Shaoheng He

Shantou University, Shantou, Guangdong Sheng, China

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Publications (47)110.2 Total impact

  • Article: Induction of Mast-Cell Accumulation by Promutoxin, an Arg-49 Phospholipase A2.
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    ABSTRACT: Local inflammation is a prominent characteristic of snakebite wound, and snake-venom phospholipase A2s (PLA2s) are some of the main component that contribute to accumulation of inflammatory cells. However, the action of an R49 PLA2s, promutoxin from Protobothrops mucrosquamatus venom, on mast-cell accumulation has not been previously examined. Using a mouse peritoneal model, we found that promutoxin can induce approximately-6-fold increase in mast-cell accumulation, and the response lasts at least for 16 h. The promutoxin-induced mast cell accumulation was inhibited by cyproheptadine, terfenadine, and Ginkgolide B, indicating that histamine and platelet-activating factor (PAF) is likely to contribute to the mast-cells accumulation. Preinjection of antibodies against adhesion molecules ICAM-1, CD18, CD11a, and L-selectin showed that ICAM-1, and CD18, CD11a are key adhesion molecules of promutoxin-induced mast-cell accumulation. In conclusion, promutoxin can induce accumulation of mast cells, which may contribute to snake-venom wound.
    BioMed research international. 01/2013; 2013:206061.
  • Article: Modulation of PAR expression and tryptic enzyme induced IL-4 production in mast cells by IL-29.
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    ABSTRACT: Interleukin (IL)-29 is a relatively newly discovered cytokine, which has been shown to be actively involved in the pathogenesis of allergic inflammation. However, little is known of the effects of IL-29 on protease activated receptor (PAR) expression and potential mechanisms of cytokine production in mast cells. In the present study, we examined potential influence of IL-29 on PAR expression and cytokine production in P815 and bone marrow derived mast cells (BMMCs) by using flow cytometry analysis, quantitative real time PCR, and ELISA techniques. The results showed that IL-29 downregulated the expression of PAR-1 by up to 56.2%, but had little influence on the expression of PAR-2, PAR-3 and PAR-4. IL-29 also induced downregulation of expression of PAR-1 mRNA. However, when mast cells were pre-incubated with IL-29, thrombin-, trypsin- and tryptase-induced expression of PAR-2, PAR-3 and PAR-4 was upregulated, respectively. IL-29 provoked approximately up to 1.9-fold increase in IL-4 release when mast cells was challenged with IL-29. Administration of IL-29 blocking antibody, AG490 or LY294002 abolished IL-29-induced IL-4 release from P815 cells. It was found that IL-29 diminished trypsin- and tryptase-induced IL-4 release from P815 cells following 16h incubation. In conclusion, IL-29 can regulate expression of PARs and tryptase- and trypsin-induced IL-4 production in mast cells, through which participates in the mast cell related inflammation.
    Cytokine 12/2012; · 3.02 Impact Factor
  • Article: Analysis of antibiotic patents issued in China from 1992 to 2011.
    Hua Xie, Huiyun Zhang, Shu Zhang, Shaoheng He
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    ABSTRACT: Introduction: The wide use of antibiotics both within and beyond the medical territory plays a significant role in the development of resistant bacteria. Therefore, there is a pressing need for the development of effective antibiotics worldwide. Areas covered: The current analysis report covers the scientific progress in supporting antibiotic patent application and the granted patent literature in China for the last 20 years. Expert opinion: Among the 2780 patents granted in China last 20 years, β-lactam antibiotics, macrolides, quinolones, aminoglycosides, sulfonamides, glycopeptides and tetracyclines constitute 44.3, 17.4, 13.5, 4.1, 3.8, 3.0 and 2.1% of total patents, respectively. Scientists have faced challenges in developing new antibiotics against increasingly growing types of drug-resistant bacteria, which may causes serious global public health disaster in future. Poor financial investment in antibiotic research has exacerbated the situation. Therefore, new antibiotic patents will be applied continuously. The combination individual β-lactam antibiotics with a β-lactamase inhibitor have been demonstrated clinically beneficial and may suggest a new way for the development of more effective antibiotics in future. Local patent applications of China are stably increasing largely through a dependence on the imitation of Western drugs. The current study may help to better understand the patent situation in China and to invent the more efficient antibiotic therapies.
