TNF-α Values Research Articles

Estimation of cystatin C and inflammation marker levels in type 2 diabetes mellitus patients with microalbuminuria

Serum cystatin C (CstC) is a type of protein produced by cells at the normal level; when the kidney is in normal condition or function, it inhibits the interstitial cysteine protease. The objective of the current study is to evaluate the levels of CstC and inflammation markers in type 2 diabetes mellitus (T2DM) patients with early diagnosed microalbuminuria (MBA) and find if there is a relationship between CstC and different parameters. Fifty T2DM patients with a mean age of 44.41 ± 6.51 years in the Al-Yarmouk Teaching Hospital were recruited according to the presence of MBA, and they were compared with 40 nondiabetic individuals with a mean age of 42.22 ± 5.33 years as control. Serum CstC, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were estimated by enzyme-linked immunosorbent assay. The mean values of serum CstC, IL-6, and TNF-α in the diabetic patients with MBA were all significantly increased compared to those of the nondiabetic individuals (P < 0.001). In T2DM patients with MBA, there were positive correlations between serum CstC levels and serum creatinine, creatinine urea, and cystatin-c/creatinine ratio. Similarly, there was a strong positive correlation between serum CstC and serum of the inflammatory markers IL-6 and TNF-α. However, there was a negative association between CstC and the estimated glomerular filtration rate-Larson equation. The results of the current study suggest that serum CstC, IL-6, and TNF-α may potentially serve as biomarkers for the early detection of MAB in patients with T2DM.

538. Human neutrophil gelatinase-associated protein (N-gal) and proinflammatory cytokines as biomarkers of disease severity in children with Hemolyitic Uremic Syndrom (HUS) and Shigatoxin-producing E.coli (STEC) infection.

Abstract Background Hemolytic Uremic Syndrome (HUS) is a complication of Shigatoxin-producing E.coli (STEC) infection which presents a characteristic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Preliminary in vitro and experimental animal studies demonstrated that Shigatoxins (STXs) induce the secretion of proinflammatory cytokines. Human neutrophil gelatinase-associated protein (N-gal) has been reported as a marker of acute kidney injury. Dosing serum levels of IL-8, TNF-α, IL-6, IL-1β and N-gal in children with STEC-associated infection and HUS would allow to establish the role of these cytokines as biomarkers of renal injury and severity Methods Prospective study during 2017 – 2020 was performed; three groups of patients < 18 years were included: bloody diarrhea (BD), HUS requiring dialysis (HUSD) and HUS and no dialysis requirement (HUSND), all of them with presence of STX in stool. Blood samples were collected at diagnosis (t1) and at 7 days (t2). An immunoassay was used for detection of TNF-α, IL-1β, IL-6, and IL-8 (Bio-Plex Pro Human®, BioRad). An immunoassay (Anti-Lipocalin-2) was used for N-gal detection Results Forty-nine children were admitted; 22 (49%) were male. Median age was 24 (IQR 13-36) months. Fourteen patients with BD, 24 patients with HUS: 12 HUSD and 12 HUSND. Eleven healthy children (HC) were included. At diagnosis, higher IL-8 values were found in HUSD vs. BD (p=0.0004), HUSND (0.003) and HC (p= 0.0043). Higher TNF-α values were detected in HUSD vs. BD (P= 0.0001), HUSND (p= 0.0011) and HC (p= 0.0002). Higher TNF-α values were found in patients with BD vs HC (p= 0.0055). HUSD exhibited higher IL-6 values as compared with BD (p= 0.0145) and HC (0.0106). N-gal concentrations were higher in HUSD vs. BD (P= 0.0120), HUSND (P= 0.0166) and HC (p= 0.0049). A decrease in IL-8 was observed in HUSD between t1 and t2 (p=0.0357). (Figure 1) Conclusion Interleukin 8, IL-6, and N-gal may be considered as potential serological markers of renal damage and dialysis requirement. TNF-α concentrations are already increased in BD without HUS complications Disclosures All Authors: No reported disclosures.

Clinical, Radiographic, and Inflammatory Peri-Implant Parameters around Narrow Diameter Implant Crowns among Prediabetic and Non-Diabetic Subjects.

