Biomedical subjects

Tian Xia

Publications and source records attributed to Tian Xia.

At least 19 recordsLinked to original sources

PubMed2026

DNA Methylation, SERPING1 Expression, and Immune-related Traits in Osteoporosis: A Mendelian Randomization Study And Supportive Ex Vivo Evidence.

INTRODUCTION: Osteoporosis (OP) is a major public health burden; however, the role of SERPIN family proteins remains incompletely understood. This study aimed to investigate genetically inferred associations between SERPINs and OP and to explore potential regulatory relationships. METHODS: Genome-wide association study (GWAS) summary statistics were used to perform two-sample Mendelian randomization (MR) and summary-data-based Mendelian randomization (SMR) analyses. Primary MR estimates were derived using inverse-variance-weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. Cancellous bone tissue from the greater trochanter of the femur was collected from three patients with OP and three non-osteoporotic controls. qPCR and WB were used to analyze the whole bone homogenate, IHC was used to detect decalcified bone sections, and mediation analysis was used to explore potential regulatory associations. RESULTS: Among the proteins of the SERPIN family, only SERPING1 had an obvious positive correlation with the risk of osteoporosis (OR = 1.06, P = 0.0012). qPCR, WB, and IHC analyses demonstrated increased SERPING1 mRNA and protein expression in bone tissue from OP patients. Mediation analyses suggested that cg15918732 DNA methylation may serve as an upstream regulatory factor for SERPING1 expression. In addition, the downstream associations also consist of the alteration of immune cell conditions, like the decrease in the quantity of natural killer cells and T cells, and the rise in the level of mononuclear cells, and so forth. DISCUSSION: These findings provide genetic evidence for the possible role of SERPING1 in OP, which may be achieved through epigenetic regulation and immune pathways. Due to the corresponding characteristics of genetic inference and the small sample size, these results are hypothetical and generative. CONCLUSION: This study shows that DNA methylation of cg15918732 may be associated with SERPING1 expression in osteoporosis and immune-related traits. These findings provide new insights into potential epigenetic and immunological pathways in osteoporosis, which may contribute to future mechanistic and translational research.

Humans↗

PubMed2007

Impairment of mitochondrial function by particulate matter (PM) and their toxic components: implications for PM-induced cardiovascular and lung disease.

Increasing evidence suggests that reactive oxygen species (ROS) and oxidative stress are involved in PM-mediated lung and cardiovascular injury. The physical characteristics and the chemical composition of particulate matter (PM) play a key role in ROS generation in vitro and in vivo. The mitochondria are major subcellular targets for PM as well as a source of ROS production. ROS production is due to interference in mitochondrial electron transfer and PT pore opening by pro-oxidative PM components. Another possible mechanism is direct physical targeting by ambient ultrafine particles that lodge in and destroy mitochondrial structure. An understanding of the mitochondrial effects of PM is key in understanding the mechanisms of PM-induced adverse health effects.

Air Pollutants↗

PubMed2006

Prevalence of selected bacterial named species and uncultivated phylotypes in endodontic abscesses from two geographic locations.

Evidence is mounting that the prevalence of some putative endodontic pathogens can significantly vary according to the geographic location in which samples were taken. This study aimed to provide additional knowledge on this subject by comparing the frequencies of 10 selected candidate endodontic pathogens in samples of acute apical abscesses obtained from two distinct geographic locations; Portland, OR, and Rio de Janeiro, Brazil. DNA was extracted from aspirates and used as template in nested PCR assays using 16S rRNA gene taxon-specific oligonucleotide primers. Of the target species/phylotypes, Treponema denticola (73% of the cases), Porphyromonas endodontalis (70%), and Tannerella forsythia (57%) were the most prevalent taxa found in Brazilian samples. Dialister invisus (70% of the cases), P. endodontalis (63%) and Dialister pneumosintes (55%) were the most frequent taxa in the Portland, OR samples. Data analysis revealed that T. denticola and T. forsythia were significantly more detected in Brazilian samples than in the Portland, OR samples. Although D. invisus, Filifactor alocis, and Synergistes oral clone W090 were detected in many more samples from the Portland, OR patients, differences were not found to be statistically significant. These findings confirmed that some bacterial taxa can markedly differ in the frequencies they occur in samples from different locations. It remains to be clarified whether this observation translates into relevant therapeutic implications.

Bacterial Infections↗

PubMed2006

Effects of hsp90 binding inhibitors on sGC-mediated vascular relaxation.

