TNF Concentrations Research Articles

Temporal effect of fructose supplementation at different concentrations on hepatic metabolism of Wistar rats.

Introduction: in the last few years important changes have occurred in nutritional patterns. There has been an increase in the consumption of simple carbohydrates such as fructose, which has been associated with numerous metabolic disorders, including hepatic steatosis. Materials and methods: we sought to evaluate the impact of fructose consumption, as diluted in water at different concentrations, for two time periods, on the metabolic parameters of Wistar rats using ANOVA. Results: our data indicate that both time and fructose concentration promote variations in animal body mass, and in food, water, and caloric intake. The time variable influenced the modulation of biochemical parameters such as serum concentrations of glucose and total cholesterol. Both fructose concentration and time of exposure influenced the concentrations of serum triglycerides, creatinine, AST, TNF, and IL-6. When evaluating redox status and oxidative damage markers, we observed that fructose concentration and exposure time had an effect on total glutathione levels, which decreased with an increase in concentration and time. For superoxide dismutase, we evaluated the effects of time and interaction. A significant interaction was observed for TBARS. For carbonylated proteins, exposure time was a fundamental factor in generating an effect. Conclusions: we demonstrated that fructose modulates the parameters of triglycerides and total liver cholesterol, and that time influences the number of hepatocytes. Our data suggest that fructose concentration, exposure time, and an interaction between these two parameters have a significant effect on the metabolic parameters responsible for the development of non-alcoholic fatty liver disease.

Single Nucleotide Polymorphisms in Tumor Necrosis Factor-α and Susceptibility to HIV Infection in Local Population of Lahore Pakistan

A single nucleotide polymorphism (SNP) is observed at -308 position of the promoter region of tumor necrosis factor (TNF- α) gene due to which TNF is categorized into TNF1 and TNF2 allele. TNF2 allele is associated with higher concentration of TNF- α which in turn is associated with HIV infection. In order to know the association between TNF2 and HIV infection n =75 HIV positive samples and n=15 HIV negative samples were observed for TNF polymorphism. It was found that among the infected patients 53 patients had TNF2.The total percentage of the patients and controls having TNF2 allele was found to be 63.34.%. Chi square value was significant showing that there is a strong correlation between HIV susceptibility and TNF SNPs (-308) of the promoter region.

13 Changes in Cytokine Profiles in Response to Ergovaline Exposure in Slick vs. Normal Hair Coat in Beef Heifers

Abstract Fescue toxicosis is a syndrome common in cattle grazing fescue containing an endophyte that produces ergot alkaloids. Our lab has previously demonstrated that chronic exposure of ergot alkaloids adversely effects innate immune response. Therefore, the objective of this study was to examine changes in cytokine profiles in heat tolerant heifers exposed to ergot alkaloids from endophyte-infected fescue compared to wildtype controls. Angus X Senepol heifers were blocked by weight and hair coat genotype, Slick (S) or Normal (N) then randomly fed novel endophyte fescue (EN) or endophyte-infected fescue (EI) haylage in a total mixed ration for 63d (n=5 per group). Weekly measurements were collected to monitor physiological responses during exposure to ergot alkaloids. Blood samples were collected for cytokine analysis on d 0, 14, 28 and 56. Cytokine concentrations were quantified using Quantibody® Bovine Cytokine Arrays. Data were analyzed using PROC MIXED of SAS with repeated measures. Statistical significance was determined at P< 0.05 and a tendency at 0.05< P< 0.10. Concentrations of TNF were greater in EN-S heifers (6.57 ng/ml) compared to other heifer groups (P< 0.05; 1.33, 2.34, 3.15 ng/ml for EN-N, EI-S, and EI-N, respectively). Concentrations of IL21 were greater in EN-S heifers (8.15 ng/ml) compared to other heifer groups (P< 0.05; 1.55, 3.43, 3.26 ng/ml for EN-N, EI-S, and EI-N, respectively). Concentrations of IFNA (P=0.0543), IFNG (P=0.0558), IL1F1 (P=0.0587), and IL1F5 (P=0.0738) tended to be greater in in EN-S heifers compared to other heifer groups. Interestingly, concentrations of chemokine CCL4 (953.5 vs. 183.7 pg/mL) and CXCL9 (2.57 vs. 0.69 ng/mL) were significantly greater in S heifers than N heifers (P< 0.05). No differences were observed for IL13 and CXCL10 (P >0.05). In contrast to previous data, exposure to ergovaline via endophyte-infected fescue, did not induce an innate immune response. Rather, cytokine concentrations were elevated in heifers with the slick hair genotype. Overall, developing a better understanding of the interaction between ergot alkaloids and the slick hair genotype will help to improve cattle health management.

