Biomedical subjects

Fang Zhang

Publications and source records attributed to Fang Zhang.

At least 19 recordsLinked to original sources

PubMed2026

Spatially resolved single-cell atlas reveals the macroevolutionary trajectory of animal hearts.

Animal hearts display diverse anatomical structures during adaptive evolution. Here, we present a multiomics atlas of adult hearts from 27 species across chordates, arthropods, and mollusks. Joint analysis indicates that Bilateria hearts share a core gene repertoire, taking a stepwise "add-on" approach as a universal evolutionary strategy. The "proto-heart" is populated by key cell types, including cardiomyocytes, fibroblasts, endothelial cells, and neural cells, which maintained core signatures while evolving with shifts in living environments and corresponding adaptations in the cardiovascular system. Additionally, we reveal an evolutionarily conserved cardiomyocyte state dynamic potentially linked to cardiac development and stress responses. Finally, we identify a common molecular program underpinning chamber evolution from a ventricular foundation. This work establishes a resource for understanding the intrinsic mechanisms of heart evolution.

Animals↗

PubMed2007

Effect of New York State regulatory action on benzodiazepine prescribing and hip fracture rates.

BACKGROUND: Medicare Part D excludes benzodiazepines from coverage, and numerous state government policies limit use of benzodiazepines. No data indicate that such policies have decreased the incidence of hip fracture. OBJECTIVE: To assess whether a statewide policy that decreased the use of benzodiazepines among elderly persons by more than 50% has decreased the incidence of hip fracture. DESIGN: A quasi-experiment comparing changes in outcomes before and after a policy change in a study U.S. state (New York) and a control state (New Jersey). SETTING: Two U.S. state Medicaid programs, 1988-1990. PATIENTS: Medicaid enrollees in New York (n = 51 529) and New Jersey (n = 42 029) who received or did not receive a benzodiazepine. MEASUREMENTS: Benzodiazepine prescribing and hazard ratios for hip fracture, adjusted for age and eligibility category. INTERVENTION: A statewide policy, implemented in New York in 1989, that required triplicate forms for benzodiazepine prescribing to allow surveillance by health authorities. RESULTS: The triplicate prescription policy immediately resulted in a 60.3% (95% CI, -66.3% to -54.2%) reduction in benzodiazepine use among women and 58.5% (-64.3% to -52.8%) among men. Benzodiazepine use in New Jersey remained stable. Hazard ratios for hip fracture that were adjusted for age and eligibility category did not change in New York or New Jersey when the periods before and after use of the triplicate prescription policy were compared (change from 1.2 to 1.1 among female benzodiazepine recipients [P = 0.70], 1.3 to 1.1 [P = 0.08] among female nonrecipients, 0.8 to 1.1 [P = 0.56] among male recipients, and 1.1 to 1.3 [P = 0.46] among male nonrecipients). LIMITATIONS: Information was lacking on race, benzodiazepine dose, and other potential determinants of continued benzodiazepine prescribing. CONCLUSIONS: Policies that lead to substantial reductions in the use of benzodiazepines among elderly persons do not necessarily lead to decreased incidence of hip fracture. Limitations on coverage of benzodiazepines under Medicare Part D may not achieve this widely assumed clinical benefit.

Aged↗

PubMed2007

A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity, and memory.

The scaffolding protein WAVE-1 (Wiskott-Aldrich syndrome protein family member 1) directs signals from the GTPase Rac through the Arp2/3 complex to facilitate neuronal actin remodeling. The WAVE-associated GTPase activating protein called WRP is implicated in human mental retardation, and WAVE-1 knock-out mice have altered behavior. Neuronal time-lapse imaging, behavioral analyses, and electrophysiological recordings from genetically modified mice were used to show that WAVE-1 signaling complexes control aspects of neuronal morphogenesis and synaptic plasticity. Gene targeting experiments in mice demonstrate that WRP anchoring to WAVE-1 is a homeostatic mechanism that contributes to neuronal development and the fidelity of synaptic connectivity. This implies that signaling through WAVE-1 complexes is essential for neural plasticity and cognitive behavior.