Vascular soluble guanylate cyclase (sGC) exists in multimeric complexes with endothelial nitric oxide (NO) synthase (eNOS) and heat shock protein 90 (hsp90). Whereas disruption of hsp90-eNOS complexes clearly attenuates eNOS-dependent vascular relaxation, the contribution of sGC-hsp90 complexes to eNOS- or NO donor-dependent relaxations remains unclear. Isolated rat thoracic aortic rings were preincubated with structurally diverse hsp90 binding inhibitors, radicicol (RA) or geldanamycin (GA), or vehicle for 0.5, 1, or 15 h. Preconstricted vessels were exposed to ACh, 8-bromo-cGMP (8-BrcGMP), forskolin, or one of three NO donors: nitroglycerin (NTG), sodium nitroprusside, or spermine NONOate (SNN). Both RA and GA inhibited endothelium-dependent relaxations dose dependently. Indomethacin or the antioxidant tiron did not affect the inhibition of ACh-induced relaxations by GA. Long-term (15 h) exposure to RA inhibited all NO donor-induced relaxations; however, GA inhibited SNN-induced relaxation only. The effects of GA and RA appeared to be selective because 15-h treatment with either agent did not affect forskolin-induced relaxations and only slightly decreased 8-BrcGMP-induced relaxations. Similarly to their effects on NO-donor-induced relaxation, 15-h exposure to RA, but not to GA, decreased hsp90-bound sGC protein expression and NTG-stimulated cGMP formation in aortic rings, whereas RA more than GA reduced SNN-stimulated cGMP formation. We conclude that RA, much more so than GA, selectively inhibits sGC-dependent relaxations of aortic rings by reducing sGC expression, disrupting sGC-hsp90 complex formation and decreasing cGMP formation. These studies suggest that hsp90 regulates both eNOS- and sGC-dependent relaxations.

Animals↗

PubMed2006

Morphology-controllable synthesis and characterization of single-crystal molybdenum trioxide.

Molybdenum trioxide nanobelts and prism-like particles with good crystallinity and high surface areas have been prepared by a facile hydrothermal method, and the morphology could be controlled by using different inorganic salts, such as KNO3, Ca(NO3)2 , La(NO3)3, etc. The possible growth mechanism of molybdenum trioxide prism-like particles is discussed on the basis of the presence of H+ and the modification of metal cations. The as-prepared nanomaterials are characterized by means of powder X-ray diffraction (PXRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), Fourier transformation infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and ultraviolet and visible spectroscopy (UV-vis). TEM and HRTEM micrographs show that the molybdenum trioxide nanobelts and prism-like particles have a relatively high degree of crystallinity and uniformity. BET specific surface areas of the as-prepared molybdenum trioxide nanocrystals are 67-79 m2 g-1. XPS analysis indicates that the hexavalent molybdenum is predominant in the nanocrystals. UV-vis spectra reveal that the direct band gap energy of the annealed molybdenum trioxide prism-like particles shows a pronounced blue shift compared to that of bulk MoO3 powder. Interestingly, molybdenum trioxide nanobelts exhibit a red shift under this condition.

Journal Article↗

PubMed2006

Toxic potential of materials at the nanolevel.

Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. These materials are increasingly being used for commercial purposes such as fillers, opacifiers, catalysts, semiconductors, cosmetics, microelectronics, and drug carriers. Materials in this size range may approach the length scale at which some specific physical or chemical interactions with their environment can occur. As a result, their properties differ substantially from those bulk materials of the same composition, allowing them to perform exceptional feats of conductivity, reactivity, and optical sensitivity. Possible undesirable results of these capabilities are harmful interactions with biological systems and the environment, with the potential to generate toxicity. The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable.

Animals↗

PubMed2006

The role of reactive oxygen species and oxidative stress in mediating particulate matter injury.

Numerous reports link oxidative stress to particulate matter (PM)-induced adverse health effects. Increasing evidence is being collected that reactive oxygen species and oxidative stress are involved in PM-mediated injury. The physical characteristics and the chemical composition of PM play a key role in reactive oxygen species generation in vitro and in vivo. According to the hierarchical oxidative stress hypothesis, antioxidant phase II enzymes protect against PM-induced inflammation and cytotoxicity. This concept is useful in understanding PM-induced disease models, susceptibility, and biomaker development to access exposures outcomes and is useful for developing therapeutic intervention in PM-induced adverse health effects.

Air Pollutants↗

PubMed2006

Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm.

