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Biomedical subjects

J Zhang

Publications and source records attributed to J Zhang.

At least 37 records · Page 2Linked to original sources

Comparative study of planar motion in monomeric and dimeric discotics.

Deuterium NMR spectra are reported in powder samples of discotic monomer and dimer as a function of temperature in their column Col(ho) phases. To simulate the observed powder patterns, a threefold jump model is used in the monomer, while in the related dimer the libration motion of the monomeric core is described using the infinitesimal jump method under a restricting potential due to the spacer. By comparing the diffusive rates for the two samples, it is concluded that the planar motion in the dimer is at least 30 times smaller than that of the monomer. This could lead to an enhancement of charge and energy transport in discotic dimer systems.

Journal Article↗

Combination chemotherapy for high-risk gestational trophoblastic tumour.

BACKGROUND: Gestational trophoblastic disease (GTD) includes gestational trophoblastic tumour and hydatidiform mole. Many women of reproductive age are affected by this disease although its incidence differs by geographical location. A number of chemotherapy regimens are used for treating the disease, such as methotrexate, actinomycin D and cyclophosphamide (MAC), methotrexate, actinomycin D, cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine (CHAMOC), etoposide, methotrexate and actinomycin (EMA) plus cyclophosphamide and vincristine (CO) (EMA-CO), etoposide, methotrexate and actinomycin (EMA) plus etoposide and cisplatin(EP) (EMA-EP). The efficacy of these drugs has not been systematically reviewed. OBJECTIVES: To determine the efficacy and safety of combination chemotherapy in treating high-risk GTT. SEARCH STRATEGY: Electronic searches of MEDLINE, EMB, Cochrane Central Register of Controlled Trials (CENTRAL) and CBM were carried out. Four journals were handsearched and other searching methods were used for identifying more studies. SELECTION CRITERIA: The review included randomized controlled trials (RCTs) or quasi-RCTs of combination chemotherapy for treating high-risk GTT. Patients with placental-site trophoblastic tumour (PSTT), who had received chemotherapy in the previous two weeks, or patients with chemotherapy intolerance were excluded. DATA COLLECTION AND ANALYSIS: Two investigators independently collected data using a data extraction form. Meta-analysis was not performed and the review was conducted as a narrative review. MAIN RESULTS: One study with 42 participants was included in this review. It indicated that a MAC regimen was better than a CHAMOCA regimen for high-risk GTT because of lower toxicity. The quality of the study was unclear. AUTHORS' CONCLUSIONS: The methodological limitations of the included study prevent any firm conclusions about the best combination chemotherapy regimen for high-risk GTT. High quality studies are required.

Antineoplastic Combined Chemotherapy Protocols↗

Zinc and cadmium accumulation and tolerance in populations of Sedum alfredii.

To investigate the variation of Zn and Cd accumulation and tolerance of Sedum alfredii (a newly reported Zn/Cd hyperaccumulator), field surveys and hydroponic experiments were conducted among three populations of this species: two originating from old Pb/Zn mines in Zhejiang (ZJ) and Hunan (HN) Provinces and one from a "clean" site in Guangdong (GD) Province, China. Under field conditions, up to 12,524 and 12,253 mg kg(-1) Zn, and 1400 and 97 mg kg(-1) Cd in shoots of ZJ and HN plants were recorded respectively. Under hydroponic conditions, ZJ and HN plants accumulated significantly higher Zn and Cd in their leaves and stems, and possessed significantly higher Zn and Cd tolerance than GD plants. Among the two contaminated populations, ZJ plants showed higher Cd tolerance and accumulation (in leaves) than HN plants. The present results indicate that significant differences in Zn and Cd accumulation and tolerance exist in populations of S. alfredii.

Biomass↗

Downregulation of Bim by brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from paclitaxel but not etoposide or cisplatin-induced cell death.

