Publications by authors named "Zahra Hosseini-Khah"

18 Publications

  • Page 1 of 1

Synthesis and biological assessment of ciprofloxacin-derived 1,3,4-thiadiazoles as anticancer agents.

Bioorg Chem 2020 12 15;105:104383. Epub 2020 Oct 15.

Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

The quinolone-3-carboxylic acid scaffold is essential structure for antibacterial activity of fluoroquinolones such as ciprofloxacin. Modification of 3-carboxylic functionality in this structure can be used for switching its activity from antibacterial to anticancer. Accordingly, a series of C-3 modified ciprofloxacin derivatives containing N-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-carboxamide moiety was synthesized as novel anticancer agents. Most of compounds showed significant activity against MCF-7, A549 and SKOV-3 cancer cells in the MTT assay. In particular, compounds 13a-e and 13g were found to be as potent as standard drug doxorubicin against MCF-7 cell line (ICs = 3.26-3.90 µM). Furthermore, the 4-fluorobenzyl derivatives 13h and 14b with IC values of 3.58 and 2.79 µM exhibited the highest activity against SKOV-3 and A549 cells, being as potent as doxorubicin. Two promising compounds 13e and 13g were further tested for their apoptosis inducing activity and cell cycle arrest. Both compounds could significantly induce apoptosis in MCF-7 cells, while compound 13e was more potent apoptosis inducer resulting in an 18-fold increase in the proportion of apoptotic cells at the IC concentration in MCF-7 cells. The cell cycle analysis revealed that compounds 13e and 13g could increase cell portions in the sub-G1 phase, inducing oligonucleosomal DNA fragmentation and apoptosis confirmed by comet assay.
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http://dx.doi.org/10.1016/j.bioorg.2020.104383DOI Listing
December 2020

Expression patterns of seven key genes, including β-catenin, Notch1, GATA6, CDX2, miR-34a, miR-181a and miR-93 in gastric cancer.

Sci Rep 2020 07 23;10(1):12342. Epub 2020 Jul 23.

Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.

Gastric cancer (GC) is one of the most prevalent cancers and a major cause of cancer related mortality worldwide. Incidence of GC is affected by various factors, including genetic and environmental factors. Despite extensive research has been done for molecular characterization of GC, it remains largely unknown. Therefore, further studies specially conducted among various ethnicities in different geographic locations, are required to know the precise molecular mechanisms leading to tumorigenesis and progression of GC. The expression patterns of seven candidate genes, including β-catenin, Notch1, GATA6, CDX2, miR-34a, miR-181a, and miR-93 were determined in 24 paired GC tissues and corresponding non-cancerous tissues by quantitative Real-Time PCR. The association between the expression of these genes and clinicopathologic factors were also investigated. Our results demonstrated that overall mRNA levels of GATA6 were significantly decreased in the tumor samples in comparison with the non-cancerous tissues (median fold change (FC) = 0.3143; P = 0.0003). Overall miR-93 levels were significantly increased in the tumor samples relative to the non-cancerous gastric tissues (FC = 2.441; P = 0.0002). β-catenin mRNA expression showed a strong positive correlation with miR-34a (r = 0.5784; P = 0.0031), and miR-181a (r = 0.5652; P = 0.004) expression. miR-34a and miR-181a expression showed a significant positive correlation (r = 0.4862; P = 0.016). Moreover, lower expression of Notch1 was related to distant metastasis in GC patients with a borderline statistical significance (p = 0.0549). These data may advance our understanding of the molecular biology that drives GC as well as provide potential targets for defining novel therapeutic strategies for GC treatment.
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http://dx.doi.org/10.1038/s41598-020-69308-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378835PMC
July 2020

Synthesis, computational study and cytotoxicity of 4-hydroxycoumarin-derived imines/enamines.

Mol Divers 2020 Apr 22. Epub 2020 Apr 22.

Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

In this study, we applied a direct condensation between 3-acetyl-4-hydroxy-2H-chromen-2-one and different amines (anilines and benzyl amines) in order to synthesize some coumarin-based imines/enamines (3a-o) as cytotoxic agents. All the compounds were characterized by means of FT-IR, NMR, mass spectroscopy and elemental analyses. Since the title compounds can exist as different forms including (s-cis)-imine and (s-trans)-imine or (E and Z)-enamines, their conformational and geometrical aspects were investigated computationally by DFT method. The optimized geometry parameters, ΔE, ΔG, ΔH, Mulliken atomic charge, HOMO and LUMO energy, and NBO analysis suggested that these compounds can exist predominantly in (E)-enamine form. All the synthesized compounds (3a-o) were evaluated in vitro for their cytotoxic activities against cancer cell lines (MCF-7 and A549) and normal cell line (BEAS-2B) using the MTT assay. The 4-hydroxybenzyl derivative 3k was found to be the most potent cytotoxic agent with no selectivity, similar to doxorubicin. However, the 4-chlorobenzyl analog 3o could be considered as an equipotent compound respect to doxorubicin with higher selectivity.
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http://dx.doi.org/10.1007/s11030-020-10086-2DOI Listing
April 2020

Association between PPARGC1A single nucleotide polymorphisms and increased risk of nonalcoholic fatty liver disease among Iranian patients with type 2 diabetes mellitus

Turk J Med Sci 2019 08 8;49(4):1089-1094. Epub 2019 Aug 8.

Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

Background/aim: Environmental and genetic factors may play a major role in the development of nonalcoholic fatty liver disease (NAFLD) among people with obesity and type 2 diabetes mellitus. Based on the fact that PGC-1α, as the protein encoded by the PPARGC1A gene, plays a key role in energy metabolism pathways, it has been hypothesized that polymorphisms within the PPARGC1Agene may be associated with increased risks of NAFLD. Thus, this study was designed to evaluate the Gly482Ser polymorphism (rs8192678) within the PPARGC1A gene and its association with the increased risk of NAFLD in Iranian patients with type 2 diabetes.

Materials And Methods: A total of 145 NAFLD patients with a history of type 2 diabetes and 145 healthy control subjects were included in the study. Gly482Ser polymorphism genotyping was done using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique.

Results: The results showed a significant difference between the PPARGC1A Gly482Serpolymorphism in NAFLD patients and the healthy controls. Accordingly, the AA genotype and A allele were increased in the NAFLD patients when compared to the healthy controls. However, no significant correlation was observed between the Gly482Ser polymorphism and the physiological and biochemical parameters.

Conclusion: Based on the results, the AA genotype, which is associated with the insertion of Ser, can be considered as a risk factor for the development of NAFLD in Iranian patients with diabetes type 2.
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http://dx.doi.org/10.3906/sag-1808-138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018303PMC
August 2019

Doxorubicin and liposomal doxorubicin induce senescence by enhancing nuclear factor kappa B and mitochondrial membrane potential.

Life Sci 2019 Sep 21;232:116677. Epub 2019 Jul 21.

Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Aims: Senescence is a state ensuing aging to eliminate age-associated damage with an irreversible cell-cycle arrest mechanism, which is historically believed to be one of the tumor responses to therapy. Doxorubicin as an anti-cancer drug has been used in cancer treatment for a long time. Liposomal doxorubicin (Ldox) is a liposomal formulation of doxorubicin, which increases the doxorubicin permanency. The aim of this study was to examine the toxicity of these two formulations by comparing them in terms of their ability to induce cellular senescence.

Main Methods: The study groups included a control group, three DOX (0.75, 0.5, 0.1 mg/kg/BW) and three Ldox groups (0.1, 0.05, 0.025 mg/kg/BW). Heart tissues were studied regarding oxidative stress assessment, mitochondrial function, inflammatory markers and biochemical and histopathological evaluation. Real-Time PCR was used for P53 and SA β-gal expression.

Key Findings: Based on the results, the highest doses of Dox and Ldox (0.75 and 0.1 mg/kg/BW respectively) significantly increased the level of inflammatory markers and according to other factors especially p53 and SA β-gal expression, both were able to induce senescence but the changes in Ldox were less tangible than the Dox.
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http://dx.doi.org/10.1016/j.lfs.2019.116677DOI Listing
September 2019

Protective effect of TSLP and IL-33 cytokines in ulcerative colitis.

Auto Immun Highlights 2019 Mar 14;10(1). Epub 2019 Mar 14.

Gut and Liver Research Center, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran.

