Original Article
Bahareh Zand; Samaneh Arab; Nasim Kheshtchin; Abazar Arabameri; Mahboubeh Ashourpour; Davoud Asemani; Ehsan Sharif-Paghaleh; Farshid Noorbakhsh; Jamshid Hadjati
Abstract
Background: Mathematical modeling offers the possibility to select the optimal dose of a drug or vaccine. Considerable evidence show that many bacterial components can activate dendritic cells (DCs). Our previous report showed that multiple doses of DCs matured with Listeria monocytogenes led to tumor ...
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Background: Mathematical modeling offers the possibility to select the optimal dose of a drug or vaccine. Considerable evidence show that many bacterial components can activate dendritic cells (DCs). Our previous report showed that multiple doses of DCs matured with Listeria monocytogenes led to tumor regression whereas multiple doses of CpG-matured DCs affected tumor reversely. Objective: To assess a combined pattern of DC vaccination proposed by a mathematical model for tumor regression. Method: WEHI164 cells were inoculated subcutaneously in the right flank of BALB/c mice. Bone marrow-derived DCs were matured by Listeria monocytogenes and CpG motifs. DCs were injected using specific patterns and doses predicted by mathematical modeling. Effector cell-mediated cytotoxicity, gene expression of T cell-related transcription factors, as well as tumor growth and survival rate, were assessed in different groups. Results: Our study indicated that the proposed mathematical model could simulate the tumor and immune system interaction, and it was verified by decreasing tumor size in the List+CpG group. However, comparing the effect of different treatment modalities on Th1/Treg transcription factor expression or cytotoxic responses revealed no advantage for combined therapy over other treatment modalities. Conclusions: These results suggest that finding new combinations of DC vaccines for the treatment of tumors will be promising in the future. The results of this study support the mathematical modelling for DC vaccine design. However, some parameters in this model must be modified to provide a more optimized therapy approach.
Original Article
Haibai Sun; Jiaqing Liu; Ranran Feng; Chunyan Wang; Yuming Li; Xiao Wang
Abstract
Background: Follicular helper T lymphocyte (Tfh) promotes antibody production by B lymphocytes in various diseases, including Pulmonary Tuberculosis (PTB). Objective: To explore the potential role of Tfh cells and assess the expression level of PD-1, and IL-21 in PTB. Methods: 54 newly diagnosed ...
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Background: Follicular helper T lymphocyte (Tfh) promotes antibody production by B lymphocytes in various diseases, including Pulmonary Tuberculosis (PTB). Objective: To explore the potential role of Tfh cells and assess the expression level of PD-1, and IL-21 in PTB. Methods: 54 newly diagnosed smear-positive PTB, 27 people with latent tuberculosis (LTB) and 27 healthy controls (HC) were enrolled. The PTB group was further divided based on the range of lung field involved (focus number>=3, PTB-X3; <3, PTB-X2). After 6-month therapy, sputum smear (positive, PTB-SP; negative, PTB-SN) or imaging examinations (lesion reduction significant, PTB-os; insignificant, PTB-s) were used to evaluate the conditions of PTB patients. Blood samples were collected from PTB group at month six. CD4+CXCR5+Tfh, and its subsets, CD4+CXCR5+PD-1+Tfh and CD4+CXCR5+ICOS+Tfh in peripheral blood mononuclear cells (PBMCs) were detected. Serum IL-21 concentrations were measured. Results: The frequencies of CD4+CXCR5+Tfh, CD4+CXCR5+ICOS+Tfh and CD4+CXCR5+PD-1+Tfh were higher in PTB group than in HC. IL-21, IL-4 and IFNγ concentrations were significantly higher in PTB group than in HC. The proportion of CD4+CXCR5+Tfh in PTB-X2 was lower than in PTB-X3 group. CD4+CXCR5+PD-1+Tfh proportion in PTB-X2 was lower than that in the PTB-X3. After treatment, CD4+CXCR5+Tfh proportion was significantly lower in the PTB-SN group. CD4+CXCR5+Tfh was lower in the PTB-os group than in the PTB-s group. However, the CD4+CXCR5+PD-1+Tfh and cytokine concentrations of IL-21 were not different. Conclusions: CD4+CXCR5+Tfh level might predict the sputum results, and lesion decrease rate while CD4+CXCR5+PD-1+Tfh subset and IL-21 were not associated with sputum results or lesion decrease after treatment.