Chemoresistance and increased expression of TrkB and brain-derived neurotrophic factor (BDNF) are biomarkers of poor prognosis in tumors from patients with neuroblastoma (NB). Previously, we found BDNF activation of TrkB through PI3K/Akt protects NB from etoposide/cisplatin-induced cell death. In this study, the role of Bim, a proapoptotic protein, was investigated. Bim was involved in paclitaxel but not etoposide or cisplatin-induced cell death in NB cells. Pharmacological and genetic studies showed that BDNF-induced decreases in Bim were regulated by MAPK and not PI3K/Akt pathway. Both MAPK and PI3K pathways were involved in BDNF protection of NB cells from paclitaxel-induced cell death, while PI3K predominantly mediated BDNF protection of NB cells from etoposide or cisplatin-induced cell death. These data indicate that different chemotherapeutic drugs induce distinct death pathways and growth factors utilize different signal transduction pathways to modulate the effects of chemotherapy on cells.

Antineoplastic Agents↗

Complex network from pseudoperiodic time series: topology versus dynamics.

We construct complex networks from pseudoperiodic time series, with each cycle represented by a single node in the network. We investigate the statistical properties of these networks for various time series and find that time series with different dynamics exhibit distinct topological structures. Specifically, noisy periodic signals correspond to random networks, and chaotic time series generate networks that exhibit small world and scale free features. We show that this distinction in topological structure results from the hierarchy of unstable periodic orbits embedded in the chaotic attractor. Standard measures of structure in complex networks can therefore be applied to distinguish different dynamic regimes in time series. Application to human electrocardiograms shows that such statistical properties are able to differentiate between the sinus rhythm cardiograms of healthy volunteers and those of coronary care patients.

Biological Clocks↗

NMR angle-dependent spectral study of core dynamics in a discotic columnar phase.

A detailed (2)H NMR study of a discotic monomer is reported in its columnar phase at 61.4 MHz. A simulation of angular-dependent spectral patterns and/or signal intensities of the aromatic deuterons is shown to provide information on the small step (or jump) diffusion rates in the low temperature region of the D(ho) phase, where the motion is in the intermediate motion regime. In the high end of this phase, the motion falls into the fast motion regime and spectral patterns become insensitive to the diffusion rate. In such a case, angular-dependent NMR signal intensities were used to give the required dynamic information. The diffusive motion about the columnar axis is found to be thermally activated with an activation energy of 69 kJ/mol. Deuteron spin-lattice relaxation rates were measured at 61.4 MHz and interpreted by a conventional rotational diffusion model in order to complement and compare with the above study when possible.

Journal Article↗

p53 is required for nerve growth factor-mediated differentiation of PC12 cells via regulation of TrkA levels.

p53 is necessary for the elimination of neural cells inappropriately differentiated or in response to stimuli. However, the role of p53 in neuronal differentiation is not certain. Here, we showed that nerve growth factor (NGF)-mediated differentiation in PC12 cells is enhanced by overexpression of wild-type p53 but inhibited by mutant p53 or knockdown of endogenous wild-type p53, the latter of which can be rescued by expression of exogenous wild-type p53. Interestingly, p53 knockdown or overexpression of mutant p53 attenuates NGF-mediated activation of TrkA, the high-affinity receptor for NGF and a tyrosine kinase, and activation of the mitogen-activated protein kinase pathway. In addition, p53 knockdown reduces the constitutive levels of TrkA, which renders PC12 cells inert to NGF. And finally, we showed that both constitutive and stimuli-induced expressions of TrkA are regulated by p53 and that induction of TrkA by activated endogenous p53 enhances NGF-mediated differentiation. Taken together, our data demonstrate that p53 plays a critical role in NGF-mediated neuronal differentiation in PC12 cells at least in part via regulation of TrkA levels.

Animals↗

Ion exchange phase transitions in water-filled channels with charged walls.

Ion transport through narrow water-filled channels is impeded by a high electrostatic barrier. The latter originates from the large ratio of the dielectric constants of the water and the surrounding media. We show that "doping," i.e., immobile charges attached to the walls of the channel, substantially reduces the barrier. This explains why most of the biological ion channels are "doped." We show that at rather generic conditions the channels may undergo ion exchange phase transitions (typically of the first order). Upon such a transition a finite latent concentration of ions may either enter or leave the channel, or be exchanged between the ions of different valences. We discuss possible implications of these transitions for the Ca-vs-Na selectivity of biological Ca channels. We also show that transport of divalent Ca ions is assisted by their fractionalization into two separate excitations.

