synthesis and its integrity maintenance. On the other hand, mt-b gene resulted significantly underexpressed (p < 0.05) in daphnids exposed to the lowest fungicide concentrations (87, 130 and 170 μg/L, respectively). In addition, hgb1 and hgb2 genes which are related with the haemoglobin synthesis weresignificantly overexpressed (p < 0.05). Results showed that hgb1 gene was overexpressed almost 100 times more in daphnids exposed for 21 days to 170, 230 and 380 μg/L than control values. However, many authors advocate for an association of these gene expression changes with the presence of contaminants in the medium, in fact they could be used as a good indicator of early contamination at low concentrations of toxicants.

Isothermal Modelling of the Adsorption of Lead (II) Onto Activated Carbon from Tridax procumbens

Hypertension and kidney damage have been linked to lead exposure in adults. Any person can be harmed by lead, but pregnant women and their unborn children are especially vulnerable. Presently, lead pollution is removed using membrane separation, ion exchange, precipitation, and biosorption. Biosorption's low operating costs, high efficiency at detoxifying low concentrations of toxicants, and small volume of disposal materials make it the least problematic of these technologies. The biosorption of lead (II) onto activated carbon from Tridax procumbens is remodeled using nonlinear regression and the optimal mode was determined by a series of error function assessments. The Freundlich model performed best in statistical tests including root-mean-square error (RMSE), adjusted coefficient of determination (adjR2), bias factor (BF), accuracy factor (AF), and corrected Akaike Information Criterion (AICc) The calculated Freundlich parameters kF value using nonlinear regression was 1.334 (1/g) (95% confidence interval from 0.821 to 1.847) and nF value of 3.872 (95% C.I. from 1.972 to 5.771). Modelling using a nonlinear approach allows for the calculation of uncertainty range in terms of 95% confidence interval that would be useful for model comparison and discriminant in future studies

Kinetic Analysis of the Adsorption of lead (II) onto Activated Carbon from Tridax procumbens

Adults who are exposed to high levels of lead may develop hypertension and kidney damage. Lead exposure is dangerous for everyone, but it can have devastating effects on pregnant women and their babies. Methods such as membrane separation, ion exchange, precipitation, and biosorption are currently in use for the removal of lead pollution. Biosorption has the fewest negative aspects of these technologies due to its low operating costs, high efficiency at detoxifying low concentrations of toxicants, and small volume of disposal materials. The biosorption of the biosorption of lead (II) onto the activated carbon from Tridax procumbens is remodeled using nonlinear regression and the optimal mode was determined by a series of error function assessments. The best kinetic model for adsorption of lead (II) was Pseudo-1st order with a reasonable difference in terms of corrected Akaike Information Criterion to the next best model, which was pseudo-2nd order, and followed by the Elovich. However, the error function analyses especially the AICc was not conclusive in ranking the pseudo-1st order model as the best model due to the low (less than 5) absolute values of differences between the model. The pseudo-1st order kinetic constants obtained were qe (mg/g) of 6.181 (95% confidence interval from 5.009 to 7.352) and k1 (per min) of 0.007 (95% confidence interval from 0.004 to 0.009). Nonlinear modeling enables the determination of a 95 percent confidence interval for the uncertainty range, which can be used in model comparison and discriminant analysis.

Comparison of the combined toxicity of polystyrene microplastics and different concentrations of cadmium in zebrafish