Purpose: Inflammatory bowel disease (IBD) primarily includes ulcerative colitis (UC) and Crohn's disease (CD). Thymic stromal lymphopoietin (TSLP) is a cytokine produced by intestinal epithelial cells (IECs) with immunomodulatory properties that plays an important role in the development of regulatory T cell (Treg) responses and tolerance in the gut. On the other hand, IL-33 has been considered as a cytokine with two different properties, inflammatory and anti-inflammatory functions, the latter may play a protective role against chronic intestinal inflammation. In the present study, we investigated the relative gene expression levels of TSLP and IL-33 molecules in ulcerative colitis.

Methods: Patients with clinical symptoms of colitis undergoing a routine diagnostic colonoscopy were included in this study. Biopsy specimens were collected and divided into two parts. One part was fixed and processed for routine histopathological examinations and the other part was stored for RNA extraction. TSLP and IL-33 gene expression were determined using the SYBR Green qRT-PCR.

Results: The expression level of TSLP and IL-33 were significantly lower in UC patients compared with the control group. Moreover, the expressions of these cytokines were more down-regulated in severe UC patients compared with mild and moderate ones and the control group. We also showed a positive correlation between low expression of TSLP and IL-33 and the severity of UC disease.

Conclusions: In this study, we showed decreased mRNA expression levels of TSLP and IL-33 in UC patients and also a negative correlation between expression of TSLP and IL-33 and severity of UC disease.
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http://dx.doi.org/10.1186/s13317-019-0110-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416230PMC
March 2019

Over-Expression of Immunosuppressive Molecules, PD-L1 and PD-L2, in Ulcerative Colitis Patients.

Iran J Immunol 2019 Mar;16(1):62-70

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are the two forms of inflammatory bowel disease (IBD). Adaptive immune responses involving helper T cells play an important role in developing IBDs. Programmed death (PD)-1 and its ligands namely PD-L1 and PD-L2 are negative costimulatory molecules that control T cell motility and formation of an immune synapse between T cells and antigen-presenting cells (APCs).

Objective: To investigate the role of PD-L1 and PD-L2 in patients with UC to clarify the mechanism of IBD development.

Methods: Biopsy specimens were obtained from 50 UC patients and 45 sex- and age-matched control subjects. Total RNA was extracted from all samples and applied for cDNA synthesis. Relative expression of PD-L1 and PD-L2 mRNA was determined using Taqman qRT-PCR.

Results: Relative gene expression levels of both PD-L1 and PD-L2 were higher in UC patients than the control groups (p<0.05 and p<0.01, respectively). Furthermore, both PD-L1 and PD-L2 expressions were positively correlated in all study subjects (r=0.339, p<0.001). However, among the groups with disease severity, the relative gene expression levels of PD-L1 and PD-L2 showed no significant difference.

Conclusions: During IBD, the occurrence of PD-L1 and PD-L2 up-regulation may modulate the chronic inflammation of colonic mucosa.
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http://dx.doi.org/10.22034/IJI.2019.39407DOI Listing
March 2019

Effect of food intake and ambient air pollution exposure on ankylosing spondylitis disease activity.

Adv Rheumatol 2019 02 18;59(1). Epub 2019 Feb 18.

Molecular immunology research center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by axial arthritis. The genetic-environmental factors seem to be involved in the pathogenesis of the disease and the disease debilitates patients during the most productive stages of their lives. The aim of this study was to examine the relationships between two environmental factors, diet and air pollution with disease activity and functional impairment in AS.

Methods: A case-control study was carried out. Thirty patients with AS and 30 age and sex-matched healthy controls were included. Disease scores including BASMI, BASDAI, BASFI, and BASG were calculated by means of the international Ankylosing Spondylitis Assessment working group consensus recommendations. The food intake was evaluated by semi-quantitative food frequency questionnaire (147 items FFQ). Level of air pollution indices, PM10 and PM2.5 information was obtained from the Tehran air quality control network.

Results: Total energy and fat intake, some vitamins (A, B1, B2, C) and mineral intake (potassium, calcium, iron, phosphorus, magnesium, zinc, copper and selenium) were significantly higher in patients with AS compared to controls. Fat component consumption especially Saturated Fat of Food was moderately correlated with BASFI score. PM2.5 long term exposure was strongly correlated with BASMI, BASFI and BASDAI scores of patients.

