Quantitative and structural changes of blood platelet cytoskeleton proteins in multiple sclerosis (MS).

Epidemiological studies show that cardiovascular events related to platelet hyperactivity remain the leading causes of death among multiple sclerosis (MS) patients. Quantitative or structural changes of platelet cytoskeleton alter their morphology and function. Here, we demonstrated, for the first time, the structural changes in MS platelets that may be related to their hyperactivity. MS platelets were found to form large aggregates compared to control platelets. In contrast to the control, the images of overactivated, irregularly shaped MS platelets show changes in the cytoskeleton architecture, fragmented microtubule rings. Furthermore, MS platelets have long and numerous pseudopodia rich in actin filaments. We showed that MS platelets and megakaryocytes, overexpress ß1-tubulin and ß-actin mRNAs and proteins and have altered post-translational modification patterns. Moreover, we identified two previously undisclosed mutations in the gene encoding ß1-tubulin in MS. We propose that the demonstrated structural changes of platelet cytoskeleton enhance their ability to adhere, aggregate, and degranulate fueling the risk of adverse cardiovascular events in MS.

Exploring the Role of MMP-9 and MMP-9/TIMP-1 Ratio in Subacute Stroke Recovery: A Prospective Observational Study.

Despite the significant changes that unfold during the subacute phase of stroke, few studies have examined recovery abilities during this critical period. As neuroinflammation subsides and tissue degradation diminishes, the processes of neuroplasticity and angiogenesis intensify. An important factor in brain physiology and pathology, particularly neuroplasticity, is matrix metalloproteinase 9 (MMP-9). Its activity is modulated by tissue inhibitors of metalloproteinases (TIMPs), which impede substrate binding and activity by binding to its active sites. Notably, TIMP-1 specifically targets MMP-9 among other matrix metalloproteinases (MMPs). Our present study examines whether MMP-9 may play a beneficial role in psychological functions, particularly in alleviating depressive symptoms and enhancing specific cognitive domains, such as calculation. It appears that improvements in depressive symptoms during rehabilitation were notably linked with baseline MMP-9 plasma levels (r = -0.36, p = 0.025), and particularly so with the ratio of MMP-9 to TIMP-1, indicative of active MMP-9 (r = -0.42, p = 0.008). Furthermore, our findings support previous research demonstrating an inverse relationship between pre-rehabilitation MMP-9 serum levels and post-rehabilitation motor function. Crucially, our study emphasizes a positive correlation between cognition and motor function, highlighting the necessity of integrating both aspects into rehabilitation planning. These findings demonstrate the potential utility of MMP-9 as a prognostic biomarker for delineating recovery trajectories and guiding personalized treatment strategies for stroke patients during the subacute phase.

Gut Microbiota Metabolites Differentially Release Gliotransmitters from the Cultured Human Astrocytes: A Preliminary Report.

Butyrate and indole-3-propionic acid represent the CNS-available gut microbiota metabolites exhibiting potentially beneficial effects on human brain function and being tested as antidepressants. Astrocytes represent one of the putative targets for the gut metabolites; however, the mechanism of action of butyrate and indole-3-propionic acid is not well understood. In order to test this mechanism, a human astrocyte cell-line culture was treated with the compounds or without them, and the supernatants were collected for the analysis of ATP and glutamate gliotransmitter release with the use of luminescent and fluorescent methods, respectively. A 10-min incubation of astrocytes with 1-5 mM butyrate increased the ATP gliotransmitter release by 78% (95%CI: 45-119%), p < 0.001. The effect was found to be mediated by the cytosolic Ca2+ mobilization. Both 10-min and 24-h treatments with indole-3-propionic acid produced no significant effects on the release of gliotransmitters. The results for glutamate release were inconclusive due to a specific glutamate release pattern discovered in the tested model. This preliminary report of butyrate-induced ATP gliotransmitter release appears to provide a novel mechanistic explanation for the beneficial effect of this gut microbiota metabolite on brain function; however, the results require further evaluation in more composed models.

Determinants of Knowledge About Dietary Supplements Among Polish Internet Users: Nationwide Cross-sectional Study.

