Exploring the synergistic effects of indole acetic acid (IAA) and compost in the phytostabilization of nickel (Ni) in cauliflower rhizosphere.

Heavy metals (HMs) contamination, owing to their potential links to various chronic diseases, poses a global threat to agriculture, environment, and human health. Nickel (Ni) is an essential element however, at higher concentration, it is highly phytotoxic, and affects major plant functions. Beneficial roles of plant growth regulators (PGRs) and organic amendments in mitigating the adverse impacts of HM on plant growth has gained the attention of scientific community worldwide. Here, we performed a greenhouse study to investigate the effect of indole-3-acetic acid (IAA @ 10- 5 M) and compost (1% w/w) individually and in combination in sustaining cauliflower growth and yield under Ni stress. In our results, combined application proved significantly better than individual applications in alleviating the adverse effects of Ni on cauliflower as it increased various plant attributes such as plant height (49%), root length (76%), curd height and diameter (68 and 134%), leaf area (75%), transpiration rate (36%), stomatal conductance (104%), water use efficiency (143%), flavonoid and phenolic contents (212 and 133%), soluble sugars and protein contents (202 and 199%), SPAD value (78%), chlorophyll 'a and b' (219 and 208%), carotenoid (335%), and NPK uptake (191, 79 and 92%) as compared to the control. Co-application of IAA and compost reduced Ni-induced electrolyte leakage (64%) and improved the antioxidant activities, including APX (55%), CAT (30%), SOD (43%), POD (55%), while reducing MDA and H2O2 contents (77 and 52%) compared to the control. The combined application also reduced Ni uptake in roots, shoots, and curd by 51, 78 and 72% respectively along with an increased relative production index (78%) as compared to the control. Hence, synergistic application of IAA and compost can mitigate Ni induced adverse impacts on cauliflower growth by immobilizing it in the soil.

Melatonin is a Neuroprotective and Antioxidant Agent against Neurotoxicity Induced by an Intrahippocampal Injection of Nickel in Rats.

The investigation into the hippocampal function and its response to heavy metal exposure is crucial for understanding the mechanisms underlying neurotoxicity, this can potentially inform strategies for mitigating the adverse effects associated with heavy metal exposure. Melatonin is an essential neuromodulator known for its efficacy as an antioxidant. In this study, we aimed to determine whether melatonin could protect against Nickel (Ni) neurotoxicity. To achieve this, we performed an intracerebral injection of Ni (300 µM NiCl2) into the right hippocampus of male Wistar rats, followed by melatonin treatment. Based on neurobehavioral and neurobiochemical assessments, our results demonstrate that melatonin efficiently enhances Ni-induced behavioral dysfunction and cognitive impairment. Specifically, melatonin treatment positively influences anxious behavior, significantly reduces immobility time in the forced swim test (FST), and improves learning and spatial memory abilities. Moreover, neurobiochemical assays revealed that melatonin treatment modulates the Ni-induced alterations in oxidative stress balance by increasing antioxidant enzyme activities, such as superoxide dismutase (SOD) and catalase (CAT). Additionally, we observed that melatonin significantly attenuated the increased levels of lipid peroxidation (LPO) and nitric oxide (NO). In conclusion, the data from this study suggests that melatonin attenuates oxidative stress, which is the primary mechanism responsible for Ni-induced neurotoxicity. Considering that the hippocampus is the main structure involved in the pathology associated with heavy metal intoxication, such as Ni, these findings underscore the potential therapeutic efficacy of melatonin in mitigating heavy metal-induced brain damage.

Identification of the single and combined acute toxicity of Cr and Ni with Heterocypris sp. and the quantitative structure-activity relationship (QSAR) model.

