Xianglin Shi

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Papers by Xianglin Shi

Effects of Welding Fumes of Differing Composition and Solubility on Free Radical Production and Acute Lung Injury and Inflammation in Rats

Toxicological Sciences, 2003

The goals of this study were to examine acute lung damage and inflammation, as well as free radic... more The goals of this study were to examine acute lung damage and inflammation, as well as free radical production, caused by weld- ing fumes of different chemical compositions and solubilities. The fumes were from a gas metal arc welding using a mild-steel (GMA-MS) or stainless-steel electrode (GMA-SS) and a manual metal arc welding using a stainless-steel electrode (MMA-SS), which was

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The role of epidermal growth factor receptor in ethanol-mediated inhibition of activator protein-1 transactivation

Biochemical Pharmacology, 2005

A potential mechanism underlying ethanol-induced alterations in gene expression is the disruption... more A potential mechanism underlying ethanol-induced alterations in gene expression is the disruption of transcription factor activity. Growth factor receptors, particularly receptor tyrosine kinases, play an important role in modulating many biological effects of ethanol. We demonstrated here that the expression of epidermal growth factor receptor (EGFR) mediated the effect of ethanol on the activity of transcription factor activator protein-1 (AP-1).

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Transport of vacuum arc plasma through an off-plane double bend filtering duct

Thin Solid Films, 1999

... In an earlier investigation [12], we studied the effects of system parameters such as the fil... more ... In an earlier investigation [12], we studied the effects of system parameters such as the filtering field, duct bias and arc current on the transport efficiency of a single 90° bend filter. ... 5. Relative transmission efficiency as a function of arc current. View Within Article. 3.3. Ion density. ...

Inhibition of AP-1 and MAPK signaling and activation of Nrf2/ARE pathway by quercitrin

International journal of oncology, 2010

Quercitrin, glycosylated form of flavonoid compounds, is widely distributed in nature. Extensive ... more Quercitrin, glycosylated form of flavonoid compounds, is widely distributed in nature. Extensive studies have demonstrated that quercitrin exhibits strong antioxidant and anti-carcinogenic activities. However, the molecular mechanism is poorly understood. The present study examines the effects of quercitrin on tumor promotion in mouse JB6 cells, a validated model for screening cancer chemopreventive agents and elucidating the molecular mechanisms. Quercitrin blocked TPA-induced neoplastic transformation in JB6 P+ cells. Pretreatment of JB6 cells with quercitrin down-regulated transactivation of AP-1 and NF-kappaB induced by UVB or TPA. In the skin of AP-1-luciferase transgenic mice, topical treatment of the mouse with quercitrin markedly blocked the TPA-induced AP-1 transactivation. Further studies indicated that these inhibitory actions appear to be mediated through the inhibition of MAPKs phosphorylation, including ERKs, p38 kinase, and JNKs. In addition, quercitrin stimulated the...

Occupational toxicology of nickel and nickel compounds

Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer, 2009

Nickel and nickel compounds are widely used in industry. The high consumption of nickel products ... more Nickel and nickel compounds are widely used in industry. The high consumption of nickel products inevitably leads to occupational and environmental pollution. In occupational settings, exposure to nickel and nickel compounds occurs primarily during nickel refining, electroplating, and welding. The most common airborne exposures to nickel in the workplace are to insoluble nickel species, such as metallic nickel, nickel sulfide, and nickel oxides from dusts and fumes. The chemical and physical properties of nickel and nickel compounds strongly influence their bioavailability and toxicity. The lung and the skin are the principal target organs upon occupational exposure. inhalation exposure is a primary route for nickel-induced toxicity in the workplace. The most important adverse health effects due to occupational exposure to nickel and its compounds are skin allergies, lung fibrosis, and lung cancer. The exact mechanisms of nickel-induced carcinogenesis are not clear. This review summ...

Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

Biochemical and Biophysical Research Communications, 2015

Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigate... more Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenictransformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H 2 O 2 ) and superoxide dismutase 2 (SOD2, antioxidant against O 2 ÅÀ ) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study has also shown that the arsenic-transformed cells acquired apoptosis resistance. The inhibition of catalase to increase ROS level restored apoptosis capability of arsenic-transformed BEAS-2B cells, further showing that ROS levels are low in these cells. The apoptosis resistance due to the low ROS levels may increase cells proliferation, providing a favorable environment for tumorigenesis of arsenic-transformed cells. j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / y b b r c Please cite this article in press as: Z. Zhang et al., Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells, Biochem. Biophys. Res. Commun. (2014), http://dx.

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Intracellular signal transduction of cells in response to carcinogenic metals

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Cr(VI) increases tyrosine phosphorylation through reactive oxygen species-mediated reactions

Molecular and Cellular Biochemistry, 2001

While Cr (VI)-containing compounds are well established carcinogens, the mechanisms of their acti... more While Cr (VI)-containing compounds are well established carcinogens, the mechanisms of their action remain to be investigated. In this study we show that Cr (VI) causes increased tyrosine phosphorylation in human lung epithelial A549 cells in a time-dependent manner. N-acetyl-cysteine (NAC), a general antioxidant, inhibited Cr (VI)-induced tyrosine phosphorylation. Catalase, a scavenger of H2O2, sodium formate and aspirin, scavengers of

The role of hydroxyl radical as a messenger in the activation of nuclear transcription factor NF-kappaB

Molecular and cellular biochemistry, 1999

Although it is generally believed that reactive oxygen species activate NF-kappaB, a primary oxid... more Although it is generally believed that reactive oxygen species activate NF-kappaB, a primary oxidative stress-responsive transcription factor, it is unclear which one among these species causes NF-kappaB activation. Our hypothesis is that hydroxyl radical (*OH) functions as a messenger for the activation of NF-kappaB. Jurkat cells, macrophages and JB6 cells were used to test this hypothesis. Cr(VI), silica and ZnO were used as sources of *OH radicals. None of these *OH generating systems involves exogenous H2O2. Cr(VI) expressed enhanced activity in induction of NF-kappaB in Jurkat cells. This activation of NF-kappaB was decreased by a metal chelator, diethylene triaminepentaacetic acid or a H2O2 scavenger, catalase, but was increased by superoxide dismutase. Mn(II), which reacts with Cr(IV) to inhibit this metal ion-mediated *OH generation, decreased the NF-kappaB activation. Sodium formate, an *OH radical scavenger, also inhibited the NF-kappaB activation. Electron spin resonance ...

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Antioxidant properties of aspirin: characterization of the ability of aspirin to inhibit silica-induced lipid peroxidation, DNA damage, NF-kappaB activation, and TNF-alpha production

Molecular and cellular biochemistry, 1999

Electron spin resonance (ESR) was used to investigate the reaction of aspirin toward reactive oxy... more Electron spin resonance (ESR) was used to investigate the reaction of aspirin toward reactive oxygen species, such as hydroxyl radicals (*OH), superoxide radicals (O2-) and H2O2. The Fenton reaction (Fe(II) + H2O2 ---> FE(III) + *OH + OR) was used as a source of *OH radicals. The results show that aspirin is an efficient *OH radical scavenger with a reaction rate constant of k = 3.6 x 10(10) M(-1) sec(-1), which is faster than several well established antioxidants, such as ascorbate, glutathione and cysteine. However, aspirin is not a good scavenger for O2- or H2O2. Through its antioxidant property, aspirin exhibited a protective effect against silica-induced lipid peroxidation and DNA strand breakage. Aspirin also inhibited the activation of nuclear transcription factor-kappaB induced by silica, lipopolysaccharide or the transition metal, Fe(II), as demonstrated by electrophoretic mobility shift assay. The results show that aspirin functions as an antioxidant via its ability to ...

