Thymoquinone suppresses migration of Lo Vo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation

AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration.METHODS Our experiments used high dose thymoquinone(TQ) as an inhibitor to arrest Lo Vo(a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce Lo Vo cancer cell growth. Cyclooxygenase 2(COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2(PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control.RESULTS Our results showed that 20 μmol/L TQ significantly reduced human LoV o colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3 K, p-Akt, p-GSK3β, and β-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of β-catenin in LoV o cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoV o cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice.CONCLUSION TQ inhibits LoV o cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.

Acute respiratory distress syndrome and lung injury: Pathogenetic mechanism and therapeutic implication

To review possible mechanisms and therapeutics for acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide(NO) through the inducible NO synthase(i NOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In con-scious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Estradiol agonists inhibit human Lo Vo colorectal-cancer cell proliferation and migration through p53

AIM: To investigate the effects of 17β-estradiol via estrogen receptors(ER) or direct administration of ER agonists on human colorectal cancer. METHODS: Lo Vo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM(Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, Lo Vo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT(Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber(Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator(u-PA), tissue-type plasminogen activator(t-PA) and matrix metalloproteinase(MMP)-9 in human Lo Vo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test.RESULTS: The structure was first compared with E2 and ER agonists. We then treated the Lo Vo cells with E2 and ER agonists(10-8 mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human Lo Vo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative therapy in the treatment of human colorectal cancer. These results demonstrate that 17β-estradiol and/or ER agonists downregulate migration-related proteins through the p53 signaling pathway in human Lo Vo colorectal cancer cells. These findings suggest that p53 plays a critical role in the 17β-estradiol and/or ER agonist-mediated protective activity against colorectal cancer progression. In addition, 17β-estradiol and/or ER agonists dramatically inhibited cell migration and reduced the expression of u-PA, t-PA and MMP-9 as well as MMP-2/9 activity in Lo Vo cells, which regulate cell metastasis. Moreover, we observed that pretreatment with a p53 inhibitor significantly blocked the anti-migration effects of E2 and/or ER agonists on Lo Vo cells. That E2 and/or ER agonists may impair Lo Vo cell migration by modulating migration-related factors via the p53 tumor suppressor gene.CONCLUSION: Direct ER treatment may prove to be an attractive alternative therapy in the treatment of human colorectal tumors in the future.

台北结核病患者治疗转归:与中断治疗2个月和死亡相关的因素

背景:2003年在台湾台北市所有登记治疗的肺结核患者目的:调查研究与中断治疗至少2个月和死亡相关的危险因素方法:由就诊病历来确定肺结核患者的治疗转归。结果:在登记的1 127例肺结核患者中,824例(73.1%)治疗成功,189例(16.8%)死亡,65例(5.8%)中断治疗,17例(1.5%)已治疗15个月仍在继续治疗,32例(2.8%)治疗失败。与治疗中断显著相关的唯一因素是在开始抗结核治疗后去了其他医疗机构。结核病患者的标化死亡比率为8.7(95%可信区间为7.5～10.0)。与其他患者相比,死亡患者中与其死亡显著相关的因素有:年龄(调整风险比为1.06,95%可信区间为1.05～1.08)、未做痰培养或结果未知(调整风险比为2.07,95%可信区间为1.47～2.92)、合并呼吸系统疾病(调整风险比为1.68,95%可信区间为1.24～2.27),合并感染性疾病(调整风险比为2.80,95%可信区间为2.07～3.78),合并肾脏疾病(调整风险比为2.58,95%可信区间为1.82～3.66)或合并癌症(调整风险比为3.31,95%可信区间为2.35～4.65)。结论:到其他医疗机构就诊是与中断治疗至少2个月相关的因素。高死亡比例是由于年龄大和合并症。