Biomedical subjects

Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 109 records · Page 6Linked to original sources

PubMed2006

Predicting and monitoring response to chemotherapy by 1,3-bis(2-chloroethyl)-1-nitrosourea in subcutaneously implanted 9L glioma using the apparent diffusion coefficient of water and 23Na MRI.

PURPOSE: To examine the effects of the alkylating anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on (23)Na MRI and the water apparent diffusion coefficient (ADC) in subcutaneously- (sc-) implanted 9L glioma in rats. MATERIALS AND METHODS: (23)Na MRI and (1)H water ADC measurements were performed on sham-treated control (N = 6) and BCNU-treated (N = 15) Fisher rats one day before BCNU injection and then one, three, and five days after BCNU injection. RESULTS: The BCNU-treated tumors were divided into BCNU-responsive (R(BCNU)) and BCNU-nonresponsive (NR(BCNU)) groups depending on the tumor volume changes that occurred after therapy. The pretreatment (23)Na MRI signal intensity (SI) and water ADC values were higher in R(BCNU) tumors compared to NR(BCNU) tumors. (23)Na MRI SI and water ADC increased with tumor growth in control and NR(BCNU) groups, but these changes were interrupted by BCNU therapy in R(BCNU) group. CONCLUSION: (23)Na MRI and water ADC measurements may be useful for predicting and monitoring response to chemotherapy in some tumors. However, the changes that occurred in (23)Na MRI SI and water ADC in sc-implanted 9L tumors are in contrast to previously published results for BCNU therapy of orthotopic 9L tumors. This may have important implications for monitoring therapy response in tumors.

Animals↗

PubMed2006

Murine Spam1 mRNA: involvement of AU-rich elements in the 3'UTR and antisense RNA in its tight post-transcriptional regulation in spermatids.

Sperm adhesion molecule1 (SPAM1), the best characterized hyaluronidase gene, is abundantly expressed in the testis. We attempted to overexpress mouse Spam1 via transgenesis using either the endogenous promoter in a BAC or a heterologous Protamine1 promoter for a Spam1 cDNA transgene. Although transgene-copy numbers ranged from 2 to 15 and transgenic transcripts were expressed, there was a general failure of overexpression of the RNA and protein in the testis of all seven founders. Also, three transgenic lines showed a modest downregulation or co-suppression of the RNA for Spam1 and Hyal5, present on the BAC. We provide evidence for the potential involvement of two co-ordinating post-transcriptional regulatory processes in the failure of overexpression: abundant endogenous antisense RNA and adenosine-uridine (AU)-rich element-mediated regulation of RNA turnover. We demonstrate that AU-rich elements (AREs) in the 3'UTR of mRNAs, well-known to interact with trans-acting proteins to target the RNA for (in)stability, are present in Spam1 RNA and specifically bind to six testicular cytoplasmic proteins. These AU-binding proteins (AUBPs) were virtually absent from the kidney where transcripts are rare, and were shown to interact with the cytoskeleton, which modulates mRNA turnover. In addition to a role in the RNAi pathway, antisense RNA can also modulate ARE-mediated regulation of mRNA by hybridizing to the AREs and specifically silencing their function. This potentially links the two processes in the regulation of Spam1 expression. We hypothesize that testicular Spam1 RNA is regulated post-transcriptionally by cis-acting ARE(s) in the 3'UTR which recognize AUBPs and which are modulated by antisense transcripts.

3' Untranslated Regions↗

PubMed2006

Effect of dexamethasone and aquaporin-1 antisense oligonucleotides on the aquaporin-1 expression in cultured human trabecular meshwork cells.

The changes in the expression of aquaporin-1 (AQP1) mRNA and protein in cultured human trabecular meshwork (HTM) cells treated with dexamethasone and transfected with antisense oligonucleotides (AS-ODN) were studied, and the implication of AQP1 regulation in corticosteroid-glaucoma and the possibility of AS-ODN inhibiting the AQP1 expression were evaluated. The cultured HTM cells in vitro were treated with different concentrations of dexamethasone and transfected with oligonucleotides for 5 days respectively. Then, total RNA and protein of HTM cells were extracted. The changes of AQP1 mRNA and protein were demonstrated qualitatively and quantitatively by RT-PCR and Western blot. Band intensities were detected by imaging analysis. There was a parallel relationship between the results of RT-PCR and those of Western blot. The expression levels of AQP1 mRNA and protein in dexamethasone-treated groups were increased initially and decreased later as dexamethasone concentration was stepped up. In the 0. 04 microg/mL and 0.4 microg/mL groups, the levels of AQP1 were higher than in control group (0 microg/mL). In the 4 microg/ mL and 40 microg/mL groups, the AQP1 expression levels were lower than in control group. AS-ODN could down-regulate the expression of AQP1 mRNA and protein in a dose-dependent manner. At 5 microg/mL, down-regulation efficiency reached the maximum. There was no statistically significant difference in the expression of AQP1 mRNA and protein between all sense oligonucleotides groups and control group. It was suggested that dexamethasone may induce the changes of the AQP1 expression in HTM cells to be involved in the occurrence of corticosteroid-glaucoma. AS-ODN can down-regulate the AQP1 expression in HTM cells to some extent.

Aquaporin 1↗

PubMed2006

Ginsenoside R(e) increases fertile and asthenozoospermic infertile human sperm motility by induction of nitric oxide synthase.

We investigated the effects of Ginsenoside R(e) on human sperm motility in fertile and asthenozoospermic infertile individuals in vitro and the mechanism by which the Ginsenosides play their roles. The semen samples were obtained from 10 fertile volunteers and 10 asthenozoospermic infertile patients. Spermatozoa were separated by Percoll and incubated with 0, 1, 10 or 100 microM of Ginsenoside R(e). Total sperm motility and progressive motility were measured by computer-aided sperm analyzer (CASA). Nitric oxide synthase (NOS) activity was determined by the 3H-arginine to 3H-citrulline conversion assay, and the NOS protein was examined by the Western blot analysis. The production of sperm nitric oxide (NO) was detected using the Griess reaction. The results showed that Ginsenoside R(e) significantly enhanced both fertile and infertile sperm motility, NOS activity and NO production in a concentration-dependent manner. Sodium nitroprusside (SNP, 100 nM), a NO donor, mimicked the effects of Ginsenoside R(e). And pretreatment with a NOS inhibitor N(omega)-Nitro-L-arginine methyl ester (L-NAME, 100 microM) or a NO scavenger N-Acetyl-L-cysteine (LNAC, 1 mM) completely blocked the effects of Ginsenoside R(e). Data suggested that Ginsenoside R(e) is beneficial to sperm motility, and that induction of NOS to increase NO production may be involved in this benefit.

Acetylcysteine↗

PubMed2006

Characterization of checkpoint responses to DNA damage in Saccharomyces cerevisiae: basic protocols.

In spite of certain special features of its cell cycle, the yeast Saccharomyces cerevisiae has proved to be an excellent and widely used model to study eukaryotic checkpoint responses to DNA damage. This chapter primarily summarizes selected cytological methods that are useful for initial characterization of cell cycle responses. These can be useful in order to study mutants, conditions, or selected DNA damaging agents and experimental examples are given. We have also included protocols for flow-cytometric cell cycle analysis and for determination of Rad53 phosphorylation, a commonly used indicator of checkpoint activation.

Blotting, Western↗

PubMed2006

Design of biocompatible chitosan microgels for targeted pH-mediated intracellular release of cancer therapeutics.

We report the rational design of a chitosan-based drug delivery system. The chitosan derivative N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride (HTCC) was ionically cross-linked by sodium tripolyphosphate (TPP) to form sub-200-nm microgels that are responsive to pH changes. When these microgels were loaded with methotrexate disodium (MTX), a cytotoxic drug for cancer treatment, and conjugated to the targeting biomolecule apo-transferrin, a protein known to enter cells via receptor-mediated endocytosis, enhanced killing of immortalized HeLa cells was observed. In this intracellular delivery method, the microgel was exposed to low-pH environments that caused the chitosan to swell and release the drug. This rational drug delivery design may be useful in enhancing cancer therapy and reducing side effects.

Antineoplastic Agents↗

PubMed2006

Proteomic profiling of regionalized proteins in rat epididymis indicates consistency between specialized distribution and protein functions.