BACKGROUND: An accurate understanding of dietary supplements (DS) is a prerequisite for informed decisions regarding their intake. However, there is a need for studies on this understanding among the public based on validated research tools. OBJECTIVE: This study aims to assess the knowledge about DS among Polish internet users with no medical education and to identify its determinants and design an appropriate predictive model. METHODS: The study protocol was prospectively registered with a statistical analysis plan. Polish users of a web-based health service and a social networking service were administered a survey consisting of the recently developed questionnaire on knowledge about DS, the questionnaire on trust in advertising DS, the beliefs about medicines questionnaire, and several other health-related single-item measures and sociodemographic questions. The results were subjected to general linear modeling. RESULTS: A total of 6273 participants were included. Of the 17 yes or no questions in the questionnaire of knowledge about DS, the mean number of correct responses was 9.0 (95% CI 8.9-9.1). Health service users performed worse than social networking users by 2.3 points (95% CI 2.1-2.5) in an analysis adjusted for potential confounders. Internet users had fewer true beliefs about DS if they presented higher trust in their advertising (adjusted ß=-.37; 95% CI -.39 to -.34), used DS (adjusted ß=-.14; 95% CI -.17 to -.12), experienced their positive effect (adjusted ß=-.16; 95% CI -.18 to -.13), were older or younger than 35 years (adjusted ß=-.14; 95% CI -.17 to -.12), expressed interest in the topic of DS (adjusted ß=-.10; 95% CI -.13 to -.08), reported getting information about the products from friends (adjusted ß=-.13; 95% CI -.15 to -.11), and believed that medicines are harmful (adjusted ß=-.12; 95% CI -.15 to -.10). The proposed 5-predictor model could explain 31.2% of the variance in knowledge about DS. The model appeared resistant to overfitting and was able to forecast most of the observed associations. CONCLUSIONS: Polish internet users with no medical education exhibit some false beliefs regarding DS. Trusting the advertising of DS appears to conflict with knowledge about them. There is an urgent need for effective web-based educational campaigns on DS and the promotion of advertising literacy. After the proposed predictive model is externally validated, it may help identify the least informed target audience.

[Metabolic safety of antidepressant medicines]. / Metabolic safety of antidepressant medicines.

Metabolic syndrome is a very serious health issue, not only from internal medicine's point of view. Patients suffering from overweight, arterial hypertension, lipids and carbohydrates metabolism disorders are also in the circle of interest of other areas of medicine, including psychiatry. Currently, one of key problems of pharmacotherapy is a comorbidity of metabolic syndrome and mental disorder. Depression is more common than schizophrenia. Despite the fact that in everyday clinical practice there are more patients with depression than schizophrenia, there is a bigger interest among scientists for metabolic syndrome after antipsychotic drugs than as an effect of use of antidepressant agents. AIM: The aim of an analysis was to review literature committed to influence of depression pharmacotherapy on development of metabolic syndrome. 169 results were provided, including 18 original publications. Final analysis consists of 9 that investigate correlation between antidepressive medicines use and metabolic syndrome development (but not its each individual component). RESULTS: In general, antidepressant pharmacotherapy is associated not only with increased risk of metabolic syndrome occurrence but also their worsening. However, it needs to be emphasized that there is a difference between antidepressants groups - tricyclic antidepressive medicines are the most commonly associated with risk of developing metabolic disorders, but also SNRIs and SSRIs are mentioned as significant contributors. Mechanisms of aforementioned changes are still unclear. However, their influence on histamine and serotonin pathways, which take part in regulation of i.e. food intake, is suggested. The search for mechanisms that are precisely responsible for metabolic changes continues, in hope of finding a way to avoid adverse effects of antidepressant medicines use.

Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway.

BACKGROUND/AIMS: The PIK3CD gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element of the neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for the treatment of schizophrenia. The aim of the study was to examine the effect of haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on the mRNA and protein expression of genes encoding the elements of ErbB4-PI3K pathway, in a human central nervous system cell line. METHODS: The U-87MG human glioblastoma cell line was used as an experimental model. Quantitative polymerase chain reaction was used to examine the expression of mRNA and enzyme-linked immunosorbent assay for protein expression. RESULTS: At concentrations reached in clinical settings in the brain, CLO, as well as OLA and QUE to a lesser extent, but not AMI and probably not HALO, decreased the mRNA expression of PIK3CD. Protein expression of the gene did not confirm the mRNA expression profile. CONCLUSIONS: The tested antipsychotic drugs (APDs) in the U-87MG glioblastoma cell line differentially regulates the mRNA expression of PIK3CD; however, the protein expression does not confirm these findings. The results of the study may help deepen the understanding of the mechanism of action of APDs.