Amino Acid Sequence↗

PubMed2006

Homoallylic alcohol isomerization in water over an immobilized Ru(II) organometallic catalyst with mesoporous structure.

PPh(2)-functionalized SBA-15 was synthesized by co-condensation of tetraethyl orthosilicate and 2-(diphenylphosphino)ethyltriethoxysilane through prehydrolysis. The as-prepared PPh(2)-SBA-15 was used as the support to immobilize the Ru(II) organometallic catalyst through the strong coordination between the Ru(II) and the PPh(2)-ligand (Ru-PPh(2)-SBA-15). During 1-phenyl-3-buten-1-ol isomerization carried out in water as an environmentally friendly medium, the Ru-PPh(2)-SBA-15 catalyst exhibited almost the same activity and selectivity as the corresponding RuCl(2)(PPh(3))(3) homogeneous catalyst and could be used repetitively nearly 7 times. On the basis of various characterizations, the correlation of the catalytic behaviors of the Ru-PPh(2)-SBA-15 to its structural characteristics was discussed briefly. Obviously, the high activity of the Ru-PPh(2)-SBA-15 could be attributed to both the high surface area of the support, which ensured the good dispersion of Ru(II) active sites, and the ordered mesoporous structure, which facilitated the diffusion of organic reactants.

Journal Article↗

PubMed2006

[Identification of the differentially expressed genes between primary breast cancer and paired lymph node metastasis through combining mRNA differential display and gene microarray].

OBJECTIVE: To identify and clone the genes related to breast cancer metastasis through comparing the mRNA expression profiling between primary breast cancer and paired lymph node metastasis. METHODS: First, primary breast cancer cells and paired lymph node metastasis tissues were used to identify their differentially expressed genes by using mRNA differential display, and fragments of differentially expressed genes were obtained by gel cutting and cloning to pGEM-T vector, then sequencing and blasting with the GenBank for their homologous genes. Then, the obtained genes were validated by using reverse dot blot hybridization and gene microarray. Finally, the mRNA expression levels in the 7 breast cancer cell lines with different metastasis behaviors were detected by real-time RT-PCR. RESULTS: The mRNA expression profiling of the metastatic breast cancers in lymph node was similar to that of their primary cancers. 16 differentially expressed gene fragments were obtained from mRNA differential display; four of them were found to be unknown genes, and had been accepted by the GenBank, with the accession numbers BG518428, BG518429, BM005520, and BM005521. Of the other 12 genes, 8 were known genes, and 4 were genes with known sequences but unknown functions. The kinesin-like DNA binding protein (KNSL4) and dihydropyrimidine dehydrogenase (DYPD) were down-regulated in the metastatic tissues in comparison with the paired primary tissues, which was identified by both radioactivity-labeled reverse dot blot hybridization and fluorescence-labeled gene microarray hybridization. KNSL4 mRNA expression had a down-regulation trend with increasing metastatic ability of breast cancer cell lines. CONCLUSIONS: The gene expression profiling of the lymph node metastasis is almost similar to that of their primary breast cancer, indicating that the metastatic cancer cells in lymph node are the subclone with higher metastasis ability of the primary cancer cells, and that some differentially expressed genes between them may be involved in the change of metastasis phenotype. KNSL4 and DYPD are potential metastasis-related genes, and KNSL4 mRNA expression is correlated with metastasis behaviors of the breast cancer cell lines, suggesting that KNSL4 may play an important role in the metastasis process of breast cancer.

Breast Neoplasms↗

PubMed2006

Inhibition of STAT3 activity with AG490 decreases the invasion of human pancreatic cancer cells in vitro.

Signal transducer and activator of transcription 3 (STAT3) is a central cytoplasmic transcription factor. Abnormal activation of STAT3 plays a critical role in oncogenesis and has been found frequently in a wide variety of human tumors including pancreatic cancer. In this study, we elucidated the significance of the STAT3 signaling pathway on metastatic potentials of pancreatic cancer. We found that phosphorylated STAT3 (p-STAT3) protein levels were significantly higher in highly metastatic SW1990 cells compared to the poorly metastatic CaPan-2 cells, which expressed weak levels of this protein. Furthermore, a Janus kinase (JAK) specific inhibitor, AG490, significantly inhibited the expression of p-STAT3, and subsequently reduced invasion and adhesion potential of SW1990 cells compared to the cells treated with vehicle only. Finally, inhibition of the STAT3 signaling pathway by AG490 also led to a decrease in matrix metalloproteinase-2 and vascular endothelial growth factor expression at the protein and mRNA levels. These results demonstrate that activation of the STAT3 signaling pathway plays an important role in the progression of pancreatic cancer and that inhibition of this pathway may be useful for an anti-invasive therapeutic option in pancreatic cancer.

Blotting, Western↗

PubMed2006

In vitro reconstitution of a transport complex containing Rab27a, melanophilin and myosin Va.

Rab27a and melanophilin (Mlph) are required in vivo to form a melanosome receptor for myosin Va in which Rab27a anchored in the melanosome membrane recruits Mlph, which in turn recruits myosin Va. Here, we show by reconstitution using purified proteins that Rab27a and Mlph are sufficient to form a transport complex with myosin Va in vitro. These results suggest that additional proteins are not required in vivo for assembly of the myosin Va receptor, although other proteins may associate with this tripartite complex to regulate its activity and/or to assist Rab27a in anchoring the complex to the melanosome membrane.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Performance evaluation of partial differential equation models in electronic speckle pattern interferometry and the delta-mollification phase map method.

The ordinary differential equation (ODE) and partial differential equation (PDE) image- processing methods have been applied to reduce noise and enhance the contrast of electronic speckle pattern interferometry fringe patterns. We evaluate the performance of a few representative PDE denoising models quantitatively with two parameters called image fidelity and speckle index, and then we choose a good denoising model. Combining this denoising model with the ODE enhancement method, we make it possible to perform contrast enhancement and denoising simultaneously. Second, we introduce the delta-mollification method to smooth the unwrapped phase map. Finally, based on PDE image processing, delta mollification and some traditional techniques, an approach of phase extraction from a single fringe pattern is tested for computer-simulated and experimentally obtained fringe patterns. The method works well under a high noise level and limited visibility and can extract accurate phase values.

Journal Article↗

PubMed2006

Cost-related medication nonadherence among elderly and disabled medicare beneficiaries: a national survey 1 year before the medicare drug benefit.

BACKGROUND: Prior to implementation of the Medicare drug benefit, we estimated the prevalence of cost-related medication nonadherence (CRN) among Medicare enrollees, including elderly and nonelderly disabled beneficiaries. METHODS: In the fall of 2004, detailed measures of CRN (skipping or reducing doses or not filling prescriptions because of cost) were added to the Medicare Current Beneficiary Survey. We examined the prevalence of CRN nationally and by Medicare eligibility subgroups (elderly vs nonelderly disabled beneficiaries), drug coverage status, socioeconomic status, self-rated health, and number of chronic medical conditions. RESULTS: In a national sample of 13 835 noninstitutionalized Medicare enrollees, 29% of the disabled and 13% of the elderly beneficiaries reported CRN; those in fair to poor health with multiple comorbidities and without coverage were most at risk. Among the disabled enrollees with 4 or more morbidities, 52% (95% confidence interval [CI], 43.3%-60.3%) without drug coverage skipped prescriptions or doses compared with 26% (95% CI, 17.7%-34.8%) with Medicaid drug coverage. Those with partial drug coverage through Medigap policies or Medicare health maintenance organizations reported intermediate rates of CRN. The adjusted odds ratio of CRN among disabled enrollees in poor (vs good) health was 3.9 (95% CI, 1.7-9.2), whereas for those with 4 or more (vs <4) comorbidities, the odds ratio of CRN was 2.7 (95% CI, 1.7-4.1). CONCLUSIONS: One year before Medicare Part D implementation, Medicare beneficiaries reported high rates of CRN. Rates are highest among nonelderly disabled beneficiaries, but among both elderly and disabled beneficiaries, CRN is exacerbated by poor health, multiple morbidities, and limited drug coverage. Given the high cost sharing under Part D, it is important to closely monitor CRN in high-risk subgroups.

Aged↗

PubMed2006

One-pot synthesis and bioapplication of amine-functionalized magnetite nanoparticles and hollow nanospheres.

To demonstrate their applications in biological and medical fields such as in immunoassays, magnetic separation of cells or proteins, drug or gene delivery, and magnetic resonance imaging, the template-free syntheses of water-soluble and surface functionalized magnetic nanomaterials have become essential and are challenging. Herein, we developed a facile one-pot template-free method for the preparation of amine-functionalized magnetite nanoparticles and hollow nanospheres by using FeCl(3)6 H(2)O as single iron source. These magnetic nanomaterials were characterized by TEM, SEM, XRD, and FTIR technologies. Their magnetic properties were also studied by using a superconducting quantum interference device (SQUID) magnetometer at room temperature. Then the amine-functionalized magnetite nanoparticles were applied to immunoassays and magnetic resonance imaging in live mice.

Amines↗

PubMed2006

Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning.

Gene therapy is a promising treatment option for monogenic diseases, but success has been seen in only a handful of studies thus far. We now document successful reconstitution of immune function in a child with the adenosine deaminase (ADA)-deficient form of severe combined immunodeficiency (SCID) following hematopoietic stem cell (HSC) gene therapy. An ADA-SCID child who showed a poor response to PEG-ADA enzyme replacement was enrolled into the clinical study. Following cessation of enzyme replacement therapy, autologous CD34(+) HSCs were transduced with an ADA-expressing gammaretroviral vector. Gene-modified cells were reinfused following one dose of preconditioning chemotherapy. Two years after the procedure, immunological and biochemical correction has been maintained with progressive increase in lymphocyte numbers, reinitiation of thymopoiesis, and systemic detoxification of ADA metabolites. Sustained vector marking with detection of polyclonal vector integration sites in multiple cell lineages and detection of ADA activity in red blood cells suggests transduction of early hematopoietic progenitors. No serious side effects were seen either as a result of the conditioning procedure or due to retroviral insertion. Gene therapy is an effective treatment option for the treatment of ADA-SCID.

Adenosine Deaminase↗

PubMed2006

Ribosomal stress couples the unfolded protein response to p53-dependent cell cycle arrest.

Protein misfolding in the endoplasmic reticulum (ER) triggers a signaling pathway termed the unfolded protein response path-way (UPR). UPR signaling is transduced through the transmembrane ER effectors PKR-like ER kinase (PERK), inositol requiring kinase-1 (IRE-1), and activating transcription factor 6 (ATF6). PERK activation triggers phosphorylation of eIF2alpha leading to repression of protein synthesis, thereby relieving ER protein load and directly inhibiting cyclin D1 translation thereby contributing to cell cycle arrest. However, PERK(-/-) murine embryonic fibroblasts have an attenuated G(1)/S arrest that is not attributable to cyclin D1 loss, suggesting a cyclin D1-independent mechanism. Here we show that the UPR triggers p53 accumulation and activation. UPR induction promotes enhanced interaction between the ribosome proteins (rpL5, rpL11, and rpL23) and Hdm2 in a PERK-dependent manner. Interaction with ribosomal proteins results in inhibition of Hdm2-mediated ubiquitination and degradation of p53. Our data demonstrate that ribosomal subunit:Hdm2 association couples the unfolded protein response to p53-dependent cell cycle arrest.

