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2.
Mol Biol Rep ; 50(10): 8319-8328, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37589934

RESUMEN

BACKGROUND: Bromodomain and extra-terminal (BET) proteins are recognized acetylated lysine of histone 4 and act as scaffolds to recruit many other proteins to promoters and enhancers of active genes, especially at the super-enhancers of key genes, driving the transcription process and have been identified as potential therapeutic targets in breast cancer. However, the efficacy of BET inhibitors such as JQ1 in breast cancer therapy is impeded by interleukin-6 (IL-6) through an as-yet-defined mechanism. METHODS AND RESULTS: We investigated the interplay between IL-6 and JQ1 in MCF-7 and MDA-MB-231 human breast cancer cells. The results demonstrate that the efficacy of JQ1 on the inhibition of cell growth and apoptosis was stronger in MDA-MB-231 cells than in MCF-7 cells. Further, MCF-7 cells, but not MDA-MB-231 cells, exhibited increased expression of CXCR4 following IL-6 treatment. JQ1 significantly reduced CXCR4 surface expression in both cell lines and diminished the effects of IL-6 pre-treatment on MCF-7 cells. While IL-6 suppressed the extension of breast cancer stem cells in MCF-7 cells, JQ1 impeded its inhibitory effect. In MCF-7 cells JQ1 increased the number of senescent cells in a time-dependent manner. CONCLUSION: Analysis of gene expression indicated that JQ1 and IL-6 synergistically increase SNAIL expression and decrease c-MYC expression in MCF-7 cells. So, the BET proteins are promising, novel therapeutic targets in late-stage breast cancers. BET inhibitors similar to JQ1 show promise as therapeutic candidates for breast cancers, especially when triple-negative breast cancer cells are increased and/or tumor-promoting factors like IL-6 exist in the tumor microenvironment.


Asunto(s)
Neoplasias de la Mama , Interleucina-6 , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Línea Celular Tumoral , Proliferación Celular , Interleucina-6/genética , Interleucina-6/farmacología , Células MCF-7 , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transducción de Señal , Microambiente Tumoral
3.
Afr Health Sci ; 22(1): 630-640, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36032502

RESUMEN

Background: The profile of inflammatory and suppressing cytokines is important to contribute to the disruption of TH1/TH2 balance in Allergic rhinitis (AR). Objective: This study aimed to assess the expression levels of IL-6, IL-18, IL-21, IL-23, and TGF-ß in nasal biopsies in AR patients and evaluate its correlation with the severity of AR. Material and method: The study included 30 patients with mild persistent allergic rhinitis (MPAR), patients with moderate-to-severe (M/S) PAR, and 30 healthy individuals. The biopsies of nasal inferior turbinate mucosa were collected from each participant. The expression of IL-6, IL-18, IL-21, IL-23, and TGF-ß was evaluated by the quantitative real-time polymerase chain reaction. The degree of eosinophil infiltration into the nasal mucosa, blood eosinophils, and total serum IgE level were also measured. Result: The expression of IL-6, IL-18, and IL-23 in patients with AR significantly increased compared to the control group. Conversely, the gene expression of the TGF-ß declined in the M/S PAR group rather than the AR- group. The data did not show a significant difference in the expression of the IL-21 gene between AR+ and AR- groups. Conclusion: We suggested that inflammatory cytokines including IL-6, IL-18, and IL-23 may be involved in the severity of AR and associated with markers of inflammation.


Asunto(s)
Citocinas , Mucosa Nasal , Rinitis Alérgica , Citocinas/análisis , Humanos , Interleucina-18 , Interleucina-23 , Interleucina-6 , Interleucinas , ARN Mensajero , Rinitis Alérgica/diagnóstico , Factor de Crecimiento Transformador beta
4.
Mol Biol Rep ; 49(6): 4161-4170, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35608747

