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Hypoxic-ischemic (HI) brain injury is a major contributor to neurodevelopmental morbidities. Inter-alpha inhibitor proteins (IAIPs) have neuroprotective effects on HI-related brain injury in neonatal rats. However, the effects of treatment with IAIPs on sequential behavioral, MRI, and histopathological abnormalities in the young adult brain after treatment with IAIPs in neonates remain to be determined. The objective of this study was to examine the neuroprotective effects of IAIPs at different neurodevelopmental stages from newborn to young adults after exposure of neonates to HI injury. IAIPs were given as 11-sequential 30-mg/kg doses to postnatal (P) day 7–21 rats after right common carotid artery ligation and exposure to 90 min of 8% oxygen. The resulting brain edema and injury were examined by T2-weighted magnetic resonance imaging (MRI) and cresyl violet staining, respectively. The mean T2 values of the ipsilateral hemisphere from MRI slices 6 to 10 were reduced in IAIP-treated HI males + females on P8, P9, and P10 and females on P8, P9, P10, and P14. IAIP treatment reduced hemispheric volume atrophy by 44.5 ± 29.7% in adult male + female P42 rats and improved general locomotor abilities measured by the righting reflex over time at P7.5, P8, and P9 in males + females and males and muscle strength/endurance measured by wire hang on P16 in males + females and females. IAIPs provided beneficial effects during the learning phase of the Morris water maze with females exhibiting beneficial effects. IAIPs confer neuroprotection from HI-related brain injury in neonates and even in adult rats and beneficial MRI and behavioral benefits in a sex-dependent manner. [ABSTRACT FROM AUTHOR]

Antimicrotubulin chemotherapeutic agents such as vincristine (VCR), often induce peripheral neuropathic pain. It is usually permanent and seriously harmful to cancer patients' quality of life and can result in the hampering of clinical treatments. Currently, there is no definitive therapy, and many of the drugs approved for the treatment of other neuropathic pain have shown little or no analgesic effect. It is therefore vital to find new and novel therapeutic strategies for patients suffering from chemotherapeutic agent-induced neuropathic pain to improve patients' quality of life. This study shows that intrathecal injections of dexmedetomidine (DEX), or intraperitoneally administered ulinastatin (UTI) significantly reduces Sprague Dawley rats' mechanical allodynia induced by VCR via upregulation of interleukin-10 expression and activating the α2-adrenergic receptor in dorsal root ganglion (DRG). Moreover, when combined there is a synergistic interaction between DEX and UTI, which acts against VCR-induced neuropathic pain. This synergistic interaction between DEX and UTI may be partly attributed to a common analgesic pathway in which the upregulation of interleukin -10 plays an important role via activating α2-adrenergic receptor in rat dorsal root ganglion. The combined use of DEX and UTI does not affect the rat's blood pressure, heart rate, sedation, motor score, spatial learning, or memory function. All of these show that the combined use of DEX and UTI is an effective method in relieving VCR-induced neuropathic pain in rats.Perspective: This article documents the synergistic interaction between 2 widely used drugs, DEX and UTI, against VCR-induced neuropathic pain. The results provide a potential target and novel drug administrated method for the clinical treatment of chemotherapy-induced peripheral neuropathic pain. [ABSTRACT FROM AUTHOR]

Hypoxic ischemic insults predispose to perinatal brain injury. Pro-inflammatory cytokines are important in the evolution of this injury. Interleukin-1β (IL-1β) is a key mediator of inflammatory responses and elevated IL-1β levels in brain correlate with adverse neurodevelopmental outcomes after brain injury. Impaired blood–brain barrier (BBB) function represents an important component of hypoxic-ischemic brain injury in the fetus. In addition, ischemia–reperfusion increases cytokine transport across the BBB of the ovine fetus. Reducing pro-inflammatory cytokine entry into brain could represent a novel approach to attenuate ischemia-related brain injury. We hypothesized that infusions of neutralizing IL-1β monoclonal antibody (mAb) reduce IL-1β transport across the BBB after ischemia in the fetus. Fetal sheep were studied 24-h after 30-min of carotid artery occlusion. Fetuses were treated with placebo- or anti-IL-1β mAb intravenously 15-min and 4-h after ischemia. Ovine IL-1β protein expressed from IL-1β pGEX-2T vectors in Escherichia coli ( E. coli ) BL-21 cells was produced, purified, and radiolabeled with 125 I. BBB permeability was quantified using the blood-to-brain transfer constant ( K i ) with 125 I-radiolabeled-IL-1β. Increases in anti-IL-1β mAb were observed in the brain of the mAb-treated group ( P < 0.001). Blood-to-brain transport of 125 I-IL-1β was lower ( P < 0.04) across brain regions in the anti-IL-1β mAb-treated than placebo-treated ischemic fetuses. Plasma 125 I-IL-1β counts were higher ( P < 0.001) in the anti-IL-1β mAb- than placebo-treated ischemic fetuses. Systemic infusions of anti-IL-1β mAb reduce IL-1β transport across the BBB after ischemia in the ovine fetus. Our findings suggest that conditions associated with increases in systemic pro-inflammatory cytokines and neurodevelopmental impairment could benefit from an anti-cytokine therapeutic strategy. [ABSTRACT FROM AUTHOR]

In this study, three typical D–π–A type heteroaromatic organic dyes containing carbazole (CBZ), phenothiazine (PTZ), and phenoxazine (POZ) moiety as electron donor cores and linked to g-C 3 N 4 with amide covalent bonds were synthesized. Thereafter, we studied the long-term photochemical stability and degradation mechanism of the associated dye-sensitised g-C 3 N 4 with covalent linkage or weak interaction. The results revealed that most of the dyes degraded and became unstable after absorption on g-C 3 N 4 under light irradiation. Interestingly, after the target dyes were linked to g-C 3 N 4 with amide covalent bonds, the photostability could be effectively promoted and improved to high levels of stability. For POZ-S dye covalent bond-linked sample g-C 3 N 4 /POZ-S, ∼90.5% percent of the dyes were reserved, whereas only ∼25.3% remained for the physically absorbed dye sample g-C 3 N 4 +POZ-S after 30 min of irradiation aging test. Moreover, the obtained g-C 3 N 4 /POZ-S sample exhibited enhanced H 2 evolution activity with photocatalytic H 2 production rates that were approximately 96- fold of that of pure g-C 3 N 4. Then, we applied various instrumental analysis and DFT calculation to clarify the mechanism involved with dye photostability and degradation pathway. The typical decarboxylation process was confirmed, and such an unfavourable reaction process could be effectively inhibited if the target dye is linked to g-C 3 N 4 with amide covalent bond instead of the weak interaction. Overall, the existed covalent bond is the key factor for enhancing both the photochemical stability and photocatalytic activity of organic dye-sensitised g-C 3 N 4 for hydrogen evolution. [Display omitted] • Three typical heteroaromatic organic dyes functionalised g-C 3 N 4 with amide covalent bonds. • The typical decarboxylation process was confirmed, which could be inhibited by proposed strategy. • The covalent bond is the key factor for enhancing durability and activity of dye-sensitised g-C 3 N 4. [ABSTRACT FROM AUTHOR]