Activation Of Inflammatory Processes Research Articles

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.

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 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 immunotherapy of various tumors. However, due to the rarity of the disease, immunotherapy for ACP is rarely researched. The discovery of the tumor immunosuppressive checkpoint KLRB1 (Killer Cell Lectin Like 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.

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.

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.

Acute post-manipulation pancreatitis after interventions on the major duodenal papilla (experimental study)

Objective. To study the morphological consequences of severe acute post-manipulation pancreatitis (APP), the morphological features of its course and the result of the compound "L-17" exposure.&#x0D; Materials and methods. Rats weighing 250–300 g were used. Forty operations were performed to create a model of APP on rats. The control group included 20 rats with APP without medication, the experimental group – 20 rats with AKI against the background of "L-17" introduced in the dose of 40 mg/kg once per day.&#x0D; Results. In all cases of application of this APP model in rats, the development of acute pancreatitis was noted. The conducted morphological studies showed that APP in rats in the experiment met the criteria for a severe course of acute pancreatitis with the development of purulent peritonitis and necrotizing parapancreatitis with morphological manifestations of systemic inflammation in all the organs studied (with a lethality of 70 %). The use of a new "L-17" in APP in experimental rats showed a decrease in the risk for developing both purulent peritonitis and purulent-necrotic parapancreatitis as well as a 2-fold decrease in mortality (from 70 % to 30 %). A new effect of "L-17" was revealed, i.e. prevention of necrosis of Langerhans islets. The study of the cellular composition of the inflammatory infiltrate showed a decrease in the activity of inflammatory process.&#x0D; Conclusions. The efficacy of a new rat model of APP, ranked by severity, was shown. "L-17" alleviates the severity of APP, reducing the risk for developing various purulent complications and systemic inflammation.

Оценка эффективности применения модифицирующей терапии (комплекса VERIS (пектин + инулин) с солевым энтеральным раствором) у пациентов с язвенным колитом

Purpose: to evaluate the effect of the use of modifying therapy (VERIS complex (Pectin + Inulin) in combination with saline enteral solution) on the effectiveness of treatment of patients with moderate ulcerative colitis (UC). Material and methods. A comparative clinical study was conducted with active effects on the observed group. This study included men and women with a moderate attack of ulcerative colitis without severe concomitant pathology and signs of reactivation of an opportunistic infection. Using a continuous sampling method, 45 patients (n = 45) aged 32 ± 7.5 years were selected who were undergoing inpatient treatment in the gastroenterological department of the State Budgetary Healthcare Institution “Research Institute-KKB No. 1” named after Professor S.V. Ochapovsky regarding inflammatory bowel diseases (IBD). Depending on the chosen treatment strategy, all patients were divided into 3 groups: group 1 included patients who, in addition to basic therapy for IBD, received VERIS (pectin + inulin) (n = 15), group 2 included patients receiving only basic therapy (n = 15), the third group included patients who, in addition to the main therapy, received the combination of VERIS (pectin + inulin) + SER (n = 15). In the groups, a comparative assessment of the volume of the lesion, symptoms of the disease, such as pain, fever, tenesmus, stool frequency and the presence of blood in it, as well as the results of laboratory tests, including data from the blood flow rate, ESR, CRP, blood electrolyte composition, nitrogenous wastes, were carried out and liver transaminases, albumin and indicators of electrolyte metabolism (K, Na, Cl). The dynamics of the above-described indicators in each of the groups was also assessed at 3 stages of observation: initially, on the 5th and 10th day of treatment. In addition to the listed parameters, in both groups the duration of hospitalization in bed days, the level of quality of life (IBDQ questionnaire), and the degree of psycho-emotional disorders according to the HADS hospital anxiety and depression scale were assessed. Results. It was found that when the combination VERIS (Pectin + Inulin) was included in the basic therapy in combination with saline enteral solution, a decrease in the activity of the systemic inflammatory process was revealed, which was manifested by positive dynamics of leukocytosis, a decrease in the average erythrocyte sedimentation rate, and an increase in hemoglobin levels. A statistically significant decrease in cytolysis markers (decrease in liver transaminases) and catabolism indicators was also noted, which was reflected in the form of a decrease in the level of nitrogenous wastes. It should be noted that no undesirable side effects or allergic reactions were registered during the study period. The revealed reduction in the length of hospitalization of patients in the group receiving VERIS (pectin + inulin) + SER, an increase in adherence to therapy due to an increase in the quality of life due to the rapid regression of symptoms can be regarded as significant indicators of the effectiveness of the therapy. The above results obtained by us indicate the modifying effect of the complex of enteroprotective drugs on the standard basic therapy of ulcerative colitis. Conclusion. The addition of the enteroprotective combination VERIS (pectin + inulin) in combination with saline enteral solution to the standard therapy of patients with moderate ulcerative colitis increases the effectiveness of treatment results by reducing the inflammatory process, the phenomena of cytolysis, catabolism and, as a consequence, leads to a decrease in hospitalization time, an increase in quality of life. All of the above allows us to consider this combination of drugs with the function of enteroprotection VERIS (pectin + inulin) + SER as a promising way to modify the basic therapy of inflammatory bowel diseases by compensating for intestinal failure during the treatment period.

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.

Transcriptomic Analysis of Hidradenitis Suppurativa: A Unique Molecular Signature with Broad Immune Activation

Hidradenitis suppurativa is a chronic inflammatory skin disease with limited treatment options. The poorly understood pathogenesis hinders the development of effective treatments; therefore, a pressing need exists to further elucidate the molecular mechanisms in hidradenitis suppurativa. This study investigated the underlying inflammatory pathways and cell types in hidradenitis suppurativa using transcriptomic approaches with RNA sequencing of lesional and non-lesional skin biopsies from hidradenitis suppurativa, which was jointly analyzed with previously published transcriptomic data from atopic dermatitis and psoriasis patients. The differential expression and pathway enrichment analyses demonstrated the activation of multiple inflammatory processes, including the innate and adaptive immune systems, implicated in the hidradenitis suppurativa pathogenesis. In agreement, hidradenitis suppurativa exhibited a unique and heterogeneous cell type signature involving lymphoid and myeloid cells such as B cells and macrophages. Furthermore, hidradenitis suppurativa displayed increased expression of TH1/2/17 signatures with no predominant TH signatures unlike psoriasis (TH1/17) and atopic dermatitis (TH2). In summary, our study provides molecular insights into the pathomechanisms in hidradenitis suppurativa, revealing a strong and widespread immune activation, which may benefit from treatment strategies offering a broad immunomodulation of various key inflammatory pathways. Our data not only corroborate previously reported findings but also enhance our understanding of the immune dysregulation in hidradenitis suppurativa, uncovering novel and potential therapeutic targets.

Saffron extract interferes with lipopolysaccharide-induced brain activation of the kynurenine pathway and impairment of monoamine neurotransmission in mice.

Although activation of inflammatory processes is essential to fight infections, its prolonged impact on brain function is well known to contribute to the pathophysiology of many medical conditions, including neuropsychiatric disorders. Therefore, identifying novel strategies to selectively counter the harmful effects of neuroinflammation appears as a major health concern. In that context, this study aimed to test the relevance of a nutritional intervention with saffron, a spice known for centuries for its beneficial effect on health. For this purpose, the impact of an acute oral administration of a standardized saffron extract, which was previously shown to display neuromodulatory properties and reduce depressive-like behavior, was measured in mice challenged with lipopolysaccharide (LPS, 830 μg/kg, ip). Pretreatment with saffron extract (6.5 mg/kg, per os) did not reduce LPS-induced sickness behavior, preserving therefore this adaptive behavioral response essential for host defense. However, it interfered with delayed changes of expression of cytokines, chemokines and markers of microglial activation measured 24 h post-LPS treatment in key brain areas for behavior and mood control (frontal cortex, hippocampus, striatum). Importantly, this pretreatment also counteracted by that time the impact of LPS on several neurobiological processes contributing to inflammation-induced emotional alterations, in particular the activation of the kynurenine pathway, assessed through the expression of its main enzymes, as well as concomitant impairment of serotonergic and dopaminergic neurotransmission. Altogether, this study provides important clues on how saffron extract interferes with brain function in conditions of immune stimulation and supports the relevance of saffron-based nutritional interventions to improve the management of inflammation-related comorbidities.

Clinical and immunological features of heart and vascular damage in children with juvenile arthritis with systemic onset

Objectives. To study the clinical and immunological features of cardiac and vascular damage in children with juvenile arthritis with systemic onset. Materials and methods. The study included 30 children with juvenile arthritis with systemic onset who were hospitalized in the cardio-rheumatology department of the Republican Specialized Scientific and Practical Medical Center of Pediatrics. All patients underwent clinical and anamnestic, functional, instrumental and laboratory research methods. Conclusion. Clinical and immunological features of lesions of the heart and blood vessels in children with JAWSO depend on the timing of the disease manifestation, the activity of the systemic inflammatory process and are characterized by impaired functional activity of the heart, overexpression of vascular endothelial growth factor - VEGF, which determines the degree of risk of cardiovascular complications in this pathology.

Sexual dimorphism of the synovial transcriptome underpins greater PTOA disease severity in male mice following joint injury

Osteoarthritis is a disease with sex-dependent prevalence and severity in both humans and animal models. We sought to elucidate sex differences in synovitis, mechanical sensitization, structural damage, bone remodeling, and the synovial transcriptome in the anterior cruciate ligament rupture (ACLR) mouse model of post-traumatic osteoarthritis (PTOA). Male and female 12-week-old C57/BL6J mice were randomized to Sham or noninvasive ACLR with harvests at 7d or 28d post-ACLR (n=9 per sex in each group - Sham, 7d ACLR, 28d ACLR). Knee hyperalgesia, mechanical allodynia, and intra-articular MMP activity (via intravital imaging) were measured longitudinally. Trabecular and subchondral bone remodeling and osteophyte formation were assessed by µCT. Histological scoring of PTOA and synovitis and anti-MMP13 immunostaining were performed. NaV1.8-Cre;tdTomato mice were used to document localization and sprouting of nociceptors. Bulk RNA-seq of synovium in Sham, 7d, and 28d post-ACLR, and contralateral joints (n=6 per group per sex) assessed injury-induced and sex-dependent gene expression. Male mice exhibited more severe joint damage at 7d and 28d and more severe synovitis at 28d, accompanied by 19% greater MMP activity, 8% lower knee hyperalgesia threshold, and 43% lower hindpaw withdrawal threshold in injured limbs compared to female injured limbs. Females had injury-induced catabolic responses in trabecular and subchondral bone, whereas males exhibited 133% greater normalized osteophyte volume relative to females and sclerotic remodeling of trabecular and subchondral bone. NaV1.8+ nociceptor sprouting in subchondral bone and medial synovium was induced by injury and comparable between sexes. RNA-seq of synovium demonstrated similar injury-induced transcriptomic programs between the sexes at 7d, but only female mice exhibited a transcriptomic signature indicative of synovial inflammatory resolution by 28d, whereas males had persistent pro-inflammatory, pro-fibrotic, pro-neurogenic, and pro-angiogenic gene expression. Male mice exhibited more severe overall joint damage and pain behavior after ACLR, which was associated with persistent activation of synovial inflammatory, fibrotic, and neuroangiogenic processes, implicating persistent synovitis in driving sex differences in murine PTOA.

Innovative Therapeutic Approaches in Non-Alcoholic Fatty Liver Disease: When Knowing Your Patient Is Key.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis may result from the dysfunction of multiple pathways and thus multiple molecular triggers involved in the disease have been described. The development of NASH entails the activation of inflammatory and fibrotic processes. Furthermore, NAFLD is also strongly associated with several extra-hepatic comorbidities, i.e., metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, cardiovascular disease and chronic kidney disease. Due to the heterogeneity of NAFLD presentations and the multifactorial etiology of the disease, clinical trials for NAFLD treatment are testing a wide range of interventions and drugs, with little success. Here, we propose a narrative review of the different phenotypic characteristics of NAFLD patients, whose disease may be triggered by different agents and driven along different pathophysiological pathways. Thus, correct phenotyping of NAFLD patients and personalized treatment is an innovative therapeutic approach that may lead to better therapeutic outcomes.

Clinical use of densitometric analysis of lung pathology and digital data processing programs for determining surgical tactics in phthisiosurgical patients with HIV status

Objective — to determine the possibilities of using densitometric indicators of computed tomography (CT) and digital software processing of CT data in lung pathology for the formulation of personalized treatment tactics for phthisiosurgical patients with concomitant HIV pathology, and to justify the indications for surgical treatment. &#x0D; Materials and methods. A retrospective analysis was conducted on the results of the examination and treatment of 11 patients with specific tuberculous lesions of the lungs. Specific therapy was initiated 2—3 months after the initial visit to the medical institution, and immunochromatographic tests for HIV and hepatitis, which were performed in advance, yielded doubtful (questionable) or negative results. Patients underwent a general clinical examination, echocardiogram, fibrobronchoscopy with examination of bronchoalveolar lavage for Mycobacterium tuberculosis, and molecular genetic tests of sputum or bronchoalveolar lavage. Express tests for HIV, hepatitis B, and hepatitis C, as well as routine blood and urine tests, were carried out. The Aquilion TSX-101A Toshiba (Japan) tomography was used as the main research tool. Densitometric analysis of lung parenchyma was performed using DICOM-VIEWER PHILIPS in the areas of interest. Digital analysis of images obtained from CT slices was conducted using the Dragonfly program. &#x0D; Results and discussions. The clinical manifestation of patients’ «radiological findings» was asymptomatic in 81.8 % of cases and mostly perceived as a «post COVID-19 syndrome». The analysis of the laboratory data did not indicate specific signs of the disease in 72.7 % of cases. The study of the verified focal lesions without signs of destruction of the lung parenchyma during densitometric analysis of CT revealed densities that characterize exudative processes in the lung parenchyma (0—15 HU), which is a characteristic sign of a specific inflammatory process in the context of HIV infection. Histologically, high activity of a specific inflammatory process was detected in operated patients. During digital software processing, we observed a shift in densitometric indicators that are characteristic of the exudative phase of inflammation. Situations of HIV-associated infection and alteration-exudative reactions were noted, which were 100 % determined by densitometric analysis and digital software processing of the chest CT scan. Six patients underwent surgery on (2 lobectomies, 1 combined resection and 3 sublobar resections). Among the non-operated patients, 3 experienced a recurrence of a specific inflammatory process, and 1 patient still exhibits significant morphological changes in the parenchyma.&#x0D; Conclusions. Densitometric analysis and digital software processing of CT scan allows you to objectify the patient's condition and reasonably prescribe personalized therapy. Identified patients with X-ray lesions of the lungs require a mandatory consultation with a thoracic surgeon and consideration of the issue of surgical treatment within 2—3 months after the start of specific therapy.