به جمع مشترکان مگیران بپیوندید!

تنها با پرداخت 70 هزارتومان حق اشتراک سالانه به متن مقالات دسترسی داشته باشید و 100 مقاله را بدون هزینه دیگری دریافت کنید.

برای پرداخت حق اشتراک اگر عضو هستید وارد شوید در غیر این صورت حساب کاربری جدید ایجاد کنید

عضویت
فهرست مطالب نویسنده:

mohammad saaid dayer

  • Zohreh Gholami, Mohammad Saaid Dayer*, Amrollah Azarm
    Background

    Head louse infestation, pediculosis, is a serious health problem worldwide. Infected children usually suf-fer from itching, allergies, and secondary infections besides psychological disorders such as depression and lack of self-confidence leading to school failure. This study aimed to investigate the status of pediculosis and its determinant factors among schoolchildren in Amol City, Northern Iran.

    Methods

    This study included 228 schools frequented by about 20017 students. Pediculosis was determined by careful examination of students’ hair on the scalp, back of the neck, and around the ears. The diagnosis was based on observa-tion of live adults, nymphs, and nits. A questionnaire was used to record the personal and demographic characteristics of participants.

    Results

    This study revealed that the prevalence of pediculosis among schoolchildren during all schooling seasons (au-tumn, winter, and spring) correlated with sex: the prevalence being higher among girls than boys (p= 0.00). In addition, the highest rates of pediculosis occurred during the autumn season (p= 0.00). The public schools accommodated higher numbers of louse-infected students than the private ones (p= 0.00). While head louse occurred at higher frequencies in long hair over the schooling year, dandruff had anti-louse effects (p= 0.00) during cold seasons, autumn, and winter. Socioeconomic status and educational level of parents played determinant roles in head louse prevalence (p= 0.00). Schoolchildren coming from socioeconomically well-situated families had lower rates of head louse infestation.

    Conclusion

    Our results showed that head pediculosis was a serious health problem among schoolchildren in Amol city and its prevalence and severity tended to be multifactorial.

    Keywords: Pediculosis, Pediculus Capitis, Schoolchildren, Mazandaran, Iran
  • توران نیری، فرحناز بینشیان، فریبا خوش زبان، عبدالحسین دلیمی اصل، محمدسعید دایر، فاطمه غفاری فر*
    زمینه و هدف

    آکانتاموبا پاتوژن فرصت طلبی است که ممکن است باعث ایجاد آنسفالیت گرانولوماتوز کشنده و کراتیت چشمی در انسان ها و حیوانات شود. افزایش روزافزون استفاده کنندگان از لنزهای تماسی باعث فراوانی کراتیت آمیبی می شود که به دلیل فقدان داروهای موثر، درمان این بیماری دشوار است. هدف از این مطالعه بررسی عصاره اتانولی گیاه چایروفیلوم ماکروپودیوم روی ژنوتیپ T4  آکانتاموبا بود.

    مواد و روش ها

     در این مطالعه تجربی، نمونه گرفته شده از بیمار روی محیط آگار غیر مغذی کشت داده شد. غلظت های مختلف (1/25، 2/5، 5 و 10 میلی گرم بر میلی لیتر) از عصاره اتانولی بر تروفوزوییت ها و کیست های آکانتاموبا در سه زمان (24، 48 و 72 ساعت) در شرایط برون تنی اثر داده شدند. تعداد انگل های زنده و مرده با رنگ آمیزی تریپان بلو و لام نیوبار محاسبه شدند. همچنین درصد آپوپتوز کیست ها با استفاده از فلوسایتومتری بررسی گردید.

    یافته ها

    در حضور 10 میلی گرم بر میلی لیتر عصاره اتانولی در محیط کشت درصد تروفوزوییت های زنده بعد از 24، 48 و 72 ساعت به ترتیب به 53/6، 15/11 و صفر درصد رسید. در حالی که در مورد کیست ها بعد از 24، 48 و 72 ساعت به ترتیب 65/31، 43/31 و صفر درصد کیست ها زنده بودند. نتایج فلوسایتومتری نشان داد که در نمونه تحت درمان با عصاره پس از 72 ساعت میزان آپوپتوز 0/09 درصد بود.

    نتیجه گیری

     عصاره اتانولی گیاه چایروفیلوم ماکروپودیوم با توجه به سمیت بالایی که برای کیست ها دارد، می تواند کاندید امیدوارکننده ای برای پیشرفت داروهای ضد آکانتاموبا باشد. از آنجایی که در این مطالعه از عصاره خام گیاه چایروفیلوم ماکروپودیوم استفاده شد، تحقیقات بیشتر جهت به دست آوردن مواد موثره گیاه و مکانیسم عمل آن ضروری است. همچنین، می توان آن را در شرایط درون تنی و یا حتی بر علیه سایر انگل ها آزمایش کرد.

