The role of Nrf2 in neural stem/progenitors cells: From maintaining stemness and self-renewal to promoting differentiation capability and facilitating therapeutic application in neurodegenerative disease

Neurodegenerative diseases (NDs) cause progressive loss of neurons in nervous system. NDs are categorized as acute NDs such as stroke and head injury, besides chronic NDs including Alzheimer's, Parkinson's, Huntington's diseases, Friedreich's Ataxia, Multiple Sclerosis. The exact etiology of NDs is not understood but oxidative stress, inflammation and synaptic dysfunction are main hallmarks. Oxidative stress leads to free radical attack on neural cells which contributes to protein misfolding, glia cell activation, mitochondrial dysfunction, impairment of DNA repair system and subsequently cellular death. Neural stem cells (NSCs) support adult neurogenesis in nervous system during injuries which is limited to certain regions in brain. NSCs can differentiate into the neurons, astrocytes or oligodendrocytes. Impaired neurogenesis and inadequate induction of neurogenesis are the main obstacles in treatment of NDs. Protection of neural cells from oxidative damages and supporting neurogenesis are promising strategies to treat NDs. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional master regulator that maintains the redox homeostasis in cells by provoking expression of antioxidant, anti-inflammatory and cytoprotective genes. Nrf2 can strongly influence the NSCs function and fate determination by reducing levels of reactive oxygen species in benefit of NSC survival and neurogenesis. In this review we will summarize the role of Nrf2 in NSC function, and exogenous and endogenous therapeutic strategies in treatment of NDs

Evaluation of diagnostic methods for the detection of Bovine Coronavirus and Rotavirus in faeces of diarrhoeic calves

The purpose of the present study was to evaluate the efficacy of Enzyme-Linked Immunosorbent Assay (ELISA), immunochromatographic (ICG), and reverse transcription-polymerase chain reaction (RT-PCR) methods for the detection of rotavirus (RV) and bovine coronavirus (BCV). Faeces samples were collected from 90 diarrhoeic calves (male and female) up to one month of age and the immune response against RV and BCV infection was as-sessed by using AgELISA, ICG, and RT-PCR. To determine the performance and accuracy of each diagnostic method in comparison to the diagnostic gold standard (RT-PCR) method, different statistical tests including receiver operating characteristic curve (ROC) and concordance correlation were used. Results revealed the prevalence of RV and BCV and RV+BCV according to RT-PCR were equal to 8.89 (95% CI: 6.64-10.07), 14.44 (95% CI: 11.23-6.90), and 2.22 (95% CI: 0.89-3.72), respectively. The best agreement and the highest sensitivity and specificity were obtained be-tween the RT-PCR and AgELISA (100% and 94.3%), and also the ICG test (95% and 94.3%) was less accurate method in comparison to ELISA method for identifying RV and BCV, but a good correlation and concordance between ICG diagnostic techniques and RT-PCR were observed. To put it in a nutshell, our results demonstrate that the AgELISA is the most accurate technique in comparison to RT-PCR, however the ICG assay can help improve the speed of diagnosis RV and BCV infections in dairy field. New scientific strategies for promoting accuracy and transparency of ICG-based technique in early diagnosis of the cause of calf diarrhoea should be used. Altogether, we suggest that positive ICG samples should be tested by AgELISA or RT-PCR techniques to avoid false results in farm animals

Dietary total antioxidant capacity interacts with a variant of chromosome 5q13-14 locus to influence cardio-metabolic risk factors among obese adults

BACKGROUND: The association between cocaine- and amphetamine-regulated transcript prepropeptide gene (CARTPT) and obesity-related outcomes has shown in the epidemiological studies. Nevertheless, there is lack of data regarding the CARTPT gene–diet interactions in terms of antioxidant potential of diet. So, this study aimed to test CARTPT gene–dietary non-enzymatic antioxidant capacity (NEAC) interactions on cardio-metabolic risk factors in obese individuals. METHODS AND MATERIAL: The present cross-sectional study was carried out among 288 apparently healthy obese adults within age range of 20–50 years. Antioxidant capacity of diet was estimated by calculating the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), total radical-trapping antioxidant parameter (TRAP) and Trolox equivalent antioxidant capacity (TEAC) using a semiquantitative food frequency questionnaire (FFQ). Genotyping for CARTPT rs2239670 polymorphism was conducted by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. RESULTS: A significant interaction was revealed between CARTPT rs2239670 and dietary ORAC on BMI (P(Interaction) = 0.048) and fat mass percent (FM%) (P(Interaction) = 0.008); in A allele carriers, higher adherence to the dietary ORAC was related to lower level of BMI and FM%. And, the significant interactions were observed between FRAP index and rs2239670 in relation to HOMA (P(Interaction) = 0.049) and QUICKI (P(Interaction) = 0.048). Moreover, there were significant interactions of rs2239670 with TRAP (P(Interaction) = 0.029) and TEAC (P(Interaction) = 0.034) on the serum glucose level; individuals with AG genotype were more respondent to higher intake of TRAP. CONCLUSION: The present study indicated that the relationships between CARTPT rs2239670 and obesity and its-related metabolic parameters depend on adherence to the dietary NEAC. Large prospective studies are needed to confirm our findings

