Biomedical subjects

Lan Gao

Publications and source records attributed to Lan Gao.

10 recordsLinked to original sources

PubMed2026

Effect of long-term sepiapterin treatment on dietary phenylalanine tolerance in patients with phenylketonuria: Interim results from the phase 3 APHENITY Extension Study.

PURPOSE: To report interim results from the ongoing, open-label, phase 3 APHENITY Extension Study (NCT05166161), evaluating long-term treatment with sepiapterin in patients with phenylketonuria. METHODS: Participants received an age-based dose of oral sepiapterin daily; those with mean blood phenylalanine (Phe) levels <360 μmol/L (<5.95 mg/dL) after 2 weeks underwent a 26-week dietary Phe tolerance assessment, wherein dietary Phe intake was adjusted and blood Phe levels monitored. Other participants continued treatment with optional diet liberalization. Primary endpoints included change from baseline to week 26 in dietary Phe intake and treatment-emergent adverse events (TEAEs). RESULTS: As of September 2, 2024, 169 participants received sepiapterin (median [minimum, maximum] age: 14.0 [0.2, 55.0] years, median exposure: 72.9 weeks); 102 participants underwent dietary Phe tolerance assessments. Mean (SD) dietary Phe intake increased from 27.6 (18.0) mg/kg/day at baseline to 62.5 (41.5) mg/kg/day at week 26 (least-squares mean change [SE]: 36.4 [2.8] mg/kg/day from baseline) (P < .0001 from post hoc analysis). The incidence of treatment-related TEAEs was 29.0%; 3 participants (1.8%) discontinued treatment owing to treatment-related TEAEs. There were no treatment-related serious TEAEs or deaths. CONCLUSION: Interim results support the long-term safety of sepiapterin and demonstrate the potential for diet liberalization in adults and children with phenylketonuria. GOV IDENTIFIER: NCT05166161 (https://www. CLINICALTRIALS: gov/study/NCT05166161; date of registration, December 8, 2021).

Humans↗

PubMed2006

An ultraefficient affinity-based high-throughout screening process: application to bacterial cell wall biosynthesis enzyme MurF.

The authors describe the discovery of a new class of inhibitors to an essential Streptococcus pneumoniae cell wall biosyn-thesis enzyme, MurF, by a novel affinity screening method. The strategy involved screening very large mixtures of diverse small organic molecules against the protein target on the basis of equilibrium binding, followed by iterative ultrafiltration steps and ligand identification by mass spectrometry. Hits from any affinity-based screening method often can be relatively nonselective ligands, sometimes referred to as "nuisance" or "promiscuous" compounds. Ligands selective in their binding affinity for the MurF target were readily identified through electronic subtraction of an empirically determined subset of promiscuous compounds in the library without subsequent selectivity panels. The complete strategy for discovery and identification of novel specific ligands can be applied to all soluble protein targets and a wide variety of ligand libraries.

Anti-Bacterial Agents↗

PubMed2006

Kinase drug discovery by affinity selection/mass spectrometry (ASMS): application to DNA damage checkpoint kinase Chk1.

Kinase enzymes are involved in a vast array of biological processes associated with human disease; therefore, selective kinase inhibition by small molecules and therapeutic antibodies is an area of intense study. The authors show that drug candidates with immediate value for biological preclinical evaluation can be identified directly through ultra-efficient affinity screening of kinase enzymes and random compound mixtures. The screening process comprises sampling and trapping equilibrium binding between candidate ligands and protein in solution, followed by removal of unbound ligands via 3 rounds of ultrafiltration and direct identification of bound ligands by mass spectrometry. Evaluation of significant peaks is facilitated by automated integration and collation of the mass spectral data and import into custom software for analysis. One Chk1-selective ligand found by using this process is presented in detail. The compound is potent in both enzymatic and Chk1-dependent cellular assays, and specific contacts in the Chk1 active site are shown by X-ray crystallography.

Amino Acid Sequence↗

PubMed2006

Sequence effects of aminofluorene-modified DNA duplexes: thermodynamic and circular dichroism properties.

Circular dichroism (CD) and UV-melting experiments were conducted with 16 oligodeoxynucleotides modified by the carcinogen 2-aminofluorene, whose sequence around the lesion was varied systematically [d(CTTCTNG[AF]NCCTC), N = G, A, C, T], to gain insight into the factors that determine the equilibrium between base-displaced stacked (S) and external B-type (B) duplex conformers. Differing stabilities among the duplexes can be attributed to different populations of S and B conformers. The AF modification always resulted in sequence-dependent thermal (T(m)) and thermodynamic (-DeltaG degrees ) destabilization. The population of B-type conformers derived from eight selected duplexes (i.e. -AG*N- and -CG*N-) was inversely proportional to the -DeltaG degrees and T(m) values, which highlights the importance of carcinogen/base stacking in duplex stabilization even in the face of disrupted Watson-Crick base pairing in S-conformation. CD studies showed that the extent of the adduct-induced negative ellipticities in the 290-350 nm range is correlated linearly with -DeltaG degrees and T(m), but inversely with the population of B-type conformations. Taken together, these results revealed a unique interplay between the extent of carcinogenic interaction with neighboring base pairs and the thermodynamic properties of the AF-modified duplexes. The sequence-dependent S/B heterogeneities have important implications in understanding how arylamine-DNA adducts are recognized in nucleotide excision repair.

Base Sequence↗

PubMed2005

Compound transfer efficiency from polystyrene surfaces: application to microarrayed compound screening.

In microarrayed compound screening (microARCS), compounds are spotted and dried onto a polystyrene sheet (ChemCard)ata high density and introduced into the assay by contacting with agarose gels that contain reagents for the assay. The authors have conducted studies to characterize the compound transfer process using 59 compounds of diverse properties. The amount of compounds remaining on the ChemCard was determined by liquid chromatography/mass spectrometry after incubation with agarose gels for predetermined time periods. The results showed good correlation with kinetics of compound transfer to phosphate-buffered saline (PBS) buffer, but only moderate correlation with equilibrium solubility of compounds in PBS buffer. These observations indicate that the major factor determining compound transfer efficiency is the kinetics of dissolution of compounds, rather than equilibrium solubility and diffusion of compounds in the gel. Compounds of lower ClogP showed a higher rate of transfer to agarose gels and vice versa. Other compound properties such as molecular weight, size, acid-base, and H-bonding properties did not significantly affect compound transfer. Importantly, the majority of the compounds studied show greater than 20% transfer after a 10-min incubation with agarose gels, providing sufficient amounts of compounds for screening purposes.

Chromatography, High Pressure Liquid↗

PubMed2005

Postoperative cognitive dysfunction after cardiac surgery.

Prolonged postoperative cognitive dysfunction (POCD) is reported to occur frequently after cardiac surgery. However, it is rarely assessed in routine clinical practice and receives little attention. Although the cerebral consequences of cardiopulmonary bypass have been measured clinically, insights into the resulting molecular and pathologic events within the brain have only begun to be investigated. POCD is likely to impair quality of life and constitutes a large burden on society when elderly patients prematurely lose their independence. Numerous studies have reported that neurocognitive deficit is associated with heightened mortality, increased length of hospital stay, and discharge to a nursing home. This is linked with a tremendous demand for health-care resources. Because of the magnitude of the clinical problem, serious consideration must be directed toward understanding its etiology and the development of neuroprotective strategies. Clearly identifying the mechanisms of POCD is challenging. The purpose of this review is to discuss recent developments in our understanding of the pathophysiologic mechanisms, prevention, and treatments that have been designed to ameliorate brain dysfunction after cardiac surgery.

Alzheimer Disease↗

PubMed2005

[Simultaneous determination of four fluoroquinolone residues in edible chicken tissues by reversed-phase high performance liquid chromatography].

A reversed-phase high performance liquid chromatographic method with fluorescence detection was developed for the simultaneous analysis of ciprofloxacin, danofloxacin, enrofloxacin and sarafloxacin residues in edible chicken tissues. The analytes were extracted from chicken muscle, skin and fat, liver, kidney by aqueous potassium dihydrogenphosphate of different pH values through homogenization. The supernatant of the extract was applied onto a C18 solid phase extraction cartridge for clean-up. The separation was achieved on a C18 column, and the detection was performed with a fluorescence detector (excitation at 280 nm and emission at 450 nm). The four fluoroquinolones were analyzed in spiked samples of four chicken tissues with mean recoveries in the range of 53.9%-93.4% at spiked levels of 20-300 microg/kg. The relative standard deviations of inter-assay were no more than 23%. The detection limits of quantification were 20 microg/kg for ciprofloxacin, enrofloxacin and sarafloxacin and 4 microg/kg for danofloxacin. The method is simple, fast, and sufficient for routine analysis.

Animals↗

PubMed2004

RDP58, a novel immunomodulatory peptide, ameliorates clinical signs of disease in the Lewis rat model of acute experimental autoimmune encephalomyelitis.

The therapeutic value of a novel immunomodulatory peptide, RDP58, was investigated in the acute experimental autoimmune encephalomyelitis (EAE) model of Multiple Sclerosis (MS). RDP58 is a 10-amino acid peptide with two major activities: (i) inhibition of inflammatory TH1 cytokines such as TNFalpha, IFNgamma, and IL12 and (ii) up-regulation of heme oxygenase-1 (HO-1) expression. Experiments in which EAE-induced Lewis rats exhibit an acute monophasic episode of disease demonstrated that a single intracerebroventricular injection of RDP58 is effective in preventing clinical signs of disease. The therapeutic effect on disease activity was observed at all pre-onset administration times and at all doses tested. Consistent with disease activity in vivo, RDP58-treated animals had reduced cellular infiltration within the spinal cord along with decreased TNFalpha expression levels. The data in this proof of concept study support the premise that RDP58, as a platform molecule, may be a promising new therapeutic intervention in autoimmune and inflammatory diseases.

Animals↗

PubMed2004

Effects of acupuncture on myelogenic osteoclastogenesis and IL-6 mRNA expression.

The effect of acupuncture and moxibustion on myelogenic osteoclastogenesis and IL-6 mRNA expression is investigated. The result turns to be that the number of myelogenic osteoclasts in the model group is obviously bigger than in the sham operation group (P<0.01), and that in the acupuncture group is markedly smaller than in the model group (P<0.01). The IL-6 mRNA expression in the marrow cells of the model group is significantly elevated, as compared with that in the sham operation group (P<0.01), while the its elevation is lower in the acupuncture group than in the model group (P<0.01). It is therefore concluded that 1) acupuncture effectively modulates the secretion of and then to reduces IL-6 mRNA expression and 2) acupuncture decreases the number of myelogenic osteoclasts.

Acupuncture↗

PubMed2003

[The application of DNA molecular marker on tomato breeding].

This paper reviewed the recent advance of the application of DNA molecular marker in various aspects of tomato breeding including genetic map construction, germplasm research and purity control of cultivars,identification markers linked to important genes and map-based gene cloning.

English Abstract↗