amrollah mostafazadeh
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International Journal of Molecular and Cellular Medicine, Volume:13 Issue: 50, Spring 2024, PP 171 -185
In a system biology-based study, we previously reported that IL-6 and IL6R -specific m-RNA levels were elevated in leukocytes of patients with Rheumatoid arthritis (RA). Here, the association of toll-like receptor4 (TLR4) rs 141534085 and cytochrome P450 family 51 subfamily A member 1(CYP51A1) rs6 with tumor necrosis factor-α (TNF- α), rheumatoid factor (RF)- and Anti- cyclic citrullinated peptide (anti-CCP) antibody -positivity was investigated in almost the same subjects. Forty-six patients and 48 normal subjects were recruited in this study. The blood leucocytes TLR4 rs 141534085 and CYP51A1 rs6 -comprising DNA sequences were amplified by using tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) technique and the PCR products were checked by Sanger DNA sequencing method. ELISA method was used to determine plasma levels of TNF- α, anti-CCP antibody and RF positivity of plasma was evaluated through a latex agglutination test. The TNF- α level was significantly higher in the patient group than control subjects (p= 0.001). Moreover, we were not able to find any correlation between TNF-α levels and RF as well as anti-CCP antibodies when we used the K2/ Fisher's exact test and Pearson test respectively. Our DNA sequencing data revealed the following new mutations in TLR4 rs141534085 comprising regions: A>T in position 1050, T>A in position 1052, and C>A in position 1054; and for CYP51A1 rs6 encompassing region, the new mutations were; G>A in position 21680, the T nucleotide was inserted in position 21762 and the G nucleotide was inserted in position 21763, G>T in position 21764. The data of this study showed that both TLR4 rs141534085 and CYP51A1 rs6 related DNA regions should be considered as hotspot areas in RA pathogenicity. Moreover, these data indicated that, TNF- α did not alter the production of anti-CCP and RF pathogenic antibodies in patients with long-term RA.
Keywords: Rheumatoid Arthritis, TLR4, CYP51A1, TNF-Α, Mutation -
Background
Despite the high prevalence of depressive and anxiety disorders among women with threatened abortion (TA), there is scant evidence regarding the efficacy of psychotherapies for this group.
ObjectivesThis research aimed to assess the effectiveness, acceptability, and feasibility of specific internet-based cognitive behavioral therapy (iCBT-Specific) and unified protocol (iUP) for women with a TA.
MethodsIn this semi-experimental study (from April to October 2023), after the treatment content was prepared, a total of 80 pregnant women with TA, over 18 years of age, having a gestational age of 5 - 12 weeks, from a hospital and two private clinics, who were diagnosed with depressive and anxiety disorders based on the short structured diagnostic interview (Mini-International Neuropsychiatric Interview), were selected. The participants were divided into two groups, undergoing iUP or iCBT-specific psychotherapies. All participants completed the Brief Symptom Inventory (BSI-18) to measure the levels of depressive and anxiety symptoms. Following eight weeks of internet-based therapy, consisting of eight 50-minute sessions, they completed the BSI-18 again, along with the Client Satisfaction Questionnaire (CSQ-8) and the System Usability Scale (SUS). Statistical analysis was performed using SPSS version 22 software, and t -test, paired t -test, and ANCOVA tests were used.
ResultsBoth the iUP and iCBT-Specific models demonstrated high acceptability, and the average feasibility of treatment was above average for both models. In terms of acceptability and feasibility of treatment for women with TA, neither model proved to be superior (all P > 0.05). Both iUP and iCBT-Specific models were effective in reducing depression and anxiety in these women (effect size for within groups were respectively Eta = 0.370, Eta = 0.536). Also, in terms of improving depression and anxiety, there was no significant difference in the effectiveness of iUP and iCBT-Specific treatments (respectively P = 0.146, Eta = 0.027 and P = 0.221, Eta = 0.019)
ConclusionsThe iUP treatment can be recognized as a reliable alternative to the iCBT-Specific method for alleviating depressive and anxiety symptoms in women with TA. Also, our results help gynecologists to use iUP as an alternative treatment when there is no definitive diagnosis of the type of disorder.
Keywords: Internet-Based Intervention, Transdiagnostic Unified Protocol, Anxiety, Depression, Threatened Abortion -
سابقه و هدف
آرتریت روماتویید(RA) یک بیماری کمپلکس و مزمن التهاب مفاصل است. فاکتورهای محیطی در افراد مستعد ژنتیکی در بروز بیماری و پیشرفت آن دخیل می باشند. این بیماری ارتباط زیادی با ژنهایی مانند آنتی ژنهای کلاس 2 انسانی دارد. در مطالعات مختلف این ارتباط حدود 60% بدست آمده است. بخصوص این ارتباط در افراد دارای آنتی بادیهای ضد پروتیینهای سیترولینه(ACPA) بیش از افراد بدون این آنتی بادیهاگزارش شده است. هدف این مطالعه بررسی ارتباط سایتوکاینها و پروتیینهای محلول در بدن بیمار مبتلا به آرتریت روماتویید پیش از بروز علایم میباشد.
مواد و روش هادر این تحقیق به منظور دستیابی به ژنهای مرتبط با بیماری از آنالیز با وب سایتهای Enrichr ، WebGestalt و GeneMania استفاده شد. به منظور بررسی میزان سایتوکاینهادر افراد بیمار تحت درمان از روش های ELISA و Real-time RT-PCR استفاده گردید.
یافته هابا بررسی سیستم بیولوژی، ژنهای IL6Rو IL6 کاندید شدند. از46 بیمار RA مراجعه کننده به بخش روماتولوژی بیمارستان روحانی بابل و 46 فرد سالم کنترل نمونه گیری شد و کاهش معنادار(P =0.1255) IL-6 در افراد بیمار در حال درمان و افزایش معنادار (P=0.4414) میزان گیرنده این سایتوکاین نسبت به افراد سالم در سرم مشاهده گردید. در حالیکه بیان ژنهای IL6 و IL6R در گروه بیمار نسبت به سالم افزایش نشان داد.
نتیجه گیریسایتوکاین IL-6 بعنوان یک سایتوکاین التهابی در بیماران تحت درمان در سرم کاهش ودر سطح RNA افزایش معناداری نشان داد. نتایج نشان دهنده افزایش بیان RNA ژن IL-6 و کاهش بیان پروتیین آن بدنبال درمان بیماری است.