Background and Objectives: To compare the clinical, radiographic, and inflammatory peri-implant parameters around narrow diameter implants (NDI) supported single and splinted crowns in non-diabetics and prediabetes. Materials and Methods: The clinical and radiographic parameters and the levels of IL-6 and TNF-α in the peri-implant crevicular fluid (PICF) of narrow diameter single (NDISCs) and splinted (NDISPs) crown implants were assessed both in non-diabetics and participants with prediabetes. The glycemic state of the patient was assessed using glycated hemoglobin (HbA1c) levels. The peri-implant soft tissue indices (Plaque index (PI), bleeding on probing (BoP), probing depth (PD)) and marginal bone loss were recorded and compared between the groups. Success of the prosthesis was assessed by the frequency of technical complications and patient satisfaction. Inter-group comparison was performed using ANOVA (one-way analysis of variance) while the normal distribution of dependent variables was calculated using Shapiro-Wilk. A p-value of less than 0.05 was considered to be statistically significant. Results: Sixty participants (30 non-diabetics and 30 with prediabetes) with a total of 178 (118 NDISCs and 60 NDISPs) platform-switched NDIs were a part of the study. Of the 118 NDISCs, 56 were placed in the non-diabetic individuals and 62 were placed in the prediabetes group whereas 30 NDISPs each were placed in both the study groups. The clinical parameters of PI, BoP and PD in the single crown and splinted crown groups showed comparable results. However, a statistically significant difference (p-value of less than 0.05) in PI, BoP and PD and in the values of IL-6 and TNF-α was found when a comparison was made between the non-diabetes and prediabetes group. A total of 91% of the patients were satisfied with the esthetics of the implants while 79% of the patients showed satisfaction with function. Conclusions: All the clinical and radiographic parameters were statistically similar in both single and splinted types of narrow diameter implants. However, the bone loss, probing depth, plaque index, and levels of inflammatory markers were statistically higher in prediabetes as compared to non-diabetes implying that a slight hyperglycemic state impacts peri-implant health.

Jade material in vitro and in vivo: A study on the anti-inflammatory and repair efficacy of jade material on the skin.

The biological safety of natural jade materials and assembled jade-activated materials on cells and their anti-inflammatory and damage repair functions, as well as the repair function on sensitive skin, were studied utilizing in vitro cell biology and in vivo. Human skin fibroblasts were used as model cells to conduct cytotoxicity experiments in vitro, and the effects on the expression of inflammatory factors and growth factor-related genes in fibroblasts were explored. The gene expression values of inflammatory factors IL-1, IL-6, TNF-α and cytokines epidermal growth factors, fibroblast growth factors and COL1A1 in fibroblasts were measured by polymerase chain reaction test. Thirty women with sensitive skin were selected to apply a mask containing jade extract three times a week. After two weeks, non-invasive measures related to skin sensitivity were tested. We confirmed the presence of anti-inflammatory effects in both jade materials, with the effects of the assembled activated jade material being superior to that of the natural jade material. Jade extracts significantly increased the gene expressions of EGF, FGF and COL1A1 in HDF. The results of the in vivo study showed that the mask containing jade extract could significantly increase the skin hydration and decrease the rate of transepidermal water loss and skin lactic acid sting test scores after two weeks of use. Subjective evaluations confirmed improvements in skin dryness, smoothness and fineness. No new sensitization occurred in subjects, and the product was non-irritating. No adverse skin reactions were observed during the test. The jade materials were able to downregulate the expression of inflammatory factor genes, up-regulate the expression of growth factor genes, and improve the anti-inflammation and repair ability of skin. Furthermore, the test results of participants with sensitive skin after using the mask containing jade extract showed that the mask has repairing ability.

The antiinflammatory and electrophysiological effects of fingolimod on penicillin-induced rats.

The fact that inflammation triggers epileptic seizures brings to mind the antiepileptic properties of anti-inflammatory drugs. To investigate the electrophysiological and anti-inflammatory effects of fingolimod on an experimental penicillin-induced acute epileptic seizure model in rats. Thirty-two male Wistar rats were divided into four groups: control (penicillin), positive control (penicillin + diazepam [5 mg/kg]), drug (penicillin + fingolimod [0.3 mg/kg]) and synergy group (penicillin + diazepam + fingolimod). The animals were anesthetized with urethane, and epileptiform activity was induced by intracortical injection of penicillin (500,000 IU). After electrophysiological recording for 125 minutes, IL-1β, TNF-α, and IL-6 were evaluated by ELISA in the serum of sacrificed animals. During the experiment, animal deaths occurred in the synergy group due to the synergistic negative chronotropic effect of diazepam and fingolimod. Although not statistically significant, fingolimod caused a slight decrease in spike-wave activity and spike amplitudes in the acute seizure model induced by penicillin (p > 0.05). Fingolimod decreased serum IL-1β (p < 0.05); fingolimod and diazepam together reduced IL-6 (p < 0.05), but no change was observed in serum TNF-α values. Even in acute use, the spike-wave and amplitude values of fingolimod decrease with diazepam, anticonvulsant and anti-inflammatory effects of fingolimod will be more prominent in chronic applications and central tissue evaluations. In addition, concomitant use of fingolimod and diazepam is considered to be contraindicated due to the synergistic negative inotropic effect.

