NF-kB affects migration of vascular smooth muscle cells after treatment with heparin and ibrutinib.

The migration of vascular smooth muscle cells (VSMCs) is one of the most important events in the remodeling of atherosclerosis plaque. The aim of study was to investigate the role of Heparin in the VSMC migration and its association with the NF-kB, collagen 1 and collagen 3 expression levels. Moreover, the incorporation of Heparin was studied in the VSMC cultures including Betulinic acid and Ibrutinib. Twelve cell groups were cultured and treated with the Heparin, Betulinic acid and Ibrutinib based on the viability and toxicity in 24-h and 48-h periods. The gene and protein expression levels were measured by RT-qPCR and western blotting techniques. The VSMC migration was determined by scratch test. In contrast with Ibrutinib (2 µM), Heparin (30 IU) increased significantly (P < 0.05) the NF-kB gene and protein expression levels and the VSMC migration during the exposure periods. Heparin (15 IU and 30 IU) also increased the collagen 1 gene expression level in the 48-h period while Heparin (5 IU and 15 IU) increased the collagen 3 gene expression levels in both periods. Incorporating Heparin into the cultures including Betulinic acid and Ibrutinib affected the collagen 1 and collagen 3 expression levels. The data suggested that the cell migration relates to NF-kB in the VSMCs treated with Heparin and Ibrutinib. Furthermore, the Heparin doses (5 IU and 15 IU) were safe for VSMCs based on the NF-kB, and collagen 3 expression levels.

Beta arrestin-related signalling axes are influenced by dexamethasone and metformin in vascular smooth muscle cells cultured in high glucose condition.

BACKGROUND: Metformin (Met) and dexamethasone (Dexa) are known to reduce blood sugar levels and anti-inflammatory effects, respectively. Based on the acceleration of atherosclerosis process in diabetes, the ß-arrestin 2 (BARR2) gene and protein expression levels were evaluated in vascular smooth muscle cells (VSMCs) treated with Met and Dexa in high glucose conditions in this study. METHODS AND MATERIALS: Human VSMCs were cultured in Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM-F12) medium and, were treated with different values of Met (1 mM, 5 mM and 7 mM) and Dexa (10-7 M, 10-6 M and 10-5 M) in 24- and 48-h periods. The BARR2 gene and protein expression levels were identified with RT-qPCR and western blotting techniques, respectively. The signalling axes were predicted from gene network made using Cytoscape software and, were annotated with Gene Ontology. RESULTS: The BARR2 gene and protein expression levels reduced in VSMCs treated with Dexa and Met after 24- and 48-h periods. These results were more changed after 48 h. Furthermore, many BARR2-related signalling axes were found from the network genes. CONCLUSION: Met and Dexa suppressed the BARR2 protein and gene expression levels in the VSMCs. Moreover, the gene network suggested some the cellular signalling axes related to BARR2 that may be affected by Met and Dexa.

The effect of metformin on the metabolism of human vascular smooth muscle cells in high glucose conditions.

OBJECTIVES: Metformin is widely used in type 2 diabetic patients as an antihyperglycemic drug. The aim of this study was to investigate the effect of metformin on the metabolism of vascular smooth muscle cells in high glucose conditions. MATERIALS AND METHODS: The vascular smooth muscle cells were cultured in DMEM F12 containing glucose as high as 25 mM. The preconditioned cells were then treated with metformin in doses of 1, 5, and 7 mM for 24 h. MTT method was used to determine cell viability. Biochemical parameters including lactate, glucose, total protein, creatinine, and triglyceride were measured in the cell culture after the treatment with metformin. Oil Red O staining method was used to stain the lipids in the cells. RESULTS: Metformin reduced significantly (p<0.001) VSMC proliferation in a concentration-dependent manner. With the increase of glucose uptake by VSMCs, the cell lipid deposition was not changed. Other biochemical parameters such as lactate, triglyceride, total protein, and creatinine were significantly changed in the cell culture (p<0.05). CONCLUSIONS: Metformin increased the glucose uptake impacting metabolic pathways in VSMCs. It also increased the lactate efflux and protein metabolism without the change in cellular lipid deposition in high glucose conditions.

