The Monocytic Cell Line THP-1 as a Validated and Robust Surrogate Model for Human Dendritic Cells.

We have implemented an improved, cost-effective, and highly reproducible protocol for a simple and rapid differentiation of the human leukemia monocytic cell line THP-1 into surrogates for immature dendritic cells (iDCs) or mature dendritic cells (mDCs). The successful differentiation of THP-1 cells into iDCs was determined by high numbers of cells expressing the DC activation markers CD54 (88%) and CD86 (61%), and the absence of the maturation marker CD83. The THP-1-derived mDCs are characterized by high numbers of cells expressing CD54 (99%), CD86 (73%), and the phagocytosis marker CD11b (49%) and, in contrast to THP-1-derived iDCs, CD83 (35%) and the migration marker CXCR4 (70%). Treatment of iDCs with sensitizers, such as NiSO4 and DNCB, led to high expression of CD54 (97%/98%; GMFI, 3.0/3.2-fold induction) and CD86 (64%/96%; GMFI, 4.3/3.2-fold induction) compared to undifferentiated sensitizer-treated THP-1 (CD54, 98%/98%; CD86, 55%/96%). Thus, our iDCs are highly suitable for toxicological studies identifying potential sensitizing or inflammatory compounds. Furthermore, the expression of CD11b, CD83, and CXCR4 on our iDC and mDC surrogates could allow studies investigating the molecular mechanisms of dendritic cell maturation, phagocytosis, migration, and their use as therapeutic targets in various disorders, such as sensitization, inflammation, and cancer.

Patch testing with the Japanese baseline series 2015: A 4-year experience.

BACKGROUND: The Japanese baseline series (JBS), established in 1994, was updated in 2008 and 2015. The JBS 2015 is a modification of the thin-layer rapid-use epicutaneous (TRUE) test (SmartPractice Denmark, Hillerød, Denmark). No nationwide studies concerning the TRUE test have previously been reported. OBJECTIVES: To determine the prevalence of sensitizations to JBS 2015 allergens from 2015 to 2018. METHODS: We investigated JBS 2015 patch test results using the web-registered Skin Safety Care Information Network (SSCI-Net) from April 2015 to March 2019. RESULTS: Patch test results of 5865 patients were registered from 63 facilities. The five allergens with the highest positivity rates were gold sodium thiosulfate (GST; 25.7%), nickel sulfate (24.5%), urushiol (9.1%), p-phenylenediamine (PPD; 8.9%), and cobalt chloride (8.4%). The five allergens with the lowest positivity rates were mercaptobenzothiazole (0.8%), formaldehyde (0.9%), paraben mix (1.1%), mercapto mix (1.1%), and PPD black rubber mix (1.4%). CONCLUSIONS: Nickel sulfate and GST had the highest positivity rates. The JBS 2015, including a modified TRUE test, is suitable for baseline series patch testing.

Effect of urea fertilization on growth of broad bean (Vicia faba L.) under various nickel (Ni) levels with or without acetic acid addition, using 15N-labeled fertilizer.

Although nickel (Ni) has direct relationship with nitrogen metabolism of plants, the high dose of Ni fertilizer in broad bean plants may affect the nitrogen use efficiency (NUE), impair plant development and even cause Ni pollution in soil. Thus, a pot experiment was set up to study the effect of urea fertilization on N-uptake, root and shoots' Ni content as well as growth of broad bean plants under different levels of Ni, using 15N tracer technique. 15N-labeled urea (5% 15N atom excess) was added at three doses (0, 30 and 60 mg N kg-1 soil). Nickel sulfate (NiSO4) was also applied at three levels (0, 50 and 100 mg Ni kg-1 soil). The experiment was laid out with or without acetic acid in randomized complete block design in three replicates. Treatment with the addition of 60 mg N + 50 mg Ni showed the highest values in dry weights of root and shoots, N-uptake by shoots, nitrogen derived from fertilizer (Ndff %) and NUE % by shoots in both with or without acetic acid solution. Higher rate of Ni addition can decrease shoot and root biomass by inhibiting the ability of the plant to uptake the nitrogen efficiently. However, addition of acetic acid solution induced the improvement of NUE % and Ndff % by shoot and root of broad bean plants. This study provides insight into how to improve plant yield without damaging the soil health and will be helpful to create a better world with sustainable agriculture.

Delayed hypersensitivity to palladium dichloride: 15-year retrospective study in a skin allergy unit.