Different positive end expiratory pressure and tidal volume controls on lung protection and inflammatory factors during surgical anesthesia.

Mechanical ventilation can lead to the severe impairment of the metabolic pathway of alveolar surfactants, inactivating alveolar surfactants and significantly reducing lung-chest compliance. The cardiopulmonary function of elderly patients usually reduced to a certain extent, and there are lung complications after surgical anesthesia, just like lung barotrauma caused by mechanical ventilation, atelectasis and postoperative hypoxemia. To investigate the effects of different positive end expiratory pressures (PEEPs) and tidal volumes (VTs) on respiratory function, the degree of the inflammatory response and hemodynamic indexes in patients undergoing surgery under general anesthesia. A total of 120 patients undergoing surgery for gastric or colon cancer under general anesthesia in Xinghua People's Hospital from January 2017 to January 2021 were randomly divided into Group A and Group B, with 60 cases in each group. The ventilation mode in Group A was VT (6.0 mL/kg) + PEEP (5.0 cmH2O), while that in Group B was VT (6.0 mL/kg) + PEEP (8.0 cmH2O). Blood gas parameters, respiratory mechanical parameters, inflammatory response indicators, hemodynamic indicators and related complications were compared between the two groups. There were no significant differences in PaCO2, PaO2, oxygen or the examined indexes at T0 between group A and group B (P > 0.05). The measured PaO2 value of patients in group A at T3 was higher than that in group B, and the difference was significant (P < 0.05). There were no significant differences in peak airway pressure (Ppeak), mean airway pressure or dynamic pulmonary compliance (Cdyn) at T0 between group A and group B (P > 0.05). The measured Ppeak value of patients in group A at T1 was higher than that in group B, and the difference was significant (P < 0.05). The measured Cdyn value at T1 and T2 was greater than that in group B (P < 0.05). Before surgery, there were no significant differences in tumor necrosis factor-α (TNF-α), interleukin (IL)-6 or IL-10 between group A and group B (P > 0.05). After 4 h, the measured values of TNF-α and IL-6 in group A were lower than those in group B, and the differences were significant (P < 0.05). The IL-10 Level in group A was higher than that in group B (P < 0.05). At T0, there were no significant differences in cardiac output, cardiac index (CI), stroke volume index (SVI) or mean arterial pressure between group A and group B (P > 0.05). The measured values of CI and SVI at T2 in patients in group A were higher than those in group B, and the differences were significant (P < 0.05). For patients undergoing surgery for gastric or colon cancer under general anesthesia, the VT (6.0 mL/kg) + PEEP (5.0 cmH2O) regimen was more effective than the VT (6.0 mL/kg) + PEEP (8.0 cmH2O) regimen in protecting the lung function and ventilatory function of patients, and it had better effects on maintaining hemodynamic stability and reducing inflammatory reactions.

Inflammatory cytokines and their correlations with different left ventricular geometries and functions in PHT patients.

To investigate relationships between hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor -α (TNF-α), interleukin-17A (IL-17A), and interferon -γ (IFN-γ), with left ventricular geometry (LVG) and function in patients with primary hypertension (PHT). A total of 396 PHT patients were assigned into four groups: Normal Geometry (NG), Concentric Remodeling (CR), Eccentric Hypertrophy (EH), and Concentric Hypertrophy (CH). The correlation between hs-CRP, TNF-α, IL-17A, IFN-γ, and clinical, biochemical parameters were analyzed by Pearson correlation analysis and Logistic regression. Receiver Operating Characteristic (ROC) curve was used to analyze the clinical values of hs-CRP, TNF-α, IL-17A, and IFN-γ for abnormal LVG prediction. NG, CR, EH, and CH group all presented increasingly higher levels of Hs-CRP, TNF-α, IL-17A, and IFN-γ, and the increase was the most prominent in the CH group. Pearson correlation analysis showed that hs-CRP, IL-17A, and IFN-γ were all positively correlated with LASct. Hs-CRP, TNF-α, and IL-17A were all negatively correlated with GLS, LASr, and LAScd. However, IFN-γ was only negatively correlated with GLS and LAScd. Logistic regression analysis showed that hs-CRP and IL-17A were independently correlated with CR; hs-CRP, TNF-α, IFN-γ, and IL-17A were independently correlated with EH and CH. ROC curve analysis showed that the area under the curve (AUC) of hs-CRP was 0.816. When the optimal diagnostic threshold of hs-CRP was 3.04mg/L, the sensitivity and specificity of the abnormal LVG were 72.1% and 81.5%, respectively. In PHT patients, hs-CRP, TNF-α, IL-17A, and IFN-γ were correlated with abnormal LVG and left ventricular function, suggesting that inflammatory cytokines may be involved in the process of PHT-induced abnormal left ventricular structure and function. In addition, hs-CRP can be used as a health screening index for patients at high risk of abnormal LVG.