Original Article
Jing Sun; Jiabao Zhao; Chao Sun; Yu ting Zhu; Ping Zhou; Shu xian Gao; Ying-Ao Fan; Hao-Yuan Jiang; Qing-Wei Zheng; Jun-Chang Guan
Abstract
Background: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype. Objective: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression ...
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Background: The methylation of IFN-γ and IL-4 genes is regarded as an epigenetic regulation that maintains the Th1 or Th2 phenotype. Objective: To explore the influence of prenatal administration of the staphylococcal enterotoxin B (SEB) in pregnant rats, on the IFN-γ or IL-4 expression in the offspring spleen. Methods: The SEB or PBS was administered intravenously to pregnant rats on the embryo-day 16. After normal delivery, the spleens from the fifth-day neonates and adult offspring were isolated under anesthesia. Quantitative PCR, western blot, ELISA and MeDIP-qPCR were applied to determine the levels of the splenic IFN-γ or IL-4 mRNAs, their protein levels, and methylation status, respectively. Results: Prenatal administration of the SEB in pregnant rats decreased the levels of the splenic IFN-γ and IL-4 proteins in neonates, but increased their mRNA levels. However, prenatal administration of the SEB significantly augmented both mRNA and protein levels of the IFN-γ and IL-4 in the adult spleen. In addition, the prenatal SEB administration decreased the methylation of the splenic IFN-γ and IL-4 in adult but not neonatal offspring. Conclusion: The prenatal administration of SEB in pregnant rats can cause a mixed Th1 and Th2 cytokines response in the offspring spleen, and alter the cytokine expression of the Th1 and Th2 via decreasing the methylation in adult but, not neonatal offspring spleen.
Original Article
Lidan Luo; Yuan Fang; Qi Yuan; Jinmao Liao; Zheng Zhang
Abstract
Background: Pyroptosis is a programmed cell death related to caspase-1, accompanied by the secretion of pro-inflammatory cytokines. Objectives: To explore the effects of LPS on the P2X7R/NLRP3 pathway in macrophages, and hepatocytes pyroptosis in mice. Methods: LPS was used to establish an animal ...
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Background: Pyroptosis is a programmed cell death related to caspase-1, accompanied by the secretion of pro-inflammatory cytokines. Objectives: To explore the effects of LPS on the P2X7R/NLRP3 pathway in macrophages, and hepatocytes pyroptosis in mice. Methods: LPS was used to establish an animal model of the acute liver injury. The macrophage RAW264.7 was induced by LPS to establish a cell model. The P2X7R inhibitor A438079 and agonist BZATP were added. RAW264.7 was co-cultured with AML-12 cells. Pyroptosis and the ratio of CD11b+CD86+/CD11b+CD206+ were analyzed by flow cytometry. ELISA, WB, and qRT-PCR were applied to analyze factors involved in the P2X7R/NLRP3 pathway. Results: LPS induced liver damage in mice, promoted cell pyroptosis and increased the levels of IL-18, IL-1β, ALT, AST, and TBIL. P2X7R, GSDMD, and GSDMD-N expressions also increased in the LPS group. LPS induced macrophage activation in vivo. NLRP3, ASC, P2X7R, and caspase-1 expressions in vitro promoted. ELISA confirmed that the IL-1β and IL-18 levels repressed in the BZATP (P2X7R agonist) group, while the trend was opposite in the A438079 (P2X7R inhibitor) group. LPS activated the P2X7R/NLRP3 pathway in macrophages. After RAW264.7 was co-cultured with AML-12 cells, the pyroptosis of AML-12 cells promoted but the proliferation decreased in the BZATP group. GSDMD and GSDMD-N expressions promoted in the BZATP group, while the trend was opposite in the A438079 group. Conclusion: LPS activated macrophages via P2X7R activation of NLRP3 and induced hepatocyte pyroptosis, which provided novel potential targets for the liver injury treatment.
