فهرست مطالب

  • Volume:9 Issue: 1, 2020
  • تاریخ انتشار: 1399/05/22
  • تعداد عناوین: 15
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  • Mona Djalali, Mahmoud Djalali, Mina Abdolahi, Hamed Mohammadi, Hajar Heidari, Shayesteh Hosseini, Majid Sadeghizadeh* Pages 1-7
    Background

    This study was designed to investigate the effect of nano-curcumin supplementation on pentraxin 3 (PTX3) gene expression and serum level in migraine patients.

    Methods

    The present study, performed as a clinical trial, included 38 episodic migraine patients in two groups that received either nano-curcumin or placebo over a two-month period. At the start and the end of the study, PTX3 gene expression and serum levels were measured.

    Results

    After two months of treatment, PTX3 gene expression and serum levels were both significantly less in the nano-curcumin than in the placebo group (P= 0.01 and P< 0.001, respectively). No significant gene expression differences were found between the two groups.

    Conclusions

    Curcumin may have a potential inhibitory effect on PTX3 gene expression and serum levels in migraine disease and can be considered as an efficient therapy in migraine management.

    Keywords: Clinical trial, Curcumin, Inflammation, Migraine, Pentraxin 3
  • Seyyed Shahram Miraghaee, Maryam Sohrabi, Cyrus Jalili, Fariborz Bahrehmand* Pages 8-13
    Background

    Glutathione S-transferases (GSTs) protect cells from oxidative stress (OS). In humans, the GST omega class contains two expressed genes, GSTO1 and GSTO2. Because OS is involved in the pathogenesis of polycystic ovary syndrome (PCOS), the aim of this study was to investigate the relationship between GSTO1 A140D (rs4925) and GSTO2 N142D (rs156697) polymorphisms in PCOS patients.

    Methods

    175 PCOS patients and 161 healthy controls were selected among women in Kermanshah province, Iran. GSTO1 and GSTO2 were genotyped using allele-specific PCR (AS-PCR) and PCR-RFLP, respectively.

    Results

    For GSTO1, the DD genotype and the D allele led to 2.17- (P= 0.02) and 1.5-fold (P= 0.01) increases, respectively, in the odds ratios for PCOS. No significant difference was found between control and patient groups for the GSTO2 N142D genotype or allele frequency. GSTO1 and GSTO2 genotype interaction analysis showed that individuals with the GSTO1 AD or DD genotypes and the GSTO2 NN or DN genotypes had a 1.53-fold (P= 0.007) increase in PCOS risk over GSTO1 AA and GSTO2 DD individuals.

    Conclusions

    The GSTO1 A140D polymorphism is a risk factor for PCOS.

    Keywords: Gene polymorphism, GSTO1, GSTO2, Oxidative stress, PCOS
  • Behrouz Etesami, Sara Ghaseminezhad, Azin Nowrouzi*, Marzieh Rashidipour, Razieh Yazdanparast Pages 14-25
    Background

    Obesity, often associated with insulin resistance and type 2 diabetes, is a metabolic disease that can result in dyslipidemia and hyperglycemia. Many reports describe the hypoglycemic and hypolipidemic properties of the Phoenix dactylifera L. seed extract in STZ-induced diabetic rat models, however, its anti-diabetic effects in other diabetic models are less characterized in the literature. This study set out to determine the possible effects of the Phoenix dactylifera L. seed extract on adipogenesis and glucose homeostasis.

    Methods

    3T3-L1 cells were cultured in adipocyte differentiation media with or without varying doses of Phoenix dactylifera L. extract (0.312-1 mg/ml). Assays were performed on days 5, 8, and 12 after induced differentiation.

    Results

    Our results demonstrate that the triglyceride content in treated groups was significantly lower compared to controls. Further, treating 3T3-L1 cells with Phoenix dactylifera L. seed extract reduced adipogenesis through the downregulation of PPAR-γ and CEBP-α, and adipocyte-specific genes involved in fatty acid metabolism including ap2, ACACA, and FAS.

    Conclusions

    Phoenix dactylifera L. seeds have the potential to inhibit adipogenesis and obesity. Overall, this study explored the inhibitory effects of Phoenix dactylifera L. seed extract on adipogenesis in 3T3-L1 cells on the molecular level.