Conclusion: High-fat diet and long term exposure to air pollution are associated with worse disease outcomes reported in patients with AS. This is an interesting area of investigation in AS pathogenesis and management.
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http://dx.doi.org/10.1186/s42358-019-0051-2DOI Listing
February 2019

Critical limb ischemia: Current and novel therapeutic strategies.

J Cell Physiol 2019 Jan 13. Epub 2019 Jan 13.

School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, SA, Australia.

Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease spectrum and is defined by limb pain or impending limb loss because of compromised blood flow to the affected extremity. Current conventional therapies for CLI include amputation, bypass surgery, endovascular therapy, and pharmacological approaches. Although these conventional therapeutic strategies still remain as the mainstay of treatments for CLI, novel and promising therapeutic approaches such as proangiogenic gene/protein therapies and stem cell-based therapies have emerged to overcome, at least partially, the limitations and disadvantages of current conventional therapeutic approaches. Such novel CLI treatment options may become even more effective when other complementary approaches such as utilizing proper bioscaffolds are used to increase the survival and engraftment of delivered genes and stem cells. Therefore, herein, we address the benefits and disadvantages of current therapeutic strategies for CLI treatment and summarize the novel and promising therapeutic approaches for CLI treatment. Our analyses also suggest that these novel CLI therapeutic strategies show considerable advantages to be used when current conventional methods have failed for CLI treatment.
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http://dx.doi.org/10.1002/jcp.28141DOI Listing
January 2019

Differentiation of Wharton's Jelly Derived Mesenchymal Stem Cells into Insulin Producing Cells.

Int J Hematol Oncol Stem Cell Res 2018 Jul;12(3):220-229

Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Diabetes caused by insulin production disturbance is considered as the most common metabolic disorder all over the world. Diabetes may outbreak because of low insulin secretion by Islets of Langerhans β-cells, insulin resistance or both of them. In this way, using stem cells, which have the capability to differentiate into pancreatic β-cells, is one of novel methods in this field. MSCs are the most important candidates for cellular therapy. Insulin level was examined using ELIZA method. In order to examine the morphology of differentiated cells, they were stained by Dithizone. Insulin-producer cells are cells which turn into red as a result of staining. Specific gene involving insulin-producing cells was evaluated by Real Time-PCR method. The ELISA results showed that the treated cells secreted more insulin than the control group. Moreover, we found differentiation of MSCs toward insulin-secreting cells. In order to evaluate insulin production in clusters on day 21 of differentiation, we used dithizone (DTZ) staining. PDX-1 gene was confirmed by RT- PCR analysis. In this study, we differentiated MSCs into insulin-producing cells in vitro. It is concluded that MSCs may be considered as an excellent candidate in β-cell therapy in diabetes patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305266PMC
July 2018

Adipose-derived stem cells for wound healing.

J Cell Physiol 2019 06 4;234(6):7903-7914. Epub 2018 Dec 4.

School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, South Australia, Australia.

Wound healing is a complex but a fine-tuned biological process in which human skin has the ability to regenerate itself following damage. However, in particular conditions such as deep burn or diabetes the process of wound healing is compromised. Despite investigations on the potency of a wide variety of stem cells for wound healing, adipose-derived stem cells (ASCs) seem to possess the least limitations for clinical applications, and literature showed that ASCs can improve the process of wound healing very likely by promoting angiogenesis and/or vascularisation, modulating immune response, and inducing epithelialization in the wound. In the present review, advantages and disadvantages of various stem cells which can be used for promoting wound healing are discussed. In addition, potential mechanisms of action by which ASCs may accelerate wound healing are summarised. Finally, clinical studies applying ASCs for wound healing and the associated limitations are reviewed.
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http://dx.doi.org/10.1002/jcp.27922DOI Listing
June 2019

Upregulation of Galectin-9 and PD-L1 Immune Checkpoints Molecules in Patients with Chronic Lymphocytic Leukemia

Asian Pac J Cancer Prev 2017 08 27;18(8):2269-2274. Epub 2017 Aug 27.

Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Deviation of host immune response by engagement of inhibitory receptors is one of the well-known mechanisms of tumor cells for immune evasion and survival. PD-1/PD-L1 and Tim-3/Gal-9 axes are two major pathways in this area which their contribution has been documented in a variety of malignancies. In this study, Gal-9 and PD-L1 expression was investigated in leukemic cells from patients with Chronic Lymphocytic Leukemia (CLL). Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 25 untreated CLL patients and 15 sex- and age-matched healthy controls. CLL patients were classified into different clinical stages based on the Rai staging system. Total RNA was extracted from all samples and applied for cDNA synthesis. Relative expression of Gal-9 and PD-L1 mRNA was determined by Real-Time PCR using β-actin as a housekeeping gene. Results: Gal-9 and PD-L1 mRNA was significantly more expressed in CLL patients compared to healthy controls (p<0.0001 and p=0.005, respectively). CLL patients in advanced clinical stages showed higher expression of Gal-9 and PD-L1 in comparison to patients in early clinical stages (p<0.0001 and p=0.004, respectively). Conclusion: Our promising results regarding over-expression of Gal-9 and PD-L1 in CLL patients call future complementary studies to more evaluate and confirm these pathways for immunotherapy approaches of this malignancy. Upregulation of both Gal-9 and PD-L1 in CLL patients with advanced clinical stages introduces them as useful prognostic biomarkers for disease progression.
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http://dx.doi.org/10.22034/APJCP.2017.18.8.2269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697491PMC
August 2017

Effects of moderate treadmill exercise and fluoxetine on behavioural and cognitive deficits, hypothalamic-pituitary-adrenal axis dysfunction and alternations in hippocampal BDNF and mRNA expression of apoptosis - related proteins in a rat model of post-traumatic stress disorder.

Neurobiol Learn Mem 2017 Mar 28;139:165-178. Epub 2017 Jan 28.

Laboratory of Learning and Memory, Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Electronic address:

Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. Currently, selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are the first-line choice in PTSD drug treatment but their moderate response rates and side effects indicate an urgent need for the development of new treatment. Physical activity is known to improve symptoms of certain neuropsychiatric disorders. The present study investigated the effects of moderate treadmill exercise, the antidepressant fluoxetine and the combined treatment on behavioural deficits, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. We also examined alternations in hippocampal brain-derived neurotrophic factor (BDNF) and mRNA expression of apoptosis - related proteins in a rat model of PTSD: the single prolonged stress (SPS) model. Rats were exposed to SPS (restraint for 2h, forced swimming for 20min and ether anaesthesia) and were then kept undisturbed for 14days. After that, SPS rats were subjected to chronic treatment with fluoxetine (10mg/kg/day, for 4weeks), moderate treadmill running (4weeks, 5day per week) and the combined treatment (fluoxetine plus treadmill exercise), followed by behavioural, biochemical and apoptosis markers assessments. SPS rats exhibited increased anxiety levels in the elevated plus maze and light/dark box, impaired fear conditioning and extinction in inhibitory avoidance (IA) task, impaired spatial memory in a recognition location memory task and enhanced negative feedback on the HPA axis following a dexamethasone suppression test. SPS rats also showed reduced hippocampal BDNF and enhanced apoptosis. Moderate treadmill exercise, fluoxetine and the combined treatment alleviated the SPS-induced alterations in terms of anxiety levels, HPA axis inhibition, IA conditioning and extinction, hippocampal BDNF and apoptosis markers. Furthermore, the combined treatment was more effective than fluoxetine alone, but in most tests, the effects of the combined treatment were similar to those of exercise alone, suggesting that exercise is the main factor in the beneficial effects of the combined therapy in PTSD patients.
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http://dx.doi.org/10.1016/j.nlm.2017.01.009DOI Listing
March 2017

A systematic review and meta-analysis of seroprevalence of varicella zoster virus: A nationwide population-based study.

J Clin Virol 2017 02 6;87:49-59. Epub 2016 Dec 6.