Journal Article↗

Observation of a fast electron beam emitted along the surface of a target irradiated by intense femtosecond laser pulses.

A novel fast electron beam emitting along the surface of a target irradiated by intense laser pulses is observed. The beam is found to appear only when the plasma density scale length is small. Numerical simulations reveal that the electron beam is formed due to the confinement of the surface quasistatic electromagnetic fields. The results are of interest for potential applications of fast electron beams and deep understanding of the cone-target physics in the fast ignition related experiments.

Journal Article↗

Identification of an ataxia telangiectasia-mutated protein mediated surveillance system to regulate Bcl-2 overexpression.

Bcl-2 can both promote and attenuate tumorigenesis. Although the former function is relatively well characterized, the mechanism of the latter remains elusive. We report here that enforced Bcl-2 expression in MCF7 cells stabilizes p53, induces phosphorylation of p53 serine 15 (p53pSer15) and inhibits MCF7 cell growth. Consistent with p53 Ser15 being a target of ataxia telangiectasia mutated protein(ATM)/ATR (ATM- and rad3-related) in the DNA damage response, Bcl-2 activates ATM by inducing ATM Ser1981 phosphorylation, which is accompanied with the phosphorylaton of two additional ATM substrates, Chk2 Thr68 and H2AX Ser139. Downregulation of ATM using a specific small interference RNA fragment (ATMRNAi) abolished Bcl-2-induced p53pSer15 and Bcl-2-mediated growth inhibition of MCF7 cells. Ectopic expression of a dominant-negative p53 mutant, p53175H, partially rescued this growth inhibition. Taken together, these observations demonstrate the contribution of ATM-p53 function to Bcl-2-mediated inhibition of MCF7 cell growth, indicating an ATM-mediated surveillance system for regulating Bcl-2 overexpression. Consistent with this concept, we found that MCF7 cells express Bcl-2 heterogeneously with 34.5% of cells being Bcl-2 negative. In general, Bcl-2-positive MCF7 cells proliferate slower than those of Bcl-2 negative. Thus, we provide evidence suggesting that activation of ATM suppresses Bcl-2-induced tumorigenesis, and that attenuation of ATM function may be an important event in breast cancer progression.

Ataxia Telangiectasia Mutated Proteins↗

Chinese herbal medicine for the treatment of pre-eclampsia.

BACKGROUND: Pre-eclampsia is a common disorder of pregnancy with uncertain etiology. In Chinese herbal medicines, a number of herbs are used for treating pre-eclampsia. Traditional Chinese medicine considers that, when a woman is pregnant, most of the blood of the mother is directed to the placenta to provide the baby with the required nutrition; other maternal organs may in consequence be vulnerable to damage. These organs include the liver, the spleen, and the kidneys. The general effects of Chinese herbal medicines that can protect these organs may be valuable in pre-eclampsia by encouraging vasodilatation, increasing blood flow, and decreasing platelet aggregation. The use of Chinese herbal medicine is often based on the individual and presence of traditional Chinese medicine symptoms. OBJECTIVES: To assess the effect of Chinese herbal medicine for treating pre-eclampsia and compare it with that of placebo, no treatment or Western medicine. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Groups Trial Register (31 March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2005), MEDLINE (1969 to December 2004), EMBASE (1984 to March 2004) and CBM (1978 to February 2005) and we handsearched several main journals published in China. SELECTION CRITERIA: Randomized controlled trials in which Chinese herbal medicine was used for treating pre-eclampsia. DATA COLLECTION AND ANALYSIS: One review author assessed trials for inclusion. The trials were also assessed by a second review author if there was any doubt about whether or not to include the trial. Analysis was not performed as there were no trials included in this review. MAIN RESULTS: No trials were suitable for inclusion in this review. AUTHORS' CONCLUSIONS: The effect of Chinese herbal medicine for treating pre-eclampsia remains unclear. There are currently no randomized controlled trials to address the efficacy and safety of Chinese herbal medicine for the treatment of pre-eclampsia. Well conducted randomized controlled trials are required.

Drugs, Chinese Herbal↗

The use of small interfering RNAs to inhibit adipocyte differentiation in human preadipocytes and fetal-femur-derived mesenchymal cells.

RNA interference (RNAi) has been used in functional genomics and offers innovative approaches in the development of novel therapeutics. Human mesenchymal stem cells offer a unique cell source for tissue engineering/regeneration strategies. The current study examined the potential of small interfering RNAs (siRNA) against human peroxisome proliferator activated receptor gamma (PPARgamma) to suppress adipocyte differentiation (adipogenesis) in human preadipocytes and fetal-femur-derived mesenchymal cells. Adipogenesis was investigated using cellular and biochemical analysis. Transient transfection with PPARgamma-siRNA using a liposomal-based strategy resulted in a significant inhibition of adipogenesis in human preadipocytes and fetal-femur-derived mesenchymal cells, compared to controls (cell, liposomal and negative siRNA). The inhibitory effect of PPARgamma-siRNA was supported by testing human PPARgamma mRNA and adipogenic associated genes using reverse transcription polymerase chain reaction (RT-PCR) to adiponectin receptor 1 and 2 as well as examination of fatty acid binding protein 3 (FABP3) expression, an adipocyte-specific marker. The current studies indicate that PPARgamma-siRNA is a useful tool to study adipogenesis in human cells, with potential applications both therapeutic and in the elucidation of mesenchymal cell differentiation in the modulation of cell differentiation in human mesenchymal cells.

Adipocytes↗

Effects of lanthanum on composition, crystal size, and lattice structure of femur bone mineral of Wistar rats.

The application of lanthanum (La) in industry, medicine, and agriculture may cause accumulation of the element in human body. This article examines the effects of La on the femur bone mineral of male Wistar rats after administration of La(NO3)3 by gavage at the dose of 2.0 mg La(NO3)3.kg(-1).day(-1) over a 6-month period. Chemical analysis confirmed La accumulation in bone and loss in bone mineral. Thermogravimetric analysis showed a decrease in the mineral-to-matrix ratio and an increase in carbonate content. Fourier-transform infrared spectrometry revealed elevation in the contents of labile carbonate and acidic phosphate. The synchrotron radiation small-angle X-ray scattering study presented a smaller mean thickness of the mineral crystals in the bone of La-treated rats. The synchrotron radiation-extended X-ray absorption fine structure analysis indicated that the La treatment resulted in a lowered disorder in the crystals. The smaller size, more adsorbed labile carbonate, and more acidic phosphate made the bone mineral easier to dissolve, as revealed in the kinetic measurement of bone demineralization. These findings suggest that La retards bone maturation of rats.

Absorptiometry, Photon↗

High-aspect-ratio aluminum borate nanowire bundles supported by sucrose.

High-aspect-ratio and single-crystal aluminum borate (Al(18)B(4)O(33)) nanowire bundles with an ordered orientation were synthesized by using an innovative sucrose-assisted growth process. The process involves the dehydration and polycondensation of aluminum borate-sucrose solution to form a highly viscous precursor. The sucrose plays a crucial role in the growth of the nanowire bundles by supporting as a polymeric substrate and a type of adhesive template. Electron microscopy was used to characterize the high-aspect-ratio nanowire bundles. A possible growth mechanism for the nanowire bundles is proposed.

Journal Article↗

Comparative proteome analysis of rat brain and coronary microvascular endothelial cells.

The endothelium of different organs displays a remarkable heterogeneity, although it presents many common functional and morphological features. However, despite our knowledge of heterogeneity among endothelial cells from different sites, the differences between brain microvascular endothelial cells (BMEC) and coronary microvascular endothelial cells (CMEC) are poorly defined. The aim of this study was to investigate whether BMEC are distinct from CMEC at the protein level. Using the proteomic approach, we comparatively analyzed the proteome of cultured BMEC and CMEC. We reproducibly separated over 2000 polypeptides by using two-dimensional electrophoresis (2-DE) at pH range of 3-10. Using PDQuest software to process the 2-DE gel images, forty-seven protein spots were differentially expressed in the two-endothelial cells. Of these, thirty-five proteins are highly expressed in BMEC, whereas twelve proteins are highly expressed in CMEC. Fifteen proteins in BMEC and seven proteins in CMEC were identified with high confidence by matrix-associated laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS). Our data suggested that BMEC and CMEC were different in several aspects including cytokine and growth-related molecules, stress-related proteins, metabolic enzymes, signal transduction proteins and others. The identification of a set of proteins preferentially expressed in BMEC and CMEC provided new data on the heterogeneity of the endothelium.

