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21.
Vivek Kumar Mukesh M. Mudgal Nidhi Rani Amrita Jha Manu Jaggi Anu T. Singh 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):763-770
A new series of functionalized amino acid derivatives N-substituted 1-N-(tert-butoxycarbonyl)-2,2-dimethyl-4-phenyl-5-oxazolidine carboxamide (1-17) and 1-N-substituted-3-amino-2-hydroxy-3-phenylpropane-1-carboxamide (18-34) were synthesized and evaluated for their in vitro cytotoxicity against human cancer cell lines. Compound 6 has shown interesting cytotoxicity (IC50 = 5.67 μm) in ovarian cancer, while compound 10 exhibited promising cytotoxicity in ovarian (IC50 = 6.1 μm) and oral (IC50 = 4.17 μm) cancers. These compounds could be of use in designing new anti-cancer agents. 相似文献
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Xinzhong Li Andrew J. Buckton Samuel L. Wilkinson Shibu John Roddy Walsh Tomas Novotny Iveta Valaskova Manu Gupta Laurence Game Paul J R. Barton Stuart A. Cook James S. Ware 《PloS one》2013,8(7)
Background
Molecular genetic testing is recommended for diagnosis of inherited cardiac disease, to guide prognosis and treatment, but access is often limited by cost and availability. Recently introduced high-throughput bench-top DNA sequencing platforms have the potential to overcome these limitations.Methodology/Principal Findings
We evaluated two next-generation sequencing (NGS) platforms for molecular diagnostics. The protein-coding regions of six genes associated with inherited arrhythmia syndromes were amplified from 15 human samples using parallelised multiplex PCR (Access Array, Fluidigm), and sequenced on the MiSeq (Illumina) and Ion Torrent PGM (Life Technologies). Overall, 97.9% of the target was sequenced adequately for variant calling on the MiSeq, and 96.8% on the Ion Torrent PGM. Regions missed tended to be of high GC-content, and most were problematic for both platforms. Variant calling was assessed using 107 variants detected using Sanger sequencing: within adequately sequenced regions, variant calling on both platforms was highly accurate (Sensitivity: MiSeq 100%, PGM 99.1%. Positive predictive value: MiSeq 95.9%, PGM 95.5%). At the time of the study the Ion Torrent PGM had a lower capital cost and individual runs were cheaper and faster. The MiSeq had a higher capacity (requiring fewer runs), with reduced hands-on time and simpler laboratory workflows. Both provide significant cost and time savings over conventional methods, even allowing for adjunct Sanger sequencing to validate findings and sequence exons missed by NGS.Conclusions/Significance
MiSeq and Ion Torrent PGM both provide accurate variant detection as part of a PCR-based molecular diagnostic workflow, and provide alternative platforms for molecular diagnosis of inherited cardiac conditions. Though there were performance differences at this throughput, platforms differed primarily in terms of cost, scalability, protocol stability and ease of use. Compared with current molecular genetic diagnostic tests for inherited cardiac arrhythmias, these NGS approaches are faster, less expensive, and yet more comprehensive. 相似文献25.
Kanjoormana Aryan Manu Muthu K. Shanmugam Tina H. Ong Aruljothi Subramaniam Kodappully Sivaraman Siveen Ekambaram Perumal Ramar Perumal Samy Pradeep Bist Lina H. K. Lim Alan Prem Kumar Kam M. Hui Gautam Sethi 《PloS one》2013,8(3)
Accumulating evidence(s) indicate that CXCL12-CXCR4 signaling cascade plays an important role in the process of invasion and metastasis that accounts for more than 80% of deaths in hepatocellular carcinoma (HCC) patients. Thus, identification of novel agents that can downregulate CXCR4 expression and its associated functions have a great potential in the treatment of metastatic HCC. In the present report, we investigated an anthraquinone derivative, emodin for its ability to affect CXCR4 expression as well as function in HCC cells. We observed that emodin downregulated the expression of CXCR4 in a dose-and time-dependent manner in HCC cells. Treatment with pharmacological proteasome and lysosomal inhibitors did not have substantial effect on emodin-induced decrease in CXCR4 expression. When investigated for the molecular mechanism(s), it was observed that the suppression of CXCR4 expression was due to downregulation of mRNA expression, inhibition of NF-κB activation, and abrogation of chromatin immunoprecipitation activity. Inhibition of CXCR4 expression by emodin further correlated with the suppression of CXCL12-induced migration and invasion in HCC cell lines. In addition, emodin treatment significantly suppressed metastasis to the lungs in an orthotopic HCC mice model and CXCR4 expression in tumor tissues. Overall, our results show that emodin exerts its anti-metastatic effect through the downregulation of CXCR4 expression and thus has the potential for the treatment of HCC. 相似文献
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Objectives
Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants.Design
CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m2) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m2)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA.Results
Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05).Conclusions
The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points. 相似文献27.