The epididymis is a key structure of the male reproductive system; its function is to mature, transport, and store sperm. Most of the research examining the epididymis to date has been limited to the study of the secreted proteins involved in the maturation of spermatozoa. However, it is also very important to understand the protein components, regulation and function of the tissue itself since these are the basis for all of its physiological processes. We investigated the differential expression of proteins among the caput, corpus, and cauda regions of rat epididymis and considered the possible links between the localization of these proteins and the different functions of these epididymal regions. High-resolution 2-D gel electrophoresis followed by mass spectrometry (MS) revealed 28 distinct proteins whose expression levels varied from the caput to the cauda epididymis. Sixteen of them were reported for first time to be expressed in the epididymis. Expression patterns of some proteins were validated by Northern blot or Western blot. Immunohistochemistry revealed that inducible carbonyl reductase (iCR), an important enzyme in the anti-oxidative system, exhibits primary and cell-type specific distribution in the distal cauda region. Moreover, analysis of iCR transcription in castrated animals showed that its expression is androgen-dependent. Together with its known functions, iCR may also be involved in androgen metabolism and maintaining a steady microenvironment in the duct of epididymis.

Alcohol Oxidoreductases↗

PubMed2006

Identification of key genes responsible for cytokine-induced erythroid and myeloid differentiation and switching of hematopoietic stem cells by RAGE.

We utilized a unique culture system to analyze the expression patterns of gene, protein, and cell surface antigen, and the biological process of the related genes in erythroid and myeloid differentiation and switching of hematopoietic stem cells (HSCs) in response to cytokine alterations. Gene-specific fragments (266) identified from five populations of cytokine-stimulated HSCs were categorized into three groups: (1) expressed specifically in a single cell population; (2) expressed in two cell populations, and (3) expressed in three or more populations. Of 145 defined cDNAs, three (2%) were novel genes. Protein two-dimensional gel electrophoresis and flow cytometry analyses showed overlapped and distinguished protein expression profiles in the cell populations studied. Biological process mapping of mRNAs expressed in erythroid and myeloid lineages indicated that mRNAs shared by both lineages attended 'core processes,' whereas genes specifically expressed in either lineage alone were related to specific processes or cellular maturation. Data from this study support the hypothesis that committed HSCs (E14 or G14) cells can still be redirected to develop into myeloid or erythroid cells when erythropoietin (EPO) is replaced with granulocyte-colony stimulating factor (G-CSF) under erythroid-cultured condition or G-CSF with EPO in myeloid-cultured environment, respectively. Our results suggest that genes or proteins co-expressed in erythroid and myeloid lineages may be essential for the lineage maintenance and switching in hematopoiesis.

Cell Differentiation↗

PubMed2006

Effects of environmental factors on organochlorine pesticide residues in soils of the Guanting Reservoir area, China.

Topsoil samples from 56 sites around the Guanting Reservoir, China, were measured for HCH and DDT concentrations. The total soil HCH content (including alpha-, beta-, gamma-, and delta-isomers) in these soil samples ranged from 0 to 7.33 ng x g(-1), with a mean of 0.69 ng x g(-1). These levels were considerably lower than those of the total DDT soil contents (including pp'-DDE, pp'-DDD, op'-DDT, and pp'-DDT), which ranged from 0 to 76.01 ng x g(-1), with a mean of 9.46 ng x g(-1). DDT was also found to be the major pollutant in the soil samples, accounting for approximately 93% of the total organochlorine pesticide (OCP) contents. Several environmental factors including land use, soil texture, soil taxonomy, and microbial biomass were considered to be responsible for the OCP levels observed. The data provide some insight into the effects of environmental conditions such as soil formation, agricultural cultivation, nutrient enrichment, and other anthropogenic activities on the degradation of OCPs in soils. Although the OCP residues currently are below the maximum limits set for use on agricultural land in China, and only rarely would such levels pose significant ecological concern, OCPs are highly persistent in soil and bioaccumulative. The data provided in this study are considered crucial for reservoir remediation, especially since the Guanting Reservoir will serve as one of the main drinking water sources for Beijing in the foreseeable future.

China↗

PubMed2006

Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells.