    Expert Opinion on Therapeutic Patents 09/2012; 22(10):1205-32. · 3.57 Impact Factor
  • Article: Self-amplification Mechanisms of Mast Cell Activation: A New Look in Allergy.
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    ABSTRACT: Allergic diseases are major diseases involving approximately 22% of world population. In recent years, accumulated evidence suggests that apart from IgE, allergens may provoke immediate allergic reactions via other pathways such as IgG, toll like receptor (TLR) dependent ones. In addition, large numbers of low molecular weight molecules (LMWM) such as sphingosine-1-phosphate and iodinated contrast agents have been observed to cause allergy. Therefore, the current definition of allergy, a group of IgE mediated diseases appears difficult to cover all allergic reactions. Since even IgE dependent allergic reactions are carried out through activation of mast cells and basophils, and all allergens mentioned above can activate these cells, we hypothesize that allergic reactions are mast cell and basophil mediated inflammatory process as it is the activated mast cells and basophils that initiate the pathological process of the immediate allergic reactions, whereas IgE only serves as one of the activators of these cells.
    Current Molecular Medicine 08/2012; · 5.10 Impact Factor
  • Article: An update on anti-allergic patents granted in China: 2009 - 2011.
    Shu Zhang, Xiaoning Zeng, Shaoheng He
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    ABSTRACT: INTRODUCTION: The prevalence of allergic diseases has increased dramatically in recent decades. Therefore, there is a pressing need for the development of effective anti-allergic services worldwide. AREAS COVERED: In previous studies, the authors had analyzed a total of 789 anti-allergic patents granted in China from 1988 to 2008. Herein, they report a further 151 anti-allergic patents issued in China during 2009 - 2011. The current analysis covers the scientific progress in supporting anti-allergic patent applications and granted patent literature, in China, for the last 3 years. EXPERT OPINION: The 151 anti-allergic patents granted from 2009 to 2011 mainly focus on seven types of products. They are: traditional Chinese medicines (TCM), plant extracts, biological products, synthetic compounds, pharmaceutical preparations, medical apparatus and new treatment modalities. Although the overall number of anti-allergic patent applications made between 2009 and 2011 in China is less than that of the USA and Europe, patents on TCM have increased. This suggests that there are demands for modernization of TCMs. Recently, studies of interesting new immunomodulators have also been conducted, and some of these are likely to represent clinically useful advances. In the last 3 years, several patents on these novel potential drugs have also been granted in China. The large number of anti-allergic patents issued in China, in recent times, suggests that the Chinese market is relatively competitive one that will help pharmaceutical companies make proper decisions for their research and development strategies.
    Expert Opinion on Therapeutic Patents 06/2012; 22(7):715-34. · 3.57 Impact Factor
  • Article: Analysis of total proteins in pollen of Humulus scandens Lour in Wuhan Region of China by two-dimensional electrophoresis
    Dongdong Li, Shaoheng He
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    ABSTRACT: Total proteins in the pollen of Humulus scandens Lour, one of the most popular aeroallergens in China, were analyzed by two-dimensional electrophoresis in the current study. The proteins were extracted by Trichloracetic acid (TCA) method, and then separated by isoelectric focusing as the first dimension and SDS-PAGE as the second dimension. The spots of proteins were visualized by staining with Coomassie Brilliant Blue. After analysis with software (ImageMaster 2D), 122 different proteins were detected; isoelectric point (pI), Molecular weight (MW) and relative volume of each protein in the pollen were also discovered. This is the first high-resolution, two-dimensional protein map of the pollen of Humulus scandens Lour in China. Our finding has built a solid foundation for identification, characterization, gene cloning and standardization of allergenic proteins in the pollen of Humulus scandens Lour for further studies.
    Frontiers of Biology in China 04/2012; 2(3):309-313.
  • Article: Mast cell tryptase induces microglia activation via protease-activated receptor 2 signaling.
