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ABSTRACT: Recent studies have been raising doubts on the safety of induced pluripotent stem cells (iPSCs) and proposing that the process of reprogramming brought about copy number variations (CNVs) in iPSCs. However, a recent paper published in Nature provided evidence showing that most CNVs were pre-existed as somatic mosaicism but not resulted from the reprogramming. This new finding would profoundly reshape some previous thoughts and endorse the confidence of iPSCs in both research and therapy.
Protein & Cell 12/2012;
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ABSTRACT: Four new abietane diterpenes (1-4) and two new cycloparvifloralone-type sesquiterpenoids (5-6) have been isolated from the twigs and leaves of Illicium majus, together with three known sesquiterpenoids and five known diterpenoids. Their structures were determined by spectroscopic analysis and chemical methods. The absolute configuration of the 15,16-diol moiety in 2 is confirmed by Snatzke's method, observing the induced circular dichroism after the addition of dimolybdenum tetraacetate in DMSO. Compound 2 exihibited significant anti-inflammatory activity with an IC50 value of 0.26 ± 0.03 µM, while compounds 10, 11, and 13 showed good anti-inflammatory activities with IC50 values ranging from 1.94 ± 0.56 to 2.60 ± 0.48 µM.
Planta Medica 12/2012; · 2.15 Impact Factor
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Dan Du,
Jun Yan,
Jinhong Ren,
Haining Lv,
Yong Li,
Song Xu,
Yadan Wang,
Shuanggang Ma, Jing Qu,
Weibin Tang,
Zhuowei Hu,
Shi-Shan Yu
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ABSTRACT: A novel series of glycyrrhizin (GL) derivatives was designed and synthesized by introducing various amine or amino acid residues into the carbohydrate chain and at C-30. Their inhibitory effects on high-mobility group box-1 (HMGB1) were evaluated using a cell-based lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α release study. Compounds 10, 12, 18-20, 23, and 24, which had substituents introduced at C-30, demonstrated moderate HMGB1 inhibition with ED50 values ranging from 337 to 141 μM, which are values comparable to that of the leading GL compound (1) (ED50 = 70 μM). Compounds 23 and 24 emerged as novel and interesting HMGB1 inhibitors. These compounds were able to extend the survival of mice with chronic heart failure (CHF) and acute heart failure (AHF), respectively. In addition, molecular modeling studies were performed to support the biological data.
Journal of Medicinal Chemistry 11/2012; · 4.80 Impact Factor
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Peng-Yu Zhuang,
Gui-Jie Zhang,
Xiao-Jing Wang,
Yan Zhang,
Shi-Shan Yu,
Shuang-Gang Ma,
Yun-Bao Liu, Jing Qu,
Yong Li,
Song Xu,
Hai-Ning Lü,
Xia Chen,
Li Li,
Yi-Kang Si,
Dan Zhang
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ABSTRACT: Eleven prenylated C(6)-C(3) compounds, illihenryifunones A, B (1, 2), illihenryifunol A (3), illihenryipyranol A (4), illihenryiones A-G (5-11), and three known prenylated C(6)-C(3) compounds (12-14), were isolated from the roots of Illicium henryi. Structures of 1-11 were elucidated by spectroscopic methods including NMR, HRESIMS, and CD. The absolute configuration of the 11,12-diol moiety in 5 was determined by observing its induced circular dichroism after addition of Mo(2)(OAc)(4) in DMSO. The absolute configuration of C-11 in 4 was determined as S based on the Rh(2)(OCOCF(3))(4)-induced CD data; the absolute configuration of 3 was determined as R by comparison of its experimental and calculated electronic circular dichroism (ECD). The antioxidant activities of compounds 1-14 were also evaluated. Compound 4 exhibited strong antioxidant activity with an IC(50) value of 2.97±1.30μM, whereas compounds 3 and 8 showed antioxidant activities with IC(50) values of 44.36±0.30 and 48.00±2.01μM, respectively.
Phytochemistry 11/2012; · 3.35 Impact Factor
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ABSTRACT: Two new alkaloids, lycojaponicumins D (1) and E (2), were isolated from the club moss Lycopodium japonicum. Their structures were elucidated by spectroscopic methods, calculated ECD, CD experiments and X-ray diffraction analysis. Lycojaponicumin D (1) possesses an unprecedented 5/7/6/6 tetracyclic skeleton formed by an unusual C3-C13 linkage, which is first reported in Lycopodium alkaloids. The plausible biogenetic pathway of 1 is proposed.
Organic Letters 11/2012; · 5.86 Impact Factor
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Guang-Hui Liu, Jing Qu,
Keiichiro Suzuki,
Emmanuel Nivet,
Mo Li,
Nuria Montserrat,
Fei Yi,
Xiuling Xu,
Sergio Ruiz,
Weiqi Zhang, [......],
Ying Li,
April Goebl,
Jessica Kim,
Rupa Devi Soligalla,
Ilir Dubova,
James Thompson,
John Yates Iii,
Concepcion Rodriguez Esteban,
Ignacio Sancho-Martinez,
Juan Carlos Izpisua Belmonte
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ABSTRACT: Nuclear-architecture defects have been shown to correlate with the manifestation of a number of human diseases as well as ageing. It is therefore plausible that diseases whose manifestations correlate with ageing might be connected to the appearance of nuclear aberrations over time. We decided to evaluate nuclear organization in the context of ageing-associated disorders by focusing on a leucine-rich repeat kinase 2 (LRRK2) dominant mutation (G2019S; glycine-to-serine substitution at amino acid 2019), which is associated with familial and sporadic Parkinson's disease as well as impairment of adult neurogenesis in mice. Here we report on the generation of induced pluripotent stem cells (iPSCs) derived from Parkinson's disease patients and the implications of LRRK2(G2019S) mutation in human neural-stem-cell (NSC) populations. Mutant NSCs showed increased susceptibility to proteasomal stress as well as passage-dependent deficiencies in nuclear-envelope organization, clonal expansion and neuronal differentiation. Disease phenotypes were rescued by targeted correction of the LRRK2(G2019S) mutation with its wild-type counterpart in Parkinson's disease iPSCs and were recapitulated after targeted knock-in of the LRRK2(G2019S) mutation in human embryonic stem cells. Analysis of human brain tissue showed nuclear-envelope impairment in clinically diagnosed Parkinson's disease patients. Together, our results identify the nucleus as a previously unknown cellular organelle in Parkinson's disease pathology and may help to open new avenues for Parkinson's disease diagnoses as well as for the potential development of therapeutics targeting this fundamental cell structure.
Nature 10/2012; · 36.28 Impact Factor
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Jian Bai,
Hui Chen,
Zhen-Feng Fang,
Shi-Shan Yu,
Shuang-Gang Ma,
Yong Li, Jing Qu,
Song Xu,
Jing-Hong Ren,
Hai-Ning Lü,
Xia Chen
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ABSTRACT: Two new sesquiterpenes, dunnianoside I (1) and 8'-oxo-6-hydroxy-dihydrophaseic acid methyl ester (2), a new glycoside, dunnianoside J (3), two new neolignans, dunnianeolignans A-B (4, 5), together with 10 known compounds (6-15), were isolated from the roots of Illicium dunnianum. The structures of these new compounds were elucidated by spectroscopic methods including 1D and 2D NMR, HR-ESI-MS, and chemical methods. Compounds 7, 8, and 13-15 exhibited potent antioxidant activities against Fe(2+)-cystine-induced rat liver microsomal lipid peroxidation, with IC(50) values ranging from 4.2 ± 0.4 to 38.4 ± 2.6 μM.
Journal of Asian natural products research 10/2012; 14(10):940-9. · 0.61 Impact Factor
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ABSTRACT: Efficient generation of functional human vascular endothelial cells and smooth muscle cells from pluripotent stem cells is an extensively studied topic and of great interest in the stem cell field. Though thought to be technically complex and difficult, substantial progress has been made towards this direction. Here we aim to summarize and discuss the most recent advances in this topic and their future perspective in research and clinic.
