Publications by authors named "Durdi Qujeq"

59 Publications

Signaling, metabolism, and cancer: An important relationship for therapeutic intervention.

J Cell Physiol 2021 Feb 12. Epub 2021 Feb 12.

Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

In cancerous cells, significant changes occur in the activity of signaling pathways affecting a wide range of cellular activities ranging from growth and proliferation to apoptosis, invasiveness, and metastasis. Extensive changes also happen with respect to the metabolism of a cancerous cell encompassing a wide range of functions that include: nutrient acquisition, biosynthesis of macromolecules, and energy generation. These changes are important and some therapeutic approaches for treating cancers have focused on targeting the metabolism of cancerous cells. Oncogenes and tumor suppressor genes have a significant effect on the metabolism of cells. There appears to be a close interaction between metabolism and the signaling pathways in a cancerous cell, in which the interaction provides the metabolic needs of a cancerous cell for uncontrolled proliferation, resistance to apoptosis, and metastasis. In this review, we have reviewed the latest findings in this regard and briefly review the most recent research findings regarding targeting the metabolism of cancer cells as a therapeutic approach for treatment of cancer.
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http://dx.doi.org/10.1002/jcp.30276DOI Listing
February 2021

Association between serum folate with inflammatory markers, disease clinical activity and serum homocysteine in patients with inflammatory bowel disease. Does folate level have an effect on maintaining clinical remission?

Acta Biomed 2020 11 10;91(4):e2020106. Epub 2020 Nov 10.

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Background Folate is an important vitamin with protective effect against some human diseases. The aim of this study was to evaluate the relationship between serum folate levels, inflammatory markers and disease clinical activity in patients with inflammatory bowel disease (IBD).   Methods The participants were classified into two groups in which 38 IBD patients and 38 healthy controls were studied. Disease clinical activities were evaluated by means of established score systems. Serum folate, homocysteine and C-reactive protein and ESR were measured. Obtained data were analyzed with proper statistical methods and P- value less than 0.05 was considered as statistical significant.   Results The level of serum folate was significantly reduced in IBD patients with active disease compared to patients with clinical remission (p=0.043) and also healthy controls (p = 0.008). Moreover, there was a significant inverse correlation between serum folate levels and C-reactive protein in IBD patients (r = -0.563 p =0.001).         Conclusion Serum folate levels is associated with inflammatory markers and disease clinical activity in IBD patients, therefore there is a possibility that disease clinical activity is reduced with adequate folate level.
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http://dx.doi.org/10.23750/abm.v91i4.8467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927538PMC
November 2020

Evaluation of MASP1, CMPF and U.A serum levels in pre-diabetic subjects in comparison to Normal individuals for early diagnosis of subjects with pre-diabetes, a case-control study.

J Diabetes Metab Disord 2020 Dec 21;19(2):1593-1598. Epub 2020 Nov 21.

Department of Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran.

Background: The present study designed to evaluate the Serum levels of CMPF, MASP1 and UA in pre-diabetic subjects was compared to normal subjects

Methods: This research is a case-control study. We studied 44 pre-diabetics with 44 normal subjects and were evaluated serum concentration of CMPF, Masp1 and U.Ain both groups andfurthermore serum concentration FPG, BUN, Cr, Cho, TG, HDLc, LDLc, AST, ALT, ALP, HbA1c was examined and correlation between of CMPF, Masp1 and U.Aand other parameters was statistically analyzed.

Results: Serum levels of MASP1, CMPF, fasting plasma glucose ( < 0.001)and uric acid ( < 0.002) were significantly increased in pre-diabetic subjects. In this study, a significant difference was found between MASP1 and CMPF in pre-diabetic subjects compared to normal subjects (P=0.005, r=0.291). There was also a significant difference between serum levels of MASP1 with HbA1C (P=0.01, r=0.269).

Conclusion: Serum levels of CMPF, MASP1 and uric acid were increased in pre-diabetic subjects. These parameters can be used as a biomarker for the diagnosis of pre-diabetes.
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http://dx.doi.org/10.1007/s40200-020-00697-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843784PMC
December 2020

Sensitivity and specificity of mean platelet volume as a laboratory marker for irritable bowel syndrome: Can it be added to Rome criteria?

Afr J Lab Med 2020 21;9(1):1001. Epub 2020 Dec 21.

Department of Biostatistics and Epidemiology, Babol University of Medical Sciences, Babol, Iran.

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder.

Objective: This study aimed to evaluate red blood cell distribution width (RDW) and mean platelet volume (MPV) as laboratory markers to discriminate IBS patients from both healthy controls and patients with inflammatory bowel disease (IBD).

Methods: This case-control study enrolled patients referred to Ayatollah Rouhani Hospital, Endoscopy Department, Babol, Iran, for colonoscopy examination from 2015 to 2017. Fifty IBS patients were selected from among patients who had undergone a normal colonoscopy and showed symptoms matching the Rome III criteria. Fifty healthy participants and 50 IBD patients, matched for sex and age, were also enrolled in this study. Both RDW and MPV were measured and analysed by independent sample -test and receiver operating characteristic curve analysis. A -value of less than 0.05 was considered statistically significant.

Results: While RDW was higher and MPV was lower among IBS patients compared to healthy controls ( = 0.047 and = 0.001), there were no significant differences in RDW or MPV levels between IBS and IBD patients. The area under the curve of RDW in the discrimination between IBS and IBD was 0.620 ( = 0.039), and the area under the curve of MPV in the discrimination between healthy controls and IBS patients was 0.801 ( = 0.001).

