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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown aetiology, with the broad range of antibodies affecting various organs and tissues, leading to rapid disability and even to lethal outcome. Our objective was to make an analysis of the results of relevant global studies about genetic mutations, spectrum of antibodies and cytokines involved in the pathogenesis of SLE. The search was conducted in PubMed and Google Scholar platforms using keywords “systemic lupus erythematosus”, “genetic mutations”, “autoantibodies”, “cytokine production”, “sequencing”, “NGS" and "exome". Several genes were found to be involved in the pathogenesis of SLE, the majority of which were associated with B- and T-cell abnormal activation. The results of different studies revealed an association of active SLE with the increase in specific circulating autoantibodies. Based on the results of the current review, a preliminary list of autoantibodies, genes and cytokines associated with the development of SLE was prepared. Future directions will include the assessment of association of genes, antibodies and cytokines in SLE patients from the local Kazakh population, and the development of genetic-immunologic panel for the early diagnosis of this disease.

Ángela María Giraldo-Montoya,1,2,&ast; Carlos A Torres-Duque,1,3,&ast; Luis F Giraldo-Cadavid,4,5 Maria E Laucho-Contreras,1 Angélica González-Flórez,1 Ana María Santos,3 Eduardo A Tuta-Quintero,1,5 Bartolomé R Celli,6 Mauricio González-García1,7 1CINEUMO, Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 2School of Medicine, Universidad Tecnológica de Pereira, Pereira, Colombia; 3Biosciences Doctoral, Universidad de La Sabana, Chía, Colombia; 4Medical Department, Fundación Neumológica Colombiana, Bogotá, Colombia; 5Epidemiology and Biostatistics Department, Universidad de La Sabana, Chía, Colombia; 6Harvard Medical School, Boston, MA, USA; 7School of Medicine, Universidad de La Sabana, Chía, Colombia&ast;These authors contributed equally to this workCorrespondence: Carlos A Torres-Duque, Research Department, Fundación Neumológica Colombiana, Bogotá, Colombia, Biosciences Doctoral, Universidad de La Sabana, Chía, Colombia, Email ctorres@neumologica.orgIntroduction: There is a need to better understand the etiotypes of chronic obstructive pulmonary disease (COPD) beyond the tobacco-smoke (TS-COPD). Wood smoke COPD (WS-COPD) is characterized by greater airway compromise, milder emphysema, and slower rate of lung function decline than TS-COPD. However, it is unclear if these two etiotypes of COPD have differences in sputum biomarker concentrations. Objective was to compare sputum levels of selected sputum biomarkers between WS-COPD and TS-COPD, and healthy controls.Methods: Eighty-eight women (69± 12 years) were recruited and classified into: WS-COPD (n=31), TS-COPD (n=29) and controls (n=28). Using ELISA, we determined induced sputum levels of metalloproteinase 9 (MMP-9), chemokine ligand 5 (CCL5), interleukin-8 (IL-8), chemokine ligand 16 (CCL16/HCC-4) and vascular endothelial growth factor (VEGF-1). Differences were analyzed by Kruskal–Wallis and Mann–Whitney-U tests and correlation between airflow limitation and biomarkers by Spearman’s test.Results: At similar degree of airflow obstruction, anthropometrics and medications use, the level of sputum CCL5 was higher in TS-COPD than WS-COPD (p=0.03) without differences in MMP-9, IL-8, CCL16/HCC-4, and VEGF-1. Women with WS-COPD and TS-COPD showed significantly higher sputum levels of MMP-9, IL-8 and CCL5 compared with controls (p< 0.001). FEV1% predicted correlated negatively with levels of MMP-9 (rho:-0.26; P=0.016), CCL5 (rho:-0.37; P=0.001), IL-8 (rho:-0.42; P< 0.001) and VEGF (rho:-0.22; P=0.04).Conclusion: While sputum concentrations of MMP-9, IL-8, and CCL5 were higher in COPD women compared with controls, women with TS-COPD had higher levels of CCL5 compared with those with WS-COPD. Whether this finding relates to differences in pathobiological pathways remains to be determined.Keywords: COPD, wood smoke, biomass fuels, tobacco smoke, biomarkers, sputum, cytokines

Osteoarthritis is caused by a complex interplay of genetic, metabolic, immunological, inflammatory, biochemical, and biomechanical factors. In recent years, a fairly large number of studies have been devoted to the role of cellular factors of the immune system in the development of osteoarthritis. The aim of the study was to analyze scientifc publications devoted to the study of cellular factors in the pathogenesis of osteoarthritis and to assess their signifcance in the development of joint pathology. Material and methods. The search for publications by keywords was carried out in the PubMed, Google Scholar, eLibrary databases and specialized journals related to therapy, rheumatology, traumatology and immunology from 2000 to 2022. Results and discussion. Summarizing modern ideas about the role of cellular factors of the immune system in the pathogenesis of osteoarthritis, it is necessary to note the presence of synovial inflammation, a key role in the development of which is assigned to macrophages. At the same time, patients with osteoarthritis are characterized by the predominance of classically activated macrophages with a pronounced pro-inflammatory effect. In addition, T lymphocytes also play an important role in the pathogenesis of joint damage. Among them, a special role is given to T helper cells, cytotoxic T lymphocytes and memory T cells. An imbalance of cytokines and chemokines produced by subpopulations of T lymphocytes is the reason for triggering a number of mechanisms for the onset and progression of osteoarthritis. A signifcant role in the development and progression of osteoarthritis is also assigned to neutrophils, which contribute to the development of inflammation. Neutrophil-produced elastase enhances cartilage degradation, chondrocyte apoptosis, unbalanced subchondral bone remodeling, and osteophyte formation. Conclusions. Knowledge of the role of cellular immune factors in the pathogenesis of osteoarthritis and ways to implement their effects determines the prospects for the use of immunotropic agents. Also, it should be taken into account that the occurrence and progression of osteoarthritis is due to the simultaneous combination of the influence of a wide range of various components, including risk factors, traumatic joint injury, etc.

Background and Aims: Necrotizing enterocolitis (NEC) is a life-threatening disease and the most common gastrointestinal emergency in premature infants. Accurate early diagnosis is challenging. Modified Bell’s staging is routinely used to guide diagnosis, but early diagnostic signs are nonspecific, potentially leading to unobserved disease progression, which is problematic given the often rapid deterioration observed. We investigated fecal cytokine levels, coupled with gut microbiota profiles, as a noninvasive method to discover specific NEC-associated signatures that can be applied as potential diagnostic markers. Methods: Premature babies born below 32 weeks of gestation were admitted to the 2-site neonatal intensive care unit (NICU) of Imperial College hospitals (St. Mary’s or Queen Charlotte’s & Chelsea) between January 2011 and December 2012. During the NICU stay, expert neonatologists grouped individuals by modified Bell’s staging (healthy, NEC1, NEC2/3) and fecal samples from diapers were collected consecutively. Microbiota profiles were assessed by 16S rRNA gene amplicon sequencing and cytokine concentrations were measured by V-Plex multiplex assays. Results: Early evaluation of microbiota profiles revealed only minor differences. However, at later time points, significant changes in microbiota composition were observed for Bacillota (adj. P = .0396), with Enterococcus being the least abundant in Bell stage 2/3 NEC. Evaluation of fecal cytokine levels revealed significantly higher concentrations of IL-1α (P = .045), IL-5 (P = .0074), and IL-10 (P = .032) in Bell stage 1 NEC compared to healthy individuals. Conclusion: Differences in certain fecal cytokine profiles in patients with NEC indicate their potential use as diagnostic biomarkers to facilitate earlier diagnosis. Additionally, associations between microbial and cytokine profiles contribute to improving knowledge about NEC pathogenesis.

