High Levels Of Pro-inflammatory Cytokines Research Articles

Clinical and etiological characteristics and cytokine profile in school-age children with community-acquired pneumonia

The urgent task of modern pediatrics is the study of the etiology and pathophysiology of community-acquired pneumonia in school-aged children due to difficulties in diagnosis and treatment, as well as the high risk of life-threatening complications and death.Purpose. To investigate the activity of pro-inflammatory and anti-inflammatory responses as measured by cytokine levels in the peripheral blood of children with community-acquired pneumococcal and non-pneumococcal pneumonia.Material and methods. The etiology of community-acquired pneumonia was confirmed by comparing the results of rapid testing of pneumococcus in urine and data from traditional bacteriological methods. The study included 118 children (57 boys and 61 girls) aged 7 to 16 years with various morphological variants of community-acquired pneumonia, which were divided into 2 groups. The first group included 28 children with pneumococcal etiology of community-acquired pneumonia, and the second group included 90 patients with non-pneumococcal community-acquired pneumonia. Levels of interleukins IL-1, IL-4, IL-8 and TNF-α were determined in all children by enzyme immunoassays.Results. In the etiology of community-acquired pneumonia in school-age children, atypical pathogens are responsible for more than 50% of cases. The clinical effectiveness of rapid testing of pneumococcal antigens in urine has been shown, and their use in routine pediatric practice has made it possible to timely identify a group of severe community-acquired pneumonia and reasonably prescribe antibacterial medications. It has been demonstrated that pneumococcal-induced pneumonia is characterized by higher levels of proinflammatory cytokines. These levels, along with the clinical course of the disease, confirm the high level of systemic inflammation. Relatively lower levels of proinflammatory cytokines corresponded to a more mild clinical picture of community-acquired pneumonia of non-pneumococcal etiology, which on the one hand may reflect a relatively «balanced» inflammatory response, and on the other hand determine the protracted and polyclinic course of the infectious process.Conclusion. The etiology of community-acquired pneumonia in school-age children is dominated by atypical pathogens. Community-acquired pneumonia of pneumococcal etiology has more severe clinical courses, and their early identification will allow for the appropriate prescription of initial antibacterial treatment.

KLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes

Although significant progress has been achieved in elucidating the genetic architecture of systemic lupus erythematosus (SLE), identifying genes underlying the pathogenesis has been challenging. The NZM2410-derived lupus susceptibility Sle3 locus is associated with T cell hyperactivity and activated myeloid cells. However, candidate genes associated with these phenotypes have not been identified. Here, we narrow the Sle3 locus to a smaller genomic segment (Sle3k) and show that mice carrying Sle3k and Sle1 loci developed lupus nephritis. We identify Klf13 as the primary candidate gene that is associated with genome-wide transcription changes resulting in higher levels of proinflammatory cytokines, enhanced T cell activation, and hyperresponsiveness of myeloid cells. Correspondingly, Klf13–/– mice display repression of genes involved in mediating immune activation, including key proinflammatory cytokines/chemokines in T cells and dysregulation in cytokine signaling pathways in myeloid cells in response to toll receptor ligands. Klf13 upregulation is associated with increased production of RANTES, a key chemokine in lupus nephritis, in activated T cells and the kidneys of lupus-prone mice. In sum, our findings reveal Klf13 as a key gene in the Sle3 interval in mediating lupus pathogenesis that may have implications in the rational design of new therapies for SLE.

Intrauterine inoculation of pseudorabies virus impairs mouse embryo implantation via inducing inflammation and apoptosis in endometrium.

Pseudorabies virus (PRV) is the pathogenic agent of pseudorabies, causing serious reproductive failure in swine. However, it is still unknown whether PRV uterine inoculation impairs blastocyst implantation. In the present study, a PRV infection mouse model was developed. Pregnant mice were inoculated with either 104 or 105 50% tissue culture infectious dose (TCID50) units of PRV on gestation day 2 (GD2). Viral DNA was detected in tissues by PCR and/or in situ hybridization. Histopathological change and expression of proinflammatory cytokines in uterus were analyzed by H.E. staining and qPCR, respectively. Apoptosis was also investigated by TUNEL assay, and the expression of apoptosis-related proteins including Bax and Bcl-2 was detected by Western blot. The results showed that intrauterine exposure of PRV on GD2 reduced the number of embryo implantation site. Abundant viral DNA was detected in spinal marrow and brain, and small amounts of PRV genomes were detected in embryo implantation site, ovary as well as thymus. Considerable inflammatory cells infiltrating in the endometrium, with high levels of pro-inflammatory cytokines of interleukin (IL)-6, IL-1β and tumor necrosis factor-α mRNA after infection. In addition, PRV infection promoted apoptosis in stroma and endothelium of the mouse endometrium. Collectively, intrauterine inoculation of PRV during early pregnancy causes cytokine release syndrome and apoptosis in endometrium, which impairs mouse embryo implantation.

