Biomedical subjects

Shufang Liu

Publications and source records attributed to Shufang Liu.

14 recordsLinked to original sources

PubMed2026

Decoding Nonlinearities in AAV-Based Gene Therapy Using PBPK Modelling.

The objective of this research was to develop a physiologically based pharmacokinetic (PBPK) model for AAV-based gene therapy, which can capture the nonlinearity observed in both viral vector and transgene product pharmacokinetics (PK) across a wide range of doses, while accounting for the effect of immunogenicity. To develop the PBPK model, previously published PK data generated in mice using AAV8 vector containing the transgene for a non-binding monoclonal antibody was used. Immunocompetent mice were administered with AAV at a wide range of doses (1E8, 1E9, 5E9, 1E10, 2E10, 1E11, 2E11, 1E12, and 1E13vg per mouse), and the PK of transgene and transgene product (i.e., antibody) in plasma and/or tissue was collected. The nonlinearity in transgene product concentrations was characterized using a saturable production process and a concentration-dependent antibody elimination rate was used to characterize the effect of anti-drug antibody (ADA) on transgene product. The model successfully described the PK of both the vector and the transgene product across all dose levels and accurately captured the sigmoidal dose-exposure-response relationship for AAV. Notably, the model described a dose-dependent ADA response, with the high dose group exhibiting an earlier onset and faster rate of transgene product elimination. Lower dose group showed delayed onset and minimal ADA-mediated elimination of transgene product. Overall, the PBPK model presented here effectively characterizes vector and transgene product kinetics in mice and demonstrates utility in preclinical-to-clinical translation and dose optimization of AAV-based gene therapies.

Animals↗

PubMed2006

Fluorescence enhancement of the protein-curcumin-sodium dodecyl benzene sulfonate system and protein determination.

Protein can greatly enhance the fluorescence of curcumin (CU) in the presence of sodium dodecyl benzene sulfonate (SDBS). Experiments indicate that under the optimum conditions, the enhanced intensity of fluorescence is proportional to the concentration of proteins in the range of 0.0050-20.0 microg mL(-1) for bovine serum albumin (BSA), 0.080-20.0 microg mL(-1) for human serum albumin (HSA), and 0.040-28.0 microg mL(-1) for egg albumin (EA). Their detection limits (S/N = 3) are 1.4 ng mL(-1), 20 ng mL(-1), and 16 ng mL(-1), respectively. The method has been satisfactorily used for the determination of proteins in actual samples. In comparison with most of fluorimetric methods, this method is quick and simple, has high sensitivity and good stability. The interaction mechanism is also studied.

Albumins↗

PubMed2006

The sensitive fluorimetric method for the determination of curcumin using the enhancement of mixed micelle.

Curcumin (C21H20O6) is a natural antioxidant, which is considered to be a very useful compound in health matters, and is employed in the treatment of cardiovascular and arthritic illnesses. It is found that the fluorescence of curcumin is greatly enhanced by mixed micelle of sodium dodecyl benzene sulfonate (SDBS) and cetyltrimethylammonium bromide (CTAB) surfactants. Based on this, a sensitive fluorimetric method for the determination of curcumin in aqueous solution is proposed. In the HOAc-NaOAc buffer, the fluorescence intensity of curcumin is proportional to the concentration of curcumin in the range of 0.00020-0.74 microg/mL and the detection limit is 0.017 ng/mL. The synthetic and actual samples are satisfactorily determined. In addition, the interaction mechanism is also studied.

Acetates↗

PubMed2006

The sensitive determination of nucleic acids using resonance light scattering quenching method.

It is found that in hexamethylene tetramine (HMTA)-HCl buffer of pH 7.00, nucleic acids can quench the resonance light scattering (RLS) of europium (III) (Eu3+)-2-thenoyltrifluoroacetne (TTA)-1,10-phenanthroline (Phen) system. Based on this, a sensitive method for the determination of nucleic acids is proposed. The experiments indicate that under the optimum conditions, the quenched RLS intensity is in proportion to the concentration of nucleic acids in the range of 1.0x10(-10) to 2.0x10(-6) g ml-1 for fish sperm (fsDNA), 1.0x10(-11) to 1.0x10(-6) g ml-1 for yeast RNA (yRNA), 5.0x10(-11) to 5.0x10(-7) g ml-1 for calf thymus DNA (ctDNA). Their detection limits (S/N=3) are 0.03, 0.006 and 0.002 ng ml-1, respectively. Therefore, the proposed method is the most sensitive RLS method for the determination of nucleic acids so far. The interaction between nucleic acids and Eu3+-TTA-Phen is also discussed.

Europium↗

PubMed2005

Molecular self-assembling and the fluorescence enhancement in morin-Al3+-cetyltrimethylammonium bromide-protein system.

