Review Article
Can Hu; Yizhi Zhang; Junjiang Liu; Yanyan You; Fanglong Wu; Hongmei Zhou
Abstract
Complementary and alternative medicine (CAM) includes a wide range of treatments that are gaining acceptance among the public. It is increasingly being recognized as a viable option for treating various diseases with minimal side effects. Common avenues of this therapy include herbal medicine, acupuncture, ...
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Complementary and alternative medicine (CAM) includes a wide range of treatments that are gaining acceptance among the public. It is increasingly being recognized as a viable option for treating various diseases with minimal side effects. Common avenues of this therapy include herbal medicine, acupuncture, physical exercise, aromatherapy, dietary therapy, and homeopathy etc. Macrophages are highly heterogeneous cells that play multiple regulatory roles. Practices such as herbal medicine, acupuncture, physical exercise, aromatherapy and dietary therapy exert curative effects by modulating the polarization status and the secretory phenotype of macrophages directly. Furthermore, herbal medicine, acupuncture, and physical exercise influence the crosstalk between macrophages and other types of cells, including cancer cells and T cells. Mechanistically, herbal medicine and acupuncture produce curative effects in diverse diseases, including inflammatory diseases and tumors, mainly by influencing the phosphorylation of signaling proteins in macrophages. Therefore, targeting macrophages offers theoretical support for advancing the scientific understanding of this therapy and aids in identifying potential therapeutic options. Hence, in this review, we systematically summarize the different regulations of macrophages in herbal medicine, acupuncture, physical exercise, aromatherapy, dietary therapy and homeopathy, and further highlight the therapeutic potential of targeting macrophages in complementary and alternative medicine.
Original Article
Ali Ariafar; Erfan Kohansal; Amirhassan Mousania; Zahra Faghih
Abstract
Background: Natural killer (NK) cells are crucial innate components in anti-tumor immunity. However, the clinical impacts and their phenotypes in bladder cancer (BC) remain unclear.Objective: To assess the clinical significance of NK cell subsets in tumor-draining lymph nodes of patients with BC.Methods: ...
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Background: Natural killer (NK) cells are crucial innate components in anti-tumor immunity. However, the clinical impacts and their phenotypes in bladder cancer (BC) remain unclear.Objective: To assess the clinical significance of NK cell subsets in tumor-draining lymph nodes of patients with BC.Methods: In a cross-sectional study, pelvic lymph nodes were obtained from 49 untreated patients with BC. Mononuclear cells were isolated and immunophenotyped using CD3, CD56, CD16, CD27, and CD11b markers. NK cells were then classified based on their expression patterns of CD56/CD16 (conventional) and CD27/CD11b (new).Results: On average, NK cells constituted 2.99±1.44% of the total lymphocytes in the draining lymph node of patients with BC. The CD56dim and regulatory NK subsets (CD27+CD11b+/-) were the predominant old and new NK, respectively. The NK cells significantly increased in patients with at least one involved node (LN+) compared with those with free nodes (LN-; p=0.022). Conversely, CD56dimCD16- subset significantly decreased in higher stages (p=0.032) and in tumors with muscle invasion (p=0.038). Significant variations were also observed in different T-stages (p<0.05). Regarding new classification, the frequency of CD11b+ regulatory NK cells was significantly lower in node-positive patients (p=0.025).Conclusion: These findings emphasize the dynamic nature of NK cell subsets in bladder cancer and their potential relevance in disease progression and management, suggesting potential implications for therapeutic strategies targeting these specific subsets.
Original Article
Soheila Yousefi; Pedram Basirjafar; Raziyeh Zandvakili; Javad Masoumi; Nahid Zainodini; Hossein Khorramdelazad; Mahsa Gheitasi; Abdollah Jafarzadeh
Abstract
Background: It is well-known that TH1 and Treg cells exert anti- and pro-tumorigenic activity, respectively. Thus, TH1 cell suppression together with Treg cell hyperactivation contribute to tumor development. Glycyrrhiza glabra (G. glabra) has various immunomodulatory and anti-tumorigenic properties.Objective: ...
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Background: It is well-known that TH1 and Treg cells exert anti- and pro-tumorigenic activity, respectively. Thus, TH1 cell suppression together with Treg cell hyperactivation contribute to tumor development. Glycyrrhiza glabra (G. glabra) has various immunomodulatory and anti-tumorigenic properties.Objective: To explore the impacts of G. glabra extract on different parameters related to TH1 and Treg cells using a breast cancer (BC) model.Methods: Four groups of Balb/C mice bearing 4T1 cell-induced BC were treated intraperitoneally with either saline or G. glabra extract at dosages of 50, 100 and 150 mg/kg (G. glabra-50, G. glabra-100, and G. glabra-150, respectively). After sacrificing animals on day 26, the frequency of splenic TH1 and Treg cells, the levels of serum IFN-γ, TGF-β, and IL-12, and intra-tumoral expressions of granzyme-B, T-bet, and FOXP3 were assessed.Results: Compared to untreated tumor control (UTC) group, treatment with G. glabra-50, G. glabra-100, or G. glabra-150 increased the survival rate, percentage of TH1 cells, and T-bet expression. Conversely, they reduced the percentage of Treg cells, and serum TGF-β levels. In comparison to the UTC group, treatment with G. glabra-50 and G. glabra-150 increased the serum IL-12 levels. Treatment with G. glabra-100 and G. glabra-150 boosted granzyme-B expression. Treatment with G. glabra-150 elevated IFN-γ levels, while treatment with G. glabra-50 decreased the FOXP3 expression. IL-12 levels were higher in mice treated with G. glabra-150 compared to those treated with G. glabra-100.Conclusion: Treatment of mice with BC using G. glabra extract improved survival rate, reduced tumor growth, and modulated T cell-mediated immune responses.
Original Article
Elham Safarzadeh; Vahid Asghariazar; Shohreh Pordel; Elham Baghbani; Asgar Fekri; Afsaneh Enteshari-Moghaddam
Abstract
Background: Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized not only by fibrosis and vasculopathy but also by inflammation. Previous studies have demonstrated monocyte involvement in SSc development, suggesting a role for immune dysfunction in SSc pathogenesis.Objective: To investigate ...
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Background: Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized not only by fibrosis and vasculopathy but also by inflammation. Previous studies have demonstrated monocyte involvement in SSc development, suggesting a role for immune dysfunction in SSc pathogenesis.Objective: To investigate the relationship between SSc’s clinical manifestations and altered levels of monocyte subpopulations.Methods: Twenty-six patients meeting the ACR/EULAR SSc criteria along with twenty healthy individuals as the control group, were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were obtained from heparinized blood samples of both the SSc patients and the control group. Subpopulations of monocytes were assessed based on HLA-DR, CD14, and CD16 expression using multi-color flow cytometry. The one-way ANOVA, Student’s t-test, and Mann-Whitney U test were employed for normally and non-normally distributed data. The Spearman correlation test was utilized to identify correlations between the variables.Results: The SSc patients showed a significant increase in the number of circulating peripheral blood monocytes (p<0.001). The percentage of CD16+ monocyte subpopulations was higher in the SSc cases compared to the control group. A significant decrease in the ratio of classic to non-classic monocytes was observed in SSc cases (7.43%) compared to the control group (52.09%, p<0.001). No association was observed between monocyte subpopulations and clinical characteristics of SSC.Conclusion: Our results showed an increase in the level of CD16+ monocytes in patients with SSc compared to healthy individuals. Further investigation is required to determine the clinical significance of this alteration.
Original Article
Aysan Jafari Harandi; Alireza Mirzaee Sedigh; Mitra Ataei; Sepideh Bayrami; Emran Esmaeilzadeh; Mohammad Hossein Sanati
Abstract
Background: The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such ...
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Background: The mechanisms of the function of interferon beta (IFN-β) and natalizumab (NTZ) in multiple sclerosis (MS) patients have not yet been fully understood. Over the past decades, many studies have been conducted to evaluate gene expression changes especially regulatory non-coding RNAs such as microRNAs (miRNAs) following therapy in MS patients.Objective: To assess the changes in the expression of miR-20b in MS patients treated with IFN-β or NTZ.Methods: Sixty patients with relapsing-remitting MS (RRMS) and 30 healthy controls (HCs) were enrolled. The patients were categorized as untreated (N=20), IFN-β-treated (N=20), and NTZtreated (N=20). For the expression analysis, real-time PCR was performed on the whole blood. The bioinformatic tools were applied for signaling pathways enrichment analysis of miR-20b targetome.Results: The relative expression of miR-20b was significantly downregulated in the untreated patients compared with the HCs (-1.726-fold, p<0.001), while IFN-β-treated and NTZ-treated patients showed no statistical difference compared with the HCs (0.733-fold, p=0.99 for IFN-β and 1.025-fold, p=0.18 for NTZ). This indicates the restoration of miR-20b expression to normal level in the treated patients. Additionally, in silico analysis demonstrated that the Jak–STAT signaling pathway is enriched with miR-20b targets (p<0.0001).Conclusion: Our findings suggest that the positive effects of IFN-β and NTZ in the RRMS patients could be potentially mediated by returning miR-20b expression to baseline.
Original Article
Narjes Soleimanifar; Sara Assaadiasl; Mohammed Sameer Al-Shammari; Abdol-Rahman Rostamian; Maryam Sadr; Sepideh Shahkarami; Hanieh Mojtahedi; Mohammad Hossein Nicknam
Abstract
Background: Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of ...
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Background: Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of autoimmune diseases such as AS pathogenesis. Objective: To investigate PD-1 gene expression and its epigenetic regulation by detecting methylated CpG islands in the regulatory sites of the gene. This will provide insight into the mechanisms involved in the disease. Methods: 30 AS patients and 30 healthy individuals were examined to detect the 16 CpG islands in intron 1 using bisulfite conversion and methylation-specific PCR technique. In addition, RNA samples were isolated from fresh peripheral blood mononuclear cells (PBMCs), and after complementary DNA (cDNA) synthesis, the expression level of the PD-1 gene was evaluated using Real-Time PCR. Results: The CpG islands located in the intronic zone of the PD-1 gene were hyper-methylated in both the patients with AS and the healthy controls. The gene expression of PD-1 was significantly downregulated in AS patients compared with the controls (p=0.017). A negative correlation between the Bath Ankylosing Spondylitis Disease Activity Index and PD-1 gene expression was also revealed. Conclusion: The low level of PD-1 gene expression is implicated in the pathogenesis of AS. However, in both groups, the methylation level of the intron 1 CpG islands of the PD-1 gene suggests that other regulatory mechanisms are more relevant to PD-1 gene expression than methylation in the intron.
Case Report
Heba M. Bahlol; Sohaila M. Khalil; Mohamed R. El-Shanshory; Mohamed L. Salem
Abstract
Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for β-thalassemia major in children. However, it often induces graft-versus-host-disease (GVHD), which is associated with complications. In the present study, we used cyclophosphamide (Cy) to treat a thalassemia patient ...
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Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for β-thalassemia major in children. However, it often induces graft-versus-host-disease (GVHD), which is associated with complications. In the present study, we used cyclophosphamide (Cy) to treat a thalassemia patient post-HSCT to reduce the adverse effects of GVHD. We monitored the numbers and phenotype of granulocytes. In this case study, an 11-year-old female patient, diagnosed with β-thalassemia major (Pesaro class II), was treated with Cy before and after HSCT with mobilized CD34+ cells. Both the relative and absolute granulocyte counts, as well as CD33+CD11b+ cell counts, increased significantly after HSCT until day 56. However, they suddenly began to decrease after day 56, accompanied by severe diarrhea, skin rash, and a decrease in bilirubin levels compared to day -12. Furthermore, compared to day -12, IL-22 levels increased until day 56, and then decreased, while IDO levels continued to rise after day 56. Our data suggest the potential use of IL-22 and IDO as biomarkers for GVHD assessment. It also indicates that Cy promotes HSCT reconstitution by increasing CD33+CD11b+ cells, which may play a crucial role in reducing GVHD risks. However, further studies are needed to elucidate the mechanism behind GVHD recurrence.