Salivary Transmembrane Mucins of the MUC1 Family (CA 15-3, CA 27.29, MCA) in Breast Cancer: The Effect of Human Epidermal Growth Factor Receptor 2 (HER2)

The MUC1 family of transmembrane glycoproteins (CA 15-3, CA 27.29, MCA) is aberrantly expressed among patients with breast cancer. Objectives: to measure the level of degradation products of MUC1, including CA 15-3, CA 27.29, and MCA, in the saliva of breast cancer patients and to describe the biochemical processes that influence their expression and the regulation of their biological functions. Methods: The case–control study included three groups (breast cancer, fibroadenomas, and healthy controls). All study participants provided saliva samples strictly before starting treatment. The levels of MUC1, including CA 15-3, CA 27.29, and MCA, free progesterone and estradiol, cytokines (MCP-1, VEGF, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18), and amino acids (Asp, Gln, Gly, His, Leu + Ile, Orn, Phe, Pro, Tyr) were determined. Results: It was shown that the levels of the MUC1 family in the saliva of patients with HER2-positive breast cancer were significantly lower compared to the control group. The level of pro-inflammatory cytokines and the level of free estradiol affected the expression of MUC1. We obtained a reliable relationship between the aggressive nature of tumor growth, an increased level of pro-inflammatory cytokines, a low level of free estradiol, and the suppressed expression of salivary MUC1. Conclusions: Among patients with aggressive breast cancer, a high level of pro-inflammatory cytokines, and a low level of free estradiol, there was an inhibition of the expression of pathologically unchanged glycoprotein MUC1 in saliva.

Genetic signatures of AKT1 variants associated with worse COVID-19 outcomes - a multicentric observational study.

The COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes. Peripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants. The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease. Our findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2.

Enhanced Gene Expression of Toll-Like Receptors 3, 7, and 9 in Thalassemia Patients: Implications for Inflammation and Potential Therapeutic Targets

Thalassemia is an inherited blood disorder marked by reduced hemoglobin synthesis, which leads to chronic anemia and systemic complications, among them immune dysregulation and chronic inflammation. The current study aims at investigating the gene expression of TLR3, 7, and 9 in thalassemia patients and their relation to the inflammatory markers. Because we used a larger, diverse sample population and a longitudinal study design, we were able to reveal significant upregulation of TLR3 and TLR9 in thalassemia patients compared to healthy controls strongly correlated with the high levels of various proinflammatory cytokines. We have further demonstrated that different genetic polymorphisms in the promoter regions of TLR3 and TLR9 alters the binding of transcription factors and thus can be possible causes of the dysregulation of these genes. Our results implicate that TLR3 and TLR9 themselves play a very important role in the inflammatory response in thalassemia and are therefore potential therapeutic targets for mitigating inflammation to improve outcomes in these patients.

Cytokine imbalance as a factor of postoperative complications of third mandibular molar extraction

Background. Tooth extraction is considered the most frequently performed operation in surgical dentistry, which can often cause inflammatory complications. Modern research has come a long way in terms of developing methods for the prevention, diagnosis and treatment of these complications, but the search for their early laboratory markers remains an urgent task to this day.The aim of the study. To determine prognostic laboratory criteria for the development of local inflammatory complications of third mandibular molar extraction.Methods. The study included 35 people who underwent extraction of a third mandibular (semi-impacted) molar. Before the surgery, immediately after the surgery, 1, 2, 3 and 4 days after the surgery, we assessed the objective status of the patients and collected oral fluid from the oral cavity, in which we determined the concentrations of cytokines using enzyme-linked immunosorbent assay. After the surgery, patients were divided into a control group and a group with complications with determination of their cytokine status.Results. Immediately after the surgery, patients from the group with complications, compared with patients from the control group, had significantly higher levels of proinflammatory cytokines – interleukin (IL) 1, IL-8 and comparable levels of tumor necrosis factor α and anti-inflammatory cytokines IL-4 and IL-10. Integral cytokine indices in both groups showed a sharp shift towards pro-inflammatory direction in patients with complications. This fact determines the protracted or progressive nature of the inflammatory process after the surgery.Conclusion. Determining the level of individual cytokines and cytokine indices in the oral fluid after the extraction of a third mandibular molar allows us to identify early markers for the chronicity of the inflammatory process, to predict its further course and to take appropriate measures to prevent the development of expected complications.

