Serum TNF-alpha Levels Research Articles

Supplementation with Citrus Low-Methoxy Pectin Reduces Levels of Inflammation and Anxiety in Healthy Volunteers: A Pilot Controlled Dietary Intervention Study.

Background/Objective: Although low-methoxy (LM) pectin (polysaccharides extracted from citrus peels) can reduce inflammation by binding to and inhibiting the TLR-2 pathway in animal models and in vitro studies, the anti-inflammatory effects of LM pectin in humans and mood have not been explored to date. The purpose of this study is to assess the role of dietary supplementation with LM pectin in healthy volunteers on inflammatory markers and on mood, specifically anxiety and depression. Methods: We carried out a 4-week dietary intervention with LM citrus pectin on healthy volunteers (N = 14, age 40 ± 16 y, BMI 24.7 ± 3.0 kg/m2, sex F 57%) comparing the effects of daily supplementation with 20 g of LM citrus pectin versus 10 g of maltodextrin as the control (N = 15 age 43.2 ± 11 y, BMI 25.18 ± 2.0 kg/m2, sex F 66%). The effects on mood and inflammation were also tested with LM pectin at 5 g, 10 g and 15 g (2 weeks each) in an independent cohort of n = 15 healthy volunteers (age 36 ± 21 y, BMI 23.5 ± 2.4 kg/m2, sex F 80%). We assessed serum levels of TNF-alpha (downstream from TLR-2 activation), IL-1 beta, IL-6, IL-10, INF-gamma, CRP, zonulin and TLR-2 concentration which were measured using ELISA in blood samples collected at both the baseline and follow-up visits. Validated measures of anxiety and depression were collected at baseline and follow-up. Results: Supplementation with 20 g of LM pectin resulted in decreases in the pro-inflammatory markers TNF-alpha, IL-1 beta, IL-6 and INF-gamma (all p < 0.05) and an increase in anti-inflammatory marker IL-10 (p = 0.01) at the end of the 4 weeks. No such effects were observed in the control group. In addition, a significant drop in anxiety scores (from 8.38 to 4.46, p < 0.006) was found with the 20 g/day intervention but not in the control arm. In the dose-response study, anti-inflammatory effects were seen only at 15 g for TNFα (p < 0.003) and a suggestive increase in IL-10 (p = 0.08), alongside a drop in TLR-2 (p < 0.027). No significant anti-inflammatory effects were observed at 5 g and 10 g doses of LM pectin supplementation. Significant dose-dependent drops in both anxiety and depression scores were found with 10 g (p < 0.001) and 15 g per day (p < 0.0002). Conclusions: The current study identifies anxiety-reducing and anti-inflammatory effects of supplementation with 15 g/day LM pectin in healthy humans. Further research is needed to elucidate the precise mechanism and to validate the efficient dose and minimum duration of supplementation.

Evaluation of sleep quality in stage II and stage III colorectal cancer patients–secondary analysis of a randomized controlled trial

Abstract Background: Sleep quality in cancer patients often does not receive sufficient attention from their treating physicians and nurses. This report aims to highlight this under-researched issue among colorectal cancer patients scheduled to receive adjuvant chemotherapy. Materials and Methods: This is a secondary analysis of data from 129 participants from a randomized controlled trial conducted to determine the nurse-led intervention’s effect on cognitive and non-cognitive functions and serum TNF-alpha levels in patients receiving chemotherapy for colorectal cancer at Tata Memorial Hospital. The Pittsburgh Sleep Quality Index was used to collect data on sleep quality. The study also explored potential reasons for the reported poor sleep quality in the selected cohort. Results: The prevalence of poor sleep quality was approximately 60%. Sleep was primarily affected due to poor sleep latency and sleep efficiency. Also, women were more likely to experience issues related to sleep. Patients did not consider it a significant issue to report to their treating physicians and nurses. Factors contributing to poor sleep quality included financial concerns, child-rearing responsibilities, and anxiety about disease outcomes. Conclusion: Cancer patients do experience poor sleep quality, and it is crucial to assess and address this issue promptly to prevent adverse responses to cancer therapy, which can lead to increased morbidity and mortality.