    Keywords: Adipocyte Differentiation, Adipogenesis, Glucose Homeostasis, Obesity, Phoenix Dactylifera Seed, 3T3-L1 Cell
  • Ahmad Lotfi Garavand, Mohammad Mohammadi, Sara Mohammadzadeh* Pages 26-32
    Background

    The tumor suppressing protein p53 and its downstream effector p21 play important roles in cell cycle regulation. Deficiency or deactivation of these proteins as a result of gene alterations has been indicated in several cancers. Such genetic variations could be considered as susceptibility indicators in acute lymphocytic leukemia (ALL). Therefore, we investigated the associations between ALL risk and TP53 codon 72, p21 codon 31, and MDM2 SNP309 polymorphisms in an Iranian population.

    Methods

    Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the MDM2 T309G (rs2279744), TP53 codon Arg72Pro (rs1042522), and p21 Ser31Arg (rs1801270) single nucleotide polymorphisms (SNPs). This study was performed in 115 ALL patients and 115 healthy controls in Khuzestan province in southwest Iran.

    Results

    In the control group and ALL patients, p21 Ser/Arg, and MDM2 TG and GG genotypes were associated with significant 1.81-fold (95% confidence interval CI= 1.008-3.267; P ˂ 0.05), 11.07-fold (95% CI= 5.10-24.05; P < 0.0001), and 19.41-fold (95% CI= 8.56-43.99; P < 0.0001) increased risks for ALL, respectively. The TP53 72 Arg allele was significantly more prevalent in ALL patients (56.96%) than in control subjects (47.39%), and was significantly associated with ALL (OR= 1.47; 95% CI = 1.017-2.121, P < 0.05).

    Conclusions

    The MDM2 T309G and the p21 Ser31Arg SNPs indicate a significantly increased risk for developing ALL in Khuzestan province.

    Keywords: Acute lymphocytic leukemia, Khuzestan, MDM2, TP53, p21
  • Zahra Taheri, Hamid Asadzadeh Aghdaei, Shiva Irani*, MohammadHossein Modarressi, Zahra Noormohammadi Pages 33-39
    Background

    Epigenetic changes in CpG islands of the promoter regions of homeostasis-related genes, including nuclear factor erythroid 2-related factor 2 (NRF2), have been shown to hold a significant role in the development of colorectal cancer. Therefore, we aimed to examine the DNA demethylation pattern of the NRF2 promoter region in cancerous lesions from patients with colorectal cancer and the association of methylation status with clinicopathological features in the Iranian population.

    Methods

    In this cross-sectional study, 114 colorectal tissue samples were collected. These samples included: 34 tumour tissue samples, 60 precancerous polyps, and 20 normal tissue samples. The promoter methylation status of the NRF2 gene was examined using methylation-specific PCR. Additionally, the relationship between the methylation status and the clinicopathological features was investigated.

    Results

    The frequency of NRF2 demethylation in the tumour samples was significantly higher compared to the polyp tissues (p= 0.003) and normal tissue (p= 0.009), indicating that cancerous colorectal tissues exhibit increased demethylation of the NRF2 promoter. After examining the demethylation status of tissue samples, the clinicopathological features were compared to the demethylation results. No significant association was found between NRF2 promoter demethylation and the clinicopathological features of patient samples.

    Conclusions

    Our findings suggest that the epigenetic modifications leading to NRF2 demethylation found in colorectal tumour samples may contribute to cancer progression from precancerous polyps to cancerous lesions.

    Keywords: Colorectal Cancer, Epigenetic, Methylation-specific PCR, NRF2
  • Maryam Rahimi, Farkhondeh Behjati, HamidReza Khorram Khorshid, Masoud Karimlou, Elahe Keyhani* Pages 40-49
    Background

    KIT is a protooncogene that encodes for the KIT oncoprotein, which is a transmembrane tyrosine kinase growth factor receptor that holds a critical role in a variety of normal physiological and pathological processes including angiogenesis. KIT has been shown to be involved in tumorigenesis, contributing to the development of gastrointestinal carcinoma and leukemia. A link between KIT overexpression and breast cancer development has previously been reported. In the current study, we explored KIT gene expression and exonic copy number variants (CNV) and the relationship with angiogenesis (CD34) and the clinicopathological features of breast cancer.

