Apoptosis, Autophagy, and Mitophagy Genes in the CA3 Area in an Ischemic Model of Alzheimer's Disease with 2-Year Survival.

Background: Currently, no evidence exists on the expression of apoptosis (CASP3), autophagy (BECN1), and mitophagy (BNIP3) genes in the CA3 area after ischemia with long-term survival. Objective: The goal of the paper was to study changes in above genes expression in CA3 area after ischemia in the period of 6-24 months. Methods: In this study, using quantitative RT-PCR, we present the expression of genes associated with neuronal death in a rat ischemic model of Alzheimer's disease. Results: First time, we demonstrated overexpression of the CASP3 gene in CA3 area after ischemia with survival ranging from 0.5 to 2 years. Overexpression of the CASP3 gene was accompanied by a decrease in the activity level of the BECN1 and BNIP3 genes over a period of 0.5 year. Then, during 1-2 years, BNIP3 gene expression increased significantly and coincided with an increase in CASP3 gene expression. However, BECN1 gene expression was variable, increased significantly at 1 and 2 years and was below control values 1.5 years post-ischemia. Conclusions: Our observations suggest that ischemia with long-term survival induces neuronal death in CA3 through activation of caspase 3 in cooperation with the pro-apoptotic gene BNIP3. This study also suggests that the BNIP3 gene regulates caspase-independent pyramidal neuronal death post-ischemia. Thus, caspase-dependent and -independent death of neuronal cells occur post-ischemia in the CA3 area. Our data suggest new role of the BNIP3 gene in the regulation of post-ischemic neuronal death in CA3. This suggests the involvement of the BNIP3 together with the CASP3 in the CA3 in neuronal death post-ischemia.

Alpha-, Beta-, and Gamma-Secretase, Amyloid Precursor Protein, and Tau Protein Genes in the Hippocampal CA3 Subfield in an Ischemic Model of Alzheimer's Disease with Survival up to 2 Years.

Background: Understanding the phenomena underlying the non-selective susceptibility to ischemia of pyramidal neurons in the CA3 is important from the point of view of elucidating the mechanisms of memory loss and the development of dementia. Objective: The aim of the study was to investigate changes in genes expression of amyloid precursor protein, its cleaving enzymes and tau protein in CA3 post-ischemia with survival of 12-24 months. Methods: We used an ischemic model of Alzheimer's disease to study the above genes using an RT-PCR protocol. Results: The expression of the amyloid precursor protein gene was above the control values at all times post-ischemia. The expression of the α-secretase gene also exceeded the control values post-ischemia. The expression of the ß-secretase gene increased 12 and 24 months post-ischemia, and 18 months was below control values. Presenilin 1 and 2 genes expression was significantly elevated at all times post-ischemia. Also, tau protein gene expression was significantly elevated throughout the observation period, and peak gene expression was present 12 months post-ischemia. Conclusions: The study suggests that the genes studied are involved in the non-amyloidogenic processing of amyloid precursor protein. Additionally data indicate that brain ischemia with long-term survival causes damage and death of pyramidal neurons in the CA3 area of the hippocampus in a modified tau protein-dependent manner. Thus defining a new and important mechanism of pyramidal neuronal death in the CA3 area post-ischemia. In addition expression of tau protein gene modification after brain ischemia is useful in identifying ischemic mechanisms occurring in Alzheimer's disease.

Association between Resistant Arterial Hypertension, Type 2 Diabetes, and Selected microRNAs.

INTRODUCTION: In recent years, a very close relationship between miRNA and cardiovascular diseases has been found. RAH and T2DM are accompanied by a change in the microRNA expression spectrum. OBJECTIVES: This study aimed to evaluate the clinical characteristics and expression of selected microRNAs in patients with idiopathic RAH and T2DM. PATIENTS AND METHODS: A total of 115 patients with RAH were included in this study. Among them were 53 patients (46.09%) with T2DM. miRNA levels were determined using quantitative real-time polymerase chain reaction. The expression of the examined genes was calculated from the formula RQ = 2-ΔΔCT. RESULTS: Analysis using the Mann-Whitney U test showed a statistically significant (p < 0.05) difference in the expression of MIR1-1 (p = 0.031) and MIR195 (p = 0.042) associated with the occurrence of T2DM in the subjects. The value of MIR1-1 gene expression was statistically significantly higher in patients with T2DM (median: 0.352; mean: 0.386; standard deviation: 0.923) compared to patients without T2DM (median: 0.147; mean: -0.02; standard deviation: 0.824). The value of MIR195 gene expression was statistically significantly higher in patients with T2DM (median: 0.389, mean: 0.442; standard deviation: 0.819) compared to patients without T2DM (median: -0.027; mean: 0.08; standard deviation: 0.942). CONCLUSIONS: The values of MIR1-1 and MIR195 gene expression were statistically significantly higher in patients with RAH and T2DM compared to patients with RAH and without T2DM. Further studies are necessary to precisely clarify the roles of miRNAs in patients with RAH and T2DM. They should demonstrate the utility of these genetic markers in clinical practice.

