ABSTRACT
Isoquercitrin (ISO) is a traditional Chinese medicine extract, that has been found to possess potent neuroprotective properties. However, its precise role in the context of ischemic stroke (IS) remains to be fully elucidated. We constructed an in vitro model of IS induced by OGD/R in SH-SY5Y cells. Cell viability, the levels of oxidative stress-related indicators (8-OHDG, MDA, SOD, GSH, and GSH-Px), ROS, and mitochondrial membrane potential were measured by using detection kits. The protein levels of GPX1, SOD, Cytc were measured. The mRNA levels of mitochondrial biogenesis-related indicators (Cytb, CO1, ND2, ND5, and ND6), and mtDNA copy number were measured by RT-qPCR. ATP levels were measured. Molecular docking between ISO and NRF1, and Co-IP assay for NRF1 and TFAM interaction were performed. Expression of NRF1 and TFAM was evaluated. ISO treatment reversed the detrimental effects of OGD/R on cell viability, attenuated the elevation of oxidative stress markers, restored antioxidant levels, and alleviated the impairment of mitochondrial biogenesis in SH-SY5Y cells. ISO interacted with NRF1 and increased its expression along with TFAM. Silencing NRF1 reversed the protective effects of ISO, suggesting its involvement in mediating the neuroprotective effects of ISO. ISO alleviates oxidative stress and mitochondrial biogenesis damage induced by OGD/R in SH-SY5Y cells by upregulating the NRF1/TFAM pathway.
ABSTRACT
Hierarchical porous materials have attracted the attention of researchers due to their enormous specific surface area, maximized active site utilization efficiency, and unique structure and properties. In this context, metal-organic frameworks (MOFs) offer a unique mix of properties that make them particularly appealing as tunable porous substrates containing highly active sites. This review focuses on recent advances in the types and synthetic strategies of hierarchical porous MOFs and their derived materials. Furthermore, it highlights the relationship between the mass diffusion and transport of hierarchical porous structures and the pore size with examples and simulations, while identifying their potential and limitations. On this basis, how the synthesis conditions affect the structure and electrochemical properties of MOFs based hierarchical porous materials with different structures is discussed, highlighting the prospects and challenges for the synthetization, as well as further scientific research and practical applications. Finally, some insights into current research and future design ideas for advanced MOFs based hierarchical porous materials are presented.
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In this paper, we report on the discovery of a spinel compound, Co0.7Al2S4, which was synthesized at high-pressure. The systematic characterizations were carried out by structural, magnetic, and heat capacity measurements. The compound crystallizes into a cubic structure with the space group Fd3Ì m (no. 227) and the lattice constant a = 9.9580(1) Å. Magnetic susceptibility measurements suggest that Co0.7Al2S4 exhibits a spin glass ground state, freezing at Tf â¼ 7.2 K with a Weiss temperature Tθ â¼ -115.9 K, which is verified by ac magnetic susceptibility and heat capacity measurements. The frustration parameter f for Co0.7Al2S4 is calculated to be about 16.6, based on the formula f = | Tθ/Tf |, indicating that Co0.7Al2S4 is a high-frustration magnet. Specific heat data displays a T2 dependence below the freezing temperature, which is different from the linear dependence observed in a common spin glass system. Compared with the similar compound CoAl2O4, it is suggested that the vacancies in the Co sites should be responsible for the occurrence of the spin glass behavior of Co0.7Al2S4.