کلید واژگان: آرتریت روماتوئید، Enrichr، WebGestalt، GeneMania، IL6R، IL6Aim and BackgroundRheumatoid arthritis(RA) is a complex and chronic disease of joint inflammation. Environmental factors that are important in genetically predisposed people are involved in the occurrence of the disease and its progress. This disease has a lot to related to genetics, including human class 2 antigens. In various studies, this relation is about 60%. This relationship is more positive in people with Anti-citrullinated protein antibodies (ACPA) than negative ones. The aim of this study is to investigate the relationship between cytokines and soluble proteins in the body of a patient with Rheumatoid arthritis before symptoms appear.
Materials and MethodsIn this research, analysis with Enrichr, WebGestalt, and GeneMANIA was used to find genes related to the disease. In order to check the amount of cytokines predicted, ELISA and Real time RT-PCR methods were applied.
ResultsBy examining the System Biology methods, the candidate genes included IL-6R, IL-6 and IL-23A. The samples were taken from 46 RA patients referred to the rheumatology department of the Babol hospital, and a significant decrease (Pv=0.1255) of IL-6 was observed in patients undergoing treatment and a significant increase (Pv=0.4414) in the amount of this cytokine receptor in the serum compared to healthy individuals. While the expression of IL6 and IL6R genes increased in the patient group compared to the healthy group.
ConclusionCytokine IL-6 as an inflammatory cytokine in treated patients decreased in serum and showed a significant increase in RNA level.
Keywords: Rheumatoid arthritis, Enrichr, WebGestalt, GeneMania, IL-6R, IL-6, Iau Science -
Background
Available data suggest that obesity is related to changes in the several adipocyte?derived proteins levels, which are involved in cancer recurrence. The purpose of this work was to investigate the correlation etween obesity with metalloproteinase?9 (MMP?9), adiponectin and adiponectin and AMP?activated protein kinase (AMPK) levels by comparing serum levels of MMP?9, AMPK in normal weight and obese breast cancer survivors.
Materials and MethodsIn this cross?sectional study, 30 normal weight breast cancer survivors (body mass index [BMI] 18.5?25 kg/m2) and 30 obese breast cancer survivors (BMI ?30 kg/m2) were investigated.Anthropometric parameters and serum levels of MMP?9, adiponectin, and AMPK were compared between the two groups.
ResultsNo differences were detected in the serum levels of MMP?9, adiponectin, and AMPK in obese patients and normal weight patients (P > 0.05). There were no correlations between MMP?9, adiponectin, and AMPK levels with anthropometric measurements in two groups (P > 0.05).
ConclusionWe found that there was a lack of correlation between obesity measures and serum levels of MMP?9, adiponectin, and AMPK. In breast cancer survivors, it seems that circulating levels of adiponectin, AMPK, and MMP?9 do not change in obesity state.
Keywords: Zeinab Babaei, Hadi Parsian, Bahare Korani, Amrollah Mostafazadeh, Dariush Moslemi -
Background
Stem cell differentiation therapy is a promising strategy in cancer treatment. we show that protein cocktail prepared from serum starved fibroblasts has therapeutic potential based on this strategy.
MethodsThe condition medium was prepared from foreskin isolated fibroblasts and analyzed by Liquid chromatography electrospray ionization mass spectrometry-mass spectrometry (LC-ESI-MS/MS). LA7 mammary gland cancer stem cells originated tumors were induced in Sprague Dawley rats. The rats treated subcutaneously with DMEM (group A), condition medium (group B), or normal saline (group C) once daily for 7 days. Then the tumors were removed and divided into the two parts, one part was used to quantify gene expression by stem-loop RT-qPCR assay and the other part was used for Hematoxylin & Eosin (H & E), Giemsa, and immunohistochemistry (IHC) staining.
ResultsAll induced tumors appeared as sarcomatoid carcinoma (SC). Immunohistochemistry staining confirmed this conclusion by recognizing the tumor as Ki67+, cytokeratin+, vimentine+, and estrogen receptor negative SC. RT-qPCR analysis revealed that Oct4-, Sox-2, Nanog- gene expression was much reduced in the condition medium treated tumors versus proper controls (p< 0.05). Tissue necrosis was more prevalent in this group while tumors volume was diminished almost by 40%. The LC-ESI-MS/MS analysis unrevealed the stemness reducing and the cell death inducing proteins such as, pigment epithelium-derived factor (PEDF), insulin like growth factor binding protein-5 (IGFBP-5) and -7 (IGFBP-7) in the condition medium.
ConclusionsThis study showed that the substances released from starved human fibroblasts were able to down-regulate the stemness-related genes and induce necrosis in LA7 derived tumors.
Keywords: Breast cancer, Cancer Stem cells, Cell differentiation, Fibroblasts, Gene expression -
Journal of Dentomaxillofacil Radiology, Pathology and Surgery, Volume:9 Issue: 3, Spring 2020, PP 26 -31Introduction
Lichen planus is an inflammatory chronic illness with unknown cause that can irritate the oral mucosa. P53 is associated with malignant changes in oral epithelial cells. MMPs can destroy intercellular junctions and cause acantholysis. It seems that MMP-3 plays a significant role in this regard. The purpose of this study was to evaluate the salivary levels of P53 and MMP-3 in the patients with Oral Lichen planus (OLP) compared with the control group.
Materials and Methods30 salivary samples were collected from patients with OLP (15 with erosive Oral Lichen planus (EOLP) and 15 with reticular Oral Lichen planus (ROLP)) and 30 salivary samples from healthy people as a control group. The salivary P53 and MMP-3 level was assayed by ELISA method. Statistical analysis of the Student’s t-test, ANOVA and Pearson correlation coefficient was performed.
ResultsThe salivary concentrations of P53 and MMP-3 in patients with EOLP were significantly higher than patients with ROLP and control group, but no significant difference was found between control group and patients with ROLP.
ConclusionThe salivary concentrations of P53 and MMP-3 were significantly different between different clinical types of OLP.
