Combination administration of alprazolam and N-Ethylmaleimide synergistically enhances sleep behaviors in mice with no potential CNS side effects.

Background: N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported.

Objective: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp).

Mitochondrial dysfunction following repeated administration of alprazolam causes attenuation of hippocampus-dependent memory consolidation in mice.

The frequently repeated administration of alprazolam (Alp), a highly effective benzodiazepine sedative-hypnotic agent, in anxiety, insomnia, and other diseases is closely related to many negative adverse reactions that are mainly manifested as memory impairment. However, the exact molecular mechanisms underlying these events are poorly understood. Therefore, we conducted a proteomic analysis on the hippocampus in mice that received repeated administration of Alp for 24 days.

Dual functionalized hyaluronic acid micelles loading paclitaxel for the therapy of breast cancer.

Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX).

A Stable Cell Line Co-expressing hTRPV1 and GCaMP6s: A Novel Cell-based Assay For High-throughput Screening of hTRPV1 Agonists.

Background: Transient receptor potential vanilloid-1 (TRPV1) is a non-selective cation channel capable of integrating various noxious chemical and physical stimuli. Recently, human TRPV1 (hTRPV1) has attracted wide attention from researchers because it is closely related to pain, inflammation, temperature perception, and tumors. Our study was aimed at generating a stable cell line co-expressing hTRPV1 receptor and GCaMP6s calcium indicator protein and, based on this, developing high-throughput screening methods for targeting hTRPV1 agonists.

Whole-Transcriptome Analysis of Repeated Low-Level Sarin-Exposed Rat Hippocampus and Identification of Cerna Networks to Investigate the Mechanism of Sarin-Induced Cognitive Impairment.

Sarin is a potent organophosphorus nerve agent that causes cognitive dysfunction, but its underlying molecular mechanisms are poorly understood. In this study, a rat model of repeated low-level sarin exposure was established using the subcutaneous injection of 0.4 × LD for 21 consecutive days.

PGC 1α-Mediates Mitochondrial Damage in the Liver by Inhibiting the Mitochondrial Respiratory Chain as a Non-cholinergic Mechanism of Repeated Low-Level Soman Exposure.

This work aimed to assess whether mitochondrial damage in the liver induced by subacute soman exposure is caused by peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and whether PGC-1α regulates mitochondrial respiratory chain damage. Toxicity mechanism research may provide theoretical support for developing anti-toxic drugs in the future. First, a soman animal model was established in male Sprague-Dawley (SD) rats by subcutaneous soman injection.

Subacute sarin exposure disrupted the homeostasis of purine and pyrimidine metabolism in guinea pig striatum studied by integrated metabolomic, lipidomic and proteomic analysis.

Sarin was used as a chemical weapon due to its high neurotoxicity and mortality. Subacute sarin induced cognitive and behavioral disorder. However, the underlying mechanism is still unclear.

Nasal Caffeine Thermo-Sensitive Gel for Enhanced Cognition after Sleep-Deprivation.

Background: Caffeine abundant in coffee has a strong excitation effect on the central nerve system (CNS).

Methods: To combat the adverse effects of sleep deprivation on physical and mental health, this article designed a new nasal temperature-sensitive gel loaded with caffeine, whose effects of awakening and improving cognition in sleep-deprived rats were evaluated.

Results: It was found that the caffeine thermo-sensitive in situ gel (TSG) stayed in the nasal cavity for a longer time and increased the contact time between the drugs and the nasal mucosa, which made it possible for caffeine TSG to exert a lasting effect.

Augmented cellular uptake and homologous targeting of exosome-based drug loaded IOL for posterior capsular opacification prevention and biosafety improvement.

Posterior capsular opacification (PCO), the most common complication after cataract surgery, is caused by the proliferation, migration and differentiation of residual lens epithelial cells (LECs) on the surface of the intraocular lens (IOL). Although drug-loaded IOLs have been successfully developed, the PCO prevention efficacy is still limited due to the lack of targeting and low bioavailability. In this investigation, an exosome-functionalized drug-loaded IOL was successfully developed for effective PCO prevention utilizing the homologous targeting and high biocompatibility of exosome.

Foldable Bulk Anti-adhesive Polyacrylic Intraocular Lens Material Design and Fabrication for Posterior Capsule Opacification Prevention.

Posterior capsular opacification (PCO) is a primary complication after phacoemulsification combined with intraocular lens (IOL) implantation, which is attributed to adhesion, proliferation, and migration of residual lens epithelial cells on IOL. Although surface hydrophilic coating is considered to be a powerful way to inhibit PCO incidence after surgery, it requires complex post-production processes, thus limiting their applicability. In comparison, bulk modification is a stable, effective, and facile IOL synthesis method for PCO prevention.

Surface Self-Assembly Construction of Therapeutic Contact Lens with Bacterial "Kill-Releasing" and Drug-Reloading Capabilities for Efficient Bacterial Keratitis Treatment.

Bacterial keratitis, an ophthalmic emergency, can cause corneal perforation and even endophthalmitis, thus leading to severe visual impairment. To achieve effective treatment of bacterial keratitis, good bioavailability of antimicrobial drugs on the ocular surface is desired. In this investigation, a layer-by-layer (LBL) self-assembly combined with the host-guest recognition was used to construct an antibacterial coating on the surface of corneal contact lens (CLs) to improve drug bioavailability and achieve successful treatment of bacterial keratitis.

Application of armodafinil-loaded microneedle patches against the negative influence induced by sleep deprivation.

