Search

Background: Alcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which is strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation and gene expression in neuroinflammation‐related pathways in the brain, biological aging represents a potentially important construct for understanding the adverse effects of substance use disorders. Epigenetic clocks have shown accelerated aging in blood samples from individuals with AUD. However, no systematic evaluation of biological age measures in AUD across different tissues and brain regions has been undertaken. Methods: As markers of biological aging (BioAge markers), we assessed Levine's and Horvath's epigenetic clocks, DNA methylation telomere length (DNAmTL), telomere length (TL), and mitochondrial DNA copy number (mtDNAcn) in postmortem brain samples from Brodmann Area 9 (BA9), caudate nucleus, and ventral striatum (N = 63–94), and in whole blood samples (N = 179) of individuals with and without AUD. To evaluate the association between AUD status and BioAge markers, we performed linear regression analyses while adjusting for covariates. Results: The majority of BioAge markers were significantly associated with chronological age in all samples. Levine's epigenetic clock and DNAmTL were indicative of accelerated biological aging in AUD in BA9 and whole blood samples, while Horvath's showed the opposite effect in BA9. No significant association of AUD with TL and mtDNAcn was detected. Measured TL and DNAmTL showed only small correlations in blood and none in brain. Conclusions: The present study is the first to simultaneously investigate epigenetic clocks, telomere length, and mtDNAcn in postmortem brain and whole blood samples in individuals with AUD. We found evidence for accelerated biological aging in AUD in blood and brain, as measured by Levine's epigenetic clock, and DNAmTL. Additional studies of different tissues from the same individuals are needed to draw valid conclusions about the congruence of biological aging in blood and brain. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of various sowing methods on the quality characteristics of second-crop cotton fiber during the 2015-2016 production seasons in the trial field of the Batı Akdeniz Agricultural Research Institute in Antalya, Turkey. Seven cotton genotypes, including five commercial cotton cultivars and two cotton lines, were employed in a randomized block experimental design with divided plots. Two different tillage processes, namely direct sowing on stubble and sowing after traditional tillage, were implemented. Significant differences were observed among genotypes for all examined fiber quality traits. Notably, short fiber ratio and elasticity properties exhibited significant differences between applications. Short fiber ratios ranged from 6.26% to 7.95%, with a significant year*genotype interaction. Fiber strengths varied between 30.65 g/tex and 37.69 g/tex, with a significant year*application interaction. These variations were attributed to the climatic environmental factors during the trial seasons and the region's extended history, indicating their substantial impact. [ABSTRACT FROM AUTHOR]

Correlation coefficient and path analysis of some potato genotypes for tuber characteristics of seed bed and field performance were investigated. Significantly, positive correlations were found between tuber yield per decare and tuber yield per seed bed; between stem number per seed bed and tuber number per seed bed and small tuber rate; between average tuber weight and big tuber rate. Path analysis of the tuber yield characters such as stem number per seed bed, tuber yield per seed bed and average tuber weight also had the large direct effects on tuber yield per decare. This may indicate that especially the direct selection for stem number and tuber yield per seed bed would likely be effective in increasing tuber yield. [ABSTRACT FROM AUTHOR]

According to the data obtained in this study, Thymus pectinatus has antioxidant and enzyme in-hibitory activities while has not showed antimicro-bial activities. The results of the current study pro-vide valuable information, showing that the major component of the water extract of T. pectinatus is "1,3-Propanediol, 2-methyl-, dipropanoate" (59.34 %). This is the first investigation of the antioxidant and enzyme inhibitory activity of T. pectinatus. The results showed that the water extract had high anti-oxidant, anti-amylase, and anticancer effects, and a higher total phenolic content. Therefore, further phy-tochemical and bioactivity-guided isolation of T. pectinatus water extract could be carried out to identify the active compounds. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ege University School of Dentistry / Ege Üniversitesi Dis Hekimligi Fakültesi Dergisi is the property of Ege University Faculty of Dentistry and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Our materials in this study were true potato seeds obtained as a result of crossbreeding between trading cultivars and seedlings from Center of International Potatoes (CIP). Field experiments were performed in randomized block design with four replications. Comparisons were made among ten clones. According to this research, investigated properties have shown significant differences among the clones except tuber yield per plant. According to duncan groups, Clone 6 has the highest value for yield per decare. Clone 6 and Clone 9 rank first as regards big tuber percentage 53.65% and 55.50%, respectively. Clone 6 and Clone 7 showed the highest values for tuber yield per plant 290.63 g and 329.25 g, respectively and shared the same letter group. As a result of this research, Clone 6 can be evaluated as a new cultivar candidate in terms of yield. [ABSTRACT FROM AUTHOR]

Epithelial adherens junctions (AJs) are cell-cell adhesion complexes that are influenced by tissue mechanics, such as those emanating from the extracellular matrix (ECM). Here, we introduce a mechanism whereby epithelial AJs can also regulate the ECM. We show that the AJ component PLEKHA7 regulates levels and activity of the key ECM remodeling components MMP1 and LOX in well-differentiated colon epithelial cells, through the miR-24 and miR-30c miRNAs. PLEKHA7 depletion in epithelial cells results in LOX-dependent ECM remodeling in culture and in the colonic mucosal lamina propria in mice. Furthermore, PLEKHA7-depleted cells exhibit increased migration and invasion rates that are MMP1- and LOX- dependent, and form colonies in 3D cultures that are larger in size and acquire aberrant morphologies in stiffer matrices. These results reveal an AJ-mediated mechanism, through which epithelial cells drive ECM remodeling to modulate their behavior, including acquisition of phenotypes that are hallmarks of conditions such as fibrosis and tumorigenesis., Competing Interests: Competing interests: OS is the founder and the president of LoxiGen, Inc, developing LOX inhibitors. The other authors declare that they have no competing interests.

