First Principles Calculations of Atomic Nickel Redox Potentials and Dimerization Free Energies: A Study of Metal Nanoparticle Growth

The redox potentials and dimerization free energies of transient transition metal cations in water shed light on the reactivity of species with unusual charge states and are particularly pertinent to understanding the mechanism and feasibility of radiolysis-assisted metal nanoparticle growth from salt solutions. A combination of quasi-chemical theory and ab initio molecular dynamics thermodynamic integration methods are applied to calculate these properties for nickel. The reduction potential for Ni2+ (aq) is predicted to be between −1.05 to −1.28 V, which is substantially lower than previous estimates. This suggests that Ni2+ reduction may possibly occur in the presence of organic radical anion electron scavengers and hydrogen atoms, not just hydrated electrons. In contrast, Ni+ is found to be stable against disproportionation. The formation of dimers Ni2 and Ni2+ from Ni and Ni+ are predicted to be favorable in water

Table5_Activation of the PPARγ Prevents Ferroptosis-Induced Neuronal Loss in Response to Intracerebral Hemorrhage Through Synergistic Actions With the Nrf2.XLSX

Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. The long-term effects of ICH-induced intracranial hematoma on patients’ neurological function are unclear. Currently, an effective treatment that significantly reduces the rates of death and disability in patients with ICH is not available. Based on accumulating evidence, ferroptosis may be the leading factor contributing to the neurological impairment caused by ICH injury. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated receptor in the nuclear hormone receptor family that synergistically interacts with the nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway to promote the expression of related genes and inhibit ferroptosis. Primary rat hippocampal neurons were treated with heme (50 μM) and erastin (50 μM) to induce ferroptosis, followed by the PPARγ agonist pioglitazone (PDZ, 10 μM) to verify the inhibitory effect of PPARγ activation on ferroptosis. ML385 (2 μM), a novel and specific NRF2 inhibitor, was administered to the inhibitor group, followed by an analysis of cellular activity and immunofluorescence staining. In vivo Assays, ICH rats injected with autologous striatum were treated with 30 mg/kg/d pioglitazone, and the inhibitor group was injected with ML385 (30 mg/kg). The results showed that PDZ inhibited ferroptosis in neurons by increasing the expression of PPARγ, Nrf2 and Gpx4 in vitro, while PDZ reduced ferroptosis in neurons after ICH and promoted the recovery of neural function in vivo. Our results suggest that PDZ, a PPARγ agonist, promotes Gpx4 expression through the interaction between PPARγ and the Nrf2 pathway, inhibits ferroptosis of neurons after ICH, and promotes the recovery of neural function.</p

Table2_Curcumin Restrains Oxidative Stress of After Intracerebral Hemorrhage in Rat by Activating the Nrf2/HO-1 Pathway.XLSX

Intracerebral hemorrhage (ICH), a severe hemorrhagic stroke, induces cerebral oxidative stress and severe secondary neurological injury. Curcumin was demonstrated to inhibit oxidative stress in the brain after ICH. However, the pharmacological mechanism needs further research. We used an intrastriatal injection of autologous blood to make the rat ICH model, and then the rat was treated with curcumin (100 mg/kg/day). Modified Neurological Severity Score (mNSS) and corner test results showed that curcumin could significantly promote the neurological recovery of ICH rats. Meanwhile, curcumin could substantially reduce ROS and MDA in the tissues around intracranial hematoma and prevent GSH depletion. To explore the pharmacological molecular mechanism of curcumin, we used HAPI cells and primary rat cortical microglia for in vitro experiments. In vitro, heme-treated cells were used as the cell model of ICH to explore the molecular mechanism of inhibiting oxidative stress by curcumin treatment. The results showed that curcumin significantly inhibited heme-induced oxidative stress, decreased intracellular ROS and MDA, and promoted Nrf2 and its downstream antioxidant gene (HO-1, NQO1, and Gpx4) expression. These results suggest that curcumin inhibits oxidative stress by activating the Nrf2/HO-1 pathway. Here, our results indicate that curcumin can promote the inhibition of oxidative stress in microglia by activating the Nrf2/HO-1 pathway and promoting neurological recovery after ICH, providing a new therapeutic target for clinical treatment of ICH.</p

