Time filter

Source Type

Wang D.,Molecular Biology Research Center | Liu Y.,Xiamen University | Li Y.,Xiamen University | He Y.,Xiamen University | And 2 more authors.
Mediators of Inflammation | Year: 2017

The Gαq-containing G protein, an important member of G q / 11 class, is ubiquitously expressed in mammalian cells. Gαq has been found to play an important role in immune regulation and development of autoimmune disease such as rheumatoid arthritis (RA). However, how Gαq participates in the pathogenesis of RA is still not fully understood. In the present study, we aimed to find out whether Gαq controls RA via regulation of Th1 differentiation. We observed that the expression of Gαq was negatively correlated with the expression of signature Th1 cytokine (IFN-γ) in RA patients, which suggests a negative role of Gαq in differentiation of Th1 cells. By using Gαq knockout (Gnaq-/-) mice, we demonstrated that loss of Gαq led to enhanced Th1 cell differentiation. Gαq negative regulated the differentiation of Th1 cell by modulating the expression of T-bet and the activity of STAT4. Furthermore, we detected the increased ratio of Th1 cells in Gnaq-/- bone marrow (BM) chimeras spontaneously developing inflammatory arthritis. In conclusion, results presented in the study demonstrate that loss of Gαq promotes the differentiation of Th1 cells and contributes to the pathogenesis of RA. © 2017 Dashan Wang et al.


Seyedmajidi M.,Babol University of Medical Sciences | Shafaee S.,Molecular Biology Research Center | Siadati S.,University of Sfax | Khorasani M.,Research Committee | And 2 more authors.
Journal of Cancer Research and Therapeutics | Year: 2014

Many evidences showed that cyclooxygenase-2 (COX-2), an enzyme that catalyzes the synthesis of prostaglandins, has an important role in carcinogenesis. It has been observed in experimental models that selective COX-2 inhibitors suppress the formation of tumors including tongue carcinoma. The aim of this study was to investigate the immunohistochemical expression of COX-2 in oral squamous cell carcinoma (OSCC) compared to normal oral mucosa and oral dysplasia. Materials and Methods: A total of 60 paraffined blocks (20 cases of OSCC, 20 cases of oral epithelial dysplasia and 20 cases of normal oral mucosa were included in this study and immunohistochemical staining was done for COX-2 expression. From each sample, 5 high power fields were assessed to determine the percentage of stained cells and staining intensity. Immunoreactivity was obtained by multiplying the above two cases. Data were analyzed with using the Kruskal-Wallis test ANOVA, Mann-Whitney test and least significant difference and P < 0.05 was declared as significant. Results: High level of COX-2 expression was found in OSCC and dysplasia compared to normal mucosa. Furthermore, a positive correlation was found between COX-2 expression and severity of dysplasia. However, no significant difference between low grade and high grade tumors was found. Conclusion: The result of the present study supports from the role of COX-2 in carcinogenesis and progression of premalignant lesion to malignancy.


Li Y.,Xiamen University | Shi G.,Xiamen University | Wang D.,Molecular Biology Research Center | Wang Y.,Chengdu Medical College
Current Pharmaceutical Biotechnology | Year: 2014

Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by mild arthralgia to severe joint deformities. Long term management of these diseases with nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) is limited due to lack of efficacy and potential organ toxicity. Recently, the approval of injectable biologics, such as T cell inhibitors and TNF-α antagonist, has changed the treatment of moderate-to- severe psoriasis and PsA. Unlike NSAIDs and DMARDs, TNF-α antagonists not only provide unambiguous benefits for the skin and joints, but also prevent the progression of structural damage in peripheral joints. Biological agents in the treatment of PsA have broad prospects. More and more biological agents are being developed for the treatment of PsA. In the current review, we will discuss the progress of biological agents on PsA. © 2014 Bentham Science Publishers.


Ranjbar R.,Molecular Biology Research Center | Davari A.,Molecular Biology Research Center | Izadi M.,Health Research Center | Jonaidi N.,Health Research Center | Alavian S.,Baqiyatallah Medical Sciences University
Iranian Red Crescent Medical Journal | Year: 2011

