scholarly journals Nrf2 Dysregulation in Major Depressive and Bipolar Disorders

2021 ◽  
Vol 10 ◽  
pp. e2074
Author(s):  
Maryam Ghanbarirad ◽  
Mehrdad Hashemi ◽  
Seyed Mehdi Saberi ◽  
Ahmad Majd

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.

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199296
Author(s):  
Juan Wang ◽  
Liu Yang ◽  
Yanjun Diao ◽  
Jiayun Liu ◽  
Jinjie Li ◽  
...  

Objective To evaluate the performance of a DNA methylation-based digital droplet polymerase chain reaction (ddPCR) assay to detect aberrant DNA methylation in cell-free DNA (cfDNA) and to determine its application in the detection of hepatocellular carcinoma (HCC). Methods The present study recruited patients with liver-related diseases and healthy control subjects. Blood samples were used for the extraction of cfDNA, which was then bisulfite converted and the extent of DNA methylation quantified using a ddPCR platform. Results A total of 97 patients with HCC, 80 healthy control subjects and 46 patients with chronic hepatitis B/C virus infection were enrolled in the study. The level of cfDNA in the HCC group was significantly higher than that in the healthy control group. For the detection of HCC, based on a cut-off value of 15.7% for the cfDNA methylation ratio, the sensitivity and specificity were 78.57% and 89.38%, respectively. The diagnostic accuracy was 85.27%, the positive predictive value was 81.91% and the negative predictive value was 87.20%. The positive likelihood ratio of 15.7% in HCC diagnosis was 7.40, while the negative likelihood ratio was 0.24. Conclusions A sensitive methylation-based assay might serve as a liquid biopsy test for diagnosing HCC.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shymaa Kamal El Din Abed El Rahman ◽  
Sanaa Sayed Abd Elshafy ◽  
Mohamed Samra ◽  
Hala Mohammed Ali ◽  
Rabab Afifi Mohamed

Abstract Background The relation between PIM2 and the transcriptional factor NF κβ have been controversial in literature. The significance of PIM2 and NF-κβ genes expression on the incidence of acute leukemia (AML and ALL) and its relevance to the response rate was evaluated. Sixty de novo acute leukemia patients were stratified in 2 groups: 30 acute myeloid leukemia (AML) and 30 acute lymphoblastic leukemia (ALL) patients and compared to 30 sex- and age-matched controls. The expression level of PIM2 and NF κβ genes was measured using quantitative real-time polymerase chain reaction (QRT-PCR). The patients were followed with clinical examination and complete blood counts. Results The expression level of PIM2 gene was significantly higher in AML patients (P<0.001) compared to the control group. The mean expression level of NF κβ gene was significantly high in AML and ALL patients compared to the healthy control group (P=0.037 and P<0.001; respectively). The overall survival in AML patients was higher in NF κβ gene low expressers compared to high expressers (P=0.047). The number of AML patients who achieved complete remission was significantly higher in PIM2 gene low expressers in comparison to PIM2 gene high expressers (P=0.042). Conclusion PIM2 and NF κβ genes might have a role in the pathogenesis of acute leukemia, poor overall survival, and failure of response to induction therapy.


Author(s):  
Mahmut Atum ◽  
Gürsoy Alagöz

Purpose: This study aimed to compare the neutrophil-to-lymphocyte (NLR) and plateletto- lymphocyte (PLR) ratios in patients with retinal artery occlusion (RAO) with those from a healthy control population and to identify the relationship between them. Methods: Forty-six patients with RAO and fifty-one healthy control subjects were included in this retrospective case-control study. RAO was diagnosed following an ophthalmic examination and fluorescein angiography (FA). Blood neutrophil, lymphocyte, and platelet counts were recorded for each of the 97 subjects, from which NLR and PLR values were calculated. Results: There were 46 patients (28 male [M], 18 female [F]) in the RAO group and 51 patients (27 M, 24 F) in the control group. No significant differences were found between patients with RAO and the control subjects in terms of gender and age (P > 0.05). Patients with RAO had significantly increased NLR values (2.85 ± 1.70) than the control subjects (1.63 ± 0.59, P < 0.001). The mean PLR in patients with RAO was 123.69 ± 64.98, while that in control subjects was 103.08 ± 36.95; there was no significant difference between the two groups (P = 0.055). A logistic regression analysis revealed that NLRs were 3.8 times higher in patients with RAO than in control subjects (odds ratio = 3.880; 95% confidence interval = 1.94 to 7.74; P < 0.001). Conclusion: NLRs were significantly increased in patients with RAO compared to the control subjects.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ravi Shankar Reddy ◽  
Jaya Shanker Tedla ◽  
Snehil Dixit ◽  
Mohammed Abohashrh

Abstract Background Cervical proprioception is critical in the maintenance of posture and movements, so its assessment in different cervical conditions has gained importance in recent clinical practice. Studies reporting this assessment in subjects with cervical spondylosis (CS) have not previously been investigated. The goals of the study are (1) comparison of joint position error (JPE) in subjects with CS to healthy control group. (2) Correlation of neck pain intensity to cervical proprioception in patients with CS. Methods In a Cross-sectional study, 132 subjects with CS and 132 healthy age-matched control subjects were evaluated for cervical JPE with the cervical range of motion device. The subjects were blindfolded and repositioned their heads to a target position, which was determined by the examiner previously and their repositioning accuracy (absolute error in degrees) was measured in the frontal (flexion and extension) and transverse planes (left rotation and right rotation). The CS subjects resting neck pain intensity was assessed using visual analog scale (VAS). Results CS subjects showed statistically significantly larger JPEs compared to healthy control subjects in all the directions tested (flexion - 95% CI = 2.38–3.55, p < 0.001, extension - 95% CI =3.26–4.33, p < 0.001, left rotation - 95% CI = 2.64 - 3.83, p < 0.001, right rotation − 95% CI = 3.77–4.76, p < 0.001). The mean JPE errors in the CS group ranged from 6.27° to 8.28° and in the control group ranged from 2.36° to 4.48°. Pearson’s correlation coefficient showed a significant and positive relationship between neck pain intensity and cervical proprioception (p ≤ 0.001). Conclusions Proprioception is impaired in subjects with CS when compared to healthy control group. Higher pain intensity was associated with greater cervical JPE in patients with CS.


Author(s):  
Suzanne N Avery ◽  
Kristan Armstrong ◽  
Maureen McHugo ◽  
Simon Vandekar ◽  
Jennifer Urbano Blackford ◽  
...  

Abstract Background Relational memory, the ability to bind information into complex memories, is moderately impaired in early psychosis and severely impaired in chronic schizophrenia, suggesting relational memory may worsen throughout the course of illness. Methods We examined relational memory in 66 early psychosis patients and 64 healthy control subjects, with 59 patients and 52 control subjects assessed longitudinally at baseline and 2-year follow-up. Relational memory was assessed with 2 complementary tasks, to test how individuals learn relationships between items (face-scene binding task) and make inferences about trained relationships (associative inference task). Results The early psychosis group showed impaired relational memory in both tasks relative to the healthy control group. The ability to learn relationships between items remained impaired in early psychosis patients, while the ability to make inferences about trained relationships improved, although never reaching the level of healthy control performance. Early psychosis patients who did not progress to schizophrenia at follow-up had better relational memory than patients who did. Conclusions Relational memory impairments, some of which improve and are less severe in patients who do not progress to schizophrenia, are a target for intervention in early psychosis.


Brain ◽  
2019 ◽  
Vol 142 (7) ◽  
pp. 2137-2148 ◽  
Author(s):  
Jeannette M Gelauff ◽  
Alan Carson ◽  
Lea Ludwig ◽  
Marina A J Tijssen ◽  
Jon Stone

Abstract Reliable data on the prognosis of functional motor disorder are scarce, as existing studies of the prognosis of functional motor disorder are nearly all retrospective, small and uncontrolled. In this study we used a prospectively recruited, controlled cohort design to assess misdiagnosis, mortality and symptomatic and health outcome in patients with functional limb weakness compared to neurological disease and healthy control subjects. We also carried out an exploratory analysis for baseline factors predicting outcome. One hundred and seven patients with functional limb weakness, 46 neurological and 38 healthy control subjects from our previously studied prospective cohort were traced for follow-up after an average of 14 years. Misdiagnosis was determined in a consensus meeting using information from records, patients and their GPs. Numbers and causes of death were collected via death certificates. Outcome of limb weakness, physical and psychiatric symptoms, disability/quality of life and illness perception were recorded with self-rated questionnaires. Outcome measures were compared within and between groups. Seventy-six patients (71%) with functional limb weakness, 31 (67%) neurological and 23 (61%) healthy controls were included in follow-up. Misdiagnosis was found in one patient in the functional limb weakness group (1%) and in one neurological control (2%). Eleven patients with functional limb weakness, eight neurological control subjects and one healthy control subject had died. Weakness had completely remitted in 20% of patients in the functional limb weakness group and in 18% of the neurological controls (P = 0.785) and improved in a larger proportion of functional limb weakness patients (P = 0.011). Outcomes were comparable between patient groups, and worse than the healthy control group. No baseline factors were independent predictors of outcome, although somatization disorder, general health, pain and total symptoms at baseline were univariably correlated to outcome. This study is the largest and longest follow-up study of functional limb weakness. Misdiagnosis in functional limb weakness is rare after long-term follow-up. The disorder is associated with a higher mortality rate than expected, and symptoms are persistent and disabling. It appears difficult to predict outcome based on common baseline variables. These data should help inform clinicians to provide a more realistic outlook of the outcome and emphasize the importance of active and targeted therapy.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Esmaeil Mortaz ◽  
Majid Malkmohammad ◽  
Hamidreza Jamaati ◽  
Parisa Adimi Naghan ◽  
Seyed MohamadReza Hashemian ◽  
...  

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 31 M patients and resulted in 961 K deaths worldwide as of 21st September 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute respiratory distress syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia is seen in the COVID-19 patients, however, patients present with a distinct phenotype. Intracellular levels of nitric oxide (NO) play an important role in the vasodilation of small vessels. To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects. Methods We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March–May 2020. Whole blood samples were harvested from patients and intracellular NO levels in 1 × 106 red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA). Results The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P ≤ 0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group. Conclusions This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future multi-centre studies should examine whether this is seen in a larger number of COVID-19 patients and whether NO therapy may be of use in these severe COVID-19 patients.


2006 ◽  
Vol 18 (2) ◽  
pp. 120-126 ◽  
Author(s):  
Po W. Wang ◽  
Napapon Sailasuta ◽  
Rebecca A. Chandler ◽  
Terence A. Ketter

Background:Animal models of depression and psychopharmacological mechanisms of action suggest the importance of the gamma-amino butyric acid (GABA) system in the pathophysiology of mood disorders. Mood stabilizers have overlapping effects on GABAergic neurotransmission, and antidepressant use has been associated with alterations in GABAB receptor function. Magnetic resonance spectroscopy (MRS) provides an opportunity to noninvasively assess cerebral GABA concentrations in anterior paralimbic circuits that have been implicated in mood disorders.Methods:In bipolar disorder patients and healthy control subjects, we used MRS with a modified GABA-edited point resolved spectroscopy sequence (TE 68 ms, TR 1500 ms, 512 averages, total scan time 26 min) to assess GABA in an 18-cm3 occipital voxel. In addition, in another cohort of bipolar disorder patients and healthy control subjects, we similarly assessed GABA in a 12.5-cm3 medial prefrontal/anterior cingulate (MPF/AC) voxel. The concentration of GABA was referenced to creatine (Cr) from unedited spectra.Results:In bipolar patients and controls, we consistently detected 3.0 p.p.m. GABA peaks in occipital lobe and MPF/AC. In 16 bipolar (nine bipolar I and seven bipolar II) disorder patients, compared with six healthy control subjects, mean occipital GABA/Cr concentration was 61% higher. In addition, in 15 bipolar (five bipolar I, nine bipolar II, and one bipolar not otherwise specified) disorder patients, compared with six healthy control subjects, mean MPF/AC GABA/Cr concentration tended to be 41% higher.Conclusions:Patients with bipolar disorders may have increased cerebral GABA concentrations. Although this was more evident in the occipital lobe, MPC/AC GABA disturbance may be of greater potential interest in view the more established role of MPF/AC in affective processing. Additional studies are warranted to assess changes in GABAergic neurotransmission and the influences of diagnosis, mood state, and medication status in bipolar disorder patients.


1994 ◽  
Vol 86 (6) ◽  
pp. 715-721 ◽  
Author(s):  
C. B. Nielsen ◽  
S. S. Sørensen ◽  
E. B. Pedersen

1. Animal studies have shown that prostaglandins are important for renal function after unilateral nephrectomy. In order to investigate the importance of prostaglandins for renal function in the fully adapted remnant kidney in healthy uninephrectomized subjects, the acute effects of indomethacin on renal haemodynamics, lithium clearance, urinary excretion rates of prostaglandin E2, sodium and water, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and arginine vasopressin were measured in 14 healthy uninephrectomized subjects (median time after nephrectomy 1.7 years) and in 14 matched healthy control subjects. In addition, nine healthy control subjects were studied without indomethacin and served as a time-control group. 2. Before indomethacin ingestion there was a significantly higher single-kidney urinary excretion rate of prostaglandin E2 in the uninephrectomized group (uninephrectomized group, 349.2 fmol/min; control group, 76.6 fmol/min; time-control group, 96.3 fmol/min). 3. Indomethacin ingestion resulted in equal changes in all parameters in both groups. These were significant decreases in glomerular filtration rate (−11.3% versus −14.6%), renal plasma flow (−6.5% versus −13.0%), urinary flow rate (−49.8% versus −49.4%), fractional sodium excretion (−44.5% versus −47.4%), lithium clearance (−33.2% versus −23.8%) and urinary excretion rate of prostaglandin E2 (−93.8% versus −86.7%) (uninephrectomized versus control subjects, values are medians). In the time-control group no changes were observed in these parameters. 4. It is concluded that healthy uninephrectomized subjects with a fully adapted remnant kidney have a normal renal response to acute indomethacin-induced inhibition of prostaglandin synthesis.


2020 ◽  
Author(s):  
Lichen Teng ◽  
Jian Wu ◽  
Huiling Li ◽  
Huiyan Wang ◽  
Ying Wang ◽  
...  

Abstract Background Endothelial progenitor cells (EPCs) play an important role in tumor angiogenesis and growth. In this study, we assessed the effect of MicroRNAs (miRNAs) on EPCs migration and angiogenesis and its signaling pathway in patients suffered from ovarian cancer (OC). Methods We cultured peripheral circulating EPCs derived from 32 OC patients and 20 healthy control subjects, respectively. The miRNA profiles of EPCs in ovarian cancer patients were compared with that in healthy control subjects, and aberrantly expressed miRNAs in both groups were identified via miRNA microarray and clustering analysis. Among these miRNAs, miR-133a-5p was considered as one of the most important miRNAs, which biological function in EPCs has been investigated. Bioinformatic analysis combined with knockdown and overexpression of miR-133a-5p were used to identify its target protein. Results An obviously downregulated expression level of miR-133a-5p has been seen in EPCs with ovarian cancer patients. Downregulated expression level of miR-133a-5p has been seen in ovarian cancer tissues and ovarian cancer cells (SKOV-3 and OVCAR-3). Downregulated of miR-133a-5p can increase TRIM59 expression, moreover, downregulated of miR-133a-5p further induce migration and angiogenesis via increase VEGF and Id1 in EPCs. MiR-133a-5p pro-angiogenesis would be diminished by TRIM59 knockdown. Conclusions The study found that miR-133a-5p was an important upstream factor regulated Id1/VEGF expression. Additionally, functional studies have revealed that TRIM59 was a direct target protein of miR-133a-5p, and TRIM59 silencing attenuated the role of miR-133a-5p in angiogenesis and Id1/VEGF expression. So we proposed that miR-133a-5p would be a new target for OC therapy.


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