Publications by authors named "Maryam Montazeri"

21 Publications

  • Page 1 of 1

Let-7d and miR-185 Impede Epithelial-Mesenchymal Transition by Downregulating Rab25 in Breast Cancer.

Asian Pac J Cancer Prev 2021 Jan 1;22(1):305-313. Epub 2021 Jan 1.

Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Objective: MicroRNAs (miRNAs) expression has deregulated in several cancer types including breast cancer (BC). The present study aims at investigating the role, mechanism, clinical value of let-7d and miR-185 in BC, and the possible correlation these miRNAs with Rab25.

Materials And Methods: Tumor samples as well adjacent normal tissues (ANT) were acquired from fresh surgical specimens from 110 patients and the expression levels of let-7d, miR-185, Rab25, and snail were evaluated using real-time PCR. The immunohistochemical (IHC) process and western blot were done to detect the level of Rab25 and Snail protein expression in BC samples.

Results: By comparing miRNAs expression profiles in clinical tissues of 110 patients using real-time PCR, let-7d, and miR-185 expression were dramatically downregulated in BC tissues (P < 0.05). Tumor size, stage, and lymph node metastasis were significantly related to miRNAs expression. Based on qRT-PCR and bioinformatics database analyses, we also recognized Rab25 as a possible target of miR-185 and let-7d. Rab25 expression was enhanced in BC cells and associated inversely with the expression level of mentioned miRNAs. qRT-PCR, immunohistochemistry, and western blot studies verified that Rab25 upregulation increased the levels of the snail, that key transcription factor of epithelial-mesenchymal transition (EMT).

Conclusion: These findings demonstrated that let-7d and miR-185 inhibited EMT by targeting Rab25 expression in BC. Therefore, targeting the let-7d and miR-185/Rab25 interaction may offer new therapeutic opportunities for treating BC patients.
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http://dx.doi.org/10.31557/APJCP.2021.22.1.305DOI Listing
January 2021

How accurate are digital symptom assessment apps for suggesting conditions and urgency advice? A clinical vignettes comparison to GPs.

BMJ Open 2020 12 16;10(12):e040269. Epub 2020 Dec 16.

Ada Health GmbH, Berlin, Germany.

Objectives: To compare breadth of condition coverage, accuracy of suggested conditions and appropriateness of urgency advice of eight popular symptom assessment apps.

Design: Vignettes study.

Setting: 200 primary care vignettes.

Intervention/comparator: For eight apps and seven general practitioners (GPs): breadth of coverage and condition-suggestion and urgency advice accuracy measured against the vignettes' gold-standard.

Primary Outcome Measures: (1) Proportion of conditions 'covered' by an app, that is, not excluded because the user was too young/old or pregnant, or not modelled; (2) proportion of vignettes with the correct primary diagnosis among the top 3 conditions suggested; (3) proportion of 'safe' urgency advice (ie, at gold standard level, more conservative, or no more than one level less conservative).

Results: Condition-suggestion coverage was highly variable, with some apps not offering a suggestion for many users: in alphabetical order, Ada: 99.0%; Babylon: 51.5%; Buoy: 88.5%; K Health: 74.5%; Mediktor: 80.5%; Symptomate: 61.5%; Your.MD: 64.5%; WebMD: 93.0%. Top-3 suggestion accuracy was GPs (average): 82.1%±5.2%; Ada: 70.5%; Babylon: 32.0%; Buoy: 43.0%; K Health: 36.0%; Mediktor: 36.0%; Symptomate: 27.5%; WebMD: 35.5%; Your.MD: 23.5%. Some apps excluded certain user demographics or conditions and their performance was generally greater with the exclusion of corresponding vignettes. For safe urgency advice, tested GPs had an average of 97.0%±2.5%. For the vignettes with advice provided, only three apps had safety performance within 1 SD of the GPs-Ada: 97.0%; Babylon: 95.1%; Symptomate: 97.8%. One app had a safety performance within 2 SDs of GPs-Your.MD: 92.6%. Three apps had a safety performance outside 2 SDs of GPs-Buoy: 80.0% (p<0.001); K Health: 81.3% (p<0.001); Mediktor: 87.3% (p=1.3×10).

