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Yang Qiu Dilip Rajagopalan Susan C. Connor Doris Damian Lei Zhu Amir Handzel Guanghui Hu Arshad Amanullah Steve Bao Nathaniel Woody David MacLean Kwan Lee Dana Vanderwall Terence Ryan 《Metabolomics : Official journal of the Metabolomic Society》2008,4(4):337-346
Recent advances in genomics, metabolomics and proteomics have made it possible to interrogate disease pathophysiology and
drug response on a systems level. The analysis and interpretation of the complex data obtained using these techniques is potentially
fertile but equally challenging. We conducted a small clinical trial to explore the application of metabolomics data in candidate
biomarker discovery. Specifically, serum and urine samples from patients with type 2 diabetes mellitus (T2DM) were profiled
on metabolomics platforms before and after 8 weeks of treatment with one of three commonly used oral antidiabetic agents,
the sulfonyurea glyburide, the biguanide metformin, or the thiazolidinedione rosiglitazone. Multivariate classification techniques
were used to detect serum or urine analytes, obtained at baseline (pre-treatment) that could predict a significant treatment
response after 8 weeks. Using this approach, we identified three analytes, measured at baseline, that were associated with
response to a thiazolidinedione after 8 weeks of treatment. Although larger and longer-term studies are required to validate
any of the candidate biomarkers, pharmacometabolomic profiling, in combination with multivariate classification, is worthy
of further exploration as an adjunct to clinical decision making regarding treatment selection and for patient stratification
within clinical trials.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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A water-insoluble glucan, PFPSIN, has been isolated from the aqueous extract of an edible mushroom Pleurotus florida. On the basis of total acid hydrolysis, methylation analysis, periodate oxidation, Smith degradation, and (13)C NMR experiments, the repeating unit of the polysaccharide was established as Conformational analysis revealed the triple helical conformation of this glucan. 相似文献
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V. L. Keny C. Vanlalnghaka Shakil S. Hakim P. V. Khare R. J. Barnabas Dilip S. Joshi 《Biological Rhythm Research》2008,39(2):143-150
Latitude dependent arrhythmicity in the circadian rhythm of oviposition of Drosophila ananassae strains originating from 8.1°N to 32.7°N was studied by inbreeding them in cycles of 12 h of light at 20 lux and 12 h of darkness. The number of inbreeding generations required to initiate arrhythmicity in oviposition rhythm was dependent on the origin of latitude of the strain. The strains from the lower latitudes became arrhythmic after notably more numbers of generations than those from the higher latitudes. This might be attributed to the higher inherent degree of oviposition rhythmicity in the F1 generation, and enhanced photic sensitivity of the circadian pacemaker mediating entrainment of oviposition rhythm of the strains from lower latitudes as compared to those from the higher latitudes. 相似文献
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Sougata Ghosh Piyush More Abhishek Derle Ajay B. Patil Pramod Markad Adersh Asok Navanath Kumbhar Mahemud L. Shaikh Boppana Ramanamurthy Vaishali S. Shinde Dilip D. Dhavale Balu A. Chopade 《PloS one》2014,9(9)
Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus. 相似文献
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The success of cisplatin (CP) based therapy is often hindered by acquisition of CP resistance. We isolated NSC109268 as a compound altering cellular sensitivity to DNA damaging agents. Previous investigation revealed an enhancement of CP sensitivity by NSC109268 in wild-type Saccharomyces cerevisiae and CP-sensitive and -resistant cancer cell lines that correlated with a slower S phase traversal. Here, we extended these studies to determine the target pathway(s) of NSC109268 in mediating CP sensitization, using yeast as a model. We reasoned that mutants defective in the relevant target of NSC109268 should be hypersensitive to CP and the sensitization effect by NSC109268 should be absent or strongly reduced. A survey of various yeast deletion mutants converged on the Rad5 pathway of DNA damage tolerance by template switching as the likely target pathway of NSC109268 in mediating cellular sensitization to CP. Additionally, cell cycle delays following CP treatment were not synergistically influenced by NSC109268 in the CP hypersensitive rad5Δ mutant. The involvement of the known inhibitory activities of NSC109268 on 20S proteasome and phosphatases 2Cα and 2A was tested. In the CP hypersensitive ptc2Δptc3Δpph3Δ yeast strain, deficient for 2C and 2A-type phosphatases, cellular sensitization to CP by NSC109268 was greatly reduced. It is therefore suggested that NSC109268 affects CP sensitivity by inhibiting the activity of unknown protein(s) whose dephosphorylation is required for the template switch pathway. 相似文献
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Piyali Chowdhury Koushik Sen Shreyasi Gupta Suravi Majumder Payel Guha Arindam Chakraborty Amar K. Chandra Dilip Mukherjee 《Proceedings of the Zoological Society》2018,71(1):48-55
Testosterone is commonly known for its role in the regulation of reproductive physiology in men. Epidemiologic studies suggest that endogenous testosterone levels may be implicated in cardiovascular diseases (CVDs). Our study aimed to investigate the relationship between serum total testosterone (TT) levels and lipid profile as well as fasting blood glucose (FBG) levels in male patients ranging from 40 to 70 years old with angiographically proven CVDs from Nadia and Murshidabad district of West Bengal, India. These data were compared with the normal men with no CVD history. We observed a significantly low serum TT levels in CVD patient group compared to the normal group. Among CVD patients, a significant (p < 0.05) negative association was found between serum TT and total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein, whereas a significant positive correlation (p < 0.05) was found between serum TT and high density lipoprotein. We also observed a highly significant negative correlation between TT and FBG levels in CVD patient group. Thus, in these two densely populated district of West Bengal with poor socio-economic condition, low levels of serum TT in elderly men is associated with CVD that appear together with an atherogenic lipid milieu that may be involved in the pathogenesis of CVD. Results further indicate that low serum TT might have a role in the development of hyperglycemia as evidenced from high FBG level in elderly men. 相似文献
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