Publications by authors named "Majid Zeinali"

32 Publications

Evaluation of Family Gene Expression under the Influence of Single-Walled and Multi-Walled Carboxylated Carbon Nanotubes in Jurkat Cell Line and Rat.

Iran J Biotechnol 2021 Apr 1;19(2):e2717. Epub 2021 Apr 1.

Institute of Biochemistry and Biophysics, Research institute in Tehran University, Tehran, Iran.

Background: Nanomaterials, e.g.carbon nanotubes (CNTs), have broad usage in medicine for diagnosis, treatment, and drug delivery. Prior to the widespread use of CNTs, any potential toxicity issues must be considered. Apoptosis is an important issue in toxicological studies, and tumor necrosis factor (TNF) family members execute crucial roles in apoptosis and inflammation. We examined the survival of Jurkat cells under the influence of single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs) as well as their impacts on the mRNA levels of TNF family transcripts in Jurkat cells and rats.

Objective: To evaluate the toxicity or safety of a specific concentration and form of CNT on the expression of one of the gene families of the apoptotic pathway.

Materials And Methods: Jurkat cells were exposed to SWCNTs and MWCNTs in carboxylated form (SWCNTS-COOH and MWCNTs-COOH). MTT assay assessed the cell survival, and using qRT-PCR, the expression levels of , , , , , , , , , , , and were examined. The housekeeping genes β-actin and glyceraldehyde 3-phosphate dehydrogenase was utilized for normalization. We also evaluated the expression levels of and in rats 30 and 60 days after being injected with CNTs.

Results: After 72 h of carboxylated CNTs at 100 µg. mL, no significant change was observed in the survival rate of treated Jurkat cells. The expression of two genes ( and ) changed significantly. Examining the expression profiles of these two genes in rats demonstrated an insignificant change in the expression of any of these genes after 30 and 60 days. The qRT-PCR analysis exhibited the elevated levels of and mRNA in the CNT-treated cells, while expression of other family members did not significantly differ from control (untreated) Jurkat cells. There was also no significant change in the gene expression levels of and in CNT-treated rats after 30 and 60 days.

Conclusions: Administration of SWCNTs-COOH and MWCNTs-COOH could result in the up-regulation of and but did not initiate apoptosis in Jurkat cells. Carboxylated SWCNTs showed more potent activity than MWCNTs in activating gene expression and probably trigger cell death through external apoptotic pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.30498/IJB.2021.2717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358176PMC
April 2021

3D structure prediction, dynamic investigation and rational construction of an epitope-masked thermostable bovine hyaluronidase.

Int J Biol Macromol 2021 Sep 21;187:544-553. Epub 2021 Jul 21.

Department of Biochemistry, Abadan University of Medical Sciences, Abadan, Iran. Electronic address:

Hyaluronidase (HAase) from bovine testes (BTH) has long been used in broad pharmaceutical areas, while it is associated with drawbacks in aspects of solubility, immunogenicity and pharmacokinetics. These issues can be addressed by gaining structural insights and designing rational modifications to the enzyme structure, as proposed in this study. A 3D structural model was built for HAase and underwent 40 ns of molecular dynamic simulation to examine its thermostability under normal, melting, and extreme conditions. The enzyme activity of BTH was measured against temperature and pH by kinetic assays. The interaction of bovine HAase with HA and chondroitin was defined by molecular docking. Furthermore, immunogenic properties of the enzyme were explored by immunoinformatics. Thermal effects on bovine HAase structural model and the HAase interactions with its substrates were described. We identified some B- and T-cell epitopes and showed that the protein could be recognized by human immune receptor molecules. Epitope masking by adding polyethylene glycol (PEG) to amine groups of residues presenting on the surface of the protein structure was adopted as a surface modification to enhance pharmacological properties of BTH. Assays showed that PEGylated BTH had higher thermostability and similar activity compared to the native enzyme.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.07.098DOI Listing
September 2021

Comparative evaluation of the protective effects of oral administration of auraptene and umbelliprenin against CFA-induced chronic inflammation with polyarthritis in rats.

Biomed Pharmacother 2021 Jul 7;139:111635. Epub 2021 May 7.

Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, P.O. Box: 1365-91775, Mashhad, Iran. Electronic address:

This study aimed to evaluate the anti-inflammatory effect of Auraptene (AUR) and Umbelliprenin (UMB) in a rat model of rheumatoid arthritis (RA) induced by using complete Freund's adjuvant (CFA). Paw swelling of adjuvant arthritis rats measured at various times after CFA injection. Over 15 days of RA induction, mediator/cytokine-mediated processes involved in managing the regulation and resolving RA's inflammation were also quantified with ELISA. Histopathological changes were also assessed under a microscope 15 days after the CFA injection. AUR at all doses and UMB administration only at a 16 mM /kg administration dose significantly reduced CFA-induced paw edema level compared to the control group. UMB (64 and 32 mM) and AUR (64, 32, and 16 mM) could reduce the PGE2 (p < .0001-.01) and NO (p < .0001-.05) levels in the treatment groups compared to the negative control group. However, these compounds showed no significant effect on the TNF-α, IFN-γ, TGF-β, IL-4, and IL-10 levels than the control group (p > .05). Unlike indomethacin and prednisolone, treatment of rats with AUR (16, 32, and 64 mM/kg) and UMB (16 and 32 mM/kg) reduced the level of IL-2 (p < .0001). In all treatment groups, the serum level of IL-17 was significantly reduced compared to the CFA group (p < .001-0.05). We suggested AUR and UMB could diminish inflammation by reducing the serum level of IL-17 and could be considered a proper alternative in the treatment of IL-17 related inflammatory diseases such as rheumatoid arthritis. Given that AUR and UMB apply their anti-inflammatory effects by changing distinct cytokine release/inhibition patterns, their potential application in diverse inflammatory diseases seems different.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.111635DOI Listing
July 2021

Improvement of Targeted Chemotherapy of HER2-positive Ovarian Malignant Cell Line by Z-Idarubicin Conjugate: An in vitro Study.

Iran J Pathol 2021 20;16(2):109-118. Epub 2020 Dec 20.

Hyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background & Objective: Overexpression of human epidermal growth factor receptor 2 (HER2) causes cell transformation and development of various types of malignancies. Idarubicin is an effective anti-neoplastic drug but its specific delivery to the targeted cells is still a great challenge. Affibody as a cost-effective peptide molecule with low molecular weight has a high affinity for HER2 receptors. Breast and ovarian cancers as wide speared types of malignancies are associated with high expression of HER2. In the current study, we assessed the cytotoxic effects of idarubicin-Z affibody conjugate on the positive-HER2 cancer cell lines.

Methods: The cytotoxic effects of constructed idarubicin-Z affibody conjugate on the SK-BR-3, SK-OV-3, and MCF-7 cells with various levels of HER2 expression were evaluated by MTT assay following 48 hours of incubation.

Results: Idarubicin showed a potent and dose-dependent cytotoxic effect against all treated cell lines while the SK-OV-3 cells were significantly more sensitive. The dimeric form of the Z affibody molecule showed a mild effect on the cell viability of all treated cells at its optimum concentration. The constructed Idarubicin-Z affibody conjugate decreased the viability of SK-OV-3 cells at its optimal concentration, more efficiently and specifically than other treated cells.

Conclusion: The Z-affibody conjugate of idarubicin has a more specific cytotoxic effect compared with idarubicin alone against HER2-overexpressing ovarian cancerous cells. It appears the Z-affibody conjugate of idarubicin has great potential to be implicated as an innovative anti-cancer agent in future clinical trials in patients with HER2-overexpressing ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.30699/IJP.2020.120392.2310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085286PMC
December 2020

Specific targeting of HER2-positive human breast carcinoma SK-BR-3 cells by amygdaline-Z affibody conjugate.

Mol Biol Rep 2020 Sep 14;47(9):7139-7151. Epub 2020 Sep 14.

Department of Clinical Biochemistry, Faculty of Medicine, Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, P.O. Box: 61335/189, Iran.

Amygdalin induces apoptotic death in several carcinoma cells. Affibody is an engineered protein with a high affinity for human epidermal receptor 2 (HER2). We assessed the cytotoxic effects of the amygdalin-Z affibody conjugate on two breast carcinoma cell lines. The Z affibody gene was synthesized and transferred into E. coli BL21 as an expression host. After purification, the Z affibody was conjugated to amygdalin. The cytotoxic effects of amygdalin and its Z affibody conjugate on the SK-BR-3, with overexpression of HER2, and MCF-7 cells were evaluated by MTT assay. The effects of amygdalin and its conjugate on apoptotic death and expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were measured. Amygdalin individually showed a potent cytotoxic effect against both MCF-7 (IC = 14.2 mg ml) and SK-BR-3 cells (IC = 13.7 mg ml). However, the amygdalin-Z affibody conjugate had a more cytotoxic effect on SK-BR-3 (IC = 8.27 mg ml) than MCF-7 cells (IC = 19.8 mg ml). Amygdalin had a significant apoptotic effect on both cell lines and the effect of its conjugate on SK-BR-3 cells was significantly more potent than MCF-7 cells. Amygdalin increased Bax and decreased Bcl-2 expression in both cell lines. However, the effect of its conjugate on the Bax and Bcl-2 expression in SK-BR-3 was more potent than MCF-7 cells. In conclusion, the amygdalin-Z affibody conjugate may be considered as a valuable candidate for specific treatment of breast cancer patients with overexpression of HER2. However, further in vivo studies are required to explain the antitumoral effects of constructed amygdalin-Z affibody conjugate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-020-05782-zDOI Listing
September 2020

Cytotoxicity evaluation of curcumin-loaded affibody-decorated liposomes against breast cancerous cell lines.

J Liposome Res 2021 Jun 3;31(2):189-194. Epub 2020 Jul 3.

Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.

Curcumin is known as an effective anticancer herbal medicine but unfortunately, its bioavailability is poor which necessitate efforts for developing more efficient and specific delivery systems. Human epidermal growth factor receptor 2 (HER 2) due to its overexpression in various types of cancers, is demonstrated to be a good candidate as a target for anticancer therapy. In this study, cytotoxicity of curcumin encapsulated in ZHER2:342 Affibody-decorated liposome was investigated against SKBR3 and MCF-7 cancerous cell lines. Curcumin-containing liposomes were prepared from soybeans lecetin and cholesterol by thin-film hydration method. Affibody ZHER2:342 molecules C-terminal cysteine residue were conjugated covalently to the prepared liposomes. Particle size analysis was performed using atomic force microscopy (AFM) and dynamic light scattering (DLS). Curcumin loading was measured using UV-Vis spectrophotometry and cytotoxic activity of curcumin formulations against cancerous cell lines was investigated by MTT assay. Induction of apoptosis was investigated using flow cytometry through Annexin V staining. Particle analysis showed the formation of spherical liposomes with a mean diameter of about 150 nm. Cytotoxic activity of curcumin was improved by its encapsulation in both liposomes and affibody-decorated liposomes. The Annexin V staining indicated the induction of apoptosis by affibody-decorated liposomes in both MCF-7 and SKBR3 cells. Decoration of curcumin-loaded liposomes with affibody ZHER2:342 may improve curcumin apoptotic function independently of HER2 expression level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08982104.2020.1755981DOI Listing
June 2021

Immunological Responses against HER2-targeted Idarubicin-ZHER2 Conjugate in BALB/c Mice.

Iran J Allergy Asthma Immunol 2019 Oct 23;18(5):501-510. Epub 2019 Oct 23.

Department of Clinical Biochemistry, Hyperlipidemia Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Targeting of cancerous cells with a high level of human epidermal growth factor receptor 2 (HER2) expressions by drug immunoconjugates is a new approach for specific delivery of chemotherapeutic agents. Our previous work indicated that idarubicin-ZHER2 affibody conjugate has a great potential for the treatment of HER2-overexpressing malignant cell lines but possible induced immune response against constructed conjugate was not addressed. In the current study, the possibility of induction of humoral and cellular immune responses against idarubicin-ZHER2 affibody conjugate in BALB/c mice was investigated. For assessment of the induced immune response, prepared and qualified idarubicin-ZHER2 affibody conjugate was administrated intravenously to BALB/c mice and the induced cellular immune response was evaluated by measuring secretion levels of interferon gamma (IFN-γ) and interleukin 10 (IL-10) cytokines by the splenocytes. Humoral response of treated mice was also assessed by measuring total immunoglobulin G (IgG) titer in mice sera. The obtained results showed that idarubicin-ZHER2 affibody conjugate at any examined concentrations could not induce secretion of IFN-γ as a pro-inflammatory cytokine. A mild increase in the level of regulatory IL-10 cytokine was seen in the treated mice although no dose dependency in the level of IL-10 production was observed. Furthermore, results showed that idarubicin-ZHER2 conjugate could not induce IgG production in the treated mice. Based on these findings, the idarubicin-ZHER2 conjugate can be considered as a candidate for the development of new therapeutics against HER2-overexpressing cancers although further in vivo studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18502/ijaai.v18i5.1919DOI Listing
October 2019

In vitro and in silico anticancer activity of amygdalin on the SK-BR-3 human breast cancer cell line.

