Biomedical subjects

Xiaoning Wang

Publications and source records attributed to Xiaoning Wang.

9 recordsLinked to original sources

PubMed2017

A New Natural Product Analog of Blasticidin S Reveals Cellular Uptake Facilitated by the NorA Multidrug Transporter.

The permeation of antibiotics through bacterial membranes to their target site is a crucial determinant of drug activity but in many cases remains poorly understood. During screening efforts to discover new broad-spectrum antibiotic compounds from marine sponge samples, we identified a new analog of the peptidyl nucleoside antibiotic blasticidin S that exhibited up to 16-fold-improved potency against a range of laboratory and clinical bacterial strains which we named P10. Whole-genome sequencing of laboratory-evolved strains of Staphylococcus aureus resistant to blasticidin S and P10, combined with genome-wide assessment of the fitness of barcoded Escherichia coli knockout strains in the presence of the antibiotics, revealed that restriction of cellular access was a key feature in the development of resistance to this class of drug. In particular, the gene encoding the well-characterized multidrug efflux pump NorA was found to be mutated in 69% of all S. aureus isolates resistant to blasticidin S or P10. Unexpectedly, resistance was associated with inactivation of norA, suggesting that the NorA transporter facilitates cellular entry of peptidyl nucleosides in addition to its known role in the efflux of diverse compounds, including fluoroquinolone antibiotics.

Bacterial Proteins↗

PubMed2006

Chemical radiculitis.

The theory of chemical radiculitis had been put forward about 30 years ago, but as yet it has not been proved by clinical studies. The aim of the current studies was to determine whether the annular tear of a painful disc proved by discography is the cause of radiating leg pain (radiculopathy) in patients with discogenic low back pain. Forty-two patients with discogenic low back pain at single disc level with concomitant radiating leg pain were studied in order to analyse the relationship between site of annular tear and side of radiating leg pain. Electromyogram and motor nerve conduction velocity were monitored to examine nerve root injury. The current studies found that there was a significant positive correlation between the site of annular tear and the side of radiation pain. Abnormalities of electromyogram and reduction of motor nerve conduction velocity were found on the side of radiating leg pain. The studies indicated that leakage of chemical mediators or inflammatory cytokines, which are produced in the painful disc, into epidural space through annular tear could lead to injury to adjacent nerve roots, and it might constitute the primary pathophysiologic mechanism of radiating leg pain in patients with discogenic low back pain but with no disc herniation.

Adult↗

PubMed2006

GM-CSF-surface-modified B16.F10 melanoma cell vaccine.

Through the specific and tight interaction between streptavidin and biotin, a novel platform was developed to allow for rapid (less than 2h), efficient and durable display of streptavidin-tagged bioactive GM-CSF on the surface of biotinylated B16.F10 tumor cells. This technology involved biotinylation of the cell membrane with a biotin derivative and surface modification of the biotinylated cells with the bi-functional fusion protein, streptavidin-tagged GM-CSF. Furthermore, the resultant GM-CSF-modified B16.F10 whole tumor cell vaccine could induce strong and long-lasting systemic protection against the wild-type tumor challenge. Therefore, the platform may represent a fast, efficient and safe approach for the whole tumor cell vaccination.

Animals↗

PubMed2006

Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2.

BACKGROUND: Streptococcus suis serotype 2 (S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure. METHODS AND FINDINGS: We investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks. CONCLUSIONS: We report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study.

Adult↗

PubMed2005

Effects of hyaluronan-fortified surfactant in ventilated premature piglets with respiratory distress.

We hypothesized that enriching surfactant with hyaluronan would restore lung function when tested in a premature animal model. Newborn piglets (85% gestation, term 112-114 days) were delivered by cesarean section, subjected to mechanical ventilation (tidal volume 6- 8 ml/kg) and randomly assigned to treatment with 50 or 100 mg/kg Curosurf (C50 and C100), 50 or 100 mg/kg Curosurf mixed with 2.5% HA (w/w, CH50 and CH100). A ventilated and not treated group (Cont) and a not treated and not ventilated group (Non) were included as controls. Six hours after treatment the lungs were removed and biochemical, biophysical, cytological and histological analyses were carried out. The CH100, CH50, C100 and C50 groups had variable but significantly improved alveolar phospholipid content, minimal surface tension, alveolar aeration and wet/dry lung weight ratios, but little histological evidence of lung injury. CH100, CH50 and C100 groups had the best effects in terms of oxygenation, lung compliance and histology and evidence of decreased inflammation (IL-8 and TNF-alpha mRNA expression). We conclude that HA added to 50 mg/kg Curosurf or use of 100 mg/kg Curosurf with or without HA provides the best effects in terms of lung function and reduction of inflammation.

Animals↗

PubMed2005

Response of memory CD8+ T cells to severe acute respiratory syndrome (SARS) coronavirus in recovered SARS patients and healthy individuals.

