Enhancing peroxidase-like activity of AuNPs through headspace reaction: A signal amplification strategy for colorimetric and fluorescent sensing of trace Hg2.

BACKGROUND: Recently, headspace single-drop microextraction (HS-SDME) has attracted some attention for developing sensitive and selective colorimetric assays due to its excellent capability to reduce matrix interference and enrich analytes. However, the single droplet limits direct visual observation of color change and its quantitative measurement suffers from reduced optical path length. Therefore, amplifying the detection signals in both volume and intensity is an important and challenging task for improving the sensitivity, stability, and accuracy of such colorimetric analysis. RESULTS: In this study, a "headspace-nanoenzyme" (HS-NE) strategy was proposed that successfully addressed these challenges and enabled the colorimetric and fluorescent dual-mode detection of trace Hg2+. Atomic Hg0, generated via chemical vapor generation (CVG), underwent headspace reaction with AuNPs droplet to form Au@HgNPs, thus catalyzing the oxidation of o-phenylenediamine (OPD) in the presence of H2O2. The absorbance and fluorescence intensity of oxidized OPD were proportion to the concentration of Hg2+ in the sample solution. Due to the greatly enhanced peroxidase-like activity by Au@HgNPs, the limit of detection was as low as 0.98 nM and 0.21 nM for the colorimetric and fluorescent modes, respectively. The applicability of this assay was further demonstrated with determination of Hg2+ in real environmental and biological samples. Moreover, a convenient and cost-effective paper-based sensing platform was fabricated for rapid on-site detection of Hg2+. SIGNIFICANCE AND NOVELTY: This novel HS-NE strategy combines HS-SDME and nanoenzyme-based sensing to achieve dual effects of eliminating matrix interference and amplifying the measurement signal, resulting in improved accuracy, enhanced stability, high sensitivity, and exceptional selectivity, with great potential for on-site determination of trace Hg2+.

Studies on Hydrophobic Silica/Silicone Rubber Composite Microspheres with Dual-Size Microstructures.

In this study, a series of microsphere composites were prepared by the hydrosilylation of nanospherical SiO2 and silicon rubber microspheres. The influence of different host-guest size ratios on the wettability of the SiO2/silicone rubber composite microspheres was explored. The structures and performance of the composite microspheres were investigated using scanning electron microscopy and contact angle testing. The results showed that the prepared SiO2/silicone rubber composite microspheres had a raspberry-like structure and exhibited a rose petal effect. When the SiO2 content was 30%, the water contact angle of the SiO2/silicone rubber composite microspheres reached a maximum, and 30% was used as the optimal ratio for compounding SiO2 having different particle diameters with silicone rubber microspheres. Wettability calculations and analyses were performed for the surface with the composite microspheres. The results indicated that the structure with dual-size roughness could significantly improve surface hydrophobicity. As the ratio of the host-guest size increased, the contact angle of the water phase also increased. However, the surface structures of the composite microspheres were not uniform because of the surface chemical composition and the uncontrollable distribution of the small spheres on the surface of the large spheres during compounding. As a result, water droplets appeared in the Cassie-impregnated state on the composite microsphere particle coating, resulting in the phenomenon of high hydrophobicity and high adhesion.

Dynamic regulation of Al-based floc cake layers by spiral rotation during ultrafiltration in drinking water treatment.

Integrated ultrafiltration (UF) membrane-based processes are promising drinking water treatment technologies. However, the membrane module always remains static, resulting in membrane fouling through the gradual formation of a thick cake layer. As floc-based cake layers are loose, in the present study, a membrane module spiral rotation was introduced with the aim of regulating the cake layers. The cake layer thickness readily decreased and the UF membrane fouling was alleviated. The results showed that Al-based flocs were not easily removed from the membrane surface during rotation due to its low density; as a result, the likelihood of humic acid (HA) reaching the membrane surface was low. Computational fluid dynamics indicated that a strong shearing force was generated with high rotation height. Thus, the cake layer thickness was easily regulated, and the UF membrane fouling was further alleviated. However, the floc-based cake layer could be broken by strong shearing forces, thereby allowing HA molecules to directly reach the membrane surface and further aggravating membrane fouling. In comparison to alkaline condition, the UF membrane performed better under acidic conditions, particularly in terms of HA removal, due to the smaller floc size and higher positive charge. Additionally, excellent UF membrane performance was also observed when treating raw water, indicating the potential application.