Clinical characteristics, immunological alteration and distinction of MOG-IgG-associated disorders and GFAP-IgG-associated disorders

The classification of autoimmune encephalitis (AE) is based on the presence of different types of antibodies. Currently, the clinical manifestations and treatment regimens of patients with all types of AE exhibit similarities. However, the presence of immunological distinctions among different types of AE remains uncertain. In this study, we prospectively collected clinical data, as well as blood and cerebrospinal fluid (CSF) samples from patients diagnosed with MOG antibody-associated disease (MOGAD) or GFAP astrocytopathy (GFAP-A), in order to assess changes in inflammatory biomarkers such as immunoglobulin oligoclonal bands, cytokines in serum and CSF, as well as peripheral blood lymphocyte subtypes within different subsets. To further distinguish the immune response in patients with MOGAD and GFAP-A from that of healthy individuals, we prospectively recruited 20 hospitalized patients diagnosed with AE. Among them, 15 (75%) tested positive for MOG antibodies, 4 (20%) tested positive for GFAP antibodies, and 1 (5%) tested positive for both MOG and GFAP antibodies. These patients were then followed up for a period of 18 months. Compared to healthy controls (HC), AE patients exhibited elevated levels of MIP-1beta, SDF-1alpha, IL-12p70, IL-5, IL-1RA, IL-8 and decreased levels of IL-23, IL-31, IFN-alpha, IL-7, TNF-beta and TNF-alpha in serum. The CSF of AE patients showed increased levels of IL-1RA, IL-6 and IL-2 while decreased levels of RANTES, IL-18,IL-7,TNF-beta,TNF-alpha,RANTES,Eotaxin,and IL-9. The level of MCP-1 in the CSF of GFAP-A patients was found to be lower compared to that of MOGAD patients, while RANTES levels were higher. And the levels of IL-17A, Eotaxin, GRO-alpha, IL-8, IL-1beta, MIP-1beta were higher in the CSF of patients with epilepsy. The presence of intrathecal immune responses is also observed in patients with spinal muscular atrophy (SMA). However, no biomarker was found to be associated with disease severity in patients with AE. Among the 17 patients, recovery was observed, while 2 patients experienced persistent symptoms after an 18-month follow-up period. Additionally, within one year of onset, 8 patients had a single recurrence. Therefore, the immunological profiles of MOGAD and GFAP-A patients differ from those of normal individuals, and the alterations in cytokine levels may also exhibit a causal association with the clinical presentations, such as seizure.

Effect of Statins on Serum Levels of TNF-alpha and Interleukin-6 in Patients with Kidney Disease: A Meta-analysis of Randomized Clinical Trials.

Some clinical trials have indicated the beneficial effects of statins in patients with kidney disease, while others have reported no positive effect of statins in these patients. We conducted this meta-analysis to identify the effects of statins on serum levels of interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) in patients with kidney disease. A systematic literature search was performed using PubMed, Scopus, and Web of Science databases to identify all studies published from inception to August, 2022. The major outcome variable was the Weighted Mean Difference (WMD). Eligible studies were stratified based on target population, intervention duration, dosage and type of statins, and solubility of statins. Meta-analysis performed on seven publications (8 studies), including 213 patients with kidney disease and 188 control individuals, indicated that the concentration of IL-6 was marginally decreased in patients with kidney disease following statin therapy disease (WMD = -1.15 pg/mL; 95% CI = -2.33 to 0.04, P = 0.05, I2 = 68.5%). The findings of subgroup analysis based on the dosage of statins showed that neither highintensity nor moderate/low-intensity statin treatment could significantly influence the serum level of IL-6. Lipophilic statins were more effective than hydrophilic statins, and they marginally decreased the levels of IL-6 (WMD = -1.21 pg/mL; 95% CI = -2.43 to 0, P = 0.05, I2 = 55.7%). Meta-analysis of four publications (five studies) with 157 patients with kidney disease and 132 control subjects showed that statins reduced the serum levels of TNF-α in patients with kidney disease when compared with control individuals (WMD= -2.66 pg/mL; 95% CI = -4.26 to -1.06, P < 0.001, I2 = 63%). Statins only marginally decreased the concentration of IL-6 in patients with kidney disease, but neither high-intensity nor moderate/low-intensity statin treatment could significantly influence the level of IL-6. However, statins reduced serum levels of TNF-α in patients with kidney disease.

Low serum irisin levels predicted newly atrial fibrillation in patients with any phenotypes of chronic heart failure

