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1.
干细胞是一类具有多向分化潜能的细胞群,如胚胎干细胞(embryonic stem cell,ESC)、诱导多潜能干细胞(induced pluripotent stem cell,i PSC)等,可在特定的条件下向包括视网膜感光细胞在内的多种细胞分化。小分子化合物是一类由组织细胞合成、分泌的小分子多肽类因子,特定的小分子化合物可作用于干细胞诱导其向视网膜感光细胞分化。目前,对干细胞体外培养,通过使用不同的诱导培养方案,探索干细胞向视网膜感光细胞分化的研究成为热点。早期,研究者们主要在共培养条件下采用小分子化合物诱导ESC向视网膜感光细胞分化,随着研究的进展,逐渐开始探索在无共培养条件下小分子化合物诱导ESC向视网膜感光细胞的分化以及小分子化合物诱导i PSC向视网膜感光细胞的分化。本文主要就小分子化合物促进ESC和i PSC向视网膜感光细胞分化的研究进展进行综述。 相似文献
2.
《Bioorganic & medicinal chemistry》2020,28(8):115401
Respiratory syncytial virus (RSV) is the main cause of lower respiratory tract diseases in infants and young children, with potentially serious and fatal consequences associated with severe infections. Despite extensive research efforts invested in the identification of therapeutic measures, no vaccine is currently available, while treatment options are limited to ribavirin and palivizumab, which both present significant limitations. While clinical and pre-clinical candidates mainly target the viral fusion protein, the nucleocapsid protein or the viral polymerase, our focus has been the identification of new antiviral compounds targeting the viral M2-1 protein, thanks to the presence of a zinc-ejecting group in their chemical structure. Starting from an anti-RSV hit we had previously identified with an in silico structure-based approach, we have designed, synthesised and evaluated a new series of dithiocarbamate analogues, with which we have explored the antiviral activity of this scaffold. The findings presented in this work may provide the basis for the identification of a new antiviral lead to treat RSV infections. 相似文献
3.
《Bioorganic & medicinal chemistry letters》2014,24(7):1724-1729
A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE). 相似文献
4.
《Bioorganic & medicinal chemistry letters》2019,29(15):1957-1961
In our efforts to further investigate the impact of the spacer and membrane anchor to the neuroprotective activities, a series of bivalent compounds that contain cholesterol and extended spacers were designed, synthesized and biologically characterized. Our results support previous studies that incorporation of a piperazine ring into the spacer significantly improved the protective potency of bivalent compounds in MC65 cell model. Spacer length beyond 21 atoms does not add further benefits with 21MO being the most potent one with an EC50 of 81.86 ± 11.91 nM. Our results also demonstrated that bivalent compound 21MO suppressed the production of mitochondria reactive oxygen species. Furthermore, our results confirmed that both of the spacer and membrane anchor moiety are essential to metal binding. Collectively, the results provide further evidence and information to guide optimization of such bivalent compounds as potential neuroprotectants for Alzheimer’s disease. 相似文献
5.
《Bioorganic & medicinal chemistry letters》2014,24(21):5063-5069
We synthesized a series of vanillin-derived compounds and analyzed them in HeLa cells for their effects on the proliferation of cancer cells. The molecules are derivatives of the lead compound SBE13, a potent inhibitor of the inactive conformation of human polo-like kinase 1 (Plk1). Some of the new designs were able to inhibit cancer cell proliferation to a similar extent as the lead structure. Two of the compounds ((({4-[(6-chloropyridin-3-yl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine) and (({4-[(4-chlorophenyl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine)) were much stronger in their capacity to reduce HeLa cell proliferation and turned out to potently induce apoptosis and reduce Plk1 kinase activity in vitro. 相似文献
6.
《Bioorganic & medicinal chemistry》2019,27(12):2340-2344
A synthetic flavone derivative 2-(benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-one (BDC) was synthesized by the one pot reaction method and assessed for α-glucosidase inhibitory activity. The BDC demonstrated dose dependent inhibition of α-glucosidase activity. A maximum inhibition (99.3 ± 0.26%) of α-glucosidase was observed at 27.6 µM. The maximum α-glucosidase inhibitory activity depicted by BDC 27.6 µM concentration was 22.4 fold over the maximum inhibition observed with acarbose (97.72 ± 0.59% at 669.57 µM), a standard commercial anti-diabetic drug. In contrast to acarbose that depicted competitive type inhibition, kinetic studies of α-glucosidase inhibition by BDC demonstrated non-competitive inhibition with Km of 0.71 mM−1 and a Vmax of 0.028 mmol/min. In silico studies suggest allosteric interaction of BDC with α-glucosidase at a minimum binding energy (ΔG) of −8.64 kcal/mol and Ki of 465.3 nM, whereas, acarbose interacted at the active site of α-glucosidase with ΔG of −9.23 kcal/mol and Ki of 172 nM. Thus BDC significantly inhibited α-glucosidase in comparison to acarbose. Moreover, BDC has been endorsed for drug likeness by evaluating it as per Lipinski rule of five. Thus, BDC can be a lead compound for the management of type-2 diabetes mellitus. 相似文献
7.
研究复合季铵盐消毒剂含量的测定与滴定误差分析。探讨了四苯硼钠标准液配制及对滴定分析终点颜色的影响,并与单季铵盐定量分析方法进行了对比。结果表明:四苯硼钠两相滴定法适合于复合季铵盐定量分析,但要注意四苯硼钠标准液配制的正确性及滴定终点颜色的判断。 相似文献
8.
Experimental and Theoretical Assessment of Ni‐Based Binary Compounds for the Hydrogen Evolution Reaction 下载免费PDF全文
Marc Ledendecker Hannah Schlott Markus Antonietti Bernd Meyer Menny Shalom 《Liver Transplantation》2017,7(5)
Metallic binary compounds have emerged in recent years as highly active and stable electrocatalysts toward the hydrogen evolution reaction. In this work, the origin of their high activity from a theoretical and experimental point of view is elucidated. Here, different metallic ceramics as Ni3S2, Ni3N, or Ni5P4 are grown directly on Ni support in order to avoid any contaminations. The correlation of theoretical calculations with detailed material characterization and electrochemical testing paves the way to a deeper understanding of possible active adsorption sites for each material and the observed catalytic activity. It is shown that heteroatoms as P, S, and N actively take part in the reaction and do not act as simple spectator. Due to the anisotropic nature of the materials, a variety of adsorption sites with highly coverage‐dependent properties exists, leading to a general shift in hydrogen adsorption free energies ΔG H close to zero. Extending the knowledge gained about the here described materials, a new catalyst is prepared by modifying a high surface Ni foam, for which current densities up to 100 mA cm?2 at around 0.15 V (for Ni3N) are obtained. 相似文献
9.
DAVID M. LESLIE JR. R. TERRY BOWYER JONATHAN A. JENKS 《The Journal of wildlife management》2008,72(6):1420-1433
Abstract: Fecal nitrogen (FN) has been applied widely as an index of dietary quality in studies of nutritional ecology of free-ranging and captive vertebrate herbivores, particularly ruminants. Three related articles in the Journal of Wildlife Management (JWM; Leslie and Starkey 1985, 1987; Hobbs 1987) have been cited (n = 150) in 87 publications and 39 peer-reviewed journals. The critique by Hobbs (1987) and the reply by Leslie and Starkey (1987) on limitations and appropriate applications of FN have been used to justify use of FN or negate its value as a nutritional proxy. We undertook a retrospective analysis of FN applications since 1985, largely because we sensed that methodological cautions noted in the 3 JWM publications were not being followed, leading to faulty conclusions and management applications, and that application protocols needed updating. From January 1986 through July 2007, the 107 species-by-continent applications of FN, citing the 3 JWM publications singly or in any combination, were diverse; FN was used in various ways on 5 continents and for 50 wild and domestic species. Cumulative rates of departure from recommended FN applications increased in recent years, largely in studies that compare different species while failing to fully acknowledge that differences likely reflected digestive capabilities rather than differences in some aspect of dietary intake. Post-1985 research on plant secondary compounds (e.g., tannins) has refined limitations to the application of FN, permitting more straightforward protocols than were possible in 1985. Although use does not necessarily reflect value, the number of published applications during the past 22 years indicates that peer reviewers from a variety of scientific disciplines view FN as a suitable proxy for nutritional status, which can be used to contrast study units when carefully defined by the study design. Any index can have shortcomings, and there are still circumstances when application of FN is problematic. Precise prediction of intake with FN under field conditions is still hampered by inherent variability, but contrasts of comparable study units and species can be appropriate. Published protocols for FN, as amended herein, should be adhered to, and conclusions are strengthened by the use of multiple nutritional indices. 相似文献
10.
Elisabetta Visalberghi Virginia Barca Patricia Izar Dorothy Fragaszy Valentina Truppa 《American journal of primatology》2021,83(1)
Tool use in humans can be optional, that is, the same person can use different tools or no tool to achieve a given goal. Strategies to reach the same goal may differ across individuals and cultures and at the intra‐individual level. This is the first experimental study at the intra‐individual level on the optional use of a tool in wild nonhuman primates. We investigated optional tool use by wild bearded capuchins (Sapajus libidinosus) of Fazenda Boa Vista (FBV; Piauí, Brazil). These monkeys habitually succeed in cracking open the mesocarp of dry cashew nuts (Anacardium spp.) by pounding them with stones and/or by biting. We assessed whether availability of a stone and resistance of the nut affected capuchins' choice to pound or to bite the nuts and their rates of success. Sixteen capuchins (1–16 years) received small and large dry cashew nuts by an anvil together with a stone (Stone condition) or without a stone (No‐Stone condition). In the Stone conditions, subjects used it to crack the nut in 89.1% (large nuts) and 90.1% (small nut) of the trials. Nut size significantly affected the number of strikes used to open it. Availability of the stone significantly increased the average percent of success. In the No‐Stone conditions, monkeys searched for and used other percussors to crack the nuts in 54% of trials. In all conditions, age affects percentage of success and number of strikes to reach success. We argue that exclusive use of stones in other sites may be due to the higher abundance of stones at these sites compared with FBV. Since capuchins opened cashews with a tool 1–2 years earlier than they succeed at cracking more resistant palm nuts, we suggest that success at opening cashew nuts with percussors may support the monkeys' persistent efforts to crack palm nuts. 相似文献