Propofol effectively inhibits lithium-pilocarpine-induced status epilepticus in rats via downregulation of N-methyl-D-aspartate receptor 2B subunit expression

Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine.The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior,electroencephalography and 24-hour survival rate.Propofol（12.5-100 mg/kg） improved status epilepticus in a dose-dependent manner,and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection.Western blot results showed that,24 hours after induction of status epilepticus,the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus.Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels,but not the increase in N-methyl-D-aspartate receptor 2A subunit levels.The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine.This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures.

Immune reactions and nerve repair in mice with sciatic nerve injury 14 days after intraperitoneal injection of Brazil

BALB/c mice were intraperitoneally injected with 10, 5 or 2.5 mg/kg Brazil for 14 days after sciatic nerve injury. Results demonstrate that the spleen T/B lymphocyte stimulation index and serum circulating immune complex concentration were significantly reduced, and the morphology of the soleus muscle was restored in mice with sciatic nerve injury. These effects of Brazil were dose-dependent. Our experimental findings indicate that Brazil can regulate immune responses after nerve injury and promote sciatic nerve repair.

A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening

In the treatment of central nervous system disease,the blood-brain barrier(BBB)is a major obstruction to drug delivery that must be overcome.In this study,we propose a brain-targeted delivery strat-egy based on selective opening of the BBB.This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material;however,the BBB still maintains the ability to completely block molecules from passing through.Based on the screening of BBB opening and matrix delivery mate-rials,we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine li-posomes can efficiently carry drugs into the brain immediately.At an effective dose,this delivery system is safe,especially with its effect on the BBB being reversible.This mix&act delivery system has a simple structure and rapid preparation,making it a strong potential candidate for drug delivery across the BBB.

Chinese herb pollen derived micromotors as active oral drug delivery system for gastric ulcer treatment

Considerable efforts have been devoted to treating gastric ulcers.Attempts in this field tend to develop drug delivery systems with prolonged gastric retention time.Herein,we develop novel Chinese herb pollen-derived micromotors as active oral drug delivery system for treating gastric ulcer.Such Chinese herb pollen-derived micromotors are simply produced by asymmetrically sputtering Mg layer onto one side of pollen grains.When exposed to gastric juice,the Mg layer can react with the hydrogen ions,resulting in intensive generation of hydrogen bubbles to propel the micromotors.Benefiting from the autonomous motion and unique spiny structure,our micromotors can move actively in the stomach and adhere to the surrounding tissues.Besides,their special architecture endows the micromotors with salient capacity of drug loading and releasing.Based on these features,we have demonstrated that our Chinese herb pollen-derived micromotors could effective deliver berberine hydrochloride and show desirable curative effect on the gastric ulcer model of mice.Therefore,these Chinese herb pollen-derived micromotors are anticipated to serve as promising oral drug delivery carriers for clinical applications.

Supramolecular liquid barrier for sulfur mustard utilizing host-guest complexation of pillar[5]arene with triethylene oxide substituents

Sulfur mustard(SM) can be absorbed by skin quickly and cause serious system damage via reacting with nearly all cell constituents. Until now, there is still lack of effective antidotal therapy for SM and skin protection is highly important to defend SM. In this article, supramolecular liquid barrier based on pillar[5]arene with triethylene oxide substituents(EGP5) has been designed to impede the skin permeation of SM and further interaction with the skin tissue. EGP5 could encapsulate SM within its cavity, with a Kavalue of(5.10 ± 0.47) × 10^(2)L/mol. In vitro skin absorption test proved that EGP5 was capable to effectively prevent SM from penetrating through skin. This supramolecular liquid barrier was employed on rat models to systematically evaluate protective effect against SM intoxication. Pretreatment of EGP5could alleviate skin and system damage induced by SM and improve survival rate of poisoned rat models from 10% to 90%. Additionally, EGP5 served as protective materials could be highly reused after recycling several times. Overall, these findings have provided the first insight into the construction of convenient liquid material for SM protection.

Antibacterial and angiogenic chitosan microneedle array patch for promoting wound healing

A patch with the capability of avoiding wound infection and promoting tissue remolding is of great value for wound healing.In this paper,we develop a biomass chitosan microneedle array(CSMNA)patch integrated with smart responsive drug delivery for promoting wound healing.Chitosan possesses many outstanding features such as the natural antibacterial property and has been widely utilized for wound healing.Besides,the microstructure of microneedles enables the effective delivery of loaded drugs into the target area and avoids the excessive adhesion between the skin and the patch.Also,vascular endothelial growth factor(VEGF)is encapsulated in the micropores of CSMNA by temperature sensitive hydrogel.Therefore,the smart release of the drugs can be controllably realized via the temperature rising induced by the inflammation response at the site of wounds.It is demonstrated that the biomass CSMNA patch can promote inflammatory inhibition,collagen deposition,angiogenesis,and tissue regeneration during the wound closure.Thus,this versatile CSMNA patch is potentially valuable for wound healing in clinical applications.

TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome

Nerve agents are used in civil wars and terrorist attacks,posing a threat to public safety.Acute exposure to nerve agents such as soman(GD)causes serious brain damage,leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation.However,data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited.Here,we evaluated the potential effects of transient receptor vanilloid 4(TRPV4)in the treatment of soman-induced status epilepticus(SE)and secondary brain injury.We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures.Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity.TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure.Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity.The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1βand IL-18 increased in soman-exposed rat hippocampus.However,TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway.In conclusion,our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation.To our knowledge,this is the first study regarding the“dual-switch”function of TRPV4 in the treatment of soman intoxication.

Engineered microneedles arrays for wound healing

Wound healing is the regenerative process of original skin structure after destructing by different damage sources.Due to their transdermal delivery capability and high specific surface area,microneedles arrays(MAs)have been recognized as encouraging biomaterials for wound healing.In this review,we have outlined the engineered MAs used for tissue regeneration and wound healing.Engineered MAs were first classified by design methodologies such as bionic design,intelligent-responsive design,actively-triggered design,matrix materials innovation,and composite smart design.Then,the MAs were divided into two categories based on the different loading substances:drug-loaded MAs and living component-loaded MAs.Finally,we have summed up the important elements of the preceding discussions and forecasted their future evolution.