Haloperidol, but not olanzapine, may affect expression of PER1 and CRY1 genes in human glioblastoma cell line.

Background: There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics. We decided to verify if haloperidol and olanzapine affect expression of CLOCK, BMAL1, PER1 and CRY1 in a human central nervous system cell line model. Methods: U-87MG human glioblastoma cell line was used as an experimental model. The cells were incubated with or without haloperidol and olanzapine in the concentration of 5 and 20 µM for 24 h. Real-time quantitative polymerase chain reaction with the ΔCT analysis was used to examine the effect of haloperidol and olanzapine on the mRNA expression of the genes. Results: At 5 µM, haloperidol decreased expression of CRY1 almost 20-fold. There was nearly a 1.5-fold increase in expression of PER1. Considering the 20 µM haloperidol concentration and both olanzapine concentrations, no other statistically significant effect was observed. Conclusions: At certain concentration, haloperidol seems to affect expression of particular clock genes in a human central nervous system cell line model, yet mechanism underlying this phenomenon remains elusive.

The ability of hyaluronan fragments to reverse the resistance of C6 rat glioma cell line to temozolomide and carmustine.

AIM OF THE STUDY: Hyaluronan (HA) is an extracellular matrix (ECM) polymer that may contribute to the emergence of anti-cancer drug resistance. Attempts to reverse drug resistance using small hyaluronan oligomers (oHA) are being made. The initial reports suggest that the oHA fraction may effectively reverse anti-cancer drug resistance in glioma models. However, the reversal effects of oHA of defined molecular length on glioma cells have not been investigated yet. In this study, we examined HA fragments containing 2 disaccharide units (oHA-2), 5 disaccharide units (oHA-5), and 68 kDa hyaluronan polymer (HA-68k) as agents possibly reversing the resistance of a C6 rat glioma cell line to temozolomide (TMZ) and carmustine (BCNU). MATERIAL AND METHODS: A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay was used to assess the cytotoxicity of TMZ and BCNU in the presence or absence of the hyaluronan fragments. By comparing viability of the cells, the reversal effects of HA fragments on TMZ and BCNU resistance in C6 glioma cells were assessed. RESULTS: We found statistically significant decreases in the viability of cells in the presence of TMZ+oHA-5 as compared to TMZ alone (51.2 ±4.5 vs. 74.2 ±5.8, p = 0.0031), BCNU+o-HA5 as compared to BCNU alone (49.3 ±4.4 vs. 65.6 ±5.7, p = 0.0119), and BCNU+HA-68k as compared to BCNU alone (55.2 ±2.3 vs. 65.6 ±5.7, p = 0.0496). CONCLUSIONS: Hyaluronan oligomers of 5 disaccharide units (oHA-5) significantly reversed the resistance of C6 cells to TMZ and BCNU. The results are only preliminary and a more thorough follow-up investigation is required to assess their actual role.

Deciphering psychobiotics' mechanism of action: bacterial extracellular vesicles in the spotlight.

The intake of psychobiotic bacteria appears to be a promising adjunct to neuropsychiatric treatment, and their consumption may even be beneficial for healthy people in terms of mental functioning. The psychobiotics' mechanism of action is largely outlined by the gut-brain axis; however, it is not fully understood. Based on very recent studies, we provide compelling evidence to suggest a novel understanding of this mechanism: bacterial extracellular vesicles appear to mediate many known effects that psychobiotic bacteria exert on the brain. In this mini-review paper, we characterize the extracellular vesicles derived from psychobiotic bacteria to demonstrate that they can be absorbed from the gastrointestinal tract, penetrate to the brain, and carry the intracellular content to exert beneficial multidirectional action. Specifically, by regulating epigenetic factors, extracellular vesicles from psychobiotics appear to enhance expression of neurotrophic molecules, improve serotonergic neurotransmission, and likely supply astrocytes with glycolytic enzymes to favor neuroprotective mechanisms. As a result, some data suggest an antidepressant action of extracellular vesicles that originate even from taxonomically remote psychobiotic bacteria. As such, these extracellular vesicles may be regarded as postbiotics of potentially therapeutic application. The mini-review is enriched with illustrations to better introduce the complex nature of brain signaling mediated by bacterial extracellular vesicles and indicates knowledge gaps that require scientific exploration before further progress is made. In conclusion, bacterial extracellular vesicles appear to represent the missing piece of the puzzle in the mechanism of action of psychobiotics.