Fidelis Akunke Atuo Samuel T Ivande Zingfa J Wala Shiiwa Manu Timothy J O’Connell 《Ostrich》2016,87(2):101-112
The Grey-necked Picathartes Picathartes oreas is a globally threatened bird species in Africa with a wild population of less than 10,000 individuals. The Nigerian population, which has been poorly studied, is restricted to the forest of Cross River. This study re-assessed the distribution, breeding population, habitat use and current threats of the Grey-necked Picathartes by revisiting the 91 breeding sites identified during the first and only survey of the species in 1987. We estimated a breeding population of 164 individuals across 82 breeding sites. Only 72 breeding sites were found in the localities where 91 had been registered in 1987. Thirteen (18%) of these 72 sites were no longer active and showed evidence of human disturbance. The occurrence of Grey-necked Picathartes’ nest sites was positively predicted by higher number of emergent trees, larger rocks and negatively related to disturbance matrices. Similarly, larger colony sizes were associated with high canopy cover and rock height. Also, the probability of finding an active nest within a breeding colony was significantly predicted by increased canopy, tree density and ground cover. Human threats included farming, wire snares, egg and juvenile removal, bush burning, and hunter’s camps. These threats, though specific to the Grey-necked Picathartes, threaten the integrity of the Cross River forest habitats. 相似文献
28.
Genetic and paleomodelling evidence of the population expansion of the cattle egret Bubulcus ibis in Africa during the climatic oscillations of the Late Pleistocene 下载免费PDF全文
Carlos Congrains Antônio F. Carvalho Elder A. Miranda Graeme S. Cumming Dominic A. W. Henry Shiiwua A. Manu Jacinta Abalaka Cristiano D. Rocha Moussa S. Diop Joãozinho Sá Hamilton Monteiro Lars H. Holbech Francis Gbogbo Silvia N. Del Lama 《Journal of avian biology》2016,47(6):846-857
Increasing aridity during glacial periods produced the retraction of forests and the expansion of arid and semi‐arid environments in Africa, with consequences for birds. Cattle egret Bubulcus ibis is a dispersive species that prefers semi‐arid environments and requires proximity to bodies of water. We expected that climatic oscillations led to the expansion of the range of the cattle egret during arid periods, such as the Last Maximum Glacial (LGM) and contraction of distribution during the Last Interglacial (LIG) period, resulting in contact of populations previously isolated. We investigated this hypothesis by evaluating the genetic structure and population history of 15 cattle egret breeding colonies located in west and South Africa using the mitochondrial DNA (mtDNA) control region, mtDNA ATPase 8 and 6, and an intron of nuclear gene transforming growth factor‐beta 2. Occurrence data and bioclimatic information were used to generate ecological niche models of three periods (present, LGM and LIG). We used the genetic and paleomodelling data to assess the responses of the cattle egret from Africa to the climatic oscillations during the late Pleistocene. Genetic data revealed low levels of genetic differentiation, signs of isolation‐by‐distance, as well as recent increases in effective population size that started during the LGM. The observed low genetic structure may be explained by recent colonization events due to the demographic expansion following the last glacial period and by dispersal capacity of this species. The paleomodels corroborated the expansion during the LGM, and a more restricted potential distribution during the LIG. Our findinds supports the hypothesis that the species range of the cattle egret expanded during arid periods and contracted during wet periods. 相似文献
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Gates AC Bernal-Mizrachi C Chinault SL Feng C Schneider JG Coleman T Malone JP Townsend RR Chakravarthy MV Semenkovich CF 《Cell metabolism》2007,6(6):497-505
Age-related disease, not aging per se, causes most morbidity in older humans. Here we report that skeletal muscle respiratory uncoupling due to UCP1 expression diminishes age-related disease in three mouse models. In a longevity study, median survival was increased in UCP mice (animals with skeletal muscle-specific UCP1 expression), and lymphoma was detected less frequently in UCP female mice. In apoE null mice, a vascular disease model, diet-induced atherosclerosis was decreased in UCP animals. In agouti yellow mice, a genetic obesity model, diabetes and hypertension were reversed by induction of UCP1 in skeletal muscle. Uncoupled mice had decreased adiposity, increased temperature and metabolic rate, elevated muscle SIRT and AMP kinase, and serum characterized by increased adiponectin and decreased IGF-1 and fibrinogen. Accelerating metabolism in skeletal muscle does not appear to impact aging but may delay age-related disease. 相似文献