RESUMEN

BACKGROUND: Vascular endothelial growth factor (VEGF) is one of the angiogenic mediators that can be secreted by leukemic cells and plays an important role in tumor invasion and metastasis. Another important agent contributing to the relapse of ALL is C-X-C chemokine receptor type-4 (CXCR-4), expression of this receptor in cancer cells has been related to metastasis. It has been identified that genistein-a soy-derived isoflavonoid-has anti-angiogenesis functions. We aimed to show the effects of this compound on VEGF and CXCR-4 in Acute lymphoblastic leukemia (ALL) cell models. METHODS AND RESULTS: The cytotoxicity of Genistein was measured using the MTS colorimetric assay. After being treated with Genistein, the expression of VEGF in mRNA and protein levels was measured in MOLT-4 and Jurkat cells. We also used flow cytometry assay to determine the expression of CXCR-4 in cell surfaces. We found that Genistein decreased cell viability in two cell models while was more effective on MOLT-4 cells. After Genistein-treatment, surface expression levels of CXCR-4 were decreased, while VEGF secretion and mRNA expression levels were increased in MOLT-4 and Jurkat cells. CONCLUSIONS: The results suggest that Genistein may not be a reliable choice for the treatment of ALL; however, this different identified pattern can be useful for the recognition of VEGF and CXCR-4 modulators and thus for planning new treatments for leukemia and other VEGF related disorders.


Asunto(s)
Antineoplásicos , Genisteína , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores CXCR4 , Factor A de Crecimiento Endotelial Vascular , Antineoplásicos/farmacología , Genisteína/farmacología , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factores de Crecimiento Endotelial Vascular
6.
Iran J Allergy Asthma Immunol ; 21(1): 20-26, 2022 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-35524374

RESUMEN

Interleukin (IL)-35 and IL-37 are two anti-inflammatory cytokines. IL-35 inhibits the development of T-effector cells such as Th1, and Th17; while increasing regulatory T cells (Tregs). IL-37 causes the suppression of inflammatory cytokines. Regarding the positive impact of Helicobacter pylori (H. pylori) infection on inflammation and considering the anti-inflammatory effects of IL-35 and IL-37, this study aimed to evaluate the expression of these two cytokines in H. pylori-infected patients with gastrointestinal problems. The case group consisted of H. pylori-infected individuals with gastric ulcer and/or gastritis (n=50) and the control group consisted of cases with gastric ulcer and/or gastritis non-H. pylori-infected (n=50). Sampling and classification of patients were based on pathology findings. A real-time polymerase chain reaction was performed for evaluating the IL-35 and IL-37 expression levels. pylori-infected gastritis patients showed lower expression of IL-35 and IL-37 than the non-infected group. There was a significant difference between the expression levels of IL-35 and IL-37 in patients with gastric ulcers and/or gastritis who were infected and non-infected by H. pylori. There were no significant differences in the expression level of IL-35 and IL-37 in H. pylori-infected patients with gastric ulcer or gastritis. Interleukins 37 and 35 were less expressed in patients with H. pylori-infection. In differentiation between patients with gastrointestinal symptoms who have H. pylori infection or with similar symptoms who do not have H. pylori-infection, mentioned interleukins can be used as diagnostic markers.


Asunto(s)
Gastritis , Infecciones por Helicobacter , MicroARNs , Úlcera Gástrica , Citocinas/metabolismo , Mucosa Gástrica/patología , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori , Humanos , Interleucina-1 , Interleucinas/metabolismo , MicroARNs/genética , Úlcera Gástrica/metabolismo , Úlcera Gástrica/microbiología
7.
Viral Immunol ; 35(2): 150-158, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35319970

RESUMEN

New strategies to increase the immune response to HIV-1 vaccine using immunological adjuvants such as Toll-like receptor agonists are needed. In this study, HIV-1 p24-Nef and conjugated form of the vaccine candidate to type-A flagellin (FLA) were injected in the BALB/c mice in different routes. Two weeks after the last immunization, lymphocyte proliferation was measured by the BrdU method. The IL-4 and IFN-γ levels, as well as the total IgG antibody and its isotypes titer, were evaluated by the enzyme-linked immunosorbent assay method. The IFN-γ ELISPOT was also performed. Our data showed that the HIV-1 p24-Nef alone and conjugated to type-A flagellin (FLA) significantly increased lymphocyte proliferation responses as well as higher levels of cytokines and IFN-γ producing lymphocytes and the level of humoral immune responses compared with the control groups. The cell-mediated immune responses through the subcutaneous route and humoral immune responses through the intramuscular route were significantly higher in the conjugated form than in the mere vaccine candidate. In conclusion, when the FLA as an adjuvant is constructed in the HIV-1 vaccine candidate, it could effectively improve both humoral and cellular immune responses. Furthermore, modification in the vaccine formulation could change the optimal route of vaccine inoculation.


