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961.
Li W Tian H Li L Li S Yue W Chen Z Qi L Hu W Zhu Y Hao B Gao C Si L Gao F 《生物化学与生物物理学报(英文版)》2012,44(7):577-583
Lung cancer is the leading cause of cancer-related mortality all over the world. In recent years, pulmonary adenocarcinoma has surpassed squamous cell carcinoma in frequency and is the predominant form of lung cancer in many countries. Epidemiological investigations have shown an inverse relationship between garlic (Allium sativum) consumption and death rate from many cancers. Diallyl trisulfide (DATS) is one of the garlic-derived compounds (also known as: organosulfer compounds, OSC). DATS can induce apoptosis and inhibit the growth of many cancer cell lines. Our study demonstrated that the apoptotic incidents induced by DATS were a mitochondria-dependent caspase cascade through a significant decrease of the anti-apoptotic Bcl-2 that resulted in up-regulation of the ratio of Bax/Bcl-2 and the activity of caspase-3, -8, and -9. Eventually, DATS induced the apoptosis and inhibited the proliferation in a concentration- and time-dependent manner. Furthermore, by establishing an animal model of female BALB/c nude mice with A549 xenografts, we found that oral gavage of DATS significantly retarded growth of A549 xenografts in nude mice without causing weight loss or any other side effects compared with the control group. All the evidence both in vitro and in vivo suggested that DATS could be an ideal anti-cancer drug. 相似文献
962.
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of a family of membrane proteins, called GABA transporters (GAT1-4). It is well established that GABA system is involved in the modulation of memory. Our previous study showed that homozygous GAT1(-/-) mice exhibited impaired hippocampus-dependent learning and memory. To evaluate the impact of endogenous reduced GABA reuptake on mice cognitive behaviors, the ability of learning and memory of heterozygous GAT1(+/-) mice was detected by the passive avoidance paradigm and Morris water maze. The hole board paradigm was also used to measure changes in anxiety-related behavior or exploratory behavior in such mice. As one form of synaptic plasticity, long-term potentiation was recorded in the mouse hippocampal CA1 area. We found that GAT1(+/-) mice displayed increased learning and memory, decreased anxiety-like behaviors, and highest synaptic plasticity compared with wild-type and homozygous GAT1(-/-) mice. Our results suggest that a moderate reduction in GAT1 activity causes the enhancement of learning and memory in mice. 相似文献
963.
Tang JM Yuan J Li Q Wang JN Kong X Zheng F Zhang L Chen L Guo LY Huang YH Yang JY Chen SY 《Journal of cellular biochemistry》2012,113(8):2704-2713
Acetylcholine (ACh) plays an important role in neural and non-neural function, but its role in mesenchymal stem cell (MSC) migration remains to be determined. In the present study, we have found that ACh induces MSC migration via muscarinic acetylcholine receptors (mAChRs). Among several mAChRs, MSCs express mAChR subtype 1 (m1AChR). ACh induces MSC migration via interaction with mAChR1. MEK1/2 inhibitor PD98059 blocks ERK1/2 phosphorylation while partially inhibiting the ACh-induced MSC migration. InsP3Rs inhibitor 2-APB that inhibits MAPK/ERK phosphorylation completely blocks ACh-mediated MSC migration. Interestingly, intracellular Ca(2+) ATPase-specific inhibitor thapsigargin also completely blocks ACh-induced MSC migration through the depletion of intracellular Ca(2+) storage. PKCα or PKCβ inhibitor or their siRNAs only partially inhibit ACh-induced MSC migration, but PKC-ζ siRNA completely inhibits ACh-induced MSC migration via blocking ERK1/2 phosphorylation. These results indicate that ACh induces MSC migration via Ca(2+), PKC, and ERK1/2 signal pathways. 相似文献
964.