Salivary levels of Interleukin-6, Interleukin-8 and Tumor Necrosis Factor-alpha in Smokers Aged 35-46 Years with Dental Caries Disease

Introduction: Dental caries is one of the most common infectious diseases prevalent in the oral cavity, andit is an inflammatory disease with a multi-factor etiology. IL-6, IL-8, and TNF-? are two types of cytokinesthat are major mediators of acute inflammation, and are necessary for the development of specific immuneresponses.Objective: The present study aimed to assess the level of pro-inflammatory cytokines (IL-6,IL-8,andTNF-?) in the saliva of smokers with dental caries and the control (non-smokers) according to different age,BMI,and sex.Materials and Method: Whole saliva from 32 smokers aged 35-46 years with dental caries and 16 healthysubjects, to measure IL-6,IL-8, and TNF-a levels by enzyme immunoassay (ELISA).Results: The mean BMI, age, and sex between the experimental group and the control group were similar,were not statistically significant (p=0.466, p=0.240, p=0.455), respectively while, there were a significantdifference in CRP between the two groups (p=0.037).Concentrations of salivary IL-6, IL-8 and TNF-? werenot affected by periodontal health. No statistically significant difference in periodontal health, assessed byCPITN, were observed between the groups (p=0.413). Salivary levels of IL-6 and IL-8 were significantlyhigher in smokers with dental caries compared with control (p<0.05).Salivary levels of IL-6 and IL-8were increased significantly in smokers with dental caries compared with control (p<0.05). No significantdifferences in salivary TNF-? in dental caries patients compared to control (p=0.063). The correlationbetween TNF-a, CRP, age, sex, and BMI with IL-8 were positive and statistically significant(p=0.01,p=0.036, p=0.009, p=0.007, and p=0.005), respectively. There was no significant correlation between IL-6and TNF-a cytokines and other parameters, except for a positive association with CRP levels (p=0.006,p=0.043), respectively.Conclusions: These data indicate links between production of tumor necrosis factor-alpha (TNF-a),interleukin-6 (IL-6), and Interleukin-8 (IL-8)in smokers’ saliva and dental caries disease. Also,the existenceof a statistically significant positive correlation between TNF-a,age, gender, and BMI with IL-8.

A cross-sectional study on the correlation between cytokines in a pelvic environment and tubal factor infertility

BackgroundThis cross-sectional study aimed to evaluate the levels of tumor necrosis factor-alpha (TNF-ɑ), interleukin-8 (IL-8), interleukin-6 (IL-6), and transforming growth factor-beta 1 (TGF-β1) in patients with primary and secondary tubal factor infertility (TFI) compared with fertile subjects, and to compare immune indexes in the serum and peritoneal fluid samples obtained from patients with TFI.MethodsThe pelvic fluid and peripheral blood of patients with TFI diagnosed by hysteroscopy and laparoscopy were taken as the study objects. The pelvic fluid and peripheral blood of patients who underwent hysteromyomectomy at the same time were taken as the control group. The contents of TNF-ɑ, IL-8, IL-6, and TGF-β1 in serum and peritoneal fluid were determined by enzyme-linked immunosorbent assay, and the levels of these cytokines in serum and pelvic fluid were compared between the two groups.ResultsPatients with secondary TFI showed significantly higher levels of TNF-ɑ, IL-8, IL-6 and TGF-β1 in the serum (26.15 ± 3.51 vs. 19.61 ± 0.157, 32.18 ± 15.13 vs. 5.73 ± 1.99, 38.84 ± 3.46 vs. 30.48 ± 0.61, and 38.37 ± 3.14 vs. 32.25 ± 1.69, respectively) and peritoneal fluid samples (129.73 ± 183.4 vs. 34.63 ± 0.56, 111.44 ± 207.42 vs. 15.34 ± 0.41, 80.01 ± 109.91 vs. 15.67 ± 0.52, and 82.54 ± 115.99 vs. 45.34 ± 0.41, respectively) compared with the control group. Patients with primary TFI exhibited significantly elevated concentration of TNF-α, IL-8, IL-6 and TGF-β1 in the peritoneal fluid samples (36.88 ± 2.67 vs. 34.63 ± 0.56, 19.47 ± 3.51 vs. 15.34 ± 0.41, 80.01 ± 109.91 vs. 15.67 ± 0.52, and 82.54 ± 115.99 vs. 45.34 ± 0.41, respectively) when compared to the controls. In patients with secondary infertility, the levels of TNF-α (26.15 ± 3.51 vs. 129.73 ± 183.4), IL-8 (32.18 ± 15.13 vs. 111.44 ± 207.42), IL-6 (38.84 ± 3.46 vs. 80.01 ± 109.91) and TGF-β1 (38.37 ± 3.14 vs. 82.54 ± 115.99) in the serum were significantly lower than those in the peritoneal fluid, whereas no significant difference was observed in the primary TFI group between the serum and peritoneal fluid cytokines levels.ConclusionThe expression of cytokines in the pelvic environment of patients with TFI is upregulated compared to patients who do not have infertility issues. The detection of cytokines TNF-ɑ, IL-6, IL-8, and TGF-β1 in the pelvic fluid of tubal infertility patients can allow for further understanding of the etiology of TFI.

Preparation and diagnosis of Xerogel nanocomposites And Studying Their Effect on TNF-? Level before and after Loading Dexamethason in Male White Rats Induced Rheumatoid Arthritis

The current study aimed to evaluate the mechanism of reducing the effect of (RA) after it was induced inmale white rat with a Complete Freund’s Adjuvant (CFA) at TNF-? level by treating Xerogel Nanoparticlesand dexamethasone nanocompounded (Xerogel / Dexa) . The free Xerogel nanoparticle had a surfaceroughness coefficient of 0.327 nm and the total percentage of volumes was 90% less than 130 nm, and theresults also indicated that induced rheumatoid arthritis causes Significant increase (p <0.05) in the meanconcentration of neoplastic necrosis factor (TNF-?) in the blood serum of male white rats, as they reacheda concentration level (10.68 ± 461.80) Pg / ml in the positive control group (G2) for six weeks of treatmentcompared with the negative control group G1)), as the concentration level in it reached (69.97±0.88) Pg /ml for the same period, and there was also a significant decrease (P <0.05) in the level of concentration ofTNF-? among members of the G5 group treated with the Xerogel / Dexa nanoparticle, as this concentrationreached (182.98 ± 6.99 ) Pg / ml compared to the positive control groups (G2) treated with the free Xerogel(G3) and the group treated with free Dexa (G4) for a six-week treatment period in these groups as theseconcentrations reached (461.80± 10.68, 483.74± 3.59, 300.32± 4.03) Pg / ml, respectively

Choice of immunoassay to evaluate porcine cytokine levels

BackgroundIn order to adequately monitor cytokines in experimental models, currently available methods and commercially available kits should be compared. AimTo compare the plasma and tissue concentrations of IL-1β, IL-6, IL-8, IL-10, and TNF as a measure of systemic inflammation in septic pigs. MethodsCytokines were quantified from blood and tissue samples obtained at 0, 60, 120, 180, and 240 min, and in postmortem biopsies of the liver, kidney, lung, heart, and spleen from 26 anesthetized landrace pigs. (24 with experimental sepsis, two sham controls). Porcine-specific ELISAs (R&D) and multiplex (9-plex from Thermo Fischer, 13-plex from Millipore) immunoassays were compared. ResultsThe assays differed for the different cytokines and between blood and tissue. In blood, the highest concentration of TNF and IL-6 was in ELISA, IL-1β equal in ELISA and 13-plex, IL-8 in 13-plex and IL-10 in 9-plex. In tissue, the highest concentration of TNF and IL-1β was in ELISA, IL-6 and IL-8 in 13-plex and IL-10 in 9-plex. ConclusionThe choice of analysis impacts the quantified cytokine responses in porcine models. ELISA and multiplex techniques supplement each other and our data suggest which assays to use for the quantification of the different cytokines.

Cerebrospinal fluid cholinergic biomarkers are associated with postoperative delirium in elderly patients undergoing Total hip/knee replacement: a prospective cohort study