Conclusion: Mean platelet volume is potentially a useful laboratory marker for distinguishing between IBS patients and healthy individuals. Red blood cell distribution width should be considered as a potential marker to distinguish among IBS and IBD patients.
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http://dx.doi.org/10.4102/ajlm.v9i1.1001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756523PMC
December 2020

Melatonin and doxorubicin co-delivered via a functionalized graphene-dendrimeric system enhances apoptosis of osteosarcoma cells.

Mater Sci Eng C Mater Biol Appl 2021 Feb 6;119:111554. Epub 2020 Oct 6.

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran. Electronic address:

A functionalized graphene-dendrimeric system was designed via FeO nanoparticle (NP) as a magnetic nanocarrier for co-delivery of doxorubicin (DOX) and melatonin (MLT). Accordingly, β-Cyclodextrin (β-CD) was modified by creating amine functional groups. The modified β-CD was grafted with Graphene oxide (GO), and the resulting platform gain many functional groups, including the hydroxyl (-OH), carboxylic acid (-COOH), and amine functional groups (-NH2). Finally, magnetic NPs were synthesized on the prepared platform to efficiently controlling and targeting drugs to tumor sites. The human osteosarcoma cell lines including Saos-2 and MG-63, as well as Human Bone Marrow Mesenchymal Stem Cells (hBM-MSC) line, were used to determine the in vitro biological effects of the functionalized graphene-dendrimeric system. The magnetic nanocarrier has encapsulation efficiency (EE) values of 99.92% for DOX and 21.5% for MLT. The biocompatibility tests of the nanocarrier revealed that the magnetic nanocarrier was appropriate as a drug carrier. Co-delivery of DOX and MLT with an efficiently anticancer performance was also was confirmed by cellular uptake, 4',6-diamidino-2-phenylindole (DAPI) staining, and apoptosis analysis in comparison with free DOX and MLT. Moreover, there was a synergy in the antitumor effect when MLT was combined with DOX, especially in the nano-formulation form, which may be due to the down-regulation of X-linked Inhibitor of Apoptosis (XIAP), survivin, and human telomerase catalytic subunit (hTERT) (p < 0.0001). Overall, the result of our study suggests that the designed carrier is a promising nanocarrier for targeted co-delivery of DOX and MLT with improved anticancer efficacy in cancer cells and thus reduced toxicity in normal cells.
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http://dx.doi.org/10.1016/j.msec.2020.111554DOI Listing
February 2021

Assessment of mucin and alpha-amylase levels in gingival crevicular fluid of chronic periodontitis patients.

Oral Dis 2020 Nov 30. Epub 2020 Nov 30.

Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

Background: Chronic periodontitis is the most common form of periodontitis. Several immune and inflammatory factors responsible for periodontal destruction have been found in gingival crevicular fluid (GCF). The current study was conducted to determine the correlation between mucin and alpha-amylase protein values in GCF with chronic periodontitis.

Method: Forty-five patients with moderate-to-severe chronic periodontitis were selected. Samples of GCF were taken from a specific part of a single root tooth and placed in a closed test tube containing phosphate-buffered saline (PBS) (pH = 7). Sampling was done again after one month. Pre- and post-treatment samples were analyzed for measuring the levels of mucin and alpha-amylase proteins.

Results: Paired t test results for these two variables showed that the difference between mucin and alpha-amylase levels before and after treatment is significant.

Conclusion: The level of both mucin and alpha-amylase in GCF in patients with chronic periodontitis was higher than that of patients who have recovered successfully; and evaluating the values of these two markers could be used to determine the activity of the periodontal disease.
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http://dx.doi.org/10.1111/odi.13740DOI Listing
November 2020

NORAD, a critical long non-coding RNA in human cancers.

Life Sci 2021 Jan 27;264:118665. Epub 2020 Oct 27.

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran. Electronic address:

The of cancer is growing worldwide, and it is becoming the most common cause of death. Long non-coding RNAs (lncRNAs) are a group of RNA transcripts with a length larger than 200 nucleotides that cannot encode proteins or peptides. LncRNAs regulate different biological functions by controlling gene expressions at transcriptional, translational, and post-translational levels. Non-coding RNA activated by DNA damage (NORAD) is a highly conserved lncRNA necessary for genome stability. LncRNA NORAD is dysregulated in various types of cancers. This biomarker has been involved in numerous processes associated with carcinogeneses, such as cell proliferation, apoptosis, invasion, and metastasis. In this paper, we reviewed the role of lncRNA NORAD and its biological functions in various human cancers to provide future research insights.
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http://dx.doi.org/10.1016/j.lfs.2020.118665DOI Listing
January 2021

Zinc and Selenium in Inflammatory Bowel Disease: Trace Elements with Key Roles?

Biol Trace Elem Res 2020 Oct 23. Epub 2020 Oct 23.

Biotechnology Research Center, Tabriz University of Medical Sciences, P.O. Box 14711, Tabriz, 5166614711, Iran.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that may emerge at a young age and often lasts for life. It often goes through phases of recurrence and remission and has a devastating effect on quality of life. The exact etiology of the disease is still unclear, but it appears that an inappropriate immune response to intestinal flora bacteria in people with a genetic predisposition may cause the disease. Managing inflammatory bowel disease is still a serious challenge. Oxidative stress and free radicals appear to be involved in the pathogenesis of this disease, and a number of studies have suggested the use of antioxidants as a therapeutic approach. The antioxidant and anti-inflammatory properties of some trace elements have led some of the research to focus on studying these trace elements in inflammatory bowel disease. Zinc and selenium are among the most important trace elements that have significant anti-inflammatory and antioxidant properties. Some studies have shown the importance of these trace elements in inflammatory bowel disease. In this review, we have attempted to provide a comprehensive overview of the findings of these studies and to gather current knowledge about the association of these trace elements with the inflammatory process and inflammatory bowel disease.
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http://dx.doi.org/10.1007/s12011-020-02444-wDOI Listing
October 2020

MicroRNAs and colorectal cancer chemoresistance: New solution for old problem.