BACKGROUND: Metal allergies are the most frequent causes of allergic contact dermatitis. Although the use of palladium is increasing, it is not included in any baseline series. OBJECTIVE: To assess the prevalence of hypersensitivity to palladium and to describe the clinical and demographic characteristics of patients who are sensitized to palladium dichloride (PdCl2 ). METHODS: A single-centre, retrospective study of 15 years of patch testing with the Spanish baseline series supplemented with PdCl2 2% pet. was performed. We collected clinical and demographic data and data on co-sensitization among the metals studied, and we compared patients who were sensitized to palladium, with or without co-sensitization to nickel, with the rest of the study population. RESULTS: Among the 3678 included patients, 730 (19.9%) were sensitized to nickel sulfate. The prevalence of sensitization to PdCl2 (n = 316, 8.6%) was higher than the prevalence of sensitization to potassium dichromate (n = 240, 6.5%) and similar to the prevalence of sensitization to cobalt chloride (n = 353, 9.6%). Only 26 (8.2%) of the patients sensitized to palladium were not co-sensitized to nickel. The percentage of men and patients aged ≥40 years was higher in this subgroup than in the patients with nickel co-sensitization. CONCLUSIONS: Given the high prevalence of hypersensitivity to PdCl2 , this metal salt should be included in the Spanish baseline series, notwithstanding the frequency of co-sensitization to nickel.

Time trends of contact allergy to the European baseline series in Lithuania.

BACKGROUND: Monitoring trends of positive patch test reactions is useful for epidemiological surveillance and contact allergy prevention, and has not previously been reported in Lithuania. OBJECTIVES: To examine and compare changes in the prevalence of contact allergy to European baseline series allergens in adults with suspected contact dermatitis during a 9-year period. METHODS: In this retrospective study, patch test results of 297 consecutive patients, tested with the European baseline series in 2014-2015, were analysed and compared with the data published earlier in Lithuania. RESULTS: The most common allergens were nickel sulfate (30.6%), methylisothiazolinone (MI) (13.5%), methylchloroisothiazolinone (MCI)/MI (7.4%), potassium dichromate (6.1%), cobalt chloride (6.1%), Myroxylon pereirae resin (5.4%), p-phenylenediamine (5.4%), fragrance mix I (4.7%), formaldehyde (4.4%), and methyldibromo glutaronitrile (3.7%). Increases in the prevalence of sensitization to MCI/MI (2.3% in 2006-2008 and 7.4% in 2014-2015; p < 0.0001) and nickel sulfate (16.4% in 2006-2008 and 30.6% in 2014-2015; p < 0.0001) and decreases in the prevalence of sensitization to paraben mix (3.2% in 2006-2008 and 0.3% in 2014-2015; p = 0.006) were observed. Prevalences for the other allergens remained stable or showed a decreasing trend (Myroxylon pereirae resin; p = 0.06). CONCLUSION: This study provides current information on the prevalence of contact allergy in Lithuania. Changing trends in sensitivity to some allergens probably reflect changes in exposure.

Comparing reliabilities of strip and conventional patch testing.

BACKGROUND: The standardized protocol for performing the strip patch test has proven to be valid, but evidence on its reliability is still missing. OBJECTIVE: To estimate the parallel-test reliability of the strip patch test as compared with the conventional patch test. METHODS: In this multicentre, prospective, randomized, investigator-blinded reliability study, 132 subjects were enrolled. Simultaneous duplicate strip and conventional patch tests were performed with the Finn Chambers® on Scanpor® tape test system and the patch test preparations nickel sulfate 5% pet., potassium dichromate 0.5% pet., and lanolin alcohol 30% pet. Reliability was estimated by the use of Cohen's kappa coefficient. RESULTS: Parallel-test reliability values of the three standard patch test preparations turned out to be acceptable, with slight advantages for the strip patch test. The differences in reliability were 9% (95%CI: -8% to 26%) for nickel sulfate and 23% (95%CI: -16% to 63%) for potassium dichromate, both favouring the strip patch test. CONCLUSIONS: The standardized strip patch test method for the detection of allergic contact sensitization in patients with suspected allergic contact dermatitis is reliable. Its application in routine clinical practice can be recommended, especially if the conventional patch test result is presumably false negative.

Nickel sulfate induced apoptosis via activating ROS-dependent mitochondria and endoplasmic reticulum stress pathways in rat Leydig cells.