To date, the pathogenesis of severe acute respiratory syndrome (SARS) in humans is still not well understood. SARS coronavirus (SARS-CoV)-specific CTL responses, in particular their magnitude and duration of postinfection immunity, have not been extensively studied. In this study, we found that heat-inactivated SARS-CoV elicited recall CTL responses to newly identified spike protein-derived epitopes (SSp-1, S978, and S1202) in peripheral blood of all HLA-A*0201(+) recovered SARS patients over 1 year postinfection. Intriguingly, heat-inactivated SARS-CoV elicited recall-like CTL responses to SSp-1 but not to S978, S1202, or dominant epitopes from several other human viruses in 5 of 36 (13.8%) HLA-A*0201(+) healthy donors without any contact history with SARS-CoV. SSp-1-specific CTLs expanded from memory T cells of both recovered SARS patients, and the five exceptional healthy donors shared a differentiated effector CTL phenotype, CD45RA(+)CCR7(-)CD62L(-), and expressed CCR5 and CD44. However, compared with the high avidity of SSp-1-specific CTLs derived from memory T cells of recovered SARS patients, SSp-1-specific CTLs from the five exceptional healthy donors were of low avidity, as determined by their rapid tetramer dissociation kinetics and reduced cytotoxic reactivity, IFN-gamma secretion, and intracellular production of IFN-gamma, TNF-alpha, perforin, and granzyme A. These results indicate that SARS-CoV infection induces strong and long-lasting CTL-mediated immunity in surviving SARS patients, and that cross-reactive memory T cells to SARS-CoV may exist in the T cell repertoire of a small subset of healthy individuals and can be reactivated by SARS-CoV infection.

Adolescent↗

PubMed2004

Identification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein.

A novel coronavirus, severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), has been identified as the causal agent of SARS. Spike (S) protein is a major structural glycoprotein of the SARS virus and a potential target for SARS-specific cell-mediated immune responses. A panel of S protein-derived peptides was tested for their binding affinity to HLA-A*0201 molecules. Peptides with high affinity for HLA-A*0201 were then assessed for their capacity to elicit specific immune responses mediated by cytotoxic T lymphocytes (CTLs) both in vivo, in HLA-A2.1/K(b) transgenic mice, and in vitro, from peripheral blood lymphocytes (PBLs) harvested from healthy HLA-A2.1(+) donors. SARS-CoV protein-derived peptide-1 (SSp-1 RLNEVAKNL), induced peptide-specific CTLs both in vivo (transgenic mice) and in vitro (human PBLs), which specifically released interferon-gamma (IFN-gamma) upon stimulation with SSp-1-pulsed autologous dendritic cells (DCs) or T2 cells. SSp-1-specific CTLs also lysed major histocompatibility complex (MHC)-matched tumor cell lines engineered to express S proteins. HLA-A*0201-SSp-1 tetramer staining revealed the presence of significant populations of SSp-1-specific CTLs in SSp-1-induced CD8(+) T cells. We propose that the newly identified epitope SSp-1 will help in the characterization of virus control mechanisms and immunopathology in SARS-CoV infection, and may be relevant to the development of immunotherapeutic approaches for SARS.

Amino Acid Sequence↗

PubMed2004

Liquid chromatography-tandem mass spectrometric method for the analysis of fluconazole and evaluation of the impact of phenolic compounds on the concentration of fluconazole in Candida albicans.

A bioanalytical method using liquid chromatography-tandem mass spectrometry was developed for the analysis of fluconazole in Candida albicans after incubation with phenolic compounds, which have been proved possessing antifungal properties and have synergetic activity against C. albicans when in combination with fluconazole. Samples of C. albicans thallus obtained by centrifuging the mixed culture after 24 h incubation were saponified and centrifuged. The supernatant was evaporated to dryness, reconstituted, and injected on a C18 column using an organic-aqueous mobile phase. The chromatographic run time was 3.5 min per injection, with retention times of 2.4 min for fluconazole. The detection was by monitoring fluconazole at m/z 305-->191. The standard curve range was 1.0-100.0 ng ml(-1) with a mean correlation coefficient 0.9992. The precision and accuracy of the quality control (QC) samples were R.S.D < 5.5%, R.E. <3% for intra-day and R.S.D. <6.2%, R.E. <4% for inter-day. The concentration of fluconazole in C. albicans was found to be increased with the increment of the tested compounds concentration when they were in combination.

Candida albicans↗

PubMed2004

Study of bovine hemoglobin dissociation by multiangle laser light-scattering method.

Hemoglobin (Hb) is an oligomeric protein, composed of four monomeric subunits. Hb molecule may undergo dissociation from a single native tetramer to two dimmers, which is called hemoglobin dissociation. In this article the dissociation of bovine Hb is studied by measurment of the average MW of the samples using the multiangle laser light-scattering method. Advanced multiangle laser light-scattering technique is a powerful method to determine the absolute molecular weights of the protein in solution. Two different methods, microbatch multiangle light-scattering (MALS) and on-line size-exclusion high-performance liquid chromatography light scattering with refractive index detector, are used to measure the average molecular weight of bovine Hb in different concentration respectively. The results of the two methods are agreed well. From the results, it can be concluded that the average molecular weigh of bovine Hb will be about 54 kDa when the bovine Hb concentration is more than 1.5 mg/mL, and will be about 36 kDa when the concentration is less than 0.03 mg/mL. The other conclusion, which can be derived from these results, is that the dissociation of bovine Hb is related with the pH and the tetramer appears to be more stable in the pH range of 6-9.

Animals↗