Publications by authors named "Saeed Namaki"

17 Publications

  • Page 1 of 1

Centrality Analysis of Protein-Protein Interaction Networks and Molecular Docking Prioritize Potential Drug-Targets in Type 1 Diabetes.

Iran J Pharm Res 2020 ;19(4):121-134

Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.

Type 1 diabetes (T1D) occurs as a consequence of an autoimmune attack against pancreatic β- cells. Due to a lack of a clear understanding of the T1D pathogenesis, the identification of effective therapies for T1D is the active area in the research. The study purpose was to prioritize potential drugs and targets in T1D via systems biology approach. Gene expression data of peripheral blood mononuclear cells (PBMCs) and pancreatic β-cells in T1D were analyzed and differential expressed genes were integrated with protein-protein interactions (PPI) data. Multiple topological centrality parameters of extracted query-query PPI (QQPPI) networks were calculated and the interaction of more central proteins with drugs was investigated. Molecular docking was performed to further predict the interactions between drugs and the binding sites of targets. Central proteins were identified by the analysis of PBMC (MYC, ERBB2, PSMA1, ABL1 and HSP90AA1) and pancreatic β-cells (HSP90AB1, ESR1, RELA, RAC1, NFKB1, NFKB2, IKBKE, ARRB2 and SRC) QQPPI networks. Thirteen drugs which targeted eight central proteins were identified by further analysis of drug-target interactions. Some drugs which investigated for diabetes treatment in the experimental models of T1D were prioritized by literature verification, including melatonin, resveratrol, lapatinib, geldanamycin, eugenol and fostaminib. Finally, according on molecular docking analysis, lapatinib-ERBB2 and eugenol-ESR1 exhibited highest and lowest binding energy, respectively. This study presented promising results for the prioritization of potential drug-targets which might facilitate T1D targeted therapy and its drug discovery process more effectively.
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http://dx.doi.org/10.22037/ijpr.2020.113342.14242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019861PMC
January 2020

Adipose-derived mesenchymal stem cell-secreted exosome alleviates dextran sulfate sodium-induced acute colitis by Treg cell induction and inflammatory cytokine reduction.

J Cell Physiol 2021 Mar 16. Epub 2021 Mar 16.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is an inflammatory condition that results in gastrointestinal tract damage. Various factors, including environmental and genetic agents, disrupt the function of the intestinal immune system that can lead to IBD. Mesenchymal stem cells (MSCs) display an immunoregulatory function and demonstrate regenerative potential by paracrine action. In this study, we evaluated the immunomodulatory effects of MSCs' derived exosomes in the acute form of dextran sulfate sodium (DSS)-induced colitis. Exosomes were isolated from adipose-derived MSCs. Acute colitis was induced by DSS. The exosome was used by intraperitoneal injection into mice with acute colitis. Stool consistency, body weight changes, bleeding severity, colon length, and weight were examined. At the experimental endpoint (Day 7), the changes in the colon tissue were evaluated. The level of cytokines of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-4, IL-12, transforming growth factor-β (TGF-β) and, IL-10, and Treg cells percentage were assayed. Results showed that exosome administration diminished colon shortening, bodyweight loss, bleeding, and colon injury. The levels of IFN-γ, TNF-α, IL-12, and IL-17 were decreased, and the level of TGF-β, IL-4, and IL-10 were increased in lymph node and spleen of mice treated with exosome.  Percentages of CD4 CD25 Foxp3 Treg cells were grown in the lymph node and spleen of mice treated with exosomes. Overall, current data suggest that MSC-derived exosome could regulate the Treg population and improves inflammation in DSS-induced acute colitis.
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http://dx.doi.org/10.1002/jcp.30275DOI Listing
March 2021

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.

Iran J Allergy Asthma Immunol 2021 Feb 11;20(1):46-66. Epub 2021 Feb 11.

Department of Biostatistics and Social Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.
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http://dx.doi.org/10.18502/ijaai.v20i1.5412DOI Listing
February 2021

The elimination of measles in Iran.

Lancet Glob Health 2020 02;8(2):e173-e174

Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1989934148, Iran. Electronic address:

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http://dx.doi.org/10.1016/S2214-109X(20)30002-4DOI Listing
February 2020

Identification of common key genes and pathways between type 1 diabetes and multiple sclerosis using transcriptome and interactome analysis.

Endocrine 2020 04 7;68(1):81-92. Epub 2020 Jan 7.

Proteomics Research Center, Department of Basic Science, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: Type 1 diabetes (T1D) and multiple sclerosis (MS) are classified as T cell-mediated autoimmune diseases. Although convergent evidence proposed common genetic architecture for autoimmune diseases, it remains a challenge to identify them. This study aimed to determine common gene signature and pathways in T1D and MS via systems biology approach.

Methods: Gene expression profiles of peripheral blood mononuclear cells (PBMCs) and pancreatic-β cells in T1D as well as PBMCs and cerebrospinal fluid (CSF) in MS were analyzed in our previous published data, and differential expressed genes were integrated with protein-protein interactions data to construct Query-Query PPI (QQPPI) networks. In this study, QQPPI networks were further analyzed to investigate more central genes, functional modules and complexes shared in T1D and MS progression. Lastly, the interaction of common genes with drugs was also explored.

Results: Several cytokines such as IL-23A, IL-32, IL-34, and IL-37 tend to be differentially expressed in both diseases. In addition, PSMA1, MYC, SRPK1, YBX1, HNRNPM, NF-κB2, IKBKE, RAC1, FN1, ARRB2, ESR1, HSP90AB1, and PPP1CA were common high central genes in QQPPI networks corresponding to each disease. Proteasome, spliceosome, immune responses, apoptosis, cellular communication/signaling transduction mechanism, interaction with environment, and activity of intercellular mediators were shared biological processes in T1D and MS. Finally, azathioprine, melatonin, resveratrol, and geldanamycin identified as prioritized drugs for the treatment of patients with T1D and MS.

Conclusions: This study represented novel key genes and pathways shared between T1D and MS, which may facilitate the identification of potential therapeutic targets in these diseases.
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http://dx.doi.org/10.1007/s12020-019-02181-8DOI Listing
April 2020

Exosomes derived from mesenchymal stem cells improved function and survival of neutrophils from severe congenital neutropenia patients in vitro.

Hum Immunol 2019 Dec 6;80(12):990-998. Epub 2019 Nov 6.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Severe congenital neutropenia (SCN) is described by the absolute neutrophil counts less than 500 cells/mm, bacterial infections, and an arrest of neutrophil differentiation. So, effective strategies for improving the function and lifespan of the existing neutrophils in these patients are necessary. Mesenchymal stem cells (MSCs) have supportive effects on neutrophils. Recently, it was determined that MSCs exert their effects, mostly by secreting soluble factors and exosomes. So, in this study, neutrophils were isolated from the bloodstream of healthy donors and SCN patients and cultured with medium, MSC-exosomes or MSC-conditioned media (MSC-CM). Then, the effects of the two treatments on neutrophil respiratory burst, apoptosis and phagocytosis percentage were assessed using nitro blue tetrazolium (NBT) assay, annexin V-propidium iodide (PI) and Giemsa staining, respectively. Both treatments could significantly augment respiratory burst of neutrophils from SCN patients and healthy donors. But, only CM could significantly enhance phagocytosis index. About the lifespan of neutrophils, only exosomes could significantly enhance it in both groups. Based on these results, both exosomes and CM derived from MSCs could be attractive candidates for rescuing SCN patients from serious infections.
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http://dx.doi.org/10.1016/j.humimm.2019.10.006DOI Listing
December 2019

Study of the immunomodulatory effects of osteogenic differentiated human dental pulp stem cells.

Life Sci 2019 Jan 20;216:111-118. Epub 2018 Nov 20.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Oral and Maxillofacial Surgery, Dental School, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background And Aims: Dental pulp stem cells (DPSC) are promising tools in regenerative medicine due to their differentiation potential and immunomodulatory properties. However, it is not clearly known whether or not DPSCs maintain their immunosuppressive effects after differentiation. In the present study, we examined the immunomodulatory effects of osteogenic differentiated DPSCs (OD-DPSCs).

Methods: OD-DPSCs and undifferentiated DPSCs were co-cultured with allogenic PBMCs in different ratios and the proliferation of the PBMCs was measured. The concentration of IL-10, TGF-β, PGE2, IL-6, and NO were then examined. Moreover, the expression of IDO, HLAG, and HGF genes were determined in undifferentiated and OD-DPSCs.

Findings: The results showed that OD-DPSCs could inhibit the proliferation of allogenic PBMCs. The levels of PGE2, IL-6, and TGF-β anti-inflammatory cytokines increased after the co-culture. Moreover, the levels of NO increased during the differentiation process and the expression of IDO, HLAG, and HGF genes remained unchanged after osteogenic differentiation.

Significance: Although, there were some differences between the OD-DPSCs and undifferentiated DPSCs in terms of their cytokine and NO production, undifferentiated DPSCs maintained their immunomodulatory activities upon differentiation.
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http://dx.doi.org/10.1016/j.lfs.2018.11.040DOI Listing
January 2019

Effect of efferocytosis of apoptotic mesenchymal stem cells (MSCs) on C57BL/6 peritoneal macrophages function.