Mol Biol Rep 2019 Dec 3;46(6):6361-6370. Epub 2019 Oct 3.

Hyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

In spite of several studies that have shown the cytotoxic effects of amygdalin on the different cancer cell lines, however, the chemopreventive potential of amygdalin on the breast cancer cell line is not completely understood. We investigated the effect of amygdalin on the cell death and the level of pro-apoptotic Bax protein and anti-apoptotic Bcl-2 protein in SK-BR-3 human breast cancer cell line. The cell viability of SK-BR-3 cells was evaluated by MTT assay in different concentration of amygdalin. The level of Bax and Bcl-2 in SK-BR-3 cells were measured by western blot analysis. For statistical analysis, One-way ANOVA was used for the comparison of Bax and Bcl-2 protein level and percent of cell viability between groups. The molecular docking studies of amygdalin within the Bcl-2 (PDB ID: 4LVT) and HER2 (PDB ID: 3RCD) active site, were performed using AutoDock 4.2.5. Amygdalin induced a significant reduction of cell viability in SK-BR-3 after 24-h treatment in a dose-dependent manner. Also, amygdalin causes an increase in pro-apoptotic Bax protein and a decrease in anti-apoptotic Bcl-2 protein expression in the SK-BR-3 cells. Molecular docking studies showed that amygdalin interacts with the active site amino acids of Bcl-2 and HER2 through hydrogen bonding and some hydrophobic interactions. Amygdalin can induce apoptotic death in SK-BR-3 cells by increasing pro-apoptotic Bax protein and decreasing anti-apoptotic Bcl-2 protein expression. The results suggest that amygdalin may be a valuable candidate for the treatment of breast cancer, especially in HER2 positive cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-019-05080-3DOI Listing
December 2019

Immunoregulatory and anti-inflammatory properties of (Saffron) and its main active constituents: A review.

Iran J Basic Med Sci 2019 Apr;22(4):334-344

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

The medicinal uses of saffron, the dried stigmas of L., have very long history in food coloring agent, and flavoring agent as well as traditional medicine for the treatment of several diseases. is rich in carotenoids that affect immunity. This review summarizes the putative immunoregulatory effects of saffron and its active its derivatives including crocin, crocetin and safranal. In modern studies, its active constituents including protective effects, anti-inflammatory activities and molecular mechanisms of saffron on thimmune system have been demonstrated. Furthermore, the beneficial effects of saffron on inhibition of serum levels nuclear transcription factor κB (NF-κB) p65 unit, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and some interleukin (IL) such as IL-1β, IL-6, IL-12, IL-17A were reported. Furthermore, saffron has been known as the antagonist of NF-κB and the agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). In addition, saffron down-regulates the key pro-inflammatory enzymes such as myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phospholipase A2, and prostanoids. This review summarizes the protective roles of and its constituents against the pathogenesis of immune diseases and understanding a better management of these problems. Taken together, the main bioactive constituents of saffron may have health-promoting with important benefits in immune-related disorders. Finally, our study indicates that these bioactive constituents can affect both cellular and humoral immunity functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22038/ijbms.2019.34365.8158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535192PMC
April 2019

Induction of caspase-2 gene expression in carboxyl-functionalized carbon nanotube-treated human T-cell leukemia (Jurkat) cell line.

Drug Chem Toxicol 2021 Jul 7;44(4):394-399. Epub 2019 May 7.

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Carbon nanotubes (CNTs) have great potential as novel diagnostic or therapeutic tools in biomedicine but, cellular toxicity must be well considered before widespread application of CNTs. Many chemical agents exert their toxicity through apoptotic pathways by induction of caspase biomolecules. In the current study, effects of carboxyl-functionalized single-walled (SW) and multi-walled (MW) CNTs at a single dose of 100 µg ml on the survival of Jurkat cells were examined using MTT assay. Additionally, the impacts of carboxylated CNTs on the gene expression levels of selected caspases were investigated. Jurkat cells were exposed to CNTs (100 µg ml for 72 h) and then expression levels of selected caspase genes () were evaluated by qRT-PCR analysis. Housekeeping genes, β-actin, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), were used as normalization controls. The results showed only a mild decrease in the viability of Jurkat cells treated with carboxylated MWCNT. The results of qRT-PCR analysis revealed the elevated level of mRNA in the cells treated with carboxylated MWCNT (6.08-fold) and carboxylated SWCNT (1.20-fold). The expression levels of , , , and genes were increased not significantly compared to the control untreated cells. Our findings suggested that exposure to carboxyl-functionalized CNTs could be resulted in up-regulation of the gene and not initiator and genes. In addition, it seems that carboxylated MWCNT was more potent than SWCNT in activation of gene expression and triggering cell death signal in a manner different from intrinsic or extrinsic apoptosis pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01480545.2019.1609025DOI Listing
July 2021

Mechanisms behind the atherothrombotic effects of acrolein, a review.

Food Chem Toxicol 2019 Jul 19;129:38-53. Epub 2019 Apr 19.

Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The majority of cardiovascular complications are secondary to atherosclerosis. Extensive evidence has showed that environmental pollutants such as cigarette smoke and automobile exhaust increase the risk of developing atherosclerosis. Acrolein, a highly reactive unsaturated aldehyde, is found as a contaminant in air, food and water. Investigations during the last decades have shown that acrolein via various mechanisms such as oxidative stress, enhancement of inflammatory processes and the activation of matrix metalloproteases can initiate and accelerate atherosclerotic lesions formation. Furthermore, exposure to acrolein has been suggested to induce or exacerbate systemic dyslipidemia, an important risk factor for the development of atherosclerosis. Finally, there are reports which indicate acrolein can increase platelet activation and stimulation of the coagulation cascade which subsequently leads to thrombosis. Even a modest reduction of pollutants such as acrolein can have substantial effects on population health. Public health efforts to reduce acrolein exposures from known sources may lower the prevalence of vascular disease. This review focuses on the potential pathways and mechanisms behind the acrolein-induced atherothrombotic effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2019.04.034DOI Listing
July 2019

Computer-aided Drug Design and Drug Pharmacokinetic Prediction: A Mini-review.