Introduction: Monitoring changes in the levels of immune markers is of great significance in evaluating the effectiveness of treatment in patients with allergic rhinitis. Objectives: Determine the change in the concentration of immune markers after treatment in patients with allergic rhinitis caused by cotton dust. Methods : A descriptive, single-group, comparative before and after intervention study on 52 patients with allergic rhinitis caused by cotton dust. Comparison of immunological markers results before and after 36 months of treatment. Results: Total IgE concentration after treatment decreased, the median decreased from 1227.756 U/mL to 676.805 UI/mL. Serum levels of IgG, IgG4, and IgG1 in patients after treatment increased compared to before (p< 0.001). The cytokines also changed in the direction of no longer responding toward allergy. Median IL-17 decreased from 1.752 mg/dL to 0.417 mg/dL. Conclusion: In patients with allergic rhinitis after specific sublingual desensitization treatment, IgE levels and cytokines such as IL-6 and IL-17 are significantly reduced and IgG, IgG4 and IgG1 levels are increased after treatment.

Our objective was to investigate the inflammatory and oxidative stress markers in patients with moderate and severe form of COVID-19. In addition, we show the correlation between changes in lymphocyte subsets and markers of oxidative stress as a tool for patient classification. IL-6 and VEGF were analysed by utilizing a High Sensitivity Evidence Investigator™ Biochip Array technology. The total antioxidant capacity (PAT) and the free radical concentrations (d-ROM) were measured in serum utilizing analytical photometric system FRAS5. Peripheral blood was used to determine CD45 + mononuclear, B, T, and NK cells using a multi-parameter flow cytometric immunophenotypic test. Statistically significant differences in IL-6 and VEGF levels were observed between the two patient groups. Decreased values of the absolute number of lymphocytes and their CD4 + and CD8 + positive T cells, NK cells, and CD8 were obtained. In the moderate group, good correlations were found between IL-6 and VEGF and NK cells (r = 0.6973, p

Yan Hu,1 Yanwen Jiang,1 Shuang Liu,1 Jiawei Shen,2 Youzhong An2 1Department of Respiratory and Critical Care Medicine, Peking University International Hospital, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jiawei Shen; Youzhong AnDepartment of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of ChinaEmail jiaweishn@gmail.com; bjicu_bmc@163.comObjective: We aim to identify phenotypes of hematopoietic stem cell transplantation (HSCT) patients with pneumonia, discover relations of microbiota composition, cytokine profile, and outcomes between phenotypes. Specific cytokines will be evaluated for their role in lung injury in a murine model.Methods: HSCT patients with pneumonia were included, and clustering of variables including cytokine levels provided the phenotypes. Outcomes were compared between phenotypes. Analysis of lung microbiota identified marker species of phenotypes. In the murine model, marker species-related cytokine regulations and the role of cytokines in lung injury were evaluated.Results: Seventy-two patients were included, and two phenotypes were identified, namely “reactive” (N=21) and “nonreactive” (N=51) phenotype. Compared to their counterparts, patients with nonreactive phenotype had lower serum IL-6, IL-8, less severe inflammation, worse outcomes and more viruses as marker species in lung microbiota. The animal study validated the pathogens specific cytokine responses that presented in the human study and the potential protective role of IL-6 in these patients.Conclusion: HSCT patients with pneumonia can be clustered into two phenotypes with different marker species and outcomes: the “nonreactive” phenotype and the “reactive” phenotype. Serum cytokine levels were different between the two phenotypes, which indicate the existence of the pathogen-related cytokine responses. For patients with the “nonreactive” phenotype, IL-6 therapy may improve their prognosis, which should be further tested in clinical studies.Keywords: hematopoietic stem cell transplantation, pneumonia, phenotype, microbiota, cytokines

Lead toxicity elicits neurological damage which is a well-known disorder that has been considered to be a major cause for multiple condition such as behavioral defect; mental retardation; and nerve insufficient activity. This research is designed to estimate potential protective effect of vinpocetine on neurotoxicity stimulated by lead acetate in rats. Eighteen adult rats of both sexes were randomly enrolled into three groups. Each group includes 6 rats as followings: Group I- Rats were given 0.3ml normal saline solution orally; then intraperitoneal injection of 100μl of the normal saline was given 1h later; this group was considered as control. Group II- Rats were given an intraperitoneal injection of 20mg/kg lead acetate for 5 days. Group III- Rats were orally given 3mg/kg vinpocetine, which was given 1hr before [(the IP injection of Pb every 24 hours at a dose of 20mg/kg) for 5 days and continued for 10 days]. On 11th day of the study, the brain of each animal has been surgically cut-out to make homogenate preparation to estimate tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-10 (IL-10) levels. Lead significantly elevated TNF-α and IL-1beta; while, it significantly decreased IL-10 levels. Vinpocetine significantly minimized IL-1beta and TNF-α; furthermore, vinpocetine significantly raise IL-10 levels at (P

MicroRNAs are small non-coding RNA regulatory molecules that play an important role in the development and function of immune cells. MicroRNA-26a (miR-26a) exhibits anti-inflammatory immune effects on immune cells. However, the exact mechanism by which miR-26a plays an anti-inflammatory role remains unclear. Here, we report that miR-26a reduces inflammatory response via inhibition of prostaglandin E2 (PGE2) production by targeting cyclooxygenase-2 (COX-2). We found that miR-26a was downregulated in vitro and in vivo. The miR-26a mimic significantly decreased COX-2 protein levels, further inhibiting pro-inflammatory cytokine production in LPS-stimulated macrophages. We predicted that miR-26a could potentially target COX-2 in LPS-stimulated macrophages. Computational algorithms showed that the 3′-UTR of COX-2 mRNA contains a binding site for miR-26a. This putative targeting relationship between miR-26a and COX-2 was further confirmed by a dual-reporter gene assay. The anti-inflammatory effects of the miR-26a mimic were diminished by PGE2 supplementation. Importantly, miR-26a mimics protected mice from lethal endotoxic shock and attenuated pro-inflammatory cytokine production. Collectively, these results suggest that miR-26a may function as a novel feedback negative regulator of the hyperinflammatory response and as a drug target for the progression of inflammation. [ABSTRACT FROM AUTHOR]

Widespread use of surgical interventions in the abdomen of dogs determines the relevance of the study. The research tested the influence of therapeutic epidural blockade with 0.2% bupivacaine after surgical interventions on the background of potentiated local anaesthesia on the body of clinically healthy dogs undergoing ovariohysterectomy. In the control group postoperative analgesia was performed with the nonsteroidal anti-inflammatory drug rimadyl on the background of potentiated thiopental anaesthesia. Wound healing rates were determined in 10 animals of both control and experimental groups; blood counts and the level of inflammatory response were indicated in 5 animals of each group. The dynamics of reparative processes and complete wound healing in dogs of the experimental group occurred earlier than in animals of the control group, which confirmed the fact that the use of bupivacaine had a beneficial effect on tissue regeneration. The results of morphological and biochemical parameters of blood in animals of the experimental group manifested only an increase of leukocytes by 1.58 times, fibrinogen by 2.02 times, while in dogs of the control group the level of erythrocytes, haemoglobin and hematocrit decreased, leukocytes increased by 1.74 times, platelets decreased by 2.87 times and fibrinogen increased by 1.72 times. Among the stress response markers in the control group there was a 1.94 times increase in glucose level after surgery. In the experimental group there was a decrease in the intensity of the inflammatory reaction in dogs, accompanied by an increase of anti-inflammatory interleukin 4 (IL-4) only on the seventh day – 1.86 times, while in the control group the level of anti-inflammatory interleukin 1 receptor antagonist (IL-1RA) after three days increased by 2.30 times, after seven days – by 2.48 times, and the level of proinflammatory interleukin 6 (IL-6) after surgery increased by 2.57 times. It will be promising to conduct further research on the influence of therapeutic blockades with bupivacaine in animals in cases of various surgical interventions and pathological conditions, which will lead to faster recovery of animals and alleviate pathological processes.