Cytokine Storm in Pathogenesis of COVID-19 Complications

The aim. To explore the current literature and key findings concerning the cytokine storm contribution to pathogenesis of COVID-19 complications and mortality, and summarize clinical and pathologic features of cytokine storm in COVID-19 patients. A cytokine storm is a hyperinflammatory state secondary to excessive production of cytokines by deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading in most severe cases even to death. Cytokine storm has recently emerged as key aspect in COVID-19 disease, as affected patients show high levels of several key pro-inflammatory cytokines, some of which also correlate with disease severity. The current review describes the role of critical cytokines in COVID-19-mediated cytokine storm. Key findings of the studies are provided further. A cytokine storm is associated with COVID-19 severity and is also a crucial cause of death from COVID-19. Impaired acquired immune responses and uncontrolled inflammatory innate responses may be associated with the mechanism of cytokine storm in COVID-19. Cytokine storm is defined as acute overproduction and uncontrolled release of pro-inflammatory markers, both locally and systemically. In COVID-19 patients, pyroptosis triggers the release of proinflammatory cytokines and affects macrophage and lymphocyte functions, causing peripheral lymphopenia. Cytokine storm is characterized by a clinical presentation of overwhelming systemic inflammation, hyperferritinemia, hemodynamic instability, and multi-organ failure. The cytokine storm clinical findings are attributed to the action of pro-inflammatory cytokines like interleukin-1, interleukin-6, tumor necrosis factor alpha, vascular endothelial growth factor.

The Consumption of the Fibrous Fraction of Solanum lycocarpum St. Hil. Does Not Preserve the Intestinal Mucosa in TNBS-Induced Rats.

Solanum lycocarpum St. Hil. is considered a natural anti-inflammatory. In traditional medicine, it is used to reduce cholesterol levels in the treatment of obesity. Foods capable of conferring a protective and nutritious effect have been used to prevent or attenuate the clinical symptoms of inflammatory bowel diseases. Ulcerative colitis is a multifactorial inflammatory bowel disease. This study investigated the impact of the consumption of the fibrous fraction (FF) and resistant starch (RS) of fruta-do-lobo in an experimental model of colitis induced with the use 2,4,6-trinitrobenzene sulphonic acid (TNBS) in rats. The different colitis groups all experienced decreased weight gain, which could be linked to the inflammatory process (p = 0.603). Additionally, the experimental model led to increased oxidative stress, higher levels of pro-inflammatory cytokines, and the elevated gene expression of these cytokines. Despite this, consuming the fibrous fraction of fruta-do-lobo (RS and FF) did not appear to protect the animals against the inflammatory process. Regarding the expression of TNF-α, only the group treated with the drug mesalamine had a reduced serum level of this inflammatory marker (p = 0.03). Our results showed that the diet containing RS and FF did not protect the intestinal mucosa against TNBS inflammation. New studies on the variation in the time of consumption or the supplemented dose of fruta-do-lobo fibers could help to elucidate their effects in protecting the mucosa.

Cytokine secretion by in vitro cultures of lung epithelial cells, differentiated macrophages and differentiated dendritic cells incubated with pneumococci and pneumococcal extracellular vesicles.

