Ultrasonic-assisted nanoencapsulation of kiwi leaves proanthocyanidins in liposome delivery system for enhanced biostability and bioavailability.

The poor biostability and bioavailability of proanthocyanidins limit their application. In this study, it was hypothesized that encapsulation in lecithin-based nanoliposomes using ultrasonic technology improves the above properties. Based on preliminary experiments, the effects of lecithin mass ratio (1-9%, wt.

Case Report: Torsade de Pointes Induced by the Third-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Osimertinib Combined With Litsea Cubeba.

Torsades de Pointes (TdP) occurred in a 68-year-old female with epidermal growth factor receptor (EGFR) mutant lung cancer administered osimertinib, the third-generation EGFR tyrosine kinase inhibitor (TKI). Electrocardiogram (ECG) recorded at Tdp showed QT prolongation (QTc = 515 ms), to which a Traditional Chinese Medicine (TCM) named "Litsea Cubeba" may have contributed. After discontinuation of osimertinib and Litsea Cubeba, magnesium supplementation, potassium supplementation, lidocaine infusion, and the pacemaker frequency adjustment, Tdp terminated.

Catalytic asymmetric coupling of vinylogous species deconjugated butenolide addition to vinylogous imines generated from arylsulfonyl indoles.

An efficient catalytic asymmetric coupling of vinylogous species is developed via deconjugated butenolide addition to vinylogous imines in situ generated from arylsulfonyl indoles. With quinine-derived bifunctional squaramide as the catalyst, a series of structurally diverse enantioenriched sec-alkyl-3-substituted indoles containing valuable γ,γ-disubstituted butenolide moieties and adjacent quaternary-tertiary stereocenters are obtained in synthetically viable results (up to 97% yield, 77 : 23 dr and 97% ee).

Benzylidene succinimides as 3C synthons for the asymmetric tandem Mannich reaction/transamidation of cyclic trifluoromethyl ketimines to obtain FC-containing polycyclic dihydroquinazolinones.

By taking advantage of benzylidene succinimides as a new class of 3C synthons, a highly diastereo- and enantioselective tandem Mannich reaction/transamidation has been established by reacting them with cyclic trifluoromethyl N-acyl ketimines. Using a Cinchona alkaloid-derived squaramide as the catalyst, the tandem reaction proceeded smoothly under mild conditions and afforded a range of F3C-containing chiral polycyclic dihydroquinazolinones with excellent results (up to 99% yield, all cases >20 : 1 dr, up to 99% ee).

Organocatalytic asymmetric tandem α-functionalization/1,3-proton shift reaction of benzylidene succinimides with β-trifluoromethyl enones.

A bifunctional thiourea-catalyzed asymmetric tandem α-functionalization/1,3-proton shift reaction of benzylidene succinimides with β-trifluoromethyl enones has been developed. A series of FC-containing chiral Rauhut-Currier type products were obtained in moderate to high yields (up to 98%) with excellent enantioselectivities (up to >99% ee). This represents the first example of benzylidene succinimides undergoing tandem α-functionalization/1,3-proton shift in catalytic enantioselective transformation.

[Effect of histone deacetylase inhibitor NL101 on rat neurons].

Objective: To investigate the protective effect of histone deacetylase inhibitor NL101 on L-homocysteine (HCA)-induced toxicity in rat neurons, and the toxic effect on normal rat neurons.

Methods: In the presence of NL101 at various concentrations, HCA (5 mmol/L)-induced changes in cell density, necrosis, and viability were determined in the mixed cultures of rat cortical cells and the primary cultures of rat neurons. The direct effect of NL101 on primary neurons was also observed in the absence of HCA.

[Antioxidative effects of cysteinyl leukotriene receptor antagonists montelukast and HAMI 3379 on ischemic injury in rat cortical neurons in vitro].

Objective: To investigate the antioxidative effects of two cysteinyl leukotriene receptors antagonists (CysLT1R and CysLT2R) montelukast and HAMI 3379 on ischemic injury of rat cortical neurons in vitro.

Methods: Cultured rat cortical neurons were pretreated with CysLT1R antagonist montelukast and CysLT2R antagonist HAMI 3379, and then exposed to oxygen-glucose deprivation/recovery (OGD/R）or H2O2. Reactive oxygen species (ROS) mitochondrial membrane potential (MMP) depolarization, neuronal viability and lactate dehydrogenase (LDH) release were determined.

Cerebral ischemia is exacerbated by extracellular nicotinamide phosphoribosyltransferase via a non-enzymatic mechanism.

Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT) is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO) and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD) induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture.

Cysteinyl leukotriene receptor 1 mediates LTD4-induced activation of mouse microglial cells in vitro.

Aim: To investigate the roles of cysteinyl leukotriene receptors CysLT1R and CysLT2R in leukotriene D4 (LTD4)-induced activation of microglial cells in vitro.

Methods: Mouse microglial cell line BV2 was transfected with pcDNA3.1(+)-hCysLT1R or pcDNA3.

HAMI 3379, a CysLT2 receptor antagonist, attenuates ischemia-like neuronal injury by inhibiting microglial activation.