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BACKGROUND: This study aims to investigate whether isoquercitrin (Iso) exerts a neuroprotective role effect after cerebral ischemia-reperfusion (CIR) via up-regulating neuroglobin (Ngb) or reducing oxidative stress. METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) model was constructed using Sprague Dawley rats. First, we divided 40 mice into 5 groups (n = 8): sham, MCAO/R, Low-dosed Iso (5 mg/kg Iso), Mid-dosed Iso (10 mg/kg Iso), and High-dosed Iso (20 mg/kg Iso). Then, 48 rats were separated into 6 groups (n = 8): sham, MCAO/R, Iso, artificial cerebrospinal fluid, Ngb antisense oligodeoxynucleotides (AS-ODNs), and AS-ODNs ± Iso. The effects of Iso on brain tissue injury and oxidative stress were evaluated using hematoxylin-eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunofluorescence, western blotting, and real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and reactive oxygen species (ROS) detection. RESULTS: The neurologic score, infarct volume, histopathology, apoptosis rate, and ROS production were reduced in Iso dose-dependent. The Ngb expression enhanced in Iso dose-dependent. The oxidative stress-related factors SOD, GSH, CAT, Nrf2, HO-1, and HIF-1α levels also increased in Iso dose-dependent, whereas the MDA levels decreased. However, related regulation of Iso on brain tissue damage and oxidative stress were reversed after low expression of Ngb. CONCLUSION: Isoquercitrin played a neuroprotective role after CIR through up-regulating of Ngb and anti-oxidative stress.
Subject(s)
Brain Ischemia , Neuroprotective Agents , Reperfusion Injury , Rats , Mice , Animals , Rats, Sprague-Dawley , Neuroglobin/metabolism , Neuroglobin/pharmacology , Reactive Oxygen Species/metabolism , Reperfusion Injury/pathology , Brain Ischemia/prevention & control , Brain Ischemia/metabolism , Brain Ischemia/pathology , Oxidative Stress , Apoptosis , Reperfusion , Neuroprotective Agents/pharmacology , Neuroprotective Agents/metabolismABSTRACT
Isoquercitrin (ISO), an extract from Chinese traditional herb, exhibits potent neuroprotective roles in various disease models. However, its role in stroke is not fully understood. We established oxygen-glucose deprivation and reoxygenation (OGD/R) model in SH-SY5Y cell to study the roles of ISO in stroke. In the experiment, the changes of LDH level and cell viability (MTT) were analyzed. Apoptotic cells stained with anti-Annexin V antibody and propidium iodide (PI) were detected by flow cytometry. The mRNA and protein level of aldolase C (ALDOC) and nuclear factor erythroid 2-related factor (Nrf2) was determined by real-time quantitative polymerase chain reaction (qPCR) and Western blotting assay, respectively. The localization of Nrf2 was investigated by immunofluorescent assay. OGD/R reduced cell viability via inducing cell apoptosis, while ISO treatment reduced the level of apoptosis in OGD/R-treated SH-SY5Y cells ISO rescued OGD/R-treated cells. Mechanistically, the expression of Nrf2 and ALDOC was upregulated upon ISO treatment, while knockdown of ALDOC diminished the activation of autophagy and hence inhibited ISO-mediated protective activity. We further demonstrated that ISO enhanced ALDOC transcription by promoting nuclear translocation of Nrf2, and suppression of Nrf2 decreased the expression of ALDOC. Our data revealed that ISO exhibited neuroprotective activity in OGD/R model through Nrf2-ALDOC-autopagy axis and highlighted the potential application of ISO in stroke treatment.
Subject(s)
Fructose-Bisphosphate Aldolase/metabolism , Glucose/deficiency , Hypoxia/drug therapy , NF-E2-Related Factor 2/metabolism , Quercetin/analogs & derivatives , Apoptosis/drug effects , Blotting, Western , Cell Line, Tumor , Glucose/metabolism , Humans , Hypoxia/metabolism , L-Lactate Dehydrogenase/metabolism , Quercetin/pharmacology , Real-Time Polymerase Chain Reaction , Up-Regulation/drug effectsABSTRACT
Retinal diseases are a leading cause of visual loss and blindness, affecting a significant proportion of the population worldwide and having a detrimental impact on quality of life, with consequent economic burden. The retina is highly metabolically active, and a number of retinal diseases are associated with metabolic dysfunction. To better understand the pathogenesis underlying such retinopathies, new technology has been developed to elucidate the mechanism behind retinal diseases. Metabolomics is a relatively new "omics" technology, which has developed subsequent to genomics, transcriptomics, and proteomics. This new technology can provide qualitative and quantitative information about low-molecular-weight metabolites (M.W. < 1500 Da) in a given biological system, which shed light on the physiological or pathological state of a cell or tissue sample at a particular time point. In this article we provide an extensive review of the application of metabolomics to retinal diseases, with focus on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), glaucoma, and retinitis pigmentosa (RP).