Curr Pharm Des 2018 ;24(26):3014-3019

Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Prediction of pharmacokinetics and drug targeting is a challenge in drug design. There are different types of software that can help to predict the pharmacokinetic profile of a drug. Quantitative structure-activity relationship (QSAR) modeling is used for drug design with less cost. Drug-excipient interactions are predicted by docking tools. Computerized drug target prediction and docking programs offer additional options to predict potential effects and adverse reactions of a given candidate as well as the best orientation of the compound on the receptor active site. Information on the absorption, distribution, metabolism and excretion of the drug in the body can enhance prediction of drug release and distribution in the blood and central nervous system (CNS). Computer- aided drug design and delivery can help to save the time and cost in the process of rational drug development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1381612824666180903123423DOI Listing
October 2019

Prescription Pattern Analysis of Nonsteroidal Anti-inflammatory Drugs in the Northeastern Iranian Population.

J Res Pharm Pract 2017 Oct-Dec;6(4):206-210

Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Inappropriate nonsteroidal anti-inflammatory drugs (NSAIDs) therapy is a common cause of actual and potential adverse effects, such as bleeding and gastrointestinal ulceration, which exacerbates the patient's medical condition and might even be life threatening. We aimed to evaluate and analyze the prescription pattern of NSAIDs in Northeastern Iranian population and also provide suggestions for a more rational prescription behavior for such drugs.

Methods: In this cross-sectional retrospective study, pattern of 1-year prescriptions was inspected based on 9.3 million prescriptions from two insurance companies. Type of NSAIDs, all dispensed doses and the number of NSAIDs ordered per prescription, and the route of administration for each patient were extracted from the databases. The prescription pattern of NSAIDs was analyzed seasonally.

Findings: Out of 9,303,585 prescriptions, 19.3% contained at least one NSAID. Diclofenac was the most commonly prescribed NSAID (49.21%). At least two NSAIDs were simultaneously prescribed in 7% of prescriptions. General practitioners prescribed NSAIDs more frequently (67%) than specialists. Orthopedic surgeons and internists more frequently prescribed NSAIDs in comparison with other physicians (6% and 4%, respectively). Gastroprotective agents (GPAs) were coprescribed to only 7.62% of prescriptions.

Conclusion: The frequency of NSAIDs prescription was relatively high in Northeast of Iran. A significant number of prescriptions were associated with irrational prescribing in both coadministration of NSAIDs and GPAs and NSAIDs combination. A strategy must be developed and implemented for prescribing and rational use of medications, e.g., continuing medical education regarding the potential risks of NSAIDs, importance of their appropriate and rational use, and necessity of appropriate prescription writing regarding both content and indication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jrpp.JRPP_17_45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787905PMC
February 2018

Protective effects of chrysin on sub-acute diazinon-induced biochemical, hematological, histopathological alterations, and genotoxicity indices in male BALB/c mice.

Drug Chem Toxicol 2018 Jul 2;41(3):270-280. Epub 2017 Nov 2.

e Pharmaceutical Research Centre , Mashhad University of Medical Sciences , Mashhad , Islamic Republic of Iran.

Chrysin (CH) is a natural flavone which possesses antioxidant, anti-cancer, and anti-inflammatory properties. The aim of the present study was to investigate the effects of CH on biochemical parameters, histopathological changes, and genotoxicity and hematological indices in diazinon (DZN)-induced toxicity in BALB/c mice. We induced sub-acute toxicity in mice using DZN (20 mg/kg/day) and treated them with CH at the 12.5, 25, and 50 mg/kg/day five times/week in 28 days. In our study, DZN increased lipid profile and liver function tests (LFTs) and creatinine (Cr) but decreased the red blood cell acetylcholinesterase (RBC-AChE) activity and glucose level. Also, CH when co-treated with DZN changed the LFTs, lipid profile, creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and bilirubin total (Bili-T). Moreover, a significant decrease in RBCs, hemoglobin (Hgb), hematocrit (HCT) level, and platelet counts were seen in DZN group but WBCs, lymphocytes, and neutrophils count increased. CH 25 and 50 mg/kg significantly improved alterations of WBCs, RBCs, Hgb, HCT, lymphocytes, neutrophils, and reticulocytes count when co-treated with DZN. Moreover, the co-administration of CH plus DZN recovered histopathological alterations in liver and kidney, as well as, improved the absolute and relative weight of kidney and liver. DZN induced the formation of bone marrow micronuclei (MN) but CH 50 mg/kg decreased the MN formation when co-treated with DZN. These results suggest that CH not only restores renal and hepatic markers, and histopathological alterations but also improves hematological and genotoxicity indices induced by DZN in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01480545.2017.1384834DOI Listing
July 2018

An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances.

Biomed Pharmacother 2017 Aug 9;92:998-1009. Epub 2017 Jun 9.

Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences (MUMS), Mashhad, Islamic Republic of Iran. Electronic address:

Inflammation and the pro-inflammatory cytokines are associated with numerous chronic diseases. Studies suggest that flavonoids, plant polyphenolic compound derivatives from natural origin, have a wide range of putative biological activities. Similar to other flavonoids, chrysin (CH) by its anti-oxidative and anti-inflammatory effects is a potential prophylactic agent in immunopathological and physicochemical injuries. This is an overview on putative immunomodulatory activities of flavonoids and beneficial health effects of these substances particularly, CH in the immune system. CH possesses potent immune-protective effects and suppresses inflammation in innate immune system which results to avoid damages induced by neutrophils and macrophages and suppresses immuno-inflammatory responses. Furthermore, beneficial effects of chrysin on inhibition of serum levels nuclear transcription factor κB (NF-κB) p65 unit, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-12, IL-17A, interferon gamma (IFN-γ) was reported. Moreover, CH has been known as the antagonist of NF-kB and the agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ) which in down regulation of the key pro-inflammatory enzymes such as myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phospholipase A2, and prostanoids. Therefore, CH can improve immune system and neurodegenerative diseases. In recent years, there has been an increasing interest in compound derivatives from natural origin. Taken together, evidences show that flavonoids may have health-promoting and disease-preventing dietary compounds with important benefits in modern life styles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2017.06.003DOI Listing
August 2017

Specific Targeting of HER2-Positive Head and Neck Squamous Cell Carcinoma Line HN5 by Idarubicin-ZHER2 Affibody Conjugate.