BackgroundPostoperative delirium (POD) is a frequent complication after surgery and its occurrence is associated with poor outcomes. The neuropathology of this complication is unclear, but it is important to evaluate relevant biomarkers for postoperative status. The purpose of this study is to explore the relationship between expression levels of cholinergic biomarkers in cerebrospinal fluid (CSF) and the occurrence and development of POD in elderly patients.MethodsFour hundred and ninety-two elderly patients aged 65 years old or older with elective total hip/knee replacement received combined spinal-epidural anesthesia. Preoperative baseline cognitive function was assessed using the Mini-Mental State Examination (MMSE) before surgery. Each patient was interviewed in post-anesthesia care unit (PACU) and on the first, second, third and seventh (or before discharge) postoperative days. POD was diagnosed using the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Preoperative CSF and plasma choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were determined by ELISA. The levels of ChAT, AChE and BuChE activities were determined by spectrophotometry.ResultsPOD was detected in 11.4% (51/447) of the patients. AChE, BuChE, ChAT, TNF-α and IL-6 concentrations in CSF and plasma have higher consistency. In preoperative CSF and preoperative and postoperative plasma, down-regulation of the concentration and activity of AChE and BuChE as well as up-regulation of the concentration and activity of ChAT and the concentrations of IL-6 and TNF-α were observed in patients who developed POD, and the decrease in BuChE was the most obvious. Logistic analysis showed the activities of ChAT, AChE and BuChE in CSF were still related to POD after adjusting for related factors such as sex, age, years of education, height, weight, body mass index (BMI), and American Society of Anesthesiologists (ASA) class. Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the Area Under Curve (AUC) of AChE, BuChE and ChAT activity in CSF was 0.679 (P < 0.01), 0.940 (P < 0.01) and 0.819 (P < 0.01) respectively and found that BuChE activity had the most accurate diagnostic value.ConclusionThe changes in preoperative activity of AChE, BuChE and ChAT in CSF were associated with the development of POD in elderly patients, and BuChE activity had the greatest diagnostic value, which may be related to central cholinergic degradation. These cholinergic biomarkers might participate in the neuropathology of POD, pending further investigations.Trial registrationThis study was registered at Chictr.org.cn (NO. ChiCTR1900023729) June 9th, 2019. (Retrospectively registered).

Computational modelling of TNF\u03b1 related pathways regulated by neuroinflammation, oxidative stress and insulin resistance in neurodegeneration

Computational and mathematical modelling towards understanding the structure and dynamics of biological systems has significantly impacted on translational neuroscience to face novel approaches toward neurological disorders such as Alzheimer’s (AD) and Parkinson’s disease (PD). In this study, a computational model of AD and PD have been modelled using biochemical systems theory, and shows how Tumour Necrosis Factor alpha (TNF훼) regulated neuroinflammation, oxidative stress and insulin pathways can dysregulate its downstream signalling cascade that lead to neurodegeneration observed in AD and PD. The experimental data for initial conditions for this model and validation of the model was based on data reported in literature. In simulations, elevations in the aggregations of major proteins involved in the pathology of AD and PD including amyloid beta, alpha synuclein, tau have been modelled. Abnormal aggregation of these proteins and hyperphosphorylation of tau were observed in the model. This aggregation may lead to developing Lewy bodies, fibrils, plaques and tangles inside neurons that trigger apoptosis. An increase in the concentrations of TNF훼 and glutamate during diseased conditions was noted in the model. Accumulation of these proteins may be related to the feedback mechanism of TNF훼 that initiates its own release and the production of excess glutamate. This could lead to the prolonged activation of microglia that result in death of surrounding neurons. With the elevation in reactive oxygen species, oxidative stress also increased. Simulations suggest insulin may be an important factor identifying neurodegeneration in AD and PD, through its action along with the neuroinflammation and oxidative stress. Low insulin level was noticed in the diseased condition due to abnormal protein aggregation that leads to TNFα release. Given the role towards better design of real experiments, accumulation of oligomers of mutated proteins in AD and PD activating microglia and secreting TNFα along with other cytokines map to oxidative stress that led to cell death.

Influence of urokinase gene knockout on levels of TNF- α and its receptors in the brain of mice with experimental melanoma developing in presence of chronic neurogenic pain

Background. Despite the functional multiplicity and complexity of TNF- α effects, its role in the central nervous system in the development of various pathological conditions of the body is still poorly understood. Objective. Analyzing the dynamics of TNF- α and its receptors in the brain of urokinase (uPA-) gene-knockout mice with malignant growth in presence of chronic neurogenic pain (CNP). Design and methods . The study included male and female mice of two strains: C57BL/6 (n = 80) and C57BL/6-PlautmI.IBug-ThisPlau6FDhu/ GFDhu (n = 56). A CNP model was created in animals of the main groups by the bilateral sciatic nerve ligation; 2 weeks after it, B16/F10 melanoma was transplanted under the skin of the back. The comparison group — sham operated animals with transplanted melanoma. Control groups — sham operated animals and animals with CNP. On day 21 of the melanoma growth, the mice were decapitated, and levels of TNF- α, sTNF- α R1 and sTNF- α R2 were determined in the cerebral tissues by ELISA. Results. High levels of TNF- α (by 5.6 times) and low TNF- α R1 (by 2.1 times) were registered in the brain of uPA- males, while no changes were registered in females. Under the influence of CNP, brain levels of TNF- α became similar in male and female mice; TNF- α levels in uPA- mice were twice higher than in animals with the normal genome. The CNP stimulating effect on the malignant process in uPA- mice was based: in females — on an increase in the cerebral concentration of TNF- α R2 (by 1.7 times, p&lt;0.05), in males — on TNF- α reduction (by 2.2 times). Conclusion. The specificity of the fibrinolytic status of mice determines the course of subcutaneously transplanted melanoma in presence of pain, and one of the mechanisms of this phenomenon involves a change in the functioning of the brain TNF- α system, depending on the animal gender.

Clinical and immunological monitoring of gingival fluid cytokines in patients with perimplantitis during photodynamic therapy

The effect of FDT on the processes of mucosal immunity, in particular, the cytokine profile, remains practically unstudied.Objective:clinical and immunological assessment of the effectiveness of FDT in the complex treatment of periimplantitis at the initial stage of the relief of the inflammatory process.Materials and research methods.The study included patients who contacted the dental institutions of the Republic of Dagestan and the clinic of the Department of Surgical Dentistry of Moscow State Medical University aged 20 to 49 years with a diagnosis of periimplantitis, a total of 61 people. 33 patients received the ABT (the main group 1), 28 patients received the PDT (the main group 2). The control group consisted of 76 patients with stable implants without signs of inflammation or periodontitis (intact periodontium). The concentration of cytokines TNF, IL-1β, IL-6, and IL-17A in the oral fluid was determined by ELISA twice using the INFINITE F50 analyzer (TECAN, Austria) and test systems (Vector-Best, Novosibirsk, Russia). Results. Differences in the state of the cytokine profile in ABT (amoxicillin / sodium clavulanate at 825/125 mg 2 times a day for 7 days) and PDT (FotoSan 350 apparatus, photosensitizer toluidine blue: 4 sessions every 1 day for 40 sec) were found. The maximum cytokine response was observed in the evaluation of IL-1β (137–139 pg/ml) and IL-17A (161–172 pg/ml). After 1 month, statistically significant differences were revealed between the groups of patients with periimplantitis receiving different treatment options. The level of TNF-α decreased by 2.5 times and corresponded to the norm in the case of PDT, but with ABT it remained significantly higher, although we also observed a downward trend. The level of IL-17A showed a statistically significant decrease in PDT, while in ABT, the decrease was not significant. 3 months after treatment, complete normalization of the levels of TNF-α, IL-6 and IL-17A was observed in both compared groups, with the exception of IL-1β, which remained elevated: 8.6 times with PDT and 25 times with ABT.Conclusion.The cytokine profile of gingival fluid in periimplantitis is an important diagnostic marker for the severity of inflammation, which can confirm the presence of periimplantitis and predict the course. The content of IL-1β and IL-17 A reflects the severity of the process. Restoring normal levels of IL-1β is slower than IL-17 A.

Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome

AIMS:Investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor- (TNF-) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers and the effect of the course use of the combined metabolic drug Kokarnit as part of complex therapy on the dynamics of the severity of symptoms of DSPN and the cytokine phenotype in patients with long-term non-healing ulcers of the lower extremities&#x0D; MATERIALS AND METHODS:121 patients with T2DM, 79 without diabetic foot syndrome (DFS) and 42 patients with DFS were included. CD14+ monocytes were isolated from patients blood and stimulated by interferon- (IFN-) and interleukine-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF- and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation in all patients before taking the combined metabolic drug Kokarnit. Then they were randomly allocated either to the control group (57 people), to whom Kokarnit was added to standard treatment, or to the comparison group. After a 9-day course of application of Kokarnit, the dynamics of indicators was evaluated on a TSS scale. Assessment of cytokine status was carried out in 18 people with long-term non-healing ulcerative defects of the lower extremities, on the first and ninth day of treatment.&#x0D; RESULTS:A correlation was found between HbA1cand levels of stimulated secretion of TNF (r=0.726, p=0.027), CCL18 (r=-0.949, p=0.051) in patients with DSPN. In all patients with different duration of VDS, an increase in secretion of TNF- and CCL18 was observed (p0.05). However, stimulation of anti-inflammatory activation was not observed in patients with ulcerative defects lasting more than 6 months (p=0.033). The use of cocarnit in these patients had a decrease in stimulated secretion of TNF and an increase in CCL18. Throughout the entire observation period with the therapy, the score for the symptoms of polyneuropathy on the TSS scale in patients of the control group was statistically significantly higher.&#x0D; CONCLUSION:Against the background of therapy in patients of the main group, a statistically significant dynamics of indicators on the TSS scale was established. The cytokine modulating ability of Kokarnit to switch the cytokine status into the category of anti-inflammatory.

