Biomedical subjects

Ping Wang

Publications and source records attributed to Ping Wang.

At least 19 recordsLinked to original sources

PubMed2026

Low-Dose Radiation-Induced Expression of Exosomal miRNAs in the Serum of Medical Radiation Workers.

Objective: Long-term low-dose ionizing radiation may alter genomes and cause diseases. This study examined serum exosomal miRNA differences among radiation-exposed medical workers by work types. Methods: High-throughput sequencing screened serum exosomal miRNAs in diagnostic radiologists, interventional radiologists, and nuclear medicine doctors. qRT-PCR validated differentially expressed miRNAs. Results: 410 differentially expressed miRNAs, including 102 downregulated and 308 upregulated miRNAs, enriched in 15 KEGG pathways. Four miRNAs were validated. miR-30e-5p, miR-155-5p and miR-486-5p differed significantly among groups(P<0.01).The expression levels of these three miRNAs were lower in the nuclear medicine group than in the diagnostic group (0.25±0.05vs3.89±8.62,0.10±0.15vs7.03±15.75,0.37±0.39vs4.46±9.64;Z=3.542,3.335,9.859;P<0.01), whereas miR-155-5p was lower in the interventional group than in the diagnostic group(1.32±2.43vs 7.03±15.75;H=11.889,P=0.003), miR-486-5p was higher(9.54±19.39vs4.46±9.64; H=9.859,P=0.007). All four miRNAs showed higher expression in the 14-31-year work-experience group, and all four also showed age-dependent differences, with miR-30d-5p and miR-486-5p showing the age-related differences (P<0.01). Combined detection of the four miRNAs improved discrimination among occupational categories (AUC=0.784). Multiple linear regression analysis showed that sex was associated with all four miRNAs, whereas work type was associated with miR-30d-5p and miR-155-5p (P<0.05). Conclusion: Serum exosomal miR-30e-5p, miR-155-5p, and miR-486-5p are promising biomarkers for monitoring radiation-induced damage, supporting occupational protection and health management.

exosomes↗

PubMed2026

Integrated salivary proteomic and metabolomic analyses reveal molecular characterization and novel biomarker panels of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by chronic inflammation, oxidative stress, and metabolic dysregulation. The lack of convenient and easily-accessible non-invasive diagnostic approaches remains a major clinical challenge. This study applied an integrated saliva-based proteomic and untargeted metabolomic strategy to identify potential biomarkers for COPD classification. Comprehensive multi-omics analyses identified 225 differentially abundant proteins and 60 differentially abundant metabolites between patients with COPD and healthy controls, including 24 biologically relevant endogenous metabolites. Functional enrichment analyses revealed pronounced dysregulation of mitochondrial energy metabolism, redox homeostasis, lipid remodeling, and inflammatory-related pathways in COPD. By integrating salivary proteomic and metabolomic biomarkers, a stepwise feature selection combined with LASSO logistic regression was used to construct diagnostic models, yielding an optimized biomarker panel consisting of 11 proteins and 2 endogenous metabolites. This integrated model achieved excellent diagnostic performance, with an area under the ROC curve of 0.96. Collectively, these findings demonstrate that integrated salivary proteomic and metabolomic profiling provides a robust, non-invasive approach for COPD classification and offers a promising foundation for the development of biosensor-based diagnostic platforms and early disease detection. SIGNIFICANCE: Chronic obstructive pulmonary disease (COPD) remains a major global health burden. Current diagnostic approaches rely largely on spirometry and clinical assessment, which are limited in sensitivity for early-stage disease and unsuitable for large-scale screening. This study employs an integrated saliva-based proteomic and metabolomic strategy to identify non-invasive biomarkers for COPD classification. Our findings reveal coordinated dysregulation of mitochondrial energy metabolism, redox homeostasis, and lipid remodeling in COPD, highlighting the interconnected roles of metabolic reprogramming, oxidative stress, and inflammation in disease pathophysiology. Notably, a robust diagnostic panel comprising 11 proteins and 2 endogenous metabolites was established, achieving excellent classification performance (AUC of 0.96). To our knowledge, the integrated application of salivary proteomics and metabolomics for COPD diagnosis remains largely unexplored, underscoring the significance and translational potential of our findings.

