The mechanism of mitochondrial autophagy regulating Clathrin-mediated endocytosis in epilepsy.

OBJECTIVE: The objective of this study is to determine whether inhibition of mitophagy affects seizures through Clathrin-mediated endocytosis (CME). METHODS: Pentylenetetrazol (PTZ) was intraperitoneally injected daily to establish a chronic PTZ-kindled seizure. The Western blot (WB) was used to compare the differences in Parkin protein expression between the epilepsy group and the control group. Immunofluorescence was used to detect the expression of MitoTracker and LysoTracker. Transferrin-Alexa488 (Tf-A488) was injected into the hippocampus of mice. We evaluated the effect of 3-methyladenine (3-MA) on epilepsy behavior through observation in PTZ-kindled models. RESULTS: The methylated derivative of adenine, known as 3-MA, has been extensively utilized in the field of autophagy research. The transferrin protein is internalized from the extracellular environment into the intracellular space via the CME pathway. Tf-A488 uses a fluorescent marker to track CME. Western blot showed that the expression of Parkin was significantly increased in the PTZ-kindled model (p < 0.05), while 3-MA could reduce the expression (p < 0.05). The fluorescence uptake of MitoTracker and LysoTracker was increased in the primary cultured neurons induced by magnesium-free extracellular fluid (p < 0.05); the fluorescence uptake of Tf-A488 was significantly decreased in the 3-MA group compared with the control group (p < 0.05). Following hippocampal injection of Tf-A488, both the epilepsy group and the 3-MA group exhibited decreased fluorescence uptake, with a more pronounced effect observed in the 3-MA group. Inhibition of mitophagy by 3-MA from day 3 to day 9 progressively exacerbated seizure severity and shortened latency. SIGNIFICANCE: It is speculated that the aggravation of seizures by 3-MA may be related to the failure to remove damaged mitochondria in time and effectively after inhibiting mitochondrial autophagy, affecting the vesicle endocytosis function of CME and increasing the susceptibility to epilepsy. SUMMARY: Abnormal mitophagy was observed in a chronic pentylenetetrazol-induced seizure model and a Mg2+-free-induced spontaneous recurrent epileptiform discharge model. A fluorescent transferrin marker was utilized to track clathrin-mediated endocytosis. Using an autophagy inhibitor (3-methyladenine) on primary cultured neurons, we discovered that inhibition of autophagy led to a reduction in fluorescent transferrin uptake, while impairing clathrin-mediated endocytosis function mediated by mitophagy. Finally, we examined the effects of 3-methyladenine in an animal model of seizures showing that it exacerbated seizure severity. Ultimately, this study provides insights into potential mechanisms through which mitophagy regulates clathrin-mediated endocytosis in epilepsy.

Physical Characteristics of Coal Reservoirs and CBM Favorable Area Prediction in the Huaibei Coalfield, Northern China.

To quantitatively characterize middle-high-ranked coal reservoirs, the physical characteristics of seven coal samples from the Huaibei Coalfield in northern China were investigated in detail based on experiments including proximate analysis, coal petrology, low-temperature nitrogen adsorption (LTNA), mercury intrusion porosimetry (MIP), nuclear magnetic resonance (NMR), and methane isothermal adsorption. The results show that coal maceral in the Huaibei Coalfield is dominated by vitrinite, with a large change in the maximum vitrinite reflectance ranging from 0.7 to 2.5%. The various coal metamorphisms can be attributed to the combined influence of magmatic activities of the Tanlu and Taihang Mountains during the Yanshanian. The coal quality can be characterized by medium-high ash yield, low to very low sulfur content, low phosphorus, and medium-high calorific value. From low-ranked coals to medium-ranked coals, the volume of adsorption and seepage pores decreases but the fracture volume increases due to the stronger dehydration and coal matrix shrinkages. From medium-ranked coals to high-ranked coals, adsorption pores have a significant advantage, suggesting a stronger CH4 adsorption capacity. There is a positive correlation among the fixed carbon content, coal rank, and Langmuir volume, which can be attributed to the transformation of coal chemical composition and structure by coal metamorphism. The deep Xiaoxi in the Suixiao coal mining area, deep Nanping, deep Taoyuan-Qinan, deep Pengqiao, northern Zhuxianzhuang in the Suxian coal mining area, deep Renlou-Zhaoji, and Xutuan deep in the Linhuan mining area are predicted to be favorable areas for CBM exploration in the Huaibei Coalfield.