Xie M Zhang L He CS Xu F Liu JL Hu ZH Zhao LP Tian Y 《Journal of cellular biochemistry》2012,113(5):1501-1513
Despite an initial response to EGFR tyrosine kinase inhibitors (EGFR-TKI) in EGFR mutant lung cancer, most patients eventually become resistant and result in treatment failure. Recent studies have shown that epithelial to mesenchymal transition (EMT) is associated with drug resistance and cancer cell metastasis. Strong multiple gene signature data indicate that EMT acts as a determinant of insensitivity to EGFR-TKI. However, the exact mechanism for the acquisition of the EMT phenotype in EGFR-TKI resistant lung cancer cells remains unclear. In the present study, we showed that the expression of Notch-1 was highly upregulated in gefitinib-resistant PC9/AB2 lung cancer cells. Notch-1 receptor intracellular domain (N1IC), the activated form of the Notch-1 receptor, promoted the EMT phenotype in PC9 cells. Silencing of Notch-1 using siRNA reversed the EMT phenotype and restored sensitivity to gefitinib in PC9/AB2 cells. Moreover, Notch-1 reduction was also involved in inhibition of anoikis as well as colony-formation activity of PC9/AB2 cells. Taken together, these results provide strong molecular evidence that gefitinib-acquired resistance in lung cancer cells undergoing EMT occurs through activation of Notch-1 signaling. Thus, inhibition of Notch-1 can be a novel strategy for the reversal of the EMT phenotype thereby potentially increasing therapeutic drug sensitivity to lung cancer cells. 相似文献
965.
Chen F Cao J Liu Q Qin J Kong J Wang Y Li Y Geng J Li Q Yang L Xiang AP Zhang C 《Journal of cellular biochemistry》2012,113(2):678-684
Recently, induced pluripotent stem cells (iPS cells) have been derived from various techniques and show great potential for therapy of human diseases. Furthermore, the iPS technique can be used to provide cell models to explore pathological mechanisms of many human diseases in vitro, such as Duchenne muscular dystrophy (DMD), which is a severe recessive X-linked form of muscular dystrophy without effective treatment. In this study, we try to determine whether there are different characteristics of myocytes from mdx iPS cells and C57BL/10 iPS cells. Our results showed that both of mdx and C57BL/10 cells could be induced into iPS cells in vitro, whereas colony-forming ability of mdx iPS cells was much weaker than that of C57BL/10 iPS cells. Meanwhile, mdx iPS cells could be induced to differentiate into myocytes, whereas their differentiation efficiency was much lower than that of C57BL/10 iPS cells. And, the number of apoptotic cells in differentiated myocytes from mdx iPS cells was significantly higher than that from C57BL/10 iPS cells. More importantly, treatment of a pan-caspase inhibitor (Z-VAD) produced a significant decrease in apoptotic cells. This study might add some insight to the biology study of dystrophin gene. 相似文献
966.
Min Lin Ying Zhao ShuQi Wang Ming Liu ZhenFeng Duan YongMei Chen Fei Li Feng Xu TianJian Lu 《Biotechnology advances》2012
Lanthanide (Ln)-doped upconversion nanoparticles (UCNPs) with appropriate surface modification can be used for a wide range of biomedical applications such as bio-detection, cancer therapy, bio-labeling, fluorescence imaging, magnetic resonance imaging and drug delivery. The upconversion phenomenon exhibited by Ln-doped UCNPs renders them tremendous advantages in biological applications over other types of fluorescent materials (e.g., organic dyes, fluorescent proteins, gold nanoparticles, quantum dots, and luminescent transition metal complexes) for: (i) enhanced tissue penetration depths achieved by near-infrared (NIR) excitation; (ii) improved stability against photobleaching, photoblinking and photochemical degradation; (iii) non-photodamaging to DNA/RNA due to lower excitation light energy; (iv) lower cytotoxicity; and (v) higher detection sensitivity. Ln-doped UCNPs are therefore attracting increasing attentions in recent years. In this review, we present recent advances in the synthesis of Ln-doped UCNPs and their surface modification, as well as their emerging applications in biomedicine. The future prospects of Ln-doped UCNPs for biomedical applications are also discussed. 相似文献
967.