Personality traits and health-related behaviors in medical students facing a stressful event.

Background: It is believed that personality traits have an impact on the propensity to change and maintain favorable lifestyle habits. This issue has been raised by multiple studies, however, none of them appeared to focus on population under severe psychological stress. The aim of the present study was to investigate the link between personality traits and health-related behaviors and measures such as dietary intake of specific food products, physical activity, body-mass index and the use of cigarettes in medical students facing a stressful event. Methods: The study included a cohort of third-year medical students from the Medical University of Lodz, Poland, facing a stressful subject exam during the first COVID-19-related lockdown. At baseline, personality traits were evaluated with the use of the Polish version of the Big Five Inventory-Short questionnaire. Then, consumption of selected food products was monitored with the use of seven-day electronic dietary record. Also, some other health-related data was collected (body-mass index, physical activity and the use of cigarettes). General Linear Modeling techniques, logistic regression and exploratory factor analysis were applied to analyze the data. Results: Four hundred and forty-four students completed the study. A two-factor pattern of food consumption was discovered by the exploratory factor analysis in the study group (34% of the variance explained). Higher conscientiousness, but not the other personality traits, was found to be significantly associated with generally healthier lifestyle manifested by higher consumption of vegetables, wholegrain products, fruits and nuts (adjusted beta 0.16, 95%CI 0.06 to 0.26, pη2 = 2.3%, p = 0.0015) and lower cigarette smoking (adjusted odds ratio 0.84, 95%CI 0.75 to 0.94, p = 0.0020), but insignificantly with physical activity and body-mass index. Conclusion: Severely stressed medical students expressing high conscientiousness tend to present healthier behaviors. Therefore, interventions aimed at improving lifestyle habits in students with low conscientiousness might be useful.

Circulating Serum VEGF, IGF-1 and MMP-9 and Expression of Their Genes as Potential Prognostic Markers of Recovery in Post-Stroke Rehabilitation-A Prospective Observational Study.

The key period in post-stroke recovery is the first three months due to the high activity of spontaneous and therapeutic-induced processes related to neuroplasticity, angiogenesis and reperfusion. Therefore, the present study examines the expression of VEGF, IGF-1 and MMP-9 proteins and their genes to identify biomarkers that can prognose brain repair ability and thus estimate the outcome of stroke. It also identifies possible associations with clinical scales, including cognitive assessment and depression scales. The study group comprised 32 patients with moderate ischemic stroke severity, three to four weeks after incident. The results obtained after three-week hospitalization indicate a statistically significant change in clinical parameter estimations, as well as in MMP9 and VEGF protein and mRNA expression, over the rehabilitation process. Our findings indicate that combined MMP9 protein and mRNA expression might be a useful biomarker for cognitive improvement in post-stroke patients, demonstrating 87% sensitivity and 71% specificity (p < 0.0001).

Mental Health of Students at Polish Universities after Two Years of the Outbreak of COVID-19.