Predictive value of TNF-\u03b1, IFN-\u03b3, and IL-10 for tuberculosis among recently exposed contacts in the United States and Canada

BackgroundWe examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis.MethodsWe prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays.ResultsOf 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P < .01; IFN-γ 231 versus 27, P < .001), and those who subsequently developed incident tuberculosis had higher median baseline TNF-α concentrations (in pg/mL, 257 vs. 71, P < .05). In multivariate analysis, contact age < 15 years, US/Canadian birth, and IFN or TNF concentrations > the median were associated with co-prevalent tuberculosis (P < .01 for each); female sex (P = .03) and smoking (P < .01) were associated with incident tuberculosis. In algorithms combining young age, positive skin test results, and elevated CFPS TNF-α, IFN-γ, and IL-10 responses, the positive predictive values for co-prevalent and incident tuberculosis were 40 and 25%, respectively.ConclusionsCytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis.

Adipose tissue macrophage burden, systemic inflammation, and insulin resistance.

Adipose tissue inflammation, as defined by macrophage accumulation, is proposed to cause insulin resistance and systemic inflammation. Because the strength of this relationship for humans is unclear, we tested whether adipose tissue macrophage (ATM) burden is correlated with these health indicators. Using immunohistochemistry, we measured abdominal subcutaneous CD68+ (total ATM), CD14+ (proinflammatory/M1), and CD206+ (anti-inflammatory/M2) ATM in 97 volunteers (BMI 20-38 kg/m2, in addition to body composition, adipocyte size, homeostasis model assessment of insulin resistance, ADIPO-IR, adipose tissue insulin resistance measured by palmitate, plasma lipids, TNF, and IL-6 concentrations. There were several significant univariate correlations between metabolic parameters to IL-6 and ATM per 100 adipocytes, but not ATM per gram tissue; adipocyte size was a confounding variable. We used matching strategies and multivariate regression analyses to investigate the relationships between ATM and inflammatory/metabolic parameters independent of adipocyte size. Matching approaches revealed that the groups discordant for CD206 but concordant for adipocyte size had significantly different fasting insulin and IL-6 concentrations. However, groups discordant for adipocyte size but concordent for ATM differeded in that visceral fat, plasma triglyceride, glucose, and TNF concentrations were greater in those with large adipocytes. Multivariate regression analysis indicated that indexes of insulin resistance and fasting triglycerides were predicted by body composition; the predictive value of ATM per 100 adipocytes or per gram tissue was variable between males and females. We conclude that the relationship between ATM burden and metabolic/inflammatory variables is confounded by adipocyte size/body composition and that ATM do not predict insulin resistance, systemic inflammation, or dyslipidemia. ATM may primarily play a role in tissue remodeling rather than in metabolic pathology.

Characterization of The Surgical Leakage Collected After Breast Cancer Surgery and Studying Their Effect on Breast Cancer Cell Line

Globally, breast cancer is the most common cancer in women and the second leading cause of death. The choice of breast cancer treatment is based on its clinical staging. Although there is a development in the adjuvant of systemic treatments, surgery is a primary choice for treatment. One of those complications is surgical leakage which is suggested to have many cell growth factors, cytokines, and chemokines in order to tissue repair process. Many studies reported that surgical leakage may have a role in tumor progression and local recurrence by inducing the lasting cancer cells. Invasion and metastasis are one of several cellular mechanisms in cancer development and progression through secretions of many inflammatory mediators. For example, TNF-α is one of the inflammatory mediators that up-regulates the expression and secretion of proteases (such as matrix metalloproteinases MMPs family) which are involved in carcinoma cell motility, invasion, and metastasis. Indeed the role of TNF-α in cancer progression and metastasis is depending on its ability to produce and stimulate (MMP) which have a role in tumor angiogenesis, invasion and metastasis process. Also one of TNF-α function is to induce epithelial-mesenchymal transition (EMT) process which known to occur through embryogenesis, metastasis. Previous studies by the authors showed that TNF- α is highly expressed and secreted by tumor microenvironment by Egyptian cancer patients. Using different concentrations of recombinant TNF-α, we test the morphological changes of cancer cells from a round shape to spindle shape (migratory cells), in addition, we studied how different concentrations of TNF- α induce invasion and migration on MDA-MB-231 breast cancer cell line using Matrigel Invasion chambers.

