Combined diosmin and bisoprolol attenuate cobalt chloride-induced cardiotoxicity and endothelial dysfunction through modulating miR-143-3P/MAPK/MCP-1, ERK5/CXCR4, Orai-1/STIM-1 signaling pathways.

Even while accelerated cardiomyocyte apoptosis is one of the primary causes of cardiac damage, the underlying mechanism is still mostly unknown. In addition to examining potential protective effects of bisoprolol and diosmin against CoCl2-induced cardiac injury, the goal of this study was to identify potential mechanisms regulating the hypoxic cardiac damage caused by cobalt chloride (CoCl2). For a period of 21 days except Cocl2 14 days from the first day of the experiment, rats were split into the following groups: Normal control group, rats received vehicle only (2 ml/kg/day, p.o.), (Cocl2, 150 mg/kg/day, p.o.), bisoprolol (25 mg/kg/day, p.o.); diosmin (100 mg/kg/day, p.o.) and bisoprolol + diosmin + Cocl2 groups. At the end of the experimental period, serum was taken for estimation of cardiac function, lipid profile, and pro/anti-inflammatory cytokines. Moreover, tissue samples were collected for evaluation of oxidative stress, endothelial dysfunction, α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Diosmin and bisoprolol, either alone or in combination, enhance heart function by reducing abnormalities in the electrocardiogram and the hypotension brought on by CoCl2. Additionally, they significantly ameliorate endothelial dysfunction by downregulating the cardiac expressions of α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Bisoprolol and diosmin produced modulatory activity against inflammatory state, redox balance, and atherogenic index concurrently. Together, diosmin and bisoprolol, either alone or in combination, significantly reduced all the cardiac alterations brought on by CoCl2. The capacity to obstruct hypoxia-induced α-SMA, PKC-α, MiR-143-3P/MAPK/MCP-1, MiR-143-3P/ERK5/CXCR4, Orai-1/STIM-1 signaling activation, as well as their anti-inflammatory, antioxidant, and anti-apoptotic properties, may be responsible for these cardio-protective results.

Transcriptomics pave the way into mechanisms of cobalt and nickel toxicity: Nrf2-mediated cellular responses in liver carcinoma cells.

Cobalt (Co) and Nickel (Ni) are used nowadays in various industrial applications like lithium-ion batteries, raising concerns about their environmental release and public health threats. Both metals are potentially carcinogenic and may cause neurological and cardiovascular dysfunctions, though underlying toxicity mechanisms have to be further elucidated. This study employs untargeted transcriptomics to analyze downstream cellular effects of individual and combined Co and Ni toxicity in human liver carcinoma cells (HepG2). The results reveal a synergistic effect of Co and Ni, leading to significantly higher number of differentially expressed genes (DEGs) compared to individual exposure. There was a clear enrichment of Nrf2 regulated genes linked to pathways such as glycolysis, iron and glutathione metabolism, and sphingolipid metabolism, confirmed by targeted analysis. Co and Ni exposure alone and combined caused nuclear Nrf2 translocation, while only combined exposure significantly affects iron and glutathione metabolism, evidenced by upregulation of HMOX-1 and iron storage protein FTL. Both metals impact sphingolipid metabolism, increasing dihydroceramide levels and decreasing ceramides, sphingosine and lactosylceramides, along with diacylglycerol accumulation. By combining transcriptomics and analytical methods, this study provides valuable insights into molecular mechanisms of Co and Ni toxicity, paving the way for further understanding of metal stress.

Exposure to different cobalt chloride levels produces oxidative stress and lipidomic changes and affects the liver structure of Cyprinus carpio juveniles.

The present investigation was undertaken to evaluate the toxic effects of CoCl2-induced hepatotoxicity and fatty acid changes in juvenile Cyprinus carpio. Fish were divided into six experimental groups in duplicate. The first group served as controls. The second group received the lowest exposure dose at 2.5 µg/L. In the third group, fish were exposed to 25 µg/L of CoCl2. The fourth group was exposed to 50 µg/L of CoCl2. The last two groups were exposed to the highest doses, 100 and 500 µg/L of CoCl2. Total antioxidant activities were estimated using a colorimetric method. Liver fatty acid compositions were analyzed by high-performance gas chromatography (GC). Hepatopathy was identified through microscopic analysis. Exposure of C. carpio to CoCl2 resulted in hepatotoxicity, indicated by increased levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), protein carbonyls (PCO), and alterations in the ferric reducing antioxidant power system (FRAP). Superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GPx), reduced glutathione (GSH), metallothioneins (MTs), and low thiol levels (L-SH) significantly increased, particularly under exposure to the highest CoCl2 doses (100 and 500 µg/L). Acetylcholinesterase activity decreased significantly in C. carpio exposed to graded CoCl2 doses. Additionally, there was a decrease in polyunsaturated fatty acids (PUFA), primarily n-3 PUFA, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), while an increase in monounsaturated (MUFA) and saturated fatty acids (SFA), including palmitic (C16:0), stearic (C18:0), palmitoleic (C16:1), and oleic (C18:1) acids, was observed. Histopathological examination of the liver confirmed hepatopathy revealing characteristic tissue changes such as leucocyte infiltration, hepatic cell membrane degradation, vacuolization, and lipid inclusions. The study provided ethnophysiology insights into the responses of C. carpio to CoCl2-induced oxidative stress and lipidomic alteration, underscoring its potential as a bioindicator for assessing environmental impacts and metal contamination.

Cobalt nanoparticles attenuate microplastic-induced vascular endothelial injury via Nrf2 pathway activation.

The widespread utilization of plastic and cobalt alloy products in industries and medicine has led to the increased presence of their degradation byproducts, microplastics (MPs), and cobalt nanoparticles (Co NPs), in the environment and organisms. While these particles can circulate throughout the body via the circulatory system, their specific adverse effects and mechanisms on the vascular system remain unclear. Employing scanning electron microscope (SEM) analysis and other methodologies, we demonstrate the potential adsorption and aggregation phenomena between MPs and Co NPs. In vitro experiments illustrate that ingestion of either MPs or Co NPs compromises vascular endothelial cell function and induces the generation of reactive oxygen species (ROS). Notably, this effect is markedly attenuated when a combination of MPs and Co NPs is administered compared to MPs alone. Additionally, zebrafish experiments validate our in vitro findings. Mechanistic studies have demonstrated that both MPs and Co NPs induce aberrant Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Intriguingly, a weaker activation level is observed when these agents are administered in combination compared to when they are administered individually. Our study provides novel insights into the interaction between MPs and Co NPs and their detrimental effects on vascular endothelial cells.

Glaucine inhibits hypoxia-induced angiogenesis and attenuates LPS-induced inflammation in human retinal pigment epithelial ARPE-19 cells.

Glaucine is an aporphine alkaloid with anti-inflammatory, bronchodilator and anti-cancer activities. However, the effects of glaucine in the regulation of age-related macular degeneration (AMD) remain unclear. Herein, we aimed to investigate the anti-angiogenetic and anti-inflammatory effects of glaucine in ARPE-19 cells. ARPE-19 cells were treated with N-(methoxyoxoacetyl)-glycine, methyl ester (DMOG) and cobalt chloride (CoCl2) for induction of hypoxia, while lipopolysaccharide (LPS) treatment was used for elicitation of inflammatory response. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by Western blot. The secretion of VEGF, interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) was detected using enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were used for tube formation analysis. Expression of HIF-1α and secretion of VEGF were significantly increased under DMOG and CoCl2 induction, whereas glaucine significantly attenuated both HIF-1α expression and VEGF secretion by DMOG- and CoCl2-induced ARPE-19 cells. In addition, glaucine suppressed the tube formation by DMOG- and CoCl2-induced HUVEC cells. Moreover, glaucine also attenuated the production of IL-6 and MCP-1 by LPS-induced ARPE-19 cells. This study indicated that glaucine exhibited anti-angiogenic and anti-inflammatory effects, suggesting that glaucine might have benefits for the treatment of AMD.

The fate and impact of Co3O4 nanoparticles in the soil environment: Observing the dose effect of nanoparticles on soybeans.

The widespread presence and distribution of metal-based nanoparticles (NPs) in soil is threatening crop growth and food security. However, little is known about the fate of Co3O4 NPs in the soil-soybean system and their phytotoxicity. The study demonstrated the effects of Co3O4 NPs on soybean growth and yield in soil after 60 days and 140 days, and compared them with the phytotoxic effects of Co2+. The results showed that Co3O4 NPs (10-500 mg/kg) had no significant toxic effect on soybeans. Soil available Co content was significantly increased under 500 mg/kg Co3O4 NPs treatment. Compared with Co2+, Co3O4 NPs mainly accumulated in roots and had limited transport to the shoots, which was related to the particle size, surface charge and chemical stability of Co3O4 NPs. The significant accumulation of Co3O4 NPs in roots further led to a significant decrease in root antioxidant enzyme activity and changes in functional gene expression. Co3O4 NPs reduced soybean yield after 140 days, but interestingly, at specific doses, it increased grain nutrients (Fe content increased by 17.38% at 100 mg/kg, soluble protein and vitamin E increased by 14.34% and 16.81% at 10 mg/kg). Target hazard quotient (THQ) assessment results showed that consuming soybean seeds exposed to Co3O4 NPs (≥100 mg/kg) and Co2+ (≥10 mg/kg) would pose potential health risks. Generally, Co3O4 NPs could exist stably in the environment and had lower environmental risks than Co2+. These results help to better understand the environmental behavior and plant effect mechanisms of Co3O4 NPs in soil-plant systems.

ALKBH5-mediated N6-methyladenosine modification of HO-1 mRNA regulates ferroptosis in cobalt-induced neurodegenerative damage.

The utilization of Cobalt (Co) has surged due to it is critical role in renewable energy technologies and other high-tech applications. Concurrently, the potential health risks associated with Co exposure have raised concerns. Previous studies, including our own, have shown that Co can impair learn and memory functions as an epigenetic hazard, even at low concentrations. In this study, we explore the mechanisms of Co-induced ferroptosis in neurodegenerative damage both in vivo and in vitro, focusing on the epigenetic regulation by N6-methyladenosine (m6A) demethylase alkB homolog 5 (ALKBH5). We identify heme oxygenase-1 (HO-1) as a direct target gene of ALKBH5, playing a crucial role in mitigating Co-induced ferroptosis. ALKBH5 deficiency affects the post-transcriptional regulation of HO-1 through m6A modification, which in turn influences mRNA's stability, intracellular distribution, and alternative splicing, thereby enhancing susceptibility to Co-induced ferroptosis. Additionally, we discuss the potential involvement of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in regulating alternative splicing of HO-1 mRNA, potentially mediated by m6A modifications. This study provides new epigenetic insights into the post-transcriptional regulatory mechanisms involved in Co-induced ferroptosis and highlights the broader implications of environmental hazards in neurodegenerative damage.

Discerning the role of a site cation in ACoO3 perovskites for boosting Co3+/Co2+ redox cycle for pollutant degradation: DFT calculation, mechanism and toxicity evolution.

The degradation of persistent and refractory pollutants, particularly plastic and resins manufacturing wastewater, poses a significant challenge due to their high toxicity and high concentrations. This study developed a novel hybrid ACoO3 (A = La, Ce, Sr)/PMS perovskite system for the treatment of multicomponent (MCs; ACN, ACM and ACY) from synthetic resin manufacturing wastewater. Synthesized perovskites were characterized by various techniques i.e., BET, XRD, FESEM with EDAX, FTIR, TEM, XPS, EIS, and Tafel analysis. Perovskite LaCoO3 exhibited the highest degradation of MCs i.e., ACN (98.7%), ACM (86.3%), and ACY (56.4%), with consumption of PMS (95.2%) under the optimal operating conditions (LaCoO3 dose 0.8 g/L, PMS dose 2 g/L, pH 7.2 and reaction temperature 55 °C). The quantitative contribution (%) of reactive oxygen species (ROS) reveals that SO4•- are the dominating radical species, which contribute to ACN (58.3% for SO4•- radicals) and ACM degradation (46.4% for SO4•- radicals). The tafel plots and EIS spectra demonstrated that perovskites LaCoO3 have better charge transfer rates and more reactive sites that are favorable for PMS activation. Further, four major degradation pathways were proposed based on Fukui index calculations, as well as GC-MS characterization of intermediate byproducts. Based on a stability and reusability study, it was concluded that LaCoO3 perovskites are highly stable, and minimal cobalt leaching occurs (0.96 mg/L) after four cycles. The eco-toxicity assessment performed using QSAR model indicated that the byproducts of the LaCoO3/PMS system are non-toxic nature to common organism (i.e., fish, daphnids and green algae). In addition, the cost of the hybrid LaCoO3/PMS system in a single cycle was estimated to be $34.79 per cubic meter of resin wastewater.

Toxicity of different-sized cobalt ferrite (CoFe2O4) nanoparticles to Oncorhynchus mykiss at early development stages.

As innovative and versatile agents with potential applications in a wide range of fields including medicine, electronics, wastewater treatment, cosmetics, and energy storage devices, magnetic nanoparticles (NPs) are significant attention. However, our knowledge of the harmful effects of different-sized NPs, particularly of their effects on aquatic animals, is limited. In this study, we evaluated the impact of different-sized (sub-2, 5, and 15 nm) cobalt ferrite (CoFe2O4) NPs on the biological parameters of rainbow trout (Oncorhynchus mykiss) embryos and larvae. The NPs were characterized using techniques such as high-resolution transmission electron microscopy (HRTEM) for imaging, X-ray diffraction (XRD) for crystallographic analysis, and energy-dispersive X-ray spectroscopy (EDX) for elemental analysis, and were tested for impact through a series of toxicity, genotoxicity, and biochemical assays at a concentration of 100 mg/L. The obtained results showed that toxicity of CoFe2O4 NPs depended on the size of NPs and the developmental stage of the fish. Our results, which revealed significant changes in biological parameters of O. mykiss under exposure to CoFe2O4 NPs, imply that these NPs may be not environmentally safe. The hierarchical cluster analysis showed that embryos of the control group were clearly separated from those exposed to NPs of various sizes. However, in the exposed larvae, the effects of control and the smallest-sized NPs (sub-2 nm) differed from those induced by larger NPs (5 nm and 15 nm). Additional research is necessary to comprehend the mechanisms underlying the observed variations, which would be advantageous for both managing the risk of NPs to humans and advancing the field of aquatic nanotoxicology.

Multi-scale analysis of acidophilic microbial consortium biofilm's tolerance of lithium and cobalt ions in bioleaching.