Curr Cancer Drug Targets 2019 ;19(1):65-73

Abadan School of Medical Sciences, Abadan, Iran.

Background: Expression of human epidermal growth factor receptor type 2 (HER2) in head and neck squamous cell carcinoma (HNSCC) cell line HN5 can be employed with great opportunities of success for specific targeting of anti-cancer chemotherapeutic agents.

Objective: In the current study, HER2-specific affibody molecule, ZHER2:342 (an engineered protein with great affinity for HER2 receptors) was selected for conjugation to idarubicin (an anti-neoplastic antibiotic).

Method: ZHER2:342 affibody gene with one added cysteine code at the its 5' end was synthesized de novo and then inserted into pET302 plasmid and transferred to E. Coli BL21 hosting system. After induction of protein expression, the recombinant ZHER2 affibody molecules were purified using Ni- NTA resin and purity was analyzed through SDS-PAGE. Affinity-purified affibody molecules were conjugated to idarubicin through a heterobifunctional crosslinker, sulfosuccinimidyl 4-(Nmaleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC). Specific toxicity of idarubicin-ZHER2 affibody conjugate against two HER2-positive cells, HN5 and MCF-7 was assessed through MTT assay after an exposure time of 48 hours with different concentrations of conjugate.

Results: Idarubicin in the non-conjugated form showed potent toxic effects against both cell lines, while HN5 cells were significantly more sensitive compared to MCF-7 cells. Dimeric ZHER2 affibody showed a mild decreasing effect on growth of both HN5 and MCF-7 cells at optimum concentration. Idarubicin-ZHER2 affibody conjugate at an optimum concentration reduced viability of HN5 cell line more efficiently compared to MCF-7 cell line.

Conclusion: In conclusion, idarubicin-ZHER2 affibody conjugate in optimum concentrations can be used for specific targeting and killing of HN5 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1568009617666170427105417DOI Listing
March 2020

Human Sperm Quality and Metal Toxicants: Protective Effects of some Flavonoids on Male Reproductive Function.

Int J Fertil Steril 2016 Jul-Sep;10(2):215-23. Epub 2016 Jun 1.

Biotechnology Research Center, Research Institute of Petroleum Industry (RIPI), Tehran, Iran.

Background: Metals can cause male infertility through affection of spermatogenesis and sperm quality. Strong evidences confirm that male infertility in metal-exposed humans is mediated via various mechanisms such as production of reactive oxygen species (ROS). Flavonoids have antioxidant and metal chelating properties which make them suitable candidates for neutralizing adverse effects of metals on semen quality. In the current study, we have evaluated the effects of five types of flavonoids (rutin, naringin, kaempferol, quercetin, and catechin) on recovery of sperm motility and prevention of membrane oxidative damage from aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4).

Materials And Methods: In this experimental study, motility and lipid peroxidation of metalexposed sperm was investigated in the presence of different concentrations of five kinds of flavonoids. Malondialdehyde (MDA) production was assessed as a lipid peroxidation marker.

Results: Aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4) diminished sperm motility. Treatment of metal-exposed sperm with rutin, naringin, and kaempferol attenuated the negative effects of the metals on sperm motility. Quercetin and catechin decreased the motility of metal-exposed sperm.

Conclusion: Based on the MDA production results, only AlCl3 significantly induced lipid peroxidation. Treatment with rutin, naringin, and kaempferol significantly decreased MDA production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948074PMC
http://dx.doi.org/10.22074/ijfs.2016.4912DOI Listing
July 2016

Effect of ascorbic acid and alpha-tocopherol supplementations on serum leptin, tumor necrosis factor alpha, and serum amyloid A levels in individuals with type 2 diabetes mellitus.

Avicenna J Phytomed 2015 Nov-Dec;5(6):531-9

Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Objective: Diabetes mellitus Type 2 is one of the most widespread chronic metabolic diseases. In most cases, this type of diabetes is associated with alterations in levels of some inflammatory cytokines and hormones. Considering anti-inflammatory properties of plant extracts rich in ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), anti-diabetic properties of these two well-known antioxidant vitamins were investigated through measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP), insulin, leptin, tumor necrosis factor alpha (TNF-α), and serum amyloid A (SAA) in patients with diabetes mellitus type 2.

Materials And Methods: Male patients (n=80) were randomly divided into two groups each consisted of 40 subjects. Test groups were supplemented with ascorbic acid (1000 mg/day) or alpha-tocopherol (300 mg/day) orally during four weeks. Before and after treatment, serum biochemical factors of subjects were measured and compared.

Results: Our results showed that both ascorbic acid and alpha-tocopherol could induce significant anti-inflammatory effects by decreasing the level of inflammatory factors such as TNF-α, SAA, and hs-CRP in diabetes mellitus type 2 patients. Effects of alpha-tocopherol and ascorbic acid in decreasing serum leptin level were similar. Ascorbic acid in contrast to alpha-tocopherol diminished fasting insulin and HOMA index but had no effect on LDL serum level.

Conclusion: Concerning the obtained results, it is concluded that consumption of supplementary vitamins C and E could decrease induced inflammatory response in patients with diabetes mellitus type 2. It is also possible that vitamin C and vitamin E supplementation can attenuate incidence of some proposed pathological effects of diabetes mellitus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678498PMC
December 2015

Enzymatic and histopathologic biomarkers in the flatfish Euryglossa orientalis from the northwestern Persian Gulf.

Toxicol Ind Health 2016 May 13;32(5):866-76. Epub 2013 Dec 13.

Biotechnology Research Center, Research Institute of Petroleum Industry (RIPI), Tehran, Islamic Republic of Iran

Most of the chemicals in the petrochemical sewages cause oxidative stress in marine organisms. Antioxidant enzymes (catalase (CAT) and superoxide dismutase (SOD)) as biomarkers of oxidative stress and liver histopathological alterations were investigated in the current study to evaluate the toxic effects of petrochemical pollutions in flatfish, Euryglossa orientalis The enzymatic and histopathological changes were assessed in the liver of E. orientalis from Khowr-e Jafari (one of the creeks from Khowr-e Musa estuary) and Sajafi harbor as polluted and clean areas, respectively. A significant increase in the antioxidant enzyme activities was observed in response to aquatic pollutions of Khowr-e Jafari. Liver lesions were diagnosed and categorized using standard methods. The results of histopathological examinations showed more lesion scores in the fish from Khowr-e Jafari. Various histopathological changes including hepatocyte degeneration, inflammatory lesions, peliosis hepatis and pancreatic acinar cell adenoma, and increase in the number of pigmented macrophage aggregates were observed in the fish from polluted site. It is suggested that activities of CAT and SOD along with semi-quantitative histopathologic analysis of E. orientalis can be used for biomonitoring programs in Persian Gulf.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0748233713513490DOI Listing
May 2016

Affinity enhancement of HER2-binding Z(HER2:342) affibody via rational design approach: a molecular dynamics study.

J Biomol Struct Dyn 2014 Dec 15;32(12):1919-28. Epub 2013 Oct 15.

a Department of Biochemistry , Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran .

Human epidermal growth factor receptor 2 (HER2) contributes to the development of breast cancers and malignancies. On the other hand, engineered affibody Z(HER2:342) that binds to HER2 can be successfully used for both diagnostic purposes and specific ablation of malignant HER2-positive cell lines. In the current study, electrostatics-based prediction was applied for improving Z(HER2:342) binding affinity using computational design. The affibody Z(HER2:342) alone and in complex with HER2 was energetically minimized, solvated in explicit water, and neutralized. After heating and equilibration steps, the system was studied by isothermal-isobaric (NPT) MD simulation. According to trajectories, Z(HER2:342) specifically binds to HER2 through hydrogen bonds and salt bridges. Based on the electrostatic binding contributions, two affinity-matured variants namely V1 (Tyr35Arg) and V2 (Asn6Asp and Met9Glu) were rationally designed. More investigations through MD simulation show that V1 interacts with HER2 receptor more strongly, compared to Z(HER2:342) and V2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2013.842499DOI Listing
December 2014

Ablation of breast cancer cells using trastuzumab-functionalized multi-walled carbon nanotubes and trastuzumab-diphtheria toxin conjugate.

Chem Biol Drug Des 2014 Mar 26;83(3):259-65. Epub 2013 Dec 26.

Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Golestan Avenue, Ahvaz 15794-61357, Iran.

Trastuzumab (Herceptin(®) ) is a monoclonal antibody (mAb) for specific ablation of HER2-overexpressing malignant breast cancer cells. Intensification of antiproliferative activity of trastuzumab through construction of immunotoxins and nano-immunoconjugates is a promising approach for treatment of cancer. In this study, trastuzumab was directly conjugated to diphtheria toxin (DT). Also, conjugates of trastuzumab and multiwalled carbon nanotubes (MWCNT) were constructed by covalent immobilization of trastuzumab onto MWCNTs. Then, antiproliferative activity of the fusion constructs against HER2-overexpressing SK-BR-3 and also HER2-negative MCF-7 cancer cell lines were examined. Cells treated with trastuzumab-MWCNT conjugates were irradiated with near-infrared (NIR) light. Efficient absorption of NIR radiation and its conversion to heat by MWCNTs can be resulted to thermal ablation of cancerous cells. Our results strongly showed that both trastuzumab-MWCNT and trastuzumab-DT conjugates were significantly efficient in the specific killing of SK-BR-3 cells. Targeting of MWCNTs to cancerous cells using trastuzumab followed by exposure of cells to NIR radiation was more efficient in repression of cell proliferation than treatment for cancer cells with trastuzumab-DT. Our results also showed that conjugation linkers can significantly affect the cytotoxicity of MWCNT-immunoconjugates. In conclusion, our data demonstrated that trastuzumab-MWCNT is a promising nano-immunoconjugate for killing of HER2-overexpressing cancerous cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cbdd.12244DOI Listing
March 2014

Production, purification, and chemical stability of recombinant human interferon-γ in low oxygen tension condition: a formulation approach.

Prep Biochem Biotechnol 2013 ;43(6):586-600

Malek-e Ashtar University of Technology, Tehran, Iran.

The low stability of recombinant human interferon-γ (rhIFN-γ) therapeutic protein imposes some restrictions in its medical applications. In the current study, the effect of oxygen tension on the stability of purified rhIFN-γ was investigated. The rhIFN-γ was purified (>99%) by a two-step chromatographic process. Storage vials were filled by purified formulated product under normal atmospheric oxygen and low oxygen tension conditions. At different time intervals, the amounts of rhIFN-γ covalent dimers and deamidated forms were analyzed using analytical high-performance liquid chromatography (HPLC; size exclusion and cation exchange) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) methods. To determine the biological activity of purified rhIFN-γ, an antiviral activity assay against vesicular stomatitis virus (VSV) was performed. Upon rhIFN-γ long-term storage in a low oxygen tension condition, the amounts of rhIFN-γ covalent dimers and deamidated forms and also the biological activity of rhIFN-γ changed a little. In contrast, by 9 months of storage of rhIFN-γ preparations under normal atmospheric condition, the amount of covalent dimers and deamidated forms increased with time and reached to approximately 3.5% and 11.5% of the initial amount, respectively. The antiviral specific activity of 9-month-old rhIFN-γ preparations decreased to 41% of the initial amount at normal storage condition, while no significant reduction was seen at the low oxygen tension condition. In conclusion, oxygen tension during storage could have a significant impact on rhIFN-γ stability and finally on the quality of pharmaceutical rhIFN-γ product.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10826068.2012.762716DOI Listing
January 2014

Design of peptidomimetics for inhibition of HER2 receptor dimerization by a combination of virtual screening, MD simulations, and QSAR in silico methods.