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    ABSTRACT: Mast cell tryptase can stimulate peripheral mononuclear cells activation to cause widespread inflammation. However, the influence of tryptase on microglia, the resident immune cells in the brain, remains uninvestigated. Since microglia plays a pivotal role in immune surveillance of CNS, we studied the effect of tryptase on microglia activation. Induction of microglia activation by tryptase was examined with primary cultured microglia. TNF-alpha and IL-6 was measured with a commercial ELISA kit. Intracellular ROS was determined by dichlorodihydrofluorescein oxidation. Mitochondrial membrane potential was assessed with the MitoProbe™ JC-1 assay kit. And MAPK and NF-kappa B phosphorylation were evaluated by Western blot. We found that tryptase stimulated microglia activation and subsequently produced proinflammatory factors TNF-alpha, IL-6 and ROS. Inhibition of PAR-2 activation reduced tryptase-induced TNF-alpha, IL-6 and ROS production, and mitochondrial membrane potential loss in microglia. Among the three members of MAPK pathway, ERK and p38, but not JNK mediated tryptase-induced microglia activation. Inhibition of PAR-2 suppressed tryptase-induced ERK and p38 MAPK pathway activation in microglia. Tryptase also activated NF-kappa B within 30 min, and ammonium pyrrolidinedithiocarbamate, an inhibitor of NF- kappa B, reduced tryptase-induced TNF-alpha and IL-6 release. Our results suggest that tryptase can induce microglia activation and pro-inflammatory mediator release via PAR-2-MAPK-NF-kappa B signaling pathway, which will contribute to the development of microglia-mediated inflammation in brain.
    Cellular Physiology and Biochemistry 01/2012; 29(5-6):931-40. · 2.86 Impact Factor
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    Article: Purification and characterization of two new allergens from the venom of Vespa magnifica.
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    ABSTRACT: Due to poor diagnostic facilities and a lack of medical alertness, allergy to Vespa wasps may be underestimated. Few allergens have been identified from Vespa wasps.Possible native allergen proteins were purified from the wasp venoms (WV) (Vespa magnifica Smith) by gel filtration, ion exchange chromatography, respectively. Their sequences were determined by Edman degradation and cDNA cloning. Their allergenicities were assayed by enzyme-linked immunosorbent assay inhibition tests (ELISA-IT), immunoblots, and skin prick tests (SPTs). Their cross allergencities with Tab y 2 and Tab y 5 purified from the horsefly (Tabanus yao Macquart) were also determined. Two native allergens were identified from the WV, respectively. They are a 25-KDa antigen 5 protein (Ag5) (Vesp ma 5) and a 35-KDa hyaluronidase (Vesp ma 2). They represented major allergens in Vespa magnifica by immunoblots and SPTs. ELISA inhibition of pooled sera IgE reactivity to both the WV and the horsefly salivary gland extracts (HSGE) using four purified allergens (Vesp ma 2, Vesp ma 5 and previously purified Tab y 2 and Tab y 5) was significant. Their cross allergenicities were confirmed by ELISA-IT, immunoblots, and SPTs. They represented the cross reactive allergens from wasp and horsefly and proved the so called wasp-horsefly syndrome.
    PLoS ONE 01/2012; 7(2):e31920. · 4.09 Impact Factor
  • Article: Cockroach allergen per a 7 down-regulates expression of toll-like receptor 9 and IL-12 release from P815 cells through PI3K and MAPK signaling pathways.
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    ABSTRACT: As a major source of indoor allergens, cockroach causes perennial rhinitis and asthma. Recently, cockroach feces were reported to contain TLR2 agonist, which could directly activate neutrophils to release cytokines. CpG oligodeoxynucleotide (ODN), a Toll-like receptor (TLR)9 activator was also found to induce proinflammatory cytokine release from mast cells. However, influence of specific cockroach allergen on Th1 cytokine release and expression of TLR9 in mast cells remains uninvestigated. To investigate effects of Per a 7 on TLR expression and cytokine release from mast cells and their cell signaling mechanisms, P815 cells were challenged by recombinant Per a 7 (rPer a 7), and expression of TLR9 mRNA and protein was assessed mainly by real time PCR and flow cytometry analysis. Detection of phosphorylation of cell signaling components was performed with Western blotting technique. The results showed that rPer a 7 induced up to 72 and 46% down-regulation of expression of TLR9 mRNA and protein, respectively following 16 h incubation period. It induced also approximately 41.1% reduction of IL-12 release. When PD98059, U0126 and LY294002 were pre-incubated with the cells for 30 min they diminished rPer a 7 induced reduction of TLR9 expression and IL-12 release, indicating these events are via activation of ERK and PI3K/Akt signaling pathways. Reduction of IL-12 production and expression of TLR9 in P815 mastocytoma cells by Per a 7 suggests that this major cockroach allergen might contribute to the development of cockroach allergy.