Non-coding RNAs are correlated to TGF-ß receptor type 2 in patients with colorectal cancer.

BACKGROUND: Multiple molecular expression alterations, particularly in non-coding RNAs, play fundamental roles in the regulations of cellular processes and may relate to the occurrence and progression of colorectal cancer (CRC). In the present study, we investigated the associations between TGFBR2, miR20a-5p and long non-coding RNA (lncRNA) LAMTOR5-AS1 in CRC patients. METHODS: Colorectal cancer and adjacent normal tissue samples (n = 34) were prepared from CRC patients. The associations between TGFBR2, miR20a-5p and lncRNA LAMTOR5-AS1 were predicted using bioinformatics tools. The expression levels of TGFBR2, miR20a-5p and lncRNA LAMTOR5-AS1 were measured using a quantitative real-time polymerase chain reaction technique. The TGFBR2 protein values were measured by western blotting. The clinical importance of lncRNA LAMTOR5-AS1 was assessed using receiver operating characteristic curve. RESULTS: The up-regulated levels of TGFBR2 (p = 0.02), TGFBR2 protein (p = 0.008) and lncRNA LAMTOR5-AS1 (p = 0.02) were significantly observed in CRC tissues compared to the adjacent normal tissues. The miR20a-5p expression level (p = 0.009) was downregulated in CRC tissues. In addition, the miR20a-5p expression level was inversely correlated to the TGFBR2 gene (r2  = 0.88, p < 0.0001), protein (r2  = 0.95, p < 0.0001) and lncRNA LAMTOR5-AS1 gene (r2  = 0.93, p < 0.0001) expression levels. Based on the area under curve, the increase of lncRNA LAMTOR5-AS1 expression level with a sensitivity of 64.52% and specificity of 65.52% was considered in CRC patients. CONCLUSIONS: We propose that miR20a-5p is inversely related to long non-coding RNA (lncRNA) LAMTOR5-AS, such that it may be involved in the regulation of TGFBR2 expression level in CRC patients.

Dexamethasone suppresses the proliferation and migration of VSMCs by FAK in high glucose conditions.

BACKGROUND: High glucose conditions cause some changes in the vessels of diabetes through the signal transduction pathways. Dexamethasone and other corticosteroids have a wide range of biological effects in immunological events. In the present study, the effects of dexamethasone were investigated on the VSMC (vascular smooth muscle cell) proliferation, and migration based on the FAK gene and protein changes in high glucose conditions. METHODS AND MATERIALS: The vascular smooth muscle cells were cultured in DMEM and were treated with dexamethasone (10-7 M, 10-6 M, and 10-5 M) for 24, and 48 h in high glucose conditions. The cell viability was estimated by MTT method. The FAK gene expression levels and pFAK protein values were determined by RT-qPCR and western blotting techniques, respectively. A scratch assay was used to evaluate cellular migration. RESULTS: The FAK gene expression levels decreased significantly dependent on dexamethasone doses at 24 and 48 h. The pFAK protein values decreased significantly with a time lag at 24- and 48-h periods as compared with gene expression levels. CONCLUSION: The results showed that the inhibition of VSMC proliferation and migration by dexamethasone in the high glucose conditions may be related to the changes of FAK.

Focal adhesion kinase-related pathways may be suppressed by metformin in vascular smooth muscle cells in high glucose conditions.

