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Biomedical subjects

C Guo

Publications and source records attributed to C Guo.

At least 37 records · Page 2Linked to original sources

Development of neurotrophic molecules for treatment of neurodegeneration.

Over the past several years, neurotrophic factors have made considerable progress from the laboratory into the clinic. Evidence from preclinical and clinical studies indicates that it may be possible to use neurotrophic factors to prevent, slow the progression of, or even reverse the effects of a number of neurodegenerative diseases and other types of insults in both the central and peripheral nervous system. Their potential importance in the development of therapeutic agents against neurodegenerative disorders and nerve injury has led to a flurry of activity towards understanding their structure, function and signalling mechanisms. Approaches to develop pharmacological agents that target neurotrophic factors, their receptors or neurotrophic factors signalling pathways have been attempted. This review focuses on some of the major themes and lines of mechanistic and therapeutic advances in this fast-moving field of neuroscience.

Animals↗

[The construction of rapid amplification of cDNA ends cDNA libraries from human fetal bone and joint].

OBJECTIVE: To construct rapid amplification cDNA ends(RACE) cDNA libraries from human fetal bone and joint and provide resources for isolation of bone- and joint-specific development-related genes. METHODS: Total RNA of bone and joint were extracted with the modified single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. The double-stranded end-blunted cDNA were synthesized using TaKaRa's cDNA synthesis kit and ligated to cassette adaptors. All of the cDNA molecules were amplified by a pair of common primers. RESULTS: A protocol for RACE cDNA library construction from bone and joint was established and two RACE cDNA libraries from human fetal bone and joint were successfully constructed. CONCLUSION: The protocol of RACE cDNA library construction from limited materials proved to be simple and efficient and the library was suitable for RACE to isolate tissue-specific genes.

Bone and Bones↗

Case-control study of ovarian cancer and polymorphisms in genes involved in catecholestrogen formation and metabolism.

Steroid hormones, such as estrogens, appear to be associated with ovarian carcinogenesis, but the precise biological mechanisms are unclear. Polymorphisms in genes that regulate the concentration of estrogens and their metabolites may contribute directly to the individual variation in ovarian cancer risk through a mechanism involving oxidative stress or indirectly by influencing ovarian cancer susceptibility associated with ovulation and reproduction. We conducted a population-based, case-control study of primary ovarian cancer between 1993 and 1999 in Hawaii to test several genetic and related hypotheses. A personal interview and blood specimen were obtained in the subjects' homes. In a sample of 129 epithelial ovarian cancer cases and 144 controls, we compared the frequencies of several polymorphisms in genes that regulate steroid hormone metabolism and catecholestrogen formation. Multivariate unconditional logistic regression was used to model the association of each genetic polymorphism separately after adjusting for age, ethnicity, and other covariates. The high-activity Val432 allele of the CYP1B1 gene, which may be linked to oxidative stress through elevated 4-hydroxylated catecholestrogen formation, was associated with an increased risk of ovarian cancer. The Val/Leu genotype for CYP1B1 was associated with an odds ratio of 1.8 (95% confidence interval, 1.0-3.3) and the Val/Val genotype with an odds ratio of 3.8 (95% confidence interval, 1.2-11.4) compared with the Leu/Leu genotype (P = 0.005). Tobacco smokers with at least one CYP1A1 (MspI) m2 allele, one CYP1B1 Val allele, one COMT Met allele, or two CYP1A2 A alleles were at significantly increased risk of ovarian cancer compared to never-smokers with CYP1A1 (MspI) ml/ml, CYP1B1 Leu/Leu, COMT Val/Val, or CYP1A2 A/A genotypes, respectively. We found a positive statistical interaction (P = 0.03) between tobacco smoking and the CYP1A1 (MspI) polymorphism on the risk of ovarian cancer. None of the other gene-environment (pregnancy, oral contraceptive pill use) or gene-gene interactions were statistically significant. Although not significant, there was a suggestion that the effect of the CYP1B1 Val allele was reduced substantially in the presence of the high-activity COMT Met allele. These findings suggest that the CYP1B1-Val allele and perhaps other genetic polymorphisms in combination with environmental or hormonal exposures are susceptibility factors for ovarian cancer.

Adult↗

Protective headgear for midwestern agriculture: a limited wear study.