Life Sci 2020 Oct 17;259:118255. Epub 2020 Aug 17.

Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Background: Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies with a significant mortality rate. Despite the great advances in cancer treatment in the last few decades, effective treatment of CRC is still under challenge. One of the main problems associated with CRC treatment is the resistance of cancer cells to chemotherapy drugs.

Methods: Many studies have been carried out to identify CRC chemoresistance mechanisms, and shed light on the role of ATP-binding cassette transporters (ABC transporters), enzymes as thymidylate synthase, some signaling pathways, and cancer stem cells (CSC) in chemoresistance and failed CRC chemotherapies. Other studies have also been recently carried out to find solutions to overcome chemoresistance. Some of these studies have identified the role of miRNAs in chemoresistance of the CRC cells and the effective use of these micro-molecules to CRC treatment.

Results: Considering the results of these studies, more focus on miRNAs likely leads to a proper solution to overcome CRC chemoresistance.

Conclusion: The current study has reviewed the related literature while discussing the efficacy of miRNAs as potential clinical tools for overcoming CRC chemoresistance and reviewing the most important chemoresistance mechanisms in CRC cells.
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http://dx.doi.org/10.1016/j.lfs.2020.118255DOI Listing
October 2020

Calprotectin in inflammatory bowel disease.

Clin Chim Acta 2020 Nov 18;510:556-565. Epub 2020 Aug 18.

Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

The term IBD is usually used for referring to a group of inflammatory gastro-intestinal diseases (mainly Crohn's disease and ulcerative colitis). Accordingly, IBD arises as a result of inappropriate immune response to intestinal commensal organisms among genetically susceptible individuals. Performing colonoscopy and histopathologic evaluation on an inflamed bowel biopsy specimen are currently considered as gold standards for diagnosis and management of IBD. Correspondingly, these techniques are known to be invasive and costly. In recent decades, fecal calprotectin, as a biomarker, has received much attention for the diagnosis and non-invasive management of IBD. Up to now, many studies have investigated the efficacy of fecal calprotectin in the areas of IBD differentiation from IBS, prediction of endoscopic and histologic activities of IBD and prediction of disease recurrence. Although some of these studies have reported promising results, some others have shown significant limitations. Therefore, in this paper, we reviewed the most interesting ones of these studies after a brief discussion of the laboratory measurement of fecal calprotectin. Moreover, we attempted to provide an answer for the question of whether fecal-calprotectin could be considered as a potential surrogate marker for colonoscopy.
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http://dx.doi.org/10.1016/j.cca.2020.08.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431395PMC
November 2020

Shelterin Complex at Telomeres: Implications in Ageing.

Clin Interv Aging 2020 3;15:827-839. Epub 2020 Jun 3.

School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Different factors influence the development‎ and control of ageing. It is well known that progressive telomere shorting is one of the molecular mechanisms underlying ageing. The shelterin complex consists of six telomere-specific proteins which are involved in the protection of chromosome ends. More particularly, this vital complex protects the telomeres from degradation, prevents from activation of unwanted repair systems, regulates the activity of telomerase, and has a crucial role in cellular senescent and ageing-related pathologies. This review explores the organization and function of telomeric DNA along with the mechanism of telomeres during ageing, followed by a discussion of the critical role of shelterin components and their changes during ageing.
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http://dx.doi.org/10.2147/CIA.S256425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276337PMC
November 2020

CRISPR/Cas9 gene editing: A new therapeutic approach in the treatment of infection and autoimmunity.

IUBMB Life 2020 Aug 28;72(8):1603-1621. Epub 2020 Apr 28.

Department of Clinical Biochemistry and Laboratory Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein9) may be viewed as an adaptive bacterial immune system. When a virus infects a bacterium, a fragment of the virus genome is inserted into the CRISPR sequence of the bacterial genome as a memory. When the bacterium becomes infected again with the same virus, an RNA molecule that is a transcript of the memory sequence, directs Cas9, an endonuclease, to the complementary region of the virus genome, and Cas9 disables the virus by a double-strand break. In recent years, studies have shown that by designing synthetic RNA molecules and delivering them along with Cas9 into eukaryotic cells, different regions of the cell's genome can be targeted and manipulated. These findings have drawn much attention to this new technology and it has been shown that CRISPR/Cas9 gene editing can be used to treat some human diseases. These include infectious diseases and autoimmune diseases. In this review article, in addition to a brief overview of the biology of the CRISPR/Cas9 system, we collected the most recent findings on the applications of CRISPR/Cas9 technology for better investigation of the pathogenesis and treatment of viral infections (human immunodeficiency virus infection, hepatitis virus infections, and onco-virus infections), non-viral infections (parasitic, fungal, and bacterial infections), and autoimmune diseases.
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http://dx.doi.org/10.1002/iub.2296DOI Listing
August 2020

Effect of Leaf Extract on Glucose Metabolism in HepG2, CRI-D2 and C2C12 Cell Lines.

Diabetes Metab Syndr Obes 2020 14;13:1109-1116. Epub 2020 Apr 14.

Metabolic Disorders Research Center, Department of Biochemistry and Biophysics, Gorgan Faculty of Medicine, Golestan University Medical Sciences, Gorgan, Iran.

Introduction: The aim of this study was to assess the effects of on glucose metabolism in HepG2, CRI-D2 and C2C12 cell lines.