Conclusions: The utility of digital symptom assessment apps relies on coverage, accuracy and safety. While no digital tool outperformed GPs, some came close, and the nature of iterative improvements to software offers scalable improvements to care.
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http://dx.doi.org/10.1136/bmjopen-2020-040269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745523PMC
December 2020

The Relationship Between Renal Arterial Resistive Index (RRI) and Renal Outcomes in Patients with Resistant Hypertension.

Iran J Kidney Dis 2020 Dec;14(6):448-453

Department of Nephrology, Clinical Research Development Unit (CRDU), Sayad Shirazi Hospital, Golestan University of Medical Sciences, Gorgan, Iran.

Introduction: There is a mutual relationship between hypertension and renal failure, so that hypertension can be considered as a common finding in patients with end-stage renal disorders. Patients with persistent hypertension despite multiple medications are at high risk for adverse cardiovascular and kidney events. Some studies suggest that there is a correlation between RI and renal function in kidney diseases. Therefore, we conducted a study to investigate the relationship between renal arterial resistive index (RRI) and renal outcomes in patients with resistant hypertension.

Methods: This 2-years cross-sectional study was performed on patients with resistant hypertension. All patients undergo GFR, serum Cr and urine Alb tests. Then Doppler ultrasound was performed by a radiologist to measure RRI and was evaluated for the relationship between RRI and renal function.

Results: Among 133 patients with resistant hypertension, 57.5% were male and the rest were female. Average age of participants and average RI were 48.26 ± 16.90 and 0.63 ± 0.80, respectively. There was no significant relationship between RI and gender (P > .05). Relationship between RI index with age, GFR, serum creatinine level, and albuminuria was significant in all cases (P < .05). Patients were divided into two groups with RI ≥ 0.7 and RI less than 0.7. Results showed a significant increase in serum creatinine and urinary albumin excretion in group with RI ≥ 0.7 (P < .05), while age, protein exertion level, and GFR in the two groups were not statistically significant (P > .05), despite the difference in the mean. Results of analysis of difference in the mean RI in 3 groups (macro-, micro-, normo- albuminuria) showed no significant difference between them (P > .05).

Conclusion: These data demonstrate the clinical importance of renal Doppler that may be an effective way to evaluate the prognosis of renal involvement in resistant hypertension.
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December 2020

Upregulation of the long noncoding RNAs DSCAM-AS1 and MANCR is a potential diagnostic marker for breast carcinoma.

Biotechnol Appl Biochem 2020 Oct 4. Epub 2020 Oct 4.

Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Breast cancer (BC) is one of the most common malignancies among women in the world. There is a global attempt to diagnose BC as early as possible. Long noncoding RNAs (lncRNAs) are emerging as novel targets and biomarkers for BC diagnosis and prognosis. Aberrant expression of lncRNAs is associated with BC development, making them a potential tumor marker for BC. To investigate this possibility, we determined the expression levels of Down syndrome cell adhesion molecule-antisense RNA-1 (DSCAM-AS1) and mitotically-associated long non-coding RNA (MANCR) lncRNAs in BC tissues. This case-control study included 50 paired tumor and adjacent nontumor tissues from female BC patients. The total RNA was isolated and the expression levels of MANCR and DSCAM-AS1 lncRNAs were assessed using quantitative real-time reverse transcription-PCR. Potential correlations between lncRNA levels and clinicopathological characteristics were also analyzed. DSCAM-AS1 and MANCR lncRNAs were significantly upregulated in BC tumor tissues compared with the adjacent nontumor tissues. We also found the significant upregulation of DSCAM-AS1 in advanced tumor-node-metastasis stage (TNM III) of BC tumor tissues. Furthermore, the expression of DSCAM-AS1 and MANCR in HER-2 positive patients was significantly higher than HER-2 negative affected individuals. Receiver operating characteristic curve analysis showed a satisfactory diagnostic efficacy (P value < 0.0001), which means that DSCAM-AS1 and MANCR lncRNAs can potentially serve as a biomarker. The present study might provide further approval for the clinical diagnostic significance of DSCAM-AS1 and MANCR lncRNAs that their high expressions were associated with aggressive clinical parameters of BC.
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http://dx.doi.org/10.1002/bab.2048DOI Listing
October 2020

Advances of exosome isolation techniques in lung cancer.

