👤 Mutay Aslan

The aim of the current study was to assess the potential neuroprotective effects of lithium chloride (LiCl) against retinal degeneration (RD) induced by N-methyl-N-nitrosourea (MNU) in the rats. 108 rats were assigned to 6 groups: Control, MNU (80 mg/kg), MNU + 30 mg/kg LiCI, MNU + 60 mg/kg LiCI, 30 mg/kg LiCI, and 60 mg/kg LiCI. The experimental groups comprised 18 rats each and the animals were euthanised on the 2nd, 7th and 14th days following the administration of MNU. Compared with the MNU group, both doses of LiCl significantly reduced retinal cell apoptosis and increased retinal thickness (P < 0.05). MNU group had a higher apoptotic index than the treatment groups, as evidenced by increased immunoreactivities of caspase-3, caspase-6, Bax, and 8-OHdG and decreased immunoreactivities of Bcl-2 at day 2. The outer nuclear layer (ONL) of the retina in rats treated with MNU exhibited a significant reduction in comparison the control group on both days 7 and 14 (P < 0.05). In contrast to the MNU-treated figgroup, the LiCl-injected rats exhibited a notable elevation in the expression levels of BDNF and Bcl-2 (P < 0.05). Conversely, the MNU-treated group exhibited markedly increased expression of GSK-3β, Bax, 8-OHdG, caspase-3, and caspase 6 (P < 0.05). In conclusion, LiCl demonstrated dose-dependent neuroprotective effects against MNU-induced RD in rats. These effects included a reduction in retinal cell apoptosis, an improvement in retinal thickness, and the potential involvement of anti-apoptotic mechanisms, glial activation inhibition, and neurotrophic factor modulation. Show less

Physical activity (PA) and sedentary behavior (SB) are associated with many diseases, including Alzheimer's disease and all-cause dementia. However, the specific biological mechanisms through which PA protects against disease are not entirely understood. This study aims to address this gap, with a specific focus on all-cause dementia. We first assessed the conventional observational associations of three self-reported and three device-based PA/SB measures with circulating levels of 2,911 plasma proteins measured in the UK Biobank (n max =39,160) and assessed functional enrichment of identified proteins. We then used bi-directional Mendelian randomization (MR) to further evaluate the evidence for causal relationships of PA/SB with protein levels. Finally, we performed mediation analyses to identify proteins that may mediate the relationship of PA with incident all-cause dementia. Our findings revealed 41 proteins consistently associated with all PA measures and 1,027 proteins associated with at least one PA measure. Both conventional observational and MR study designs converged on proteins that appear to increase as a result of PA, including integrins such as ITGAV and ITGAM, as well as MXRA8, CLEC4A, CLEC4M, LPL, and ADGRG2; on proteins that appear to decrease as a result of PA such as LEP, INHBC, CLMP, PTGDS, ADM, OGN, and PI3; and on proteins that are more responsive to high-intensity PA, such as CA14, CA6, CA4, KIT, and ANGPT2. Functional enrichment analyses revealed processes such as cell-matrix adhesion, integrin-mediated signaling, and collagen binding. Finally, GDF15, ITGAV, ITGAM, ITGA11, HPGDS, GFAP, ADM, AHNAK, and DPP4 were among 21 unique proteins found to mediate the relationship of PA with all-cause dementia, implicating processes such as synaptic plasticity, neurogenesis, and inflammation. Our results provide insights into how PA affects biological processes and protects against dementia, and provide avenues for future research into the health-promoting effects of PA. Show less

Subclinical atherosclerosis is a key predictor of cardiovascular events. While inflammation plays a crucial role in atherosclerosis, the involvement of Human Neutrophil Peptides 1-3 (HNP1-3) in its progression remains unclear. The study investigates the association of HNP1-3 and PCSK9 with coronary atherosclerotic burden and explores the potential mediatory role of PCSK9 in HNP1-3's effect on atherogenesis. Patients who underwent coronary computed tomographic angiography (CCTA) and had subclinical atherosclerosis (luminal stenosis < 50%) or normal coronary arteries were included in this cross-sectional study. HNP1-3 and PCSK9 levels were measured using ELISA, and coronary plaque burden was quantified using the modified Gensini score. Patients with subclinical atherosclerosis had significantly higher levels of HNP1-3 (p < 0.001), PCSK9 (p < 0.001), and lipoprotein(a) [Lp(a)] (p < 0.001) compared to controls. HNP1-3 was an independent predictor of subclinical atherosclerosis (p < 0.001), and its levels positively correlated with the modified Gensini score (p < 0.001). In multinomial logistic regression, higher levels of HNP1-3, PCSK9, and Lp(a) were independently associated with higher modified Gensini score tertiles. Mediation analysis revealed that PCSK9 mediated 48.7% of the effect of HNP1-3 on the modified Gensini score. After adjusting for hsCRP and cardiovascular risk factors, the direct effect of HNP1-3 became statistically insignificant, while the indirect effect via PCSK9 remained significant, suggesting that PCSK9 fully mediates the pro-atherogenic effects of HNP1-3. In conclusion, HNP1-3 is a novel independent predictor of subclinical atherosclerosis and coronary plaque burden, with its effects being mediated through PCSK9. These findings suggest that targeting PCSK9 could mitigate the inflammatory actions of HNP1-3, offering potential therapeutic insights for atherosclerosis prevention. Show less