Cell Cycle↗

PubMed2006

[Refined mapping of loss of heterozygosity of 1p36.33-36.31 in sporadic colorectal carcinoma].

OBJECTIVE: To screen the candidate tumor suppressor gene (TSG) related to colorectal cancer (CRC). METHODS: Seven fluorescent labeled polymorphic markers (1p36.33-36.31) were analyzed in the samples of tissues of CRC and adjacent normal tissues obtained during operation performed on 83 CRC patients, 40 males and 43 females, aged 31 - 84. The PCR products were electrophoresed. The softwares Genescan 3.1 and Genotype 2.1 were used for loss of heterozygosity (LOH) scanning and analysis. Comparison between the LOH frequency and the clinicopathological factors was performed by Chi-square test. RESULTS: The average LOH frequency in the 1p36.33-36.31 was 31.47%, with the highest LOH frequency of 47.22% at the D1S243 locus and the lowest LOH frequency of 7.35% at the locus D1S1347. Two obvious high LOH regions were detected: D1S1347 locus (1p36.33, about 1 cM) and a region between D1S468 and D1S2660 (1p36.32-36.31 about 3 cM). The LOH rats of the loci in 1p36.33-36.31 region were not correlated with the age and sex of the patient, and the size, growth pattern, and Dukes stage of the tumor. CONCLUSION: Two obvious high frequency LOH regions, 1p36.32-36.31 and 1p36.33 have been detected in sporadic CRC where tumor-suppressor-gene (s) may exist.

Adult↗

PubMed2006

Blockage of oncostatin M-induced LDL receptor gene transcription by a dominant-negative mutant of C/EBPbeta.

OM (oncostatin M) activates the human LDLR [LDL (low-density lipoprotein) receptor] gene transcription in HepG2 cells through the SIRE (sterol-independent regulatory element) of LDLR promoter. The SIRE sequence consists of a C/EBP (CCAAT/enhancer-binding protein)-binding site and a CRE (cAMP-response element). Our previous studies [Zhang, Ahlborn, Li, Kraemer and Liu (2002) J. Lipid Res. 43, 1477-1485; Zhang, Lin, Abidi, Thiel and Liu (2003) J. Biol. Chem. 278, 44246-44254] have demonstrated that OM transiently induces EGR-1 (early growth response gene product 1) expression and EGR-1 activates LDLR transcription primarily through a protein-protein interaction with C/EBPbeta, which serves as a co-activator of EGR-1. In the present study, we examined the direct role of C/EBPbeta as a transactivator in OM-regulated LDLR gene transcription independent of EGR-1. We show that OM induces C/EBPbeta expression with kinetics slower than EGR-1 induction. A significant increase in C/EBPbeta protein level is detected by 2 h of OM treatment and remains elevated for 24 h. Chromatin immunoprecipitation assays demonstrate that the amount of C/EBPbeta bound to the LDLR SIRE sequence is increased 2.8-fold of control by 2 h of OM treatment, reached the highest level of 8-fold by 4 h, and slowly declined thereafter. To further examine the requirement of C/EBPbeta in OM-stimulated LDLR expression, we developed a His-tagged dominant-negative mutant of C/EBPbeta (His-C/EBPbeta-P4; where P4 is plasmid 4 in our mutation series), consisting of the DNA-binding and leucine zipper domains of C/EBPbeta (amino acids 246-345). Expression of His-C/EBPbeta-P4 in HepG2 cells significantly diminishes the OM-induced increase in LDLR promoter activity and the elevation of endogenous LDLR mRNA expression. Taken together, these new findings identify C/EBPbeta as an OM-induced transactivator in LDLR gene transcription and provide a better understanding of the molecular mechanism underlying the sterol-independent regulation of LDLR expression.

Antineoplastic Agents↗

PubMed2006

Nanostructure origins of C60 fluorescence in pyridine.

