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Biomedical subjects

B Zhang

Publications and source records attributed to B Zhang.

At least 19 recordsLinked to original sources

Fourier-transform infrared-based genome-wide association study identifies candidate genes and variants for sow colostrum composition.

Sows with high prolificacy and better lactation traits are beneficial for weaned piglet number. Because the genetic basis of sow lactation traits remains elusive, genetic improvement for lactation traits lags behind that for litter traits, constraining the full realisation of genetic potential for large litters. Here, we measured 1&#xa0;060 Fourier-transform infrared (FTIR) wavenumbers and five predicted colostrum composition traits from sow colostrum samples. Heritability estimates for both the FTIR spectra and predicted traits ranged from moderate to high. Correlation analysis revealed that lactose percentage was negatively genetically correlated with the other four predicted traits (fat percentage, protein percentage, total solid content, and urea nitrogen content) and with 24&#xa0;h litter weight, which was positively genetically correlated with both protein and total solid content. Genome-wide association studies on the FTIR spectra and predicted traits identified 134 significant single-nucleotide polymorphisms (SNPs) (False discovery rate < 0.05), with most clustering on Sus scrofa chromosomes (SSC) 5 and 7. Among the candidate genes, two expressed in lactating mammary tissue have established roles in milk trait determination: (1) LALBA, which encodes a major colostrum protein and is responsible for lactose synthesis, and (2) BTN1A1, which mediates milk fat secretion. Additionally, the study detected two important candidate variants on SSC7: (1) rs691487382, which was colocalised with the expression quantitative trait locus signal for TRIM26 in the liver, a key metabolic organ supporting lactation, and (2) rs327923027, a missense variant located in a phylogenetically conserved domain of TRIM26, an E3 ubiquitin ligase implicated in liver homeostasis. Taken together, this study identifies, for the first time, candidate genes and variants for sow colostrum, providing genomic markers useful for genetic improvement.

Association analysis↗

Long latency of evoked quantal transmitter release from somata of locus coeruleus neurons in rat pontine slices.

The locus coeruleus (LC) harbors a compact group of noradrenergic cell bodies projecting to virtually all parts of the central nervous system. By using combined measurements of amperometry and patch-clamp, quantal vesicle release of noradrenaline (NA) was detected as amperometric spikes, after depolarization of the LC neurons. After a pulse depolarization, the average latency of amperometric spikes was 1,870 ms, whereas the latency of glutamate-mediated excitatory postsynaptic currents was 1.6 ms. A substantial fraction of the depolarization-induced amperometric spikes originated from the somata. In contrast to glutamate-mediated excitatory postsynaptic currents, NA secretion was strongly modulated by the action potential frequency (0.5-50 Hz). Somatodendritic NA release from LC upon enhanced cell activity produced autoinhibition of firing and of NA release. We conclude that, in contrast to classic synaptic transmission, quantal NA release from LC somata is characterized by a number of distinct properties, including long latency and high sensitivity to action potential frequency.

Action Potentials↗

Hepatitis B virus (HBV) antigen-pulsed monocyte-derived dendritic cells from HBV-associated hepatocellular carcinoma patients significantly enhance specific T cell responses in vitro.

To investigate whether hepatitis B virus (HBV) antigen-pulsed monocyte-derived dendritic cells (MoDC) could mount a T cell response in hepatocellular carcinoma (HCC) patients associated with chronic HBV infection, peripheral blood mononuclear cells (PBMCs) from 36 HBV-associated HCC patients were induced into MoDC and pulsed with hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg), alone and in combination. Co-stimulatory molecules CD80, CD86 and CD40, as well as human leucocyte antigens D-related (HLA-DR) were found to express at the highest level on MoDC pulsed with HBcAg or HBsAg + HBcAg, at a median level on MoDC pulsed with HBcAg or HBsAg alone, and at the lowest level on non-antigen-pulsed MoDC. Interleukin (IL)-10 and IL-12 cytokines were released by antigen-pulsed MoDC at increased levels in the order: no-antigen < HBsAg < HBcAg < HBcAg + HBsAg. MoDC pulsed with HBcAg or HBsAg + HBcAg also had the strongest ability to stimulate autologous T cell proliferation and intracellular interferon (IFN)-gamma production. HBcAg- or HBsAg + HBcAg-pulsed MoDC could also induce HBV core peptide-specific CD8(+) T cell proliferation determined by tetramer staining. In addition, the antigen-pulsed MoDC were found to have a stronger capacity to produce IL-12 and induce T cell response in vitro for patients with higher alanine transaminase (ALT) levels than those with lower ALT levels, indicating that antigen pulse could substantially reverse the impaired function of MoDC in primary HCC patients with active chronic hepatitis B. In conclusion, HBV antigen-pulsed MoDC from HCC patients with chronic hepatitis B could induce HBV-specific T cell response in vitro.