Original Article
Dijiao Tang; Qi Tang; Long Zhang; Hongxu Wang
Abstract
Background: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE).The neutrophil to lymphocyte ratio (NLR) is a promising predictor and prognostic factor. An increased NLR is associated with a poor prognosis of several inflammatory diseases. Objective: ...
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Background: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE).The neutrophil to lymphocyte ratio (NLR) is a promising predictor and prognostic factor. An increased NLR is associated with a poor prognosis of several inflammatory diseases. Objective: To evaluate the value of NLR in the diagnosis and pre-assessment of the disease severity of LN. Methods: This retrospective study included 88 patients with LN, 51 SLE patients without kidney involvement, 79 patients with primary chronic nephritis (CN), and 52 healthy controls (HC). The differences among these four groups and diagnostic value of NLR for patients with LN were evaluated. Results: The NLR of patients with LN before treatment was significantly higher than that of the other three groups. NLR positively correlated with C-reactive protein (CRP), complement 3(C3), C4, and serum creatinine (SCr) (CRP: r=0.337, p=0.007; C3: r=0.222, p=0.042; C4: r=0.230, p=0.035; SCr: r=0.408, p <0.0001) but negatively correlated with total serum IgG (r=-0.226, p=0.041). The level of NLR increased with the severity of renal dysfunction NLR (area under the curve: 0.785, 95% CI: 0.708-0.862) was useful for the diagnosis of LN, and its optimal cut-off value was 5.44 (sensitivity: 65.9%, specificity: 86.3%). Conclusions: NLR would be useful for the diagnosis of LN and reflects the severity of renal dysfunction Therefore, evaluating NLR before treatment could help clinicians to identify potential renal involvement in patients with SLE and distinguish LN from CN.
Original Article
Saeid Taghiloo; Abolghasem Ajami; Reza Alizadeh-Navaei; Ehsan Zaboli; Hossein Asgarian-Omran
Abstract
Background: Several PI3K/Akt/mTOR pathway inhibitors and TLR agonists induce tumor cell death. However, the mechanisms of these therapeutic approaches in acute myeloid leukemia (AML) cells are still unknown. Objectives: To investigate the effects of BEZ235, as a dual inhibitor of PI3K and mTOR pathways, ...
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Background: Several PI3K/Akt/mTOR pathway inhibitors and TLR agonists induce tumor cell death. However, the mechanisms of these therapeutic approaches in acute myeloid leukemia (AML) cells are still unknown. Objectives: To investigate the effects of BEZ235, as a dual inhibitor of PI3K and mTOR pathways, and TLR7/8 agonist R848 on the expression and regulation of the immune inhibitory molecules in myeloid leukemia cells. Methods: WEHI-3 leukemia cells were incubated with dual PI3K and mTOR inhibitor BEZ235 and TLR7/8 agonist R848 for 48 hrs. Firstly, cell viability was assessed by MTT method. The semi-quantitative relative mRNA expression of Galectin-9 (Gal-9), PD-L1, PVR, and STAT3 was assessed according to HPRT as a housekeeping gene. Finally, the protein expression of phosphorylated STAT3 was evaluated by western blotting analysis. Results: WEHI-3 cells showed growth inhibition following treatment with BEZ235 and R848 whose combination exerted more proliferation arrest. The mRNA expression of Gal-9, PD-L1 and PVR immune checkpoint molecules significantly reduced in treated cells with BEZ235 and R848. Combined treatment indicated more reduction compared with the single treatment. Finally, the expression and phosphorylation of STAT3 were down-regulated after a single or dual treatment with BEZ235 and R848. Conclusion: Our results conclude that treatment with the combination of BEZ235 and R848 interferes with immune evasion mechanisms through STAT3-signaling pathway in WEHI-3 leukemia cells.