Investigation on Adsorption Pore and Fractal Analyses of Low-Rank Coals in the Northern Qaidam Basin.

The northern Qaidam Basin has abundant coal and coalbed methane (CBM) resources, and quantitative evaluation of adsorption pore characteristics has great significance for optimum selection of CBM-favorable areas. Based on vitrinite reflectance, coal maceral, proximate analysis, low-temperature N2 adsorption, and methane isothermal adsorption experiments, the heterogeneities of adsorption pores (pore diameter <100 nm) were quantitatively characterized, and relationships between fractal dimensions and physical parameters of low-ranked coal reservoirs were revealed. The results show that the micropore volume percentage ranges between 33.70 and 86.44% with an average of 64.94%. Based on N2 adsorption/desorption curves and pore diameter distribution characteristics, the adsorption pore structures of low-ranked coals were divided into 3 types. According to the FHH model, fractal dimension D1 (relative pressure between 0 and 0.5) and D2 (relative pressure between 0.5 and 1) were calculated. Fractal dimension D1, representing adsorption pore surface area, ranges from 2.001 to 2.345, with lower values. Fractal dimension D2 (adsorption pore structure) is from 2.641 to 2.917, with relatively high values, which has a decreasing tendency from west to east in the study area. There are positive relationships between fractal dimension D1 and Langmuir volume and specific surface area, whereas negative correlations are found between fractal dimension D2 and Langmuir pressure, ash yield, moisture content, volatile content, and average pore diameter. Combined with the related data for middle- and high-rank coals, the characteristics of pore surface and methane adsorption capacity can be analyzed based on the variation of vitrinite reflectance. Furthermore, the complexity of pore structure can also be predicted according to the averaged pore size and micropore content to some degree.

A High-Rate and Long-Life Aqueous Rechargeable Mg-Ion Battery Based on an Organic Anode Integrating Diimide and Triazine.

Aqueous Mg-ion batteries (MIBs) lack reliable anode materials. This study concerns the design and synthesis of a new anode material - a π-conjugate of 3D-poly(3,4,9,10-perylenetracarboxylic diimide-1,3,5-triazine-2,4,6-triamine) [3D-P(PDI-T)] - for aqueous MIBs. The increased aromatic structure inhibits solubility in aqueous electrolytes, enhancing its structural stability. The 3D-P(PDI-T) anode exhibits several notable characteristics, including an extremely high rate capacity of 358 mAh g-1 at 0.05 A g-1 , A 3D-P(PDI-T)‖Mg2 MnO4 full cell exhibits a reversible capacity of 148 mAh g-1 and a long cycle life of 5000 cycles at 0.5 A g-1 . The charge storage mechanism reveals a synergistic interaction of Mg2+ and H+ cations with C-N/C=O groups. The assembled 3D-P(PDI-T)‖Mg2 MnO4 full cell exhibits a capacity retention of around 95 % after 5000 cycles at 0.5 A g-1 . This 3D-P(PDI-T) anode sustained its framework structure during the charge-discharge cycling of Mg-ion batteries. The reported results provide a strong basis for a cutting-edge molecular engineering technique to afford improved organic materials that facilitate efficient charge-storage behavior of aqueous Mg-ion batteries.

In situ growth of Prussian blue analogue-derived Fe-doped NiS on Ni(OH)2 for efficient hydrogen evolution reaction.