Adult↗

Predictive factors for prognosis of hilar cholangiocarcinoma: postresection radiotherapy improves survival.

AIMS: Several studies have analyzed the determinants of long-term survival in hilar cholangiocarcinoma (HCCA) patients, but the majority of these have not speculated adjuvant therapy on prognosis. We conduct this study to identify potential predictive factors for prognosis of HCCA focusing on aspects dealing with adjuvant therapy. PATIENTS AND METHODS: Data from 75 consecutive HCCA patients undergoing surgical resection with curative intent were recorded prospectively. The survivals of patients were comparable with respect to different factors followed by a univariate and multivariate analysis. RESULTS: Actual 1-year, 3-year, and 5-year survival rates were 84.0, 44.4 and 12.0%, respectively. By Cox proportional hazards survival analysis, the most powerful predictors of outcome was resection type (Hazard Ratio [HR] 17.4, 95% confidence interval [CI] 16.8-17.8), followed by adjuvant radiotherapy (RT) (HR 4.3, 95% CI 3.6-4.9), regional lymph nodes involvement (HR 2.1, 95% CI 1.7-2.6), and preoperative maximum serum total bilirubin level (HR 2.0, 95% CI 1.5-2.5). CONCLUSIONS: Our study showed overall a highly significant benefit in survival in favor of RT, and the difference was especially significant after R1/R2 resection and in patients with Bismuth III/IV type tumors. Postresection chemotherapy (CTx) did not show any clinical benefits. R0 resection still significantly improves survival. Lower total serum bilirubin level, no regional lymph nodes involvement conferred survival advantage.

Adult↗

Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target.

Glioblastoma is the most common primary malignant brain tumor of adults and one of the most lethal of all cancers. Patients with this disease have a median survival of 15 months from the time of diagnosis despite surgery, radiation, and chemotherapy. New treatment approaches are needed. Recent works suggest that glioblastoma patients may benefit from molecularly targeted therapies. Here, we address the compelling need for identification of new molecular targets. Leveraging global gene expression data from two independent sets of clinical tumor samples (n = 55 and n = 65), we identify a gene coexpression module in glioblastoma that is also present in breast cancer and significantly overlaps with the "metasignature" for undifferentiated cancer. Studies in an isogenic model system demonstrate that this module is downstream of the mutant epidermal growth factor receptor, EGFRvIII, and that it can be inhibited by the epidermal growth factor receptor tyrosine kinase inhibitor Erlotinib. We identify ASPM (abnormal spindle-like microcephaly associated) as a key gene within this module and demonstrate its overexpression in glioblastoma relative to normal brain (or body tissues). Finally, we show that ASPM inhibition by siRNA-mediated knockdown inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM as a potential molecular target in glioblastoma. Our weighted gene coexpression network analysis provides a blueprint for leveraging genomic data to identify key control networks and molecular targets for glioblastoma, and the principle eluted from our work can be applied to other cancers.

Animals↗

Oxidative-induced retinal degeneration is attenuated by epigallocatechin gallate.

The aim of this investigation was to determine whether an ingredient of green tea, epigallocatechin gallate (EGCG) could attenuate oxidative stress-induced degeneration of the retina as occurs in age-related macular degeneration (AMD) and glaucoma. Initial in vitro studies on brain membranes showed that EGCG was approximately 10 times more potent than trolox (vitamin E analogue) at attenuating lipid peroxidation caused by the nitric oxide donor, sodium nitroprusside (SNP). Subsequent immunohistochemical studies revealed that following an intraocular injection of SNP retinal photoreceptors are affected. This was supported by electroretinogram (ERG) recordings which showed both the a- and b-wave amplitudes to be significantly reduced. RT-PCR and Western blotting techniques showed that SNP caused a significant decrease in photoreceptor-specific markers (RET-P1, rhodopsin kinase), an increase in the cell death marker caspase-3, and no change in the ganglion cell specific markers, neurofilament (NF-L) and Thy-1. Importantly, when EGCG was co-injected, the detrimental effects to the retina caused by SNP were significantly blunted. The conclusion reached from this study is that EGCG is a powerful antioxidant and when injected into the eye with SNP attenuated the detrimental influence of SNP to retinal photoreceptors. Since oxidative stress has been implicated in retinal diseases like AMD and glaucoma this study provides "proof of principle" for the idea that daily intake of EGCG may help individuals suffering from retinal diseases where oxidative stress is implicated.