Streptococcus pneumoniae is an important human pathogen that can colonize the respiratory tract of healthy individuals. The respiratory tract mucosa is thus the first barrier for this pathogen. In this study, we have tested three models of the respiratory epithelium with immune cells: (i) monolayer of A549 human lung epithelial cells, (ii) A549 + macrophages differentiated from the human monocytic THP-1 cell line (dMφ) and (iii) A549 + dMφ + dendritic cells differentiated from THP-1 (dDC) using a two-chamber system. Pneumococcal strains Rx1 (non-encapsulated) and BHN418 (serotype 6B) were incubated with the cells and secretion of IL-6, IL-8, IL-1β, TNF-α and IL-10 was evaluated. Overall, the models using co-cultures of A549 + dMφ and A549 + dMφ + dDC elicited higher levels of pro-inflammatory cytokines and the non-encapsulated strain elicited an earlier cytokine response. BHN418 pspA (pneumococcal surface protein A) and pspC (pneumococcal surface protein C) knockouts elicited similar cytokine secretion in the co-culture models, whereas BHN18 ply (pneumolysin) knockout induced much lower levels. The results are in accordance with the activation of the inflammasome by Ply. Finally, we evaluated pneumococcal extracellular vesicles (pEVs) in the co-culture models and observed secretion of pro-inflammatory cytokines in the absence of cytotoxicity. Since pEVs are being studied as vaccine candidate against pneumococcal infections, the co-cultures of A549 + dMφ and A549 + dMφ + dDC are simple models that could be used to evaluate pEV vaccine batches.

Intestinal and hepatic benefits of BBR-EVO on DSS-induced experimental colitis in mice.

Ulcerative colitis (UC), characterized by disrupted intestinal barrier integrity and chronic inflammation, was modeled in mice via dextran sulfate sodium (DSS) induction. This study explored the therapeutic potential of berberine-evodiamine (BBR-EVO), bioactive components of the traditional Chinese medicine Yulian decoction, in DSS colitis. BBR-EVO intervention ameliorated weight loss, diarrhea, colonic shortening, and histopathological damage in colitic mice. The substance increased antioxidant activity while reducing high levels of pro-inflammatory cytokines in the colon, including as TNF-α, IL-1β, and IL-6. BBR-EVO inhibited the DSS-induced decrease in the tight junction proteins ZO-1 and occludin, according to immunohistochemistry. 16S rRNA sequencing demonstrated BBR-EVO partially attenuated DSS-elicited intestinal dysbiosis, reducing opportunistic pathogens and restoring diminished beneficial taxa. Critically, BBR-EVO alleviated secondary hepatic injury in colitic mice, mitigating immune cell infiltration, oxidative stress, cytokine production, and ultrastructural damage, likely by beneficially modulating gut-liver crosstalk. This study reveals BBR-EVO, derived from a traditional Chinese medicine, confers multi-target protective effects in experimental colitis and associated hepatic pathology, warranting further evaluation as a potential therapy for inflammatory bowel diseases like UC. The mechanisms may involve simultaneous augmentation of intestinal barrier integrity, inhibition of inflammation, microbiota regulation, and gut-liver axis optimization.

Fibrin Scaffolds Perfused with Transforming Growth Factor-β1 as an In Vitro Model to Study Healthy and Tendinopathic Human Tendon Stem/Progenitor Cells.

A limited understanding of tendon cell biology in healthy and pathological conditions has impeded the development of effective treatments, necessitating in vitro biomimetic models for studying tendon events. We established a dynamic culture using fibrin scaffolds, bioengineered with tendon stem/progenitor cells (hTSPCs) from healthy or diseased human biopsies and perfused with 20 ng/mL of human transforming growth factor-β1 for 21 days. Both cell types showed long-term viability and upregulated Scleraxis (SCX-A) and Tenomodulin (TNMD) gene expressions, indicating tenogenic activity. However, diseased hTSPCs underexpressed collagen type I and III (COL1A1 and COL3A1) genes and exhibited lower SCX-A and TNMD protein levels, but increased type I collagen production, with a type I/type III collagen ratio > 1.5 by day 14, matching healthy cells. Diseased hTSPCs also showed constant high levels of pro-inflammatory cytokines, such as IL-8 and IL-6. This biomimetic environment is a valuable tool for studying tenogenic and inflammatory events in healthy and diseased tendon cells and identifying new therapeutic targets.

TolC facilitates the intracellular survival and immunomodulation of Salmonella Typhi in human host cells

ABSTRACT Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a systemic infection that affects millions of people worldwide. S. Typhi can invade and survive within host cells, such as intestinal epithelial cells and macrophages, by modulating their immune responses. However, the immunomodulatory capability of S. Typhi in relation to TolC-facilitated efflux pump function remains unclear. The role of TolC, an outer membrane protein that facilitates efflux pump function, in the invasion and immunomodulation of S. Typhi, was studied in human intestinal epithelial cells and macrophages. The tolC deletion mutant of S. Typhi was compared with the wild-type and its complemented strain in terms of their ability to invade epithelial cells, survive and induce cytotoxicity in macrophages, and elicit proinflammatory cytokine production in macrophages. The tolC mutant, which has a defective outer membrane, was impaired in invading epithelial cells compared to the wild-type strain, but the intracellular presence of the tolC mutant exhibited greater cytotoxicity and induced higher levels of proinflammatory cytokines (IL-1β and IL-8) in macrophages compared to the wild-type strain. These effects were reversed by complementing the tolC mutant with a functional tolC gene. Our results suggest that TolC plays a role in S. Typhi to efficiently invade epithelial cells and suppress host immune responses during infection. TolC may be a potential target for the development of novel therapeutics against typhoid fever.

Increased intestinal permeability and lipopolysaccharide contribute to swainsonine-induced systemic inflammation

Long-term consumption of swainsonine could be poisonous to livestock, including facilitating apoptosis by impairing lysosomal function and inhibiting autophagic degradation, leading to liver inflammation and even death in livestock. However, the mechanism by swainsonine induced systemic inflammatory responses remained unclear, especially the effects of swainsonine on intestinal permeability, lipopolysaccharide (LPS) level and oxidative stress response were unknown. In this study, swainsonine increased intestinal permeability as evidenced by the significant down-regulation of colonic goblet cells, Akkermansia muciniphila and intestinal tight junction protein Occludin, Claudin 1 and ZO-1, and the significant up-regulation of mRNA expression level of the intestinal permeability indicator protein tyrosine phosphatase receptor type H (Ptprh) in the ileum of mice. Simultaneously, the elevated LPS biosynthetic genes in intestinal microbiota and increased intestinal permeability facilitated more bacterial endotoxin LPS to enter the blood. High concentration of free-form LPS induced high levels of proinflammatory cytokines and oxidative stress response, thereby causing the systemic inflammation. These findings provided a new perspective on swainsonine-induced systemic inflammation, suggesting that intestinal permeability and free-form LPS level may be the potential trigger factors.

Cytokines as markers of non-functional overstrain in rowing athletes

BACKGROUND: Regular high-intensity exercise, combined with other stressors and lack of adequate recovery time, can cause a sustained pro-inflammatory response, leading to systemic inflammation and immune dysregulation. AIM: The aim of this study is to establish the prognostic effectiveness of proinflammatory IL-1β, TNFα, IL-8, anti-inflammatory cytokine IL-4 and myokine IL-6 as markers of dysfunctional overstrain and overtraining in rowing athletes. MATERIALS AND METHODS: A total of 47 male athletes aged 18–22 years were examined, specializing in rowing, 1st category, candidates for master of sports. Of these, 28 were dynamic (4 times). The control group included 24 healthy donors, men aged 18–22 years. Cardiac overstrain was diagnosed based on 24-hour ECG data: identification of ventricular and supraventricular extrasystoles in the absence of organic changes in the heart. The content of cytokines in blood serum was determined using the Human Cytokine/Chemokine Magnetic Bead Panel 1 reagents (Merck, Millipore) on a MagPix device. The research results were processed using parametric statistics methods. RESULTS: Rowing athletes show an increase in pro-inflammatory cytokines, which can be both a consequence of adaptive changes and a sign of long-term systemic inflammation. Determination of IL-6, IL-8, TNFα may be useful for assessing the body’s adaptation to training loads. The greatest changes in the level of pro-inflammatory cytokines are observed during the competitive period, and it should be taken into account that an increase in the anti-inflammatory cytokine IL-4 occurs in response to high levels of pro-inflammatory cytokines and is a sign of good adaptation. CONCLUSIONS: The greatest importance in the diagnosis of non-functional cardiac overstrain in rowing athletes should be given to an increase in IL-1α and IL-6 and an increase in TNFα against the background of a decrease in IL-4.

Radiation-Induced miRNAs Changes and cf mtDNA Level in Trauma Surgeons: Epigenetic and Molecular Biomarkers of X-ray Exposure.

