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Articles by Li Fan
Total Records ( 5 ) for Li Fan
  Pin-Fang Lin , Beata Nowicka-Sans , Brian Terry , Sharon Zhang , Chunfu Wang , Li Fan , Ira Dicker , Volodymyr Gali , Helen Higley , Neil Parkin , Daniel Tenney , Mark Krystal and Richard Colonno
  Entecavir (ETV) was developed for the treatment of chronic hepatitis B virus (HBV) infection and is globally approved for that indication. Initial preclinical studies indicated that ETV had no significant activity against human immunodeficiency virus type 1 (HIV-1) in cultured cell lines at physiologically relevant ETV concentrations, using traditional anti-HIV assays. In response to recent clinical observations of anti-HIV activity of ETV in HIV/HBV-coinfected patients not receiving highly active antiretroviral therapy (HAART), additional investigative studies were conducted to expand upon earlier results. An extended panel of HIV-1 laboratory and clinical strains and cell types was tested against ETV, along with a comparison of assay methodologies and resistance profiling. These latest studies confirmed that ETV has only weak activity against HIV, using established assay systems. However, a >100-fold enhancement of antiviral activity (equivalent to the antiviral activity of lamivudine) could be obtained when assay conditions were modified to reduce the initial viral challenge. Also, the selection of a M184I virus variant during the passage of HIV-1 at high concentrations of ETV confirmed that ETV can exert inhibitory pressure on the virus. These findings may have a significant impact on how future assays are performed with compounds to be used in patients infected with HIV. These results support the recommendation that ETV therapy should be administered in concert with HAART for HIV/HBV-coinfected patients.
  Shuangfen Yue , Saifei Li , Huaan Wen and Li Fan
  The strain of Xylaria Y-4 was isolated from an active termite nest and identified as Xylaria escharoidea based on ITS1-5.8S-ITS2 sequences. Intracellular Polysaccharide (IPS) and Extracellular Polysaccharide (EPS) were extracted from Xylaria escharoidea (strain Y-4) in submerged culture. Antioxidant potency was investigated by assays of various established antioxidant in vitro systems such as hydroxyl (AOH) and DPPH radical scavenging ability, reducing power and ferrous ion chelating ability. Results revealed that the antioxidant activities of IPS extracts were generally more potent than EPS extracts in in vitro assays. IPS exhibited stronger scavenging activity towards DPPH radicals with EC50 of 0.75 mg mL-1.
  Zhaoling Meng , Hui Quan , Li Fan , Robert Kringle and Gordon Sun
  Using historical studies, we compared the impact of using the average baseline or time-matched baseline on diurnal effect correction, treatment effect estimation, and analysis of variance/covariance (ANOVA/ANCOVA) efficiency in a parallel thorough QT/QTc (TQT) study. Under a multivariate normal distribution assumption, we derived conditions for achieving unbiasness and better efficiency when using the average baseline, and confirmed these conditions using historical TQT studies. Furthermore, simulations were conducted under the randomized trial with and without observed imbalanced baseline settings. We conclude that the analyses using average baseline yield better efficiency and unbiased or less biased results under our TQT study conditions.
  Qiang Zeng , Ying Yuan , Xi Wang , Hong Mei Wu , Li Fan , Yong Fen Qi , Chao Shu Tang , Yan Cai and Chun Shui Pan
  Intermedin (IMD), also called adrenomedullin 2 (ADM2), is a 47-amino acid peptide belonging to the calcitonin/calcitonin gene-related peptide (CGRP) family. IMD has similar or more potent vasodilatory and hypotensive actions compared with adrenomedullin (ADM) and CGRP. This study was designed to explore the role of IMD and its receptor in the pathogenesis of spontaneous hypertension and cardiac hypertrophy. Radioimmunoassay was employed to determine plasma immunoreactive IMD concentration and tissue immunoreactive IMD levels in the myocardium and aorta as well as cAMP concentration in the cardiovascular tissues in 13-week-old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). The mRNA expression of IMD, its receptor, calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP)) were determined by semi-quantitative RT-PCR. Protein levels of CRLR and RAMPs were assayed by Western blotting. Our results showed that immunoreactive IMD concentration was enhanced in the SHR myocardium, aortas and plasma. Both the mRNA and protein levels of IMD, as well as those of CRLR and RAMP 1–3 were upregulated in SHRs. IMD affected cAMP generation in the myocardium and aorta, which were not attenuated by prior addition of either CGRP8–37 or ADM22–52 alone. These results indicate that the elevation of IMD and its receptor in the cardiovascular tissue may play an important role in the pathogenesis of spontaneous hypertension.
  Yuichi Matsushima , Carol L. Farr , Li Fan and Laurie S. Kaguni
  Mitochondrial DNA helicase, also called Twinkle, is essential for mtDNA maintenance. Its helicase domain shares high homology with helicases from superfamily 4. Structural analyses of helicases from this family indicate that carboxyl-terminal residues contribute to NTP hydrolysis required for translocation and DNA unwinding, yet genetic and biochemical information is very limited. Here, we evaluate the effects of overexpression in Drosophila cell culture of variants carrying a series of deletion and alanine substitution mutations in the carboxyl terminus and identify critical residues between amino acids 572 and 596 of the 613 amino acid polypeptide that are essential for mitochondrial DNA helicase function in vivo. Likewise, amino acid substitution mutants K574A, R576A, Y577A, F588A, and F595A show dose-dependent dominant-negative phenotypes. Arg-576 and Phe-588 are analogous to the arginine finger and base stack of other helicases, including the bacteriophage T7 gene 4 protein and bacterial DnaB helicase, respectively. We show here that representative human recombinant proteins that are analogous to the alanine substitution mutants exhibit defects in nucleotide hydrolysis. Our findings may be applicable to understand the role of the carboxyl-terminal region in superfamily 4 DNA helicases in general.
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