Original Article
Zeinab Amirkhani; Mehrosadat Alavi; Mehdi Kalani; Ali Alavianmehr; Shirin Farjadian
Abstract
Background: Thyroid cancer and radioactive iodine (RAI) ablation for postsurgical management may lead to uncontrolled inflammation. Objective: This study was intended to assess the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid ...
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Background: Thyroid cancer and radioactive iodine (RAI) ablation for postsurgical management may lead to uncontrolled inflammation. Objective: This study was intended to assess the prophylactic and therapeutic immunomodulatory effects of omega-3 fatty acids in patients with differentiated thyroid cancer (DTC). Methods: A total of 85 patients with DTC were allocated into two groups based on RAI dosage after thyroidectomy. Patients in each group were randomly distributed into three subgroups: G1 with RAI ablation only, G2 treated with omega-3 for 30 days before RAI ablation, and G3 treated with omega-3 for 30 days after RAI ablation. Fifteen healthy individuals were included as controls. Serum cytokine levels including IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, TNF-α and IFN-γ were determined by cytometric bead assay. Results: IL-4, IL-6, IL-21 and IL-22 levels in patients with DTC were higher than in the healthy controls. Regardless of RAI dosage, IL-6 showed an increasing trend after RAI ablation. IL-4, IL-22, and IL-17A remained at considerably higher levels than in the healthy controls after RAI ablation. Within-group comparisons showed a significant reduction in Th1+Th17/Th2+Th22 ratio in G2 patients 1 week after RAI ablation. Between-group comparisons showed increased IL-10 levels in G3 compared with G1 patients one week after high-dose RAI ablation. In G3, Th1+Th17/Th2+Th22 and Th1+Th17/Th2+Th9+Th22 ratios were remarkably lesser than in G2 patients 1 month after intermediate-dose RAI ablation. Conclusion: Our results showed better anti-inflammatory effects of omega-3 when it was used therapeutically after RAI ablation in patients with DTC than when it was used prophylactically before RAI.
Review Article
Zhi-Hui Wang; Yue Wu; Zi-Wei Dai; Yuan-Yuan Dong; Bin Wang
Abstract
This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in ...
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This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in allelic, recessive, dominant, homozygous, heterozygous, over-dominant models of IL-10-1082G/A and-592C/A gene locus as odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The correlation was not significant between -1082G/A polymorphism and HIV-1 susceptibility (allelic model (G vs. A: OR (95% CI)=0.968 (0.878-1.067)); recessive model (GG vs. AA+AG: OR (95% CI)=0.940, (0.771-1.146)); dominant model (GG+AG vs. AA: OR (95% CI)=0.967(0.846-1.106)); homozygous model (GG vs. AA: OR (95% CI)=0.971(0.780-1.209)); heterozygous model (AG vs. AA: OR (95% CI)=0.988(0.797-1.224)) and over-dominant model (GG+AA vs. AG: OR (95% CI)=0.969(0.781-1.201)). IL-10-592C/A polymorphism might be related to HIV-1 in allelic model, dominant model, homozygous model and heterozygous model (OR (95% CI)(0.796-0.965); OR (95% CI)=0.793(0.664-0.948); OR (95% CI)=0.755,(0.612-0.930); OR (95% CI)=0.820(0.679-0.991), respectively), but not to recessive model and over-dominant model (OR (95% CI)=0.882(0.770-1.010) and OR (95% CI)=1.009(0.897-1.148)).
Original Article
Wei Li; Lin Li; Lin He; Yun Du; Hai-Dong Fu; Zhao-Yang Peng; Wen-Qing Xiang; Jian-Hua Mao
Abstract
Background: Cytokines play a role in the progression of idiopathic-nephrotic syndrome (INS). Objectives: To investigate the association of different cytokine genes polymorphisms with INS incidence and response to steroid therapy in Chinese children. Methods: 182 children with INS and 100 healthy ...