Mol Biol Rep 2020 Sep 12;47(9):7229-7251. Epub 2020 Aug 12.

Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, P.O. Box: 14115-154, Tehran, Iran.

Lung cancer (LC) is among the leading causes of death all over the world and it is often diagnosed at advanced or metastatic stages. Exosomes, derived from circulating vesicles that are released from the multivesicular body, can be utilized for diagnosis and also the prognosis of LC at early stages. Exosomal proteins, RNAs, and DNAs can help to better discern the prognostic and diagnostic features of LC. To our knowledge, there are various reviews on LC and the contribution of exosomes, but none of them are about the exome techniques and also their efficiency in LC. To fill this gap, in this review, we summarize the recent investigations regarding isolation and also the characterization of exosomes of LC cells. Furthermore, we discuss the noncoding RNAs as biomarkers and their applications in the diagnosis and prognosis of LC. Finally, we compare the efficacy of exosome isolation methods to better fi + 6 + guring out feasible techniques.
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http://dx.doi.org/10.1007/s11033-020-05715-wDOI Listing
September 2020

Effects of journal therapy counseling with anxious pregnant women on their infants' sleep quality: a randomized controlled clinical trial.

BMC Pediatr 2020 05 18;20(1):229. Epub 2020 May 18.

School of Nursing and Midwifery, Tabriz University of Medical Science, Tabriz, Iran.

Background: Sleep is especially important for infants, since it stimulates the development of neural connections in their brains. Psychological stress such as anxiety could affect sleep quality. This study investigated the effects of journal therapy counseling sessions on the infants' sleep quality based on mothers' perception (primary outcome), maternal anxiety, infants' anthropometric and developmental parameters, and the frequency of exclusive breastfeeding (secondary outcomes).

Methods: A total of 70 healthy women with gestational age of 28-31 weeks participated in this randomized controlled trial. The participants were randomly allocated into intervention and control groups using randomized block design. Three in-person journal therapy sessions and three telephone counseling sessions (2 between in-person sessions and 1 one month postpartum) were provided to those in the intervention group, while the control group only received routine care. The Infant Sleep Questionnaire (ISQ), Exclusive Breastfeeding Checklist, and Infant Anthropometric Parameters Checklist were completed at two and four months postpartum. The Beck Anxiety Inventory (BAI) was completed during pregnancy, at the end of the intervention, and at two and four months postpartum, and the Ages and Stages Questionnaire (ASQ) was completed at 4 months postpartum. Data were analyzed using chi-square, independent t-test, ANCOVA and repeated measure ANOVA.

Results: There was no significant difference between the two groups in demographic characteristics and baseline anxiety scores. The mean sleep quality score in infants two months of age (MD: -4.2; 95%CI: - 1.1 to - 7.2; P = 0.007) and four months of age (MD: -5.5; 95%CI: - 8.4 to - 2.7; P < 0.001) was significantly lower in the intervention group than that of those in the control group. Based on the repeated measure ANOVA results, the mean postpartum anxiety score of mothers in the intervention group was significantly lower than that of those in the control group (AMD: -7.7; 95%CI: - 5.5 to - 10.1; P < 0.001). There was no significant difference between the two groups regarding other outcomes including the frequency of exclusive breastfeeding, and anthropometric and developmental parameters (P > 0.05).

Conclusion: Journal therapy can decrease mothers' anxiety and improve the infants' sleep quality based on their perception. However, further studies are required before drawing any definitive conclusion.

Trial Registration Number: Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N45. Date of registration: August 11, 2018. URL: https://en.irct.ir/trial/33211.
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http://dx.doi.org/10.1186/s12887-020-02132-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236485PMC
May 2020

Recent advances in electrospun nanofiber-mediated drug delivery strategies for localized cancer chemotherapy.

J Biomed Mater Res A 2020 05 15;108(7):1444-1458. Epub 2020 Apr 15.

Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.