    Methods

    MLPA technique was used to determine the CNV in 64 breast cancer tumor samples from patients diagnosed with primary sporadic breast cancer. Results were confirmed by quantitative PCR. Expression of KIT and CD34 was determined using immunohistochemistry (IHC).

    Results

    Our results show that 28.1% of the tumor samples from patients with primary sporadic breast cancer had CNV in the KIT gene. Among the breast tumor samples, 54.7% showed positive KIT expression. The expression of the CD34 angiogenesis marker was reported in 43.8% of the tumor samples as low, 42.2% as moderate and 14.1% as high. A significant correlation between increased CNV of KIT exons, a high level of angiogenesis (CD34) and increased tumor grade was observed (p< 0.05).

    Conclusions

    A significant correlation between the KIT CNV and the angiogenesis marker was found. Examining KIT expression and CNV has the potential to function as a biomarker for tyrosine kinase inhibitor drugs in breast cancer.

    Keywords: Angiogenesis, Breast Cancer, CD34, KIT
  • Mina Bahrololoumi Shapourabadi, Farzin Roohvand, Arash Arashkia, Nasir Mohajel, Shahriyar Abdoli, Zahra Shahosseini, Frank Momburg, Mostafa Jarahian, Mohsen Abolhassani, Kayhan Azadmanesh* Pages 50-57
    Background

    Immunotherapy of cancer by bispecific antibodies (bsAb) is an attractive approach for retargeting immune effector cells including natural killer (NK) cells to the tumor if the proper expression and purification of the bsAb for such applications could be addressed. Herein, we describe E. coli expression of a recombinant bsAb (bsHN-CD16) recognizing NK-CD16 and hemagglutinin neuraminidase (HN) of Newcastle Disease Virus (NDV). This bsAb might be efficient for ex vivo stimulation of NK cells via coupling to HN on the surface of the NDV-infected tumor cells.

    Methods

    A bsAb-encoding pcDNA3.1 vector (anti-HN scFv-Fc-anti-CD16 scFv) was used as a template, and the scFv segments (after enzymatic digestion and cutting of the Fc part) were rejoined to construct the Fc-deprived bsAb (anti-HN scFv-anti-CD16 scFv; bsHN-CD16). The constructed bsHN-CD16 was inserted into the HindIII and BamHI site of the T7 promoter-based pET28a plasmid. Following restriction analyses and DNA sequencing to confirm the cloning steps, bsHN-CD16 encoding pET28a was transformed into the E. coli (Rosetta DE3 strain), induced for protein expression by IPTG, and the protein was purified under native condition by Ni/NTA column using imidazole.

    Results

    Analyses by SDS-PAGE and Western Blotting using Rabbit anti-human whole IgG-HRP conjugate, confirmed the expression and purification of the bsAb with the expected full size of 55 kDa and yields around 8% of the total protein.

    Conclusions

    Results showed efficient production of the bsAb in E. coli for future large-scale purification.

    Keywords: Bispecific Antibody, Escherichia Coli, Immunotherapy, Natural Killer Cell (NK Cell), Newcastle Disease Virus (NDV)
  • Farbod Yaghoubi Hariri, Iman Salahshourifar*, Shohreh Zare Karizi Pages 58-63
    Background

    Coronary arteries disease (CAD) has been recognized as one of the most common causes of death worldwide, with an estimated seven million deaths annually.

    Methods

    Two hundred blood samples from Iranian CAD patients and normal healthy controls were collected. CAD and the 9p21 locus variants rs1333049 and rs10757278 were analyzed for potential associations.

    Results

    No significant differences in rs10757278 and rs1333049 polymorphisms were found between patients and controls, but a significant relationship was found between rs10757278 and rs1333049 in CAD patients at the genotype level (p= 0.0323). At the haplotype level and on the basis of diplotype analysis, a significant relationship was found between patients and controls (OR= 5.16, p= 0.047, 95% CI: 1.02-26.0). In CAD patients, rs10757278 and rs1333049 were associated at locus 9p21.

    Conclusions

    The inconsistency between the results of this and other studies on different CAD populations may be due to high population, different ethnicities, low prevalence of some alleles in populations, and interactions of different genes.