Animals↗

Extended vertical lower trapezius island myocutaneous flap for reconstruction of cranio-maxillofacial defects.

This study explored an effective method for repairing cranio-maxillofacial soft-tissue defects following radical craniofacial surgery in four patients with malignant tumours involving the skull base and frontal region. The large cranio-maxillofacial soft-tissue defects were reconstructed using an extended vertical lower trapezius island myocutaneous flap based on the transverse cervical artery. The flap was 8-12 cm long and 5-7 cm wide. No major flap failure occurred, and there was no shoulder dysfunction. The patients were followed for 3-12 months. One patient suffered a local recurrence, and another died of lung metastasis 12 months postoperatively. The extended vertical lower trapezius island myocutaneous flap is a simple, reliable and large flap. It is preferred for reconstructing cranio-maxillofacial soft-tissue defects when a pedicled flap is used following craniofacial surgery for cancer.

Adult↗

Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer.

Animals↗

The association of GRB 060218 with a supernova and the evolution of the shock wave.

Although the link between long gamma-ray bursts (GRBs) and supernovae has been established, hitherto there have been no observations of the beginning of a supernova explosion and its intimate link to a GRB. In particular, we do not know how the jet that defines a gamma-ray burst emerges from the star's surface, nor how a GRB progenitor explodes. Here we report observations of the relatively nearby GRB 060218 (ref. 5) and its connection to supernova SN 2006aj (ref. 6). In addition to the classical non-thermal emission, GRB 060218 shows a thermal component in its X-ray spectrum, which cools and shifts into the optical/ultraviolet band as time passes. We interpret these features as arising from the break-out of a shock wave driven by a mildly relativistic shell into the dense wind surrounding the progenitor. We have caught a supernova in the act of exploding, directly observing the shock break-out, which indicates that the GRB progenitor was a Wolf-Rayet star.

Journal Article↗

Individual fracture risk and the cost-effectiveness of bisphosphonates in patients using oral glucocorticoids.

OBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. METHODS: Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses.

Adult↗

Cloning and characterization of the genes for biosynthesis of the compatible solute ectoine in the moderately halophilic bacterium Halobacillus dabanensis D-8(T).

A 11.2-kb fragment containing the ectABC genes of the biosynthetic pathway of ectoine from the Gram-positive, moderately halophilic bacterium Halobacillus dabanensis D-8(T) was obtained by inverse polymerase chain reaction. Subsequently, the entire ectABC cluster was cloned and analyzed. It revealed that the intergenic regions of the ectABC genes from H. dabanensis D-8(T) are more tightly spaced than those of Chromohalobacter salexigens, Halomonas elongata, Marinococcus halophilus, and Salibacillus pasteurii. The amino-acid sequence deduced from ectABC was highly homologous that from Virgibacillus pantethenticus (EctA 52%, EctB 60%, EctC 67%, respectively). The ectABC genes were cloned in the expression plasmid pMXB10 resulting in pMXB10ectABC. The ectoine was detected from cell extract in Escherishia coli ER2566 containing pMXB10ectABC using (13)C nuclear magnetic resonance spectroscopy.

Amino Acid Sequence↗

The coronary risk of cyclo-oxygenase-2 inhibitors in patients with a previous myocardial infarction.