Humans↗

PubMed2026

Integrated Multi-omics Profiling of 2,4-dinitrochlorobenzene (DNCB)-induced Atopic Dermatitis in Mice Reveals a Coordinated Network of Barrier Dysfunction, Immune Activation, and Metabolic Reprogramming.

Atopic dermatitis (AD) is caused by a combination of epidermal barrier defect and immune imbalance. However, the molecular networks between these structural abnormalities and metabolic variations are unclear. This study aim of this research was to examine the concurrent molecular alterations in skin barrier damage and metabolic disorders in an AD-like mouse model by a multi-omics strategy. A 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model was established and the skin tissues were examined through the combination of transcriptomic, quantitative proteomic, and metabolomic analyses. Cross-omics correlation and network analyses were performed to identify consistently abnormal molecular pathways and crucial regulatory molecules. DNCB treatment caused severe epidermal hyperplasia, and prominent infiltration of CD3⁺ T cells, F4/80⁺ macrophages, and mast cells. Transcriptomic and proteomic analysis indicated significant disruption in keratinocyte differentiation, extracellular matrix organization, and cornified envelope formation pathways. Combined analysis detected 171 molecules which were simultaneously altered at both mRNA and protein levels, and network analysis identified FLG2 and KRT6B as central barrier-related molecules. Pathway enrichment analysis consistently showed the participation of AMPK and PPAR signaling pathways. Metabolomic analysis also revealed coordinated changes in lipid and amino acid metabolism which were closely associated with cornified envelope-associated genes and collagen-modifying enzymes. These findings indicate a close relationship between barrier, immune and metabolic regulation in DNCB-induced dermatitis and provide a multi-omics resource for future mechanistic studies of atopic skin inflammation.

Animals↗

PubMed2026

Pedigree-assisted genotype imputation enables cost-effective genomic prediction in Penaeus vannamei.

Genomic selection in Penaeus vannamei has long been constrained by the high cost of dense genotyping. To address this limitation, we evaluated genotype imputation from a low-density 1 K panel to a medium-density 55 K panel of the "Yellow Sea Array No. 1" and examined its impact on genomic prediction for harvest body weight in P. vannamei. A four-generation pedigree including 30 great-grandparents, 39 grandparents, 100 parents, and 608 offspring was genotyped using the 55 K panel. A two-step experimental design was implemented to (i) assess the performance of different imputation algorithms under reference population scenarios with varying proportions of siblings, and (ii) compare six alternative reference population structures incorporating parents, ancestors, and siblings. Genotype imputation using the pedigree-based method FImpute v3.0 consistently achieved higher accuracy than the population-based method Beagle v5.5. Using this pedigree-assisted approach, imputation accuracy increased from 0.73 when only parental genotypes were used to 0.84 with the inclusion of 10% siblings, and subsequently plateaued at 0.87-0.90 when sibling representation reached 20%. Across the six reference population structures, imputation accuracy was primarily driven by the availability of parental genotypes, ranging from 0.50 to 0.56 in the absence of parents to 0.88-0.89 when both parents and ancestral generations were included. Accuracy remained high when both parents were available (0.84-0.87 with siblings; 0.73 without siblings) but declined substantially when only one parent was genotyped (0.65-0.68). Imputation accuracy was positively associated with both minor allele frequency (MAF) and linkage disequilibrium (max r2LD), with LD exerting the stronger influence. Heritability estimates derived from imputed 55 K genotypes were highly consistent with those obtained from the original 55 K data (0.39 ± 0.14 vs. 0.41 ± 0.14), indicating that genotype imputation did not compromise variance component estimation. In predictive ability analyses, pedigree-based BLUP (PBLUP) achieved higher predictive ability than genomic BLUP (GBLUP) based on the 1 K panel, with predictive abilities of 0.42-0.44 for PBLUP compared with 0.34-0.35 for GBLUP. Using imputed genotypes for genomic prediction further improved predictive ability relative to the true 1 K panel, yielding values ranging from 0.35 to 0.47. Notably, when parental genotypes were included in the reference population, GBLUP based on imputed genotypes surpassed the predictive ability of PBLUP and approached that achieved with the original 55 K genotypes (0.45-0.47). Collectively, these results provide the first empirical evidence that low- to medium-density genotype imputation, combined with pedigree information, can effectively support genomic prediction in P. vannamei. This study establishes a cost-efficient and scalable framework for implementing genomic selection in P. vannamei and provides a practical reference for the application of genomic selection in other aquaculture species with constrained breeding budgets.