Abstract Background Atrial fibrillation (AF) continues to be a major health problem among patients with known cardiovascular disease including heart failure (HF). AF is not only powerful risk factor for newly HF, but also it contributes to untoward clinical course of the condition. Although, natriuretic peptides are well-validated biomarkers to predict poor clinical outcomes of HF, their accuracy for AF in patients with different phenotypes of HF is not optimal. Recent studies showed that adipocytokines including irisin affect the risk of AF occurrence. We hypothesized that serum irisin can have additional discriminative potency for AF among HF in patients. Methods The study group comprised 541 consecutive patients with chronic HF aged 41 to 76 years recruited for the study from October 2020 to December 2022. We included 153 patients with any phenotypes of HF who were hospitalized due to paroxysmal or persistent AF and a control group of 388 age- and sex-matched individuals admitted to hospitals due to exacerbation of HF. All patients included in the study were examined by conventional general clinical and physical investigations, B-mode echocardiography and Doppler. The plasma levels N-terminal-natriuretic pro-peptide (NT-proBNP), high sensitivity (hs) C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), hs-troponin T, adropin, apelin, leptin, adiponectin, and irisin were measured using ELISA. Results Compared with patients from control groups, patients with AF had greater left atrial volume index (LAVI), higher serum levels of NT-proBNP, hs-CRP, TNF-alpha, and lower left ventricular ejection fraction (LVEF), irisin and apelin levels. There were no significant difference between groups in left ventricular mass index, the serum levels of hs-troponin T, adropin, leptin, and adiponectin. Multivariate linear regression adjusted to LVEF and LAVI revealed that irisin and NT-proBNP were the predictors for AF. We found that the well-balanced cut-off point for serum concentration of irisin (AF versus non-AF) were 10.5 ng/mL (area under curve [AUC] = 0.96, sensitivity = 81.0%, specificity = 88.0%; P = 0.0001). Cutoff point of NT-proBNP that distinguished patients with AF and without AF was 750 pmol/L (AUC = 0.96; sensitivity = 72.7%, specificity 76.5%, р = 0.0001). Multivariate Cox regression model yielded that the serum levels of irisin &amp;lt; 10.5 ng/mL (odds ratio [OR] = 1.40; P = 0.001) and NT-proBNP &amp;gt; 750 pmol/mL (OR = 1.22; P = 0.012), LAVI &amp;gt; 34 mL/m2 (OR = 1.06; P = 0.010) remained to be strong predictors for newly AF. Add-on of irisin &amp;lt; 10.5 ng/mL to the predictive model constructed from NT-proBNP (&amp;gt; 750 pg/mL) significantly improved discriminatory potency of the whole model for HF. Conclusion We found that decreased serum levels of irisin significantly predicted newly AF in patients with any phenotypes of HF.

564 Platelets and Leukocytes Interact to Modulate Inflammation in Patients with CKD

OBJECTIVES/GOALS: Platelets interact with leukocytes in the circulation to modulate inflammation in chronic diseases. In previous clinical study, we showed that platelet leukocyte interaction is reduced in the circulation of patients with CKD. Preclinical studies are needed to show whether these findings are a precursor to or a result of CKD. METHODS/STUDY POPULATION: We used mouse models (wild type and platelet-defect) and induced CKD with intraperitoneal cisplatin injections. We measured platelet leukocyte interactions before and after CKD induction in the two models. RESULTS/ANTICIPATED RESULTS: We found platelet-leukocyte interaction to reduce after CKD induction in both wild type and platelet-defect mice. This coincided with a pro-inflammatory state in these mice, as measured by serum TNFalpha levels. Specifically, pro-inflammatory state was exacerbated in CKD of mice with platelet-defects compared to the wild type. DISCUSSION/SIGNIFICANCE: These findings recapitulate translational findings in human CKD samples and confirm that CKD state results in reduced platelet-leukocyte interactions in the circulation, and this change imparts a pro-inflammatory state in the CKD state.

Evaluation of maternal serum VEGF, TNF-alpha, IL-4, and IL-10 levels in differentiating placenta accreta spectrum from isolated placenta previa

ObjectiveOur study aimed to differentiate patients with placenta accreta spectrum (PAS) from those with placenta previa (PP) using maternal serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), and IL-10. MethodsThe case group consisted of 77 patients with placenta previa, and the control group consisted of 90 non-previa pregnant women. Of the pregnant women in the case group, 40 were diagnosed with PAS in addition to placenta previa and 37 had placenta previa with no invasion. The maternal serum VEGF, TNF-alpha, IL-4, and IL-10 levels were compared between the case and control groups. Then the success of these markers in differentiating between PP and PAS was evaluated. ResultsWe found the VEGF, TNF-alpha, and IL-4 levels to be higher and the IL-10 level to be lower in the case group compared to the control group (p < 0.001). We observed a statistically significantly lower IL-10 level in the patients with PAS than those with PP (p = 0.029). In the receiver operating characteristic analysis, the optimal cut-off of IL-10 in the detection of PAS was 0.42 ng/mL). In multivariate analysis, the risk of PAS was significant for IL-10 (odds ratio (OR) 0.45, 95 % confidence interval (CI) 0.25–0.79, p = 0.006) and previous cesarean section (OR 2.50, 95 % Cl 1.34–4.66, p = 0.004). The model’s diagnostic sensitivity and specificity, including previous cesarean section, preoperative hemoglobin (Hb), TNF-alpha, and IL-10 were 75 % and 72.9 %, respectively. ConclusionThe study showed that the IL-10 level was lower in patients with PAS than in those with PP. A statistical model combining risk factors including previous cesarean section, preoperative Hb, TNF-alpha, and IL-10 may improve clinical diagnosis of PAS in placenta previa cases. Cytokines may be used as additional biomarkers to the clinical risk factors in the diagnosis of PAS.