Fluorescence enhancement effect of the morin-Al3+-cetyltrimethylammonium bromide (CTAB)-bovine serum albumin (BSA) system is reported here and the interaction mechanism is studied using fluorescence, resonance light scattering (RLS), absorption spectroscopy, Far-UV circular dichroism (CD) spectrum and small angle X-ray scattering (SAXS) measurement. It is considered that protein can bind with Al3+, morin and CTAB through self-assembling function with electrostatic attraction, hydrogen bond, hydrophobic interaction and Vander Waal force etc, and forms a supermolecular association with multilayer structure, in which morin-Al3+ is clamped between BSA and CTAB. In this system, the fluorescence enhancement of morin originates from both intermolecular energy transfer between BSA and morin, and the hydrophobic microenvironment provided by BSA and CTAB. Whereas Al3+ plays a key role for the enhancement of energy transfer efficiency because it provides an efficient channel for the energy transfer between BSA and morin.

Aluminum Compounds↗

PubMed2005

Unfolding and refolding of bovine serum albumin induced by cetylpyridinium bromide.

The interaction of bovine serum albumin (BSA) with cationic surfactant cetylpyridinium bromide (CPB) in aqueous solution (pH 7.00) was studied quantitatively with ultraviolet (UV)-visible, far-UV, and near-UV circular dichroism, fluorescence, small angle x-ray scattering, and nuclear magnetic resonance measurement. It was found that CPB at low and high concentrations could induce the unfolding and refolding of BSA, respectively. We suggest that in the unfolding process, there existed BSA-CPB complex with the "necklace and bead" structure in which the unfolded BSA wrapped around CPB micelles, and that the hydrophobic interaction between the complexes led to the formation of large aggregates. The aromatic headgroup of CPB interacted with the tryptophan residues of BSA, resulting in the aromatic ring stacking between BSA and CPB. During the refolding process, the BSA molecule was penetrated into the rod micelle of CPB and the hydrophobic moiety of the BSA molecule was exposed outside while its hydrophilic part was hidden inside, thereby disrupting the aromatic ring stacking.

Animals↗

PubMed2005

Resonance light scattering technique for the determination of protein with rutin and cetylpyridine bromide system.

A new resonance light scattering (RLS) assay of protein is presented. In Tris-NaOH (pH = 10.93) buffer, the RLS of rutin-cetylpyridine bromide (CPB) system can be greatly enhanced by protein, including bovine serum albumin (BSA) and human serum albumin (HSA). The enhanced RLS intensities are in proportion to the concentration of proteins in the range of 5 x 10(-9) to 2.5 x 10(-6) g ml(-1) for BSA and 2.5 x 10(-8) to 3.5 x 10(-6) g ml(-1) for HSA. The detection limits (S/N = 3) are 3.0 ng ml(-1) for BSA and 10.0 ng ml(-1) for HSA. Samples are determined satisfactorily.

Animals↗

PubMed2004

Study of the interaction of proteins with curcumin and SDS and its analytical application.

It is found that protein and sodium dodecyl sulphonate (SDS) can enhance resonance light scattering (RLS) of curcumin (CU). Based on this phenomenon, a new quantitative method for protein in aqueous solution has been developed. In the BR (pH 3.5) buffer, the RLS intensity of CU-SDS system is greatly enhanced by protein. The enhanced RLS is proportional to the concentration of protein in the range of 0.00020-20.0 microgml(-1) for bovine serum albumin (BSA) and 0.00040-1.0 microgml(-1) for human serum albumin (HSA) and their detection limits are 0.16 and 0.041 ngml(-1), respectively. An actual sample is satisfactorily determined. In addition, the interaction mechanism between protein and CU-SDS is also studied by using multi-techniques such as RLS, absorption spectroscopy and fluorescence, zeta potential assay measurement.

Animals↗

PubMed2004

The fluorescence enhancement effect of the Tb-Gd-guanosine-5'-triphosphate-phen system and its analytical application.

It has been found that Tb(3+) can react with guanosine-5'-triphosphate (GTP) and o-phenanthroline (phen), resulting in the intrinsic fluorescence of Tb(3+). This fluorescence can be enhanced by adding La(3+), Gd(3+), Lu(3+), Sc(3+), Y(3+), and so on, among which Gd(3+) produces the greatest enhancement. These are new co-luminescence systems. The experiments indicate under optimum conditions, the fluorescence intensity of the Tb-Gd-GTP-phen system is proportional to the concentration of GTP over the range 1x10(-9) to 3x10(-5) mol/l. The detection limit is 3.1x10(-10) mol/l. The proposed method provides the most sensitive fluorimetry of GTP so far. The mechanism of the Tb-Gd-GTP-phen system has also been studied. The data indicates that there is a large congeries of Tb-Gd-GTP-phen, and the fluorescence enhancement of the Tb-Gd-GTP-phen system is considered to originate from intramolecular and intermocular energy transfers, and the energy-insulating sheath of the Gd complex.

Gadolinium↗

PubMed2004

Advances in the study of luminescence probes for proteins.

