Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

PRMT5和CDKN2B在宫颈癌组织的表达及临床意义

目的研究蛋白精氨酸甲基转移酶5(PRMT5)、细胞周期蛋白依赖性激酶抑制剂2B(CDKN2B)在宫颈癌中的表达及临床意义。方法收集2019年3月—2020年3月南京大学医学院附属鼓楼医院妇产科诊治宫颈癌患者88例。免疫组织化学法检测宫颈癌和癌旁组织中PRMT5、CDKN2B表达;采用Spearman相关分析PRMT5与CDKN2B表达的相关性;比较不同临床特征宫颈癌癌组织中PRMT5、CDKN2B表达的差异;Kaplan-Meier曲线评估PRMT5、CDKN2B表达对宫颈癌患者无进展生存预后的影响;多因素Cox回归分析宫颈癌患者无进展生存预后的影响因素。结果癌组织中PRMT5蛋白阳性率70.45%(62/88),高于癌旁组织6.82%(6/88)(χ^(2)=75.155,P<0.001)。宫颈癌组织中CDKN2B阳性率22.73%(20/88),低于癌旁组织79.55%(71/88)(χ^(2)=75.336,P<0.001)。宫颈癌中PRMT5与CDKN2B呈负相关(r=-0.734,P<0.001)。FIGOⅠB2~ⅡA期、有淋巴结转移宫颈癌组织中PRMT5阳性率高于FIGOⅠA~ⅠB1期、无淋巴结转移者,而CDKN2B阳性率则降低(χ^(2)/P=6.359/0.012、4.606/0.032、5.205/0.023、3.893/0.048)。PRMT5阳性组3年累积无进展生存率74.19%(46/62),低于PRMT5阴性组92.31%(24/26)(Log-Rankχ^(2)=4.386,P=0.017)。CDKN2B阴性组3年累积无进展生存率75.00%(51/68),低于CDKN2B阳性组95.00%(19/20)(Log-Rankχ^(2)=4.423,P=0.012)。FIGO分期ⅠB2~ⅡA期、合并淋巴结转移、PRMT5阳性、CDKN2B阴性是影响宫颈癌患者无进展生存预后的独立危险因素[OR(95%CI)=1.407(1.159~1.696),1.464(1.201~1.784),1.614(1.189~2.192),1.595(1.191~2.136)]。结论宫颈癌组织中PRMT5表达升高,CDKN2B表达降低,两者与宫颈癌患者的不良临床病理特征有关,是评估宫颈癌预后的标志物。

磷酸二酯酶5在心力衰竭中作用的研究进展

磷酸二酯酶5(PDE5)是环磷酸鸟苷(cGMP)特异性水解酶,是由一氧化氮(NO)激活的可溶性鸟苷酸环化酶(sGC)靶向cGMP产生的。PDE5催化cGMP中磷酸二酯键的水解,从而将cGMP转化为无活性的5′-GMP形式,cGMP-PKG轴功能障碍将引起心脏重塑,是心力衰竭(HF)的主要原因之一。但PDE5抑制剂治疗心力衰竭的临床疗效存在争议。本文总结了近年来PDE5在心力衰竭中的作用机制和研究进展,对未来临床应用PDE5靶向治疗心力衰竭具有重要的指导意义。

老年经皮冠状动脉介入治疗术后支架内再狭窄患者胱抑素C、基质金属蛋白酶抑制剂-1、分泌型卷曲相关蛋白5表达及临床意义

目的探讨老年经皮冠状动脉介入治疗(PCI)术后支架内再狭窄(ISR)患者胱抑素C(CysC)、基质金属蛋白酶抑制剂-1(TIMP-1)、分泌型卷曲相关蛋白5(SFRP-5)表达及对靶血管病变的预测价值。方法选取2020年5月至2022年5月保定市第一中心医院PCI术后1年内发生ISR的65例老年冠心病患者作为观察组,选取同期65例PCI术后1年内未发生ISR的老年冠心病患者作为对照组,比较两组一般资料、术后血清CysC、TIMP-1、SFRP-5水平,分析血清CysC、TIMP-1、SFRP-5水平与ISR发生的相关性,并比较观察组不同Mehran分型患者血清CysC、TIMP-1、SFRP-5水平,分析各指标水平与Mehran分型的相关性,分析血清CysC、TIMP-1、SFRP-5水平预测靶血管发生ISR的价值。结果观察组血清CysC水平高于对照组(t=6.949,P<0.05),TIMP-1、SFRP-5水平低于对照组(t=7.301、8.765,P<0.05);血清CysC水平与ISR的发生呈正相关(r=0.587,P<0.05),TIMP-1、SFRP-5水平与ISR的发生呈负相关(r=-0.609、-0.640,P<0.05)。观察组四种Mehran分型的患者CysC、TIMP-1、SFRP-5水平差异有统计学意义(F=10.759、8.326、19.764,P<0.05)。随着Mehran分型Ⅰ型到Ⅳ型的变化,CysC水平逐渐升高,TIMP-1、SFRP-5水平逐渐下降,差异有统计学意义(P<0.05)。血清CysC水平与ISR患者Mehran分型呈正相关关系(r=0.722,P<0.05),TIMP-1、SFRP-5水平与Mehran分型呈负相关关系(r=-0.799、-0.826,P<0.05)。血清CysC、TIMP-1、SFRP-5水平预测老年冠心病患者PCI术后1年内靶血管发生ISR的曲线下面积(AUC)分别为0.807(95%CI=0.729~0.871)、0.786(95%CI=0.706~0.853)、0.811(95%CI=0.733~0.874),联合预测的AUC最大,为0.943(95%CI=0.887~0.976)。结论老年冠心病PCI术后患者血清CysC水平升高,TIMP-1、SFRP-5水平降低与ISR的发生发展相关,术后早期检测各指标水平有助于预测靶血管发生ISR风险。

NDM-5-C208A突变大肠埃希菌的构建及大蒜辣素与NDM-5相互作用位点分析

[目的]产新德里金属β-内酰胺酶5(NDM-5)的革兰阴性耐药菌对人畜健康产生巨大威胁。本文旨在初步探究大蒜辣素对NDM-5的抑制作用及其相关作用位点,为临床开发新型β-内酰胺酶抑制剂提供理论支持。[方法]通过AutoDock模拟分子对接,预测大蒜辣素与NDM-5的结合位点;构建突变型载体pET21a-NDM-5-C208A,测序验证无误后转入感受态大肠埃希菌BL21(DE3),通过药敏试验进行突变表型确认;采用微量肉汤棋盘法和时间杀菌曲线测定大蒜辣素与美罗培南对NDM-5突变型细菌的联合抑菌效果。通过体外表达突变蛋白NDM-5-C208A,建立酶活性测定体系,比较大蒜辣素对C208突变型NDM-5和野生型NDM-5酶活性的抑制效果。[结果]经测序证实NDM-5的C208A突变株BL21(DE3)pET21a-NDM-5-C208A构建成功,C208A突变株恢复了对头孢类和碳青霉烯类抗生素的敏感性,且大蒜辣素与美罗培南联用的联合抑菌指数由0.375增加至2,联用表现为独立作用而非协同作用;体外酶活测定结果显示NDM-5-C208A突变不仅使酶活性下降约85%,而且该位点突变导致大蒜辣素对NDM-5失去抑制作用。[结论]Cys208位点是维持NDM-5水解酶活性的关键位点,且大蒜辣素可通过与该位点结合发挥抑制酶活性的作用。该结果为大蒜辣素作为新型β-内酰胺酶抑制剂的开发和应用提供试验依据。

The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia

Benign prostatic hyperplasia(BPH)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.Common in older men,BPH is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPH-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DHT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DHT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPHdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPH-related surgery.Therefore,either alone or in combination with other BPH medications,5-ARIs are a mainstay of BPH management.

Histone deacetylase inhibitor pracinostat suppresses colorectal cancer by inducing CDK5-Drp1 signaling-mediated peripheral mitofission

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofissionassociated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of paninhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynaminrelated protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

Medical therapy for clinical benign prostatic hyperplasia:α1 Antagonists,5α reductase inhibitors and their combination

Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing urologist must decide on the most appropriate medication for his patients,taking into consideration various factors like efficacy,dosing regime,adverse effects,cost,patient’s socioeconomic background,expectations,drug availability and his own clinical experience.The use of combination therapy added further to the complexity in clinical judgment when prescribing.We highlight some of the key points in prescribing a1 antagonists,5ARi and their combination,based on our viewpoints and experience as urologists in an Asian clinical setting.

Beneficial long term effect of a phosphodiesterase-5-inhibitor in cirrhotic portal hypertension:A case report with 8 years follow-up

Non-selective beta-blockers are the mainstay of medical therapy for portal hypertension in liver cirrhosis. Inhibitors of phosphodiesterase-5(PDE-5-inhibitors) reduce portal pressure in the acute setting by > 10% which may suggest a long-term beneficial effect. Currently, there is no available data on long-term treatment of portal hypertension with PDE-5-inhibitors. This case of a patient with liver cirrhosis secondary to autoimmune liver disease with episodes of bleeding from esophageal varices is the first documented case in which a treatment with a PDE-5-inhibitor for eight years was monitored. In the acute setting, the PDE-5-inhibitor Vardenafil lowered portal pressure by 13%. The portal blood flow increased by 28% based onDoppler sonography and by 16% using MRI technique. As maintenance medication the PDE-5-inhibitor Tadalafil was used for eight consecutive years with comparable effects on portal pressure and portal blood flow. There were no recurrence of bleeding and no formation of new varices. Influencing the NO-pathway by the use of PDE-5 inhibitors may have long-term beneficial effects in compensated cirrhosis.

Effects of phosphodiesterase 5 inhibitors on sperm parameters and fertilizing capacity

这评论研究的目的是阐明效果那磷酸二酯酶 5 (PDE5 ) 禁止者在精子上施加活动性， capacitation 过程并且在他们使肥沃的能力上卵母细胞。第二个送信人系统象 cAMP/adenylate cyclase (交流) 那样系统和 cGMP/guanylate cyclase (GC ) 系统看起来调整精子功能。intracytosolic 营地的增加的层次导致精子活动性和生存能力的改进。由氮的氧化物的低剂量的 GC 的刺激(没有) 导致精子活动性的改进或维护，而更高的集中在精子参数上有不利效果。几在活体内和在试管内研究被执行了以便检验 PDE5 禁止者是否断然或否定地影响精子参数和精子使肥沃能力。这些研究的结果是争论的。一些这些研究不在从与 PDE5 禁止者被对待的人收集的精子的活动性，生存能力，和形态学上表明 PDE5 禁止者的重要效果。在另一方面，几研究在精子活动性上表明 PDE5 禁止者的积极效果在活体内和在试管内。sildenafil 柠檬酸盐的在试管内研究随在除 PDE5 以外的 PDE 对碘氧基苯甲醚上建议 sildenafil 柠檬酸盐的一个禁止的行动的细胞内部的营地的增加在精子活动性上表明 stimulatory 效果。在另一方面， tadalafil 的行动看起来在 PDE11 上与这混合物的禁止的效果被联系。在在一个每日的基础与 vardenafil 对待的人的在活体内研究每精液，量的精子活动性，和质的精子活动性表明了精子的一个显著地更大的全部的数字；vardenafil 管理提高前列腺的能分泌的功能并且随后增加精子的质、量的活动性，这被建议了。PDE5 禁止者在精子参数上施加的效果可以导致帮助繁殖技术(艺术) 的结果的改进程序。在未来 PDE5，禁止者可能为男不孕的缓和用作附属物 therapeutical 代理人。

3D-QSAR Studies on 4-([1,2,4]Triazolo[1,5-α]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole Analogues as Potent Inhibitors of Transforming Growth Factor-β Type Ⅰ Receptor Kinase

The transforming growth factor-β(TGF-β) plays a crucial role in the beginning and progression of fibrosis in various organ systems such as lung, heart, liver and kidney. TGF-β type I receptor kinase(activin receptor-like kinase 5, ALK5) inhibitors might have potential activity for the treatment of relevant diseases. In this paper, the three-dimensional quantitative structure-activity relationship(3 D-QSAR) including comparative molecular field analysis(Co MFA) and comparative molecular similarity indices analysis(Co MSIA) were used to analyze the structural requirements based on a dataset of 123 4-([1,2,4]Triazolo[1,5-α]pyridine-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole analogues which acted as ALK5 inhibitors. The obtained Co MFA model(q^2 = 0.652, r^2 = 0.876, r^2 pred = 0.845) and Co MSIA model(q^2 = 0.648, r^2 = 0.884, r^2 pred = 0.853) were robust and satisfactory. The predictive ability of the derived models was validated using a test set of 28 compounds. Additionally, potentially important structural features required to enhance activity were also elucidated by the contour maps derived from Co MFA and Co MSIA models. The results will be helpful to guide drug design strategies aimed at obtaining potent and selective ALK5 inhibitors.

Peptide Inhibitors of HIV-1 Virus Infection Based on Cullin-5

Virion infectivity factor(Vif) is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G(h-APOBEC3G) is a cytidine deaminase only expressed in "nonpermissive" cells and exhibits virus suppressive activity. With the aid of a Cullin-5 E3 ligase, Vif induces h-APOBEC3G degradation and with the destruction of this ligase, Vif is functionally inactive. Therefore, it is expected that blocking this E3 pathway would be a new therapeutic strategy against HIV-1 infection. In this article, the authors' took sequence alignment of the N-termini of Cullin-5 and three other members of the Cullin protein family, respectively. A set of small peptides has been synthesized based on the sequence comparison results and possible Vif-Cullin-5 interaction domains. Moreover, it has been demonstrated that several peptides can reduce virus infectivity in "nonpermissive" cells with a dose-responsive manner, but not in "permissive" cells. The results also indicate that the loss of viral infectivity may be because of the increase of APOBEC3G amount in the peptide-treated cells. It is concluded that peptides derived from Cullin-5 can block the APOBEC3G degradation induced by Vif and suppress HIV-1 infectivity. Therefore this study starts a novel strategy for the development of a new HIV-1 inhibitor.

Evaluation and diagnostic testing of erectile dysfunction in the era of phosphodiesterase type 5 inhibitors

自从安全、有效的口头的治疗的可获得性，可勃起的机能障碍的诊断和处理戏剧性地变化了。不幸地，不是都，人们能足够地这样被对待，并且可能要求诊断并且对待他们的机能障碍的特定的原因的更侵略的测试。这评论看测试和为不能被口头的治疗独自对待的人可得到的策略。

Pre-Androgen Ablation Prostate Cancer Patients Who Bleed Do Well with 5 Alpha Reductase Inhibitors

Background: Patients with gross haematuria are sometimes found to have prostate cancer after clinical evaluation. The treatment of such haematuria could be very challenging. Use of a 5 alpha reductase inhibitor like dutasteride has been found helpful in bleeding prostate cancer patients if they have not undergone hormonal manipulation before they developed haematuria. Patients and Method: 26 patients with gross haematuria of prostatic origin who had histologic confirmation of adenocarcinoma of the prostate but who have not had chemical or surgical castration were randomized to receive daily dutasteride in addition to vigorous saline irrigation and antibiotics on one arm and vigorous saline irrigation and antibiotics only as control on the other arm. The time taken before haematuria resolved and the amount of irrigation fluid used were noted. Statistical analysis was done using SPSS. Student’s t-test and Kaplan Meier survival analysis were used to test various variables at 0.5 significant levels. Results: Of the 26 patients 12(46.2%) received 0.5 mg oral dutasteride in addition to saline irrigation while 14 (53.8%) received saline irrigation only. Haematuria stopped in all of 12 (100%) patients on dutasteride arm but on 12 (85.7%) of the 14 patients on the control arm. It took significantly shorter time and lesser volume of irrigation fluid before haematuria resolved in those treated with dutasteride than in those on the control arm. Conclusion: Dutasteride is effective in the control of acute haematuria in pre-androgen ablation prostate cancer patients.

Are phosphodiesterase type 5 inhibitors effective for the management of lower urinary symptoms suggestive of benign prostatic hyperplasia?

AIM: To review the efficacy of phosphodiesterase type 5 inhibitors(PDE5-Is) in lower urinary tract symptoms(LUTS) suggestive of benign prostate hyperplasia(LUTS/BPH). METHODS: A comprehensive research was conducted to identify all publications relating to benign prostate hyperplasia and treatment with sildenafil, vardenafil and tadalafil. To assess the efficacy, the changes in total international prostate symptom score(IPSS), IPSS subscore including voiding, storage and quality of life(Qo L), Benign prostatic hyperplasia Impact Index(BII), maximum urinary flow rate(Qmax) and the International Index of Erectile Function(IIEF) were extracted. A meta-analytical technique was used for the analysis of integrated data from the included studies to evaluate the mean difference in the results. RESULTS: Total IPSS score, IIEF and BII showed a significant improvement in trials in which LUTS/BPH with or without erectile dysfunction(ED) were compared with the placebo. For LUTS/BPH, the mean differences of total IPSS score, IIEF and BII are-2.17, 4.88 and-0.43, P < 0.00001, respectively. For LUTS/BPH with comorbid ED, the mean difference are-1.97, 4.54 and-0.52, P < 0.00001, respectively. PDE5-Is appear to improve IPSS storage, voiding and Qo L subscore(mean difference =-0.71,-1.23 and-0.33, P < 0.00001, respectively). Although four doses of tadalafil(2.5, 5, 10 and 20 mg) failed to reach significance in Qmax(mean difference = 0.22, P = 0.10), the 5 mg dose of tadalafil significantly improved the Qmax(mean difference = 0.33, P = 0.03).CONCLUSION: PED5-Is demonstrated efficacy for improving LUTS in BPH patients with or without ED and could be considered to be the first line treatment for LUTS/BPH.

Structure-Based Pharmacophore Modeling to Discover Novel CCR5 Inhibitors for HIV-1/Cancers Therapy

CC chemokine receptor 5 (CCR5), a member of G protein-coupled receptors (GPCRs), not only plays a significant role in inflammatory responses, but also correlates with HIV-1 infection and cancer progression. Recently, blocking of CCR5 has been considered as an effective strategy in HIV-1/cancers therapy. So far, only Maraviroc has been approved by FDA in 2007, while the other CCR5 inhibitors have failed in their clinical trials. In this study, a highly selective structure-based pharmacophore model was constructed, validated, and applied for virtual screening to retrieve novel CCR5 inhibitors from NCI database. Finally, one potential CCR5 inhibitor candidate, NSC13165, was identified after molecular docking, molecular dynamics (MD) simulations, binding free energy analyses and ADMET prediction. Docking and MD simulation results not only suggested that NSC13165 reserves the common binding mode of the most known CCR5 inhibitors, but also provided important insights toward the allosteric inhibition mechanism of CCR5. The results of binding free energy analyses indicated that the binding affinity of NSC13165 is much better than that of Maraviroc and that van der Waals interaction is the key driving force during the binding process. ADMET prediction suggested that NSC13165 exhibits very low risk of causing lethal side effects. Altogether, our results strongly suggest that NSC13165 has great potential to serve as a novel CCR5 inhibitor, which may be further tested in vitro/in vivo as a drug target for HIV-1/cancers therapy or be used as a lead compound for improving its efficacy through chemical modifications.

Synthesis and Biological Evaluation of Novel 1, 5-Diarylpyrazole-3- carboxamide Compounds as Inhibitors of ALK5

Ten new 1, 5-diarylpyrazole-3-carboxamide compounds were synthesized and their structures were identified by 1H-NMR and FAB-MS. The primary biological tests showed that compound 4j exhibited some ALK5 inhibitory activity at concentration of 1μmol/L.

High performance thin layer chromatography as an effective tool for rapid screening of 5α-reductase inhibitors

Benign prostatic hyperplasia(BPH)is a common disease in men,and is known to be related to 5α-reductase,which can affect steroid metabolism.Under the promotion of 5α-reductase,testosterone can be converted into dihydrotestosterone(DHT),and excessive DHT will cause related diseases.Since BPH seriously affects the quality of life of patients,it is essential to discover effective 5α-reductase inhibitors.In this study,the simple analytical method of high performance thin layer chromatography(HPTLC)was used to screen active compounds,and seven compounds with strong activity were screened out.This research will provide a reference for studying the material basis of drugs for the treatment of BPH.

5-苯基-1,2,4-噁二唑衍生物的合成及其作为乙酰辅酶A羧化酶抑制剂的生物活性

乙酰辅酶A羧化酶(Acetyl-CoA Carboxylase,ACC)是一种脂肪酸合成限速酶,是肿瘤治疗的热门靶点之一。本文以3-氯苯胺和亚甲基丁二酸为起始原料,经环化、缩合和酰胺化等反应获得了一系列5-苯基-1,2,4-噁二唑类化合物(9a~9i),其中,化合物9a、9b、9e~9h为全新结构,经^(1)H MNR、^(13)C MNR和MS(ESI)进行了表征。通过Molsoft软件计算目标化合物9a~9i的脂水分配系数和类药性分数,使用ADP-Glo^(TM)激酶检测试剂盒检测化合物ACC抑制活性。结果表明:化合物9g在10μM浓度下对ACC抑制活性达到95.26%,与阳性对照药CP-640186相当。

Comparative dissolution study on counterfeit medicines of PDE-5 inhibitors

Counterfeit medicines are a growing problem in both developing and industrialised countries.In general the evaluation of these medicines is limited to the identification and the dosage of the active ingredients.In this study in vitro dissolution tests were conducted on two sets of counterfeit medicines containing PDE-5 inhibitors(sildenafil citrate and tadalafil).The dissolution profiles were statistically compared to the ones of the genuine products using the f_2-method and a comparison at each time point using the Cochran test.The results showed low equivalences between counterfeit and genuine products as well as higher variations around the mean dissolution value at the different time points for the counterfeit products.