Keywords: MMP3 protein, human, Matrix Metalloproteinase 3, Lichen Planus -
هدف
پیوند مغز استخوان و سلول های ایمنی یک روش رایج برای درمان برخی از بیماری های خونی در سراسر جهان است. با این حال به دلیل بدتنظیمی سیستم ایمنی استفاده از آن همیشه کارآمد نمی باشد. در این مطالعه برآنیم تا پتانسیل استرس کشت در محیط فاقد سرم را در تنظیم سیستم ایمنی ارزیابی کنیم.
مواد و روش ها:
سلول های تک هسته ای طحال با استفاده از روش گرادیان فایکول از موش های Balb/C و C57bl/6 جدا شدند. سلول های موش C57bl/6 در شرایط دارای سرم و فاقد سرم در نقاط زمانی مشخص کشت یافتند و میزان بقاء سلول ها به روش MTT تعیین گردید. سپس جهت تعیین آلوژنیسیته ی سلول های مذکور، کشت مختلط لنفوسیتی (مدل آزمایشگاهی پیوند) با سلول های طحال موش Balb/C انجام شد و با استفاده از روش MTT تکثیر سلولی مورد بررسی قرار گرفت و عکس های لازم تهیه گردید.
یافته ها:
میزان بقاء سلول های ایمنی پس از 72 ساعت کشت در محیط فاقد سرم نسبت به گروه کنترل 1/82% بود. هم چنین پس از 24 ساعت، آلوژنیسیته ی این سلول ها نسبت به سلول های کنترل به طور معنی داری کاهش یافت (01/0<P). این کاهش در نقاط زمانی 48و 72 ساعت بارزتر شد (0001/0<P)؛ به میزانی که پاسخ لنفوسیت های موش Balb/C به سلول های استرس یافته کم تر از سلول هایی بوده است که هیچ گونه محرکی دریافت نکرده اند (0001/0<P). یافته های مورفولوژی به وضوح این کاهش را تایید می کنند.
نتیجه گیری:
استرس ناشی از کشت در محیط فاقد سرم موجب کاهش آلوژنیسیته و تعدیل آلوری اکتیویتی سلول های ایمنی می شود. در آینده استفاده ازمدل حیوانی موش می تواند کاربرد این تکنیک را در پیوند مغز استخوان روشن تر سازد.
کلید واژگان: پیوند، تکنیک کشت سلول، موش، تنظیم ایمنیKoomesh, Volume:23 Issue: 1, 2020, PP 124 -130IntroductionBone marrow and immune cell transplants are a common method of treating some blood diseases around the world. However, due to the malfunction of the immune system, its use is not always effective. In this study, we evaluated the potential of culture stress in serum-free medium in regulating the immune system.
Materials and MethodsSpleen immune cells were isolated from Balb/C and C57bl/6 mice using the Ficol gradient method. C57bl/6 mice splenocytes were cultured in serum starved and non-starved conditions at indicated time points. Cell viability was determined by MTT assay. Then the allogenicity of these cells was determined by mixed lymphocytic culture (in vitro model of bone marrow transplantation) with Balb/C mouse splenocytes and cell proliferation was then examined using MTT method and necessary photographs were prepared too.
ResultsThe viability rate of starved immune cells after 72 h was 82.1% of the control group. After 24h, the allogenicity of these cells decreased significantly compared to the control cells (P<0.01). This decrease was more pronounced at 48h and 72 h (P<0.0001). Even the response of Balb/C lymphocytes to stressed cells was less than that of background control, (P<0.0001). Morphological findings clearly confirm this reduction.
ConclusionSerum starvation induced-stress decrease allogenicity and modulates immune cells allo-reactivity. In the future, the use of mouse model could shed light on the application of this technique in bone marrow transplantation.
Keywords: Transplantation, Cell culture Technique, Mouse, Immunoregulation -
Background
Epstein-Barr virus (EBV) is a herpes virus, which is the cause of infectious mononucleosis. Seroepidemiological studies show that more than 95% of adults in the world are infected with this virus. This virus is a modifying virus that is associated with some malignancies such as Burkitt lymphoma, tumors in HIV-infected patients, Hodgkin's lymphoma, head and neck tumors, and T-cell lymphoma.
ObjectivesThis study aimed to determine the prevalence of EBV and its relation to the type of cancer in patients with head and neck tumors, which were treated in the years 2015 to 2016 at Shahid Rajaee Radiation Hospital in Babolsar.
MethodsDuring one year, all patients with head and neck tumors were monitored, and finally, a total of 37 patients who had pathologically confirmed diagnoses were entered into the study after obtaining written informed consent. In this descriptive study, specific anti-EBV viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA). Also, other patients' information was obtained from their records.
ResultsThe mean age of the patients was 59 years, and the number of men (70.23%) was higher than that of women (29.77%). Regarding the histopathology information and the frequency of tumors, most of the patients had squamous cell carcinoma (SCC) (73%) in the sites of the nasopharynx (27.02%) and pharynx (18.91%). The results of the ELISA test showed that IgG antibodies were positive in most of the patients (86.5 %). About the relation between the sites of the tumors and the IgG antibody, all patients (100%) with nasopharyngeal, tongue, and lips cancers were positive while they were the least in pharyngeal cancer (5.4%).
ConclusionsThis study showed that a significant number of patients with head and neck tumors (86.5%) were infected with this virus, which indicates that EBV as a carcinogenic agent in head and neck tumors has a high prevalence in our society and requires preventive and therapeutic actions.
Keywords: EBV, Head Neck Tumors, Shahid Rajaee Radiation Therapy Hospital of Babolsar -
مقدمه
پریودنتیت بیماری شایع در مبتلایان به دیابت است. رابطه معنی داری بین درجه هایپرگلایسمی و شدت پریودنتیت وجود دارد. اما مکانیسم پایه این ارتباط کاملا مشخص نشده است. با توجه به نقش مهم سایتوکاین ها در پاتوژنز پریودنتیت و با توجه به اینکه تاکنون مطالعه ای در مورد مقایسه اینترلوکین 35 در این بیماری ها انجام نشده است هدف از انجام مطالعه حاضر، بررسی سطح این سایتوکاین در بزاق بیماران دیابتی نوع 2 مبتلا به پریودنتیت مزمن متوسط جنرالیزه است.
