Correlation between long-term in vivo amalgam restorations and the presence of heavy elements in the dental pulp

ProjectTo measure the levels of heavy metals (Hg, Sn) in the dental pulp and blood samples of patients with long-term amalgam restorations.Procedure12 amalgam restored and 12 non-restored, sound teeth were chosen and access cavity preparation to the pulp chamber was made. The contents were transferred and dissolved in 5 mL of concentrated nitric acid followed by placement in an oven at 180 °C for tissue digestion. After cooling the tubes each digested sample was transferred to an atomic absorption system to measure the levels of heavy metals. The blood samples of five patients in each group were randomly analyzed to determine the levels of these heavy metals in the blood and if there were a correlation between these levels in blood and pulp. Data were analyzed by t-test at a P < 0.05 level of significance.ResultsNo significant difference was seen between the levels of Hg and Sn in pulp tissues (P > 0.05); however, the blood analysis showed higher level of Hg amalgam group (P = 0.009). The analysis between the pulp and blood samples showed positive correlations for both Hg and Sn elements in dental pulp and the blood (P = 1.000) (P = 0.900).ConclusionsThe long-term presence of dental amalgam (at least 5 years) did not result in any remarkable changes in the levels of mercury and tin in the pulp tissue; however, there were increases in the level of mercury in the blood circulation even five years following the placement of the restoration.     

Vocal fold fibroblasts immunoregulate activated macrophage phenotype

Recent evidence suggests that fibroblasts play a critical role in regulating inflammation during wound healing because they express several inflammatory mediators in response to bacteria. The objective of this study was to analyze the effects of lipopolysaccharide (LPS) on the immunomodulatory properties of vocal fold fibroblasts (VFFs) derived from polyps, scar and normal tissue co-cultured with macrophages, to provide insight into their interactions during the inflammatory process. Fibroblasts were co-cultured with CD14+ monocytes and after 7 days, wells were treated with LPS for 24 and 72 h. Culture supernatants were collected and concentrations of TNF-α, IL-6, IL-8, IL-10, IL-12, IL-1β and MCP-1 were quantified by ELISA. Normal VFF and CD14+ monocultures were used as controls. Twenty-four hours after LPS activation, macrophages co-cultured with polyp VFF had significantly increased expression of TNF-α, IL-1β, IL-12 and IL-10 compared to controls (p < 0.0001). In contrast, macrophages co-cultured with scar VFF had significantly lower expression of TNF-α, IL-1β and IL-12 with significantly higher IL-10 compared to control (p < 0.0001). After 72 h, macrophages co-cultured with polyp VFF increased expression of TNF-α, IL-1β, IL-10, IL-6, IL-8, MCP-1 and TGF-β (p < 0.01) and macrophages co-cultured with scar VFF significantly decreased their expression of IL-1β and IL-12 compared to control (p < 0.0001). Scar VFF at both time points produced significantly lower levels of IL-8, MCP-1, IL-6 and TGF-β compared to controls (p < 0.05). Based on our findings, VFF and macrophages secrete several inflammatory mediators that modify their diverse functions. Polyp and scar VFF may play a role in regulating abnormal inflammatory responses, which could result in excessive ECM deposition that disrupts the function of the vocal folds.     

Vasoactive intestinal peptide (VIP) differentially affects inflammatory immune responses in human monocytes infected with viable Salmonella or stimulated with LPS

We compared the effect of VIP on human blood monocytes infected with Salmonella typhimurium 4/74 or stimulated with LPS. VIP (10⁻⁷ M) increased monocyte viability by 24% and 9% when cultured for 24 h with 4/74 or Salmonella LPS (100 ng/ml), respectively. Significantly increased (P < 0.05) numbers of 4/74 were also recovered from monocytes co-cultured with VIP after 6 h post-infection (pi) and this remained high after 24 h pi. Both 4/74 and LPS increased (P < 0.05) the concentration of TNF-α, IL-1β and IL-6 measured in monocyte supernatants. However, LPS induced this effect more rapidly while, with the exception of IL-6, 4/74 induced higher concentrations (P < 0.05). VIP significantly decreased (P < 0.05) TNF-α and IL-1β production by 4/74-infected monocytes after 6 pi, but only after 24 h in LPS-cultured monocytes. This trend was reversed for IL-6 production. However, TNF-α and IL-1β production by 4/74-infected monocytes, cultured with VIP, still remained higher (P < 0.05) than concentrations measured in supernatants cultured only with LPS. VIP also increased (P < 0.05) production of anti-inflammatory IL-10 in both 4/74 and LPS cultures after 24 h. We also show a differential effect of VIP on the expression of TNFα and IL-6 receptors, since VIP was only able to decreased expression in LPS-stimulated monocytes but not in 4/74-infected monocytes.In conclusion, we show a differential effect of VIP on human monocytes infected with virulent Salmonella or stimulated with LPS. Our study suggests that the use of VIP in bacteraemia and/or sepsis may be limited to an adjunctive therapy to antibiotic treatment.     

