Anil Demir; Husnu Sevik; Mert Guler; Furkan Turkoglu; Coskun Cakir; Mert Mahsuni Sevinc; Erdem Kinaci; Ufuk Oguz Idiz
Abstract
Background: Breast cancer is the leading cause of cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies ...
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Background: Breast cancer is the leading cause of cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies among different subtypes of breast cancer.Objective: To assess cytokine levels in breast cancer patients according to their subtypes and investigate the potential role of these cytokines in treatment.Methods: Patients with stage 1-2 breast cancer and healthy volunteers were included in the study. The breast cancer patients were classified as luminal A, luminal B, and triple negative based on ER, PR, HER2 receptor status, and Ki67 score of trucut biopsy results. Multiplex assay and flow cytometry were used to quantify the concentrations of IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, IL-23, and IL-33 in serum samples collected from all participants. Age, menopausal status, and hematologic parameters were also compared between groups.Results: The study involved 19 luminal A, 20 luminal B, 18 triple-negative patients and 21 healthy volunteers. TNF-α, IL-6, IL-8, IL-10, IL-12p (p70), IL-18, and IL-23 cytokines were significantly higher in breast cancer patients than in healthy volunteers. Significant differences in IFN-γ, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, and IL-23 were observed between subtypes, with triple-negative patients showing lower cytokine levels, except for MCP-1.Conclusion: The decreased levels of cytokines in triple-negative breast cancer indicate lower immunogenicity leading to more aggressive tumor progression as a result of an insufficient immune response.
Guizhen Lin; Lei Zhang; Zheng Yan; Wei Jiang; Beibei Wu; Xiaofang Xiong
Abstract
Background: CD8+ T cells have been found to accumulate in atherosclerotic plaques. However, the specific role of CD8+ T cell subsets in the development of atherosclerosis is still not fully understood.Objective: To investigate the presence and functions of type 1 CD8+ T (Tc1) cells and interleukin-17 ...
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Background: CD8+ T cells have been found to accumulate in atherosclerotic plaques. However, the specific role of CD8+ T cell subsets in the development of atherosclerosis is still not fully understood.Objective: To investigate the presence and functions of type 1 CD8+ T (Tc1) cells and interleukin-17 (IL-17)-producing CD8+ T (Tc17) cells.Methods: Apolipoprotein E-deficient mice were fed a high-fat diet to induce atherosclerosis. Flow cytometry was used to identify and isolate aortic CD8+ T cell subsets, which were then cultured in vitro to assess their pro-inflammatory activities. The cholesterol content of the CD8+ T cell subsets was quantified.Results: T-box expressed in T cells (T-bet)+ Tc1 cells and retinoic acid-related orphan receptor gamma t (RORγt)+ Tc17 cells were found in the atherosclerotic aorta. Aortic CD8+ T cells showed lower pro-inflammatory activity compared to splenic counterparts, with less interferon-gamma (IFN-γ) (P <0.01) and tumor necrosis factor-alpha (TNF-α) production (P <0.01). Surprisingly, aortic CD8+ T cells expressed little IL-17 and interleukin-21 (IL-21) despite the presence of Tc17 cells. Aortic Tc1 and Tc17 cells expressed high levels of 2B4 and programmed cell death protein 1 (PD-1). Furthermore, aortic Tc1 and Tc17 cells had higher cholesterol contents than splenic CD8+ T cells (P <0.05, respectively). Cholesterol treatment decreased IFN-γ expression in Tc1 cells (P <0.001) and reduced IL-17 expression in Tc17 cells (P <0.001). Additionally, cholesterol up-regulated 2B4 and PD-1 on Tc1 (P <0.001) and Tc17 cells (P <0.001).Conclusion: Aortic CD8+ T cells, particularly aortic Tc17 cells, are functionally exhausted in atherosclerosis, possibly due to the influence of cholesterol.
Zhe Xue; Yuyan Guo; Fangyun Wang; Qinping Yang; Qiuhong Chen; Tingting Lin; Shunhe Lin
Abstract
Background: miR-196b-5p was found to be significantly reduced in endometriosis, but its function and the mechanisms involved remained unclear.Objective: To explore the effect of miR-196b-5p on manipulating macrophage phenotype and the underlying mechanisms in endometriosisMethods: The endometriosis mice ...