مواد و روش هادر مجموع 88 نفر) 44 زن، 44 مرد (با میانگین سنی 5 /10±5/ 42سال در این مطالعه موردی شاهدی شرکت داشته اند. افراد به 4 گروه تقسیم شدند و هر گروه شامل 22 نفر بودند. گروه 1: بیماران واجد پریودنتیت مزمن متوسط جنرالیزه دارای دیابت نوع 2،گروه 2: بیماران واجد پریودنتیت مزمن متوسط جنرالیزه فاقد دیابت ،گروه 3: بیماران دیابتی با پریودنشیوم نرمال وگروه 4: افراد فاقد دیابت با پریودنشیوم نرمال (گروه کنترل)، سپس نمونه های بزاق، جمع آوری و پس از سانتریفیوژ کردن، میزان اینترلوکین 35 با کیت تجاری بر اساس ELISA تعیین شد و داده ها تحلیل شدند. تست آماری آنوا و تست تعقیبی توکی برای مقایسه گروه ها مورد استفاده قرار گرفتند.
یافته هامیانگین±انحراف معیار اینترلوکین 35 در گروه کنترل (36/ 8±59/ 22و0.05< p) از سه گروه دیگر بیشتر بود.(گروه یک: 62/ 5±12/ 13، گروه دو: 55/ 8 ±27/ 14،گروه سه: 13/ 8±12/ 15) مقایسه میانگین اینترلوکین 35 در گروه های دیگر تفاوت معناداری را نشان نداد (0.05> p).
نتیجه گیریسطح IL-35 بزاق در پریودنتیت و دیابت نوع 2 کاهش می یابد. با این حال،دیابت ملیتوس این کاهش را در بیماران مبتلا به پریودنتیت تشدید نمی کند.
کلید واژگان: دیابت ملیتوس، پریودنتیت مزمن، بزاقIntroductionPeriodontitis is a common disease in patients with diabetes. There is a significant relationship between hyperglycemic degree and severity of periodontitis, but the base of mechanism of this relationship has not been fully defined. Considering the important role of cytokines in periodontal pathogenesis and considering that there has been no study on the comparison of interleukin 35 (IL-35) in these diseases, the aim of this study was to determine the level of this salivary cytokine in patients with type 2 diabetes mellitus with generalized moderate chronic periodontitis.
Material & MethodsTotally, 88 subjects (44 female, 44 males) with a mean age of 42.5±10.5 years old participated in this case control study. The subjects were divided into four groups and each group included 22 subjects: Group 1: generalized moderate chronic periodontitis patients with type 2 diabetes, Group 2: generalized moderate chronic periodontitis patients without diabetes, Group 3: diabetic patients with normal periodontium, Group 4: healthy periodontium and non-diabetic group (control) Then saliva were collected and centrifuged, the amount of IL-35 was determined with commercial ELISA kit. Data were analyzed . ANOVA and Tukey post-hoc tests were used to compare the groups.
ResultsThe Mean±SD of IL-35 was significantly higher in the control group (22.59±8.36, p<0.05) than other groups (Group1: 13.12±5.62, Group2: 14.27±8.55, Group3: 15.12±8.13). Mean comparison of IL-35 in other groups had no significant difference (P>0.05).
ConclusionThe salivary IL-35 level is decreased in both periodontitis and type 2 diabetes. However, diabetes mellitus does not exacerbate this decline in patients with periodontitis.
Keywords: Diabetes mellitus, Chronic periodontitis, Saliva -
Background
The present study aimed to investigate and compare the effect of starved
fibroblast culture supernatant (SFS), DMEM and normal saline alone or along with LA7 on dexamethasone-treated immunosuppressed Wistar rats.MethodsAfter the isolation of fibroblasts from the fresh foreskin of children, it was cultured in serum-free DMEM, and the supernatant collected after 16 hours (16h-SFS). This solution and the other treatments were injected subcutaneously into the rats from each group once daily for 14 days. The liver, intestine and lung histology along with blood cellular and biochemical characteristics were studied.
ResultsThe results showed that dexamethasone as immunosuppressant reduced the body weight. The histological change in the liver was mild fibrosis induced by LA7+16h-SFS. Also, among the different blood cellular and biochemical indices measured, the eosinophil percentage in the 16h-SFS treated rats , glucose levels in the 16h-SFS+LA7 group and triglyceride concentrations in the 16h-SFS group were changed (p<0.05).
ConclusionThis study showed that the secretions of starved fibroblasts especially that combined with LA7 cancer stem cells could induce some minor histological and biochemical changes in immunosuppressed rats, and also it opened a new window for subsequent investigations on unknown mechanisms related to this work.
Keywords: starved fibroblast, LA7, fibrosis, metastasis -
BACKGROUND
Postpartum period and recurrent abortion are stressful conditions that affect women’s mental health. Stress and depression lead to the release of stress biomarkers that may be dangerous for the mother and fetus. The aim of this study was to determine stress in the after recurrent pregnancy loss (RPL) and normal vaginal delivery (NVD) in the north of Iran.
MATERIALS AND METHODSThis case–control study was done on forty women with NVD and forty women with RPL. Stress was measured through measuring serum cortisol, Perceived Stress Scale‑14 (PSS‑14), and the revised version of the Symptom Checklist‑90 (SCL‑90‑R). Data were analyzed using the Statistical Package for the Social Sciences (SPSS) 22.0 software. Chi‑square test, independent‑samples t‑test, Mann–Whitney U‑test, and Pearson correlation were used to analyze the data.
RESULTSFindings showed that nonpregnant healthy women had significantly higher cortisol level than RPL women (mean ± standard deviation [SD]: 155.80 ± 84.97 ng/ml and 126.02 ± 50.44 ng/ml, P < 0.011), respectively. Furthermore, they had higher PSS‑14 and SCL‑90 scores than PRL women (mean ± SD: 25.87 ± 7.48 and 25.5 ± 9.19, P = 0.745, and mean ± SD: 1.27±0.63 and 1.20 ± 0.53, P = 0.624), respectively.
CONCLUSIONHigh levels of cortisol reflect the acute stress caused by the care of the baby in women. Therefore, social support for the pregnant woman by the health‑care team is an essential factor for reducing postpartum depression.
