gholamhossein hassanshahi
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Multiple sclerosis (MS) is a complex clinical immune system disorder. The most common symptoms of MS are recurrent loss of myelin in conjunction with inflammation in the central nervous system (CNS). Chemokines, as important immune system components, play a role in immune responses. This project aimed to examine and compare the serum levels of CXCL1 and CXCL9 in patients with relapse-remitting MS (RRMS) following therapy with IFN-β formulations. Clinical specimens were collected from 50 unrelated healthy controls, as well as 40 RRMS patients treated with Cinnovex™ (CVX, Interferon beta-1a, made in Iran) and Avonex® (AVX, Interferon beta-1a, made in the USA). The fold changes in gene expression of CXCL1 and CXCL9 compared to the β-actin gene were determined using real-time PCR. The protein expression and serum levels of CXCL1 and CXCL9 were measured using the ELISA method. Data analysis was performed using the ANOVA test. The levels of CXCL1 and CXCL9 significantly increased, with greater upregulation observed with AVX and, to a lesser extent, with CVX. Our study results suggest that AVX is more effective than CVX in regulating the immune system, and the dosage of CVX may need to be increased to achieve a more pronounced therapeutic response in RRMS patients.
Keywords: Avonex®, Cinnovex™, CXCL1, CXCL9, IFN-Β Formulations, Multiple Sclerosis -
BackgroundThe CXCR4 receptor along with CXCL12 is believed to have an effect on the onset, progression, migration, and treatment complications and improve acute myeloid leukemia (AML) treatment outcomes. In this study, we investigated the impact of (7+3) chemotherapy protocol on the expression of CXCR4 and its related ligand CXCL12.MethodIn this case-control study, specimens were collected before and after the first cycle of chemotherapy of AML-M4 and AML-M5 patients. Reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry techniques tested the CXCR4 expression. ELISA was used for measuring the serum level of CXCL12. Two samples, t-test and paired t-test, were utilized for data analysis.ResultsWe found that CXCR4 expression by lymphocyte cells after chemotherapy was approximately similar to the CXCR4 expression in the healthy subjects. Moreover, CXCR4 expression was high prior to chemotherapy. The serum level of CXCL12 considerably increased in the patients before chemotherapy. However, after chemotherapy, CXCL12 was found to reach the baseline level in comparison to the healthy control group.ConclusionThe (7+3) current chemotherapy inhibited CXCL12. Therefore, controlling chemokines along with chemotherapy in AML patients might be conducive to the treatment process or even prevent the relapse of the disease.Keywords: Acute myeloid leukemia, Chemotherapy, Chemokine, CXCL12, CXCR4
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Background
The genus Pistacia is from the family Anacardiaceae, which contains about 70 genera and over 600 species. Various genera of Pistacia are widely spread from the Mediterranean region to the Central Asia, some of which including Pistacia lentiscus L., P. atlantica Desf., P. terebinthus L., P. vera L., and P. khinjuk.
Materials and MethodsThe present study aims to collect the latest information from databases regarding beneficial effects of pistachio plant parts and nuts.
ResultsDifferent plant parts of pistachios are beneficial for various diseases. The P. vera fruit extracts exerted favorable effects on HDL and LDL levels in a rabbit model of atherosclerosis. The oleogum resin, being obtained from Pistacia lentiscus, is widely used as an effective therapeutic remedy for curing inflammatory bowel disease in traditional Iranian medicine. Serum glucose levels significantly decreased in diabetic patients who received P. lentiscus var. chia gum.
ConclusionsAgainst this backdrop, in this review article, we aim to investigate beneficial effects of pistachio fruit and its plant parts on different clinical states, such as gastrointestinal disorders, liver diseases, diabetes, and blood pressure.
Keywords: Pistachio, Liver diseases, Gastrointestinal disorders, Inflammatory bowel disease, Diabetes Mellitus, blood pressure -
Background
Anesthesiologists should obtain the best technique for cesarean section (CS). This study designed to compare the effect of general anesthesia (GA) and spinal anesthesia (SA) on immune system function in elective CS.
Materials and MethodsThis descriptive study was performed on forty candidates for elective CS. They were randomly divided into GA and SA groups. The serum concentrations of interleukin (IL)‑4, IL‑6, IL‑10, and IL‑17 and interferon‑gamma (IFN‑γ) were measured using ELISA method prior to anesthesia (T0), immediately after the uterine incision (T1), 2 h post CS (T2), and 24 h post CS (T3). Data were analyzed using descriptive statistics and Chi‑square, independent t‑test, and repeated measures.
ResultsNo significant differences were observed between the GA and SA groups regarding the serum levels of IL‑4, IL‑6, IL‑10, IL‑17, and IFN‑γ. The serum levels of transforming growth factor beta (TGF‑β) in the SA group were significantly (P = 0.003) more than that of the GA group at T3.
ConclusionAccording to the angiogenesis properties of TGF‑β, it seems that SA probably affects the rate of recovery more than that of the GA.
Keywords: Cesarean section, cytokine, general anesthesia, interleukin, spinal anesthesia -
Background
Due to their self-renewal and differentiation ability, the mesenchymal stem cells (MSCs) have been studied extensively. However, the MSCs lifespan is restricted; they undergo several divisions in vitro that cause several alternations in cellular features and relatively lessens their application. Thus, this study was aimed to assess the effect of platelet-derived microparticles (PMPs), a valuable source of proteins, microRNAs (miRNAs), and growth factors, on the expression of hTERT, c-MYC, p16, p53, and p21 as the most important aging and cell longevity genes alongside with population doubling time (PDT) of PMP-treated cells in comparison to a control group.
MethodsUmbilical cord MSCs (UC-MSCs) were used in this study, whereby they reached a confluency of 30%. MSCs were treated by PMPs (50 µg/mL), and then, PDT was determined for both groups. Quantitative expression of hTERT, c-MYC, p16, p53, and p21 was examined through quantitative real-time PCR at various intervals (i.e. after five and thirty days as well as freezingthawing process).