Spectral probes (or labels) have been widely used for the investigation and determination of proteins and have made considerable progress. Traditional luminescence probes include fluorescent derivatizing reagents, fluorescent probes and chemiluminescence probes which continue to develop. Of them, near infrared (NIR) fluorescent probes are especially suitable for the determination of biomolecules including proteins, so their development has been rapid. Novel luminescence probes (such as nanoparticle probes and molecular beacons) and resonance light scattering probes recently appeared in the literature. Preliminary results indicate that they possess great potential for ultrasensitive protein detection. This review summarizes recent developments of the above-mentioned probes for proteins and 195 references are cited.

Luminescent Measurements↗

PubMed2004

Study on the fluorescent enhancement effect in terbium-gadolinium-protein-sodium dodecyl benzene sulfonate system and its application on sensitive detection of protein at nanogram level.

The co-luminescence effect in a terbium-gadolinium-protein-sodium dodecyl benzene sulfonate (SDBS) system is reported here. Based on it, the sensitive quantitative analysis of protein at nanogram levels is established. The co-luminescence mechanism is studied using fluorescence, resonance light scattering (RLS), absorption spectroscopy and NMR measurement. It is considered that protein could be unfolded by SDBS, then a efficacious intramolecular fluorescent energy transfer occurs from unfolded protein to rare earth ions through SDBS acting as a "transfer bridge" to enhance the emission fluorescence of Tb3+ in this ternary complex of Tb-SDBS-BSA, where energy transfer from protein to SDBS by aromatic ring stacking is the most important step. Cooperating with the intramolecular energy transfer above is the intermolecular energy transfer between the simultaneous existing complexes of both Tb3+ and Gd3+. The fluorescence quantum yield is increased by an energy-insulating sheath, which is considered to be another reason for the resulting enhancement of the fluorescence. Förster theory is used to calculate the distribution of enhancing factors and has led to a greater understanding of the mechanisms of energy transfer.

Absorption↗

PubMedDate not supplied

Study on the interaction between protein and Eu(III)-chlorotetracycline complex and the determination of protein using the fluorimetric method.

Chlorotetracycline (CTC) can react with europium ions Eu3+, and the complex emits the intrinsic fluorescence of Eu3+. The intensity is greatly enhanced by proteins and this forms the basis of a new fluorimetric method for determination of protein. Further research indicates that under optimum conditions, the enhanced intensity of fluorescence is in proportion to the concentration of proteins, in the range 2.0 x 10(-7)-1.0 x 10(-5) g/mL for bovine serum albumin (BSA) (linear equation, I(f) = 34.35933 + 11.54467 x 10(6)C)(r = 0.99895) and 8.0 x 10(-7)-1.0 x 10(-5) g/mL for human serum albumin (HSA) (linear equation, I(f) = 76.58881 + 5.3569 x 10(6)C) (r = 0.99283). Detection limits (S/N = 3) were 8.9 x 10(-9) g/mL for BSA and 3.3 x 10(-8) g/mL for HSA. In an assay for BSA in calf serum, this method gave a value close to that determined by the UV spectrophotometric method.

Buffers↗

PubMedDate not supplied

Fluorescence enhancement effect of the morin-Al3+ -sodium dodecyl benzene sulphonate-protein system and the determination of proteins.

The fluorescence intensity of the morin-Al(3+) complex was greatly enhanced by proteins in the presence of sodium dodecyl benzene sulphonate (SDBS). Based on this, a new fluorimetric method for the determination of protein was developed. Under optimum conditions, the enhanced intensity of fluorescence was in proportion to the concentration of proteins in the range 1.0 x 10(-8)-1.3 x 10(-5) g/mL for bovine serum albumin (BSA), 4.0 x 10(-8)-1.2 x 10(-5) g/mL for egg albumin (EA) and 5.0 x 10(-8)-1.2 x 10(-5) g/mL for human serum albumin (HSA). Their detection limits (S:N = 3) were 5.0 x 10(-9), 1.8 x 10(-8) and 1.6 x 10(-8) g/mL, respectively. The interaction mechanism was also studied.

Aluminum↗

PubMedDate not supplied

The sensitive determination of nucleic acids using a fluorescence-quenching method.

Experiments indicated that nucleic acids can quench the fluorescence of the Eu3+ -2-thenoyltrifluoroacetone (TTA)-1,10-phenanthroline (Phen) system. Based on this, a sensitive method for the determination of nucleic acids was proposed. The experiments indicated that under the optimum conditions, the quenched fluorescence intensity was in proportion to the concentration of nucleic acids in the range 1.0 x 10(-11)-1.0 x 10(-6) g/mL for yeast RNA (yRNA), 5.0 x 10(-11)-5.0 x 10(-7) g/mL for fish sperm (fsDNA) and 1.0 x 10(-10)-1.5 x 10(-6) g/mL for calf thymus DNA (ctDNA). Their detection limits were 3.0 x 10(-12), 4.0 x 10(-12) and 5.0 x 10(-11) g/mL, respectively. Therefore, the proposed method is one of the most sensitive methods available. The interaction between nucleic acids and Eu3+ -TTA-Phen is also discussed.

Europium↗