Trastuzumab emtansine (T-DM1) was the first and one of the most successful antibody-drug conjugates (ADC) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells, T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form of cell death. The payload of T-DM1 mediated ICD by inducing eIF2α phosphorylation, surface exposure of calreticulin, ATP and HMGB1 release, and secretion of ICD-related cytokines, all of which were lost in resistance. Accordingly, ICD-related gene signatures in pretreatment samples correlated with clinical response to T-DM1-containing therapy, and increased infiltration of antitumor CD8+ T cells in posttreatment samples was correlated with better T-DM1 response. Transforming acidic coiled-coil containing 3 (TACC3) was overexpressed in T-DM1-resistant cells, and T-DM1 responsive patients had reduced TACC3 protein expression whereas nonresponders exhibited increased TACC3 expression during T-DM1 treatment. Notably, genetic or pharmacologic inhibition of TACC3 restored T-DM1-induced SAC activation and induction of ICD markers in vitro. Finally, TACC3 inhibition in vivo elicited ICD in a vaccination assay and potentiated the antitumor efficacy of T-DM1 by inducing dendritic cell maturation and enhancing intratumoral infiltration of cytotoxic T cells. Together, these results illustrate that ICD is a key mechanism of action of T-DM1 that is lost in resistance and that targeting TACC3 can restore T-DM1-mediated ICD and overcome resistance., Significance: Loss of induction of immunogenic cell death in response to T-DM1 leads to resistance that can be overcome by targeting TACC3, providing an attractive strategy to improve the efficacy of T-DM1., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objective: Vitamin D status has been implicated in the pathophysiology of heart failure (HF). The aim of this study was to investigate the association between vitamin D levels with heart rate variability and heart rate turbulence in patients with heart failure whom had ischemic and non-ischemic dilated cardiomyopathy., Methods: Study designed as an observational cross-sectional study. Seventy-one patients [36 non-ischemic dilated cardiomyopathy (NIDCM), 35 ischemic dilated cardiomyopathy (IDCM)] with chronic heart failure and 25 control subject were included. It was evaluated the association between 25 hydroxyvitamin D [25(OH)D] and calcitriol levels with heart rate variability time domain (SDNN, SDANN, RMSSD) and heart rate turbulence [turbulence onset (TO), turbulence slope (TS)] parameters. Statistical analysis was performed using Kruskal-Wallis test and ANOVA., Results: Calcitriol levels in NIDCM patients with abnormal TO and TS were significantly lower than NIDCM patients with normal TO (17.1 ± 11.3 vs. 27.6 ± 15.5 pg/mL, p=0.05) and TS (16.6 ± 9.1 vs. 29.4 ± 16.9 pg/mL, p=.018). There was a positive correlation between 25 (OH) D with heart rate variability parameters SDNN (r=0.368, p=0.027) and SDANN (r=0.360, p=0.031). It was not found any association between vitamin D and parameters of heart rate variability and heart rate turbulence in IDCM patients., Conclusion: Insufficiency of vitamin D may have deleterious effects on cardiac autonomic functions which were showed with heart rate turbulence and heart rate variability in patients with NIDCM. Vitamin D levels might be a predictor to determine the sudden cardiac death in patients with non-ischemic etiology.

Background: While the adverse prognostic impact of a high level of high sensitivity C-reactive protein (hs-CRP) in coronary artery disease is well known, we lack data about the prognostic importance of hs-CRP in chronic heart failure (CHF) patients. The aim was to investigate the relationship between hs-CRP and prognosis in CHF patients., Material/methods: Patients (n=258, 74 females) with CHF of both ischemic and non-ischemic etiology were followed up for a mean period of 17 + or - 13 months. The primary end-point was cardiac mortality., Results: During the follow-up period, 71 patients died of cardiac causes. Left ventricular ejection fractions of these patients were lower, but not significantly so (23 + or - 10 vs. 26 + or - 10%, p=0.09). hs-CRP (4.57 + or - 5.35 vs. 1.88 + or - 2.75 mg/dl, p<0.001), brain natriuretic peptide (BNP) (1621 + or - 1361 vs. 736 + or - 914 pg/ml, p<0.001), and creatinine (1.7 + or - 1.7 vs. 1.2 + or - 0.6 mg/dl, p=0.015) levels were significantly higher in CHF patients with cardiac mortality. Using stepwise multivariate Cox proportional hazards regression analyses, hs-CRP proved to be a significant independent predictor of cardiac death (hazard ratio: 1.1, 95%CI: 1.05-1.15, p<0.001)., Conclusions: hs-CRP can provide additional prognostic information for the risk stratification of CHF patients. These insights might ultimately also affect the treatment of CHF patients.

The inhibition of renin-angiotensin system (RAS) has an effect beyond reducing blood pressure in the treatment of cardiovascular diseases; it also reduces mortality and morbidity. Although the classic RAS blockage is effective, due to blockage of negative feedback inhibition, it increases plasma renin activity and as a result generates a residual cardiovascular risk. Different from ACE-i and ARB treatments, aliskiren, a direct renin inhibitor, is the only pharmacologic agent that noticeably reduces the plasma renin activity, an independent cardiovascular risk factor. This creates a new option in RAS blockage. The efficacy and safety of aliskiren in the treatment of hypertension has been well established. The effect of aliskiren on cardiovascular mortality and morbidity is being researched. At this point there are many experimental and clinical studies to answer questions on this subject.