    Keywords: rs1333049, rs10757278, 9p21, Coronary artery disease (CAD), Tetra ARMS
  • Fatemeh Sadabadi, Aida Gholoobi, Alireza Heidari Bakavol, Mohsen Mouhebati, Ali Javandoost, Zahra Asadi, Maryam Saberi Karimian, Susan Darroudi, MohammadSadegh Khorrami Mohebbseraj, Farzad Rahmani, Najmeh Malekzadeh Gonabadi, Fatemehalsadat Jafari Sheshtamad, Sara Samadi, Afsane Bahrami, Gordon Ferns, Majid Ghayour Mobarhan, Habibollah Esmaeili* Pages 64-70
    Background

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally, and specifically in Iran. Generally, diabetes mellitus is the result of impaired glucose tolerance which together with dyslipidemia are considered as important risk factors of CVD. The aim of this study was to determine the relationship between fasting serum glucose (FSG), lipid profile and CVD endpoints, and to establish an optimal FSG cut-off in the MASHAD cohort study after nearly 6 years of follow-up.

    Methods

    All the participants of MASHAD study were followed up for 6 years to determine their cardiovascular status. FSG, fasting lipids, and physical examinations were all recorded. To identify the optimal cut- off point of FSG, we carried out receiver operating curve (ROC) analysis

    Results

    We determined MASHAD cutoff point of blood glucose as 90 mg/dl predicting the CVD outcome. The sensitivity and specificity of the FSG criterion were 54.34% and 71.68%, respectively. The AUC was 0.665 (95% CI 0.656-0.675, P< 0.0001). The adjusted hazard ratio show that FSG is associated with 2.34 increase in CVD risk using MASHAD cutoff point (HR 2.34, 95% 1.73–3.17, P< 0.001).

    Conclusions

    These findings suggest that not only FSG and lipid profile are related to CVD outcome in the MASHAD study, but also elevated fasting glucose levels is strongly associated with cardiovascular events in this population. Besides, the fasting glucose at a threshold of 90 mg/dl can be used for screening cardiovascular events among the Iranian population.

    Keywords: Fasting Serum Glucose, Lipid profile, Cardiovascular disease (CVD), MASHAD cohort study
  • Seyed Mohammad Masoodian, Karamollah Toolabi, Abolfazl Omidifar, Hossein Zabihi, Ali Rahimipour, Mehrnoosh Shanaki* Pages 71-81
    Background

    Obesity, a medical condition with impaired adipokine secretion and function, has a detrimental effect on insulin and glucose metabolism. CTRP3 and CTRP9 are adipokines with possible roles in energy homeostasis regulation. We sought to compare CTRP3, CTRP9, and inflammatory gene expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery and non-obese women as controls.

    Methods

    For this study, the investigators recruited 20 morbidly obese women (BMI> 35) who qualified for bariatric surgery and 20 normal-weight women (BMI< 25) who underwent elective surgeries. Real-time PCR was performed to investigate mRNA expression of CTRP3, CTRP9, and the inflammatory genes IL1-β, IL-6, MCP-1, and TNF-α in SAT and VAT from both obese patients and controls.

    Results

    We observed that CTRP3 mRNA levels were significantly greater in VAT from obese patients than from controls (P< 0.0003). Also, patient group had higher levels of CTRP9 that control group (P< 0.0026). Inflammatory cytokines were markedly increased in SAT of obese patients compared to controls (P< 0.05). In addition, our results revealed a positive correlation of CTRP9 with HOMA-IR and waist circumference in VAT and CTRP3 with IL-1β, MCP-1, and TNF-α in SAT.

    Conclusions

    Both CTRP3 and CTRP9 expression were significantly higher in VAT from obese patients than from controls, and CTRP3 expression positively correlated with inflammatory parameters. Our findings indicate that CTRP3 and CTRP9 might be important in regulating glucose metabolism and obesity-related conditions such as inflammation.