ResultsOur results demonstrated that the treated group had a shorter PDT in comparison to the control group (P<0.050). The real-Time PCR data also indicated that PMPs were able to remarkably up-regulate hTERT and c-MYC genes expression while down-regulating the expression of p16, p21, and p53 genes (P<0.050), especially following five days of treatment.
ConclusionAccording to these data, it appears that PMPs are a safe and effective candidate for prolonging the lifespan of UCMSCs; however, further investigations are needed to corroborate this finding.
Keywords: Aging, Blood platelets, Cell-derived microparticle, Gene expression, Mesenchymal stem cell -
Background and objectives
Acute myeloid leukemia (AML) is a malignancy that involves the bone marrow and peripheral blood. Some chemokines play a role in the progression, migration and tumor initiation and are therefore associated with poor prognosis. CCL2 promotes tumor growth and is associated with poor prognosis in AML patients. We investigated effects of chemotherapy on serum level of CCL2 in AML patients.
MethodsThroughout this case-control study, blood samples were collected from 25 healthy individuals and 25 AML (M4 and M5) patients before and after the first stage of the current chemotherapy regimen (7+3). Serum level of CCL2 was measured using commercial ELISA kits. Data were analyzed in SPSS 22 using the two-sample t-test and paired t-test.
ResultsBefore chemotherapy, serum level of CCL2 was significantly higher in the patients than in the healthy controls. Following chemotherapy, the serum level of CCL2 reduced significantly to a level comparable to that of the healthy controls.
ConclusionThe current chemotherapy (7+3) can effectively inhibit CCL2 in AML patients.
Keywords: Leukemia, Myeloid, Acute, Chemokine CCL2, Chemokines -
Context
According to the previous studies, general anesthesia influences the immune system. Evaluating such impacts on the immune system helps to improve the management of anesthesia.
Evidence AcquisitionThe current review aimed to summarize the literature related to the effects of general anesthesia agents on the cytokines. Google Scholar, PubMed, and ISI/Web of Sciences databases were searched using the following keywords: cytokine, general anesthesia, immune response, intravenous anesthetics, volatile anesthetics, opioids, benzodiazepines, and controlled ventilation.
ResultsLong-term administration of general anesthesia drugs, due to their effects on cytokines, can lead to disease progression in patients with immune deficiency. Due to the conflicting results of various studies and the increasing number of patients with immune deficiency, the choice of the appropriate general anesthesia agents facilitates achieving the more favorable function of the cytokines.
ConclusionsIt seems that the effect of general anesthesia on the immune system in healthy patients and short-term surgeries is not considerable and changes in the immune system are related to surgical trauma, particularly in major surgery.
Keywords: Cytokine, General Anesthesia, Inherent Immune System, Acquired Immune System -
Background
The purpose of this study was to investigate the role of eotaxin family members including C-C motif chemokine 11 (CCL11), C-C motif chemokine 24 (CCL24), and C-C motif chemokine 26 (CCL26) as the subgroups of CC-chemokine in patients affected with osteoporosis and osteopenia.
MethodsOverall, 19 osteoporotic patients, 18 osteopenic individuals, and 20 healthy subjects were recruited in this study. The bone mineral density (BMD) was then measured at the lumbar spine (L1-L4) and the hip (femoral neck and total hip) using dual-energy X-ray absorptiometry for diagnosis of bone density and related disorders. Additionally, enzyme-linked immunosorbent assay (ELISA) technique was employed to measure the serum levels of CCL11, CCL24, and CCL26.
ResultsThe circulating levels of CCL11, CCL24, and CCL26 had been increased in both groups of patients with osteopenia and osteoporosis compared to those in healthy subjects (P<0.05); while no significant difference was observed between serum levels of these chemokines in such patients.
ConclusionEotaxins can play a role in the pathogenesis of osteoporosis and osteopenia; however, further studies are needed to clarify various roles of eotaxins in the pathophysiology of osteoporosis and osteopenia.
Keywords: Eotaxins, Protein, Human, Osteopenia, Osteoporosis -
Fluoroquinolones (FQs) are widely used in the treatment of infections caused by Escherichia coli. FQs are broad spectrum antibiotics with high tissue penetration, and ease of use. Therefore, given the concerns existing about drug resistance, we aim to review the latest findings about resistance patterns to levofloxacin (LVX) along with other FQs in E. coli infections in different parts of Iran. Evidence shows that quinolones have been used in Iran for nearly 50 years, and that 0-65% of E. coli isolates show resistance to FQs. In the western parts of Iran, the highest rate of resistance to LVX (66.7%) has been reported among patients having urinary tract infections with E. coli isolates. Few studies and information exist on the antimicrobial resistance of E. coli to LVX in different geographical locations of Iran. However, the findings of various studies on this subject show that E. coli resistance to LVX is more in the western part of Iran than in central and southern regions, but it is similar among inpatients and outpatients. Therefore, it is reasonable advisable to limit the overuse, inappropriate prescription, and self-medication of LVX to prevent the induction of FQ-resistant strains. Accordingly, in order to obtain a clearer image of resistance to FQs, especially LVX in E. coli in Iran, more extensive investigations in different geographical locations and periods of time are required. In addition, antimicrobial stewardship would be helpful in this regard.