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Background: miR-196b-5p was found to be significantly reduced in endometriosis, but its function and the mechanisms involved remained unclear.Objective: To explore the effect of miR-196b-5p on manipulating macrophage phenotype and the underlying mechanisms in endometriosisMethods: The endometriosis mice and End1/E6E7 cells were used for in vivo and in vitro experiments, respectively. QRT-PCR was used to detect miR-196b-5p, suppressor of cytokine signaling 1 (SOCS1), high mobility group AT-Hook 1 (HMGA1), and CCL2 expressions. Western blot was used to detect SOCS1 and HMGA1 protein levels while luciferase reporter assay was performed to determine the interaction between miR-196b-5p and SOCS1/ HMGA1. ELISA was used to measure CCL2, IL-10, and IL-6 levels and immunohistochemical staining and flow cytometry were used to examine CD86 and CD206 expressions.Results: Significantly reduced levels of miR-196b-5p, and increased levels of SOCS1, HMGA1, and CCL2 were observed in the ectopic endometrium of mice with endometriosis. The miR-196b-5p mimic significantly reduced the lesion size, increased M1 macrophages, and decreased M2 macrophages in the ectopic endometrium of mice with endometriosis. End1/E6E7 cells transfected with miR196b-5p mimic significantly increased M1 macrophages, decreased M2 macrophages and reduced the migration in PMA-treated THP1 cells. Conversely, transfection with a miR-196b-5p inhibitor led to the opposite outcomes. miR-196b-5p targeted SOCS1/HMGA1, and miR-196b-5p inhibitor significantly up-regulated CCL2 and IL-10, and down-regulated IL-6 levels in End1/E6E7 cells. These effects were markedly reversed by si-SOCS1/si-HMGA1.Conclusion: miR-196b-5p elevates M1 macrophages and decreases M2 macrophages in endometriosis, possibly by targeting SOCS1/ HMGA1. This research may provide a novel insight into the pathological mechanisms of endometriosis.
Ali Fotouhi; Maryam Hosseini; Ali Aghebati-Maleki; Mohammad Sadegh Soltani-Zangbar; Sara Parsania; Amirhossein Mardi; Leili Aghebati-Maleki
Abstract
Background: Osteoarthritis (OA) is the most common joint disease worldwide. Routine treatment options are limited, and total knee replacement surgeries often come with complications. In recent years, the use of biologics, such as Wharton’s jelly (Wj) derived from the umbilical cord (UC), has gained ...
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Background: Osteoarthritis (OA) is the most common joint disease worldwide. Routine treatment options are limited, and total knee replacement surgeries often come with complications. In recent years, the use of biologics, such as Wharton’s jelly (Wj) derived from the umbilical cord (UC), has gained popularity. While mesenchymal stem cells (MSCs) derived from Wj show promise in restoring articular cartilage, they also have some limitations. Recent studies have indicated that exosomes isolated from acellular Wj may offer advantages under certain conditions.Objective: To investigate the anti-inflammatory properties of exosomes isolated from Wj in synoviocytes.Methods: Decellularization of Wj was performed using sterile umbilical cords obtained from patients. Next, the exosomes were isolated from Wj using ultracentrifugation. After characterizing the exosomes, they were co-cultured with inflammatory synovial fibroblast cells (HIG-82) for 24 hours. Then, the gene expression levels and protein contents of some important inflammatory mediators including metalloproteinase-13 (MMP-13), cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) were measured in the cells using real-time PCR and ELISA tests, respectively.Results: The expression levels of MMP-13, COX-2, and iNOS genes were significantly reduced in the cultured cells treated with exosomes compared to untreated cells. Moreover, the content of MMP-13, COX-2, and iNOS proteins were significantly lower in the supernatant of the cultured cells compared to the control.Conclusion: Wj-derived exosomes exhibit notable anti-inflammatory properties, which can help mitigate inflammation in the synovial environment of joints. However, further research is required to fully understand their benefits and potential applications in treating osteoarthritis.
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.
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.