    Keywords: Adipokine, CTRP3, CTRP9, Obesity, Obese women
  • Elham Samadi, Hessam Mirshahabi*, Nima Motamed, Hamid Sadeghi Pages 82-88
    Background

    Occult hepatitis B infection (OBI) is defined as the lack of detectable HBsAg in serum, despite the presence of intrahepatic viral DNA, and low levels of covalently closed circular DNA (cccDNA). Since the hemodialysis patients are at a greater disadvantage if they are a carrier of Hep B, as it can lead to OBI this study was designed to determine the prevalence of OBI in hemodialysis patients residing in Zanjan, Iran.

    Methods

    We conducted an anti-HBc test (ELISA) on 166 HBsAg negative hemodialysis patient samples. OBI was evaluated using seropositive (anti-HBc and/or anti-HBs) and seronegative (anti-HBc and anti-HBs) using nested PCR.

    Results

    Out of the total hemodialysis patients sampled, the study consisted of 58.4% male and 41.6% female participants. The age of the study group ranged from 58.89±15.49, and had received approximately 28.27±27.43 years of dialysis. Additionally, 5.4% of patients had a history of blood transfusions, while 58.4% were vaccinated against the hepatitis B virus (HBV). Moreover, 23.5% patients were anti-HBc positive, while 76.5% patients tested negative. Lastly, 66.3% of the patients were positive for anti-HBs, whereas 33.7% were negative for anti-HBs. Overall, the study revealed that the prevalence of OBI was 6%, and HBV DNA was detected in 2.1% of individuals who were vaccinated against hepatitis B (p < 0.01).

    Conclusions

    Though no significant difference between the prevalence of OBI to the patients’ age, sex, duration of dialysis, or history of blood transfusion was identified, however, a strong correlation between the prevalence of OBI to HBV vaccination was found.

    Keywords: ELISA, Hemodialysis, Nested PCR, Occult hepatitis B infection
  • Kamelia Banihashemi, Behnam Sobouti, Iraj Mehregan, Ronak Bakhtiari, Nour Amirmozafari* Pages 89-96
    Background

    Pseudomonas aeruginosa is an opportunistic human pathogen that causes severe acute and chronic nosocomial infections, especially in immunocompromised burn patients. and can lead to severe mortality and morbidity. The emergence of antibiotic resistant P. aeruginosa infections has created significant challenges in treating these patients. A potential alternative treatment for antibiotic resistant pathogens includes the use of carbon nanotubes (CNTs), which have received considerable attention due to their potent antibacterial activity. The aim of this study was to construct a novel CNT containing an anti-bacterial chemical component to effectively combat drug resistant P. aeruginosa infections.

    Methods

    In this study, a novel chemical component was synthesized and coated the CNT. The antimicrobial effects were then evaluated on MDR, XDR, and PDR strains of P. aeruginosa isolated from burn patients. Antibiotic susceptibility was evaluated using the disk diffusion test and minimum inhibitory concentration (MIC) testing. In order to determine the potential cytotoxicity, an MTT assay was performed on Human Dermal Fibroblasts. The effect of treatment on the expression of wound healing genes was analyzed via qRT-PCR.

    Results

    Experimental data indicates that our CNT coated chemical compound had antibacterial properties, negligible cytotoxicity, and could accelerate the wound healing process.

    Conclusions

    Given the antibacterial properties of our CNT chemical compound, it has the potential to treat and reduce the occurrence of multi-drug resistant P. aeruginosa burn wound infections and aid in wound healing by turning on genes (VEGFA, EGF and PDEGF) involved in the wound healing process.

    Keywords: Anti-Bacterial drugs, Drug resistance, Nanotubes Carbon, Pseudomonas aeruginosa, MDR, XDR
  • Gomaa Mostafa Hedeab* Pages 97-105
    Background

    Since its first appearance in December of 2019, regular updates around the world demonstrates that the number of new Corona Virus 2019 (COVID-19) cases are increasing rapidly, indicating that not only does COVID-19 exhibit a rapid spread pattern, but human intervention is necessary for its resolution. Up until today (27-5-2020) and according to the World Health Organization (WHO), the number of confirmed COVID-19 cases has surpassed 4.5 million with more than 307, 500 deaths. Almost all countries have been affected by COVID-19, and resultingly, various drug trials have been conducted, however, a targeted treatment remains to be made accessible to the public. Recently, Angiotensin-Converting Enzyme-2 (ACE2) has gained some attention for its discovery as a potential attachment target of COVID-19.