    کلید واژگان: آکانتاموبا, کراتیت, عصاره اتانولی, چایروفیلوم ماکروپودیوم, شرایط برون تنی
    Tooran Nayeri, Farahnaz Bineshian, Fariba Khoshzaban, Abdolhossein Dalimi Asl, MohammadSaaid Dayer, Fatemeh Ghaffarifar*
    Background and Aim

    Acanthamoeba is an opportunistic pathogen that may cause fatal granulomatous encephalitis and ocular keratitis in humans and animals. Increasing number of contact lens wearers can lead to increased frequency of amoebic keratitis and due to lack of effective drugs treatment of this disease is difficult. This study aimed to investigate the effect of ethanolic extract of Chaerophyllum macropodum on Acanthamoeba genotype T4.

    Materials and Methods

    In this experimental study, samples taken from the patients with keratitis were cultured on 1.5% non-nutrient agar medium. Different concentrations of the ethanolic extract (1.25, 2.5, 5, 10 mg/ml) were tested three times (24, 48, and 72 h) on trophozoites and cysts of Acanthamoeba in vitro. The number of live and dead parasites were counted by using trypan blue staining and neobar lam. Also, the percentage of cysts apoptosis was assessed by flow cytometry.

    Results

    In the presence of 10 mg/ml ethanolic extract in the culture medium, the percentages of live trophozoites after 24, 48, and 72 h were 53.6, 15.11, and 0 percent, respectively. In the case of cysts, after 24, 48, and 72 h, 65.31, 43.31, and 0 percent of the cysts were alive, respectively. The results of flow cytometry showed that the apoptosis rate was 0.09% in the sample treated with extract after 72 h.

    Conclusion

    Ethanolic extract of Chirophyllum macropodium can be a promising candidate for the development of anti-Acanthamoeba drugs due to its high toxic effects on the cysts. However, since the crude extract of Chaerophyllum macropodum was used in this study, further investigations are needed to find the effective fractions of the plant and determine their mechanisms of action. It can also be tested in vivo or even against other parasites

    Keywords: Acanthamoeba, Keratitis, Ethanolic extract, Chaerophyllum macropodum, In vitro
  • Delshad Hesami, Fatemeh Ghaffarifar*, Abdolhossein Dalimi, Mohammad Saaid Dayer, Vahid Nasiri, Shagayegh Sheikh
    Background

    The extract of myrtle plant contains polyphenolic compounds that show antibacterial, antiviral, and anti-parasitic properties. We aimed to investigate the therapeutic effect of aqueous and ethanolic myrtle extract against leishmaniasis caused by L. major in vivo and in vitro conditions.

    Methods

    This study was carried out in Tarbiat Modares University, Tehran, Iran in 2018. Aqueous and ethanolic extract of myrtle plant at 6.25 to 400 mg/ml concentrations were tested on Leishmania major promastigotes, non-infected macrophages, and macrophages infected with amastigotes in vitro using counting, MTT and flow cytometry techniques. Then, BALB/c mice were treated with ethanolic, aqueous and a mixture of both extracts of myrtle plant. The treatment was carried out for four weeks. Then, the effectiveness of the herbal medicine was assessed by measuring wounds diameters, mice weights and their mortality rate on weekly basis.

    Results

    The IC50 values of aqueous and ethanolic extracts for promastigotes were 7.86 and 11.66 μg/mL respectively. The IC50 values of the aqueous and ethanolic extracts for amastigotes were 12.5 and 47.2 μg/mL respectively. Flow cytometry indicates 62.88% and 60.16% apoptosis induced by ethanolic and aqueous extract of myrtle plant respectively. The lowest parasitic load was seen in the group treated with ethanolic extract.

    Conclusion

    The lesion sizes for treated groups with extracts were similar to those treated with glucantime. Oral administration instead of injection is another advantage of myrtle plant over glucantime, which makes the herb easy and more practical.

    Keywords: Ethanolic, aqueousextracts, Myrtus communis, Leishmania major, In vitro, BALB, c mice
  • Fatemeh Ghaffarifar, Soheila Molaei *, Zuhair Mohammad Hassan, Mohammad Saaid Dayer, Abdolhossein Dalimi, Vahid Nasiri, Masooud Foroutan, Homa Hajjaran
    Background

    The adverse effects and increased resistance of drugs necessities the discovery of novel combination therapy.

    Objectives

    This study aimed to examine the effects of Artemisinin plus glucantime or shark cartilage extract on the Iranian strain of Leishmania major (MRHO/IR/75/ER) in vitro and in vivo.

