Nrf2 Dysregulation in Major Depressive and Bipolar Disorders

Background: Major depressive disorder (MDD) and bipolar disorder (BPD) are two of the most important mental disorders that greatly impact different aspects of life. These conditions imply heavy health and economic burden and are heterogeneous in nature. Inflammation is reported as the etiology of mental disorders. Nrf2 transcription factor plays a key role in the defense mechanisms against inflammation and oxidative stress. So, this study aimed to evaluate the expression level of Nrf2 in MDD and BPD patients and compared it with healthy control subjects. Materials and Methods: In this study, real-time PCR was conducted to evaluate the expression level of Nrf2 in 100 MDD and 100 BPD patients compared to 100 healthy control subjects. Statistical analysis conducted on GraphPad Prism 8 and SPSS21 included ANOVA, Tukey’s test, receiver operating characteristic (ROC), and odds ratio. Results: Results suggest a significant downregulation of Nrf2 in these conditions compared to the control group. ROC curve analysis demonstrates Nrf2 as a biomarker of these psychiatric disorders. Conclusion: The elevated levels of reactive oxygen species and downregulation of detoxifying enzymes were observed in MDD and BPD, which can be associated with the downregulation of Nrf2. Concerning its role in inflammatory response pathways, alternation of Nrf2 expression can be associated with the pathology of these conditions.

The Expression Changes of CX3CL1 and Interlukin-6 Genes During Remission Induction Therapy in Patients With Acute Myeloid Leukemia

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

Anticipation of High-Sensitivity C-Reactive Protein Effect on Post Myocardial Infarction Depression Disorder

Background: The natural history of acute myocardial infarction (AMI) as the most prevalent public health issue in Iran has changed with the introduction of novel therapeutic strategies that have reduced its mortality significantly. Major depressive disorder (MDD) is a prevalent and disabling psychiatric disorder and frequently co-exist with AMI. There are proposed pathophysiological links between the two diseases among which inflammation is the most important. With more patients surviving a myocardial infarction (MI) event, post-MI depression has become an important determinant of disability and mortality. Materials and Methods: In this study we defined a 1-month post-MI depressive scale of 200 patients using Beck’s inventory questionnaire II and measured serum high Sensitivity C-Reactive Protein (hs-CRP) and carotid intima-media thickness (CIMT) to look for the association between inflammatory state and atherosclerosis in different depression score categories. Results: Minimum and maximum Beck scores were 1 and 43, respectively with a mean of 13±8. The mean CIMT was 0.77±0.26 mm. Serum hs-CRP level was measured with a mean of 1.51±1.6 mg/L. According to BDI-II scores, 44.2% of patients 1-month post-MI suffered from more than mild depression. Being affected was not correlated with either the level of hs-CRP or CIMT. Nearly 44 percent of patients suffered more than mild depression. There was a negative association between serum hs-CRP level and CIMT as a measure of atherosclerosis in groups of depressed versus non-depressed patients. This may indicate that the extent of atherosclerosis is not correlated with the inflammatory state after MI in depressed versus non-depressed patients. Conclusions: The results of this study indicate that the extent of atherosclerosis is not correlated with the inflammatory state after MI in depressed versus non-depressed patients. Nonetheless, the prognostic indications of increased hs-CRP and depression after AMI remains to be investigated further. [GMJ.2021;10:e1512]

Curcumin Along With Fe3O4 Nanoparticles Improved Sperm Parameters In Rats With Testicular Ischemia

Background: Ischemic/reperfusion (I/R) in testicular tissue is one reason for the worldwide increase in male infertility. In the present study, we assessed the effects of curcumin and Fe3O4 nanoparticles (NPs) on sperm parameters in rats with I/R damage. Materials and Methods: Forty-eight adult male rats were divided into two groups (n=24 per group): control and torsion/detorsion. The control and torsion/detorsion groups were divided into four subgroups include sham, Fe3O4 NPs, curcumin, and Fe3O4 NPs+curcumin. After the rats were sacrificed, semen was collected from their epididymal tissues to assess sperm viability, motility, concentration, and morphology. Results: Curcumin significantly improved viability, motility, and normal sperm morphology in rats with I/R damage compared to the control group; however, it did not have a significant effect on sperm concentration (P<0.001). Fe3O4 NPs alone decreased all sperm parameters in the control and I/R rats (P<0.001). However, concomitant administration of Fe3O4 nanoparticles with curcumin significantly improved sperm parameters in rats with I/R damage (P<0.001). Conclusion: The increase in all semen parameters in the experimental groups with concomitant use of Fe3O4 NPs plus curcumin indicated that green synthesis of NPs could be recommended for future clinical studies.