Asunto(s)
Vacunas contra el SIDA , VIH-1 , Adyuvantes Inmunológicos , Animales , Flagelina , Proteína p24 del Núcleo del VIH , Inmunización , Ratones , Ratones Endogámicos BALB C , Pseudomonas aeruginosa
8.
Int J Exp Pathol ; 102(6): 249-259, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34762773

RESUMEN

Bladder cancer (BC) is one of the most prevalent cancers around the world and, if not treated well, has high morbidity and mortality. Many studies have indicated that there may be various roles for the aryl hydrocarbon receptor (AHR) in the immune system. The aim of this study was to determine the frequency of Foxp3+ regulatory T (Treg) and T helper 17 cells (Th17) in BC tissue in comparison with controls and determine the relationship between AHR, Foxp3+ Treg and Th17 cells in BC. A total of 40 patients with BC were enrolled in this study. The control group was selected from non-tumoural parts of bladder tissues from the patients who have undergone cystoscopy. The percentage of regulatory T cells (Foxp3+ /CD4+ ) and Th17 (IL-17+ /CD4+ ), as well as AHR+ cells in BC tissues and controls, were determined by immunohistochemistry. The results of this study showed that the number of Foxp3+ Treg and Th17 is significantly higher in bladder tumour tissues in comparison with non-tumoural tissues. Also, the percentage of AHR+ lymphocytes and AHR+ cells was increased significantly in bladder tumour tissues rather than non-tumoural tissues. This study also found a relation between AHR and Foxp3+ /CD4+ T lymphocytes ratio cells in BC. The percentage of Foxp3+ Tregs and AHR+ cells were significantly correlated with the grade and stage of BC. An increase in the percentage of Foxp3+ Treg and Th17 cells may play an important role in tumour immunity; and determining the relationship between AHR and differentiation of Th17/Foxp3+ Treg in BC can lead to a potential cancer therapeutic possibility.


Asunto(s)
Factores de Transcripción Forkhead/metabolismo , Interleucina-17/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Linfocitos T Reguladores/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Diferenciación Celular/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T Reguladores/patología , Neoplasias de la Vejiga Urinaria/patología
9.
Cell Biol Int ; 45(10): 2086-2095, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34184811

RESUMEN

Prostate cancer (PCa) is one of the most epidemic types of cancer in men. The tumor microenvironment (TME) of PCa is involved in the emergence of immunosuppressive factors such as myeloid-derived suppressor cells (MDSC), which regulate the immune system by several mechanisms, including interleukin (IL)-10 production. On the other hand, IL-17+ helper T cells (Th17) induce MDSCs and chronic inflammation in TME by producing IL-17. This study demonstrated that the frequency of CD33+ pSTAT3+ MDSC and IL-17+ lymphocyte as well as IL-10 messenger RNA (mRNA) expression were significantly higher in the PCa patients than in the benign prostatic hyperplasia (BPH) group. Moreover, there was no significant relationship between the frequency of CD33+ pSTAT3+ MDSC, and IL-17+ lymphocyte with Gleason scores in the PCa group. We suggested that the higher frequency of CD33+ pSTAT3+ MDSC and IL-17+ lymphocyte and the more frequent expression of IL-10 mRNA in PCa patients may play roles in tumor progression from BPH to PCa.


Asunto(s)
Interleucina-17/metabolismo , Linfocitos/inmunología , Células Supresoras de Origen Mieloide/inmunología , Hiperplasia Prostática/patología , Neoplasias de la Próstata/patología , Factor de Transcripción STAT3/metabolismo , Células Th17/inmunología , Apoptosis , Estudios de Casos y Controles , Proliferación Celular , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-17/genética , Masculino , Células Supresoras de Origen Mieloide/metabolismo , Pronóstico , Hiperplasia Prostática/inmunología , Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/metabolismo , Factor de Transcripción STAT3/genética , Lectina 3 Similar a Ig de Unión al Ácido Siálico/genética , Lectina 3 Similar a Ig de Unión al Ácido Siálico/metabolismo , Células Tumorales Cultivadas , Microambiente Tumoral
10.
Hum Immunol ; 82(1): 46-53, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33127161