The energy industry is placing more and more emphasis on the need for effective and affordable electrocatalysts for hydrogen evolution reactions (HER). In this work, an iron-doped NiS/Ni(OH)2/CC composite material was synthesized by simple hydrothermal sulfurization processes of bimetallic Prussian blue analogue (PBAs) precursors grown in situ on three-dimensional (3D) Ni(OH)2 nanosheets. The overpotential can be 103 mV to attain current densities of 10 mA cm-2. The excellent catalytic activity of Fe-NiS/Ni(OH)2/CC is because of the unique 3D structure and the uniform doping of iron caused by the in situ growth of PBA, as well as the high conductivity of the self-supported electrode carbon cloth.

Design of Ni(OH)2 Nanosheets@NiMoO4 Nanofibers' Hierarchical Structure for Asymmetric Supercapacitors.

Transition-metal-based materials show great promise for energy conversion and storage due to their excellent chemical properties, low cost, and excellent natural properties. In this paper, through simple strategies such as classical electrospinning, air calcination, and the one-step hydrothermal method, a large area of Ni(OH)2 nanosheets were grown on NiMoO4 nanofibers, forming NiMoO4@Ni(OH)2 nanofibers. The one-dimensional nanostructure was distributed with loose nanosheets, and this beneficial morphology made charge-transfer and diffusion more rapid, so the newly developed material showed good capacitance and conductivity. Under the most suitable experimental conditions, the optimal electrode exhibited the highest specific capacitance (1293 F/g at 1 A/g) and considerable rate capability (56.8% at 10 A/g) under typical test conditions. Most interestingly, the corresponding asymmetrical capacitors exhibited excellent electrochemical cycle stability, maintaining 77% of the original capacitance. NiMoO4@Ni(OH)2 nanofibers were verified to be simple to prepare and to have good performances as energy-storage devices within this experiment.

Growth dynamics and tissue localization of a Coxiella-like endosymbiont in the tick Haemaphysalis longicornis.

A Coxiella-like endosymbiont (Coxiella-LE hereinafter) stably infects and influences Haemaphysalis longicornis development, indicating a mutualistic relationship of Coxiella-LE and ticks. To further elucidate the patterns of growth dynamics and tissue localization of Coxiella-LE in H. longicornis, 16S rRNA high-throughput sequencing, quantitative PCR (qPCR), and fluorescence in situ hybridization (FISH) were used in this study. The density of Coxiella-LE varied among different tick life stages, and fed female ticks had the highest density, followed by unfed female and unfed larval ticks. In the four organs that were dissected from fed female ticks, the ovary carried the highest density of Coxiella-LE, which was significantly different from salivary glands, midgut and Malpighian tubules. The high abundance of Coxiella-LE in fed female ticks and in the ovaries of fed female ticks in the bacterial microbiota analyses further confirmed that Coxiella-LE rapidly proliferates in the ovary after blood feeding. The ovaries continued to develop after engorgement and oviposition began on day 5, with a significant decrease in the density of Coxiella-LE in the ovaries occurring on day 7. FISH results indicated that Coxiella-LE is mainly colonized in the cytoplasm of the oocyte and proliferates with oogenesis. Coxiella-LE was expelled from the body with the mature oocyte, ensuring its vertical transmission. In the Malpighian tubules at different days after engorgement, the white flocculent materials were increasing, and the density of Coxiella-LE raised significantly on day 7. Unlike the localization pattern in the ovary, Coxiella-LE was initially distributed in a mass and continually increased during the development of Malpighian tubules until it filled the Malpighian tubules. These findings provide new insights on the growth dynamics and tissue localization of Coxiella-LE in ticks and are useful for further investigation on the interactions of symbiont and ticks .

Manipulation of microstructure of MXene aerogel via metal ions-initiated gelation for electromagnetic wave absorption.