Chronic intestinal schistosomiasis caused by co-infection with Schistosoma intercalatum and Schistosoma mansoni.

The Grand Round concerns a 24-year-old man from Zimbabwe who was studying and living in Poland. The patient had been complaining of abdominal pain, fatigue, alternating diarrhoea and constipation, and presence of blood in his stool for 3 years. The patient had the following diagnostic tests: colonoscopy, CT scan, histopathology, and parasitological and molecular tests. Results of the examinations showed that the cause of the patient's complaints was chronic intestinal schistosomiasis due to the co-infection with Schistosoma intercalatum and Schistosoma mansoni. The patient had two cycles of praziquantel therapy (Biltricide) and responded well to the treatment. In the Grand Round, we describe full diagnostics as well as clinical and therapeutic management in the patient with S intercalatum and S mansoni co-infection. This case allows us to draw attention to cases of forgotten chronic tropical diseases (including rare ones) in patients from regions with a high endemic index staying in non-endemic regions of the world for a long time. Co-infection with S intercalatum and S mansoni should be considered as a very rare clinical case.

LRP1 and RAGE Genes Transporting Amyloid and Tau Protein in the Hippocampal CA3 Area in an Ischemic Model of Alzheimer's Disease with 2-Year Survival.

Explaining changes at the gene level that occur during neurodegeneration in the CA3 area is crucial from the point of view of memory impairment and the development of post-ischemic dementia. An ischemic model of Alzheimer's disease was used to evaluate changes in the expression of genes related to amyloid transport in the CA3 region of the hippocampus after 10 min of brain ischemia with survival of 2, 7 and 30 days and 12, 18 and 24 months. The quantitative reverse transcriptase PCR assay revealed that the expression of the LRP1 and RAGE genes involved in amyloid transport was dysregulated from 2 days to 24 months post-ischemia in the CA3 area of the hippocampus. LRP1 gene expression 2 and 7 days after ischemia was below control values. However, its expression from day 30 to 24 months, survival after an ischemic episode was above control values. RAGE gene expression 2 days after ischemia was below control values, reaching a maximum increase 7 and 30 days post-ischemia. Then, after 12, 18 and 24 months, it was again below the control values. The data indicate that in the CA3 area of the hippocampus, an episode of brain ischemia causes the increased expression of the RAGE gene for 7-30 days during the acute phase and that of LRP1 from 1 to 24 months after ischemia during the chronic stage. In other words, in the early post-ischemic stage, the expression of the gene that transport amyloid to the brain increases (7-30 days). Conversely, in the late post-ischemic stage, amyloid scavenging/cleaning gene activity increases, reducing and/or preventing further neuronal damage or facilitating the healing of damaged sites. This is how the new phenomenon of pyramidal neuronal damage in the CA3 area after ischemia is defined. In summary, post-ischemic modification of the LRP1 and RAGE genes is useful in the study of the ischemic pathways and molecular factors involved in the development of Alzheimer's disease.

Surgical resection of lung cancer inhibits mRNA expression of GOT2 gene encoding kynurenine aminotransferase in leukocytes.