Keywords: Escherichia coli, Fluoroquinolones, Levofloxacin, Iran, Antibiotic resistance -
The severity of postoperative pain and hemodynamic changes during and post-cesarean section have a direct effect on the neonatal and maternal condition. This study aimed to compare pain severity, hemodynamic changes, and patient satisfaction following two anesthesia techniques in elective cesarean section. In this blinded study, 60 women who were candidate for cesarean section were allocated into two equal groups of general anesthesia (GA) and spinal anesthesia (SA). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and O2 Saturation at pre cesarean (T0), the uterine incision time (T1), end of surgery (T2), 6h (T3), 12h (T4), and 24 hours post-cesarean (T5) were measured. A Visual Analog Scale assessed post-cesarean pain, 6, 12, and 24 hours post-cesarean. Gender, birth weight, first- and fifth- minutes’ apgar score was recorded in the checklists. The VAS score was significantly higher in the GA group at 6h, 12h, and 24 hours post-cesarean (P=0.014, P=0.002, P=0.017, respectively). SBP and DBP at T1 in the GA group were significantly higher than in the S.A group (P<0.001). The heart rate at T0 and T1 in the GA group was lower than the SA group (P=0.001, P=0.045 respectively). The difference between the apgar scores of the two groups was not significant. SA for cesarean section was associated with lower postoperative pain, systolic and diastolic blood pressure. However, the two groups had no significant difference in terms of patients’ satisfaction and apgar scores.
Keywords: Pain, Hemodynamic changes, Spinal anesthesia, General anesthesia, Cesarean section, Patient satisfaction -
BackgroundSepsis is regarded as a critical clinical status in neonates. Since blood culture is a time-consuming method, the present study was conducted to investigate the serum level of Ferritin, Procalcitonin, and CRP in the peripheral blood of term neonates suspected with sepsis to have a quicker diagnosis for the disease.MethodsIn the present cross-sectional study, a total of 60 neonates suspected with sepsis who had been hospitalized in Ali ibn Abi Talib Hospital of Rafsanjan/ Iran in 2015-2016 were randomly selected. Before conducting the treatment processes, blood samples were taken from all neonates and sent for blood culture. The intended markers were measured both before and after the treatments and the results were recorded in special forms for each neonate. Data were analyzed through SPSS20 and using chi-squared test, Paired t-test, and drawing a ROC curve for determining the best cut-off point and measuring the sensitivity and specificity.ResultsIn this study, 70% of the neonates suspected with sepsis were male, 56.7% were younger than 7 days old and 96.7% had natural weight. The most common symptoms were poor feeding and reduced sucking reflexes. Data analysis of the markers indicate that they reduced significantly after the treatment (p<0.001). The sensitivity, specificity, and the best cut-off point were respectively 64.3%, 43.5%, and 257.8 for Ferritin, 78.6%, 50%, and 23 for Procalcitonin and 85.7%, 65.2%, and 21.5 for CRP.ConclusionAccording to the obtained findings, applying these markers can be of a great use in diagnosing neonatal sepsis. However, given the low sensitivity and specificity of Ferritin, Procalcitonin and CRP in the present study, further studies need to be conducted to obtain more definite results.Keywords: Sepsis, neonate, Ferritin, procalcitonin, CRP, Rafsanjan
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زمینه و هدفتلومراز آنزیمی است که در 90-80% سرطان ها افزایش بیان دارد. فعالیت همزمان تلومراز و NF-Κb برای پیشرفت بسیاری از سرطان ها ضروری است. محققین در سال های اخیر به ارتباط تنگاتنگ تلومراز با فاکتور رونویسیNF-κB پی برده اند. با افزایش بیان تلومراز، افزایش قابل توجهی در بیان NF-κB و ژن های هدف، ازجملهIL-6 و TNFαمشاهده می شود. در سال های اخیر روش های متعددی جهت مهار تلومراز در سلول های سرطانی ارائه شده است. بنابراین، اگر بتوان با مهار تلومراز بیان سایتوکاین های التهابی، مسیر سیگنالینگ NF-κB و بیان ژن های هدف آن را در بیماری مالتیپل میلوما کاهش داد، گامی موثر در درمان این بدخیمی برداشته شده است. در این مطالعه MST-312 (مشتقی از چای سبز) با خاصیت مهارکنندگی تلومراز بر روی رده سلولی U266 تیمارشده و بیان سایتوکاین های التهابی بررسی گردید.روش بررسیدر این مطالعه تجربی، سلول های U266 با دوزهای مختلف MST-312، به مدت 48 ساعت تیمار شدند و آپوپتوز سلولی با استفاده از کیت انکسینV بررسی گردید، سپس برای مطالعه بیان ژن های IL-6 و TNFα، سلول ها (با دوز 2 میکرومولار به مدت 48 ساعت) با داروی MST-312 مجاور و RNA این سلول ها استخراج شد. در ادامه، میزان بیان ژن باروشReal Time PCR بررسی گردید.یافته هادر این مطالعه، افزایش آپوپتوز و کاهش بیان ژن های IL-6 و TNFα در سلول های U266 بعد از مواجه 48 ساعته با غلظت 2 میکرومولار MST-312 مشاهده گردید. همچنین هیچ اثر سیتوتوکسیکی بر روی سلول های نرمال تک هسته ای خون دیده نشد.نتیجه گیرینتایج مطالعه حاضر نشان داد مهار فعالیت تلومراز به وسیله MST-312 می تواند به عنوان یک راهبرد جدید برای درمان مالتیپل میلوما در نظرگرفته شود.