Nickel can induce apoptosis of testicular Leydig cells in mice, whereas the mechanisms remain unclear. In this study, we investigated the role of nickel-induced reactive oxygen species (ROS) generation in mitochondria and endoplasmic reticulum stress (ERS) mediated apoptosis pathways in rat Leydig cells. Fluorescent DCF and Annexin-V FITC/PI staining were performed to measure the production of ROS and apoptosis in Leydig cells. RT-qPCR and Western blot were conducted to analyze the key genes and proteins involved in mitochondria and ERS apoptotic pathways. The results showed that nickel sulfate induced ROS generation, consequently resulted in nucleolus deformation and apoptosis in testicular Leydig cells, which were then attenuated by ROS inhibitors of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). Nickel sulfate-triggered Leydig cells apoptosis via mitochondria and ERS pathways was characterized by the upregulated mRNA and proteins expression of Bak, cytochrome c, caspase 9, caspase 3, GRP78, GADD153, and caspase 12, which were inhibited by NAC and TEMPO respectively. The findings indicated that nickel-induced ROS generation was involved in apoptosis via mitochondria and ERS pathways in rat Leydig cells.

Low patch test reactivity to nickel in unselected adolescents tested repeatedly with nickel in infancy.

BACKGROUND: It is questionable how repeated patch tests with nickel sulfate in infancy affect nickel patch test reactivity at a later age. METHODS: The Danish Allergy Research Center (DARC) cohort encompasses 562 infants invited to a clinical examination including patch tests with nickel sulfate six times during the first 36 months of life. At the follow-up investigation at 14 years of age (2013-2014), participants were offered re-patch tests with nickel sulfate. The Odense Adolescence Cohort Study TOACS cohort encompasses 1501 schoolchildren evaluated for the first time at 14 years of age (1995-1996) including clinical examination and nickel sulfate patch tests. The prevalence of nickel sensitization in the DARC cohort was compared to the prevalence in the TOACS cohort at 14 years of age. RESULTS: Nickel sulfate sensitization was found in 1.2% of the participants from the DARC cohort tested repeatedly with nickel sulfate in early childhood and retested at 14 years of age compared to 8.6% of the participants from the TOACS cohort patch-tested for the first time at 14 years of age using the same patch test system and test concentration. CONCLUSION: The significant difference in nickel patch test reactivity comparing the two cohorts may reflect an immunologic effect or the effect of nickel regulation.

Concentrations and stability of methyl methacrylate, glutaraldehyde, formaldehyde and nickel sulfate in commercial patch test allergen preparations.

BACKGROUND: Epicutaneous patch tests are used to reproduce allergy and diagnose allergic contact dermatitis. Reliable allergen test preparations are required. OBJECTIVES: The purpose of the present study was to measure the actual concentrations of nickel(II) sulfate hexahydrate (NiSO4 ), methyl methacrylate, formaldehyde, and glutaraldehyde, and to compare them with the labelled concentrations, in commercial patch test allergen preparations found in dermatology clinics where patch testing is routinely performed. MATERIALS AND METHODS: The commercial in-date and out-of-date patch test allergen preparations concentrations of NiSO4 , methyl methacrylate, formaldehyde and glutaraldehyde from one to three participating clinics were analysed with chromatographic or wet chemical techniques. RESULTS: NiSO4 and formaldehyde concentrations were at or above the labelled concentrations; however, formaldehyde loss occurred with storage. NiSO4 particulate was uniformly distributed throughout the petrolatum. 'In-use' methyl methacrylate reagent syringes all contained ≤ 56% of the 2% label concentration, with no observable relationship with expiration date. Lower methyl methacrylate cocentrations were consistently measured at the syringe tip end, suggesting loss resulting from methyl methacrylate's volatility. The concentrations of glutaraldehyde patch test allergen preparations ranged from 27% to 45% of the labelled (1% in pet.) concentration, independently of expiration date. CONCLUSIONS: Some false-negative methyl methacrylate, formaldehyde or glutaraldehyde patch test results may be attributable to instability of the test preparations.

Optimized preparation of Ni-Febm bimetallic particles by ball milling NiSO4 and iron powder for efficient removal of triclosan.

