Biomedical subjects

Jun Liu

Publications and source records attributed to Jun Liu.

385 records · Page 22Linked to original sources

PubMedDate not supplied

Timing of FSH-stimulation and follicular development in cryopreserved human ovarian grafts.

Cryopreserved human primordial follicles grafted into immunodeficient hosts are susceptible to gonadotrophic stimulation but the optimal interval between grafting and stimulation has not been determined. The effect of stimulation with FSH at different time intervals after grafting was therefore investigated. Cryopreserved human ovarian cortical grafts from an androgen pre-treated female-to-male transsexual patient were transplanted into four groups of four non-obese, diabetic severe combined immune deficiency (NOD-SCID) mice. Ten, 12, 14 and 17 weeks after grafting, stimulation was started with daily intra-peritoneal injections of 5 IU of recombinant FSH for 14 days. Grafts were recovered and serially sectioned for counting the number of follicles and determining the different stages of development. Significantly more primary and secondary follicles were found in all stimulated groups compared with the non-stimulated control. This progression from the primordial to growing primary and secondary stages was most significant in the 14 weeks interval group. Formation of antral follicles was scarce and was only noticed in the 10 and 17 week groups. Cystic follicles and follicles with structural oocyte abnormalities were encountered in each group. Whether this phenomenon is related to the hormonal state of the tissue donor or to the cryopreservation and transplantation procedures is the subject of further investigation. It is concluded that the interval between grafting of ovarian tissue and the start of gonadotrophic stimulation may be important for an optimal follicular development after grafting.

Animals↗

PubMedDate not supplied

Structure-function engineering of interferon-beta-1b for improving stability, solubility, potency, immunogenicity, and pharmacokinetic properties by site-selective mono-PEGylation.

Recombinant interferon-beta-1b (IFN-beta-1b) is used clinically in the treatment of multiple sclerosis. In common with many biological ligands, IFN-beta-1b exhibits a relatively short serum half-life, and bioavailability may be further diminished by neutralizing antibodies. While PEGylation is an approach commonly employed to increase the blood residency time of protein therapeutics, there is a further requisite for molecular engineering approaches to also address the stability, solubility, aggregation, immunogenicity and in vivo exposure of therapeutic proteins. We investigated these five parameters of recombinant human IFN-beta-1b in over 20 site-selective mono-PEGylated or multi-PEGylated IFN-beta-1b bioconjugates. Primary amines were modified by single or multiple attachments of poly(ethylene glycol), either site-specifically at the N-terminus, or randomly on the 11 lysines. In two alternate approaches, site-directed mutagenesis was independently employed in the construction of designed IFN-beta-1b variants containing either a single free cysteine or lysine for site-specific PEGylation. Optimization of conjugate preparation with 12 kDa, 20 kDa, 30 kDa, and 40 kDa amine-selective PEG polymers was achieved, and a comparison of the structural and functional properties of the IFN-beta-1b proteins and their PEGylated counterparts was conducted. Peptide mapping and MALDI-TOF mass spectrometric analysis confirmed the attachment sites of the PEG polymer. Independent biochemical and bioactivity analyses, including antiviral and antiproliferation bioassays, circular dichroism, capillary electrophoresis, flow cytometric profiling, reversed phase and size exclusion HPLC, and immunoassays demonstrated that the functional activities of the designed IFN-beta-1b conjugates were maintained, while the formation of soluble or insoluble aggregates of IFN-beta-1b was ameliorated. Immunogenicity and pharmacokinetic studies of selected PEGylated IFN-beta-1b compounds in mice and rats demonstrated both diminished IgG responses, and over 100-fold expanded AUC exposure relative to the unmodified protein. The results demonstrate the capacity of this macromolecular engineering strategy to address both pharmacological and formulation challenges for a highly hydrophobic, aggregation-prone protein. The properties of a lead mono-PEGylated candidate, 40 kDa PEG2-IFN-beta-1b, were further investigated in formulation optimization and biological studies.

Amides↗

PubMedDate not supplied

Elevated level of plasma C-reactive protein in patients with unstable angina: its relations with coronary stenosis and lipid profile.

C-reactive protein (CRP) is a sensitive marker of inflammation, and elevated levels have been associated with future risk of cardiovascular events. To explore the role and relationship of CRP and coronary stenosis in the development of unstable angina (UA), plasma levels of CRP were determined on admission in 45 patients with UA, and in 42 patients with stable angina (SA) using high-sensitivity ELISA. Coronary angiography was performed in all patients with coronary heart disease (CHD), and severity of coronary stenosis was evaluated by a quantitative analysis. Lipid measurement was performed using automatic biochemical analyzer. Data available from patients with CHD were compared with those of 41 control subjects. The results showed that plasma levels of CRP are significantly higher in patients with UA than those in patients with SA and control subjects (5.1 +/- 1.4 mg/L vs 1.7 +/- 0.4 mg/L and 1.3 +/- 0.2 mg/L, p<0.01, respectively) with no difference between the latter two groups (p>0.05); the total incidence of clinical events during in-hospital follow-up was higher in the group A (p<0.01); the scores of coronary stenosis are significantly higher in patients with SA than those in patients with UA (4.9 +/- 2.1 vs 3.4 +/- 1.4, p<0.05); there is no correlation between plasma levels of CRP and serum total cholesterol (TC) as well as high-density lipoprotein cholesterol (HDL-C) in both groups (p>0.05 respectively); there was no correlation between plasma levels of CRP and severity of coronary stenosis was found in patients with UA (p>0.05) but a significant positive association in patients with SA (p<0.001); and the patients with persistent, severe, treatment-unresponsive UA had significantly higher CRP levels as well as incidence of clinical events than patients with treatment-responsive UA (7.4 +/- 1.8 mg/L vs 2.6 +/- 1.3 mg/L, p<0.01; 0 vs 22.2%, p<0.05). The present data suggested that inflammation may play an important role in the pathogenesis of UA, and the plasma levels of CRP might have a higher prognostic value than the severity of coronary stenosis correlated with the clinical outcome of instability despite of lipid profile status.

