Publications by authors named "Hamid Reza Rahimi"

80 Publications

Para-Clinical and Immunological Evaluation in Buerger's Disease as a Suspected Autoimmune Disease: Case Series.

Rep Biochem Mol Biol 2021 Jan;9(4):379-384

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

Background: Autoimmunity causes the loss of normal immune homeostasis and involves the presence of autoantibodies and inflammation. Thromboangiitis obliterans or Buerger's disease (BD) refers to a type of vascular obstructive syndrome, with tobacco exposure accounting for disease formation and progression. However, the current understanding of autoimmunity is unclear in the context of BD, and the scientific findings are not enough to support autoimmune mechanisms. This study was aimed at investigating autoimmunity factors in patients with BD.

Methods: Clinical and experimental examinations were performed on 80 patients with BD. The diagnostic work-up for autoimmunity was composed of IgM rheumatoid factor (RF), anti-nuclear antibodies (ANA), The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (CCP) antibodies, Antiphospholipid antibodies (APA), Anti-cardiolipin antibodies (ACLA), anti-double-stranded DNA (ds-DNA), and extractable nuclear antigen (ENA) profile. Immunomarkers were detected using the quantitative enzyme-linked immunosorbent assay (ELISA).

Results: Raynaud's phenomenon (84.93%), cold sensitivity (76.25%), and claudication (73.75%) were the most common symptoms in the BD patients. Also, 64.29% represented with high ANA levels and positive RF, while 42.11% were found with increased ANA and ESR levels. The ANA/RF positive BD patients had ESR> 15 mm/hr and a high prevalence of cold sensitivity, claudication, and Raynaud's phenomenon (p> 0.05).

Conclusion: There is a possibility of a non-specific autoimmune disposition among BD patients. RF and ANA could be considered for predicting disease progression.
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http://dx.doi.org/10.52547/rbmb.9.4.373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068440PMC
January 2021

The effects of nano-curcumin supplementation on glycemic control, blood pressure, lipid profile, and insulin resistance in patients with the metabolic syndrome: A randomized, double-blind clinical trial.

Phytother Res 2021 Apr 13. Epub 2021 Apr 13.

Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Metabolic syndrome (MetS) is one of the most important health hazards. Curcumin is extracted from Curcuma longa (turmeric), which can affect the components of MetS. To increase the oral bioavailability of curcumin, nano-micelle curcumin is used instead of curcumin powder. In this randomized, double-blind, controlled clinical trial, 50 patients with MetS were randomly assigned to two groups to receive either 80 mg/day nano-curcumin (n = 25) or placebo (n = 25), for 12 weeks anthropometric measurements, blood pressure, and biochemical factors-including fasting blood sugar (FBS), Hemoglobin A1c (HbA1c), homeostatic model assessment (HOMA) for insulin resistance (HOMA-IR), pancreatic β cell function (HOMA-β) and lipid profile-were assessed at the baseline and the end of the study. Statistical analyses were done using SPSS software (Version 23). The analysis between the two groups has illustrated a significant reduction in the average change of triglyceride (TG) levels (-60.5 ± 121.7 vs. 13.1 ± 78.1 mg/dL; p < .05) and HOMA-β (-5.7 ± 48.2 vs. -4.01 ± 16.9; p < .05). But there were no significant differences in anthropometric measurements, blood pressure and biochemical factors-including FBS, HbA1c, HOMA-IR, HOMA-β, and lipid profile variables include (total cholesterol, LDL-C, and HDL-C) at the end of the study. In conclusion, supplementation with nano-micelle curcumin significantly improved serum TG in MetS patients.
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http://dx.doi.org/10.1002/ptr.7109DOI Listing
April 2021

Bioactive anti-oxidative polycaprolactone/gelatin electrospun nanofibers containing selenium nanoparticles/vitamin E for wound dressing applications.

J Biomater Appl 2021 Mar 15:8853282211001359. Epub 2021 Mar 15.

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

In this study, polycaprolactone/gelatin (PCL/GEL) electrospun nanofibers containing biogenic selenium nanoparticles (Se NPs) and Se NPs/vitamin E (VE) with average diameters of 397.8 nm and 279.5 nm, respectively (as determined by SEM inspection) were prepared and their effect on wound healing was evaluated using in-vivo studies. The energy dispersive X-ray (EDX) mapping, TEM micrograph, and FTIR spectra of the prepared nanofibers strongly demonstrated well entrapment of Se NPs and VE into scaffolds. An amount of 57% Se NPs and 43% VE were gradually released from PCL/GEL/Se NPs/VE scaffold after 4 days immersion in PBS solution (pH 7.4). The both PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds supported 3T3 cell proliferation and attachment as confirmed by MTT assay and SEM imaging. Complete re-epithelialization, low level of edema and inflammatory cells in coordination with high level of oriented collagens demonstrated the wound healing activity of PCL/GEL/Se NPs/VE. Besides, significant antioxidant efficacy of PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds was demonstrated according to GSH and MDA assays. To sum up, the prepared PCL/GEL/Se NPs/VE scaffold in the present study represented suitable healing effect on animal model which candidate it for further studies.
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http://dx.doi.org/10.1177/08853282211001359DOI Listing
March 2021

Chemokines as the critical factors during bladder cancer progression: an overview.

Int Rev Immunol 2021 Feb 16:1-15. Epub 2021 Feb 16.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Bladder cancer (BCa) is one of the most frequent urogenital malignancies which is mainly observed among men. There are various genetic and environmental risk factors associated with BCa progression. Transurethral endoscopic resection and open ablative surgery are the main treatment options for muscle invasive BCa. BCG therapy is also employed following the endoscopic resection to prevent tumor relapse. The tumor microenvironment is the main interaction site of tumor cells and immune system in which the immune cells are recruited via chemokines and chemokine receptors. In present review we summarized the main chemokines and chemokine receptors which have been associated with histopathological features of BCa patients in the world. This review highlights the chemokines and chemokine receptors as critical markers in early detection and therapeutic purposes among BCa patients and clarifies their molecular functions during BCa progression and metastasis.
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http://dx.doi.org/10.1080/08830185.2021.1877287DOI Listing
February 2021

Genetic and molecular biology of systemic lupus erythematosus among Iranian patients: an overview.