Cell Research 09/2012; · 8.19 Impact Factor
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Jian Bai,
Zhen-Feng Fang,
Hui Chen,
Shi-Shan Yu,
Dan Zhang,
Huai-Ling Wei,
Shuang-Gang Ma,
Yong Li, Jing Qu,
Song Xu,
Jing-Hong Ren,
Fen Zhao,
Nan Zhao,
Jun-Hong Liu
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ABSTRACT: Eight new phenolic glycosides, dunnianosides A-H (1-8), and nine known phenolic glycosides (9-17), were isolated from the roots of Illicium dunnianum. The structures of these new compounds were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, and chemical methods. Compounds 1-5, 7, and 9 exhibited potent antioxidant activities against Fe(2+)-cystine-induced rat liver microsomal lipid peroxidation, with IC(50) values ranging from 3.8±0.6 to 23.0±2.2μM.
Carbohydrate research 09/2012; 361C:206-211. · 2.03 Impact Factor
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ABSTRACT: Most of the world's natural fiber comes from cotton (Gossypium spp.), which is an important crop worldwide. Characterizing genes that regulate cotton yield and fiber quality is expected to benefit the sustainable production of natural fiber. Although a huge number of expressed sequence tag sequences are now available in the public database, large-scale gene function analysis has been hampered by the low-efficiency process of generating transgenic cotton plants. Tobacco rattle virus (TRV) has recently been reported to trigger virus-induced gene silencing (VIGS) in cotton leaves. Here, we extended the utility of this method by showing that TRV-VIGS can operate in reproductive organs as well. We used this method to investigate the function of KATANIN and WRINKLED1 in cotton plant development. Cotton plants with suppressed KATANIN expression produced shorter fibers and elevated weight ratio of seed oil to endosperm. By contrast, silencing of WRINKLED1 expression resulted in increased fiber length but reduced oil seed content, suggesting the possibility to increase fiber length by repartitioning carbon flow. Our results provide evidence that the TRV-VIGS system can be used for rapid functional analysis of genes involved in cotton fiber development.
Plant physiology 07/2012; 160(2):738-48. · 6.53 Impact Factor
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ABSTRACT: The combination of disease-specific human induced pluripotent stem cells (iPSC) and directed cell differentiation offers an ideal platform for modeling and studying many inherited human diseases. Wilson's disease (WD) is a monogenic disorder of toxic copper accumulation caused by pathologic mutations of the ATP7B gene. WD affects multiple organs with primary manifestations in the liver and central nervous system (CNS). In order to better investigate the cellular pathogenesis of WD and to develop novel therapies against various WD syndromes, we sought to establish a comprehensive platform to differentiate WD patient iPSC into both hepatic and neural lineages. Here we report the generation of patient iPSC bearing a Caucasian population hotspot mutation of ATP7B. Combining with directed cell differentiation strategies, we successfully differentiated WD iPSC into hepatocyte-like cells, neural stem cells and neurons. Gene expression analysis and cDNA sequencing confirmed the expression of the mutant ATP7B gene in all differentiated cells. Hence we established a platform for studying both hepatic and neural abnormalities of WD, which may provide a new tool for tissue-specific disease modeling and drug screening in the future.
Protein & Cell 07/2012;
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Jian Bai,
Hui Chen,
Zhen-Feng Fang,
Shi-Shan Yu,
Wen-Jie Wang,
Yang Liu,
Shuang-Gang Ma,
Yong Li, Jing Qu,
Song Xu,
Jun-Hong Liu,
Fen Zhao,
Nan Zhao
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ABSTRACT: Six allo-cedrane sesquiterpenes, four seco-prezizaane-type sesquiterpenes, two monocyclofarnesane sesquiterpenes, together with four known sesquiterpenes, were isolated from the roots of Illicium dunnianum. The structures were elucidated by spectroscopic methods including 1D and 2D NMR. The absolute configuration of 10 was determined by a CD experiment. Compounds 11 and 13 showed potent activities against the release of β-glucuronidase in rat polymorphonuclear leukocytes induced by platelet-activating factor in vitro, with IC₅₀ values of 2.10±0.40 and 1.93±0.57 μM, respectively. All compounds were evaluated for cytotoxicities against five human cancer cell lines (A549, Bel-7402, BGC-823, HCT-8, and A2780) in the MTT assay, but none of them exhibited activity at concentrations tested (10⁻⁵-10⁻⁷ M).