Porcine circovirus type 2 (PCV2) is recognized as a key infectious agent in postweaning multisystemic wasting syndrome (PMWS), but not all pigs infected with PCV2 will develop PMWS. The aim of this work was to explore the relationships among PCV2 infection, oxidative stress, and selenium in a PK-15 cell culture model of PCV2 infection. The results showed that oxidative stress induced by H(2)O(2) treatment increased PCV2 replication as measured by PCV2 DNA copies and the number of infected cells. Furthermore, PCV2 replication was inhibited by selenomethionine (SeMet) at a high concentration (6μM) and the increase in PCV2 replication by oxidative stress was blocked by SeMet at physiological concentrations (2 or 4μM). PCV2 infection caused a decrease in glutathione peroxidase 1 (GPx1) activity but an increase in GPx1 mRNA levels, suggesting that GPx1 may represent an important defense mechanism during PCV2 infection. SeMet did not significantly block the promotion of PCV2 replication in GPx1-knockdown cells. This observation correlates with the observed influence of SeMet on GPx1 mRNA and activity in GPx1-knockdown cells, indicating that GPx1 plays a key role in blocking the promotion of PCV2 replication. We conclude that differences in morbidity and severity of PMWS observed on different pig farms may be related to variations in oxidative stress and that selenium has a potential role in the control of PCV2 infection. 相似文献
968.
Atrial fibrillation (AF) affects more than 5 million people worldwide; however, none of the anti-arrhythmic drugs available
now are entirely optimal in terms of efficacy and safety. A better understanding of the molecular mechanism of AF will facilitate the
process of finding new strategies to prevent AF. As the non-familial AF is the major form of AF, identifying common variants
for AF in these populations by genome-wide association studies will definitely accelerate this process. This review summarizes
the recently identified common AF variants on 4q25, 16q22, and 1q21 and discusses their implications for the clinic. 相似文献
969.
Although a growing body of evidence supports the importance of the Wnt/β-catenin signaling pathway and oxidative stress in the pathogenesis of autism, it is unclear whether a relationship exists between the Wnt/β-catenin pathway and oxidative homeostasis. The present study examines the effects of sulindac, a small molecule inhibitor of the Wnt/β-catenin signaling pathway, on the oxidative status of rats that are prenatally exposed to valproic acid (VPA), which is used in an animal model of autism. Our data show that sulindac treatment downregulated the canonical Wnt/β-catenin signaling pathway by enhancing the expression of Glycogen Synthase Kinase 3β and attenuating the expression of β-catenin in comparison to levels in VPA-treated rats. Concomitantly, a marker of lipid peroxidation, 4-hydroxynonenal, was reduced as well. Sulindac treatment ameliorated the pain threshold, repetitive/stereotypic activity, learning and memory abilities and behavioral abnormalities of rats in our autism model. Our working model suggests that the upregulation of the Wnt/β-catenin signaling pathway induced by VPA administration during early pregnancy produces an imbalance of oxidative homeostasis that facilitates susceptibility to autism. This information may be instrumental in designing appropriate therapeutic regimens with small molecule inhibitors of the Wnt/β-catenin pathway for the treatment of autism-like behavioral phenotypes. 相似文献
970.
The effect of molecular oxygen on the electron transfer activity of the cytochrome bc(1) complex was investigated by determining the activity of the complex under the aerobic and anaerobic conditions. Molecular oxygen increases the activity of Rhodobacter sphaeroides bc(1) complex up to 82%, depending on the intactness of the complex. Since oxygen enhances the reduction rate of heme b(L), but shows no effect on the reduction rate of heme b(H), the effect of oxygen in the electron transfer sequence of the cytochrome bc(1) complex is at the step of heme b(L) reduction during bifurcated oxidation of ubiquinol. 相似文献