The nanostructure origins of three distinct and strong fluorescence bands of C60 in room-temperature pyridine are reported for the first time. Fluorescence study and in-situ TEM observation on C60-pyridine solutions with different setting times exhibit that the blue fluorescence peaks centered at 440 nm originate from C60 nanoparticles; the yellow-green fluorescence band located at 575 nm derives from C60 lace-like cluster; and the salmon pink fluorescence band around 700 nm arises from C60 microbulk in solution. The conclusions are supported further by investigation on the C60-toluene system as well.

Fluorescence↗

PubMed2006

Synthesis, crystal structure and DNA binding studies of a binuclear copper(II) complex with phenanthroline.

A new binuclear copper(II) complex, [Cu2Phen2Cl4] (Phen=1,10-phenanthroline), has been synthesized and characterized. Single crystal X-ray diffraction results suggest that this complex structure belongs to monoclinic crystal system, Cc (no. 9) with the cell dimensions: a=9.849(2)A, b=17.833(4)A, c=13.374(3)A, beta=106.61(3) degrees , V=2251.0(8)A(3), Dc=1.8569 Mgm(-3), F(000)=1256.0, Z=4. One Cu(II) central atom situated in a distorted square planar geometry is four-coordinated. The other situated in a distorted square pyramidal geometry is five-coordinated. Only one bridging Cl atom exists in the complex. Spectroscopic studies, including electronic absorption and fluorescence spectra, conductivity measurements and parallel factor analysis (PARAFAC) of fluorescence excitation-emission three-way data array, were carried out on the DNA binding behavior of the complex. All the results suggested that the breakage of DNA secondary structure took place at low molar ratio of complex to DNA (0.3 at most) and intercalation into the base pair of DNA took place at high molar ratio. Additionally, the equilibrium concentration of EB-DNA and EB (EB: ethidium bromide) could be directly obtained by PARAFAC algorithm, proved to be a convincing method for studying the interaction of complexes with DNA.

Copper↗

PubMed2006

Dimerized Drosophila myosin VIIa: a processive motor.

The molecular mechanism of processive movement of single myosin molecules from classes V and VI along their actin tracks has recently attracted extraordinary attention. Another member of the myosin superfamily, myosin VII, plays vital roles in the sensory function of Drosophila and mammals. We studied the molecular mechanism of Drosophila myosin VIIa, using transient kinetics and single-molecule motility assays. Myosin VIIa moves along actin filaments as a processive, double-headed single molecule when dimerized by the inclusion of a leucine zipper at the C terminus of the coiled-coil domain. Its motility is approximately 8-10 times slower than that of myosin V, and its step size is 30 nm, which is consistent with the presence of five IQ motifs in its neck region. The kinetic basis for the processive motility of myosin VIIa is the relative magnitude of the release rate constants of phosphate (fast) and ADP (slow) as in myosins V and VI. The ATPase pathway is rate-limited by a reversible interconversion between two distinct ADP-bound actomyosin states, which results in high steady-state occupancy of a strongly actin-bound myosin species. The distinctive features of myosin VIIa (long run lengths, slow motility) will be very useful in video-based single-molecule applications. In cells, this kinetic behavior would allow myosin VIIa to exert and hold tension on actin filaments and, if dimerized, to function as a processive cargo transporter.

Animals↗

PubMed2006

Contrast enhancement for electronic speckle pattern interferometry fringes by the differential equation enhancement method.

Electronic speckle pattern interferometry fringe patterns usually have poor contrast so it is important to enhance fringe contrast for the extraction of phase from a single fringe pattern. We present new enhancement methods based on differential equations (called DE enhancement methods) to electronic speckle pattern interferometry fringes. The DE enhancement methods transform the image processing to solve differential equations. With the proposed methods, the visibility of the correlation speckle fringe patterns can be improved significantly. We tested the proposed methods on computer-simulated speckle correlation fringes and experimentally obtained fringes, and we compared the new method with other contrast enhancement techniques. The experimental results illustrate the performance of this approach.

Journal Article↗