Original Article
Shamsi Noorpisheh Ghadimi; Shirin Farjadian; Gholam Reza Hatam; Mehdi Kalani; Bahador Sarkari
Abstract
Background: Toll like receptors play a major role in immune responses against Leishmania parasites. Objective: To evaluate the efficacy of vaccination with live attenuated L. major and TLR4 agonist in protection against L. major infection. Methods: Attenuated L. major was prepared by continuous sub-culturing ...
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Background: Toll like receptors play a major role in immune responses against Leishmania parasites. Objective: To evaluate the efficacy of vaccination with live attenuated L. major and TLR4 agonist in protection against L. major infection. Methods: Attenuated L. major was prepared by continuous sub-culturing of the parasite. A total of 90 mice were assigned to 9 groups including 6 groups of BALB/c (G1-6) and 3 groups (G7-9) of C57BL/6 mice. Group 1 was the control groups, group 2 received the wild-type L. major promastigotes, group 3 the attenuated line, group 4 the TLR4 agonist, group 5 the wild-type L. major and TLR4 agonist, and group 6 the attenuated line along with TLR4 agonist. Group 7 was control, group 8 received wild-type L. major and group 9 the wild-type along with TLR4 agonist. Vaccinated mice were then challenged with wild-type of L. major. Lesion size, parasite burden, and the expression levels of IL-4, IFN-γ, IL-2, 1L-17A, IL-10, TGF-β and TLR4 were evaluated before the challenge while parasite burden and lesion size were evaluated. Results: Vaccinated mice with a TLR4 agonist or attenuated L. major plus TLR4 agonist produced the highest levels of IFN-γ, IL-2, and IL-17A. Post-challenge analysis revealed that mice vaccinated with the attenuated line along with TLR4 agonist displayed the lowest lesion size and parasite load. These mice developed a predominant Th1 immune response. Conclusion: Vaccination with the attenuated L. major along with TLR4 agonist promotes a Th1-mediated immune response which leads to the protection of BALB/c mice against L. major infection.
Original Article
Gege Li; Jiahui Pan; Qiuling Tang; Xinchan Liu; Liuran Wang; Yang Meng; Weixian Yu
Abstract
Background: C5areceptor antagonistPMX205 is a synthetic hexapeptidecapable of blocking C5a-C5a receptor (C5aR) axis by simulating C5a active C-terminal amino acid residues. This hexapeptide presents good anti-inflammatory effects in a myriad inflammation models. The anti-inflammatory effect of PMX205 ...
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Background: C5areceptor antagonistPMX205 is a synthetic hexapeptidecapable of blocking C5a-C5a receptor (C5aR) axis by simulating C5a active C-terminal amino acid residues. This hexapeptide presents good anti-inflammatory effects in a myriad inflammation models. The anti-inflammatory effect of PMX205 on periodontitis is yet to be fully fathomed. Objective: To examine the anti-inflammatory effects of PMX205 on RAW264.7 murine macrophages exposed togingipain extracts and Porphyromonas gingivalis (P. gingivalis). Methods: MTT assay was carried out so as to specify the cytotoxicity of PMX205. RAW264.7 cells were co-cultured in vitro with gingipain extracts or P. gingivalis to simulate the periodontitis inflammatory milieu. Real-time quantitative PCR, ELISA and Griess assay were performed in order to detect tumor necrosis factor-α (TNF-α), IL-6, IL-23, nitric oxide (NO), IL-10, transforming growth factor-β1 (TGF-β1), andarginase-1 (Arg-1). Furthermore, phagocytosis assay was done to evaluate the phagocytic capacity of RAW 264.7 cells. Finally, western blot analysis was conducted to evaluate myeloid differentiation factor 88 (MyD88). Results: PMX205 increased the expression levels of bacteriostatic substances (NO and IL-23) and anti-inflammatory cytokines (TGF-β1, IL-10 and Arg-1); however, it reduced the expression levels of proinflammatory cytokines TNF-α and IL-6once RAW 264.7 macrophages were stimulated via gingipain extracts or P. gingivalis. In addition, PMX205 promoted the macrophage phagocytosis and down-regulated protein expression of MyD88. Conclusion: PMX205 has recognizable anti-inflammatory effects in RAW 264.7 cell inflammation model, a finding which probably opens doors to future investigations on new targets for the prevention and treatment of chronic periodontitis.