Dan Luo; Jun Li; Manli Hu; You Wang; Pei Pi; Min Ning; Jun Wu
Abstract
Background: Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN.Objective: To investigate the detailed role and ...
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Background: Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN.Objective: To investigate the detailed role and regulatory mechanism of ANGPTL4 in experimental models of LN.Methods: MRL/lpr mice 11-week-old were injected with adeno-associated virus (AAV)-mediated ANGPTL4 short hairpin RNA (shRNA). At 16 and 20 weeks of age, 24-h urine samples were harvested to measure proteinuria levels. After the mice were sacrificed, blood and kidney tissues were harvested to examine serum creatinine (cr) and blood urea nitrogen (BUN) levels, kidney histological changes, and pro-inflammatory cytokine production. Additionally, the levels of NLRP3 inflammasome-associated molecules in mouse renal tissues were detected to clarify the underlying mechanism.Results: The AAV-sh-ANGPTL4 injection significantly reduced the proteinuria, cr, and BUN levels in MRL/lpr mice. ANGPTL4 silencing ameliorated glomerular, tubular, and interstitial damage in mice, mitigating the pathological alternations of LN. In addition, ANGPTL4 knockdown repressed pro-inflammatory cytokine production in the kidneys. Mechanically, ANGPTL4 suppression inhibited NLRP3 inflammasome expression in renal tissues of mice.Conclusion: ANGPTL4 silencing inhibits the NLRP3 inflammasome-mediated inflammatory response, thereby ameliorating LN in MRL/lpr mice.
Mahnaz Bayat; Niloufar Razavi Moosavi; Najmeh Karimi; Moosa Rahimi; Afshin Borhani-Haghighi
Abstract
Background: The initial inflammatory reaction starts following occlusion in ischemic stroke (IS). Interleukin-1β (IL-1β) is a pro-inflammatory cytokine with a crucial role in the pathogenesis of neurodegenerative disorders.Objective: To investigate the levels of IL-1β and vitamin D (VitD) ...
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Background: The initial inflammatory reaction starts following occlusion in ischemic stroke (IS). Interleukin-1β (IL-1β) is a pro-inflammatory cytokine with a crucial role in the pathogenesis of neurodegenerative disorders.Objective: To investigate the levels of IL-1β and vitamin D (VitD) in patients with IS compared with controls and their correlation.Methods: The serum level of 25-OH VitD and IL-1β was assessed in 102 IS patients (0-24 h after stroke) and 102 controls with an enzyme-linked immunosorbent assay (ELISA) kit.Results: We found a significant increase in IL-1β (80.14±6.8 vs. 60.32±4.1 pg/ml, p<0.05) and a decrease in VitD level (24.3±1.4 vs. 29.9±1.5 ng/ml, p<0.01) in the IS patients compared with the controls. There was a significantly positive correlation between the National Institutes of Health Stroke Scale (NIHSS) and IL-1β according to both the Spearman correlation (r=0.35, p=0.0003) and the linear regression (beta=0.255, p=0.014). Also, a significant negative association between VitD and NIHSS was detected by the Spearman correlation (r=-0.41, p<0.0001) and the linear regression (beta=-0.381, p=0.000). Moreover, we found a significant negative correlation (r=-0.26, p=0.006) between the serum levels of VitD and IL-1β in the patient group.Conclusion: Ischemic stroke correlates positively with IL-1β and negatively with VitD levels. The speculated role of VitD deficiency in the evolution and severity of stroke may be justified by its role in the modification of inflammation.
Zivar Zangeneh; Gholamreza Khamisipour
Abstract
Background: Heat shock proteins (HSPs) are involved in innate and adaptive immune responses, especially inflammatory responses due to immune cell activation. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was one of the most important causes of death in the recent pandemic. Increased cellular ...