Exposure to ionizing radiation can result in the development of a number of diseases, including cancer, cataracts and neurodegenerative pathologies. Certain occupational groups are exposed to both natural and artificial sources of radiation as a consequence of their professional activities. The development of non-invasive biomarkers to assess the risk of exposure to ionizing radiation for these groups is of great importance. In this context, our objective was to identify epigenetic and molecular biomarkers that could be used to monitor exposure to ionizing radiation. The impact of X-ray exposure on the miRNAs profile and the level of cf mtDNA were evaluated using the RT-PCR method. The levels of pro-inflammatory cytokines in their blood were quantified using the ELISA method. A significant decrease in miR-19a-3p, miR-125b-5p and significant increase in miR-29a-3p was observed in the blood plasma of individuals exposed to X-ray. High levels of pro-inflammatory cytokines and cf mtDNA were also detected. In silico identification of potential targets of these miRNAs was conducted using MIENTURNET. VDAC1 and ALOX5 were identified as possible targets. Our study identified promising biomarkers such as miRNAs and cf mtDNA that showed a dose-dependent effect of X-ray exposure.

Prognostic Value of Anti-Chlamydia Trachomatis IgG in Breast Cancer and the Modification Effects of Pro-Inflammatory Cytokines: A 13-Year Prospective Cohort Study.

Chlamydia trachomatis (C. trachomatis) is associated with several gynecological tumors; yet its prognostic role in breast cancer remains unclear. Thus, we investigated the prognostic role of anti-C. trachomatis immunoglobulin G (IgG) in breast cancer patients and the modification effects of pro-inflammatory cytokines. The serum levels of C. trachomatis IgG and four pro-inflammatory cytokines were measured. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), including product terms to assess the modification effects of pro-inflammatory cytokines on the association between C. trachomatis IgG and breast cancer prognosis. From 2008 to 2018, 1121 breast cancer patients were recruited and followed up until December 31, 2021, with a median follow-up time of 63.91 months (interquartile range: 39.16-90.08 months). Patients positive for C. trachomatis IgG showed HRs of 1.09 (95% CI, 0.67-1.78) for overall survival (OS) and 1.24 (0.87-1.78) for progression-free survival (PFS), compared to those who were negative. These associations became statistically significant in women aged 50 years or younger (HR=1.43, 95% CI=0.79-2.58 for OS; HR=1.79, 95% CI=1.16-2.77 for PFS). Positive C. trachomatis IgG serology was associated with adverse prognostic effects among patients with higher levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1β), but with favorable prognostic effects for those with low levels. These interactions were particularly significant in those aged 50 years or younger. In breast cancer patients younger than 50 years of age or with higher levels of pro-inflammatory cytokines, C. trachomatis infection appeared to have a negative prognostic impact. These findings highlight the significance of C. trachomatis in predicting prognosis and personalized therapy for breast cancer patients.

The role of immune-inflammatory markers in children with complicated and uncomplicated malaria in Enugu, Nigeria

BackgroundThere is currently insufficient data regarding immune parameters and relationship with severity of malaria infection in Enugu, Nigeria where the economic and social costs of the disease and its management are extremely high. This study was conducted to determine the relationship between malaria severity and some immune-inflammatory markers among malaria-infected children in Enugu, Nigeria.MethodsThe study adopted a case control design. Eligible children were categorized into three groups — complicated, uncomplicated and healthy children. Pro-inflammatory cytokines –interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α); and anti-inflammatory cytokine — interleukin-10 (IL-10) were assayed using enzyme-linked immunosorbent assay (ELISA) technique, while immune cell ratios — neutrophil lymphocyte ratio (NLR) and monocyte lymphocyte ratio (MLR) were calculated from full blood count results.ResultsThe overall mean age of the participants was 7.3 ± 3.4 (range: 6 months − 12 years) and the male-female ratio was 1:1. There was no significant difference between the ages of the three groups (P = 0.44). The Mean levels of IFN-γ, TNF-α, and NLR were higher in complicated than uncomplicated malaria (266.9 ± 66.3pg/ml vs. 62.5 ± 6.4pg/ml, p < 0.001; 140.3 ± 30.0pg/ml vs. 42.0 ± 9.0pg/ml, p < 0.001; and 32.9 ± 16.2pg/ml vs. 17.8 ± 6.0pg/ml, p < 0.001, respectively); and higher in uncomplicated malaria than healthy children (62.5 ± 6.4pg/ml vs. 40.6 ± 9.1pg/ml, p < 0.001; 42.0 ± 9.0pg/ml vs. 105.7 ± 32.1, p < 0.001; 17.8 ± 6.0pg/ml vs. 18.7 ± 6.2pg/ml, p < 0.001, respectively). On the other hand, the mean level of IL-10 is higher in uncomplicated than complicated malaria (105.73 ± 32.06pg/ml vs. 40.60 ± 9.11pg/ml, p < 0.001). There was a positive correlation between NLR and IFN-γ (r = 0.815; p = 0.003), as well as NLR and TNF-α (r = 0.745; p = 0.002).ConclusionComplicated malaria is associated with higher levels of pro-inflammatory cytokines while uncomplicated malaria is associated with higher levels of anti-inflammatory cytokines. NLR correlates positively with pro-inflammatory cytokines, and could be useful in evaluation for the severity of malaria infection.

