Inhibition of nuclear factor-κB activity enhanced chemosensitivity to cisplatin in human lung adeno-carcinoma A549 cells under chemical hypoxia conditions

Background Tumor hypoxia,one of the features of solid tumors,is associated with chemo-resistance.Recently,nuclear factor-KB (NF-kB) was found to be activated during hypoxia.However,the impact of NF-kB ...     

Dioscin-induced Apoptosis of Human LNCaP Prostate Carcinoma Cells through Activation of Caspase-3 and Modulation of Bcl-2 Protein Family简

Dioscin is a natural steroid saponin derived from several plants, showing potent anti-cancer effect against a variety of tumor cell lines. In the present study, we investigated the anti-cancer activity of dioscin against human LNCaP cells, and evaluated the possible mechanism involved in its antineoplastic action. It was found that dioscin（1, 2 and 4 μmol/L） could significantly inhibit the viability of LNCaP cells in a time- and concentration-dependent manner. Flow cytometry revealed that the apoptosis rate was increased after treatment of LNCaP cells with dioscin for 24 h, indicating that apoptosis was an important mechanism by which dioscin inhibited cancer. Western blotting was employed to detect the expression of caspase-3, Bcl-2 and Bax in LNCaP cells. The expression of cleaved caspase-3 was significantly increased, and meanwhile procaspase-3 was markedly decreased. The expression of anti-apoptotic protein Bcl-2 was down-regulated, whereas the pro-apoptotic protein Bax was up-regulated. Moreover, the Bcl-2/Bax ratio was drastically decreased. These results suggested that dioscin possessed potential anti-tumor activity in human LNCaP cells through the apoptosis pathway, which might be associated with caspase-3 and Bcl-2 protein family.     

Cbl-b and PI3K/Akt pathway are differently involved in oxygen-glucose deprivation preconditioning in PC12 cells

Background Transient sublethal ischemia is known as ischemic preconditioning, which enables cells and tissues to survive subsequent prolonged lethal ischemic injury. Ischemic preconditioning exerts neuroprotection through phosphatidylinositol 3-kinase （PI3K）/Akt pathway. Cbl-b belongs to the Casitas B-lineage lymphoma （Cbl） family, and it can regulate the cell signal transduction.The roles of ubiquitin ligase Cbl-b and PI3K/Akt pathway and the relationship between them in oxygen-glucose deprivation preconditioninq （OGDPC） in PC12 cells were investiaated in the ore.~e.nt study     

miR-21 targets Fas ligand-mediated apoptosis in breast cancer cell line MCF-7

Over-expression of Fas ligand （FasL） on tumor cell surface can induce the apoptosis of spe- cific activated tumor infiltrating lymphocytes （TILs） via the Fas/FasL pathway, leading to the formation of a site of immune privilege surrounding the tumor mass for escaping immune surveillance and pro- moting tumor proliferation, invasion and metastasis. The blocking effect of miR-21 on FasL-mediated apoptosis in breast cancers was investigated in this study. The expression levels of miR-21 and FasL in human breast carcinoma cell lines were detected by using RT-PCR and Western blotting. FasL as a tar- get gene of miR-21 was identified by Luciferase assay. The apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was determined by flow cytometry. It was found that in four human breast cancer cell lines, FasL expression level in MCF-7 cells was the highest, while miR-21 was down-regulated the most notably. After miR-21 expression in MCF-7 cells was up-regulated, FasL was identified as a target gene of miR-21. When the effector/target （E/T） ratio of MCF-7 cells and Jurkat cells was 10：1, 5：1 and 1：1, the inhibitory rate of apoptosis of Jurkat T lymphocytes induced by MCF-7 cells was 95.81%, 93.16% and 91.94%, respectively. It is suggested that in breast cancers miR-21 expression is negatively associ- ated with FasL expression, and FasL is a target gene of miR-21, miR-21 targeting and regulating FasL-mediated apoptosis will bring us the possibility of a new tumor immunotherapy via breaking tu- mor immune privilege.     