    Methods

    We reviewed the most recent evidence regarding ACE2 distribution and action, the binding mechanism of COVID-19 and its correlation to cellular injury, ACE2 polymorphisms and its association to fatal COVID-19 and susceptibility and, finally, current ACE2-based pharmacotherapies against COVID-19.

    Results

    Blocking the ACE2 receptor-binding domain (RBD) using a specific ligand can prevent COVID-19 from binding, and consequently cellular entry and injury. Comparatively, soluble ACE2, which has a higher affinity to COVID-19, can neutralize COVID-19 without affecting the homeostatic function of naturally occurring ACE2. Lastly, ACE2 mutations and their possible effect on the binding activity of COVID-19 may enable researchers to identify high-risk groups before they become exposed to COVID-19.

    Conclusions

    ACE2 represents a promising target to attenuate or prevent COVID-19 associated cellular injury.

    Keywords: ACE, ACE2, COVID-19
  • Nazila Ariaee, Mojtaba Sankian, Abdolreza Varasteh, Malihe Moghadam, Farahzad Jabbari* Pages 106-114
    Background

    Sensitization to common mold allergens is one of the major causes of allergic rhinitis and asthma. Therefore, there is a critical need for standard sensitivity tests including skin prick tests to improve the stability of fungi extracts in traditional allergenic formulations. To address this concern, the present study aimed to develop a formulation to preserve allergenic activity of mold extracts.

    Methods

    48 stabilizer formulations were designed and monitored for allergenic activity during a 40-days incubation period at 37 ˚C using an ELISA. Specifically, the IgE reactivity of allergenic A. alternata extracts were examined. After establishing the most effective stabilizer formulation, we evaluated whether it could protect the allergenic activity of Alt a1, A. fumigatus, and C. herbarum using an IgE inhibition ELISA after 40 days at 37 ˚C.

    Results

    We demonstrated that the most effective stabilizer formulation was a glycerol-based extract containing Arg and Glu. This formulation had an equal ratio of sucrose, sorbitol and protein and was able to preserve more than 95% of allergenic A. alternata extract activity during a 40-days incubation period at 37 ˚C.

    Conclusions

    The present study reveals a novel formulation that is an efficient stabilizer of allergenic mold extract activity and has practical applications in mold skin prick tests, ELISAs, immunotherapies, and RAST.

    Keywords: Allergy, Allergic Rhinitis, Mold, Stabilization, Skin Prick test
  • Maysa Ahmed Mobasher*, Hala Galal El Tantawi, Karim Samy El Said Pages 115-128
    Background

    Several studies have found an association between Diabetes mellitus (DM) and an increased risk for hepatocellular carcinoma (HCC). Evidence suggests that Metformin (Met) may have a therapeutic and protective effect against both DM and HCC. Therefore, the aim of this study was to evaluate the antioxidant effect of Met against DM and HCC-induced oxidative stress in rat model.

    Methods

    Forty-two male albino rats were randomly divided into six groups. Group 1 (Gp1) was the control group, Gp2 received an intraperitoneal (i.p.) injection with streptozotocin (STZ), Gp3 was injected i.p. with diethyl nitrosamine (DEN), Gp4 received an oral administration of Met, Gp5 and Gp6 received the same injections as Gp2 and Gp3, respectively, then received an additional injection of Met. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA), were examined. Furthermore, biochemical parameters including liver function tests were assessed. Histopathological and immunohistochemical alterations of the liver were also examined.

    Results

    Our results demonstrate that Gp2 and Gp3 had significant signs of liver dysfunction and had elevated levels of MDA and reduced levels of SOD, CAT, and GSH. Additionally, Gp2 and Gp3 showed significant alterations in the liver architecture shown by high PCNA and caspase-3 expression. In the Gp5 and Gp6, treatment with Met showed an improvement in liver function, oxidative stress biomarkers, and reduced histopathological changes in hepatocytes.

    Conclusions

    This study offers insight into the potential for Metformin as a novel therapeutic against the oxidative stress induced by DM or HCC.

    Keywords: Diabetes Mellitus, Diethyl nitrosamine, Hepatocellular Carcinoma, Metformin, Streptozotocin