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Epigenetic targets of arsenic: emphasis on epigenetic modifications during carcinogenesis

Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer, 2015

DNA methylation and histone modification promote opening and closure of chromatin structure, whic... more DNA methylation and histone modification promote opening and closure of chromatin structure, which affects gene expression without altering the DNA sequence. Epigenetic markers regulate the dynamic nature of chromatin structure at different levels: DNA, histone, noncoding RNAs, as well as the higher-order chromatin structure. Accumulating evidence strongly suggests that arsenic-induced carcinogenesis involves frequent changes in the epigenetic marker. However, progress in identifying arsenic-induced epigenetic changes has already been made using genome-wide approaches; the biological significance of these epigenetic changes remains unknown. Moreover, arsenic-induced changes in the chromatin state alter gene expression through the epigenetic mechanism. The current review provides a summary of recent literature regarding epigenetic changes caused by arsenic in carcinogenesis. We highlight the transgenerational studies needed to explicate the biological significance and toxicity of ars...

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New Insights into the Role of Nuclear Factor-kB, a Ubiquitous Transcription Factor in the Initiation of Diseases

Nuclear factor-kB (NF-kB) is a ubiquitous transcription factor that governs the expression of gen... more Nuclear factor-kB (NF-kB) is a ubiquitous transcription factor that governs the expression of genes encoding cytokines, chemokines, growth factors, cell adhesion molecules, and some acute phase proteins in health and in various disease states. NF-kB is activated by several agents, including cytokines, oxidant free radicals, in- haled particles, ultraviolet irradiation, and bacterial or viral products. Inappropriate activation of NF-kB has

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Expression of Cyr61, CTGF, and WISP-1 Correlates with Clinical Features of Lung Cancer

PLoS ONE, 2007

Background. CCN family, comprising six members (Cyr61, CTGF, Nov, WISP-1, WISP-2, WISP-3), is inv... more Background. CCN family, comprising six members (Cyr61, CTGF, Nov, WISP-1, WISP-2, WISP-3), is involved in the stimulation of cell proliferation, migration, adhesion, angiogenesis, and tumorigenesis. Several studies have shown that expression of Cyr61, CTGF, and WISP-1 affects the tumorigenic potential of lung cancer cells in vitro. However, the correlation of expression of CCN family proteins and clinical features of lung cancer remains unknown. Methodology and Principal Findings. In the present work, we quantified the mRNA levels of Cyr61, CTGF, and WISP-1 in samples from 60 primary lung cancers and their matched normal lung tissues by quantitative real-time PCR assay. Downregulation of the Cyr61 and CTGF genes and upregulation of the WISP-1 gene were found in primary lung cancers compared to the paired normal lung tissues. Immunohistochemistry analysis also disclosed a similar expression pattern of Cyr61, CTGF, and WISP-1 protein in paired lung cancer tissues. Statistical analysis revealed significant associations between expression of either Cyr61 or CTGF with tumor stage, tumor histology, metastasis, smoking, and family history at diagnosis. A significant correlation also existed between WISP-1 expression with tumor histology, and patient age. Moreover, expression levels of Cyr61 and CTGF correlated with survival of the lung-cancer patients. Conclusions. Our results suggest that Cyr61, CTGF, and WISP-1 might be implicated in the development and progression of primary lung cancers, and their levels might serve as valuable prognostic markers, as well as potential targets for therapeutic intervention.

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Ultraviolet-induced phosphorylation of p70(S6K) at Thr(389) and Thr(421)/Ser(424) involves hydrogen peroxide and mammalian target of rapamycin but not Akt and atypical protein kinase C

