Docosahexaenoic Acid (DHA) Reduces LPS-Induced Inflammatory Response Via ATF3 Transcription Factor and Stimulates Src/Syk Signaling-Dependent Phagocytosis in Microglia.

BACKGROUND/AIMS: Microglial cells play a crucial role in the development of neuroinflammation in response to harmful stimuli, such as infection, ischemia or injury. Their chronic activation, however, is associated with a progression of neurodegenerative diseases. Therefore, looking for potential factors limiting microglial activation, the effect of docosahexaenoic acid (DHA) on the inflammatory response and TREM2-dependent phagocytic activity in microglia was investigated. METHODS: In LPS-induced primary microglia preincubated with DHA, or without preincubation the expression of ATF3 and TREM2 genes and TREM2, Syk, Akt proteins were determined by RT-PCR and WB, respectively. Cell viability was assayed by MTT and cytokine and chemokine expression was determined by the Proteome Profiler assay. Moreover, the phagocytic activity of microglia was assayed using immunofluorescence. RESULTS: We found that DHA significantly increased the expression of ATF3 , and decreased the levels of CINC-1, CINC-2αß, CINC-3 chemokines, IL-1α and IL-1ß cytokines, and ICAM-1 adhesion protein. Additionally, preincubation of microglia with DHA resulted in increased Src/Syk kinases activation associated with increased phagocytic microglia activity. CONCLUSION: These findings indicate that DHA efficiently inhibits ATF3-dependent release of proinflammatory mediators and enhances phagocytic activity of microglia. The study provides a new mechanism of DHA action in reactive microglia, which may help limit neuronal damage caused by the pro-inflammatory milieu in the brain.

Low Exercise Tolerance as a Marker of Erectile Dysfunction and Depression among Post-Myocardial Infarction Men.

Evidence has grown recently on the correlation between lifestyle and physical activity, and their impact on the functioning of the entire organism. In addition, a decrease in physical efficiency may be an indicator of the early diagnosis of systemic diseases. The aim of this study was to determine whether there is a relationship between exercise tolerance and possible erectile dysfunction or mental disorders. A cross-sectional study was conducted among 254 men in 4 cardiac rehabilitation centers in Poland using the standardized International Index of Erectile Function 5 (IIEF-5) and Beck Depression Inventory (BDI) questionnaires. Erectile dysfunction was directly proportional to the metabolic equivalent of the task (MET) variable. An increase in exercise tolerance by 1 point was associated with an increase in the IIEF-5 score by 1.62 points, indicating a reduction in the severity of erectile dysfunction. The 1-point increase in MET was associated with a 1.8-point decrease in BDI, indicating that an increase in exercise tolerance is associated with a decrease in the severity of depressive disorders. Increasing the tolerance of physical effort has a beneficial effect not only on the general well-being, but also on the sexual and mental health of men. An increase in exercise tolerance is associated with a reduction in the incidence of erectile dysfunction. On the other hand, in patients with depressive disorders, the improvement of exercise tolerance reduces the intensity of depression symptoms. Exercise tolerance can be an early and simple marker at the onset of erectile dysfunction or mood disorders.

Internet Addiction and Polish Women's Sexual Functioning: The Role of Social Media, Online Pornography, and Game Use during the COVID-19 Pandemic-Online Surveys Based on FSFI and BSMAS Questionnaires.

In this study, we investigated the relationship between social media use and women's sexual functioning during the COVID-19 pandemic. Data were collected between April and November 2021. Online surveys including the Female Sexual Functioning Index (FSFI) and Bergen Social Media Addiction Scale (BSMAS) questionnaires were distributed to young, sexually active women. Information was collected on their demographics, sexual life, and use of social media. We enrolled 546 women (mean age 23.07 ± 4.69). In general, 5.68% of the women were at high risk of social media addiction. Social media addiction had a negative impact on FSFI scores, while pornography use had a positive effect on women's sexual functioning. Users of dating apps also obtained lower FSFI scores than non-users. No differences in FSFI scores were observed between gamers and non-gamers. The impact of time spent on social media on FSFI scores was not significant. We conclude that social media addiction negatively affected women's sexual functioning during the COVID-19 pandemic.

Regulation of the Bud Dormancy Development and Release in Micropropagated Rhubarb 'Malinowy'.

Culinary rhubarb is a vegetable crop, valued for its stalks, very rich in different natural bioactive ingredients. In commercial rhubarb stalk production, the bud dormancy development and release are crucial processes that determine the yields and quality of stalks. To date, reports on rhubarb bud dormancy regulation, however, are lacking. It is known that dormancy status depends on cultivars. The study aimed to determine the dormancy regulation in a valuable selection of rhubarb 'Malinowy'. Changes in carbohydrate, total phenolic, endogenous hormone levels, and gene expression levels during dormancy development and release were studied in micropropagated rhubarb plantlets. Dormancy developed at high temperature (25.5 °C), and long day. Leaf senescence and dying were consistent with a significant increase in starch, total phenolics, ABA, IAA and SA levels. Five weeks of cooling at 4 °C were sufficient to break dormancy, but rhizomes stored for a longer duration showed faster and more uniformity leaf growing, and higher stalk length. No growth response was observed for non-cooled rhizomes. The low temperature activated carbohydrate and hormone metabolism and signalling in the buds. The increased expression of AMY3, BMY3, SUS3, BGLU17, GAMYB genes were consistent with a decrease in starch and increase in soluble sugars levels during dormancy release. Moreover, some genes (ZEP, ABF2, GASA4, GA2OX8) related to ABA and GA metabolism and signal transduction were activated. The relationship between auxin (IAA, IBA, 5-Cl-IAA), and phenolic, including SA levels and dormancy status was also observed.