Determination of inflammation by TNF-alpha and IL-10 levels in obese children and adolescents.

Background: childhood obesity is one of the major health problem worldwide. Obesity is associated with low-level chronic inflammation resulting from inflammatory cytokine release in white adipose tissue. We aim to specify inflammatory markers tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in children and adolescents to determine their relationship with obesity. Materials and methods: forty obese patients and 46 controls were included in the study from the pediatric clinic. Blood samples from the study group were centrifuged, and the sera were stored at -80 °C after separation. Serum levels of TNF-alpha and IL-10 were determined using Human ELISA kits for TNF-alpha and IL-10. Results: serum samples from 86 children, including 45 girls (52.3 %) in the study group, were analyzed for TNF-alpha and IL-10 levels. TNF-alpha levels in the obese and control groups were 1.04 ± 0.79 and 0.60 ± 0.72 pg/ml, respectively (p = 0.010). Also, IL-10 levels in the obese and control groups were 0.76 ± 0.62 and 1.54 ± 0.71 pg/ml, respectively (p < 0.001). Gender was not identified as a factor for serum TNF-alpha and IL-10 levels (p = 0.281 and p = 0.477, respectively). Moreover, white blood cell (WBC) and serum C-reactive protein (CRP) levels were higher in the obese patient group than in the control group (p = 0.002 and p = 0.010, respectively). Conclusion: TNF-alpha levels were higher than control in obese patients and it was important in terms of showing that obesity triggers inflammation in the body. IL-10 levels, which inhibit inflammation, were lower in obese patients than controls.

Особенности течения COVID-19 у больных с хроническими вирусными гепатитами

Objective. To study the features of clinical picture and levels of proinflammatory cytokines (interleukin-1 and -6) and tumor necrosis factor-alpha in COVID-19 patients with CVH. Patients and Methods. A prospective case-control study included 222 patients admitted between 2020 and 2024 with a diagnosis of COVID-19 presenting with CVH at Zangiota Multidisciplinary Infectious Disease Clinic No. 1. The diagnosis of COVID-19 in all patients was verified either by polymerase chain reaction revealing SARS-CoV-2 ribonucleic acid (nasopharyngeal swabs) or by specific immunoglobulins of class M to coronavirus detected by enzyme immunoassay. The severity of the course of the disease was determined in accordance with the temporary methodological recommendations of the Republic of Uzbekistan “Prevention, diagnosis and treatment of new coronavirus infection (COVID-19 Group I included 103 (46.39%) patients with chronic viral hepatitis C (CVHC), Group II included 104 (46.85%) patients with chronic viral hepatitis B (CVHB), and Group III included 15(6.76%) patients with mixt-hepatitis. The examination included: history taking; clinical examination of patients; standard clinical and biochemical blood tests; multispiral computed tomography and/or lung radiography. Serum levels of TNF-alpha and interleukins (hereinafter referred to as IL) -1, and -6 were determined using diagnostic test systems manufactured by VECTOR-BEST LLC (Novosibirsk, Russia) according to the attached instructions. Statistical processing of the obtained results was performed using Statstica.12 program. Methods of descriptive and variation statistics were used; Fisher's criterion and Pearson's linear correlation coefficient were calculated. Differences were considered reliable at p &lt; 0.05. Results. In groups I and II, the moderately severe form of COVID-19 was significantly (p &lt; 0.05) redominant; in the whole sample, as well as in the moderately severe course of the disease, women were significantly (p &lt; 0.05) predominant; 9 out of 10 patients who died were men. The later a patient was admitted to the hospital, the more often severe COVID-19 was diagnosed. In all groups, men were hospitalized significantly (p &lt; 0.05) later than women. In 12(5,41%) patients the diagnosis of “CVH” was detected for the first time in hospital by ELISA method: in 11 cases – CVHC, in another 1 – CVHB. Thirtysix(16.21%) patients had diabetes mellitus, 17 of them had moderate COVID-19, and 19 had severe COVID-19. There was a significant (p &lt; 0.05) predominance of type 2 diabetes mellitus in patients from group I (25.2% vs. 3.6:% in group II, and 13.3% in group III, respectively). In 26 patients with diabetes mellitus from group I, the level of IL-6 was significantly (p &lt; 0.05) higher (59.45 ± 18.15 pg/mL, versus 30.61 ± 4.24 and 31.0 pg/mL for groups II and III, respectively). The level of C-reactive protein in the general group amounted to 41.21 ± 1.68 IU/mL; the dynamics of this index had a wave-like character, increasing with aggravation of the condition and decreasing with increasing saturation and decreasing intoxication syndrome. In 78 (35.13%) patients at hospital discharge the level of CRP remained elevated (24.03 ± 1.47 mg/L). Conclusion. Timely detection of disorders in the systems of cytokine regulation and hemostasis in patients with the combination of COVID-19 and CVH will allow increasing the effectiveness of treatment (hepatoprotectors, anticoagulants) both in hospital and in the rehabilitation period. Key words: COVID-19, diagnosis, proinflammatory cytokines, tumor necrosis factor-alpha, chronic viral hepatitis