The Combination Neuroprotective Abilities of Resveratrol and Naringenin in Attenuation of Sleep Deprivation Complications in Rats

Background: Sleep loss is one of the most important health problems in the world, and about 30 to 40 percent of ordinary people suffer from it. This study aimed to investigate the neuroprotective effects of the combination of resveratrol and naringenin in attenuation of sleep deprivation (SD) complications in rats. Materials and Methods: In this experimental study, 72 Wistar male rats were randomly divided into three main groups, including control, sham, and 7-days SD group. Each of its main groups consisted of three subgroups, including without drug, vehicle, and combination therapy groups (naringenin [100 mg/kg], resveratrol [100 mg/kg]). The day after the latest injection, the fear conditioning memory tests, locomotor activity test, hot plate, and forced swimming tests (FST) were carried out on all rats, and then sham and SD groups were induced 48 hours of non-REM SD (device off and on, respectively) and these behavioral tests were repeated for all rats again. Finally, the brains of all rats were removed and histopathologically examined, and stained with nissl and TUNNEL. Results: To assess fear condition memory, the rate of latency to first freezing in the visual and auditory phase increased in sham and SD rats that received vehicle or no drug (P<0.001), which indicates memory corruption. Injection of the combination of naringenin and resveratrol reduced the latency to first freezing (P<0.001), which means improved memory. In the FST test, injection of naringenin and resveratrol reduced the rate of immobility (P<0.001), which means improved depressive behavior. The naringenin and resveratrol reduced the pain perception threshold. Also, the naringenin and resveratrol reduced apoptosis compared to the control and vehicle groups (P<0.001). Conclusions: The combination of naringenin and resveratrol compared to other groups could improve memory and mood as well as reduce apoptosis, depression, and pain perception threshold. [GMJ.2021;10:e2315]

Impact of NiO2 Nanoparticles and Curcumin on Testis Torsion/Detorsion Injury: Role of miR-34 and circRNA 0001518

Background: Testicular torsion is one cause of infertility without proper treatment. In this study, we investigate the effects of NiO2 nanoparticles (NPs) and curcumin on sperm parameters in rats and the expressions of genes involved in the apoptotic pathway, as well as expressions of miR-34 and circRNA 0001518. Materials and Methods: Forty-eight rats were randomly divided into eight groups: control (healthy rats), control rats that received NiO2-NPs, healthy rats that received curcumin, rats that received simultaneous NiO2-NPs and curcumin, untreated testicular ischemia/reperfusion (I/R) rats, testicular I/R rats that received NiO2-NPs, testicular I/R rats that received curcumin, and testicular I/R rats that received NiO2-NPs and curcumin. Then, sperms were extracted from the rats’ epididymides to analyze concentration, viability, morphology, and motility. The cellular apoptosis level was studied using flow cytometry. Also, Bad and Bcl-X gene expressions, as well as miR-34 and circRNA 0001518 levels were measured. Results: We observed improved sperm parameters in the testicular I/R) rats that received curcumin and NiO2-NPs. Administration of NiO2-NPs to healthy rats increased both apoptosis and the Bad/Bcl-X expression ratio. However, its administration to testicular I/R rats alone or in combination with curcumin decreased apoptosis and the Bad/Bcl-X expression ratio and increased expressions of miR-34 and circRNA 0001518. Conclusion: Administration of NiO2-NPs and curcumin, alone or in combination, can have therapeutic effects in testicular I/R conditions by altering the expressions of genes in the mitochondrial apoptotic pathway and their regulatory elements.

Long Noncoding RNAs-LET Behave as a Noncoding Signature for Early-Onset Menarche and Late-Onset Menopause in Breast Cancer Patients

Background: Breast cancer (BC) as a major cause of cancer-related death in women shows a very complex molecular and clinical phenotype, which has reduced the effectiveness of medical interventions. Evidence suggests that long noncoding RNAs (lncRNAs) are responsible for an important part of this complexity. This study aims to assess the expression and clinical implication of lncRNA LET in the pathobiology of BC. Materials and Methods: Quantitative real-time polymerase chain reaction was used to measure the expression of lncRNA-LET in breast tumors and adjacent normal-appearing tissues from 4 BC patients, as well as normal mammary tissues. Moreover, a bioinformatics approach was applied to uncover the potential lncRNA-LET-mediated sponge regulatory network as LET/miRNA/mRNA crosstalk. Results: Our study revealed that lncRNA-LET was significantly down-expressed not only in breast tumors but also in normal appearing breast tissues samples from BC subjects compared with true normal breast tissues obtained from healthy women. The low level of lncRNA-LET was meaningfully associated with early-onset menarche (≤13 years) and late-onset menopause (≥50) in patients. Moreover, the bioinformatics analyses support that lncRNA-LET could function as a tumor suppressor miRNA sponge. Conclusion: The results indicate that normal appearing breast tissues can undergo tumor-related molecular changes. Furthermore, they reveal the potential role of the dysregulation in LET-mediated ceRNA network in the pathophysiology of BC.