INTRODUCTION AND OBJECTIVE: Lung cancer is the most common malignant tumour. More than 80% of all diagnosed cases are non-small cell carcinoma which can be effectively treated by radical resection. Despite significant progress in the field of diagnostic and therapeutic methods, the results of lung cancer treatment are still unsatisfactory. Lung cancer is detected relatively late, which leads to an unfavourable prognosis. Kynurenine aminotransferases are an important element of the kynurenine pathway of tryptophan metabolism, which has recently aroused great interest from the aspect of possible use as a target point of personalized therapies in malignant tumours.The aim of the study was to analyze the expression of the selected gene of kynurenine aminotransferases GOT 2 at the mRNA level in peripheral blood leukocytes of patients with lung cancer. MATERIAL AND METHODS: The mRNA expression of the GOT 2 gene was tested on blood samples from 50 patients treated surgically for non-small cell lung cancer.The control group consisted of 15 healthy individuals.The determination of mRNA expression of the GOT 2 gene was performed using the real-time PCR method.The GAPDH gene was used as the endogenous reference level. RESULTS: The mRNA expression of the GOT2 gene on the 6th day after surgery was statistically significantly lower than before surgery (p = 0,05). In the study group, the average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.192082±0.292174 in woman. This was statistically significantly higher than in men whose average LogRQ mRNA expression of the GOT2 gene before the procedure was 0.004210±0.235065 (p=0.0183). CONCLUSIONS: Surgical resection of lung cancer results in inhibition of GOT2 mRNA expression in leukocytes. Further studies are expected to show whether it may be used as a target point for personalized therapies in lung cancer.

Novel inflammatory markers in patients with severe COVID-19 and a pulmonary thrombotic event.

Venous thromboembolism (VTE), clinically manifested as deep vein thrombosis (DVT) or acute pulmonary embolism (PE), is the third most common acute cardiovascular syndrome following myocardial infarction and stroke. The annual incidence of PE is between 39 and 115 per 100,000 inhabitants. The incidence of VTE is almost eight times higher in people aged 80 and older than in the fifth decade of life. We performed a retrospective study of 226 COVID-19 patients and selected group of patients who experienced a pulmonary thrombotic event. The incidence of PE in hospitalized COVID-19 patients was approximately 1.9-8.9%. The retrospective nature of the analyzed cohorts and relatively short observation periods could have led to underestimation of the actual incidence of PE. This study underlines the role of novel inflammatory biomarkers such as neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in patients with a pulmonary thrombotic event in COVID-19. We suggest that these biomarkers may have high assessment value and complement routinely used biomarkers.

Preservation of Biomarkers Associated with Alzheimer's Disease (Amyloid Peptides 1-38, 1-40, 1-42, Tau Protein, Beclin 1) in the Blood of Neonates after Perinatal Asphyxia.

Perinatal asphyxia is a complex disease involving massive death of brain cells in full-term newborns. The most impressive consequence of perinatal asphyxia is a neurodegenerative brain injury called hypoxic-ischemic encephalopathy. Management of newborns after perinatal asphyxia is very difficult due to the lack of measurable biomarkers that would be able to assess the severity of the brain injury in the future, help in the selection of therapy, assess the results of treatment and determine the prognosis for the future. Thus, these limitations make long-term neurodevelopmental outcomes unpredictable during life. Quantifying biomarkers that can detect subclinical changes at a stage where routine brain monitoring or imaging is still mute would be a major advance in the care of neonates with brain neurodegeneration after asphyxia. Understanding the effect of perinatal asphyxia on changes in blood neurodegenerative biomarkers over time, which would be commonly used to assess the severity of postpartum encephalopathy, would be an important step in developing precision in predicting the consequences of brain injuries. We urgently need more accurate early predictive markers to guide clinicians when to use neuroprotective therapy. The needed neurodegenerative biomarkers may represent neuronal pathological changes that can be recognized by new technologies such as genomic and proteomic. Nevertheless, the simultaneous blood tau protein and various amyloid changes with the addition of an autophagy marker beclin 1 after perinatal asphyxia have not been studied. We decided to evaluate serum biomarkers of neuronal injury characteristic for Alzheimer's disease such as amyloid peptides (1-38, 1-40 and 1-42), tau protein and beclin 1, which can predict the progression of brain neurodegeneration in future. In this paper, we report for the first time the significant changes in the above molecules in the blood after asphyxia compared to healthy controls during the 1-7, 8-14 and 15+ days ELISA test.

Synthesis and anthelmintic activity of novel thiosemicarbazide and 1,2,4-triazole derivatives: In vitro, in vivo, and in silico study.