INTRODUCTION: Cardiovascular diseases are known as one of the important causes of death in patients with diabetes mellitus. Metformin is used as an oral medication for reducing blood sugar. In this study, the effects of metformin were investigated on the FAK gene expression levels, pFAK protein values, cell viability and migration rate of VSMCs in high glucose conditions. MATERIALS AND METHODS: The FAK gene expression levels and pFAK protein values were evaluated in VSMCs treated with different doses of metformin (1, 5 and 7 mM), based on cell viability using RT-qPCR, western blotting and MTT techniques. The cellular migration was evaluated by scratch assay. RESULTS: The FAK gene expression levels reduced significantly in metformin-treated VSMCs at 24 h and 48 h periods (p < .0008 and p < .0001, respectively). The pFAK protein values reduced significantly at 24 h (5 mM and 7 mM metformin doses) and 48 h periods (p < .001). In agreement with pFAK protein values, cellular migration reduced significantly at 24 h and 48 h periods (p < .001). CONCLUSION: The results showed that metformin may suppress the proliferation and migration of VSMCs via FAK-related pathways and may retard the progression of vessel stenosis in diabetes.

Upregulation of TGF-ß type II receptor in high glucose-induced vascular smooth muscle cells.

BACKGROUND: Mortality in patients with diabetes mellitus is estimated above 65% due to cardiovascular diseases. The aim of study was to investigate the effects of high-glucose conditions on TGF-ß type II receptor (TGFBR2) expression levels, cell viability, and migration rate in vascular smooth muscle cells (VSMCs). METHODS: VSMCs were incubated in 30 mM and 50 mM of glucose for 24 h, 48 h, and 72 h periods. The gene and protein expression levels were investigated by Real-time qRT-PCR and western blotting techniques, respectively. The cell viability was evaluated by MTT assay. VSMC migration rate was also studied by wound healing assay. RESULTS: The TGFBR2 gene and protein expression levels were significantly upregulated in all the groups treated with glucose in 24 h, 48 h, and 72 h periods. The cell viability was not significantly affected in values of 30 mM and 50 mM of glucose. The increase of migration rate of VSMCs was not significant. CONCLUSION: The results suggested the increased expression levels of TGFBR2 in the response to high glucose conditions may modulate the cellular events through the signaling pathway network in VSMCs.

Public Intention to Prepare for Earthquakes: Psychometric Properties of Persian Version.

BACKGROUND: People are still not prepared for earthquakes in vulnerable areas although preparedness considered an effective way of reducing the disastrous consequences. A proper tool was needed to assess the predicting factors of mitigation behaviors in a large vulnerable community who speak Persian. This study aimed to introduce the valid and reliable Persian version of public intention to prepare against earthquakes. METHODS: Translation, validation and reliability checking articulated according to the standard methodology for Forward-Backward translation and psychometric evaluation. Totally, 369 Tehran households were selected through stratified random sampling from Oct 2016 to Jun 2017. Exploratory Factor Analysis used to check the construct validity of all scales. RESULTS: Face, content and construct validity of all scales confirmed (S-CVR: .65) and (S-CVI/Universal: .98). The finalized Persian version (69 items in 8 scales) showed good reliability over time in test-retest (ICC: .92) and high internal consistency both in the pilot (α: .94) and main studies (α: .94). No significant floor and ceiling effects were found in any of scales. CONCLUSION: Persian version of Earthquake Public Intention to Prepare is applicable as a valid and reliable instrument for research regarding disaster preparedness in Persian speaking communities.

Correlations between vitronectin, miR-520, and miR-34 in patients with stenosis of coronary arteries.

BACKGROUND: In-stent restenosis usually occurs by platelet activation, neointima formation, VSMC migration, and proliferation in the position of the vessel stent. The monocytes have a magnificent role in neointimal hyperplasia since these cells recruit to the site of vessel injury through chemokines and other secretion proteins. This study is focused on the investigation of vitronectin, miR-193, miR-34, and miR-520 expression levels in PBMCs isolated from stenosed patients. METHODS: A total of sixty subjects undergoing coronary artery angiography containing patients with stent no restenosis (n = 20), in-stent restenosis (n = 20), and healthy participants (n = 20) participated in the study. The vitronectin, miR-193, miR-34, and miR-520 expression levels were measured by the RT-qPCR technique. Data were analyzed by SPSS software. RESULTS: The vitronectin, miR-34, and miR-520 expression levels changed significantly in patients with vessel in-stent restenosis (p = 0.02, p = 0.02, and p = 0.01, respectively). Furthermore, there were inverse correlations between the expression levels of vitronectin gene and miR-34 (r = - 0.44, p = 0.04) as well as miR-520 (r = - 0.5, p=0.01). CONCLUSIONS: The molecular events in the vessel stenosis may be affected by targeting vitronectin with miR-520 and miR-34.