    Cellular Physiology and Biochemistry 01/2012; 29(3-4):561-70. · 2.86 Impact Factor
  • Article: Increased interleukin (IL)-8 and decreased IL-17 production in chronic obstructive pulmonary disease (COPD) provoked by cigarette smoke.
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    ABSTRACT: Recently, involvement of IL-17 in development of COPD has been noticed. Unlike IL-8, the role of IL-17 in COPD remains controversial. In order to further understand mechanisms in cigarette smoke (CS) induced COPD, we investigated IL-17 and IL-8 levels in different stages of COPD patients, and time courses of IL-17 and IL-8 release in CS induced COPD rats. A total of 73 elderly patients with COPD and 31 healthy volunteers were recruited in the study. IL-17 and IL-8 levels in the sputum and plasma were measured, and number of differential cells was counted. A newly developed CS induced rat COPD model was employed to study time courses of IL-17 and IL-8 release and nucleated cell accumulation. The results showed that IL-8 levels in the sputum of severe COPD patients were elevated by 16.5-fold, but IL-17 levels were reduced by 4.8-fold. While IL-8 correlated with neutrophils, IL-17 correlated with monocytes and lymphocytes. Similarly, level of IL-8 was increased, but IL-17 was decreased in the bronchoalveolar lavage fluid (BALF) of CS rats. Time course study showed that increased IL-8 production in the BALF initiated at 6 weeks, but decreased IL-17 production started at 10 weeks following CS exposure. In conclusion, increased IL-8 level in COPD patients appears mainly secreted from neutrophils and macrophages, whereas decreased IL-17 level seems resulted from reduced number of monocytes or damaged epithelial cells. Increased IL-8 (a proinflammatory cytokine) secretion and decreased IL-17 (a protective cytokine of airways) release can both contribute to development of COPD.
    Cytokine 12/2011; 56(3):717-25. · 3.02 Impact Factor
  • Article: Analysis of properties and proinflammatory functions of cockroach allergens Per a 1.01s.
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    ABSTRACT: Cockroaches have been identified as one of the major indoor allergens inducing perennial rhinitis and asthma. Per a 1s are a group of the major allergens from American cockroach. Although Per a 1s are major allergens from American cockroach, factors contributing to the allergenicity of Per a 1s are still poorly defined. To investigate the effects of Per a 1s on the expression of PARs and the release of proinflammatory cytokines from mast cells. Per a 1.0101 and Per a 1.0104 were cloned from American cockroach and then expressed in Eschericia coli. The purified allergens were used to stimulate P815 mast cells, and the expression of protease-activated receptors (PARs) was determined by real-time RT-PCR and flow cytometry. The levels of IL-4 and IL-13 in culture media were detected with ELISA. Sera from 80 and 77.3% of cockroach allergy patients reacted to recombinant Per a (rPer a) 1.0101 and rPer a 1.0104, confirming they are major allergens. Both rPer a 1.0101 and rPer a 1.0104 had no enzymatic activity, but rPer a 1.0101 upregulated the expression of PAR-1 and PAR-2, and rPer a 1.0104 enhanced the expression of PAR-1 and PAR-4 proteins. Both recombinant allergens were able to increase the release of IL-4 and IL-13 from P815 mast cells. This is the first study aiming to investigate functions of group 1 allergens of American cockroach. rPer a 1.0101 and rPer a 1.0104 have the capacity to upregulate the expression of PARs and to enhance Th2 cytokine production in mast cells.
    Scandinavian Journal of Immunology 04/2011; 74(3):288-95. · 2.23 Impact Factor
  • Article: Tryptase enzyme activity is correlated with severity of chronic obstructive pulmonary disease.
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    ABSTRACT: Tryptic enzymes, including tryptase, a signature enzyme in mast cells, are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic inflammatory airway disease. However, the relationship between tryptase enzyme activity and COPD remains to be investigated. We therefore measured the enzyme activity and immunoreactivity of tryptase in the sputum and plasma of COPD patients in the present study. The results showed that tryptase enzyme activity in the sputum of severe COPD patients (FEV(1)s being recorded at ≤ 30% prediction values) was 3.4 times greater than that in patients with mild COPD (FEV(1)s being recorded at ≥ 80% of predicted values), whereas tryptic activity was 2.0 times higher in the severe COPD patients than in mild COPD patients. Moreover, tryptase enzyme activity, but not tryptic enzyme activity, was significantly elevated in the plasma of severe COPD patients compared with that of mild COPD patients. The level of immunoreactive tryptase was 1.9 times higher in the sputum of the severe COPD patients at admission than that at remission stage. We also employed a rat model of cigarette smoke-induced COPD. After 36 weeks of daily challenges with cigarette smoke, a well-established risk factor of COPD, tryptic and tryptase activities in the bronchoalveolar lavage fluid were elevated 1.5 and 2.6 times, respectively. These results indicate that smoking induces tryptase enzyme activity in the airway. In conclusion, tryptase enzyme activity is markedly increased in sputum and plasma of severe COPD patients. Enhanced tryptase enzyme activity may contribute to the pathogenesis of COPD.
    The Tohoku Journal of Experimental Medicine 01/2011; 224(3):179-87. · 1.24 Impact Factor
  • Article: Methods for protein identification using expressed sequence tags and peptide mass fingerprinting for seed crops without complete genome sequences
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    ABSTRACT: Proteomic approaches based on two-dimensional gel electrophoresis, mass spectrometry and database search are widely used to address questions about the development, physiology and quality of seeds. Identification of proteins is of great importance in proteomic analyses. For seed crops without full genome information, cross-species protein identification by mass spectrometry-driven sequence similarity search can be used. However, this approach is risky due to protein polymorphism between different species. Species-specific expressed sequence tag (EST) databases are an invaluable resource, which complements mass spectrometry data analysis for protein identification. Here, we illustrate a modified method of protein identification and characterization using species-specific EST databases and peptide mass fingerprinting with an example of protein identification. This method is reliable, supplements the existing methods, and improves the efficiency and accuracy of protein identification for seed crops for which complete genome information is not available.
    Seed Science Research 11/2010; 20(04):257 - 262. · 1.06 Impact Factor
  • Article: Induction of IL-13 production and upregulated expression of protease activated receptor-1 by RANTES in a mast cell line.
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    ABSTRACT: RANTES is a potent chemoattractant for various important inflammatory cells such as eosinophils, memory T cells and mast cells. It has been long recognized as a crucial player in the pathogenesis of allergy. However, little is known of its effects on cytokine secretion and protease activated receptor (PAR) expression in mast cells. In the present study, we examined potential influence of RANTES on IL-13 and IL-12 release from P815 cells and PAR expression on P815 cells by using flow cytometry analysis, quantitative real-time PCR, ELISA and cellular activation of signaling ELISA (CASE) techniques. The results showed that RANTES induced up to 2.2-fold increase in IL-13, but not IL-12 release from P815 cells. Blocking antibodies against RANTES and CCR5 diminished RANTES induced IL-13 release. Furthermore, RANTES upregulated expression of PAR-1, PAR-2 and PAR-3 mRNAs, but enhanced only PAR-1 protein expression. At 1 ng/ml, RANTES can abolish tryptase induced IL-13 release, but enhance trypsin, tryptase and thrombin induced PAR-1, -2 and -4 expression. LY204002 abolished RANTES induced IL-13 release, indicating an Akt cell signaling pathway may be involved in the event. In conclusion, RANTES can stimulate IL-13 release from mast cells through a CCR5 and Akt cell signaling pathway dependent mechanism. It can also enhance trypsin, tryptase and thrombin-induced expression of PARs in mast cells. RANTES may contribute to modulation of IL-13 production and PAR expression in mast cells, through which participates in the mast cell related inflammation.
    Cytokine 11/2010; 53(2):231-8. · 3.02 Impact Factor
  • Article: Identification of a novel mutation in the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria.
    Journal of the American Academy of Dermatology 09/2010; 63(3):529-30. · 3.99 Impact Factor
  • Article: Trans-Zeatin attenuates ultraviolet induced down-regulation of aquaporin-3 in cultured human skin keratinocytes.