Baseball caps are popular with farm workers, but have been criticized because they do not sufficiently shade the face, neck, and ears. U.S. Environmental Protection Agency standards require workers to wear chemical-resistant hoods or chemical-resistant hats with wide brims during the application of pesticides whose labels call for head protection. In this study, four farm workers wore baseball caps and two alternative types of headgear with wide brims for 20 to 36 hours during planting of corn and soybeans to compare performance features and practicality. Afterwards, researchers analyzed the headgear fabrics by gas chromatography or high-performance liquid chromatography to determine the levels at which five herbicides were deposited on the headgear: 2,4-D, metolachlor, acetochlor, ethalfluralin, and glyphosate. Chemical analysis revealed that 12 percent of specimens had detectable residue: levels of glyphosate in the nanograms-per-square-centimeter (ng/cm2) range and levels of 2,4-D in the micrograms-per-square-centimeter (microgram/cm2) range. Workers, however, preferred the baseball caps because of problems with the wind and feelings of embarrassment about wearing other types of headgear. An acceptable, protective substitute for the baseball cap has yet to be designed.

Adult↗

[Analysis on genetic polymorphism of 13 STR loci on chromosomes 11 and 19 in Chinese Hans].

OBJECTIVE: To analyze the genetic polymorphism of 8 STR loci on chromosome 11 and 5 STR loci on chromosome 19 in Chinese Hans. METHODS: Polymerase chain reaction-single strand length polymorphism(PCR-SSLP) was used to genotype 100 randomly selected individuals of the Han nationality at 8 STR loci(D11S1984, D11S1999, D11S1392, D11S1985, D11S2002, D11S1986, D11S4464 and D11S2359) on chromosome 11 and 5 STR loci(D19S247, D19S714, D19S433, D19S246, D19S254) on chromosome 19. RESULTS: Eight alleles and 26 genotypes, 9 alleles and 15 genotypes, 6 alleles and 16 genotypes, 12 alleles and 40 genotypes, 6 alleles and 19 genotypes, 12 alleles and 48 genotypes, 8 alleles and 20 genotypes, 7 alleles and 13 genotypes were observed at D11S1984, D11S1999, D11S1392, D11S1985, D11S2002, D11S1986, D11S4464 and D11S2359. The heterozygosities for the 8 STR loci were 87%, 68%, 73%, 92%, 71%, 86%, 75% and 71%, respectively. Ten alleles and 19 genotypes, 10 alleles and 26 genotypes, 10 alleles and 24 genotypes, 11 alleles and 29 genotypes, 8 alleles and 18 genotypes were observed at D19S247, D19S714, D19S433, D19S246, D19S254. The heterozygosities for the 5 STR loci were 63%, 82% 72%, 81% 74%, respectively. CONCLUSION: The distribution of allele frequencies of 8 STR loci on chromosome 11 and 5 STR loci on chromosome 19 was consistent with the Hardy-Weinberg equilibrium and the highly genetic polymorphism was observed in Chinese Han population.

China↗

Inhibition of telomerase is related to the life span and tumorigenicity of human prostate cancer cells.

PURPOSE: Telomerase, the enzyme that catalyzes the elongation of telomeres, is illegitimately activated in the majority of cancers, including that of the prostate, where it may greatly extend the life span of malignant cells. The inhibition of telomerase by molecular intervention has been shown to lead eventually to cell death in several tumor or in vitro immortalized cell lines and in 1 case prevent tumor growth in vivo. Therefore, we tested whether a similar strategy may be used to limit the tumorigenic potential of late stage prostate cancer cells. MATERIALS AND METHODS: PC-3, LNCaP and DU-145 human prostate cancer cells were infected with a retrovirus encoding a dominant-negative version of the catalytic subunit of telomerase (DN-hTERT). Subclones or polyclonal populations were assayed for DN-hTERT expression, telomerase activity, telomere length, cell life span and in most cases tumorigenicity in nude mice. RESULTS: DN-hTERT expression levels directly correlated with cell life span and tumorigenic growth. PC-3 cells expressing high levels of DN-hTERT died rapidly and failed to form tumors in nude mice, whereas cells expressing the lowest levels proliferated the longest and generated tumors that later spontaneously regressed. Similarly the inhibition of telomerase activity in LNCaP cells was greater than in DU-145 cells and correspondingly LNCaP cells had a shorter life span. CONCLUSIONS: DN-hTERT expression limits the life span and tumorigenic potential of human prostate cancer cells, although the onset of these effects appears to be dictated by the expression level of DN-hTERT. Therefore, telomerase represents an attractive target for potentially managing prostate cancer. Nevertheless, effective means of inhibiting the enzyme may be required for a therapeutically useful outcome.

Animals↗

Antifibrotic effects of matrine on in vitro and in vivo models of liver fibrosis in rats.

AIM: To study the antifibrotic effects of matrine in vitro a nd in vivo. METHODS: Rat hepatic stellate cell HSC-T6 and mouse fibroblast cell NIH3T3 proliferation stimulated with serum and platelet-derived growth factor (PDGF) was measured b y crystal violet staining assay. Collagen synthesis stimulated with serum and transforming growth factor beta1 (TGF-beta1) was determined by [3H]proline incorporation. Liver fibrosis was induced by carbon tetrachloride (CCl4) in rats an d evaluated with plasma hyaluranic acid level and hepatic hydroxyproline content. RESULTS: Matrine (1-2 mmol/L) markedly reduced serum-driven proliferation and collagen synthesis of HSC-T6 cells as well as NIH3T3 cells. PDGF-driven proliferative activity and TGF-beta1-driven collagen synthesis in HSC-T6 cel ls were attenuated by matrine (0.25-2 mmol/L) in a concentration-dependent manner. In vivo matrine (50 mg/kg and 100 mg/kg) significantly decreased serum hyaluranic acid levels and hepatic hydroxyproline contents in rats treated with CCl4. CONCLUSION: Inhibition of PDGF and TGF-beta1 actions on hepatic stellate cell by matrine might provide a possible mechanism of its antifibrotic activities.

3T3 Cells↗

Matrine inhibits production and actions of fibrogenic cytokines released by mouse peritoneal macrophages.

AIM: To study the effects of matrine (Mat) on production and actions of fibrogenic cytokines from mouse peritoneal macrophages. METHODS: Mouse peritoneal macrophages were primed with calcimycin 1 micromol/L for 8 h then elicited by lipopolysaccharides (LPS) 100 microg/L for 6 h to induce fibrogenic cytokines. Proliferative and collagen stimulating activity in the macrophage culture supernatants was determined by crystal violet staining assay and [3H]-proline incorporation assay using rat hepatic stellate HSC-T6 cell or mouse fibroblast NIH3T3 cell. Transforming growth factor beta (TGFbeta) activity was measured by [3H]-thymidine incorporation assay using Mv-1-Lu mink lung epithelial cell. RESULTS: Mat (0.5-2 mmol/L) was shown to significantly inhibit LPS-induced collagen stimulating activities and TGFbeta production (P < 0.01) whereas did not inhibit proliferative activities induced by macrophages. Macrophage conditioned medium (MCM)-driven proliferation and collagen synthesis of HSC-T6 cells as well as NIH3T3 cells were attenuated by Mat (0.5-2 mmol/L) in a concentration-dependent manner. CONCLUSION: Antifibrotic effects of Mat on hepatic stellate cells may be related to reduction of fibrogenic cytokine production and blockade of their actions.

Alkaloids↗

[Telomerase activity of common malignant tumors].

OBJECTIVE: To study the usefulness of detection of telomerase activity in the diagnosis of malignant tumors. METHODS: Modified telomeric repeat amplification protocol (TRAP) was employed to examine telomerase activity in 283 malignant tumor tissues, 42 adjacent tissues and 61 benign tumor tissues. RESULTS: Of the 283 malignant tumors and 42 adjacent tissues, telomerase was positive in 264 (93.3%) and 11 (26.1%), respectively. Only 4 of the 62 (6.6%) benign tumors were telomerase positive. CONCLUSION: Telomerase activity may be used as tumor marker in the diagnosis of malignant tumors.

Biomarkers, Tumor↗

A potential role of nuclear matrix-associated protein kinase CK2 in protection against drug-induced apoptosis in cancer cells.

Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation. Its activity is generally elevated in rapidly proliferating tissues, and nuclear matrix (NM) is an important subnuclear locale of its functional signaling. In the prostate, nuclear CK2 is rapidly lost commensurate with induction of receptor-mediated apoptosis after growth stimulus withdrawal. By contrast, chemical-induced apoptosis in prostate cancer and other cells (by etoposide and diethylstilbestrol) evokes an enhancement in CK2 associated with the NM that appears to be because of translocation of CK2 from the cytoplasmic to the nuclear compartment. This shuttling of CK2 to the NM may reflect a protective response to chemical-mediated apoptosis. Supporting evidence for this was obtained by employing cells that were transiently transfected with various expression plasmids of CK2 (thereby expressing additional CK2) prior to treatment with etoposide or diethylstilbestrol. Cells transfected with the CK2alpha or CK2alphabeta showed significant resistance to chemical-mediated apoptosis commensurate with the corresponding elevation in CK2 in the NM. Transfection with CK2beta did not demonstrate this effect. These results suggest, for the first time, that besides the commonly appreciated function of CK2 in cell growth, it may also have a role in protecting cells against apoptosis.

Adenocarcinoma↗

How does a beta -hairpin fold/unfold? competition between topology and heterogeneity in a solvable model.

We study the competition between topological effects and sequence inhomogeneities in determining the thermodynamics and the un/folding kinetics of a beta-hairpin. Our work utilizes a new exactly solvable model that allows for arbitrary configurations of native contacts. In general, the competition between heterogeneity and topology results in a crossover of the dominant transition state. Interestingly, near this crossover, the single reaction coordinate picture can be seriously misleading. Our results also suggest that inferring the folding pathway from unfolding simulations is not always justified.

Animals↗

Multielectron effects on single-electron strong field ionization

An apparently simple phenomenon of single-electron strong field ionization involves subtle factors related to multielectron effects. A single electron in an atom or molecule can feel a distinctly different screening strength when exposed to strong fields as opposed to weak fields, and this electron screening due to multielectron motion influences single-electron ionization. The concept and a corresponding model developed in the paper allow a generalization of the Ammosov-Delone-Krainov model for predicting strong field ionization rates of more complicated atoms and molecules. This general approach explains the recently observed anomalous low single ionization rate in O2.

Journal Article↗

Structural phase transition of aluminum induced by electronic excitation

The dynamics of a structural phase transition induced by interband electronic excitation in aluminum is studied by determining the time evolution of the dielectric constant at 1.55 eV through the measurement of the transient reflectivity induced by an ultrafast pump pulse. The threshold fluence and the time scale for this transition are significantly less than the values necessary for ultrafast heat-induced melting, indicating that this phase change is caused by band structure collapse and lattice instability resulting from strong electronic excitation.

Journal Article↗

Thiopyran route to polypropionates: aldol diastereoselectivity of linear and two-directional iterative homologations

[formula: see text] Aldol reaction of tetrahydro-4H-thiopyran-4-one with racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde is easily controlled to give the 2,3-anti-3,4-syn or the 2,3-syn-3,4-syn adduct. Aldol homologations of these beta-hydroxy ketones with the same aldehyde occur with considerable mutual kinetic enantioselection (MKE) and, in each case, selectively give one of the eight possible diastereomers. Similar reactions of related beta-methoxy ketones are also very diastereoselective but proceed without significant MKE, resulting in two diastereomers. The adducts can be used for polypropionate synthesis.

Journal Article↗

Two state behavior in a solvable model of beta-hairpin folding.

Understanding the mechanism of protein secondary structure formation is an essential part of the protein-folding puzzle. Here we describe a simple model for the formation of a beta hairpin, motivated by the fact that folding of a beta hairpin captures much of the basic physics of protein folding. The modeled hairpin is composed of two interacting Gaussian chains with one pairwise (two-body) and two many-body interactions. We show that these many-body interactions, arising from side chain packing effects, are responsible for producing an "all-or-none" folding transition. We also estimate the (single exponential) folding/unfolding rate via calculating the thermodynamic weight of the "critical" droplet/bubble.

Kinetics↗

Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes.

New proteins and modules have been invented throughout evolution. Gene "birth dates" in Caenorhabditis elegans range from the origins of cellular life through adaptation to a soil habitat. Possibly half are "metazoan" genes, having arisen sometime between the yeast-metazoan and nematode-chordate separations. These include basement membrane and cell adhesion molecules implicated in tissue organization. By contrast, epithelial surfaces facing the environment have specialized components invented within the nematode lineage. Moreover, interstitial matrices were likely elaborated within the vertebrate lineage. A strategy for concerted evolution of new gene families, as well as conservation of adaptive genes, may underlie the differences between heterochromatin and euchromatin.

Animals↗