THSG alleviates cerebral ischemia/reperfusion injury via the GluN2B-CaMKII-ERK1/2 pathway.

BACKGROUND: The potential therapeutic targeting of PINK1-PARK2-mediated mitophagy against cerebral ischemia/reperfusion (CI/R) injury involves the pathophysiological processes of neurovascular unit (NVU) and is closely associated with N-methyl-D-aspartate receptors (NMDARs) commonly expressed in NVU. 2,3,5,4'-Tetrahydroxy-stilbene-2-O-ß-D-glucoside (THSG), a compound derived from the traditional Chinese medicine Polygonum multiflorum Thunb., has demonstrated notable neuroprotective properties against CI/R injury. However, it remains unclear whether THSG exerts its protective effects through GluN2B related PINK1/ PARK2 pathway. PURPOSE: This study aims to explore the pharmacological effects of THSG on alleviating CI/R injury via the GluN2B-CaMKII-ERK1/2 pathway. METHODS: THSG neuroprotection against CI/R injury was studied in transient middle cerebral artery occlusion/reversion (tMCAO/R) model rats and in oxygen and glucose deprivation/ reoxygenation (OGD/R) induced neurons. PINK1-PARK2-mediated mitophagy involvement in the protective effect of THSG was investigated in tMCAO/R rats and OGD/R-induced neurons via THSG and 3-methyladenine (3-MA) treatment. Furthermore, the beneficial role of GluN2B in reperfusion and its contribution to the THSG effect via CaMKII-ERK1/2 and PINK1-PARK2-mediated mitophagy was explored using the GluN2B-selective antagonist Ro 25-6981 both in vivo and in vitro. Finally, the interaction between THSG and GluN2B was evaluated using molecular docking. RESULTS: THSG significantly reduced infarct volume, neurological deficits, penumbral neuron structure, and functional damage, upregulated the inhibitory apoptotic marker Bcl-2, and suppressed the increase of pro-apoptotic proteins including cleaved caspase-3 and Bax in tMCAO/R rats. THSG (1 µM) markedly improved the neuronal survival under OGD/R conditions. Furthermore, THSG promoted PINK1 and PARK2 expression and increased mitophagosome numbers and LC3-II-LC3-I ratio both in vivo and in vitro. The effects of THSG were considerably abrogated by the mitophagy inhibitor 3-MA in OGD/R-induced neurons. Inhibiting GluN2B profoundly decreased mitophagosome numbers and OGD/R-induced neuronal viability. Specifically, inhibiting GluN2B abolished the protection of THSG against CI/R injury and reversed the upregulation of PINK1-PARK2-mediated mitophagy by THSG. Inhibiting GluN2B eliminated THSG upregulation of ERK1/2 and CaMKII phosphorylation. The molecular docking analysis results demonstrated that THSG bound to GluN2B (binding energy: -5.2 ± 0.11 kcal/mol). CONCLUSIONS: This study validates the premise that THSG alleviates CI/R injury by promoting GluN2B expression, activating CaMKII and ERK1/2, and subsequently enhancing PINK1-PARK2-mediated mitophagy. This work enlightens the potential of THSG as a promising candidate for novel therapeutic strategies for treating ischemic stroke.

Synthesis of salicylaldehyde tailored PAMAM dendrimers/chitosan for adsorption of aqueous Hg(II): Performance and mechanism.

Water pollution caused by Hg(II) exerts hazardous effect to environmental safety and human health. Herein, a family of salicylaldehyde tailored poly(amidoamine) (PAMAM) dendrimers/chitosan composites (G0-S/CTS, G1-S/CTS, and G2-S/CTS) were prepared and used for the removal of Hg(II) from water solution. The adsorption performance of the as-prepared composites for Hg(II) was thoroughly demonstrated by determining various influencing factors. G0-S/CTS, G1-S/CTS and G2-S/CTS exhibited competitive adsorption capacity and good adsorption selective property for Hg(II). The maximum adsorption capacity of G0-S/CTS, G1-S/CTS and G2-S/CTS for Hg(II) were 1.86, 2.18 and 4.47 mmol‧g-1, respectively. The adsorption for Hg(II) could be enhanced by raising initial Hg(II) concentration and temperature. The adsorption process was dominated by film diffusion processes with monolayer adsorption behavior. The functional groups of NH2, CONH, CN, OH, CO and CN were mainly responsible for the adsorption of Hg(II). G0-S/CTS, G1-S/CTS and G2-S/CTS displayed good regeneration property and the regenerate rate maintained 95.00 % after five adsorption-desorption cycles. The as-prepared adsorbents could be potentially used for the efficient removal of Hg(II) from aqueous solution.

Synthesis of hyperbranched polyamine dendrimer/chitosan/silica composite for efficient adsorption of Hg(II).

The pollution of water system with Hg(II) exerts hazardous effect to ecosystem and public health. Adsorption is considered to be a promising strategy to remove Hg(II) from aqueous solution. Herein, hyperbranched polyamine dendrimer/chitosan/silica composite (SiO2-FP) was synthesized for the adsorption of aqueous Hg(II). The adsorption performance of SiO2-FP was comprehensively determined by considering various influencing factors. SiO2-FP displays good adsorption performance for Hg(II) with the adsorption capacity of 0.79 mmol·g-1, which is higher than the corresponding chitosan functionalized silica (SiO2-CTS) by 46.30 %. The optimal solution pH for the adsorption of Hg(II) is 6. Adsorption kinetic indicates the adsorption for Hg(II) can reach equilibrium at 250 min. Adsorption kinetic process can be well fitted by pseudo-second-order (PSO). Adsorption isotherm reveals the adsorption for Hg(II) can be promoted by increasing initial Hg(II) concentration and adsorption temperature. The adsorption isotherm indicates the adsorption process can be described by Langmuir model and the adsorption is a spontaneous, endothermic and entropy-increased process. SiO2-FP displays excellent adsorption selectivity and can 100 % adsorb Hg(II) with the coexisting of Ni(II), Zn(II), Pb(II), Mn(II), and Co(II). Adsorption mechanism demonstrates -NH-, -NH2, CN, CONH, -OH, and CO participated in the adsorption. SiO2-FP exhibits good regeneration property and the regeneration rate can maintain approximately 90 % after five adsorption-desorption cycles.

Feasible synthesis of bifunctional polysilsesquioxane microspheres for robust adsorption of Hg(II) and Ag(I): Behavior and mechanism.

The pollution of Hg(II) and Ag(I) to water system exerts hazardous effect to aquatic ecosystem and public security. Simple strategy for constructing adsorbents to efficient remove them is greatly desired. Thus, a series of thiol and amino groups containing bifunctional polysilsesquioxanes (ASPSS) microspheres with adjustable porous structure and functional group content were synthesized by one-step feasible sol-gel process. The adsorption behavior and mechanism of ASPSS microspheres toward Hg(II) and Ag(I) was thoroughly determined. The maximum adsorption capacity of ASPSS for Hg(II) and Ag(I) are 4.32 and 3.86 mmol·g-1 under 25 â„ƒ. The as-prepared ASPSS microspheres can 100% selectively capture Hg(II) with the coexisting of Mn(II), Co(II), Pb(II), Cd(II), Cu(II), Fe(III). And they can 100% adsorb Ag(I) with the presence of Cd(II), Pb(II), Co(II), Ni(II), and Zn(II). Moreover, the ASPSS microspheres exhibit good removal efficiency for Hg(II) and Ag(I) from simulated industrial wastewater with the coexistence of multiple pollutants. Adsorption mechanism suggests the adsorption for Hg(II) and Ag(I) is the synergistic coordination effect of amino and thiol groups. The excellent adsorption selectivity for Hg(II) and Ag(I) is attributed to the super binding ability of these functional group. ASPSS microspheres also exhibit good regeneration ability and could be reused for removing Hg (II) and Ag(I) from aqueous solution with practical value.