Врожденный иммунитет у больных эссенциальной артериальной гипертонией и эффективность антигипертензивной фармакотерапии

The purpose of the study was to assess the parameters of innate immunity in patients with essential arterial hypertension and to establish a relationship with the effectiveness of antihypertensive pharmacotherapy. Materials and methods. The study included 48 patients with essential arterial hypertension stage II, arterial hypertension 2 degree and hypertrophy of the left ventricular myocardium, which were divided into 2 groups: the first group (25 patients) - these are patients whose blood pressure reached the target values, and the second group (23 patients) are patients whose blood pressure did not reach the target values against the background of antihypertensive therapy (perindopril - 5 mg/day and amlodipine - 5 mg/day) (group 2). Indicators of 18 healthy donors were used as a comparison group (control group). Results. In patients with essential arterial hypertension of group 1, compared with the control group, the concentration of IL-1α, IL-6, IL-8, IL-10, IL-1 receptor antagonist, IL-2, C4- and C5a-components of the complement system and factor H is significantly higher and the level of C3 is lower-component of the complement system. In patients with essential arterial hypertension of group 2, more pronounced changes in the cytokine link of the immunity and the complement system were established before the start of antihypertensive therapy. After the antihypertensive therapy in patients with essential arterial hypertension of the 1st group in the blood plasma, the concentration of TNF, IL-1α, IL-8, IL-10, IL-1 receptor antagonist significantly decreased, but not to the values of the control group, and in patients of the 2nd group, the effectiveness of antihypertensive therapy in correcting parameters innate immunity was found to be less effective. Conclusion. Revealing the participation of innate immunity indicators in the formation of arterial hypertension opens up new possibilities for the pathogenetic therapy of this disease and developing measures to prevent or level the damage to target organs.

Cytokine profile in cows with necrobacterious fi ngers

Orthopedic diseases in cows signifi cantly reduce the profitability of dairy cattle breeding, causing signifi cant technological and economic damage. The aim of the study was to establish a cytokine profi le in cows with necrobacterioses of fi nger lesions. The work was performed in typical dairy farms, on cows with various clinical forms of purulent-necrotic lesions of the extremities of a necrobacterious nature. Diagnostic studies included a complex of clinical, bacteriological biopsy samples of purulent-necrotic foci and determination of the level of cytokines in the blood using enzyme-linked immunosorbent assay. A bacteriological study revealed various associations of F. necrophorum with E. coli, Clostridium spp., Diplococcus lans., Staphylococcus aureus and streptococci, which verifi ed the necrobacterious nature of limb lesions in cows. It was established that in cows with an acute course of purulent-necrotic infl ammatory process in the fi nger area, the concentrations of TNF-α and IL-10 sharply increase. The generalized form of necrobacillary lesions is characterized by a critical increase in the level of TNF-α in the blood by 16.8 times, IL-1β by 17.8 times compared with its level in the acute form of the concentration of IL-10. The cytokine index IL-10: TNF-α acquired a critical value of 0.4: 1, and IL-10 to IL-1β - 1: 1. The development of uncontrolled phlogogenic cytokinemia is noted, which refl ects a systemic infl ammatory response syndrome. A recurrent type of purulent-necrotic lesion of the extremities is characterized by rather low levels of IL-1β and IL-10. The content of IL-1β was 2.4 times greater (p &lt;0.05). However, the concentration of TNF remained quite large and prevailed over the norm by 12.6 times (p &lt;0.001), which was refl ected in the extremely low corresponding index of 0.3: 1. That is, in this case, in a chronic course of necrobacteriosis of the extremities of cows, uncompensated permanent cytokinemia due to TNF-α is formed, which leads to the recurrent nature of the purulent-necrotic process. So, the mechanism of development of the cytokine profi le in cattle requires further research. Key words: phlogogenic and anti-infl ammatory purulent-necrotic lesions, cytokines, cows, infl ammation, fi ngers.

High-frequency repetitive transcranial magnetic stimulation improves functional recovery by inhibiting neurotoxic polarization of astrocytes in ischemic rats

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment for ischemic stroke. Astrocytes regulation has been suggested as one mechanism for rTMS effectiveness. But how rTMS regulates astrocytes remains largely undetermined. There were neurotoxic and neuroprotective phenotypes of astrocytes (also denoted as classically and alternatively activated astrocytes or A1 and A2 astrocytes) pertaining to pro- or anti-inflammatory gene expression. Pro-inflammatory or neurotoxic polarized astrocytes were induced during cerebral ischemic stroke. The present study aimed to investigate the effects of rTMS on astrocytic polarization during cerebral ischemic/reperfusion injury.MethodsThree rTMS protocols were applied to primary astrocytes under normal and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Cell survival, proliferation, and phenotypic changes were assessed after 2-day treatment. Astrocytes culture medium (ACM) from control, OGD/R, and OGD/R + rTMS groups were mixed with neuronal medium to culture neurons for 48 h and 7 days, in order to explore the influence on neuronal survival and synaptic plasticity. In vivo, rats were subjected to middle cerebral artery occlusion (MCAO), and received posterior orbital intravenous injection of ACM collected from different groups at reperfusion, and at 3 days post reperfusion. The apoptosis in the ischemic penumbra, infarct volumes, and the modified Neurological Severity Score (mNSS) were evaluated at 1 week after reperfusion, and cognitive functions were evaluated using the Morris Water Maze (MWM) tests. Finally, the 10 Hz rTMS was directly applied to MCAO rats to verify the rTMS effects on astrocytic polarization.ResultsAmong these three frequencies, the 10 Hz protocol exerted the greatest potential to modulate astrocytic polarization after OGD/R injury. Classically activated and A1 markers were significantly inhibited by rTMS treatment. In OGD/R model, the concentration of pro-inflammatory mediator TNF-α decreased from 57.7 to 23.0 рg/mL, while anti-inflammatory mediator IL-10 increased from 99.0 to 555.1 рg/mL in the ACM after rTMS treatment. The ACM collected from rTMS-treated astrocytes significantly alleviated neuronal apoptosis induced by OGD/R injury, and promoted neuronal plasticity. In MCAO rat model, the ACM collected from rTMS treatment decreased neuronal apoptosis and infarct volumes, and improved cognitive functions. The neurotoxic astrocytes were simultaneously inhibited after rTMS treatment.ConclusionInhibition of neurotoxic astrocytic polarization is a potential mechanism for the effectiveness of high-frequency rTMS in cerebral ischemic stroke.

