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Biomedical subjects

Fei Gao

Publications and source records attributed to Fei Gao.

At least 55 records · Page 3Linked to original sources

Microbial stimulation by Mycoplasma fermentans synergistically amplifies IL-6 release by human lung fibroblasts in response to residual oil fly ash (ROFA) and nickel.

Mycoplasma (MP), such as the species M. fermentans, possess remarkable immunoregulatory properties and can potentially establish chronic latent infections with little signs of disease. Atmospheric particulate matter (PM) is a complex and diverse component of air pollution associated with adverse health effects. We hypothesized that MP modulate the cellular responses induced by chemical stresses such as residual oil fly ash (ROFA), a type of PM rich in transition metals. We assessed the release of interleukin-6 (IL-6), a prototypic immune-modulating cytokine, in response to PM from different sources in human lung fibroblasts (HLF) deliberately infected with M. fermentans. We found that M. fermentans and ROFA together synergistically stimulated production of IL-6 compared to either stimuli alone. Compared to several other PM, ROFA appeared most able to potentiate IL-6 release. The potentiating effect of live MP infection could be mimicked by M. fermentans-derived macrophage-activating lipopeptide-2 (MALP-2), a known Toll-like receptor-2 agonist. The aqueous fraction of ROFA also contained potent IL-6 inducing activity in concert with MALP-2, and exposure to several defined metal salts indicated that Ni and, to a lesser extent V, (but not Cu) could synergistically act with MALP-2 to induce IL-6. These data indicate that microorganisms like MP can interact with environmental stimuli such as PM-derived metals to synergistically activate signaling pathways that control lung cell cytokine production and, thus, can potentially modulate adverse health effects of PM exposure.

Air Pollutants, Occupational↗

Hemi[hexaaquamagnesium(II)] (mu-2,6-bis[[bis(carboxylatomethyl)amino]methyl]-4-chlorophenolato)bis[diaquamagnesium(II)] decahydrate.

The crystal structure of the title compound, [Mg(H2O)6]0.5[Mg2(C16H14ClN2O9)(H2O)4].10H2O, shows that this binuclear complex consists of two Mg centres in distorted octahedral geometry, joined by an oxo bridge which is a derivative of the deprotoned hydroxy group of the phenolate in the ligand molecule. In the anion, the coordination sphere of each MgII ion is completed by two carboxylates, a tertiary N atom and two water molecules. The inner coordination spheres for the MgII ions are very similar, both in ligand sets and in geometry. Each unit of the binuclear complex has one negative charge neutralized by a neighbouring hydrated cation, [Mg(H2O)6]2+, in which the Mg atom lies on an inversion centre. In each cell, there are 34 water molecules and most of them participate in the formation of hydrogen bonds, which contribute greatly to the stability of the whole structure.

Biomimetic Materials↗

A novel Na-O-Ni-O-Ni bridging complex of Cl-HXTA, where Cl-HXTA is 2,6-bis[[bis(carboxylatomethyl)amino]methyl]-4-chlorophenolate.

In the structure of the title compound, heptaaqua-1kappa3O,2kappa2O,3kappa2O-(mu3-2,6-bis[[bis(carboxylatomethyl)amino]methyl]-4-chlorophenolato-1kappaO;2kappa4O,O',N,O1;3kappa4O1N',O",O"')dinickel(II)sodium(I) pentahydrate, [NaNi2(C16H14ClN2O9)(H2O)7].5H2O or [Ni2(Cl-HXTA)(H2O)4[Na(H2O)3]].5H2O, the trinuclear complex unit consists of two distorted NiNO5 octahedra bridged by a phenolate O atom and an NaO4 tetrahedron bridged to one of the Ni octahedra by a carboxylate O atom. There are four intramolecular hydrogen bonds forming four six-membered rings in the complex and the complex molecules are connected to each other by a very complicated hydrogen-bond network.

Journal Article↗

A novel thiocyanate-bridged one-dimensional chain complex: [Cu(NCS)2(Hambi)] (Hambi is 2-aminomethyl-1H-benzimidazole).

Using 2-aminomethyl-1H-benzimidazole as the ligand, a new thiocyanate-bridged copper(II) complex, namely bis(2-aminomethyl-1H-benzimidazole-kappa(2)N(2),N(3))dithiocyanatocopper(II),[Cu(NCS)(2)(C(8)H(9)N(3))], has been synthesized and structurally characterized. The Cu atom is five-coordinated and exhibits a distorted square-pyramidal geometry. The thiocyanate ions (NCS(-)) act as either bridging or terminal ligands. The bridging NCS(-) ligands connect neighboring Cu atoms, constructing chains, while the terminal NCS(-) ligands form hydrogen bonds with amine H atoms, leading to a complicated network.