RESUMEN

INTRODUCTION AND PURPOSE: Indoleamine 2, 3- dioxygenase (IDO) plays an importantrole in immunosuppressive pathway, as inhibits responsesof T cells and promotes immune tolerance. Host responsetoHelicobacter pylori (H. pylori) is involved in the infection persistenceand it is also associatedwith different clinical outcomes. The aim of this study was to investigate the role of IDO in H. pylori-infected patients with gastritis diseases and peptic ulcer diseases (PUD) through the assessment of the relationship among IDO protein expression and the numbers of T helper (Th)-1, Th17, Th22, and T regulator (Treg) cells. MATERIALS AND METHODS: Antrum biopsy was obtained from H. pylori-negative patients (n = 48) and H. pylori-positive subjects (55 patients with gastritis and 47 patients with PUD), for performing H. pylori status and histopathological assessments. IDO protein expression was evaluated by Western blotting. RESULTS: IDO protein expression was significantly higher in gastric biopsies from H. pylori-positive subjects compared to the H. pylori-negative subjects, and also in H. pylori-positive subjects with gastritis disease compared to H. pylori-positive subjects with PUD. Moreover, in H. pylori-positive subjects, a positive correlation was observed between IDO protein expression and the frequency of Treg cells. In addition, a negative correlation was observed between IDO protein expression and the number of Th1, Th17, and Th22. CONCLUSION: Increased IDO protein expression is able to change the number of Th1, Th17, Th22, and Treg cells and these changes are possibly associated with an increase in the risk of PUD development in H. pylori-infected patients.


Asunto(s)
Mucosa Gástrica/patología , Gastritis/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Adulto , Anciano , Biopsia , Femenino , Mucosa Gástrica/diagnóstico por imagen , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Gastritis/diagnóstico , Gastritis/microbiología , Gastritis/patología , Gastroscopía , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Humanos , Tolerancia Inmunológica/genética , Interleucinas/metabolismo , Masculino , Persona de Mediana Edad , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células TH1/inmunología , Células TH1/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Regulación hacia Arriba/inmunología , Interleucina-22
11.
Am J Med Sci ; 361(1): 43-54, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32928496

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) infection causes inflammation and increases the risk of developing peptic ulcer disease (PUD); however, the exact molecular mechanisms of PUD development remain unclear. The aim of this study was to investigate the expression of CCL18, CCL28, and CXCL13 in H. pylori-positive subjects in comparison with H. pylori-negative subjects, and to determine its association with different clinical outcomes and virulence factors. METHODS: In total, 55 H. pylori-positive subjects with gastritis, 47 H. pylori-positive subjects with PUD, and 48 H. pylori-negative subjects were enrolled in this study. CCL18, CCL28, and CXCL13 expression were determined using real time polymerase chain reaction (PCR). The virulence factors of H. pylori such as cytotoxin-associated gene A (cagA), outer inflammatory protein A (oipA), blood group antigen-binding adhesin (babA), and vacuolating cytotoxin A (VacA) genes were evaluated using PCR. RESULTS: CCL18, CCL28, and CXCL13 expression in H. pylori-positive subjects were significantly higher than H. pylori-negative subjects. CCL18 and CXCL13 expression in H. pylori-positive subjects with oipA+ and babA2+were significantly higher than H. pylori-positive subjects with oipA¯ and babA2¯. CCL18 and CXCL13 expression were found to be significantly elevated in H. pylori-positive subjects with gastritis compared with H. pylori-positive subjects with PUD. CCL28 expression was significantly higher in H. pylori-positive subjects with PUD compared with H. pylori-positive subjects with gastritis. CONCLUSIONS: The increased of CCL18 and CXCL13 may be involved in the pathogenesis of H. pylori-associated gastritis, while the increased of CCL28 may be involved in the pathogenesis of H. pylori-associated PUD.