Cytokines and neurotrophic factors in the severity assessment of children autism.

Due to the steady increase in the number of children with autism and the high heterogeneity of clinical groups, the diagnosis of these disorders and their severity is an urgent problem in modern medicine. In the course of the work, 126 children from 3 to 13 years old with typical neurodevelopment and with severe and mild autism spectrum disorders (ASD) were examined. Disease severity was determined according to the Childhood Autism Rating Scale (CARS). The levels of pro-/anti-inflammatory cytokines and neurotrophic factors (nerve growth factor beta and brain-derived neurotrophic factor) in blood plasma were assessed by enzyme immunoassay. Associations between indicators in each group of patients were assessed using the Spearman test and visualized as a heatmap of correlations. Statistical data processing was carried out in the R software. Significantly high levels of IL-4 in blood plasma and a decrease in the number of significant correlations within/between systems were revealed in children with mild autism compared with children with typical neurodevelopment. Such data can probably reflect the theory that some children with ASD are characterized by slow brain development, as a variant of the evolutionary norm. On the contrary, in children with severe ASD, high systemic levels of IL-6 and IFNg are shown against the background of low values of IL-10, IL-1β, TNFα and NGFβ, supported by the almost complete absence of intra/ and intersystem interactions. This may act as an indicator of maladaptation of the immune and nervous systems in severe autism, which contributes to the pathogenesis of the disease. Thus, a set of indicators: high levels of key pro-inflammatory cytokines - IL-6 and IFNg, low levels of IL-10, NGFβ and disintegration of the cytokine and nervous systems in the periphery can be proposed as an approach to indicate the severity of the condition in children with ASD.

ЦИТОКИНЫ И МАРКЕРЫ ЩИТОВИДНОЙ ЖЕЛЕЗЫ В СЫВОРОТКЕ КРОВИ У ЖЕНЩИН С АУТОИММУННЫМ ТИРЕОИДИТОМ В ДИНАМИКЕ ЛЕЧЕНИЯ

The study involved 147 women aged 31-47 with newly diagnosed AIT and hypothyroidism in the dynamics of replacement therapy with levothyroxine (before and after 6 months). The control group consisted of 63 conditionally healthy women, examined once at the beginning of the study. In peripheral blood serum, the concentrations of TNF-α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17A, RANKL, OPG, TSH and TPOAb were determined.&#x0D; It was found that the initially increased values (p&lt;0,001) of IL-1β and IL-6 remained in patients after substitu- tion therapy at higher levels than in the control group (p&lt;0,001). The tendency to an increase in the levels of IL-10 (p=0,056) and IL-17A (p=0,067) revealed at the beginning of therapy was leveled out (p&gt;0,05) by the end of the ob- servation. TNF-α values did not significantly differ from those of the control group both at baseline and after 6 months&#x0D; (p=0,166 and p=0,184, respectively). The concentrations of IL-4 (p=0,376 and p=0,179, respectively), IL-8 (p=0,102 and p=0,116, respectively) and OPG (p=0,988 and p=0,661, respectively) remained at the level of the results of healthy women before and after treatment. RANKL concentrations before treatment were elevated (p=0,029), having lost their significant significance after therapy (p=0,096). The initially decreased values of the OPG/RANKL index (p=0,017) also did not differ on repeated examination from the indicators of the control group (p=0,253). After 6 months of taking levo- thyroxine in women with AIT, a significant (p&lt;0,001) decrease in initially elevated TSH levels to the values characteris- tic of the control group was recorded against the background of a significant (p&lt;0,001) increase in the concentrations of initially elevated autoimmune antibodies (p&lt;0,001).&#x0D; When examining women with AIT and confirmed hypothyroidism, it was found that replacement therapy with levothyroxine for 6 months did not significantly affect the production of most of the studied cytokines against the back- ground of a decrease in the initially increased TSH values to the values of the control group and a significant increase in the initially increased TPOAb.