Original Article
mahdi aminikhah; Mir Saeed Yekaninejad; M.Hosein Nicknam; Farideh Khosravi; Mehrnaz naroei nejad; Bita Ansaripour; batol moradi; Behrouz Nikbin; Aliakbar Amirzargar
Abstract
Background: The high polymorphism in the human leukocyte antigen (HLA) genes can be used as an identity of individuals to compare with other populations. This extreme polymorphism in the HLA system is accountable for the differences in alleles and haplotypes among ethnic groups, populations, and the ...
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Background: The high polymorphism in the human leukocyte antigen (HLA) genes can be used as an identity of individuals to compare with other populations. This extreme polymorphism in the HLA system is accountable for the differences in alleles and haplotypes among ethnic groups, populations, and the inhabitants of many regions. Objective: To define the frequency of HLA alleles and haplotypes among the Sistanis, Sistani/Zaboli population in Iran. Methods: In this study, genotyping of class I (A, B, C) and class II HLA (DRB1, DQA1, DQB1) loci were determined in 90 unrelated Iraninan Sistani people and the results were compared with 474,892 HLA chromosomes from a diverse worldwide population. Results: The highest frequently observed alleles in this study were A*02:01, B*35:01, C*12:03, C*06:02, DRB1*11, DQA1*05:05, and DQB1*03:01. Furthermore, the most frequent 3-locus haplotypes were A*02:01-B*50:01*C*06:02, DRB1*11-DQB1*03:01-DQA1*05:05, and A*02:01-B*50:01-DRB1*07. The most occurring 4-locus haplotypes were A*02:01-B*50:01-C*06:02-DRB1*07 and A*02:01-B*50:01-DRB1*07-DQB1*02:01. A*02:01-B*50:01-C*06:02-DRB1*07-DQB1*02:01 and A*02:01-B*50:01-C*06:02-DRB1*07-DQB1*02:01-DQA1*02:01 were determined to be the predominant 5- and 6-locus haplotypes, respectively. The heat maps and multiple correspondence analyses based on the frequency of HLA alleles showed that Sistanis share a common genetic inheritance with other Iranian ethnic groups such as the people from Yazd and Fars except some differences with Baluchis, Iranian Jews, Lurs of Kohgiluyeh/Buyerahmad, and Arabs of Fars, which may arise from the admixture of these groups or with foreign subgroups over centuries, and also a close relatedness with some European populations. Conclusion: These data could be useful for finding better donor matches for organ transplantation among Sistanis or other related Iranian ethnic groups, epidemiological studies of HLA-associated diseases, handling HLA genomics and mapping the migration pattern of different ethnic group.
Original Article
yunlong zhuang; xixi li; huicong xu; hui ye; di sun; xiangzhng liu; Guijie Ren
Abstract
Background: Entecavir (ETV) is commonly used to treat chronic hepatitis B (CHB) in China. However, certain percentages of e-Antigen (HBeAg) positive CHB patients do not respond to ETV therapy. Objective: To investigate whether the killer immunoglobulin-like receptor (KIR) genes were associated with seroconversion ...
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Background: Entecavir (ETV) is commonly used to treat chronic hepatitis B (CHB) in China. However, certain percentages of e-Antigen (HBeAg) positive CHB patients do not respond to ETV therapy. Objective: To investigate whether the killer immunoglobulin-like receptor (KIR) genes were associated with seroconversion in HBeAg positive CHB responder patients treated with ETV. Methods: Polymerase chain reaction with sequence-specific primers (PCR-SSP) method was performed to genotype KIR genes in 200 healthy controls and 198 HBeAg-positive CHB patients which 59 were defined as the complete response group (CRG) to the treatment with ETV and 139 were defined as null or partial response group (NPRG). Results: The frequencies of KIR2DS2 and KIR2DS3 were significantly higher (P=0.030, OR=1.57，95%CI=2.36-1.05 and P=0.018, OR=1.773，95%CI=2.77-1.13, respectively), while, the frequencies of KIR2DL3, KIR2DS1 and KIR3DS1 were significantly lower (P=0.038, OR=0.525, 95%CI=0.96-0.29,and P=0.031, OR=0.640, 95%CI =0.95-0.43, and P=0.035, OR=0.641, 95%CI =0.96-0.43, respectively) in HBeAg-positive CHB patients than those in healthy controls. The frequency of KIR2DS3 gene was significantly higher in NPRG than that in CRG (P=0.018, OR=0.402, 95%CI=0.83-0.20). The frequencies of KIR2DL3 and KIR3DS1 genes were significantly higher in CRG than those in NPRG (P=0.019, OR=3.625, 95%CI=10.83-1.21 and P=0.041, OR=1.949, 95%CI=3.65-1.04, respectively). Conclusion: Patients with KIR2DS3 might have negative responses to anti-HBV therapy with ETV and patients with KIR2DL3 and KIR3DS1 might have advantage in the therapy with ETV.
Original Article
Yan Tan; Si-Wei Tan; Bo-Ya Fan; Lei Li; Yuan-Guo Zhou
Abstract
Background: Hemin is an important sterile component that induces a neuroinflammatory response after intracerebral hemorrhage, in which NLRP3 inflammasome activation has also proved to be involved. Although microglial activation acts as a key contributor in the neuroinflammatory response, the relationship ...
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Background: Hemin is an important sterile component that induces a neuroinflammatory response after intracerebral hemorrhage, in which NLRP3 inflammasome activation has also proved to be involved. Although microglial activation acts as a key contributor in the neuroinflammatory response, the relationship between hemin and NLRP3 in microglia remains poorly understood. Objective: To investigate whether or not hemin regulates microglia-mediated secondary injury through activating the NLRP3/caspase-1 signaling pathway in microglia. Methods: In this study, N9 microglial cells were treated with hemin, and subsequently used to detect the production of caspase-1 p10 and NLRP3 inflammasome assembly. An ELISA was subsequently performed to measure the secretion of IL-1β. Results: It was found that the production of activated caspase-1 was dose- and time-dependent with regards to hemin. Moreover, hemin was observed to be capable of inducing the assembly of the NLRP3 inflammasome without any increase in IL-1β. Similarly, the supernatant of hemin-treated primary microglial cells did not increase in IL-1β secretion. Furthermore, hemin-induced NLRP3 inflammasome activation did not significantly affect pyroptosis. Conclusion: Hemin is a potential sterile danger signal molecule that can induce inflammasome activation without directly mediating inflammation damage on microglia.
Original Article
Muhammad Hussain; Jiangshan Xiao; Yixuan Zhang; Peng Chen; Hongwu Du
Abstract
Background: Ribonucleoproteins particles that form the spliceosomes are among the most frequently targeted molecules of the autoimmune response. In the last few years, autoantibodies against all A/B hnRNP proteins have been found in the sera of patients with rheumatoid arthritis (RA), systemic lupus ...
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Background: Ribonucleoproteins particles that form the spliceosomes are among the most frequently targeted molecules of the autoimmune response. In the last few years, autoantibodies against all A/B hnRNP proteins have been found in the sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and serve as diagnostic markers for several rheumatic diseases. However, the functional role of hnRNP C1/C2 in autoimmune diseases is still not clearly understood. Objective: To identify hnRNP C1/C2 as an autoantigen in patients with Behcet’s Disease (BD). Methods: First, HaCaT and EA.hy926 cells were cultured and RNA was extracted. Second, amplification of the corresponding gene by RT-PCR, cloning, and purification techniques was applied to acquire the recombinant protein hnRNP C1/C2. Third, the target protein band was excised from gel electrophoresis, digested with trypsin, and analyzed by (MALDI-TOF/). Finally, Western blotting and ELISA were performed to verify the immunoreactivity of BD serum with recombinant hnRNPC1/C2. Results: Results demonstrated that the reactivity of BD serum against recombinant hnRNP C1/C2 protein was significantly higher as compared to healthy control (P<0.001). Conclusion: hnRNP C1/C2 can be considered as a self antigen which might be involved in BD pathology in Hans Chinese population.
Original Article
Yolanda Cataño Cañizalez; Edith Uresti Rivera; Rocio Garcia Jacobo; Diana Portales Perez; Yadira Bastian; J Rodriguez Rivera; Roberto Gonzalez Amaro; Jose Enciso Moreno; Mariana Garcia Hernandez
Abstract
Background: Chronic inflammation has critical role in Type 2 diabetes (T2D), in which IL-1β contributes in insulin resistance and beta cell dysfunction. The activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the release of active form of IL-1β. Objective: To evaluate ...
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Background: Chronic inflammation has critical role in Type 2 diabetes (T2D), in which IL-1β contributes in insulin resistance and beta cell dysfunction. The activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the release of active form of IL-1β. Objective: To evaluate AIM2 expression and activation as well as circulating mtDNA levels in T2D patients. Methods: AIM2 expression was analyzed by flow cytometry, it’s activity was assessed by measuring in vitro release of IL-1β induced by Poly (dA:dT), and mtDNA copy number was determined by quantitative real-time polymerase chain reaction. Results: Increased percent of AIM2+ cells were detected in monocytes from patients with T2D. Moreover, increased levels of IL-1β in monocytes cultures from T2D patients compared to healthy controls were observed. Also, association between AIM2+ cells and hyperglycemia (r=0.4385, P=0.0095) and triglycerides levels (r=0.5112, P=0.002) and waist-hip ratio (r=0.4710, P=0.0049) were detected. Likewise, the mtDNA copy number was augmented in T2D patients compared to control group. The mtDNA copies number was associated with body mass index (r=0.4231, P=0.0008) and TNF-α levels (r=0.5231, P=0.0005). In addition, increased levels of IL-12p70, TNF-a, IL-10, IL-6, IL-8 and IL-1β were detected in a serum from T2D patients. Conclusion: These results suggest the involvement of AIM2 and mtDNA in the inflammatory process seen in T2D.
Short Paper
adel ebrahimpour; Ahamadreza Mirbolook; mohammadali okhovatpour; mohammadreza sajadi; kamyar makvandi; mohamad sadegh mousavi; sepehr saghari; mehrdad sadighi
Abstract
Background: Interleukin 6 (IL-6) functions as both a pro-inflammatory cytokine and an anti-inflammatory cytokine. Objective: To evaluate the levels of IL-6 in patients with multiple organ dysfunction syndrome (MODS). Methods: Level of IL-6 was assessed and recorded for 14 days subsequent to the injury ...
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Background: Interleukin 6 (IL-6) functions as both a pro-inflammatory cytokine and an anti-inflammatory cytokine. Objective: To evaluate the levels of IL-6 in patients with multiple organ dysfunction syndrome (MODS). Methods: Level of IL-6 was assessed and recorded for 14 days subsequent to the injury in 161 multiple trauma patients. MODS were diagnosed using Marshal Score. Injury Severity Scoring (ISS) was measured for all patients. Results: The results of this study indicated that there was a significant relationship between the level of IL-6 and ISS on the post trauma days number one and two (P=0.0001). The high level of IL-6 on the post trauma day number 2 was associated with high mortality rate. Conclusion: Our study suggests the second day as the golden time for measuring the serum levels of IL-6. These findings warn us to take more health care actions in patients with higher serum levels of IL-6 on the second day.