Autosomal dominant Parkinson disease (PD) is caused by duplication or triplication of the alpha-synuclein gene as well as by the A30P, E46K, and A53T mutations. The mechanisms are unknown. Reactive astrocytes in the substantia nigra of PD and MPTP-treated monkeys display high levels of the inflammatory mediator intercellular adhesion molecule-1 (ICAM-1), indicating that chronic inflammation contributes to the degeneration. Here we report that alpha-synuclein strongly stimulates human astrocytes as well as human U-373 MG astrocytoma cells to up-regulate both interleukin (IL)-6 and ICAM-1 (ED50=5 microg ml(-1)). The mutated forms are more potent stimulators than wild-type (WT) alpha-synuclein in these assays. We demonstrate by immunoblotting analysis that this up-regulation is associated with activation of the major mitogen-activated protein kinase (MAPK) pathways. It is also attenuated by PD 98059, an inhibitor of the MAPK/extracellular-regulated kinase kinase MEK1/2, SP 600125, an inhibitor of c-Jun N-terminal kinase (JNK), and SB 202190, an inhibitor of p38 MAPK. The inhibitory effects on human astrocytes have IC50 values of 2, 5, and 1.5 microM respectively. We hypothesize that the neuroinflammation stimulated by release of an excess of normal alpha-synuclein or by release of its mutated forms can be involved in the pathobiology of PD.

Astrocytes↗

PubMed2006

Sophorolipids block lethal effects of septic shock in rats in a cecal ligation and puncture model of experimental sepsis.

OBJECTIVE: Sophorolipids, a family of natural and easily chemoenzymatically modified microbial glycolipids, are promising modulators of the immune response. The potential of the therapeutic effect of sophorolipids was investigated in vivo in a rat model of sepsis and in vitro by analysis of nitric oxide and cytokine production. DESIGN: Prospective, randomized animal study. SETTING: Experimental laboratory. SUBJECTS: Male Sprague-Dawley rats, 200-240 g. INTERVENTIONS: Intra-abdominal sepsis was induced in vivo in 166 rats via cecal ligation and puncture (CLP); 60 rats were used to characterize the model. The remaining rats were treated with sophorolipids or vehicle (dimethylsulfoxide [DMSO]/physiologic saline) by intravenous (iv) tail vein or intraperitoneal (IP) injection immediately post-CLP (25/group). Survival rates were compared at 36 hrs after surgery. In vitro, macrophages were cultured in lipopolysaccharide (LPS) +/- sophorolipid and assayed for nitric oxide (NO) production and gene expression profiles of inflammatory cytokines. In addition, splenic lymphocytes isolated from CLP rats +/- sophorolipid treatment (three per group) were analyzed for cytokine production by RNase protection assay. MEASUREMENTS AND MAIN RESULTS: CLP with 16-gauge needles optimized sepsis induction and resultant mortality. Sophorolipid treatment improved rat survival by 34% (iv) and 14% (IP) in comparison with vehicle controls (p < .05 for iv treatment). Sophorolipids decreased LPS-induced macrophage NO production by 28% (p < .05). mRNA expression of interleukin (IL)-1beta was downregulated by 42.5 +/- 4.7% (p < .05) and transforming growth factor (TGF)-beta1 was upregulated by 11.7 +/- 1.5% (p < .05) in splenocytes obtained 6 hrs postsophorolipid treatment. LPS-treated macrophages cultured 36 hrs with sophorolipids showed increases in mRNA expression of IL-1alpha (51.7%), IL-1beta (31.3%), and IL-6 (66.8%) (p < .05). CONCLUSIONS: Administration of sophorolipids after induction of intra-abdominal sepsis significantly decreases mortality in this model. This may be mediated in part by decreased macrophage NO production and modulation of inflammatory responses.

Animals↗

PubMed2006

Community exposure to perfluorooctanoate: relationships between serum concentrations and exposure sources.