Mining wastewater with heavy metals poses a serious threat to the ecological environment. However, the acute single and combined ecological effects of heavy metals, such as chromium (Cr) and nickel (Ni), on freshwater ostracods, and the development of relevant prediction models, remain poorly understood. In this study, Heterocypris sp. was chosen to investigate the single and combined acute toxicity of Cr and Ni. Then, the quantitative structure-activity relationship (QSAR) model was used to predict the combined toxicity of Cr and Ni. The single acute toxicity experiments revealed high toxicity for both Cr and Ni. In addition, Cr exhibited greater toxicity compared to Ni, as evidenced by its lower 96-hour half-lethal concentration (LC50) of 1.07 mg/L compared to 4.7 mg/L for Ni. Furthermore, the combined acute toxicity experiments showed that the toxicity of Cr-Ni was higher than Ni but lower than Cr. Compared with the concentration addition (CA) and independent action (IA) models, the predicted results of the QSAR model were more consistent with the experimental results for the Cr-Ni combined acute toxicity. So, the high accuracy of QSAR model identified its feasibility to predict the toxicity of heavy metal pollutants in mining wastewater.

The mechanism of nickel-induced autophagy and its role in nephrotoxicity.

Nickel (Ni), an environmental health hazard, is nephrotoxic to humans, but the exact mechanism is unknown. This study aims to identify whether nephrotoxicity is associated with autophagy. Here, nickel chloride (NiCl2) increased autophagy in TCMK-1 cells. NiCl2 induces autophagy through Akt and AMPK/mTOR pathways. Next, oxidative stress was investigated in NiCl2-induced autophagy. The findings demonstrated that the antioxidant (NAC) or mitochondrial targeted antioxidant (Mito-TEMPO) attenuated NiCl2-induced autophagy, reversed the influence on AMPK-mTOR and Akt pathways. Additionally, our study examined the role of autophagy in NiCl2-induced nephrotoxicity. Autophagy inhibition with 3-MA could inhibit cell viability and increase apoptosis in the TCMK-1 cells, however, autophagy promotion with rapamycin relieved cytotoxicity and decreased apoptosis. Additionally, co-treatment with Z-VAD-FMK reduced cytotoxicity, but did not affect autophagy. Besides, NiCl2 can increase the level of mitophagy in vivo and vitro. Mitophagy inhibition could inhibit cell viability and increase apoptosis in the TCMK-1 cells, whereas, promotion of mitophagy could increase cell viability and decrease apoptosis. In summary, above-mentioned results showed that NiCl2 induces autophagy in TCMK-1 cells through oxidative stress-dependent AMPK/AKT-mTOR pathway, autophagy plays a role in reducing NiCl2-induced renal toxicity, and a major mechanism in autophagy's inhibitory effect on NiCl2-induced apoptosis may be mitophagy.

A Predictive Toxicokinetic Model for Nickel Leaching from Vascular Stents.

In vitro testing methods offer valuable insights into the corrosion vulnerability of metal implants and enable prompt comparison between devices. However, they fall short in predicting the extent of leaching and the biodistribution of implant byproducts under in vivo conditions. Physiologically based toxicokinetic (PBTK) models are capable of quantitatively establishing such correlations and therefore provide a powerful tool in advancing nonclinical methods to test medical implants and assess patient exposure to implant debris. In this study, we present a multicompartment PBTK model and a simulation engine for toxicological risk assessment of vascular stents. The mathematical model consists of a detailed set of constitutive equations that describe the transfer of nickel ions from the device to peri-implant tissue and circulation and the nickel mass exchange between blood and the various tissues/organs and excreta. Model parameterization was performed using (1) in-house-produced data from immersion testing to compute the device-specific diffusion parameters and (2) full-scale animal in situ implantation studies to extract the mammalian-specific biokinetic functions that characterize the time-dependent biodistribution of the released ions. The PBTK model was put to the test using a simulation engine to estimate the concentration-time profiles, along with confidence intervals through probabilistic Monte Carlo, of nickel ions leaching from the implanted devices and determine if permissible exposure limits are exceeded. The model-derived output demonstrated prognostic conformity with reported experimental data, indicating that it may provide the basis for the broader use of modeling and simulation tools to guide the optimal design of implantable devices in compliance with exposure limits and other regulatory requirements.

Inhalation exposure to toxic heavy metals in nail salon technicians and health risk assessment using Monte Carlo simulation.

OBJECTIVE: Nail salons offer a developing and diverse occupation for many women, especially the new generation. Due to the increasing apprehension surrounding heavy metals in dust caused by filing nails containing dried nail polish, the present study was designed aimed to health risk assessment of heavy metals in breathing zone of nail salon technicians (NSTs). METHODS: This is a cross-sectional study that was conducted in NSTs. The concentration of Cadmium (Cd), Lead (Pb), Nickel (Ni), Chromium (Cr) and Manganese (Mn)in breathing zone of 20 NSTs was determined using ICP-OES. RESULTS: The metal concentrations were in the following order: Mn > Pb > Ni > Cr > Cd with corresponding arithmetic mean values of0.008, 0.0023, 0.0021, 0.001 and 0.0006 mg m-3, respectively, which are exceeded the recommended levels stated in the indoor air guidelines. The average lifetime carcinogenic risk (LCR) for Cr, Cd, Ni and Pb was calculated 0.0084, 0.00054, 0.00026 and 1.44 E - 05, respectively. The LCR values of all metals (except Pb) exceeded the acceptable level set by the USEPA. The mean of Hazard quotients (HQ) for Mn, Cd, Cr, Ni and Pb were calculated to be23.7, 4.74, 2.19, 0.51 and 0.0.24, respectively. The sensitivity analysis showed that, the exposure frequency (EF) for Cr and Ni had the strong effects on generation of both LCR and HQ. Furthermore, the concentrations of Mn, Cd and Pb had strong impacts on the HQ generation and the concentration of Cd and Pb had main effects on LCR generation. CONCLUSION: To effectively reduce pollutant concentration, it is recommended to install a ventilation system near nail salon work tables and conduct continuous monitoring and quality control of nail products.

Physiological and biochemical responses of Leersia hexandra Swartz to nickel stress: Insights into antioxidant defense mechanisms and metal detoxification strategies.

Phytoremediation is widely considered as a cost-effective method for managing heavy metal soil pollution. Leersia hexandra Swartz shows a promising potential for the remediation of heavy metals pollution, including chromium (Cr), copper (Cu), and nickel (Ni). It is vital to understand the physiological and biochemical responses of L. hexandra to Ni stress to elucidate the mechanisms underlying Ni tolerance and accumulation. Here, we examined the metabolic and transcriptomic responses of L. hexandra exposed to 40 mg/L Ni for 24 h and 14 d. After 24-h Ni stress, gene expression of glutathione metabolic cycle (GSTF1, GSTU1 and MDAR4) and superoxide dismutase (SODCC2) was significantly increased in plant leaves. Furthermore, after 14-d Ni stress, the ascorbate peroxidase (APX7), superoxide dismutase (SODCP and SOD1), and catalase (CAT) gene expression was significantly upregulated, but that of glutathione metabolic cycle (EMB2360, GSTU1, GSTU6, GSH2, GPX6, and MDAR2) was downregulated. After 24-h Ni stress, the differentially expressed metabolites (DEMs) were mainly flavonoids (45%) and flavones (20%). However, after 14-d Ni stress, the DEMs were mainly carbohydrates and their derivatives (34%), amino acids and derivatives (15%), and organic acids and derivatives (8%). Results suggest that L. hexandra adopt distinct time-dependent antioxidant and metal detoxification strategies likely associated with intracellular reduction-oxidation balance. Novel insights into the molecular mechanisms responsible for Ni tolerance in plants are presented.

Sp1-activated FGFR2 is involved in early-life exposure to nickel-induced craniosynostosis by regulating the ERK1/2 signaling pathway.

Nickel, a common environmental hazard, is a risk factor for craniosynostosis. However, the underlying biological mechanism remains unclear. Here, we found that early-life nickel exposure induced craniosynostosis in mice. In vitro, nickel promoted the osteogenic differentiation of human mesenchymal stem cells (hMSCs), and its osteogenic ability in vivo was confirmed by an ectopic osteogenesis model. Further mRNA sequencing showed that ERK1/2 signaling and FGFR2 were aberrantly activated. FGFR2 was identified as a key regulator of ERK1/2 signaling. By promoter methylation prediction and methylation-specific PCR (MSP) assays, we found that nickel induced hypomethylation in the promoter of FGFR2, which increased its binding affinity to the transcription factor Sp1. During pregnancy and postnatal stages, AZD4547 rescued nickel-induced craniosynostosis by inhibiting FGFR2 and ERK1/2. Compared with normal individuals, nickel levels were increased in the serum of individuals with craniosynostosis. Further logistic and RCS analyses showed that nickel was an independent risk factor for craniosynostosis with a nonlinear correlation. Mediated analysis showed that FGFR2 mediated 30.13% of the association between nickel and craniosynostosis risk. Collectively, we demonstrate that early-life nickel exposure triggers the hypomethylation of FGFR2 and its binding to Sp1, thereby promoting the osteogenic differentiation of hMSCs by ERK1/2 signaling, leading to craniosynostosis.

Combined effect of endophytic Bacillus mycoides and rock phosphate on the amelioration of heavy metal stress in wheat plants.

BACKGROUND: Zinc (Zn) and nickel (Ni) are nutrients that are crucial for plant growth; however, when they are present at higher concentrations, they can cause toxicity in plants. The present study aimed to isolate plant growth promoting endophytic bacteria from Viburnum grandiflorum and assess its plant and defense promoting potential alone and in combination with RP in zinc (Zn) and nickel (Ni) toxic soil. The isolated endophytic bacteria were identified using 16s rRNA gene sequencing. For the experiment, twelve different treatments were applied using Zn, Ni, isolated endophytic Bacillus mycoides (Accession # MW979613), and rock phosphate (RP). The Ni, Zn and RP were used at the rate of (100 mg/kg) and (0.2 g/kg) respectively. A pot experiment with three replicates of each treatment was conducted using a complete randomized design (CRD). RESULTS: The results indicated that Ni (T5 = seed + 100 mg/kg Ni and T9 = seed + 100 mg/kg Zn) and Zn concentrations inhibited plant growth, but the intensity of growth inhibition was higher in Ni-contaminated soil. Bacillus mycoides and RP at 100 mg/Kg Zn (T12 = inoculated seed + 100 mg/kg Zn + RP0.2 g/kg.) increased the shoot length, leaf width, protein and sugar content by 57%, 13%, 20% and 34%, respectively, compared to the control. The antioxidant enzymes superoxide dismutases (SOD), peroxidase (POD) were decreased in contaminated soil. Furthermore, Ni and Zn accumulation was inhibited in T11 (seed + 100 mg/kg Zn + RP0.2 g/Kg) and T12 (inoculated seed + 100 mg/kg Zn + RP0.2 g/Kg) by 62 and 63% respectively. The Cu, Ca, and K, contents increased by 128, 219 and 85, Mn, Na, and K by 326, 449, and 84% in (T3 = inoculated seed) and (T4 = inoculated seed + RP 0.2 g/Kg) respectively. CONCLUSIONS: Ni was more toxic to plants than Zn, but endophytic bacteria isolated from Viburnum grandiflorum, helped wheat (Triticum aestivum) plants and reduced the toxic effects of Ni and Zn. The effect of Bacillus mycoides was more prominent in combination with RP which promoted and suppressed heavy-metal toxicity. The reported combination of Bacillus mycoides and RP may be useful for improving plant growth and overcoming metal stress.

Nickel in ambient particulate matter and respiratory or cardiovascular outcomes: A critical review.

Exposure to ambient particulate matter (PM) has been associated with respiratory and cardiovascular outcomes, and nickel has been more frequently associated with these outcomes than other metal constituents of ambient PM. Because of this, we evaluated whether the evidence to date supports causal relationships between exposure to nickel in ambient PM and respiratory or cardiovascular outcomes. We critically reviewed 38 studies in human populations published between 2012 and 2022. Although a large variety of respiratory and cardiovascular outcomes were examined, data were sparse for many. As a result, we focused our evaluation on seven respiratory outcomes and three cardiovascular outcomes that were each examined in ≥3 studies. Of these health outcomes, exposure to nickel in ambient PM has been statistically significantly associated with respiratory mortality, respiratory emergency hospital visits, asthma, lung function (i.e., forced expiratory volume in 1 s, forced vital capacity), cardiovascular mortality, and ischemic heart disease mortality. Studies of the health outcomes of focus are subject to multiple methodological limitations, primarily ecological fallacy (short-term exposure studies), exposure measurement error, confounding, model misspecification, and multiple comparisons issue. While some statistically significant associations were reported, they were not strong, precise, or consistent. Statistically significant findings for long-term exposure to nickel in PM were largely reported in studies that could not establish temporality, despite their cohort study design. Statistically significant findings for short-term exposure to nickel in PM were largely reported in studies that could establish temporality, although this cannot inform causal inference at the individual level due to the aggregate level data used. The biological plausibility of the associations is only supported at high concentrations not relevant to ambient exposures. Overall, the literature to date does not provide adequate support for a causal relationship between nickel in ambient PM and respiratory or cardiovascular outcomes.

Microbial colony sequencing combined with metabolomics revealed the effects of chronic hexavalent chromium and nickel combined exposure on intestinal inflammation in mice.

The pollution and toxic effects of hexavalent chromium [Cr(VI)] and divalent nickel [Ni(II)] have become worldwide public health issues. However, the potential detailed effects of chronic combined Cr(VI) and Ni exposure on colonic inflammation in mice have not been reported. In this study, 16S rDNA sequencing, metabolomics data analysis, qPCR and other related experimental techniques were used to comprehensively explore the mechanism of toxic damage and the inflammatory response of the colon in mice under the co-toxicity of chronic hexavalent chromium and nickel. The results showed that long-term exposure to Cr(VI) and/or Ni resulted in an imbalance of trace elements in the colon of mice with significant inflammatory infiltration of tissues. Moreover, Cr(VI) and/or Ni poisoning upregulated the expression levels of IL-6, IL-18, IL-1ß, TNF-α, IFN-γ, JAK2 and STAT3 mRNA, and downregulated IL-10 mRNA, which was highly consistent with the trend in protein expression. Combined with multiomics analysis, Cr(VI) and/or Ni could change the α diversity and ß diversity of the gut microbiota and induce significant differential changes in metabolites such as Pyroglu-Glu-Lys, Val-Asp-Arg, stearidonic acid, and 20-hydroxyarachidonic acid. They are also associated with disorders of important metabolic pathways such as lipid metabolism and amino acid metabolism. Correlation analysis revealed that there was a significant correlation between gut microbes and metabolites (P < 0.05). In summary, based on the advantages of comprehensive analysis of high-throughput sequencing sets, these results suggest that chronic exposure to Cr(VI) and Ni in combination can cause microbial flora imbalances, induce metabolic disorders, and subsequently cause colonic damage in mice. These data provide new insights into the toxicology and molecular mechanisms of Cr(VI) and Ni.

Nickel uptake in leafy greens from contaminated soil: an investigation into phytoavailability and health risk assessment using in vitro digestion model.