کلید واژگان: مالتیپل میلوما, تومور نکروزینگ فاکتور آلفا, اینترلوکین, 6, MST, 312Background And ObjectivesTelomerase is an enzyme, which is overexpressed in 80-90% of cancers. Simultaneous activities of telomerase and NF-κB are required for progression of many cancers. In recent years, researchers have found out a close relationship between telomerase and the transcription factor NF-κB. Increased expression of telomerase is associated with significant increases in the expression level of NF-κB and endogenous genes, such as IL-6 and TNF-α. In recent years, several methods have been proposed to inhibit telomerase in cancer cells. Therefore, If it is possible to inhibit telomerase activity and consequently reduce the expression of inflammatory cytokines, the NF-κB signaling pathway, and the expression of target genes in the multiple myeloma disease. In this study, the effect of MST-312 (a derivative of green tea) with telomerase inhibition activity, was investigated on the treated U266 cell line and the expression of inflammatory cytokines.MethodsIn this experimental study, U266 cells, were treated with different dosed of MST-312 for 48 hours, and cellular apoptosis, was assessed by Annexin V Apoptosis Detection Kit. Then, to assess the expression of IL-6 and TNF-α genes, cells were treated with MST-312 (2μM for 48 hours) and the RNA of these cells, was extracted. In the following, real-time PCR method was used to investigate gene expression level.ResultsIn this study, an increase in apoptosis and a decrease in the expression of IL-6 and TNF-α genes in U266 cells, was observed after 48 hours of exposure with 2μM MST-312. In addition, no cytotoxic effect was observed on normal blood mononuclear cells.ConclusionThe results of the present study indicated that inhibition of telomerase activity by MST-312, can be considered as a novel treatment strategy for multiple myeloma.Keywords: Multiple myeloma, Tumor necrosis factor, alpha, Interleukin, 6, MST, 312
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BackgroundAcute myeloblastic leukemia (AML) is a clonal disorder due to bone marrow failure and uncontrolled proliferation of myeloid lineage. Acute promyelocytic leukemia (APL) is a subtype of AML. Heterocyclic compounds, such as indole, are considered as attractive candidates for cancer therapy, due to their abundance in nature and known biological activity. Sal-like protein (SALL4) is a zinc finger transcription factor involving in the multi-potency of stem cells, in the NB4 cell line. This study was aimed to evaluate the effects of basal indole and its new derivative, 2-(1-((2, 4-Aril)imino)-2,2,2-trifluoroethyl) phenyl-1H Indole-3- carbaldehyde (TFPHC), on the expression of SALL4.MethodsCells were cultured and treated with different concentrations (75, 150, and 300 µg/mL) of the new indole derivative and DMSO, as a vehicle control, for 24 and 48 hours. Cell proliferation was evaluated by using Trypan blue exclusion and MTT assays. The percentage of apoptotic cells was determined by flowcytometry analysis using the Annexin V/PI apoptosis detection kit; mRNA expression of SALL4 was studied using absolute quantitative RT-PCR.ResultsOur findings demonstrated the effects of new indole derivatives on SALL4 mRNA expression. Expression of SALL4 mRNA was significantly decreased at 75, 150, and 300 µg/mL concentrations.ConclusionSALL4 plays a role in the survival of APL cells. SALL4 expression could be suppressed by the novel indole derivative. Additionally, SALL4 gene suppression can serve as a target in APL therapy.Keywords: SALL4 protein, Indoles, Leukemia, Acute promyelocytic
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Journal of Advanced Medical Sciences and Applied Technologies, Volume:3 Issue: 4, Dec 2017, PP 197 -204ObjectivesCerebral ischemic preconditioning lessens stroke-induced injuries, but it is clinically feasible only when the occurrence of stroke is predictable. Reperfusion plays a critical role against cerebral injury after stroke; we tested the hypothesis that interrupting ischemia during early reperfusion, i.e. Postconditioning (POCO) affects CXC chemokine expression and further reduce inflammation in rat model of ischemia/reperfusion. Materials &MethodsAdult male Wistar rats (250-300 g) were used in this experiment. Using 4-vessel occlusion method, global cerebral ischemia was induced and POCO was performed by applying 3 cycles of 15-s/15-s reperfusion/reocclusion after a 45-s reperfusion (POCO-45-15/15). Western blotting analysis was used to investigate CXCL1, CXCL10 and CXCL12 expression 24 h, 48 h and one week after ischemic postconditioning (iPOCO).ResultsBased on the results, iPOCO attenuates the expression of inflammatory chemokines CXCL1 and CXCL10 in hippocampus area of postconditioned rats, while the CXCL12 was not affected by iPOCO.ConclusionCurrent findings may support chemokines role in iPOCO via reduction of inflammation. Also there could be a link between postconditioning, stress and inflammation through chemokines.Keywords: Chemokine, Global cerebralischemia, Postconditioning
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BackgroundThe hepatocellular carcinoma is believed to be the third cause of death due to cancer, worldwide. A new derivative of the (2R,4S)-N-(2,5-difluorophenyl)-4-hydroxy-1-(2,2,2-trifluoroacetyl) pyrrolidine-2-carboxamide compound were synthesized, employing a facile one-pot reaction of trans-4-hydroxy proline and N-(2,5-difluorophenyl)-2,2,2-trifluoroacetimidoyl chloride in the presence of TiO2 as catalysts and sodium hydrogen carbonate.ObjectivesTherefore, in the present study we aimed to explore whether if the above new derivative pyrrolidine-2-carboxamide can affect cellular viability and apoptosis in cancerous HepG2 cell line.MethodsHepG2 cells were cultured in RPMI 1640 medium containing fetal bovine serum. Cultured cells were then treated with 7.8 µM to 125 µM of pyrrolidine-2-carboxamide. The toxicity of the compound was assayed by MTT method and detection of annexin V signal, using a flowcytometry system.ResultsWe found the pyrrolidine-2-carboxamide derived inhibition of HepG2 cells following a dose and time dependent fashion. The highest numbers of dead cells were observed in 125 µM dose, after 48 hours of treatment. Flow cytometric analysis also revealed that massive numbers of apoptotic cells were detectable in response to treatment with this pyrrolidine derivative.ConclusionsOverall, according to the data presented here, the pyrrolidine-2-carboxamide could possibly control cellular viability/apoptosis. Thus it can potentially be concerned as a useful therapeutic tool for hepatocellular carcinoma treatment.Keywords: Apoptosis, HepG2 Cell Line