Topiramate for the Treatment of Dually Dependent on Opiates and Cocaine: A Single-center Placebo-controlled Trial.

BACKGROUND: Topiramate facilitates gamma aminobutyric acid (GABA) transference and an ideal candidate for reducing cocaine use in methadone patients. The present study evaluated topiramate in Dual dependence on opiate and cocaine. METHODS: This placebo-controlled study (Clinical Trial Registration Code: TCTR20170201001) conducted during the period 2013-2014, Cocaine-dependent individuals maintained on methadone (n=50) were randomized to receive topiramate or identical placebo capsules. Participants' dosage ranged between 25-300 mg/day (12 wk) in escalating doses. Methadone Doses started at 30 mg/day (median 100 mg/day; range 20 -140 mg/day). In addition, all subjects received brief behavioral compliance enhancement treatment (BBCET). The data were analyzed by Chi-square Test, generalized estimating equations (GEE) models, linear mixed effects (LME) model and Analysis of covariance (ANCOVA). Primary outcome measures included twelve weekly urine drug screens (cocaine abstinence, detection of benzoylecgonine) and treatment retention. Secondary outcome measures included correlation between cocaine craving with cocaine urine samples and Side effects of depression. RESULTS: Topiramate was not better than placebo in reducing cocaine use. The secondary outcome showed that Topiramate was better than placebo in reducing cocaine craving. The mean [99% confidence interval (CI)] scores of cocaine craving were 24.31 (18.61-30.01) in experimental group and 21.84 (16.86-26.81) in control group (all P > 0.01). Retention and correlation between cocaine craving and cocaine urine samples were not significantly different between the groups. Topiramate usage was not associated with increase in depression symptoms as a side effect (P>0.05). CONCLUSION: The efficacy of topiramate in cocaine treatment is limited and needs the similar controlled clinical trials and can be used as a complementary intervention.

The predictors of earthquake preparedness in Tehran households.

BACKGROUND: The high risk of an earthquake happening and the harmful consequences that it leaves, besides the unsuccessful policies for preparing the community for mitigation, suggested that social factors should be considered more in this regard. Social trust is an influencing factor that can have significant impact on people's behavior. OBJECTIVE: To determine the relationship of the influencing factors on the preparedness of Tehran households against earthquake. METHODS: This was a cross-sectional study with 369 participants (February to April 2017) involved through stratified random sampling from selected urban districts of Tehran. The Persian version of an 'Intention to be prepared' measurement tool and a standard checklist of earthquake preparedness behaviors were used. The tool was evaluated for internal consistency and test-retest reliability in a pilot study (Cronbach's α =0.94 and Intra Class Correlation Coefficient =0.92). RESULTS: Multivariate linear regression analysis showed that social trust is the most important predictor for the preparedness mean of changes in Tehran (R2=0.109, p<0.001, ß: 0.187 for the Preparedness behavior; R2=0.117, ß: 0.298, p<0.001 for Intention to be prepared; and R2=0.142, ß: 0.345, p<0.001 for the Perceived preparedness). CONCLUSION: The relationship between social trust and preparedness dimensions suggested that changing a social behavior is not possible through considering only individual characteristics of community members and not their social networks relations. The programs and policies which try to enhance the social trust in general, may be able to increase public preparedness against earthquakes in the future.

