Publications by authors named "Xiangping Yang"

17 Publications

  • Page 1 of 1

Genetic association analysis between IL9 and coronary artery disease in a Chinese Han population.

Cytokine 2021 Nov 20;150:155761. Epub 2021 Nov 20.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Interleukin-9 (IL-9) plays important role in coronary artery disease (CAD). However, the exact relationship between them is not explored yet. Here, four tag SNPs covering IL9 (rs31563, rs2069868, rs2069870 and rs31564) were selected to conduct case-control association analyses in a total of 3704 individuals from Chinese Han population (1863 CAD vs 1841 control). Results showed that: first, rs2069868 was associated with CAD combined with hypertension (P = 0.027); second, IL9 haplotype (CGAT) was associated with CAD (P = 0.035), and the combination genotype of "rs31563_CC/rs31564_TT" would remarkably decrease the risk of CAD (P = 0.001); third, significant associations were found between rs2069870 and decreased LDL-c levels and decreased total cholesterol levels, and between rs31563 and increased HDL-c levels (P < 0.05). Therefore, we conclude that IL9 might play a causal role in CAD by interacted with CAD traditional risk factors, which might confer a new way to improve the prevention and treatment of CAD.
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http://dx.doi.org/10.1016/j.cyto.2021.155761DOI Listing
November 2021

Inhibition of fibroblast IL-6 production by ACKR4 deletion alleviates cardiac remodeling after myocardial infarction.

Biochem Biophys Res Commun 2021 04 18;547:139-147. Epub 2021 Feb 18.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Fibrotic scarring is tightly linked to the development of heart failure in patients with post-myocardial infarction (MI). Atypical chemokine receptor 4 (ACKR4) can eliminate chemokines, such as C-C chemokine ligand 21 (CCL21), which is independently associated with heart failure mortality. However, the role of ACKR4 in the heart during MI is unrevealed. This study aimed to determine whether ACKR4 modulates cardiac remodeling following MI and to illuminate the potential molecular mechanisms. The expression of ACKR4 was upregulated in the border/infarct area, and ACKR4 was predominantly expressed in cardiac fibroblasts (CFs). Knockout of ACKR4 protected against adverse ventricular remodeling in mice post-MI. These protective effects of ACKR4 deficiency were independent of dendritic cell immune response but could be attributed to downregulated CF-derived IL-6, affecting CF proliferation and endothelial cell (EC) functions, which consequently inhibited cardiac fibrosis. ACKR4 promoted IL-6 generation and proliferation of CFs. Besides, ACKR4 induced endothelial-to-mesenchymal transition (EndMT) in ECs through IL-6 paracrine effect. The p38 MAPK/NF-κB signaling pathway was involved in ACKR4 facilitated IL-6 generation. Moreover, ACKR4 overexpression in vivo via AAV9 carrying a periostin promoter aggravated heart functional impairment post-MI, which was abolished by IL-6 neutralizing antibody. Therefore, our study established a novel link between ACKR4 and IL-6 post-MI, indicating that ACKR4 may be a novel therapeutic target to ameliorate cardiac remodeling.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.013DOI Listing
April 2021

A Unique Population of Regulatory T Cells in Heart Potentiates Cardiac Protection From Myocardial Infarction.

Circulation 2020 11 28;142(20):1956-1973. Epub 2020 Sep 28.

Department of Cardiology, Union Hospital, and Key Laboratory of Biological Targeted Therapy of the Ministry of Education (N.X., Y. Lu, M.G., N.L., M.L., J.J., Z.Z., J.L., D.L., T.T., B.L., S.N., M.Z., M.L., Y. Liao, X.C.), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Regulatory T cells (Tregs), traditionally recognized as potent suppressors of immune response, are increasingly attracting attention because of a second major function: residing in parenchymal tissues and maintaining local homeostasis. However, the existence, unique phenotype, and function of so-called tissue Tregs in the heart remain unclear.

Methods: In mouse models of myocardial infarction (MI), myocardial ischemia/reperfusion injury, or cardiac cryoinjury, the dynamic accumulation of Tregs in the injured myocardium was monitored. The bulk RNA sequencing was performed to analyze the transcriptomic characteristics of Tregs from the injured myocardium after MI or ischemia/reperfusion injury. Photoconversion, parabiosis, single-cell T-cell receptor sequencing, and adoptive transfer were applied to determine the source of heart Tregs. The involvement of the interleukin-33/suppression of tumorigenicity 2 axis and Sparc (secreted acidic cysteine-rich glycoprotein), a molecule upregulated in heart Tregs, was further evaluated in functional assays.

Results: We showed that Tregs were highly enriched in the myocardium of MI, ischemia/reperfusion injury, and cryoinjury mice. Transcriptomic data revealed that Tregs isolated from the injured hearts had plenty of differentially expressed transcripts in comparison with their lymphoid counterparts, including heart-draining lymphoid nodes, with a phenotype of promoting infarct repair, indicating a unique characteristic. The heart Tregs were accumulated mainly because of recruitment from the circulating Treg pool, whereas local proliferation also contributed to their expansion. Moreover, a remarkable case of repeatedly detected T-cell receptor of heart Tregs, more than that of spleen Tregs, suggests a model of clonal expansion. Besides, HeliosNrp-1 phenotype proved the mainly thymic origin of heart Tregs, with a small contribution of phenotypic conversion of conventional CD4 T cells, proved by the analysis of T-cell receptor repertoires and conventional CD4 T cells adoptive transfer experiments. The interleukin-33/suppression of tumorigenicity 2 axis was essential for sustaining heart Treg populations. Last, we demonstrated that Sparc, which was highly expressed by heart Tregs, acted as a critical factor to protect the heart against MI by increasing collagen content and boosting maturation in the infarct zone.

Conclusions: We identified and characterized a phenotypically and functionally unique population of heart Tregs that may lay the foundation to harness Tregs for cardioprotection in MI and other cardiac diseases.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046789DOI Listing
November 2020

Interleukin 35 ameliorates myocardial ischemia-reperfusion injury by activating the gp130-STAT3 axis.

FASEB J 2020 02 9;34(2):3224-3238. Epub 2020 Jan 9.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Myocardial ischemia-reperfusion injury (MIRI) is common clinical complication, which represents significant challenge in the treatment of acute myocardial infarction (AMI) diseases. Interleukin 35 (IL-35) exhibits anti-inflammatory properties via the engagement of the gp130, IL-12Rβ2 and IL-27Rα receptors. However, whether IL-35 plays a beneficial role in the treatment of MIRI and potential underling mechanism are unclear. We showed that IL-35 conferred protection from MIRI as demonstrated by reduced infarct size and cardiac troponin T, improved cardiac function and decreased cardiomyocyte apoptosis in a mouse model. Despite activation of both STAT3 and STAT5 phosphorylation in the heart by IL-35, signal transducers and activators of transcription 3 (STAT3) was essential for mediating the IL-35-mediated protective effect on MIRI using cardiomyocyte-specific STAT3 deficient mice. Furthermore, gp130 was required for the STAT3 activation and cardio-protection induced by IL-35. Interestingly, IL-35 induced gp130 homodimer and gp130/IL-12Rβ2 heterodimers in cardiomyocyte. Our results indicate that IL-35 can execute a protective role against MIRI through a novel signaling pathway, IL-35-gp130-STAT3 pathway, in cardiomyocytes, which may be beneficial for the development of novel and effective therapeutic approaches to treat the MIRI.
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http://dx.doi.org/10.1096/fj.201901718RRDOI Listing
February 2020

IL (Interleukin)-33 Suppresses Abdominal Aortic Aneurysm by Enhancing Regulatory T-Cell Expansion and Activity.

Arterioscler Thromb Vasc Biol 2019 03;39(3):446-458

From the Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (J.L., N.X., S.W., D.L., Y.L., M.G., T.T., J.J., B.L., S.N., M.L.,Y.L., X.C.).