Life Sci 2018 Nov 1;212:203-212. Epub 2018 Oct 1.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Phagocytic clearance of apoptotic cells (Efferocytosis) could affect the polarization of macrophages and promote M2 anti-inflammatory and regulatory phenotype and function. Here we tested the hypothesis that efferocytosis of apoptotic Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) promotes macrophage M2 polarization. In this study, Macrophages were incubated with apoptotic MSCs and after 48 h interleukin-10 (IL-10), transforming growth factor-alpha (TNFα), and nitric oxide (NO) production were measured. Furthermore, phagocytosis ability and arginase activity were analyzed. The results showed that apoptotic MSCs could reduce TNFα and NO production, and increase IL-10 levels. Moreover, arginase activity and phagocytosis ability were also increased in tested macrophages compared to controls. In Conclusion efferocytosis of AD-MSCs can alter the macrophages phenotype toward regulatory and anti-inflammatory phenotype.
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http://dx.doi.org/10.1016/j.lfs.2018.09.052DOI Listing
November 2018

The immunomodulatory effects of adipose-derived mesenchymal stem cells and mesenchymal stem cells-conditioned medium in chronic colitis.

J Cell Physiol 2018 11 24;233(11):8754-8766. Epub 2018 May 24.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Inflammatory bowel disease (IBD) as a chronic recurrent disorder is characterized by mucosal immune response dysregulation, which is more prevalent in the youth. Adipose-derived mesenchymal stem cells (ADMSCs) are the multipotent cells that can be effective in immune response regulation via cell-cell interaction and their secretions. In this study, the effects of ADMSCs and mesenchymal stem cell-conditioned medium (MSC-CM) were evaluated on dextran sulfate sodium (DSS)-induced colitis in mice. Chronic colitis was induced in female C57BL/6 mice using 2% DSS in drinking water for three cycles; there were 4 days of DSS-water administration that was followed by 7 days of DSS-free water, in a cycle. ADMSCs, 10 cells per mouse, were injected intraperitoneally (IP), whereas the MSC-CM injection was also performed six times from the last day of DSS in Cycle 1. Clinical symptoms were recorded daily. The colon pathological changes, cytokine levels, and regulatory T (Treg) cell percentages were then analyzed. After receiving ADMSCs and MSC-CM in colitis mice, the clinical symptoms and disease activity index were improved and the survival rate was increased. The histopathological examination also showed tissue healing in comparison with the nontreated group. In addition, the increased level of transforming growth factor beta, increased percentage of Treg cells, increased level of interleukin (IL)-10, and decreased level of IL-17 were observed after the treatment. This study showed the regulatory effects of ADMSCs and MSC-CM on inflammatory responses. Therefore, the use of ADMSCs and MSC-CM can be introduced as a new and effective therapeutic approach for patients with colitis.
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http://dx.doi.org/10.1002/jcp.26765DOI Listing
November 2018

Study the effects of mesenchymal stem cell conditioned medium injection in mouse model of acute colitis.

Int Immunopharmacol 2018 Jan 4;54:86-94. Epub 2017 Nov 4.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background And Aim: Inflammatory bowel disease (IBD) is an autoimmune-inflammatory disorder that results in inflammatory responses in individuals who are genetically susceptible. Uncontrolled inflammation in Crohn's disease (CD) or Ulcerative colitis (UC) affects the patient quality of life. Current therapies are not completely effective while cell therapy, especially the treatment with mesenchymal stem cells (MSCs) absorb lots of attention due to its immunomodulatory properties. So, we examined the effects of mesenchymal stem cells-conditioned medium (MSC-CM) in the experimental model of acute colitis.

Material And Method: MSC-CM was isolated from C57Bl/6 male mice and stored. The acute colitis induction in C57BL/6 mice was performed by dissolving dextran sulfate sodium (DSS) in drinking water and then CM injected intraperitoneally. During the study body weight changes, bleeding, stool consistency, disease activity index (DAI), mortality rate, weight and length of the colon and histopathological analysis were recorded as well as changes in the percentage of Treg cells. The level of IL-17, IL-10, and TGF-β were measured, too. Data were reported as mean±SD and analyzed by One-Way ANOVA test.

Results: Based on the results it is recognized CM inhibited the weight loss and bleeding and improved fecal consistency and DAI. Macroscopic examination of the colon showed that after infusion, colon inflammation was reduced and histopathological analysis showed a decrease in mucosal degeneration. The percentage of Treg cells, secretion of IL-10 and TGF-β was increased while the IL-17 level was reduced.