Journal Article↗

Maspin plays an essential role in early embryonic development.

Maspin (Mp) is a member of the serpin family with inhibitory functions against cell migration, metastasis and angiogenesis. To identify its role in embryonic development in vivo, we generated maspin knockout mice by gene targeting. In this study, we showed that homozygous loss of maspin expression was lethal at the peri-implantation stage. Maspin was specifically expressed in the visceral endoderm after implantation; deletion of maspin interfered with the formation of the endodermal cell layer, thereby disrupting the morphogenesis of the epiblast. In vitro, the ICM of the Mp(-/-) blastocysts failed to grow out appropriately. Data from embryoid body formation studies indicated that the Mp(-/-) EBs had a disorganized, endodermal cell mass and lacked a basement membrane layer. We showed that the embryonic ectoderm lineage was lost in the Mp(-/-) EBs, compared with that of the Mp(+/+) EBs. Re-expression of maspin partially rescued the defects observed in the Mp(-/-) EBs, as evidenced by the appearance of ectoderm cells and a layer of endoderm cells surrounding the ectoderm. In addition, a maspin antibody specifically blocked normal EB formation, indicating that maspin controls the process through a cell surface event. Furthermore, we showed that maspin directly increased endodermal cell adhesion to laminin matrix but not to fibronectin. Mp(+/-) endodermal cells grew significantly slower than Mp(+/+) endodermal cells on laminin substrate. We conclude that deletion of maspin affects VE function by reducing cell proliferation and adhesion, thereby controlling early embryonic development.

Animals↗

Emodin enhances arsenic trioxide-induced apoptosis via generation of reactive oxygen species and inhibition of survival signaling.

Although arsenic trioxide (As(2)O(3)) induces apoptosis in a relatively wide spectrum of tumors, the sensitivity of different cell types to this treatment varies to a great extent. Because reactive oxygen species (ROS) are critically involved in As(2)O(3)-induced apoptosis, we attempted to explore the possibility that elevating the cellular ROS level might be an approach to facilitate As(2)O(3)-induced apoptosis. Emodin, a natural anthraquinone derivative, was selected because its semiquinone structure is likely to increase the generation of intracellular ROS. Its independent and synergistic effects with As(2)O(3) in cytotoxicity were studied, and the plausible signaling mechanism was investigated in HeLa cells. Cell Proliferation Assay and flow cytometry were used to assess cell viability and apoptosis. Electrophoretic mobility shift assay, luciferase reporter assay, and Western blotting were performed to analyze signaling alteration. The results demonstrated that coadministration of emodin, at low doses of 0.5-10 micro M, with As(2)O(3) enhanced As(2)O(3)-rendered cytotoxicity on tumor cells, whereas these treatments caused no detectable proproliferative or proapoptotic effects on nontumor cells. ROS generation was increased, and activation of nuclear factor kappaB and activator protein 1 was suppressed by coadministration. All enhancements by emodin could be abolished by the antioxidant N-acetyl-L-cysteine. Therefore, we concluded that emodin sensitized HeLa cells to As(2)O(3) via generation of ROS and ROS-mediated inhibition on two major prosurvival transcription factors, nuclear factor kappaB and activator protein 1. This result allows us to propose a novel strategy in chemotherapy that uses mild ROS generators to facilitate apoptosis-inducing drugs whose efficacy depends on ROS.

Apoptosis↗

The cell cycle related apoptotic susceptibility to arsenic trioxide is associated with the level of reactive oxygen species.

Double staining flow cytometry was performed using 7-amino actinomycin D and 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate, to detect the level fluctuation of reactive oxygen species (ROS) during the cell cycle of normal NB4 cells. Our results showed that NB4 cells possessed higher level of ROS in G2/M phase than in G1 and S phases. Double staining flow cytometry, with TdT mediated dUTP nick end labeling (Tunel) and propidium iodide (PI), indicated that As2O3 (2 microM) could induce apoptosis in NB4 cells prevailingly from G2/M phase, and this efficacy was enhanced upon co-administration of 2, 3-dimethoxy-1, 4-naphthoquinone (DMNQ) (2.5 microM) which could produce the endogenous ROS. These results suggested that different ROS level in different cell cycle phases of NB4 cells might determine the selective induction of G2/M apoptosis and the cells' susceptibility to apoptosis by As2O3.