Evaluating the Effect of Electroconvulsive Shock and Duloxetine Combination Therapy on Behavioral, Cardiovascular, and Brain Oxidative Stress Markers in the Rats

Background: Electroconvulsive Therapy (ECT) as a well-established and effective therapeutic approach for the treatment of various psychiatric disorders is an excellent option to treat the major depressive disorder (MDD). The goal of this experimental study was to determine the possible sides effects of electroconvulsive shock (ECS) and duloxetine, a serotonin-norepinephrine Reuptake Inhibitors (SNRIs), and evaluate the safety of this therapeutic approach on behavioral factors, cardiovascular function, and brain oxidative stress markers on mice. Materials and Methods: Animals were divided into different groups receiving either ECS or different doses (10, 20, 40, 80, or 120 mg) of duloxetine alone or together. We evaluated the behavioral factors associated with administration of ECS with or without duloxetine. In addition, we monitored the ECGs (electrocardiogram) of animals prior to and after the experiment and also evaluated the oxidative stress markers including TAC, MDA, and GSH mice’s brains. Results: We did not detect any significant differences in terms of heart rate, RR interval, PR interval, QT, or corrected QT (QTc) between groups that received different doses of duloxetine in combination with ECS compare to the control group. Our findings suggest that while administration of ECS solely increased the oxidative stress markers and decreased the antioxidant capacity of the brain, a combination of duloxetine and ECS at certain doses alleviates the oxidative stress condition and increases the antioxidant capacity of the brain. Conclusion: Overall, this study suggests that the combination of ECS and duloxetine is safe and considerable for further studies on human subjects.

Major Dietary Patterns Are Associated with Acute Ischemic Stroke

Background: Dietary patterns play an essential role in vascular diseases; however, the association of specific dietary patterns and the risk of stroke is unknown. We designed the current study to evaluate several dietary patterns and their association with ischemic stroke. Materials and Methods: This case-control study was performed on 300 subjects, including 150 cases with ischemic stroke admitted to a tertiary referral center in Shiraz, Southern Iran, and 150 age- and sex-matched stroke-free individuals as controls. Using a 62-item Simple Stroke Food Frequency Questionnaire (SS-FFQ), we collected data regarding the dietary habits of all the participants. We extracted the major dietary patterns via principal component analysis using the varimax rotation technique with Kaiser Normalization. Finally, adherence to dietary patterns among the participants was divided into quartiles. We investigated the association between dietary patterns and ischemic stroke using multiple logistic regression analyses. Results: One-hundred and fifty ischemic stroke patients (91 males and 59 females, mean age of 63.9±16.04 years) and 150 age- and sex-matched controls (91 males and 59 females, mean age of 61.99±16.04 years) were included. After adjusting five major dietary patterns for vascular risk factors, we found that diets rich in fibers and plant-based proteins (P<0.001) and micronutrients (P<0.001) had a lower odds of ischemic stroke as compared to high-fat proteins (P=0.003) and empty calories (P<0.001) diets, but consuming healthy animal proteins (P=0.115) had no effects on the occurrence of ischemic stroke. Conclusion: Based on our study, we suggest that fibers and plant-based proteins, and micronutrient diets could reduce the odds of stroke, so public awareness about the effects of different dietary patterns should be raised.

Prevalence of Helicobacter Pylori Infection Among Patients with Dyspepsia by Stool Antigen and Serology Tests

Background: Helicobacter pylori is the most common chronic bacterial infection globally and is the underlying cause of many disorders, including dyspepsia. Also, the prevalence of gastric cancer in Zanjan city is high. Therefore, this study investigates the prevalence of H. pylori infection in patients with dyspepsia by the H. pylori stool antigen (HpSA) test. Materials and Methods: This cross-sectional study was performed on patients over 18 years of age who were referred to Shafieieh Special Clinic in Zanjan with dyspepsia during 2019-2020. First, the HpSA test was examined for H. pylori infection. Since the results of two separate tests are needed to prove that H. pylori infection is negative, the serological test was used in the patients with HpSA negative results. Results: Based on the demographic information of the present study, most patients (70.1%) were under 40 years old, and most (55.1%) were women. Smoking, alcohol, drug, and non-steroidal anti-inflammatory drugs (NSAIDs) use in patients were 16.5%, 6.3%, 7.9%, and 39.4%, respectively. The highest and lowest symptoms were abdominal pain (44.9%) and burp (22%), respectively. Except for the relationship between positive serological results and age (P˂0.001), no significant relationship was found between other variables (P≥0.05). Based on the HpSA test, H. pylori infection was seen in 56.7% of patients. By the serological test, another 29 patients had H. pylori infection. Therefore, the total number of patients was 101, and the overall prevalence of H. pylori increased to 79.5%. Conclusion: The results of the present study showed that the overall prevalence of H. pylori infection was high compared to previous studies. Also, above the age of 40 years, female gender in HpSA test and male gender in serology test, higher education level, and the presence of risk factors (smoking, alcohol, and NSAIDs) have a higher positive test for H. pylori.