谷氨酸及NMDA受体拮抗剂MK-801对大鼠伏核痛兴奋神经元电活动的影响

本文研究了谷氨酸(glutamic acid,Glu)及其NMDA受体拮抗剂5-甲基二氢丙环庚烯亚胺马来酸(MK-801)对人鼠伏核(nucleus accumbens,NAc)痛兴奋神经元(pain-excitation neurons,PEN)痛诱发反应的影响。电刺激坐骨神经作为伤害性刺激,用玻璃微电极记录NAc的PEN放电,观察脑室内注射Glu和NAc内注射MK-801对大鼠NAc中PEN伤害性诱发活动的影响。结果显示,伤害性刺激可使NAc的PEN电活动增强;脑室内注射Glu(10nmol／10μl)可使NAc的PEN伤害性诱发放电频率增加;NAc内注射MK-801(1．0nmol／0．5μl)可阻断这种作用;MK-801本身也可部分抑制PEN伤害性诱发反应。上述结果表明,Glu对PEN伤害性反应的易化作用是通过NMDA受体介导的：Glu和NMDA受体参与NAc伤害性信息传递的调制。     

The combination therapy of oncolytic HSV-1 armed with anti-PD-1 antibody and IL-12 enhances anti-tumor efficacy

Cancer immunotherapy is a new therapeutic strategy for cancer treatment that targets tumors by improving or restoring immune system function. Therapies targeting immune checkpoint molecules have exerted potent anti-tumor effects and prolonged the overall survival rate of patients. However, only a small number of patients benefit from the treatment. Oncolytic viruses exert anti-tumor effects by regulating the tumor microenvironment and affecting multiple steps of tumor immune circulation. In this study, we engineered two oncolytic viruses that express mouse anti-PD-1 antibody (VT1093M) or mouse IL-12 (VT1092M). We found that both oncolytic viruses showed significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Importantly, the intratumoral combined injection with VT1092M and VT1093M inhibited growth of the primary tumor, prevented growth of the contralateral untreated tumor, produced a vaccine-like response, activated antigen-specific T cell responses and prolonged the overall survival rate of mice. These results indicate that combination therapy with the engineered oncolytic virus may represent a potent immunotherapy strategy for cancer patients, especially those resistant to PD-1/PD-L1 blockade therapy.     

重组骆驼蓬脂转移蛋白对宫颈癌HeLa细胞化疗的增敏作用

[目的]研究重组骆驼蓬脂转移蛋白(recombinant Peganum harmala lipid transfer protein,r Ph LTP)与顺铂(DDP)协同对宫颈癌He La细胞的抑制作用及可能的作用机制。[方法]四甲基偶氮咗蓝(MTT)法检测He La细胞生长的抑制率;Annexin-V/PI双染法检测细胞凋亡率,流式细胞术检测细胞内活性氧(ROS)的变化情况。[结果]r Ph LTP与DDP联合应用后与相应的DDP组相比,对细胞生长的抑制率显著增强(P0.01),低浓度r Ph LTP联合2.5μg/m L顺铂对He La细胞的抑制率为(42.50±0.059)%,远高于高浓度顺铂(10μg/m L)对He La细胞的抑制率(36.88±0.134)%,细胞的凋亡率显著增加(P0.01),细胞内ROS极明显升高(P0.001)。[结论]r Ph LTP能够显著增强顺铂对He La细胞的化疗敏感性(P0.001),这种作用可能与r Ph LTP增强顺铂诱导细胞内活性氧的产生导致细胞凋亡有关。     

Immobilization of laccase onto modified PU/RC nanofiber via atom transfer radical polymerization method and application in removal of bisphenol A