Correlation between Alzheimer's Disease and Gastrointestinal Tract Disorders.

Alzheimer's disease is the most common cause of dementia globally. The pathogenesis is multifactorial and includes deposition of amyloid-β in the central nervous system, presence of intraneuronal neurofibrillary tangles and a decreased amount of synapses. It remains uncertain what causes the progression of the disease. Nowadays, it is suggested that the brain is connected to the gastrointestinal tract, especially the enteric nervous system and gut microbiome. Studies have found a positive association between AD and gastrointestinal diseases such as periodontitis, Helicobacter pylori infection, inflammatory bowel disease and microbiome disorders. H. pylori and its metabolites can enter the CNS via the oropharyngeal olfactory pathway and may predispose to the onset and progression of AD. Periodontitis may cause systemic inflammation of low severity with high levels of pro-inflammatory cytokines and neutrophils. Moreover, lipopolysaccharide from oral bacteria accompanies beta-amyloid in plaques that form in the brain. Increased intestinal permeability in IBS leads to neuronal inflammation from transference. Chronic inflammation may lead to beta-amyloid plaque formation in the intestinal tract that spreads to the brain via the vagus nerve. The microbiome plays an important role in many bodily functions, such as nutrient absorption and vitamin production, but it is also an important factor in the development of many diseases, including Alzheimer's disease. Both the quantity and diversity of the microbiome change significantly in patients with AD and even in people in the preclinical stage of the disease, when symptoms are not yet present. The microbiome influences the functioning of the central nervous system through, among other things, the microbiota-gut-brain axis. Given the involvement of the microbiome in the pathogenesis of AD, antibiotic therapy, probiotics and prebiotics, and faecal transplantation are being considered as possible therapeutic options.

Macrophage-derived exosomes exacerbate postoperative cognitive dysfunction in mice through inflammation

This study investigated the impact of two-hit inflammation on postoperative cognitive dysfunction (POCD) in mice and the role of macrophage-derived exosomes in regulating this process. Mice models were used to mimic the state of two-hit inflammation, and cognitive function was assessed through behavioral experiments. Proinflammatory cytokine expression levels and blood-brain barrier (BBB)-associated functional proteins were measured using ELISA and Western blot, respectively. An in vitro macrophage inflammation two-hit model was created, and the role of exosomes was examined using the previously mentioned assays. Additionally, exosomes were injected into mice to further understand their impact in the two-hit inflammation model. Mice exposed to two-hit inflammation experienced impaired cognitive function, increased BBB permeability, and elevated levels of proinflammatory cytokines. Macrophages subjected to two-hit inflammation released higher levels of proinflammatory cytokines compared to the control group and other treatment groups. Treatment with an exosome inhibitor GW4869 effectively reduced the expression levels of proinflammatory cytokines in macrophages exposed to two-hit inflammation. Moreover, injection of macrophage-released exosomes into healthy mice induced inflammation, hippocampal damage, and cognitive disorders, which were mitigated by treatment with GW4869. In mice with two-hit inflammation, macrophage-released exosomes worsened cognitive disorders by promoting inflammation in the peripheral blood and central nervous system. However, treatment with GW4869 protected cognitive function by suppressing exosome release. These findings highlight the importance of two-hit inflammation in POCD and emphasize the critical role of exosomes as regulatory factors. This research provides valuable insights into the pathogenesis of POCD and potential intervention strategies.