    Methods

    In in vitro experiments, the effects of drugs and their combination in different concentrations (3.12 - 400 µg/mL) on the promastigotes, amastigotes, and un-infected macrophage cells were evaluated. In in vivo experiments, infected BALB/c mice were used as a cutaneous leishmaniasis model to evaluate the effects of the drugs and their combinations with different routes of administrations (namely Artemisinin: oral, ointment, and intraperitoneal; glucantime: intraperitoneal, intramuscular, intralesional, and subcutaneous; shark cartilage extract: oral) on parasite burden, lesion size, and immune system modulation.

    Results

    The results revealed that Artemisinin and glucantime in combination with shark cartilage extract had greater effects on promastigotes than either Artemisinin or glucantime (P < 0.05), and that the combinations also had high cytotoxic effects on promastigotes and uninfected macrophages (P = 0.001). These combinations had more inhibitory effects on amastigotes and infected macrophages than promastigotes. The lesion sizes and parasite burden in the spleen decreased against the combinations of the drugs in different administrations. It was also noticed that the best combination administration route of Artemisinin and glucantime, as strong inducers of INF-γ and Th1 immune response, were ointment and IM, respectively (P < 0.05).

    Conclusions

    The findings indicate that Artemisinin- glucantime or Artemisinin- Shark cartilage combinations are effective inhibitors of L. major. However, further clinical trials are recommended to evaluate the effects of these combinations in human subjects.