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The Achillea millefolium L. (Yarrow) is a common herb which is widely being used, worldwide. Achillea is being used for treatment of many disorders since centuries. It is considered safe for supplemental use and flavonoids such as kaempferol, luteolin and apigenin are of main constituents present in Achillea. Most of both antioxidant and anti-inflammatory properties of this herb have been attributed to its flavonoid content. Oxidative and inflammatory processes play important roles in pathogenesis of neurodegenerative diseases. Present review was aimed to review the latest literature evidences regarding application of Achillea and/or its three main flavonoid constituents on epilepsy, Alzheimer's disease, multiple sclerosis, Parkinson's disease and stroke.Keywords: Achillea millefolium, Flavonoids, Medicinal, Neurodegenerative disease, Plants
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BackgroundThe exact pathogenesis of epilepsy is not clear well. Recent studies showed the possible involvement of transient receptor potential vanilloid type 1 (TRPV1) receptors in this disease.ObjectivesThe aim of this study was to measure the expression of TRPV1 receptors in hippocampus following pentylenetetrazole (PTZ)-induced kindling in male rats.Materials And MethodsIn this experimental study, 14 male Wistar rats were allocated into two groups of experimental and control (seven rats in each group). The kindling group received a subconvulsive dose of PTZ (35 mg/kg, intraperitoneally) every 48 hours for 15 sessions, while the control rats were injected with an equal dose of saline. At the end of the injections, rats were decapitated, and their brains were removed. TRPV1 receptor expression in hippocampus region was assessed by real-time polymerase chain reaction method.ResultsThe results of the current study showed that expressions of TRPV1 receptors were increased in hippocampus following PTZ-induced kindling in male rats.ConclusionsSince the expression of TRPV1 receptors increased in hippocampus of epileptic rats, the TRPV1 receptors may be good candidates for epilepsy treatment.Keywords: Kindling, Pentylenetetrazole, Hippocampus, TRPV1
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هدفیکی از دلایل ایجاد سرطان، بیان نابجای ژنهای کنترل کننده مسیر خود بازآفرینی در سلول سرطانی است. لذا در این مطالعه بیان ژن های اصلی کنترل کننده مسیر خود بازآفرینی شامل OCT4، NANOG، KLF4، SOX2 و NUCLEOSTEMIN در دو رده سلولی 5637 و HT1376، بافت سرطانی و بافت سالم پنچ نمونه توده بیوپسی بافت سرطانی مثانه، مورد بررسی قرار گرفت.مواد وروش هادر این مطالعه آزمایشگاهی، رده های سلولی در فلاسک های کشت و محیط کشت کامل RPMI1640 کشت و نگه داری شدند و نمونه های بیوپسی بافت سرطان از میان نمونه های سرطانی ارسالی به آزمایشگاه پاتولوژی و به صورت بافت تازه (Fresh)، با توجه به علائم بالینی و یافته های آزمایشگاهی، انتخاب و مورد بررسی قرار گرفتند. حاشیه های نمونه های بیوپسی به عنوان بافت سالم انتخاب گردید. بیان ژن های مورد نظر با استفاده از پرایمرهای اختصاصی، دستگاه Real-Time PCR و فرمول 2- -delta ct مورد بررسی قرار گرفت.نتایجارزیابی نتایج Real-Time PCR نشان داد ژن های مورد مطالعه در رده های سلول سرطانی و نیز بافت سرطانی توده های بیوپسی سرطانی مورد مطالعه بیان می شوند در حالیکه در بافت سالم توده های بیوپسی مورد اشاره، بیان این ژنها مشاهده نمی شود..نتیجه گیریبیان ژن های OCT4، NANOG، KLF4، SOX2 و NUCLEOSTEMIN لازمه القاء توان خود بازآفرینی است. نتایج این تحقیق نشان می دهد این ژن ها در بافت سرطانی و رده های سلول سرطانی در مقایسه با بافت سالم بیان بالاتری از خود نشان می دهند. لذا به نظر میرسد مطالعه علت فعال شدن مجدد این ژنها میتواند در شناسایی ماهیت سرطان کمک کننده باشد.کلید واژگان: رده سلول سرطانی, ژن های مسیر خودبازآفرینی, سرطان مثانهBackground And AimsRe-expression of self-renewal genes is one of the causes of cancer. So, expressional profile of self-renewal genes including, OCT4, NANOG, KLF4, SOX2 and Nucleostemin in two cell lines (5637 and HT1376), cancer and normal tissues of five bladder cancer biopsy tissues were analyzed.MethodsIn this experimental study, the cell lines were cultured in RPMI1640 medium. Cancer tissue samples were selected from samples referred to the pathology laboratory, according to clinical symptoms and laboratory findings. Tissue edges were selected as healthy tissue. Expressional profile of interested genes (mRNA expression) was carried down by Real-Time PCR, data were analyzed by ∆∆ct formula and expressional rate reported as fold changes.ResultsThe Real-Time PCR results showed that the expression of studied genes in cancer cell lines and tumor tissues were down by similar pattern but did not expressed in healthy tissue.ConclusionThe expression of OCT4, NANOG, KLF4, SOX2 and Nucleostemin genes were necessary for induction of self-renewal potency. The results showed that these genes were expressed in cancer tissue and cancer cell lines in compared to normal tissues. The investigation of re-expression of mentioned genes is recommended.Keywords: Cancer cell lines, Self, renewal genes, Bladder cancer
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مقدمهشبکه پیچیده کموکاین ها و رسپتور آن ها نقش مهمی در گسترش و متاستاز تومورها دارد. این مطالعه به بررسی میزان بیان mRNA ی CCR2 و CCR5 و هم چنین سطح سرمی CCL2 و CCL5 در بیماران مبتلا به کارسینوم سلول های ترانزیشنال مثانه قبل و بعد از عمل TUR می پردازد.مواد و روش هادر این تحقیق پیش رو 40 نفر بیمار مرد مبتلا به Transitional Cell Carcinoma (TCC) و 40 نفر مرد سالم وارد مطالعه شدند. نمونه های خون قبل از TUR و 28 روز بعد از آن جمع آوری شد. هم چنین از 12 نفر از این بیماران، بافت توموری و بافت نرمال در حین عمل گرفته شد. بیان ژن CCR2 و CCR5 از نمونه بافت سالم و توموری به صورت ظاهری(Gross) و هم چنین در PBLs با استفاده از تکنیک Real-Time PCR مشخص شد. سطح پروتئین CCL2 و CCL5 در PBLs با استفاده از تکنیک الیزا بررسی شد. یافته ها با استفاده از نرم افزار آماری SPSS با سطح معنی داری P<0.05 آنالیز شد.
یافته های پژوهش: بیان ژن CCR2 و CCR5در بافت توموری نسبت به بافت سالم و در PBLs بعد از عمل TUR نسبت به قبل از عمل، افزایش معنی داری نشان می دهد(P<0.05). در بررسی سطح سرمی CCL2 و CCL5 در افراد مبتلا به TCC نسبت به افراد نرمال افزایش معنی داری نشان می دهد(P<0.05). در این بررسی سطح سرمی CCL2 و CCL5 رفتار متمایزی نشان می دهد، بدین صورت که سطح سرمی CCL2 بعد از عمل TUR به طور معنی داری افزایش و سطح سرمی CCL5، به طور معنی داری کاهش دارد(P<0.05).بحث و نتیجه گیریمطالعه حاضر نشان دهنده تغییرات محور کموکاین/رسپتور CCL2/CCR2 در بافت توموری نسبت به بافت سالم و هم چنین در PBLs است که بعد از عمل TUR نسبت به قبل از عمل، افزایش معنی داری نشان می دهد تغییرات محور کموکاین/رسپتور CCL5/CCR5 متفاوت می باشد و سطح سرمی CCL5، به طور معنی داری کاهش پیدا کرده است. به نظر می رسد ماهیت سلول های توموری در تولید و بیان CCL2/CCR2 و CCL5/CCR5 متفاوت عمل کرده است. در حالی که به طور کلی انتظار داریم با پیشرفت تومور میزان لیگاند و رسپتور افزایش پیدا کرده باشد که حائز اهمیت بوده و نیاز به بررسی های بیشتر آن به خصوص در تومورهای توپر را نشان می دهد. از طرفی حذف فیزیکی تومور نقش عمیقی در بیان و ترشح کموکاین های مورد نظر نداشته است.کلید واژگان: کارسینوم سلول های ترانزیشنال, CCR5, CCR2, CCL5, CCL2IntroductionThe complex network of chemokines and their receptors play an important role in development and metastasis of tumors. This study examines the mRNA expression rate of CCR2 and CCR5 and also the serum levels of CCL2 and CCL5 in patients with bladder transitional cells carcinoma before and after transurethral resection (TUR) surgery.Materials and MethodsIn the present study, 40 male patients with transitional cell carcinoma (TCC) and 40 healthy subjects were included in the study. The blood samples were collected before TUR surgery and 28 days thereafter. Also, tumor and normal tissue samples were collected during the operation from12 of these patients. The CCR2 and CCR5 gene expressions of normal and tumor tissues were determined grossly and also in PBLs using real-time PCR technique. The protein levels of CCL2 and CCL5 in PBLs were investigated using ELISA technique.
Findings: The CCR2 and CCR5 gene expression in tumor tissue compared to normal tissue, and in PBLs after TUR surgery compared to pre-surgery rate showed a significant increase (P Discussion &ConclusionsThis study showed variations of chemokine / receptor axis of CCL2 / CCR2 which in tumor tissue compared to normal tissue, and in PBLs after TUR surgery compared to pre-surgery rate showed a significant increase. variations of chemokine / receptor axis of.CCL5 / CCR5 is so different, serum levels of CCL5 significantly reduced. It seems that the nature of the tumor cells acts differently in producing and expressing CCL2 / CCR2 and CCL5 / CCR5. While it is generally expected that with tumor progression, the ligand and the receptor rates will increase which is important and requires further research, particularly regarding solid tumors. However, physical removal of the tumor has not a profound role in expression and secretion of studied chemokines.Keywords: Transitional cells carcinoma, CCL2, CCL5, CCR2, CCR5 -
زمینه و هدفهیپرگلیسمی دیابتی باعث قندی شدن پروتئین های بدن و به نوبه خود موجب تغییر در ساختمان و عملکرد آن ها می گردد. برخی از عوارض بیماری دیابت از جمله نفروپاتی و رتینوپاتی به دلیل واکنش قندی شدن غیر آنزیمی پروتئین ها است. یکی از راه های درمانی برای مهار این واکنش، شکستن پیوند قند-پروتئین با استفاده از ترکیبات موجود در گیاهان دارویی می باشد. بنابراین مطالعه حاضر با هدف بررسی اثر عصاره هیدروالکلی موسیر ایرانی (Allium hirtifolium) بر مهار واکنش قند دار شدن آلبومین و توانایی شکستن پیوند آلبومین و گلوکز انجام شده است.روش بررسیدر این مطالعه آزمایشگاهی تاثیر غلظت های 1/0، 2/0، 5/0، 1 گرم بر دسی لیتر از عصاره موسیر ایرانی در دو حالت مختلف:الف) مهار واکنش قندی شدن آلبومین ب) تاثیر آن بر شکستن پیوند آلبومین و گلوکز در زمان های 72،48،24 و 144 ساعت بررسی گردید. میزان قندی شدن با روش تیوباربیتوریک اسید سنجیده شد. جهت تجزیه و تحلیل داده ها از آزمون آنالیز واریانس یک طرفه و سپس آزمون توکی استفاده گردید. 05/0P < نمایان گر اختلاف معنی دار بود.یافته هاعصاره هیدروالکلی موسیر ایرانی در غلظت های 1/0 و 2/0 باعث مهار واکنش قندی شدن آلبومین شد. به عبارت دیگر تمامی غلظت های مورد استفاده، پیوند آلبومین و گلوکز را شکستند که بیش ترین تاثیر، در زمان های 72 و 144 ساعت پس ازتیمار با عصاره موسیر در غلظت 5/0 گرم بر دسی لیتر مشاهده شد .میزان شکستن پیوند، ارتباط مستقیم با زمان تیمار داشت.نتیجه گیرینتایج نشان داد که موسیر ایرانی مانع از قندی شدن آلبومین شده و پیوند بین آلبومین و گلوکز را می شکند.بنابراین پیشنهاد می شود که تحقیقات بالینی بیشتر جهت ارزیابی اثر موسیر ایرانی بر کاهش قندی شدن آلبومین انجام شود.کلید واژگان: موسیر ایرانی, آلبومین, گلوکز, واکنش قندی شدن غیر آنزیمیBackground And AimsThe diabetic hyperglycemia leading to body proteins glycation which in turn alters their structure and function. Some of diabetes complications such as nephropathy and retinopathy are due to non-enzymatic glycation of proteins. One of the treatments to inhibit this reaction is breaking the link glucose- protein compounds in medicinal plant. Therefore, the present study was aimed to examine the effect of hydroalcoholic extract of Allium hirtifolium Boiss on inhibition of albumin glycation reaction as well as breaking of the linkage between albumin and glucose.MethodsIn this experimental study, the effects of 0.1, 0.2, 0.5 and 1 g/dl concentrations of hydroalcoholic extract of Allium hirtifolium Boiss in two different statuses: A- inhibition of the reaction of albumin glycation and B- breaking the linkage between albumin and glucose were examined In times of 24, 48, 72 and 144 hours. The measures of glycation were assayed by (TBA= Thio Barbituric Acid). For data analysis, one-way ANOVA and Tukeys statistical tests were used. A PResultsThe hydroalcoholic extract of Allium hirtifolium Boiss with 0.1 and 0.2 g/dl concentrations inhibited the glycation of albumin. On the other hand, all of applied concentration was broken the bound between albumin and glucose, but the 0.5 g/dl concentration after 72 and 144 hours had the most effect. The rate of linkage breaking had direct relation with the duration of treatment.ConclusionThe findings of the present study demonstrated that Allium hirtifolium Boiss prevents albumin glycation and also breaks the linkage in albumin and glucose. Therefore, it is suggested that clinical studies to evaluate the effects of Iranian shallot reduction albumin glycosylation be designed.Keywords: Persian shallot (Allium hirtifolium Boiss), Albumin, glucose, Nonenzymatic glycation
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Chemokines are biologically active peptides involved in the pathogenesis of various pathologies including brain malignancies. They are amongst primitive regulators of the development of immune responses against malignant glial tumors. The present study aimed to examine the expression of CC chemokines in anaplastic astrocytoma and glioblastoma multiform patients at both mRNA and protein levels. Blood specimens in parallel with stereotactic biopsy specimens were obtained from 123 patients suffering from glial tumors and 100 healthy participants as a control. The serum levels of CCL2, CCL5, and CCL11 were measured by ELISA and stereotactic samples subjected to western and northern blotting methods for protein and mRNA, respectively. Demographic characteristics were also collected by a researcher-designed questionnaire. Results of the present study indicated that, however,CCL2 andCCL5 are elevated in serum and tumor tissues of patients suffering from a glial tumor at both mRNA and protein levels, theCCL11 was almost undetectable. According to the findings of the present investigation, it could presumably be reasonable to conclude that chemokines are good predictive molecules for expecting disease severity, metastasis, and response to treatment.Keywords: Glioblastoma, Anaplastic astrocytoma, Chemokine
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زمینه و هدفگلایکه شدن غیر آنزیمی، واکنش بین قندهای احیا کننده و گروه آمین پروتئین ها است. محصولات نهایی گلایکه شدن (AGE) در فرآیند پیری و پاتوژنز بیماری ها موثر است. مهار تشکیل AGE ها یا شکستن پیوند قند-پروتئین، در کاهش روند بهبود عوارض بیماری ها از جمله اختلالات دیابت موثر خواهد بود. در این مطالعه تاثیر عصاره هیدروالکلی موسیر ایرانی بر تشکیل هموگلوبین گلایکه شده در شرایط برون تنی بررسی گردید.مواد و روش هاتاثیر غلظت های 1/0، 3/0 و 5/0 گرم بر دسی لیتر عصاره موسیر ایرانی بر مهار تشکیل هموگلوبین A1c در این مطالعه تجربی بررسی شد. تشکیل هموگلوبین A1c با کروماتوگرافی تعویض یونی سنجش گردید. از روش های آماری آنالیز واریانس یک طرفه و آزمون توکی استفاده شد. 05/0P < نمایان گر اختلاف معنی دار بود.نتایجدر غلظت 40 میلی مولار گلوکز، عصاره موسیر با غلظت 5/0 گرم بر دسی لیتر باعث کاهش معنی دار در میزان تشکیل هموگلوبین A1c پس از 7 و 14 روز انکوباسیون گردید. عصاره موسیر در تمام غلظت ها باعث کاهش مقدار هموگلوبین گلایکه شد.نتیجه گیرینتایج نشان داد موسیر می تواند مانع از تشکیل هموگلوبین A1c در شرایط هایپرگلایسمیک شود. بنابراین پیشنهاد می شود که موسیر می تواند برای بهبود عوارض دیابت مفید باشد.