Conclusion: This study showed that mesenchymal stem cell secretion with immunomodulatory properties has the potential to reduce inflammatory responses.
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http://dx.doi.org/10.1016/j.intimp.2017.11.001DOI Listing
January 2018

Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis.

PeerJ 2016 22;4:e2775. Epub 2016 Dec 22.

Immunology Department, Faculty of Medical Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran.

Background: The involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein-protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease.

Methods: Gene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed. Differentially expressed genes which determined only in CSF (MS control) and PBMCs (relapse remission) separately integrated with PPI data to construct the Query-Query PPI (QQPPI) networks. The networks were further analyzed to investigate more central genes, functional modules and complexes involved in MS progression.

Results: The networks were analyzed and high centrality genes were identified. Exploration of functional modules and complexes showed that the majority of high centrality genes incorporated in biological pathways driving MS pathogenesis. Proteasome and spliceosome were also noticeable in enriched pathways in PBMCs (relapse remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MS control) and CDC37, MAP3K3, MYC genes in PBMCs (relapse remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways.

Discussion: This study showed that network-based analysis could explicate the complex interplay between biological processes underlying MS. Furthermore, an experimental validation of candidate genes can lead to identification of potential therapeutic targets.
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http://dx.doi.org/10.7717/peerj.2775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5183126PMC
December 2016

Identification of new key genes for type 1 diabetes through construction and analysis of protein-protein interaction networks based on blood and pancreatic islet transcriptomes.

J Diabetes 2017 Aug 21;9(8):764-777. Epub 2016 Nov 21.

Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic β-cells are destroyed by infiltrating immune cells. Bilateral cooperation of pancreatic β-cells and immune cells has been proposed in the progression of T1D, but as yet no systems study has investigated this possibility. The aims of the study were to elucidate the underlying molecular mechanisms and identify key genes associated with T1D risk using a network biology approach.

Methods: Interactome (protein-protein interaction [PPI]) and transcriptome data were integrated to construct networks of differentially expressed genes in peripheral blood mononuclear cells (PBMCs) and pancreatic β-cells. Centrality, modularity, and clique analyses of networks were used to get more meaningful biological information.

Results: Analysis of genes expression profiles revealed several cytokines and chemokines in β-cells and their receptors in PBMCs, which is supports the dialogue between these two tissues in terms of PPIs. Functional modules and complexes analysis unraveled most significant biological pathways such as immune response, apoptosis, spliceosome, proteasome, and pathways of protein synthesis in the tissues. Finally, Y-box binding protein 1 (YBX1), SRSF protein kinase 1 (SRPK1), proteasome subunit alpha1/ 3, (PSMA1/3), X-ray repair cross complementing 6 (XRCC6), Cbl proto-oncogene (CBL), SRC proto-oncogene, non-receptor tyrosine kinase (SRC), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), phospholipase C gamma 1 (PLCG1), SHC adaptor protein1 (SHC1) and ubiquitin conjugating enzyme E2 N (UBE2N) were identified as key markers that were hub-bottleneck genes involved in functional modules and complexes.

Conclusions: This study provide new insights into network biomarkers that may be considered potential therapeutic targets.
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http://dx.doi.org/10.1111/1753-0407.12483DOI Listing
August 2017

Cytotoxic Effects of the Ethanol Bane Skin Extract in Human Prostate Cancer Pc3 Cells.

Iran J Cancer Prev 2016 Apr 23;9(2):e4755. Epub 2016 Feb 23.

Young Researchers and Elite Club, Andimeshk Branch, Islamic Azad University, Andimeshk, IR Iran.

Background: It is extensively supposed that vegetarian diet could affect cancer progress and increase the influence of formal chemotherapy.

Objectives: The present study was designed to determine the effect of the ethanol Bane skin extract against chemo resistant prostate cancer PC3 cells.

Materials And Methods: PC3 and L929 cells were cultivated and then incubated in the ethanol Bane skin extract with various concentrations of 0.78, 1.5, 3.13, 6.25, 12.5 mg/mL in 3 times 24, 48, 72 hours. Cytotoxic effect of the ethanol Bane skin extract on PC3 and L929 cells was examined by MTT assay after 24, 48, and 72 hours. Morphology of PC3 cells was evaluated by Gimsa staining.

Results: The ethanol Bane skin extract inhibited proliferation and caused cell death with IC50 values of 2.8 mg/mL on PC3 cells and the IC50 was 6.1 mg/mL on l929 cells. Morphological changes and apoptotic bodies were observed in PC3 cells faced with the ethanol Bane skin extract by staining with Gimsa.

