Effects of Rubus coreanus on sperm parameters and cAMP-responsive element modulator (CREM) expression in rat testes

Rubi Fructus (RF), the dried, unripe fruit of Rubus coreanus M IQ. (Rosaceae), has been used to improve male reproductive function in traditional Korean medicine. In this study, we investigated the effects of RF on sperm parameters and expression of cAMP-responsive element modulator (CREM), which has a crucial role in spermatogenesis. RF was administered to 8-week-old male Wistar rats for 56 consecutive days (1.0 g/kg, daily, p.o.). Sperm analysis, RT-PCR, and Western blot assays were then carried out. The RF-treated animals showed significant increases in the weight of the testes, epididymal sperm count, and sperm motility compared to the control group. RF also increased the expression of CREM at both the mRNA and protein levels. These results suggest that RF may improve male fertility by enhancing spermatogenesis.     

A novel dual-target steroid sulfatase inhibitor and antiestrogen: SR 16157, a promising agent for the therapy of breast cancer

Endocrine therapy is the ideal treatment choice for estrogen receptor α (ERα)-positive breast cancer patients. Principal used therapies target either the ERα e.g. by selective ERα modulators (SERMs) such as tamoxifen or target estrogen biosynthesis with aromatase inhibitors. Steroid sulfatase (STS) plays a crucial role in formation of compounds with estrogenic properties, converting inactive sulfate-conjugated steroids to active non-conjugated forms. Steroid sulfates are considered as a reservoir for active steroids due to their prolonged half-life and increased concentration in plasma. STS is present in several tissues including the breast, and the STS the mRNA level and enzyme activity is significantly increased in ERα-positive breast tumors. Inhibition of STS is therefore a new approach for decreasing estrogenic steroids that stimulate breast cancer. The novel dual-acting compound SR 16157 is designed as a sulfamate-containing STS inhibitor that releases a tissue-selective SERM SR 16137. Use of a dual-target STS inhibitor and SERM represents a new strategy in the treatment of hormone-dependent breast cancer. In this study, we tested the potential of SR 16157 and SR 16137 on STS activity, cell growth and ERα function in MCF-7 breast cancer cells. We confirmed that the dual-target compound SR 16157 exerts STS inhibition and antiestrogenic effects. SR 16157 was a highly effective growth inhibitor, being 10 times more potent than the antiestrogens SR 16137 and tamoxifen. Relative to tamoxifen, SR 16137 displays profoundly improved ERα binding affinity and antiestrogenic effects on expression of estrogen-regulated genes. Thus, the dual-target SR 16157 is possibly a promising new treatment alternative, superior to tamoxifen.     

活性氧调控因子1在人退变椎间盘中的表达及意义

目的　探讨活性氧调控因子1（reactive oxygen species modulator 1,ROMO1）在退变椎间盘髓核中的表达。 方法　采用免疫组化和荧光探针DCFH-DA检测不同退变髓核组织中ROMO1的表达与(reactive oxygen species, ROS)含量,并分析ROMO1表达水平与ROS含量、椎间盘退变程度的相关性。 结果　各组ROMO1的平均光密度值依次为0.192±0.089、0.328±0.048、0.399±0.053、0.468±0.098;各组ROS结果分别为132.961±15.149、191.889±17.880、218.056±12.845、243.501±30.279。随着椎间盘退变程度的加重, ROMO1蛋白表达量与ROS含量逐渐升高,且差异具有显著性(P<0.05)。ROMO1的表达水平与ROS的含量及椎间盘退变程度均呈正相关关系（P＜0.05）。 结论　ROMO1的表达水平与椎间盘的退变程度呈正相关,这可能与其增加髓核组织内ROS含量而加重氧化应激损伤有关。     

Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy

Objectives. To evaluate the neuronal nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy in patients with major depressive disorder (MDD) and inadequate response to prior antidepressant treatment. Methods. Study 004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised, active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.1, 1 or 4 mg in Study 005) or placebo, adjunct to ongoing SSRI/SNRI. Primary efficacy endpoint was change in MADRS total score from randomisation (Week 8) to treatment end (Week 16). Secondary endpoints included MADRS response and remission, and changes in SDS and HAM-D-17-item scores. Safety and tolerability were monitored throughout. Results. Studies 004 and 005 randomised 640 and 696 patients, respectively, to TC-5214 or placebo. No statistically significant improvements in MADRS total score or any secondary endpoints were seen with TC-5214 versus placebo in either study at treatment end. The most commonly reported adverse events (> 10%) with TC-5214 were constipation, dizziness and dry mouth. Conclusions. TC-5214 adjunct to antidepressant was generally well tolerated. However, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy.     

PUMA与Caspase-3在乳腺癌组织中的表达及临床意义

目的:探讨乳腺癌组织中p53正向细胞凋亡调控因子(PUMA)和Caspase-3的表达及临床意义.方法:采用免疫组织化学方法检测65例浸润性乳腺癌、25例乳腺纤维腺瘤及20例乳腺癌旁组织中PUMA和Caspase-3的表达情况.结果:PUMA在浸润性乳腺癌组织中的表达明显低于乳腺纤维腺瘤组织(15.4％ vs 36.0％,P＜0.05),乳腺纤维腺瘤组织中的表达明显低于乳腺癌旁组织(36.0％ vs 70.0％,P＜0.05).PUMA的表达与肿瘤淋巴结转移、TNM分期、术后复发、雌激素受体(ER)及人类表皮生长因子受体-2(HER-2)密切相关(P＜0.05).Caspase-3在乳腺癌组织中的表达明显低于乳腺纤维腺瘤组织(21.5％ vs 44.0％,P＜0.05),乳腺纤维腺瘤组织中的表达明显低于乳腺癌旁组织(44.0％ vs 80.0％,P＜0.05).Caspase-3的表达与淋巴结转移、术后复发、ER、HER-2及肿瘤分化程度密切相关(P＜0.05).PUMA与Caspase-3在浸润性乳腺癌组织中的表达呈正相关(r=0.491,P＜0.05).结论:PUMA和Caspase-3在浸润性乳腺癌的发生、发展中起着重要作用,可能成为乳腺癌的分子标志物或治疗的新靶点.     

PUMA在唾液腺腺样囊性癌中的表达及临床意义

目的:研究p53上调凋亡调控因子(p53 up-regulated modulator of apoptosis,PUMA)在唾液腺腺样囊性癌(salivary cystic carcinoma,SACC)癌组织及癌旁组织中的表达,探讨PUMA在SACC发生、发展中的作用.方法:利用实时定量PCR(RT-PCR)和Western免疫印迹法分别检测27例SACC癌旁组织和27例SACC癌组织中PUMA基因和PUMA蛋白的表达.采用SPSS19.0软件包对数据进行统计学分析.结果:以SACC癌旁组织作为对照样本.其PUMA基因表达相对定量为1,SACC癌组织中PUMA基因表达相对定量为0.57±0.17.PUMA蛋白在SACC癌旁组织和癌组织中表达的相对量分别为0.94±0.12和0.36±0.12.SACC癌组织中PUMA基因和PUMA蛋白的表达显著低于SACC癌旁组织(P＜0.05).结论:PUMA基因在SACC中的表达下调,与SACC的发生呈负相关.     

p53、PUMA、MCL-1对于凋亡途径的调控

p53是一个众所周知的肿瘤抑制基因,目前的研究表明,其在控制细胞周期动力学、细胞凋亡和肿瘤发生中起着重要的作用。p53的诱导凋亡作用对抑制肿瘤发生至关重要,其能激活多种凋亡相关基因的表达,但其决定性作用的机制尚不明确。p53上调凋亡调控因子(PUMA)与髓细胞白血病基因1(MCL-1)作为p53的靶分子,在决定细胞是否凋亡的过程中起重要作用。该文对细胞凋亡过程中p53基因的激活及其对下游PUMA、MCL-1作用的研究进行综述。