The excessive usage and emissions of triclosan (TCS) pose a serious threat to aquatic environments. Iron-based bimetallic particles (Pd/Fe, Ni/Fe, and Cu/Fe, etc.) were widely used for the degradation of chlorophenol pollutants. This study proposed a novel synthesis method for the preparation of Ni/Fe bimetallic particles (Ni-Febm) by ball milling microscale zero valent iron ZVI (mZVI) and NiSO4. Ball-milling conditions such as ball-milling time, ball-milling speed and ball-to-powder ratio were optimized to prepare high activity Ni-Febm bimetallic particles. During the ball-milling process, Ni2+ was reduced to Ni0 and formed a coupled structure with ZVI. The amount of Ni0 on ZVI significantly affected the activity of Ni-Febm bimetallic particles. The highest activity Ni-Febm bimetallic particles with Ni/Fe ratio of 0.03 were synthesized under optimized conditions, which could remove 86.56% of TCS (10 µM) in aerobic aqueous solution within 60 min. In addition, higher particle dosage, lower pH condition and higher reaction temperature were more conducive for TCS degradation. The higher corrosion current and lower electron transfer impedance of Ni-Febm bimetallic particles were the main reasons for its high activity. The hydrogen atom (•H) on the surface of Ni-Febm bimetallic particles was mainly contributed to the removal of TCS, as reductive transformation products of TCS were detected by LC-TOF-MS. Notably, a small amount of oxidation products were discovered. The total dechlorination rate of TCS was calculated to be 39.67%. After eight reaction cycles, the residual Ni-Febm bimetallic particles could still degrade 28.34% of TCS within 6 h. Low Ni2+ leaching during reaction indicated that Ni-Febm bimetallic particles did not pose potential environmental risks. The prepared environmental-friendly Ni-Febm bimetallic particles with high activity have great potential in the degradation of other chlorinated organic compounds in wastewater.

Comparative Study of Different Ion-Exchange Membrane Types in Diffusion Dialysis for the Separation of Sulfuric Acid and Nickel Sulfate.

The possibility of using various types of ion-exchange membranes in diffusion dialysis for the separation of sulfuric acid and nickel sulfate has been evaluated. The process of the dialysis separation of a real waste solution from an electroplating facility containing 252.3 g/L of sulfuric acid, 20.9 g/L of nickel ions and small amounts of zinc, iron, copper ions, etc. has been studied. Heterogeneous cation-exchange membrane containing sulfonic groups and heterogeneous anion-exchange membranes with different thicknesses (from 145 µm to 550 µm) and types of fixed groups (four samples with quaternary ammonium base and one sample with secondary and tertiary amines) have been used. The diffusion fluxes of sulfuric acid, nickel sulfate, and the total and osmotic fluxes of the solvent have been determined. The use of a cation-exchange membrane does not allow the separation of the components, since the fluxes of both components are low and comparable in magnitude. The use of anion-exchange membranes makes it possible to efficiently separate sulfuric acid and nickel sulfate. Anion-exchange membranes with quaternary ammonium groups are more effective in the diffusion dialysis process, while the thin membrane turns out to be the most effective.

The Association Between Thyroid Injury and Apoptosis, and Alterations of Bax, Bcl-2, and Caspase-3 mRNA/Protein Expression Induced by Nickel Sulfate in Wistar Rats.

To study the toxicity induced by Nickel sulfate (NiSO4) on thyroid tissue, and investigate the role of apoptosis as the possible mechanism, thirty-two male Wistar rats were randomly divided into control group (normal saline, ip), low dose group (2.5 mg/kg day NiSO4, ip), middle dose group (5 mg/kg day NiSO4, ip), high dose group (10 mg/kg day NiSO4, ip). After 40 consecutive days of treatment, there were obvious pathological changes in the thyroids of high dose group. Free T4 (FT4) and thyroid-stimulating hormone (TSH) were significantly lower in the NiSO4-treated groups than those in the control group (F = 4.992, p = 0.016; F = 4.524, p = 0.012). The mRNA expression of Caspase-3 was significantly higher (F = 10.259, p = 0.014) in all NiSO4-treated groups, and the mRNA expression of Bcl-2 was significantly lower (F = 9.225, p = 0.018) only in the high dose group. Both control group and the NiSO4-treated groups showed no changes in the mRNA expression of Bax gene. The ratio of Bcl-2/Bax decreased with the increase in exposure dose of NiSO4 (F = 13.382, p = 0.015). The mRNA expression of Fas went up in high dose group (F = 66.632, p < 0.001). The Caspase-3, Fas, and the Bax protein expressions measured by immunohistochemistry were consistent with the mRNA expression. The expression of Bcl-2 protein was significantly lower in the test groups than in the control group (F = 3.873, p = 0.025). NiSO4 as an Endocrine Disrupting Chemical may induce the thyroid injury through apoptosis and lead to hypothyroidism. Also, apoptosis in thyroid tissues was closely related to the alternations of Caspase-3, Bcl-2, and Fas mRNA and protein expression.