Metal ions stress will inhibit the oxidation capacity of iron and sulfur of an acidophilic microbial consortium (AMC), which leads to reduced bioleaching efficiency. This work explored the impacts of Li+ and Co2+ on the composition and function of AMC biofilms with a multi-scale approach. At the reactor scale, the results indicated that the oxidative activity, the adsorption capacity, and the biofilm formation ability of AMC on pyrite surfaces decreased under 500 mM Li+ and 500 mM Co2+. At the biofilm scale, the electrochemical measurements showed that Li+ and Co2+ inhibited the charge transfer between the pyrite working electrode and the biofilm, and decreased the corrosion current density of the pyrite working electrode. At the cell scale, the content of proteins in extracellular polymers substrate (EPS) increased as the concentrations of metal ions increased. Moreover, the adsorption capacity of EPS for Li+ and Co2+ increased. At the microbial consortium scale, a BugBase phenotype analysis showed that under 500 mM Li+ and 500 mM Co2+, the antioxidant stress capacity and the content of mobile gene elements in AMC increased. The results in this work can provide useful data and theoretical support for the regulation strategy of the bioleaching of spent lithium-ion batteries to recover valuable metals.

In Vitro Inflammatory Cell-Induced Corrosion Using a Lymphocyte and Macrophage Coculture.

BACKGROUND: Cobalt-chromium-molybdenum (CoCrMo) and titanium alloys have been used for orthopaedic implants for decades. However, recent evidence has shown that inflammatory cell-induced corrosion (ICIC) can damage these metal alloys. This study aimed to investigate the mechanisms of ICIC by coculturing macrophages with lymphocytes. We hypothesized that macrophages would be able to alter the surface oxide layer of CoCrMo and titanium alloy (Ti6Al4V) disks, with greater oxide layer damage occurring in groups with a coculture compared to a macrophage monoculture and in groups with inflammatory activators compared to nonactivated groups. METHODS: Murine macrophages were cultured on American Society for Testing and Materials F1537 CoCrMo and F136 Ti6Al4V disks for 30 days and activated with interferon gamma and lipopolysaccharide. Interferon gamma and lipopolysaccharide were added to the culture medium to simulate local inflammation. Macrophages were either cultured alone or in a coculture with T helper lymphocytes. After the 30-day experiment, scanning electron microscopy was used to examine the disk surfaces, and oxide levels were found using energy dispersive x-ray spectroscopy. RESULTS: Pitting features consistent with previous reports of ICIC were found on disks cultured with cells. Both CoCrMo and Ti6Al4V disks had significantly lower oxide levels in all groups with cells compared to control groups with no cells (P < .01). Additionally, CoCrMo disks had significantly lower oxide levels when cultured with activated macrophages and lymphocytes compared to nonactivated macrophages alone (P < .001), activated macrophages alone (P < .01), and nonactivated macrophages and lymphocytes (P < .05). No differences in the oxide levels were found among the Ti6Al4V groups. CONCLUSIONS: This study demonstrates the ability of macrophages to alter the surface chemistry of commonly used orthopaedic alloys. We found that the addition of lymphocytes and a simulated local inflammatory response may contribute to the ICIC of CoCrMo implants.

Single is not combined: The role of Co and Ni bioavailability on toxicity mechanisms in liver and brain cells.

The two trace elements cobalt (Co) and nickel (Ni) are widely distributed in the environment due to the increasing industrial application, for example in lithium-ion batteries. Both metals are known to cause detrimental health impacts to humans when overexposed and both are supposed to be a risk factor for various diseases. The individual toxicity of Co and Ni has been partially investigated, however the underlying mechanisms, as well as the interactions of both remain unknown. In this study, we focused on the treatment of liver carcinoma (HepG2) and astrocytoma (CCF-STTG1) cells as a model for the target sites of these two metals. We investigated their effects in single and combined exposure on cell survival, cell death mechanisms, bioavailability, and the induction of oxidative stress. The combination of CoCl2 and NiCl2 resulted in higher Co levels with subsequent decreased amount of Ni compared to the individual treatment. Only CoCl2 and the combination of both metals led to RONS induction and increased GSSG formation, while apoptosis and necrosis seem to be involved in the cell death mechanisms of both CoCl2 and NiCl2. Collectively, this study demonstrates cell-type specific toxicity, with HepG2 representing the more sensitive cell line. Importantly, combined exposure to CoCl2 and NiCl2 is more toxic than single exposure, which may originate partly from the respective cellular Co and Ni content. Our data imply that the major mechanism of joint toxicity is associated with oxidative stress. More studies are needed to assess toxicity after combined exposure to elements such as Co and Ni to advance an improved hazard prediction for less artificial and more real-life exposure scenarios.

Pollution control performance of solidified nickel-cobalt tailings on site: Bioavailability of heavy metals and microbial response.

There has been increasing attention given to nickel-cobalt tailings (NCT), which pose a risk of heavy metal pollution in the field. In this study, on site tests and sampling analysis were conducted to assess the physical and chemical characteristics, heavy metal toxicity, and microbial diversity of the original NCT, solidified NCT, and the surrounding soil. The research results show that the potential heavy metal pollution species in NCT are mainly Ni, Co, Mn, and Cu. Simultaneous solidification and passivation of heavy metals in NCT were achieved, resulting in a reduction in biological toxicity and a fivefold increase in seed germination rate. The compressive strength of the original tailings was increased by 20 times after solidification. The microbial diversity test showed that the abundance of microbial community in the original NCT was low and the population was monotonous. This study demonstrates, for the first time, that the use of NCT for solidification in ponds can effectively solidification of heavy metals, reduce biological toxicity, and promote microorganism diversity in mining areas (tended to the microbial ecosystem in the surrounding soil). Indeed, this study provides a new perspective for the environmental remediation of metal tailings.

New sensitive tools to characterize meta-metabolome response to short- and long-term cobalt exposure in dynamic river biofilm communities.

Untargeted metabolomics is a non-a priori analysis of biomolecules that characterizes the metabolome variations induced by short- and long-term exposures to stressors. Even if the metabolite annotation remains lacunar due to database gaps, the global metabolomic fingerprint allows for trend analyses of dose-response curves for hundreds of cellular metabolites. Analysis of dose/time-response curve trends (biphasic or monotonic) of untargeted metabolomic features would thus allow the use of all the chemical signals obtained in order to determine stress levels (defense or damage) in organisms. To develop this approach in a context of time-dependent microbial community changes, mature river biofilms were exposed for 1 month to four cobalt (Co) concentrations (from background concentration to 1 × 10-6 M) in an open system of artificial streams. The meta-metabolomic response of biofilms was compared against a multitude of biological parameters (including bioaccumulation, biomass, chlorophyll a content, composition and structure of prokaryotic and eukaryotic communities) monitored at set exposure times (from 1 h to 28 d). Cobalt exposure induced extremely rapid responses of the meta-metabolome, with time range inducing defense responses (TRIDeR) of around 10 s, and time range inducing damage responses (TRIDaR) of several hours. Even in biofilms whose structure had been altered by Co bioaccumulation (reduced biomass, chlorophyll a contents and changes in the composition and diversity of prokaryotic and eukaryotic communities), concentration range inducing defense responses (CRIDeR) with similar initiation thresholds (1.41 ± 0.77 × 10-10 M Co2+ added in the exposure medium) were set up at the meta-metabolome level at every time point. In contrast, the concentration range inducing damage responses (CRIDaR) initiation thresholds increased by 10 times in long-term Co exposed biofilms. The present study demonstrates that defense and damage responses of biofilm meta-metabolome exposed to Co are rapidly and sustainably impacted, even within tolerant and resistant microbial communities.

Meta-metabolomic responses of river biofilms to cobalt exposure and use of dose-response model trends as an indicator of effects.