Objective. To study the levels of some cytokines (IL-6, TNF-α) and endogenous antimicrobial peptides (zonulin, calprotectin and lactoferrin) in patients, suffering hepatic echinococcosis, and to follow-up their changes in dynamics of postoperative treatment. Materials and methods. There were examined 29 patients, ageing 35 - 65 yrs old, operated for hepatic echinococcosis. In accordance to scheme of the treatment conducted after laparoscopic echinococcectomy the patients were distributed into two Groups: the first one - 13 patients, who obtained the standard treatment, and the second - 16 patients, to whom, besides the standard treatment, preparation for immunocorrection was prescribed. Antibodies towards the echinococcus IgG, concentration of endogenous antimicrobal peptides and cytokines in the blood serum were studied, using immuno-enzymal analysis in dynamics. Results. There was established, that in preoperative period in patients, suffering hepatic echinococcosis, high levels of the studied inflammation mediators are revealed, comparing with the indices in healthy persons. Conduction of postoperative treatment promotes a staged lowering of the antimicrobal peptides and cytokines concentrations. Standard treatment is less effective in lowering of the inflammation mediators levels, than combination of conventional treatment with immunocorrection. Conclusion. In the patients, suffering hepatic echinococcosis, the levels of cytokines and antimicrobal peptides are raised. Combined treatment with immunocorrection after echinococcusectomy leads to significant lowering of the inflammation mediators levels.

Recent studies have shown that alterations of the immune response in the gastrointestinal mucosa are key components of the mechanism of the probiotic action of beneficial bacteria. Most of the beneficial effects of probiotics are due to the action of their structural components and metabolites. Macrophages are first-line defense cells of the immune system, which not only participate in the detection, phagocytosis and destruction of harmful microorganisms, but also determine the nature of the subsequent immune response by presenting antigens to T-cells and initiating inflammation by releasing cytokines. We researched the effect of two types of cell-free extracts (CFEs) containing probiotic derivatives (structural components and metabolites of bacteria) Bifidobacterium bifidum 1 (BbCFE) and Lactobacillus reuteri DSM 17938 (LrCFE) on the activity of mouse peritoneal macrophages and on the ability of peripheral human blood mononuclear cells to produce cytokines. CFEs were obtained by culturing probiotics in their own disintegrates and then removing cells and cell debris by centrifugation and filtration. Peritoneal macrophages were isolated from mice. Some of them were infected in vitro by Salmonella thyphimurium. Uninfected and infected macrophages were incubated in culture medium containing (30% vol) or not containing CFEs at 37 °С in a microaerobic atmosphere (5% СО2) for 18 hours. After incubation, peritoneal macrophages were lysed. The obtained suspensions were centrifuged and supernatants were carefully collected. Macrophages activity was assessed by the nitrites level, superoxide dismutase (SOD), lactate dehydrogenase (LDH) activity and antiinflammatory cytokines levels in supernatants using spectrophotometric method. Peripheral mononuclear cells were isolated from the blood of healthy volunteers. The ability of peripheral mononuclear blood cells to produce antiinflammatory cytokines was evaluated after cell stimulation with lipopolysaccharide (LPS) and incubation with or without CFEs. Cytokine levels in supernatants were determined using enzyme-linked immunosorbent assay (ELISA). After infection with S. thyphimurium in macrophages, nitrite levels increased 5.5-fold, SOD activity 4.8-fold, and LDH 2-fold. Both studied CFEs exerted a similar effect on the macrophages’ activity. Addition of BbCFE to the incubation medium of infected macrophages resulted in a 4-fold decrease in nitrite levels, and the addition of LrCFE was accompanied by a decrease in nitrite levels to levels in intact cells. Under the influence of both CFEs, the activity of SOD and LDH was significantly reduced and did not differ significantly from the activity of these enzymes in intact cells. BbCFE and LrCFE did not have a significant effect on nitrite levels, SOD and LDH activity in intact macrophages. Under the influence of BbCFE, there was a 2-fold decrease in the production of TNF, a 2-fold increase in IL10 production, and a 30% increase in IL6 production by mononuclear cells. LrCFE caused a decrease in TNF production by 26.7% and IL6 by 36%, and IL10 by 1.9 times. Thus, the studied CFEs normalized the nitrite levels in peritoneal macrophages infected with S. thyphymurium and infection-induced activation of SOD and LDH enzymes. This demonstrates their ability to modulate oxidative processes in macrophages. In addition, under the influence of the investigated CFEs, there was a decrease in the production of pro-inflammatory cytokines (TNFα and IL-6) and increased production of anti-inflammatory cytokine (IL-10) by human peripheral mononuclear cells. The results of the study indicate the ability of CFEs by influencing the functions of innate immunity cells to restrict the inflammatory response and oxidative stress. Based on this, CFEs can be considered as promising agents for the treatment of inflammatory diseases.

Objective: This study aimed to investigate the potential therapeutic efficacy of rutin in the management of psoriasis and elucidate its underlying molecular mechanisms., Methods: A systems biology approach, utilizing network pharmacology, was employed to identify and analyze putative targets of rutin relevant to psoriasis. The impact of rutin on the Psoriasis Area and Severity Index (PASI) scores was assessed in an imiquimod (IMQ)-induced murine psoriasis model. Histopathological alterations in the skin lesions were examined using hematoxylin and eosin (H&E) staining. Expression levels of key inflammatory mediators, including Tnf, Hif1a, Ptgs2, Tlr4, Nfkb1, Mtor, and Il2, were quantified using quantitative real-time polymerase chain reaction (qRT-PCR)., Results: A comprehensive analysis revealed 62 potential targets of rutin in the context of psoriasis, with these targets being part of 72 interconnected signaling pathways. In vivo studies demonstrated a significant reduction in PASI scores in rutin-treated mice compared to those in the control group. Additionally, rutin treatment was associated with marked improvements in skin lesions, characterized by reduced crust formation and epidermal thickness. qRT-PCR analysis indicated that rutin administration downregulated the mRNA expression of Tnf, Hif1a, Ptgs2, Tlr4, Nfkb1, Mtor, and Il2 in the lesional skin., Conclusion: These findings suggest that rutin holds promise as a therapeutic agent for psoriasis, as it effectively ameliorates IMQ-induced psoriasis-like skin inflammation in mice through modulation of multiple signaling pathways and inflammatory mediators., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of this study was to evaluate the effect of an oral preparation containing a naturally occurring matrix of hydrolyzed collagen type II, chondroitin sulfate (CS), and hyaluronic acid (HA), and bioactive oligopeptides of natural hydrolyzed keratin (K) in patients affected by knee OA through the evaluation of synovial fluid (SF) and clinical changes before and after treatment. Thirty patients with knee OA and swollen joint were included in the study and submitted to arthrocentesis. Patients were randomized in two groups: 1) the treatment group (N.15) took a dietary supplement containing 120 mg HA, 240 mg CS and 300 mg K once a day for 4 weeks; 2) the control group (N.15) was only submitted to arthrocentesis. Patient symptoms were evaluated at the beginning and at the end of the study by the WOMAC self-assessment questionnaire, the Lequesne algofunctional index, and the VAS forms. SF changes were evaluated by measuring local inflammatory indices, cytokines IL-1β, IL-8, IL-6, IL-10 and GM-CSF. The group of patients treated with the oral supplement showed an improvement in the clinical indices WOMAC (p

In this review, we have considered and discussed the existing data to achieve a deeper understanding of the role of intestinal microbiota in the development and progression of chronic heart failure (CHF). The key moments of the CHF pathogenesis (an imbalance of neurohumoral systems, inflammatory theory and metabolic disorders) and the respective changes of the intestinal microflora composition were compared. Here, we also present the latest results of the positive influence of the microflora modulations on the course and prognosis of CHF with the prescribing antibiotics, probiotics and prebiotics.

A total of 70 pregnant women with toxoplasmosis were studied to evaluate of some immunological aspects. The women were distributed into three groups: 37 women were IgG positive, 18 women were IgM positive and 15 women were IgG and IgM positive as well as 25 healthy women were considered as control group. Serum samples were collected and ELISA method was employed to assess levels of interleukins 4, 6, 10, Interferon gamma-induced protein 10 (IP-10), Granulocyte-macrophage colony-stimulating factor (GM-CSF) and Vascular endothelial growth factor (VEGF). As compared with control the levels of cytokines were significantly increased in serum of three pregnant women groups with toxoplasmosis and the highest increase was observed in the IgM positive group. [ABSTRACT FROM AUTHOR]

Christelle Audi,1,* Nour Baïz,1,* Cara N Maesano,1 Ollivier Ramousse,2 Damien Reboulleau,3 Antoine Magnan,3 Denis Caillaud,4 Isabella Annesi-Maesano1 1Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, UMRS 1136, Epidemiology of Allergic and Respiratory Diseases Department, Medical School Saint-Antoine, Paris, 2Mutualité Sociale Agricole, Clermont-Ferrand, Auvergne, 3Centre du Thorax de Nantes INSERM, UMR1087, Institut du thorax, Nantes, 4Respiratory Diseases Department, CHU Clermont-Ferrand, Clermont-Ferrand, Auvergne, France *These authors contributed equally to this work Abstract: Although French farmers smoke less on average than individuals from the general population, they suffer more from COPD. Exposure to biological and chemical air pollutants in the farm may be the cause of these higher COPD rates. This study investigates the role of biocontaminants, including the relationship of exposure to volatile organic compounds (VOCs) and fine particulate matter (of diameter of 2.5 µm [PM2.5]) objectively measured in the farm settings (dwellings and workplaces) to serum cytokines involved in COPD, in a sample of 72 farmers from 50 farms in the Auvergne region, France. Mean concentrations of VOCs were highest inside the home, while levels of PM2.5 were highest in workplaces (stables and granaries). After adjusting for confounders, high exposure to PM2.5 was significantly associated with a decreased level of serum cytokines (among others, IL13: β: –0.94, CI: –1.5 to –0.2, P-value =0.004; IL8: β: –0.82, CI: –1.4 to –0.2, P-value =0.005) and high exposure to VOCs according to a VOC global score with a decreased IL13 level (β: –0.5, CI: –0.9 to –0.1, P-value =0.01). Moreover, respiratory symptoms and diseases, including COPD, were associated with a decreased level of serum cytokines significantly in the case of IL5. An alteration of immune response balance in terms of cytokine levels in relation to indoor chemical air pollution exposure may contribute to respiratory health impairment in farmers. Keywords: indoor rural air pollution, COPD, French farmers, VOCs, PM2.5, cytokines

Lauran Vogelaar, 1,* Colin de Haar,2,* Bas RJ Aerts,1 Maikel P Peppelenbosch,1 Reinier Timman,3 Bettina E Hanssen,1 C Janneke van der Woude1 1Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, 2Applied Tumor Immunology, Laboratory of Translational Immunology, UMC Utrecht, Utrecht, 3Department of Psychiatry, Section of Medical Psychology and Psychotherapy, Erasmus MC, Rotterdam, the Netherlands *These authors contributed equally to this work Background: Although it is well recognized that fatigue is an important problem in many of the quiescent inflammatory bowel disease (IBD) patients, it is unknown whether the immune status is different in fatigued versus non-fatigued patients. In this study, we contrasted various characteristics of the immune system in fatigued against non-fatigued patients with IBD in clinical remission.Patients and methods: Patients with IBD in clinical remission were phenotyped according to the Montreal classification, and the checklist individual strength-fatigue (CIS-fatigue) was used to assess fatigue (CIS-fatigue ≥ 35). Flow cytometry on peripheral blood samples was used to investigate differences in leukocyte subsets. The expression of various cytokines was determined in stimulated whole blood and serum samples using enzyme-linked immunosorbent assay. Differences between fatigued and non-fatigued patients with IBD were assessed.Results: In total, 55 patients were included in the fatigue group (FG) and 29 patients in the non-fatigue group (NFG). No differences in demographic and clinical characteristics were observed between the groups. Flow cytometry data showed a significantly lower percentage of monocytes (p = 0.011) and a higher percentage of memory T-cells (p = 0.005) and neutrophils (p = 0.033) in the FG compared with the NFG. Whole blood stimulation showed increased TNF-α (p = 0.022) and IFN-γ (p = 0.047) in the FG. The median serum level was significantly higher for IL-12 (p

Chemerin is an adipokine secreted by adiopose tissue and has a role in obesity and hypertension. This study aims at assessing the level of the adipokine chemerin in obesity and/or hypertension and correlating its level with the inflammatory marker hs-CRP and predictors of atherosclerosis as lipid profile, insulin resistance, systolic (SBP) and diastolic blood pressure (DBP).Volunteers were divided into 4 equal groups according to body mass index (BMI) and blood pressure: normal weight group (BMI ≤ 24.9 kg/m2), overweight group (BMI = 25.0 – 29.9 kg/m2), normotensive obese group (BMI ≥ 30.0 kg/m2) and hypertensive obese group (BMI ≥ 30.0 kg/m2). Chemerin, high-sensitivity C-reactive protein (hs-CRP), lipid profile, fasting blood glucose (FBG) and fasting insulin (FI) were evaluated in the mentioned groups.The results showed that there were significant increases of chemerin, hs-CRP, low density lipoprotein (LDL), SBP and DBP in hypertensive obese group compared to normotensive obese , overweight and normal weight groups. Moreover the only significant positive correlation between chemerin and hs-CRP was observed in the obese hypertensive group. The normotensive obese group showed significant increases of hs-CRP, LDL, triglyceride (TG), FBG, FI and the homeostasis model assessment-insulin resistance index (HOMA-IR) compared to the overweight and normal weight groups. Regarding the overweight group, there were significant increases in chemerin, hs-CRP, cholesterol, LDL, TG compared to the normal weight group, while the HDL levels were significantly lower compared to the two obese groups. These results revealed that the pro-inflammatory adipokine chemerin increases in obesity associated with hypertension, leading to the suggestion that there is a definite dysregulation of the pro-inflammatory and anti-inflammatory parameters towards the pro-inflammatory when hypertension and obesity are associated.

The positive impact of exposure to low-dose gamma irradiation (LDR) on tumor regression and immune response has recently been emphasized. The present study aimed to investigate the T-helper 1 / T-helper 2 (Th1/ Th2) cytokine balance, serum protein changes in male BALB/c Ehrlich Ascites Carcinoma (EAC) bearing mice exposed to two low doses(0.4Gy or 0.8Gy) of gamma irradiation. Seventy two male BALB/C mice were divided into six groups. Group1: normal control; Group2&3:mice were exposed to γ-irradiation at 0.4 and 0.8 Gray, respectively two times weekly for 3 weeks; Group4 (malignant control):mice were injected subcutaneously with 2×106 Ehrlich Ascites Carcinoma (EAC) cells/mouse; Group5&6: mice were injected by EAC cells and exposed to γ-irradiation at 0.4 and 0.8 Gray, respectively two times weekly for 3 weeks, eight days after tumor transplantation. Data from the present study reported that two low-doses of γ- irradiation significantly increase the levels of serum IL2, IL6 and TNFα and a decrease the serum IL10 level in comparison to malignant control mice. The IL2 /IL-10,IL-6/IL-10 and TNFα/IL-10 (Th1/Th2 balance), were significantly increased in all tested groups when compared with control (P