Acetylcysteine↗

The Wt1+/R394W mouse displays glomerulosclerosis and early-onset renal failure characteristic of human Denys-Drash syndrome.

Renal failure is a frequent and costly complication of many chronic diseases, including diabetes and hypertension. One common feature of renal failure is glomerulosclerosis, the pathobiology of which is unclear. To help elucidate this, we generated a mouse strain carrying the missense mutation Wt1 R394W, which predisposes humans to glomerulosclerosis and early-onset renal failure (Denys-Drash syndrome [DDS]). Kidney development was normal in Wt1(+/R394W) heterozygotes. However, by 4 months of age 100% of male heterozygotes displayed proteinuria and glomerulosclerosis characteristic of DDS patients. This phenotype was observed in an MF1 background but not in a mixed B6/129 background, suggestive of the action of a strain-specific modifying gene(s). WT1 encodes a nuclear transcription factor, and the R394W mutation is known to impair this function. Therefore, to investigate the mechanism of Wt1 R394W-induced renal failure, the expression of genes whose deletion leads to glomerulosclerosis (NPHS1, NPHS2, and CD2AP) was quantitated. In mutant kidneys, NPHS1 and NPHS2 were only moderately downregulated (25 to 30%) at birth but not at 2 or 4 months. Expression of CD2AP was not changed at birth but was significantly upregulated at 2 and 4 months. Podocalyxin was downregulated by 20% in newborn kidneys but not in kidneys at later ages. Two other genes implicated in glomerulosclerosis, TGFB1 and IGF1, were upregulated at 2 months and at 2 and 4 months, respectively. It is not clear whether the significant alterations in gene expression are a cause or a consequence of the disease process. However, the data do suggest that Wt1 R394W-induced glomerulosclerosis may be independent of downregulation of the genes for NPHS1, NPHS2, CD2AP, and podocalyxin and may involve other genes yet to be implicated in renal failure. The Wt1(R394W) mouse recapitulates the pathology and disease progression observed in patients carrying the same mutation, and the mutation is completely penetrant in male animals. Thus, it will be a powerful and biologically relevant model for investigating the pathobiology of the earliest events in glomerulosclerosis.

Adaptor Proteins, Signal Transducing↗

Risk factors for breast cancer associated with mammographic features in Singaporean chinese women.

BACKGROUND: Mammographic density has been found to be a strong risk factor for breast cancer and to be associated with age, body weight, parity, and menopausal status. Most studies to date have been carried out in Western populations. The purpose of the study described here was to determine in a cross-sectional study in a Singaporean Chinese population the demographic, menstrual, reproductive, and anthropometric factors that are associated with quantitative variations in age-adjusted percentage mammographic densities and to examine the association of these factors with the dense and nondense areas of the mammogram. METHOD: We used mammograms and questionnaire data collected from subjects in the Singapore Breast Screening Project. Women ages 45 to 69 years participated and 84% of those screened were Chinese. Mammograms were digitized and percentage density was measured and analyzed in relation to the questionnaire data. RESULTS: Percentage mammographic density was associated with several risk factors for breast cancer, most of them also associated, in opposite directions, with the dense and nondense components of the image. Percentage density was associated with age and weight (both negatively), height and age at first birth (both positively), and number of births and postmenopausal status (both negatively). Percentage density was weakly associated with a previous breast biopsy but was not associated with age at menarche or menopause, with use of hormones, or with a family history of breast cancer. CONCLUSION: Percentage mammographic density in Singaporean Chinese women has similar associations with risk factors for breast cancer to those seen in Caucasians.

Aged↗

Spectral studies on aluminum ion binding to the ligands with phenolic group(s): implications for the differences between N- and C-terminal binding sites of human serum apotransferrin.