Evaluation of diagnostic methods for the detection of Bovine Coronavirus and Rotavirus in faeces of diarrhoeic calves

The purpose of the present study was to evaluate the efficacy of Enzyme-Linked Immunosorbent Assay (ELISA), immunochromatographic (ICG), and reverse transcription-polymerase chain reaction (RT-PCR) methods for the detection of rotavirus (RV) and bovine coronavirus (BCV). Faeces samples were collected from 90 diarrhoeic calves (male and female) up to one month of age and the immune response against RV and BCV infection was as-sessed by using AgELISA, ICG, and RT-PCR. To determine the performance and accuracy of each diagnostic method in comparison to the diagnostic gold standard (RT-PCR) method, different statistical tests including receiver operating characteristic curve (ROC) and concordance correlation were used. Results revealed the prevalence of RV and BCV and RV+BCV according to RT-PCR were equal to 8.89 (95% CI: 6.64-10.07), 14.44 (95% CI: 11.23-6.90), and 2.22 (95% CI: 0.89-3.72), respectively. The best agreement and the highest sensitivity and specificity were obtained be-tween the RT-PCR and AgELISA (100% and 94.3%), and also the ICG test (95% and 94.3%) was less accurate method in comparison to ELISA method for identifying RV and BCV, but a good correlation and concordance between ICG diagnostic techniques and RT-PCR were observed. To put it in a nutshell, our results demonstrate that the AgELISA is the most accurate technique in comparison to RT-PCR, however the ICG assay can help improve the speed of diagnosis RV and BCV infections in dairy field. New scientific strategies for promoting accuracy and transparency of ICG-based technique in early diagnosis of the cause of calf diarrhoea should be used. Altogether, we suggest that positive ICG samples should be tested by AgELISA or RT-PCR techniques to avoid false results in farm animals

Multiplex Analysis of Cerebrospinal Fluid and Serum Exosomes MicroRNAs of Untreated Relapsing Remitting Multiple Sclerosis (RRMS) and Proposing Noninvasive Diagnostic Biomarkers

Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for neurodegenerative diseases. In this study, we aimed to detect relapsing-remitting multiple sclerosis (RRMS)-specific miRNAs in cerebrospinal fluid (CSF) and serum exosomes with diagnostic potential. One ml of CSF and serum sample were collected from each of the 30 untreated RRMS patients and healthy controls (HCs). A panel of 18 miRNAs affecting inflammatory responses was applied, and qRT-PCR was conducted to detect differentially expressed exosomal miRNAs in CSF and serum of RRMS patients. We identified that 17 out of 18 miRNAs displayed different patterns in RRMS patients compared to HCs. Let-7 g-5p, miR-18a-5p, miR-145-5p, and miR-374a-5p with dual pro-inflammatory and anti-inflammatory actions and miR-150-5p and miR-342-3p with anti-inflammatory action were significantly upregulated in both CSF and serum-derived exosomes of RRMS patients compared to corresponding HCs. Additionally, anti-inflammatory miR-132-5p and pro-inflammatory miR-320a-5p were significantly downregulated in both CSF and serum-derived exosomes of RRMS patients compared to HCs. Ten of 18 miRNAs were differentially expressed in CSF and serum exosomes of the patients. Furthermore, miR-15a-5p, miR-19b-3p, and miR-432-5p were upregulated, and miR-17-5p was downregulated only in CSF exosomes. Interestingly, U6 housekeeping gene was differentially expressed in CSF and serum exosomes, in both RRMS and HCs. As the first report describing CSF exosomal miRNAs expression profile compared to that of serum exosomes in untreated RRMS patients, we showed that CSF and serum exosomes are not identical in terms of biological compounds and display different patterns in miRNAs and U6 expression

Evaluation of T helper17 as skeletal homeostasis factor in peripheral blood mononuclear cells and T helper cells of end-stage renal disease cases with impaired parathyroid hormone

Background Chronic renal failure is mainly connected with high and low parathyroid hormone (PTH) levels and immunological impairments. The present study aimed to evaluate T helper 17 (Th17) cells as a crucial modulator of the immune system and skeletal homeostasis in hemodialysis patients with impaired intact PTH (iPTH).Methods In this research, blood samples were taken from ESRD patients with high (> 300 pg/mL), normal (150-300 pg/mL), and low (< 150 pg/mL) serum intact parathyroid hormone (iPTH( levels (n = 30 in each group). The frequency of Th17 (CD4(+) IL17(+)) cells was evaluated by flow cytometry in each group. The expression levels of Th17 cell-related master transcription factors, cytokines in peripheral blood mononuclear cells (PBMC), and Th cells, and the level of the mentioned cytokines were determined in the supernatant of PBMCs.Results The number of Th17 cells remarkably increased in subjects with high iPTH against low and normal iPTH. Also, ROR?t and STAT3 levels were significantly higher in high iPTH ESRD patients than in other groups in the expression of mRNA and protein levels. These findings are confirmed by evaluating the IL-17 and IL-23 in the supernatant of cultured PBMCs and isolated Th cells.Conclusion Our findings indicated that increased serum PTH levels in hemodialysis cases may be involved in increasing the differentiation of CD4 + cells to Th17 cells in PBMC