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Biomedical subjects

Jian Yu

Publications and source records attributed to Jian Yu.

80 records · Page 5Linked to original sources

Compartmentalization of surface envelope glycoprotein of human immunodeficiency virus type 1 during acute and chronic infection.

Human immunodeficiency virus type 1 is characterized by extensive genetic heterogeneity. Having previously demonstrated that, in the peripheral blood, the initial viral population is more homogeneous than at subsequent stages of infection, we have extended our studies to tissue samples, allowing comparisons between viral populations in peripheral blood and tissues during both the acute and chronic stages of infection. We found that homogeneity in gp120 sequences during the acute infection phase is not just restricted to the peripheral blood but also extends to other tissue compartments. However, in chronically infected individuals, heterogeneous and distinct viral populations were found in different compartments. We therefore conclude that the dominant and homogeneous viral population observed during the acute infection phase is likely to infiltrate lymphoid tissues and form the genetic bases for subsequent diversification. It is therefore likely that the compartmentalization of viral sequences observed in chronically infected patients reflects a gradual diversification of a common dominant viral variant rather than the preferential migration of distinct viral populations to different tissue compartments at the beginning of infection.

Acute Disease↗

Peginterferon-alpha-2a (40kD) and ribavirin in patients with chronic hepatitis C: a phase II open-label study.

BACKGROUND AND AIMS: Addition of a 40kD polyethylene glycol moiety to interferon-alpha-2a [peginterferon-alpha-2a (40kD)] improves pharmacokinetic properties over those of standard interferon. We conducted a phase II study to assess the safety and initial efficacy of peginterferon-alpha-2a (40kD) plus ribavirin combination therapy in patients with chronic hepatitis C (CHC). METHODS: Twenty patients received open-label 180 microg peginterferon-alpha-2a (40kD) subcutaneously once weekly and oral ribavirin 1000 or 1200mg daily for patients weighing <75 or > or =75kg, respectively, for a period of 24 weeks. Patients with hepatitis C virus (HCV) genotype 1 and a virological response at week 24 received study drugs for an additional 24 weeks. RESULTS: A sustained virological response, defined as undetectable HCV RNA 24 (i.e. <100 copies/ml) weeks after completing the therapy, was achieved in 50% of patients in an intent-to-treat analysis (6/16 genotype 1 and 4/4 genotype non-1). Adverse events were similar to those reported with unmodified interferon plus ribavirin combination therapy. Anaemia led to ribavirin dose reduction in five patients. Neutropenia led to dose reduction in three patients treated with peginterferon-alpha-2a (40kD). CONCLUSIONS: The addition of ribavirin to a once-weekly peginterferon-alpha-2a (40kD) regimen should be investigated in larger clinical trials.

Adult↗

[Production of SAM by recombinant Pichia pastoris].

To utilize Pichia pastoris to produce S-adenosyl-L-methionine (SAM), an intracellular expression vector harboring S. cerevisiae SAM2 was transformed into GS115. A recombinant strain having 2 copies of expression cassette was obtained through G418 resistance screening. This strain had higher SAM synthetase activity and higher SAM production capacity than the original strain, when cultured in medium containing methanol and methionine. The carbon source and nitrogen source of medium was optimized. The results showed SAM production by this strain was closely related to carbon metabolism. With supplementation of 0.2% glycerol every day from the beginning of 3rd day, this strain produced 1.58 g/L SAM when cultured in a medium containing 0.75% L-methionine and optimized carbon and nitrogen source after 6 days.

Methionine Adenosyltransferase↗

Metabolic carbon fluxes and biosynthesis of polyhydroxyalkanoates in Ralstonia eutropha on short chain fatty acids.