Asunto(s)
Quimiocina CXCL13/genética , Quimiocinas CC/genética , Gastritis/genética , Infecciones por Helicobacter/genética , Úlcera Péptica/genética , Adulto , Anciano , Quimiocina CXCL13/metabolismo , Quimiocinas CC/metabolismo , Femenino , Gastritis/epidemiología , Gastritis/microbiología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/fisiología , Humanos , Irán/epidemiología , Masculino , Persona de Mediana Edad , Úlcera Péptica/epidemiología , Úlcera Péptica/microbiología , Regulación hacia Arriba
12.
Mol Biol Rep ; 47(9): 6941-6947, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32888128

RESUMEN

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) with increasing incidence and prevalence in developed countries. The presence of inflammatory cytokines is considered the main detrimental factor in severe types of IBD. The Nrf2 transcription factor plays an important role in reducing the expression of inflammatory agents such as interleukin (IL)-1ß and increasing reparative factors such as IL-11. Resveratrol, a plant-derived phenolic compound, reduces the damage in chronic experimentally induced colitis. Twenty patients with UC and also 20 healthy controls were recruited in this study. The proteins expression of Nrf2 and IL-1ß was assessed in colonic biopsies by Western blotting. Caco-2 cells were challenged with TNF-α (in vitro simulation of UC), in the presence or not of 190 nM (24 h) and 75 nM (48 h) Resveratrol. Then, Nrf2 and IL-1ß in gene and protein expression were measured by real time-PCR and Western blotting in different treatments. Finally, IL-11 proteins expression was measured in culture supernatant by ELISA. A significant increase of IL-1ß protein was detected in inflamed colonic tissues from UC patients compared with the control individuals. In Caco-2 cells challenged with TNF-α, protein expression of IL-1ß and p-Nrf2 showed an increase, while gene expression of Nrf2 did not show a significant difference. After treatment with Resveratrol, both IL-1ß mRNA and protein levels were reduced, while IL-11 protein levels showed any increase. The p-Nrf2 is a dominant form which is prevalent in inflamed tissues from UC patients. Resveratrol can reverse the inflammatory effects of TNF-α by reducing IL-1ß and increasing IL-11 production.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-1beta/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Resveratrol/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Adulto , Células CACO-2 , Colitis Ulcerosa/genética , Colitis Ulcerosa/prevención & control , Regulación hacia Abajo , Femenino , Regulación de la Expresión Génica/genética , Humanos , Interleucina-11/metabolismo , Interleucina-1beta/genética , Masculino , Factor 2 Relacionado con NF-E2/genética , Regulación hacia Arriba
13.
Cell Signal ; 66: 109492, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31809874

RESUMEN

T cell acute lymphoblastic leukemia (T-ALL) is one of the most frequent malignancies in children, and the CXCR4 receptor plays an important role in the metastasis of this malignancy. Ghrelin is a hormone with various functions including stimulation of the release of growth hormone and autophagy in cancer cells. Moreover, SIRT1 and AMPK (AMP-activated protein kinase) stimulate expression of proteins involved in autophagy. On the other hand, autophagic cell death can be an alternative target for cancer therapy, in the absence of apoptosis. The relationship between ghrelin and the SIRT1/AMPK axis and the resulting effects on autophagy, apoptosis, proliferation, and expression of CXCR4 and the ghrelin receptor (GHS-R1a), in Jurkat and Molt-4 human lymphoblastic cell lines was not previously clear. Here we demonstrate that SIRT1 expression is upregulated during the induction of autophagy by ghrelin, an effect that is inhibited by inactivation of SIRT1/AMPK axis. In addition, ghrelin can affect CXCR4 and GHS-R1a expression. In conclusion, this work reveals that ghrelin induces autophagy, invasion, and downregulation of ghrelin receptor expression via the SIRT1/AMPK axis in lymphoblastic cell lines. However, in these cell lines ghrelin-induced autophagy does not lead to cell death due to weak induction of apoptosis.


Asunto(s)
Autofagia/efectos de los fármacos , Ghrelina/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores CXCR4/metabolismo , Receptores de Ghrelina/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Apoptosis/efectos de los fármacos , Humanos , Células Jurkat , Sirtuina 1/metabolismo
14.
Immunol Invest ; 49(1-2): 46-57, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31267789