Adult↗

PubMedDate not supplied

In vitro differentiation and mineralization of human dental pulp cells induced by dentin extract.

In this study, the progenitor cells isolated from the human dental pulp were used to study the effects of ethylenediaminetetraacetic acid-soluble dentin extract (DE) on their differentiation and mineralization to better understand tissue injury and repair in the tooth. Mineralization of the matrix was increasingly evident at 14, 21, and 28 d after treatment with a mineralization supplement (MS) (ascorbic acid [AA], beta-glycerophosphate [beta-GP]) and MS + DE. Real-time polymerase chain reaction results showed type I collagen upregulation after the addition of MS + DE at 7 d. Alkaline phosphatase was downregulated after the mineralization became obvious at 14 d. Bone sialoprotein was shown to be upregulated in the mineralized cell groups at all time points and dentin sialophosphoprotein after 7 d. Core binding factor a 1 was upregulated by the treatment of MS and DE at 7, 14, and 21 d. These results indicated that the MS of AA, beta-GP, and DE synergistically induced cell differentiation of pulp progenitor cells into odontoblast-like cells and induced in vitro mineralization.

Alkaline Phosphatase↗

PubMedDate not supplied

Metabolites produced by the phytopathogenic fungus Rhizoctonia solani: isolation, chemical structure determination, syntheses and bioactivity.

The isolation, structure determination, syntheses and biological activity of Nb-acetyltryptamine and three proline containing dioxopiperazines, cyclo(S-Pro-S-Leu) (2), cyclo(S-Pro-S-Ile) (3), and cyclo(S-Pro-S-Val) (4), from cultures of Rhizoctonia solani Kuhn are reported here for the first time. Despite the small amounts isolated, the absolute stereochemistry of these naturally occurring dioxopiperazines was established by 1H NMR using for the first time the chiral solvating agent (R)-(-)-2,2,2-trifluoro-1-(9-anthryl)ethanol.

Dipeptides↗

PubMedDate not supplied

Predictive functional control (PFC) and its application in chlorinated polyethylene process.

The main principle and the characteristic of Predictive Functional Control (PFC) strategy are presented in this paper and the corresponding control system aid design software APC-PFC is also introduced. For a chlorinated polyethylene (CPE) process, a design scheme of cascade predictive functional control system is described and the control performance is improved obviously.

Algorithms↗

PubMedDate not supplied

Chimpanzee (Pan troglodytes) spermatozoa osmotic tolerance and cryoprotectant permeability characteristics.

Osmotic properties of chimpanzee spermatozoa were studied at 22 degrees C. An electronic particle counter was used to determine the isosmotic cell volume, and the volume response after exposure to four commonly used cryoprotectants: dimethyl sulfoxide, glycerol, propylene glycol, and ethylene glycol. The data were analyzed to determine the hydraulic conductivity and the permeability coefficients for the four cryoprotectants. The osmotically inactive volume fraction was determined using a Boyle van't Hoff plot of cells exposed to sodium chloride solutions. A computer-assisted semen analysis system was used to determine the osmotic tolerance of chimp spermatozoa, as well as the effects of a one-step addition and removal of 1 M permeating cryoprotectant on sperm motility. The isosmotic volume of chimpanzee sperm is 27.7 microm3. The osmotically inactive cell fraction is 69%. Hydraulic conductivity was higher in the presence of ethylene glycol: 4.09 +/- 0.76 (mean +/- SEM) and propylene glycol: 3.91 +/- 0.71 as compared to dimethyl sulfoxide: 3.49 +/- 0.79 and glycerol: 2.83 +/- 0.40 microm/min per atmosphere. The permeability of chimpanzee sperm in ethylene glycol (2.18 +/- 0.40 x 10(-3) cm/min) and propylene glycol (1.75 +/- 0.17 x 10(-3) cm/min) was higher than in glycerol (1.42 +/- 0.12 x 10(-3) cm/min) and dimethyl sulfoxide (0.82 +/- 0.015 x 10(-3) cm/min). Although chimpanzee sperm tolerated osmotic stress in the range of 169-400 mOsm very well, loss of motility was observed as the solution concentrations diverged from isosmotic condition. Exposure to the four cryoprotectants at 1 M did not cause a significant reduction in sperm motility. This information on membrane permeability characteristics and cryoprotectant tolerance will aid in designing more reliable cryopreservation protocols for chimpanzee sperm.

Animals↗