Animals↗

PubMed2025

Cancer-testis antigen ACRBP: Cytotoxic response to its HLA-A2 restricted peptide and immune features in ovarian cancer.

While our prior study identified the HLA-A *0201-restricted ACRBP epitope peptide and demonstrated its capacity to generate cytotoxic T lymphocytes (CTLs) in vitro, the clinical relevance of the peptide-induced T cell reactivity in ovarian cancer (OC) patients and the in vivo anti-tumor efficacy of these CTLs remain unexplored. In this study, dendritic cells were sensitized with ACRBP peptide (ALLVLCYSI) and co-cultured with autologous CD8+T cells to induce the production of specific cytotoxic T lymphocytes (Pep-CTLs). The anti-tumor effects of Pep-CTLs were evaluated in SCID mice bearing human ovarian cancer (OC) OVCAR-3 cells. Concurrently, we co-cultured ALLVLCYSI peptide with peripheral blood mononuclear cells (PBMCs) from OC patients (HLA-A2+, ACRBP+) and assessed the number of specific T cells using ELISPOT assays. The immunological impact of the ACRBP peptide against human OC was validated through both in vitro and in vivo experiments. These findings establish a preclinical foundationfor developing ACRBP peptide-based vaccines in OC immunotherapy. To further elucidate ACRBP's role in OC treatment, the study analyzed single-cell RNA sequencing data from 8 OC patients and bulk RNA sequencing data from the Cancer Genome Atlas Project (TCGA) comprising 308 ovarian cancer cases. This analysis aimed to explore the heterogeneity among ACRBP-expressing tumor cell populations and to investigate the correlation between ACRBP expression and immune molecule expression (including MHC and chemokines) alongside chemotherapy response. These insights furnish a theoretical framework supporting the future application of ACRBP in tumor immunotherapy and strategies to prevent immune escape.

Humans↗

PubMed2007

Crosslinked enzyme aggregates in hierarchically-ordered mesoporous silica: a simple and effective method for enzyme stabilization.

alpha-chymotrypsin (CT) and lipase (LP) were immobilized in hierarchically-ordered mesocellular mesoporous silica (HMMS) in a simple but effective way for the enzyme stabilization, which was achieved by the enzyme adsorption followed by glutaraldehyde (GA) crosslinking. This resulted in the formation of nanometer scale crosslinked enzyme aggregates (CLEAs) entrapped in the mesocellular pores of HMMS (37 nm), which did not leach out of HMMS through narrow mesoporous channels (13 nm). CLEA of alpha-chymotrypsin (CLEA-CT) in HMMS showed a high enzyme loading capacity and significantly increased enzyme stability. No activity decrease of CLEA-CT was observed for 2 weeks under even rigorously shaking condition, while adsorbed CT in HMMS and free CT showed a rapid inactivation due to the enzyme leaching and presumably autolysis, respectively. With the CLEA-CT in HMMS, however, there was no tryptic digestion observed suggesting that the CLEA-CT is not susceptible to autolysis. Moreover, CLEA of lipase (CLEA-LP) in HMMS retained 30% specific activity of free lipase with greatly enhanced stability. This work demonstrates that HMMS can be efficiently employed as host materials for enzyme immobilization leading to highly enhanced stability of the immobilized enzymes with high enzyme loading and activity.

Chymotrypsin↗

PubMed2007

Cell death after co-administration of cisplatin and ethacrynic acid.

Ethacrynic acid (EA) significantly enhances the ototoxic effects of cisplatin. To gain insights into the mechanisms underlying Cis/EA ototoxicity, cochleas were labeled with several apoptotic markers. Cis/EA treatment caused extensive outer hair cell (OHC) and inner hair cell (IHC) damage; OHC lesions decreased from the base towards apex of the cochlea whereas the IHC lesion was relatively constant (25-60%) along the length of the cochlea. Propidium iodide labeled OHC nuclei appeared relatively normal at 6h post-treatment, were condensed and fragmented at 12h post-treatment and were frequently missing 48 h post-treatment. Initiator caspase 8, associated with membrane death receptors, and TRADD, a protein that recruits caspase 8, were present in OHC at 6h post-treatment. Caspase 8 labeling increased from 6 to 24h, but was largely absent at 48 h post-treatment. Executioner caspase 3 and caspase 6, which lie downstream of caspase 8, were expressed in OHC 12-24h post-treatment. Initiator caspase 9, associated with mitochondrial damage, was only expressed at low levels at 48 h post-treatment. These results suggest that the rapid onset of Cis/EA induced programmed cell death is initiated by membrane death receptors associated with TRADD and caspase 8.

Animals↗

PubMed2006

Asian Tobacco Education and Cancer Awareness Research Special Population Network. A model for reducing Asian American cancer health disparities.

Asian Americans are the fastest growing and the second largest foreign-born ethnic group in the United States. Cancer is a leading cause of death among Asian Americans. The Asian Tobacco Education and Cancer Awareness Research (ATECAR) Special Population Network, Center for Asian Health, aimed to reduce or eliminate cancer health disparities in these diverse, underserved populations in Pennsylvania, New Jersey, Delaware, and New York. The ATECAR logic model was adapted from a variety of conceptual frameworks to develop and implement the network's multifaceted cancer health disparities research, training, awareness, and outreach programs. The model was the basis for the developmental phases of the network that included (1) needs assessment, infrastructure, and partnership building; (2) intervention research, training, and mentorship; and (3) evaluation, dissemination, and diffusion. Community involvement occurred at every operational level to ensure program and network sustainability. Between 2000 and 2005, the ATECAR network consisted of 88 partners, representing a cross-section of Asian communities, academia, cancer centers, and health service agencies, ensuring a viable infrastructure for the network's multidimensional cancer health disparities programs. ATECAR's research covered tobacco control, cancer prevention and intervention, and clinical trials. More than 22 research projects were conducted and their results disseminated in peer-reviewed journals. ATECAR also trained 76 junior researchers and special population investigators and 1014 community professionals in disparity issues. ATECAR's multimedia cancer awareness education program reached over 116,000 Asians. The ATECAR network's achievements have had a profound impact on Asian Americans and established a trend toward reducing cancer health disparities, especially among underserved Asian Americans. Cancer 2006. (c) 2006 American Cancer Society.

Asian↗

PubMed2006

Suppressor of cytokine signaling-3 suppresses the ability of activated signal transducer and activator of transcription-3 to stimulate neurite growth in rat primary sensory neurons.

The actions of the neuropoietic cytokines are mediated by the gp130 receptor, which activates several signaling molecules including the transcription factor STAT3 (signal transducer and activator of transcription), which, in turn, is subject to feedback inhibition by SOCS3 (suppressor of cytokine signaling). Activation of the gp130 receptor has been implicated in axonal growth particularly during regeneration, but the specific contribution of STAT3 is the subject of conflicting reports. Measurements of SOCS3 mRNA in rat dorsal root ganglia showed a significant induction in this inhibitory molecule after peripheral nerve injury. The functions of STAT3 and SOCS3 in adult rat primary sensory neurons were investigated in vitro through transduction of lentiviruses yielding a conditionally activated STAT3, native SOCS3, or a mutant SOCS3 with dominant-negative actions. The SOCS3 construct was effective in inhibiting tyrosine phosphorylation of STAT3 in a neuroblastoma cell line and in blocking nuclear accumulation of endogenous STAT3 or of the conditionally activated STAT3 chimera in primary sensory neurons. In such neurons, transduction and activation of STAT3 enhanced neurite growth, transduction with SOCS3 reduced neurite outgrowth, and transduction with mutant SOCS3 enhanced neurite growth, at least under basal conditions. In conclusion, STAT3 signaling is beneficial to axonal growth through activating transcription of unidentified genes, and SOCS3 is detrimental to axonal growth through inhibition of STAT3 and/or other transcription factors.

Active Transport, Cell Nucleus↗

PubMed2006

Thyroid transcription factor in differentiating type II cells: regulation, isoforms, and target genes.

Thyroid transcription factor-1 (TTF-1, product of the Nkx2.1 gene) is essential for branching morphogenesis of the lung and enhances expression of surfactant proteins by alveolar type II cells. We investigated expression of two TTF-1 mRNA transcripts, generated by alternative start sites and coding for 42- and 46-kD protein isoforms in the mouse, during hormone-induced differentiation of human fetal lung type II cells in culture. Transcript for 42-kD TTF-1 was 20-fold more abundant than TTF-1(46) mRNA by RT-PCR. Only 42-kD protein was detected in lung cells, and its content increased during in vivo development and in response to in vitro glucocorticoid plus cAMP treatment. To examine TTF-1 target proteins, recombinant, phosphorylated TTF-1(42) was expressed in nuclei of cells by adenovirus transduction. By microarray analysis, 14 genes were comparably induced by recombinant TTF-1 (rTTF-1) and hormone treatment, and 9 additional hormone-responsive genes, including surfactant proteins-A/B/C, were partially induced by rTTF-1. The most highly (approximately 10-fold) TTF-1-induced genes were DC-LAMP (LAMP3) and CEACAM6 with induction confirmed by Western analysis and immunostaining. Treatment of cells with hormones plus small inhibitory RNA directed toward TTF-1 reduced TTF-1 content by approximately 50% and inhibited hormone induction of the 23 genes induced by rTTF-1. In addition, knockdown of TTF-1 inhibited 72 of 274 other genes induced by hormones. We conclude that 42-kD TTF-1 is required for induction of a subset of regulated genes during type II cell differentiation.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2006

Expression cloning of cholesterol alpha-glucosyltransferase, a unique enzyme that can be inhibited by natural antibiotic gastric mucin O-glycans, from Helicobacter pylori.

Helicobacter pylori infects over half the world's population, but only 3% of those infected develop peptic ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. In H. pylori, alpha-glucosyl cholesterol constitutes more than 25% of cell wall lipids, and it has been suggested that alpha-glucosyl cholesterol is essential for H. pylori viability. Here, we identified cholesterol alpha-glucosyltransferase (CHLalphaGcT) using an expression cloning strategy and showed that this enzyme is distinctively inhibited by mucin-type O-glycans similar to those present in deeper portions of the gastric mucosa. Moreover, inactivation of CHLalphaGcT by homologous recombination led to H. pylori lethality. These results indicate that H. pylori CHLalphaGcT is a unique enzyme targeted by a natural antibiotic mucin and constitutes an excellent therapeutic target to prevent H. pylori-induced peptic ulcer, gastric carcinoma, and MALT lymphoma.

Amino Acid Sequence↗

PubMed2006

Gib2, a novel Gbeta-like/RACK1 homolog, functions as a Gbeta subunit in cAMP signaling and is essential in Cryptococcus neoformans.

Canonical G proteins are heterotrimeric, consisting of alpha, beta, and gamma subunits. Despite multiple Galpha subunits functioning in fungi, only a single Gbeta subunit per species has been identified, suggesting that non-conventional G protein signaling exists in this diverse group of eukaryotic organisms. Using the Galpha subunit Gpa1 that functions in cAMP signaling as bait in a two-hybrid screen, we have identified a novel Gbeta-like/RACK1 protein homolog, Gib2, from the human pathogenic fungus Cryptococcus neoformans. Gib2 contains a seven WD-40 repeat motif and is predicted to form a seven-bladed beta propeller structure characteristic of beta transducins. Gib2 is also shown to interact, respectively, with two Ggamma subunit homologs, Gpg1 and Gpg2, similar to the conventional Gbeta subunit Gpb1. In contrast to Gpb1 whose overexpression promotes mating response, overproduction of Gib2 suppresses defects of gpa1 mutation in both melanization and capsule formation, the phenotypes regulated by cAMP signaling and associated with virulence. Furthermore, depletion of Gib2 by antisense suppression results in a severe growth defect, suggesting that Gib2 is essential. Finally, Gib2 is shown to also physically interact with a downstream target of Gpa1-cAMP signaling, Smg1, and the protein kinase C homolog Pkc1, indicating that Gib2 is also a multifunctional RACK1-like protein.