Growth Cessation and Dormancy Induction in Micropropagated Plantlets of Rheum rhaponticum 'Raspberry' Influenced by Photoperiod and Temperature.

Dormancy development in micropropagated plantlets at the acclimatization stage and early growth ex vitro is undesirable as it lowers their survival rate and restricts the efficient year-round production of planting material. Thus far, little is known about the factors and mechanisms involved in the dormancy development of micropropagated herbaceous perennials, including rhubarb. This study determined physiological and molecular changes in the Rheum rhaponticum (culinary rhubarb) 'Raspberry' planting material in response to photoperiod and temperature. We found that the rhubarb plantlets that were grown under a 16-h photoperiod (LD) and a temperature within the normal growth range (17-23 °C) showed active growth of leaves and rhizomes and did not develop dormancy. Rapid growth cessation and dormancy development were observed in response to a 10-h photoperiod (SD) or elevated temperature under LD. These morphological changes were accompanied by enhanced abscisic acid (ABA) and starch levels and also the upregulation of various genes involved in carbohydrate synthesis and transport (SUS3, AMY3, BMY3, BGLU17) and ABA synthesis and signaling (ZEP and ABF2). We also found enhanced expression levels of heat shock transcription factors (HSFA2 and HSFA6B), heat shock proteins (HSP22, HSP70.1, HSP90.2 and HSP101) and antioxidant enzymes (PRX12, APX2 and GPX). This may suggest that dormancy induction in micropropagated rhubarb plantlets is a stress response to light deficiency and high temperatures and is endogenously coordinated by the ABA, carbohydrate and ROS pathways.

Omega-3 PUFAs Suppress IL-1ß-Induced Hyperactivity of Immunoproteasomes in Astrocytes.

The role of immunoproteasome (iP) in astroglia, the cellular component of innate immunity, has not been clarified. The results so far indicate that neuroinflammation, a prominent hallmark of Alzheimer's disease, strongly activates the iP subunits expression. Since omega-3 PUFAs possess anti-inflammatory and pro-resolving activity in the brain, we investigated the effect of DHA and EPA on the gene expression of constitutive (ß1 and ß5) and inducible (iß1/LMP2 and iß5/LMP7) proteasome subunits and proteasomal activity in IL-1ß-stimulated astrocytes. We found that both PUFAs downregulated the expression of IL-1ß-induced the iP subunits, but not the constitutive proteasome subunits. The chymotrypsin-like activity was inhibited in a dose-dependent manner by DHA, and much strongly in the lower concentration by EPA. Furthermore, we established that C/EBPα and C/EBPß transcription factors, being the cis-regulatory element of the transcription complex, frequently activated by inflammatory mediators, participate in a reduction in the iP subunits' expression. Moreover, the expression of connexin 43 the major gap junction protein in astrocytes, negatively regulated by IL-1ß was markedly increased in PUFA-treated cells. These findings indicate that omega-3 PUFAs attenuate inflammation-induced hyperactivity of iPs in astrocytes and have a beneficial effect on preservation of interastrocytic communication by gap junctions.

Apple Autotetraploids with Enhanced Resistance to Apple Scab (Venturia inaequalis) Due to Genome Duplication-Phenotypic and Genetic Evaluation.

Among the fungal diseases of apple trees, serious yield losses are due to an apple scab caused by Venturia inaequalis. Protection against this disease is based mainly on chemical treatments, which are currently very limited. Therefore, it is extremely important to introduce cultivars with reduced susceptibility to this pathogen. One of the important sources of variability for breeding is the process of polyploidization. Newly obtained polyploids may acquire new features, including increased resistance to diseases. In our earlier studies, numerous tetraploids have been obtained for several apple cultivars with 'Free Redstar' tetraploids manifesting enhanced resistance to apple scab. In the present study, tetraploids of 'Free Redstar' were assessed in terms of phenotype and genotype with particular emphasis on the genetic background of their increased resistance to apple scab. Compared to diploid plants, tetraploids (own-rooted plants) were characterized with poor growth, especially during first growing season. They had considerably shorter shoots, fewer branches, smaller stem diameter, and reshaped leaves. In contrast to own-rooted plants, in M9-grafted three-year old trees, no significant differences between diplo- and tetraploids were observed, either in morphological or physiological parameters, with the exceptions of the increased leaf thickness and chlorophyll content recorded in tetraploids. Significant differences between sibling tetraploid clones were recorded, particularly in leaf shape and some physiological parameters. The amplified fragment length polymorphism (AFLP) analysis confirmed genetic polymorphism of tetraploid clones. Methylation-sensitive amplification polymorphism (MSAP) analysis showed that the level of DNA methylation was twice as high in young tetraploid plants as in a diploid donor tree, which may explain the weaker vigour of neotetraploids in the early period of their growth in the juvenile phase. Molecular analysis showed that 'Free Redstar' cultivar and their tetraploids bear six Rvi genes (Rvi5, Rvi6, Rvi8, Rvi11, Rvi14 and Rvi17). Transcriptome analysis confirmed enhanced resistance to apple scab of 'Free Redstar' tetraploids since the expression levels of genes related to resistance were strongly enhanced in tetraploids compared to their diploid counterparts.