Letter To The Editor
Hineptch Daungsupawong; Viroj Wiwanitkit
Abstract
Dear EditorWe are writing to discuss the article titled “Comparative Immunogenicity and Neutralization Potency of Four Approved COVID-19 Vaccines in BALB/c Mice” (1). The study examined the immunogenicity and neutralization efficacy of four COVID-19 vaccines licensed in Iran in BALB/c mice. ...
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Dear EditorWe are writing to discuss the article titled “Comparative Immunogenicity and Neutralization Potency of Four Approved COVID-19 Vaccines in BALB/c Mice” (1). The study examined the immunogenicity and neutralization efficacy of four COVID-19 vaccines licensed in Iran in BALB/c mice. The vaccines included PastoCovac Plus, Sinopharm, SpikoGen, and Noora. The results showed that all four vaccines induced seroconversion in immunized animals and generated significant levels of anti-vaccine antibodies. Notably, PastoCovac Plus and Sinopharm produced higher levels of anti-RBD antibody titer compared to Noora and SpikoGen. One limitation of the study is the lack of detailed explanation for the differences in antibody responses and neutralization effectiveness among the vaccines. Future research could focus on identifying specific components of the vaccines that contribute to their immunogenicity and neutralizing efficacy. Understanding these mechanisms may lead to the development of more effective vaccines or vaccine combinations. Another limitation of the study is its exclusive focus on antibody responses and neutralization efficacy in BALB/c mice. To validate the findings, future studies could include human clinical trials or other animal models. Additionally, testing the vaccines against various viral variants could provide valuable information on their effectiveness against emerging strains.In conclusion, our study revealed significant sociodemographic disparities in COVID-19 vaccination rates, particularly in relation to booster shots. Individuals identifying as Black or Latinx, as well as those facing poverty or food insecurity, were less likely to receive multiple vaccine doses compared to their White and Asian counterparts. Additionally, vaccine uptake was lower among individuals without health insurance or regular healthcare providers. These findings highlight the importance of addressing and reducing disparities in vaccine access and compliance to ensure equitable protection against COVID-19. References:Dashti N, Golsaz-Shirazi F, Jeddi-Tehrani M, Zarnani AH, Amiri MM, Shokri F. Comparative Immunogenicity and Neutralization Potency of Four Approved COVID-19 Vaccines in BALB/c Mice. Iran J Immunol. 2024 Mar 4;21(1). doi: 10.22034/iji.2024.101060.2728. Online ahead of print. Author’s responseDear EditorWe appreciate the comments raised on our paper accepted for publication in IJI (doi: 10.22034/iji.2024.101060.2728). The commenters pointed out some limitations of our study regarding the clarification of the processes responsible for the variations in antibody response and virus neutralization potency of the vaccines included in this study. They suggested investigating the constituents of the vaccines to gain further insight into the components responsible for enhancement of vaccine efficacy. In fact, we have discussed all these issues in detail in the discussion of our article, taking into account the structure of the immunizing antigens, their expression profile in either eukaryotic or prokaryotic systems, the nature of the adjuvants, and the possibility of degradation or denaturation of the antigens, etc. The commenters also proposed validating the results through clinical trials in human as well as investigating the neutralization potency on different viral variants. Conducting a comparative assessment on human samples has also been highlighted in our paper. However, we did not recommend performing experiments on other virus variants, such as Omicron or its subtypes, because two of the vaccines (SpikoGen and Noora) failed to induce an appreciable virus neutralization response to the SARS-CoV-2 Delta variant. Thus, we could not expect any neutralization effect against highly mutated variants, such as Omicron.Finally, the conclusion paragraph provided by the commenters, regarding their data on the influence of sociodemographic and nutrition parameters on the immunogenicity of COVID-19 vaccines is not relevant to our study and cannot be interpreted in light of the findings reported in our paper.