Auto Immun Highlights 2021 Jan 30;12(1). Epub 2021 Jan 30.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Systemic lupus erythematosus (SLE) is a clinicopathologically heterogeneous chronic autoimmune disorder affecting different organs and tissues. It has been reported that there is an increasing rate of SLE incidence among Iranian population. Moreover, the Iranian SLE patients have more severe clinical manifestations compared with other countries. Therefore, it is required to introduce novel methods for the early detection of SLE in this population. Various environmental and genetic factors are involved in SLE progression.

Main Body: In present review we have summarized all of the reported genes which have been associated with clinicopathological features of SLE among Iranian patients.

Conclusions: Apart from the reported cytokines and chemokines, it was interestingly observed that the apoptosis related genes and non-coding RNAs were the most reported genetic abnormalities associated with SLE progression among Iranians. This review clarifies the genetics and molecular biology of SLE progression among Iranian cases. Moreover, this review paves the way of introducing an efficient panel of genetic markers for the early detection and better management of SLE in this population.
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http://dx.doi.org/10.1186/s13317-020-00144-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847600PMC
January 2021

The effects of nanomicelle of curcumin on the matrix metalloproteinase (MMP-2, 9) activity and expression in patients with coronary artery disease (CAD): A randomized controlled clinical trial.

ARYA Atheroscler 2020 May;16(3):136-145

Associate Professor, Pharmacological Research Center of Medicinal Plants AND Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Coronary artery disease (CAD) is the most common type of cardiovascular disease. Increasing the expression and activity of matrix metalloproteinases (MMPs) facilitates vascular remodeling and cardiovascular complications. Curcumin (the active ingredient of turmeric) is a potent natural anti-inflammatory agent, with cardiovascular protective effects. The present study was a clinical trial for investigating the effects of curcumin on activity and gene expression of MMP-2 and MMP-9 in patients with CAD.

Methods: In this study, 70 patients with CAD (with 40%-50% stenosis) were randomly divided into two groups of curcumin (80 mg nanomicelle per day) and placebo. The intervention lasted 3 months. The activity levels of MMP-2 and MMP-9 in serum samples of patients were measured using gelatin zymography assay before and after the intervention. MMP-2 and MMP-9 gene expression in peripheral blood mononuclear cells (PBMCs) was also analyzed using real-time polymerase chain reaction (PCR). Statistical significance was set at P < 0.0500.

Results: After 3 months of medication, the expression of MMP-9 produced by PBMCs significantly decreased in the curcumin group (0.811 ± 0.25) in comparison with the placebo group (2.23 ± 0.94) (P < 0.0001). Furthermore, the zymographic analysis showed that the administration of curcumin significantly inhibited the activity levels of MMP-2 (12469.7 ± 5308.64 pixels) and MMP-9 (14007.2 ± 5371.67 pixels) in comparison with that in patients receiving placebo (MMP-2: 17613.8 ± 5250.68 pixels; MMP-9: 20010.1 ± 3259.37 pixels) (P < 0.0500).

Conclusion: Our results show that curcumin can significantly reduce the expression and activity of MMP-2 and MMP-9. Because of the anti-inflammatory effects of curcumin, this compound can be considered as a new strategy for the prevention of cardiovascular events.
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http://dx.doi.org/10.22122/arya.v16i3.1938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778509PMC
May 2020

Controlled and cellulose eco-friendly synthesis and characterization of BiOCO quantum dot nanostructures (QDNSs) and drug delivery study.

Sci Rep 2020 12 4;10(1):21302. Epub 2020 Dec 4.

Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

This work aimed to prepare solvent-free or green BiOCO for quantum dot nanostructures (QDNSs) based on cellulose as a stabilizer and green capping agent to sorafenib delivery for liver targeting. Because the walnut tree is one of the most abundant trees in Iran, it was tried to synthesize BiOCO QDNSs using a walnut skin extract. The saturation magnetization for BiOCO QDNSs was calculated to be 68.1. Also, the size of products was measured at around 60-80 nm with the Debye-Scherrer equation. Moreover, the morphology, functional groups, and crystallography of the BiOCO nanoparticles were investigated using atomic force microscopy, scanning electron microscopy, vibrating-sample magnetometer, and Uv-vis spectroscopy. The results demonstrated that BiOCO QDNSs have opto-magnetic properties and they can be suggested as the candidate materials for the sorafenib delivery on the liver tissue. The optical band gap estimated for BiOCO QDNSs was found to be red-shift from 3.22 eV. This study suggests the preparation of the BiOCO QDNSs based on cellulose as new opto-magnetic materials at different temperatures of 180 °C, 200 °C, 220 °C, and 240 °C for sorafenib delivery as a type of biological therapy drug.
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http://dx.doi.org/10.1038/s41598-020-78266-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718884PMC
December 2020

Cytokine analysis in patients with different stages of thromboangiitis obliterans.

Curr Mol Med 2020 Nov 19. Epub 2020 Nov 19.

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

Background: Studies suggest that cytokines are involved in the development of both inflammatory disorders and vascular diseases.

Objective: The changes in transforming growth factor β (TGFβ), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) with the progression of the thromboangiitis obliterans (TAO) symptomswereinvestigated in this research.

Methods: This study included 80 patients with TAO, who were selected from the Vascular and Endovascular Research Center in Alavi Hospital between 2012 and 2016. They were then categorized into three groups: mild (migratory thrombophlebitis, cold sensitivity or Raynaud's phenomenon, and skin discoloration), moderate (chronic ulcers, claudication, and burning pain of the feet at night), and severe (pain at rest and spontaneous gangrene) symptoms. The serum levels of TGFβ, IL6, TNFα, and IFNγwere determinedby the ELISA method and compared among the groups.