Introduction: The macrophage migration inhibitory factor (MIF) plays a pivotal role in the development of rheumatoid arthritis (RA). Previous research indicates that MIF can trigger the expression of cytokine profiles associated with Th1, Th2, and Th17 responses in peripheral blood mononuclear cells (PBMC) from both RA patients and control subjects (CS). Despite these, few studies to date precisely elucidate the molecular mechanisms involved. The present study aimed to associate the expression of Th differentiation TF (T-bet, GATA-3, RORγt) with MIF receptors (CD44, CD74, CXCR2, 4, 7) and Th1, Th2, and Th17 cytokines in PBMC from CS and RA patients., Method: PBMC from both groups was cultured for 24 h. The expression of the canonical and non-canonical MIF receptors and the TF was determined by flow cytometry. Additionally, multiplex bead analysis was employed to assess the levels of cytokines in the culture supernatants. The findings revealed that T CD4+ lymphocytes in the CS group exhibited a heightened expression of CD74 (p<0.05), whereas RA patients displayed an elevated expression of CXCR7 (p<0.001). Furthermore, T CD4+ lymphocytes from RA patients exhibited greater expression of GATA3, RORγt, and FOXP3, along with elevated levels of pro-inflammatory cytokines compared to the CS group (p<0.001)., Result: These results indicate that CD74 is more prominently expressed in PBMC from the CS group, whereas CXCR7 is more expressed in PBMC from RA patients., Conclusion: We also noted an increased secretion of Th17 profile cytokines in RA, potentially influenced by the activation of FOXP3 via CD74 and RORγt through CXCR7 using the endocytic pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tumor metastasis is a complex process that is controlled at the molecular level by numerous cytokines. Primary breast and prostate tumors most commonly metastasize to bone, and the development of increasingly accurate targeted nanocarrier systems has become a research focus for more effective anti-bone metastasis therapy. This review summarizes the molecular mechanisms of bone metastasis and the principles and methods for designing bone-targeted nanocarriers and then provides an in-depth review of bone-targeted nanocarriers for the treatment of bone metastasis in the context of chemotherapy, photothermal therapy, gene therapy, and combination therapy. Furthermore, this review also discusses the treatment of metastatic and primary bone tumors, providing directions for the design of nanodelivery systems and future research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Systemic Sclerosis (SSc) is a systemic autoimmune disease of unknown etiology with a highly complex pathogenesis that despite extensive investigation is not completely understood. The clinical and pathologic manifestations of the disease result from three distinct processes: 1) Severe and frequently progressive tissue fibrosis causing exaggerated and deleterious accumulation of interstitial collagens and other extracellular matrix molecules in the skin and various internal organs; 2) extensive fibroproliferative vascular lesions affecting small arteries and arterioles causing tissue ischemic alterations; and 3) cellular and humoral immunity abnormalities with the production of numerous autoantibodies, some with very high specificity for SSc. The fibrotic process in SSc is one of the main causes of disability and high mortality of the disease. Owing to its essentially universal presence and the severity of its clinical effects, the mechanisms involved in the development and progression of tissue fibrosis have been extensively investigated, however, despite intensive investigation, the precise molecular mechanisms have not been fully elucidated. Several recent studies have suggested that cellular transdifferentiation resulting in the phenotypic conversion of various cell types into activated myofibroblasts may be one important mechanism. Here, we review the potential role that cellular transdifferentiation may play in the development of severe and often progressive tissue fibrosis in SSc., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the past decades, scientists have made outstanding efforts to treat diabetes. However, diabetes treatment is still far from satisfactory due to the complex nature of the disease and the challenges encountered in resolving it. Inflammatory factors are key regulators of the immune system's response to pathological insults, organ neogenesis, rejuvenation of novel cells to replace injured cells and overwhelming disease conditions. Currently, the available treatments for type 1 diabetes include daily insulin injection, pancreatic beta cell or tissue transplantation, and gene therapy. Cell therapy, exploiting differentiation, and reprogramming various types of cells to generate pancreatic insulin-producing cells are novel approaches for the treatment of type 1 diabetes. A better understanding of the inflammatory pathways offers valuable and improved therapeutic options to provide more advanced and better treatments for diabetes. In this review, we investigated different types of inflammatory factors that participate in the pathogenesis of type 1 diabetes, their possible dual impacts on the differentiation, reprogramming, and fusion of other stem cell lines into pancreatic insulin-producing beta cells, and the possibility of applying these factors to improve the treatment of this disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Renal disease in T2DM could arise independently of hyperglycemia, aka non diabetic kidney disease. Its prevalence ranges from 33% to 72.5% among T2DM patients. Specific molecular signatures that distinguish Diabetic Nephropathy from NDKD (FSGS) in T2DM might provide new targets for CKD management., Methods: Five original GEO microarray DN and FSGS datasets were evaluated (GSE111154, GSE96804, GSE125779, GSE129973 and GSE121233). Each of the three groups (DN, FSGS, and Controls) had equal renal transcriptome data (n=32) included in the analysis to eliminate bias. The DEGs were identified using TAC4.0. Pathway analysis was performed on the discovered genes aligned to official gene symbols using Reactome, followed by functional gene enrichment analysis using Funrich, Enrichr..STRING and Network analyst investigated PPI, followed by Webgestalt's pathway erichment. Finally, using the Targetscan 7.0 and DIANA tools, filtered differential microRNAs downregulated in DN were evaluated for target identification., Result: Between the three groups, DN, FSGS, and Control, a total of 194 DEGs with foldchange, >2 & <-2 and P-value 0.01 were found in the renal transcriptome. In comparison to control, 45 genes were elevated, particularly in DN, whereas 43 were upregulated specifically in FSGS. DN datasets were compared to FSGS in a separate analysis. FABP4, EBF1, ADIRF, and ART4 were shown to be among the substantially up-regulated genes unique to DN in both analyses. The transcriptional regulation of white adipocytes was discovered by pathway analysis., Conclusion: The molecular markers revealed might be employed as specific targets in the aetiology of DN, as well as in T2DM patients' therapeutic care., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose. To study clinical features of ophthalmic and laboratory changes after cataract phacoemulsification in patients with diabetic retinopathy associated with hypertension.Material and methods. It was selected 130 patients with the diagnosis of complicated cataract, non-proliferative diabetic retinopathy and they were divided into 3 groups: the group I – patients with non-proliferative diabetic retinopathy without hypertensive disease, the group II – patients with non-proliferative diabetic retinopathy and hypertension, who took angiotensin-converting enzyme (ACE) inhibitors, the group III – patients who took other antihypertensive drugs (a1-adrenoblockers and agonists I1-imidazoline receptors). The study included clinical and functional examinations: visometry, tonometry, refractometery, perimetry, bio-microscopy and direct ophthalmoscopy, optical coherence tomography, autofluorescence, UBM. Samples of lacrimal fluid and blood serum were collected. Clinical and laboratory parameters of homeostasis: endothelial factors, cytokines (IL-6, TGF-β, VEGF, PEDF), adhesion molecules: sICAM, sVCAM. All patients underwent micro-invasive cataract phacoemulsification with implantation of Acrysof Natural IOL (Alcon).Results. Based on the obtained results the stability of proand anti-angiogenic balance after phacoemulsification was determined in patients with diabetic retinopathy without hypertension. Opposite changes of proangiogenic potential were noted in the group of patients with diabetic retinopathy and hypertension after phacoemulsification. The group of patients with diabetic retinopathy and hypertension, who took angiotensin-converting enzyme inhibitors in the postoperative period showed an insignificant change of immune-bio-chemical indices early stabilized on the 3rd day, which allowed us to predict a favorable course of diabetic retinopathy. It is possible to ascertain a growth of pro-angiogenic potential and endothelial dysfunction by the nature of the changes in the balance of the studied parameters and to predict an aggravation of vascular changes in the group of patients with diabetic retinopathy and hypertensive disease, who received othergroups of drugs. All laboratory identified patterns were confirmed in the parallel dynamic ophthalmic studies which demonstrated a higher incidence of vascular disorders after phacoemulsification in patients with diabetic retinopathy and hypertension who were not treated with ACE inhibitors. Accordingly, a stable course of the disease clinically was observed in the group of patients treated with ACE inhibitors to normalize vascular hypertension. Conclusion. The performed evaluation of vascular changes factors after phacoemulsification and the effect of antihypertensive drugs on the balance of laboratory parameters in patients with diabetic retinopathy and hypertensive disease allowed to determine a beneficial effect of ACE inhibitors on the stability of the angiogenic potential. It can be assumed that a basis of the described picture is in pharmacological properties of ACE inhibitors which have a positive effect on the stabilization of the angiogenic potential and reduce endothelial dysfunction.