Animals↗

Progression of kidney dysfunction in the community-dwelling elderly.

Despite the high prevalence of chronic kidney disease among the elderly, few studies have described their loss of kidney function. We sought to determine the progression of kidney dysfunction among a community-based cohort of elderly subjects. The cohort included 10 184 subjects 66 years of age or older, who had one or more outpatient serum creatinine measurements during each of two time periods: 1 July to 31 December 2001 and 1 July to 31 December 2003. A mixed effects model, including covariates for age, gender, diabetes mellitus, and comorbidity, was used to determine the rate of decline in estimated glomerular filtration rate (eGFR, in ml/min/1.73 m2) per year over a median follow-up of 2.0 years. Subjects with diabetes mellitus had the greatest decline in eGFR of 2.1 (95% CI 1.8-2.5) and 2.7 (95% CI 2.3-3.1) ml/min/1.73 m2 per year in women and men, respectively. The rate of decline for women and men without diabetes mellitus was 0.8 (95% CI 0.6-1.0) and 1.4 (95% CI 1.2-1.6) ml/min/1.73 m2 per year. Subjects with a study mean eGFR<30 ml/min/1.73 m2, both those with and without diabetes mellitus, experienced the greatest decline in eGFR. In conclusion, we found that the majority of elderly subjects have no or minimal progression of kidney disease over 2 years. Strategies aimed at slowing progression of kidney disease should consider underlying risk factors for progression and the negligible loss of kidney function that occurs in the majority of older adults.

Aged↗

ERK activity facilitates activation of the S-phase DNA damage checkpoint by modulating ATR function.

Although Erk kinase has been recently reported to function in the DNA damage response, the mechanism governing this process is unknown. We report here that hydroxyurea (HU) activates Erk via MEK1, a process that is sensitized by a constitutively active MEK1 (MEK1Q56P) and attenuated by a dominant-negative MEK1 (MEK1K97M). While ectopic MEK1Q56P sensitized HU-induced S-phase arrest, inhibition of Erk activation via U0126, PD98059, and MEK1K97M attenuated the arrest, and thereby enhanced cells to HU-induced toxicity. Taken together, we demonstrate an important contribution of Erk to the activation of the S-phase DNA damage checkpoint. This can be attributed to Erk's regulatory role in modulating ATR function. Inhibition of Erk activation with U0126/PD98059 and MEK1K97M substantially reduced HU-induced ATR nuclear foci, leading to a dramatic reduction of gammaH2AX and its nuclear foci. Reduction of MEK1 function by a small interference RNA (siRNA) MEK1 and ectopic MEK1K97M significantly decreased HU-induced gammaH2AX. Conversely, ectopic MEK1Q56P enhanced gammaH2AX foci. Furthermore, immunofluorescent and cell fractioning experiments revealed cytosolic and nuclear localization of ATR. HU treatment caused the redistribution of ATR from the cytosol to the nucleus, a process that is inhibited by U0126. Collectively, we show that Erk kinase modulates HU-initiated DNA damage response by regulating ATR function.

3T3 Cells↗

Family-based association studies of the TCP1 gene and schizophrenia in the Chinese Han population.

A previous case-control study by Yang et al. indicated that the TCP1 gene in 6q25 was associated with schizophrenia in the Han population. To replicate this result, we selected eight SNPs (rs2273828, rs3818298, rs1547094, rs1547093, rs2295898, rs2295899, rs4832, rs15982) spanning the whole gene and performed a family-based study using 325 trios samples. Our transmission disequilibrium test showed neither allele nor haplotype association with schizophrenia, and suggests that the TCP1 locus is not associated with schizophrenia in the Chinese population. Since 6q25 has consistently been found to be a susceptible region for schizophrenia, we suggest that other genes within this region should be the focus of attention.

Adult↗