SEC Faculty, Penrhyn Road, Kingston University London, Kingston upon Thames, KT1 2EE, UK. Electronic address:

Varicella zoster virus (VZV) causes chicken pox as a primary infection following which it becomes latent in neurons. It may then reactivate to cause shingles (herpes zoster). Severity of lesions and VZV pathogenicity are depended on the host's immune response and variant in VZV Dr Athina Myrto ChioniIdentification of VZV seroprevalance rate in general population may lead to develop new health strategic managements such as vaccination. Therefore, we aimed to provide a systematic review of the seroprevalence of VZV infection among Iranian population and estimate age- and gender- specific prevalence of VZV. Keywords "seroprevalence"; "varicella zoster virus" and "Iran"; were searched in international electronic databases and also in national Persian databases. Twenty two pooled studies among 262 total studies containing (240 published articles; 18 dissertations; and 4 proceedings abstracts) from 1992 to 2014 with total sample size of 7867 individuals were included in the final review. Data was analyzed using random effect method. The heterogeneity was calculated using I-square statistics The overall IgG seroprevalence rate of VZV infection in general population of Iran was 78.50% (95% CI; 77.74%-79.25%). There was significant heterogeneity among the studies (P<0.0001; I=99.4%). Furthermore, the relative risk of VZV infection is high in females (80.47%, 95% CI; 79.40%-81.54%) and older adults (95.30%, 95% CI; 94.11% -96.48%). Our results may represent a true background and estimation of VZV infection in Iran and generate the cost-benefits immunization program. Moreover, the ensuing data suggests further attention on disease seroprevalence in order to obtain efficient data for therapeutic intervention targeted against VZV.
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http://dx.doi.org/10.1016/j.jcv.2016.12.001DOI Listing
February 2017

Hepatitis B Virus Genotypes Distribution with HBsAg Positive in the North of Iran (Mazandaran) During 2011-2014.

Med Arch 2014 Dec 16;68(6):376-80. Epub 2014 Dec 16.

Molecular and Cell-Biology, Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences Sari, Iran.

Background: HBV infection is a major global health problem and ten genotypes (A to J) and multiples subtypes of HBV have been identified, and they show some distinct geographic distributions. The available data on HBV genotype in Iran are very heterogeneous and limited. Therefore in this study, we tried to identify the HBV genotypes by using polymerase chain reaction.

Methods: In this cross-sectional study, HBV- positive serum samples of 122 patients with chronic hepatitis from 2011 to 2014 were studied. HBV-DNA was extracted from plasma samples using QIAamp(®) MiniElute(®) Virus Spin Kit (Qiagen). Plasma samples from HBsAg positive were confirmed the presence of HBV nucleic acid and determined the genotypes of HBV genome by PCR using the DNA PCR kit (Cinagene) with Taq-DNA polymerase enzyme and type of specific primers. All samples were examined in the virology laboratory of Sari Medical School.

Results: The mean age of patients were 45 ± 25 (range, 20 to 70) year that 70 (57.37%) patients were male and 52 (42.62%) were female. The majority of HBV positive patients had a major surgery (44% patients) and then 32% patients followed by intra familial of hepatitis B virus infected and 11% of HBV positive patients had a history of blood transfusions. In this study, 91(74.59%) had genotype D, 7(5.73%) genotype B and 24(19.67%) genotype D and B.

Conclusion: This study indicates that the genotype D is the most frequent followed by the mixed genotypes D and B and genotype B in our region. Prevalence and incidence of HBV genotypes are with distributed among of areas and different genotypes may show different responses with antiviral therapy.
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http://dx.doi.org/10.5455/medarh.2014.68.376-380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314167PMC
December 2014

Toll like receptor-4 896A/G gene variation, a risk factor for migraine headaches.

Iran J Immunol 2012 Sep;9(3):159-67

Neurology Ward, Department of Internal Medicine, Buali Hospital, Sari, Iran, e-mail:

Background: The pathogenesis of migraine involves immune-mediated mechanisms in the vascular endothelium. Toll like receptor 4 (TLR-4) is a signaling receptor of innate immunity which plays a role in various neuropathologies related to neuron inflammation.

Objective: This case/control study is aimed to investigate whether TLR-4 896A/G variation is related to migraine headaches in an Iranian population.

Methods: A total of 170 migraine patients (130 females, mean age 33.24 ± 11 years) and 170 age, sex, and ethnicity matched healthy controls (118 females, mean age of 31 ± 10 years) were recruited. Genotyping was carried out using the tetra primer amplification refractory mutation system (ARMS)-PCR.

Results: The frequency of G allele was higher in migraine patients than the controls (15% vs. 4.7%; p<0.0001). Interestingly, the distribution of heterozygous 896A/G genotype statistically differed between migraineurs and controls (25.3% vs. 8.2%, p=0.00002, OR 3.87, 95% CI; 2.02-7.4). Multivariate logistic regression analysis indicated that G allele in affected female migraineurs is an independent factor associated with increased risk of migraine (OR 3.2, 95% CI 1.23-8.24, p=0.01).