Materials and methods: was collected in Golestan province, Iran. Three different cell lines HepG2 (human liver cell), CRI-D2 (mice pancreatic cell) and C2C12 (rat myoblast) were used for cell culture experiments. Cell viability was measured using MTT assay. Cells were treated with various concentrations of the extract (6.25-400 μg/mL) and then the extracellular glucose level and intracellular glycogen content were measured using colorimetric methods. The insulin level of the culture medium was measured using the ELISA method.

Results: Our findings showed that extract enhances glucose uptake and consumption by all three cell lines. The extract exposure also elevated cellular glycogen content in HepG2 and C2C12 cells (for 200 and 100 μg/mL) significantly. We found a significant increase in glucose uptake and consequently higher stimulation of insulin secretion in CRI-D2 cell pancreatic cells treated with extract.

Conclusion: The appears to activate glucose uptake and cellular glycogen synthesis probably by activating the glycogenesis or inhibition of glycogenolysis pathways. The extract enhances insulin secretion in the pancreatic cells by increased glucose uptake.
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http://dx.doi.org/10.2147/DMSO.S244850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166088PMC
April 2020

The anticancer effects of curcumin via targeting the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.

Pharmacol Res 2020 06 8;156:104798. Epub 2020 Apr 8.

Food Safety Research Center (Salt), Semnan University of Medical Sciences, Semnan, Iran; Department of Nutrition, School of Nutrition and Food Sciences, Semnan University of Medical Sciences, Semnan, Iran.

The mammalian target of rapamycin (mTOR) is a protein kinase that has been considered as a key regulator of a large number of cellular processes, including cell growth, proliferation, differentiation, survival, and motility. Overactivation of mTOR (especially mTORC1) signaling is related to oncogenic cellular processes. Therefore targeting mTORC1 signaling is a new promising strategy in cancer therapy. In this regard, various studies have shown that curcumin, a polyphenol produced from the turmeric rhizome, has anti-inflammatory, antioxidant and anticancer properties. Curcumin may exert its anticancer function, at least in part, by suppressing mTOR-mediated signaling pathway in tumor cells. However, the exact underlying mechanisms by which curcumin blocks the mTORC1 signaling remain unclear. According to literature, curcumin inhibits insulin-like growth factor 1 (IGF-1)/phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 pathway which leads to apoptosis and cell cycle arrest via suppression of erythroblastosis virus transcription factor 2 and murine double minute 2 oncoprotein. In addition, activation of unc-51-like kinase 1 by curcumin, as a downstream target of IGF-1/PI3K/Akt/mTORC1 axis, enhances autophagy. Curcumin induces AMP-activated protein kinase, a negative regulator of mTORC1, via inhibition of F0F1-ATPase. Interestingly, curcumin suppresses IκB kinase β, the upstream kinase in mTORC1 pathway. Moreover, evidence revealed that curcumin downregulates the E3-ubiquitin ligases NEDD4, neural precursor cell-expressed developmentally downregulated 4. NEDD4 is frequently overexpressed in a wide range of cancers and degrades the phosphatase and tensin homolog, which is a negative regulator of mTORC1. Finally another suggested mechanism is suppression of MAOA/mTORC1/hypoxia-inducible factor 1α signaling pathway by curcumin.
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http://dx.doi.org/10.1016/j.phrs.2020.104798DOI Listing
June 2020

The regulatory functions of circular RNAs in osteosarcoma.

Genomics 2020 07 31;112(4):2845-2856. Epub 2020 Mar 31.

Student Research Committee, Babol University of Medical Sciences, Babol, Iran; Department of Medicine, Babol University of Medical Sciences, Babol, Iran.

Osteosarcoma (OS) is known as a malignant bone tumor affecting mainly children and younger adults. Despite all the improvements in the treatment of OS, the overall survival among patients remained mostly unsatisfied. It involves different mechanisms and signaling pathways. Some recent studies confirmed that circular RNAs (circRNAs) have a revelatory role in controlling OS cell proliferation, invasion, and metastasis. CircRNAs consist of a covalently closed-loop structure with neither 5' nor 3' poly adenylated tail, lacking protein-encoding ability formed by back-splicing mechanisms. They mainly act as microRNA (miRNA) sponges and modulate the downstream biological processes. Up/down regulation of some circRNAs demonstrated to serve as the oncogenic factor in some tumor tissues such as OS. In this article, we review the regulatory functions of circRNAs resulting in OS cell progression or restraint and the potential for being used in vitro or in vivo as diagnostic or therapeutic biomarkers.
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http://dx.doi.org/10.1016/j.ygeno.2020.03.024DOI Listing
July 2020

Association of serum 25-OH vitamin D₃ with serum IgE and the Pediatric Asthma Severity Score in patients with pediatric asthma.

Allergy Asthma Proc 2020 03;41(2):126-133

Department of Clinical Biochemistry and Laboratory Medicine, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran, and.

Pediatric asthma is a prevalent disease and has a significant immunologic and inflammatory nature. In recent years, the role of vitamin D₃ in immunologic processes has been studied, and many aspects of this role have been clarified in some human diseases. The aim of this study was to evaluate the relationship among the vitamin D₃ status, Pediatric Asthma Severity Score (PASS), and inflammatory indicators of pediatric asthma. Among all of the pediatric patients with asthma and with asthma exacerbation, 100 patients were randomly enrolled in the study and subdivided into three groups according to serum levels of 25-OH vitamin D₃. The control group consisted of 100 sex- and age-matched healthy subjects. Asthma exacerbation severity was evaluated based on the PASS before starting the medical care. The count of the white blood cells, eosinophil count, and serum levels of total immunoglobulin E (IgE) plus 25-OH vitamin D₃ were measured in all the subjects. The obtained data were then compared via proper statistical tests. A p value of <0.05 was considered as statistically significant. The median level of serum IgE was increased in patients with vitamin D₃ deficiency compared with other groups. There was a significant inverse correlation between serum levels of 25-OH vitamin D₃ and IgE in pediatric patients with asthma (r = -0.483, p = 0.001). Furthermore, the serum levels of 25-OH vitamin D₃ also significantly inversely correlated with the PASS (r = -0.285, p = 0.004). Vitamin D₃ deficiency is associated with exacerbation severity and serum IgE levels in patients with pediatric asthma; hence, it can have an important role in pediatric asthma pathogenesis, possibly through IgE.
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http://dx.doi.org/10.2500/aap.2020.41.190025DOI Listing
March 2020

Measurement of serum irisin in the different stages of chronic kidney disease.