Results: The first three predominant symptoms were pulse disorder (n = 76, 95.00%), cold intolerance (n = 61, 76.25%), and claudication (n = 59, 73.75%). A comparison of the analysis of covariance (ANCOVA) revealed that both TGFβ and IL6 were dysregulatedas the severity of the symptoms increased from the moderate to the severe stages; however, such changes were not significant(p > 0.05). In the multiple logistic regression model, increased TNFαlevelswere seen in the presence of the moderatesymptoms as compared to the severe ones (p < 0.05).

Conclusion: It could be concluded that TNFα, as part of the defining cytokine-production profile of Thelper cells, can be significantly involved in the progression of TAO from the moderate to the severe stages.
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http://dx.doi.org/10.2174/1566524020666201120112828DOI Listing
November 2020

Non coding RNAs as the critical factors in chemo resistance of bladder tumor cells.

Diagn Pathol 2020 Nov 12;15(1):136. Epub 2020 Nov 12.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Bladder cancer (BCa) is the ninth frequent and 13th leading cause of cancer related deaths in the world which is mainly observed among men. There is a declining mortality rates in developed countries. Although, the majority of BCa patients present Non-Muscle-Invasive Bladder Cancer (NMIBC) tumors, only 30% of patients suffer from muscle invasion and distant metastases. Radical cystoprostatectomy, radiation, and chemotherapy have proven to be efficient in metastatic tumors. However, tumor relapse is observed in a noticeable ratio of patients following the chemotherapeutic treatment. Non-coding RNAs (ncRNAs) are important factors during tumor progression and chemo resistance which can be used as diagnostic and prognostic biomarkers of BCa.

Main Body: In present review we summarized all of the lncRNAs and miRNAs associated with chemotherapeutic resistance in bladder tumor cells.

Conclusions: This review paves the way of introducing a prognostic panel of ncRNAs for the BCa patients which can be useful to select a proper drug based on the lncRNA profiles of patients to reduce the cytotoxic effects of chemotherapy in such patients.
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http://dx.doi.org/10.1186/s13000-020-01054-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659041PMC
November 2020

Verapamil Inhibits Mitochondria-Induced Reactive Oxygen Species and Dependent Apoptosis Pathways in Cerebral Transient Global Ischemia/Reperfusion.

Oxid Med Cell Longev 2020 17;2020:5872645. Epub 2020 Oct 17.

Anatomical Sciences Department, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

The prefrontal cortex is the largest lobe of the brain and is consequently involved in stroke. There is no comprehensive practical pharmacological strategy for ameliorating prefrontal cortex injury induced by cerebral ischemia. Therefore, we studied the neuroprotective properties of verapamil (Ver) on mitochondrial dysfunction and morphological features of apoptosis in transient global ischemia/reperfusion (I/R). Ninety-six Wistar rats were allocated into four groups: control, I/R, I/R+Ver (10 mg/kg twice 1 hour prior to ischemia and 1 hour after reperfusion phase), and I/R+NaCl (vehicle). Animals were sacrificed, and mitochondrial dysfunction parameters (i.e., mitochondrial swelling, mitochondrial membrane potential, ATP concentration, ROS production, and cytochrome c release), antioxidant defense (i.e., superoxide dismutase, malondialdehyde, glutathione peroxidase, catalase, and caspase-3 activation), and morphological features of apoptosis were determined. The results showed that mitochondrial damage, impairment of antioxidant defense system, and apoptosis were significantly more prevalent in the I/R group in comparison with the other groups. Ver decreased mitochondrial damage by reducing oxidative stress, augmented the activity of antioxidant enzymes in the brain, and decreased apoptosis in the I/R neurons. The current study confirmed the role of oxidative stress and mitochondrial dysfunction in I/R progression and indicated the possible antioxidative mechanism of the neuroprotective activities of Ver.
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http://dx.doi.org/10.1155/2020/5872645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591985PMC
May 2021

Dietary Inflammatory Index is associated with Healthy Eating Index, Alternative Healthy Eating Index, and dietary patterns among Iranian adults.

J Clin Lab Anal 2020 Dec 27;34(12):e23523. Epub 2020 Aug 27.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Recent investigations have evaluated the effect of the inflammatory potential of diet in several populations by calculating the Dietary Inflammatory Index (DII) score. We aimed to evaluate the association of the DII with the Healthy Eating Index (HEI), the Alternative Healthy Eating Index (AHEI), and dietary pattern (DP) among healthy Iranian adults.

Methods: A cross-sectional study was conducted among 4365 middle-aged adults. Major DPs and DII score were identified using a validated semi-quantitative food frequency questionnaire (FFQ). Poisson regression was used to evaluate the association of DPs, HEI, and AHEI across tertiles of DII.

Results: After adjustment for confounding variables, a low HEI (HEI < 55) and AHEI (AHEI < 56.5) were more prevalent among the participants in the highest tertile of DII compared to the first tertile (PR: 1.13, P-value <.05; PR: 1.10, P-value <.05; respectively). Adherence to a balanced healthy dietary pattern was significantly lower in subjects with a diet that was more pro-inflammatory compared to those with anti-inflammatory diet (PR: 0.85, P-value P < .01). No significant association was found between the DII and a western DP. High levels of HDL and hip and waist circumference were observed in the highest tertile of DII, and high levels of dietary intake of protein and fiber, minerals, fasting blood glucose, and monounsaturated fat were reported in the lowest tertile of DII.

Conclusion: The highest tertile of the DII (a pro-inflammatory diet) was associated with a lower HEI, AHEI, and lower adherence to balanced DP in a representative sample of adults in Iran.
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http://dx.doi.org/10.1002/jcla.23523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755771PMC
December 2020

Role of tyrosine kinases in bladder cancer progression: an overview.