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INTRODUCTION: Melatonin (Mel) and its receptors are promising for glycaemic control in patients with type 2 diabetes mellitus (T2DM) and its complications, but there is significant heterogeneity among studies. This study aims to investigate the effects of Mel receptor agonist Neu-P11 on glucose metabolism, immunity, and islet function in T2DM rats. MATERIAL AND METHODS: In this study, SD rats were treated with a high-fat diet and streptozotocin (STZ) to establish a T2DM model. The glucose oxidase method was used to measure blood glucose levels. Glucose and insulin tolerance tests were used to assess glucose metabolism. Haematoxylin-eosin staining was used to observe pancreatic tissue injury. The apoptosis of isletß cells was analysed by TUNEL and insulin staining. Reactive oxygen species (ROS) levels and immune cell expression were analysed by flow cytometry. IF was used to analyse the activation of microglia. The immunoglobulins: IgA, IgG, IgM, tumour necrosis factorα (TNF-α), interleukins IL-10 and IL-1ß, interferonγ (IFN-γ), C-peptide, and insulin levels were determined by ELISA. The expression of CD11b, CD86, cleaved caspase 3, p21, and P16 proteins were analysed by western blot. RESULTS: The results showed that the blood glucose level increased, insulin resistance occurred, spleen coefficient and ROS levels increased, humoral immunity in peripheral blood decreased, and inflammation increased in the model group compared to the control group. After Mel and Neu-P11 treatment, the blood glucose level decreased significantly, insulin sensitivity improved, spleen coefficient and ROS levels decreased, humoral immunity in peripheral blood was enhanced, and inflammation improved in T2DM rats. Brain functional analysis of T2DM rats showed that microglia cells were activated, TNF-α and IL-ß levels were increased, and IL-10 levels were decreased. Mel and Neu-P11 treatment reversed these indexes. Functional analysis of islets in T2DM rats showed that islet structure inflammation was impaired, isletß cells were apoptotic, p21 and p16 protein expressions were increased, and blood C-peptide and insulin were decreased. Mel and Neu-P11 treatment restored the function of pancreatic b cells and improved the damage of pancreatic tissue. CONCLUSION: Melatonin and its receptor Neu-P11 can reduce the blood glucose level, enhance humoral and cellular immunity, inhibit microglia activation and inflammation, and repair isletß cell function, and this improve the characterization of T2DM-related diseases.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Indoles/therapeutic use , Melatonin/pharmacology , Pyrans/therapeutic use , Receptors, Melatonin/agonists , Streptozocin/adverse effects , Animals , Blood Glucose/metabolism , C-Peptide/blood , Diabetes Mellitus, Experimental , Diet, High-Fat , Disease Models, Animal , Glycemic Control , Insulin Resistance , Rats , Rats, Sprague-DawleyABSTRACT
INTRODUCTION: The study aimed to explore the effects of treatment with black bamboo rhizome extracts on learning and memory and determine the underlying mechanisms in rats with cerebral ischaemia-reperfusion injury. METHODS: Sprague-Dawley rats were randomly divided into the following four groups: control, middle cerebral artery occlusion (MCAO), low-dose drug, and high-dose drug groups. Rats underwent MCAO using a suture method before drug treatment. Then, neurological impairment was assessed using the Longa scoring method, and triphenyl tetrazolium chloride staining was used to analyse the cerebral infarction area. The Elliott formula was used to calculate water content in the brain tissue. A Morris water maze (MWM) was used to assess changes in learning and memory abilities, and Western blotting was used to detect cyclic adenosine phosphate response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of MCAO rats. RESULTS: After treatment with black bamboo rhizome extracts, the neurological dysfunction score was lower in the drug groups than in the MCAO group, and a significant difference was observed between the high-dose drug and MCAO groups (P<0.05). Additionally, the cerebral infarction area was significantly smaller in the drug groups than in the MCAO group (P<0.01), and the effect was more obvious in the high-dose drug group than in the low-dose drug group. There was also a significant difference in water content between the high-dose drug and MCAO groups, and cerebral oedema was significantly reduced in the high-dose drug group (P<0.05). In the MWM, the incubation period was significantly reduced, the number of platform crossings was significantly increased, and the search time was prolonged in the drug groups compared with those in the MCAO group (P<0.05). Moreover, the expression of BDNF and CREB was significantly increased in the drug groups compared to that in the MCAO group, and the increase was more obvious in the high-dose group than in the low-dose group (P<0.05). DISCUSSION: Black bamboo rhizome extracts significantly improved cognitive dysfunction, reduced cerebral oedema, decreased the cerebral infarction area, and improved the neurological function score and learning and memory abilities in rats with cerebral ischaemia-reperfusion injury.
