Selective blockade of spinal D2DR by levocorydalmine attenuates morphine tolerance via suppressing PI3K/Akt-MAPK signaling in a MOR-dependent manner

Wen-Ling Dai,Xin-Tong Liu,Yi-Ni Bao,Bing Yan,Nan Jiang,Bo-Yang Yu,Ji-Hua Liu 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Morphine tolerance remains a challenge in the management of chronic pain in the clinic. As shown in our previous study, the dopamine D2 receptor (D2DR) expressed in spinal cord neurons might be involved in morphine tolerance, but the underlying mechanisms remain to be elucidated. In the present study, selective spinal D2DR blockade attenuated morphine tolerance in mice by inhibiting phosphatidylinositol 3 kinase (PI3K)/serine–threonine kinase (Akt)-mitogen activated protein kinase (MAPK) signaling in a μ opioid receptor (MOR)-dependent manner. Levocorydalmine (l-CDL), which exhibited micromolar affinity for D2DR in D2/CHO-K1 cell lines in this report and effectively alleviated bone cancer pain in our previous study, attenuated morphine tolerance in rats with chronic bone cancer pain at nonanalgesic doses. Furthermore, the intrathecal administration of l-CDL obviously attenuated morphine tolerance, and the effect was reversed by a D2DR agonist in mice. Spinal D2DR inhibition and l-CDL also inhibited tolerance induced by the MOR agonist DAMGO. l-CDL and a D2DR small interfering RNA (siRNA) decreased the increase in levels of phosphorylated Akt and MAPK in the spinal cord; these changes were abolished by a PI3K inhibitor. In addition, the activated Akt and MAPK proteins in mice exhibiting morphine tolerance were inhibited by a MOR antagonist. Intrathecal administration of a PI3K inhibitor also attenuated DAMGO-induced tolerance. Based on these results, l-CDL antagonized spinal D2DR to attenuate morphine tolerance by inhibiting PI3K/Akt-dependent MAPK phosphorylation through MOR. These findings provide insights into a more versatile treatment for morphine tolerance.

Effects of Oxidative Stress on Growth Performance, Nutrient Digestibilities and Activities of Antioxidative Enzymes of Weanling Pigs

Yuan, Shi-bin,Chen, Dai-wen,Zhang, Ke-ying,Yu, Bing Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.10

This study was undertaken to investigate the effects of oxidative stress on growth performance, nutrient digestibilities and activities of antioxidant enzymes of weanling pigs. In the experiment, 24 male $Landrance{\times}Yorkshire $weanling pigs were allotted to three groups of 8 animals each. Pigs were fed individually. According to a single factorial arrangement, pigs received diets with 5% of either fresh (group 1 and group 3) or oxidized fish oil (peroxide value was 786.50 meq $O_2/kg$ before inclusion in the diet, group 2). At the beginning of the experiment, pigs in group 3 received an intraperitoneal injection of diquat at 12 mg/kg of body weight. The trial lasted for 26 d. A metabolism test was carried out during the last 4 days of the second week. The results showed that feeding diets containing oxidized fish oil or injection with diquat depressed the growth performance and nutrient digestibilities of weanling pigs, decreased activities of antioxidant enzymes and increased concentration of malondialdehyde in plasma and liver. Intraperitoneal injection of diquat would induce more serious oxidative stress than oral intake of oxidized fish oil in the diet. In conclusion, administration of oxidized fish oil or diquat could induce oxidative stress in weanling pigs, and oxidative stress could depress growth performance and impact anti-oxidative ability of young pigs.

Effects of Dietary Zinc Level and an Inflammatory Challenge on Performance and Immune Response of Weanling Pigs

Sun, Guo-jun,Chen, Dai-wen,Zhang, Ke-ying,Yu, Bing Asian Australasian Association of Animal Productio 2009 Animal Bioscience Vol.22 No.9

Two experiments were conducted to determine the effect of dietary zinc level on growth performance and immune function in normal (Experiment 1) and immunologically challenged (Experiment 2) weanling pigs. Treatments consisted of the following: i) a corn-soybean meal basal diet containing 36.75 mg/kg total Zn, ii) basal diet+60 mg/kg added Zn as $ZnSO_{4}$, iii) basal diet+120 mg/kg added Zn as $ZnSO_{4}$. Each diet was fed to six pens of four pigs per pen (Exp. 1) or six pens of three pigs per pen (Exp. 2). In Exp. 1, the dietary zinc level had no effect on average daily growth (ADG), average daily feed intake (ADFI), or feed conversion ratio (FCR). Concentrations of tissue and serum zinc were not affected. Peripheral blood lymphocyte proliferation (PBLP) was not affected by dietary treatments. Supplementation of 120 mg/kg Zn decreased (p<0.05) the antibody response to bovine serum albumin (BSA) on d 7 compared with pigs fed the basal diet, but not on d 14. In Exp. 2, LPS challenge had no effect on ADG, ADFI and FCR in the entire trial (from d 0 to 21). LPS challenge significantly decreased ADG and ADFI (p<0.01) from d 7 to 14, but FCR was not affected. LPS challenge increased PBLP (p<0.05) and serum concentration of interleukin-1 (IL-1) (p<0.01), whereas the antibody response to BSA and serum concentration of interleukin-2 (IL-2) were not affected. Supplementation of Zn did not affect ADFI and FCR from d 7 to 14, but there was a trend for ADG to be enhanced with Zn supplementation (p<0.10). Supplementation of Zn tended to increase PBLP (p<0.10). Dietary treatment had no effect on the antibody response to BSA or concentrations of serum IL-1 and IL-2. Results indicate that the level of Zn recommended by NRC (1998) for weanling pigs was sufficient for optimal growth performance and immune responses. Zn requirements may be higher for pigs experiencing an acute phase response than for healthy pigs.