Objective- Inflammation occurs during the progression of abdominal aortic aneurysm (AAA). IL (interleukin)-33 is a pleiotropic cytokine with multiple immunomodulatory effects, yet its role in AAA remains unknown. Approach and Results- Immunoblot, immunohistochemistry, and immunofluorescent staining revealed increased IL-33 expression in adventitia fibroblasts from mouse AAA lesions. Daily intraperitoneal administration of recombinant IL-33 or transgenic IL-33 expression ameliorated periaorta CaPO injury- and aortic elastase exposure-induced AAA in mice, as demonstrated by blunted aortic expansion, reduced aortic wall elastica fragmentation, enhanced AAA lesion collagen deposition, attenuated T-cell and macrophage infiltration, reduced inflammatory cytokine production, skewed M2 macrophage polarization, and reduced lesion MMP (matrix metalloproteinase) expression and cell apoptosis. Flow cytometry analysis, immunostaining, and immunoblot analysis showed that exogenous IL-33 increased CD4Foxp3 regulatory T cells in spleens, blood, and aortas in periaorta CaPO-treated mice. Yet, ST2 deficiency muted these IL-33 activities. Regulatory T cells from IL-33-treated mice also showed significantly stronger activities in suppressing smooth muscle cell inflammatory cytokine and chemokine expression, macrophage MMP expression, and in increasing M2 macrophage polarization than those from vehicle-treated mice. In contrast, IL-33 failed to prevent AAA and lost its beneficial activities in CaPO-treated mice after selective depletion of regulatory T cells. Conclusions- Together, this study established a role of IL-33 in protecting mice from AAA formation by enhancing ST2-dependent aortic and systemic regulatory T-cell expansion and their immunosuppressive activities.
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http://dx.doi.org/10.1161/ATVBAHA.118.312023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393188PMC
March 2019

[Design of new-style embedded acupoint recognition device].

Zhongguo Zhen Jiu 2018 Jun;38(6):675-8

College of Mechanical Engineering, Donghua University, Shanghai 201600, China.

A new type of embedded acupoint recognition device was developed for acupoint recognition and teaching. Through improving the acupoint electric resistance detection technique of the two-electrode method, combined with mechanical structure design and embedded control technology, the human acupoint database was assembled in the embedded chip with the international symbol, acupoint name, , location, chart, manuscript and audio information included, a new type of embedded acupoint recognition device was designed. The device was composed of 3 modules, named the acupoint electric resistance detection system, the embedded control system and mechanical system. It achieved skin contact sensation, the collection of electric resistance at the required skin region, the wireless communication, the liquid crystal display (LCD) human-computer interaction and acupoint magnetic head massage. When used, the resistance value of the detected skin is read on LCD to determine whether the detected skin resistance meets the features of low resistance of acupoint and further to identify the acupoint zone. Afterward, the data collected are matched with the human acupoint database to determine the information of acupoint. The control mechanical structure achieves the acupoint pressing and kneading. After verified by many operation staff, it is shown that the device not only improves the recognition speed and precision of acupoint, but also contributes to the acupoint teaching with the human acupoint database displayed on LCD. The achievements benefit the promotion of meridians and acupoints as well as the development of acupuncture devices.
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http://dx.doi.org/10.13703/j.0255-2930.2018.06.031DOI Listing
June 2018

Analysis of Peripheral B Cell Subsets in Patients With Allergic Rhinitis.

Allergy Asthma Immunol Res 2018 May;10(3):236-243

Department of Otolaryngology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Purpose: Recent evidence suggests that B cells can both promote and inhibit the development and progression of allergic disease. However, the characteristics of B cell subsets in patients with allergic rhinitis (AR) have not been well documented. This study aimed to analyze the characteristics of B cell subsets in the peripheral blood of AR patients.

Methods: Forty-seven AR patients and 54 healthy controls were enrolled in this study, and the B cell subsets in peripheral blood of all subjects were analyzed by flow cytometry. Moreover, the serum total immunoglobulin E (IgE) and IgE concentrations secreted into the cultured peripheral blood mononuclear cells (PBMCs) were measured by using enzyme-linked immunosorbent assay.

Results: We found the peripheral blood of AR patients contained higher percentages of memory B cells, plasma cells, and CD19⁺CD24(hi)CD27⁺ regulatory B cells (Bregs) than those of age-matched healthy controls (P<0.05), while the percentages of naïve B cells and CD19⁺CD24(hi)CD38(hi) Bregs were significantly lower in AR patients than in healthy individuals (P<0.05). In addition, the serum total IgE and IgE concentrations secreted into the cultured PBMCs were elevated in AR patients than in the healthy controls (P<0.05).