Caspian J Intern Med 2019 ;10(3):314-319

Department of Statistics and Epidemiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran.

Background: Irisin is a myokine that regulates energy metabolism by inducing browning of adipose tissue. The aim of this study was to evaluate the relationship between irisin level and biochemical parameters of chronic kidney disease (CKD) patients in stage 2 and stage 4

Methods: The research was a cross-sectional study; the study population included patients with CKD who were over 18 years of age, included 90 individuals with CKD, of these participants, 45 were in the second stage of the CKD while the other 45 subjects were in the fourth stage. Serum irisin concentration plus the level of glucose (Glu), urea, creatinine (Cr) and hemoglobin (Hb) were measured.

Results: In the present study, the serum irisin level of patients in stage 4 was significantly reduced (13.00 ng / ml) compared with patients in stage 2(21.41 ng / ml).

Conclusion: With the progression of CKD from stage 2 to stage 4, parameters such as serum Cr, TG, LDL, FBS, BUN and urea levels significantly increased. Inversely, factors such as irisin, GFR, Alb, HDL and Hb levels significantly decreased. These findings suggest that irisin may be involved in the regulation of biochemical factor levels in CKD patients through the progression from stage 2 to stage 4.
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http://dx.doi.org/10.22088/cjim.10.3.314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729156PMC
January 2019

The interplay of Klotho with signaling pathway and microRNAs in cancers.

J Cell Biochem 2019 09 24;120(9):14306-14317. Epub 2019 May 24.

Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

Klotho (KL) gene has been accepted as an "aging suppressor" gene that encodes a single transmembrane protein in human known as Klotho which is commonly expressed in renal tubes. The interruption in the secretion of Klotho protein expedites aging whereas its high expression extends lifespan. The family of Klotho proteins has been reported to act as distinct receptors for endocrine fibroblast growth factors (FGFs), which manage multifarious metabolic processes. Further, the secreted Klotho is a hormonal factor that takes part in the ion channel organization. Numerous studies determined that this protein affects the function of a number of important signaling pathways, which may present an impact in tumorigenesis via the coordination of receptors located on them. This review article focuses on the effects of microRNAs on the performance of Klotho and how the interplay between Klotho and certain pathways like insulin-like growth factor, FGF, Wnt, and transforming growth factor β contribute to the biogenesis of cancer. The present study is also pointed at defining the molecular mechanisms of these interactions.
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http://dx.doi.org/10.1002/jcb.29022DOI Listing
September 2019

The role of microRNAs in the healing of diabetic ulcers.

Int Wound J 2019 Jun 28;16(3):621-633. Epub 2019 Feb 28.

Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

MicroRNAs (miRNAs) are small protected molecules with a length of 18 to 25 nucleotides. Many studies have recently been conducted on miRNAs, illustrating their role in regulating many biological, physiological, and pathological activities, such as maintaining cellular signalling and regulating cellular pathways. The main role of miRNAs is to regulate the expression of genes after translation, which can lead to the destruction or suppression of translation by binding to mRNAs. As any change in the regulation of miRNAs is associated with several physiological abnormalities, such as type 2 diabetes and its complications, these molecules can be used for therapeutic purposes or as biomarkers for the diagnosis of diseases such as diabetes and its complications. In this review article, we will discuss important findings about the miRNAs and the role of these molecules in different phases of the wound-healing process of chronic wounds, especially diabetic ulcer.
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http://dx.doi.org/10.1111/iwj.13070DOI Listing
June 2019

Inducible nitric oxide synthase as a potential blood-based biomarker in inflammatory bowel diseases.

Gastroenterol Hepatol Bed Bench 2018 ;11(Suppl 1):S124-S128

Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: Here, we evaluated the role of (iNOS) as a blood-based biomarker of inflammatory bowel diseases (IBD).

Background: Up-regulation of inducible nitric oxide synthase (iNOS) in the intestinal epithelial cells has been closely associated with the initiation and maintenance of intestinal inflammation in IBD.

Methods: In a case-control design, 59 IBD patients and 30 healthy control subjects were participated in this study. A total of 10 ml blood sample was taken from each participant. Blood leukocytes were isolated and iNOS mRNA expression level was evaluated in the isolated leukocytes using relative quantitative Real-time PCR.

Results: The patients' population included 40 ulcerative colitis (UC) and 19 Crohn's disease (CD) patients. The flare and remission phase of disease were seen in 43 and 16 patients, respectively. The mean iNOS mRNA expression was not significantly different between the IBD patients and healthy controls (p=0.056). The mean iNOS mRNA expression was significantly higher in the flare phase of the disease compared to the remission phase (p=0.039). No significant difference was observed between the mean iNOS mRNA expression in the blood leukocytes of UC and CD patients (p=0.82).

Conclusion: iNOS is differently expressed in the blood leukocytes of active vs. inactive IBD disease. Thus, it could be potentially used as a non-invasive blood-based biomarker of IBD.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347994PMC
January 2018

Paraoxonase-2 variants potentially influence insulin resistance, beta-cell function, and their interrelationships with alanine aminotransferase in type 2 diabetes.