The cysteinyl leukotrienes (CysLTs) are inflammatory mediators closely associated with neuronal injury after brain ischemia through the activation of their receptors, CysLT1R and CysLT2R. Here we investigated the involvement of both receptors in oxygen-glucose deprivation/recovery (OGD/R)-induced ischemic neuronal injury and the effect of the novel CysLT2R antagonist HAMI 3379 [3-({[(1S,3S)-3- carboxycyclohexyl]amino}carbonyl)-4-(3-{4-[4-(cyclo-hexyloxy)butoxy]phenyl}propoxy)benzoic acid] in comparison with the CysLT1R antagonist montelukast. In primary neurons, neither the nonselective agonist leukotriene D4 (LTD4) nor the CysLT2R agonist N-methyl-leukotriene C4 (NMLTC4) induced neuronal injury, and HAMI 3379 did not affect OGD/R-induced neuronal injury.

Nicotinamide phosphoribosyltransferase may be involved in age-related brain diseases.

Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme for nicotinamide adenine dinucleotide (NAD) biosynthesis, and can be found either intracellularly (iNAMPT) or extracellularly (eNAMPT). Studies have shown that both iNAMPT and eNAMPT are implicated in aging and age-related diseases/disorders in the peripheral system. However, their functional roles in aged brain remain to be established.

Intracerebroventricular injection of HAMI 3379, a selective cysteinyl leukotriene receptor 2 antagonist, protects against acute brain injury after focal cerebral ischemia in rats.

Cysteinyl leukotrienes (CysLTs) induce inflammatory responses by activating their receptors, CysLT(1)R and CysLT(2)R. We recently reported that CysLT(2)R is involved in neuronal injury, astrocytosis and microgliosis after focal cerebral ischemia in rats. Here, we determined whether HAMI 3379, a selective CysLT(2)R antagonist, protects against acute brain injury after focal cerebral ischemia in rats.

Transforming growth factor β1-induced astrocyte migration is mediated in part by activating 5-lipoxygenase and cysteinyl leukotriene receptor 1.

Background: Transforming growth factor-β 1 (TGF-β 1) is an important regulator of cell migration and plays a role in the scarring response in injured brain. It is also reported that 5-lipoxygenase (5-LOX) and its products, cysteinyl leukotrienes (CysLTs, namely LTC₄, LTD₄ and LTE₄), as well as cysteinyl leukotriene receptor 1 (CysLT₁R) are closely associated with astrocyte proliferation and glial scar formation after brain injury. However, how these molecules act on astrocyte migration, an initial step of the scarring response, is unknown.

[Effect of montelukast on morphological changes in neurons after ischemic injury].

Objective: To determine the effect of montelukast, a cysteinyl leukotriene receptor 1 antagonist, on morphological changes in rat neurons after ischemic injury.

Methods: The in vivo ischemia injury was induced by oxygen-glucose deprivation (OGD) for 2 h and reperfusion (R) for 24 h (OGD/R) in rat neurons primary culture and mixed cortex culture. In the presence or absence of various concentrations of montelukast, neuron number, area of neuron, number of neuritis per neuron, branch number of primary neuritis and primary neurite length were determined for evaluating morphological changes in neurons.

[Cysteinyl leukotriene receptor 1 is involved in rotenone-induced injury of PC12 cells].

Objective: To investigate whether cysteinyl leukotriene receptor 1 (CysLT₁ receptor) is involved in rotenone-induced injury of PC12 cells.

Methods: After 24 h treatment with rotenone or with rotenone and the CysLT₁ receptor antagonist montelukast, PC12 cell viability was determined by the colorimetric MTT reduction assay. After PC12 cells were treated with various concentrations of rotenone for 24 h or with 3 μmol/L rotenone for various durations, the expression of CysLT(1) receptor was determined by Western blotting, and its intracellular distribution was detected by immunocytochemistry.

[Effects of agonist and antagonist of cysteinyl leukotriene receptors on differentiation of rat glioma C6 cells].

Objective: To investigate the role of cysteinyl leukotriene (CysLT) receptors in the differentiation of rat glioma C6 cells.

Methods: Rat glioma C6 cells were treated with the agonist LTD(4), the CysLT(1) receptor antagonist montelukast and the differentiation inducer forskolin. Cell morphology and GFAP protein expression were determined after treatments.

CysLT2 receptor-mediated AQP4 up-regulation is involved in ischemic-like injury through activation of ERK and p38 MAPK in rat astrocytes.

Aims: We previously reported that cysteinyl leukotriene receptor 2 (CysLT(2)) mediates ischemic astrocyte injury, and leukotriene D(4)-activated CysLT(2) receptor up-regulates the water channel aquaporin 4 (AQP4). Here we investigated the mechanism underlying CysLT(2) receptor-mediated ischemic astrocyte injury induced by 4-h oxygen-glucose deprivation and 24-h recovery (OGD/R).

Main Methods: Primary cultures of rat astrocytes were treated by OGD/R to construct the cell injury model.

[Studies on characteristics of volatile oil and micro-identification between Herba Pogostemonis and Herba Agastachis rugosae].

Objective: To compare the chemical components of Herba Pogostemonis and Herba Agastachis rugosae, and develop a new method for the identification of them.

Methods: Comparing the chemical components in volatile oil of Herba Pogostemonis and Herha Agastachis rugosae by GC-MS, and identifying leaves of them by micro-characteristics.

Results: Patchouli alcohol (71.