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Background: Heat shock proteins (HSPs) are involved in innate and adaptive immune responses, especially inflammatory responses due to immune cell activation. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was one of the most important causes of death in the recent pandemic. Increased cellular stress and excessive inflammation are common in coronavirus disease-19 (COVID-19), although the underlying mechanisms are still poorlyunderstood.Objective: To evaluate the relationship between HSP and the pathological effects of COVID-19.Methods: A group of 107 patients was categorized to two populations (mild and severe) based on their chest high-resolution computed tomography (HRCT) results. The HSP70, HSP90 alpha, and serum levels of C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay (ELISA). Lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were measured by the automated analyzer.Results: Our data showed increased levels of HSP70 and HSP90 in patients with COVID-19. The HSPs levels were elevated in the severe group compared to the mild group. This study demonstrated a positive correlation between both elevated levels of HSP70, HSP90, and HRCT grade and also a positive correlation with CRP and CPK in the severe group.Conclusion: HSP90 and HSP70 contribute to excessive immune responses and cytokine storms. They may serve as prognostic serum markers for COVID-19 lung injury. Additionally, they arecandidates for anti-inflammatory therapy.
Shole Daneshvar-ghahfarokhi; Amir Rahnama; Vahid Mohammadi-Shahrokhi
Abstract
Background: One of the inflammatory diseases of the respiratory system is asthma. Teucrium polium (TP) has anti-inflammatory and anti-allergic properties and its anti-asthmatic effects have not been investigated yet. RORγt is an inflammatory transcription factor for Th17 differentiation. By secreting ...
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Background: One of the inflammatory diseases of the respiratory system is asthma. Teucrium polium (TP) has anti-inflammatory and anti-allergic properties and its anti-asthmatic effects have not been investigated yet. RORγt is an inflammatory transcription factor for Th17 differentiation. By secreting IL-17, Th17 leads to neutrophilic inflammation in the lungs. As an anti-inflammatory cytokine, IL-10 reduces the dissemination of inflammatory elements in the airways.Objective: To evaluate the effect of TP extract in asthma treatment.Methods: Thirty female Balb/c mice were distributed into 5 groups (n=6) including the control, treated with ovalbumin (OVA), and OVA+ various doses of TP (50, 150, and 300 mg/kg). All groups except the control group were sensitized to OVA solution on days 0, 7, and 14 by subcutaneous injection. The challenge was performed on days 18 to 21 by the inhalation of 1% OVA and the treatment was done with TP extract in the treatment groups, half an hour before the challenge. On day 22, the serum and spleen samples were collected to determine IL-10 serum levels and RORγt gene expression, respectively.Results: In the treatment groups, the expression of RORγt significantly decreased when using OVA+ Tp extract (150 mg/kg and 300 mg/kg), and IL-10 serum levels significantly increased when using OVA+ TP extract (150 mg/kg) compared with the OVA group.Conclusion: It is possible that TP extract can be effective in improving asthma by reducing inflammation.
Jian-Hua Lu; Xiao-Xiao Rui; Ting-Ting Wang; Xiao-Qin Wang; Yu-Ping Peng; Yi-Hua Qiu
Abstract
Background: Recent research in our laboratory shows that CD4+ T cells express the β2 adrenergic receptor (β2-AR), and the sympathetic neurotransmitter norepinephrine regulates the function of T cells via β2-AR signaling. However, the immunoregulatory effect of β2-AR and its related ...
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Background: Recent research in our laboratory shows that CD4+ T cells express the β2 adrenergic receptor (β2-AR), and the sympathetic neurotransmitter norepinephrine regulates the function of T cells via β2-AR signaling. However, the immunoregulatory effect of β2-AR and its related mechanisms on rheumatoid arthritis is unknown.Objective: To explore the effects of β2-AR in collagen-induced arthritis (CIA) on the imbalance of T helper (Th) 17/ regulatory T (Treg) cells.Methods: In DBA1/J mice, collagen type II was injected intradermally at the tail base to prepare the CIA model. The specific β2-AR agonist, terbutaline (TBL), was administered intraperitoneally beginning on day 31 and continuing until day 47 after primary vaccination, twice a day. Magnetic beads were used to sort CD3+ T cells subsets from spleen tissues.Results: In vivo, β2-AR agonist TBL alleviated arthritis symptoms in the CIA mice including histopathology of the ankle joints, four limbs’ arthritis score, the thickness of ankle joints, and rear paws. After TBL treatment, in the ankle joints, the levels of proinflammatory factors (IL-17/22) notably decreased and the levels of immunosuppressive factors (IL-10/TGF-β) significantly increased. In vitro, ROR-γt protein expression, Th17 cell number, mRNA expression and the releasing of IL-17/22 from CD3+ T cells reduced following TBL administration. Moreover, TBL enhanced the anti-inflammatory responses of Treg cells.Conclusion: These results suggest that β2-AR activation exerts anti-inflammatory effects through the amelioration of Th17/Treg imbalance in the CIA disease.