Conclusions: Our findings indicate that AR patients were characterized by increase in terminally differentiated memory B cells or plasma cells and decreases in CD19⁺CD24(hi)CD38(hi) Breg cells in the peripheral blood.
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http://dx.doi.org/10.4168/aair.2018.10.3.236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911442PMC
May 2018

Neonatal tactile stimulation alleviates the negative effects of neonatal isolation on novel object recognition, sociability and neuroendocrine levels in male adult mandarin voles (Microtus mandarinus).

Physiol Behav 2013 Mar 21;112-113:14-22. Epub 2013 Feb 21.

Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.

Neonatal isolation results in long-lasting negative alterations to the brain and behavior. Some of these changes include effects on non-spatial learning and memory, sociability and neuroendocrine levels. Theoretically, neonatal tactile stimulation should reverse the impacts of neonatal isolation; however, this remains unknown for changes relating to learning, memory, sociability and hormones in social animals. Using socially monogamous mandarin voles (Microtus mandarinus), the long-lasting effects of these early manipulations on anxiety-like behavior, novel object recognition, sociability, and neuroendocrine levels were investigated. Compared with neonatal-isolated males, males subjected to the same manipulation but accompanied with tactile stimulation had heavier body weights across PND4-18 and displayed significantly less anxiety-like behavior in an open field test. In addition, tactile stimulation increased the preference index for novel object recognition reduced by neonatal isolation. Compared with control males, neonatal-isolated males engaged in less body contact with unfamiliar same-sex individuals and this effect was reversed by neonatal tactile stimulation. Tactile stimulation enhanced aggressive behavior in neonatal-isolated males and increased the levels of AVP and OT in the paraventricular nucleus (PVN) which were decreased by neonatal isolation. This early manipulation also reduced serum CORT levels that were significantly up-regulated by neonatal isolation in both neonatal and adult offspring. These results indicate that adequate tactile stimulation in early life plays an important role in the prevention of behavioral disturbances induced by neonatal isolation, possibly through the alteration of central OT, AVP and the serum corticosterone levels.
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http://dx.doi.org/10.1016/j.physbeh.2013.02.005DOI Listing
March 2013

Effects of group housing on stress induced emotional and neuroendocrine alterations.

Brain Res 2013 Mar 1;1502:71-80. Epub 2013 Feb 1.

Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.

Chronic restraint stress can induce depressive and anxiety-like behavior and neurophysiological disturbances. The social living shows the health-promoting and stress-protective effects on both human and animal. However, whether group housing exerts effects on development of depression and anxiety induced by chronic restraint treatments and its detailed neuroendocrine mechanism remain unclear. Following repeated restraint, the anxiety and depression-like behaviors of single and group housing mice were examined using the elevated plus-maze, open field test and forced swimming test. The levels of central oxytocin (OT) expression in the paraventricular nucleus (PVN), glucocorticoid receptors (GR) in the hippocampus and serum OT and corticosterone (CORT) were also measured using immunohistochemistry and ELISA methods. Our results show that chronic restraint significantly decreased time in open arm of elevated plus maze and increased immobility time in forced swimming test in single-housed mice. However, chronic restraint exerted no effects on these aspects in group-housed mice. Accompanying the changes of behaviors, chronic restraint up-regulated levels of serum CORT and reduced the hippocampus GR in single-housed animals, but did not change these measures in group-housed mice. Furthermore, repeated restraint had no effect on OT levels in these two housing conditions although group-housing significantly increased the PVN OT levels. Taken together, these results provide substantial evidence that group housing can reduce levels of anxiety and depression induced by chronic restraint stress in mice. The elevation of central GR and OT, and decrease of circulating CORT may possibly be involved in these buffering effects.
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http://dx.doi.org/10.1016/j.brainres.2013.01.044DOI Listing
March 2013

Effects of bilobalide on anxiety, spatial learning, memory and levels of hippocampal glucocorticoid receptors in male Kunming mice.

Phytomedicine 2012 Dec 17;20(1):89-96. Epub 2012 Oct 17.

Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China.

With various constituents in ginkgo biloba extract, the detailed internal mechanism underlying a reduction in anxiety and improvements to learning and memory from GBE is not well understood. The present study investigated whether bilobalide, an important constituent in GBE, could affect anxiety, spatial learning and memory in male mice and whether hippocampal glucocorticoid receptor expression is associated with alteration in these behaviors. Mice were treated orally either with sesame seed oil or one of three dosages of bilobalide (2.5, 5.0 and 10.0 mg/kg) daily until testing. A series of behavioral tests showed that repeated bilobalide treatment decreased levels of anxiety-like behavior and increased locomotor activity in open field and elevated plus maze tests. Treatment with bilobalide also shortened the time taken to find the platform in a Morris water-maze test. Mice exposed to bilobalide showed higher and dose-dependent levels of glucocorticoid receptor expression in the hippocampus. These results suggest that bilobalide reduces anxiety levels and enhances spatial learning and memory, possibly through an increase in hippocampal glucocorticoid receptor expression. This finding sheds light on the mechanisms underlying the effect of ginkgo biloba extract on behavior and also provides an important candidate drug in treatment of anxiety, depression, hypomnesia and amnesia.
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http://dx.doi.org/10.1016/j.phymed.2012.09.015DOI Listing
December 2012

Up-regulation of Tim-3 expression contributes to development of burn-induced T cell immune suppression in mice.

J Huazhong Univ Sci Technolog Med Sci 2011 Oct 25;31(5):642. Epub 2011 Oct 25.

Lymphocyte Cell Biology Section, NIAMS, NIH, Bethesda, MD, 20892, USA.

T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3(+) T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4(+) and CD8(+) T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3(+) T cells subsets were more prone to spontaneous apoptosis than Tim-3(-) T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.
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http://dx.doi.org/10.1007/s11596-011-0575-0DOI Listing
October 2011

Human health risk of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in edible fish from Huairou Reservoir and Gaobeidian Lake in Beijing, China.

Food Chem 2008 Jul 25;109(2):348-54. Epub 2007 Dec 25.

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China.

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured by a gas chromatography-mass spectometry (GC-MS) in some edible fish from Huairou Reservoir and Gaobeidian Lake in Beijing, China. The concentrations of OCPs and PCBs were higher in fish (except Misgurnus anguillicaudatus) from Gaobeidian Lake than in those from Huairou Reservoir. The average concentrations of HCHs, DDTs and PCBs in fish ranged from 0.58 to 8.48, 7.54 to 88.3, below limit of detection (nd) to 22.7ng/g wet weight, respectively. β-HCH, p,p'-DDE and PCB153 were the most abundant compounds among HCHs, DDTs and PCBs, respectively. Risk assessments of OCPs and PCBs for humans were estimated according to three different guidelines. The results indicated that fish intake would not pose a health risk to humans with a consumption of 7.4±8.6g/person day according to the acceptable daily intake (ADI) and minimal risk level (MRL) in the two environments. However, the hazardous ratio of the 95th percentile for PCBs in fish from Gaobeidian Lake exceeded 1, which suggested that daily exposure to PCBs had a lifetime cancer risk of greater than 1 in 1,000,000.
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http://dx.doi.org/10.1016/j.foodchem.2007.12.047DOI Listing
July 2008

Pesticide contamination profiles of water, sediment and aquatic organisms in the effluent of Gaobeidian wastewater treatment plant.

Chemosphere 2008 Jul 9;72(8):1145-51. Epub 2008 May 9.

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.

Organochlorine pesticides (OCPs, including DDT, HCH and HCB) and six indicator polychlorinated biphenyls (PCB 28, 52, 101, 138, 153, and 180) were measured in water, sediment, zooplankton, fish and Chinese softshell turtle (Pelodiscus sinensis) from Gaobeidian Lake, which is located in the effluent of Gaobeidian wastewater treatment plant (WWTP) in Beijing, China. DDTs were dominant except for in water. In water, the concentrations of DDTs (6.22 ng l(-1)) and HCHs (18.0 ng l(-1)) were less than the limits (l000 ng l(-1) for DDTs and 5000 ng l(-1) for HCHs). However, PCBs concentration (20.8 ng l(-1)) exceeded the limit (14 ng l(-1)) suggested by the United States Environmental Protection Agency (USEPA). The high ratio of p,p'-DDT/DDTs (0.80) in water suggested that DDTs had recently been discharged into the ambient environment despite a longtime ban in China. For fish and Pelodiscus sinensis, the accumulation patterns of OCPs and PCBs were different in muscle and liver. And HCB and PCB 153 were significant different in different species (p<0.05). PCBs were dominated by PCB 52 in zooplankton, but by PCB 138 and 153 in Pelodiscus sinensis. The highest food web magnification factor (FWMF) was 4.83 for p,p'-DDT and the second highest was 4.36 for PCB 101 in Gaobeidian Lake. As compared with the other studies, biomagnification in the present study was not obvious. Trophic levels and age were two important factors that might contribute to the bioaccumulation in the present study.
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http://dx.doi.org/10.1016/j.chemosphere.2008.03.049DOI Listing
July 2008

Activation of NF-kappaB by IL-1beta blocks IL-6-induced sustained STAT3 activation and STAT3-dependent gene expression of the human gamma-fibrinogen gene.

Cell Signal 2007 Sep 1;19(9):1866-78. Epub 2007 May 1.

Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University, 40255 Düsseldorf, Germany.

Despite the essential role of the fibrinogen gamma-chain as a blood clotting factor, the fibrinogen gamma-chain contains a number of interaction sites to recruit other factors such as leukocytes important for prevention of pathogen entry and propagation of the repair process. Interleukin-6 (IL-6) is known as the major inducer of gamma-fibrinogen synthesis in hepatocytes, whereas IL-1beta has been shown to act as a potent inhibitor of gamma-fibrinogen expression. Studies on the rat fibrinogen gamma-chain promoter suggest that nuclear factor (NF)-kappaB replaces the signal transducer and activator of transcription (STAT) 3 from binding to overlapping NF-kappaB/STAT3 binding sites within the 5' regulatory region of the rat gamma-chain gene promoter. However, despite its physiological relevance, the underlying mechanism responsible for the inhibitory effect of IL-1beta in humans is still not understood and apparently more complex. In contrast to the mechanism described for the rat gene our results indicate that IL-1beta suppresses the IL-6-induced activation of the human gamma-fibrinogen gene particularly by blocking the late phase STAT3-tyrosine phosphorylation NF-kappaB-dependently but independent from de novo protein synthesis. Consequently, blocking NF-kappaB activation restores specifically late phase STAT3 activation as well as the induction of the human gamma-fibrinogen gene. In contrast, specifically early STAT3 activation could be restored by a block of the p38 mitogen-activated protein kinase (p38(MAPK)) pathway. In summary, our results indicate that expression of the gamma-fibrinogen gene is mainly controlled by the strength of late phase STAT3 activation, which in turn is negatively regulated by the extent of IL-1beta-mediated NF-kappaB activity.
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http://dx.doi.org/10.1016/j.cellsig.2007.04.007DOI Listing
September 2007

PCDD/F, PAH and heavy metals in the sewage sludge from six wastewater treatment plants in Beijing, China.

Chemosphere 2007 Jan 13;66(2):353-61. Epub 2006 Jun 13.

Key laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 25 Beisihuan Xilu, Beijing 100080, PR China.

In order to better understand land application of sewage sludge, the characterization of heavy metals, PCDD/F and PAHs in sewage sludge was investigated from six different wastewater treatment plants (WWTP) in Beijing City, China. It was found that the total concentrations of Zn in Wujiacun (WJC) sewage sludge, and Cd and Hg in sewage sludge generated from all of the six different places are higher than Chinese regulation limit of pollutants for sludge to be used for agriculture (GB18918-2002). The levels of 16 PAHs that have been categorized as priority pollutants by US EPA in the sewage sludge samples varied from 2467 to 25923 microg/kg (dry weight), the highest values of 25923 microg/kg being found in WJC WWTP. The concentrations of Benzo[a]pyrene were as high as 6.1mg/kg dry weight in WJC sewage sludge, exceeding the maximum permitted content by GB18918-2002. Individual PAH content varies considerably with sewage samples. The ratios of anthracene to anthracene plus phenanthrene (An/178), benz[a]anthracene to benz[a]anthracene plus chrysene (BaA/228), indene[1,2,3-cd]pyrene to indene[1,2,3-cd]pyrene plus benzo[g,h,i]perylene (In/In+BP), and fluoranthene to fluoranthene plus pyrene (Fl/Fl+Py) suggest that petroleum and combustion of fossil fuel were the dominant contributions for the PAHs in sewage sludge. The concentrations of total PCDD/F in the sewage sludge ranged from 330 to 4245 pg/g d.w. The toxicity equivalent concentrations is between 3.47-88.24 pg I-TEQ according to NATO/CCMS, which is below Chinese legislation limit value proposed for land application. The PCDD/F congener/homologue profiles found in the Beijing samples indicated that the high chlorinated PCDD/F contamination might originate mainly from PCP-related source and depositional sources while the low chlorinated PCDD/F homologues could be originating from incineration or coal combustion. The major source of PCDD/Fs in Beijing sludge is still unclear.
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http://dx.doi.org/10.1016/j.chemosphere.2006.04.072DOI Listing
January 2007

Stereoselective synthesis and fungicidal activities of (E)-alpha-(methoxyimino)-benzeneacetate derivatives containing 1,3,4-oxadiazole ring.

Bioorg Med Chem Lett 2006 Apr 7;16(8):2278-82. Epub 2006 Feb 7.

Key Laboratory of Synthesis and Application of Organic Functional Molecules of the Education Ministry, Hubei University, Wuhan, Hubei 430062,China.

Fifteen novel (E)-alpha-(methoxyimino)-benzeneacetate derivatives, the analogues of strobilurins, which contain two pharmacophoric substructures of (E)-methyl methoxyiminoacetate moiety and 1,3,4-oxadiazole ring were stereoselectively synthesized. It was first found that the coupling reaction could give stereoselectively the key intermediate (E) and (Z)-methyl 2-(hydroxyimino)-2-o-tolylacetate 2 with a ratio of 14:1. The preliminary bioassays indicated that all the compounds 1 showed potent fungicidal activity against Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Physalospora piricola and Bipolaris mayclis, and all of the tested compounds 1a-1o had more potent fungicidal activities against R. solani than Kresoxim-methyl.
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http://dx.doi.org/10.1016/j.bmcl.2006.01.026DOI Listing
April 2006

Frequency of loss expression of the DPC4 protein in various locations of biliary tract carcinoma.

Zhonghua Yu Fang Yi Xue Za Zhi 2002 Dec;36(7):481-4

Department of General Surgery, Tongji Hospital, Wuhan 430030, China (Email:

Objective: To clarify the relationship between the loss of expression of the deleted in pancreatic carcinoma locus 4 (DPC4) proteins and the pathogenesis of biliary tract carcinoma.

Methods: 71 primary biliary tract carcinoma (BTCa), including 38 common bile duct (CBD) carcinomas, 18 gallbladder carcinomas, 15 hilar bile ducts (HBD) carcinomas were examined by immunohistochemical staining. In addition, the CBD carcinomas were divided into two groups: tumors with metastasis (M(+) group, 27 cases) and tumors without metastasis (M(-) group, 11 cases).

Results: The frequency of loss of the expression of DPC4 protein was 32.8% in BTCa, 47.3% in CBD carcinoma, 11% in gallbladder carcinoma, 13% in HBD carcinoma. Comparison of the frequency of loss expression of DPC4 was significant statistical difference in CBD carcinoma versus gallbladder carcinoma and HBD carcinoma (P < 0.01). The frequency of loss expression of DPC4 was 48.1% in the M(+) group and 45.4% in the M(-) group.

Conclusion: There are a close relationship between pathogenesis of BTCa and inactivation of DPC4 and different frequencies of DPC4 gene alternation in various locations of the biliary tract, which are not significantly increased with tumor metastasis in BTCa.
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December 2002
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