Keywords: Cortisol, postpartum, Perceived Stress Scale‑14, recurrent pregnancy loss, Symptom Checklist‑90‑R, stress -
BACKGROUND
The age-related autoinflammation-mediated atherosclerosis is associated with some immunological, nutritional, and metabolic parameters and redox status. Here, we evaluated the association of circulatory interleukin 10 (IL-10) levels with lipid profile, some nutrients, and total anti-oxidant capacity in elderly people who presented cardiovascular disease (CVD) with or without metabolic syndrome (MetS) and in healthy subjects.
METHODSIn this cross-sectional case-control study, 258 sera prepared from elderly people (144 healthy and 114 patient subjects) who participated in a community-based study, the Amirkola Health and Ageing Project (AHAP), were analyzed for IL-10, lipid profile, vitamin D, selenium (Se), antioxidant capacity, and MetS.
RESULTSCompared to patients, the healthy subjects exhibited higher levels of circulatory IL-10 among individuals with detectable serum IL-10 (P = 0.036). However, this difference was not observed when total subjects from both groups were compared, since more than 90% of those people were IL-10-negative. Se, vitamin D, and antioxidant levels were similar in both groups. There was a negative association between IL-10 and body mass index (BMI) (P < 0.050) and an equivocal association with vitamin D levels, whereas the association between IL-10 and other indicated variables was not significant. Significant association was observed between MetS and CVD prevalence (P < 0.001). There was a positive correlation between Se and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (P < 0.010) in healthy subjects and with TC in patients (P < 0.050).
CONCLUSIONA major proportion of elderly people were serum IL-10-negative, whereas independently to IL-10, MetS was most common in patients with CVD. Weight loss may have the potential to increase IL-10 levels in the elderly.
Keywords: Interleukin 10, Lipids, Cardiovascular Diseases, Antioxidants, Metabolic Syndrome, Elderly -
ObjectivesTemporomandibular joint (TMJ) disorders, known as TMDs, are significant public health problems and may result in pain and disability. In order to determine the prevalence of clinical/subjective TMD in rheumatoid arthritis (RA), we used the research diagnostic criteria (RDC)/TMD axes. We assessed the anti-cyclic citrullinated protein (anti-CCP)-related TMD in RA for the first time.Materials and MethodsFifty-two RA patients were compared to 47 healthy controls with regard to complete blood count (CBC), serology, acute phase reactants (APR), and TMJ dysfunction.ResultsThe anti-CCP antibody showed a significant correlation with the development of clinical TMD (P=0.001, 95% confidence interval (CI)=12.4%-35.6%). A prevalence of 50% was calculated through the RDC/TMD for such disorders. In RA patients, statistically significant differences were observed between the groups with and without clinical TMD regarding psychological depression and physical symptoms.ConclusionsAccording to the results, a significant correlation was found between the anti-CCP antibody and TMD. Therefore, when this antibody is detected in the blood serum, the treatment must be initiated. The RDC/TMD used in this study assessed the prevalence of TMJ dysfunction in conformity with RA-associated TMJ findings previously obtained through other conventional methodsKeywords: Rheumatoid Arthritis, Temporomandibular Joint Disorders, Anti-Cyclic Citrullinated Protein Antibodies, Rheumatoid Factor
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Spontaneous Mesenchymal to Epithelial Like Tissue Transition (MET) in a Long Term Human Skin CultureIn an attempt to isolate multipotent stem cells from foreskin in a long-term culture, we encountered an interesting phenomenon which was the conversion of the fibroblast dominant condition to epithelial-like tissue formation. However, the basic mechanism(s) which may be involved in this conversion is not clear. This study was designed to evaluate the cells protein secretion activity and examine the role of oxidant/antioxidant capacity in this mesenchymal to epithelial cells transition (MET)-like phenomenon. The explanted tissues were obtained by spread out of the small sized foreskin derived tissue onto the cell culture dishes upona 40 day incubation period in DMEM. After this period, the supernatant was collected and the amounts of glucose, total proteins, antioxidant capacity and protein profiles were determined and compared to the baseline medium. Also, routine hematoxylin and eosin staining was performed. Fibroblasts and uncharacterized fibers emerged from beneath of the specimen during the first week, and gradually overgrew within the first month. Surprisingly, these cells began to disappear around day 30 while epithelial-like cells turned out to be the major cells in cell culture dishes. Ultimately on day 40, the epithelial-like cells appeared. Total protein concentration was 1.44 mg/dl in the old medium versus 0.97 mg/dl in the baseline medium. The concentrations of glucose were 1.6 and 119.2 mg/dl for the old and the baseline medium, respectively. The antioxidant activity of the old medium was 176.29 μM, in comparison with the baseline medium 96.63 μM. There were differences in protein patterns between the two media on SDS-PAGE. The density of some proteins with molecular weight of 8-89 kDa was higher in the old medium corresponding to 40-day culture. The generated data showed that MET can take place in vitro probably through secretion of some small to intermediated sized proteins in a redox favored microenvironment. This can be considered as a good model for in vitro study of MET in metastatic tumors.Keywords: Dermal fibroblast, epithelial cell, foreskin culture
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BackgroundIn this study, we determined the serum levels of IL-17A and IL-10 in context with 1, 2 dihydroxy vitamin D3, parathormone and Ca2ﳸ ions to investigate their pathological or protective roles respectively in bone metabolism.MethodsThe bone mineral density (BMD) was determined for 1203 participants using energy X-ray absorptiometry. Subjects with a history of diseases and using bone metabolism medications were excluded and finally serum IL-10 was measured in 82 osteoporotic and 74 healthy individuals (mean age ±SD of 71.04±6.9 and 68.58±6.9 respectively). Also, the serum level of IL-17A was assessed in 42 osteoporotic and 39 non-osteoporotic subjects (mean age±SD of 69.40±6.7 and 70.77±7.1, respectively). Serum levels of 1, 25-dihydroxyvitamin D3, Ca2ﳸ ions and parathormone were extracted from AHAP cohort data bank.ResultsIL-17A was detectable in 7.42(16.67%) osteoporotic subjects and 3.39(7.69%) normal subjects. Surprisingly, patient subjects exhibited a higher level of serum IL-10 than normal subjects (P=0.023). We found that the serum parathormone levels tend to increase in patient group (P=0.003) in comparison to normal control with no correlation with Il-10 levels. There was no significant difference between the two groups in the serum levels of 1, 25-dihydroxyvitamin D3, Ca2橷 Pi ions.ConclusionIn reaction to chronic inflammation old osteoporotic patients independent of 1, 25 dihydroxy vitamin D3 may produce a higher level of IL-10 to dampen production of inflammatory cytokines including IL-17A which in turn leads to speeding up parathormone production ultimately reaching a new homeostasis status in bone metabolism with normal serum Ca2 /Pi ions.Keywords: Osteoporosis, IL, 10, IL, 17A, Parathormone, 1, 25dihydroxy vitamin D3, Elderly
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BackgroundThe human leukocyte antigen (HLA) matching between organ donor and recipient is an acceptable strategy in clinical transplantation since 1964. However, in bone marrow transplantation, finding matched donors is often problematic. Thus new method for down regulation of HLA can be an alternative strategy to solve this problem.ObjectivesTo examine the effect of serum starvation on HLA class I expression in human peripheral blood mononuclear cells (PBMCs).MethodsPBMCs were cultured in RPMI-1640 supplemented with 10% FBS (non-starved cells) as well as in medium only (starved cells) for 16, 24, 48, 72, 96h under standard cell culture conditions. The pattern of cell death and HLA class I expression was determined by flowcytometry. Antigenicity of the starved PBMCs was evaluated in one-way mixed lymphocyte culture by MTT assay.ResultsMean fluorescence intensity (MFI) of different indicated starved PBMCs gradually decreased and this reduction was stable after 96h of re-feeding with FBS. Under serum starvation condition, PBMCs showed apoptosis cell death pattern. There was a linear correlation between percentages of cells, which exhibited the late apoptosis death pattern and serum starvation period (r=0.88, p 0.01). Surprisingly the starved PBMCs lost their stimulatory property in mixed culture with allo-reactive lymphocyte.ConclusionsMembrane HLA class I expression could be stably reduced in 96h starved human PBMCs culture condition, decreasing their alloreactivity while their viability rate is enough for possible clinical application.Keywords: Down, Regulation, HLA class I, PBMC, Transplantation
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Peripheral blood lymphocytes are able to maintain their viability and basic function in normal urineBackgroundSimilar to inflammatory cells, peripheral blood mononuclear cells (PBMCs) can also infiltrate in to kidney and urinary tracts and subsequently excreted by urine. In this study we determined the viability rate and response to phytohemagglutinin-A (PHA) of human PBMCs in normal urine.MethodsA number of 1×106 ficoll-hypaque isolated PBMCs were dispensed in 1 ml normal urine and 6 molar urea and RPMI-1640+FBS10 % were considered as negative and positive control, respectively. After 20, 60 and 120 minutes the viability of these cells was measured by trypan blue dye exclusion assay. 1×105 of PBMCs were isolated from urine and cultured as triplicate in RPMI-1640`supplemented with FBS 10% and PHA for 96hr. MTT assay was performed to determine the PBMCs response to PHA. These experiments were repeated three times independently.ResultsThere was no significant difference between the viability rates of the PBMCs incubated in urine and positive control after 20, 60 and 120 minutes while after 60 minutes they exhibited 75.6% of reactivity to PHA versus positive control. Overall, there was a significant difference in trends of viability rate across the three groups (p<0.05).ConclusionOur results showed that not only PBMCs remained alive in urine after 120 minutes, but can also respond to PHA up to 60 minutes at a remarkable level. These data open a new avenue in the designation for cell culture-based techniques in urine cell analysis.Keywords: urine, lymphocyte, viability
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سابقه و هدفعوامل روحی و روانی در کنار اجزاء مختلف بدن از جمله سیستم ایمنی، سیستم عصبی، سیستم اندوکرین وسیستم گوارش، می تواند در سلامت انسان نقش مهمی ایفا کند. با توجه به آیات قرانی، روایات، احادیث و دستورالعمل های اسلامی می توان به ارزش و جایگاه ویژه سلامت در دین مبین اسلام پی برد یکی از احکام متعالی اسلامی «روزه داری» است که مانند نماز و سایر احکام الهی از اهمیت بسزایی دررشد و تعالی فردی و اجتماعی انسان برخوردار می باشد. دین مبین اسلام روزه داری را اسباب سلامت جسم و روح انسان بیان داشته که به طور مستقیم در آیات قران و بسیاری از روایات اسلامی به آن اشاره شده است. امروزه سازمان بهداشت جهانی نیز معنویت را یکی از ابعاد مهم سلامتی برشمرده و به اهمیت تاثیر گذاری آن بر سلامت بیش از پیش تاکید دارد.ما نیز در این مقاله مروری درصدد آنیم تا با توجه به آیات قرآنی، روایات و احادیث اسلامی و یافته ها و مقالات معتبرعلمی وپژوهشی به بررسی اثر و روزه داری به عنوان یکی از احکام مهم و والای اسلامی بر سلامت جسم و روح انسان و ارتباط این دو با افزایش سطح ایمنی بدن و در نتیجه ارتقاء سطح سلامت بپردازیم.مواد و روش هادر این پژوهش مروری، برای بررسی ارتباط بین روزه داری با سلامت جسمی و معنوی و تاثیر ان بر افزایش سطح ایمنی از آیات قرآن کریم، احادیث دینی، کتب و منابع معتبر دینی و همچنین کتب و مقالات معتبر علمی - پژوهشی استفاده شده است.
یافته هادر آیات متعدد قرآنی و احادیث شریف و کتب معتبر دینی به اهمیت روزه داری و ارتباط آن با سلامت جسم و روح اشاره شده است. در سوره الطارق آیه 4 به سیستم ایمنی اشاره شده است اما باتوجه به شواهد علمی میتوان بر نقش روزه داری درارتقاء سیستم ایمنی و سلامت تاکید کرد.بحث و نتیجه گیریمزایای معنوی روزه داری که در ارتباط با اعتقادات مذهبی و باور های دینی فرد روزه دار است بسیار با اهمیت تر از تاثیرات فیزیکی آن بر سلامت جسم بوده و می توان گفت که هدف اصلی روزه داری می باشد. در این میان بسیاری از تحقیقات نشان دهنده تاثیر معنوی و مادی روزه داری بر ارتقاء سطح سیستم ایمنی می باشد. با توجه به تعریف سلامت از دیدگاه سازمان بهداشت جهانی و در نظر گرفتن معنویت به عنوان بعد چهارم سلامتی، باید جنبه های معنوی روزه داری و ارتباط آن با افزایش سطح سلامت بیشتر مورد بحث و بررسی قرار گرفته و در مراکز آموزشی و علمی به اهمیت روزه داری از دیدگاه سلامت معنوی و تاثیر آن بر افزایش سطح ایمنی بدن بیشتر از پیش پرداخته شود.
کلید واژگان: اسلام، روزه داری، سلامت معنوی، سیستم ایمنیBackground andPurposePsychological factors in addition to various parts of the body، including the immune system، nervous system، endocrine system and digestive system play a major role in human health. According to the Quran، hadith and Islamic guidelines، the special position of health in Islam can be realized. One of the sublime precepts of Islam is «fasting» which has a key role in personal and social growth and human progress such as prayer and other divine commandments. Islam has expressed fasting as an important factor for the health of body and soul، which has been mentioned directly on the many of Quran and Islamic traditions. Nowadays The World Health Organization knows spirituality a، s an important aspect of health and emphasizes the importance of its impact on health more than ever before. In this article we are going to investigate fasting impact as one of the Important and noble precepts of Islam on body and soul health of human Associated with increased levels of the immune system and thus promoting health، According to the Qur''an، Hadith، Islamic traditions and scientific and research findings and papers.Materials And Methodsthis study is review study and in this paper، investigates the relationship between fasting with the physical and spiritual health and its effect on increasing the level of safety so the Quran verses، religious traditions، religious books and resources، as well as books and scientific-research papers have been used.Findingsin this review paper excerpts from the Quran verses and the authentic religious traditions and hadith about the importance of fasting and its relationship to health of body and soul، not overeating، the importance of the spiritual dimension in health and immune system have been investigated.ConclusionSpiritual benefits of fasting which are in connection with religious beliefs of the fast person is much more important than its physical effects on the human body and it can be said that the main purpose of fasting is Spiritual benefits. Many studies show the moral and material effect of fasting on the promotion of the immune system. According to the World Health Organization''s definition of health and considering spirituality as a fourth dimension of health، spiritual aspects of fasting and its relation increasing level of health must be discussed further and scientific and educational centers must pay more attention to the importance of fasting from spiritual health perspective and its impact to maximize the immune level of body.Keywords: Islam, fasting, spiritual health, immune system -
International Journal of Molecular and Cellular Medicine, Volume:3 Issue: 10, Spring 2014, PP 74 -80Fibroblasts could be considered as connective tissue cells that are morphologically heterogeneous with diverse functions depending on their location and activity. These cells play critical role in health and disease such as cancer and wound by Production of collagen, fibronectin, cytokines and growth factors. Absence of insulin and other growth factors in serum deprivation condition and similarity of this condition to the environment of tumor cells and ulcer made us to investigate anaerobic glycolysis in these cells. To this end, we cultured fibroblasts isolated from fresh human newborn foreskin in serum free medium for 16, 24, 48 and 72 hrs and measured glucose consumption, lactate secretion and intracellular LDH in these cells. The results showed despite the lack of insulin, the 16hr serum starved fibroblasts consumed glucose similar to non-starved fibroblasts control. Moreover, in this condition these cells secreted higher levels of lactate and exhibited higher levels of intracellular LDH in comparison to non-starved fibroblasts control. Thus it could be concluded that in serum starvation condition, the newborn human dermal fibroblasts may change the metabolic strategy to Warburg effect. This finding opens a new perspective to further understanding the basic mechanisms involved in communication between tumor cells and fibroblasts.Keywords: Fibroblast, serum starvation, lactate, warburg effect
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International Journal of Molecular and Cellular Medicine, Volume:3 Issue: 10, Spring 2014, PP 102 -107Phenolic compounds including flavonoids and phenolic acids are plants secondary metabolites. Due to their ability to act as antioxidant agents, there is a growing interest to use those components in traditional medicine for cancer prevention or treatment. The aim of this study was to measure the amounts of total phenolics and flavonoids as well as anti-proliferative effect of aqueous extract of Stinging nettle on BT-474 and Hela cell lines. The amounts of phenolics content and total flavonoids were determined by folin ciocalteu and aluminium chloride methods, respectively. The free radical scavenging activity was measured by using diphenyl - picrylhydrazyl (DPPH). The reducing power of the extract was measured in the presence of potassium hexacyanoferrate and its antiproliferative activity was assessed on BT-474 and Hela cell lines using MTT assay. Total phenolic content was 322.941± 11.811 mg gallic acid/g extract. Total flavonoid content was 133.916±12.006 mg Catechin/g. The IC50 of DPPH radical was 1.2 mg/ ml and the reducing power was 218.9± 15.582 μg ascorbic acid/ g. Cell viability of BT-474 cells decreased to less than half of the control (no added extract) at the presence of 3 mg/ ml extract while no significant changes were detected for Hela cells at similar conditions. There was no significant difference in the percentage of surviving cells between consecutive days (day 1, 2 and 3) for both BT-474 and Hela cells (P>0.05). Although the relatively high amount of phenolic and flavonoid contents of the aqueous extract make this plant a promising candidate for diseases treatment; however, there is not a direct relationship between the amounts of these antioxidant components and the efficiency in in vitro cancer treatment.Keywords: Polyphenols, Flavonoids, Antioxidant activity, Stinging nettle, Antiproliferative Effect
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It has been widely thought that diabetic patients are prone to infections due to hyperglycemia induced immunodeficiency; the present study was designed to examine this opinion.In diabetic patients and normal control groups T-cell reactivity to hsp-60 molecule, tetanus toxoid recall antigen (TT) and phytohemagglutinin-A (PHA) mitogen were evaluated The number of circulating IFN-γ, IL-10 and IL-13 cytokine producing cells stimulated with above antigens or mitogen as well as the serum levels of Th1/Th2 type cytokines were determined. Total serum immunoglobulins (IgG, IgA, IgM), C3, C4 and CH50 were also measured.Diabetic patients showed a positive circulating T-cell reactivity to human recombinant hsp60 However, this reactivity was significantly lower in comparison to control group (p<0.001). All other examined factors were not significantly different between diabetic and normal subjects except for the number of IFN-γ and IL-13 producing cells in response to PHA stimulation, which was higher in control gtroup (p=0.006, 0.018, respectively). The mean serum concentration of IgA in diabetic patients was 245.86±115.05 mg/dl versus 192.96±105.33 mg/dl in healthy control group (p<0.018).We were not able to demonstrate any substantial mitigation in cellular arms of immune reaction to some prominent T-cell antigens and mitogens, as well as, in main parameters of humoral immunity of diabetic patients, thus, the common notion of believing that patients with diabetes suffering from immunodeficiency should be revised. It is much more appropriate that “altered immunity“is applied instead of “immunodeficiency” to explain the immunity condition in this group of patients.Keywords: Adaptive Immunity, Complement System Proteins, Cytokines, Diabetes Mellitus, Infection
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سابقه و هدف
سرطان معده سومین سرطان شایع در ایران و چهارمین سرطان شایع و دومین سرطان کشنده در سراسر جهان است. غضروف کوسه ماهی، پروتئینی دارد که آنژیوژنز (رگ زایی) را در شرایط آزمایشگاهی و مدل های حیوانی متوقف می سازد. اما نقش آن درمهار آنژیوژنزو یا پاسخ های ایمنی ضد توموری انسان معلوم نشده است. هدف از این مطالعه تاثیرخوراکی این دارو بر روی تعداد سلول های Treg گردش خون محیطی همراه با پاسخ سایتوکاینی TGF-β معرف فعالیت مهاری لنفوسیت های T مهارکننده و همراه با آن تغییر در توازن بین الگوی سایتوکاینی سلول های TH1 وTH2در بیماران مبتلا به سرطان معده است.
