High Levels Of Pro-inflammatory Cytokines Research Articles

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.

IL-10 indirectly modulates functional activity of CD4+CD28null T-lymphocytes through LFA-3 and HLA class II inhibition.

Expansion of CD4+CD28null T-lymphocytes is common in chronic heart failure (CHF) patients. Its ability to produce high levels of proinflammatory cytokines is probably the key role of these cells in CHF. IL-10 is a candidate for limiting CD4+CD28null T-lymphocyte responses, whereas tumour necrosis factor (TNF) is the cytokine most closely involved in the loss of CD28 expression. Serum levels of TNF and IL-10 were measured in 65 CHF patients (mean age, 65.2 ± 13.84 years). Patients with an IL-10/TNF ratio ≥1 had significantly lower levels of CD4+CD28null T-lymphocytes than those with a ratio <1. In vitro, IL-10 reduced the frequency of proliferative CD4+CD28null T-lymphocytes stimulated with anti-CD3. Pre-treatment with IL-10 before anti-CD3 stimulation was required for the cytokine to inhibit TNF production by CD4+CD28null T-lymphocytes. In addition to the previously described effect of IL-10 on HLA-DR and ICAM-1 expression, LFA-3 protein and mRNA levels were reduced in the presence of the cytokine in monocytes. IL-10 inhibition on CD4+CD28null T-lymphocytes may be mediated by a reduction in HLA class II and LFA-3 expression because blocking interactions with these costimulators has similar effects to those of IL-10 treatment. Moreover, costimulation through CD2/LFA-3 interaction is enough to induce proliferation and cytokine production in CD4+CD28null T-lymphocytes.

Inflammatory imbalance in tracheal aspirate of very preterm newborns is associated with airway obstruction and lung function deficiencies at school age: a cohort study

ObjectiveA low expression of club cell secretory protein (CC16) and high levels of proinflammatory cytokines at preterm birth are associated with airway inflammation and more severe neonatal lung disease. The...

Microenvironment Responsive Hydrogel Exerting Inhibition of Cascade Immune Activation and Elimination of Synovial Fibroblasts for Rheumatoid Arthritis Therapy

Rheumatoid arthritis (RA) is a progressive autoimmune disease and drug therapy has been restricted due to poor therapeutic efficacy and adverse effects. In RA synovium, dendritic cells present self-antigens to activate cascade immune pathway. Furthermore, downstream macrophages secrete high levels of pro-inflammatory cytokines; Hyperplasia of activated synovial fibroblasts (FLS) is responsible for hypoxic synovium microenvironment, secretion of cytokines/chemokines and erosion of bone/cartilage tissues. Positive feedback loop of inflammation between macrophages and FLS independent of antigen-presentation is constructed. Herein, an injectable pH-sensitive peptide hydrogel encapsulating siRNA/Methotrexate-polyethyleneimine (siMP, including sip65MP, sip38MP, siCD86MP) and Bismuthene nanosheet/Methotrexate-polyethyleneimine (BiMP) is successfully developed. Among them, siCD86MP reduces protein level of co-stimulatory molecule CD86 while sip65MP and sip38MP separately inhibit NF-κB and MAPK-p38 pathways of macrophages and FLS to suppress secretion of cytokines and MMPs. Meanwhile, reduction in anti-apoptotic property of FLS induced by inhibition of NF-κB pathway has a synergistic effect with photodynamic therapy (PDT) and photothermal therapy (PTT) mediated by BiMP for FLS elimination, effectively ameliorating hypoxic synovium microenvironment. After being injected into synovium, hydrogel responds to acidic microenvironment and serves as a reservoir for sustained drug release and inherent retention capacity of which enables cationic nanoparticles to bypass tissue barrier for precise synovium targeting. This brand-new drug delivery system combines modulating cascade immune pathway from beginning to end by RNAi and eliminating FLS for improving synovium microenvironment by phototherapy together, providing a robust strategy for clinical RA treatment.

Use of the CytoSorb adsorber in patients with acute-on-chronic liver failure.

CytoSorb is a hemoadsorptive column used to remove high concentrations of proinflammatory cytokines in septic shock. Data on CytoSorb application in acute-on-chronic liver failure (ACLF) is lacking. This retrospective observational study analyzed 21 ACLF patients admitted to ICUs at the Vienna General Hospital who received CytoSorb adsorber therapy between 2017 and 2023. Median ICU length of stay was 8days (IQR: 3-13), the ICU survival rate was 23.8% (n = 5). Significant decreases in bilirubin (median peak: 20.7mg/dL to median post-treatment: 10.8mg/dL; - 47.8%; p < 0.001), procalcitonin (1.34 to 0.74pg/mL; - 44.6%; p < 0.001), interleukin-6 (385 to 131ng/mL; - 66.0%; p = 0.0182)-but also of platelets (72 to 31 G/L; - 56.9%; p = 0.0014) and fibrinogen (230 to 154mg/dL; - 33.0%; p = 0.0297) were detected. ICU survivors had a trend towards a stronger relative decrease in bilirubin (- 76.1% vs. - 48.2%), procalcitonin (- 90.6% vs. - 23.5%), and IL-6 (- 54.6% vs. - 17.8%) upon CytoSorb treatment. Moreover, no serious CytoSorb-attributed complications were detected. In conclusion, use of CytoSorb adsorber in ACLF patients results in a significant decrease in bilirubin and proinflammatory cytokines, while platelets and fibrinogen were also lowered. Prospective trials are warranted to investigate the impact of CytoSorb on clinical outcomes of ACLF patients with high proinflammatory cytokine levels.

The Effect of Virgin Coconut Oil on TNFα and Cytochrome P450 Aromatase Levels in Obese Female White Rats (Rattus norvegicus) Induced with a High-Fat Diet

Background: The high level of various proinflammatory cytokines due to adipocyte hypertrophy such as TNFα in obesity increases cytochrome-P450-aromatase, further inducing increased estrogen production, hypersecretion of Luteinizing Hormone and decreased Follicle Stimulating Hormone, resulting in impaired folliculogenesis, and chronic anovulation. Virgin Coconut Oil is rich in Medium Chain Fatty Acid and phytochemicals as anti-inflammatory. Aim: The aim of this study was to determine the effect of VCO on reducing TNFα and cytochrome-P450-aromatase levels in obese female white rats. Methods: Post test only control group, 24 rats were divided into 3 groups, namely: negative control group (K-), positive control group (K+), and treatment group (P). The K+ and P groups were induced using a high-fat diet for 10 weeks, then the P group was given VCO in weeks 7-10. On the first day of week 11, blood was taken from the orbital vein of the eyes of all rats for TNFα levels. Both examinations used ELISA kits. Data analysis used Shapiro Wilks normality test. The value of p&gt;0.05, followed by hypothesis testing using one-way annova and post hoc Bonferroni. Results: Mean TNFα in the K- group: 141.71±8.87, K+ group: 15.09±19.30, P group: 162,09±13,57. Mean cytochrome-P450-aromatase levels in the K- group: 9.00±0.77, K+ group: 12.22±1.69, P group: 10.58±0.97. The mean levels of one way ANOVA analysis showed that the administration of VCO can significantly reduce TNFα levels (p=0.001) and significantly reduce Cytochrome-P450-aromatase levels (p=0.001). Conclusion: VCO administration can reduce TNFα levels and cytochorme-P450-aromatase levels in obese female white rats. Keywords: TNFα, cytochrome-P450-aromatase, infertility, obesity

Comparative assessment of the effects of two intrauterine systems for long-term contraception on some haematological, biochemical, and immunological markers