European Standard Series Patch Test Results in Contact Dermatitis Patients in a Tertiary Care Hospital.

OBJECTIVES: Sensitization of allergens varies among societies and also it is influenced by various factors, such as age and gender. It may even change over the years. In this study, we aimed to evaluate the patch test results in patients with contact dermatitis (CD) in our center. METHODS: European standard series patch test results of patients with CD between 2017 and 2018 were evaluated retrospectively. RESULTS: Of the 135 patients, 65 (48.1%) were males, 70 (51.9%) were females. The mean age of patients was 41.43±14.26 (11-78) years. In 78 (57.8%) patients, a positive reaction against at least one allergen was detected. The most common allergens were nickel sulfate (27.4%), potassium dichromate (14.8%), cobalt chloride (11.9%), textile dye mix (8.1%), fragrance mix i, ii (6.7%) and balsam of Peru (4.4%). The sensitization of nickel sulfate was higher in females and sensitization of cobalt chloride and potassium dichromate in males (p=0.03, 0.05, 0.03, respectively). In the multivariate logistic regression analysis, age was independently related to a positive reaction against at least one allergen. CONCLUSION: Nickel sulfate, potassium dichromate, cobalt chloride and textile dye mix were the most common allergens. Legal regulations should be made to decrease exposure to allergens.

Effect of L-Ascorbic Acid on Nickel-Induced Alteration of Cardiovascular Pathophysiology in Wistar Rats.

Nickel, a widely used heavy metal is suspected as a cardiotoxic element. The aim of the present study was to assess the possible protective role of l-ascorbic acid on nickel-induced alterations of cardiovascular pathophysiology in male albino rats. Twenty-four albino rats (b.wt. 170-250 g) were randomized into four groups: control; l-ascorbic acid (50 mg/100 g b.wt., orally); NiSO4 (2.0 mg/100 g b.wt., i.p.); NiSO4 with l-ascorbic acid. Cardiovascular electrophysiology, serum and cardiac tissue malondialdehyde (MDA), nitric oxide (NO), ascorbic acid, serum α-tocopherol and serum vascular endothelial growth factor (VEGF) were evaluated. Histopathology of cardiac and aortic tissues was also assessed. NiSO4-treated rats showed a significant increase in heart rate, LF/HF ratio and blood pressure (SBP, DBP and MAP). A significant increase of serum MDA, NO and VEGF in NiSO4 treatment with a concomitant decrease of serum ascorbic acid and α-tocopherol as compared to their respective controls were also observed. Simultaneous supplementation of l-ascorbic acid with NiSO4 significantly decreased LF/HF ratio, BP and oxidative stress parameters, whereas ascorbic acid and α-tocopherol concentration was found to be increased. Histopathology of cardiac and aortic tissues showed nickel-induced focal myocardial hypertrophy and degeneration in cardiac tissue with focal aneurism in aortic tissues. Supplementation with l-ascorbic showed a protective action in both cardiac and aortic tissues. Results indicated the possible beneficial effect of l-ascorbic acid on nickel-induced alteration of the cardiovascular pathophysiology in experimental rats.

Nickel allergy in lipid transfer protein sensitized patients: Prevalence and clinical features.

Nickel (Ni), the main responsible for allergic contact dermatitis worldwide, is also involved in systemic condition called "Systemic Nickel Sulfate Allergy Syndrome (SNAS)." Likewise, IgE-mediated reactivity to Lipid Transfer Protein (LTP) represents the main cause of primary food allergy in adults of Mediterranean countries. We evaluated the prevalence of SNAS in LTP allergic patients and investigated patients' clinical features with double sensitization (LTP and Ni). A retrospective, single-center, observational study was conducted performing a complete allergological work-up including: (1) skin prick tests; (2) serum specific IgE for plant food allergens and rPru p3 (LTP); (3) patch test with 5% Ni sulfate in petrolatum. We enrolled 140 LTP allergic patients of which 36 patients (25.7% of sample) showed additional positivity to Ni patch test. Patients with double sensitization were more frequently females and reported fewer cutaneous symptoms. Higher values of sIgE for peach, apple, peanut, walnut, grain, corn, and garlic were found in LTP allergic patients, while higher values for hazelnut in the other subgroup. The prevalence of SNAS in the LTP allergic population is clinically relevant. Moreover, the clinical and immunological profiles of patients with double sensitization were different from patients monosensitized to LTP.

