The Potential of Targeting Autophagy-Related Non-coding RNAs in the Treatment of Alzheimer's and Parkinson's Diseases.

Clearance of accumulated protein aggregates is one of the functions of autophagy. Recently, a clearer understanding of non-coding RNAs (ncRNAs) functions documented that ncRNAs have important roles in several biological processes associated with the development and progression of neurodegenerative disorders. Subtypes of ncRNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), are commonly dysregulated in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulation of these non-coding RNAs has been associated with inhibition or stimulation of autophagy. Decreased miR-124 led to decreased/increased autophagy in experimental model of Alzheimer and Parkinson diseases. Increased BACE1-AS showed enhanced autophagy in Alzheimer disease by targeting miR-214-3p, Beclin-1, LC3-I/LC3-II, p62, and ATG5. A significant increase in NEAT1led to stimulated autophagy in experimental model of PD by targeting PINK1, LC3-I, LC3-II, p62 and miR-374c-5p. In addition, increased BDNF-AS and SNHG1 decreased autophagy in MPTP-induced PD by targeting miR-125b-5p and miR-221/222, respectively. The upregulation of circNF1-419 and circSAMD4A resulted in an increased autophagy by regulating Dynamin-1 and miR-29c 3p, respectively. A detailed discussion of miRNAs, circRNAs, and lncRNAs in relation to their autophagy-related signaling pathways is presented in this study.

Polymorphism in neutrophil cytosolic factor 4 (NCF4) of dairy cows had mastitis in previous lactations, and the relationship with the respiratory burst.

Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), as a key factor in innate immunity, consists of several components, one of them is p40phox which is encoded by neutrophil cytosolic factor 4 (NCF4). Respiratory burst and reactive oxygen species (ROS) production are antimicrobial mechanisms associated with NADPH oxidase. This study evaluated the effects of g.18174 A > G and g.18270C > T single-nucleotide polymorphisms (SNP) in NCF4 on bovine mastitis and the respiratory burst capacity of neutrophils. SNPs of 160 dairy cattle were determined using a novel PCR-RFLP protocol by employing restriction enzymes, MboI and FokI. Also, the flow cytometry measured respiratory burst in 82 blood samples. Our results indicated that only g.18174 A > G SNP reduced the respiratory burst capacity. However, both SNPs were not significantly correlated with clinical mastitis. We concluded that g.18174 A > G decreases the function of NADPH oxidase. However, both SNPs were not significantly correlated with clinical mastitis.

Comparison of Lapse Rate in Drug Dependent Patients in 2 Methods of Methadone Maintenance Treatment and Buprenorphine Maintenance Treatment.

Background: Lapse has been one of the major challenges in the treatment of drug dependence sometimes leading to its relapse. Objectives: The aim of this study was to determine the lapse rate in drug dependent patients as for the 2 methods of methadone maintenance treatment (MMT) and buprenorphine maintenance treatment (BMT) in Yazd city. Methods: In this cross-sectional study, 626 female and male patients who had referred to 5 SUD treatment centers in Yazd and had been treated with methadone and buprenorphine maintenance were studied. Participants were divided into 2 groups of MMT and BMT and were evaluated based on lapse within 6 months. Results: In this study, 60.9% of patients were treated with methadone but the rest were treated with buprenorphine. Overall, 33.1% of patients lapsed (35.2% for methadone and 29.8%for buprenorphine). Lapse in methadone treatment was correlated with age, occupational status, and duration of treatment (P < .05); it failed to correlated with any other demographic and clinical characteristics (P > .05). Lapse rate in buprenorphine treatment was also related to marital status and the drug used (P < .05). The mean dose of buprenorphine consumed showed no significant relationship with lapse (P > .05). The results demonstrated that given the low dose, lapse stood higher in the buprenorphine group than the methadone group; however, as to high dose, the buprenorphine group showed lower lapse than the other group. Conclusions: In regard with the high rate of lapse, it is recommended to consider the factors related to the 2 methods of treatments, and provide counseling and training programs to lower lapse in the patients.Ethics Committee (REC) approval code: IR.SSU.REC.1394.158.

Patients with Active Rheumatoid Arthritis Have Lower Frequency of nTregs in Peripheral Blood.

BACKGROUND: Patients with rheumatoid arthritis (RA) suffer from wide ranges of autoimmune reactions in joints. The mechanism of which is generally unknown and maybe associated with Treg deregulation. OBJECTIVE: To compare the frequency of nTregs in peripheral blood of patients with active rheumatoid disease with healthy individuals. METHODS: Twenty five newly diagnosed patients with active RA disease were selected based on the clinical and laboratory criteria before starting their therapies. Treg cells in peripheral blood samples were enumerated by immune staining and flowcytometry analysis. RESULTS: Clinical and laboratory results were in favor of active disease in all the studied patients although they showed variations in Disease Activity Score-28 (DAS-28). Compared to the healthy controls, RA patients had significantly lower frequency of CD4+CD25hi or CD4+CD25+FoxP3+ natural regulatory T cells. In spite of that, there were no significant differences between patients and healthy controls in respect to the CD4/CD8 ratio. Interestingly, more CD4+CD25-FoxP3+ cells were found in peripheral blood of patients. The frequencies of the Tregs did not show strong associations with the DAS-28. CONCLUSION: We showed lower abundance of nTregs in peripheral blood of RA patients which highlights the significance of these cells in RA.