Both the binding and releasing of ferric ions in C-, and N-terminal binding sites of human serum transferrin are different. To understand the difference here the interactions of aluminum with the ligands containing phenolic group(s), including 8-hydroxyquinoline, salicylic acid, N,N'-di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid, N,N'-ethylenebis[2-(o-hydroxyphenolic)glycine], and human serum apotransferrin, respectively, are investigated by using UV difference and fluorescence spectra methods in 0.1 M N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid at pH 7.4. Aluminum binding produces a UV difference peak near 235 nm that is characteristic of phenolic groups binding to aluminum. The peak at 235 nm has been used to determine conditional binding constants of log K(Al-HBED)=8.88+/-0.74 and log K(Al-EHPG)=9.38+/-0.03. However, the effects of aluminum binding on the fluorescence intensity of N,N'-ethylenebis[2-(o-hydroxyphenolic)glycine], salicylic acid and N,N'-di(2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid, 8-hydroxyquinoline are disparate, the former showing a decrease and the latter an increase. At pH 7.4, there is N cdots, three dots, centered H-O type intramolecular hydrogen bond in 8-hydroxyquinoline, N,N'-di(2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid and O cdots, three dots, centered H-O type intramolecular hydrogen bond in salicylic acid, N,N'-ethylenebis[2-(o-hydroxyphenolic)glycine]. The effects of salts on the fluorescence intensity of the ligands containing phenolic group(s) show that fluorescence emission increases with the breaking of an N cdots, three dots, centered H-O type intramolecular hydrogen bond and fluorescence emission decreases with the breaking of an O cdots, three dots, centered H-O type intramolecular hydrogen bond. Fluorescence titrations of apotransferrin and both forms of monoferric transferrin with aluminum indicated that there is O cdots, three dots, centered H-O type intramolecular hydrogen bonds for the phenolic groups of Tyr426 and Tyr517 in the C-terminal binding site. While N cdots, three dots, centered H-O type intramolecular hydrogen bonds are found for the phenolic groups of Tyr95 and Tyr188 in the N-terminal binding site.

Aluminum↗

[Exploratory study of factors related sexual dysfunction among cancer patients].

OBJECTIVE: To investigate the factors related to the sexual dysfunction among cancer patients and make preparation for its prevention and treatment to improve the quality of life of cancer patients. METHODS: Self-designed questionnaires about sexual function were used and 130 patients in their rehabilitation period interviewed. These patients were suffering from different kinds of cancer. RESULTS: Age of patients and their perception of sex are two important factors resulting in significant difference of suffering rate of sexual dysfunction among these cancer patients. The total suffering rate of sexual dysfunction among patients suffering from reproductive cancer is significantly higher than that of patients suffering from cancer in other systems. Of all the factors we analyzed in the research, we found that stage of cancer; physical strength and perception of sex had significant correlation with newly emerging sexual dysfunction. From the patient's point of view, those newly suffering from sexual dysfunction after their cases were diagnosed as cancer thought that cancer treatment had negative effect on their sexual function. CONCLUSION: Stage of cancer, physical strength and perception of sex had significant correlation with sexual dysfunction of cancer patients who have received cancer treatment. This suggests that, intervention in patients' wrong perception of sex is the first aspect we should pay attention to in treating and preventing sexual dysfunction among cancer patients.

Adult↗

[The role of nuclear factor kappa B in secretion of interleukin-8 by gastric cancer cell line SGC 7901 induced by Helicobacter pyiori].

OBJECTIVE: To investigate the role of nuclear factor kappaB (NF-kappaB) in the gastric inflammation induced by Helicobacter pylori (H. pylori). METHODS: SGC-7901 was transfected with IkappaB (NF-kappaB inhibitor gene) by electroporation, (beta)lacZ activity assay was used to examine transfected efficacy. Expression of IkappaB was assessed by Western-blot. Different concentration of live and heat-killed Hp (ATCC 43504) and supernatant of liquid culture were cocultured with SGC7901-IkappaB and its negative control SGC7901- neo. Activation of intracellular NF-kappaB was examined by electrophoretic mobility shift analyses (EMSA) and luciferase report gene assay at different time point. IL-8 levels were measured by ELISA at different time point. RESULTS: IL-8 release was evident 4 hours after infection of SGC-7901-neo with H. pylori, and this effect was dose-time dependent. SGC-7901-IkappaB in which NF-kappaB has not been activated could not secret IL-8 after infection with H. pylori. CONCLUSION: Secretion of IL-8 by gastric epithelial cell upon H pylori infection is dependent on activation of NF-kappaB.

Cell Line, Tumor↗

Age at diagnosis and the choice of survival analysis methods in cancer epidemiology.

A young age at diagnosis of cancer is often seen as an indicator of the aggressiveness of the tumor. However, empirical studies have shown conflicting results on the association between age at diagnosis and survival. There are two choices of time scale for a Cox regression model: time since diagnosis, and age. The regression analysis of relative survival rates is an alternative to the Cox model. Using breast cancer data from a population-based cancer registry, we illustrate the features of Cox models using the two time scales and compare them with the relative survival approach. Using a Cox model with time since diagnosis as the time scale, a younger age at diagnosis is associated with a lower mortality; using age as the time scale gives the opposite result. The relative survival approach agrees with the Cox model with age as the time scale. We maintain that a careful clarification of research purpose and a careful choice of methods are necessary.

Adult↗