Coronary artery plaque rupture and erosion: Role of wall shear stress profiling and biological patterns in acute coronary syndromes

AimsWall shear stress (WSS) is involved in coronary artery plaque pathological mechanisms and modulation of gene expression. This study aims to provide a comprehensive haemodynamic and biological description of unstable (intact-fibrous-cap, IFC, and ruptured-fibrous-cap, RFC) and stable (chronic coronary syndrome, CCS) plaques and investigate any correlation between WSS and molecular pathways. Methods and resultsWe enrolled 24 CCS and 25 Non-ST Elevation Myocardial Infarction-ACS patients with IFC (n = 11) and RFC (n = 14) culprit lesions according to optical coherence tomography analysis. A real-time PCR primer array was performed on peripheral blood mononuclear cells for 17 different molecules whose expression is linked to WSS. Computational fluid dynamics simulations were performed in high-fidelity 3D-coronary artery anatomical models for three patients per group.A total of nine genes were significantly overexpressed in the unstable patients as compared to CCS patients, with no differences between IFC and RFC groups (GPX1, MMP1, MMP9, NOS3, PLA2G7, PI16, SOD1, TIMP1, and TFRC) while four displayed different levels between IFC and RFC groups (TNFα, ADAMTS13, EDN1, and LGALS8). A significantly higher WSS was observed in the RFC group (p < 0.001) compared to the two other groups. A significant correlation was observed between TNFα (p < 0.001), EDN1 (p = 0.036), and MMP9 (p = 0.005) and WSS values in the RFC group. ConclusionsOur data demonstrate that IFC and RFC plaques are subject to different WSS conditions and gene expressions, suggesting that WSS profiling may play an essential role in the plaque instability characterization with relevant diagnostic and therapeutic implications in the era of precision medicine.

The role of immune profile in predicting outcomes in cancer patients treated with immunotherapy.

Despite the efficacy of immunotherapy, only a small percentage of patients achieves a long-term benefit in terms of overall survival. The aim of this study was to define an immune profile predicting the response to immune checkpoint inhibitors (ICIs). Patients with advanced solid tumors, who underwent ICI treatment were enrolled in this prospective study. Blood samples were collected at the baseline. Thirteen soluble immune checkpoints, 3 soluble adhesion molecules, 5 chemokines and 11 cytokines were analyzed. The results were associated with oncological outcomes. Regardless of tumor type, patients with values of sTIM3, IFNα, IFNγ, IL1β, IL1α, IL12p70, MIP1β, IL13, sCD28, sGITR, sPDL1, IL10 and TNFα below the median had longer overall survival (p<0.05). By using cluster analysis and grouping the patients according to the trend of the molecules, two clusters were found. Cluster A had a significantly higher mean progression free survival (Cluster A=11.9 months vs Cluster B=3.5 months, p<0.01), a higher percentage of disease stability (Cluster A=34.5% vs. Cluster B=0%, p<0.05) and a lower percentage of disease progression (Cluster A=55.2% vs. Cluster B = 94.4%, p=0.04). The combined evaluation of soluble molecules, rather than a single circulating factor, may be more suitable to represent the fitness of the immune system status in each patient and could allow to identify two different prognostic and predictive outcome profiles.

The effect of silymarin given before partial hepatectomy on liver regeneration in rats with ischemic preconditioning during liver resection

Background: The regeneration capacity of liver tissue after partial hepatectomy closely affects morbidity and mortality. We aimed to investigate the effect of silymarin and ischemic preconditioning (IPC) before partial hepatectomy on liver regeneration.Methods: Thirty rats were randomly divided into 5 groups (n=6). Serum AST, bilirubin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) values were studied 48 hours after hepatectomies. Mitotic count, congestion, necrosis, cytoplasmic vacuolization, and presence of neutrophils were evaluated histopathologically. Proliferating cell nuclear antigen (PCNA) antibody was studied immunohistochemically.Results: The AST value (2071.5±938.4) was the highest in the partial hepatectomy (PH) group. The Ischemic Preconditioning Partial Hepatectomy Group (IPC) (1535.5±204.8) and the Silymarin+Partial Hepatectomy Group (Silymarin group) (1192.3±526.3) had lower levels of AST values; however, the AST values were the lowest in the Silymarin+Ischemic Preconditioning+ Partial Hepatectomy Group (IPC+ Silymarin group) (1002.8±348.9). Likewise, the highest improvement in bilirubin levels was observed in the IPC+ Silymarin group (0.33±0.11). IL-6 (11.54±2.89) and TNF-α (39.2±22.73) values were the lowest in the IPC group, and interestingly, both were higher in the silymarin-treated groups. It was observed that these values increased in Silymarin group and IPC+ Silymarin group who received silymarin treatment compared to PH group and IPC group who did not receive silymarin. In histopathological analysis, it was found that the mitosis rate and PCNA percentage were higher in the Silymarin and IPC+ Silymarin groups.Conclusions: The use of silymarin before hepatectomy and IPC during partial hepatectomy increase liver regeneration.