The response of the meta-metabolome is rarely used to characterize the effects of contaminants on a whole community. Here, the meta-metabolomic fingerprints of biofilms were examined after 1, 3 and 7 days of exposure to five concentrations of cobalt (from background concentration to 1 × 10-5 M) in aquatic microcosms. The untargeted metabolomic data were processed using the DRomics tool to build dose-response models and to calculate benchmark-doses. This approach made it possible to use 100% of the chemical signal instead of being limited to the very few annotated metabolites (7%). These benchmark-doses were further aggregated into an empirical cumulative density function. A trend analysis of the untargeted meta-metabolomic feature dose-response curves after 7 days of exposure suggested the presence of a concentration range inducing defense responses between 1.7 × 10-9 and 2.7 × 10-6 M, and of a concentration range inducing damage responses from 2.7 × 10-6 M and above. This distinction was in good agreement with changes in the other biological parameters studied (biomass and chlorophyll content). This study demonstrated that the molecular defense and damage responses can be related to contaminant concentrations and represents a promising approach for environmental risk assessment of metals.

Curcumin abrogates cobalt-induced neuroinflammation by suppressing proinflammatory cytokines release, inhibiting microgliosis and modulation of ERK/MAPK signaling pathway.

Curcumin, a bioactive polyphenol derived from turmeric, has been reported to have anti-inflammatory properties. The current study investigated the anti-inflammatory effect of curcumin in the hippocampal subfields (CA1 and CA3) after exposure to cobalt (Co) and the impact of ERK protein. Twenty-eight albino Wistar rats were divided into four groups, each with seven randomly selected rats as follows: Control (distilled water), Cobalt (Co) only (40 mg/kg), 120 mg/kg or 240 mg/kg curcumin + Co (40 mg/kg). Treatment was via oral gavage for 28 days. We performed a biochemical investigation to determine the levels of proinflammatory cytokines (TNFα and IL-1ß). Furthermore, we conducted an immunohistochemical evaluation to assess the expression of IBA1 by microglial cells and the immunoexpression of ERK protein in the hippocampus. Results revealed a significant (p<0.05) elevation in the tissue level of TNFα and IL-1ß, an increase in the number of IBA1-positive microglia, and upregulation of ERK protein in the hippocampal subfields of the rats after exposure to cobalt-only. Nevertheless, pretreatment with curcumin restored these parameters to levels comparable to control. In conclusion, our results showed that curcumin abrogated the Co-induced neuroinflammation by suppressing the release of proinflammatory biomarkers, reducing microgliosis, and modulating the ERK/MAPK pathway.

Exogenous application of sulfur-rich thiourea (STU) to alleviate the adverse effects of cobalt stress in wheat.

Heavy metal stress affects crop growth and yields as wheat (Triticum aestivum L.) growth and development are negatively affected under heavy metal stress. The study examined the effect of cobalt chloride (CoCl2) stress on wheat growth and development. To alleviate this problem, a pot experiment was done to analyze the role of sulfur-rich thiourea (STU) in accelerating the defense system of wheat plants against cobalt toxicity. The experimental treatments were, i) Heavy metal stress (a) control and (b) Cobalt stress (300 µM), ii) STU foliar applications; (a) control and (b) 500 µM single dose was applied after seven days of stress, and iii) Wheat varieties (a) FSD-2008 and (b) Zincol-2016. The results revealed that cobalt stress decreased chlorophyll a by 10%, chlorophyll b by 16%, and carotenoids by 5% while foliar application of STU increased these photosynthetic pigments by 16%, 15%, and 15% respectively under stress conditions as in contrast to control. In addition, cobalt stress enhances hydrogen peroxide production by 11% and malondialdehyde (MDA) by 10%. In comparison, STU applications at 500 µM reduced the production of these reactive oxygen species by 5% and by 20% by up-regulating the activities of antioxidants. Results have revealed that the activities of SOD improved by 29%, POD by 25%, and CAT by 28% under Cobalt stress. Furthermore, the foliar application of STU significantly increased the accumulation of osmoprotectants as TSS was increased by 23% and proline was increased by 24% under cobalt stress. Among wheat varieties, FSD-2008 showed better adaptation under Cobalt stress by showing enhanced photosynthetic pigments and antioxidant activities compared to Zincol-2016. In conclusion, the foliar-applied STU can alleviate the negative impacts of Cobalt stress by improving plant physiological attributes and upregulating the antioxidant defense system in wheat.

Associations between multiple metal exposure and fertility in women: A nested case-control study.

Metal pollution can cause a decline in female fertility, however, previous studies have focused more on the effect of a single metal on fertility. In this study, we evaluated the effect of metal mixtures on female fertility based on nested case-control samples. The plasma levels of 22 metal elements from 180 women were determined by an inductively coupled plasma mass spectrometer (ICP-MS). Minimum absolute contraction and selection operator (LASSO) penalty regression selected metals with the greatest influence on clinical outcome. Logistic regression was used to analyze the correlation between single metals and fertility while a Bayesian kernel function regression (BKMR) model was used to analyze the effect of mixed metals. Eight metals (Calcium (Ca), Chromium (Cr), Cobalt (Co), Copper (Cu), Zinc (Zn), Rubidium (Rb), Strontium (Sr) and Zirconium (Zr)) were selected by LASSO regression for subsequent analysis. After adjusting for covariates, the logistic model showed that Cu (Odds Ratio(OR):0.33, 95% CI: 0.13 - 0.84) and Co (OR:0.38, 95% CI: 0.15 -0.94) caused a significant reduction in fertility, and identified the protective effect of Zn (OR: 2.96, 95% CI:1.21 -7.50) on fertility. Trend tests showed that increased Cr, Cu, and Rb levels were associated with reduced fertility. The BKMR model showed that Cr, Co, Cu, and Rb had a nonlinear relationship with fertility decline when controlling for the concentrations of other metals and suggested that Cu and Cr might exert an influence on fertility. Analysis showed a negative correlation between Cu, Cr, Co, Rb, and fertility, and a positive correlation between Zn and fertility. Furthermore, we found evidence for the interaction between Cu and Cr. Our findings require further validation and may identify new mechanisms in the future.

Cobalt-chromium toxicity following revision of total hip replacement.

Systemic cobalt-chromium (Co-Cr) toxicity following a total hip replacement is a rare complication that may sometimes lead to fatal consequences. We report a case of a 64-year-old woman, who presented with Co-Cr toxicity after revision of fractured ceramic components with metal-on-polyethylene. Systemic toxicity occurred a year after surgery and was expressed brutally with mostly central neurological symptoms. Revision surgery allowed rapid regression of all symptoms. Prosthetic revision with a metal bearing surface after a history of fracture of the ceramic bearing component should be avoided. Orthopedic surgeons and the different medical actors should be aware of this rare but serious complication to allow earlier management. Above all, multidisciplinary management is primordial to allow correct diagnosis and appropriate treatment.

Hypoxia-Mediated Upregulation of Xanthine Oxidoreductase Causes DNA Damage of Colonic Epithelial Cells in Colitis.

Xanthine oxidoreductase (XOR) serves as the primary source of hydrogen peroxide and superoxide anions in the intestinal mucosa. However, its specific contribution to the progression of colonic disease remains unclear. In this study, we investigated the role of XOR in ulcerative colitis (UC) and attempted to identify the underlying mechanisms. We used the dextran sulfate sodium (DSS)-induced mouse model to mimic UC and observed that XOR inhibitors, allopurinol and diphenyleneiodonium sulfate (DPI), significantly alleviated UC in mice. In addition, treatment with cobalt chloride (CoCl2) and 1% O2 increased the expression of XOR and induced DNA oxidative damage in colonic epithelial cells. Furthermore, we identified that XOR accumulation in the nucleus may directly cause DNA oxidative damage and regulates HIF1α protein levels. In addition, allopurinol effectively protected colon epithelial cells from CoCl2-induced DNA damage. Altogether, our data provided evidence that XOR could induce DNA damage under hypoxic conditions, indicating a significant role of XOR in the initiation and early development of colitis-associated colorectal cancer (CAC).