Conclusion: Our results showed TLR-4 polymorphism as a genetic risk factor for migraine. However, further studies in different populations are required to elucidate the precise role of TLR-4 896A/G mutation in susceptibility to migraine.
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http://dx.doi.org/IJIv9i3A2DOI Listing
September 2012

Inducible nitric oxide synthetase genotype and Helicobacter pylori infection affect gastric cancer risk.

World J Gastroenterol 2012 Sep;18(35):4917-24

Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Aim: To investigate the association of the inducible nitric oxide synthetase (iNOS) C150T polymorphism with Helicobacter pylori (H. pylori) infection and gastric cancer (GC) risk in Iran.

Methods: In order to determine whether there was a correlation between iNOS genotype and GC in Iran, we conducted a case-control study using samples from 329 individuals. For each sample, the C150T iNOS polymorphism was genotyped by polymerase chain reaction (PCR) and restriction digestion. Patients were grouped by cancer presence, demographic and behavior characteristics, and H. pylori infection status. Statistical tests were conducted to determine whether any behavioral factors or a particular iNOS genotype was associated with GC in the study population.

Results: In this population, we found that smoking, hot beverage consumption, a familial history of GC and H. pylori infection status were significantly associated with GC development (P = 0.015, P < 0.001, P = 0.0034, and P < 0.015, respectively). The distribution of the C150T iNOS genotypes among the two study groups was not statistically significant alone, but was impacted by H. pylori infection status. When compared to the non-H. pylori infected group, cancer patients who had a heterozygous CT genotype and were also infected with H. pylori were 2.1 times more at risk of developing GC [odds ratio (OR) = 2.1, P = 0.03] while those with a homozygous TT genotype and infected with H. pylori were 5.0 times more at risk of developing GC (OR = 5.0, P = 0.029). In contrast, this association was not seen in patients in the control group.

Conclusion: A CT or TT polymorphism at position 150 in the iNOS gene significantly increases the risk of GC and may be a marker for GC susceptibility.
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http://dx.doi.org/10.3748/wjg.v18.i35.4917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447275PMC
September 2012

The effect of magnesium sulfate on bleeding time and nitric oxide production in preeclamsia.

Pak J Biol Sci 2011 Jan;14(2):106-11

Department of Gynecology and Obstetrics, Imam Khomeini Teaching Hospital, Mazandaran University of Medical Sciences, Sari, Iran.

Unlabelled: Preeclampsia is a disease regarding with altered vascular reactivity leading to hypertension of the mother and metabolic alterations in the fetus. This study aimed to assess nitric oxide and bleeding time following administration of magnesium sulfate to preeclamtic patients compared to normotensive pregnant women. A total of 112 subjects (56 preeclamtic patients and 56 normotensive pregnant controls) were enrolled in this case-control study. Cases and controls were matched for age, BMI, gestational age, parity and gravidity. Total concentration of nitrite and nitrate (NOx) was measured before and during magnesium sulfate (MgSO4) treatment using a modified Griess-based method.

Results: Systolic and diastolic blood pressures were significantly decreased during MgSO4 treatment in preeclamtic patients (p < 0.0001). NOx levels were significantly increased in preeclamtic women after MgSO4 administration (33.7 +/- 18.5 vs. 50.2 +/- 21.6, p < 0.0001) but it was not seen in normotensive parturients (52.4 +/- 28.9 vs. 57.3 +/- 21.7, p = 0.362). The bleeding time was scarcely increased following magnesium sulfate treatment in preeclamptic patients compared to normotensive pregnant women but it was not significant (p = 0.18). In addition, there was only a significantly reverse correlation between NOx levels and systolic or diastolic blood pressure in preeclamtic parturients after MgSO4 treatment (r = -0384; p = 0.003 and r = -0.29; p = 0.03, respectively). This study demonstrates that administrating MgSO4 to preeclamtic patients induced significant changes in NOx production which had a major role in modulating vasculature changes in preeclamsia.
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http://dx.doi.org/10.3923/pjbs.2011.106.111DOI Listing
January 2011