    Keywords: Artemisinin, Glucantime, Shark Cartilage Extract, Leishmania major
  • Sayed Hamid Mousavi, Mohammad Saaid Dayer*, Fatemeh Pourhaji, Mohammad, Hossein Delshad, Seyed Alireza Mesbah
    Background
    Hemophilia is a rare inherited disorder associated with abnormal repeated bleeding and debilitating joint pain due to deficiency in coagulating factors VIII and IX. This study aimed to provide an updated account on the health-related quality of life (HRQoL) in children with hemophilia in Afghanistan.
    Methods
    This cross-sectional study included 65 randomly selected hemophiliacs out of 350 children registered with the Afghanistan Hemophilia Patient Association (AHPA). The patients were 8–16 years old and voluntarily entered the study. Data were collected through a demographic questionnaire and a Persian version of Haemo-QoL Questionnaire (short version) for children aged 8-16 years.
    Results
    The patients’ age averaged 12.9 ± 3.9 years with a mean QoL score of 75.9 ± 17.4. The patients were suffering from hemophilia A, mostly the severe type (80%). They were born to low income families (95 %) with high illiteracy rates (>50%) and hemophilia family history (90%). Spearman test showed a significant correlation between age and QoL scores (r = 0.8, P = 0.02). One-way ANOVA indicated no significant difference between QoL scores of patients categorized based on hemophilia severity (P = 0.2, F = 1.3), family incomes (P = 0.9, F = 0.01) and parents’ levels of education (P = 0.2–0.4, F = 0.82–1.3). The Cronbach alpha for the instrument was 0.82.
    Conclusion
    Regardless of hemophilia severity, Family and Sports were the most impaired domains of QoL. Herein, we have presented the first reliable and updated data on hemophiliacs’ demographic characteristics and their quality of life in Kabul.
    Keywords: Adolescent, Children, Healthcare, Hemophilia, Kabul, Quality of life
  • Fatemeh Ghafarifar *, Mohammad Jafarimodrek, Hossein Vazini, Zohreh Sharifi, Abdolhossein Dalimi, Mohammad Saaid Dayer
    Objective(s)
    Toxoplasma gondii is an obligate intracellular protozoan parasite that causes toxoplasmosis in humans and animals. Micronemes (MICs) are effective candidates for DNA vaccine.
    Materials and Methods
    In this study, we evaluated the immune response of BALB/c mice against MIC3 gene of Toxoplasma gondii and interleukin 12 (IL-12) as DNA vaccine. The MIC3 gene was cloned into the PTZ57R/T vector before sub-cloning in pcDNA3. Recombinant pc-MIC3 was transformed into Escherichia coli (TOP10 strain). The pc-MIC3 plasmid was then transfected into Chinese Hamster Ovary (CHO) cells, and the expression of the MIC3 gene was evaluated by SDS-PAGE and Western blotting. Sixty female BALB/c mice were divided into 6 groups. Each group received 3 intramuscular immunizations on days 0, 21st and 42nd using one of the following stimulants: phosphate-buffered saline, pcDNA3, pCAGGS-IL12, pc-MIC3 (100 µg), pc-MIC3 (50 µg), or combined pCAGGS-IL12 (50 µg) and pc-MIC3 (50 µg). The enzyme-linked immunosorbent assays was applied to evaluate  interferon gamma (IFN-γ) and IL-4 cytokines excretion of lymphocytes stimulated with tachyzoites lysate antigen, as well as the total levels of immunoglobulin G (IgG), IgG2a and IgG1 in immunized mice sera.
    Results
    Our results showed that mice challenged with pc-MIC3 (100 µg) had the highest longevity and quantity of immunoglobulin. Moreover, the highest expression level of IFN-γ was found in mice injected with combined pcMIC3 and pCAGGS-IL12 (P<0.05).
    Conclusion
    The MIC3 gene can be an efficient DNA vaccine candidate against toxoplasmosis. While, the single-gene vaccine can confer partial protection to mice against toxoplasmosis, the multigene vaccine can significantly enhance immune responses.
    Keywords: BALB, c mice, DNA vaccine, Immunization, pCAGGS-IL12, pc-MIC3, Toxoplasma gondii
  • Lima Asgharpour Sarouey, Khadijeh Khanaliha, Parvaneh Rahimi, Moghaddam, Samaneh Khorrami, Mohammad Saaid Dayer, Fatemeh Tabatabaie *
    Background
    The first line treatment against cutaneous leishmaniasis is meglumine antimoniate. This drug is expensive and has serious side effects, including development of drug resistance.
    Objectives
    In this research, because of paucity of information, the apoptotic and leishmanicidal effects of ketotifen and cromolyn sodium, as cell membrane stabilizer drugs, were investigated on standard strain of Leishmania major.
    Methods
    In this experimental study, L. major parasites were first cultured in RPM1 1640 media, supplemented with 10% fetal bovine serum (FBS) and antibiotics at 24 ± 1ºC. Drug concentrations of 5, 10, 15, and 20 µg/mL were then added to L. major culture at 24-, 48- and 72-hour intervals. The 3 - (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) tetrazolium assays were performed to determine parasite viability and drug toxicity. Leishmania major promastigotes were augmented to the in vitro cultured macrophages (J774 cells) and then incubated for 72 hours. Half maximal inhibitory concentration (IC50) were ascertained by counting the parasites. The inhibitory effect of the drugs were compared with that of glucantime. Flow cytometry was performed in the next step, to evaluate apoptosis. Each test was repeated three times.
    Results