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    ABSTRACT: Solar ultraviolet (UV) irradiation is one of the most significant extrinsic factors contributing to skin photoaging. One major characteristic of photoaging induced by UV is water loss of the skin. Water movement across the plasma membrane can occur via two pathways: by diffusion through the lipid bilayer and by membrane-inserted water channels (aquaporins). In this study we demonstrate that UV induces aquaporin-3 (AQP3) downregulation in cultured keratinocytes (HaCaT cells). PD98059 and U0126, MEK/ERK inhibitors, inhibit UV-induced AQP3 loss. Trans-Zeatin (tZ), which alone induces AQP3 expression, attenuates UV-induced loss of AQP3. We found that tZ inhibits UV-induced MEK/ERK activation; the latter serves as the key signal pathway mediating UV-induced AQP3 loss. Using specific AQP3 siRNA knockdown, we found AQP3 is involved in wound healing in human skin keratinocytes. Loss-of-AQP3-mediated delayed wound healing in UV-radiated skin keratinocytes is attenuated by tZ pretreatment. tZ pretreatment also attenuates UV-induced decreased water permeability in HaCaT cells. We concluded that UV radiation downregulates AQP3 in HaCaT cells. MEK/ERK activation is involved in this process. tZ treatment attenuates UV-induced AQP3 loss, in vitro wound healing delay and water permeability decrease. This work provides a new explanation for the anti-photoaging potential of tZ.
    International Journal of Molecular Medicine 08/2010; 26(2):257-63. · 1.98 Impact Factor
  • Article: Analysis of trends and opportunities of anti-allergy patents in China from 1998 to 2008.
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    ABSTRACT: The prevalence of allergic diseases has increased dramatically in recent decades. Holding patents is one of the means to protect good anti-allergy products. However, little is known of anti-allergy patent situation in China. The paper summarized and analyzed anti-allergy patents issued in China from January 1988 to September 2008. A total of 789 anti-allergy patents have been granted in China during the 20 years. China, European countries, USA, Japan and other countries possesses 44%, 21%, 19%, 12% and 4% of all of these anti-allergy patents respectively. Interestingly, 88% anti-allergy patents issued to Chinese are held by civilians, whereas vast majority of the patents issued to foreigners were held by pharmaceutical companies. All anti-allergy patents are focused on synthetic compounds, Traditional Chinese Medicines (TCM),combinations of synthetic compounds and TCM (CST), biological products and medical apparatus. The anti-allergy patents in China mainly focus on well-known targets, such as histamine receptor and leukotrienes, which consist of 93% of patents for validated targets. Approximately 93% targeting diseases are bronchial asthma, allergic rhinitis and atopic dermatitis. Our analyzing results indicate that there are great opportunities for application of patents on development of novel anti-allergic compounds and modernization of TCM in China.
    Recent Patents on Inflammation & Allergy Drug Discovery 06/2010; 4(2):130-7.
  • Article: Analysis of patents on anti-allergic therapies issued in China from 1988 to 2008.
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    ABSTRACT: The prevalence of allergic diseases has increased dramatically in recent decades. Therefore, there is a pressing need for the development of effective anti-allergic services worldwide. However, little is known what anti-allergic products have been patented in China and what the potential drug candidates for patents are in China. To analyze the patents of anti-allergic products for the last 20 years and help pharmaceutical companies and individuals to understand the potential candidates for anti-allergic patents in China. Data were obtained from the People's Republic of China Country Intellectual Property Rights Bureau website and United States Patent and Trademark Office website. Results: A total of 789 anti-allergic patents have been granted in China during the past 20 years, which all focused on synthetic compounds, traditional Chinese medicines (TCM), combinations of synthetic compounds and TCM, biological products and medical apparatus. It appears that more and more effective therapeutic components of TCM rather than whole herbs have been patented in recent years and alteration of natural molecules to produce more therapeutically effective molecules has emerged as a novel trend for the modernization of TCM. The patents on synthetic anti-allergic compounds in China mainly focus on well-known targets, such as histamine receptor and leukotrienes, which consist of 93% of patents for validated targets. The number of anti-allergic patents applied in China is far lower than that in the US. Therefore, there are great opportunities for obtaining anti-allergic patents, particularly patents on active ingredients from TCM in China.