MXene aerogels with 3D network structure have gained much attention as lightweight electromagnetic wave (EMW) absorbers. It is still challenging to construct MXene aerogel monoliths with excellent EMW absorption capability in a simple way. Herein, the assembly of MXene aerogels was realized by gelation initiated by various metal ions in an aqueous dispersion, where metal ions link the MXene sheets together by bonding with OH groups on the MXene surface. It is found that metal ions have a great influence on the assembly microstructures of MXene aerogels, which are closely related with the complex permittivity of MXene aerogel absorbers. Versus divalent metal ions, MXene aerogels assembled with trivalent metal ions possess relative lower complex permittivity and deliver superior EMW absorption performance. Typically, a broadest EAB of 7.12 GHz can be achieved by MX-Fe3+, ascribing to its good impedance matching and multiple dissipation modes. Overall, this work provides an effective way to fabricate MXene-based aerogels to satisfy the lightweight requirement of future high-performance EMW absorption materials.

Bacterial microbiota analysis demonstrates that ticks can acquire bacteria from habitat and host blood meal.

Ticks have a diversity of habitats and host blood meals. Whether and how factors such as tick developmental stages, habitats and host blood meals affect tick bacterial microbiota is poorly elucidated. In the present study, we investigated the bacterial microbiotas of the hard tick Haemaphysalis longicornis, their blood meals and habitats using 16S rRNA gene high-throughput sequencing. The bacterial richness and diversity in ticks varied depending on the tick developmental stage and feeding status. Results showed that fed ticks present a higher bacterial richness suggesting that ticks may acquire bacteria from blood meals. The significant overlap of the bacteria of fed ticks and the host blood also supports this possibility. Another possibility is that blood meals can stimulate the proliferation of certain bacteria. However, most shared bacteria cannot transmit throughout the tick life cycle, as they were not present in tick eggs. The most shared bacteria between ticks and habitats are members of the genera Staphylococcus, Pseudomonas, Enterobacter, Acinetobacter and Stenotrophomonas, suggesting that these environmental bacteria cannot be completely washed away and can be acquired by ticks. The predominant proportion of Coxiella in fed females further demonstrates that this genus is involved in H. longicornis physiology, such as feeding activity and nutritional provision. These findings further reveal that the bacterial composition of ticks is influenced by a variety of factors and will help in subsequent studies of the function of these bacteria.

In situ integration of cobalt diselenide nanoparticles on CNTs realizing durable hydrogen evolution.

Cobalt diselenide (CoSe2) is considered to be a promising economical and efficient electrocatalyst for the hydrogen evolution reaction (HER). Here carbon nanotubes (CNTs) were employed as a conductive skeleton to optimize the electrocatalytic performance of CoSe2 through a simple one-step hydrothermal method. Beyond the expected, the introduction of CNTs not only accelerates electron transportation and ion diffusion, but also improves the reaction kinetics for HER by forming a CoSe2/CNT heterointerface. Consequently, the CoSe2/CNTs composite exhibits an optimal overpotential of 153 mV with a weight ratio of 10 : 1, and sustains a long period of 48 hours with an negligible overpotential deterioration. In addition, a Faraday efficiency of 97.67% is achieved with a H2/O2 molar ratio of 2 : 1. Therefore, these results open up further opportunities for yielding efficient and durable hydrogen evolving electrocatalysts from low-cost transition metal compounds.

ZIF-8-derived carbon-modified g-C3N4 heterostructure with enhanced photocatalytic activity for dye degradation and hydrogen production.

In this study, a metal-organic framework (ZIF-8)-derived nitrogen-doped carbon (C-ZIF)-modified g-C3N4 composite was directly prepared by pyrolysis. C-ZIF@g-C3N4 composites with different loadings were prepared by changing the precursor content. The charge transfer process that occurs at the interface of the ZIF-8-derived nitrogen-doped carbon/g-C3N4 heterostructures strongly hinders the recombination of photoinduced electron-hole pairs, thereby effectively enhancing the photocatalytic activity of C-ZIF@g-C3N4. Meanwhile, the unique hierarchical inorganic/organic heterostructure provides an abundance of active sites for photocatalytic reactions. Upon visible-light irradiation, C-ZIF@g-C3N4 with an optimal ratio of g-C3N4 to C-ZIF components exhibits both enhanced photocatalytic activity and excellent separability during the degradation of dye and hydrogen evolution compared to unmodified g-C3N4.