Table7_Activation of the PPARγ Prevents Ferroptosis-Induced Neuronal Loss in Response to Intracerebral Hemorrhage Through Synergistic Actions With the Nrf2.XLSX

Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. The long-term effects of ICH-induced intracranial hematoma on patients’ neurological function are unclear. Currently, an effective treatment that significantly reduces the rates of death and disability in patients with ICH is not available. Based on accumulating evidence, ferroptosis may be the leading factor contributing to the neurological impairment caused by ICH injury. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated receptor in the nuclear hormone receptor family that synergistically interacts with the nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway to promote the expression of related genes and inhibit ferroptosis. Primary rat hippocampal neurons were treated with heme (50 μM) and erastin (50 μM) to induce ferroptosis, followed by the PPARγ agonist pioglitazone (PDZ, 10 μM) to verify the inhibitory effect of PPARγ activation on ferroptosis. ML385 (2 μM), a novel and specific NRF2 inhibitor, was administered to the inhibitor group, followed by an analysis of cellular activity and immunofluorescence staining. In vivo Assays, ICH rats injected with autologous striatum were treated with 30 mg/kg/d pioglitazone, and the inhibitor group was injected with ML385 (30 mg/kg). The results showed that PDZ inhibited ferroptosis in neurons by increasing the expression of PPARγ, Nrf2 and Gpx4 in vitro, while PDZ reduced ferroptosis in neurons after ICH and promoted the recovery of neural function in vivo. Our results suggest that PDZ, a PPARγ agonist, promotes Gpx4 expression through the interaction between PPARγ and the Nrf2 pathway, inhibits ferroptosis of neurons after ICH, and promotes the recovery of neural function.</p

Image5_Activation of the PPARγ Prevents Ferroptosis-Induced Neuronal Loss in Response to Intracerebral Hemorrhage Through Synergistic Actions With the Nrf2.TIF

Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. The long-term effects of ICH-induced intracranial hematoma on patients’ neurological function are unclear. Currently, an effective treatment that significantly reduces the rates of death and disability in patients with ICH is not available. Based on accumulating evidence, ferroptosis may be the leading factor contributing to the neurological impairment caused by ICH injury. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated receptor in the nuclear hormone receptor family that synergistically interacts with the nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway to promote the expression of related genes and inhibit ferroptosis. Primary rat hippocampal neurons were treated with heme (50 μM) and erastin (50 μM) to induce ferroptosis, followed by the PPARγ agonist pioglitazone (PDZ, 10 μM) to verify the inhibitory effect of PPARγ activation on ferroptosis. ML385 (2 μM), a novel and specific NRF2 inhibitor, was administered to the inhibitor group, followed by an analysis of cellular activity and immunofluorescence staining. In vivo Assays, ICH rats injected with autologous striatum were treated with 30 mg/kg/d pioglitazone, and the inhibitor group was injected with ML385 (30 mg/kg). The results showed that PDZ inhibited ferroptosis in neurons by increasing the expression of PPARγ, Nrf2 and Gpx4 in vitro, while PDZ reduced ferroptosis in neurons after ICH and promoted the recovery of neural function in vivo. Our results suggest that PDZ, a PPARγ agonist, promotes Gpx4 expression through the interaction between PPARγ and the Nrf2 pathway, inhibits ferroptosis of neurons after ICH, and promotes the recovery of neural function.</p

Table6_Curcumin Restrains Oxidative Stress of After Intracerebral Hemorrhage in Rat by Activating the Nrf2/HO-1 Pathway.XLSX

