Review article epithelial to mesenchymal transition­associated microRNAs in breast cancer.

Despite major advances, breast cancer (BC) is the most commonly diagnosed carcinoma and remains a deadly disease among women worldwide. Many researchers point toward an important role of an epithelial to mesenchymal transition (EMT) in BC development and promoting metastasis. Here, will be discussed that how functional changes of transcription factors, signaling pathways, and microRNAs (miRNA) in BC promote EMT. A thorough understanding the EMT biology can be important to determine reversing the process and design treatment approaches. There are frequent debates as to whether EMT is really relevant to BC in vivo, in which due to the intrinsic heterogeneity and tumor microenvironment. Nevertheless, given the importance of EMT in cancer progression and metastasis, the implementation of therapies against cancer-associated EMT will continue to help us develop and test potential treatments.

Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies.

Metastatic breast cancer remains a serious health concern and numerous investigations recommended medicinal plants as a complementary therapy. Crocin is one of the known anticancer bio-component. Recently, the inhibitory effect of metformin has been studied on the various aspects of cancer. However, no study reported their combination effects on metastatic breast cancer. In the present study, we have assessed their anti-metastatic effects on in vitro and in vivo breast cancer models. Using MTT assay, scratch, and adhesion tests, we have evaluated the cytotoxic, anti-invasive and anti-adhesion effects of crocin and metformin on 4T1 cell line, respectively. Their protective effects and MMP9 as well as VEGF protein expression levels (Western blotting) investigated in the 4T1 murine breast cancer model. Our results showed that both crocin and metformin reduced cell viability, delayed scratch healing and inhibited the cell adhesion, in vitro. While crocin alone restored the mice's weight reduction, crocin, metformin, and their combination significantly reduced the tumor volume size and enhanced animal survival rate in murine breast cancer model, responses that were associated with VEGF and MMP9 down-regulation. These findings suggest that a combination of crocin and metformin could serve as a novel therapeutic approach to enhance the effectiveness of metastatic breast cancer therapy.

Effect of medication therapy combined with transcranial direct current stimulation on depression and response inhibition of patients with bipolar disorder type I: a clinical trial.

OBJECTIVE: Bipolar Disorder (BD) is one of the most common mental disorders associated with depressive symptoms and impairment in executive functions such as response inhibition. This study aimed to investigate the effectiveness of medication therapy combined with Transcranial Direct Current Stimulation (tDCS) on depression and response inhibition of patients with BD. METHOD: This is a double-blinded randomized clinical trial with pretest, posttest, and follow-up design. Participants were 30 patients with BD randomly assigned to two groups of Medication+tDCS (n = 15, receiving medications plus tDCS with 2 mA intensity over dorsolateral prefrontal cortex for 10 days, two sessions per day each for 20 min) and Medication (n = 15, receiving mood stabilizers including 2-5 tables of 300 mg (mg) lithium, 200 mg sodium valproate, and 200 mg carbamazepine two times per day). Pretest, posttest and 3-month follow-up assessments were the 21-item Hamilton Depression Rating Scale (HDRS) and a Go/No-Go test. Collected data were analyzed in SPSS v.20 software. RESULTS: The mean HDRS score in both groups was reduced after both interventional techniques, where the group received combined therapy showed more reduction (P < 0.01), although their effects were not maintained after 3 months. In examining response inhibition variable, only the combined therapy could reduce the commission error of patients under a go/no-go task (p < 0.05), but its effect was not maintained after 3 months. There was no significant difference in the group received medication therapy alone. CONCLUSION: Medication in combination with tDCS can reduce the depressive symptoms and improve the response inhibition ability of people with BD. TRIAL REGISTRATION: This study was registred by Iranian Registry of Clinical Trials (Parallel, ID: IRCT20191229045931N1 , Registration date: 24/08/2020).

Positive correlation between vitamin D receptor gene TaqI variant and gastric cancer predisposition in a sample of Iranian population.

Gastric cancer is the second cause of cancer-related mortality and the fourth most common cancers worldwide. Owing to the immune modulatory effect of vitamin D in the body, the role of vitamin D receptor gene in vitamin D regulation receives a great deal of research interest. The aim of the current study was to highlight the association between two variants of TaqI and FokI in the vitamin D receptor gene and gastric cancer predisposition in a sample of South Khorasan population. The present investigation consisted of 69 patients affected with gastric cancer and 100 healthy individuals. The genomic DNA was extracted by salting out the protocol from peripheral venous blood. Genotyping of TaqI and FokI variants were performed by PCR-RFLP method. Our findings manifested that TC genotype of TaqI polymorphism was statistically significant between the case and the control groups (p = 0.002). Moreover, the frequency of TC + CC genotypes was statistically significant between the two groups (p = 0.009). Furthermore, we could not find any meaningful association between FokI variant and the participant groups. The present results declared that, in our population, TC genotype of TaqI polymorphism has an association with gastric cancer susceptibility. In addition, more investigation with greater sample sizes is needed to confirm our results.

A Randomized Clinical Trial to Assess the Effect of Medication Therapy Plus tDCS on Problem-solving and Emotion Regulation of Patients with Bipolar Disorder Type I.