Serum level of certain cytokines associated with psoriasis progression in Iraqi patients

Introduction and Aim: Psoriasis is a skin ailment that typically affects the scalp, lower back, knees, elbows, and results in flaky skin patches. The purpose of this study was to compare cytokines, leptin, and adiponectin levels, as well as several physiological characteristics, in psoriasis patients with and without treatment to levels in healthy people in Iraq. Materials and Methods: The study included 310 subjects, males and females aged (25-65) years. The patients were attending a dermatology consultant at Al-Yarmouk Teaching Hospital in Baghdad. Blood samples were collected by venipuncture from all individuals. The Sandwich ELISA was used to estimate serum levels of IL-2, IL-8, IL-22, TNF-alpha, IFN-gamma, ADP and Leptin. Results: Patients with psoriasis had considerably decreased lymphocyte and RBC counts while having significantly higher neutrophil, platelet, NLR, and PLR counts. WBC mean values in females and males among control groups were 7.16 ± 3.09x 103/µl and 8.6 ±3.62 x103/µl respectively. In psoriasis patients the WBC counts varied from 3.69 x103/µl to 12.8 x103/µl with a mean of 7.27 x 103/µl in female patients and from 6.47 x 103/µl to 13.62 x103/µl in males. Serum levels of cytokines, leptin and adiponectin were significantly higher in Group I patients, while in Group II it was almost like levels in the control group. Conclusion: Smoking is a risk factor for psoriasis. Lymphocytes, erythrocytes, and hemoglobin levels are decreased in patients with psoriasis, while platelets and cytokines are elevated, signifying a relationship between these immunological parameters and development and severity of psoriasis disease.

Effect of autologous bone marrow derived mesenchymal stem cells in treatment of rheumatoid arthritis

IntroductionChronic inflammation causes articular bone and cartilage degeneration in people with rheumatoid arthritis (RA). Despite recent advancements in the management of RA, adverse side effects and ineffective treatments remain a problem. Effective treatment is usually hampered by financial issues. As a result, less expensive medications that reduce both inflammation and bone resorption are required. Mesenchymal stem cells (MSCs) have recently been identified as a potential therapy for RA. Aim of the studyThis study aimed to examine the anti-arthritic effect of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides (Os), and human placental extract (HPE), individually and combined, on an RA model, using Complete Freund's adjuvant (CFA)-induced arthritis in rats. Materials and methodsIn female rats, RA was induced by injecting CFA in the paw of the hind limb. Rat bone marrow-MSCs, oligosaccharides, and human placental extract (HPE) were given individually and in combination via the intraperitoneal route. A complete blood count (CBC), erythrocyte sedimentation rate (ESR), serum cortisol, urea, uric acid, and other biochemical parameters were measured to determine the safety and efficacy of the different treatments. Histopathological analysis of bone sections was carried out. ResultsCombining oligosaccharides and HPE therapy with the infusion of rat-bone marrow MSCs had beneficial antiarthritic and anti-inflammatory effects in CFA-induced arthritis in rats: overall such triple therapy significantly reduced serum levels of IL-6, IL-10, and TNF-alpha in comparison with all other combinations (all P > 0.05). Meanwhile, the triple therapy did not have negative effects on levels of CBC, serum cortisol, ESR, and liver enzymes (all NS) as well as on renal functions (NS). Also, the histopathological analysis showed significant improvements in the healing and remodelling of osteoporotic lesions in arthritic rats. As shown by counting apoptotic cells as a histopathological substitute for measuring apoptotic or regeneration markers, the lowest count was found in the group treated with a triple therapy of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides, and HPE. ConclusionThe combination of rat MSCs, oligosaccharides, and HPE has the potential to be an effective treatment for rheumatoid arthritis.

#3195 PATIENTS ON HD WITH CENTRAL CATHETERS LOCKED WITH TAUROLIDINE HAVE A SIMILAR INFLAMMATORY PROFILE TO SUBJECTS WITH NATIVE ARTERIOVENOUS FISTULA

Abstract Background and Aims Inflammation is a near-universal condition in haemodialysis (HD) patients, which contributes to increased complications, morbidity and mortality. The inflammatory profile is enhanced in subjects who need a central venous catheter (CVC) as vascular access in comparison with patients with native arteriovenous fistula (AVF), the optimal vascular access for HD. The aim of the present study was to analyse the inflammatory profile of HD patients according to their vascular access (CVC vs AVF), and to evaluate whether Taurolidine-citrate-heparin lock solution (TCH; taurolidine 1.35%, citrate 4% and heparin 500 IU) is able to modulate the inflammatory state of patients with CVC towards an inflammatory profile similar to that observed in subjects with AVF. Method A total of 109 patients with AVF or tunneled CVC under regular haemodialysis for more than 6 months were screened. Exclusion criteria included intercurrent infections in the previous 3 months, active inflammatory or immunologic diseases, and treatment with antibiotics or drugs affecting the immune system. Finally, 85 patients were included in the study and classified according to the vascular access: 25 patients with AVF and 60 with CVC. Subsequently, two subgroups were formed from the group of patients with tunneled CVC according to a heparin-containing catheter lock solution with (CVC-TCH) and without taurolidine-citrate (CVC-Hep). Subsequently, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) concentrations in serum and messenger ribonucleic acid (mRNA) gene expression levels of IL-6 and TNF-alpha in peripheral blood mononuclear cells (PBMC) were measured at inclusion and after three months follow-up. Results Altogether eighty-five subjects (42 males and 43 females; mean age 61 ± 9 yrs; 39% diabetics) were initially included in the study. In 25 subjects the vascular access was AVF, while the rest used tunneled CVC; of these 31 used standard CVC-Hep and 29 used CVC-TCH. Five patients dropped out the study and thus 80 patients completed the 3-month follow-up and were finally evaluated. At inclusion, patients with CVC had significantly higher serum and expression levels of inflammatory parameters compared to subjects with AVF. After 3 months, there were no significant changes in inflammatory markers in subjects with AVF compared to baseline, whereas in subjects with CVC-Hep a significant increase in serum and gene expression of IL-6 could be observed. On the contrary, subjects with CVC-TCH experienced a decrease of all parameters compared to baseline, of which differences in serum IL-6 and gene expression levels of IL-6 and TNF-alpha were significant. After 3 months of follow-up there was no significant difference in any inflammatory parameter when comparing patients with CVD-TCH with those with AVF (Table). Conclusion In patients under HD with cuffed tunneled CVC, the use of TCH lock solution after each HD session is associated with a significant improvement in the inflammatory serum and gene expression state. Thus, the inflammatory profile of patients with CVC using TCH does not differ from that of patients with native AVF after at least three months of CVC-TCH use.

Role of Pellino-1 in Inflammation and Cardioprotection following Severe Sepsis: A Novel Mechanism in a Murine Severe Sepsis Model †.

Intra-abdominal sepsis is commonly diagnosed in the surgical population and remains the second most common cause of sepsis overall. Sepsis-related mortality remains a significant burden in the intensive care unit despite advances in critical care. Nearly a quarter of the deaths in people with heart failure are caused by sepsis. We have observed that overexpression of mammalian Pellino-1 (Peli1), an E3 ubiquitin ligase, causes inhibition of apoptosis, oxidative stress, and preservation of cardiac function in a myocardial infarction model. Given these manifold applications, we investigated the role of Peli1 in sepsis using transgenic and knockout mouse models specific to this protein. Therefore, we aimed to explore further the myocardial dysfunction seen in sepsis through its relation to the Peli 1 protein by using the loss of function and gain-of-function strategy. A series of genetic animals were created to understand the role of Peli1 in sepsis and the preservation of heart function. Wild-type, global Peli1 knock out (Peli1-/-), cardiomyocyte-specific Peli1 deletion (CP1KO), and cardiomyocyte-specific Peli1 overexpressing (alpha MHC (αMHC) Peli1; AMPEL1Tg/+) animals were divided into sham and cecal ligation and puncture (CLP) surgical procedure groups. Cardiac function was determined by two-dimensional echocardiography pre-surgery and at 6- and 24-h post-surgery. Serum IL-6 and TNF-alpha levels (ELISA) (6 h), cardiac apoptosis (TUNEL assay), and Bax expression (24 h) post-surgery were measured. Results are expressed as mean ± S.E.M. AMPEL1Tg/+ prevents sepsis-induced cardiac dysfunction assessed by echocardiographic analysis, whereas global and cardiomyocyte-specific deletion of Peli1 shows significant deterioration of cardiac functions. Cardiac function was similar across the sham groups in all three genetically modified mice. ELISA assay displayed how Peli 1 overexpression decreased cardo-suppressive circulating inflammatory cytokines (TNF-alpha, IL-6) compared to both the knockout groups. The proportion of TUNEL-positive cells varied according to Peli1 expression, with overexpression (AMPEL1Tg/+) leading to a significant reduction and Peli1 gene knockout (Peli1-/- and CP1KO) leading to a significant increase in their presence. A similar trend was also observed with Bax protein expression. The improved cellular survival associated with Peli1 overexpression was again shown with the reduction of oxidative stress marker 4-Hydroxy-2-Nonenal (4-HNE). Our results indicate that overexpression of Peli1 is a novel approach that not only preserved cardiac function but reduced inflammatory markers and apoptosis following severe sepsis in a murine genetic model.