    IC50 values of ketotifen and cromolyn sodium after 72 hours were calculated to be 2.04 and 17.67 µg/mL for promastigotes and 0.12 and 14.79 µg/mL for amastigotes, respectively. The results of MTT assays showed 20% and 35% promastigote viability after 72 hours of exposure to ketotifen and cromolyn sodium at 20 µg/mL concentration. Apoptosis in ketotifen and cromolyn sodium was quantified to be 11.52% and 9.96% in promastigotes and 99.5% and 98.6% in amastigote-infected macrophages, respectively. The results indicated that the drugs induce early and late apoptosis in parasites. All treatments produced results, which differed significantly from the control groups (P < 0.05).
    Conclusions
    Drugs used in this study, especially Ketotifen, showed lower toxicity yet similar anti-leishmanial effects on both forms, as cromolyn sodium did. It could be suggested that further investigations about the in vivo effects of these drugs, as candidates for cutaneous leishmaniasis treatment, are required.
    Keywords: Ketotifen, Cromolyn sodium, MTT, Apoptosis, IC50
  • Ghazal Tashakori, Mohammad Saaid Dayer *, Vahid Mashayekhi-Goyonlo
    Background
    Head lice infestation constitutes a serious health problem in marginalized areas where schoolchildren and their families are mostly affected. This study aimed to compare 3 lice control protocols approved by Ministry of Health and Medical Education, based on 1% permethrin shampoo, 4% dimethicone lotion and (1:1) vinegar wet combing for the treatment of outpatients of Imam Reza Hospital of Mashhad city (Iran).
    Materials And Methods
    The quasi-experimental before-and-after design was applied to evaluate the effectiveness of protocols, using SPSS software version 16.0. The study involved 154 infested individuals from both sexes during 2015 and 2016. The patients were clustered into 4-age categories; 13-year-old and their demographics were recorded. The results were recorded on weekly basis by a hospital-based dermatologist and an entomologist. Application times of permethrin, dimethicone and vinegar were 8-10 min, 8 h and 20-30 min respectively.
    Results
    Age, gender, familly size and hair length were the most significant demographic variants involved in treatments outcomes at P ≤ 0.05. The protocols showed different efficacies a week after intervention keeping the same trend to the end. The dimethicone treated group indicated the highest control levels (86% and 74%). The recovery rates at first endpoint were 86, 64.2 and 60.8%, and at the second endpoint were 74, 45.3 and 45.1% for dimethicone, permethrin and vinegar respectively. Dimethicone was 4.3 times more potent than either of vinegar or permethrin (P
    Conclusion
    Pediculosis infected school age children of both sexes. Permethrin was as effective as vinegar wet combing, but significantly weaker than dimethicone. Given its efficay on both adult and nit stages, dimethicone can be the drug of choice for pediculosis control.
    Keywords: Children, Head lice, 4% dimethicone lotion, Pediculosis, Permethrin 1% lotion
  • Mohammad Reza Dayer *, Sara Taleb-Gassabi, Mohammad Saaid Dayer
    Background
    The severe acute respiratory syndrome (SARS) is a life threatening viral infection caused by a positive, single stranded RNA virus from the enveloped coronaviruse family. Associated with fever, cough, and respiratory complications, the illness causes more than 15% mortality worldwide. So far, there is no remedy for the illness except supportive treatments. However, the main viral proteinase has recently been regarded as a suitable target for drug design against SARS infection due to its vital role in polyproteins processing necessary for coronavirus reproduction.
    Objectives
    The present in silico study was designed to evaluate the effects of anti HIV-1 proteases inhibitors, approved for clinical applications by US FDA, on SARS proteinase inhibition.
    Methods
    In the present study, docking and molecular dynamic experiments were applied to examine the effect of inhibitors on coronavirus proteinase under physiological conditions of similar pH, temperature, and pressure in aqueous solution. Hex software version 5.1 and GROMACS 4.5.5 were used for docking analysis throughout this work.
    Results
    The calculated parameters such as RMSD, RMSF, MSD, dipole moment, diffusion coefficient, binding energy, and binding site similarity indicated effective binding of inhibitors to SARS proteinase resulting in their structural changes, which coincide with proteinase inhibition.
    Conclusions
    The inhibitory potency of HIV 1 protease inhibitors to cronovirus proteinase was as follows: LPV > RTV > APV > TPV > SQV. Lopinavir and Saquinavir were the most and the least powerful inhibitors of cronovirus proteinase, respectively.
    Keywords: Severe Acute Respiratory Syndrome, Anti HIV, 1 Protease Inhibitors, Lopinavir, Molecular Dynamic Simulation
  • Mohammad Reza Dayer *, Fatemeh Dehghani, Daryush Daer, Mohammad Saaid Dayer, Sayed Mohammad Reza Alavi
    Background
    Androgenetic alopecia is the main cause of hair loss and common baldness that affects psychological more than physiological aspects of people’s lives. Studies have shown that this multi factorial disorder is initiated by androgens secretion in pubertal period, minerals limitations, autoimmunity, mental stress, genetic predisposition and some alterations in hematological factors.
    Objectives