    Expert Opinion on Therapeutic Patents 06/2010; 20(6):727-37. · 3.57 Impact Factor
  • Article: Integrative genomic analyses on IL28RA, the common receptor of interferon-lambda1, -lambda2 and -lambda3.
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    ABSTRACT: Interferon (IFN)-lambdas, including INF-lambda1, -lambda2, and -lambda3, are a newly described group of cytokines distantly related to the type I IFNs and IL-10 family members. IFN-lambda1, -lambda2, and -lambda3 bind to the same receptor (known as IL28RA) to exert their antiviral, antitumor and immunomodulatory effects. Here, we identified IL28RA genes from the genome of human, chimpanzee, macaque, orangutan, mouse, horse, rat, dog, chicken, and found that only one IL28RA existed in each genome. All the identified IL28RAs are single-pass type I membrane proteins except chicken IL28RA. They belong to the type II cytokine receptor family and contain one fibronectin type-III domain. We found human IL28RA was expressed in lymphs, testes, lymphoma, teratocarcinoma, pediatric pre-B cell acute lymphoblastic leukemia, germinal center B cells, embryonic stem cells, fetal lung, and also expressed in bladder, blood and breast cancers, glioma, head and neck cancer and lung cancer tissues. Three tumor-related transcriptional factor binding sites (AP-2, c-Jun and P53) were identified within the 1.0-kb regions upstream of the transcriptional start site of human IL28RA. Meta-analysis of the prognostic value of IL28RA genes in various cancers found that the expression of IL28RA was indeed related to the cancer prognosis in certain cancers. The STAT1 binding sites in the promoter region of IL28RA implied a specific mechanism for the amplifying effects of IFN-lambdas. The LyF-1 binding sites in the promoter region of IL28RA imply that IFN-lambdas were involved in the differentiation of early B and T cells.
    International Journal of Molecular Medicine 05/2010; 25(5):807-12. · 1.98 Impact Factor
  • Article: Integrative genomic analyses on interferon-lambdas and their roles in cancer prediction.
    Liming Yang, Jifu Wei, Shaoheng He
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    ABSTRACT: Interferon (IFN)-lambdas, including IFN-lambda1, IFN-lambda2, and IFN-lambda3, are a newly described group of cytokines distantly related to the type I IFNs and IL-10 family members. Besides the antiviral activity, IFN-lambdas were reported to inhibit various tumor growths in vitro and in vivo. Herein, we identified IFN-lambda genes from the genome sequences of the human, chimpanzee, macaque, orangutan, mouse, rat and dog, and found that the locations and copy of a specific IFN-lambda varied in different genomes, not just the copy of IFN-lambdas. We found human IFN-lambdas were expressed in fetal retina, fetal brain and T cells by ESTs search. Moreover, IFN-lambdas were also found to express in bladder cancer, blood cancer, breast cancer, glioma, head and neck cancer and lung cancer tissues. Three tumor-related transcriptional factors (steroidogenic factor-1, Wilms tumor 1 and P53) binding sites were identified within the 1.0-kb regions upstream of the transcriptional start site of human IFN-lambdas. Meta-analysis of the prognostic value of IFN-lambda genes in various cancers showed that the expression of IFN-lambdas are indeed related to the cancer prognosis in certain types of cancer. It can be predicted that IFN-lambdas take part in the cancer development by the regulation of expression of IFN-lambdas related to the SF-1, P53 and WT-1.
    International Journal of Molecular Medicine 02/2010; 25(2):299-304. · 1.98 Impact Factor

Institutions

  • 2005–2013
    • Shantou University
      • Allergy and Inflammation Research Institute
      Shantou, Guangdong Sheng, China
  • 2012
    • General Hospital of Shenyang Military Region
      Shenyang, Liaoning, China
    • Hainan University
      Haikou, Hainan, China
  • 2009–2012
    • Hainan Medical College
      Haikou, Hainan, China
  • 2007–2012
    • Nanjing Medical University
      • • Clinical Research Center
      • • Department of Rheumatology
      Nanjing, Jiangsu Sheng, China
  • 2011
    • 301 Military Hospital
      Beijing, Beijing Shi, China
  • 2010
    • Huaiyin Normal University
      Beijing, Beijing Shi, China
  • 2001–2008
    • Southampton University Hospitals NHS
      Southampton, ENG, United Kingdom