RESUMEN

YKL-40 is an important protein that plays a critical role in chronic inflammation in hypersensitivity disease. In this study, the expression of YKL-40 was investigated among patients with moderate/severe persistent allergic rhinitis (M/S PAR), patients with mild (M) PAR and healthy individuals. Moreover, the association between YKL-40 and immunopathogenesis of M/S PAR was meticulously surveyed. For this purpose, surgical samples were tested by real-time polymerase chain reaction to evaluate YKL-40 mRNA expression. The presence and location of YKL-40 protein in the tissue samples were determined by immunohistochemistry. Additionally, we measured the number of eosinophils per field in the tissue samples, blood eosinophils, total serum IgE, specific serum IgE, total nasal syndrome score (TNSS) and YKL-40 serum levels. The data indicated that production of YKL-40 in patients with M/S PAR increased significantly when compared with the control group. Furthermore, local production of YKL-40 correlated with specific IgE, nasal eosinophil count and TNSS. The results of the present study indicate that YKL-40, for its correlation with allergic clinical manifestations and symptom severity in M/S PAR patients, should be considered as a trigger factor in AR.


Asunto(s)
Proteína 1 Similar a Quitinasa-3/metabolismo , Mucosa Nasal/metabolismo , Rinitis Alérgica/metabolismo , Adulto , Proteína 1 Similar a Quitinasa-3/inmunología , Femenino , Humanos , Masculino , Mucosa Nasal/inmunología , Rinitis Alérgica/inmunología
15.
Arch Med Res ; 50(3): 113-121, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-31495388

RESUMEN

BACKGROUND: Peptic ulcer disease (PUD) is a common disease worldwide moreover known as stomach ulcer or peptic ulcer. Increased the number of T CD4+ helper cells in response to gastric infection by Helicobacter pylori (H. pylori) play an important role in the development of PUD. The aim of this study was to determine the frequency of T-bet+ cells in H. pylori-infection, its interaction with Th17/Treg cells and its association with the clinical consequences of the infection. METHODS: A total of 63 patients with PUD, 89 patients with gastritis and 48 H. pylori-negative subjects were enrolled in this study. The number of T-bet+ cells were determined by immunohistochemistry. RESULTS: The numbers of T-bet+ cells and INF-γ expression in infected patients were significantly higher than uninfected. Moreover, the number of T-bet+ cells and INF-γ expression in infected patients with PUD were significantly higher than infected patients with gastritis. Additionally, the number of T-bet+ cells and INF-γ expression were found to be inversely correlated with degree of H. pylori density and chronic inflammation score (CIS) in infected patients with gastritis disease, but this correlation was positive in the infected patients with PUD. The number of T-bet+ cells was found to be positively correlated with the number of Th17 cells and inversely correlated with the number of Treg cells in infected patients with gastritis and PUD. CONCLUSION: Abnormal hyper-activation of T-bet+ cells during H. pylori-infection may lead to tissue damage caused by immunopathologic reactions.


Asunto(s)
Gastritis/patología , Úlcera Péptica/epidemiología , Úlcera Péptica/microbiología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Adulto , Femenino , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Mucosa Gástrica/fisiología , Gastritis/inmunología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/inmunología , Humanos , Inmunohistoquímica , Interferón gamma/biosíntesis , Masculino , Persona de Mediana Edad
16.
Mult Scler Relat Disord ; 35: 233-238, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31421626

RESUMEN

BACKGROUND: Mesenchymal stem cells (MSCs) have the capacity to migrate into the inflammatory regions in response to chemokines such as, IP-10 and SDF-1α and function as anti-inflammatory and immunomodulatory cells. METHODS: In this study we investigated the MSCs frequency in peripheral blood of Relapsing-Remitting Multiple Sclerosis (RRMS) patients in clinically active and not on disease-modifying therapy (DMT) (n = 22) and clinically stable on DMT (Interferon-ß (IFN-ß) therapy) for at least 6 months (n = 22) in comparison to sex and age-matched healthy controls (n = 25) using flow cytometry. The serum and gene expression levels of IP-10 and SDF-1a were also measured in studied groups by ELISA and Real time- PCR. RESULTS: We obtained significant high levels of circulating CD45-CD34- CD90+ and CD45-CD34- CD105+ cells in clinically active patients, not on DMT and patients under IFNß therapy compared with control group. Furthermore, a significant increase in the percentage of circulating CD45-CD34- CD105+ CD90+ cells was found in clinically active patients and not on DMT compared with control group. Serum analysis of IP-10 and SDF-1α showed a significant increase in IP10 concentration in both clinically active not on DMT (P = 0.02) and on DMT (P = 0.005) RRMS patients in comparison with controls. The expression level of SDF-1α mRNA significantly increased in clinically active not on DMT (P = 0.03), while decreased in patients under IFNß therapy (P = 0.04). The mRNA expression of IP-10 only increased in patients on DMT compared with controls (P = 0.05). CONCLUSION: Circulating MSCs, IP-10 and SDF-1α levels, increased in RRMS patients with clinically active not on DMT and IFN-ß therapy reduced circulating MSCs and SDF-1α levels.