Nanomaterial properties differ from those bulk materials of the same composition, allowing them to execute novel activities. A possible downside of these capabilities is harmful interactions with biological systems, with the potential to generate toxicity. An approach to assess the safety of nanomaterials is urgently required. We compared the cellular effects of ambient ultrafine particles with manufactured titanium dioxide (TiO2), carbon black, fullerol, and polystyrene (PS) nanoparticles (NPs). The study was conducted in a phagocytic cell line (RAW 264.7) that is representative of a lung target for NPs. Physicochemical characterization of the NPs showed a dramatic change in their state of aggregation, dispersibility, and charge during transfer from a buffered aqueous solution to cell culture medium. Particles differed with respect to cellular uptake, subcellular localization, and ability to catalyze the production of reactive oxygen species (ROS) under biotic and abiotic conditions. Spontaneous ROS production was compared by using an ROS quencher (furfuryl alcohol) as well as an NADPH peroxidase bioelectrode platform. Among the particles tested, ambient ultrafine particles (UFPs) and cationic PS nanospheres were capable of inducing cellular ROS production, GSH depletion, and toxic oxidative stress. This toxicity involves mitochondrial injury through increased calcium uptake and structural organellar damage. Although active under abiotic conditions, TiO2 and fullerol did not induce toxic oxidative stress. While increased TNF-alpha production could be seen to accompany UFP-induced oxidant injury, cationic PS nanospheres induced mitochondrial damage and cell death without inflammation. In summary, we demonstrate that ROS generation and oxidative stress are a valid test paradigm to compare NP toxicity. Although not all materials have electronic configurations or surface properties to allow spontaneous ROS generation, particle interactions with cellular components are capable of generating oxidative stress.

Animals↗

PubMed2006

[Effects of Bushen Tiaochong Recipe contained serum on proliferation and secretion of ovarian granulocyte cultured with excessive androgen].

OBJECTIVE: To observe the effect of Bushen Tiaochong Recipe (BTR) on proliferation and secretion of ovarian granulocyte (OGC) cultured with excessive androgen by serum pharmacologic technique. METHODS: Follicular stimulating hormone (FSH) contained and BTR contained (high, moderate or low dose) serum prepared on 6-week-old Sprague Dawley rats by serum pharmacologic method were respectively added into cultured OGC cell-line after treatment with testosterone propionat (TP). Then the cells were incubated for 48 hrs. The quantity of 3 H-thymidine incorporated DNA was determined with a scintillation counter; the cell cycle distribution and proliferation index (PI) were estimated with flow cytometer (FCM); and the contents of estrodial and progestogen in culture fluid and intracellular cAMP were detected by radioimmuoassay. RESULTS: Excessive androgen obviously inhibited the proliferation and secretion of OGC, and reduced the intracellular cAMP. BTR contained serum could improve above-mentioned inhibition of androgen to promote the cell proliferation and secretion of E2 and P in dose-dependant manner. CONCLUSION: BTR could alleviate the inhibitory action of excessive androgen on OGC, the ovarian function may be adjusted by BTR through promoting follicular development, increasing the levels of estrogen and progestogen, improving the ratio of estrogen/androgen.

Animals↗

PubMed2005

Sp1 and AP2 enhance promoter activity of the mouse GM3-synthase gene.

Promoters of the glycosyltransferase genes for ganglioside synthesis are TATA-less and often have multiple binding sites for transcription factors Sp1 and AP2 in their proximal regions. However, the function of Sp1 and AP2 in the promoters has not yet been defined. Here, we cloned 5'-flanking fragments of the mouse GM3-synthase gene and assessed the promoter activity of these fragments in mouse Neuro-2a cells. This promoter is TATA-less and contains a number of potential transcription factor-binding sites. Multiple putative transcriptional initiation sites for this gene were identified, including several downstream initiation sites. We then set out to dissect the regulatory elements important for GM3-synthase promoter function. We found that a 5'-flanking 254-bp DNA fragment of the gene contained regulatory elements including two Sp1-binding and six AP2-binding sites that were essential for the basal activity of the promoter in mouse Neuro-2a cells. The effects of the individual Sp1- and AP2-binding sites on basal activity of the GM3-synthase gene were investigated. Mutations in the juxtaposed Sp1/AP2-binding site and in an AP2-binding site decreased the activity of the proximal promoter to approximately 50%. In vitro and in vivo interactions between transcription factors Sp1 and AP2 and these regulatory elements were confirmed by EMSA and the chromatin immunoprecipitation approach, respectively. Therefore, our results demonstrate that Sp1 and AP2 enhance the basal activity of the TATA-less mouse GM3-synthase promoter.

5' Flanking Region↗

PubMed2005

[Effect of silencing HIF-1alpha by RNA interference on expression of vascular endothelial growth factor in osteosarcoma cell line SaOS-2 under hypoxia].

BACKGROUND & OBJECTIVE: Hypoxia-inducible factor-1 alpha (HIF-1alpha) is a key regulator for hypoxia tolerance and angiogenesis of tumor. This study was to investigate the expression of HIF-1alpha and vascular endothelial growth factor (VEGF) in human osteosarcoma cell line SaOS-2 under hypoxia, to explore the effect of HIF-1alpha on hypoxia-activated angiogenesis regulation pathway in osteosarcoma. METHODS: CoCl2 was used as chemical hypoxia-inducing reagent to mimic tumor hypoxic microenvironment. mRNA and protein levels of HIF-1alpha and VEGF at different hypoxic culture phases were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Small hairpin RNAs (shRNAs) eukaryotic expression vector targeting HIF-1alpha was constructed, and transfected into SaOS-2 cells. Western blot was used to detect gene silencing effect on HIF-1alpha. RT-PCR and enzyme-linked immunosorbent assay (ELISA) were used to observe the change of VEGF gene expression after HIF-1alpha gene silence. RESULTS: Under hypoxia, mRNA level of HIF-1alpha kept stable, while its protein level increased obviouslyu both mRNA and protein levels of VEGF were up-regulated. The shRNAs plasmid targeting HIF-1alpha gene was constructed successfully, and down-regulated HIF-1alpha gene in SaOS-2 cells efficiently followed by VEGF gene down-regulation. CONCLUSIONS: Hypoxia can increase protein level of HIF-1alpha in osteosarcoma. HIF-1alpha up-regulates the gene expression of VEGF via transcription activation which promotes angiogenesis in osteosarcoma under hypoxic microenvironment.

Bone Neoplasms↗

PubMed2005

[Effects of alcohol on the expression of heat shock protein 70 and super microstructure of astrocytes in rat embryonic brain].

OBJECTIVE: To explore effects of alcohol on the expression of heat shock protein 70 (HSP70) and super microstructure of astrocytes. METHODS: Different dosage of alcohol (1, 5, 25, 50mmol/L) was administered to astrocytes of rat embryos. Effects of alcohol on expression of HSP70 were studied by immunocytochemistry, and changes of super microstructure of astrocytes were observed by electron microscope. RESULTS: The results showed that with increase of alcohol dosage, the expression of HSP70 increased, hepatin granule and survival astrocytes in 25mmol/L and 50mmol/L dosage group decreased, cell membrane and mitochondrion were damaged, and even apoptosis and necrosis occurred. CONCLUSION: It suggested that alcohol could increase expression of HSP of astrocytes, which could depress the expression of normal function protein, and mainly impaired cell membrane and mitochondrion, which could lead to apoptosis and necrosis.

Animals↗

PubMed2004

Expression of the mouse WNK1 gene in correlation with ganglioside GD3 and functional analysis of the mouse WNK1 promoter.

WNK1 is one of WNK (With No K=Lysine) protein kinases which comprise a newly described subfamily. Our studies showed that expression of the mouse WNK1 gene was dramatically suppressed in a tumor cell line when its phenotype was altered by suppression of the GD3-synthase gene expression. The mouse WNK1 gene was expressed at a high level at early stage of embryonic brain and its expression decreased as brain developed, similar to the expression pattern of the GD3-synthase gene. To study transcriptional regulation, we cloned a 5'-flanking 1239-bp fragment of the mouse WNK1 gene. This fragment contains a number of potential consensus binding sites for transcription factors, including Sp1, AP2, CCAAT, Est-1, Oct-1, CNBP, and NFkB, but lacks a TATA box. Primer extension identified multiple putative transcriptional initiation sites, including several sites downstream of the ATG codon. Activities of the promoter fragments were assessed in mouse breast Sa/R-MT cells by transient transfection and the results showed that the promoter elements between -700 and -977 is required for maintaining a high level of promoter activity of the TATA-less mouse WNK1 gene.

5' Flanking Region↗

PubMed2004

Regulation of ganglioside biosynthesis in the nervous system.

Ganglioside biosynthesis is strictly regulated by the activities of glycosyltransferases and is necessarily controlled at the levels of gene transcription and posttranslational modification. Cells can switch between expressing simple and complex gangliosides or between different series within these two groups during brain development. The sequential biosynthesis of gangliosides in parallel enzymatic pathways, however, requires fine-tuned subcellular sequestration and orchestration of glycosyltransferases. A popular model predicts that this regulation is achieved by the vectorial organization of ganglioside biosynthesis: sequential biosynthetic steps occur with the traffic of ganglioside intermediates through subsequent subcellular compartments. Here, we review current models for the subcellular distribution of glycosyltransferases and discuss results that suggest a critical role of N-glycosylation for the processing, transport, and complex formation of these enzymes. In this context, we attempt to illustrate the regulation of ganglioside biosynthesis as well as the biological significance of N-glycosylation as a posttranslational regulatory mechanism. We also review the results of analyses of the 5' regulatory sequences of several glycosyltransferases in ganglioside biosynthesis and provide insights into how their synthesis can be regulated at the level of transcription.