Long-Term Effect of Endoscopic Evacuation for Large Basal Ganglia Hemorrhage With GCS Scores ≦ 8.

Aims: The surgical evacuation, including stereotactic aspiration, endoscopic evacuation, and craniotomy, is the most effective way to reduce the volume of intracerebral hemorrhage. However, credible evidence for the effects of these techniques is still insufficient. The present study explored the long-term outcomes of these techniques in the treatment of basal ganglia hematoma with low Glasgow Coma Scale (GCS) scores (≤8) and large-volume (≥40 ml), which were predictors of high mortality. Methods: Two hundred and fifty-eight consecutive patients were reviewed retrospectively. The primary and secondary outcomes were 6-months mortality and 6-months modified Rankin Scale score, which were assessed by a multivariate logistic regression model. Results: Compared with the endoscopic evacuation group, the mortality was significantly higher in the stereotactic aspiration group (OR 6.858, 95% CI 3.146-14.953) and open craniotomy group (OR 3.315, 95% CI 1.497-7.341). Age (OR = 2.237, 95% CI 1.290-3.877) and herniation (OR = 2.257, 95% CI 1.172-4.348) were independent predictors for mortality. No significant difference in the neurological functional outcome was found in the stereotactic aspiration group (OR 0.501, 95% CI 0.192-1.308) and the craniotomy group (OR 0.774, 95% CI 0.257-2.335) compared with the endoscopic evacuation group. Conclusion: Endoscopic evacuation significantly decreased the 6-months mortality in patients with hemorrhage ≥40 ml and GCS ≤ 8.

Pterostilbene Attenuates Cocultured BV-2 Microglial Inflammation-Mediated SH-SY5Y Neuronal Oxidative Injury via SIRT-1 Signalling.

Microglial inflammation plays an important part in the progression of multiple neurological diseases, including neurodegenerative diseases, stroke, depression, and traumatic encephalopathy. Here, we aimed to explore the role of pterostilbene (PTE) in the microglial inflammatory response and subsequent damage of cocultured neural cells and partially explain the underlying mechanisms. In the coculture system of lipopolysaccharide-activated BV-2 microglia and SH-SY5Y neuroblastoma, PTE (only given to BV-2) exhibited protection on SH-SY5Y cells, evidenced by improved SH-SY5Y morphology and viability and LDH release. It also attenuated SH-SY5Y apoptosis and oxidative stress, evidenced by TUNEL and DCFH-DA staining, as well as MDA, SOD, and GSH levels. Moreover, PTE upregulated SIRT-1 expression and suppressed acetylation of NF-κB p65 subunit in BV-2 microglia, thus decreasing the inflammatory factors, including TNF-α and IL-6. Furthermore, the effects above were reversed by SIRT-1 inhibitor EX527. These results suggest that PTE reduces the microglia-mediated inflammatory response and alleviates subsequent neuronal apoptosis and oxidative injury via increasing SIRT-1 expression and inhibiting the NF-κB signalling pathway.

Influence of floc dynamic protection layer on alleviating ultrafiltration membrane fouling induced by humic substances.

Cake layer formation is inevitable over time for ultrafiltration (UF) membrane-based drinking water treatment. Although the cake layer is always considered to cause membrane fouling, it can also act as a "dynamic protection layer", as it further adsorbs pollutants and dramatically reduces their chance of getting to the membrane surface. Here, the UF membrane fouling performance was investigated with pre-deposited loose flocs in the presence of humic acid (HA). The results showed that the floc dynamic protection layer played an important role in removing HA. The higher the solution pH, the more negative the floc charge, resulting in lower HA removal efficiency due to the electrostatic repulsion and large pore size of the floc layer. With decreasing solution pH, a positively charged floc dynamic protection layer was formed, and more HA molecules were adsorbed. The potential reasons were ascribed to the smaller floc size, greater positive charge, and higher roughness of the floc layer. However, similar membrane fouling performance was also observed for the negative and positive floc dynamic protection layers due to their strong looseness characteristics. In addition, the molecular weight (MW) distribution of HA also played an important role in UF membrane fouling behavior. For the small MW HA molecules, the chance of forming a loose cake layer was high with a negatively charged floc dynamic protection layer, while for the large MW HA molecules it was high with a positively charged floc dynamic protection layer. As a result, slight UF membrane fouling was induced.

Influence of sedimentation with pre-coagulation on ultrafiltration membrane fouling performance.

Coagulation plays an important role in effectively alleviating ultrafiltration (UF) membrane fouling due to the existence of flocs. In comparison to traditional filtration, direct filtration (no sedimentation tank) is generally considered to result in less membrane fouling due to the looser cake layer formed on the membrane surface. However, cake layer characteristics are easily influenced by operating conditions (e.g., sedimentation time, temperature), resulting in different fouling loads and the still very limited knowledge about the fouling behavior. Here, a detailed investigation of UF membrane performance was carried out to analyze the differences between traditional filtration and direct filtration. The results showed that a critical settling time indeed existed when flocs gradually settled, leading to severe membrane fouling induced by a dense and thick cake layer. Therefore, the traditional filtration performed worse when the settling time was shorter than the critical time, while it performed better when the settling time was longer. In comparison to room temperature water, the proportion of membrane fouling caused by the cake layer increased at low water temperature due to the contracted membrane pore size, and the cake layer thickness became the main fouling load. The longer the settling time, the fewer pollutants reached the membrane surface, the thinner the cake layer, and the lower the potential for membrane fouling. Thus, traditional filtration performed better than direct filtration, and the critical settling time was not obvious. Although solution pH played an important role in floc properties, the fouling load was influenced little and traditional filtration still performed better. This work shows that the cake layer properties/fouling loads vary with the settling time during the coagulation-UF process, and this finding is of great significance to the improvement of membrane technology in drinking water plants.

[Effects of Microplastics on Membrane Fouling During a Shortened Ultrafiltration Membrane Process].

Microplastics have garnered much attention worldwide as a new emerging pollutant. As they are gradually detected in freshwaters, understanding how microplastics will behave during current drinking water treatment processes is urgently needed. In recent years, the shortened process with an ultrafiltration (UF) membrane has shown excellent performance because of its low land use and high water purification efficiency. In this work, the membrane performance induced by microplastics was investigated with a shortened UF membrane process. The results showed that membrane fouling was always induced by the cake layer before and after coagulating with microplastics. Owing to the small UF membrane pore size (d<0.1 µm), slight membrane fouling was caused by microplastics (d<5 mm) alone. However, although the loose cake layer was formed because of the existence of flocs, the cyberspace formed by flocs was easily entered by small microplastics with increasing coagulant dosage. As a result, server membrane fouling was induced because of the formation of a dense cake layer. It was shown that the specific membrane flux induced by flocs alone was 0.82 and 0.76 in the presence of 0.1 mmol·L-1 and 0.9 mmol·L-1 FeCl3·6H2O, respectively. However, after coagulation the specific membrane fouling induced by the 0.1 g small microplastics (d<0.5 mm) was 0.76 and 0.62 with 0.1 mmol·L-1 and 0.9 mmol·L-1 FeCl3·6H2O, respectively. In addition, microplastics were always negatively charged in water. In comparison with alkaline conditions, Fe-based flocs were positively charged under acidic conditions, which were also much smaller. Therefore, microplastics were more easily adsorbed by Fe-based flocs under acidic conditions, leading to severe membrane fouling because of the dense cake layer formed. After coagulating with 0.3 mmol·L-1 FeCl3·6H2O, the specific membrane flux induced by 0.1 g small microplastics (d<0.5 mm) was 0.55 and 0.79 at pH 6.0 and 8.0, respectively.

Pterostilbene Attenuates Astrocytic Inflammation and Neuronal Oxidative Injury After Ischemia-Reperfusion by Inhibiting NF-κB Phosphorylation.