Xiaolei Shi; Lina Zhao; Liyan Niu; Jhao Wei; Xuwen Li; Yongri Jin
Abstract
Background: Asthma is a heterogeneous disorder of the airways related to inflammation; it affects millions of people worldwide. Due to the side effects of inhaled corticosteroids, researchers focused on the therapeutic effects of compounds derived from natural products. Objective: To investigate the ...
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Background: Asthma is a heterogeneous disorder of the airways related to inflammation; it affects millions of people worldwide. Due to the side effects of inhaled corticosteroids, researchers focused on the therapeutic effects of compounds derived from natural products. Objective: To investigate the therapeutic benefits of Narirutin a valuable flavonoid in Citri Reticulatae Pericarpium for asthma. Methods: Narirutin was extracted using the enzyme-assisted method with the L9 (34) orthogonal array to optimize the temperatures, pH, and reaction time. The mechanism of action of Narirutin was investigated via ELISA, flow cytometry, and Western blot analysis in vivo. Results: Narirutin suppressed inflammatory cell infiltration in the lung tissue and decreased IgE and IgG1 levels in serum in vivo. It can also alleviate interleukin (IL)-4, IL-5, and interferon-γ concentrations in bronchoalveolar lavage fluid in mice. Moreover, it increased the ratio of CD4+/CD8+ T cells. Additionally, Narirutin significantly suppressed p-ERK1/2 and p-JNK expression in the MAPK signaling pathway. Conclusion: Narirutin affects the Th1/Th2 imbalance through the p-ERK and p-JNK suppression in the MAPK signaling pathway.
Amir Hossein Norooznezhad; Alireza A Shamshirsaz; Sedigheh Hantoushzadeh
Abstract
Pregnant women with coronavirus disease 2019 (COVID-19) have a higher risk of morbidity and mortality compared with the general population. Possible pathways are: I) in patients with COVID-19, cytokine storm defined as the excess release of pro-inflammatory cytokines such as interleukin 1β (IL-1β), ...
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Pregnant women with coronavirus disease 2019 (COVID-19) have a higher risk of morbidity and mortality compared with the general population. Possible pathways are: I) in patients with COVID-19, cytokine storm defined as the excess release of pro-inflammatory cytokines such as interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) has been associated with morbidities and an even higher rate of mortality. II) Labor, despite being a term/preterm, has an inflammatory nature, although, inflammation is more prominent in preterm delivery. During labor, different pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are involved which as mentioned, all are crucial role players in the cytokine storm. III) Tissue injury, and during labor, (especially cesarean section) is shown to cause inflammation via pro-inflammatory cytokines release including those involved in the cytokine storm through the activation of nuclear factor κB (NFκB). IV) post-partum hemorrhage with a notable amount of blood loss which can cause significant hypoxemia. In this condition, hypoxia-inducible factor 1α which has a cross-talk with NFκB, leads to the expression of IL-1β, IL-6, and TNF-α as both angiogenic and pro-inflammatory factors. Considering all the mentioned issues and pathways, we suggest that clinicians be careful about the escalation of the inflammatory status in their pregnant COVID-19 patients during/following labor.
Javad Charostad; Azarakhsh Azaran; Mohsen Nakhaei; Akram Astani; Gholam Abbas Kaydani; Azim Motamedfar; manoochehr makvandi
Abstract
Background: Interleukin-6 (IL-6) is a well-known proinflammatory cytokine with tumor promoting capacity in various forms of malignancies including breast cancer (BC). Data highlighted the substantial role of HPV in the pathogenesis of BC. Compelling evidence suggests the contribution of HPV in carcinogenesis ...
