Heterogalactan WPEP-N-b from Pleurotus eryngii enhances immunity in immunocompromised mice.

This study reports on in vivo immunomodulatory activities mediated by WPEP-N-b, a heterogalactan from Pleurotus eryngii. Using cyclophosphamide (CTX)-induced immunosuppressed mice, we demonstrate here that WPEP-N-b enhances immunity as determined by the immune organ index, peripheral blood immune cell content, splenocyte proliferation, NK cell activity and T lymphocyte subpopulations. WPEP-N-b prevented apoptosis of bone marrow cells induced by CTX. The level of cytokines (i.e. TNF-α, IL-6 and IL-1ß) and macrophage activity in these immunocompromised mice were restored upon treated with WPEP-N-b. Mechanistically, it appears that WPEP-N-b enhances splenocyte proliferation and NK cell activity might through the Toll-like receptor 4 (TLR4)-PKC signaling axis, and increases macrophage activity by activating JNK, p38 and NF-κB signaling pathways and Toll-like receptor 2 (TLR2) is the possible receptor of WPEP-N-b in macrophages. Our findings indicate that WPEP-N-b may function as a natural immune stimulant.

Dexmedetomidine prevents hemorrhagic brain injury by reducing damage induced by ferroptosis in mice.

Intracerebral hemorrhage (ICH) is a devastating condition with significant morbidity and mortality for which few effective treatments are clinically available. After ICH, iron overload within the perihaematomal region can induce lethal reactive oxygen species (ROS) production and lipid peroxidation, which contribute to secondary brain injury. An iron-dependent form of non-apoptotic cell death known as ferroptosis was recently identified. Ferroptosis plays an important role in ICH pathology. It is characterized by an accumulation of iron-induced lipid ROS, which leads to intracellular oxidative stress. Dexmedetomidine (DEX), an α2-adrenergic agonist, is widely used for anesthesia, pain control, and intensive care unit sedation. DEX has numerous beneficial activities, including anti-inflammatory, anti-oxidative, and anti-cell death activities. Here, we established a mouse model of ICH using collagenase VII and evaluated the effect of DEX in preventing ICH-induced brain injury. Our study showed that administering DEX reduced the damage induced by ferroptosis after ICH by regulating iron metabolism, amino acid metabolism and lipid peroxidation processes.

Dexmedetomidine Alleviates Intracerebral Hemorrhage-Induced Anxiety-Like Behaviors in Mice Through the Inhibition of TRPV4 Opening.

Post-stroke anxiety severely affects recovery in patients with intracerebral hemorrhage (ICH). Dexmedetomidine (Dex), a highly selective alpha 2 adrenal receptor (α2-AR) agonist, was recently found to exert an excellent protective effect against mental disorders including anxiety. The transient receptor potential vanilloid 4 (TRPV4) channel is involved in a series of diseases such as asthma, cancer, anxiety, and cardiac hypertrophy. This study examines whether Dex improved ICH-induced anxiety via the inhibition of TRPV4 channel opening. A rodent model of moderate ICH in the basal ganglia was established using autologous blood injection (20 µl). Mice were treated with Dex (25 µg/kg, intraperitoneal injection) every day for 3 days post-ICH. GSK1016790A (1 µmol/2 µl), an agonist of TRPV4, was administered via the left lateral ventricle. Thirty days post-ICH, post-stroke anxiety was evaluated by elevated plus-maze and open-field tests. Following behavioral tests, superoxide dismutase (SOD), malondialdehyde (MDA), astrocytic activation, and A1-and A2-type astrocytes were determined. Primary astrocytes were exposed to hemin to simulate ICH in vitro. Compared with sham-treated mice, Dex administration ameliorates ICH-induced decreases of distance and time in the open-arm, reduces distance and time in the central zone, increases astrocytic activation and A1-type astrocytes, elevates MDA content, downregulates total SOD contents, and decreases A2-type astrocytes. However, GSK1016790A partially reversed the neuroprotective effects of Dex. In addition, Dex significantly inhibited hemin-induced astrocytic activation in vitro. Dex improves ICH-induced anxiety-like behaviors in mice, and the mechanism might be associated with the inhibition of TRPV4-channel opening.

Parental presence and intranasal dexmedetomidine for the prevention of anxiety during anesthesia induction in children undergoing tonsillectomy and/or adenoidectomy surgery: A randomized controlled trial.

Background: During the perioperative period of pediatric surgery, it is extremely stressful for children and parents to enter the operating room and receive the anesthesia induction. This study was designed to evaluate the perioperative outcomes with parental presence at induction of anesthesia (PPIA), intranasal dexmedetomidine, and combined use of PPIA and intranasal dexmedetomidine. Methods: In this prospective study, 124 children were randomly divided into four groups: control (no parental presence or intranasal dexmedetomidine), PPIA (parental presence), DEX (intranasal dexmedetomidine (1.0 µg/kg)), and PPIA + DEX (parental presence and intranasal dexmedetomidine (1.0 µg/kg)). The anxiety of children was mainly evaluated by the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary evaluation methods were, for example, the Induction Compliance Checklist (ICC), the Pediatric Anesthesia Emergence Delirium Scale (PAED), the COMFORT Behavior Scale (COMFORT-B Scale), the State-Trait Anxiety Inventory (STAI), and the Visual Analog Scale (VAS). Results: Children in the PPIA + DEX group exhibited significantly lower mYPAS-SF and ICC scores compared with all three other groups (p < 0.001), and children in that group exhibited significantly lower mYPAS-SF and ICC scores compared with the PPIA and DEX groups (p < 0.05). The children's PAED scores in the PPIA, DEX, and PPIA + DEX groups were significantly lower than the control group (p < 0.001).The STAI-S scores of the PPIA, DEX, and PPIA + DEX groups were significantly lower than the score of the control group (p < 0.001). The VAS scores of the PPIA, DEX, and PPIA + DEX groups were significantly higher than that of the control group (p < 0.001), while the score of the PPIA + DEX group was significantly higher than those of the PPIA and DEX groups (p < 0.05). Conclusion: The combined use of PPIA and intranasal dexmedetomidine is more effective than PPIA or intranasal dexmedetomidine for alleviating the preoperative anxiety of children, improving children's induction compliance and parental satisfaction.