BACKGROUND: Cyclo-oxygenase-2 selective inhibitors have been associated with cardiovascular side effects, but previous studies have generally excluded people with previous myocardial infarction, thereby limiting our knowledge of their cardiotoxicity in this population. OBJECTIVES: To determine whether a history of myocardial infarction modified the risk of acute myocardial infarction associated with the use of various non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A population-based cohort of 122 079 elderly people with and without previous myocardial infarction newly treated with an NSAID between 1 January 1999 and 30 June 2002 were identified using the computerised health databases of Québec, Canada. A nested-case-control approach was used for the analysis, with controls matched by cohort entry and age. Current users of NSAIDs, those whose last prescription overlapped with the index date, were compared with those who were not exposed to NSAIDs in the year preceding the event. Rate ratios of acute myocardial infarction were estimated using conditional logistic regression and adjusted for potential confounders. RESULTS: Users of rofecoxib, both with and without previous myocardial infarction, were at increased risk of myocardial infarction, with a trend for greater risk among those with a previous event (rate ratio (RR) 1.59, 95% confidence interval (CI) 1.15 to 2.18 v RR 1.23, 95% CI 1.05 to 1.45; p = 0.14 for interaction). By contrast, celecoxib was only associated with an increased risk in people with previous myocardial infarction (RR 1.40, 95% CI 1.06 to 1.84 v RR 1.03, 95% CI 0.88 to 1.20; p = 0.04 for interaction). The available power was insufficient to reliably assess risks among patients with previous myocardial infarction treated with other NSAIDs, dose-response relationships or interaction with aspirin. CONCLUSIONS: Although only rofecoxib use was associated with an increased risk of myocardial infarction in those without a previous event, both rofecoxib and celecoxib were associated with an excess risk of acute myocardial infarction for current users with a history of myocardial infarction. A large randomised trial is required to more completely and reliably assess the cardiovascular safety of celecoxib and traditional NSAIDs in this population of high-risk patients.

Aged↗

Gamma-ray bursts: huge explosion in the early Universe.

Long gamma-ray bursts (GRBs) are bright flashes of high-energy photons that can last for tens of minutes; they are generally associated with galaxies that have a high rate of star formation and probably arise from the collapsing cores of massive stars, which produce highly relativistic jets (collapsar model). Here we describe gamma- and X-ray observations of the most distant GRB ever observed (GRB 050904): its redshift (z) of 6.29 means that this explosion happened 12.8 billion years ago, corresponding to a time when the Universe was just 890 million years old, close to the reionization era. This means that not only did stars form in this short period of time after the Big Bang, but also that enough time had elapsed for them to evolve and collapse into black holes.

Journal Article↗

X-ray flares from postmerger millisecond pulsars.

Recent observations support the suggestion that short-duration gamma-ray bursts are produced by compact star mergers. The x-ray flares discovered in two short gamma-ray bursts last much longer than the previously proposed postmerger energy-release time scales. Here, we show that they can be produced by differentially rotating, millisecond pulsars after the mergers of binary neutron stars. The differential rotation leads to windup of interior poloidal magnetic fields and the resulting toroidal fields are strong enough to float up and break through the stellar surface. Magnetic reconnection-driven explosive events then occur, leading to multiple x-ray flares minutes after the original gamma-ray burst.

Journal Article↗

The p53-inducible apoptotic protein AMID is not required for normal development and tumor suppression.

AMID is an apoptosis-inducing factor (AIF)-homologous and mitochondria-associated protein that has been implicated in caspase-independent apoptosis. Transcription of human AMID gene is upregulated by p53 and downregulated in tumors in comparison to their matched normal tissues, suggesting the possibility that AMID is involved in the downstream effects of p53. To investigate the physiological functions of AMID, we generated AMID-deficient mice by gene targeting. AMID-deficient mice are viable and fertile, develop normally and lack obvious phenotypic changes compared to wild-type mice up to 1 year old. AMID(-/-) mice up to 1 year old have no spontaneous tumors and show similar fibrosarcoma incidence after MCA inoculation compared to wild-type mice. AMID(-/-) embryonic fibroblasts exhibit normal proliferation but slightly increased resistance to genotoxin-induced growth arrest. These findings suggest that AMID is not required for normal development and p53-mediated tumor suppression.

Amino Acid Sequence↗

Synergistic adsorption of phenol from aqueous solution onto polymeric adsorbents.

Adsorption of phenol from aqueous solution onto a nonpolar adsorbent, aminated adsorbent and weak base adsorbent (Amberlite XAD4, NDA103 and Amberlite IRA96C, respectively) at temperatures from 293 to 313K was studied for the weak interactions between the phenol molecules and the polymeric adsorbents. Isotherms of Langmuir and Freundlich equation with characteristic parameters for different adsorbents were well fitted to the batch equilibrium adsorption data. The adsorption capacity on NDA103 driven by hydrogen bonding and van der Waals interaction together is higher than that on IRA96C driven by hydrogen bonding interaction only and on XAD4 driven by van der Waals interaction only. For evaluating synergistic adsorption for phenol-water systems onto polymeric adsorbents, the adsorption capacity is normalized to the amounts of specific surface area and amino groups of adsorbents. The synergistic effect with other weak interactions would contribute more to the adsorption as acting simultaneously than that of acting individually.

Adsorption↗