Size-controllable porous flower-like NiCo2O4 fabricated via sodium tartrate assisted hydrothermal synthesis for lightweight electromagnetic absorber.

Although the performance of NiCo2O4-based absorbers with multiple components has made great progress, the property of pure NiCo2O4 is still far from the requirements of high-performance electromagnetic wave absorbers. It is recognized that morphology control is an effective strategy to improve electromagnetic absorbing capacity of absorbers. Herein, this work reported the fabrication of porous flower-like pure NiCo2O4 via simple hydrothermal reaction with the assistant of sodium tartarate in where tartaric acid served as a structure-directing agent. It was demonstrated that size distribution and electromagnetic absorbing capacity of the obtained NiCo2O4 could be modulated easily by controlling addition of sodium tartrate. It was verified that dipole polarization originated from lattice defect and oxygen vacancy as well as interfacial polarization ascribing to adjacent and interconnected flakes are responsible for the excellent electromagnetic absorbing performance. The obtained porous flower-like NiCo2O4 exhibited broad absorption bandwidth at thin thickness as well as proper dissipation ability. This work offers a new strategy to fabricate size-controllable porous flower-like NiCo2O4 electromagnetic absorber. It is believed the obtained NiCo2O4 will be a promising candidate as a lightweight electromagnetic absorbing material.

Controllable adjustment of cavity of core-shelled Co3O4@NiCo2O4 composites via facile etching and deposition for electromagnetic wave absorption.

Core-shell structural cobalt- and nickel-based metal oxides with different compositions have rarely been reported as electromagnetic wave absorption materials. Herein, core-shell structural Co3O4@NiCo2O4 composites have been successfully fabricated via simple etching and deposition reaction of Co-based metal-organic framework with subsequent calcination in air. According to morphological evolution, it is verified that the cavity volume between Co3O4 core and NiCo2O4 shell could be modulated effectively by simply controlling proton etching and deposition reaction. The electromagnetic wave absorption properties of the Co3O4@NiCo2O4 composites were investigate. It was demonstrated that multiple interfacial polarization of heterogeneous interfaces involving cavities, such as Co3O4/Void, Void/NiCo2O4 and Co3O4/NiCo2O4 have made great contribution to the excellent electromagnetic wave absorption performance. Co3O4@NiCo2O4 with optimized microstructure exhibited RL value as strong as -34.42 dB with a broad effective absorption bandwidth up to 4.88 GHz at a layer thickness of 2.6 mm. It is believed that core-shell structural cobalt- and nickel-based metal oxides will become an excellent candidate for high-performance electromagnetic wave absorber.

Effects of Simulated Weightlessness on Metabolizing Enzymes and Pharmacokinetics of Folic Acid in SD Rats.

Folic acid (FA) affect human physiology and drug metabolism. Up to now, the effect of microgravity on the pharmacokinetics of FA remains unclear. The pharmacokinetics of FA in Sprague-Dawley (SD) rats are laying a foundation for safe medicine administration of astronauts. Proteins expression of such FA metabolic enzymes as Methyltetrahydrofolate reductase (MTHFR), Cystathionine beta synthase (CBS) and Methionine synthase (MS) in a variety of organs was analyzed with Western-Blot, and mRNA expression was detected by RT-PCR. The plasma concentration-time profile of FA in normal or tail-suspended SD rats was acquired by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after oral administration of FA. Area under curve (AUC) and Cmax of FA in SD rats decreased significantly with extending period of tail-suspension. In terms of expressed level of metabolic enzymes over four suspension terms, as well as the level of the corresponding mRNAs, the following regularities were found: an obvious sharp decline of MTHFR tissue in kidney, a time-dependent increase of CBS in liver tissue and duodenum tissues, the resemblance of MS fluctuation to that of CBS in tested tissues. A four-week simulated microgravity of SD rats exhibits an unequivocal diminish of bioavailability of FA, and simulated microgravity shows a varying effect on the expression of FA-metabolizing enzyme in a variety of tissues.

Opsoclonus-myoclonus syndrome associated with herpes simplex virus infection: a case report.

Purpose: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease that can be associated with autoimmunity, paraneoplastic tumour, infection or unknown aetiology.Methods: We describe a 54-year-old woman who developed severe OMS, with the clinical onset occurring 2 months and 15 days after she experienced dizziness, vomiting and fever related to a herpes simplex virus infection. The patient was treated with hormones and clonazepam, and the symptoms of myoclonus and ataxia disappeared.Results: The patient was followed up for 1 year with no recurrence of symptoms.Conclusions: The case suggests that herpes simplex virus infection is a possible cause of OMS.

Enrichment and purification of red pigments from defective mulberry fruits using biotransformation in a liquid-liquid-solid three-phase system.

A large number of defective mulberries are discarded each year because mulberries are easy to break. The red pigments from defective mulberries are recognized as the sustainable sources of anthocyanins extracted from nature. Cyanidin-3-O-rutinoside and cyanidin-3-O-glucoside are the main components of mulberry red pigments, accounting for 50% and 40% of the total, respectively. Cyanidin-3-O-glucoside exhibits anticancer, hypoglycemic, and liver and visceral protection properties. Cyanidin-3-O-glucoside can be prepared by enzymatically hydrolyzing the rhamnosidase bond of cyanidin-3-O-rutinoside. To obtain mulberry red pigment with a high purity of cyanidin-3-O-glucoside, immobilized α-L-rhamnosidase was added to the aqueous two-phase system to construct a liquid-liquid-solid three-phase enzyme catalytic system. After optimization, the three-phase system was composed of 27.12% (w/w) ethanol, 18.10% (w/w) ammonium sulfate, 15% (w/w) mulberry juice, 4.24% (w/w) immobilized α-L-rhamnosidase, and 35.54% (w/w) pure water. The three-phase system was employed to enrich and purify cyanidin-3-O-glucoside at pH 5 and 45 °C for 1 h. The purity of cyanidin-3-O-glucoside was increased from 40 to 82.42% with cyanidin-3-O-rutinoside conversion of 60.68%. The immobilized α-L-rhamnosidase could be reused seven times, maintaining a relative activity of over 50%. Overall, the developed system provided an efficient and simple approach for high purity mulberry red pigment production and recycling in the field of sustainable agriculture. Graphical abstract.

One-dimensional zinc-manganate oxide hollow nanostructures with enhanced supercapacitor performance.

Hollow electrode materials with structural advantages of large contact interface and sufficient cavity structures are significant for electrochemical energy storage. Herein, ultra-long one-dimensional zinc-manganese oxide (ZnMn2O4) hollow nanofibers were successfully prepared by electrospinning at an appropriate temperature (500 °C). The optimal electrode of ZnMn2O4 exhibited a larger specific capacitance (1026 F g-1) as compared to ZnMn2O4 powder (125 F g-1) at a current density of 2 A g-1 in three-electrode configuration. Moreover, the optimal electrode of the ZnMn2O4 hollow nanofibers also possessed long-term cycling stability with a slight upward capacitance (100.8%) after 5000 cycles. Their higher specific capacitance and the outstanding cycle stability may be attributed to the unique 1D hollow nanostructure, which enhanced the charge transfer and improved the diffusion of the electrolyte ions at the surface. Thus, this work designed a high-performance electrode with unique hollow nanostructure that can be applied to the field of energy storage.

The novel ALK inhibitor ZX-29 induces apoptosis through inhibiting ALK and inducing ROS-mediated endoplasmic reticulum stress in Karpas299 cells.