INTRODUCTION: Intestinal parasitic infections are neglected diseases and, due to the increasing resistance of parasites to available drugs, they pose an increasing therapeutic challenge. Therefore, there is a great need for finding new compounds with antiparasitic activity. OBJECTIVES: In this work, new thiosemicarbazide and 1,2,4-triazole derivatives were synthesized and tested for their anthelmintic activity. METHODS: The synthesis was carried out by classical methods of organic chemistry. Anthelmintic activity tests were carried out in vitro (Rhabditis sp., Haemonchus contortus, Strongylidae sp.) in vitro (Heligmosomoides polygyrus/bakeri), and in silico analysis was performed. RESULTS: Quinoline-6-carboxylic acid derivative compounds were designed and synthesized. The highest activity in the screening tests in the Rhabditis model was demonstrated by compound II-1 with a methoxyphenyl substituent LC50 = 0.3 mg/mL. In the next stage of the research, compound II-1 was analyzed in the H. contortus model. The results showed that compound II-1 was active and had ovicidal (percentage of dead eggs > 45 %) and larvicidal (percentage of dead larvae > 75 %) properties. Studies in the Strongylidae sp. model confirmed the ovicidal activity of compound II-1 (percentage of dead eggs ≥ 55 %). In vivo studies conducted in the H. polygyrus/bakeri nematode model showed that the number of nematodes decreased by an average of 30 % under the influence of compound II-1. In silico studies have shown two possible modes of action of compound II-1, i.e. inhibition of tubulin polymerization and SDH. The test compound did not show any systemic toxic effects. Its influence on drug metabolism related to the activity of cytochrome CYP450 enzymes was also investigated. CONCLUSION: The results obtained in the in vitro, in vivo, and in silico studies indicate that the test compound can be described as a HIT, which in the future may be used in the treatment of parasitic diseases in humans and animals.

'Be the Match'. Predictors of Decisions Concerning Registration as a Potential Bone Marrow Donor-A Psycho-Socio-Demographic Study.

(1) Background: The study was aimed at a better understanding of the factors determining making a decision to become a potential bone marrow donor, in a Polish research sample; (2) Methods: The data was collected using a self-report questionnaire among persons who voluntarily participated in the study concerning donation, conducted on a sample of the Polish population via Internet. The study included 533 respondents (345 females and 188 males), aged 18-49. Relationships between the decision about registration as potential bone marrow donor and psycho-socio-demographic factors were estimated using the machine learning methods (binary logistic regression and classification & regression tree); (3) Results. The applied methods coherently emphasized the crucial role of personal experiences in making the decision about willingness for potential donation, f.e. familiarity with the potential donor. They also indicated religious issues and negative health state assessment as main decision-making destimulators; (4) Conclusions. The results of the study may contribute to an increase in the effectiveness of recruitment actions by more precise personalization of popularizing-recruitment actions addressed to the potential donors. It was found that selected machine learning methods are interesting set of analyses, increasing the prognostic accuracy and quality of the proposed model.

Analysis of Changes in the Expression of Selected Genes from the ABC Family in Patients with Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is characterized by a lack of expression of hormone receptors (estrogen and progesterone), as cancer cells also do not overexpress the HER2 receptor. Due to their molecular profile, treatments for this type of breast cancer are limited. In some cases, the pharmacotherapy of patients with TNBC is hindered by the occurrence of multidrug resistance, which is largely conditioned by proteins encoded by genes from the ABC family. The aim of our study was to determine the expression profile of 14 selected genes from the ABC family using real-time PCR in 68 patients with TNBC by comparing the obtained results with clinical data and additionally using bioinformatics tools (Ualcan and The Breast Cancer Gene Expression Miner v4.8 (bc -GenExMiner v4.8)), as well as by comparing experimental data with data in the Cancer Genome Atlas (TCGA) database. Based on the conducted studies, we found different levels of gene expression depending on the age of patients, tumor sizes, metastases to lymph nodes, cell infiltration into adipose tissue, tumor stages, or lymphovascularinvasion. The results of the presented studies demonstrate the effect of the expression level of the studied genes on the clinical course and prognosis of patients with TNBC, and suggest how profiling the expression level of genes from the ABC family may be a useful tool in determining personalized TNBC treatment.

Psychological consequences of hospital isolation during the COVID-19 pandemic - research on the sample of polish firefighting academy students.