Expression of Prophetic Variables of Analytical Importance and their Potential Role in Breast Cancer Patient Underwent Surgical Procedure

Objective: Study the role of prophetic variables and their role in breast cancer patients especially those underwent surgical procedures. Study Design: Cross-sectional study Place and Duration: Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore. Martials and Methods: Twenty diagnosed patients of breast cancer facing surgical procedure were selected from the surgical department, Jinnah hospital, Lahore and twenty normal females were included in the study. Complete blood count (CBC) of the selected individuals was performed. Other biochemical markers Malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-Hydroxynonenol (4-HNE), Isoprostanes F2α (IsoP- F2α), Interleukin-6 (IL-6), Matrix metalloproteinases-9 (MMP-9), Tumor Necrosis factor-alpha (TNF-α), Prostaglindin-E2 (PGE-2) were measured by commercially available kits. Results: The mean weight, BMI, WBCs, platelet count, lymphocyte and neutrophil value were higher in patients compared to the controls with statistically significant differences (p&lt; 0.05). However, the mean MDA, 8-OHdG, 4-HNE, Iso-P2α, IL-6, MMP-9, TNF-α and PGE-2 value significantly higher than the control subjects (p &lt; 0.05). Conclusion: Findings of the study demonstrated the significant role of the said prophetic variables that were having their medicinal importance in the invagination of breast cancer among the patients undergone surgical interventions. It shows the significant increases in the levels of discussed markers that show increased oxidative stress leading to cell damage that can be observed within the studied group. Therefore, early investigation of the said variables and ruling out the true causes could help in addressing the oncological complications that one undergoes after being through the surgical interventions and in providing the best possible treatments Keywords: Epidermal growth factor receptor, metastatic invasion, breast cancer surgery, matrix metalloproteinase, DNA adduct

Cardiovascular adaptations and inflammation in marathon runners.

Long-distance running has become increasingly popular. Cardiovascular adaptations to exercise are relevant to the specific sports and this is also the case in long-distance running. Significant changes regarding inflammatory and endothelial markers along with indices of oxidative stress are observed in marathon and ultra-marathon runners. However, data linking inflammatory marker levels with cardiovascular adaptations to marathon running are limited. The aim of the present study was to describe the cardiovascular adaptations observed in a group of ultra-marathon runners and the association with a series of inflammatory and endothelial markers measured in their plasma. A total of 43 ultra-marathon runners were assessed by echocardiography and a treadmill exercise test. Blood samples were used for tumor necrosis factor-α (TNF-α), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, IL-10, C-reactive protein, creatine phosphokinase (CPK) and oxidative stress indice measurements. Ultra-marathon runners who presented augmented left ventricular (LV) end diastolic diameters >55 mm had higher ADMA values (1.07±0.07 vs. 0.99±0.08 µmol/ml, P<0.01) and lower CPK values (192.5±21.3 vs. 219.1±37.3 mg/dl, P<0.05) compared with those with normal LV diameters. Runners with a moderate and severe abnormal indexed LV mass >131 g/m2 had statistically significant higher TNF-α values compared with runners, with mildly elevated and a normal LV mass indexed (16.2±1.42 vs. 14.0+1.16 pg/ml, P<0.05). Runners with an abnormal left atrial volume index (LAVI; >29 ml/m2) had higher IL-6 values compared with runners with a normal LAVI (1.09+0.19 vs. 0.99±0.08 pg/ml, P<0.05). ROC curves analysis revealed that ADMA values were able to predict an abnormal LV diameter detected by echocardiography [P<0.05; area under the curve (AUC), 0.763], while TNF-α values could predict an abnormal LV mass in marathon runners (P<0.05; AUC, 0.78). On the whole, the present study demonstrates that, in ultra-marathon runners, cardiovascular adaptations to running are characterized by a specific pattern of changes in inflammatory and endothelial markers, which in turn can be used to predict the occurrence of the observed adaptations.

Immuno-Mediated Inflammation in Hypertensive Patients with 1-h Post-Load Hyperglycemia.