Cytokine expression profile over time in burned mice

The persistent inflammatory response induced by a severe burn increases patient susceptibility to infections and sepsis, potentially leading to multi-organ failure and death. In order to use murine models to develop interventions that modulate the post-burn inflammatory response, the response in mice and the similarities to the human response must first be determined. Here, we present the temporal serum cytokine expression profiles in burned mice in comparison to sham mice and human burn patients. Male C57BL/6 mice were randomized to control (n = 47) or subjected to a 35% TBSA scald burn (n = 89). Mice were sacrificed 3, 6, 9, 12, 24, and 48 h and 7, 10, and 14 days post-burn; cytokines were measured by multi-plex array. Following the burn injury, IL-6, IL-1β, KC, G-CSF, TNF, IL-17, MIP-1α, RANTES, and GM-CSF were increased, p < 0.05. IL-2, IL-3, and IL-5 were decreased, p < 0.05. IL-10, IFN-γ, and IL-12p70 were expressed in a biphasic manner, p < 0.05. This temporal cytokine expression pattern elucidates the pathogenesis of the inflammatory response in burned mice. Expression of 11 cytokines were similar in mice and children, returning to lowest levels by post-burn day 14, confirming the utility of the burned mouse model for development of therapeutic interventions to attenuate the post-burn inflammatory response.     

Interleukin (IL)-19 promoted skin wound healing by increasing fibroblast keratinocyte growth factor expression

BackgroundInterleukin (IL)-19, a member of the IL-10 cytokine family, is involved in keratinocyte proliferation in psoriasis.ObjectivesWe investigated the role of IL-19 in the wound-healing process in vivo and in vitro.MethodsTwo full-thickness circular wounds (4 mm in diameter) were punched into the skin of BALB/C mice. IL-19 and keratinocyte growth factor (KGF) mRNA in wounded skin were determined using real-time PCR. The wounds were treated with PBS, vehicle, IL-19 (400 ng/mL), or IL-20 (400 ng/mL) (n = 6 in each group) twice daily and the percentage of wound healing was measured daily for 7 days. In vitro, human skin fibroblast CCD966-SK cells and keratinocyte HaCaT cells were treated with IL-19 or KGF. Cell proliferation and migration were determined using bromodeoxyuridine (BrdU) and transwell assays, respectively. The expression of IL-19 and KGF mRNA was also analyzed.ResultsIn wounded mouse skin, IL-19 mRNA was upregulated at 12 h, and KGF at 24 h after the injury. Both increases in gene expression declined 72 h after the skin had been wounded. The percentage of wound healing in IL-19-treated mice was higher than in control mice. In vitro, IL-19 upregulated KGF expression in the CCD966-SK cells; IL-19 was upregulated in KGF-treated HaCaT cells. KGF but not IL-19 promoted HaCaT cell proliferation. However, IL-19 significantly increased the migration of HaCaT cells. HaCaT cells treated with the cultured supernatants of IL-19-stimulated CCD966-SK cells showed significantly more proliferation than in controls.ConclusionsIL-19 is important for cutaneous wound healing because it upregulates KGF expression.     

Neutrophil CD64 expression and serum IL-8: Sensitive early markers of severity and outcome in sepsis

The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24 h of septic onset, Interleukins (IL)-8, -1β, -6, -10, and -12p70, tumor necrosis factor-α (TNF-α), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p < 0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p < 0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p < 0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR = 1.3, p = 0.01 for CD64 and OR = 1.26, p = 0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.     