OBJECTIVE: The objective of this study was to determine serum (perfluorooctanoate [PFOA]) in residents near a fluoropolymer production facility: the contributions from air, water, and occupational exposures, personal and dietary habits, and relationships to age and gender. METHODS: The authors conducted questionnaire and serum PFOA measurements in a stratified random sample and volunteers residing in locations with the same residential water supply but with higher and lower potential air PFOA exposure. RESULTS: Serum (PFOA) greatly exceeded general population medians. Occupational exposure from production processes using PFOA and residential water had additive effects; no other occupations contributed. Serum (PFOA) depended on the source of residential drinking water, and not potential air exposure. For public water users, the best-fit model included age, tap water drinks per day, servings of home-grown fruit and vegetables, and carbon filter use. CONCLUSIONS: Residential water source was the primary determinant of serum (PFOA).

Adult↗

PubMed2006

Community exposure to perfluorooctanoate: relationships between serum levels and certain health parameters.

OBJECTIVE: The objective of this study was to determine whether certain biomarkers of toxicity and/or a past diagnosis of liver or thyroid disease were associated with serum perfluorooctanoate concentrations (PFOA) in a community with longstanding environmental exposure to PFOA. METHODS: Serum (PFOA), hematologic and biochemical biomarkers, and a questionnaire were administered to 371 residents selected by stratified random sampling and a lottery among volunteers. Median PFOA was 354 ng/mL (interquartile range, 181-571 ng/mL). RESULTS: No significant positive relationships between serum (PFOA) and liver or renal function tests, cholesterol, thyroid-stimulating hormone, or with red cell indices, white cell, or platelet counts. Mean serum (PFOA) was not increased in those with a history of liver or thyroid disease. CONCLUSIONS: No toxicity from PFOA was demonstrated using the measured end points; other end points need to be addressed.

Adolescent↗

PubMed2006

A fast and effective model for wavelet subband histograms and its application in texture image retrieval.

This paper presents a novel, effective, and efficient characterization of wavelet subbands by bit-plane extractions. Each bit plane is associated with a probability that represents the frequency of 1-bit occurrence, and the concatenation of all the bit-plane probabilities forms our new image signature. Such a signature can be extracted directly from the code-block code-stream, rather than from the de-quantized wavelet coefficients, making our method particularly adaptable for image retrieval in the compression domain such as JPEG2000 format images. Our signatures have smaller storage requirement and lower computational complexity, and yet, experimental results on texture image retrieval show that our proposed signatures are much more cost effective to current state-of-the-art methods including the generalized Gaussian density signatures and histogram signatures.

Algorithms↗

PubMed2006

Alleviation of pre-exposure of mouse brain with low-dose 12C6+ ion or 60Co gamma-ray on male reproductive endocrine damages induced by subsequent high-dose irradiation.

Irradiation has been widely reported to damage organisms by attacking on proteins, nucleic acid and lipids in cells. However, radiation hormesis after low-dose irradiation has become the focus of research in radiobiology in recent years. To investigate the effects of pre-exposure of mouse brain with low-dose (12)C6+ ion or 60Co gamma (gamma)-ray on male reproductive endocrine capacity induced by subsequent high-dose irradiation, the brains of the B6C3F1 hybrid strain male mice were irradiated with 0.05 Gy of (12)C6+ ion or 60Co gamma-ray as the pre-exposure dose, and were then irradiated with 2 Gy as challenging irradiation dose at 4 h after pre-exposure. Serum pituitary gonadotropin hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), testosterone, testis weight, sperm count and shape were measured on the 35th day after irradiation. The results showed that there was a significant reduction in the levels of serum FSH, LH, testosterone, testis weight and sperm count, and a significant increase in sperm abnormalities by irradiation of the mouse brain with 2 Gy of (12)C6+ ion or 60Co gamma-ray. Moreover, the effects were more obvious in the group irradiated by (12)C6+ ion than in that irradiated by 60Co gamma-ray. Pre-exposure with low-dose (12)C6+ ion or 60Co gamma-ray significantly alleviated the harmful effects induced by a subsequent high-dose irradiation.

Animals↗

PubMed2006

AtCHIP functions as an E3 ubiquitin ligase of protein phosphatase 2A subunits and alters plant response to abscisic acid treatment.