Cell Commun Signal 2020 08 14;18(1):127. Epub 2020 Aug 14.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Bladder cancer (BCa) is a frequent urothelial malignancy with a high ratio of morbidity and mortality. Various genetic and environmental factors are involved in BCa progression. Since, majority of BCa cases are diagnosed after macroscopic clinical symptoms, it is required to find efficient markers for the early detection. Receptor tyrosine-kinases (RTKs) and non-receptor tyrosine-kinases (nRTKs) have pivotal roles in various cellular processes such as growth, migration, differentiation, and metabolism through different signaling pathways. Tyrosine-kinase deregulations are observed during tumor progressions via mutations, amplification, and chromosomal abnormalities which introduces these factors as important candidates of anti-cancer therapies.

Main Body: For the first time in present review we have summarized all of the reported tyrosine-kinases which have been significantly associated with the clinicopathological features of BCa patients.

Conclusions: This review highlights the importance of tyrosine-kinases as critical markers in early detection and therapeutic purposes among BCa patients and clarifies the molecular biology of tyrosine-kinases during BCa progression and metastasis. Video abstract.
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http://dx.doi.org/10.1186/s12964-020-00625-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427778PMC
August 2020

ADME and toxicity considerations for tramadol: from basic research to clinical implications.

Expert Opin Drug Metab Toxicol 2020 Jul 27;16(7):627-640. Epub 2020 Jun 27.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences , Kerman, Iran.

Introduction: Tramadol is widely being used in chronic pain management for improving patients' life quality and reducing trauma. Although it is listed in several medicinal guidelines, its use is controversial because of the conflicting results obtained in pharmacokinetic/pharmacodynamic studies. This multi-receptor drug acts as µopioid receptor agonist, monoamine reuptake inhibitor, and inhibitor of ligand-gated ion channels and some special protein-coupled receptors.

Areas Covered: This review provides a comprehensive view on the pharmacokinetic, pharmacodynamic, and toxicity of tramadol with a deep look on its side effects, biochemical and pathological changes, and possible drug interactions. In addition, the main ways of tramadol poisoning management describe according to  and clinical trial studies.

Expert Opinion: Given the broad spectrum of targets, increasing the cases of overdoses and toxicity, and probable drugs interaction, it is necessary to take another look at the pharmacology of tramadol. Regarding the adverse effects of tramadol on different tissues, especially the nervous system and liver tissue, more attentions to tramadol metabolites, their interaction with other drugs, and active agents seem critical. Seizure as the most cited effect of tramadol and its destructive effects on tissues would alleviate by co-administration with drugs with antioxidant properties.
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http://dx.doi.org/10.1080/17425255.2020.1776700DOI Listing
July 2020

Dyslipidemia and cardiovascular disease risk among the MASHAD study population.

Lipids Health Dis 2020 Mar 16;19(1):42. Epub 2020 Mar 16.

Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Introduction: Dyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran.

Material And Methods: This prospective cohort study comprised a population of 8698 men and women aged 35-65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence.

Results: After 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19-2; P-value< 0.01; HR: 1.53; 95% CI: 1.18-1.98; P < 0.01; HR: 1.57; 95% CI: 1.27-2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12-6.57; P-value< 0.05).

Conclusion: In the present study, TC baseline level was significantly associated with the risk of MI among men.
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http://dx.doi.org/10.1186/s12944-020-01204-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075010PMC
March 2020

The effect of nanomicelle curcumin, sorafenib, and combination of the two on the cyclin D1 gene expression of the hepatocellular carcinoma cell line (HUH7).

Iran J Basic Med Sci 2019 Oct;22(10):1198-1202

Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: Hepatocellular carcinoma (HCC) is one of the most significant health condition around the world. As the only curative therapies, liver transplantation and surgical resection are the clinical treatments of HCC. Due to the systemic toxicity and severe side effects of these treatments, it is vital to establish new therapeutic approaches. The present study aimed to compare cyclin D1 (CCN D1) gene expression in hepatocellular carcinoma cell line (HUH7) when it is treated with nanomicelle curcumin and sorafenib. The purpose was to identify toxicity risk and antioxidant activity of these drugs.

Materials And Methods: The toxic dose (IC) of nanomicelle curcumin and sorafenib were detected after treatment of HUH7 cell lines with different dose of mentioned agents followed by MTT assay. CCN D1 gene expression was evaluated using real-time PCR. Following the Tukey's multiple comparison tests, statistical analysis is done through Student's t-test or ANOVA.

Results: The expression of the CCN D1 gene was statistically significant (<0.001) at 289.31, 128 and 152.36 for sorafenib, nanomicelle curcumin and SNC (sorafenib-nanomicelle curcumin) respectively. The finding of this study revealed that, in comparison to sorafenib alone, the treatment of HUH7 with a nanomicelle curcumin IC dose, in combination with sorafenib, might down-regulate CCN D1 gene expression.

Conclusion: The present research indicates that the treatment of the cell line with only nanomicelle curcumin results in the down-regulation of cyclin D1. To further decrease cyclin D1 expression, the co-delivery of curcumin and sorafenib appears to induce the apoptotic process. As a result, the effect of sorafenib cytotoxicity and CCN D1 gene expression decreases twofold.
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http://dx.doi.org/10.22038/ijbms.2019.35808.8530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885396PMC
October 2019

The Association of HLA-A, B and DRB1 with Buerger's Disease.

Rep Biochem Mol Biol 2019 Jul;8(2):153-160

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

Background: Thromboangiitis obliterans (TAO), also known as Burger's disease, is a devastating disease affecting the arteries and veins of the upper and lower distal limbs most commonly afflicting young male smokers of low socioeconomic status. The expression of human leukocyte antigen (HLA)-A, B and -DRB1 genes have been implicated in the pathogenesis of TAO. Our study aimed to examine the association of different HLA-A, B and -DRB1 genes in TAO patients in the Iranian population.

Methods: A case-control study examining 55 Iranian patients with TAO and 500 healthy subjects was performed in Imam Reza hospital, Mashhad, Iran. The prevalence of major histocompatibility complex (MHC) class I (-A, -B) and class II (-DRB) alleles were determined for each participant.