miR-200c inhibits metastasis of breast cancer cells by targeting HMGB1

miR-200c has been shown to regulate the epithelial-mesenchymal transition （EMT） by inhibiting ZEB1 and ZEB2 expression in breast cancer cells. This study further examined the role of miR-200c in the invasion and metastasis of breast cancer that goes beyond the regulation on ZEB1 and ZEB2 expression. In this study, the bioinformatics software （miRanda） was used to predict the target gene of miR-200c and Renilla luciferase assay to verify the result. The metastatic breast cancer cells MDA-MB-231 were cultured and transfected with the miR-200c mimic or inhibitor. The expressions of miR-200c and HMGB 1 were detected by RT-PCR and Western blotting, respectively. Transwell assay and wound healing assay were employed to examine the invasive and migrating ability of transfected cells. Target prediction and Renilla luciferase analysis revealed that HMGB1 was a putative target gene of＇miR-200c. After transfection of MDA-MB-231 cells with the miR-200c mimic or inhibitor, the expression of miR-200c was significantly increased or decreased when compared with cells transfected with the miR-200c mimic NC or inhibitor NC. Moreover, the expression of HMGB1 was reversely correlated with that of miR-200c in transfected cells. Tranwell assay showed that the number of invasive cells was significantly reduced in miR-200c mimic group when compared with miR-200c inhibitor group. It was also found that the migrating ability of cells transfected with miR-200c mimics was much lower than that of cells transfected with miR-200c inhibitors. It was suggested that miR-200c can suppress the invasion and migration of breast cancer cells by regulating the expression of HMGB1. miR-200c and HMGB1 may become useful biomarkers for progression of breast cancer and targets of gene therapy.     

MicroRNA-215 is a potential prognostic marker for cervical cancer

Recently, microRNAs （miRNAs） have been shown to be involved in multiple biological pathways that can influence tumor progression and metastasis and they can serve as prognostic bio- markers in many cancers. The present study examined the prognostic significance of miR-215 in cervi- cal cancer. The paraffin-embedded paired cervical scrape samples and tumor tissue samples from 302 patients with stage II cervical cancer were detected for the expression of miR-215 by using qRT-PCR. A miR-215-based classifier was established by using the Cox regression model. The prognostic and pre- dictive accuracy of this classifier was determined in both the internal testing group of 138 patients, and the external independent group of 280 patients. Moreover, cervical cancer HeLa cells overexpressing miR-215 （HeLa-miR-215） were constructed and subcutaneously injected into the nude mice to examine the effect of miR-215 on tumor growth and metastasis in vivo. The results showed that the expression level of miR-215 was significantly higher in cervical cancer tissues than in paired normal tissues （P〈0.0001）. When patients were classified into high- and low-risk cancer progression groups according to miR-215 level, the 5-year disease-free survival in high- and low-risk groups were 43% （95% CI： 32.1-51.6） and 67% （95% CI： 48.6-77.3） （hazard ratio [HR] 2.02, 95% CI： 1.16-3.52; P=0.013） re- spectively. Moreover, the expression level of miR-215 was negatively associated with survival rate in patients at TNM stage T3 （HR： 3.317; 95% CI： 1.18-5.14, P=0.017） and TNM stage T4 （HR： 3.48; 95% CI： 1.49-4.45, P=-0.008）. Tumor volume in nude mice injected with HeLa-miR-215 cells was signifi- cantly larger than that in mice injected with control HeLa cells. It was concluded that the expression level of miR-215 is associated with cervical tumor progression and worse survival rate, suggesting that it may serve as a potential prognostic marker to identify patients at higher risk of recurrence.     