    The aim of this study was to evaluate the involvement of hematologic parameters in this disease using a case control study design.
    Methods
    In this case-controlled study, two groups each of 80 individuals with androgenetic alopecia were voluntarily included in the study based on their medical histories and clinical examinations and subjected to blood tests for routine hematological parameters. The results were then compared and analyzed using SPSS version 16.0.
    Results
    Our findings indicated that all the parameters for both groups fall in normal ranges (Mean ± SD) but the values for RBC, HGB, MCH, MCHC, WBC, LYM and TIBC were significantly higher in patients than in normal group. The average counts of PLT was significantly lower in patients compared with the normal group. Otherwise, Person’s tests for statistical correlations between two groups indicated that the pattern of correlations were abnormal in patients.
    Conclusions
    Our findings indicated the presence of a chronic, immunologic and slowly progressing disorder that causes hair loss, the disease which is in turn triggered in pubertal period upon androgen secretion. We suggest, therefore, that the conditions may be ameliorated by prescription of iron tablet, platelet transfusion and anti-inflammation therapy.
    Keywords: Alopecia, Platelet Transfusion, Iron, Inflammation
  • Mohadese Kabiri, Mohammad Saaid Dayer *, Fatemeh Ghaffarifar
    Background
    Cutaneous Leishmaniasis (CL) is an endemic disease in Iran. The pentavalent antimonials as first-line drugs are losing efficacy because of side effects, disease relapse and drug resistance. Application of Lucilia sericata larvae (maggot therapy) to diabetic and refractory wounds approved to be satisfactory for accelerating healing process. In this study, therapeutic effects of L. sericata maggot was evaluated in vivo against leishmanial ulcer using BALB/c mice as animal model.
    Methods
    Female BALB/c mice were inoculated with promastigotes at the base of tails and kept for 28 days until the emergence of early ulcers. The mice were then underwent 4 treatments as follows: Glucantime alone, Glucantime plus maggots, maggot alone and positive control. The control and treated mice were monitored for a period of 5 weeks during which the wound diameters were measured and recorded on a weekly basis. Data were analyzed using Kolmogorov-Smirnov test and ANOVA T- test.
    Results
    Statistical analysis showed significant difference (P
    Conclusion
    Maggot therapy accelerated closure and healing process of leishmanial wounds in BALB/c mice and appeared promising as a new combinatorial therapeutics for leishmaniasis. However, further clinical trials are needed to evaluate the efficacy of maggot therapy modalities for leishmanial lesion care.
    Keywords: Cutaneous leishmaniasis, Lucilia sericata, Drug resistance, BALB-c Mice, Maggot therapy
  • Fatemeh Kouhestani, Mohammad Saaid Dayer *, Hossein Kamali
    Chemical insecticides application for pest control pose serious impacts on human health and environment. Nowadays, intensified efforts to find safer and environmentally friendly alternatives have resulted in identification and production of some plant-derived natural ingredients that can use against insect pests. Amongst these plants, feverfew, Tanacetum parthenium (L.) Sch.Bip., from Asteraceae family is reputed to have insecticidal properties in addition to its excellent medicinal values. In this study, we quantitatively evaluated the extract of T. parthenium collected from Northern Khorasan province (Northeast of Iran) for its pyrethrin content using RP-HPLC chromatography.
    Flowers and leaves of T. parthenium harvested at flowering stage were dried at cool and dark place and subjected to 3 steps maceration with (30ml) chloroform and shaking for 1 hr. followed by filtration. Pyrethrin contents were then read by chromatographic method at 230 nm wavelength against the background of calibration regression equations. Our results indicated that dry flowers contain 0.46% total pyrethrin (I II), whereas leaves and stems include 0.06% pyrethrum. Pyrethrin was more concentrated in flower than stem. The wild population of T. parthenium of Northern Khorasan province demonstrates high potentiality to be commercially cultivated if it undergoes a plant-breeding program to manipulate phenotypic variation in the concentration of bioactive compounds present at harvest.
    Keywords: Tanacetum parthenium, Pyrethrin, RP-HPLC, Feverfew, Botanical insecticides
  • Mohammad Reza Dayer, Mohammad Saaid Dayer, Bahador Taheri
    Hemoglobin is a tetrameric oxygen transport protein in animal bodies. However, there is a paucity of information regarding differences between alpha and beta subunits of hemoglobin in terms of oxygen affinity. The sequential model of Koshland, Nemthy and Filmer (KNF model) has attributed similar affinities to both alpha and beta subunits. The main purpose of the present study is to construct a new sequential model for hemoglobin oxygenation based on higher oxygen affinities for alpha subunits. To this end, coordinate files of 19 oxy and 41 deoxy hemoglobin structures were used as starting structures. These files were processed using Microsoft Excel and SPSS software in order to calculate Euclidean distances between each pair of proximal and distal histidine Fe2 as well as other pairs of atoms of interest. The calculated distances were then compared for either set of hemoglobin conformations, i.e. oxy and deoxy conformations. Our results showed that α2 subunit show higher structural changes that could be related to oxygen affinity. This subunit could be introduced as initiator of hemoglobin oxygenation and cooperativity. Subunit α2 in our sequential model induces relaxed conformation in α1, β2 and β1 respectively. The order of oxygen affinity in our model is as follow: α2 > α1 > β1 > β2.