It is a well-known fact that 60%-85% of anaplastic large cell lymphoma (ALCL) is mainly driven by the anaplastic lymphoma kinase (ALK) fusion protein. Although ALK-positive ALCL patients respond significantly to ALK inhibitors, the development of resistance is inevitable, which requires the development of new therapeutic strategies for ALK-positive ALCL. Here, we investigated the anticancer activities of N-(2((5-chloro-2-((2-methoxy-6-(4-methylpiperazin-1-yl)pyridin-3yl)amino)pyrimidin-4-yl)amino)phenyl)methanesulfonamide (ZX-29), a newly synthesized ALK inhibitor, against nucleophosmin-ALK-positive cell line Karpas299. We demonstrated that ZX-29 decreased Karpas299 cells growth and had better cytotoxicity than ceritinib, which was mediated through downregulating the expression of ALK and related proteins, inducing cell cycle arrest, and promoting cell apoptosis. Moreover, ZX-29-induced cell apoptosis by inducing endoplasmic reticulum stress (ERS). In addition, ZX-29 increased the generation of reactive oxygen species (ROS), and cells pretreatment with N-acetyl- l-cysteine could attenuate ZX-29-induced cell apoptosis and ERS. Taken together, ZX-29 inhibited Karpas299 cell proliferation and induced apoptosis through inhibiting ALK and its downstream protein expression and inducing ROS-mediated ERS. Therefore, our results provide evidence for a novel antitumor candidate for the further investigation.

Inhibition of p38 MAPK regulates epileptic severity by decreasing expression levels of A1R and ENT1.

Epilepsy is a chronic nervous system disease. Excessive increase of the excitatory neurotransmitter glutamate in the body results in an imbalance of neurotransmitters and excessive excitation of neurons, leading to epileptic seizures. Long­term recurrent seizures lead to behavior and cognitive changes, and even increase the risk of death by 2­ to 3­fold relative to the general population. Adenosine A1 receptor (A1R), a member of the adenosine system, has notable anticonvulsant effects, and adenosine levels are controlled by the type 1 equilibrative nucleoside transporter (ENT1); in addition the p38 MAPK signaling pathway is involved in the regulation of ENT1, although the effect of its inhibitors on the expression levels of A1R and ENT1 is unclear. Therefore, in the present study, SB203580 was used to inhibit the p38 MAPK signaling pathway in rats, and the expression levels of A1R and ENT1 in the brain tissue of rats with acute LiCl­pilocarpine­induced status epilepticus was detected. SB203580 decreased pathological damage of hippocampal neurons, prolonged seizure latency, reduced the frequency of seizures, and decreased levels of A1R and ENT1 protein in rats.

Dynamic-related protein 1 inhibitor eases epileptic seizures and can regulate equilibrative nucleoside transporter 1 expression.

BACKGROUND: Dynamic-related protein 1 (Drp1) is a key protein involved in the regulation of mitochondrial fission, and it could affect the dynamic balance of mitochondria and appears to be protective against neuronal injury in epileptic seizures. Equilibrative nucleoside transporter 1 (ENT1) is expressed and functional in the mitochondrial membrane that equilibrates adenosine concentration across membranes. Whether Drp1 participates in the pathogenesis of epileptic seizures via regulating function of ENT1 remains unclear. METHODS: In the present study, we used pilocarpine to induce status epilepticus (SE) in rats, and we used mitochondrial division inhibitor 1 (Mdivi-1), a selective inhibitor to Drp1, to suppress mitochondrial fission in pilocarpine-induced SE model. Mdivi-1administered by intraperitoneal injection before SE induction, and the latency to firstepileptic seizure and the number of epileptic seizures was thereafter observed. The distribution of Drp1 was detected by immunofluorescence, and the expression patterns of Drp1 and ENT1 were detected by Western blot. Furthermore, the mitochondrial ultrastructure of neurons in the hippocampal CA1 region was observed by transmission electron microscopy. RESULTS: We found that Drp1 was expressed mainly in neurons and Drp1 expression was significantly upregulated in the hippocampal and temporal neocortex tissues at 6 h and 24 h after induction of SE. Mitochondrial fission inhibitor 1 attenuated epileptic seizures after induction of SE, reduced mitochondrial damage and ENT1 expression. CONCLUSIONS: These data indicate that Drp1 is upregulated in hippocampus and temporal neocortex after pilocarpine-induced SE and the inhibition of Drp1 may lead to potential therapeutic target for SE by regulating ENT1 after pilocarpine-induced SE.