Currently, a very important thread of research on COVID-19 is to determine the dimension of the psychopathological emotional reactions induced by the COVID-19 pandemic. A non-experimental online research project was designed to determine the predictors of the severity of psychopathological symptoms, such as depression and PTSD symptoms, and the nature of the feedback mechanism between them in groups of men, remaining in hospital isolation due to infection and at-home isolation during the COVID-19 epidemic. The presence of symptoms of depression, post-traumatic stress disorder (PTSD) and a sense of threat due to the pandemic were assessed using the following screening tests: IES-R by Weiss and Marmar, PHQ-9 by Spitzer et al., and a self-constructed sliding scale for assessing COVID-19 anxiety. The study was carried out on a group of 57 firefighting cadets, hospitalized in a COVID-19 isolation room (Mage = 23.01), staying in isolation due to SARS-CoV-2 virus infection and a control group of 57 healthy men (Mage = 41.38) staying at home during quarantine and national lockdown. COVID-19 pandemic causes many psychopathological reactions. The predictive models revealed that the predictors of symptoms of PTSD in isolated patients included depression and the experienced sense of COVID-19 threat resulting from the disease, while in the control group the symptoms of depression were the only predictor of PTSD. PTSD experiences are usually associated with depression. It may also be a form of the re-experiencing process or the effect of high affectivity, indirectly confirmed by the participation of hyperarousal in the feedback loop. Our findings highlight the importance of mental health aspects in patients treated during the COVID-19 pandemic. The COVID-19 pandemic requires social distancing, quarantine and isolation, which may cause psychopathological symptoms not only in affected people, but also in the general population. Moreover, the need for greater psychological support can be emphasized for both: the sick and the general population.

To Vaccinate or Not to Vaccinate-Reasons of Willingness and Reluctance of Students against SARS-CoV-2 Vaccination-An International Experience.

Despite the vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) being reported to be safe and effective, the unwillingness to vaccinate and doubts are still common. The aim of this international study was to assess the major reasons for the unwillingness to vaccinate in a group of students from Poland (n = 1202), Bangladesh (n = 1586), India (n = 484), Mexico (n = 234), Egypt (n = 566), Philippines (n = 2076), Pakistan (n = 506), Vietnam (n = 98) and China (n = 503). We conducted an online cross-sectional study that aimed to assess (1) the percentage of vaccinated and unvaccinated students and (2) the reasons associated with willingness/unwillingness to the vaccine. The study included 7255 respondents from 9 countries with a mean age of 21.85 ± 3.66 years. Only 22.11% (n = 1604) of students were vaccinated. However, the majority (69.25%, n = 5025) expressed a willingness to be vaccinated. More willing to vaccinate were students in informal relationships who worked mentally, used psychological/psychiatric services before the pandemic, and studied medicine. There are cultural differences regarding the reasons associated with the unwillingness to vaccinate, but some 'universal' might be distinguished that apply to the whole group.

Elastography as a possible useful method of assessment of skin involvement in systemic sclerosis.

Introduction: Scleroderma (Sc) is a connective tissue disorder associated with internal organ involvement, increased mortality, and unknown pathogenesis. It has been found that the more extensive the skin involvement the more severe internal organ manifestations and increased disability. The Rodnan skin score (RSS) is one of the established methods to examine skin thickness among patients with Sc. Due to RSS limitations, for instance, lack of detection of subclinical changes, a new tool is needed for the evaluation of Sc. In recent studies, shear wave elastography (SWE) has been examined as a potential tool to assess skin involvement through the evaluation of skin strain. Aim: To verify whether elastography is a reliable method to examine Sc progression and possibly provide one useful site to perform the examination - as an easy, cheap, and reliable examination tool. Material and methods: Forty Sc patients were examined, and 28 healthy individuals were recruited for the control group. Among the patients and control group, skin thickness was assessed using the RSS and skin strain measurements using elastography in 20 body locations. Results: SWE in the right-hand finger can be treated as an important diagnostic indicator of the severity of Sc. Conclusions: SWE is a reliable method for evaluating skin involvement among patients with systemic sclerosis (SSc). Right finger measurements correlate positively with Rodnan's results and can be a predictor of the severity of SSc. This study found SWE to be a reliable method for examining SSc progression and possibly one useful site for the examination.

Hypothermia after Perinatal Asphyxia Does Not Affect Genes Responsible for Amyloid Production in Neonatal Peripheral Lymphocytes.

In this study, the expression of the genes of the amyloid protein precursor, ß-secretase, presenilin 1 and 2 by RT-PCR in the lymphocytes of newborns after perinatal asphyxia and perinatal asphyxia treated with hypothermia was analyzed at the age of 15-21 days. The relative quantification of Alzheimer's-disease-related genes was first performed by comparing the peripheral lymphocytes of non-asphyxia control versus those with asphyxia or asphyxia with hypothermia. In the newborns who had perinatal asphyxia, the peripheral lymphocytes presented a decreased expression of the amyloid protein precursor and ß-secretase genes. On the other hand, the expression of the presenilin 1 and 2 genes increased in the studied group. The expression of the studied genes in the asphyxia group treated with hypothermia had an identical pattern of changes that were not statistically significant to the asphyxia group. This suggests that the expression of the genes involved in the metabolism of the amyloid protein precursor in the peripheral lymphocytes may be a biomarker of progressive pathological processes in the brain after asphyxia that are not affected by hypothermia. These are the first data in the world showing the role of hypothermia in the gene changes associated with Alzheimer's disease in the peripheral lymphocytes of newborns after asphyxia.

Increased Markers of Oxidative Stress and Positive Correlation Low-Grade Inflammation with Positive Symptoms in the First Episode of Schizophrenia in Drug-Naïve Patients.

Schizophrenia is a severe and chronic mental illness usually diagnosed in adolescents and young adults. Many studies indicate that oxidative stress causes membrane dysfunction and cell damage, which is implicated in the pathophysiology of schizophrenia. The purpose of our study was to evaluate oxidative stress markers (the main primary products of lipid peroxidation, lipid hydroperoxides (LOOH), and end products of lipid peroxidation, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and Ferric Reducing Ability of Plasma (FRAP)) in the plasma of patients with the first episode of schizophrenia in drug-naïve patients (22 men and 12 women aged 17-29). The control group (Ctrl) comprised 26 healthy subjects (19 men and 7 women, aged 18-30 years). The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Analyses of the oxidative stress variables revealed an increased level of SOD (U/mL) in subjects with schizophrenia versus control group. In addition, lipid damage measured as LOOHs µ (mol/L) and MDA was significantly higher in patients with schizophrenia in comparison to control subjects. There was a positive correlation between MDA µmol/L and PANSS P and a positive correlation between C-reactive protein (CRP) and the PANSS P scale. The elevated level of superoxide dismutase in patients with the first episode of schizophrenia can be explained by compensatory mechanisms to counteract oxidative stress. Malondialdehyde can be used as a simple biomarker of low-grade systemic inflammation associated with oxidative stress. A positive correlation between CRP and PANSS P scale and MDA and PANSS P scale may indicate a significant relationship between the development of low-grade inflammation and damage associated with oxidative stress in the development of the first symptoms of schizophrenia.

Chronic Alcohol Abuse Alters Hepatic Trace Element Concentrations-Metallomic Study of Hepatic Elemental Composition by Means of ICP-OES.

Trace element accumulation varies in different human tissues. Distribution of several elements was found to be disrupted in the case of excessive alcohol consumption, causing negative effects and exacerbation of pathological processes in the liver. In this study, we analyzed the levels and interactions between seven trace elements including calcium (Ca), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), potassium (K), and magnesium (Mg), manganese (Mn), sodium (Na), zinc (Zn), and selenium (Se) in individuals with alcohol-use disorder (AUD) and patients without AUD (control group). The liver samples were collected during autopsy from 39 individuals with AUD and 45 control subjects. Elemental composition inductively coupled plasma optical emission spectrometry (ICP-OES) after wet mineralization by nitric acid was applied for the evaluation of the samples. Positive correlations dominated in the AUD group, mainly in relation to Mg, which strongly positively correlated with Ca, Mn, Fe; K correlated with Mn and Zn, and Cu positively correlated with K and Zn. The strongest positive correlation in the AUD group was observed for the Mg-Mn pair (r = 0.87). Significant statistical differences (p < 0.05) between the groups concerned the average concentration of Co, Cu, Mn, and Mg, which were lower in the AUD group, and Fe, the level of which was significantly higher in the AUD group compared to the control group. Evaluation of the chronic alcohol consumption effect on the accumulation of trace elements in the liver allows a better understanding of the pathological processes taking place in this organ.

PD-L1/miR-155 Interplay in Pediatric High-Grade Glioma.

High-grade pediatric glioma (p-HGG-WHO 2021, formerly GBM-WHO 2016), as a common, aggressive, and highly lethal primary brain malignancy in adults, accounts for only 3-15% of primary brain tumors in pediatric patients. After leukemia, brain malignancies are the second most common in the pediatric population and first in incidences concerning solid tumors. This study was designed on the basis of 14 pediatric patients hospitalized at Children's Memorial Health Institute in Warsaw, Poland, due to p-HGG treatment. All the patients had a histopathological diagnosis performed by an experienced neuropathologist according to WHO guidelines (WHO 2016 Grade IV Glioblastoma). A significant correlation was found between the miR-155 concentration and the level of PD-L1 expression in p-HGG tumor tissue. Very few reports have indicated PD-L1 expression in pediatric patients.

The analysis of Fe-dependent serum enzymes in severe COVID-19 with a pulmonary thrombotic event.

Introduction: COVID-19 patients in critical condition requiring ICU admission are more likely to experience thromboembolic complications, especially pulmonary embolism. Since the outbreak of coronavirus disease 2019 (COVID-19), clinicians have struggled with the attempt to diagnose and manage the severe and fatal complications of COVID-19 appropriately. Several reports have described significant procoagulatory events, including life-threatening pulmonary embolism, in these patients. The aim of the study was to analyze the results of selected serum enzymes in patients with a radiologically confirmed pulmonary thrombotic event based on the pulmonary tissue involvement assessed in a computed tomography (CT) scan. Material and methods: The retrospective study covered a group of 226 COVID-19 patients. Groups were divided based on the degree of lung tissue involvement in CT examinations, including patients with confirmed pulmonary embolism. The analyzed group consisted of 136 men and 90 women with mean age of 70 years. Results: The group consisted of patients with < 50% of lung volume changes who had higher parameter values in each analyzed parameter, except red blood cells (RBC) (p < 0.05). Especially, the level of ferritin was much higher in the first group (p = 0.000008). Elevated ferritin levels were observed in all patients with lung tissue involvement. Discussion: This line of research is critical in order to assess the predisposing conditions for pulmonary embolism occurrence in COVID-19, which can be used as a predictive factor for course of the disease. The conducted research will resolve whether there is a relationship between the selected laboratory parameters and the occurrence of pulmonary embolism in patients with COVID-19. Conclusions: The study demonstrated that elevated levels of several inflammatory and thrombotic parameters such as ferritin, D-dimer, C-reactive protein (CRP) as well as hemoglobin do not correlate with the degree of lung tissue involvement in the computed tomography image.

Next-Generation Sequencing in the Assessment of the Transcriptomic Landscape of DNA Damage Repair Genes in Abdominal Aortic Aneurysm, Chronic Venous Disease and Lower Extremity Artery Disease.

Vascular diseases are one of the most common causes of death and morbidity. Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA) and chronic venous disease (CVD) belong to this group of conditions and exhibit various presentations and courses; thus, there is an urgent need for revealing new biomarkers for monitoring and potential treatment. Next-generation sequencing of mRNA allows rapid and detailed transcriptome analysis, allowing us to pinpoint the most pronounced differences between the mRNA expression profiles of vascular disease patients. Comparison of expression data of 519 DNA-repair-related genes obtained from mRNA next-generation sequencing revealed significant transcriptomic marks characterizing AAA, CVD and LEAD. Statistical, gene set enrichment analysis (GSEA), gene ontology (GO) and literature analyses were applied and highlighted many DNA repair and accompanying processes, such as cohesin functions, oxidative stress, homologous recombination, ubiquitin turnover, chromatin remodelling and DNA double-strand break repair. Surprisingly, obtained data suggest the contribution of genes engaged in the regulatory function of DNA repair as a key component that could be used to distinguish between analyzed conditions. DNA repair-related genes depicted in the presented study as dysregulated in AAA, CVD and LEAD could be utilized in the design of new biomarkers or therapies associated with these diseases.