    Keywords: hemoglobin, Tens, Relax, Conformation, Cooperativity
  • Mohammad Reza Dayer, Mohammad Saaid Dayer
    Human immunodeficiency virus type 1 (HIV-1) protease inhibitors comprise an important class of drugs used in HIV treatments. However, mutations of protease genes accelerated by low fidelity of reverse transcriptase yield drug resistant mutants of reduced affinities for the inhibitors. This problem is considered to be a serious barrier against HIV treatment for the foreseeable future. In this study, molecular dynamic simulation method was used to examine the combinational and additive effects of all known mutations involved in drug resistance against FDA approved inhibitors. Results showed that drug resistant mutations are not randomly distributed along the protease sequence; instead, they are localized on flexible or hot points of the protein chain. Substitution of more hydrophobic residues in flexible points of protease chains tends to increase the folding, lower the flexibility and decrease the active site area of the protease. The reduced affinities of HIV-1 protease for inhibitors seemed to be due to substantial decrease in the size of the active site and flap mobility. A correlation was found between the binding energy of inhibitors and their affinities for each mutant suggesting the distortion of the active site geometry in drug resistance by preventing effective fitting of inhibitors into the enzymes'' active site. To overcome the problem of drug resistance of HIV-1 protease, designing inhibitors of variable functional groups and configurations is proposed.
    Keywords: HIV, 1 Protease, Inhibitors, AIDS Treatment, Drug Resistance
  • محمدرضا دایر*، نوشین آذری، نعمت الله رزمی، محمدسعید دایر
    زمینه و هدف
    بیماری های پریونی گروهی از اختلالات تحلیل برنده دستگاه عصبی بوده که منجر به مرگ بیمار می شوند. این بیماری ها تبدیل پروتئین پریون سلولی طبیعی (PrPC) به ایزوفرم غیرطبیعی آن با صفحات بتای فراوان (PrPSc)، تشکیل و تجمع رشته های آمیلوییدی با مکانیسمی ناشناخته در سلول های عصبی را به دنبال دارند. هدف از این مطالعه، بررسی تاثیر افزایش یا کاهش موضعی درجه حرارت بر این فرآیند تبدیل می باشد.
    مواد و روش ها
    در این مطالعه علمی-پژوهشی، ساختار بلوری پروتئین پریون انسانی از بانک اطلاعات پروتئین (با کد 2LEJ) به عنوان ساختار اولیه استفاده و به طور جداگانه در دماهای27، 37 و 47 درجه سانتی گراد در بازه زمانی 10 نانو ثانیه و با کمک نرم افزار گرومکس شبیه سازی گردید. نتایج حاصل از شبیه سازی با استفاده از دستورات گرومکس از فایل مسیر استخراج و با کمک نرم افزارهای SPSS، SPDBV و WebLab تحلیل گردید.
    یافته ها
    تغییر درجه حرارت از 37 به 27 یا 47 درجه سانتی گراد باعث ایجاد تغییرات قابل توجهی در ساختار PrPC می گردد و PrPC ساختار سوم بسیار تاخورده تری در مقایسه با ساختار طبیعی آن در 37 درجه سانتی گراد، پیدا می کند. علاوه براین، کاهش در تعداد پیوندهای هیدروژنی بین پروتئین و حلال در این دو دما میزان سطح قابل دسترس حلال هیدروفوبیک PrPC را افزایش می دهد که این می تواند دلیلی برای افزایش مقاومت پروتئین به هیدرولیز پروتئولیتیک و کاهش قابلیت انحلال آن در آب باشد.
    نتیجه گیری
    نتایج نشان داد که تغییرات درجه حرارت باعث تسریع تغییرات ساختاری PrPC و کاهش حلالیت آن می شود و آن را مستعد تبدیل شدن به PrPSc می سازد.
    کلید واژگان: پروتئین پریون انسانی, شبیه سازی دینامیک مولکولی, بیماری های پریونی, درجه حرارت
    Mohammad Reza Dayer *, Nooshin Azari, Nematollah Razmi, Mohammad Saaid Dayer
    Background
    Prion diseases are neurodegenerative disorders which ultimately results in the death of their victims. They are caused by structural transformation of cellular prion (PrPC) to its β-rich and anomalous isoform (PrPSc) and the accumulation of amyloid fibrillar deposits in the central nervous system. The precise mechanism underling this conversion is yet to be well understood. This study aimed to investigate the effect of non physiological temperatures on the misfolding mechanism of the human prion protein.
    Materials And Methods
    The crystal structure of human prion protein (90-231), (PDB code: 2Lej) in pdb format was used as a starting structure in this study. Three model structures of this coordinate structure were used separately to simulate PrPC at 27, 37 and 47. Molecular dynamic simulations were then performed using double-precision MPI version of GROMACS 4.5.5 for 10 ns and the results were analyzed using SPSS software, SPDBV and VebLab programs.
    Results
    The change of temperature from 37 to 27 or 47 induced significant structural changes to PrPC. These tempratures caused PrPC to attain a more folded and less flexible tertiary structure compared to its native structure at 37. They, also, reduce protein-solvent hydrogen bonds and therefore increasing access of hydrophobic solvent to PrPC which may be behind the lower water solubility of PrPC and its increased resistance to proteolytic degradations.
    Conclusion
    This study shows that changes of temperatures accelerate structural changes of PrPC and reduce its solubility while rendering it vulnerable to transition into PrPSc.