Microplastic particles (MPs) are widely distributed in the environment. The high surface ratio of MPs make them effective transmission mediums for many toxic pollutants. The combined toxicity of MPs and heavy metals have received increasing attention in recent years. In this study, effects of MPs (100 μg/L) on the toxicity of low (15 μg/L) and high (150 μg/L) concentrations of cadmium (Cd) to zebrafish were evaluated based on a 10-day subacute exposure. The survival rate, growth, antioxidant capacity, reactive oxygen species (ROS) accumulation, histology and Cd biological enrichment in different tissues were investigated with the objective to understand the effect and mechanism of MPs on Cd toxicity to zebrafish. The results showed that the effect of MPs on Cd toxicity mainly depended on the concentration of Cd. MPs significantly enhanced the toxicity of low concentrations of Cd (LCd), including lower antioxidant enzyme activities, higher ROS levels, more severe tissue damage, inhibited growth rate and lower survival rate. However, the effects of MPs on the toxicity of high concentrations of Cd (HCd) were exactly opposite to LCd. Cd enrichment analysis showed that MPs could significantly increase LCd accumulation in intestine, gill, skin and muscle tissues, while decrease the enrichment of HCd in liver, intestine, gill and muscle tissues. Free Cd in the exposure water was significantly decreased by MPs in the HCd and MPs combined exposure group. These results suggest that effect of MPs on Cd toxicity to zebrafish depending on Cd concentration, MPs can increase the enrichment of LCd in zebrafish and enhance its toxicity, but can decrease the enrichment of HCd in zebrafish and attenuate its toxicity. The present study will broaden our understanding of the interaction between MPs and heavy metals.

Close association between the synergistic toxicity of zearalenone-deoxynivalenol combination and microRNA221-mediated PTEN/PI3K/AKT signaling in HepG2 cells

Mycotoxins can impart different types of combined toxicity to humans and animals, therefore, it is critical to understand the underlying mechanisms to eliminate the harm. Herein a combination of zearalenone (ZEA) at 2 μM and deoxynivalenol (DON) at 0.1 μM decreased cell viability and increased ROS level in HepG2 cells, suggesting synergistic toxicity exerted by ZEA and DON even at their low toxic concentrations. Moreover, apoptosis and inflammatory response were promoted after the co-exposure of ZEA and DON, indicated by the increased expression of BAX, Caspase-3, IL-1β and IL-6 genes. Such synergistic toxicity was closely associated with miR-221-mediated PTEN/PI3K/AKT signal pathway, with a negative regulatory relationship between PTEN and PI3K/AKT signaling. MiR-221 could influence cell viability and ROS level to counter the combined toxicity of ZEA and DON through targeting directly PTEN gene. This study demonstrated the toxicological impact of mycotoxin interactions on cells, and critical role of the interplay between miRNAs and PTEN in monitoring the synergistic toxicity of mycotoxin mixture.

Contribution of household drinking water intake to arsenic and lead exposure among Uruguayan schoolchildren

BackgroundFood and water are common exposure sources of arsenic and lead among children. Whereas dietary sources of these toxicants are fairly well-studied, the contribution of drinking water to toxicant exposures is not well characterized in many populations, particularly in the Global South. ObjectiveTo assess the extent to which consumption of household drinking water contributes to arsenic and lead exposure among Uruguayan schoolchildren with low-level exposure. MethodsChildren, aged 5–8 years, were enrolled into the Salud Ambiental Montevideo study during 2009–2013 from schools in Montevideo, Uruguay. Participants reported water intake as part of two 24-h dietary recalls. Concentrations of arsenic were measured in first morning void urine samples, and adjusted for urinary specific gravity. Lead concentrations were measured in venous blood samples. Drinking water samples were collected from participants’ homes and toxicant concentrations measured. Data analyses involved a triangulation approach. First, multivariable linear regressions estimated the associations between toxicant exposure through drinking water, calculated for each child as the product of water intake and water toxicant concentration, and the respective toxicant biomarker concentrations among children with complete data on all variables (Sample A; n = 40). Second, regressions were repeated for participants with complete data on all variables except water intakes (Sample B; n = 195), after water intakes were imputed. Finally, models were constructed for participants of Sample B (n = 195) based on drinking water intakes assumed to be fixed at 25th, 50th, 75th percentile intakes of participants in sample A. ResultsToxicant exposure via drinking water intake was low. The triangulation approach revealed no associations between toxicant exposure through household water intake and the respective toxicant biomarker concentrations. ConclusionStudies with larger samples and repeated measures are needed to confirm these findings. Nevertheless, it appears that at low water toxicant concentrations, typical water consumption is not a major contributor to children's exposure.