Conclusions: The ethanol Bane skin extract could repress the growth of PC3 cell line. This inhibitory effect of the Bane extract depended on the dose and the time on PC3. The result of this study shows that the ethanol Bane skin extract includes photochemical and inhibitory function against proliferation and inducer of apoptosis in human prostate cancer PC3 cells and also has less cytotoxic effect on l929 than PC3 cells. The ethanol Bane skin extract might be a good candidate for the new herbal anticancer drug.
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http://dx.doi.org/10.17795/ijcp-4755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951764PMC
April 2016

HLA antigens and anti-sperm antibody production in Iranian vasectomized men.

J Biomed Res 2015 Jan;29(1):87-90

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.7555/JBR.29.20140113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342441PMC
January 2015

Impact of Pegylated Interferon-alfa-2a on Perforin Level in Patients With Chronic Hepatitis B; Preliminary Study.

Hepat Mon 2013 23;13(11):e11903. Epub 2013 Nov 23.

Faculty of Medicine, Ilam University of Medical Sciences, Ilam, IR Iran.

Background: Chronic hepatitis B is one of the most common causes of cirrhosis and hepatocellular toxicity in many countries, including Iran. Cytotoxic T lymphocyte (CTL) and Natural killer (NK) cells are the two of main cell populations considered as cytotoxic cells. One of the distinct pathways CTL and NK cells exert cytotoxicity is perforin/granzyme. After the cytotoxic cell/target cell junction, perforin is released from granules by exocytosis. Once it is anchored, perforin forms cylindrical pores through which granzymes and granulysin enter and induce apoptosis.

Objectives: Large controlled trials have demonstrated the efficacy of PEG-IFN-α-2a in treatment of chronic hepatitis B. This study was aimed to examine whether the enhancement of cytotoxicity by PEG-IFN-α-2a is mainly due to the perforin pathway.

Patients And Methods: This research work was performed on 50 patients and five healthy people. Patients with chronic hepatitis B were further subdivided into two groups: patients with inactive chronic hepatitis B (carriers, n = 30), and those with active chronic hepatitis B who were under treatment with PEG-IFN-alfa-2a (n = 20) for minimum six and maximum 12 months. Serum perforin level was measured using ELISA method (CUSABIO Company), HBV viral load was assessed using COBAS Taq-man, and we used Elecsys hepatitis B surface antigen (HBs Ag) II quantitative assay method for HBs Ag determination. HBeAg was evaluated by ELISA method, and AST and ALT were measured by routine laboratorymethods.

Results: Based on the results obtained serum perforin level in healthy group was 0.64 ng/mL, the mean of serum perforin level in inactive HBs Ag carriers was 2.63ng/mL, and 4.63 ng/mL in patients with active chronic hepatitis B under treatment with PEG-IFN-α-2a. The mean of serum perforin level in patients with and without virologic response to treatment were 5.45 ng/mL,and 3.4 ng/mL respectively. Finally in patients with virologic response and seroconverted serum perforin level was 7.23 ng/mL.

Conclusions: Based on our results higher perforin level in patients under treatment with PEG-IFN-α-2a, could be an indication of elevated cytotoxicity via perforin/granzyme pathway.
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http://dx.doi.org/10.5812/hepatmon.11903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858956PMC
December 2013

Kinetic, thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac.

J Enzyme Inhib Med Chem 2007 Aug;22(4):395-406

Faculty of Chemistry, Damghan University of Basic Science, Damghan, Iran.

The kinetic and thermodynamic effects of aspirin and diclofenac on the activity of adenosine deaminase (ADA) were studied in 50 mM phosphate buffer pH = 7.5 at 27 and 37 degrees C, using UV-Vis spectrophotometry and isothermal titration calorimetry (ITC). Aspirin exhibits competitive inhibition at 27 and 37 degrees C and the inhibition constants are 42.8 and 96.8 microM respectively, using spectrophotometry. Diclofenac shows competitive behavior at 27 degrees C and uncompetitive at 37 degrees C with inhibition constants of 56.4 and 30.0 microM, at respectively. The binding constant and enthalpy of binding, at 27 degrees C are 45 microM, - 64.5 kJ/mol and 61 microM, - 34.5 kJ/mol for aspirin and diclofenac. Thermodynamic data revealed that the binding process for these ADA inhibitors is enthalpy driven. QSAR studies by principal component analysis implemented in SPSS show that the large, polar, planar, and aromatic nucleoside and small, aromatic and polar non-nucleoside molecules have lower inhibition constants.
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http://dx.doi.org/10.1080/14756360701229085DOI Listing
August 2007