Lichen sclerosus et atrophicus and allergic contact dermatitis: A significant association.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin disease of unknown etiology. It mainly affects the anogenital area, while the extragenital involvement is uncommon. It manifests as pale, ivory-colored lesions and partially atrophic skin. We report a case of a woman presenting to our department with LSA lesions at the level of the armpit. Furthermore, the patient was allergic to nickel sulfate and balsam of Peru. We assume the presence of an association between nickel allergy and onset of LSA.

Long-term outcome after implantation of a nickel-containing cemented hip stem on the right in a patient with type IV sensitization to nickel sulphate.

Type IV allergies to nickel sulfate, potassium dichromate and/or cobalt chloride are supposed to be associated with aseptic loosening, pain or infections in patients with hip arthroplasty. However, there is debate on any causal relation between type IV sensitization to metals and any of these complications. We report on a patient with suspicion of pre-existing type IV sensitization to nickel sulfate and potassium dichromate who did not show any complications after hip arthroplasty.

Ultrasound augmented leaching of nickel sulfate in sulfuric acid and hydrogen peroxide media.

A new method of preparation high purity nickel sulfate assisted by ultrasonic was studied. The process mechanism was analyzed by Inductively Coupled Plasma (ICP), X-ray diffraction (XRD), Scanning electron microscopy (SEM), and Energy dispersive X-ray spectrometry (EDS).The reaction mechanisms of oxidizing leaching and ultrasonic leaching were explored, respectively. Results showed that ultrasonic treatment peel off the oxide film on the surface of nickel. The leachate under strongly agitated, the yield rate of nickel sulfate was accelerate. And the reaction area was increased by the cavitation effect, the liquid-solid reaction was promoted, and the activation energy was reduced. The leaching rate of nickel reached 46.29% by conventional leaching, which takes about 5h. Under the same conditions, the ultrasonic leaching rate reached 40%, only half of the conventional leaching time. Concentration of leaching agent, reaction temperature, ultrasonic power, leaching time had significant effect on the enhancement of the leaching reaction with ultrasonic radiation. The leaching rate of 60.41% under the optimum experiment conditions as follows: sulfuric acid concentration 30%, hydrogen peroxide 10%, leaching temperature 333K, ultrasonic power 200W and leaching time 4h. The kinetic study of the system was investigated, and the reaction rates of conventional leaching and ultrasonic leaching were controlled by diffusion, and the apparent activation energies were 16.2kJ/mol and 11.83kJ/mol.

Interaction of gold nanoparticles and nickel(II) sulfate affects dendritic cell maturation.

Despite many investigations have focused on the pristine toxicity of gold nanoparticles (GNPs), little is known about the outcome of co-exposure and interaction of GNPs with heavy metals which can possibly detoxify or potentiate them. Here, the combined exposure of nickel (II) sulfate (NiSO4) and GNPs on the maturation response of dendritic cells (DCs) was explored. Exposure to GNPs or NiSO4 separately induced cell activation. When cells were exposed to a mixture of both, however, the observed cell activation pattern indicated a competitive rather than an additive effect of both inducers with levels similar to those induced by NiSO4 alone. Quantification of the GNP uptake by DCs demonstrated a significant decrease in intracellular gold content during co-incubation with NiSO4. An extensive physiochemical characterization was performed to determine the interaction between GNPs and NiSO4 in the complex physiological media using nanoparticle tracking analyses, disc centrifugation, UV-visible spectroscopy, ICP-MS analyses, zeta potential measurements, electron microscopy, and proteomics. Although GNPs and NiSO4 did not directly interact with each other, the presence of NiSO4 in the physiological media resulted in changes in GNPs' charge and their associated protein corona (content and composition), which may contribute to a decreased cellular uptake of GNPs and sustaining the nickel-induced DC maturation. The presented results provide new insights in the interaction of heavy metals and NPs in complex physiological media. Moreover, this study highlights the necessity of mixture toxicology, since these combined exposures are highly relevant for human subjection to NPs and risk assessment of nanomaterials.