Results: Our results revealed the -A*03 (odds ratio [OR]=5.394), -A*24 (OR=5.143), -A*31 (OR=4.251), -A*11 (OR=3.034), HLA-B*27 (OR=6.680), HLA-B*15 (OR=3.959), -B*07 (OR=3.698), -B*51 (OR=3.370), -B*44 (OR=3.326), -DRB1*16 (OR=20.583), HLADRB1* 04 (OR=8.960), -DRB1*14 (OR=3.746), -DRB1*03 (OR=2.303), and -DRB1*15 (OR=2.111) alleles to occur at a significantly higher frequency in TAO patients compared to controls (p<0.05). The -A*25, -A*66, -DRB1*08, -DRB1*10, and -DRB1*12 alleles resulted in infinite OR, and was associated with an increased risk of TAO. However, the alleles -A*30, -B*08, -B*45, -B*46, and -B*53 were associated with a protective role against TAO with an OR = 0.

Conclusion: This is the first study examining the pattern in patients with Burger's disease in the Iranian population. Our findings have revealed an association between class I and II alleles with TAO.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844607PMC
July 2019

Antioxidant, cytotoxic and hyperalgesia-suppressing activity of a native Shilajit obtained from Bahr Aseman mountains.

Pak J Pharm Sci 2019 Sep;32(5):2167-2173

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Shilajit, a blackish-brown exudation obtained from steep rocks of different mountains, has been longly used as a therapeutic agent in traditional medicine. The present study was designed to evaluate the antioxidant, cytotoxic and hyperalgesia-suppressing activity of the aqueous and DMSO extracts of a native Shilajit. The antioxidant and cytotoxic effects of Shilajit extracts was determined using DPPH scavenging activity and MTT assay methods, respectively. In order to examine the hyperalgesia-suppressing activity of the Shilajit aqueous extract the STZ-induced diabetic animals were subjected to oral administration of the extract (50, 100 and 200 mg/kg daily) for six weeks followed by evaluating the behavioral examination (hot plate and tail flick tests) compared to those of diabetic control (Sham) and vehicle groups. The obtained results of antioxidant evaluation of Shilajit represented scavenging activity of 50% at concentration of 2500 μg/mL and 6000 μg/mL in the case of aqueous and DMSO extracts, respectively. Cytotoxic study of water extract of Shilajit revealed IC50 of 727.5±1.9 μg/mL and 1103±3.2 μg/mL on cell lines of MCF-7 (breast cancer) and A549 (lung cancer), respectively. Thermal pain response examination of diabetic rats treated with aqueous extract of Shilajit (100 mg/kg and 200 mg/kg) for six weeks reduced hyperalgesia compared to vehicle and Sham groups. To sum up, considering the moderate antioxidant and hyperalgesia-suppressing activity of this native Shilajit make it as a suitable candidate for further investigation after isolation and characterization of the active compounds.
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September 2019

Rapid and Facile Microwave-Assisted Synthesis of Palladium Nanoparticles and Evaluation of Their Antioxidant Properties and Cytotoxic Effects Against Fibroblast-Like (HSkMC) and Human Lung Carcinoma (A549) Cell Lines.

Biol Trace Elem Res 2020 Sep 28;197(1):132-140. Epub 2019 Nov 28.

Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran.

We report here a simple microwave irradiation method (850 W, 3 min) for the synthesis of palladium nanoparticles (Pd NPs) using ascorbic acid (as reducing agent) and sodium alginate (as stabilizer agent). The synthesized nanoparticles were characterized using transmission electron microscopy (TEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-Visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. Antioxidant properties and cytotoxic effects of as-synthesized Pd NPs and Pd (II) acetate were also assessed. UV-Vis study showed the formation of Pd NPs with maximum absorption at 345 nm. From TEM analysis, it was observed that the Pd NPs had spherical shape with particle size distribution of 13-33 nm. Based on DPPH radical scavenging activity and reducing power assay, the antioxidant activities of Pd NPs were significantly higher than the Pd (II) acetate (p < 0.05). At the same concentration of 640 μg/mL, the scavenging activities were 32.9 ± 3.2% (Pd (II) acetate) and 27.2 ± 2.1% (Pd NPs). For A549 cells treated 48 h with Pd NPs, Pd (II) acetate, and cisplatin, the measured concentration necessary causing 50% cell death (IC) was 7.2 ± 1.7 μg/mL, 32.1 ± 2.1 μg/mL, and 206.2 ± 3.5 μg/mL, respectively. On HSkMC cells, the IC of the Pd NPs (320 μg/mL) was higher compared to Pd (II) acetate (228.7 ± 3.6 μg/mL), which confirmed lower cytotoxicity of the Pd NPs.
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http://dx.doi.org/10.1007/s12011-019-01984-0DOI Listing
September 2020

Novel mutation in AIRE gene with autoimmune polyendocrine syndrome type 1.

Immunobiology 2019 11 6;224(6):728-733. Epub 2019 Sep 6.

Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Purpose: Autoimmune polyendocrine type 1 (APS-1) is a complex inherited autosomal recessive disorder. Classically, it appears within the first decade of life followed by adrenocortical insufficiency, mucocutaneous candidiasis, Addison's disease, and hypoparathyroidism. The clinical phenotype of APS-1 varies depending upon mutations in the autoimmune regulator gene (AIRE) on chromosome 21q22.3.

Methods: In this study, we performed Sanger sequencing ofAIRE in Iranian patients to identify different variants and probable new mutations corresponding to a clinical diagnosis of APS-1.

Results: After analyzing 14AIRE exons, we detected a novel insertion mutation in exon 2 in a patient who presented with severe APS-1, Lys50AsnfsX168. Furthermore, the known mutations in AIRE, including Arg139X, Arg257X, and Leu323SerfsX51, were detected in enrolled patients.