Inhibition of Cell Proliferation and Metastasis by Scutellarein Regulating PI3K/Akt/NF-κB Signaling through PTEN Activation in Hepatocellular Carcinoma.

Scutellarein (SCU) is a well-known flavone with a broad range of biological activities against several cancers. Human hepatocellular carcinoma (HCC) is major cancer type due to its poor prognosis even after treatment with chemotherapeutic drugs, which causes a variety of side effects in patients. Therefore, efforts have been made to develop effective biomarkers in the treatment of HCC in order to improve therapeutic outcomes using natural based agents. The current study used SCU as a treatment approach against HCC using the HepG2 cell line. Based on the cell viability assessment up to a 200 μM concentration of SCU, three low-toxic concentrations of (25, 50, and 100) μM were adopted for further investigation. SCU induced cell cycle arrest at the G2/M phase and inhibited cell migration and proliferation in HepG2 cells in a dose-dependent manner. Furthermore, increased PTEN expression by SCU led to the subsequent downregulation of PI3K/Akt/NF-κB signaling pathway related proteins. In addition, SCU regulated the metastasis with EMT and migration-related proteins in HepG2 cells. In summary, SCU inhibits cell proliferation and metastasis in HepG2 cells through PI3K/Akt/NF-κB signaling by upregulation of PTEN, suggesting that SCU might be used as a potential agent for HCC therapy.

Are simple biomarkers sensitive to detect toxicity of low concentration of metal?

Biomarkers are considered as appropriate and sensitive tools to detect contaminants which effects are recorded on a sentinel organism. Research on simple biomarkers has been conducted in the laboratory to detect the toxicity of low concentrations of Arsenic by using green mussels, Perna Viridis, as sentinel organisms. The simple biomarkers used are biogenesis, Stress On Stress (SOS), and the condition index. Green mussels of 2.5-3.5 cm were exposed to concentrations of 0, 0.008, 0.038 and 0.19 mg/L of arsenic for 14 days. The results revealed that biogenesis was not sensitive to arsenic toxicity in green mussels. The air survival test or Stress on Stress was tested in terms of LT50 of Kaplan-Meier test. The results showed that LT50 for treatments of 0, 0.008, 0.038 and 0.19 mg/L were 3.15, 2.76, 2,63 and 3.03 days respectively. It demonstrated that the air survival of mussels in control was longer than those were exposed to a series of arsenic concentrations descriptively, but statistically, they were not significantly different. However, the condition index of the green mussel revealed a significant difference statistically between control and 0.19 mg/L of Arsenic. This suggested that the condition index can detect the toxicity of Arsenic to the green mussel.

Oroxylin A reversed Fibronectin-induced glioma insensitivity to Temozolomide by suppressing IP3R1/AKT/β-catenin pathway

AimsCell adhesion mediated-drug resistance (CAM-DR) is one of main reasons for.the limitation to chemotherapy, but the underlying mechanism remains unclear in glioma. In this study, we investigated the mechanism of CAM-DR induced by Fibronectin (Fn). Besides, we studied the reversal effect of Oroxylin A, a natural flavonoid extracted from Scutellaria radix, on Temozolomide (TMZ) insensitivity of glioma cells. Main methodsHuman Fn protein was used to mimic cell adhesion model and investigate its effect on the insensitivity of glioma cells to TMZ. Moreover, Oroxylin A was studied regarding its reversal effect on TMZ insensitivity of glioma via multiple molecular biological methods such as MTT, cell apoptosis assay, siRNA transfection, western blot, immunofluorescence assay. Key findingsFn could decrease the apoptosis-inducing effect of TMZ and led to the CAM-DR in glioma cells. Further studies showed that up-regulations of IP3R1 and intracellular Ca2+ level induced the activation of AKT kinase which increased the phosphorylation of GSK-3β and subsequently caused the entry of β-catenin into the nucleus. Knocking down IP3R1 significantly improved the sensitivity of glioma cells to TMZ. Meanwhile, after treatment with low-toxic concentration of Oroxylin A, the apoptosis induced by TMZ under Fn condition increased dramatically. Furthermore, our results revealed that Oroxylin A markedly inhibited the expression of IP3R1 and the activation of AKT/β-catenin pathway. SignificanceOroxylin A could reverse the insensitivity of TMZ via suppressing IP3R1/AKT/β-catenin pathway and it might be helpful for enhancing the anti-cancer effect of TMZ in glioma.