Importance of IL-10 and IL-6 during chronic hepatitis c genotype-1 treatment and their relation with IL28B

This paper investigates serum levels of interleukin 10 (IL-10) and interleukin 6 (IL-6) in patients with chronic hepatitis C genotype 1 (CHC-GT1), the relation of each with clinical and virological characteristics, how they affect the response to combined therapy and their relation with the IL28B polymorphisms rs12979860. Serum level expression and the polymorphism of IL-10, IL-6 and IL28B were determined in 138 CHC-GT1 patients, treated with pegylated interferon/ribavirin (pegIFN-α/RBV) for 48 weeks, in the following samples: baseline, week-12 (during treatment) and week-72 (post-treatment). 77 patients (56%) presented Sustained Virological Response (SVR) and 61 (44%) were non-SVR. Multivariate logistic regression showed that age ? 40 years (aOR = 3.7, 95%CI = 1.5–8.9, P = 0.004), low activity of gamma glutamyl transferase (GGT) (aOR = 0.9, 95%CI = 0.98–0.99, P = 0.028), CC genotype of IL28B polymorphim (aOR = 2.7, 95%CI = 1.0–7.2, P = 0.044) and low IL-6 (aOR = 0.5, 95%CI = 0.3–1.0, P = 0.038) were predictor factors of virological response. In all patients, following treatment, IL-6 decreased at week-12 (P = 0.004) from baseline and had returned to basal values at week-72. Serum IL-10 concentration was significantly decreased at week-72 only in SVR patients (P ? 0.001). When patients were stratified by IL28B polymorphisms rs12979860 CC vs non-CC patients, a statistically significant decrease in IL-10 at week-72 in both groups was observed (P = 0.003 and P ? 0.001, respectively). None of the polymorphisms of IL-10 or IL-6 studied were associated with SVR.ConclusionsCC genotype of IL28B and low IL-6 serum concentration are factors associated independently with SVR. Moreover, decreased IL-10 at week-72 is associated with SVR in both CC and non-CC patients, and both factors are important to determine the effectiveness of treatment.     

The roles of aerobic exercise training and suppression IL-6 gene expression by RNA interference in the development of insulin resistance

ObjectiveTo demonstrate the hypothesis that aerobic exercise training inhibits the development of insulin resistance through IL-6 and probe into the possible molecular mechanism about it.MethodsRats were raised with high-fat diets for 8 weeks to develop insulin resistance, and glucose infusion rates (GIRs) were determined by hyperinsulinemic–euglycemic clamping to confirm the development of insulin resistance. Aerobic exercise training (the speed and duration time in the first week were respectively 16 m/min and 50 min, and speed increased 1 m/min and duration time increased 5 min every week following it) and/or IL-6shRNA plasmid injection (rats received IL-6shRNA injection via the tail vein every two weeks) were adopted during the development of insulin resistance. The serum IL-6, leptin, adiponectin, fasting blood glucose, fasting serum insulin, GIR, IL-6 gene expression levels, p-p38 in various tissues and p-STAT3/t-STAT3 ratio in the liver were measured.ResultsRats fed with high-fat diets for 8 weeks were developed insulin resistance and the IL-6mRNA levels of IL-6shRNA injection groups in various tissues were significantly lower than those of control group (P < 0.05), respectively. The development of insulin resistance in exercise rats significantly decreased, however, compared with that, the GIR of exercise rats injected by IL-6shRNA was lower (P < 0.05). The IL-6mRNA levels were highest in the fat tissue and lowest in the skeletal muscles in all the rats. The serum adiponectin levels decreased (P < 0.05) following the development of insulin resistance, and it increased (P < 0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time. However, there were not significant differences when serum leptin concentrations were compared (P > 0.05). The p-p38 significantly increased in the rats fed with high-fat diets, however, p-p38 of the exercise high-fat diets rats in the liver and fat tissues significantly decreased than that (P < 0.05). The changes of p-p38 in exercise rats injected by IL-6shRNA were irregular. The activation of STAT3 in the liver significantly increased (P < 0.05) following the development of insulin resistance, and it decreased (P < 0.05) when the rats were intervened by aerobic exercise training for 8 weeks at the same time, and the gene silencing of IL-6 did not have effects on the activation of STAT3 in the liver (P > 0.05).ConclusionsIn conclusion, aerobic exercise training prevented the development of insulin resistance through IL-6 to a certain degree. The gene expression and secretion of IL-6 could inhibit the development of insulin resistance. The mechanism of the effects were possibly related with elevating the levels of serum adiponectin, and/or inhibiting the activation of STAT3 in the liver and p38MAPK in the skeletal muscles, liver and fat tissues.     

