LC3 and ATG5 overexpression and neuronal cell death in the prefrontal cortex of postmortem chronic methamphetamine users

Methamphetamine (METH) abuse is accompanied by oxidative stress, METH-induced neurotoxicity, and apoptosis. Oxidative stress has devastating effects on the structure of proteins and cells. Autophagy is an evolutionarily conserved intracellular regulated mechanism for orderly degradation of dysfunctional proteins or removing damaged organelles. The precise role of autophagy in oxidative stress-induced apoptosis of dopaminergic neuronal cells caused by METH has not clarified completely. In this study, we sought to evaluate the effects of METH abuse on autophagy in the prefrontal cortex of postmortem users, mainly focusing on the ATG5 and LC3 during neuroinflammation. Postmortem molecular and histological examination was done for two groups containing 12 non-addicted and 14 METH addicted cases. ATG5 and LC3 expression were analyzed by real-time PCR and immunohistochemistry (IHC) methods. Histopathological analysis was performed by stereological cell counting of neuronal cells using Hematoxylin and Eosin (H & E) staining technique. In order to detect DNA damage in the prefrontal lobe, Tunnel staining was performed. Real-time PCR and IHC assay showed overexpression of ATG5 and LC3 protein in the prefrontal cortex of Meth users. The cell death and neuronal degeneration were increased significantly based on Tunel assay and the stereological analysis in the Prefrontal cortex. Chronic METH exposure probably induces ATG5 and LC3 overexpression and neuronal cell death in the Prefrontal cortex of the postmortem cases

Association of NFKB1 gene polymorphism (rs28362491) with cardiometabolic risk factor in patients undergoing coronary angiography

Introduction: Genetic and environmental factors are involved in the pathogenesis of cardiovascular diseases (CVDs). The aim of the study was to investigate between the genotype of the NFKB1 gene and the cardiometabolic risk factor in patients undergoing coronary angiography. Methods: This cross-sectional study was conducted on 462 adults (male and women) aged between 35 and 75 years who referred to Afshar Hospital for coronary angiography in 2021- 2022. The polymerase chain reaction restriction fragment length polymorphism method was used to detect the genotype of rs28362491. Biochemical parameters were measured using commercial kits. Gensini and Syntax scores were calculated using the angiography result to assess the extent of coronary artery stenosis. We used multivariate logistic regression analysis to examine the relationship between genotype variants and cardiometabolic risk factors. Results: There was no association between variant genotypes and abnormally levels of serum alanine aminotransferase (ALT) (P value=0.51), aspartate aminotransferase (AST) (P value=0.99), triglyceride (TG) (P value=0.48), total cholesterol (P value=0.79), low density lipoprotein-cholestero (LDL-C) (P value=0.31), high-density lipoprotein-cholesterol (HDL-C) (P value=0.53), fast blood sugar (FBS) (P value=0.39), systolic blood pressure (P value=0.14), diastolic blood pressure (P value=0.64), Gensini score (P value=0.48) and syntax score (P value=0.74) in the crude model even after adjustment for confounding factors. Conclusion: We found no association between the ATTG polymorphism and cardiometabolic risk factors in patients who had coronary angiography. Further investigations are needed to assess the association between variants of 28362491 and cardiometabolic markers

Evaluation the status of medical library of Shahid Babai faculty of medicine and its dependent Therapeutic Centers in comparison with standards for Iranian Academic libraries

Background: The matching criteria for the standard academic libraries and university libraries in the principles that the library can achieve long-term goals help University research & education and lack of attention to this issue will lead to delays or failure to achieve these goals. Objective: The aim of this study was to evaluate the status of medical library of Shahid Babaee faculty of medicine and its six dependent hospital libraries of Qazvin University of medical sciences, and its comparison with the Standards of Academic Library. Methods: A descriptive epidemiology method was used in this study. The study population consisted of libraries of Shahid Babaee faculty of medicine and its dependent clinical centers. Standardized questionnaire and a check list were used to collect data. Findings: The findings indicate that, in connection with the human specialist, all 7 managers of official's library have not librarian education degree. 57% of the libraries surveyed (4 libraries) have organizational charts and division of work in the library, and 71.4 % (5 libraries) had written procedures and policies which were provided for their staff and managers. Libraries have not an independent budget for their selves. 71.4% (5 libraries) of the library have a reading hall. In 71.4% a separated space has not been either for library materials technology or for staffs. Conclusion: however some factors are near to standards level, but the staff –student ratio, specialist staff, standard spaces, in these libraries are below the standards level and its need more and properly Attention of managers of Qazvin University of medical sciences to improve and to reach to the standard goals of medical libraries. Keywords: faculty libraries, hospital libraries, standard

Antiatherogenic properties of high-density lipoproteins from arterial plasma are attenuated as compared to their counterparts of venous origin

International audienceBackground and aims: High-density lipoprotein (HDL) particles play atheroprotective roles by their ability to efflux cholesterol from foam cells and to protect low-density lipoproteins (LDLs) from oxidative damage in the arterial intima. We hypothesized that antioxidative properties of HDLs can be attenuated in the oxygen-rich prooxidative arterial environment, contributing to the development of atherosclerosis. To evaluate this hypothesis, we compared antioxidative activity of HDLs from arterial and venous plasmas.Methods and results: Arterial and venous blood samples were simultaneously obtained from 16 patients (age 68 ± 10 years; 75% males) presenting with ischemic or valvular heart disease. Major HDL subfractions and total HDLs were isolated by density gradient ultracentrifugation and their chemical composition and the capacity to protect LDLs from in vitro oxidation were evaluated. HDL-cholesterol, triglycerides and apolipoprotein (apo) B-100 levels were slightly but significantly reduced by -4 to -8% (p < 0.01) in the arterial vs. venous samples. Total mass of HDL subpopulations was similar and HDL subpopulations did not reveal marked compositional differences between the arterial and venous circulation. Potent antioxidative activity of the small, dense HDL3c subpopulation was significantly reduced in the particles of arterial origin vs. their counterparts from venous plasma (increase of +21% in the propagation rate of LDL oxidation, p < 0.05). Interestingly, antioxidative properties of venous HDLs were enhanced in statin-treated patients relative to untreated subjects.Conclusion: Antioxidative properties of small, dense HDLs from arterial plasma are attenuated as compared to the particles of venous origin, consistent with the development of atherosclerosis in the arterial wall

Distinct phospholipid and sphingolipid species are linked to altered HDL function in apolipoprotein A-I deficiency

International audienceBACKGROUND:Familial apolipoprotein A-I (apoA-I) deficiency (FAID) involving low levels of both apoA-I and high-density lipoprotein (HDL) cholesterol is associated with accelerated atherosclerosis.OBJECTIVE:The objective of this study was to define distinctive patterns in the lipidome of HDL subpopulations in FAID in relationship to antiatherogenic activities.METHODS:Five HDL subfractions were isolated by ultracentrifugation from plasma of FAID Caucasian patients (n = 5) and age-matched healthy normolipidemic Caucasian controls (n = 8), and the HDL lipidome (160 molecular species of 9 classes of phospholipids and sphingolipids) was quantitatively evaluated.RESULTS:Increased concentrations of numerous molecular species of lysophosphatidylcholine (up to 12-fold), ceramides (up to 3-fold), phosphatidylserine (up to 34-fold), phosphatidic acid (up to 71-fold), and phosphatidylglycerol (up to 20-fold) were detected throughout all five HDL subpopulations as compared with their counterparts from controls, whereas concentrations of phosphatidylethanolamine species were decreased (up to 5-fold). Moderately to highly abundant, within their lipid class, species of phosphatidylcholine, sphingomyelin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, and ceramide featuring multiple unsaturations were primarily affected by apoA-I deficiency; their HDL content, particularly that of phosphatidylcholine (34:2), was strongly correlated with HDL function, impaired in FAID. Metabolic pathway analysis revealed that sphingolipid, glycerophospholipid, and linoleic acid metabolism was significantly affected by FAID.CONCLUSION:These data reveal that altered content of specific phospholipid and sphingolipid species is linked to deficient antiatherogenic properties of HDL in FAID

Interaction of dietary patterns with rs28362491 on severity of coronary artery stenosis in patients undergoing coronary angiography

Abstract Coronary artery disease (CAD) is one of the most important cardiovascular diseases. Lifestyle and genetic factors play important roles in the development of CAD. The aim of the study is to examine the interaction of dietary patterns and genes on the likelihood of abnormal lipid profile and coronary artery stenosis in Iranians undergoing coronary angiography. This cross-sectional study was performed on 440 patients who underwent coronary angiography. The factor analysis method was used to extract dietary patterns. Commercial kits have been used to assess biochemical parameters. The detection of the rs28362491 genotype was carried out by the method of restriction fragment length polymorphism. Traditional (TDP) and western dietary pattern (WDP) were extracted. We observed an interaction of adherence to TDP and rs28362491 on the odds of having a high Gensini score. These interactions indicated that higher adherence to TDP was associated with higher odds of having a high Gensini score for patients with DD genotype than for those with II genotype. (OR 2.33, 95%CI 1.00–5.44; P = 0.05). These interactions remained statistically significant even after confounder variables. We observed an interaction between higher adherence to TDP and rs28362491 variants on the odds of high low-density lipoprotein cholesterol levels (P = 0.04) in the unadjusted model. We found a significant interaction of this polymorphism and higher adherence to WDP on the odds of having a high Gensini score in the unadjusted model (P = 0.04). This study provides a basis for future research on NF-KB1 gene and diet interaction. More large-scale longitudinal studies are needed to validate these findings

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Background: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. Objective: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. Methods: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. Results: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 μ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with μ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with μ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). Conclusions: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort

Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses