Stilbenes and oligostilbenes from leaf and stem of <Emphasis Type="Italic">Vitis amurensis</Emphasis> and their cytotoxic activity

Chromatographic separation of the EtOAc fraction from the leaf and stem of Vitis amurensis led to the isolation of six oligostilbenoids (i.e., r-2-viniferin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), gnetin H (4), amurensin G (5), (+)-ampelopsin A (8)) and four stilbenoids (i.e., trans-resveratrol (6), (+)-ampelopsin F (7), piceatannol (9), and trans-piceid (10)). The structures have been identified on the basis of spectroscopic evidence and physicochemical properties. The isolates were investigated for cytotoxic activity against three cancer cell lines in vitro using the MTT assay method. Amurensin G (5) and trans-resveratrol (6) showed significant cytotoxic activity against L1210, K562 and HTC116 cancer cell lines with IC₅₀ values ranging from 15.7 ± 2.1 to 30.9 ± 1.8 μM. (+)-Ampelopsin A (8) and trans-piceid (10) exhibited considerable cytotoxic activity against L1210 (IC₅₀ values of 30.6 ± 4.1 and 28.7 ± 2.81 μM, respectively) and K562 (IC₅₀ values of 38.6 ± 0.82 and 24.6 ± 0.76 μM, respectively). Gnetin H (4) showed only weak cytotoxic activity against L1210 with an IC₅₀ value of 40.1 ± 4.23 μM. On the other hand, r-2-viniverin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), (+)-ampelopsin F (7), and piceatannol (9) exhibited no activity on three cancer cell lines.     

质子泵抑制剂市场前景看好

目的：消化性溃疡是一种常见病和多发病,质子泵抑制剂是目前治疗消化性溃疡病抑制胃酸分泌最强的药物,质子泵抑制剂市场的现状和进展是人们关注的热点。方法：调查近年来长江流域上海、杭州、南京、武汉、成都和重庆六城市样本医院质子泵抑制剂品种用药金额、排序、份额、增长率及临床评价。结果：常用品种为奥美拉唑、泮托拉唑、埃索美拉唑、雷贝拉唑和兰索拉唑,其中用药金额名列第1是奥美拉唑,第2是泮托拉唑。结论：质子泵抑制剂市场前景看好。     

β射线敷贴治疗婴幼儿血管瘤的疗效观察

目的评价放射性核素。2P、90Y对婴幼儿皮肤血管瘤的治疗效果。方法采用32P、90Y放射性核素局部近距离照射治疗不同类型的婴幼儿血管瘤,总吸收剂量10～25Gv,2～3个月为1个治疗周期,观察治疗效果。结果弛P治疗172例患儿治疗总有效率为89．5％;90Y治疗110例患儿治疗总有效率为78．2％,与其它类型血管瘤相比,草莓状血管瘤患儿32P敷贴治疗有效率可达94．3％。结论32P、90Y敷贴治疗婴幼儿皮肤血管瘤特别是豫P敷贴治疗对草莓状血管瘤是一种疗效确切、不良反应少的治疗手段,但得在治疗过程中严格控制剂量。     

CYP1A1 and CYP1B1 genetic polymorphisms and uterine leiomyoma risk in Chinese women

Purpose  The aim of the study was to evaluate the association of CYP1A1 and CYP1B1 polymorphisms with uterine leiomyoma in Chinese women. Methods  We investigated 100 women with clinically diagnosed uterine leiomyoma and 110 healthy normal subjects from Chinese women. The genetic distribution of two CYP1A1 polymorphisms at MspI, Ile462Val and four CYP1B1 polymorphisms at Arg48Gly, Ala119Ser, Leu432Val, Asp449Asp were analyzed by polymerase chain reaction–restriction fragment length polymorphism and DNA sequencing method. Results  All the SNPs showed polymorphisms in Chinese women. The genotype A/G and the allele G on Ile462Val was significantly different between uterine leiomyoma patients and controls (P < 0.05). Conclusion  These results suggest that the genotype of CYP1A1 Ile462Val was associated with the increased risk of uterine leiomyomas in Chinese women. Capsule This is the first report that demonstrates the polymorphism at Ile462Val of CYP1A1 to be associated with uterine leiomyoma in Chinese women.     

Thailandepsins are new small molecule class I HDAC inhibitors with potent cytotoxic activity in ovarian cancer cells: a preclinical study of epigenetic ovarian cancer therapy

Background

New treatment strategies are emerging to target DNA damage response pathways in ovarian cancer. Our group has previously shown that the class I biased HDAC inhibitor romidepsin (FK228) induces DNA damage response and has potent cytotoxic effects in ovarian cancer cells. Here, we investigated newly discovered HDAC inhibitors, thailandepsin A (TDP-A) and thailandepsin B (TDP-B), to determine the effects on cell viability, apoptosis and DNA damage response in ovarian cancer cells.

Methods

FK228, TDP-A and TDP-B were tested in five ovarian cancer cell lines. Cellular viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Immunofluorescence assays were used to assess activated caspase 3. Western blots were performed to detect protein expression of PARP cleavage, pH2AX, P-glycoprotein and tubulin acetylation.

Results

Treatment with TDPs decreased cell viability at nanonomolar concentrations in four of the five ovarian cancer cell lines studied. Similar to FK228, both TDP compounds exerted minimal effects on NCI/ADR-RES ovarian cancer cells. Across the four cell lines sensitive to the TDPs, TDP-B consistently had a greater inhibitory effect than TDP-A on cell viability. TDP-B also had relatively greater effects on promoting cell apoptosis and induction of pH2AX (a mark of DNA damage response), than TDP-A. These antitumor effects of TDP-B were of similar magnitude to those induced by an equal concentration of FK228. Similar to FK228, the nanomolar concentrations of the TDPs had little effect on tubulin acetylation (a mark of class II HDAC6 inhibition).

Conclusions

The new small molecule HDAC inhibitors TDP-A and TDP-B are FK228 analogues that suppress cell viability and induce apoptosis at nanomolar drug concentrations. TDP-B showed the most similarity to the biological activity of FK228 with greater cytotoxic effects than TDP-A in vitro. Our results indicate that FK228-like small molecule class I HDAC-biased HDAC inhibitors have therapeutic potential for ovarian cancer.     

尿皮素对体外培养的人脐静脉内皮细胞一氧化氮及一氧化氮合酶的影响

目的:通过检测尿皮素(UCN)对人脐静脉内皮细胞(HUVEC)一氧化氮(NO)生成及一氧化氮合酶(NOS)表达的影响,探讨UCN调节胎儿-胎盘血管张力的分子机制。方法:在离体培养的HUVEC中加入不同浓度的UCN(0、0.1、1、10nmol/L)、10nmol/L促肾上腺皮质激素释放激素(CRH)及向以上各组UCN/CRH同时加α-helical-CRH进行体外培养,用硝酸还原酶法检测细胞上清液中NO的水平,蛋白印迹法检测内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)蛋白表达水平的变化。结果:在与UCN共同培养4~8h后,HUVEC细胞上清液中NO水平呈时间和剂量依赖性变化,随着培养时间的延长,UCN浓度增加,NO水平逐渐升高;UCN组HUVEC iNOS表达水平比对照组明显升高(P<0.05),且呈浓度依赖性升高。而各组eNOS表达水平与对照组比较无明显变化(P>0.05)。UCN/CRH α-helical-CRH组HUVEC上清液中NO水平和HU-VEC iNOS表达水平与对照组比较无明显变化,差异无统计学意义(P>0.05),与相同浓度UCN/CRH组比较NO水平和iNOS蛋白表达水平明显降低,差异有统计学意义(P<0.05)。结论:UCN可促HUVEC合成及释放NO,NO生成增多与UCN通过促进肾上腺皮质激素释放激素2β受体(CRH-R2β)正相调节iNOS蛋白表达有关,这可能是UCN调节胎儿-胎盘血管张力的分子机制之一。     

儿童肾癌的临床及CT和病理特点分析

目的 探讨儿童肾癌的临床、CT及病理特点,积累其临床诊治经验.方法 回顾性分析2014年至2016年单中心收治的7例儿童肾癌患儿的临床、CT、病理资料,并随访其生存情况.就诊时年龄5～12岁,女4例,男3例,左侧5例,右侧2例.临床表现多为血尿(4/7)、腹部包块(3/7)、腰痛(1/7).CT平扫肿瘤呈低密度,多位于上下极,可见钙化(6/7)及坏死区,增强特点多为“快进快出”(4/7),部分为“快进慢出”(2/7).结果 7例患儿全部获得随访,随访时间8～35个月.1例肿瘤位于左腹膜后,确诊时已发生腹膜后及颈部淋巴结转移,行肿瘤部分切除活检,术后5个月死亡.1例为复发性肾癌,行肾窝肿瘤切除加腹膜后淋巴结清扫,术后5个月出现淋巴结转移,予放化疗后带瘤生存.余5例患儿均行根治性肾切除加淋巴结清扫,术后均无瘤生存.病理多为肾透明细胞(5/7)及乳头状肾细胞癌(2/7),癌细胞呈巢团状、乳头状、腺管样结构分布,可见砂粒体(6/7),核级多为3～4级.4例患儿淋巴结转移,共清扫出60枚淋巴结,淋巴结阳性率为16.7％.5例加做免疫组化,TFE3 (4/5)、CD10 (5/5)、Kb67 (4/5)、E-cardherin (4/5)、Vinentin (3/5)、CK(3/5)阳性率较高,4例确诊为MiT家族异位性肾癌.结论 儿童肾癌多发生于年长患儿,有其特有的临床、CT及病理特点,MiT家族异位性肾癌常见,病理及免疫组化是确诊和分型的主要手段.     

雷珠单抗联合光动力疗法对年龄相关性黄斑变性CNV的治疗效果

目的:探讨雷珠单抗联合光动力疗法治疗年龄相关性黄斑变性对脉络膜新生血管(choroidal neovascularization,CNV)渗漏及视力的影响.方法:选取2012-01/2015-12在我院接受治疗的78例86眼年龄相关性黄斑变性患者作为研究对象,采用随机数字表分为联合组(雷珠单抗联合光动力疗法)39例42眼、对照组(单用雷珠单抗治疗)39例44眼,对比两组患者治疗前后的视力、CNV渗漏情况变化.结果:治疗后第6、12wk,联合组患者的最佳矫正视力(best corrected visual acuity,BCVA)测定值均大于对照组,差异具有统计学意义(P<0.05);联合组患者的黄斑中心凹视网膜厚度(central macular retinal thick,CRT)测定值均小于对照组,差异具有统计学意义(P<0.05);治疗12wk后,联合组的CNV渗漏治疗总有效率(90%)与对照组(82%)比较,差异无统计学意义(P>0.05).结论:雷珠单抗联合光动力疗法治疗年龄相关性黄斑变性对CNV渗漏、视力及CRT均具有较好的改善作用.     

Three-year follow-up in advanced pediatric keratoconus: thin corneas may not have pachymetry properly assessed after crosslinking

AIM: To analyze the crosslinking (CXL) effects in pediatric keratoconus, and to identify the patients’ corneal characteristics whose pachymetry could not be adequately evaluated by Scheimpflug method after procedure. METHODS: Consecutive pediatric patients with progressive keratoconus underwent CXL were included. Best-corrected visual acuity (BCVA) and spheric equivalent (SE) were measured before and after CXL. After CXL, groups 1 and 2 were divided based on the posterior surface Pentacam quality specifications (QS): “OK” (Group 1) and “not OK” (Group 2). The mean (RmF and RmB) and minimum (RminF and RminB) radius of curvatures of the anterior and posterior corneal surfaces, and the thinnest pachymetry (Pmin) were measured preoperatively at 3, 6, 12, 24, and 36mo. Haze was annotated. RESULTS: Twenty-six patients (14 men, mean age 14±1.8y) and median Kmax of 59.9 D initially and 61.4 D preoperatively were treated. BCVA was not different before and 24mo after CXL. Group 2 statistically differed to group 1 in that SE was more myopic before and with no difference 24mo after CXL; RmF and RmB were steeper and Pmin was thinner pre-surgically. Group 2, in which pachymetric changes could not be adequately evaluated after surgery, presented with significant RmF flattening, a shift to hyperopia, and more haze after CXL. CONCLUSION: Patients whose pachymetry could not be adequately evaluated after CXL had steeper and thinner corneas before surgery. The predictive factors for impaired QS after CXL are RmF, RmB, and Pmin. In advanced keratoconus, alternative methods to analyze pachymetry and the posterior surface should be considered.     

Intestinal Peptide Transport Systems and Oral Drug Availability

The intestinal peptide transport system has broad substrate specificities. In addition to its physiological function of absorbing di- and tripeptides resulting from the digestion of dietary proteins, this transport system also absorbs some orally administered peptidomimetic drugs, including -lactam antibiotics, angiotensin converting enzyme inhibitors, renin inhibitors, bestatin, thrombin inhibitors, and thyrotropin-releasing hormone and its analogues. There have been several studies on the mechanism and substrate structure-affinity relationship for this transport system. Rapid progress has been made recently in studies on the molecular basis of the intestinal peptide transport system. A protein apparently involved in peptide transport has been isolated from rabbit small intestines, and genes for human intestinal peptide transporters have been cloned, sequenced and functionally expressed. This review summarizes these studies and addresses the pharmaceutical potential of the intestinal peptide transport system.