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Ischaemic stroke is a common condition leading to human disability and death. Previous studies have shown that oleanolic acid (OA) ameliorates oxidative injury and cerebral ischaemic damage, and miR-186-5p is verified to be elevated in serum from ischaemic stroke patients. Herein, we investigated whether OA regulates miR-186-5p expression to control neuroglobin (Ngb) levels, thereby inhibiting neuronal pyroptosis in ischaemic stroke. Three concentrations of OA (0.5, 2, or 8 µM) were added to primary hippocampal neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R), a cell model of ischaemic stroke. We found that OA treatment markedly inhibited pyroptosis. qRT-PCR and western blot revealed that OA suppressed the expression of pyroptosis-associated genes. Furthermore, OA inhibited LDH and proinflammatory cytokine release. In addition, miR-186-5p was downregulated while Ngb was upregulated in OA-treated OGD/R neurons. MiR-186-5p knockdown repressed OGD/R-induced pyroptosis and suppressed LDH and inflammatory cytokine release. In addition, a dual luciferase reporter assay confirmed that miR-186-5p directly targeted Ngb. OA reduced miR-186-5p to regulate Ngb levels, thereby inhibiting pyroptosis in both OGD/R-treated neurons and MCAO mice. In conclusion, OA alleviates pyroptosis in vivo and in vitro by downregulating miR-186-5p and upregulating Ngb expression, which provides a novel theoretical basis illustrating that OA can be considered a drug for ischaemic stroke.
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Hierarchical nanostructured materials, which possess the porous structure of multiscale porosities on different pore diameters from micro-, meso- to macropores based on International Union of Pure and Applied Chemistry, are much desired to present the synergistic attractive advantages of each scale of hierarchical pores in the development of catalysis, adsorption, separation, energy, and biochemistry. The use of hierarchical nanostructured materials as oxygen reduction reaction (ORR) electrocatalysts is advanced to increase specific surface area for active sites dispersion and exposure as well as enhance reactants/products transfer. However, complex and costly templateincorporated methods and relatively uncontrollable template-free methods motive us to develop novel and efficient preparation methods. Herein, recent developments and synthesis strategies that have been made in the field of hierarchical nanostructured materials as well as their application for ORR electrocatalysts are reviewed.
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Three-dimensional (3D) porous carbon-based materials with tunable composition and microstructure are of great interest for the development of oxygen involved electrocatalytic reactions. Here, we report the synthesis of 3D porous carbon-based electrocatalyst by self-assembling Co-metal organic frameworks (MOF) building blocks on graphene via a layer-by-layer technique. Precise control of the structure and morphology is achieved by varying the MOF layer to tune the electrocatalytic properties. The as-produced electrocatalyst exhibits an excellent catalytic activity for the oxygen reduction reaction in 0.1â¯molâ¯L-1 KOH, showing a high onset potential of 0.963â¯V vs. reversible hydrogen electrode (RHE) and a low tafel slope of 54â¯mVâ¯dec-1, compared to Pt/C (0.934â¯V and 52â¯mVâ¯dec-1, respectively). Additionally, it shows a slightly lower potential vs. RHE (1.72â¯V) than RuO2 (1.75â¯V) at 10â¯mAâ¯cm-2 in an alkaline electrolyte. A rechargeable Zn-air battery based on the as-produced 3D porous catalyst demonstrates a high peak power density of 119â¯mWâ¯cm-2 at a cell voltage of 0.578â¯V while retaining an excellent stability over 250 charge-discharge cycles.