Nanotechnology empowered localized cancer chemotherapy has indicated a promising performance for targeting and controlled release of anticancer agents over a period of time to eliminate local-regional recurrence of cancers and also to improve the tissue regeneration during/after treatment. Electrospun nanofiber-based implantable drug-delivery systems have been established as one of the most effective approaches for localized cancer treatment, allowing the on-site delivery of anticancer agents and reducing systemic toxicities and side effects to normal cells. The present review aimed to summarize the latest cutting-edge research on applications of electrospun-based systems for local chemotherapy. Meantime, in vitro and in vivo studies conducted using various anticancer agents along with the capability of electrospun nanofibers for combinatorial/synergistic chemotherapy as well as existing challenges and the potential dramatic advances in applying this pioneering approach for clinical transition in localized treatments of cancer is also discussed.
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http://dx.doi.org/10.1002/jbm.a.36912DOI Listing
May 2020

Recent advances on nanomaterials-based fluorimetric approaches for microRNAs detection.

Mater Sci Eng C Mater Biol Appl 2019 Nov 19;104:110007. Epub 2019 Jul 19.

Cellular and Molecular Research Center, Research Institute for Cellular and Molecular Medicine, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

MicroRNAs are types of small single-stranded endogenous highly conserved non-coding RNAs, which play main regulatory functions in a wide range of cellular and physiological events, such as proliferation, differentiation, neoplastic transformation, and cell regeneration. Recent findings have proved a close association between microRNAs expression and the development of many diseases, indicating the importance of microRNAs as clinical biomarkers and targets for drug discovery. However, due to a number of prominent characteristics like small size, high sequence similarity and low abundance, sensitive and selective identification of microRNAs has rather been a hardship through routine traditional assays, including quantitative polymerase chain reaction, microarrays, and northern blotting analysis. More recently, the soaring progression in nanotechnology and fluorimetric methodologies in combination with nanomaterials have promised microRNAs detection with high sensitivity, efficiency and selectivity, excellent reproducibility and lower cost. Therefore, this review will represent an overview of latest advances in microRNAs detection through nanomaterials-based fluorescent methods, like gold nanoparticles, silver and copper nanoclusters, graphene oxide, and magnetic silicon nanoparticles.
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http://dx.doi.org/10.1016/j.msec.2019.110007DOI Listing
November 2019

FORESEE: a tool for the systematic comparison of translational drug response modeling pipelines.

Bioinformatics 2019 10;35(19):3846-3848

Joint Research Center for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Aachen, Germany.

Summary: Translational models that utilize omics data generated in in vitro studies to predict the drug efficacy of anti-cancer compounds in patients are highly distinct, which complicates the benchmarking process for new computational approaches. In reaction to this, we introduce the uniFied translatiOnal dRug rESponsE prEdiction platform FORESEE, an open-source R-package. FORESEE not only provides a uniform data format for public cell line and patient datasets, but also establishes a standardized environment for drug response prediction pipelines, incorporating various state-of-the-art pre-processing methods, model training algorithms and validation techniques. The modular implementation of individual elements of the pipeline facilitates a straightforward development of combinatorial models, which can be used to re-evaluate and improve already existing pipelines as well as to develop new ones.

Availability And Implementation: FORESEE is licensed under GNU General Public License v3.0 and available at https://github.com/JRC-COMBINE/FORESEE and https://doi.org/10.17605/OSF.IO/RF6QK, and provides vignettes for documentation and application both online and in the Supplementary Files 2 and 3.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btz145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761955PMC
October 2019

Expression Analysis of PVT1, CCDC26, and CCAT1 Long Noncoding RNAs in Acute Myeloid Leukemia Patients.

Genet Test Mol Biomarkers 2018 Oct 14;22(10):593-598. Epub 2018 Sep 14.

1 Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences , Tehran, Iran .

Background: Recent evidence indicates that the PVT1, CCDC26, and CCAT1 long noncoding RNAs (lncRNAs) are involved in the leukemogenic process. This study quantified the expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs in patients with acute myeloid leukemia (AML) and also correlated their expression levels with the clinicopathological features of the patients.

Materials And Methods: The expression levels of the PVT1, CCDC26, and CCAT1 lncRNAs were analyzed using quantitative reverse transcription-polymerase chain reaction of bone marrow specimens obtained from 86 AML patients, 48 AML-M3 patients, and 40 normal controls.