Animals↗

PubMed2004

Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine particle toxicity.

Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)-enriched aromatic fraction in O2 .- generation, decrease of membrane potential (Delta-Psi m), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)-sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on Delta-Psi m at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in Delta-Psi m at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and Delta-Psi m are mediated by adsorbed chemicals rather than the particles themselves.

Animals↗

PubMed2004

[Experimental study on xiaoliu decoction in treating tumor and modulating immune function].

OBJECTIVE: To study the anti-tumor effect and immune function modulation of Xiaoliu decoction (XLD) and to explore the possible mechanism. METHODS: S180 tumor bearing mice were treated with large or small dose of XLD and cyclophosphamide (CTX) to observe the tumor suppressive rate, lymphocyte transformation rate, natural killer cell (NK) activity, tumor necrosis factor alpha (TNFalpha) level in the mice, as well as the tumor cell apoptosis in vitro. RESULTS: The tumor suppressive rate of XLD on tumor bearing mice was over 30%. XLD showed obvious trend in enhancing the tumor suppressing rate of chemotherapy, could increase the lymphocyte transformation rate, NK activity, and TNFalpha level. It also could accelerate the tumor cell apoptosis in vitro. CONCLUSION: XLD has significant anti-tumor effect, it could elevate the immune function or organism and alleviate the chemotherapy induced lowering of immune function.

Adjuvants, Immunologic↗

PubMed2003

Cadmium directly induced the opening of membrane permeability pore of mitochondria which possibly involved in cadmium-triggered apoptosis.

The mitochondrial damage induced by cadmium has been well established, but its mechanism and its relationship with cadmium-induced apoptosis are elusive until now. Our research showed that cadmium could directly lead to the dysfunction of isolated mitochondria from mouse liver, including the inhibition of respiration, the opening of permeability transition pore (PTP), the loss of transmembrane potential, and the release of cytochrome c. These mitochondrial changes were completely suppressed by Bcl-xL and Ruthenium Red (RR). Bongkrekic acid (BK), an inhibitor of the PTP opening directly via adenine nucleotide translocator (ANT), also completely inhibited the PTP opening and loss of transmembrane potential. However, cyclosporin A (CsA), another inhibitor of the PTP opening indirectly via ANT, had not any inhibitory effect. When cadmium being pre-incubated with proteins containing abundant thiol groups, its effect was partially reversed. These results revealed that mitochondria pathway may involve in cadmium-induced apoptosis, and cadmium caused the PTP opening possibly through its binding to thiol groups of ANT. Furthermore, the mechanism of the PTP opening induced by cadmium was probably distinct from that of the calcium-induced PTP opening.

Animals↗

PubMed2003

Characterization of the promoter and the transcription factors for the mouse UDP-Gal:betaGlcNAc beta1,3-galactosyltransferase gene.

Galbeta1-3Gal-NAcbeta1-4Gal(3-2alphaNeuAc)beta1-4Glcbeta1-1Cer (GM1) is one of the most extensively investigated gangliosides that plays critical roles in the development and functions of the nervous system. UDP-Gal:betaGlcNAc beta1,3-galactosyltransferase (Gal-T-II) is responsible for synthesis of ganglioside GM1 in the ganglioside biosynthetic pathway. To understand the transcriptional regulation of Gal-T-II gene expression, we cloned a 1448 bp 5'-flanking fragment from the mouse Gal-T-II gene. The transcriptional activity of the fragment was demonstrated in mouse Neuro-2a cells by a luciferase assay. The proximal 550 bp fragment showed the highest transcriptional activity as determined by a series of 5'-truncated constructs of the promoter. One negative regulatory region was also identified. Primer extension assay revealed a transcription initiation site approximately 242 bp upstream from the ATG translation start codon. Analysis of the promoter sequence revealed a number of potential binding sites for known transcription factors. To determine which transcription factors bind to the promoter, we carried out a systematic search for the binding proteins using the 1142 bp Gal-T-II promoter fragment containing both positive and negative regulatory regions in a combination of DNA pull-down assay and transcription factor array analysis. Twenty-seven transcription factors bound to consensus sites in the promoter region. In addition, four other factors without consensus binding sites in this region were also recruited, possibly as components of transcription factor complexes. These data indicate that the basal regulation of Gal-T-II gene transcription involves multiple transcription factors, some of which may be present in complexes.

Animals↗