Hepatitis B virus (HBV) infection, one of the major health priorities, accounts approximately for 350 million chronic cases and a global total of 33 million people were living with human immunodeficiency virus (HIV) in the world. Co-infection with HIV and the HBV presents a significant challenge to health care providers, with different prevalence rates in different parts of the world. It is important to screen all HIV infected individuals for HBV infection and reverse. Infection with HBV becomes more violent in patients co-infected with human immunodeficiency syndrome. HIV/HBV co-infected individuals are at increased risk of chronic hepatitis, cirrhosis, and hepatocellular carcinoma, and of experiencing HAART toxicity. In this review, the latest statistics on epidemiology of HIV, HBV and their co-infection has been presented along with prominent characteristics of HBV. Transmission routes which are the common between HBV and HIV are described and the most important ones are described according to the regional and age features. Also, there is a series of actions being performed once HBV infections occur to prevent HIV or to diagnose if the HBV-infected individuals are also infected with HIV. As in treatment case, some of the frequent treatment methods including applying interferon and using nucleoside and nucleotide analogues have been discussed. Finally, we would explain the new recommendations for treating patients who were co-infected with HBV and HIV, including staging HBV and HIV treatment, based on the stage of each disease. It also outlines the optimal treatment options, whether the patient is treated for HBV first, HIV first, or HIV and HBV together. ©Iranian Red Crescent Medical Journal.


Wang D.,Molecular Biology Research Center | Li Y.,Xiamen University | Liu Y.,Xiamen University | Shi G.,Xiamen University
Current Pharmaceutical Biotechnology | Year: 2014

The use of biologic agents has revolutionized the management of rheumatoid arthritis (RA) in the past two decades. These biologic agents directly target molecules and cells involved in the pathogenesis of RA. Biologic agents indeed lead to a better prognosis and clinical remission in patients with RA, especially in patients who are not well-controlled with traditional disease-modifying anti-rheumatic drugs (DMARDs). Currently, five TNF inhibitors (infliximab, etanercept, adalimumab, golimumab and certolizumab pegol), an IL-6 receptor antagonist (tocilizumab), an IL-1 receptor antagonist (anakinra), a B cell depleting agent (rituximab) and a T cell co-stimulation inhibitor (abatacept) have been approved for the treatment of RA. With the increased understanding of the pathogenic mechanisms of RA and advantages in manufacturing biotechnology of pharmaceutical companies, a series of novel biologic therapeutic approaches are being developed. In the present paper, we will summarize the biologic agents currently available to treat RA, and the prospective biologic therapies that might be used in the management of RA in future. © 2014 Bentham Science Publishers.


Wang D.,Molecular Biology Research Center | Zhang Y.,Luzhou Medical College | He Y.,Xiamen University | Li Y.,Xiamen University | And 2 more authors.
Immunology and Cell Biology | Year: 2014

We have previously reported that Gαq, the α subunit of the Gq protein, had important roles in dendritic cell migration, B-cell survival and autoimmunity. In this study, we showed that the deficiency of Gαq led to enhanced T-cell survival. Cultured Gnaq-/- T cells exhibited survival advantages both in medium alone and in the presence of anti-CD3 stimulation. Gnaq-/- T cells still exhibited a survival advantage when they were cultured in the presence of interleukin (IL)-2 or IL-7. Gnaq-/- T cells were more resistant to activation-induced cell death (AICD) in vitro. The survival advantage of Gnaq-/- T cells was further confirmed by transferring T cells into syngeneic hosts in vivo. Gαq deficiency might promote T-cell survival by upregulated Bcl-x L expression and downregulated Fas and FasL expressions. Furthermore, upon T-cell receptor (TCR) ligation, Akt activity was increased in Gnaq-/- T cells in comparison with wild-type (WT) T cells. The survival advantage of Gnaq-/- T cells was significantly attenuated after adding Akt inhibitor. Taken together, our data demonstrated a negative role of Gαq in regulating T-cell survival. © 2014 Australasian Society for Immunology Inc.


Wang D.,Molecular Biology Research Center | Li Y.,Xiamen University | Liu Y.,Xiamen University | He Y.,Xiamen University | Shi G.,Xiamen University
PLoS ONE | Year: 2016

Rheumatoid arthritis (RA) is a chronic, systematic autoimmune disease that mainly affects joints and bones. Although the precise etiology is still unknown, Th17 cell is being recognized as an important mediator in pathogenesis of RA. VSTM1-v2 is a novel cytokine which has recently been reported to promote the differentiation of Th17 cells. This study is performed to study whether VSTM1-v2 can be recognized as a biomarker of RA, and is correlated to IL-17 expression. We obtained peripheral blood mononuclear cells (PBMCs) from 40 patients with RA and 40 age- and sex-matched healthy controls by standard Ficoll-Paque Plus density centrifugation. The mRNA expression levels of VSTM1-v2 and IL-17A in PBMCs were detected by real time-PCR. Disease activity parameters of RA were measured by routine methods. Our results showed that VSTM1-v2 mRNA expression in PBMCs from RA patients was significantly increased in comparison of that in healthy individuals. The VSTM1-v2 mRNA expression level was positively correlated with IL-17A mRNA expression level, DAS28, CRP and ESR, but was not correlated to RF, Anti-CCP or ANA. VSTM1-v2 might be a biomarker of RA and a novel factor in the pathogenesis of RA. © 2016 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Liu Y.,Xiamen University | Wang D.,Molecular Biology Research Center | Li F.,Chongqing Medical University | Shi G.,Xiamen University
Immunology and Cell Biology | Year: 2015

Gαq, the α-subunit of Gq protein, is ubiquitously expressed in mammalian cells. It initially attracted attention for its physiological significance in cardiovascular system. In recent years, studies have also indicated the important roles of Gαq in regulating immunity, supplying us a new insight into the mechanism of immune regulation. T helper type 17 (Th17) cells are potent inducers of tissue inflammation. Many studies have shown that Th17 cells are major effector cells in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions such as rheumatoid arthritis (RA). One of our previous studies has shown that Gαq negatively controls the disease activity of RA. However, how Gαq controls the pathogenesis of autoimmune disease is not clear. Whether this effect is via the regulation of Th17 differentiation is still not known. We aimed to find out the role of Gαq in control of Th17 differentiation. We investigated the relationship between Gαq and Th17 in RA patients. We then investigated the mechanism of how Gαq regulated Th17 differentiation by using Gnaq-/- mice. We observed that the expression of Gαq was negatively associated with interleukin-17A expression in RA patients, indicating that Gαq negatively controlled the differentiation of Th17 cells. By using Gnaq-/- mice, we demonstrated that Gαq inhibited the differentiation of Th17 cell via regulating the activity of extracellular signal-regulated kinase-1/2 to control the expression of STAT3 (signal transducer and activator of transcription 3) and RORα (RAR-related orphan receptor-α). These data suggest the possibility of targeting Gαq to develop a novel therapeutic regimen for autoimmune disease.


PubMed | Molecular Biology Research Center, Chongqing Medical University and Xiamen University
Type: Journal Article | Journal: Immunology and cell biology | Year: 2015

Gq, the -subunit of Gq protein, is ubiquitously expressed in mammalian cells. It initially attracted attention for its physiological significance in cardiovascular system. In recent years, studies have also indicated the important roles of Gq in regulating immunity, supplying us a new insight into the mechanism of immune regulation. T helper type 17 (Th17) cells are potent inducers of tissue inflammation. Many studies have shown that Th17 cells are major effector cells in the pathogenesis of many experimental autoimmune diseases and human inflammatory conditions such as rheumatoid arthritis (RA). One of our previous studies has shown that Gq negatively controls the disease activity of RA. However, how Gq controls the pathogenesis of autoimmune disease is not clear. Whether this effect is via the regulation of Th17 differentiation is still not known. We aimed to find out the role of Gq in control of Th17 differentiation. We investigated the relationship between Gq and Th17 in RA patients. We then investigated the mechanism of how Gq regulated Th17 differentiation by using Gnaq(-/-) mice. We observed that the expression of Gq was negatively associated with interleukin-17A expression in RA patients, indicating that Gq negatively controlled the differentiation of Th17 cells. By using Gnaq(-/-) mice, we demonstrated that Gq inhibited the differentiation of Th17 cell via regulating the activity of extracellular signal-regulated kinase-1/2 to control the expression of STAT3 (signal transducer and activator of transcription 3) and ROR (RAR-related orphan receptor-). These data suggest the possibility of targeting Gq to develop a novel therapeutic regimen for autoimmune disease.


PubMed | Molecular Biology Research Center
Type: Journal Article | Journal: Minerva medica | Year: 2015

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic inflammation of joint synovial tissue and subsequent destruction of associated bone, cartilage and soft tissues. RA is commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs), traditional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids and biologic inhibitors of TNF, IL-1, IL-6, T cells and B cells. The use of these drugs especially biological agents has greatly improved the treatment of RA. Although the pathogenesis of RA remains unclear, T-cell mediated immune response is considered as a critical contributor in RA initiation and progression. It has been hypothesized that arthritogenic T cells (autoreactive T cells) escaping negative selection can recognize arthritogenic antigens and lead to autoimmunity and tissue destruction. Due to the important role of autoreactive T cells in the mechanisms of RA, they might be a novel therapeutic target. Many vaccines targeting autoreactive T cells which can establish immunological self tolerance have been developed. The efficacy of these vaccines has been justified in experimental models of RA and clinical trials. Inhibition of autoreactive T cell response by vaccination might provide a new treatment opinion in RA.

Loading Molecular Biology Research Center collaborators
Loading Molecular Biology Research Center collaborators