Photoactivated disinfection (PAD) of dental root canal system – An ex-vivo study

AimTo investigate the efficacy of photo activated disinfection (PAD) in reducing colony-forming unit (CFU) counts of Enterococcus faecalis (E. faecalis) in infected dental root canals. The study compared the efficacy of PAD with conventional endodontic treatment (CET) and also a combination of CET along with PAD.Material and Methods53 maxillary incisors were taken for the study. Teeth were divided into 3 groups, CET (Group I) (n = 11), PAD (Group II) (n = 21), and a combination of CET and PAD (Group III) which consisted of (n = 21) samples, Group II and Group III were further divided into 2 subgroups, Group IIa, IIb and Group IIIa, IIIb. Strains of E. faecalis were inoculated in all the root canals. CET group samples were treated by chemo-mechanical preparation (CMP) alone, PAD samples were treated with laser alone at 2 different exposure time (4 min and 2 min). In the combination treatment, samples were treated initially by CET and then by PAD for a time period of 4 min and 2 min. Contents of the root canal were aspirated, diluted and plated in Tryptone Soya Broth (TSB) and plates were incubated for 24 h to observe the bacterial regrowth.ResultsShowed PAD used along with CMP reduced the bacterial load of E. faecalis by 99.5% at 4 min and 98.89% at 2 min.ConclusionPAD may be an adjunctive procedure to kill residual bacteria in the dental root canal systems after standard endodontic root canal preparation.     

Chemical compositions and characteristics of organic compounds in propolis from Yemen

Propolis is a gummy material made by honeybees for protecting their hives from bacteria and fungi. The main objective of this study is to determine the chemical compositions and concentrations of organic compounds in the extractable organic matter (EOM) of propolis samples collected from four different regions in Yemen. The propolis samples were extracted with a mixture of dichloromethane and methanol and analyzed by gas chromatography–mass spectrometry (GC–MS). The results showed that the total extract yields ranged from 34% to 67% (mean = 55.5 ± 12.4%). The major compounds were triterpenoids (254 ± 188 mg g⁻¹, mainly α-, β-amyryl and dammaradienyl acetates), n-alkenes (145 ± 89 mg g⁻¹), n-alkanes (65 ± 29 mg g⁻¹), n-alkanoic acids (40 ± 26 mg g⁻¹), long chain wax esters (38 ± 25 mg g⁻¹), n-alkanols (8 ± 3 mg g⁻¹) and methyl n-alkanoates (6 ± 4 mg g⁻¹). The variation in the propolis chemical compositions is apparently related to the different plant sources. The compounds of these propolis samples indicate that they are potential sources of natural bio-active compounds for biological and pharmacological applications.     

Severe preeclampsia: Association of genes polymorphisms and maternal cytokines production in Brazilian population

IntroductionPreeclampsia (PE) is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Healthy pregnancy is associated with a controlled inflammatory process, which is exacerbated in PE in response to excessive placental stimuli. Gene expression levels can affect inflammation and immune regulation. It is known that differences in cytokine allele frequencies amongst populations may contribute to difference in the incidence of several diseases.ObjectiveThe aim of this study was to investigate the frequency of TNF-α, IL-6, IFN-γ and IL-10 genes polymorphisms and their relationship with the cytokines plasma levels in PE.MethodsA total of 281 women were included in this study; 116 with severe PE, 107 normotensive pregnant and 58 non-pregnant women. Cytokine genotyping was carried out by the polymerase chain reaction. The analyzed polymorphisms were: TNF-α (−308 G → A), IL-10 (−1082 G → A), IL-6 (−174 G → C), and IFN-γ (+874 A → T). Cytokine plasma levels were measured by Cytometric Bead Array method.ResultsA higher frequency of the IFN-γ (+874) T/T genotype in severe PE comparing to normotensive pregnant women was found (P < 0.001). TNF-α, IL-6 and IFN-γ plasma levels were higher in PE women compared to non-pregnant women (P < 0.001; P < 0.001; P = 0.004). IL-6 and IFN-γ levels were also higher in PE women compared to normotensive pregnant (P < 0.001; P = 0.010). IL-10 levels were higher in normotensive pregnant women compared to PE (P < 0.001). IFN-γ and IL-6 genes polymorphisms influenced the genic expression in PE and normotensive pregnant women, respectively.ConclusionsThese results suggest that IFN-γ seems to play a role in PE occurrence.     