Discussion: According to our results, sequencing analysis ofAIRE provides a useful screening method to diagnose patients with incomplete or unusual clinical presentations of APS-1.
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http://dx.doi.org/10.1016/j.imbio.2019.09.004DOI Listing
November 2019

Ondansetron enhanced diclofenac-induced nephrotoxicity in mice.

J Biochem Mol Toxicol 2019 Sep 23;33(9):e22378. Epub 2019 Jul 23.

Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

This study was performed to investigate the effect of ondansetron, a serotonin receptor (5-HT3) antagonist, in the alleviation of diclofenac-induced kidney injuries. NMRI mice were randomly divided into six groups and treated with (A) untreated control group, (B) diclofenac (100 mg/kg), (C) ondansetron (1 mg/kg), (D to F) ondansetron (0.1, 0.5, and 1 mg/kg, respectively) and diclofenac (100 mg/kg) for last 3 days of experiment. The oxidative stress tests strongly demonstrated the negative synergistic effects of diclofenac and ondansetron, regarding the observation of dose-dependent enhancement of malondialdehyde concentration, and reduction of glutathione content, and superoxide dismutase and catalase activity. Histopathological analyses revealed dose-dependent tubular epithelial cells degeneration, outstanding mononuclear cells infiltration, clear necrosis at the papillary region of kidney, dilation, and vascular hyperemia in mice kidney tissues treated with ondansetron and diclofenac. Conclusively, these findings suggested the possible ondansetron-diclofenac interaction through the induction of oxidative stress.
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http://dx.doi.org/10.1002/jbt.22378DOI Listing
September 2019

Molecular mechanisms regulating immune responses in thromboangiitis obliterans: A comprehensive review.

Iran J Basic Med Sci 2019 Mar;22(3):215-224

Immunology Research Group, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Thromboangiitis obliterans (TAO) is a thrombotic-occlusive as well as an inflammatory peripheral vascular disease with unknown etiology. Recent evidence has supported the immunopathogenesis of the disease, however, the factors contributing to the altered immune function and vascular tissue inflammation are still unclear. This review was intended to collate the more current knowledge on the regulatory molecules involved in TAO from an immunoreactive perspective. The homeostasis of the immune system as well as a variety of progenitor cell populations appear to be affected during TAO and these alterations are associated with intrinsic signaling defects that are directing to an improved understanding of the crosstalk between angiogenesis and the immune system, as well as the potential of new co-targeting strategies applying both immunotherapy and angiogenic therapy.
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http://dx.doi.org/10.22038/ijbms.2019.31119.7513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528722PMC
March 2019

Toxicity of microwave-assisted biosynthesized zinc nanoparticles in mice: a preliminary study.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):1846-1858

c Department of Pharmaceutical Biotechnology, Faculty of Pharmacy , Kerman University of Medical Sciences , Kerman , Iran.

This study was designed to describe the oral acute and subacute toxicities and underlying toxicological mechanisms of biogenic Zn NPs in mice. The Zn NPs were prepared by a green microwave-assisted synthesis method in the presence of Lavandula vera leaf extract. Determination of median lethal dose (LD) of Zn NPs and the subacute toxicity after 14 days of exposure was performed as a measurement of substance toxicity through general toxicological, hematological, serum, and histopathological investigations. The western blotting was used to determine the cleaved-caspase-3 expression in the sampled tissues. Flame atomic absorption spectrophotometer (AAS) was applied to estimate the Zn levels in tissues. The SEM analyses revealed that the biogenic Zn NPs were spherical-shaped with the size range of 30-80 nm. The LD value above 5 g/kg indicated that biogenic Zn NPs could be classified as non-toxic chemicals. In subacute toxicity, no significant differences were found in the body weight as well as hematological and oxidative stress (OS) biomarkers after exposure to Zn NPs at the dose of 1 g/kg in comparison to the control. The AAS results indicated that Zn NPs were mainly distributed in the testis, liver, and brain. The findings of histology images of Zn NPs at the dose of 1 g/kg were similar to those of the control. Furthermore, no significant differences were observed in cleaved-caspase-3 expression after exposure to Zn NPs at the dose of 5 g/kg. The results demonstrated that changes in the OS were not related to caspase pathway and the no-observed-adverse-effect level (NOAEL) dose of biogenic Zn NPs in 14-days subacute toxicity study was lower than 1 g/kg.
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http://dx.doi.org/10.1080/21691401.2019.1611592DOI Listing
December 2019

Evaluation of antitumor effect of oxygen nanobubble water on breast cancer-bearing BALB/c mice.

J Cell Biochem 2019 09 3;120(9):15546-15552. Epub 2019 May 3.

Department of Biology, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran.

Hypoxia is a condition of low oxygen level which poses a common feature of most cancers. In the current study, we investigated effect of water containing oxygen nanobubble (ONB) on tumor growth in breast cancer 4T1-bearing mice during 14-day treatment period. Tumor-bearing mice were randomly divided into three groups (six mice per group), including the ONB group drinking water containing ONB, the air nanobubble (ANB) group drinking water containing ANB, and control group drinking normal water. Tumor weight and size were measured in 2-day interval during 14-day treatment. mRNA expression of p53, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), and cyclin D/Cdk2 genes were measured in the treated and control mice. After 8, 12, and 14 days of treatment, tumor size in ONB group was significantly decreased by 40.5%, 32.8%, and 28%, respectively, when compared with the control group. In addition, ANB group showed a significant reduction in tumor burden as well. The messenger RNA (mRNA) level of p53 in tumor cells of ONB and ANB group was found to be 36-fold (P = 0.0001) and 33-fold (P = 0.0001) higher than that in the control group, respectively. There was a ninefold increase in mRNA expression of VEGF gene in tumor cells of ANB mice than that in control mice; however, there was no significant changes in ONB group. Expression of HIF gene was significantly lower in tumor cells of ONB and ANB group than in the control group. It is concluded that drinking ONB water has potential to inhibit tumor growth, however more preclinical and proof-of-concept studies are needed to confirm its safety and therapeutic effect.
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http://dx.doi.org/10.1002/jcb.28821DOI Listing
September 2019

Cytotoxicity investigations of biogenic tellurium nanorods towards PC12 cell line.