Intermittent fasting combined with exercise training reduces body mass and alleviates hypothalamic disorders induced by high-fat diet intake

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF=HF diet mice submitted to IF; HF-T=HF diet mice submitted to ET; HF-IFT=HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei.

Phagocyte-related S100 proteins and cytokines in acute lymphoblastic leukemia and their prognostic value

In this retrospective cohort study, we evaluated the level of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of cytokines in 128 children with pre-B ALL and 22 with T-ALL. The biomarkers were evaluated at diagnosis and during antileukemic therapy (day 29 and after six months) and we evaluated their correlation with basic laboratory values. Further, for the children with pre-B ALL, we evaluated whether the biomarkers could predict the outcome of ALL expressed as minimal residual disease (MRD), relapse, and death. The levels of S100A9, S100A12, IL-1beta, IL-12p70, IL-13, IL-17, IL-18, and MPO serum levels increased significantly as chemotherapy was initiated. The difference was most pronounced for S100A9 and S100A12, which had strong positive correlations with the neutrophil counts. In contrast, TNF-alpha, IL-6, IL-10, CCL-2, MMP-3, and CD25 serum levels decreased after chemotherapy. Although none of these biomarkers appear to be an independent predictor of outcomes, in predictive models with MRD as the outcome, AUC increased from 76% (95% CI 68–84%) when using initial risk group stratification alone to 83% (95% CI 73–91%) in a multivariate predictive model including initial risk group stratification and the biomarkers S100A12, TNF-alpha, and IL-10.

Daily phytate intake increases adiponectin levels among patients with diabetes type 2: a randomized crossover trial

AimAdiponectin, a major adipokine secreted by adipose tissue, has been shown to improve insulin sensitivity. Myo-inositol hexaphosphate (phytate; InsP6) is a natural compound that is abundant in cereals, legumes, and nuts that has demonstrated to have different beneficial properties in patients with diabetes type 2.MethodsWe performed a randomized crossover trial to investigate the impact of daily consumption of InsP6 on serum levels of adiponectin, TNF-alpha, IL-6, and IL-1beta in patients with type 2 diabetes mellitus (T2DM; n = 39). Thus, we measure serum levels of these inflammatory markers, classic vascular risk factors, and urinary InsP6 at baseline and at the end of the intervention period.ResultsPatients who consumed InsP6 supplements for 3 months had higher levels of adiponectin and lower HbA1c than those who did not consume InsP6. No differences were found in TNF-alpha, IL-6, and IL-1beta.ConclusionThis is the first report to show that consumption of InsP6 increases plasma adiponectin concentration in patients with T2DM. Consequently, our findings indicate that following a phytate-rich diet has beneficial effects on adiponectin and HbA1c concentrations and it could help to prevent or minimize diabetic-related complications.

Protective effect of lactoferrin administration against brain tissue damage in diabetic rats

Bovine lactoferrin (bLf), a glycoprotein with iron, Several of Lf's functions intervene through various cell receptors. Its antibacterial, antiparasitic, anti-inflammatory, and antioxidant effects Additionally, it has been found that Lf has immunomodulating. We looked into the protective effects of Lf on various brain tissue indicators and histopathological examination of streptozotocin (STZ) induced diabetic rats. This research aimed to check the potential protective effect of lactoferrin verses brain lesion in STZ induced diabetic rat. The rats were split into five groups: Control (C), Diabetic rat (T2D), T2D + Insulin, T2D + Lactoferrin, and T2D + Insulin + Lactoferrin. Diabetes was created in rat groups by administration STZ (60 mg/kg body weight), then rat was sacrificed. The tissues of the Brain and serum had been chosen to analyze biochemical brain tissue indicators, Serum Neuron-Specific Enolase (SNE), Serum Brain-Derived Neurotrophic Factor (BDNF), and Tissue Necrosis Factor-Alpha (TNF-Alpha). Also, H&E staining was utilized to measure the histological changes of the brain and Comet assay of brain tissue samples for detection of DNA damage. In T2D rat, Lactoferrin corrected aberrant serum levels of SNE, BDNF and TNF-Alpha, in addition, Lactoferrin improves brain pathological changes might be through hypoglycemic, and/or anti-inflammatory actions and reduced DNA damage as compared to diabetic untreated rats. It could be concluded that oral administration of lactoferrin to diabetic rats alone or in combination with insulin treatment for six weeks was found to attenuate the harmful effects of diabetes on brain biomarkers as well as the pathological lesions that occur in the brain tissues of diabetic rats.