Inflammation plays a key role in the pathogenesis/progression of atherosclerosis, and inflammatory molecules contribute to the progression of cardiovascular disease. Subjects with normal post-load glucose tolerance and 1-h post-load plasma glucose >155 mg/dL have an increased risk of subclinical target organ damage and incident diabetes. We aimed to test possible differences in immune-mediated inflammatory parameters in newly-diagnosed hypertensives with or without 1-h post-load hyperglycemia. We enrolled 25 normotensives (NGT) and 50 hypertensives normotolerant on oral glucose tolerance test, further divided into two groups based on 1-h post-load plasma glucose: NGT 1-h ≥ 155 (n = 25) and NGT 1-h < 155 (n = 25). We measured toll-like receptor (TLR) 2, TLR4, nuclear factor kβ (NF-kβ), interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α. Hypertensives showed significantly worse metabolic and lipid profiles, and higher values of body mass ass index (BMI), creatinine, and inflammatory parameters, compared to controls. NGT 1-h ≥ 155 had a worse glycometabolic profile and higher values of TLR2 (9.4 ± 4.2 vs. 5.9 ± 2.6 MFI), TLR4 (13.1 ± 3.9 vs. 7.8 ± 2.3 MFI), NF-kβ (0.21 ± 0.07 vs. 0.14 ± 0.04), IL-1β (6.9 ± 3.4 vs. 3.2 ± 2.1 pg/mL), IL-6 (10.8 ± 2.6 vs. 4.1 ± 1.6 pg/mL), IL-8 (27.6 ± 9.3 vs. 13.3 ± 5.6 pg/mL), TNF-α (6.4 ± 2.9 vs. 3.3 ± 1.4 pg/mL), and high-sensitivity C-reactive protein (hs-CRP) (4.8 ± 1.5 vs. 2.7 ± 1.0 mg/dL) in comparison with NGT 1-h < 155. Matsuda-index and 1-h post-load glycemia were retained as major predictors of TLRs and NF-kβ. These results contribute to better characterizing cardiovascular risk in hypertensives.

Evaluation of the oxytocin effect in a rat model with experimental periodontitis.

The aim of the present study was to evaluate the inhibitory effects of oxytocin on the development of periodontitis based on its properties against bone loss and resorption. Thirty-two Wistar albino rats were divided into four equal groups: control, periodontitis + saline, periodontitis + 0.5mg/kg/day oxytocin, and periodontitis + 1mg/kg/day oxytocin. Periodontitis groups received 4.0 silk ligatures around their cervixes of the right and left mandibular incisors in an "8" shape, kept for 14days. Animals in oxytocin groups were injected once every day during 14days with oxytocin. The mandibles were fixed and scanned using microcomputed tomography to quantify bone resorption and volumetric measurements. Blood samples were collected to analyze the concentrations of macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-κΒ ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase-8 (MMP-8), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA). Histopathological evaluations were conducted to examine the gingiva and alveolar bone. Oxytocin prevented the development of periodontitis by decreasing ligament deteriorations and leukocytes in the gingival connective tissue and promoting reintegration with the alveolar bone. Bone resorption in all regions was less in the periodontitis + 1mg/kg/day oxytocin group than in the periodontitis + saline group. Although TNF-α, IL-6, and RANKL values were lower in the periodontitis + 1mg/kg/day oxytocin group, OPG was higher than that in the periodontitis + saline group. M-CSF, MMP-8, and MDA were lower in the oxytocin groups than in the periodontitis + saline group. Oxytocin may be an effective agent for periodontal diseases because it decreased bone resorption, oxidative stress, and inflammation in an experimental periodontitis.

The Assessment of Serum Cytokines in Oral Squamous Cell Carcinoma Patients: An Observational Prospective Controlled Study.

Background: The oral squamous cell carcinoma (OSCC) tumor microenvironment (TME) is a complex interweb of cells and mediators balancing carcinogenesis, inflammation, and the immune response. However, cytokines are not only secreted within the TME but also released by a variety of other cells that do not comprise the TME; therefore, a thorough assessment of humoral changes in OSCC should include the measurement of serum cytokines. Methods: We assessed the role of various serum cytokines in the evolution of OSCC, before and after treatment, versus a control group. We measured the serum concentrations of MIP-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, and TNF-α. Results: Significantly higher values (p < 0.01) were noted for IL-1β, IL-6, IL-8, IL-10, and TNF-α in the OSCC group before treatment (n = 13) compared with the control group (n = 14), and the increased concentrations persisted after treatment (n = 11). Furthermore, the variations in the values of MIP-1α, IL-1β, IL-10, and TNF-α are correlated both before and after treatment (p < 0.01). In the pretherapeutic group, IL-6 and IL-8 concentrations also correlate with IL-1β and IL-10 serum levels (p < 0.01), while in the posttherapeutic group, IL-4 varies with MIP-1α and TNF-α (p < 0.01). Conclusion: In OSCC patients, serum cytokine levels are significantly higher compared with control, but they are not significantly altered by treatment, therefore implying that they are also influenced by systemic factors. The interactions between all involved cytokines and the various pathways they regulate warrant further studies to clarify their definitive roles.

Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia.