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Background: Cytokines play a role in the progression of idiopathic-nephrotic syndrome (INS). Objectives: To investigate the association of different cytokine genes polymorphisms with INS incidence and response to steroid therapy in Chinese children. Methods: 182 children with INS and 100 healthy controls were enrolled in this study. Blood genomic DNAs were used to analyze20 single nucleotide polymorphisms (SNPs) in 8 cytokine genes includingIL-21, IL-18, IL-6, IFN-γ, IL-4, IL-10, IL-17F, IL-17A d by multi-PCR with next-generation sequencing. Results: Among 182 children with INS, 89 (48.6%) were steroid-sensitive (SS), 73 (39.9%) were steroid-dependent (SD) and 21 (11.5%) were steroid-resistant (SR). In 20 SNPs, IL-4-rs2243283 exhibited a significantly different genotype distribution between INS and the healthy controls (CC is a risk genotype: 66.5% of INS VS 51% of the control; OR=1.91, p=0.012). Patients carrying AG genotype (rs2275913, IL-17A) had a significantly higher risk of steroid-dependent response (69.1% of SD VS 46.4% of SS; OR=2.58, p=0.014). Similarly, patients carrying A allele of IL-10-rs1800872 (39.0% of SD VS 26.7% of SS; OR=1.76, p=0.018) and C allele of IL-10-rs1800896 (12.3% of SD VS 3.9% of SS; OR=3.44, p=0.004) had a higher risk of steroid-dependent response. However, none of these 20 SNPs showed a significant difference between SS group and SR group. Conclusion: Among the 20 cytokine gene SNPs, IL-4-rs2243283 might increase the susceptibility to INS in Chinese children; rs2275913 of IL-17A, rs1180972, and rs1800896 of IL-10 show association with the steroid -response in Chinese INS children.
Case Report
Yu Zhang; Li Zhang; Zhen zhen Wu; Jianping Tang; Xuan Wang
Abstract
A male patient had suffered miscellaneous ocular symptoms for 20 years with auricular dysmorphosis and was diagnosed with Relapsing Polychondritis (RP) in the ear, nose, joints, and costal cartilage. The patient lost his vision owing to recurrent ocular symptoms for decades. He presented an increased ...
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A male patient had suffered miscellaneous ocular symptoms for 20 years with auricular dysmorphosis and was diagnosed with Relapsing Polychondritis (RP) in the ear, nose, joints, and costal cartilage. The patient lost his vision owing to recurrent ocular symptoms for decades. He presented an increased IgA and was diagnosed with monoclonal gammopathy of undetermined significance (MGUS) and treated by prednisone and cyclophosphamide. His ocular symptoms relieved and serum IgA decreased after six months. In conclusion, RP is a systemic disease with a wide range of clinical symptoms and may lead to serious complications.
Case Report
Haibai Sun; Hongjie Li; Shuping Huang; Lixia Shi; Zhiyan Xing; Jun Shen
Abstract
COVID-19 is a new acute respiratory infectious disease caused by a novel Coronavirus (2019-COV-2) infection. On November 26, 2021, the World Health Organization announced a new 2019-COV-2 variant strain Omicron (B.1.1.529). Omicron's emergence added further uncertainty to the outbreak. Here we report ...
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COVID-19 is a new acute respiratory infectious disease caused by a novel Coronavirus (2019-COV-2) infection. On November 26, 2021, the World Health Organization announced a new 2019-COV-2 variant strain Omicron (B.1.1.529). Omicron's emergence added further uncertainty to the outbreak. Here we report the first case infected with Omicron in China, a 17-year-old female student. In this paper, the clinical symptoms, laboratory and imaging examinations and treatment of the first Omicron-infected patient in China were analyzed. This report might provide a reference for the diagnosis and treatment of patients infected with Omicron strain across the world. The novel Coronavirus antibody tests were performed on the day of admission: IgM level was normal, novel Coronavirus antibody IgG was 132.666s /CO and IgG was 148.47s /CO on the 7th day of admission. IgG showed an increasing trend, which is consistent with the results of multiple novel Coronavirus non-Omicron strain infections.