کلید واژگان: دیابت ملیتوس, موسیر ایرانی, هموگلوبین A1c, هموگلوبین گلایکه شدهBackground and ObjectivesNon enzymatic glycation is a reaction that occurs between reducing sugars and amino groups of proteins. Advanced Glycation End-products (AGE) have been accounted for principal biological processes like aging and pathogenesis of some diseases. Accumulation of AGE during hyperglycemia can cause structural and functional changes of long-lived proteins. Therefore، it will be effective to inhibit protein glycation formation in order to reduce or to improve diabetes complications. The aim of this study is to determine the effects of hydroalcoholic extract of Allium Hirtifolium on the formation of glycated hemoglobin.Materials and MethodsIn this experimental study، the effects of the various concentrations of 0. 1، 0. 3، and 0. 5 gr/dl of hydroalcoholic extract of Allium Hirtifolium on the inhibition of hemoglobin glycation were examined. Hemoglobin A1c formation was assayed by ion exchange chromatography. The P-value < 0. 05 was considered as the significant level.Results10 and 14 days after incubation، at the concentration of 40 millimollar glucose، hemoglobin A1c formation decreased significantly by using 0. 5 gr/dl of hydroalcoholic extract of Allium Hirtifolium.ConclusionThe results revealed that Allium Hirtifolium can inhibit hemoglobin A1c formation in hyperglycemic condition. Therefore، it is suggested that Allium Hirtifolium can be useful for preventing the complications of diabetes.Keywords: Diabetes mellitus, Allium Hirtifolium, Hemoglobin A1c, Glycated hemoglobin -
Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (D 32) in the exon 1 of the CCR5 gene, which is known as CCR5 D 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 D 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 D 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.Keywords: CCR5, 32 mutation, Polymorphism, Iran
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سابقه و هدفOCT4B1 یکی از واریانت های ژن OCT4 است که به میزان بالایی در رده های سلول سرطانی و نیز بافت های سرطانی بیان می شود. مطالعات اخیر نشان داده اند که این واریانت قدرت آنتی آپوپتوتیکی دارد. هدف از این مطالعه بررسی تاثیر مهار این واریانت بر الگوی بیانی ژنهای خانواده آنتی آپوپتوزیس در سه رده سلول سرطانی انسان می باشد.مواد و روش هادر این مطالعه آزمایشگاهی سه رده سلول سرطانی، AGS، 5637 و U87MG از بانک سلولی انستیتو پاستور ایران خریداری و پس از کشت در دو گروه تست و کنترل با استفاده از تکنولوژی siRNA و روش لیپوفکشن به منظور مهار واریانت OCT4B1، مورد ترانسفکشن قرار گرفتند. پس از تایید مهار ژنی، تخلیص RNA و سنتز cDNA انجام شد و نهایتا بیان ژنهای مورد نظر با استفاده از پرایمرهای اختصاصی و روش Real-Time PCR، تعیین و میزان بیان هر ژن (با مقایسه گروه های تست و کنترل) تعیین گردید.یافته هانتایج نشان داد الگوی تغییرات بیان ژنی در سه رده سلول سرطانی مورد مطالعه تقریبا مشابه است و ژنهای BCL2، BRAF وBFAR به ترتیب با 20/87، 18/33و 15/11 برابر بیشترین کاهش بیان را داشته اند. در کل بیان 20 ژن از 26 ژن مورد بررسی کاهش و چهار ژن CASP2، IGF1R، TNF و MCL1 افزایش بیان جزیی یا بیان بدون تغییر داشته اند. بیان ژن CFLAR در رده سلول سرطانی U87MG، افزایش بیان اما در دو رده سلول سرطانی دیگر کاهش بیان جزیی را نشان داد.نتیجه گیریطبق نتایج بدست آمده احتمالا مهار OCT4B1 با ممانعت از بیان ژنهای خانواده آنتی آپوپتوزیس موجب کمک به القاء مرگ برنامه ریزی شده در رده های سلول سرطانی می شود.
کلید واژگان: ژن OCT4B1, خانواده ژنی آنتی آپوپتوزیس, رده های سلول سرطانیBackground And ObjectiveOCT4B1, as one of the variants of OCT4 gene, is expressed at higher levels in cancer tissues and cancer cell lines, compared to other OCT4 variants. Recent studies have revealed the anti-apoptotic role of OCT4B1. The aim of this study was to evaluate the effect of OCT4B1 suppression on the expression profile of anti-apoptotic genes in three human tumor cell lines.MethodsIn this in-vitro study, three human tumor cell lines including AGS (stomach adenocarcinoma), 5637 (bladder cancer), and U87MG (brain tumor) were purchased from the National Cell Bank of Iran (Pasteur Institute) and cultured in test and control groups. In order to suppress OCT4B1 expression, the cultures were transfected, using siRNA technology and lipofection method. After confirming the suppression process, total RNA was extracted and cDNA was synthesized. Finally, the expression rates of anti-apoptotic genes were determined, using specific primers and real-time PCR technique.FindingsOur data revealed an almost similar pattern of alteration in the expression profile of anti-apoptotic genes in all three cell lines. Also, BCL2, BRAF, and BFAR genes exhibited the most significant down-regulation by 20.87, 18.33, and 15.11 folds, respectively. The expression of at least 20 genes (out of 26 genes) decreased, while the expression rates of CASP2, IGF1R, TNF, and MCL1 were up-regulated or remained unchanged. Also, the expression of CFLAR gene was up-regulated in U87MG and down-regulated in other cell lines (5637 and AGS).ConclusionBased on our findings, OCT4B1 suppression by blocking the expression of anti-apoptotic genes may result in the induction of apoptosis in cancer cell lines.Keywords: Anti, apoptotic Gene Family, Cancer Cell Lines, OCT4B1 -
BackgroundChemokines play important roles in immune system activation against microbial infections..ObjectivesThe current study aimed to evaluate seminal levels of CXC chemokines CXCL1, CXCL9, CXCL10 and CXCL12 in Chlamydia trachomatis infected patients..Materials And MethodsThe C. trachomatis infection was determined employing Polymerase Chain Reaction (PCR)-based methods. Seminal concentrations of CXCL1, CXCL9, CXCL10 and CXCL12 were measured by Enzyme-Linked Immunosorbent Assay (ELISA)..ResultsThe current study results demonstrated that the semen levels of CXCL1 and CXCL9, but not CXCL10 and CXCL12, significantly increased in C. trachomatis infected patients compared to the healthy controls..ConclusionsBased on the current study results, it may be concluded that both CXCL1 and CXCL9 play more important roles than CXCL10 and CXCL12 in induction of immune responses against C. trachomatis and could possibly be considered as future targets for immunotherapy of C. trachomatis infection..Keywords: Chlamydia trachomatis, Chemokine, CXCL1, CXCL9, CXCL10, CXCL12
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