Intracerebral hemorrhage (ICH), a severe hemorrhagic stroke, induces cerebral oxidative stress and severe secondary neurological injury. Curcumin was demonstrated to inhibit oxidative stress in the brain after ICH. However, the pharmacological mechanism needs further research. We used an intrastriatal injection of autologous blood to make the rat ICH model, and then the rat was treated with curcumin (100 mg/kg/day). Modified Neurological Severity Score (mNSS) and corner test results showed that curcumin could significantly promote the neurological recovery of ICH rats. Meanwhile, curcumin could substantially reduce ROS and MDA in the tissues around intracranial hematoma and prevent GSH depletion. To explore the pharmacological molecular mechanism of curcumin, we used HAPI cells and primary rat cortical microglia for in vitro experiments. In vitro, heme-treated cells were used as the cell model of ICH to explore the molecular mechanism of inhibiting oxidative stress by curcumin treatment. The results showed that curcumin significantly inhibited heme-induced oxidative stress, decreased intracellular ROS and MDA, and promoted Nrf2 and its downstream antioxidant gene (HO-1, NQO1, and Gpx4) expression. These results suggest that curcumin inhibits oxidative stress by activating the Nrf2/HO-1 pathway. Here, our results indicate that curcumin can promote the inhibition of oxidative stress in microglia by activating the Nrf2/HO-1 pathway and promoting neurological recovery after ICH, providing a new therapeutic target for clinical treatment of ICH.</p

Image4_Activation of the PPARγ Prevents Ferroptosis-Induced Neuronal Loss in Response to Intracerebral Hemorrhage Through Synergistic Actions With the Nrf2.JPEG

Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. The long-term effects of ICH-induced intracranial hematoma on patients’ neurological function are unclear. Currently, an effective treatment that significantly reduces the rates of death and disability in patients with ICH is not available. Based on accumulating evidence, ferroptosis may be the leading factor contributing to the neurological impairment caused by ICH injury. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated receptor in the nuclear hormone receptor family that synergistically interacts with the nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway to promote the expression of related genes and inhibit ferroptosis. Primary rat hippocampal neurons were treated with heme (50 μM) and erastin (50 μM) to induce ferroptosis, followed by the PPARγ agonist pioglitazone (PDZ, 10 μM) to verify the inhibitory effect of PPARγ activation on ferroptosis. ML385 (2 μM), a novel and specific NRF2 inhibitor, was administered to the inhibitor group, followed by an analysis of cellular activity and immunofluorescence staining. In vivo Assays, ICH rats injected with autologous striatum were treated with 30 mg/kg/d pioglitazone, and the inhibitor group was injected with ML385 (30 mg/kg). The results showed that PDZ inhibited ferroptosis in neurons by increasing the expression of PPARγ, Nrf2 and Gpx4 in vitro, while PDZ reduced ferroptosis in neurons after ICH and promoted the recovery of neural function in vivo. Our results suggest that PDZ, a PPARγ agonist, promotes Gpx4 expression through the interaction between PPARγ and the Nrf2 pathway, inhibits ferroptosis of neurons after ICH, and promotes the recovery of neural function.</p

Image2_Activation of the PPARγ Prevents Ferroptosis-Induced Neuronal Loss in Response to Intracerebral Hemorrhage Through Synergistic Actions With the Nrf2.JPEG

Intracerebral hemorrhage (ICH) is a subtype of stroke characterized by high mortality and disability rates. The long-term effects of ICH-induced intracranial hematoma on patients’ neurological function are unclear. Currently, an effective treatment that significantly reduces the rates of death and disability in patients with ICH is not available. Based on accumulating evidence, ferroptosis may be the leading factor contributing to the neurological impairment caused by ICH injury. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated receptor in the nuclear hormone receptor family that synergistically interacts with the nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway to promote the expression of related genes and inhibit ferroptosis. Primary rat hippocampal neurons were treated with heme (50 μM) and erastin (50 μM) to induce ferroptosis, followed by the PPARγ agonist pioglitazone (PDZ, 10 μM) to verify the inhibitory effect of PPARγ activation on ferroptosis. ML385 (2 μM), a novel and specific NRF2 inhibitor, was administered to the inhibitor group, followed by an analysis of cellular activity and immunofluorescence staining. In vivo Assays, ICH rats injected with autologous striatum were treated with 30 mg/kg/d pioglitazone, and the inhibitor group was injected with ML385 (30 mg/kg). The results showed that PDZ inhibited ferroptosis in neurons by increasing the expression of PPARγ, Nrf2 and Gpx4 in vitro, while PDZ reduced ferroptosis in neurons after ICH and promoted the recovery of neural function in vivo. Our results suggest that PDZ, a PPARγ agonist, promotes Gpx4 expression through the interaction between PPARγ and the Nrf2 pathway, inhibits ferroptosis of neurons after ICH, and promotes the recovery of neural function.</p