J Res Med Sci 2018 28;23:107. Epub 2018 Dec 28.

Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: The aim of this study was to determine whether insulin resistance, beta-cell function, and their associations with alanine aminotransferase (ALT) are affected by the functional variants of paraoxonase-2 (PON2) as an intracellular antioxidant in patients with type 2 diabetes (T2D).

Materials And Methods: Quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment for beta-cell function (HOMA-BCF) were assessed in T2D patients. Insulin levels were determined using ELISA. The variants PON2-A148G and PON2-S311C were genotyped using polymerase chain reaction-based restriction fragment length polymorphism.

Results: According to the PON2-G148A variant, ALT was found to be significantly correlated with QUICKI ( = -0.616, = 0.005) and HOMA-BCF ( = 0.573, = 0.01) in the GA + GG group; however, the correlations were not statistically significant in the AA genotypes. Based on the genotypes of PON2-S311C, there was a significant correlation between ALT with QUICKI ( = -0.540, = 0.031) and HOMA-BCF ( = 0.567, = 0.022) in the SC + CC group. In the multiple adjusted logistic regression analyses, considering the variants PON2-G148A and PON2-C311S as independent variables and QUICKI and HOMA-BCF as the dependent variables, both variants were significantly associated with the QUICKI ( = 0.019 for PON2-G148A and = 0.041 for PON2-C311S). Furthermore, PON2-C311S remained significantly associated with HOMA-BCF ( = 0.03).

Conclusion: These data implicate a role for the functional variants of PON2 in insulin resistance and beta-cell function as well as underscore the effective role of these variants in the associations between them and ALT. Our data contribute to our understanding of the important physiologic functions of PON2 in glucose metabolism and its related metabolic diseases.
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http://dx.doi.org/10.4103/jrms.JRMS_88_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327680PMC
December 2018

MiRNAs and inflammatory bowel disease: An interesting new story.

J Cell Physiol 2019 04 11;234(4):3277-3293. Epub 2018 Nov 11.

Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Inflammatory bowel disease (IBD), as a chronic and recurrent inflammatory disorder, is caused by a dysregulated and aberrant immune response to exposed environmental factors in genetically susceptible individuals. Despite huge efforts in determining the molecular pathogenesis of IBD, an increasing worldwide incidence of IBD has been reported. MicroRNAs (miRNAs) are a set of noncoding RNA molecules that are about 22 nucleotides long, and these molecules are involved in the regulation of the gene expression. By clarifying the important role of miRNAs in a number of diseases, their role was also considered in IBD; numerous studies have been performed on this topic. In this review, we attempt to summarize a number of studies and discuss some of the recent developments in the roles of miRNAs in the pathophysiology, diagnosis, and treatment of IBD.
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http://dx.doi.org/10.1002/jcp.27173DOI Listing
April 2019

The crosstalk between trace elements with DNA damage response, repair, and oxidative stress in cancer.

J Cell Biochem 2018 Oct 30. Epub 2018 Oct 30.

Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

DNA damage response (DDR) is a regulatory system responsible for maintaining genome integrity and stability, which can sense and transduce DNA damage signals. The severity of damage appears to determine DDRs, which can include damage repair, cell-cycle arrest, and apoptosis. Furthermore, defective components in DNA damage and repair machinery are an underlying cause for the development and progression of various types of cancers. Increasing evidence indicates that there is an association between trace elements and DDR/repair mechanisms. In fact, trace elements seem to affect mediators of DDR. Besides, it has been revealed that oxidative stress (OS) and trace elements are associated with cancer development. In this review, we discuss the role of some critical trace elements in the risk of cancer. In addition, we provide a brief introduction on DDR and OS in cancer. Finally, we will further review the interactions between some important trace elements including selenium, zinc, chromium, cadmium, and arsenic, and DDR, and OS in cancer.
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http://dx.doi.org/10.1002/jcb.27617DOI Listing
October 2018

Some of the effective factors in the pathogenesis of gastro-oesophageal reflux disease.

J Cell Mol Med 2018 12 15;22(12):6401-6404. Epub 2018 Oct 15.

Student Research Committee, Babol University of Medical Sciences, Babol, Iran.

Oesophageal adenocarcinoma is one of the most fatal tumours to affect the digestive tract and is the eighth most common malignancy worldwide. Gastro-oesophageal reflux has an important role in the incidence of adenocarcinoma of the oesophagus. Gastro-oesophageal reflux disease (GERD) is a multifactorial, acid-peptic disorder that results from the reflux of noxious material from the stomach into the oesophagus. The refluxed material causes the occurrence of oesophageal inflammation which creates a condition that is called reflux oesophagitis. The prevalence of this disease has increased dramatically in recent decades, mostly in the western world, where it affects about 10% to 30% of the population. The aetiology of oesophageal mucosal damage is complicated. Many inflammatory mediators are produced within the gastrointestinal (GI) tract, but their contributions in pathophysiology and disease pathogenesis have not been well investigated. Despite the protective barrier provided by the oesophageal mucosa, refluxed materials can cause oxidative injury and in?ammatory responses that involve the epithelium and immune cells. The analysing cellular events in gastro- oesophageal reflux disease and physiological responses to such conditions are important and necessary for a better grasp of the pathogenesis of GERD and the expansion of new treatments. Therefore, we want to discuss some of the important and key factors of GERD disease in this article.
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http://dx.doi.org/10.1111/jcmm.13939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237569PMC
December 2018

Genotype and phenotype of salt-stimulated paraoxonase 1 (PON1) is associated with atherogenic indices in type 2 diabetes.

J Diabetes Metab Disord 2018 Jun 26;17(1):1-10. Epub 2018 Mar 26.

4Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Km 17 Khazarabad Road, Sari, Iran.

Background: Paraoxonase 1 (PON1) and lipid abnormalities contribute to the development of cardiovascular disease, which is the principal cause of mortality in patients with type 2 diabetes (T2D). Data are not available on the potential association between salt-stimulated activity of PON1 (PON1-salt) and the atherogenic indices in T2D, therefore, we focused on these associations and evaluated whether the functional variants PON1-Q192R and PON1-L55M influence the associations.

Methods: Paraoxonase activity (PON1-para), arylesterase activity (PON1-aryl) and salt-stimulated activity (PON1-salt) were measured by spectrophotometric assays. The atherogenic index of plasma (AIP) was calculated from the log (TG/HDL-C). The genetic analyses were made by the restricted fragment length polymorphism after PCR amplification.

Results: We observed that PON1-salt was negatively correlated with total cholesterol (TC)/HDL-C ( = -0.441, = 0.006), LDL-C/HDL-C ( = -0.415,  = 0.011), and AIP ( = -0.422,  = 0.009). Correlations between PON1-salt and all three atherogenic indices were significantly affected by PON1-L55M and PON1-Q192R. Linear regression showed that AIP ( = 0.002), LDL-C/HDL-C ( = 0.005), and TC/HDL-C (p = 0.002) were independently associated with PON1-salt. Based on Ridge regression, the standardized coefficients -0.358, -0.297, and - 0.044 were obtained for AIP, LDL-C/HDL-C, and TC/HDL-C, respectively, and this shows that AIP could have more negative effect on PON1-salt than the others.

Conclusions: The decreased PON1-salt may be considered as a risk factor for atherosclerosis in T2D, therefore, understanding the associations between PON1-salt as an important although neglected property and atherogenic indices may be valuable in T2D. Accordingly, detection of PON1-salt status (phenotype and genotype) together with the atherogenic indices particularly AIP could be beneficial in identifying the increased atherogenicity in T2D.
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http://dx.doi.org/10.1007/s40200-018-0332-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154515PMC
June 2018

Assessing the Levels of L-Carnitine and Total Antioxidant Capacity in Adults With Newly Diagnosed and Long-Standing Type 2 Diabetes.

Can J Diabetes 2019 Feb 29;43(1):46-50.e1. Epub 2018 Mar 29.

Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Internal Medicine, Ayatollah Rouhhani Hospital, Babol University of Medical Sciences, Babol, Iran.

Objectives: This study is essentially a correlative study that examines the potential of reduced levels of L-carnitine (LC) when combined with the pathophysiology of type 2 diabetes. The aim of the study was to assess the levels of LC, total antioxidant capacity (TAOC), fasting blood sugar (FBS), triglycerides and cholesterol in people with newly diagnosed and long-standing type 2 diabetes and in healthy controls.

Methods: The study was done in 90 adult subjects, including 30 with newly diagnosed diabetes, 30 with long-standing type 2 diabetes and 30 healthy controls. Plasma samples were used to assay the biochemical parameters.

Results: In this study, both groups (newly diagnosed and long-standing type 2 diabetes) were significantly different in baseline characteristics, such as age, height, weight, body mass index, FBS, cholesterol and triglycerides, compared to the healthy controls. Plasma LC levels in patients with newly diagnosed and long-standing type 2 diabetes were significantly lower than in healthy controls (p<0.001). Also, the mean plasma TAOC level in the patients with newly diagnosed and long-standing type 2 diabetes was slightly lower than in the healthy controls. Nevertheless, TAOC levels were not significantly different across all the groups (p=0.87). The plasma LC levels were significantly positive when compared to the plasma TAOC levels (r=0.516), which means that an increase in LC levels is associated with an increase in TAOC levels. However, a negative correlation was observed between LC levels and FBS (r=-0.387), triglycerides (-0.159) and body mass indexes (r=-0.068). This means that a decrease in LC levels is associated with increases in FBS, triglyceride and body mass index levels.

Conclusions: According to the effects of reduced LC levels on the metabolic profiles of patients with long-standing type 2 diabetes, setting the LC content value to prevent diabetes through the use of effective drugs or nutrition containing LC can be useful in managing diabetes.
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http://dx.doi.org/10.1016/j.jcjd.2018.03.009DOI Listing
February 2019

An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in β-thalassemia major patients: A double-blind randomized controlled clinical trial.

Phytother Res 2018 Sep 28;32(9):1828-1835. Epub 2018 May 28.

Clinical Biochemistry, Faculty of medicine, Babol University of Medical sciences, Babol, Iran.

This study investigated the effects of curcumin, the active polyphenol in turmeric, on iron overload, hepcidin level, and liver function in β-thalassemia major patients. This double-blind randomized controlled clinical trial was conducted on 68 β-thalassemia major patients. The subjects were randomly divided into 2 groups to receive either 500 mg curcumin capsules (total: 1,000 mg) twice daily or placebo for 12 weeks. Dietary intakes and biochemical variables including hemoglobin, transferrin saturation, total iron binding capacity, nontransferrin bound iron (NTBI), ferritin, hepcidin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed at the beginning and end of the trial. Curcumin significantly reduced serum levels of NTBI (2.83 ± 1.08 compared with 2.22 ± 0.97 μmol/L, p = .001), ALT (42.86 ± 11.15 compared with 40.60 ± 9.89 U/L, p = .018), and AST (49.45 ± 12.39 compared with 46.30 ± 10.85 U/L, p = .002) at the end of the study. Based on analysis of covariance, a significant decrease was also observed in levels of NTBI (2.22 ± 0.97 vs. 2.55 ± 0.94 μmol/L, p = .026), ALT (40.60 ± 9.89 vs. 45.01 ± 10.42 U/L, p = .004), and AST (46.30 ± 10.85 vs. 50.99 ± 9.36 U/L, p = .009) in curcumin group in comparison with placebo group. There were no significant changes in hepcidin and other variables in any of the 2 groups. Curcumin administration alleviated iron burden and liver dysfunction by reducing NTBI, ALT, and AST levels in patients with β-thalassemia major.
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http://dx.doi.org/10.1002/ptr.6118DOI Listing
September 2018

Positive Correlation of Fecal Calprotectin With Serum Antioxidant Enzymes in Patients With Inflammatory Bowel Disease: Accidental Numerical Correlation or a New Finding?