Association between intervertebral disc degeneration and disturbances of blood supply to the vertebrae

Low back pain is a common public health problem in western industrialized societies and the world as well.Studies indicate that the prevalence rate ranges to 35%, with around 10% of patients from 12% becoming chronically disabled. It also places an enormous economic burden on society. Although the exact cause of low back pain has yet to be defined, intervertebral disc degeneration is considered a major source of it. Since patients with degenerative discs are often asymptomatic, the mechanisms of it are still unclear.     

Diagnosis and treatment of epistaxis caused by non-traumatic pseudoaneurysms of carotid artery

Epistaxis remains one of the most common otolaryngology emergencies. Severe epistaxis may be caused by internal carotid artery （ICA） pseudoaneurysm or cavernous fistula, which is clinically rare but life threatening if it is not diagnosed and treated timely. Most ICA pseudoaneurysms are mainly caused by trauma with few other causes. From January 1998 to December 2005, a total of 8 cases with non-traumatic carotid artery pseudoaneurysm were correctly diagnosed through digital subtraction angiography （DSA） in Ganzhou People＇s Hospital. The patients had suffered from serious nose bleeding repeatedly and had been resistant to routine treatments.     

MiR-181b suppresses proliferation of and reduces chemoresistance to temozolomide in U87 glioma stem cells

MicroRNAs regulate self renewal and differentiation of cancer stem cells.There,we sought to identify the expression of miR-181b in glioma stem cells and investigate the biological effect of miR-181b on glioma stem cells in this study.MiR-181b expression was measured by real-time PCR in glioma stem cells isolated from U87 cells by FACS sorting.After miR-181b was overexpressed in U87 glioma stem cells by miR-181b lentiviral expression vector and/or treatment of temozolomide,secondary neurosphere assay,soft agar colony assay and MTT assay were performed.Compared with U87 cells,the expression of miR-181b was significantly decreased in U87 glioma stem cells.Overexpression of miR-181b decreased neurosphere formation by U87 glioma stem cells in vitro and suppressed colony formation in soft agar,and the cell growth inhibition rates increased in a time-dependent manner in U87 glioma stem cells infected with miR-181b lentivirus.Furthermore,miR-181b had a synergistic effect on temozolomide-induced inhibition of secondary neurosphere and soft agar colony,and on cell growth inhibition rates.MiR-181b functions as a tumor suppressor that suppresses proliferation and reduces chemoresistance to temozolomide in glioma stem cells.     

Saffron （Crocus sativus L.） and major depressive disorder： a meta-analysis of randomized clinical trials

Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder （MDD）. Of these, accumulating trials reveal positive effects of the spice saffron （Crocus sativus L.） for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE： The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY： We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA： The criteria for study selection included the following： （1） adults （aged 18 and older） with symptoms of depression, （2） randomized controlled trial, （3） effects of saffron supplementation on depressive symptoms examined, and （4） study had either a placebo control or antidepressant comparison group. DATA EXTRACTION AND ANALYSIS： Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta- analysis 2 was used to analyze the data. RESULTS： Based on our pre-specified criteria, five randomized controlled trials （n = 2 placebo controlled trials, n = 3 antidepressant controlled trials） were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms （M ES = 1.62, P 〈 0.001）, revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups （M ES = -0.15） indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials. CONCLUSION： Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron＇s efficacy and safety for treating depressive symptoms.     

高维列联表资料的统计分析与SAS软件实现（六）

非条件logistic回归分析方法的主要算法是采用最大似然法对参数进行估计。最大似然法在大样本前提下进行参数估计是非常有效的,但当处理样本量小的数据,特别是按多个定性变量进行分层且每一层中样本量很小时,     

痘苗病毒天坛株的减毒与其作为疫苗载体研究进展

1痘苗病毒天坛株的历史天花是人类历史上最可怕的传染病之一。天花由天花病毒（variola virus）引起,人是该病毒的惟一宿主。人感染天花病毒后的死亡率达到30%~40%[1]。世界上公认的对天花最早的准确记录来自中国,晋代药学家葛洪于公元430年左右,在《肘后备急方》中对天花有清楚的描述[1]。     