Background. Due to the wide use of nitrate fertilizers in agriculture and their migration into groundwater and food, the spreading of nitrate poisoning has become epidemic. However, people in the process of life get into bad habits: smoking, alcohol, drugs abuse. All these factors affect health and can cause fatal outcome. In real life, people are often exposed to more toxic factors that lead to general poisoning of the body and damage of many organs. Objective. The research was aimed to study the activity of free radicals and inflammation in rats of different age in cases of sodium nitrite affection with underlying 45-day tobacco intoxication. Methods. The content of nitrite ion (NO2-) was evaluated by Gris reaction. The level of pro-inflammatory (interleukin 6 (IL-6) and anti-inflammatory (interleukin 4 (IL-4) cytokines was determined in serum by ELISA method using test kits. Results. It was proved that in rats of different age affected by sodium nitrite with underlying 45-day tobacco smoke intoxication, the content of nitrite ion in serum, liver, lungs and myocardium is increased. After poisoning the animals with the studied toxicants, inflammation was activated in the body that was evidenced by the increased pro-inflammatory cytokine IL-6 and decreased inflammatory cytokine IL-4 in serum. Conclusions. The nitrite ion content in organs was the most significant and inflammation was manifested in the immature rats. In these animals the content of anti-inflammatory cytokines was the lowest.

Research of prevalence of a polymorphic marker of a gene of the factor of a necrosis of tumors-α G-308A at 201 children is carried out at the uncomplicated and complicated current of influenza A H1N1pdm09. It is established, that frequency of prevalence of genotypes G/G and G/A at children with not serious forms of influenza A H1N1pdm09 and at a seasonal influenza corresponds population. In case of development of a pneumonia in children at influenza A H1N1pdm09, irrespective of gravity of its current, and also at a serious current of a bacterial pneumonia, distribution of genotypes G/G and G/A differed from healthy population of children. It is revealed, that an allele A polymorphism G-308A of a gene of the factor of a necrosis of tumors-α associations with development of the serious and complicated current of influenza A H1N1pdm09.

The paper discusses the new mechanisms of osteoarthritis (OA) pathogenesis. Particular emphasis is placed on the role of subchondral bone remodeling, inflammatory mediators, bone morphogenetic proteins, etc. These data may be of great importance for elaborating new approaches to OA treatment.

Epilepsy is a common chronic consequence of traumatic brain injury (TBI), contributing to increased morbidity and mortality for survivors. As post-traumatic epilepsy (PTE) is drug-resistant in at least one-third of patients, there is a clear need for novel therapeutic strategies to prevent epilepsy from developing after TBI, or to mitigate its severity. It has long been recognized that seizure activity is associated with a local immune response, characterized by the activation of microglia and astrocytes and the release of a plethora of pro-inflammatory cytokines and chemokines. More recently, increasing evidence also supports a causal role for neuroinflammation in seizure induction and propagation, acting both directly and indirectly on neurons to promote regional hyperexcitability. In this narrative review, we focus on key aspects of the neuroinflammatory response that have been implicated in epilepsy, with a particular focus on PTE. The contributions of glial cells, blood-derived leukocytes, and the blood−brain barrier will be explored, as well as pro- and anti-inflammatory mediators. While the neuroinflammatory response to TBI appears to be largely pro-epileptogenic, further research is needed to clearly demonstrate causal relationships. This research has the potential to unveil new drug targets for PTE, and identify immune-based biomarkers for improved epilepsy prediction.

ABSTRACT Purpose. To measure concentrations of transforming growth factor-β1 (TGF-β1), matrix-metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in the lacrima of cataract patients with pseudoexfoliation syndrome (PEX). Material and methods. Determination of the concentrations of IL-6, TGF-β1 and MMP-9 in lacrima was performed by the immune-enzyme analysis method in 71 cataract patients (71 eyes) with pseudoexfoliation syndrome (PEX) aged from 50 to 92 years (76±0.91). Results. It was found a significant increase of the concentrations of IL-6, TGF-β1 and MMP-9 in lacrima of patients with PEX. Conclusions. Increase of IL-6 and MMP-9 level may play an important role in the PEX pathogenesis. These cytokines are involved in the development of «subclinical» inflammatory process and activate the processes of destruction and proliferation. TGF-β1 has significant proliferative and anti-inflammatory activity. Increase of TGF-β1 level activates the processes of fibrosis and may be one of the pathogenetic factors in the formation of pseudoexfoliation material.

Randia dumetorum Lam. (RD) (Rubiaceae) is traditionally used by some tribes of Assam and Manipur of North East India for the treatment of liver ailments. In this context, to scientifically validate this indigenous traditional knowledge, we have evaluated the antioxidant and hepatoprotective activity of RD leaf and bark. The methanol extracts of RD leaf and bark were evaluated for in vitro antioxidant activity which exhibited good anti-oxidant activity in terms of reducing power assay, total antioxidant assay and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay. Total phenolic and flavonoid content were found to be 112 ± 3.24 mg and 138 ± 2.46 mg gallic acid equivalents/g extract and 2.6 ± 0.26 mg and 3.34 ± 0.31 mg rutin equivalents/g extract respectively for RD leaf and bark methanol extracts. The In vivo hepato protective activity of the RD leaf and bark extract was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in male wistar rats. CCl4 administration induced hepatic damage in rats resulted in increased levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, thiobarbituric acid reacting substances, albumin, bilirubin, TNF-α, IL-1β and decreased levels of total protein and antioxidant enzymes like superoxide dismutase, catalase and glutathione reductase. RD leaf and bark methanol extracts pre-treatment exhibited protection against CCl4 induced hepatotoxicity by reversing all the abnormal parameters to significant levels. Histopathological results revealed that RD leaf and bark extracts at 400 mg/kg protects the liver from damage induced by CCl4. The results of this study scientifically validate the traditional use of RD leaf and bark for the treatment of liver ailments.

OBJECTIVE To analyze the expression and levels of serum proinflammatory cytokines including tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6 in patients with hepatocellular carcinoma (HCC), who received orthotopic liver transplantation (OLT). METHODS The blood samples of 20 consecutive HCC patients who underwent liver transplantation were detected and analyzed for the clinical serum biochemical parameters, TNF-α and IL-6. Blood samples were drawn from the radial artery at planned time points: preoperatively, intraoperatively, and postoperatively. Levels of serum TNF-α and IL-6 were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS The levels of serum TNF-α and IL-6 increased significantly at reperfusion phase compared with those detected preoperatively (P < 0.01), and the level of serum IL-6 remained significantly higher until the third day after the liver transplantation. There was a significant correlation between TNF-α and IL-6 (P < 0.001).CONCLUSION This research into the effects of the proinflammatory cytokines on liver transplantation has provided new insights into the mechanisms of ischemia and reperfusion injury to OLT.