In this study, 2‐hydroxyethyl methacrylate (HEMA) was used as the monomers for surface grafting on electrospun PU/RC nanofiber membrane via atom transfer radical polymerization (ATRP) method, and the PU/RC‐poly(HEMA) nanofiber membrane was investigated as a carrier for LAC. Free and immobilized LAC was characterized, and efficiency of bisphenol A (BPA) removal was determined. The results indicated that the PU/RC‐poly(HEMA)‐LAC showed relatively higher pH stability, temperature stability, and storage stability than free and PU/RC‐LAC; moreover, more than 60% of the PU/RC‐poly(HEMA)‐LAC activity was retained after 10 cycles of ABTS treatment. Notably, the BPA removal efficiency of PU/RC‐poly(HEMA)‐LAC membrane generally ranged from 87.3 to 75.4% for the five cycles. Therefore, the PU/RC‐poly(HEMA) nanofiber membrane has great potential as a carrier for the LAC immobilization for various industrial applications and bioremediation.     

ROCK1 induces ERK nuclear translocation in PDGF-BB-stimulated migration of rat vascular smooth muscle cells

It has been known that Rho-associated protein kinase (ROCK) signaling regulates the migration of vascular smooth muscle cells (VSMCs). However, the isoform-specific roles of ROCK and its underlying mechanism in VSMC migration are not well understood. The current study thus aimed to investigate the roles of ROCK1/2 and their relationship to the MAPK signaling pathway in platelet-derived growth factor (PDGF)-induced rat aorta VSMC migration by manipulating ROCK gene expression. The results revealed that ROCK1 small interfering ribonucleic acid (siRNA) rather than ROCK2 siRNA decreased PDGF-BB-generated VSMC migration, and upregulation of ROCK1 expression via transfection of constructed pEGFP-C1/ROCK1 plasmid further increased the migration of PDGF-BB-treated VSMCs. In PDGF-treated VSMCs, ROCK1 siRNA did not affect the phosphorylation levels of ERK and p38 in the cytoplasm, but decreased the level of ERK phosphorylation in the nucleus. These findings demonstrate that activated ROCK1 can promote VSMC migration through facilitating phosphorylation and nuclear translocation of ERK protein.     

Reduced Regional Homogeneity in Bilateral Frontostriatal System Relates to Higher Impulsivity Behavior in Codeine-Containing Cough Syrups Dependent Individuals

Background

In the past twenty years, codeine-containing cough syrups (CCS) was recognized as a new type of addictive drugs. However, the exact neurobiologic mechanisms underlying CCS-dependence are still ill-defined. The aims of this study are to identify CCS-related modulations of neural activity during the resting-state in CCS-dependent individuals and to investigate whether these changes of neural activity can be related to duration of CCS use, the first age of CCS use and impulse control deficits in CCS-dependent individuals. We also want to observe the impact of gray matter deficits on these functional results.

Methodology/Principal Findings

Thirty CCS-dependent individuals and 30 control subjects participated. Resting-state functional MRI was performed by using gradient-echo echo-planar imaging sequence. Regional homogeneity (ReHo) was calculated by using REST software. Voxel-based analysis of the ReHo maps between controls and CCS-dependent groups was performed using two-sample t tests (p<0.05, corrected for multiple comparisons). The Barratt Impulsiveness Scale 11 (BIS.11) was surveyed to assess participants'' impulsivity trait soon after MR examination. Abnormal clusters revealed by group comparison were extracted and correlated with impulsivity, duration of CCS use, and age of first CCS use. ReHo was diminished in the bilateral medial orbitofrontal cortex (mOFC) and left dorsal striatum in CCS-dependent individuals. There were negative correlations between mean ReHo in the bilateral medial OFC, left dorsal striatum and duration of CCS use, BIS.11 total scores, and the subscale of attentional impulsivity in CCS-dependent individuals. There was a significantly positive correlation between mean ReHo in the left dorsal striatum and age of first CCS use in CCS-dependent individuals. Importantly, these results still remain significant after statistically controlling for the regional gray matter deficits.

Conclusion

Resting-state abnormalities in CCS-dependent individuals revealed in the present study may further improve our understanding about the neural substrates of impulse control dysfunction in CCS-dependent individuals.