Effect of Topical Simvastatin Therapy on Patients with Psoriasis

Objective: Study the effect of simvastatin ointment on tissue expression of inflammatory mediators associated with pathogenesis of Psoriasis such as TNF-?, , IL-6 and ICAM-1. Background: Psoriasis is a common and complex inflammatory disease, which was described as the chronic systemic T-cell-mediated inflammatory condition characterized by the skin and joint manifestation. The patients with psoriasis are usually presented with a white-silvery scaly lesion covering various parts of the body. In psoriatic lesions, epidermal Keratinocytes produce a variety of inflammatory mediators, such as TNF-?, IL-6, ICAM-1 will stimulate the abnormal proliferation which will cause the psoriasis characteristics to appear. Simvastatin is an anti-hyperlipidemic agent that acts by competitive, reversible inhibition of the HMG-CoA, the rate-limiting step in cholesterol biosynthesis. Materials and Method: The study has been carried out on 44 patients suffering from mild to moderate chronic plaque psoriasis; patients with plaque psoriasis will be randomly divided into two groups, the first group was the Placebo group (n 22) whose patients have directed to have placebo plus topical steroid (Dermosalic ointment) ® ( Betamethasone dipropionate 0.5 mg /g and salicylic acid 30 mg /g) two times for a period of 8 weeks. The second group was the Simvastatin group (n-22) whose patients have been directed to have Simvastatin ointment 5% two times per day in addition to (Dermosalic ointment)® ( Betamethasone dipropionate 0.5 mg /g and salicylic acid 30 mg /g) for a period of 8 weeks. Before and after the eight weeks; The skin biopsy samples have been taken from patients in the two groups at baseline and after eight weeks of treatment used to measure concentrations of TNF-?, IL-6, and ICAM-1. Conclusion: The present study indicated the fact that Simvastatin ointment plus topical steroid improvement of psoriasis by reduce concentration of inflammatory mediators.

EphB4/ TNFR2/ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-\u03b1 on osteogenic differentiation

BackgroundLow concentrations of tumor necrosis factor-alpha (TNF-α) and its receptor TNFR2 are both reported to promote osteogenic differentiation of osteoblast precursor cells. Moreover, low concentrations of TNF-α up-regulate the expression of EphB4. However, the molecular mechanisms underlying TNF-α-induced osteogenic differentiation and the roles of TNFR2 and EphB4 have not been fully elucidated.ResultsThe ALP activity, as well as the mRNA and protein levels of RUNX2, BSP, EphB4 and TNFR2, was significantly elevated in MC3T3-E1 murine osteoblast precursor cells when stimulated with 0.5 ng/ml TNF-α. After TNFR2 was inhibited by gene knockdown with lentivirus-mediated shRNA interference or by a neutralizing antibody against TNFR2, the pro-osteogenic effect of TNF-α was partly reversed, while the up-regulation of EphB4 by TNF-α remained unchanged. With EphB4 forward signaling suppressed by a potent inhibitor of EphB4 auto-phosphorylation, NVP-BHG712, TNF-α-enhanced expressions of TNFR2, BSP and Runx2 were significantly decreased. Further investigation into the signaling pathways revealed that TNF-α significantly increased levels of p-JNK, p-ERK and p-p38. However, only the p-ERK level was significantly inhibited in TNFR2-knockdown cells. In addition, the ERK pathway inhibitor, U0126 (10 μM), significantly reversed the positive effect of TNF-α on the protein levels of RUNX2 and BSP.ConclusionsThe EphB4, TNFR2 and ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation.