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982.
983.
《Bioorganic & medicinal chemistry letters》2019,29(22):126728
One of the regulatory mechanisms of epigenetic gene expression is the post-translational methylation of arginine residues, which is catalyzed by protein arginine methyltransferases (PRMTs). Abnormal expression of PRMT4/CARM1, one of the PRMTs, is associated with various diseases, including cancers. Here, we designed and synthesized a Förster resonance energy transfer (FRET)-based probe, FRC, which contains coumarin and fluorescein fluorophores at the N-terminus and C-terminus of a peptide containing an arginine residue within an appropriate amino acid sequence to serve as a substrate of CARM1; the two fluorophores act as a FRET donor and a FRET acceptor, respectively. Since trypsin specifically hydrolyzes the arginine residue, but not a monomethylarginine or dimethylarginine residue, CARM1 activity can be evaluated from the change of the coumarin/fluorescein fluorescence ratio of FRC in the presence of trypsin. 相似文献
984.
Inhibitory Effect of Hsa‐miR‐590‐5p on Cardiosphere‐derived Stem Cells Differentiation Through Downregulation of TGFB Signaling 下载免费PDF全文
985.
986.
Geetha Nalairndran Ivy Chung Azad Hassan Abdul Razack Felicia Fei-Lei Chung Ling-Wei Hii Wei-Meng Lim Chin King Looi Chun-Wai Mai Chee-Onn Leong 《Journal of cellular and molecular medicine》2021,25(17):8187-8200
Prostate cancer (PCa) is the second most common malignancy and is the fifth leading cause of cancer mortality among men globally. Docetaxel-based therapy remains the first-line treatment for metastatic castration-resistant prostate cancer. However, dose-limiting toxicity including neutropenia, myelosuppression and neurotoxicity is the major reason for docetaxel dose reductions and fewer cycles administered, despite a recent study showing a clear survival benefit with increased total number of docetaxel cycles in PCa patients. Although previous studies have attempted to improve the efficacy and reduce docetaxel toxicity through drug combination, no drug has yet demonstrated improved overall survival in clinical trial, highlighting the challenges of improving the activity of docetaxel monotherapy in PCa. Herein, we identified 15 lethality hits for which inhibition could enhance docetaxel sensitivity in PCa cells via a high-throughput kinome-wide loss-of-function screen. Further drug-gene interactions analyses identified Janus kinase 1 (JAK1) as a viable druggable target with existing experimental inhibitors and FDA-approved drugs. We demonstrated that depletion of endogenous JAK1 enhanced docetaxel-induced apoptosis in PCa cells. Furthermore, inhibition of JAK1/2 by baricitinib and ruxolitinib synergizes docetaxel sensitivity in both androgen receptor (AR)–negative DU145 and PC3 cells, but not in the AR-positive LNCaP cells. In contrast, no synergistic effects were observed in cells treated with JAK2-specific inhibitor, fedratinib, suggesting that the synergistic effects are mainly mediated through JAK1 inhibition. In conclusion, the combination therapy with JAK1 inhibitors and docetaxel could be a useful therapeutic strategy in the treatment of prostate cancers. 相似文献
987.
988.
Michael Remesic Giorgia Macedonio Adriano Mollica Frank Porreca Victor Hruby Yeon Sun Lee 《Bioorganic & medicinal chemistry》2018,26(12):3664-3667
In an effort to improve biphalin’s potency and efficacy at the µ-(MOR) and δ-opioid receptors (DOR), a series of cyclic biphalin analogues 1–5 with a cystamine or piperazine linker at the C-terminus were designed and synthesized by solution phase synthesis using Boc-chemistry. Interestingly, all of the analogues showed balanced opioid agonist activities at all opioid receptor subtypes due to enhanced κ-opioid receptor (KOR) activity. Our results indicate that C-terminal flexible linkers play an important role in KOR activity compared to that of the other cyclic biphalin analogues with a hydrazine linker. Among them, analogue 5 is a potent (Ki?=?0.27, 0.46, and 0.87?nM; EC50?=?3.47, 1.45, and 13.5?nM at MOR, DOR, and KOR, respectively) opioid agonist with high efficacy. Based on the high potency and efficacy at the three opioid receptor subtypes, the ligand is expected to have a potential synergistic effect on relieving pain and further studies including in vivo tests are worthwhile. 相似文献
989.
Effects of C10‐ and C12‐chain length alkyl analogs of monochamol on attraction of longhorn pine sawyer Monochamus saltuarius (Coleoptera: Cerambycidae) 下载免费PDF全文
Sung‐Min Lee Do Kyung Hong Sei‐Heon Jang Kyeong‐Yeoll Lee ChangWoo Lee 《Entomological Research》2018,48(5):446-450
The aggregation pheromone of Monochamus (Coleoptera: Cerambycidae) beetles, 2‐(undecyloxy) ethanol (hereafter referred to as monochamol), has gained considerable attention because of its usefulness in monitoring and population control of pine sawyer beetles. The hydroxyether structural motif is conserved in pheromones of the subfamily Lamiinae of the Cerambycidae. In this study, we investigated the effects of C10‐ and C12‐chain length alkyl analogs of monochamol, 2‐(decyloxy) ethanol and 2‐(dodecyloxy) ethanol, on attracting M. saltuairus in Andong, Gyeongsangbuk‐do, Korea. The C10 and C12 analogs attracted M. saltuarius when used in combination with α‐pinene and ethanol, but the responses of these alkyl chain analogs were lower than those of monochamol. Furthermore, the addition of either C10 or C12 analog to the use of monochamol with α‐pinene and ethanol had no effect on attraction of M. saltuarius, indicating high sensitivity of M. saltuarius to monochanol. Taken together, the results of this study suggest that chemical communication within a Monochamus species depends not only on monochamol, but also on other semiochemicals. 相似文献
990.
摘要 目的:探讨益心康泰胶囊联合硫氮唑酮对不稳定型心绞痛(UAP)患者心功能及血清ET-1、Hcy、cTnT水平的影响。方法:选择2019年3月到2021年3月期间在我院接受治疗的UAP患者84例,按照随机数字表法分为研究组和对照组各42例,对照组给予阿司匹林、硝酸酯类、?茁-受体阻滞剂及他汀类药物等常规治疗,研究组在其基础上给予益心康泰胶囊联合硫氮唑酮治疗,两组均治疗30 d。对比两组患者的心绞痛疗效、心功能指标、血清学指标、心绞痛发作次数和持续时间、不良反应发生率。结果:研究组临床总有效率高于对照组(P<0.05)。研究组治疗后的QT间期离散度(QTd)、左室舒张末径(LVEDD)、左室收缩末径(LVESD)均低于对照组,而左室射血分数(LVEF)高于对照组 (P<0.05)。治疗后研究组心绞痛发作次数和持续时间均低于对照组(P<0.05)。治疗后研究组患者的血管内皮素1(ET-1)、同型半胱氨酸(Hcy)、心肌肌钙蛋白T(cTnT)水平均低于对照组(P<0.05)。两组不良反应总发生率无明显差异(P>0.05)。结论:益心康泰胶囊联合硫氮唑酮治疗UAP患者疗效较好,能减少患者心绞痛持续时间和发作次数,增强患者的心功能,降低ET-1、Hcy、cTnT水平,且具有较好的安全性,具有一定临床应用价值。 相似文献