Objective: This study aims to evaluate the effectiveness of medication therapy combined with transcranial Direct Current Stimulation (tDCS) in improving problem-solving and emotion regulation abilities of patients with bipolar disorder (BD) type I. Methods: This is a randomized clinical trial conducted on 30 patients with BD I, randomly assigned into two groups of Medication (n = 15, receiving mood stabilizers including 2-5 tablets of lithium 300 mg, sodium valproate 200 mg, and carbamazepine 200 mg) and Medication + tDCS (n = 15, receiving mood stabilizers plus tDCS with 2 mA intensity over the right dorsolateral prefrontal cortex for 10 days, two sessions per day each for 20 minutes). The Tower of London (TOL) test and Emotion Regulation Questionnaire (ERQ) were used for assessments before, immediately, and 3 months after interventions. Results: There was a significant difference between groups in total ERQ (p = 0.001) and its cognitive reappraisal domain (p = 0.000) which were increased, but the difference was not significant in its expressive suppression domain (p > 0.05). After 3 months, their level decreased. In examining problem-solving variable, the combined therapy could significantly reduce only the total number of errors under TOL test (p = 0.00), but it remained unchanged after 3 months. Conclusion: Medication therapy plus tDCS is effective in improving problem-solving and emotional regulation (cognitive reappraisal) skills of patients with BD I.

Therapeutic potential of Ferula foetida(Bunge) Regel on gastric ulcer model in rats.

The plant Ferula foetida(Bunge) Regel (FFBR) has a long history in Asian traditional medicine. This study aimed to evaluate the ulcer healing potential of FFBR umbel ethanolic extract on acetic acid-induced chronic gastric ulcer in rats. First, the gastric ulcer model was imitated by serosal application of acetic acid in male Wistar rats. Then, the animals were orally fed by ethanolic extract of FFBR umbel (100 mg/kg, 200 mg/kg, and 300 mg/kg), omeprazole (40 mg/kg), or saline for 12 days. Eventually, on the 13th day, animals were sacrificed, and their stomachs were taken out. The macroscopic and microscopic appearances of gastric ulcers and the levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in gastric tissues were assessed. In addition, the expression of NF-κB p65 was investigated by immunohistochemistry. Compared to the untreated rats with gastric ulcer, FFBR extract significantly decreased ulcer area even superior to omeprazole in a dose-dependent manner. Moreover, histological examination revealed that the extract (300 mg/kg) accelerated the epithelialization and differentiation of proliferative cells to mucosal tissue. The FFBR extract (300 mg/kg) increased tissue levels of VEGF and PGE2, but it did not affect MDA levels in rats with gastric ulcers. FFBR treatment (all doses) could significantly inhibit the expression of NF-κB p65 in gastric tissue. Taken together, experimental findings suggested that FFBR could accelerate the healing process of gastric ulcers in rats through mediating NF-κB and VEGF/PGE2 pathways.

The effect of risperidone and electroconvulsive therapy on corrected QT interval in electrocardiogram of psychiatric patients.

BACKGROUND: Some types of antidepressants and antipsychotic medications have cardiovascular side effects that can be life-threatening. Electroconvulsive therapy (ECT) is capable of generating physiological stress and may lead to increased QT interval followed by arrhythmias. Risperidone can also increase the risk of arrhythmia by increasing the corrected QT (QTc) interval. Since many patients require co-administration of risperidone and ECT, this study aimed to investigate the concurrent effect of ECT and risperidone administration on the QTc interval. METHODS: For this cross-sectional study, 60 patients (18-65 years) admitted in 22 Bahman Psychiatric Hospital (Qazvin, Iran) that were candidate for treatment with risperidone, ECT, or both methods were concurrently divided into three groups. The groups included patients treated with ECT, risperidone, and combination treatment (risperidone and ECT). At the beginning of the study, electrocardiogram (ECG) was obtained for all patients and QT was performed manually, and finally, QTc interval was measured two times for each group. Required information was collected through medical records. Then, inferential statistics, analysis of variance (ANOVA), was used to determine differences between different variables. RESULTS: A significant increase in heart rate (HR) in the third group compared to first and second groups was observed. None of the treatments had a significant effect on QTc interval, but the QTc interval increased slightly in groups treated with the ECT alone and particularly, the ECT plus risperidone in comparison to the baseline values. CONCLUSION: Our study showed that risperidone, ECT, and their concomitant combination did not affect the QTc interval. Therefore, risperidone and ECT are safe and their combination can also be a good option for refractory patients undergoing ECG monitoring and cardiopulmonary devices.

Effect of tannic acid-templated mesoporous silica nanoparticles on iron-induced oxidative stress and liver toxicity in rats.

The present study sought to investigate the effects of amino-functionalized tannic acid-templated mesoporous silica nanoparticles (TA-MS-NH2 NPs) on giving rats protection against iron-induced liver toxicity. To this end, the TA-MS-NH2 NPs were characterized using field-emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR). Moreover, 50 Wistar rats were randomly divided into one control group (group 1) and four experimental groups (groups 2- 5) (n = 10), each of which received 100 mg/kg oral normal saline and FeSO4, respectively. Then, post-exposure hepatotoxicity and oxidative stress markers were measured in two intervals, i.e., after 4 and 24 h, followed by the measurement of the acute iron toxicity. Furthermore, hepatotoxicity markers, including the alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total antioxidant capacity (TAC), were measured via Ferric Reducing Antioxidant Power (FRAP) and 2,2,1-diphenyl-1-picrylhydrazyl (DPPH) assays. Also, malondialdehyde (MDA), total thiol groups, advanced oxidation protein products (AOPP), and nitrite/nitrate (NOx) levels were measured as oxidative stress markers in the serum samples. The results indicated that oral administration of iron significantly elevated the liver enzymes and altered the level of oxidative stress markers. It was also found that treatment with TA-MS-NH2 NPs meaningfully protected against hepatotoxicity, decreased ALT, AST, ALP, and significantly improved oxidative stress markers by decreasing MDA, AOPP, and NOx levels and increasing TAC and thiol group contents, proving that TA-MS-NH2 NPs could protect rats against iron-induced acute liver toxicity through their antioxidant features.