Relevance of muscle biopsy for diagnosing multifocal motor neuropathy

Multifocal motor neuropathy （MMN） is a rare,.focal,inflammatory,demyelinating disease of the peripheral nerves with pure motor involvementJ MMN is clinically characterized by slowly progressive,asymmetric,distal,upper limb predominant weakness,in the absence of sensory disturbances） Weakness is usually multifocal and connected to a distinct motor nerve,such as the musculocutaneous nerve resulting in biceps weakness,the posterior interosseus nerve resulting in finger drop,the median,ulnar,or radial nerve resulting in dexterity problems or grip weakness,or the peroneal nerve resulting in a foot drop.Onset of clinical manifestations is between 20 and 50 years of age.The prevalence of MMN is reported as 1-2 per 100 000.2 MMN is three times more frequent in men as compared to women.     

WHO西太区与世界中医药学会联合会中医名词术语国际标准比较研究：八纲辨证（三）

The Chinese characters 寒 and 热, 虚, and 实 are quite common concepts in Chinese language. However in traditional Chinese medicine （TCM）, they are used as four principles in syndrome differentiation. In terms of translation, 寒 and 热 are very easy to understand and can be simply translated as ＂cold＂ and ＂heat＂. But the transla- tion of 虚 and 实 used to be a problem. For a quite long time in translation practice,     

更好地报告针刺临床试验中的干预措施

“针刺临床试验干预措施报告的标准”(STandardsfor Reporting Interventions in Clinical Trials ofAcupuncture,STRICTA)为作者报告针刺临床试验提供指南。STRICTA旨在帮助临床试验的作者明晰地报告针刺临床试验中所提供的治疗的特定组成部分。我们需要从已发表的试验报告中得到有关干预措施的完整、准确而又透明的信息,从而更好地解释并严格评价其研究结果。CONSORT(Consolidated Standards of ReportingTrials,临床试验报告的统一标准)工作组已着手应对发表的临床试验报告质量低下的问题。CONSORT声明于1996年首次发表[1],之后于2001年[2]和2010年[3]作了修订,该声明为提高平行对照随机临床试验的报告质量制定了指南。最近的修订版即CONSORT2010,包括一份含25项条目的对照检查清单和一张流程图,以及对全部条目的解释和良好报告的实例[3,4]。清单中的条目5涉及干预措施的报告质量。在西医领域中,临床试验干预措施的报告存在诸多问题并已引起注意。有一项研究对这类临床试验报告作了仔细审读,发现...     

Comparison in vitro permeation of curcumin from topical gels by liquid chromatography tandem mass spectrometry

Objective： To fred a more effective method of topical transdermal delivery of curcumin. Methods： We prepared curcumin carbopol （CRB） 974P and hydroxypropylcellulose （HPC） gel formulations containing menthol or Azone as permeation enhancers In this study, negative mode electrospray ionization and a triple quadruple LC/MS/MS instrument operated in multiple reaction mode was used for curcumin detection. The assay was linear over a concentration range of 10 ng/mL to 400 ng/mL for curcumin （average R2 = 0.997 2）. Excised nude mouse dorsal side skin was used in an in vitro skirt permeation study performed using the method of Franz. Results： Our results showed that all of the topical gel formulations we developed were free from skin irritation. The percutaneous flux and enhancement ratio of curcumin across nude mouse epidermis were enhanced markedly by the addition of menthol or Azone to both types of gel formulations. We found that the HPC gels containing quantities of Azone showed an enhanced permeation effect as compared to gels containing menthol. In the case of HPC gels containing Azone, the increase in permeability was significant （P〈0.05） as compared to the gels containing menthol. Conclusion： Azone shows a significantly more remarkable permeation effect than menthol. As such, this novel delivery strategy offers significant promise and is worthy of further exploration in attempts to enhance the medicinal application of curcumin