Growth performance, bioavailability of toxic and essential elements and nutrients, and biofortification of iodine of rainbow trout (Onchorynchus mykiss) fed blends with sugar kelp (Saccharina latissima)

Aquaculture production is demanding novel feed ingredients that reflect natural marine nutrient levels, that are also essential to humans. In this regard, biofortification through addition of iodine-rich sugar kelp in feed formulations was assessed in a 12 week rainbow trout trial. Yttrium inclusion in feed allowed determinations of apparent absorption coefficients of essential and potentially toxic elements and apparent digestibility coefficient of nutrients. E.g. apparent absorption coefficients in trouts fortified feed with 1–4% dw kelp were 67–61% As, 32–40% Cd, <5% Fe; 80–83% I; 66-58% Se. Iodine concentrations in feed up to 239 mg/kg (~4% kelp) was proportional to iodine accumulation in trout fillets (R2 = 1.00) with 0.5% transfer ratio. Feed iodine concentrations up to 117 mg/kg (~2% kelp) did not affect growth performance negatively, but increased significantly protein efficiency ratio after eight weeks feeding. However, 4% kelp meal inclusion affected final growth and hepato somatic index, and caused histomorphological changes in the intestine. All fillets had low toxic element concentrations (As, Cd, Hg, Pb). The potential applicability of Saccharina latissima as feed ingredient to tailor iodine concentration in farmed fish is evident. Consuming of a 160 g fillet (2% kelp) contributes ~60% of recommended daily iodine intake for adults.

Polychlorinated biphenyls in a grassland food network: Concentrations, biomagnification, and transmission of toxicity

The production of polychlorinated biphenyls (PCBs) is prohibited by the Stockholm Convention in 2001, but the unintentionally produced PCBs are still continuously discharged into the environment. In this study, the distributions, biomagnification and toxicity amplification in a grassland food network (including inorganic environment, animals and vegetation) were investigated. PCB concentrations in various samples were determined, and PCBs appeared to be enriched as the trophic level increased. The PCB concentrations in the inorganic environment samples ranged from below the detection limit to 0.329 ng g−1, and the PCB concentrations in vegetation were 0.0829–4.45 ng g−1. The PCB concentration in snake subcutaneous fat (8.74 ng g−1 lipid weight) was higher than the concentrations in other animal samples, and the next highest concentration was found in yellow weasel muscle (7.31 ng g−1 lipid weight). Biomagnification factors were calculated for different PCBs and different organisms. Biomagnification was most obvious for organisms at the top of the food chain (the snake/mouse biomagnification ratio was >1000). The PCB-126 toxic equivalent concentration increased markedly as the trophic level increased. The toxic equivalent concentrations were 1200 times higher for high trophic level biota than low trophic level biota. PCB-169 had the highest toxic equivalent concentrations for the animal hair samples (0.00001 pg toxic equivalents g−1). However, PCB-81 had the highest toxicity equivalent concentrations for the herdsmen hair samples. PCBs found at relatively low concentrations and low toxic equivalent concentrations at low trophic levels can be biomagnified as they are transferred through the food chain and can reach high actual and toxic equivalent concentrations at high trophic levels.