Estimating the role of single-nucleotide polymorphism (rs1800629)-308 G/A of TNF-alpha gene as genetic marker associated with angina pectoris in a sample of Iraqi patients

BackgroundAngina pectoris (AP) occurs when oxygen and other nutrients are insufficient to meet the metabolic needs of the heart muscle. Stable angina is the most common, while the unstable angina is less frequent. Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine plays a vital function in the immune response regulation. TNF gene cluster contains many polymorphisms; the most commonly investigated polymorphism is the rs1800629 SNP. This SNP, located at − 308 position with regard to the TNF promoter region, replaces guanine (G) with adenine (A), with the allelic types − 308 G/A, and has been linked to a variety of inflammatory condition and autoimmune diseases. The − 308 G/A SNP was investigated in AP and interconnected to the TNF level to figure out the responsibilities of TNF-alpha gene polymorphism in the pathogenesis of AP. MethodThe current work design as a case–control study that involves 300 participant divided to 200 patients evaluated as (stable angina n = 100 and unstable angina n = 100) compared with 100 apparently healthy control subjects. The serum level of TNF-alpha was assessed via enzyme-linked immunosorbent assay (ELISA)/sandwich method. The genotype and allele frequency distribution of TNF-alpha rs1800629 gene polymorphism were investigated by TaqMan probe of allelic discrimination method. ResultsThe levels of TNF-alpha were significantly higher in patients with stable and unstable angina pectoris in comparison with controls. The deviation from Hardy–Weinberg equilibrium (HWE) of TNF-alpha genotypes was obvious in control and unstable angina pectoris groups. Moreover, the significant differences between patients with AP and controls under the five genetic models consider the association between TNF-alpha (rs1800629) − 308 G/A and AP with OR > 1. However, data analysis of allelic and genotypic of (rs1800629) − 308 G/A revealed higher significantly differences of GG homozygous and GA heterozygous proportions between stable angina patients and control. The A allele was more represented as etiological allele, and G allele was represented as protective allele. The serum levels of TNF-alpha were significantly higher in subjects with genetically mutated AA genotypes than in subjects with wild GG genotypes in the study groups. ROC curve analysis found the best cutoff value of TNF-alpha level was 77.25 pg/ml. ConclusionAs the results, our data observed a linked of TNF-alpha (rs1800629) − 308 G/A genetic variant with angina pectoris patients, and the A allele has been linked to the production or expression of TNF-alpha serum level and represented an etiological factor of angina pectoris.

Effect of pancreatin on acute pancreatitis resulting from L-arginine administration in mice, a morpho-histopathological and biochemical study

Acute pancreatitis (AP) is a life-unpleasant situation with contradictory and inadequate treatments. In this regard, the present study evaluated the effect of the possible pretreatment of lipase-pancreatin on L-arginine-induced AP. Forty adult mice were selected and divided into five groups: I) control group, II and III) AP groups (i.p.) receiving L-arginine of 2×300 and 2×400 mg/100 g body weight (b.w.), IV) AP (2×300 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase), and V) AP (2×400 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase). All AP groups displayed a significant increase in serum levels of ALT, AST, TBARS, and TNF-alpha compared to the control group. Moreover, pancreatic tissue edema, inflammation, and vacuolization of acinar cells were significantly higher in the untreated L-arginine group compared to the control and pancreatin groups. Conversely, the diameter of pancreatic islets significantly declined after induction of pancreatitis compared with control and pancreatin groups. Pancreatin treatment can be used in pancreatic dysfunction, however, this medicine showed no protective effect against L-arginine-induced AP in the mouse model.

Quercetin and polycystic ovary syndrome; inflammation, hormonal parameters and pregnancy outcome: A randomized clinical trial.

Women with PCOS have a reduced total antioxidant level in addition to higher oxidative stress. Quercetin is a flavonol-type antioxidant that may be found in many foods. Does quercetin affect inflammatory and hormonal factors and clinical outcomes in PCOS patients? Seventy-two women with PCOS were randomly allocated to one of two intervention groups, and each received a daily dosage of 500mg of Quercetin for the intervention group or a placebo for the control group for a period of 40 days from the start of the menstrual cycle until the day of ovulation. Serum levels of IL-6, TNF-alpha, LH, FSH, and AMH were measured using ELISA. In addition, oocyte and embryo grade before IVF and pregnancy rate have been examined. LH levels reduce significantly in the quercetin group (4.351.62 at baseline to 3.061.43 after 3 months) (p=.029). The results indicated that Quercetin significantly decreased TNF alpha levels in comparison to the pretest (p=.008). Following capsule administration, IL-6 levels significantly decreased in the quercetin group (p=.001). Except for Δ LH, ΔIL6, and ΔFSH, there was no significant difference in any of the hormones and inflammations parameter changes. Quercetin consumption causes improvement in oocyte and embryo grade and the pregnancy rate in PCOS patients. As a result, regular consumption of Quercetin has been shown to decrease inflammatory and LH parameters, making it beneficial for the management of PCOS and related diseases.