Nickel (Ni) is a toxic metal that not only pollutes the environment but also causes harmful impacts on plant growth and human health. Therefore, it is crucial to assess the relationship between the phytoavailability of Ni in soil and its accumulation in edible and non-edible parts of vegetables. A pot experiment was conducted to investigate Ni uptake in three different leafy vegetables, spinach (Spinacia oleracea L.), lettuce (Lactuca sativa L.), and fenugreek (Trigonella foenum-graecum L.), grown in soil artificially contaminated with Ni at three different treatment levels (100 mg kg-1, 200 mg kg-1, and 300 mg kg-1). The potential dietary toxicity of these vegetables in humans was examined by using an in vitro digestion model. The lowest and highest chlorophyll contents were detected in lettuce at 300 mg kg-1 of Ni concentration and in control plants of spinach. Their values were 34.16 ± 3.01 (SPAD unit) and 53 ± 3.7673 (SPAD unit), respectively. Among the three vegetables, lettuce and spinach at 300 mg kg-1 exhibited the highest accumulation of Ni, with 43 mg kg-1 in edible parts and 182 mg kg-1 in non-edible parts. Furthermore, health risk index (HRI) values were found to be > 1 for lettuce and fenugreek at Ni concentrations of 200 and 300 mg kg-1 for both children and adults. The average bioaccessibility of Ni in lettuce, fenugreek, and spinach during the gastrointestinal phase was 32-23%, 24-10%, and 45-37%, respectively, at a Ni concentration of 300 mg kg-1. All three vegetables grown on Ni-contaminated soil may potentially contribute to food chain toxicity. The HRI values being > 1 suggest that these vegetables are unsafe for consumption. Monitoring of Ni concentration in leafy vegetables is essential to minimize human health risks associated with food chain contamination.

Isolation and identification of a new Bacillus glycinifermentans strain from date palm rhizosphere and its effect on barley seeds under heavy metal stress.

Soil contamination by heavy metals is one of the major problems that adversely decrease plant growth and biomass production. Inoculation with the plant growth-promoting rhizobacteria (PGPR) can attenuate the toxicity of heavy metals and enhancing the plant growth. In this study, we evaluated the potential of a novel extremotolerant strain (IS-2 T) isolated from date palm rhizosphere to improve barley seedling growth under heavy metal stress. The species-level identification was carried out using morphological and biochemical methods combined with whole genome sequencing. The bacterial strain was then used in vitro for inoculating Hordeum vulgare L. exposed to three different Cr, Zn, and Ni concentrations (0.5, 1, and 2 mM) in petri dishes and different morphological parameters were assessed. The strain was identified as Bacillus glycinifermentans species. This strain showed high tolerance to pH (6-11), salt stress (0.2-2 M), and heavy metals. Indeed, the minimum inhibitory concentrations at which bacterium was unable to grow were 4 mM for nickel, 3 mM for zinc, more than 8 mM for copper, and 40 mM for chromium, respectively. It was observed that inoculation of Hordeum vulgare L. under metal stress conditions with Bacillus glycinifermentans IS-2 T stain improved considerably the growth parameters. The capacity of the IS-2 T strain to withstand a range of abiotic stresses and improve barley seedling development under lab conditions makes it a promising candidate for use as a PGPR in zinc, nickel, copper, and chromium bioremediation.

Isolated and combined effects of cobalt and nickel on the microalga Raphidocelis subcapitata.

Aquatic organisms are exposed to several compounds that occur in mixtures in the environment. Thus, it is important to investigate their impacts on organisms because these combined effects can be potentiated. Cobalt (Co) and nickel (Ni) are metals that occur in the environment and are used in human activities. To the best of our knowledge, there are no studies that investigated the combined effects of these metals on a freshwater Chlorophyceae. Therefore, this study analyzed the isolated and combined effects of Co and Ni in cell density, physiological and morphological parameters, reactive oxygen species (ROS), carbohydrates and photosynthetic parameters of the microalga Raphidocelis subcapitata. Data showed that Co affected the cell density from 0.25 mg Co L-1; the fluorescence of chlorophyll a (Chl a) (0.10 mg Co L-1); ROS production (0.50 mg Co L-1), total carbohydrates and efficiency of the oxygen evolving complex (OEC) at all tested concentrations; and the maximum quantum yield (ΦM) from 0.50 mg Co L-1. Ni exposure decreased ROS and cell density (0.35 mg Ni L-1); altered Chl a fluorescence and carbohydrates at all tested concentrations; and did not alter photosynthetic parameters. Regarding the Co-Ni mixtures, our data best fitted the concentration addition (CA) model and dose-ratio dependent (DR) deviation in which synergism was observed at low doses of Co and high doses of Ni and antagonism occurred at high doses of Co and low doses of Ni. The combined metals affected ROS production, carbohydrates, ΦM, OEC and morphological and physiological parameters.