Short chain fatty acids such as acetic, propionic, and butyric acids can be synthesized into polyhydroxyalkanoates (PHAs) by Ralstonia eutropha. Metabolic carbon fluxes of the acids in living cells have significant effect on the yield, composition, and thermomechanical properties of PHA bioplastics. Based on the general knowledge of central metabolism pathways and the unusual metabolic pathways in R. eutropha, a metabolic network of 41 bioreactions is constructed to analyze the carbon fluxes on utilization of the short chain fatty acids. In fed-batch cultures with constant feeding of acid media, carbon metabolism and distribution in R. eutropha were measured involving CO2, PHA biopolymers, and residual cell mass. As the cells underwent unsteady state metabolism and PHA biosynthesis under nitrogen-limited conditions, accumulative carbon balance was applied for pseudo-steady-state analysis of the metabolic carbon fluxes. Cofactor NADP/NADPH balanced between PHA synthesis and the C3/C4 pathway provided an independent constraint for solution of the underdetermined metabolic network. A major portion of propionyl-CoA was directed to pyruvate via the 2-methylcitrate cycle and further decarboxylated to acetyl-CoA. Only a small amount of propionate carbon (<15% carbon) was directly condensed with acetyl-CoA for 3-hydroxyvalerate. The ratio of glyoxylate shunt to TCA cycle varies from 0 to 0.25, depending on the intracellular acetyl-CoA level and acetic acid in the medium. Malate is the node of the C3/C4 pathway and TCA cycle and its decarboxylation to dehydrogenation ranges from 0.33 to 1.28 in response to the demands on NADPH and oxaloacetate for short chain fatty acids utilization.

Alkanes↗

Cost-effective recovery and purification of polyhydroxyalkanoates by selective dissolution of cell mass.

Highly efficient separation and purification of polyhydroxyalkanoates (PHAs) from PHA-containing cell mass is essential to production of the bioplastics from renewable resources in a cost-effective, environmentally friendly way. Based on selective dissolution of non-PHA cell mass (NPCM) by protons in aqueous solution and crystallization kinetics of PHA biopolymers, a simple process is developed and demonstrated to recover PHAs from cell mass to high purity (>97 wt %) with high yield (>95 wt %). The average molecular weight of biopolyesters is controlled, which follows an exponential function of process severity, a combined factor of processing conditions. Compared with conventional chemical treatment such as sequential surfactant and hypochlorite treatment, this new technology substantially reduces the chemical cost for PHA recovery and purification from PHA-containing cell mass.

Alkalies↗

Influences on childhood asthma in low-income communities in China and the United States.

For comparison of childhood asthma, the same case-finding survey and parent interview questionnaires were used to collect data from 639 children with asthma in 21 elementary schools in Beijing and 835 children with asthma in 14 elementary schools in Detroit, Michigan. Asthma prevalence in Beijing (7.3%) was more than three times lower than in Detroit (24%) despite a high level of smoking among Chinese parents. Body mass index (BMI; weight in kilograms divided by height in meters squared) levels were higher in Detroit but were not associated with persistent asthma in either country. Higher levels of past infection in Beijing and household allergens in Detroit were noted and may be associated with differences in prevalence. Despite less severe disease observed in Beijing, hospitalizations and office visits did not differ from Detroit. This may be partially associated with less use of anti-inflammatory medicine and lower levels of parental asthma management in China.

Air Pollution, Indoor↗

Differential apoptotic response to the proteasome inhibitor Bortezomib [VELCADE, PS-341] in Bax-deficient and p21-deficient colon cancer cells.

Targeting the ubiquitin-proteasome pathway has emerged as a promising approach for treating cancer. Bortezomib (VELCADE, formerly known as PS-341), a potent and reversible proteasome inhibitor, is being evaluated in clinical trials for treating multiple myeloma, and various other types of hematologic and solid tumors. Proteasome inhibitors are known to induce apoptosis in human cancer cells. Nevertheless, the mechanisms of apoptosis induced by proteasome inhibitors remain unclear. In this study, we investigated the role of p53 and its downstream targets in bortezomib-induced apoptosis in HCT116 human colon cancer cells. We demonstrated that bortezomib induced p53, and activated its downstream genes p21, PUMA and Bax in a p53-dependent fashion. However, apoptotic response to bortezomib was not affected by the deletion of p53. Surprisingly, we found that bortezomib-induced apoptosis was markedly enhanced in the p21-knockout cells, while significantly decreased in the BAX-knockout cells. Furthermore, in the cells deficient for both Bax and p21, apoptosis was restored to the level in the parental or the p53-deficient cells. The opposite effects of Bax and p21 were unrelated to the extent of proteasome inhibition, and were also observed in cells treated with different proteasome inhibitors. These results indicate that p53 downstream targets can collectively modulate apoptotic response to bortezomib and other proteasome inhibitors.

Acetylcysteine↗