Cancer research, Jan 15, 2002

The p70 S6 kinase (p70(S6k)) is a Ser/Thr kinase that plays an important role in cell growth, tra... more The p70 S6 kinase (p70(S6k)) is a Ser/Thr kinase that plays an important role in cell growth, transformation, and the transition of the cell cycle in mammalian cells. Because UV radiation has been reported to induce activation of p70(S6k), which is believed to play some role in the carcinogenic effects of sun exposure, the present study investigated the signaling pathways involved in this activation induced by UV radiation in mouse epidermal JB6 Cl41 cells. Exposure of cells to UV radiation led to marked increases in p70(S6k) activity and phosphorylation at Thr(389) and Thr(421)/Ser(424). UV radiation also generated reactive oxygen species as measured by electron spin resonance and by H(2)O(2) and O( minus sign, dot below )(2) fluorescence staining assays in JB6 Cl 41 cells. The scavenging of UV-generated H(2)O(2) by N-acety-L-cyteine (a general antioxidant) or catalase (a specific H(2)O(2) scavenger) inhibited p70(S6k) phosphorylation at Thr(389) and Thr(421)/Ser(424), whereas pret...

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On the mechanism of Cr (VI)-induced carcinogenesis: dose dependence of uptake and cellular responses

Molecular and cellular biochemistry, 2001

Cr (VI) compounds are widely used industrial chemicals and are recognized human carcinogens. The ... more Cr (VI) compounds are widely used industrial chemicals and are recognized human carcinogens. The mechanisms of carcinogenesis associated with these compounds remain to be investigated. The present study focused on dose-dependence of Cr (VI)-induced uptake and cellular responses. The results show that Cr (VI) is able to enter the cells (human lung epithelial cell line A549) at low concentration (< 10 microM) and that the Cr (VI) uptake appears to be a combination of saturable transport and passive diffusion. Electron spin resonance (ESR) trapping measurements showed that upon stimulation with Cr (VI), A549 cells were able to generate reactive oxygen species (ROS). The amount of ROS generated depended on the Cr (VI) concentration. ROS generation involved NADPH-dependent flavoenzymes. Cr (VI) affected the following cellular parameters in a dose-dependent manner, (a) activation of nuclear transcription factors NF-kappaB, and p53, (b) DNA damage, (c) induction of cell apoptosis, and (...

Tribological behaviour of different diamond-like carbon materials

ABSTRACT This paper comparatively studies the tribological behaviour of different types of diamon... more ABSTRACT This paper comparatively studies the tribological behaviour of different types of diamond-like carbon (DLC) coatings in a reciprocating sliding wear test. The results are interpreted in terms of structure and surface morphological characteristics. At the beginning of each reciprocating sliding wear test, the higher coefficient of friction of the DLC coatings reflects the original surface conditions of contacting counterfaces, whereas the low coefficient of friction achieved under the steady regime is linked to the presence of wear debris and an enlarged real contact area. sp2 carbon bonding has been related to the occurrence of a higher coefficient of friction and surface damage of DLC materials compared to bulk diamond. The a-C coatings and ta-C films have a lower coefficient of friction at the steady regime than the a-C:H coatings, possibly due to a significant amount of hydrogen in the a-C:H coatings.

Suppressed NF-kB and sustained JNK activation contribute to the sensitization effect of parthenolide to TNF-a-induced apoptosis in human cancer cells

Parthenolide (PN) is the main sesquiterpene lactone found in feverfew with potent anti-inflammato... more Parthenolide (PN) is the main sesquiterpene lactone found in feverfew with potent anti-inflammatory function. The anticancer property of PN has been demonstrated in both in vitro cell culture and in vivo animal model, while the molecular mechanisms remain to be further elucidated. In the present study, we evaluated the involvement of nuclear transcription factor-kB (NF-kB) and c-Jun N-terminal kinase (JNK) in the anticancer activity of PN by examining the sensitization effect of PN on tumor necrosis factor (TNF)-a-induced apoptosis in human cancer cells. Pretreatment with PN greatly sensitized various human cancer cells to TNF-a-induced apoptosis. Such sensitization is closely associated with the inhibitory effect of PN on TNF-amediated NF-kB activation. Our study revealed a new mechanism that PN inhibits TNF-a-mediated NF-kB activation via disrupting the recruitment of the IkB kinases (IKK) complex to TNF receptor, which then blocked the subsequent signaling events including IKK kinase activation, IkBa degradation, p65 nuclear translocation, DNA binding and transactivation. Moreover, PN also markedly enhanced and sustained TNF-a-mediated JNK activation. A specific JNK inhibitor (SP600125), as well as overexpression of dominant-negative forms of JNK1 and JNK2 abolished the sensitization effect of PN on TNF-ainduced apoptosis. It is thus believed that suppressed NF-kB activation and sustained JNK activation contribute to the sensitization effect of PN to TNF-a-mediated cell death in human cancer cells.

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Freshly Fractured Crystalline Silica Induces Activator Protein1 Activation through ERKs and p38 MAPK

by Xianglin Shi and Min Ding

Journal of Biological Chemistry, 1999

The transcription factor activator protein-1 (AP-1) re- portedly plays an important role in the i... more The transcription factor activator protein-1 (AP-1) re- portedly plays an important role in the induction of neoplastic transformation and multiple genes involved in cell proliferation, differentiation, and inflammation. To investigate the mechanisms of silica-induced carci- nogenesis, AP-1-luciferase reporter transgenic mice were used as an in vivo model, whereas the JB6 mouse epidermal cell line and a rat lung epithelial cell

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Blackberry extract inhibits UVB-induced oxidative damage and inflammation through MAP kinases and NF-κB signaling pathways in SKH-1 mice skin

Toxicology and applied pharmacology, Jan 11, 2015

Extensive exposure of solar ultraviolet-B (UVB) radiation to skin induces oxidative stress and in... more Extensive exposure of solar ultraviolet-B (UVB) radiation to skin induces oxidative stress and inflammation that play a crucial role in the induction of skin cancer. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. In this study, we investigated whether blackberry extract (BBE) reduces chronic inflammatory responses induced by UVB irradiation in SKH-1 hairless mice skin. Mice were exposed to UVB radiation (100mJ/cm(2)) on alternate days for 10weeks, and BBE (10% and 20%) was applied topically a day before UVB exposure. Our results show that BBE suppressed UVB-induced hyperplasia and reduced infiltration of inflammatory cells in the SKH-1 hairless mice skin. BBE treatment reduced glutathione (GSH) depletion, lipid peroxidation (LPO), and myeloperoxidase (MPO) in mouse skin by chronic UVB exposure. BBE significantly decreased the level of pro-inflammatory cytokines IL-6 and TNF-α in UVB-exposed skin. ...

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Constitutive Activation of Epidermal Growth Factor Receptor Promotes Tumorigenesis of Cr(VI)-transformed Cells through Decreased Reactive Oxygen Species and Apoptosis Resistance Development

by Kazuya Kondo and Xianglin Shi

The Journal of biological chemistry, Jan 23, 2015

Hexavalent chromium (Cr(VI)) compounds are well-established lung carcinogens. Epidermal growth fa... more Hexavalent chromium (Cr(VI)) compounds are well-established lung carcinogens. Epidermal growth factor receptor (EGFR) is a tyrosine kinase transmembrane receptor that regulates cell survival, tumor invasion, and angiogenesis. Our results show that chronic exposure of human bronchial epithelial (BEAS-2B) cells to Cr(VI) is able to cause malignant cell transformation. These transformed cells exhibit apoptosis resistance with reduced poly ADP-ribose polymerase cleavage (C-PARP) and Bax expression and enhanced expressions of Bcl-2 and Bcl-xL. These transformed cells also exhibit reduced capacity of reactive oxygen species (ROS) generation along with elevated expression of antioxidant manganese superoxide dismutase 2 (SOD2). The expression of this antioxidant was also elevated in lung tumor tissue from a worker exposed to Cr(VI) for 19 years. EGFR was activated in Cr(VI)-transformed BEAS-2B cells, lung tissue from animals exposed to Cr(VI) particles, and human lung tumor tissue. Further ...

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