In patients with acute promyelocytic leukemia (APL), intracranial hemorrhage (ICH), if not identified promptly, could be fatal. It is the leading cause of failure of induction and early death. Thus, biomarkers that could promptly predict severe complications are critical. Here, cytokine differences between patients with APL with and without ICH were investigated to develop predictive models for this complication. The initial cytokine profiling using plasma samples from 39 patients and 18 healthy donors found a series of cytokines that were remarkedly different between patients with APL and healthy controls. The APL patients were subsequently divided into high and low white blood cell count groups. Results showed that tumor necrosis factor a and interleukin 8 (IL-8) were vital in distinguishing patients with APL who did or did not develop ICH. In addition, verification in 81 patients with APL demonstrated that the two cytokines were positively correlated with the cumulative incidence of ICH. Finally, in-vitro and in-vivo experimental evidence were provided to show that IL-8 influenced the migration of APL-derived NB4 cells and impaired the blood-brain barrier in PML/RARα positive blast-transplanted FVB/NJ mice. These assessments may facilitate the early warning of ICH and reduce future mortality levels in APL.

Evaluation of the combination effect of rutin and vitamin C supplementation on the oxidative stress and inflammation in hemodialysis patients.

Background: Hemodialysis (HD) patients are at risk of malnutrition, cardiovascular complications, and all-cause mortality due to oxidative stress and inflammation. Some studies have demonstrated that rutin attenuates oxidative stress and inflammation in CKD rats, but its effects in HD patients are unknown to date. Aim: The aim of this study was to evaluate the effect of rutin and vitamin C versus vitamin C alone on oxidative stress and inflammation in HD patients. Methods: A prospective randomized, open-label, controlled trial enrolled on hundred and five HD patients divided into three groups as follows: patients in group 1 were given a rutin/vitamin C combination (Ruta C group as the combination trade name is known as Ruta C 60 tablets), patients in group 2 were given vitamin C (1 g) (vitamin C group), and group 3 was the control group; the study period was 16 weeks. The following were assessed at baseline and at the end of the study: serum malondialdehyde (MDA), glutathione peroxidase (GPx), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), lipid profile levels, and erythrocyte sedimentation rate. Results: It was found that vitamin C significantly increased serum GPx in group 2 (p = 0.001) compared to a non-significant result in both group 1 and 3; in addition, serum MDA and TNF-α values had decreased significantly in the three groups compared to their baselines; however, a non-significant difference was seen among the studied groups at the end of the study. On the other hand, MDA levels were reduced by 50% in interventional groups compared to 28% in the control group, while the Ruta C group showed an 80% reduction in the level of TNF α compared to the 78% reduction observed in the vitamin C group, and finally, the interventional drugs showed a significant improvement in the lipid profile. Conclusion: Vitamin C supplementation alone for 16 weeks had a potential effect on the antioxidant’s GPx activity. Moreover, it was reported that both vitamin C alone or the rutin/vitamin C combination (Ruta C) showed a protective role against lipid peroxidation, evidenced by the reduced levels of MDA. Finally, rutin had a favorable synergistic effect with vitamin C in reducing TG and TNF-α levels and increasing HDL-C level.

Indonesian Propolis Inhibit Proinflammatory Cytokines, Apoptosis and Oxidative Stress in Anthrax Animal Model

BACKGROUND: Anthrax is a zoonotic disease caused by Bacillus anthracis, whose endospores stimulate the release of pro-inflammatory cytokines and promote oxidative stress. Propolis, a natural resource that can be found in Indonesia, has been proven to have anti-apoptotic and antioxidant role which might be a potential adjuvant therapy for anthrax treatment. Hence in this study we aimed to investigate effect of propolis as an anti-inflammatory, anti-apoptotic, and antioxidant in anthrax rats model by examining the level of tumor necrosis factor (TNF)-α, caspase-3, and malondialdehyde (MDA), respectively.METHODS: This was an experimental post-test only study with 40 male rats weighed 180-200 g that were induced by anthrax spores injected subcutaneously. The rats were divided into one control positive group and four intervention groups that were administered with 200 mg/kgBW propolis extract for 7 to 14 days. The levels of serum TNF-α, caspase-3, and MDA were measured using enzyme-linked immunosorbent assay (ELISA) and analyzed with bivariate analysis.RESULTS: TNF-α, caspase-3, and MDA level were found lower in anthrax rats model given ethanol extract of propolis than the control group. The lowest concentration of TNF-α value was found in group administered with propolis extract 200 mg/kgBW for 7 days before the anthrax induction (6.136±0.205 pg/mL). The results were similar to the MDA serum and caspase-3 which were the lowest when the propolis was administered 7 days earlier (1.893±0.188 nmol/mL and 2.040±0.067 ng/mL). There was significant difference in the TNF-α, caspase-3, and MDA serum levels (p≤0.001) compared to control group.CONCLUSION: Propolis has anti-apoptotic and antioxidant effects which can be used as complementary therapy in anthrax infection.KEYWORDS: propolis, anthrax, anti-apoptotic, antioxidants