A Comparison of Effectiveness of Parent Behavioral Management Training and Methylphenidate on Reduction of Symptomsof Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is one of the most common psychological disorders of childhood. Methylphenidate is highly effective in the treatment of ADHD. This study aimed to determine the effectiveness of combined Parent behavioral management training (PBMT) and medication treatment (Methylphenidate) in reducing ADHD symptoms in 6-12-year-old children, using randomized sampling. A total of 50 children with ADHD were assigned into two groups: an experimental group of PBMT and a control group of medication treatment (Methylphenidate) without other interventions. Conners' Parent Rating Scale (CPRS-48) was employed before and after interventions to determine the effects. Descriptive Statistics method (consisting of Mean and Standard deviation) and Statistical inference method, (including t-test and Levene's Test) were used for data analysis.  Findings revealed that the combined behavioral intervention of PBMT and methylphenidate treatment is more effective in reduction of ADHD in children. The difference of means between pre-test and post-test of CPRS in the experimental group was equal to 10.77, and it was equal to 1.88 in the control group. In addition, PBMT was more effective in the case of younger parents (P<0.025). However, parents' education level did not affect the behavioral intervention (P<0.025).The findings suggest that combined intervention of PBMT and methylphenidate is effective in reducing the symptoms of ADHD in children.

The cortisol level and its relationship with depression, stress and anxiety indices in chronic methamphetamine-dependent patients and normal individuals undergoing inguinal hernia surgery.

BACKGROUND: Stimulants addition and abuse can cause some functional and morphological changes in the normal function of glands and hormones. Methamphetamine as an addictive stimulant drug affects the Hypothalamic- pituitary-adrenal (HPA) axis and consequently makes some changes in the psychological state of the drug users. The present study aims to examine the relationship between plasma levels of cortisol with depression, stress and anxiety symptoms in chronic methamphetamine-dependent patients and normal individuals who have undergone the inguinal hernia surgery. METHODS: To meet the purpose of the study, 35 chronic methamphetamine-dependent patients in the active phase of drug abuse and 35 non-users (N=70) who were homogenized regarding the demographic features were purposefully selected from among the patients referred to undergo inguinal hernia surgery since March 15 to June 9, 2015. The participants were then divided into the control and experiment group. The changes in cortisol levels in plasma were measured using Radioimmunoassay (RIA) in three-time series including 0 (upon the induction of anesthesia), 12 and 24 hours after the surgery. Further, three behavioral indices of depression, anxiety and stress were measured using the Depression Anxiety Stress Scale 21 (DASS-21) and then the data were analyzed using t-test and Pearson Correlation coefficient. RESULTS: The plasma level of cortisol in the chronic methamphetamine-dependent patients (experiment group) had a significant increase in 24 hours after surgery (p<0.05). This study showed that cortisol levels in chronic methamphetamine-dependent patients were significantly higher than non-dependent patients in response to alarming events such as inguinal surgery. Changes in cortisol levels were intensified due to a confrontation with the phenomenon of pain and anxiety. In addition, depression index was higher in the chronic methamphetaminedependent patients than that in the non-dependent patients. However, there was no significant relationship between the cortisol level and depression index (p=0.001). CONCLUSION: The Hypothalamic-pituitary-adrenal (HPA) axis is considered as a key structure in the addiction to simulants, the reason which can explain the faster response of the chronic methamphetamine-dependent patients to the stressors such as surgery.

The Efficacy of Contingency Management on Cocaine Craving, using Prize-based Reinforcement of Abstinence in Cocaine Users.

INTRODUCTION: Contingency management (CM) is one of the most common therapies in the domain of drug addiction. This study has been carried out with the purpose of evaluating the efficacy of contingency management intervention. METHOD: In an experimental design, between December 15, 2014 and November 20, 2015, fifty men (between 18 and 31 with an average age of 24.6) with a history of cocaine use, were selected voluntarily and were randomly assigned into two groups of CM and control group. The CM group were awarded coupons for negative urine tests, over a period of twelve weeks. The urine tests were taken from the participants twice per week, with cutoff concentrations for positive set at 300 ng/ml and self-reporting index of cocaine craving (response rate = 96%) were evaluated in two phase, through pretest and posttest measures. The data were analyzed by parametric covariance test. Additionally, the qualitative data, resulted from demographic measures, were coded and were analyzed with the help of an analysis instrument of qualitative data i.e. ATLAS.ti-5.2. RESULTS: The primary outcome was the number of negative urine tests and the secondary outcome included the cocaine usage craving index over twelve weeks. The mean of (95% of confidence) number of negative cocaine urine tests was 15.4 (13.1-17.8) in the CM group and 19.7 (17.7-21.6) in the control group (P = 0.049). Also, results showed that CM has a significant effect on reducing craving (p<0.01). CONCLUSION: The findings of this study, while having practical aspects in this domain, can be valuable in planning remedial procedures.