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Background: Interleukin-6 (IL-6) is a well-known proinflammatory cytokine with tumor promoting capacity in various forms of malignancies including breast cancer (BC). Data highlighted the substantial role of HPV in the pathogenesis of BC. Compelling evidence suggests the contribution of HPV in carcinogenesis through triggering inflammatory cytokines such as IL-6. Objective: Here, we assessed the correlation between the presence of HPV infection and the status of IL-6 expression and serum level in BC. Methods: 72 tissue specimens including tumoral (Case; n=36) and their adjacent normal tissues (Control; n=36) were used. Nested-PCR and Real-Time PCR were employed to identify HPV DNA and assess the expression of IL-6, respectively. In addition, 72 sera samples from BC patients (n=36) and an age-matched healthy control group (n=36) were taken to measure the IL-6 serum level by ELISA. Results: Overall, the HPV DNA was detected in 19.4% (14/72) of samples. 33.33% (12/36) of cases and 5.5% (2/36) of the controls were found to be positive for HPV (P=0.003). The overexpression of IL-6 was observed in HPV+ samples compared to HPV- samples (P=0.05). However, the concentration of IL-6 serum level was remarkably different between patients and normal controls (P=0.0001). Intriguingly, IL-6 serum level was connected to the advanced clinical stage (III/IV), high grade (II/III), metastasis and, ER+ status of patients. Conclusions: Our finding indicated that the overexpression of the IL-6 may be connected to HPV infection in BC. Furthermore, the results reinforced the clinical significance and prognostic value of the serum IL-6 in BC patients.
Fabio Barra; Simone Ferrero
Annamaria Marton; Csongor Kolozsi; Erzsebet Kusz; Zoltan Olah; Tamas Letoha; Csaba Vizler; Laszlo Pecze
Volume 11, Issue 2 , June 2014, , Pages 113-122
Abstract
Background : Propylene glycol (1,2-propanediol, PG) is a commonly used solvent for oral, intravenous, as well as topical pharmaceutical preparations. While PG is generally considered to be safe, it has been known that large intravenous doses given over a short period of time can be toxic. Objective: ...
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Background : Propylene glycol (1,2-propanediol, PG) is a commonly used solvent for oral, intravenous, as well as topical pharmaceutical preparations. While PG is generally considered to be safe, it has been known that large intravenous doses given over a short period of time can be toxic. Objective: To evaluate the effect of PG in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS). Methods: Balb/c mice were treated with LPS (1 mg/kg b.w., i.p.) with or without PG (5 g/kg b.w. i.v.). The survival rate and the production of inflammatory cytokines were measured. In RAW264.7 mouse macrophages encoding NF- B-luc reporter gene, the nuclear transcription factor kappa- B (NF- B) activation was measured. Results: We found that intravenous PG increased the mortality rate in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS) in mice. In accordance with that, PG enhanced LPS -induced production of inflammatory cytokines, including tumor necrosis factor-α (TNF -α) and interleukin-6 (IL -6) in vivo. PG also increased the LPS-induced macrophage activation in vitro as detected by measuring NF- B activation. Conclusion: Our results indicate that drugs containing high doses of PG can pose a risk when administered to patients suffering from or prone to Gram negative bacterial infection.
Nadeem Afzal; Shakeela Zaman; Aneela Asghar; Khursheed Javed; Faheem Shahzad; Abu Zafar; Abdul Hanan Nagi
Volume 11, Issue 1 , March 2014, , Pages 40-48
Abstract
Background: Diabetes mellitus (DM) is a health concern which leads to complications such as retinopathy. Pakistan has 6.9 million people living with DM and this toll will be doubled by 2025. Objective: To determine serum IL-6 and IL-17 of type 2 diabetes mellitus (T2DM) patients with retinopathy. Methods: ...
