Upconversion-Mediated Optogenetics for the Treatment of Surgery-Induced Postoperative Neurocognitive Dysfunction.

Perioperative neurocognitive disorder (PND) is a common complication in surgical patients. While many interventions to prevent PND have been studied, the availability of treatment methods is limited. Thus, it is crucial to delve into the mechanisms of PND, pinpoint therapeutic targets, and develop effective treatment approaches. In this study, reduced dorsal tenia tecta (DTT) neuronal activity was found to be associated with tibial fracture surgery-induced PND, indicating that a neuronal excitation-inhibition (E-I) imbalance could contribute to PND. Optogenetics in the DTT brain region was conducted using upconversion nanoparticles (UCNPs) with the ability to convert 808 nm near-infrared light to visible wavelengths, which triggered the activation of excitatory neurons with minimal damage in the DTT brain region, thus improving cognitive impairment symptoms in the PND model. Moreover, this noninvasive intervention to modulate E-I imbalance showed a positive influence on mouse behavior in the Morris water maze test, which demonstrates that UCNP-mediated optogenetics is a promising tool for the treatment of neurological imbalance disorders.

Sugarcane molasses essential oils: mesoporous silica nanoparticles as carriers to improve their slow-release activity and the study on their anti-inflammatory activities in vivo.

In this study, sugarcane molasses essential oils (SMEOs) were extracted by microwave-assisted hydrodistillation (MAHD); the components of SMEOs were identified and analyzed by gas chromatography-mass spectrometry (GC-MS). SMEOs were loaded into mesoporous silica nanoparticles (MSNPs) and their sustained-release activity was evaluated. In vivo anti-inflammatory activity assays pertained to inhibiting the auricle swelling caused by xylene in mice, the peritoneal permeability increased inflammation in mice induced by acetic acid and the inflammation caused by granuloma hyperplasia in mice. We demonstrated that the main components of SMEOs were isoamylol, ethyl acetate, isobutanol, isovaleraldehyde, 2-methyl-butanal, furfural and 2-acetylpyrrole. The SMEOs loaded into MSNPs formed MSNP-SMEOs, which enhanced the stability and slow-release performance compared with SMEOs. The main components of SMEOs can inhibit inflammation, and the development and application of SMEOs in the fields of food and medicine have certain potential.

The Programmed Cell Death Ligand-1/Programmed Cell Death-1 Pathway Mediates Pregnancy-Induced Analgesia via Regulating Spinal Inflammatory Cytokines.

BACKGROUND: The maternal pain threshold gradually increases during pregnancy, especially in late pregnancy. A series of mechanisms underlying pregnancy-induced analgesia have been reported. However, these mechanisms are still not completely clear, and the underlying molecular mechanisms need further investigation. We examined the relationship between the antinociceptive effect and the expression level of programmed cell death ligand-1 (PD-L1) during pregnancy and further observed the changes in pain thresholds and expression levels of cytokines in late-pregnant mice before and after blockade of PD-L1 or programmed cell death-1 (PD-1). METHODS: Part 1: Female mice were assigned to 3 groups (nonpregnant, late-pregnant, and postpartum). Part 2: Late-pregnant mice were assigned to 3 treatment groups (control [phosphate buffer solution], RMP1-14 [mouse anti-PD-1 antibody], and soluble PD-1 [sPD-1]). Behavioral testing (mechanical and thermal) and tissue (serum and spinal cord) analysis were performed on all groups. PD-L1, interleukin (IL)-10, tumor necrosis factor-α (TNF-α), and IL-6 expression levels in tissue were examined via reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot analysis. RESULTS: The mechanical and thermal pain thresholds were significantly increased in late pregnancy and decreased after delivery. PD-L1 expression was also elevated in late pregnancy and decreased after delivery. In addition, in the late stage of gestation, the maternal inflammatory microenvironment was dominated by anti-inflammatory factors. After administration of RMP1-14 or sPD-1, the pain thresholds of late-pregnant mice were significantly reduced. In late-pregnant mice, the high level of IL-10 was obviously reduced, and the low levels of TNF-α and IL-6 were elevated. CONCLUSIONS: The PD-L1/PD-1 pathway mediates pregnancy-induced analgesia, partially via the regulation of cytokines.