Chem Biol Drug Des 2013 Apr;81(4):455-62

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Malfunction or overexpression of ErbB receptors (epidermal growth factor receptors) is associated with occurrence and severity of several types of cancer. Initiation of signal cascades by ErbB2 (also known as human epidermal growth factor receptor 2/neu) in breast cancer has been blocked by monoclonal antibodies such as Trastuzumab (Herceptin), which interact with the extracellular domain of human epidermal growth factor receptor 2. Due to some disadvantages of monoclonal antibodies, a new approach in blocking human epidermal growth factor receptor 2 dimerization and activation is designing peptidomimetic ligands based on human epidermal growth factor receptor 2-Trastuzumab interaction model. Growth of human epidermal growth factor receptor 2(+) SK-BR3 cells could be specifically inhibited by peptidomimetic herceptin-based peptidomimetic 5. In this study, herceptin-based peptidomimetic 5 was used as a benchmark peptidomimetic compound to perform a ligand-based virtual screening followed by structure-based screening by applying the molecular docking approach. The study aimed to explore more potent peptidomimetic molecules against extracellular part of human epidermal growth factor receptor 2. Our results showed that the newly designed peptidomimetic herceptin-based peptidomimetic n33B in comparison with herceptin-based peptidomimetic 5 binds more tightly to the extracellular domain of human epidermal growth factor receptor 2. Mechanistic aspects of herceptin-based peptidomimetic n33B interaction with human epidermal growth factor receptor 2 were more investigated through 20-ns molecular dynamic simulations. Additionally, a quantitative structure-activity relationships study was performed to develop a model for identification of structural determinants in herceptin-based peptidomimetic 5-based peptidomimetics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cbdd.12062DOI Listing
April 2013

Efficient biodegradation of naphthalene by a newly characterized indigenous Achromobacter sp. FBHYA2 isolated from Tehran Oil Refinery Complex.

Water Sci Technol 2012 ;66(3):594-602

Department of Environmental Engineering, Islamic Azad University, Tehran, Iran.

A bacterial strain, FBHYA2, capable of degrading naphthalene, was isolated from the American Petroleum Institute (API) separator of the Tehran Oil Refinery Complex (TORC). Strain FBHYA2 was identified as Achromobacter sp. based on physiological and biochemical characteristics and also phylogenetic similarity of 16S rRNA gene sequence. The optimal growth conditions for strain FBHYA2 were pH 6.0, 30 °C and 1.0% NaCl. Strain FBHYA2 can utilize naphthalene as the sole source of carbon and energy and was able to degrade naphthalene aerobically very fast, 48 h for 96% removal at 500 mg/L concentration. The physiological response of Achromobacter sp., FBHYA2 to several hydrophobic chemicals (aliphatic and aromatic hydrocarbons) was also investigated. No biosurfactant was detected during bacterial growth on any aliphatic/aromatic hydrocarbons. The results of hydrophobicity measurements showed no significant difference between naphthalene- and LB-grown cells. The capability of the strain FBHYA2 to degrade naphthalene completely and rapidly without the need to secrete biosurfactant may make it an ideal candidate to remediate polycyclic aromatic hydrocarbon (PAH)-contaminated sites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2166/wst.2012.217DOI Listing
August 2012

Magnetic nanocomposite of anti-human IgG/COOH-multiwalled carbon nanotubes/Fe₃O₄ as a platform for electrochemical immunoassay.

Anal Biochem 2012 Feb 28;421(2):446-53. Epub 2011 Dec 28.

Laboratory of Microanalysis, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

An electrochemical immunosensing method was developed based on a magnetic nanocomposite. The multiwalled carbon nanotubes (MWCNTs) were treated with nitric acid to produce carboxyl groups at the open ends. Then, Fe₃O₄ nanoparticles were deposited on COOH-MWCNTs by chemical coprecipitation of Fe²⁺ and Fe³⁺ salts in an alkaline solution. Goat anti-human IgG (anti-hIgG) was covalently attached to magnetic nanocomposite through amide bond formation between the carboxylic groups of MWCNTs and the amine groups of anti-hIgG. The prepared bio-nanocomposite was used for electrochemical sensing of human tetanus IgG (hIgG) as a model antigen. The anti-hIgG magnetic nanocomposite was fixed on the surface of a gold plate electrode using a permanent magnet. The hIgG was detected using horseradish peroxidase (HRP)-conjugated anti-hIgG in a sandwich model. Electrochemical detection of hIgG was carried out in the presence of H₂O₂ and KI as substrates of HRP. Using this method, hIgG was detected in a concentration range from 30 to 1000 ng ml⁻¹ with a correlation coefficient of 0.998 and a detection limit of 25 ng ml⁻¹ (signal/noise=3). The designed immunosensor was stable for 1 month.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ab.2011.12.031DOI Listing
February 2012

Effectiveness of Brucella abortus lipopolysaccharide as an adjuvant for tuberculin PPD.

Biologicals 2011 Jan 20;39(1):23-8. Epub 2010 Oct 20.

Immunology Lab, Institute of Biochemistry and Biophysics, University of Tehran, Enghelab Ave, PO Box 13145-1384, Tehran, Iran.

Bacterial lipopolysaccharide (LPS) has T-helper 1 (Th1) immunostimulatory activities but because of toxicity and pyrogenicity cannot be used as an adjuvant. Brucella abortus LPS has less toxicity and no pyrogenic properties in comparison to other bacterial LPS. In the current study, the immunostimulatory properties of B. abortus LPS were evaluated for its adjuvant activity. Tuberculin purified protein derivative (PPD) from Mycobacterium tuberculosis was extracted and after anion-exchange chromatography on Q-sepharose column, two fractions (17 and 23), which dominantly contained 30- and 70-kDa antigens, were collected for immunological studies. BALB/c mice were immunized with four different antigen preparations (BCG, PPD, 17th and 23rd PPD fractions) along with complete Freund's adjuvant or B. abortus LPS. The T-cell immune response of mice was assessed by measurement of Th1-type cytokine (IFN-γ) and Th2-type cytokines (IL-5 and IL-10) levels. Also, the humoral immunity was evaluated by measuring the specific IgG levels. Our results showed that immunization of mice with 17th PPD fraction along with B. abortus LPS can induce a Th1-type cytokine response characterized with a high IFN-γ/IL-5 ratio, while immunization with PPD or 23rd PPD fraction along with the same adjuvant resulted to a mixed Th1/Th2-type cytokine response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biologicals.2010.08.005DOI Listing
January 2011

Immunological and cytotoxicological characterization of tuberculin purified protein derivative (PPD) conjugated to single-walled carbon nanotubes.