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Efficient, durable and inexpensive electrocatalysts that accelerate sluggish oxygen reduction reaction kinetics and achieve high-performance are highly desirable. Here we develop a strategy to fabricate a catalyst comprised of single iron atomic sites supported on a nitrogen, phosphorus and sulfur co-doped hollow carbon polyhedron from a metal-organic framework@polymer composite. The polymer-based coating facilitates the construction of a hollow structure via the Kirkendall effect and electronic modulation of an active metal center by long-range interaction with sulfur and phosphorus. Benefiting from structure functionalities and electronic control of a single-atom iron active center, the catalyst shows a remarkable performance with enhanced kinetics and activity for oxygen reduction in both alkaline and acid media. Moreover, the catalyst shows promise for substitution of expensive platinum to drive the cathodic oxygen reduction reaction in zinc-air batteries and hydrogen-air fuel cells.
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Highly efficient noble metal-free bifunctional catalysts for expediting the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in metal-air batteries or fuel cells are still challenging and imperative. In this work, we report a facile and scalable method for syntheizing three-dimensional (3D) macroporous Co-embedded N-doped carbon interconnecting with in situ growth carbon nanotubes (CNTs). The as-synthesized material exhibits great electrocatalytic performance for ORR with an onset potential of 0.901 V vs RHE as well as a high limited current density of 4.83 mA/cm2 in an alkaline electrolyte under a rotation speed of 1600 rpm at 5 mV/s. Furthermore, this 3D porous carbon also shows good electrocatalytic performance for OER in an alkaline electrolyte. This high electrocatalytic performance is mainly attributed to its large specific surface area and highly conductive CNTs and the synergistic effect between Co-active species and the carbon framework. The result of a two-electrode Zn-air battery based on this carbon material achieves a peak density of 163 mW/cm2 at a voltage of 0.63 V, indicating the great potential of the catalyst for battery application.
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A new class of dual metal and N doped carbon catalysts with well-defined porous structure derived from metal-organic frameworks (MOFs) has been developed as a high-performance electrocatalyst for oxygen reduction reaction (ORR). Furthermore, the microbial fuel cell (MFC) device based on the as-prepared Ni/Co and N codoped carbon as air cathode catalyst achieves a maximum power density of 4335.6 mW m-2 and excellent durability.
Subject(s)
Adipocytes/drug effects , Adipocytes/metabolism , Indoles/pharmacology , Insulin Resistance/physiology , Pyrans/pharmacology , Tryptamines/pharmacology , 3T3-L1 Cells , Animals , Glycogen Synthase Kinase 3 beta/metabolism , Insulin/metabolism , Insulin Receptor Substrate Proteins/metabolism , Melatonin/metabolism , Mice , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/drug effectsABSTRACT
Robust and efficient catalysts for the oxygen reduction reaction (ORR) are required for the development of various energy storage and conversion devices. In this study, a durable and high-performance Fe3 C@graphene ORR catalyst has been developed by the carbonization of urea- and agar-modified Fe2 O3 nanorods. The influence of the carbonization temperature and annealing time on the activity and stability of the resulting Fe/C catalyst was studied in detail. The Fe/C catalyst synthesized at a temperature of 700 °C (holding time: 60â min) showed better ORR activity and improved stability compared to a commercial Pt/C catalyst. The improved ORR catalytic activity of the catalyst is due to its high Fe3 C content and its good durability results from the unique microstructure of the Fe3 C@graphene hybrid.