IET Nanobiotechnol 2018 Dec;12(8):1144-1149

Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

The authors evaluated the cytotoxicity underlying mechanisms of biogenic tellurium (Te) nanorods (NRs) produced by the strain Te on the PC12 cell line. The half-maximal inhibitory concentration (IC) value was estimated at 5.05 ± 0.07 ng/ml for biogenic Te NRs and 2.44 ± 0.38 ng/ml for KTeO, respectively. The viability of PC12 was inhibited concentration dependent at doses of 1, 2.5, 5, 10, and 20 ng/ml. Te NRs principally induced late apoptosis or necrosis at IC concentration, without effect on caspase-3 activities. Furthermore, Te NRs reduced glutathione and enhanced malondialdehyde levels, and also reduced superoxide dismutase and catalase activities. These findings revealed that biogenic Te NRs were less toxic than KTeO. Additionally, they induced cytotoxity towards the PC12 cell line through the activation of late apoptosis independent of the caspase pathway, and may also enhance oxidative stress in the nervous system.
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http://dx.doi.org/10.1049/iet-nbt.2018.5137DOI Listing
December 2018

Nano-curcumin's suppression of breast cancer cells (MCF7) through the inhibition of cyclinD1 expression.

Breast Cancer (Dove Med Press) 2019 13;11:137-142. Epub 2019 Mar 13.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran,

Background: Breast cancer is the leading cause of cancer worldwide. The high expenses associated with chemotherapy as well as its side effects make the management of breast cancer a daunting challenge. The most common overexpressed gene in breast cancer is cyclinD1, which induces cell proliferation. Recent investigations into cancer treatment have revealed that curcumin demonstrates potential anti-cancer properties through different pathways. However, the oral bioavailability of curcumin is negligible due to its high hydrophobic structure. Nanotechnology has been employed to overcome this barrier. Nano-formulated curcumin (SinaCurcumin) has been shown to provide a significantly higher bioavailability for oral consumption. However, the efficacy of this nano-formulated drug in breast cancer has not yet been determined. In relation to the breast cancer cell line, the present study compared nano-curcumin's anti-cancer properties with those of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF).

Methods: After treating MCF7 with nano-curcumin and CAF, the present work assessed cell viability via an MTT assay. The effects of these drugs on cyclinD1 expression were measured by real-time PCR. SPSS 16.0 was used to perform ANOVA and multiple range tests.

Results: Nano-curcumin and the CAF regimen both lowered the viability of MCF7. Nano-curcumin decreased cell proliferation by 83.6%, which was more than that achieved by cyclophosphamide (63.31%), adriamycin (70.75%), and 5-fluorouracil (75.04%). In addition, curcumin was able to significantly reduce the expression of cyclinD1, whereas CAF did not alter cyclinD1 expression.

Conclusion: Nano-curcumin has a relatively high cytotoxic effect on MCF7 breast cancer cells, suppressing the expression of cyclinD1, a critical gene in the development and metastasis of breast cancer. The current study demonstrated that nano-curcumin can be an effective drug in the CAF regimen for the treatment of breast cancer. However, further in vivo research is needed for determining its efficacy and safety in clinical applications.
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http://dx.doi.org/10.2147/BCTT.S195800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420787PMC
March 2019

Prevalence, characteristics and antimicrobial susceptibility patterns of Clostridioides difficile isolated from hospitals in Iran.

J Glob Antimicrob Resist 2019 12 27;19:22-27. Epub 2019 Feb 27.

Department of Research and Technology, Kerman Branch, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Kerman, Iran.

Objectives: Clostridioides (previously Clostridium) difficile is a major growing cause of nosocomial diarrhoea known as C. difficile infection (CDI). This study investigated the prevalence and antimicrobial resistance patterns of C. difficile isolated from patients suffering from diarrhoea in Iran between 2016-2018.

Methods: A total of 151 stool specimens were collected and were screened for the presence of C. difficile. Specimens were examined for toxins by culture, enzyme immunoassay (EIA) and PCR. Antimicrobial susceptibility testing was performed for 12 antibiotics (metronidazole, vancomycin, clindamycin, tetracycline, erythromycin, ciprofloxacin, levofloxacin, moxifloxacin, fusidic acid, piperacillin, piperacillin/tazobactam and rifampicin) by the disk diffusion method according to the guidelines of the CLSI, EUCAST and CA-SFM.

Results: Of 151 stool specimens, 66 (43.7%) were positive for C. difficile by PCR, whereas 2 (1.3%) were only positive for C. difficile toxins based on EIA. A total of 292 clostridial isolates were obtained from specimens by culture, of which 133 (45.5%) were finally confirmed as C. difficile by PCR. Of 121 isolates resistant to at least one antibiotic, 107 (88.4%) were resistant to three or more antimicrobials and thus were defined as multidrug-resistant (MDR). Different and diverse resistance patterns to the antimicrobial drugs were seen among the isolates.

Conclusion: This is the first report of the isolation of C. difficile from different governmental hospitals of Iran and indicates that CDI might be an important nosocomial infection in different hospital wards. Moreover, this study provides a comprehensive picture of the MDR phenotype characteristics of C. difficile isolates in Iran.
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http://dx.doi.org/10.1016/j.jgar.2019.02.013DOI Listing
December 2019

The effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina: A randomized clinical trial.

Avicenna J Phytomed 2019 Jan-Feb;9(1):1-9

Department of Internal Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Inflammation along with oxidative stress has an important role in the pathophysiology of unstable angina which leads to acute myocardial infarction, arrhythmias and eventually heart failure. Curcumin has anti-inflammatory and anti-oxidant effects and thereby, it may reduce cardiovascular complications. This randomized controlled trial aimed to investigate the effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina.