Am J Med Sci 2018 05 27;355(5):449-455. Epub 2017 Dec 27.

Departments of Biostatistics and Epidemiology, Babol University of Medical Sciences, Babol, Iran.

Background: Oxidative stress occuring in patients diagnosed with inflammatory bowel disease (IBD), but the relationship between oxidative stress, disease activity and inflammatory markers has not been well established.

Materials And Methods: A total of 30 patients diagnosed with IBD and 30 volunteers who had normal colonoscopies, selected as controls, were used for this study. The serum levels of antioxidant enzymes (catalase and glutathione peroxidase) and oxidative markers (malondialdehyde [MDA] and total antioxidant capacity) were compared between the 2 groups. Furthermore, their correlations with disease activity scores and inflammatory markers, especially the fecal calprotectin, were examined.

Results: Catalase and glutathione peroxidase concentrations were significantly correlated with the level of fecal calprotectin in patients with IBD. Nevertheless, there were no significant correlations between the concentrations of the above-mentioned enzymes and C-reactive protein, erythrocyte sedimentation rate or the activity scores of IBD patients. It should be noted that MDA and total antioxidant capacity levels did not correlate with the inflammatory markers or the disease activity scores.

Conclusions: There was a positive correlation between fecal calprotectin and serum antioxidant enzymes in patients with IBD, but, there was no correlation between antioxidant and oxidative markers in terms of disease activity scores. Hence, the observed significant correlation between the antioxidant enzymes and the fecal calprotectin may be due to either the pro-oxidant potential of calprotectin or its antioxidant role.
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http://dx.doi.org/10.1016/j.amjms.2017.12.009DOI Listing
May 2018

Direct correlation between serum homocysteine level and insulin resistance index in patients with subclinical hypothyroidism: Does subclinical hypothyroidism increase the risk of diabetes and cardio vascular disease together?

Diabetes Metab Syndr 2018 Nov 5;12(6):863-867. Epub 2018 May 5.

Department of Endocrinology, Internal Medicine, Ayatollah Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran.

Background: Subclinical hypothyroidism known as mild thyroid disorder without significant sign and symptoms. The correlation between subclinical hypothyroidism and some of cardiovascular disease risk factors such as serum lipids, homocysteine levels and also insulin resistance index is not well established and the current study was conducted to clarify this issue.

Methods And Materials: Seventy four patients with mild elevation in levels of thyroid stimulating hormone (TSH) along with normal levels of T3 and T4 were selected as patients group and 74 age and sex matched individuals were selected as healthy control group. Serum insulin, triglyceride, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and homocysteine levels were measured. Obtained data compared between groups with independent sample t-test. For evaluation of the correlation between mentioned parameters Pearson correlation coefficient method was used.

Results: Serum levels of LDL-C and total cholesterol significantly increased in SCH group compared to healthy control group. Homeostatic Model Assessment of Insulin Resistance (HOM-IR) and serum homocysteine level significantly elevated in patients with SCH compared to control group. There was a significant direct correlation between HOM-IR and serum homocysteine levels in SCH patients.

Conclusion: Subclinical hypothyroidism likely have significant effect on insulin resistance as major diabetes risk factors and also cardiovascular disease risk factors such as homocysteine. The direct correlation between HOM-IR with serum homocysteine level indicate the possible role of insulin resistance in elevation of serum homocysteine in SCH patient group.
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http://dx.doi.org/10.1016/j.dsx.2018.05.002DOI Listing
November 2018

Effect of Popping Chocolate and Candy on Enamel Microhardness of Primary and Permanent Teeth.

J Int Soc Prev Community Dent 2017 Nov-Dec;7(6):370-376. Epub 2017 Dec 29.

Student Research Committee, Babol University of Medical Sciences, Babol, Iran.

Aims And Objectives: Dental erosion is a common disease in children. Food diets, due to high amounts of juice, soft drinks, chewing gum, and acidic chocolate, are one of the most important risk factors in erosive processes among children. The aim of this study was to evaluate the effect of candy and chocolate on the microhardness of tooth enamel.

Materials And Methods: Two types of popping candy and one type of popping chocolate were used in this study. Thirty-three healthy permanent premolar teeth and 33 primary incisor teeth (A or B) were selected. Five grams of each popping chocolate or candy was dissolved with 2 ml of artificial saliva. Subsequently, their pH and titrable acidity (TA) as well as microhardness and surface roughness of enamel were examined in the laboratory. Data were analyzed and evaluated Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY through independent -test, paired -test, Tukey test, and ANOVA.

Results: The results of this study showed that only the pH of the candies was below the critical pH of the enamel (5.5) and their TA was B = 0.20 and C = 0.21. The most significant effect on the enamel microhardness of the permanent and primary teeth was by the following types of candy: orange flavor (C), strawberry flavor (B), and chocolate (A), respectively. This difference was significant ( < 0.001) and the surface roughness increased after exposure.

Conclusions: This study showed that popping chocolate and candy reduces microhardness of enamel.
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http://dx.doi.org/10.4103/jispcd.JISPCD_386_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774060PMC
December 2017