Amino Acid Sequence↗

PubMed2006

Direct evidence for endothelial vascular endothelial growth factor receptor-1 function in nitric oxide-mediated angiogenesis.

Vascular endothelial growth factor-A (VEGF) is critical for angiogenesis but fails to induce neovascularization in ischemic tissue lesions in mice lacking endothelial nitric oxide synthase (eNOS). VEGF receptor-2 (VEGFR-2) is critical for angiogenesis, although little is known about the precise role of endothelial VEGFR-1 and its downstream effectors in this process. Here we have used a chimeric receptor approach in which the extracellular domain of the epidermal growth factor receptor was substituted for that of VEGFR-1 (EGLT) or VEGFR-2 (EGDR) and transduced into primary cultures of human umbilical vein endothelial cells (HUVECs) using a retroviral system. Activation of HUVECs expressing EGLT or EGDR induced rapid phosphorylation of eNOS at Ser1177, release of NO, and formation of capillary networks, similar to VEGF. Activation of eNOS by VEGFR-1 was dependent on Tyr794 and was mediated via phosphatidylinositol 3-kinase, whereas VEGFR-2 Tyr951 was involved in eNOS activation via phospholipase Cgamma1. Consistent with these findings, the VEGFR-1-specific ligand placenta growth factor-1 activated phosphatidylinositol 3-kinase and VEGF-E, which is selective for VEGFR-2-activated phospholipase Cgamma1. Both VEGFR-1 and VEGFR-2 signal pathways converged on Akt, as dominant-negative Akt inhibited the NO release and in vitro tube formation induced following activation of EGLT and EGDR. The identification Tyr794 of VEGFR-1 as a key residue in this process provides direct evidence of endothelial VEGFR-1 in NO-driven in vitro angiogenesis. These studies provide new sites of modulation in VEGF-mediated vascular morphogenesis and highlight new therapeutic targets for management of vascular diseases.

Amino Acid Sequence↗

PubMed2006

Diffusion and solubility coefficients determined by permeation and immersion experiments for organic solvents in HDPE geomembrane.

The chemical resistance of eight organic solvents in high density polyethylene (HDPE) geomembrane has been investigated using the ASTM F739 permeation method and the immersion test at different temperatures. The diffusion of the experimental organic solvents in HDPE geomembrane was non-Fickian kinetic, and the solubility coefficients can be consistent with the solubility parameter theory. The diffusion coefficients and solubility coefficients determined by the ASTM F739 method were significantly correlated to the immersion tests (p<0.001). The steady state permeation rates also showed a good agreement between ASTM F739 and immersion experiments (r(2)=0.973, p<0.001). Using a one-dimensional diffusion equation based on Fick's second law, the diffusion and solubility coefficients obtained by immersion test resulted in over estimates of the ASTM F739 permeation results. The modeling results indicated that the diffusion and solubility coefficients should be obtained using ASTM F739 method which closely simulates the practical application of HDPE as barriers in the field.

Diffusion↗

PubMed2006

Protease-activated receptor-2 simultaneously directs beta-arrestin-1-dependent inhibition and Galphaq-dependent activation of phosphatidylinositol 3-kinase.