Cognition maintenance is essential for healthy and safe life if sleep deprivation happens. Armodafinil is a wake-promoting agent against sleep deprivation related disorders. However, only the tablet formulation is available, which may limit its potential in some circumstances.

Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD.

3D printing-based drug-loaded implanted prosthesis to prevent breast cancer recurrence post-conserving surgery.

Systemic chemotherapy of breast cancer is commonly delivered as a large dose and has toxic side effects. Local chemotherapy would overcome the shortcomings of systemic reconstruction and could play an important role in breast cancer surgery according to personalized demand. The application of three-dimensional (3D) printing technology makes personalized customization possible.

Effects of armodafinil nanocrystal nasal hydrogel on recovery of cognitive function in sleep-deprived rats.

Armodafinil is typically used in clinical practice to maintain cognition and wakefulness in patients suffering from sleep deprivation. However, its poor water solubility and large dosage limit its effective application. Herein, we formulated armodafinil in a nanocrystal hydrogel (NCsG) with appropriate fluidity and viscosity, capable of rapidly dissolving after staying in the nasal cavity for > 4 h and then penetrating the mucosa as quickly as possible in vitro.

Surface Modification of Intraocular Lens with Hydrophilic Poly(Sulfobetaine Methacrylate) Brush for Posterior Capsular Opacification Prevention.

The intraocular lens (IOL) is a common, yet important, implantable device used in treatment of cataract in clinics. However, the unexpected adhesion of postoperative residual lens epithelial cells (LECs) often causes serious complications, such as posterior capsular opacification (PCO), which lead to vision loss again. In this investigation, a poly(sulfobetaine methacrylate) (PSBMA) brush coating was fabricated on an IOL to generate a hydrophilic surface coating on the IOL for enhanced cell adhesion resistance so as to decrease PCO incidence.

Antiproliferative drug-loaded multi-functionalized intraocular lens for reducing posterior capsular opacification.

Posterior capsule opacification (PCO) is one of the most frequent complications in cataract surgery and likely to cause the second loss of vision. Proliferation and migration of postoperative remnants of lens epithelial cells (LECs) on the implanted intraocular lens (IOL) are the leading causes of PCO. Antiproliferative drugs can be an effective solution but also possess some problems including sudden release and accompanying adverse effects to surrounding normal tissues, which greatly limit the clinical trials.

Comparative study of oral and intranasal puerarin for prevention of brain injury induced by acute high-altitude hypoxia.

Human activities in the areas of high altitude have increased significantly recently. Brain is highly sensitive to changing of oxygen pressure due to high altitude, and this physiological response may lead to serious brain injury, such as learning and memory disabilities. Puerarin is a phytoestrogen with many pharmacological activities, such as treatment of neurological disorders.

Are Poly(amidoamine) Dendrimers Safe for Ocular Applications? Toxicological Evaluation in Ocular Cells and Tissues.

The human eye is a sophisticated and sensitive sensory organ. Because of the existence of the blood-ocular barrier and corneal-scleral barrier, safe and efficient ocular drug delivery system is highly desired; yet, it remains an unsolved issue. Due to the unique structure and drug loading property, Poly(amidoamine) (PAMAM) has received much attention in the ocular drug delivery investigation.

Topical photodynamic therapy combined with ablative "light needles" against basal cell carcinoma.

Basal cell carcinoma (BCC), a non-melanoma cancer with high morbidity in the elders, is a type of limited skin cancer with a projected appearance. Traditional treatments such as oral or injection administration are likely to result in serious side effects. Here, we developed a strategy that combined photodynamic therapy (PDT) with ablative light "needles" (carbon-dioxide laser) for the treatment of BCC, involving β-Tetra-(4-carboxyl-phenoxy)-zinc phthalocyanine (ZnPC) cubic phases with high drug loading, easy preparation, long local retention, good spreading ability and little toxicity.

ICG-loaded photodynamic chitosan/polyvinyl alcohol composite nanofibers: Anti-resistant bacterial effect and improved healing of infected wounds.

Photodynamic antimicrobial chemotherapy (PACT) has advantages of strong targeting, low resistance to drugs. Electrospinning nanofibers is favorable for wound healing. The combination of PACT and electrospinning nanofibers is appropriate for wound healing, especially infected wound.

Electroporation-enhanced transdermal drug delivery: Effects of logP, pK, solubility and penetration time.

Electroporation is an important physical technique to improve drug transdermal delivery, although its mechanism remains unclear. Here, some types of polar drugs, including aspirin, diclofenac sodium, metformin hydrochloride, ibuprofen and zidovudine, were used as the model drugs for the exploration of electroporation mechanisms. Electroporation had great influences on the structure of stratum corneum to improve the cumulative permeability due to the formation of pores maintaining for at least 2 h, depending on the power and time, and then the permeation gradually recovered to the normal value after 12 h.

Intranasal tetrandrine temperature-sensitive in situ hydrogels for the treatment of microwave-induced brain injury.

The brain is the most sensitive organ to microwave radiation. However, few effective drugs are available for the treatment of microwave-induced brain injury due to the poor drug permeation into the brain. Here, intranasal tetrandrine (TET) temperature-sensitive in situ hydrogels (ISGs) were prepared with poloxamers 407 and 188.

Wound healing of laser injured skin with glycerol monooleicate cubic liquid crystal.

Laser has found increasingly wider applications in the medical filed, but laser is likely to cause damage to patients' skin. In this experiment, we were surprised to find that glyceryl monooleate (GMO)-based cubic liquid crystal had excellent healing effect on the skin of guinea pigs damaged by laser. Transepidermal water loss (TEWL), H.