Immunol Lett 2009 Sep 5;126(1-2):48-53. Epub 2009 Aug 5.

Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran; Biotechnology Center, Research Institute of Petroleum Industry, Tehran, Iran.

Tuberculosis (TB) represents one of the leading killers among all infectious disease. Protection against TB depends on the activation of T-helper type I (Th1) immune response. Carbon nanotubes (CNTs) have attracted considerable attention because of their potential applications as new nanovehicle. In the current study, tuberculin purified protein derivative (PPD) was conjugated to carboxylated single-walled carbon nanotubes (SWCNTs). Cytotoxicity of the carboxylated SWCNT and SWCNT-PPD conjugate was analyzed with MTT assay and by reactive oxygen species (ROS) and nitric oxide (NO) generation. Male BALB/c mice were immunized with BCG, PPD, SWCNT-PPD conjugate and PPD in complete Freund's adjuvant (CFA). Induction of cellular immune response was analyzed by measuring the levels of Th1 cytokines (IFN-gamma and IL-12) and Th2 cytokines (IL-10 and IL-5). Immunization with non-conjugated PPD or PPD in Freund's adjuvant induced a Th2 cytokine response while immunization with BCG resulted to a mixed Th1/Th2 cytokine response. In contrast, PPD in conjugation with SWCNT generated preferentially a Th1-type cytokine response in the absence of potential cytotoxic effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2009.07.012DOI Listing
September 2009

Leishmania major: effects of proteophosphoglycan on reactive oxygen species, IL-12, IFN-gamma and IL-10 production in healthy individuals.

Exp Parasitol 2008 Sep 4;120(1):62-6. Epub 2008 May 4.

Immunology Lab, Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran.

Protozoan parasites of the genus Leishmania secrete a range of proteophosphoglycans (PPG) known to be important for successful colonization of Leishmania in the sandfly and for virulence in the mammalian host. PPGs are a large family of extensively glycosylated proteins with some unusual and unique features. In this study we purified PPG from culture supernatant of Leishmania major metacyclic promastigotes. In discontinuous SDS-PAGE, PPG could not enter the resolving gel but after mild acid hydrolysis several bands resolved. Agarose gel electrophoresis and immunoblot analysis using monoclonal antibody (WIC 79.3) indicated that the PPG preparation consisted of heterogeneous molecules. Compositional analysis showed that the PPG preparation contained 67% glycan, 28% protein and 5% phosphate. Additionally, the effect of PPG on reactive oxygen species (ROS) production and induction of IL-10, IL-12 and IFN-gamma secretion by human peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals was investigated. The water-soluble secreted form of PPG at a concentration of 1 microg glycan/ml seems to be a potent inducer of ROS and IL-10 and to a lesser extent of IFN-gamma and IL-12. Cytokines and ROS production was decreased in a dose-dependent manner as the concentration of PPG was increased to 100 microg glycan/ml.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exppara.2008.04.022DOI Listing
September 2008

Naphthalene metabolism in Nocardia otitidiscaviarum strain TSH1, a moderately thermophilic microorganism.

Chemosphere 2008 Jun 8;72(6):905-9. Epub 2008 May 8.

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

The thermophilic bacterium Nocardia otitidiscaviarum strain TSH1, originally isolated in our laboratory from a petroindustrial wastewater contaminated soil in Iran, grows at 50 degrees C on a broad range of hydrocarbons. Transformation of naphthalene by strain TSH1 which is able to use this two ring-polycyclic aromatic hydrocarbon (PAH) as a sole source of carbon and energy was investigated. The metabolic pathway was elucidated by identifying metabolites, biotransformation studies and monitoring enzyme activities in cell-free extracts. The identification of metabolites suggests that strain TSH1 initiates its attack on naphthalene by dioxygenation at its C-1 and C-2 positions to give 1,2-dihydro-1,2-dihydroxynaphthalene. The intermediate 2-hydroxycinnamic acid, characteristic of the meta-cleavage of the resulting diol was identified in the acidic extract. Apart from typical metabolites of naphthalene degradation known from mesophiles, benzoic acid was identified as an intermediate for the naphthalene pathway of this Nocardia strain. Neither phthalic acid nor salicylic acid metabolites were detected in culture extracts. Enzymatic experiments with cell extract showed the catechol 1,2-dioxygenase activity while transformation of phthalic acid and protocatechuic acid was not observed. The results of enzyme activity assays and identification of benzoic acid in culture extract provide strong indications that further degradation goes through benzoate and beta-ketoadipate pathway. Our results indicate that naphthalene degradation by thermophilic N. otitidiscaviarum strain TSH1 differs from the known pathways found for the thermophilic Bacillus thermoleovorans Hamburg 2 and mesophilic bacteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2008.03.038DOI Listing
June 2008

Purification and biochemical characterization of two novel antigens from Leishmania major promastigotes.

Korean J Parasitol 2007 Dec;45(4):287-93

Immunology Laboratory, Institute of Biochemistry and Biophysics, University of Tehran, Iran.

The identification and characterization of antigens that elicit human T cell responses is an important step toward understanding of Leishmania major infection and ultimately in the development of a vaccine. Micropreparative SDS-PAGE followed by electrotransfer to a PVDF membrane and elution of proteins from the PVDF, was used to separate 2 novel proteins from L. major promastigotes, which can induce antibodies of the IgG2a isotype in mice and also are recognized by antisera of recovered human cutaneous leishmaniasis subjects. Fractionation of the crude extract of L. major revealed that all detectable proteins of interest were present within the soluble Leishmania antigens (SLA). Quantitation of these proteins showed that their expression in promastigotes is relatively very low. Considering the molecular weight, immunoreactivity, chromatographic and electrophoretic behavior in reducing and non-reducing conditions, these proteins are probably 2 isoforms of a single protein. A digest of these proteins was resolved on Tricine-SDS-PAGE and immunoreactive fragments were identified by human sera. Two immunoreactive fragments (36.4 and 34.8 kDa) were only generated by endoproteinase Glu-C treatment. These immunoreactive fragments or their parent molecules may be ideal candidates for incorporation in a cocktail vaccine against cutaneous leishmaniasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532619PMC
http://dx.doi.org/10.3347/kjp.2007.45.4.287DOI Listing
December 2007
-->