Phytochemistry 06/2012; 80:137-47. · 3.35 Impact Factor
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ABSTRACT: The maintenance of pluripotency relies on an intricate transcriptional network hinged on a key set of transcription factors. Pluripotent stem cells have been shown to be sensitive to modulations of the cellular abundance and transcriptional activity of these key pluripotency factors. Recent evidence highlights the important role of post-translational modifications, including ubiquitination, sumoylation, phosphorylation, methylation, and acetylation, in regulating the levels and activity of pluripotency factors to achieve a balance between pluripotency and differentiation.
Journal of Molecular Cell Biology 06/2012; 4(4):262-5.
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ABSTRACT: Recent applications of new tools for genome-wide mapping of long-range and spatial interactions have shed light onto the fundamental mechanisms of three dimensional chromatin organizations in pluripotent stem cells and their derivatives.
Protein & Cell 06/2012; 3(7):483-6.
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ABSTRACT: To study the chemical constituents of the n-BuOH fraction of 95% ethanolic extract of leaves of Neoalsomitra integrifoliola.
The compounds were isolated with kinds of column chromatography. The structures were determined by MS and NMR spectroscopic techniques.
Eight compounds were isolated from the n-BuOH fraction of 95% ethanolic extract and their structures were identified as 2-phenylethyl rutinoside (1), rutin (2), kaempferol-3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (3), isorhamnetin-3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (4), methyl chlorogenate (5), guanosine (6), adenosine (7), myo-inositol (8), respectively.
All compounds were isolated from this genus for the first time.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 06/2012; 37(11):1593-6.
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Xiao-Jing Wang,
Gui-Jie Zhang,
Peng-Yu Zhuang,
Yan Zhang,
Shi-Shan Yu,
Xiu-Qi Bao,
Dan Zhang,
Yu-He Yuan,
Nai-Hong Chen,
Shuang-Gang Ma, Jing Qu,
Yong Li
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ABSTRACT: Lycojaponicumins A-C (1-3), three trace alkaloids isolated from Lycopodium japonicum, represent a unique heterocyclic skeleton formed by the new linkage C4-C9. Notably, lycojaponicumins A and B (1 and 2) are the first examples of natural products possessing a 5/5/5/5/6 pentacyclic ring system with a 1-aza-7-oxabicyclo[2.2.1]heptane moiety. These structures were elucidated by spectroscopic methods and X-ray diffraction analysis. A plausible biogenetic pathway was proposed.
Organic Letters 05/2012; · 5.86 Impact Factor
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Cell Research 05/2012; 22(7):1087-91. · 8.19 Impact Factor
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Jun-Hong Liu,
Nan Zhao,
Gui-Jie Zhang,
Shi-Shan Yu,
Li-Jun Wu, Jing Qu,
Shuang-Gang Ma,
Xiao-Guang Chen,
Tian-Qi Zhang,
Jian Bai,
Hui Chen,
Zhen-Feng Fang,
Fen Zhao,
Wei-Bin Tang
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ABSTRACT: Six new quassinoids (1-6) and eight known compounds of this type (7-14) were isolated from the seeds of Brucea javanica. Their structures were elucidated by analysis of their spectroscopic data and from chemical evidence. Compounds 1-5 were found to be unusual quassinoids with a 2,3-seco A ring. The configurations at C-4 in 4 and 5 were determined by a difference circular dichroism method. In in vitro bioassays, 8 and 10 showed inhibitory activities for nitric oxide production in LPS-activated macrophages, with IC(50) values of 1.9 and 5.0 μM, respectively, while compounds 6, 8-11, 13, and 14 exhibited cytotoxicity against five human tumor cell lines (HCT-8, HepG2, BGC-823, A549, and SKVO3), having IC(50) values in the range 0.12-9.3 μM.
Journal of Natural Products 04/2012; 75(4):683-8. · 3.13 Impact Factor
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Protein & Cell 04/2012; 3(4):241-5.
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Cell Research 04/2012; 22(6):941-4. · 8.19 Impact Factor