An intrauterine system (IUS) is a type of contraception tool that is used in order to control fertility and prevent concep¬tion in women for a long period. The aim of this study was to assess the influence of copper- versus levonorgestrel-releasing IUSs on women’s health. This is a descriptive cross-sectional study of 75 women that were randomly se¬lected (50 women that used a copper-releasing IUS and the remaining 25 that used a levonorgestrel-releasing IUS) amongst those attending out patient’s clinics at Hillah, Iraq, from March to July 2016. All women were between 18 to 46 years of age, and have had an IUS for at least three months. The measurement of serum ceruloplasmin (SCerP), haemoglobin, vitamin D (VD), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) levels was undertaken. Our results revealed that the copper-releasing IUS group has low haemoglobin and VD levels, along with high levels of SCerP and proinflammatory cytokines. One the other hand, the levonorgestrel-releasing IUS group displayed no significant changes on the above markers. We can conclude that the levonorgestrel-releasing IUS is free of any adverse effect when compared to a copper-releasing IUS, at least with regard to the parameters examined by our study.

Cotargeting EBV lytic as well as latent cycle antigens increases T-cell potency against lymphoma

AbstractThe remarkable efficacy of Epstein-Barr virus (EBV)-specific T cells for the treatment of posttransplant lymphomas has not been reproduced for EBV-positive (EBV+) malignancies outside the transplant setting. This is because of, in part, the heterogeneous expression and poor immunogenicity of the viral antigens expressed, namely latent membrane proteins 1 and 2, EBV nuclear antigen 1, and BamHI A rightward reading frame 1 (type-2 [T2] latency). However, EBV lytic cycle proteins are also expressed in certain EBV+ malignancies and, because several EBV lytic cycle proteins are abundantly expressed, have oncogenic activity, and likely contribute to malignancy, we sought and identified viral lytic-cycle transcripts in EBV+ Hodgkin lymphoma biopsies. This provided the rationale for broadening the target antigen–specific repertoire of EBV-specific T cells (EBVSTs) for therapy. We stimulated, peripheral blood mononuclear cells from healthy donors and patients with EBV+ lymphoma with both lytic and latent cycle proteins to produce broad repertoire (BR) EBVSTs. Compared with T2 antigen-specific EBVSTs, BR-EBVSTs more rapidly cleared autologous EBV+ tumors in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice and produced higher levels of proinflammatory cytokines that should reactivate the immunosuppressive tumor microenvironment leading to epitope spreading. Our results confirm that lytic cycle antigens are clinically relevant targets for EBV+ lymphoma and underpin the rationale for integrating BR-EBVSTs as a therapeutic approach for relapsed/refractory EBV+ lymphoma (www.clinicaltrials.gov identifiers: #NCT01555892 and #NCT04664179), as well as for other EBV-associated malignancies.

The Role of α-Enolase on the Production of Interleukin (IL)-32 in Con A-Mediated Inflammation and Rheumatoid Arthritis (RA).

Interleukin (IL)-32 is produced by T lymphocytes, natural killer cells, monocytes, and epithelial cells. IL-32 induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-8, and IL-32 expression is highly increased in rheumatoid arthritis (RA) patients. Enolase-1 (ENO1) is a glycolytic enzyme and the stimulation of ENO1 induces high levels of pro-inflammatory cytokines in concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and macrophages in RA patients. In addition, there are many reports that anti-ENO1 antibody is correlated with the disease progression of RA. It implies that ENO1 could regulate IL-32 production during inflammation related to the pathogenesis of RA. Therefore, we investigated the role of ENO1 in IL-32 production using Con A-activated PBMCs and RA PBMCs. IL-32 expression is increased by ENO1 stimulation using real-time PCR and ELISA. In addition, we confirmed that IL-32 production was decreased in Con A-activated PBMCs and RA PBMCs pre-treated with NF-κB or p38 MAPK pathway inhibitors. Taken together, these results suggest that ENO1 plays an important role in inflammation through the induction of IL-32 production by the activation of the NF-κB and p38 MAPK pathways.