Asunto(s)
Quimiocina CXCL10/sangre , Quimiocina CXCL12/sangre , Factores Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico , Células Madre Mesenquimatosas , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Femenino , Citometría de Flujo , Humanos , Masculino , Esclerosis Múltiple/sangre , Adulto Joven
17.
Mol Biol Rep ; 46(6): 5703-5712, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31359381

RESUMEN

Helicobacter pylori (H. pylori) has been shown to be one of the leading causes of peptic ulcer diseases (PUDs) and gastritis. T helper-22 (Th22) cells and its most important cytokine, interleukin-22 (IL-22) are importantly active in inflammation and inflammatory tissues. Since inflammation is one of the main attributes of infection caused by H. pylori and resulting complications (gastritis and gastrointestinal ulcer), this study was designed to evaluate the Th22 cells count and the IL-22 protein expression in people suffering from PUD and gastritis. The present study was conducted on 55 patients with gastritis, 47 patients with PUD and 48 uninfected subjects. After preparation of section and extraction of protein from antral biopsies, immunohistochemistry and western blot methods were used to evaluate the Th22 cells and IL-22 protein expression level, respectively. According to findings, the Th22 cells count and the IL-22 protein expression level in the infected subjects were siginficantly more than in the uninfected subjects. It should be noted that the Th22 cells count and the IL-22 protein expression level in the infected subjects with PUD were significantly greater than those in the infected subjects with gastritis. In addition, the Th22 cells count had positive correlation with the density of H. pylori, chronic inflammation score and acute inflammatory score in the infected subjects with PUD. The Th22 cells count had positive correlation with the Th17 cells count and inverse correlation with the Treg cells count in the infected subjects with PUD and gastritis. Our data demonstrated that abnormal hyper-activation of Th22 cells as well as its correlation with the Th17 cells during infection caused by H. pylori might damage tissues through immunopathological responses.


Asunto(s)
Gastritis/inmunología , Infecciones por Helicobacter/inmunología , Interleucinas/inmunología , Úlcera Péptica/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Adulto , Anciano , Femenino , Mucosa Gástrica/química , Mucosa Gástrica/inmunología , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Gastritis/fisiopatología , Infecciones por Helicobacter/fisiopatología , Helicobacter pylori , Humanos , Inflamación/inmunología , Inflamación/fisiopatología , Interleucinas/metabolismo , Masculino , Persona de Mediana Edad , Úlcera Péptica/fisiopatología , Antro Pilórico/química , Antro Pilórico/inmunología , Antro Pilórico/metabolismo , Antro Pilórico/patología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Linfocitos T Colaboradores-Inductores/metabolismo , Interleucina-22
18.
Res Pharm Sci ; 14(1): 55-63, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30936933

RESUMEN

Treatment of acute lymphoblastic leukemia (ALL) has been promising in last decades, but side effects still persist and searching for the least toxic agents continue. Pterostilbene (PTE) is a natural compound with several anti-cancer and anti-oxidant properties. Fas, as a member of death inducing family of tumor necrosis factor (TNF) receptors with an intracellular death domain, can initiate the extrinsic apoptosis signaling pathway. Here after the half maximal inhibitory concentration (IC50) determination in cell lines, we searched for PTE effects on Fas, both in mRNA and surface levels in two ALL cell lines, Jurkat and Molt-4. After harvesting cells in optimum situations, MTS assay was used to determine IC50 concentrations. Real-time polymerase chain reaction (RT-PCR) and flow cytometry were performed for Fas mRNA and surface expression variations after exposure to PTE. The findings showed that PTE decreases cell viability with different extent in two ALL cell lines. In addition to inducing apoptosis, it can increase Fas in both gene and cell surface expression in the same concentrations. Pterostilbene as a natural anti-cancer agent can increase Fas expression both in mRNA and surface levels that results in apoptosis signal transduction improvement which sensitizes cells to apoptosis by immune effector cells. As a result, abnormal cells removal would be more efficiently with the minimum side effects on normal cells.