    Keywords: Human Prion Protein, Molecular Dynamic Simulation, Prion Disease, Temperature
  • Mohammad Reza Dayer, Mohammad Saaid Dayer, Ali Akbar Moosavi-Movahedi
    Hemoglobin is a porphyrin containing protein with an a2b2 tetrameric structure and like other porphyrin compounds shows spectral behavior of species specific characteristics. Researchers tend to relate bands in the hemoglobin spectra to certain structural and/or functional features. Given the fact that hemoglobin is the main oxygen carrier in animals functioning through the Oxy«Deoxy equilibrium, the determination of oxy and deoxy conformations of hemoglobins of different animals may shed light on their oxygen binding properties. Absorption spectra at 280 and 373nm have been widely used to quantitate the formation of hemoglobin deoxy conformation. In the present work, however, we used an optical density ratio of OD373/OD280 as an index for deoxy formation. This ratio was determined for Barbus sharpeyi and human hemoglobins at different SDS concentrations, pH levels and temperatures to compare them from a structure-function point of view. Our data showed that under low concentrations of SDS (Barbus sharpeyi hemoglobin folds in a tri-state pattern while human hemoglobin folds through a two-state phenomenon. This finding indicates that in contrast to those of other non aquatic animals, the hemoglobin of Barbus sharpeyi has a loosely folded tetrameric structure with remarkably more oxygen affinity
    Keywords: Barbus sharpeyi, Hemoglobin, Tri State Mechanism
  • Mohammad Reza Dayer*, Maysam Mard-Soltani, Mohammad Saaid Dayer, Sayed Mohammad Reza Alavi
    Background
    Type 2 diabetic mellitus patients are amongst the most susceptible groups to vascular abnormalities, which predominantly lead to myocardial disease. The hypercoagulable state has been widely studied by researchers as being the major suspicious mechanism facilitating the consecutive chain of molecular events leading to these complications. However, there is no consensus on the definition of the hypercoagulable state with respect to coagulation quantities, their interrelations and basic factor(s) initiating this pathogenic event, by which the prognosis of myocardial complications could be determined.
    Methods
    Path analysis was used to study the interactions between coagulation factors as well as other factors beyond coagulation factors in relation with pathogenic events in both diabetics and healthy subjects. In the present work, coagulation factors of 40 healthy and 40 type 2 diabetics were determined experimentally. The data were then analyzed using SPSS and AMOS software. Multivariate regression analysis was done to draw path diagrams.
    Results
    Our results show that FII, as the main cause for hypercoagulable state, is directly induced by FX and FVIII in normal individuals and by FX, FXI, FV and VWF cofactors in diabetic patients.
    Conclusion
    In general, our findings showed complicated relationship between coagulation factors and their effects either separately or combined.
    Keywords: Hypercoagulable State, Path analysis, vascular Complication, Myocardial Infarction, Coagulation Factors
  • Nooshin Azari, Mohammad Reza Dayer, Nematollah Razmi, Mohammad Saaid Dayer
    PrPC conversion to PrPSc isoform is the main known cause for prion diseases including Crutzfeldt-Jakob, Gerstmann-Sträussler-Sheinker syndrome and fatal familial insomnia in human. The precise mechanism underling this conversion is yet to be well understood. In the present work, using the coordinate file of PrPC (available on the Protein Data Bank) as a starting structure, separate molecular dynamic simulations were carried out at neutral and acidic pH in an explicit water box at 37°C and 1 atmosphere pressure for 10ns second period. Results showed that the acidic pH accelerates PrPC conversion to PrPSc by decreasing the protein gyration radius, flexibility and protein-solvent hydrogen bonds. In acidic conditions, PrPC attains a more folded and less flexible tertiary structure compared to its native structure at neutral pH; otherwise, the decrease of protein-solvent hydrogen bonds at acidic pH will enhance the hydrophobic character of PrPC that may exhibit association as multimeric assemblies. It can also lower water solubility and increase resistance to proteolytic degradations. Data indicated that there was no sensible protein denaturation during this conversion. It is hypothesized that the formation of slightly misfolded conformations with minor structural changes in secondary and/or tertiary structures are enough to menace scrapie formation in PrPC. Our findings show that scrapie formation seems to be a theoretically reversible process.
    Keywords: Human Prion Protein, Prion Disease, pH, Misfolded Structure, Molecular Dynamic Simulation
بدانید!
  • در این صفحه نام مورد نظر در اسامی نویسندگان مقالات جستجو می‌شود. ممکن است نتایج شامل مطالب نویسندگان هم نام و حتی در رشته‌های مختلف باشد.
  • همه مقالات ترجمه فارسی یا انگلیسی ندارند پس ممکن است مقالاتی باشند که نام نویسنده مورد نظر شما به صورت معادل فارسی یا انگلیسی آن درج شده باشد. در صفحه جستجوی پیشرفته می‌توانید همزمان نام فارسی و انگلیسی نویسنده را درج نمایید.
  • در صورتی که می‌خواهید جستجو را با شرایط متفاوت تکرار کنید به صفحه جستجوی پیشرفته مطالب نشریات مراجعه کنید.
درخواست پشتیبانی - گزارش اشکال