Table1_Curcumin Restrains Oxidative Stress of After Intracerebral Hemorrhage in Rat by Activating the Nrf2/HO-1 Pathway.DOCX

Intracerebral hemorrhage (ICH), a severe hemorrhagic stroke, induces cerebral oxidative stress and severe secondary neurological injury. Curcumin was demonstrated to inhibit oxidative stress in the brain after ICH. However, the pharmacological mechanism needs further research. We used an intrastriatal injection of autologous blood to make the rat ICH model, and then the rat was treated with curcumin (100 mg/kg/day). Modified Neurological Severity Score (mNSS) and corner test results showed that curcumin could significantly promote the neurological recovery of ICH rats. Meanwhile, curcumin could substantially reduce ROS and MDA in the tissues around intracranial hematoma and prevent GSH depletion. To explore the pharmacological molecular mechanism of curcumin, we used HAPI cells and primary rat cortical microglia for in vitro experiments. In vitro, heme-treated cells were used as the cell model of ICH to explore the molecular mechanism of inhibiting oxidative stress by curcumin treatment. The results showed that curcumin significantly inhibited heme-induced oxidative stress, decreased intracellular ROS and MDA, and promoted Nrf2 and its downstream antioxidant gene (HO-1, NQO1, and Gpx4) expression. These results suggest that curcumin inhibits oxidative stress by activating the Nrf2/HO-1 pathway. Here, our results indicate that curcumin can promote the inhibition of oxidative stress in microglia by activating the Nrf2/HO-1 pathway and promoting neurological recovery after ICH, providing a new therapeutic target for clinical treatment of ICH.</p

DataSheet1_Curcumin Restrains Oxidative Stress of After Intracerebral Hemorrhage in Rat by Activating the Nrf2/HO-1 Pathway.PDF

Intracerebral hemorrhage (ICH), a severe hemorrhagic stroke, induces cerebral oxidative stress and severe secondary neurological injury. Curcumin was demonstrated to inhibit oxidative stress in the brain after ICH. However, the pharmacological mechanism needs further research. We used an intrastriatal injection of autologous blood to make the rat ICH model, and then the rat was treated with curcumin (100 mg/kg/day). Modified Neurological Severity Score (mNSS) and corner test results showed that curcumin could significantly promote the neurological recovery of ICH rats. Meanwhile, curcumin could substantially reduce ROS and MDA in the tissues around intracranial hematoma and prevent GSH depletion. To explore the pharmacological molecular mechanism of curcumin, we used HAPI cells and primary rat cortical microglia for in vitro experiments. In vitro, heme-treated cells were used as the cell model of ICH to explore the molecular mechanism of inhibiting oxidative stress by curcumin treatment. The results showed that curcumin significantly inhibited heme-induced oxidative stress, decreased intracellular ROS and MDA, and promoted Nrf2 and its downstream antioxidant gene (HO-1, NQO1, and Gpx4) expression. These results suggest that curcumin inhibits oxidative stress by activating the Nrf2/HO-1 pathway. Here, our results indicate that curcumin can promote the inhibition of oxidative stress in microglia by activating the Nrf2/HO-1 pathway and promoting neurological recovery after ICH, providing a new therapeutic target for clinical treatment of ICH.</p