Results: No differences were found between the combined AML patient populations and the healthy controls with respect to the expression levels of PVT1, CCDC26, and CCAT1 (p = 0.35, p = 0.09, and p = 0.77, respectively). However, compared with the controls, the AML-M3 patients had higher PVT1 expression (p = 0.017). Furthermore, high-risk AML-M3 patients manifested higher expression levels of PVT1 than low- and intermediate-risk groups. In addition, distinctive CCDC26 and CCAT1 expression levels were observed among patients with different French-American-British subtypes (p = 0.001 for CCDC26 and p = 0.013 for CCAT1). Compared with the healthy controls, AML-M4 and M5 had higher CCAT1 expression (p = 0.04) and AML-M2 and AML-M4/M5 patients had higher CCDC26 expression (p < 0.001 and p = 0.02, respectively). In addition, different patterns of CCDC26 expression were found among the different cytogenetic risk subtypes (p = 0.005). Finally, patients with intermediate cytogenetic risk showed higher CCDC26 expression levels.

Conclusion: The differential expression of the PVT1, CCDC26, and CCAT1 lncRNAs in different AML subtypes suggests that the deregulation of these transcripts may function in the multistep leukemogenic process and that they may serve as new therapeutic targets for this malignancy.
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http://dx.doi.org/10.1089/gtmb.2018.0143DOI Listing
October 2018

Low Expression of Long Noncoding RNA IRAIN Is Associated with Poor Prognosis in Non-M3 Acute Myeloid Leukemia Patients.

Genet Test Mol Biomarkers 2018 May 10;22(5):288-294. Epub 2018 Apr 10.

1 Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences , Tehran, Iran .

Aims: Deregulation of the long noncoding RNA IRAIN has been identified in several cancers. However, the expression pattern of IRAIN and its clinical implication in acute myeloid leukemia (AML) are unknown. The purpose of this study was to investigate the expression status of IRAIN and its clinical significance in non-M3 AML patients.

Methods: Quantitative reverse transcription-polymerase chain reaction was performed to examine IRAIN transcript levels in 64 de novo non-M3 AML patients and 51 healthy controls. The association of IRAIN expression with clinicopathological factors was statistically analyzed.

Results: Compared with the controls, IRAIN was significantly downregulated in non-M3 AML patients (p < 0.001). The median of IRAIN expression divided the non-M3 AML patients into IRAIN low-expressing (IRAIN) and IRAIN high-expressing (IRAIN) groups. The IRAIN group tended to have higher white blood cell count and blast counts and had markedly shorter overall survival (OS) and relapse-free survival (RFS) (p = 0.044 and 0.009, respectively). In addition, patients with refractory response to chemotherapies and those with subsequent relapse had lower initial IRAIN expression. Multivariate analysis further identified IRAIN transcript levels as an independent prognostic factor for both RFS and OS.

Conclusions: Our finding suggests that IRAIN transcript levels may be a useful biomarker for the prognosis of non-M3 AML patients.
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http://dx.doi.org/10.1089/gtmb.2017.0281DOI Listing
May 2018

Up-regulation of miR-21 decreases chemotherapeutic effect of dendrosomal curcumin in breast cancer cells.

Iran J Basic Med Sci 2017 Apr;20(4):350-359

Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Objectives: Despite the good results of anticancer activities by curcumin, there are some hurdles that limit the use of curcumin as an anticancer agent. Many methods were examined to overcome this defect like the use of the dendrosomal curcumin (DNC). There is increasing evidence that miRNAs play important roles in biological processes. In this study, we focus on the roles of microRNA-21 in the anti-cancer effects of DNC in breast cancer.

Materials And Methods: Also, we have used different methods such as MTT, apoptosis, cell cycle analysis, transwell migration assay and RT-PCR to find out more.

Results: We observed that miR-21 decreased apoptotic cells in both cells (from 6.35% to 0.34 % and from 7.72% to 1.32% orderly) and DNC increased it. As well as, our findings indicated that cell migration capacity was increased by miR-21 over expression and was decreased by DNC. The combination of miR-21 vector transfection and DNC treatment showed lower percentage of apoptotic cells or a higher level of penetration through the membrane compared with DNC treatment alone. Furthermore, DNC induced a marked increase in the number of cells in sub G1/G1 phase and a decrease in G2/M phase of the cell cycle in both; but, we observed reverse results compared it, after transfection with miR-21 vector.

Conclusion: We observed that miR-21 suppress many aspects of anti-cancer effects of DNC in breast cancer cells, it seems that co-treatment with DNC and mir-21 down-regulation may provide a clinically useful tool for drug-resistance breast cancer cells.
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http://dx.doi.org/10.22038/IJBMS.2017.8574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425916PMC
April 2017

Antiproliferative and Apoptotic Effect of Dendrosomal Curcumin Nanoformulation in P53 Mutant and Wide-Type Cancer Cell Lines.

Anticancer Agents Med Chem 2017 ;17(5):662-673

Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Objective: The aim of this paper is to investigate the effect of dendrosomal curcumin (DNC) on the expression of p53 in both p53 mutant cell lines SKBR3/SW480 and p53 wild-type MCF7/HCT116 in both RNA and protein levels.

Background: Curcumin, derived from Curcumin longa, is recently considered in cancer related researches for its cell growth inhibition properties. p53 is a common tumor-suppressor gene involved in cancers and its mutation not only inhibits tumor suppressor activity but also promotes oncogenic activity.

Method: Here, p53 mutant/Wild-type cells were employed to study the toxicity of DNC using MTT assay, Flow cytometry and Annexin-V, Real-time PCR and Western blot were used to analyze p53, BAX, Bcl-2, p21 and Noxa changes after treatment.

Results: During the time, DNC increased the SubG1 cells and decreased G1, S and G2/M cells, early apoptosis also indicated the inhibition of cell growth in early phase. Real-Time PCR assay showed an increased mRNA of BAX, Noxa and p21 during the time with decreased Bcl-2. The expression of p53 mutant decreased in SKBR3/SW480, and the expression of p53 wild-type increased in MCF7/HCT116.

Conclusion: Consequently, p53 plays an important role in mediating the survival by DNC, which can prevent tumor cell growth by modulating the expression of genes involved in apoptosis and proliferation.
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http://dx.doi.org/10.2174/1871520616666160815124537DOI Listing
September 2017

Dendrosomal curcumin nanoformulation modulate apoptosis-related genes and protein expression in hepatocarcinoma cell lines.

Int J Pharm 2016 Jul 24;509(1-2):244-254. Epub 2016 May 24.

Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

The side-effects observed in conventional therapies have made them unpromising in curing Hepatocellular carcinoma; therefore, developing novel treatments can be an overwhelming significance. One of such novel agents is curcumin which can induce apoptosis in various cancerous cells, however, its poor solubility is restricted its application. To overcome this issue, this paper employed dendrosomal curcumin (DNC) was employed to in prevent hepatocarcinoma in both RNA and protein levels. Hepatocarcinoma cells, p53 wild-type HepG2 and p53 mutant Huh7, were treated with DNC and investigated for toxicity study using MTT assay. Cell cycle distribution and apoptosis were analyzed using Flow-cytometry and Annexin-V-FLUOS/PI staining. Real-time PCR and Western blot were employed to analyze p53, BAX, Bcl-2, p21 and Noxa in DNC-treated cells. DNC inhibited the growth in the form of time-dependent manner, while the carrier alone was not toxic to the cell. Flow-cytometry data showed the constant concentration of 20μM DNC during the time significantly increases cell population in SubG1 phase. Annexin-V-PI test showed curcumin-induced apoptosis was enhanced in Huh7 as well as HepG2, compared to untreated cells. Followed by treatment, mRNA expression of p21, BAX, and Noxa increased, while the expression of Bcl-2 decreased, and unlike HepG2, Huh7 showed down-regulation of p53. In summary, DNC-treated hepatocellular carcinoma cells undergo apoptosis by changing the expression of genes involved in the apoptosis and proliferation processes. These findings suggest that DNC, as a plant-originated therapeutic agent, could be applied in cancer treatment.
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http://dx.doi.org/10.1016/j.ijpharm.2016.05.039DOI Listing
July 2016

Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia.

Sci Rep 2016 Apr 6;6:24057. Epub 2016 Apr 6.

Joint Research Center for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, 52062 Aachen, Germany.

Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34(+) similarity as a disease progression marker to patient-derived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients' disease history within chronic phase (CP) and significantly separates "early" from "late" CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis.
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http://dx.doi.org/10.1038/srep24057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822142PMC
April 2016

The Association Between Primary Open Angle Glaucoma and Clustered Components of Metabolic Syndrome.

Open Ophthalmol J 2015 6;9:149-55. Epub 2015 Oct 6.

Department of Ophthalmology, Jundishapur University of Medical Sciences, Ahvaz, Iran.

Purpose: There is conflicting evidence whether components of metabolic syndrome (MetS) increase or decrease the risk of primary open-angle glaucoma (POAG). The aim of the present study was to determine the association between metabolic syndrome and primary open-angle glaucoma.

Methods: A total of 200 participants comprising 100 controls and 100 patients with POAG documented by clinical tests and examined by an experienced ophthalmologist using standard ophthalmologic equipment were included in the study. MetS was defined and based on ATP III criteria and POAG was defined by the criteria of the International Society of Geographic and Epidemiological Ophthalmology (ISGEO). The data were entered into the SPSS software and analyzed.

Results: The prevalence of MetS in the glaucoma group was 53% in comparison to 38% in the control group (p=0.037). MetS was associated with an increased odds ratio for an IOP higher than 21 mmHg (OR: 1.72; 95% CI 1.03-2.79; p=0.034). The mean IOP was 24.91±4.29 mmHg in the patients without MetS, and 27.23±4.81 mmHg in those with MetS (p=0.027). The mean values of CCT were 603.64±63.16 µm in MetS patients and 579.27±72.87 µm in controls (p=0.018).

Conclusion: Data showed an increased prevalence of components of metabolic syndrome in patients with glaucoma. The mechanisms underlying these associations need to be established in future studies. Our results support the recommendation that patients with metabolic syndrome undergo regular ophthalmological exams to monitor for the onset or progression of glaucoma.
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http://dx.doi.org/10.2174/1874364101509010149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627385PMC
November 2015

The effect of Se salts on DNA structure.

J Photochem Photobiol B 2012 Aug 8;113:36-41. Epub 2012 May 8.

Department of Chemistry, Islamic Azad University, Central Tehran Branch (IAUCTB), Tehran 14676-86831, Iran.

There is considerable interest in the role of selenium in cancer prevention. Various organic and inorganic Se compounds are considered to be antioxidants. In the present study, the binding modes, the binding constants and the stability of Se-DNA complexes have been determined by Fourier transform infrared (FTIR) and UV-Visible spectroscopic methods. Spectroscopic evidence showed that Na(2)SeO(4) and Na(2)SeO(3) bind to the minor and major grooves of DNA and the backbone phosphate (PO(2)) with overall binding constants of K(Na(2)SeO(4)-DNA)=5.20×10(4) M(-1) and K(Na(2)SeO(3)-DNA)=1.87×10(3) M(-1). DNA aggregations occurred at high selenium concentrations. No biopolymer conformational changes were observed upon Na(2)SeO(3) and Na(2)SeO(4) interactions, while DNA remained in the B-family structure.
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http://dx.doi.org/10.1016/j.jphotobiol.2012.04.012DOI Listing
August 2012

Is 8860 variation a rare polymorphism or associated as a secondary effect in HCM disease?

Arch Med Sci 2011 Apr 17;7(2):242-6. Epub 2011 May 17.

National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.

Introduction: mtDNA defects, both deletions and point mutations, have been associated with hypertrophic cardiomyopathies. The aim of this study was to establish a spectrum for mtDNA mutations in Iranian hypertrophic cardiomyopathy (HCM) patients.

Material And Methods: The control group was chosen among the special medical centre visitors who did not have hypertrophic cardiomyopathy or any related heart disease. Hypertrophic cardiomyopathy (HCM) is widely accepted as a pluricausal or multifactorial disease. Because of the linkage between energy metabolism in the mitochondria and cardiac muscle contraction, it is reasonable to assume that mitochondrial abnormalities may be responsible for some forms of HCM. Point mutations and deletions in the two hot spot regions of mtDNA were investigated by PCR and sequencing methods.