Saturska H. S., Bondarenko Yu. I., Pelykh V. E. Изменения цитокинового профиля крови при экспериментальном диффузном кардиосклерозе у крыс с различной устойчивостью к гипоксии = Changes of cytokine blood profile in experimental diffuse cardiosclerosis in rats with different resistance to hypoxia. Journal of Education, Health and Sport. 2015;5(2):66-78. ISSN 2391-8306. DOI: 10.5281/zenodo.15412 http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%282%29%3A66-78 https://pbn.nauka.gov.pl/works/536525 http://dx.doi.org/10.5281/zenodo.15412 Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011 – 2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive Deklaracja. Specyfika i zawartość merytoryczna czasopisma nie ulega zmianie. Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., że w roku 2014 nie będzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktów co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r. The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014). © The Author (s) 2015; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland and Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 20.10.2014. Revised 18.01.2015. Accepted: 25.01.2015. УДК 616.12-004-097-02:616.152.21]-092.9 UDC 616.12-004-097-02:616.152.21]-092.9 ИЗМЕНЕНИЯ ЦИТОКИНОВОГО ПРОФИЛЯ КРОВИ ПРИ ЭКСПЕРИМЕНТАЛЬНОМ ДИФФУЗНОМ КАРДИОСКЛЕРОЗЕ У КРЫС С РАЗЛИЧНОЙ УСТОЙЧИВОСТЬЮ К ГИПОКСИИ Changes of cytokine blood profile in experimental diffuse cardiosclerosis in rats with different resistance to hypoxia Сатурская А. С., Бондаренко Ю. И., Пелых В. Е. Saturska H. S., Bondarenko Yu. I., Pelykh V. E. ГВУЗ «Тернопольский государственный медицинский университет имени И.Я. Горбачевского МЗ Украины», г. Тернополь SHEI “I. Horbachevsky Ternopil State Medical University of the Ministry of Public Health of Ukraine”, Ternopil, Ukraine saturska.gs@gmail.com Ключевые слова: гипоксия, диффузный кардиосклероз, цитокины. Key words: hypoxia, diffuse myocardial fibrosis, cytokines. Резюме В работе изложены особенности изменений цитокинового статуса в динамике развития экспериментального кардиосклероза у лабораторных животных (белых крыс) с различной устойчивостью к гипоксии на этапах моделирования данной патологии (7, 14, 30 суток наблюдения). Выявлено, что развитие кардиосклеротического процесса сопровождается различным по степени повышением синтеза цитокинов – ИЛ-1β, ИЛ-6 в зависимости от чувствительности животных к гипоксии, а также от периода наблюдения. Особенностями реакции противовоспалительного звена на моделирование диффузного кардиосклероза является повышение содержания ИЛ-10 на всех этапах развития патологии, за исключением низкоустойчивых к гипоксии животных, у которых содержание ИЛ-10 немного снижено. Abstract The article presents peculiarities of changes of cytokine status in the dynamics of experimental cardiosclerosis in laboratory animals (white rats) with different resistance to hypoxia at stages of modeling of the disease (7, 14, 30 days of observation). It has been discovered that the development of experimental diffuse ischemic necrotic cardiosclerosis is accompanied by different degrees of increase of synthesis of IL-1β and IL-6 cytokines in blood serum depending on the sensitivity of animals to hypoxia and on the observation period. Increased level of IL-10 inblood serum in animals with high and medium resistance to hypoxia at all stages of the disease, and decreased level of IL-10 inblood serum in animals with low resistance to hypoxia are the main peculiarities of an anti-inflammatory response due to diffuse cardiosclerosis modeling.

In the summer of June 2011, the first case of Crimean-Congo hemorrhagic fever (CCHF) was observed in Oman since the last fifteen years. The first blood sample using reverse transcriptase polymerase chain reaction (PCR) test were sent looking for CCHF, tick-borne encephalitis, dengue, Japanese encephalitis, Chikungunya and West Nile. All resulted as negative. The repeated serology for CCHF came strongly positive after five days from the initial negative test, and accordingly patient started on ribavirin and he responded to it. His condition improved dramatically.

BACKGROUND: Markers of an acute phase reaction, such as C-reactive protein (CRP) or tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6, are predictive for cardiovascular morbidity and mortality in normal subjects and in chronic renal failure patients. In this study, we aimed to investigate serum TNF-α, IL-6, IL-10 and CRP levels in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) patients.

Background: Multiple sclerosis (MS) is an autoimmune disorder, with a considerable genetic influence on susceptibility and disease course. Cytokines play an important role in MS pathophysiology, and genes encoding various cytokines are logical candidates to assess possible associations with MS susceptibility and disease course. We previously reported an association of a combination of polymorphisms in the interleukin (IL)-1B and IL-1 receptor antagonist (IL−1RN) genes (i.e. IL−1RN allele 2+/IL−1B+3959allele 2−) with disease severity in MS. Extending this observation, we investigated whether IL-1β and IL-1ra production differed depending on carriership of this gene combination.

Background: The IL-17 (interleukin 17) family consists of six structurally related pro-inflammatory cytokines, namely IL-17A to IL-17F. These cytokines have garnered significant scientific interest due to their pivotal role in the pathogenesis of various diseases. Notably, a specific subset of T-cells expresses IL-17 family members, highlighting their importance in immune responses against microbial infections., Introduction: IL-17 cytokines play a critical role in host defense mechanisms by inducing cytokines and chemokines, recruiting neutrophils, modifying T-cell differentiation, and stimulating the production of antimicrobial proteins. Maintaining an appropriate balance of IL-17 is vital for overall health. However, dysregulated production of IL-17A and other members can lead to the pathogenesis of numerous inflammatory and autoimmune diseases., Method: This review provides a comprehensive overview of the IL-17 family and its involvement in several inflammatory and autoimmune diseases. Relevant literature and research studies were analyzed to compile the data presented in this review., Results: IL-17 cytokines, particularly IL-17A, have been implicated in the development of various inflammatory and autoimmune disorders, including multiple sclerosis, Hashimoto's thyroiditis, systemic lupus erythematosus, pyoderma gangrenosum, autoimmune hepatic disorders, rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, osteoarthritis, and graft- versus -host disease. Understanding the role of IL-17 in these diseases is crucial for developing targeted therapeutic strategies., Conclusion: The significant involvement of IL-17 cytokines in inflammatory and autoimmune diseases underscores their potential as therapeutic targets. Current treatments utilizing antibodies against IL-17 cytokines and IL-17RA receptors have shown promise in managing these conditions. This review consolidates the understanding of IL-17 family members and their roles, providing valuable insights for the development of novel immunomodulators to effectively treat inflammatory and autoimmune diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Aims: Necrotizing enterocolitis (NEC) is a life-threatening disease and the most common gastrointestinal emergency in premature infants. Accurate early diagnosis is challenging. Modified Bell's staging is routinely used to guide diagnosis, but early diagnostic signs are nonspecific, potentially leading to unobserved disease progression, which is problematic given the often rapid deterioration observed. We investigated fecal cytokine levels, coupled with gut microbiota profiles, as a noninvasive method to discover specific NEC-associated signatures that can be applied as potential diagnostic markers., Methods: Premature babies born below 32 weeks of gestation were admitted to the 2-site neonatal intensive care unit (NICU) of Imperial College hospitals (St. Mary's or Queen Charlotte's & Chelsea) between January 2011 and December 2012. During the NICU stay, expert neonatologists grouped individuals by modified Bell's staging (healthy, NEC1, NEC2/3) and fecal samples from diapers were collected consecutively. Microbiota profiles were assessed by 16S rRNA gene amplicon sequencing and cytokine concentrations were measured by V-Plex multiplex assays., Results: Early evaluation of microbiota profiles revealed only minor differences. However, at later time points, significant changes in microbiota composition were observed for Bacillota (adj. P  = .0396), with Enterococcus being the least abundant in Bell stage 2/3 NEC. Evaluation of fecal cytokine levels revealed significantly higher concentrations of IL-1α ( P  = .045), IL-5 ( P  = .0074), and IL-10 ( P  = .032) in Bell stage 1 NEC compared to healthy individuals., Conclusion: Differences in certain fecal cytokine profiles in patients with NEC indicate their potential use as diagnostic biomarkers to facilitate earlier diagnosis. Additionally, associations between microbial and cytokine profiles contribute to improving knowledge about NEC pathogenesis., (© 2023 The Authors.)

This study intended to characterize pharmacologically the mediator(s ) released in the inflammation induced by Soluble Egg Antigen (SEA), the main antigen released from eggs of Schistosoma mansoni, in rat hindpaws . A single intraplantar injection of 0.1–100 μg SEA at day zero induced a dose-dependent increase in the volume of rat hindpaws characterizing an oedema of quick onset (within 15 min) and 4 h-duration, which was confirmed by his topathological analys is of the paws . A second injection of SEA in the same paw (1–10 μg) 28 days later induced an increased dose -dependent oedematogenic response. The early oedematogenic response following SEA sensitization was derived from serotonin release and interleukin-1 (IL-1), since treatment with either pizotifen or anantibody against IL-1, reduced the response by 60% and 48%, respectively. The increased oedematogenic response derived from SEA-challenge (10 μg) of rat paws derived from a local rather than systemic reaction, since it was not observed if the sensitization was in the contralateral paw or the peritoneal cavity of the animals. Chronic tre atment with inhibitors of IL-2 synthesis / release such as cyclosporin or dexamethasone during the sens itization phase reduced the oedematogenic response due to SEA challenge by 51% and 55%, respectively. These data suggested that SEA-challenge was immune-derived and dependent of IL-2 release. It is discussed the association between cytokine release and the resistance of rats to S. mans o ni infe ction.