Astrocyte-mediated inflammation and oxidative stress elicit cerebral ischemia-reperfusion (IR) injury after stroke. Nuclear factor (NF)-κB activates astrocytes and generates pro-inflammatory factors. The purpose of the present study is to elucidate the effect of pterostilbene (PTE, a natural stilbene) on astrocytic inflammation and neuronal oxidative injury following cerebral ischemia-reperfusion injury. A middle cerebral artery occlusion-reperfusion (MCAO/R) mouse model and HT22/U251 co-culture model subjected to oxygen-glucose deprivation and re-introduction (OGD/R) were employed, with or without PTE treatment. The data showed that PTE delivery immediately after reperfusion, at 1 h after occlusion, decreased infarct volume, brain edema, and neuronal apoptosis and improved long-term neurological function. PTE decreased oxidation (i.e., production of reactive oxygen species, malondialdehyde) and inflammatory mediators (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) and increased anti-oxidative enzyme activities (i.e., of superoxide dismutase, glutathione peroxidase), by inhibiting phosphorylation and nuclear translocation of NF-κB. In conclusion, PTE attenuated astrocyte-mediated inflammation and oxidative injury following IR via NF-κB inhibition. Overall, PTE is a promising neuroprotective agent.

Adiponectin Attenuates Oxygen-Glucose Deprivation-Induced Mitochondrial Oxidative Injury and Apoptosis in Hippocampal HT22 Cells via the JAK2/STAT3 Pathway.

Ischemic stroke is among the leading causes of morbidity and mortality worldwide. Improving the tolerance of neurons to ischemia and reperfusion injury could be a feasible strategy against ischemia. Adiponectin (APN) is a major adipokine that regulates glucose and lipid metabolism and plays an important role in the protection of the cerebral nervous system. We aimed to investigate the effects of APN on oxygen and glucose deprivation (OGD)-induced neuronal injury in hippocampal neuronal HT22 cells. APN displayed neuroprotective effects against OGD, evidenced by increased cell viability and decreased lactate dehydrogenase release and apoptotic rate. Additionally, APN also maintained mitochondrial ultrastructure and transmembrane potential, attenuated reactive oxygen species and malondialdehyde, and increased superoxide dismutase and glutathione peroxidase activity. Moreover, APN promoted Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) phosphorylation, enhanced STAT3 nuclear translocation, increased the Bcl-2/Bax ratio, and decreased cleaved caspase-3. The aforementioned APN-induced effects were almost reversed by a JAK2 inhibitor, AG490. APN may attenuate OGD-induced hippocampal HT22 neuronal impairment by protecting cells against mitochondrial oxidative stress and apoptosis, mediated by JAK2/STAT3 signaling.

Remote limb ischemic postconditioning protects against cerebral ischemia-reperfusion injury by activating AMPK-dependent autophagy.

Remote limb ischemic postconditioning (RIPoC) is a promising adjunct treatment for cerebral ischemia-reperfusion (IR) injury. However, the underlying mechanisms have not been fully elucidated yet. The present study aims to investigate potential involvement and regulatory mechanisms of autophagy in RIPoC treatment against cerebral IR injury in mice. Mice were subjected to 2 h middle cerebral artery occlusion (MCAO) then treated with vehicle, 3-methyladenine (3-MA, an autophagy inhibitor), or compound C (an AMPK inhibitor) at the onset of reperfusion. RIPoC was carried out by 3 cycles of 10-min occlusion-reperfusion of bilateral femoral artery at the beginning of the reperfusion. Infarct volume, neurological score, and brain water content of the mice were assessed after 12 h reperfusion. Autophagy markers, cell apoptosis markers, and AMPK pathway activity were also evaluated. Our results indicated that RIPoC treatment reduced neurological deficits, brain water content, and infarct volume after IR. Meanwhile, RIPoC was proved to induce autophagy and activate AMPK pathway. Furthermore, the RIPoC-induced autophagy and neuroprotection were abolished by 3-MA and partially blocked by compound C. In conclusion, the present study suggests that RIPoC attenuates cerebral IR injury by activating AMPK-dependent autophagy.

Adiponectin attenuates NADPH oxidase-mediated oxidative stress and neuronal damage induced by cerebral ischemia-reperfusion injury.

Adiponectin (APN), which is a major adipokine that regulated glucose and lipid metabolism, plays an important role in the protection of the cerebral nervous system. It also has been suggested to have anti-inflammatory effects and ameliorate oxidative stress. Stroke is a universal cause of death and permanent disability. Ischemic stroke accounts for most cases of stroke, and is characterized by cerebral ischemia and neurological deficits. We aimed to investigate the effects of APN-peptide (APN-P) in neurons following ischemia reperfusion (I/R) in C57BL/6J mice, and to study the potential mechanisms underlying its effects. Mice were treated with vehicle, 2.5, 5, or 10mg/kg of APN-P and 2.5mg/kg of apocynin or vehicle before middle cerebral artery occlusion. Neurological deficits, infarct size, neuronal injury, and the ultrastructure of neurons were assessed. In addition, the levels of reactive oxygen species, superoxide dismutase, and malondialdehyde were measured. We assessed neuronal apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling. The levels of oxidative stress- and apoptosis-related proteins were measured by western blot. Our results suggest that APN-P at 5mg/kg markedly improved neurological deficits, decreased infarct size, and attenuated neuronal injury after cerebral I/R injury. APN-P treatment also decreased neuronal apoptosis. Additionally, the increased levels of oxidative stress- and apoptosis-related proteins levels following I/R were alleviated by APN-P treatment. In conclusion, APN-P inhibits neuronal apoptosis and alleviates oxidative stress in neurons subjected to I/R, suggesting that it may be beneficial for the treatment of brain damage following ischemic stroke.

Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein.

Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro. SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

Pterostilbene attenuates high glucose-induced oxidative injury in hippocampal neuronal cells by activating nuclear factor erythroid 2-related factor 2.

In the present study, neuroblastoma (SH-SY5Y) cells were used to investigate the mechanisms mediating the potential protective effects of pterostilbene (PTE) against mitochondrial metabolic impairment and oxidative stress induced by hyperglycemia for mimicking the diabetic encephalopathy. High glucose medium (100mM) decreased cellular viability after 24h incubation which was evidenced by: (i) reduced mitochondrial complex I and III activities; (ii) reduced mitochondrial cytochrome C; (iii) increased reactive oxygen species (ROS) generation; (iv) decreased mitochondrial membrane potential (ΔΨm); and (v) increased lactate dehydrogenase (LDH) levels. PTE (2.5, 5, and 10µM for 24h) was nontoxic and induced the nuclear transition of Nrf2. Pretreatment of PTE (2.5, 5, and 10µM for 2h) displayed a dose-dependently neuroprotective effect, as indicated by significantly prevented high glucose-induced loss of cellular viability, generation of ROS, reduced mitochondrial complex I and III activities, reduced mitochondrial cytochrome C, decreased ΔΨm, and increased LDH levels. Moreover, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and glutathione S-transferase (GST) were elevated after PTE treatment. In addition, the elevation of nuclear Nrf2 by PTE treatment (10µM for 2h) was abolished by Nrf2 siRNA. Importantly, Nrf2 siRNA induced the opposite changes in mitochondrial complex I and III activities, mitochondrial cytochrome C, reactive species generation, ΔΨm, and LDH. Overall, the present findings were the first to show that pterostilbene attenuated high glucose-induced central nervous system injury in vitro through the activation of Nrf2 signaling, displaying protective effects against mitochondrial dysfunction-derived oxidative stress.

Melatonin Attenuates Early Brain Injury via the Melatonin Receptor/Sirt1/NF-κB Signaling Pathway Following Subarachnoid Hemorrhage in Mice.

Melatonin (Mel) has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of silent information regulator 1 (Sirt1), a histone deacetylase, has been suggested to be beneficial in SAH. However, the precise role of Sirt1 in Mel-mediated protection against EBI following SAH has not been elucidated. The present study aims to evaluate the role of melatonin receptor/Sirt1/nuclear factor-kappa B (NF-κB) in this process. The endovascular perforation SAH model was used in male C57BL/6J mice, and melatonin was administrated intraperitoneally (150 mg/kg). The mortality, SAH grade, neurological score, brain water content, and neuronal apoptosis were evaluated. The expression of Sirt1, acetylated-NF-κB (Ac-NF-κB), Bcl-2, and Bax were detected by western blot. To study the underlying mechanisms, melatonin receptor (MR) antagonist luzindole and Sirt1 small interfering RNA (siRNA) were administrated to different groups. The results suggest that Mel improved the neurological deficits and reduced the brain water content and neuronal apoptosis. In addition, Mel enhanced the expression of Sirt1 and Bcl-2 and decreased the expression of Ac-NF-κB and Bax. However, the protective effects of Mel were abolished by luzindole or Sirt1 siRNA. In conclusion, our results demonstrate that Mel attenuates EBI following SAH via the MR/Sirt1/NF-κB signaling pathway.

Pterostilbene Attenuates Early Brain Injury Following Subarachnoid Hemorrhage via Inhibition of the NLRP3 Inflammasome and Nox2-Related Oxidative Stress.

Pterostilbene (PTE), one of the polyphenols present in plants such as blueberries and grapes, has been suggested to have various effects, such as anti-oxidation, anti-apoptosis, and anti-cancer effects. Subarachnoid hemorrhage (SAH) is a severe neurological event known for its high morbidity and mortality. Recently, early brain injury (EBI) has been reported to play a significant role in the prognosis of patients with SAH. The present study aimed to investigate whether PTE could attenuate EBI after SAH was induced in C57BL/6 J mice. We also studied possible underlying mechanisms. After PTE treatment, the neurological score and brain water content of the mice were assessed. Oxidative stress and neuronal injury were also evaluated. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity was assessed using western blot analysis. Our results indicated that PTE treatment reduces the SAH grade, neurological score, and brain water content following SAH. PTE treatment also reduced NLRP3 inflammasome activation. PTE alleviated the oxidative stress following SAH as evidenced by the dihydroethidium staining, superoxide dismutase activity, malondialdehyde content, 3-nitrotyrosie and 8-hydroxy-2-deoxyguanosine levels, and gp91phox and 4-hydroxynonenal expression levels. Additionally, PTE treatment reduced neuronal apoptosis. In conclusion, our study suggests that PTE attenuates EBI following SAH possibly via the inhibition of NLRP3 inflammasome and Nox2-related oxidative stress.

Neuroprotective effects of pterostilbene against oxidative stress injury: Involvement of nuclear factor erythroid 2-related factor 2 pathway.

UNLABELLED: Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) regulates multiple anti-oxidative enzymes and has neuroprotective effects. Pterostilbene (PTE) is a natural anti-oxidant found in blueberries. Its non-metabolized form exhibits high distribution in the brain after dietary administration. In this study, we aimed to explore the potential of PTE in protecting murine hippocampal neuronal HT22 cells against glutamate-induced oxidative stress injury and possible underlying mechanisms. PTE was nontoxic and induced the nuclear translocation of Nrf2 when HT22 cell cultures were incubated with different concentrations of PTE. Further, PTE displayed a dose-dependent neuroprotective effect, as indicated by increased cell viability and a reduction in lactate dehydrogenase (LDH) release after glutamate treatment. Nrf2 siRNA treatment inhibited PTE-induced neuroprotective effects. Moreover, the levels of nuclear Nrf2 and downstream heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were elevated after PTE treatment. The PTE-induced elevation of nuclear Nrf2, as well as the increases in HO-1 and NQO1 levels, was abolished by Nrf2 siRNA. PTE treatment reduced the production of reactive oxygen species (ROS) and significantly enhanced the activities of the cellular anti-oxidants glutathione (GSH) and superoxide dismutase (SOD), indicating an attenuation of glutamate-induced oxidative stress. These changes in ROS and GSH and SOD activity were reversed by Nrf2 siRNA. Our results indicate that PTE treatment attenuates glutamate-induced oxidative stress injury in neuronal cells via the Nrf2 signaling pathway.

Bakuchiol attenuates myocardial ischemia reperfusion injury by maintaining mitochondrial function: the role of silent information regulator 1.

Ischemia reperfusion (IR) injury (IRI) is associated with poor prognoses in the settings of both cardiac surgery and ischemic heart disease and causes mitochondrial oxidative stress and cell death. Silent information regulator 1 (SIRT1), a member of the histone deacetylase family, exerts anti-IRI effects. Bakuchiol (BAK), an analog of resveratrol and a monoterpene phenol isolated from the seeds of Psoralea corylifolia (Leguminosae), protects tissues from injury. This study was designed to investigate the protective effects of BAK treatment in the setting of myocardial IRI and to elucidate the potential mechanism of those effects. Prior to induction of IR, isolated rat hearts or cardiomyocytes were exposed to BAK in either the absence or presence of the SIRT1 inhibitors Sirtinol and SIRT1 siRNA. BAK exerted cardioprotective effects, as evidenced by the improvements noted in cardiac function following ischemia, attenuated myocardial apoptosis, and changes in several biochemical parameters (including increases in the level of the anti-apoptotic protein Bcl2, decreases in the level of the pro-apoptotic protein Bax, and decreases in the cleaved Caspase 3 level). However, Sirtinol and SIRT1 siRNA each blocked BAK-induced cardioprotection by inhibiting SIRT1 signaling. Additionally, BAK significantly increased the activities of mitochondrial succinate dehydrogenase, cytochrome c oxidase, and mitochondrial superoxide dismutase and decreased the production of malondialdehyde. These findings suggested that BAK significantly attenuated IR-induced mitochondrial oxidative damage. However, Sirtinol and SIRT1 siRNA abolished BAK-dependent mitochondrial function. In summary, our results demonstrate that BAK treatment attenuates IRI by attenuating IR-induced mitochondrial oxidative damage via the activation of SIRT1/PGC-1α signaling.

HO-1 Signaling Activation by Pterostilbene Treatment Attenuates Mitochondrial Oxidative Damage Induced by Cerebral Ischemia Reperfusion Injury.

Ischemia reperfusion (IR) injury (IRI) is harmful to the cerebral system and causes mitochondrial oxidative stress. The antioxidant response element (ARE)-mediated antioxidant pathway plays an important role in maintaining the redox status of the brain. Heme oxygenase-1 (HO-1), combined with potent AREs in the promoter of HO-1, is a highly effective therapeutic target for protection against cerebral IRI. Pterostilbene (PTE), a natural dimethylated analog of resveratrol from blueberries, is a strong natural antioxidant. PTE has been shown to be beneficial for some nervous system diseases and may regulate HO-1 signaling. This study was designed to investigate the protective effects of PTE on cerebral IRI and to elucidate potential mechanisms underlying those effects. Mouse brains and cultured HT22 neuron cells were subjected to IRI. Prior to this procedure, the brains or cells were exposed to PTE in the absence or presence of the HO-1 inhibitor ZnPP or HO-1 small interfering RNA (siRNA). PTE conferred a cerebral protective effect, as shown by increased neurological scores, viable neurons and decreased brain edema as well as a decreased ion content and apoptotic ratio in vivo. PTE also increased the cell viability and decreased the lactate dehydrogenase (LDH) leakage and apoptotic ratio in vitro. ZnPP and HO-1 siRNA both blocked PTE-mediated cerebral protection by inhibiting HO-1 signaling and further inhibited two HO-1 signaling-related antioxidant molecules: NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs), which are induced by PTE. PTE also promoted a well-preserved mitochondrial membrane potential (MMP), mitochondria complex I activity, and mitochondria complex IV activity, increased the mitochondrial cytochrome c level, and decreased the cytosolic cytochrome c level. However, this PTE-elevated mitochondrial function was reversed by ZnPP or HO-1 siRNA treatment. In summary, our results demonstrate that PTE treatment attenuates cerebral IRI by reducing IR-induced mitochondrial oxidative damage through the activation of HO-1 signaling.

Adiponectin Protects against Glutamate-Induced Excitotoxicity via Activating SIRT1-Dependent PGC-1α Expression in HT22 Hippocampal Neurons.

Glutamate- (Glu-) induced excitotoxicity plays a critical role in stroke. This study aimed to investigate the effects of APN on Glu-induced injury in HT22 neurons. HT22 neurons were treated with Glu in the absence or the presence of an APN peptide. Cell viability was assessed using the MTT assay, while cell apoptosis was evaluated using TUNEL staining. Levels of LDH, MDA, SOD, and GSH-Px were detected using the respective kits, and ROS levels were detected using dichlorofluorescein diacetate. Western blot was used to detect the expression levels of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), cleaved caspase-3, Bax, and Bcl-2. In addition to the western blot, immunofluorescence was used to investigate the expression levels of SIRT1 and PGC-1α. Our results suggest that APN peptide increased cell viability, SOD, and GSH-Px levels and decreased LDH release, ROS and MDA levels, and cell apoptosis. APN peptide upregulated the expression of SIRT1, PGC-1α, and Bcl-2 and downregulated the expression of cleaved caspase-3 and Bax. Furthermore, the protective effects of the APN peptide were abolished by SIRT1 siRNA. Our findings suggest that APN peptide protects HT22 neurons against Glu-induced injury by inhibiting neuronal apoptosis and activating SIRT1-dependent PGC-1α signaling.