Activation Of Inflammatory Processes Research Articles

Oxidative stress disrupts vascular microenvironmental homeostasis affecting the development of atherosclerosis.

Atherosclerosis is primarily an inflammatory reaction of the cardiovascular system caused by endothelial damage, leading to progressive thickening and hardening of the vessel walls, as well as extensive necrosis and fibrosis of the surrounding tissues, the most necessary pathological process causing cardiovascular disease. When the body responds to harmful internal and external stimuli, excess oxygen free radicals are produced causing oxidative stress to occur in cells and tissues. Simultaneously, the activation of inflammatory immunological processes is followed by an elevation in oxygen free radicals, which directly initiates the release of cytokines and chemokines, resulting in a detrimental cycle of vascular homeostasis abnormalities. Oxidative stress contributes to the harm inflicted upon vascular endothelial cells and the decrease in nitric oxide levels. Nitric oxide is crucial for maintaining vascular homeostasis and is implicated in the development of atherosclerosis. This study examines the influence of oxidative stress on the formation of atherosclerosis, which is facilitated by the vascular milieu. It also provides an overview of the pertinent targets and pharmaceutical approaches for treating this condition.

Acute Phase Peyronie's Disease: Where Do We Stand?

Peyronie's disease (PD) is a common benign condition characterized by superficial fibrosis and scar formation at the tunica albuginea of the penis, eventually leading to penile curvature. It is believed that penile micro-traumas during intercourse and subsequent activation of inflammatory processes constitute the pathogenetic basis of the disease. Routinely, PD is divided into acute and chronic phases, with pain during erection or flaccid state being the hallmark of the former. Surgical intervention should be avoided during the acute phase, as the risk of recurrence or progression of penile deformity during this stage might affect the optimal outcomes of the procedure. During this stage, many conservative treatment options have been suggested, including oral, topical, and intralesional therapies, extracorporeal shock wave therapy (ESWT), and penile traction therapy (PTT). Currently, the optimal treatment consists of a combined treatment strategy with phosphodiesterase type 5 inhibitors (PDE5Is), ESWT for pain management, PTT, and intralesional therapies. Large, well-designed randomized controlled trials (RCTs) are necessary to further elucidate the most efficient treatment option for acute phase PD.

IL-17 is associated with disease severity and targetable inflammatory processes in heart failure.

Heart failure (HF) is recognized as an inflammatory disease in which cytokines play an important role. In animal HF models, interleukin-17A (IL-17) has been linked to deterioration of cardiac function and fibrosis, whereas knock-out of IL-17 showed beneficial cardiac effects. However, there is limited evidence of IL-17 involvement in patients with HF. This study aims to investigate the clinical characteristics, outcomes, and pathophysiological processes associated with circulating IL-17 concentrations in patients with HF. IL-17 was measured by ELISA in 2082 patients diagnosed with HF along with 363 circulating proteins using proximity extension assay technology for differential expression and pathway analysis. Data were validated in an independent cohort of 1737 patients with HF. Patients with elevated IL-17 concentrations had more severe HF, as reflected by more frequent current or previous hospitalizations for HF, higher New York Heart Association functional class (NYHA) and higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). High IL-17 concentrations were independently associated with an increased risk of hospitalization for HF and mortality. In both cohorts, the most strongly up-regulated proteins in patients with high IL-17 were fibroblast growth factor 21 (FGF-21), interleukin-6 (IL-6), C-X-C motif chemokine ligand 13 (CXCL13), tumour necrosis factor receptor superfamily member 6B (TNFRSF6B) and interleukin-1 receptor antagonist (IL-1RA). Pathway over-representation analysis showed increased activity of pathways related to lymphocyte-mediated immunity, leukocyte activation and regulation of the immune response. In patients with HF, elevated IL-17 concentrations indicate more severe HF and increased activity of inflammatory processes known to be involved in the pathophysiology of HF. IL-17 might hold potential for identifying and targeting inflammation in HF.

Type-specific inflammatory responses of vascular cells activated by interaction with virgin and aged microplastics

Microplastics (MPs) are recognized as a major environmental problem due to their ubiquitous presence in ecosystems and bioaccumulation in food chains. Not only humans are continuously exposed to these pollutants through ingestion and inhalation, but recent findings suggest they may trigger vascular inflammation and potentially worsen the clinical conditions of cardiovascular patients. Here we combine headspace analysis by needle trap microextraction-gas chromatography-mass spectrometry (HS-NTME-GC-MS) and biological assays to evaluate the effects of polystyrene, high- and low-density polyethylene MPs on phenotype, metabolic activity, and pro-inflammatory status of Vascular Smooth Muscle Cells (VSMCs) the most prominent cells in vascular walls. Virgin and artificially aged MPs (4 weeks at 40 °C and 750 W/m2 simulated solar irradiation) were comparatively tested at 1 mg/mL to simulate a realistic exposure scenario. Our results clearly show the activation of oxidative stress and inflammatory processes when VSMCs were cultured with aged polymers, with significant overexpression of IL-6 and TNF-α. In addition, volatile organic compounds (VOCs), including pentane, acrolein, propanal, and hexanal as the main components, were released by VSMCs into the headspace. Type-specific VOC response profiles were induced on vascular cells from different MPs.

Analysis of KLRB1-Mediated Immunosuppressive Regulation in Adamantinomatous Craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is the most common type of craniopharyngioma (CP). Under the current surgery and/or radiotherapy strategies, the survival rate is high, but the long-term quality of life is poor because of the relationship between the hypothalamic-pituitary axis and the tumor. Many studies had shown that endocrine deficiencies caused by craniopharyngiomas of the hypothalamic-pituitary axis persist throughout almost the entire life of the patients after surgery, requiring them to receive hormone replacement therapy. Thus, we need to explore new treatments to improve the prognosis of patients. In recent years, there are more and more studies on the immunotherapy of various tumors. However, due to the rarity of the disease, immunotherapy for ACP is rarely researched. The discovery of the tumor immune-suppressive checkpoint KLRB1 (killer cell lectinlike receptor B1), which encodes CD161, may provide a novel target for the treatment of ACP. Data analysis of retrospective RNA sequencing was conducted in a cohort of 51 pediatric samples in the GSE94349 dataset, and the results were well validated in the GSE68015 dataset including 31 pediatric samples. We used R language as the main tool for statistical analysis and graphical work. Our research showed that KLRB1 was enriched in ACP. Additionally, the expression of KLRB1 was positively related to immune functions and most inflammatory responses of ACP. We found that most of the T lineage-related immune responses were positively correlated with KLRB1 expression, and KLRB1 played an important role in the activation of inflammatory processes. KLRB1 is a promising target for immunotherapeutic strategies.

Pericardial Effusion in COVID-19 Hospitalized Patients in ICU: Prevalence, Related Factors, and Outcomes

Purpose: COVID-19 disease is associated with pericardial effusion through both direct invasions of myocardial tissue and activation of inflammatory processes and oxidative stress. However, its exact mechanism and related implications are unclear. We aimed to evaluate the pericardial effusion in hospitalized patients with a definite diagnosis of COVID-19 and finally to determine underlying factors related to this cardiac event. Finally, the hospital outcome of patients with and without pericardial involvement was compared. Materials and Methods: The hospital records of 1824 patients suffering from COVID-19 were reviewed with respect to pieces evidence of pericardial effusion. Baseline characteristics, cardiovascular risk profiles, laboratory and echocardiography parameters as well as hospital outcomes were reviewed. Results: Out of 1824 patients hospitalized with COVID-19 in our medical center in Intensive Care Unit (ICU) sections, a total of 300 cases (16.4%) (P value <0.05) had evidence of pericardial effusion. Patients with pericardial effusion had much higher mean age, higher mean heart rate and also a higher prevalence of hypertension, diabetes mellitus, and a history of ischemic heart disease compared to those without this complication. The changes in some echocardiography parameters, including left ventricular end-diastolic diameter, E/A ratio, E/Ep ratio, and tricuspid annular plane systolic excursion were more prominent in those with pericardial effusion. Those with pericardial effusion experienced longer hospitalization and ICU admission and the death rate was significantly higher in such patients. Conclusion: The occurrence of pericardial effusion is predictable in about 16.4% of patients with COVID-19, which occurs mainly in older people and people with a history of cardiovascular risk profiles. Pericardial effusion in COVID-19 patients leads to poorer in-hospital outcome.

Особливості діагностики та лікування жінок з синдромом полікістозних яєчників в умовах підвищеного рівня експонування нікелем

Abstract. Polycystic ovary syndrome (PCOS) refers to endocrinopathies that women of reproductive age could have. These disorders can be caused by both endogenous (endocrine disorders, chronic infections, stress, etc.) and exogenous factors (environmental, smoking, etc.). Aim. Determination of serum nickel values in women with polycystic ovary syndrome and investigation of the mechanisms underlying the toxic effects of nickel on the reproductive system. Explore potential sources of nickel exposure and develop recommendations for the prevention and treatment of PCOS caused by increased levels of nickel exposure. Materials and Methods. The research was conducted on the bases of State Institution “O.M. Lukianova Institute of Pediatrics, Obstetrics and Gynecology of NAMS of Ukraine” 52 women who were diagnosed with PCOS were selected for the study. The control group consisted of 38 women of reproductive age without reproductive system pathology. Determination of serum nickel values in women with PCOS was performed using a Bruker MS 820 inductively coupled plasma mass spectrometer (Australia) using special ICP-MS Expert software. The study of indicators of environmental pollution with nickel was carried out by processing data published in open sources of information. Results. Women with PCOS showed elevated serum nickel values (median ‒ 0.036 mg/l, 95-percentile ‒ 0.194 mg/l), which significantly exceeded the control group (median ‒ 0.001 mg/l, 95-percentile ‒ 0.097 mg/l, p=0.0012). The study of exposure possible sources showed that elevated levels of nickel were found in drinking water from surface water sources. Contamination of surface waters and soils used in agriculture was also detected. The authors propose a set of measures for the prevention and treatment of complications caused by nickel exposure. Conclusions. Nickel exposure occurs mainly by alimentary and inhalation. When exposed to nickel, there is a violation of the function of the endocrine system, activation of inflammatory processes and oxidative stress. In women with PCOS with an increased level of nickel exposure, it is necessary to carry out a set of measures aimed at reducing the level of exposure, accelerating nickel excretion and treating complications that have occurred. Keywords: polycystic ovary syndrome, nickel, exposure, principles of prevention and treatment.

Use of Densitometric Indicators Free DICOM-Viewer’s and Digital Data Processing Programs in Surgical Treatment of Patients with Pulmonary Tuberculosis

Objective — to determine the potential of using freely distributed specialised digital data processing programs and free DICOM-viewers for assessing densitometric indicators obtained from computed tomogra­phy of the thoracic organs. This aims to facilitate the planning of surgical treatment for patients with pulmonary tuberculosis and to substantiate methods for preventing pulmonary-pleural complications. Materials and methods. A retrospective analysis was conducted on the examination and treatment results of 103 patients with specific tuberculous lesions of the lungs. Histological examination of the resected material determined the degree of the specific inflammatory process in the affected tissue, based on which patients were categorised into groups. Group I included 32 patients with low activity of the specific inflammatory process, Group II comprised 37 patients with moderate activity and Group III included 34 patients with high activity. Using five common digital processing programs, densitometric indicators of the thoracic organs' structures were obtained. The accuracy of density indicators displayed by these programs was analysed in comparison with the results of histological examinations. Results and discussion. According to our data, the densitometric indicators obtained using free DICOM-viewers and digital data processing programs show a strong correlation with the reference standard and among themselves. The determined density indicators have a strong association with histological findings of emphysema and fibrosis of the lung parenchyma. These indicators are reliably identified both in cases of high activity of specific inflammation in the lung parenchyma and in inactive processes, allowing for patient stratification. It was found that the average density values of the mediastinal lymph nodes in cases of inactive specific inflammatory processes in 80 % of cases were (54.4 ± 17.8) HU. Values of (15.0 ± 2.5) HU characteri­sed high activity of specific inflammatory processes and the progressive phase of the disease. Clinically, 89 (86.4 %) of the patients with significant deviations in the densitometric density indicators of the lung parenchyma from the norm experienced prolonged air leakage in the postoperative period. In 96 (93.2 %) patients with altered density of mediastinal lymph nodes, prolonged postoperative exudation through pleural drains was noted. Patients with altered densitometric indicators had complicated intraoperative and postoperative courses. Changes in the density of the lung parenchyma detected on computed tomography of the thoracic organs were confirmed in 96.1 % of cases by histological examination of the resected material. These changes were reliably detected by all the programs studied. Conclusions. Densitometric indicators obtained using DICOM-viewers and digital data processing programs enable the planning of surgical treatment for patients with pulmonary tuberculosis and the reasoned application of methods to prevent pulmonary-pleural complications.

Efficacy and safety of a new heterologous fibrin biopolymer on socket bone healing after tooth extraction: An experimental pre-clinical study.

To assess the efficacy of heterologous fibrin biopolymer (HFB) in promoting alveolar bone healing after tooth extraction in rats. The upper right incisors of 48 Wistar rats were extracted. Toothless sockets were filled with HFB (HFBG, n = 24) or blood clot (BCG, n = 24). The tooth extraction sites were subjected to micro-computed tomography (micro-CT), histological, histomorphometric and immunohistochemical (for Runt-related transcription factor 2/Runx2 and tartrate-resistant acid phosphatase/TRAP) analyses on days 0, 7, 14 and 42 after extraction. Socket volume remained similar between days 0 and 14 (69 ± 5.4 mm3), except in the BCG on day 14, when it was 10% lower (p = .043). Although the number of Runx2+ osteoblasts was high and similar in both groups (34 × 102 cells/mm2), the HFBG showed lower inflammatory process and osteoclast activity than BCG at 7 days. On day 14, the number of Runx2+ osteoblasts remained high and similar to the previous period in both groups. However, osteoclast activity increased. This increase was 55% lower in the HFBG than BCG. In the BCG, the presence of an inflammatory process and larger and numerous osteoclasts on day 14 led to resorption of the alveolar bone ridge and newly formed bone. On day 42, numbers of Runx2+ osteoblast and TRAP+ osteoclasts decreased dramatically in both groups. Although the BCG exhibited a more mature cortical bone formation, it exhibited a higher socket reduction (28.3 ± 6.67%) and smaller bone volume (37 ± 5.8 mm3) compared with HFBG (socket reduction of 14.8 ± 7.14% and total bone volume of 46 ± 5.4 mm3). HFB effectively suppresses osteoclast activity and reduces alveolar bone resorption compared with blood clot, thus preventing three-dimensional bone loss, particularly during the early healing period. HFB emerges as a promising biopharmaceutical material for enhancing healing processes after tooth extraction.

Relationship between the outcomes of intensive phase therapy in patients with newly diagnosed infiltrative pulmonary tuberculosis and activity of purine metabolism enzymes as well as CD3+CD8+ lymphocyte level

Monitoring activity of inflammatory process and lymphocyte subsets can help assess the effectiveness of intensive phase therapy (IPT) already in the early stages of treatment. The goal is to evaluate changes in the concentration and activity of enzymes associated with purine metabolism and peripheral blood lymphocyte subset composition, and to determine their relationship with IPT effectiveness in patients with newly diagnosed infiltrative pulmonary tuberculosis (IPTb). Materials and methods. In 141 IPTb patients, the IPT data were presented as follows: “significant improvement” (SI) — disappearance of intoxication symptoms, abacillation, closure of decay cavities; “less pronounced improvement” (LMI) — eliminated symptoms of intoxication, abacillation, pronounced resorption of focal and infiltrative changes, reduction of decay cavities. We assessed the activity of adenosine deaminase in blood serum (eADA-1, 2), mononuclear cells and neutrophils, the concentration of blood serum ecto-5'-nucleotidase (eHT5E), CD26 (DPPV) in blood serum (s, soluble form) and mononuclear cells (m, membrane form), subpopulation composition. Results. Patients exhibit increased concentrations of eNT5E, mCD26 (DPPIV) and eADA-2 activity, and decreased intracellular ADA-1 activity. In the “LMI” group, after IPT, an increased sCD26 (DPPV) level was noted. The groups differed in lymphocyte counts and percentage of CD3+CD8+ cells. eADA-2 activity was higher in the LMI group and increased after IPT, in contrast to comparison group. mCD26 (DPPIV) concentrations are higher in PD patients before therapy and after IPT. Conclusion. Thus, the outcome of IPT in IPTb patients is associated with altered T-lymphocyte populations and severity of the inflammatory process. Studying the activity of membrane and soluble eADA-2, CD26 (DPPIV) and percentage of CD3+CD8+ T-lymphocytes in the early stages of therapy can provide the necessary information for correcting personalized pathogenetic therapy of patients with newly diagnosed IPTb.

Identification of prognostic factors for survival in patients with metastatic gastric adenocarcinoma in a Mexican population

Introduction and aimsGastric adenocarcinoma is among the high-ranking tumors, with respect to frequency and mortality, worldwide. The inflammatory process and immune system activity are associated with oncologic control. Our aim was to identify whether the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and other variables are prognostic factors for survival in patients with metastatic gastric cancer in a Mexican population. Material and methodsPatients diagnosed with metastatic gastric adenocarcinoma, hospitalized within the time frame of December 2011 to 2021, were analyzed. The NLR, PLR, and albumin and hemoglobin levels obtained from blood samples were calculated. Functional status (ECOG and Karnofsky), sex, histology, and the presence of signet ring cells were also considered possible prognostic factors. Each factor’s prognostic value for overall survival was determined through univariate and multivariate analyses. ResultsThe study included 956 patients diagnosed with metastatic gastric cancer, of whom 494 (51.7%) were men and 462 (48.3%) were women. The main histologic finding was diffuse adenocarcinoma (n = 619, 64.7%), followed by intestinal adenocarcinoma (n = 293, 30.6%), and the presence of signet ring cells was found in 659 (68.9%) patients. Diagnostic laparoscopy was performed on 238 patients (24.9%) to confirm peritoneal carcinomatosis. The multivariate analysis showed that an NLR above 3.2 (HR 1.51, 95% CI 1.27–1.8; p < 0.001), albumin below 3.5 g/dl (HR 1.25, CI 1.06–1.47; p = 0.006), and an ECOG performance status of 2 or higher (HR 1.39, CI 1.10–1.76; p = 0.005) were independent factors that predicted a lower survival rate, whereas a Karnofsky score above 70% (HR 0.69, CI 0.53–0.91; p = 0.008) was associated with a better survival rate. Lastly, the PLR was not statistically significant in the multivariate analysis. ConclusionsThe NLR, nutritional status assessed through albumin measurement, and functional status can act as independent prognostic survival factors in hospitalized Mexican patients diagnosed with metastatic gastric adenocarcinoma and be taken into account during therapeutic decision-making.

SGLT2 inhibitors and their possible use in prevention and treatment of neurological diseases

&#x0D; Neurological diseases, neurological complications of diabetes and cardiovascular disease complications affecting the central nervous system (CNS) are one of the greatest challenges of modern medicine. Many of these diseases require the introduction of new therapies to improve the prognosis and quality of life of patients. Drugs with the increasing use in recent years are the SGLT2 inhibitors (SGLT2i): canagliflozin, dapagliflozin, empagliflozin. They demonstrate multiple pleiotropic actions with potential applications in CNS diseases. In addition to renal tubules, SGLT receptors are also found within the central nervous system. In numerous studies in animal models, SGLT2i have had promising results in the treatment of neurological conditions such as Alzheimer's disease, autism spectrum disorders, lesions caused by vascular diseases or complications of ischaemic stroke. SGLT2 inhibitors reduce oxidative stress and activation of inflammatory processes within the CNS, which may in the future be used to treat neurological diseases. So far, published studies on the effects of SGLT2 inhibitors on the nervous system are promising, but extensive, multicentre randomised trials on large groups of patients are needed to understand the exact mechanisms of action, therapeutic effects and potential side effects of SGLT2i.&#x0D;

P204 Utility of Rotational Thrombo-Elastometry as an Objective Measure of Hypercoagulability in Patients with Ulcerative Colitis-A Prospective Case Control Study

Abstract Background Inflammatory bowel disease (IBD) has an increased risk of venous thromboembolism (VTE) with factors like hospitalization and surgery increasing this risk. Although few recent guidelines recommend anticoagulation thromboprophylaxis for hospitalised IBD patients, there is wide variation in reported practices for VTE prophylaxis. This study was aimed to evaluate Rotational Thrombo-Elastometry (ROTEM) for assessing blood coagulation status in ulcerative colitis (UC) and to evaluate the relationship between ROTEM, disease severity and response to treatment. Methods This was a prospective age- and sex-matched study with 60 patients each in UC and irritable bowel syndrome (IBS) groups, latter being controls. Clinical details, blood investigations including ROTEM and D-dimer were collected and analysed after taking informed consent. Hypercoagulable state was defined using Kaufmann’s classification. ROTEM parameters [clotting time (CT), clot formation time (CFT), alpha angle (AA), maximum clot firmness (MCF), maximum lysis (ML)] and D-dimer levels were compared between the two groups. Results Of the 60 UC patients (age: 38.6±11.64 years, 44 males); 15(25%) were in remission, 18(30%), 17(28.3%) and 10(16.7%) had mild, moderate, and severe disease respectively. The UC group had significantly more hypercoagulable ROTEM than the control group (66.7% vs. 36.7%, p=0.001). Hypercoagulable ROTEM was found in 9(60%), 8(44.4%), 14(82.3%) and 9(90%) of those in remission, with mild, moderate and severe UC respectively. Compared to controls; CT [292.36±70.45 vs 337.56±77.89, p=0.001], CFT [103.15±30.31 vs 128.61±40.18, p=0.0001], AA [69.88±5.19 vs 65.36±6.4, p=0.00004], MCF [65.75±5.64 vs 63.25±4.43, p=0.008] and D-dimer levels [329(63-2358) vs 145.5(54-1304), p=0.00001) were significantly abnormal in UC group. Among UC patients with mild, moderate and severe disease; only CFT, AA and D-dimer were significantly different between the groups. There was no significant difference in ROTEM values and D-dimer level in patients with severe UC after one week of treatment. On univariate analysis; partial Mayo score [OR: 1.49, 95% CI: 1.04-2.12, p=0.028], serum albumin [OR: 0.32, 95% CI: 0.10-0.98, p=0.04], hemoglobin [OR: 0.59, 95% CI: 0.40-0.86, p=0.007], and platelets [OR: 1, 95% CI: 1.01-1.02, p=0.035], were predictors of hypercoagulable state in active UC. On multivariate analysis; only haemoglobin [OR: 0.61, 95% CI: 0.38-0.98, p=0.04] was found to be significant independent predictor. Conclusion UC patients had hypercoagulable ROTEM regardless of activity of inflammatory process. The degree of hypercoagulability increased with disease activity. Low haemoglobin was found to predictive of hypercoagulable state in active UC patients.

Evaluation of Metabolic and Cardiovascular Risk Measured by Laboratory Biomarkers and Cardiopulmonary Exercise Test in Children and Adolescents Recovered from Brain Tumors: The CARMEP Study.

In recent decades, the improvement of treatments and the adoption of therapeutic protocols of international cooperation has led to an improvement in the survival of children affected by brain tumors. However, in parallel with the increase in survival, long-term side effects related to treatments have been observed over time, including the activation of chronic inflammatory processes and metabolic alterations, which can facilitate the onset of metabolic syndrome and increased cardiovascular risk. The aim of this study was to find possible statistically significant differences in the serum concentrations of early biomarkers of metabolic syndrome and in the results of cardiopulmonary exercise testing between survivors of childhood brain tumors and healthy controls. This is a prospective and observational study conducted on a group of 14 male patients who survived childhood brain tumors compared with the same number of healthy controls. The concentrations of early metabolic syndrome biomarkers [adiponectin, leptin, TNF-α, IL-1, IL-6, IL-10, endothelin-1, apolipoprotein B, and lipoprotein (a)] were measured and a cardiopulmonary exercise test (CPET) was performed. Results: Childhood brain tumor survivors performed worse on average than controls on the CPET. Furthermore, they showed higher endothelin-1 values than controls (p = 0.025). The CPET results showed an inverse correlation with leptin. The differences found highlight the greater cardiovascular risk of brain tumor survivors, and radiotherapy could be implicated in the genesis of this greater cardiovascular risk.

Accumulation of extracellular elastin-derived peptides disturbed neuronal morphology and neuron-microglia crosstalk in aged brain.

Extracellular elastin-derived peptides (EDPs) accumulate in the aging brain and have been associated with vascular dementia and Alzheimer's disease (AD). The activation of inflammatory processes in glial cells with EDP treatment has received attention, but not in neurons. To properly understand EDPs' pathogenic significance, the impact on neuronal function and neuron-microglia crosstalk was explored further. Among the EDP molecules, Val-Gly-Val-Ala-Pro-Gly (VGVAPG) is a typical repeating hexapeptide. Here, we observed that EDPs-VGVAPG influenced neuronal survival and morphology in a dose-dependent manner. High concentrations of VGVAPG induced synapse loss and microglia hyperactivation invivo and invitro. Following EDP incubation, galectin 3 (Gal-3) released by neurons served as a chemokine, attracting microglial engulfment. Blocking Gal-3 and EDP binding remedied synapse loss in neurons and phagocytosis in microglia. In response to the accumulation of EDPs, proteomics in matrix remodeling and cytoskeleton dynamics, such as a disintegrin and metalloproteinase (ADAM) family, were engaged. These findings in extracellular EDPs provided more evidence for the relationship between aging and neuron dysfunction, increasing the insight of neuroinflammatory responses and the development of new specialized extracellular matrix remolding-targeted therapy options for dementia or other neurodegenerative disease.

Multi-strain probiotic combined with dietary fiber is an effective factor in the nutritional support of immunity in athletes

A priority in the prevention and correction of immune disorders in athletes is the use of products with high nutrient density, fortified with various nutrients or bioactive compounds, as well as probiotic microorganisms. Probiotics help to maintain the gut microbiota, which is actively involved in the absorption of substances and energy and increases the host immune resistance. Dietary fiber, resistant to digestion in the small intestine, is fully or partially fermented in the large intestine and acts as an essential substrate for the growth and regulation of metabolic activity of normal flora, improves peristalsis and digestion. The purpose of the study was to evaluate the impact of a multi-strain probiotic in combination with dietary fiber on the immune status of basketball athletes during the training period. Material and methods. The study was conducted with the participation of 30 male basketball athletes aged 18 to 24 years. The athletes were randomly divided into 2 groups of 15 people. Athletes in the main group received 1 capsule of multi-strain probiotic (≥1.25×1010 CFU of 10 probiotic strains of bifidobacteria and lactobacilli) and 40 g of corn bran (as a source of dietary fiber) for 23 days. Athletes in the control group received 1 placebo capsule containing maltodextrin and breadcrumbs (40 g/day). Subpopulations of peripheral blood lymphocytes were studied by flow cytometry: T lymphocytes, T helper cells, T cytotoxic lymphocytes, NK cells, NKT cells, B lymphocytes, as well as lymphocytes carrying activation markers and apoptosis marker antigen. The content of cytokines in blood serum [FGF, Eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1ra, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17A, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, VEGF] was determined using a multiplex immunoassay. Results. Calculation of the absolute number of lymphocytes revealed a tendency (0.05<p<0.10) to a decrease in T helper cells by the end of the observation period in athletes of the main group (497.60±27.67 vs 632.67±65.20 cells/μL), as well as a decrease (p<0.05) in the expression of the CD95/Fas apoptotic marker on peripheral blood lymphocytes of athletes of the main group compared to the beginning of the study (41.53±5.78 vs 69.53±11.79 cells/μL). At the end of the study, a significant increase in IL-9 level was found in the control group [(Me; min-max) = (0.33; 0.21-0.48) vs (0.26; 0.09-0.38) pg/ml; p<0.05; in comparison with the initial indicator]; as well as the tendency (0.05<p<0.10) towards an increase in the levels of IL-15, IL-1ra and RANTES was revealed. In the main group, at the end of the study, the level of G-CSF significantly decreased [(0.36; 0.03-0.95) vs (0.53; 0.14-1.36) pg/ml, p<0.05]. At the end of the observation period, blood serum levels of FGF, G-CSF, IL-13, IL-2 and RANTES in the athletes of the control group exceeded these indicators in the athletes of the main group whereas no significant differences in the studied cytokines were detected between the control and the main groups at the beginning of the study. Conclusion. The results of observation of basketball athletes who consumed a multi-strain probiotic in combination with corn bran (sources of arabinoxylans) in addition to the main diet for 23 days indicate a decrease in the inflammatory process activity and peripheral blood lymphocyte apoptosis, which confirms the effectiveness of probiotics and dietary fiber in sports nutrition.

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Tuberculosis (TB) remains a global medical problem and is one of the leading causes of death from infectious diseases worldwide. One of the main factors preventing successful control of the infection is the progressive increase in cases of drug-resistant TB. In order to increase the effectiveness of treatment of patients with resistant forms of TB, more and more attention is paid to a complex approach in the treatment of such patients, using surgical methods of treatment. The aim of the work is to determine and compare the clinical and pathological characteristics of pulmonary tuberculosis with different grade of drug resistance to antituberculosis drugs and additional surgical treatment. Materials and methods. This was a cohort retrospective study, which enrolled 49 patients with different clinical forms of pulmonary TB and defined antituberculosis drug resistance profile (MDR-TB or pre-XDR-TB groups according to the the results of drug susceptibility test). The 1-st group included MDR-TB cases (n=25) and the 2-nd group � pre-XDR-TB cases (n=24). The 1-st group consisted of 15 men and 10 women, 2nd group � 10men and 14 women, respectively. The mean age of patients in both groups was approximately the same: 32.2�2.3 years in grouo 1, and 30.6�1.8 years in group 2. Surgery was performed after completion of a standardized 6-month or individualized chemotherapy. Clinical-morphological forms of pulmonary TB were determined based on a comprehensive analysis of the results of chest X-ray, macroscopic examination of the operative material and histological examination of the affected tissue. Morphological signs determined the activity of a specific inflammatory process during histological examination. Results. The clinical-morphological forms of pulmonary TB were established in both groups based on radiological and pathomorphological examination data and a comparative analysis between the groups was carried out. Fibro-caseous TB was diagnosed almost three times more often in the group with pre-XDR-TB by chest X-ray examination. Single or multiple tuberculomas, on the contrary, were 2 times more common in the MDR-TB group. Regardless of the resistance profile, the most common surgical intervention was a resection of a segment or several segments of the lung (77.5 % of cases). The forms of pulmonary tuberculosis established by means of radiological and morphological examination were compared. In MDR-TB group, complete coincidence of diagnosis occurred in 19 out of 25 cases (76.0 %). In pre-XDR-TB group, complete agreement of radiological and morphological diagnosis observed in 11 out of 24 cases (45.8 %). Moreover, the diagnosis of tuberculoma in both groups most often coincided. In cases with pre-XDR-TB, tuberculosis mycobacteria were detected by the cultural method in the operative material almost 2 times more often. In both groups, morphological signs of high or moderate activity of specific inflammation were observed in 70�80 % of cases. Conclusions. In cases of MDR-TB, progression of specific inflammation persisted in 32 %, and in cases of pre-XDR-TB � in 21 %, respectively. Stabilization of the process before surgical treatment was established in almost half of the cases of both MDR-TB (48.0 %) and pre-XDR-TB (50.0 %) groups. Only in 20-29 % of cases was the regression of a specific process was registared. Regardless of the drug-resistant profile, different forms of pulmonary TB were presented in both study groups. Thus, just a complex of clinical and morphological examinations makes can objectively determine the form of pulmonary tuberculosis and the grade of morphological activity of specific inflammation at the time of surgical intervention. Key words: drug-resistant pulmonary tuberculosis, clinical-morphological forms, surgical treatment, histological examination.

Magnetic resonance imaging of the musculoskeletal system in the diagnosis of rheumatic diseases in the pediatric population.

Magnetic resonance imaging (MRI) of the musculoskeletal system is an examination increasingly performed for suspected juvenile idiopathic arthritis, chronic nonbacterial osteomyelitis and juvenile idiopathic inflammatory myopathies, as well as other rheumatic diseases of developmental age. T1-, T2- and PD-weighted with or without fat suppression or short tau inversion recovery/turbo inversion recovery magnitude (STIR/TIRM) sequences and post-contrast sequences are evaluated to diagnose pathological changes in the synovial membrane, subchondral bone marrow and surrounding soft tissues. Magnetic resonance imaging allows detection of synovitis, tenosynovitis, bursitis, and enthesitis as well as bone marrow edema and soft tissue edema. Several pediatric-specific MRI scoring systems have been developed and validated to standardize and facilitate the assessment of the extent of the inflammatory process and disease activity in MRI. Early detection of inflammatory changes allows the inclusion of comprehensive pharmacotherapy giving the possibility of permanent remission and objective measurement of the effectiveness of treatment.

Identificación de factores pronósticos para supervivencia en pacientes con adenocarcinoma gástrico metastásico en la población mexicana

Introduction and aimsGastric adenocarcinoma is among the high-ranking tumors, with respect to frequency and mortality, worldwide. The inflammatory process and immune system activity are associated with oncologic control. Our aim was to identify whether the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and other variables are prognostic factors for survival in patients with metastatic gastric cancer in a Mexican population. Material and methodsPatients diagnosed with metastatic gastric adenocarcinoma, hospitalized within the time frame of December 2011 to 2021, were analyzed. The NLR, PLR, and albumin and hemoglobin levels obtained from blood samples were calculated. Functional status (ECOG and Karnofsky), sex, histology, and the presence of signet ring cells were also considered possible prognostic factors. Each factor's prognostic value for overall survival was determined through univariate and multivariate analyses. ResultsThe study included 956 patients diagnosed with metastatic gastric cancer, of whom 494 (51.7%) were men and 462 (48.3%) were women. The main histologic finding was diffuse adenocarcinoma (n=619, 64.7%), followed by intestinal adenocarcinoma (n=293, 30.6%), and the presence of signet ring cells was found in 659 (68.9%) patients. Diagnostic laparoscopy was performed on 238 patients (24.9%) to confirm peritoneal carcinomatosis. The multivariate analysis showed that an NLR above 3.2 (HR 1.51, 95% CI 1.27-1.8; p<0.001), albumin below 3.5g/dl (HR 1.25, 95% CI 1.06-1.47; p=0.006), and an ECOG performance status of 2 or higher (HR 1.39, 95% CI 1.10-1.76; p=0.005) were independent factors that predicted a lower survival rate, whereas a Karnofsky score above 70% (HR 0.69, 95% CI 0.53-0.91; p=0.008) was associated with a better survival rate. Lastly, the PLR was not statistically significant in the multivariate analysis. ConclusionsThe NLR, nutritional status assessed through albumin measurement, and functional status can act as independent prognostic survival factors in hospitalized Mexican patients diagnosed with metastatic gastric adenocarcinoma, and be taken into account during therapeutic decision-making.

The relationship between morphological manifestations, clinical and hematological indicators and lymphocyte indices in ulcerative colitis

Background. The purpose of the study was to identify correlational parallels between morphological manifestations, clinical and hematological indicators and lymphocyte indices in patients with ulcerative colitis (UC). Materials and methods. Ninety patients with UC were examined. Morphologically, the degree of damage to the intestinal mucosa, the presence of crypt abscesses, atrophic changes, and changes in crypt architectonics were determined. The number of cells of the inflammatory infiltrate, linear measurements of the mucosa were assessed by morphometric method. Clinical blood parameters were evaluated in the inpatients of the department of intestinal diseases at the Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine. The severity of the disease was assessed according to the Mayo score. Statistical processing of the results was carried out using the Statistica 6.1 program. Results. In patients with UC, histological changes in the intestinal mucosa were found. The activity of the disease was evaluated by the presence of an increased number of inflammatory cells in the infiltrate of the mucosa: neutrophils (212.20 ± 20.93), lymphocytes (2922.80 ± 76.63), eosinophils (332.50 ± 17.24), macrophages (369.70 ± 16.21). Multiple crypt abscesses, deformation of the musocal epithelium in the form of erosions and ulcers were also noted. Clinical indicators of peripheral blood also confirmed the exacerbation of the disease (anemic state, increased inflammatory markers). An increased depth of the crypts correlated with such a morphometric indicator as mucosal thickness (r = 0.46; p &lt; 0.01). At the same time, correlations were found between mucosal thickness and the height of the surface epithelium (r = 0.35; p &lt; 0.01). There was a relationship between the morphological and clinical and hematological indicators of UC: mucosal thickness and erythrocyte sedimentation rate (r = 0.38; р &lt; 0.01), band cells (r = 0.37; р &lt; 0.01) and blood neutrophils (r = 0.21; p &lt; 0.05). The Mayo core, as an indicator of the severity of the disease, correlated with the height of the epithelium (r = 0.37; p &lt; 0.05); neutrophils (r = 0.49; p &lt; 0.01) and basophils (r = 0.28; p &lt; 0.05) of the intestinal mucosa; N/L tissue index (r = 0.50; p &lt; 0.01). Conclusions. Correlative parallels were found, which confirm our assumption regarding the connection between morphological manifestations and clinical and hematological indicators of UC. The use of T/L and N/L indices in both tissue and peripheral blood can be used as a marker of the activity of inflammatory processes in UC.