Physical activity (PA), including sedentary behavior, is associated with many diseases, including Alzheimer's disease and all-cause dementia. However, the specific biological mechanisms through which PA protects against disease are not entirely understood. To address this knowledge gap, we first assessed the conventional observational associations of three self-reported and three device-based PA measures with circulating levels of 2,911 plasma proteins measured in the UK Biobank (n Show less

Carbamoyl phosphate synthetase 1 (CPS-1) deficiency is a rare urea cycle disorder with an estimated prevalence of one in 150,000-200,000 live births. Patients often present with hyperammonemia shortly after protein feeding in the early days of life, and early-onset type is associated with high mortality rate. We present here a case of a newborn male with a history of two deceased siblings whose ammonium level exceeded 200 μmol/L on the first day after birth, and who was started on dextrose infusion and ammonia-scavenging therapy after oral feeding was discontinued. Peritoneal dialysis was initiated after the patient's ammonia level exceeded 500 μmol/L. At the age of five months, the patient underwent hemodialysis due to elevated ammonia levels accompanied by lethargy. The patient's ammonia levels were successfully brought under control, and the patient underwent a liver transplantation at the age of six month, donated by the father. We present this case to emphasize the efficacy of liver transplantation from a parent carrying a CPS-1 deficiency. The authors believe that, with further support from future studies, the use of carglumic acid can improve the prognosis in the chronic management of CPS-1 deficiency. Show less

Tuberculosis (TB) poses significant health challenges globally, contributing significantly to illness and mortality. Approximately one-fourth of the world's population is believed to carry the tuberculosis bacterium, with a 5-10% lifetime risk of developing active TB disease. Timely identification of TB and rapid detection of drug resistance are crucial in mitigating its global impact. Clinical, radiological, bacteriological, and molecular methods are used to screen and diagnose TB. Microscopy, culture, and immunological methods are commonly employed. Although microscopy has been used for approximately a century, it has limitations, necessitating its use and evaluation alongside other diagnostic techniques for a complete and accurate diagnosis. Bacterial culture in solid and liquid media is still the gold standard recommended by the World Health Organization (WHO) for the diagnosis of TB, as it enables the isolation of Show less

The aim of the study was to investigate changes in serum sphingolipid levels and high density lipoprotein (HDL) subtypes with relation to low-density lipoprotein cholesterol (LDL-C), non-HDL-C and triglyceride (TG) levels in type 2 diabetes mellitus (T2DM) patients. Blood was obtained from 60 patients with T2DM. Levels of sphingosine-1-phosphate (S1P), C16-C24 sphingomyelins (SMs), C16-C24 ceramides (CERs), and C16 CER-1 P were determined by LC-MS/MS. Serum concentrations of cholesterol ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-1 (apoA-I) were analyzed by enzyme-linked immunosorbent assay (ELISA). HDL subfraction analysis was performed by Disc polyacrylamide gel electrophoresis. C16 SM, C24 SM, C24-C16 CER and C16 CER-1 P levels were significantly increased in T2DM patients with LDL-C above 160 mg/dL, compared to those with LDL-C below 100 mg/dL. A significant correlation was observed between C24:C16 SM, C24:C16 CER ratios and LDL-C, non HDL-C levels. Higher serum levels of C24 SM, C24-C18 CER and C24:C16 SM ratio was seen in obese T2DM patients (BMI>30) compared to those with BMI 27-30. Patients with fasting TG levels below 150 mg/dL had significantly increased HDL-large and significantly decreased HDL-small fractions compared to those with fasting TG levels above 150 mg/dL. Obese dyslipidemic T2DM patients had increased levels of serum sphingomyelins, ceramides and HDL-small fractions. The ratio of serum C24:C16 SM, C24:C16 CER and long chain CER levels may be used as diagnostic and prognostic indicators of dyslipidemia in T2DM. Show less

Epigenetic mechanisms are important in aging and may be involved in late-life changes in cognitive abilities. We conducted an epigenome-wide association study of leukocyte DNA methylation in relation to level and change in cognitive abilities, from midlife through late life in 535 Swedish twins. Methylation levels were measured with the Infinium Human Methylation 450 K or Infinium MethylationEPIC array, and all sites passing quality control on both arrays were selected for analysis (n = 250,816). Empirical Bayes estimates of individual intercept (age 65), linear, and quadratic change were obtained from latent growth curve models of cognitive traits and used as outcomes in linear regression models. Significant sites (p < 2.4 × 10 Leukocyte DNA methylation was associated with level, but not change in cognitive abilities. The associations were substantially attenuated in within-pair analyses, indicating they are influenced in part by genetic factors. Show less

Post-traumatic stress disorder (PTSD) is a major problem among military veterans and civilians alike, yet its pathophysiology remains poorly understood. We performed a genome-wide association study and bioinformatic analyses, which included 146,660 European Americans and 19,983 African Americans in the US Million Veteran Program, to identify genetic risk factors relevant to intrusive reexperiencing of trauma, which is the most characteristic symptom cluster of PTSD. In European Americans, eight distinct significant regions were identified. Three regions had values of P < 5 × 10 Show less