مواد و روش هادر این مطالعه مورد شاهدی بیست وسه بیمار مبتلا به سرطان معده از نوع Intestinal انتخاب و به دو گروه تحت درمان با غضروف شارک (14= n) و گروه کنترل (9= n) تقسیم شده اند. حداقل یک ماه پس از اتمام درمان استاندارد، به بیماران گروه درمانی، 60 عدد قرص 150 میلی گرمی غضروف کوسه ماهی روزی سه بار به مدت 20 روز تجویز گردیده و یک هفته پس از مصرف دارو، با جداسازی سلول های تک هسته ای گردش خون بیماران و کشت این سلول ها در مجاورت آنتی ژن مختص تومور، سلول های تنظیم کننده T (Treg) با فلوسایتومتری و سایتوکاین های TGF-β،IFN-γ،IL-4 به روش الیزا اندازه گیری شدند. جهت تعیین تکثیر لنفوسیت ها در برابر آنتی ژن مختص تومور آزمایش MTT به عمل آمد. سپس داده ها توسط آزمون های آماری توصیفی و استنباطی تجزیه و تحلیل شدند.
یافته هادر گروه تحت درمان با غضروف کوسه ماهی در مقایسه با گروه کنترل بعد درمان میزان γ-IFN افزایش و IL-4کاهش یافته بود (05/0< P)، اما تعداد سلول های Treg و میزان TGF-β تغییری نیافت. تفاوت معنی داری در اندازه گیری ها در گروه کنترل به دست نیامد (05/0> P).
استنتاجاین دوز مصرفی از غضروف کوسه ماهی در انسان های مبتلا به سرطان معده، با کاهش IL-4 (ایمونیتی سلول های TH2) و افزایش تولید IFN-γ (ایمونیتی سلول های TH1) موجب تقویت پاسخ های ایمنی سلولی ضد توموری می شود.
کلید واژگان: غضروف کوسه ماهی، سلول های Treg، سایتوکاین های TGF، β، IFN، γ، IL، 4، سرطان معدهBackground and
PurposeGastric cancer is the third most common cancer in Iran and the second leading cause cancer-related death worldwide. Shark cartilage prevents angiogenesis in vivo and in vitro، however، its role on angiogenesis or anti-tumor responses in human is not clear yet. We studied the effects of oral treatment of shark cartilage on peripheral Treg frequency and TGF-β as suppressor activity and Treg cells inducer associated with TH1/TH2 cytokines pattern in patients with gastric cancer.
Materials And MethodsThis study included 23 patients suffering from intestinal gastric cancer who were assigned into intervention (n=14) and control group (n=9). A month after conventional treatment the patients in intervention group were given three tablets (150mg) of shark cartilage daily for 20 days. Then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly.
ResultsThe results demonstrated that γ-IFN increased and IL-4 decreased in the intervention group. But، no changes were seen in Treg cells frequency and amounts of TGF-β. The evaluations for control group showed no significant difference.
ConclusionShark cartilage amplified anti-tumor responses in patients with gastric cancer by increase in γ-IFN (TH1 immunity) and decrease in IL-4 (TH2 immunity).
Keywords: Shark cartilage, Treg cell, TGF, β, γ, IFN, IL, 4, gastric cancer -
Coronary atherosclerotic disease is one of the most endangering health disorder worldwide. This study was designed to investigate the correlation between HLA-DR1 alleles and circulating Th1/Th2 type cytokines in coronary atherosclerosis. By Elisa, Th1/Th2 type cytokines were determined in serum samples of 31 subjects with unstable angina, 27 subjects with chronic stable angina and 24 individuals as normal control. By SSP-PCR, more than 100 alleles of HLA-DRB1 were typed in 24 subjects who had skewed serum levels of Th1/Th2 type cytokines. Lipid profiles were determined by the routine methods of clinical laboratory in all subjects. The mean serum concentration of IL-10 in normal control subjects was higher in comparison to the patient groups.0.33±0.59 pg/ml versus 0.064±0.3 pg/ml in unstable angina pectoris group (p<0.028) and 0.22±0.6 pg/ml in chronic stable subjects. There was no statistically significant difference among the groups in serum levels of other desired cytokines (IFN-, IL-4). 33.33% of normal control subjects were HLA-DR16 positive whereas none of the subjects with chronic stable angina or individuals with unstable angina pectoris was positive for this antigen. The mean concentration of serum LDL-cholesterol in normal control group was high 142.046±35.40 (pg/ml).This preliminary study shows that the atherogenic effect of the LDL- cholesterol may be dampened by HDL-cholesterol through anti inflammatory cytokine IL-10 and HLA-DR16, a phenomenon interpretable via immunological homunculus theory.
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