Protease-activated receptor-2 (PAR-2) is a G-protein-coupled receptor (GPCR) activated upon proteolytic cleavage of its N-terminus by a number of serine proteases. We have previously reported that formation of a beta-arrestin-dependent signaling scaffold is required for PAR-2-stimulated activation of extracellular signal regulated kinases 1 and 2 and chemotaxis. beta-Arrestin-dependent pathways downstream of some GPCRs have been shown to function independently and sometimes in opposition to classic signaling through heterotrimeric G-proteins; however, this possibility has not been addressed with respect to PAR-2. Here we demonstrate that PAR-2 can increase PI3K activity through a Galphaq/Ca(2+)-dependent pathway involving PYK2 and a Src-family kinase, while inhibiting PI3K activity through a beta-arrestin-dependent mechanism, and that beta-arrestin-1 can directly associate with and inhibit the catalytic activity of p110alpha. Using size exclusion chromatography and co-immunoprecipitation, we demonstrate that the PI3K is recruited into a scaffolding complex containing PAR-2 and beta-arrestins. Inhibition of PI3K activity blocks PAR-2-stimulated chemotaxis, and beta-arrestin-1 colocalizes with p85 within the pseudopodia, suggesting that beta-arrestin-1 association with PI3K may spatially restrict its enzymatic activity and that this localized inhibition may be crucial for PAR-2-stimulated chemotaxis.

Animals↗

PubMed2006

Phenol quaternary ammonium derivatives: charge and linker effect on their DNA photo-inducible cross-linking abilities.

We report here that phenol derivatives with two and four quaternary ammoniums were synthesized and their abilities to bind and cross-link DNA were investigated. Thermal denaturizing studies indicated that derivatives possess similar DNA binding abilities and gel electrophoresis revealed that more charges (series B) and electronic donation substitute linkers (like -S-) dramatically increase the DNA cross-linking abilities.

Cross-Linking Reagents↗

PubMed2006

Metal inhibition of human N-methylpurine-DNA glycosylase activity in base excision repair.

Cadmium (Cd2+), nickel (Ni2+) and cobalt (Co2+) are human and/or animal carcinogens. Zinc (Zn2+) is not categorized as a carcinogen, and rather an essential element to humans. Metals were recently shown to inhibit DNA repair proteins that use metals for their function and/or structure. Here we report that the divalent ions Cd2+, Ni2+, and Zn2+ can inhibit the activity of a recombinant human N-methylpurine-DNA glycosylase (MPG) toward a deoxyoligonucleotide with ethenoadenine (varepsilonA). MPG removes a variety of toxic/mutagenic alkylated bases and does not require metal for its catalytic activity or structural integrity. At concentrations starting from 50 to 1,000 microM, both Cd2+ and Zn2+ showed metal-dependent inhibition of the MPG catalytic activity. Ni2+ also inhibited MPG, but to a lesser extent. Such an effect can be reversed with EDTA addition. In contrast, Co2+ and Mg2+ did not inhibit the MPG activity in the same dose range. Experiments using HeLa cell-free extracts demonstrated similar patterns of inactivation of the varepsilonA excision activity by the same metals. Binding of MPG to the substrate was not significantly affected by Cd2+, Zn2+, and Ni2+ at concentrations that show strong inhibition of the catalytic function, suggesting that the reduced catalytic activity is not due to altered MPG binding affinity to the substrate. Molecular dynamics (MD) simulations with Zn2+ showed that the MPG active site has a potential binding site for Zn2+, formed by several catalytically important and conserved residues. Metal binding to such a site is expected to interfere with the catalytic mechanism of this protein. These data suggest that inhibition of MPG activity may contribute to metal genotoxicity and depressed repair of alkylation damage by metals in vivo.

Catalysis↗

PubMed2006

Polyhedra formation and transient cone ejection of a resonant microdrop forced by an ac electric field.

New deformation or fission phenomena are reported for microdrops driven by an ac electric field at their resonant frequencies. The Maxwell forces that pull out the vertices from a drop can be enhanced when the ac frequency is comparable to both the drop resonant frequency and the inverse charge relaxation time of the diffuse layer. The selected polyhedra possess symmetries that ensure a global force balance of the Maxwell forces and a linear dimension consistent with a sphere whose nth harmonic (n is up to six in the observation) coincides with the applied ac frequency. At high voltages, the resonant focusing of charges by the vibration modes produces evenly distributed and transient Taylor cones that can eject charged nanodrops.

Acetonitriles↗