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Background: Diabetes mellitus (DM) is a health concern which leads to complications such as retinopathy. Pakistan has 6.9 million people living with DM and this toll will be doubled by 2025. Objective: To determine serum IL-6 and IL-17 of type 2 diabetes mellitus (T2DM) patients with retinopathy. Methods: In this cross-sectional casecontrol study, 212 subjects enrolled which were categorized into 3 groups. Group-I included 30 subjects without diabetes, group-II consisted of 30 subjects with T2DM without retinopathy and group-III consisted of 152 subjects with T2DM and retinopathy. Serum IL-6 and IL-17 levels were determined by ELISA. Data was analysed using SPSS 17.0 and one way ANOVA to observe group mean differences. Results: Longer mean duration of disease was detected in group-III than group-II (p=0.007). Highest IL-6 level was detected in group-II and highest IL-17 level was detected in group-I. For IL-6, significant differences were detected among groups in total, between Group-I and Group-III and between Group-II and Group-III (p<0.0001 each). Regarding IL-17, significant differences were found among groups in total (p=0.002) and between Group-I and Group-III (p=0.001). No significant difference in the percentages of HbA1c observed between groups. Conclusions: Age, gender and duration of diabetes contribute to T2DM retinopathy. Serum IL-6 and IL-17 were inversely associated with T2DM retinopathy.
Bahador Bagheri; Bahram Sohrabi; Aliakbar Movassaghpur; Siminozar Mashayekhi; Afagh Garjani; Mehriar Shokri; Mohammad Noori; Alireza Garjani
Volume 9, Issue 3 , September 2012, , Pages 149-158
Abstract
Background: Toll like receptors (TLRs) are well recognized players in inflammatory conditions. Among them TLR-4 is involved in chronic inflammatory processes such as formation of atherosclerotic plaques. Objective: The present study was aimed to examine the effects of percutanoeus coronary intervention ...
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Background: Toll like receptors (TLRs) are well recognized players in inflammatory conditions. Among them TLR-4 is involved in chronic inflammatory processes such as formation of atherosclerotic plaques. Objective: The present study was aimed to examine the effects of percutanoeus coronary intervention (PCI) as a revascularization method on monocyte expression of hTLR-4 and on the serum levels of two proinflammatory cytokines (TNF-α and IL-1β). Methods: Blood samples were obtained from 41 patients with stable angina who were candidates for PCI. The samples were collected immediately before and 2h and 4h after PCI. The expression of hTLR-4 on CD14+ monocytes and the serum levels of TNF-α and IL-1β were measured using flowcytometry and ELISA techniques, respectively. Results: By comparing the frequency of circulating hTLR-4+/CD14+ monocytes at different time points, it was observed that PCI procedure up regulates the monocyte expression of hTLR-4 (p<0.05). The increase in expression was associated with the elevation of the serum levels of proinflammatory cytokines (p<0.05). There was a significant correlation between monocyte expression of hTLR-4 and serum levels of TNF-α and IL-1β only before PCI. In spite of parallel increase in the serum levels of proinflammatory cytokines and the monocyte expression of hTLR-4, the correlation did not attain a significant level after PCI intervals. Conclusion: PCI is positively associated with an increase in the monocyte expression of hTLR-4. It is also associated with the elevation in the serum levels of proinflmmatory cytokines. These findings suggest that hTLR-4 monocyte expression may be used as a potential prognostic tool in patients with stable angina undergoing PCI.
Alireza Rafiei; Mahoud Abedini; Seyed Hamzeh Hosseini; Zahra HosseiniKhah; Behrouz Bazrafshan; Mohsen Tehrani
Volume 9, Issue 3 , September 2012, , Pages 159-167
Abstract
Background: The pathogenesis of migraine involves immune-mediated mechanisms in the vascular endothelium. Toll like receptor 4 (TLR-4) is a signaling receptor of innate immunity which plays a role in various neuropathologies related to neuron inflammation. Objective: This case/control study is aimed ...
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Background: The pathogenesis of migraine involves immune-mediated mechanisms in the vascular endothelium. Toll like receptor 4 (TLR-4) is a signaling receptor of innate immunity which plays a role in various neuropathologies related to neuron inflammation. Objective: This case/control study is aimed to investigate whether TLR- 4 896A/G variation is related to migraine headaches in an Iranian population. Methods: A total of 170 migraine patients (130 females, mean age 33.24 ± 11 years) and 170 age, sex, and ethnicity matched healthy controls (118 females, mean age of 31 ± 10 years) were recruited. Genotyping was carried out using the tetra primer amplification refractory mutation system (ARMS)-PCR. Results: The frequency of G allele was higher in migraine patients than the controls (15% vs. 4.7%; p<0.0001). Interestingly, the distribution of heterozygous 896A/G genotype statistically differed between migraineurs and controls (25.3% vs. 8.2%, p=0.00002, OR 3.87, 95% CI; 2.02-7.4). Multivariate logistic regression analysis indicated that G allele in affected female migraineurs is an independent factor associated with increased risk of migraine (OR 3.2, 95% CI 1.23-8.24, p=0.01). Conclusion: Our results showed TLR-4 polymorphism as a genetic risk factor for migraine. However, further studies in different populations are required to elucidate the precise role of TLR-4 896A/G mutation in susceptibility to migraine.