Materials And Methods: Forty patients with unstable angina who met the trial inclusion and exclusion criteria, participated in this double-blind randomized clinical trial. The patients were randomized into two groups: curcumin (80 mg/day for 5days) and placebo (80 mg/day for 5days). Cardiac function was evaluated by two-dimensional echocardiography devices at baseline (immediately after hospitalization) and 5 days after the onset of the trial. Atrial and ventricular arrhythmias were recorded by Holter monitors in cardiology ward, Ghaem academic hospital, Mashhad, Iran. Progression to heart failure, myocardial infarction, and pulmonary and cardiopulmonary resuscitation events as well as mortality were recorded daily throughout the study.

Results: There were no significant differences between the two groups in atrial and ventricular arrhythmias (p=0.2), and other echocardiographic parameters (Ejection fraction, E, A, E/A ratio, Em, and pulmonary artery pressure) at baseline and five days after the start of the trial.

Conclusion: Nanocurcumin administered at the dose of 80 mg/day for five days had no effect in the incidence of cardiovascular complications in patients with unstable angina.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369319PMC
February 2019

Determining the interaction behavior of calf thymus DNA with berberine hydrochloride in the presence of linker histone: a biophysical study.

J Biomol Struct Dyn 2020 02 17;38(2):364-381. Epub 2019 Feb 17.

Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

The binding of small molecules with histone-DNA complexes can cause an interference in vital cellular processes such as cell division and the growth of cancerous cells that results in apoptosis. It is significant to study the interaction of small molecules with histone-DNA complex for the purpose of better understanding their mechanism of action, as well as designing novel and more effective drug compounds. The fluorescence quenching of ct-DNA upon interaction with Berberine has determined the binding of Berberine to ct-DNA with  = 9.46 × 10 M. value of ct-DNA-Berberine in the presence of H1 has been observed to be 3.10 × 10 M, indicating that the H1 has caused a reduction in the binding affinity of Berberine to ct-DNA. In the competitive emission spectrum, ethidium bromide (EB) and acridine orange (AO) have been examined as intercalators through the addition of Berberine to ct-DNA complexes, which includes ctDNA-EB and ctDNA-AO. Although in the presence of histone H1 , we have observed signs of competition through the induced changes within the emission spectra, yet there has been apparently no competition between the ligands and probes. The viscosity results have confirmed the different behaviors of interaction between ctDNA and Berberine throughout the binary and ternary systems. We have figured out the IC50 and viability percent values at three different time durations of interaction between Berberine and MCF7 cell line. The molecular experiments have been completed by achieving the results of MTT assay, which have been confirmed to be in good agreement with molecular modeling studies.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2019.1574240DOI Listing
February 2020

Oral administration of nanomicelle curcumin in the prevention of radiotherapy-induced mucositis in head and neck cancers.

Spec Care Dentist 2019 Mar 14;39(2):166-172. Epub 2019 Feb 14.

Department of New Science and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Oral mucositis (OM) is a complication of head and neck cancer (HNC) therapy with negative impact on the quality of life. Although definitive treatment has not yet been established, there is interest towards the use of natural compounds owing to their few side effects. Curcumin has a variety of biological and pharmacological properties including anticancer and anti-inflammatory effects.

Aim: The aim of this study is to evaluate the effect of curcumin in the form of nanomicelle on OM in HNC patients receiving radiotherapy.

Methods: In this clinical trial, 32 HNC patients were allocated to case and control groups, and respectively received nanocurcumin or placebo during radiotherapy.

Results: We found a statistically significant difference in the severity of mucositis between the 2 groups at all visits. In contrast to the control-group patients, who all developed OM in the 2nd week of radiotherapy, only 32% of the case group developed OM with no obvious oral or systemic side effects.

Conclusion: Our data show that nanomicelle curcumin is an effective agent in the prevention of OM or reducing its severity. Thus, the administration of nanocurcumin can be considered as a reasonable approach to hinder the development of OM in HNC patients requiring radiotherapy.
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http://dx.doi.org/10.1111/scd.12358DOI Listing
March 2019

Impact of Ondansetron on Withdrawal Signs, Fentanyl Requirement and Pain Relief in Opioid-addicted Patients under General Anesthesia.

Curr Clin Pharmacol 2019 ;14(3):232-241

Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Background: Serotonin 5-HT3 receptor antagonists such as ondansetron have been investigated to attenuate opioid withdrawal signs in studies.

Objective: Therefore, we designed a randomized double-blinded placebo-controlled trial to evaluate this effect on opioid-addicted patients who were admitted to the orthopedic department for surgery due to bone fractures.

Methods: Male adults who were addicted to opioids, aged 18 to 79 years were enrolled (n=96) and randomized into intravenous doses (4 & 8 mg) of ondansetron (n=32) and placebo (n=32). The vital signs, withdrawal symptoms and the frequency requirement of fentanyl were recorded during anesthesia, and opioid (pethidine) analgesic was received during the recovery period. Outcome parameters were analyzed for reduction of withdrawal symptoms in addicted adults.

Results: We indicated that ondansetron demonstrated significant differences with few vital outcomes including systolic blood pressure (SBP) 20 (SBP3) and 50 min (SBP4) after injection of ondansetron during the period of surgery. Ondansetron could also significantly reduce the frequency requirement of fentanyl at 20 min (dose 3) in general anesthesia. Furthermore, requirement for further administration of opioid analgesic drugs such as pethidine was significantly reduced in the ondansetron groups. Objective opioid withdrawal scale (OOWS) results indicated that few clinical parameters including tremor, hot and cold flushes and anxiety were significantly attenuated in addicted patients who received ondansetron.

Conclusion: This study demonstrated supporting evidence for the beneficial treatment of ondansetron for the control of withdrawal symptoms and pain in addicted patients, and more clinical studies are suggested in this regard.
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http://dx.doi.org/10.2174/1574884714666190131122846DOI Listing
August 2020