The Effectiveness of Emotionally Focused Couples Therapy on Sexual Satisfaction and Marital Adjustment of Infertile Couples with Marital Conflicts.

BACKGROUND: The purpose of this investigation is to determine the efficacy of emotionally focused couples therapy (EFT-C) on enhancement of marital adjustment in infertile couples. MATERIALS AND METHODS: This was a semi-experimental study with a pre- and post-test design. We selected 30 infertile couples (60 subjects) by purposive sampling. Couples were randomly assigned to two groups, sample and control. Each group consisted of 15 couples who had marital maladjustment and low sexual satisfaction. Couples answered the marital adjustment and sexual satisfaction questionnaires at baseline after which the sample group received 10 sessions of EFT-C. RESULTS: Results of pre-test and post-test showed that EFT-C significantly impacted marital adjustment and sexual satisfaction. CONCLUSION: EFT-C had a significant effect on enhancement of satisfaction, cohesion and affectional expression. This approach impacted physical and emotional sexual satisfaction of infertile couples.

The Effectiveness of Emotionally Focused Therapy on Enhancing Marital Adjustment and Quality of Life among Infertile Couples with Marital Conflicts.

BACKGROUND: The purpose of this study is to investigate the efficacy of emotionally fo- cused therapy (EFT-C) on promoting marital adjustment of infertile couples with marital conflicts by improving quality of life. MATERIALS AND METHODS: This is a semi-experimental study with a pre- and post-test design in which 30 infertile couples (60 individuals) were chosen by purposive sampling. Couples were randomly divided into two groups, sample and control, of 15 couples each. Next, couples in the sample population answered questionnaires for marital adjustment, sexual satisfaction and quality of life after which they received 10 sessions of EFT-C. RESULTS: Pre- and post-tests showed that EFT-C had a significant effect on marital adjust- ment and quality of life. CONCLUSION: According to the results, EFT-C had a significant, positive effect on en- hancement of marital adjustment. Life quality of infertile couples significantly increased via application of EFT-C. This approach improved the physical, psychological and social relationships of infertile couples and enhanced their social environment.

Comparison between family power structure and the quality of parent-child interaction among the delinquent and non-delinquent adolescents.

BACKGROUND: Few studies indicate that most behavioral problems are due to family dysfunction and inappropriate family environment. It seems that the family of the delinquent adolescent is unbalanced in the power structure and parenting style. OBJECTIVES: The present study compares the family power structure and parent-child relationship quality in delinquent and non-delinquent young subjects in Tehran. PATIENTS AND METHODS: Eighty students of secondary schools aged between 15 and 18 in Tehran were enrolled with cluster sampling method and 80 delinquent adolescents of the Correction and Rehabilitation Centers aged between 15 and 18 were chosen with a convenience sampling method. They responded to an instrument of family power structure (Child-parents relationship inventory). Data was compared between these two groups by utilizing the independent and dependent t-test and Levene's test. RESULTS: The findings indicated there is a significant difference between delinquent and non-delinquent adolescents in family power structure and its subscales (P < 0.001) and father-child relationship quality (P < 0.005). Also, there is no statistically significant difference between these two groups in mother-child relationship quality (P < 0.005). Besides, the results revealed that delinquent adolescents were significantly different regarding the quality of parent-child relationship (P < 0.001). CONCLUSIONS: These results emphasize that an inappropriate decision making process pattern in a family has a significant effect on deviant behavior in adolescents. The fathers' parenting is more strongly linked to their sons' delinquency. So, family power structure and parent-child relationship can be considered in therapeutic interventions (prevention and treatment) for adolescents' delinquency.