DNMT3a-mediated upregulation of the stress inducible protein sestrin-2 contributes to malignant transformation of human bronchial epithelial cells following nickel exposure.

BACKGROUND: Nickel is a confirmed human lung carcinogen. Nonetheless, the molecular mechanisms driving its carcinogenic impact on lung tissue remain poorly defined. In this study, we assessed SESN2 expression and the signaling pathways responsible for cellular transformation in human bronchial epithelial cells (HBECs) as a result of nickel exposure. METHODS: We employed the Western blotting to determine the induction of SESN2 by nickel. To clarify the signaling pathways leading to cellular transformation following nickel exposure, we applied techniques such as gene knockdown, methylation-specific PCR, and chromatin immunoprecipitation. RESULT: Exposure to nickel results in the upregulation of SESN2 and the initiation of autophagy in human bronchial epithelial cells (HBECs). This leads to degradation of HUR protein and consequently downregulation of USP28 mRNA, PP2AC protein, ß-catenin protein, and diminished VHL transcription, culminating in the accumulation of hypoxia-inducible factor-1α (HIF-1α) and the malignant transformation of these cells. Mechanistic studies revealed that the increased expression of SESN2 is attributed to the demethylation of the SESN2 promoter induced by nickel, a process facilitated by decreased DNA methyl-transferase 3 A (DNMT3a) expression, while The downregulation of VHL transcription is linked to the suppression of the PP2A-C/GSK3ß/ß-Catenin/C-Myc pathway. Additionally, we discovered that SESN2-mediated autophagy triggers the degradation of HUR protein, which subsequently reduces the stability of USP28 mRNA and inhibits the PP2A-C/GSK3ß/ß-Catenin pathway and c-Myc transcription in HBECs post nickel exposure. CONCLUSION: Our results reveal that nickel exposure leads to the downregulation of DNMT3a, resulting in the hypomethylation of the SESN2 promoter and its protein induction. This triggers autophagy-dependent suppression of the HUR/USP28/PP2A/ß-Catenin/c-Myc pathway, subsequently leading to reduced VHL transcription, accumulation of HIF-1α protein, and the malignant transformation of human bronchial epithelial cells (HBECs). Our research offers novel insights into the molecular mechanisms that underlie the lung carcinogenic effects of nickel exposure. Specifically, nickel induces aberrant DNA methylation in the SESN2 promoter region through the decrease of DNMT3a levels, which ultimately leads to HIF-1α protein accumulation and the malignant transformation of HBECs. Specifically, nickel initiates DNA-methylation of the SESN2 promoter region by decreasing DNMT3a, ultimately resulting in HIF-1α protein accumulation and malignant transformation of HBECs. This study highlights DNMT3a as a potential prognostic biomarker or therapeutic target to improve clinical outcomes in lung cancer patients.

The combined effects of polystyrene nanoplastics with nickel on oxidative stress and related toxic effects to earthworms from individual and cellular perspectives.

Nanoplastics may adsorb other pollutants in the environment due to their high specific surface area and small size. We used earthworms as experimental organisms to evaluate the ecotoxicity of NPs and Ni combined pollution at the individual and cellular levels. The results showed that when only 20 mg/L Ni2+ was added to the combined pollution system, the antioxidant system of earthworm coelomocytes was destroyed to a certain extent, the ROS level increased, the cell viability decreased significantly, and the redox balance was destroyed. With the introduction of PS-NPs and the increase of concentration, the oxidative damage in the coelomocytes of earthworms gradually increased, and finally tended to be stable when the maximum concentration of 50 mg/L PS-NPs and Ni were exposed together. At the animal level, the activities of CAT and SOD decreased within 28 days of exposure, and the combined pollution showed a synergistic effect. At the same time, it promoted the synthesis of GST in earthworms, improved their detoxification ability and reduced oxidative damage. The changes of T-AOC and MDA showed that the combined pollution caused the accumulation of ROS and caused more serious toxicological effects. With the increase of exposure time, the antioxidant system of earthworms was continuously destroyed, and the oxidative damage was serious, which induced more serious lipid peroxidation and caused the damage of earthworm body wall structure.