CHIP proteins are E3 ubiquitin ligases that promote degradation of Hsp70 and Hsp90 substrate proteins through the 26S proteasome in animal systems. A CHIP-like protein in Arabidopsis, AtCHIP, also has E3 ubiquitin ligase activity and has important roles to play under conditions of abiotic stress. In an effort to study the mode of action of AtCHIP in plant cells, proteins that physically interact with it were identified. Like its animal orthologs, AtCHIP interacts with a unique class of ubiquitin-conjugating enzymes (UBC or E2) that belongs to the stress-inducible UBC4/5 class in yeast. AtCHIP also interacts with other proteins, including an A subunit of protein phosphatase 2A (PP2A). This PP2A subunit appears to be a substrate of AtCHIP, because it can be ubiquitylated by AtCHIP in vitro and because the activity of PP2A is increased in AtCHIP-overexpressing plants in the dark or under low-temperature conditions. Unlike the rcn1 mutant, that has reduced PP2A activity due to a mutation in one of the A subunit genes of PP2A, AtCHIP-overexpressing plants are more sensitive to ABA treatment. Since PP2A was previously shown to be involved in low-temperature responses in plants, the low-temperature-sensitive phenotype observed in AtCHIP-overexpressing plants might be partly due to the change in PP2A activity. These data suggest that the E3 ubiquitin ligase AtCHIP may function upstream of PP2A in stress-responsive signal transduction pathways under conditions of low temperature or in the dark.

Abscisic Acid↗

PubMed2006

Identification of a new spore wall protein from Encephalitozoon cuniculi.

Microsporidia form environmentally resistant spores that are critical for their host-to-host transmission and persistence in the environment. The spore walls of these organisms are composed of two layers, the exospore and the endospore. Two spore wall proteins (SWP1 and SWP2) have been previously identified in members of the Encephalitozoonidae family. These proteins localize to the exospore. The endospore is known to contain chitin, and a putative glycosylphosphatidylinositol (GPI)-anchored chitin deacetylase has been localized to the plasmalemma-endospore interface. Using proteomic techniques, we have identified a new spore wall protein (SWP3) that is located in the endospore. The gene for this protein is located on chromosome 1 and corresponds to the open reading frame ECU01_1270. SWP3 is predicted to have a signal peptide and to be GPI anchored. Consistent with these modifications, two-dimensional electrophoresis demonstrated that SWP3 has an acidic pI and a molecular mass of <20 kDa. By immunoelectron microscopy, this protein was found on the cell surface during sporogony and in the endospore in mature spores. SWP3 has several potential O-glycosylation sites, and it is possible that it is a mannosylated protein like the major polar tube protein (PTP1).

Amino Acid Sequence↗

PubMed2006

Crystal structure of a type III pantothenate kinase: insight into the mechanism of an essential coenzyme A biosynthetic enzyme universally distributed in bacteria.

Pantothenate kinase (PanK) catalyzes the first step in the five-step universal pathway of coenzyme A (CoA) biosynthesis, a key transformation that generally also regulates the intracellular concentration of CoA through feedback inhibition. A novel PanK protein encoded by the gene coaX was recently identified that is distinct from the previously characterized type I PanK (exemplified by the Escherichia coli coaA-encoded PanK protein) and type II eukaryotic PanKs and is not inhibited by CoA or its thioesters. This type III PanK, or PanK-III, is widely distributed in the bacterial kingdom and accounts for the only known PanK in many pathogenic species, such as Helicobacter pylori, Bordetella pertussis, and Pseudomonas aeruginosa. Here we report the first crystal structure of a type III PanK, the enzyme from Thermotoga maritima (PanK(Tm)), solved at 2.0-A resolution. The structure of PanK(Tm) reveals that type III PanKs belong to the acetate and sugar kinase/heat shock protein 70/actin (ASKHA) protein superfamily and that they retain the highly conserved active site motifs common to all members of this superfamily. Comparative structural analysis of the PanK(Tm) active site configuration and mutagenesis of three highly conserved active site aspartates identify these residues as critical for PanK-III catalysis. Furthermore, the analysis also provides an explanation for the lack of CoA feedback inhibition by the enzyme. Since PanK-III adopts a different structural fold from that of the E. coli PanK -- which is a member of the "P-loop kinase"superfamily -- this finding represents yet another example of convergent evolution of the same biological function from a different protein ancestor.

Amino Acid Sequence↗