Suppression of NF-kappaB and AP-1 activation in monocytic cells persistently infected with measles virus

HIV-1 evolution in the envelope gene (env) was analyzed in four asymptomatic antiretroviral therapy na?ve patients with typical and slow disease progression rates. In typical progressors, viral populations were monophyletic and two distinct evolutionary patterns were observed. In one patient, HIV-1 evolution displayed a strong temporal structure similar to the consistent pattern previously described. In the other, viral evolution displayed a lack of temporal structure with no increase in genetic heterogeneity and divergence over time. In slow progressors, several clades were observed in viral populations. However, analysis within the major sub-population revealed the same two evolutionary patterns described for typical progressors. Synonymous and non-synonymous substitution rate analyses indicated that positive selection was the major force driving HIV-1 evolution in viral populations with temporal structure, while evolution in viral populations with an atemporal structure was dominated by genetic drift and purifying selection. These results support the existence of distinct patterns of env evolution in untreated HIV-1-infected patients.     

Activation of non-canonical NF-kappaB pathway mediated by STP-A11, an oncoprotein of Herpesvirus saimiri

Although Saimiri Transforming Protein (STP)-A11, an oncoprotein of Herpesvirus saimiri, has been known to activate NF-kappaB signaling pathway, the detailed mechanism has not been reported yet. We herein report that STP-A11 activates non-canonical NF-kappaB pathway, resulting in p100 processing to p52. In addition, translocation of p52 protein (NF-kappaB2) into the nucleus is observed by the expression of STP-A11. STP-A11-mediated processing of p100 to p52 protein requires proteosome-mediated proteolysis because MG132 treatment clearly blocked p52 production in spite of the expression of STP-A11. Analysis of STP-A11 mutants to activate NF-kappaB2 pathway discloses the requirement of TRAF6-binding site not Src-binding site for STP-A11-mediated NF-kappaB2 pathway. Blockage of STP-A11-mediated p52 production using siRNA against p52 enhanced a chemotherapeutic drug-mediated cell death, suggesting that p52 production induced by the expression of STP-A11 would contribute to cellular transformation, which results from a resistance to cell death.     

丹皮酚对动脉粥样硬化大鼠脂质代谢和核因子-κB的影响

目的：探讨丹皮酚对动脉粥样硬化（AS）大鼠脂质代谢和核因子-κB（NF-κB）的影响。方法：采用高脂饲料喂养和维生素D3腹腔注射的方法建立大鼠AS模型,分为正常组、模型组、辛伐他汀组（10 mg·kg-1）、丹皮酚高剂量组和低剂量组（20,10 mg·kg-1）,每组8只。灌胃给药4周后,各组取血清,测定血脂水平;取主动脉切片,光镜下作病变分级评分,免疫组化法检测NF-κB的表达。结果：丹皮酚高剂量组能改善AS大鼠的主动脉病变,与模型组比较有统计学意义（P〈0.05）;丹皮酚高、低剂量组可明显降低AS大鼠血清三酰甘油（TG）、总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平（P〈0.05或P〈0.01）;丹皮酚可下调主动脉NF-κB表达,高剂量组IOD值（1.96±0.55）和低剂量组IOD值（2.50±0.80）与模型组（3.65±1.14）比较,差异均有统计学意义（P〈0.05或0.01）。结论：丹皮酚治疗大鼠AS的作用机制与调节脂质代谢、下调主动脉NF-κB的表达有关。     

Quinovic acid glycosides purified fraction from Uncaria tomentosa induces cell death by apoptosis in the T24 human bladder cancer cell line

Bladder cancer is the second most prevalent malignancy in the genitourinary tract and remains a therapeutic challenge. In the search for new treatments, researchers have attempted to find compounds with low toxicity. With this goal in mind, Uncaria tomentosa is noteworthy because the bark and root of this species are widely used in traditional medicine and in adjuvant therapy for the treatment of numerous diseases. The objective of this study was to investigate the antitumor effect of one purified bioactive fraction of U. tomentosa bark on cell proliferation in two human bladder cancer cell lines, T24 and RT4. Quinovic acid glycosides purified fraction (QAPF) of U. tomentosa decreased the growth and viability of both T24 and RT4 cell lines. In T24 cells, QAPF induced apoptosis by activating caspase-3 and NF-κB. Further study showed that this fraction does not induce cell cycle arrest and does not alter PTEN and ERK levels. In conclusion, we demonstrated that QAPF of U. tomentosa has a potent inhibitory effect on the growth of human bladder cancer cell lines by inducing apoptosis through modulation of NF-κB, and we suggest that QAPF may become a potential therapeutic agent for the prevention and/or treatment of this cancer.     

Hybrid Molecule from Farnesylthiosalicylic Acid-diamine and Phenylpropenoic Acid as Ras-related Signaling Inhibitor with Potent Antitumor Activities

Novel series of Farnesylthiosalicylic acid-diamine/phenylpropenoic acid hybrids were designed and synthesized. Their in vitro growth inhibitory assays showed that most compounds displayed strong antiproliferation activity against seven cancer cells. Especially, the new hybrid 12f , by the conjugation of 10a with ferulic acid, could selectively suppress the proliferation of tumor cells and display significantly lower toxicities to normal cells than its intermediate 10a . Furthermore, 12f dose-dependently induced SMMC-7721 cell apoptosis. Additionally, our observations demonstrated that 12f inhibited both Ras-related signaling and phosphorylated NF-κB synergistically, which may be advantageous to the strong antitumor activities of 12f . Our findings suggest that these novel hybrids may hold a great promise as therapeutic agents for the intervention of human cancers.