Mojgan Mohammadi; Mohammad Mahdi Hayatbakhsh; Mohammad Javad Zahedi; Mohammad Reza Jalalpour; Amin Pakgohar
Volume 8, Issue 3 , September 2011, , Pages 183-188
Abstract
Background: Patients with ulcerative colitis are at increased risk of inflammation. Interleukin 23 (IL-23) is a newly identified cytokine with increased expression in inflamed biopsies of colon mucosa in patients with Crohn's disease; however, there is inconsistent evidence on its role in ulcerative ...
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Background: Patients with ulcerative colitis are at increased risk of inflammation. Interleukin 23 (IL-23) is a newly identified cytokine with increased expression in inflamed biopsies of colon mucosa in patients with Crohn's disease; however, there is inconsistent evidence on its role in ulcerative colitis. Objective: We aimed to compare serum IL-23 level in patients with ulcerative colitis and normal controls and determine if serum IL-23 level increases with the severity of disease according to endoscopic findings. Methods: We quantified serum IL-23 levels from 60 patients with ulcerative colitis and 20 control individuals. All patients underwent endoscopic procedure to define the severity of disease. Patients were then stratified into 2 groups of "Mild" and "Severe" according to the endoscopic findings. Results: For comparison of serum IL-23 levels, Platelet count, ESR and CRP between the groups, Mann-Whitney U test and independent sample t test were employed, as appropriate. Pearson’s and spearman's correlation tests were employed to test the association of IL-23 with platelet count, CRP and ESR in patients. Our findings showed that serum IL-23 levels were increased in patients with ulcerative colitis compared to normal control. Moreover, patients in "Severe" group had higher serum IL-23 levels and ESR compared with those in "Mild" group. There was no significant sexual dimorphism in any of studied variables. Conclusion: We suggest that IL-23 plays an important role in the p
Alireza Salek Moghaddam; Mohammad Shabani; Farahdokht Fateminasab; Mohammad Reza Khakzad
Volume 2, Issue 2 , June 2005, , Pages 103-110
Abstract
Background: Asthma is a chronic inflammatory disease with multifactorial and complicated mechanisms. Elevated level of exhaled Nitric Oxide (NO) in asthma and other inflammatory lung diseases has led to many studies examining NO as a potential marker of airway inflammation. Objective: This study was ...
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Background: Asthma is a chronic inflammatory disease with multifactorial and complicated mechanisms. Elevated level of exhaled Nitric Oxide (NO) in asthma and other inflammatory lung diseases has led to many studies examining NO as a potential marker of airway inflammation. Objective: This study was designed to determine the level of NO in Bronchoalveolar Lavage (BAL) fluid during early and late stages of asthmatic attack in mouse model. Methods: In this study male BALB/c mice were used. The level of NO was determined in BAL fluid of asthmatic mice five minutes, six and sixteen hours after challenge with methacholine, as irritant and smoke and 5% ovalbumin as allergens, using colorimetric assay. Results: The level of NO increased upon exposure to all three irritants used in this study (52.3 μM for smoke and 49.5 μ Mfor methacholine) as compared to 22.8 μM for the baseline. Our results showed that NO levels were increased during early phase of asthmatic condition and reached to its maximum level after six hours and decreased at the late stage of asthma (16hrs) possibly by activating a feedback regulatory loop. In addition, high level of NO led to the hypertrophy of smooth muscle that can account for the pathological changes associated with asthma. Conclusion: Thus, NO is an inflammatory marker in asthma and its measurement, as a non-invasive method during asthmatic attack is suggested. A careful development of specific inhibitors for iNOS enzyme during asthmatic attack is also necessary.