Effects of STF and Fiber Characteristics on Quasi-Static Stab Resistant Properties of Shear Thickening Fluid (STF)-Impregnated UHMWPE/Kevlar Composite Fabrics

Ting-Ting Li,Wenna Dai,Liwei Wu,Hao-Kai Peng,Xiayun Zhang,Bing-Chiuan Shiu,Jia-Horng Lin,Ching-Wen Lou 한국섬유공학회 2019 Fibers and polymers Vol.20 No.2

In order to deeply explore the fiber characteristics influencing on stab resistance of shear thickening fluid (STF)-impregnated fabrics, two different weaving fabrics, ultra-high molecular weight polyethylene (UHMWPE) fabric and Kevlar fabrics are saturate the various concentrations and particle size of STFs. Result shows that, SiO2/PEG-200 blends demonstrate quick shear-thickening property, and the critical shear rate lowers to 1.2-45 s-1 with higher concentration of 75 nm SiO2. STF concentration and particle size significantly affect spike puncture resistance property, but the knife stab resistance mainly depends on fiber characteristics. Comparatively, STF-UHMWPE composite fabrics exhibit better knife stab resistance but weaker spike puncture resistance than STF-Kevlar fabrics. This study can provide an optimization for structure design of stab resistance armors in the future.

Baicalin attenuates TNBS-induced colitis in rats by modulating the Th17/Treg paradigm

Ying Zou,Shi-Xue Dai,Hong-Gang Chi,Tao Li,Zhi-Wei He,Jian Wang,Cai-Guo Ye,Guo-Liang Huang,Bing Zhao,Wen-Yang Li,Zheng Wan,Jin-Shan Feng,Xue-Bao Zheng 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.10

Baicalin, a flavonoid, has a wide range ofpharmacological properties, including immunomodulation. The objective of this study was to investigate the effect ofbaicalin on the balance of T helper 17 (Th17) and regulatoryT (Treg) cells in a colitis model. The rat colitis modelwas induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS). Baicalin (10 ml/kg, each) or mesalazine (positivecontrol) was then administered orally for 7 days. Inflammatoryand immunological responses were evaluated bypathology, enzyme-linked immunosorbent assay, real-timepolymerase chain reaction, western blot analysis, and flowcytometry. Our study showed that baicalin not only significantlyattenuated TNBS-induced colitis by reducing thedisease activity index as well as macroscopic and microscopicscores, but it also improved the weight loss andshortening of the colon. Baicalin treatment also induced asignificant decrease in the levels of inflammatory mediators,including the myeloperoxidase activity, the levels oftumor necrosis factor a, IL-1b, and Th1-related cytokinesIL-12 and IFN-c. Furthermore, the beneficial effects ofbaicalin seem to be associated with regulation of the Th17and Treg paradigm. We found that administration ofbaicalin significantly downregulated the number of Th17cells and the levels of Th17-related cytokines (IL-17 andIL-6) and retinoic acid receptor-related orphan receptor ct. In contrast, there was an increase in Treg cells numbers,Treg-related cytokines transforming growth factor-b andIL-10, and forkhead box P3. Our results suggest that theanti-inflammatory effect of baicalin may be linked tomodulation of the balance between Th17 and Treg cells inTNBS-induced ulcerative colitis.

Profile of disposition, tissue distribution and excretion of the novel anti-human immunodeficiency virus (HIV) agent W-1 in rats

Ying-Yuan Lu,Xiao-Wei Wang,Xin Wang,Wen-Bing Dai,Qiang Zhang,Pu Li,Ya-Qing Lou,Chuang Lu,Jun-Yi Liu,Guo-Liang Zhang 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.7

The purpose of this study was to characterize the disposition, distribution, excretion and plasma protein binding of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W- 1) in rats. Concentrations of W-1 within biological samples were determined using a validated high performance liquid chromatography method. The plasma protein binding of W-1 was examined by equilibrium dialysis method. After oral administration of W-1 (50, 100 and 200 mg/kg, respectively) in self-microemulsifying drug delivery system formulation, the pharmacokinetic parameters of W-1 were as follows: the peak plasma concentrations (Cmax) were 0.42, 1.50 and 2.55 μg/mL, the area under the curve (AUC0-t) were 0.89, 2.27 and 3.96 lg/h mL and the plasma half-life (t1/2) were 5.15, 3.77 and 3.77 h, respectively. Moreover, the prototype of W-1 was rapidly and extensively distributed into fifteen tissues, especially higher concentrations were detected in intestine, stomach and liver, respectively. The plasma protein binding of W-1 in rat, beagle dog and human were in the range of 97.96–99.13 %. This study suggested that W-1 has an appropriate pharmacokinetics in rats, such as rapid absorption, moderate clearance, and rapid distribution to multiple tissues. Those properties provide important information for further development W-1 as an anti-HIV-1 drug candidate.