Results: Some unreported point mutations have been found in this study but no deletion was detected. Meanwhile some of these point mutations have been investigated among HCM patients for the first time.

Conclusions: A8860G transition was detected in a high proportion, raising the question whether this rare polymorphism is associated as a secondary effect in HCM disease.
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http://dx.doi.org/10.5114/aoms.2011.22074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258716PMC
April 2011

A novel mutation in the transactivation-regulating domain of the androgen receptor in a patient with azoospermia.

J Androl 2011 Jul-Aug;32(4):367-70. Epub 2010 Dec 2.

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

Genetic factors including Y chromosome microdeletions and androgen receptor (AR) gene mutations are responsible for male infertility. In the present study, genetic analysis was performed in an infertile Iranian male with azoospermia. Multiplex polymerase chain reaction with 6 sequence-tagged site markers on the Yq11 chromosome revealed no microdeletions in the Y chromosome. Single-strand conformational polymorphism and sequencing analyses detected a 1510C→A transversion in exon 1 of the AR gene, which resulted in a p.Pro504Thr substitution in the transactivation domain of the protein. The present study suggested that mutations in the AR gene might be responsible for some cases of idiopathic infertility, and therefore, molecular analyses may be useful for genetic counseling of candidates with regard to the use of assisted reproductive techniques.
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http://dx.doi.org/10.2164/jandrol.110.010645DOI Listing
September 2011

Mutations in the gene encoding paired box domain (PAX8) are not a frequent cause of congenital hypothyroidism (CH) in Iranian patients with thyroid dysgenesis.

Arq Bras Endocrinol Metabol 2010 Aug;54(6):555-9

Clinical Genetic Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

Objective: Congenital hypothyroidism (CH) may be caused by defects in the thyroid or in one of the stages in the synthesis of thyroid hormones. Thyroid dysgenesis may be associated with mutation in the paired box transcription factor 8 (PAX8) gene. We attempted to screen PAX8 gene mutation in 50 CH patients with thyroid dysgenesis.

Subjects And Methods: The patients were classified in two groups as agenesis and ectopic based on biochemical and para clinical tests. By employing PCR, Single Strand Conformation Polymorphism (SSCP) and sequencing, exons 3 to 12 of PAX8 gene with their exon-intron boundaries were studied.

Results: No mutation was found in these patients in any of the exons.

Conclusion: Our results, once again, indicate that the PAX8 mutation rate is very low and can only explain a minority of the cases. Therefore, it is highly needed to further investigate the genes controlling development and function of thyroid.
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http://dx.doi.org/10.1590/s0004-27302010000600008DOI Listing
August 2010

High prevalence of AZFb microdeletion in Iranian patients with idiopathic non-obstructive azoospermia.

Indian J Med Res 2010 Sep;132:265-70

Biology Department Islamic Azad University (IAU), Science & Research Branch, Tehran, Iran.

Background & Objectives: Genetic factors contribute about 10 per cent of male infertility. Among these, genes in azoospermia factor (AZF) region including AZFa, AZFb, AZFc and AZFd on the long arm of Y chromosome are considered most important for spermatogenesis. Deletions in these regions are thought to be involved in some cases of male infertility associated with azoospermia or oligozoospermia. We studied the incidence of AZF deletions among Iranian infertile men with idiopathic non-obstructive azoospermia.

Methods: A total of 100 Iranian azoospermic infertile men were selected for the molecular study of Y chromosome microdeletions. The presence of 13 sequence tagged site (STS) markers from AZF region was investigated using multiplex polymerase chain reaction (M-PCR). One hundred fertile men were also studied as control group.

Results: Twelve (12%) patients showed Y chromosome microdeletions and among these, deletion in AZFb region was the most frequent (66.67%) followed by AZFc (41.67%), AZFd (33.33%) and AZFa (8.33%), respectively.

Interpretation & Conclusions: Because of relatively high incidence of Y chromosome microdeletions among Iranian azoospermic patients, molecular screening may be advised to infertile men before using assisted reproductive treatments.
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September 2010