19.
Am J Rhinol Allergy ; 33(3): 286-293, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30648403

RESUMEN

BACKGROUND AND AIMS: The roles of Fas in immune system are multifaceted, and the interaction between Fas receptor and Fas ligand is essential for maintaining the immune tolerance. We aimed to assess the level of the expression of Fas receptor on nasal inferior turbinate mucosa in patients with mild persistent allergic rhinitis (M PAR) and moderate to severe (M/S) PAR and determined the relationship between disease severity and production of Fas. METHODS: A total of 70 patients with M/S PAR, 70 patients with M PAR, and 70 healthy individuals were enrolled in this study. We obtained biopsies of nasal inferior turbinate mucosa from the participants. The expression of Fas mRNA was evaluated by real-time polymerase chain reaction. The presence and location of Fas were determined by immunohistochemistry. The number of eosinophils per field, blood eosinophils, total serum IgE levels, and specific serum IgE levels were measured. Clinical manifestations of patients were assessed by Total Nasal Syndrome Score (TNSS). RESULTS: The expression of Fas in patients with M/S PAR was decreased significantly compared to the control group and patients with M PAR. Local mucosal expression of Fas was correlated with specific IgE, nasal eosinophil count, and TNSS. CONCLUSION: According to the results of this study, there might be a relationship between the expression of Fas receptor on nasal turbinate mucosa and the severity of persistent allergic rhinitis.


Asunto(s)
Rinitis Alérgica/genética , Rinitis Alérgica/fisiopatología , Receptor fas/genética , Receptor fas/metabolismo , Adulto , Animales , Eosinófilos/metabolismo , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunohistoquímica , Recuento de Leucocitos , Masculino , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , ARN Mensajero/metabolismo , Rinitis Alérgica/metabolismo , Cornetes Nasales/metabolismo , Cornetes Nasales/patología , Adulto Joven
20.
Biosci Rep ; 39(1)2019 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-30459240

RESUMEN

Some medicinal herbs and compounds are known to target cancer cells, but the success of them as anticancer compounds depends to a large extent on their ability to activate pathways that kill cancer cells by arresting cell cycle and inducing apoptosis. The aim of the present study was to determine the anticancer effects of Euphorbia szovitsii Fisch. & C.A.Mey. on the breast cancer cells to reveal the underlying mechanism of its anti-breast cancer properties. In this experimental study, triple negative breast cancer cell line (MDA-MB-231) was cultivated in RPMI-1640 medium. Hydroalcoholic extract (70:30) of aerial parts of the plant was prepared. The cultured cells were treated with different concentrations (0-1000 µg/ml) of E. szovitsii extract for 24 and 48 h. Toxicity of the extract on MDA-MB-231 cells was examined using MTT (3-[4,5-dimethyl-2-thiazolyl]-2, 5 diphenyl tetrazolium bromide) test. The Annexin V-FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to differentiate different phases of the cell cycle in the cells. Data were analyzed by GraphPad Prism and SPSS software. After 24 and 48 h, the IC50 values were respectively 76.78 (95% CI = 60.75-97.05; R = 0.8588) and 59.71 (95% CI = 46.25-77.09; R = 0.8543) µg/ml for E. szovitsii The extract exhibited antiproliferative effects against MDA-MB-231 cells in a dose-dependent manner. Annexin V-FITC/PI assay confirmed that the extract was able to induce apoptosis in MDA-MB-231 cells. Moreover, treatment with the extract resulted in cell cycle arrest at G1 phase. Therefore, E. szovitsii could induce apoptosis and cycle arrest in the MDA-MB-231 cell line. It might be a good resource of natural products for producing anti-breast cancer drugs.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Células Epiteliales/efectos de los fármacos , Euphorbia/química , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Extracción Líquido-Líquido/métodos , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Epiteliales/patología , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Humanos , Irán , Glándulas Mamarias Humanas/efectos de los fármacos , Glándulas Mamarias Humanas/patología , Componentes Aéreos de las Plantas/química , Extractos Vegetales/química , Plantas Medicinales
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