BACKGROUND: Mental health deterioration in young adults in the aftermath of the COVID-19 pandemic is being increasingly studied. It is clear that the psychological consequences of the pandemic will be evident for many years, especially among the younger generation, who did not have time to acquire adaptive coping strategies before the outbreak of COVID-19. The purpose of this study was to assess the condition of the mental health of students at Polish universities after two years of the pandemic. The types of coping strategies used by the respondents to deal with stress were also evaluated in order to establish which of them could have a beneficial effect on the psyche of young people. METHODS: This study included 721 participants (age [years]: M = 25.7, SD = 5.3; 269 (37.2%) males) recruited using snowball sampling from students at two universities in Lodz, Poland, and full-time doctoral students from across Poland (phase I of the study was conducted in March 2019 (N = 352); phase II of the study was conducted in April 2022 (N = 369)). The following tools were used in this study: The General Health Questionnaire (GHQ-28) by D. Goldberg, the Perceived Stress Scale (PSS-10), and the Inventory for Measuring Coping with Stress (Mini-COPE) by Carver et al. Pearson's chi-square test and multivariate logistic regression were used in the statistical analysis. RESULTS: The results detailing the condition of the mental health of the subjects, as measured using GHQ-28, were significantly worse in the group surveyed after two years of the pandemic than the results of the survey conducted in March 2019 (adjusted odds ratio for GHQ-28 ≥ 5: 3.66, 95%CI 2.12-6.30, p < 0.001). Statistically significant differences were seen for each of the subscales of the GHQ-28 questionnaire. Most often, the subjects complained of anxiety symptoms and sleep disorders, in addition to somatic symptoms. The risk factors for worsening mental health included female (odds ratio 1.70, 95%CI 1.20-2.40, p = 0.003) and professional inactivity (odds ratio 1.55, 95%CI 1.04-2.31, p = 0.031). On the other hand, the ages of the people surveyed, their relationship status, whether they had children, or the type of university they attended all proved to be insignificant. The following coping strategies had a positive impact on the mental health of the respondents: positive reframing (Z = -2.951; p = 0.003) and seeking emotional support (Z = -2.351; p = 0.019). In contrast, strategies such as self-distraction (Z = 2.785; p = 0.005), denial (Z = 2.948; p = 0.003), venting (Z = 2.337; p = 0.019), self-blame (Z = 5.511; p < 0.001) and behavioral disengagement (Z = 4.004; p < 0.001) were associated with poorer mental health among the respondents. CONCLUSIONS: 1. Of the students surveyed, 33% reported elevated stress levels after two years of the COVID-19 pandemic. 2. The overall mental health of students at Polish universities, as measured by GHQ-28, was significantly worse in the group evaluated after two years of the COVID-19 pandemic, mainly in respect of anxiety symptoms and sleep disorders. 3. Female gender and professional inactivity appeared to be risk factors for the students' worsening mental health, which may be an indication of the need for further research and planning of psychotherapeutic interventions.

The Association of Salivary Serotonin With Mood and Cardio-Autonomic Function: A Preliminary Report.

Background: Serotonin plays an important role in mood regulation and depression. However, it is not clear whether the levels of serotonin in saliva are related to current mood. Aim: To test the association of salivary serotonin concentrations with mood, as well as cardiovascular and autonomic parameters. Materials and Methods: Saliva samples were obtained from collegiate runners and output parameters were examined before and after physical activity. Results: Salivary serotonin concentration was negatively associated with current mood (ß = -0.32, 95%CI -0.62 to -0.02, p = 0.037, analysis adjusted for potential confounders), but insignificantly with measured cardiovascular and autonomic parameters. Conclusions: Salivary serotonin may reflect current mood. The results are preliminary and require further evaluation.

Who Benefits from Fermented Food Consumption? A Comparative Analysis between Psychiatrically Ill and Psychiatrically Healthy Medical Students.

Probiotic therapies and fermented food diets hold promise for improving mental health. Although in this regard psychiatric patients appear to benefit more than healthy individuals, no research has been performed to directly evaluate this hypothesis. The present study examined a cohort of medical students facing a stressful event, and some of the students reported suffering from chronic psychiatric diseases. The amount of fermented food consumption was calculated with the use of seven-day dietary records, while depressive and anxiety symptoms were assessed with the use of the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. In psychiatrically healthy medical students under psychological stress (n = 372), higher fermented food consumption was associated with more depressive and anxiety symptoms. In contrast, psychiatrically ill medical students (n = 25, 6.3% of all the participants) were found to present a negative association between the amount of fermented food consumed and the severity of depressive symptoms (adjusted ß -0.52, 95% CI -0.85 to -0.19, p = 0.0042); however, this relationship was insignificant for anxiety symptoms (adjusted ß -0.22, 95% CI -0.59 to 0.15, p = 0.22). A significant interaction was found between the consumption of fermented food and psychiatric diagnosis in predicting depressive symptoms (p = 0.0001), and a borderline significant interaction for anxiety symptoms (p = 0.053). In conclusion, psychiatrically ill people, but not healthy ones, may benefit from fermented food consumption in terms of alleviation of depressive symptoms. Our findings require cautious interpretation and further investigation.

Association Between Consumption of Fermented Food and Food-Derived Prebiotics With Cognitive Performance, Depressive, and Anxiety Symptoms in Psychiatrically Healthy Medical Students Under Psychological Stress: A Prospective Cohort Study.

Background: Gut microbiota-based therapeutic strategies, such as probiotic and prebiotic preparations, may benefit mental health. However, commonly consumed fermented and prebiotic-containing foods have not been well-tested. The aim of the present study was to determine whether consumption of fermented food and food-derived prebiotics is associated with cognitive performance, depressive, and anxiety symptoms in psychiatrically healthy medical students under psychological stress. Methods: The study protocol with data analysis plan was prospectively registered. Food consumption was evaluated with a 7-day dietary record. Cognitive performance was modeled with academic examination performance in relation to subject knowledge. Pre-exam depressive and anxiety symptoms were assessed with the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Results: In total, 372 medical students (22.7 ± 1.1 years of age, 66% female) completed the study. No relationship was observed between cognitive performance under stress and either fermented food (adjusted ß 0.02, 95% CI -0.07-0.11, p = 0.63) or food-derived prebiotics consumption (adjusted ß -0.00, 95% CI -0.09-0.09, p = 0.99). High intake of fermented food was associated with more severe depressive (adjusted ß 0.11, 95% CI 0.01-0.20, p = 0.032) and anxiety symptoms under stress (adjusted ß 0.13, 95% CI 0.04-0.22, p = 0.0065); however, no such link was observed for food-derived prebiotics (adjusted ß 0.03, 95% CI -0.07-0.13, p = 0.50 and -0.01, 95% CI -0.11-0.08, p = 0.83, for depression and anxiety, respectively). Conclusions: Under psychological stress in medical students, consumption of fermented food and food-derived prebiotics appears to be not associated with cognitive performance. High intake of fermented food, but not food-derived prebiotics, may be associated with severity of depressive and anxiety symptoms. The safety of fermented food in this regard therefore requires further clarification.

Mechanisms of Cognitive Impairment in Depression. May Probiotics Help?

Depression is the major cause of disability globally. Apart from lowered mood and accompanying symptoms, it leads to cognitive impairment that altogether predicts disadvantaged social functioning. Reduced cognitive function in depression appears a bit neglected in the field of clinical and molecular psychiatry, while it is estimated to occur in two-thirds of depressed patients and persist in at least one third of remitted patients. This problem, therefore, requires elucidation at the biomolecular and system levels and calls for improvement in therapeutic approach. In this review study, we address the above-mentioned issues by discussing putative mechanisms of cognitive decline in depression: (1) increased oxidative stress and (2) inflammation, (3) disturbed hypothalamus-pituitary-adrenals axis, and (4) reduced monoamines functionality. Moreover, we acknowledge additional underpinnings of cognitive impairment in depressed elderly: (5) vascular-originated brain ischemia and (6) amyloid-beta plaque accumulation. Additionally, by reviewing molecular, pre-clinical and clinical evidence, we propose gut microbiota-targeted strategies as potential adjuvant therapeutics. The study provides a consolidated source of knowledge regarding mechanisms of cognitive impairment in depression and may path the way toward improved treatment options.

Dysregulation in the Expression of Platelet Surface Receptors in Acute Coronary Syndrome Patients-Emphasis on P2Y12.

The pathological conditions caused by blood platelet activation constitute a fundamental core in the pathogenesis of Acute Coronary Syndrome (ACS). The hyperactivity of platelets in ACS is well-documented, but there is still little research into the molecular basis of phenotypic changes in platelet functionality. To expand the knowledge of this phenomenon, we analyzed the disturbances in the expression of several key platelet receptors and the aspect of regulating potential abnormalities. Platelet surface receptors are responsible for maintaining the hemostatic balance, platelet interaction with immune cells, and support of the coagulation cascade leading to occlusion of the vessel lumen. Due to their prominent role, platelet receptors constitute a major target in pharmacological treatment. Our work aimed to identify the molecular alteration of platelet surface receptors, which showed augmented mRNA expression of P2Y12, GP1BB, ITGA2B, and ITGB3 and increased protein concentrations of P2Y12 and GP IIb/IIIa in ACS. The upregulation of the P2Y12 level was also confirmed by confocal and cytometric visualization. Furthermore, we evaluated the expression of two microRNAs: miR-223-3p and miR-126-3p, which were suggested to regulate platelet P2Y12 expression. Results of our study present new insight into the molecular background of ACS.

New insights into the regulation of TGF-ß/Smad and MPK signaling pathway gene expressions by nasal allergen and methacholine challenge test in asthma.

Background: Asthma is a heterogeneous chronic inflammatory disease of the bronchi, the course of which is significantly influenced by extrinsic factors (specific and non-specific). Methods: The aim of this study was to evaluate the effect of these factors represented by nasal allergen challenge (specific factors) and methacholine challenge test (non-specific) on changes in mRNA expression of genes encoding the TGF-ß (TGF-ß1 and TGF-ß3)‒Smad (mitogen-activated protein kinase 1/3 [MPK1/3], Smad1/3/6/7) signaling pathway in asthmatic patients. Results: Seventy-five subjects were included in the study, of whom 27 were applied an intranasal allergen provocation and 48 a methacholine provocation. There were 9 men and 18 women in the intranasal provocation group, and 17 men and 31 women in the methacholine test group. We found that both examined the types of challenges contributed to changes in the relative expression of genes of the TGF-ß (TGF-ß1 and TGF-ß3)‒Smad (MPK1/3, Smad1/3/6/7) signaling pathway in asthmatic patients. A decrease was noted for MAPK1, MAPK3, Smad3, Smad6, and Smad7 genes and an increase of up to 2.5 times for TGF-ß1 gene. Conclusions: Our experiment allows us to conclude that the change in the mRNA expression of the TGF-ß1-MPK1/3 and Smad3/6/7 genes occurs after an intranasal allergen and bronchial methacholine challenge.

Mental Health of PhD Students at Polish Universities-Before the COVID-19 Outbreak.

BACKGROUND: A group particularly exposed to the occurrence of disorders in the sphere of the psyche are young people with a newly developing personality structure and a sense of identity. In the available literature there are few reports describing the mental health of doctoral students-a group that is affected by a particular group of stressors. The aim of the research was to assess the mental health of PhD students at Polish universities. MATERIAL AND METHODS: The Polish adaptation of the GHQ Questionnaire-28, developed by David Goldberg et al. was used in the research. PhD students from all universities associated in the National Representation of Doctoral Students were invited to take part in the research. A total of 576 completed questionnaires were received. RESULTS: It was found that depression is statistically more frequent in doctoral students who are not in any relationship with another person; anxiety/insomnia is more common in women than men and less frequently in doctoral students of general than in technical universities. CONCLUSIONS: (1) More than half of the surveyed students complain about the deterioration of mental health. The most commonly reported symptom groups are anxiety and insomnia, followed by social dysfunctions and somatic symptoms. (2) Depression is statistically more common in people who are not in any relationship with another person and anxiety and insomnia are statistically more common in women than in men and statistically less frequent in doctoral students of general universities than technical universities. (3) In view of the presented results, educating young adults in the field of self-awareness in the field of mental health seems to be particularly important.

Health-, medication- and dietary supplement-related behaviors and beliefs relatively unchanged during the COVID-19 pandemic lockdown.

BACKGROUND: The lockdown imposed to counter the coronavirus disease 2019 (COVID-19) pandemic has evoked an unprecedented phenomenon that could affect health behaviors and beliefs. OBJECTIVE: To examine how medication-, dietary supplement- and health-related behaviors, beliefs and other psychological constructs changed in Polish online health service users during the COVID-19 pandemic lockdown. METHODS: A one-time online survey accessed through a health service website was completed before and during the pandemic lockdown by separate samples of respondents. The survey examined beliefs about medicines and dietary supplements, consumption of dietary supplements, trust and contact with their advertisements, sources of dietary supplement knowledge as well as perceived health, diet, physical activity and smoking, among other things. RESULTS: The study included 1560 participants. Most examined outcomes remained unchanged over COVID-19 pandemic lockdown. Beliefs that the dietary supplement quality is well controlled became significantly more pronounced during the lockdown (adjusted ratio of estimates 1.16, 95%CI 1.06-1.27, p = 0.001). Fewer people reported having contact with dietary supplement advertisements (adjusted odds ratio 0.59, 95%CI 0.43-0.83, p = 0.002). CONCLUSIONS: The results may help understand some health-related issues associated with COVID-19 pandemic lockdown and may be used to shape aspects of health-related policy.