We evaluated whether the short-term use of dexmedetomidine and propofol may attenuate inflammatory response and improve lung morphofunction in experimental acute lung injury (ALI). Thirty-six Wistar rats were randomly divided into five groups. Control (C) and ALI animals received sterile saline solution and Escherichia coli lipopolysaccharide by intraperitoneal injection respectively. After 24 h, ALI animals were randomly treated with dexmedetomidine, propofol, or thiopental sodium for 1 h. Propofol reduced static lung elastance and resistive pressure and was associated with less alveolar collapse compared to thiopental sodium and dexmedetomidine. Dexmedetomidine improved oxygenation, but did not modify lung mechanics or histology. Propofol was associated with lower IL (interleukin)-6 and IL-1β expression, whereas dexmedetomidine led to reduced inducible nitric oxide (iNOS) and increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression in lung tissue compared to thiopental sodium. In conclusion, in this model of mild ALI, short-term use of dexmedetomidine and propofol led to different functional effects and activation of biological markers associated with pulmonary inflammation. [ABSTRACT FROM AUTHOR]

Smoking has either a beneficial or harmful effect on the course and recurrence of ulcerative colitis and Crohn's disease respectively. Transdermal application of nicotine had similar effects in ulcerative colitis and therefore was considered to be an effective basic drug which could be further developed in the search for new compounds in the treatment of acute exacerbations of corticosteroid resistant ulcerative colitis. In this communication the short-term use of nicotine in ulcerative colitis is reviewed.

Severe asthma represents a distinct, poorly-understood phenotype of asthma that has higher morbidity, mortality and a disproportionate need for health care support. Studies have indicated the presence of a specific inflammatory response in severe asthmatics, including the paucity of expression of classical Th-2 type cytokines. Following antigenic stimulation, naive CD4+ T cells proliferate and differentiate into various effector subsets such as Th-1 and Th-2 cells. A third subset of CD4+ T cells has recently been identified and designated as Th-17 cells, which produce IL-17A and F, IL-6, and TNF-α. In severe asthma, there may be a predominant Th-17 phenotype. These cells may promote the release of neutrophil chemotactic factors and induce the expression of GR-β, which is responsible for corticosteroid hyporesponsiveness in immune and structural cells. If the role of Th-17 cytokines is confirmed, it might provide a new option in controlling this refractory subtype of asthma. [ABSTRACT FROM AUTHOR]

Chloroquine, due to its basic properties, has been shown to prevent the release of iron from holotransferrin, thereby interfering with normal iron metabolism in a variety of cell types. We have studied the effects of chloroquine on the evolution of experimental paracoccidioidomycosis by evaluating the viable fungal recovery from lung, liver and spleen from infected mice and H2O2, NO production, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10 levels and transferrin receptor (TfR) expression from uninfected and infected peritoneal macrophages. Chloroquine caused a significant decrease in the viable fungal recovery from all organs tested, during all periods of evaluation. Peritoneal macrophages from chloroquine-treated infected mice showed higher H2O2 production and TfR expression, and decreased levels of NO, endogenous and stimulated-TNF-α, IL-6 and IL-10 during the three evaluated periods. However, despite its suppressor effects on the macrophage function, the chloroquine therapeutic effect upon murine paracoccidioidomycosis was probably due to its effect on iron metabolism, blocking iron uptake by cells, and consequently restricting iron to fungus growth and survival. [ABSTRACT FROM AUTHOR]

Weak immunogenicity of chronic lymphocytic leukaemia (CLL) cells may contribute to disease progression and inhibit the effectiveness of immunotherapies, such as vaccines. Agents that can enhance the antigen presenting capabilities of CLL cells might then help to improve the clinical results of immunotherapies. This study investigated the effects of the common gamma chain-binding cytokines, interleukin (IL)-2 and IL-15, on costimulatory properties of primary CLL cells from 51 patients. IL-2 improved the ability of CLL cells to stimulate T cell proliferation and increased the expression of costimulatory molecules (particularly CD80) in a dose-dependent fashion, especially in CLL cells with weak expression of CD38. CD80 and CD86 induction by IL-2 were positively regulated through the mitogen-activated protein kinase pathway, while CD86 expression was negatively regulated through Janus kinase pathways. However, further activation with protein kinase C agonists was required for IL-2 activated CLL cells to stimulate autologous T cells sufficiently to clear bystander CLL cells from mixed lymphocyte responses. IL-15 had similar effects on the costimulatory properties of CLL cells. These results suggest a role for IL-2, or IL-15, in immunotherapeutic strategies for CLL. [ABSTRACT FROM AUTHOR]

Background: Lidocaine has actions potentially of benefit during ischaemia-reperfusion. Neutrophils and endothelial cells have an important role in ischaemia-reperfusion injury. Methods: Isolated human neutrophil CD11b and CD18, and human umbilical vein endothelial cell (HUVEC) ICAM-1 expression and supernatant IL-1β concentrations in response to hypoxia-reoxygenation were studied in the presence or absence of different concentrations of lidocaine (0.005, 0.05 and 0.5 mg mL-1). Adhesion molecule expression was quantified by flow cytometry and IL-1β concentrations by ELISA. Differences were assessed with analysis of variance and Student-Newman-Keuls as appropriate. Data are presented as mean ± SD. Results: Exposure to hypoxia-reoxygenation increased neutrophil CD11b (94.33 ± 40.65 vs. 34.32 ± 6.83 mean channel fluorescence (MCF), P = 0.02), CD18 (109.84 ± 35.44 vs. 59.05 ± 6.71 MCF, P = 0.03) and endothelial ICAM-1 (146.62 ± 16.78 vs. 47.29 ± 9.85 MCF, P < 0.001) expression compared to normoxia. Neutrophil CD18 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL-1) treated cells compared to control (71.07 ± 10.14 vs. 109.84 ± 35.44 MCF, P = 0.03). Endothelial ICAM-1 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mgmL ) treated cells compared to control (133.25 ± 16.05 vs. 146.62 ± 16.78 MCF. P = 0.03). Hypoxia-reoxygenation increased HUVEC supernatant IL-1β concentrations compared to normoxia (3.41 ± 0.36 vs. 2.65 ± 0.21 pgmL-1 P = 0.02). Endothelial supernatant IL-1β concentrations in lidocaine-treated HUVECs were similar to controls. Conclusions: Lidocaine at clinically relevant concentrations decreased neutrophil CD18 and endothelial ICAM-1 expression but not endothelial IL-1β concentrations. [ABSTRACT FROM AUTHOR]

Dengue viruses(DV) infection is an important public health issue all over the world. Although the pathogenesis remains unclear, the overwhelmingly triggered immune responses have been consistently observed. Recently, we and other researchers demonstrated that the natural hosts for DV are dendritic cells(DC), the primary sentinels of immune system. In light of the significance of T cells in dengue virus pathogenesis, here, we examine the possible consequences of DC-T cell interaction that is supposed to be happening in lymphoid tissues after infection. We showed that DV-infected DC induced the interacting T cells to proliferate, to produce interleukin-2 as well as to express activation markers on cell surface. Compared to mock-infected DC, the infection of DC by DV also induced T cells to produce interleukin-4, interleukin-10 and interferon-gamma, a cytokine pattern suggesting Th0 phenotype. Such an effect was either totally abolished or greatly reduced when DV were pre-inactivated with heat or ultraviolet before infection. In addition, we demonstrated that such a Th0 phenotype shift of T cells was affected neither by different dosages of viruses that infected DC nor by different durations of DC-T cell interaction. Our results provide a basic support for clinical observations and may be of help in understanding the pathogenesis of DV infection. [ABSTRACT FROM AUTHOR]