Malic acid inhibits accumulation of cadmium, lead, nickel and chromium by down-regulation of OsCESA and up-regulation of OsGLR3 in rice plant.

Malic acid (MA) plays an important role in plant tolerance to toxic metals, but its effect in restricting the transport of harmful metals remains unclear. In this study, japonica rice NPB and its fragile-culm mutant fc8 with low cellulose and thin cell wall were used to investigate the influence of MA on the accumulation of 4 toxic elements (Cd, Pb, Ni, and Cr) and 8 essential elements (K, Mg, Ca, Fe, Mn, Zn, Cu and Mo) in rice. The results showed that fc8 accumulated less toxic elements but more Ca and glutamate in grains and vegetative organs than NPB. After foliar application with MA at rice anthesis stage, the content of Cd, Pb, Ni significantly decreased by 27.9-41.0%, while those of Ca and glutamate significantly increased in both NPB and fc8. Therefore, the ratios between Cd and Ca in grains of NPB (3.4‰) and fc8 (1.5‰) were greatly higher than that in grains of NPB + MA (1.1‰) and fc8+MA (0.8‰) treatments. Meanwhile, the expression of OsCEAS4,7,8,9 for the cellulose synthesis in secondary cell walls were down-regulated and cellulose content in vegetative organs of NPB and fc8 decreased by 16.7-21.1%. However, MA application significantly up-regulated the expression of GLR genes (OsGLR3.1-3.5) and raised the activity of glutamic-oxalacetic transaminease for glutamate synthesis in NPB and fc8. These results indicate that hazard risks of toxic elements in foods can be efficiently reduced through regulating cellulose biosynthesis and GLR channels in plant by combining genetic modification in vivo and malic acid application in vitro.

Nickel-induced oxidative stress causes cell death in testicles: implications for male infertility.

Aligarh region is well known for its lock industry. This lock industry utilises nickel for electroplating. There have been informal reports of infertility in men and women living near the lock industry. We analysed field water samples to investigate this link, and the results showed considerable nickel contamination. To further validate our results, we exposed male rats to relevant nickel levels in drinking water. This experimental exposure resulted in abnormal sperm morphology, decline in sperm count, significant change in activities of antioxidant enzymes, pronounced oxidative stress in the rat spermatocytes and decrease in serum testosterone level, as well as damage in the hypothalamus and pituitary (in all cases, the changes were most significant at the highest concentration used i.e 2.5 mg/l). The breeding experiments showed decline in live birth rate, while pups did not survive post birth in cages where males were given 2 and 2.5 mg/l concentrations of nickel in drinking water prior to mating. Our data strongly indicate a link between industrial nickel exposure and male infertility.

Biosynthesis cobalt-doped nickel nanoparticles and their toxicity against disease.

The nanostructures have the great potential for novel medical and drug delivery applications. In present paper a green approach for the preparation of pure nickel oxide (NiO) and 5% cobalt-doped NiO (Co╫NiO) nanoparticles (NPs) by using Prosopis fracta extract have been study. The product of Co╫NiO NPs was proved through the PXRD, Raman, UV-Vis, FESEM, and EDX analyses. The results of XRD, EDX, and UV-Visible spectra displayed well doped cobalt in NiO NP. The particle sizes of Co╫NiO NPs were observed to be about 80 nm. The MTT test results for the cytotoxicity of Co╫NiO NPs on breast cancer cells (MCF-7) affirmed the stronger impact of doped NiO-NPs on cancer cells compared to NiO NPs. Thus, it is indicated that the doping process on NiO NPs caused an increase in its inhibitory effect against MCF-7 cells. RESEARCH HIGHLIGHTS: Cobalt-doped NiO nanoparticles were prepared using ecofriendly synthesis method and their cytotoxicity studied against MCF-7 cells.