Tumor Necrosis Factor-α, Interleukins-12(p40), 6, and 10 levels in cerebrospinal fluid and outcome prediction in Ossimi sheep with encephalitic listeriosis

Encephalitic listeriosis in sheep is a life-threatening disease. However, little is known about the cytokine response and their predictive value in this disease. The aim of present study was to assess the prognostic significance of Tumor Necrosis Factor-α (TNF-α), Interleukin-12(p40) (IL-12 p40), Interleukin-6 (IL-6), and Interleukin 10 (IL-10) levels in cerebrospinal fluid (CSF) in sheep with encephalitic listeriosis. Fifty-nine ewes in 14 flocks were diagnosed clinically as having listeriosis. CSF was collected and subjected to bacteriological examination and estimation of selected cytokines. Twenty-eight ewes were confirmed to be infected with Listeria monocytogenes. Based on antimicrobial sensitivity test, sheep were treated and the outcome was recorded as survivors (n = 10) and non-survivors (n = 18). Cutoff points for CSF cytokines were determined by Receiver operating characteristic analysis (ROC). Association between levels of CSF cytokines and outcome of listeriosis was assessed by logistic regression. TNF-α, IL-6 and IL-12(p40) levels as well as TNF-α/IL-10 ratio were significantly higher in non-survivors than survivors (p = 0.002, 0.0021, 0.0033, and 0.001, respectively). However, IL-10 level was significantly lower in non-survivors than survivors (p = 0.0058). ROC analysis revealed that IL-6 and TNF-α/IL-10 ratio had the highest AUC values (0.98, 0.984, respectively). Final multivariate logistic regression model showed that TNF-α/IL-10 ratio was the only variable that has predictive value for mortality in diseased sheep (p: 0.001; OR: 7.2; 95% CI: 5.7–9.8). TNF-α showed a positive correlation with IL-12β (r = 0.917) and IL-6 (r = 0.965). IL-12 (p40) showed also a positive correlation with IL-6 (r = 0.906). However, IL-10 showed a negative correlation with TNF-α (r = −0.915), IL-12(p40) (r = −0.790), and IL-6 (r = −0.902). In conclusion, TNF-α/IL-10 ratio may provide predictive information about outcome of encephalitic listeriosis in sheep.     

Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

AimImbalance of T-helper-cell (TH) subsets (TH1/TH2/TH17) and regulatory T-cells (Tregs) is suggested to contribute to the pathogenesis of Systemic lupus erythematosus (SLE). Therefore, we evaluated their cytokine secretion profile in SLE patients and their possible association with disease activity.MethodsSixty SLE patients, 24 rheumatoid arthritis (RA) patients and 24 healthy volunteers were included in this study. Demographic, clinical, disease activity and serological data were prospectively assessed. Plasma cytokines levels of TH1 (IL-12, IFN-γ), TH2 (IL-4, IL-6, IL-10), TH17 (IL-17, IL-23) and Treg (IL-10 and TGF-β) were measured by enzyme linked immunosorbent assays (ELISA).ResultsSLE patients were found to have significantly higher levels of IL-17 (p < 0.001), IL-6 (p < 0.01), IL-12 (p < 0.001) and IL-10 (p < 0.05) but comparable levels of IL-23 and IL-4 and slight reduction (but statistically insignificant) of TGF-β levels compared to controls. IL-6, IL-10 and IL-17 were significantly increased (p < 0.05) with disease activity. The RA group exhibited significantly higher levels of plasma IL-4 (p < 0.01), IL-6 (p < 0.05), IL-17 (p < 0.001), IL-23 (p < 0.01) and TGF-β (p < 0.5) and lower IFN-γ (p < 0.001) and IL-10 (p < 0.01) than those of healthy subjects.ConclusionOur study showed a distinct profile of cytokine imbalance in SLE patients. Reduction in IFN-γ (TH1) and TGF-β1 (Treg) with the elevation in IL-6 and IL-17 (TH17) could imply skewing of T-cells toward TH17 cells. Breaking TH17/Treg balance in peripheral blood may play an important role in the development of SLE and could be responsible for an increased pro-inflammatory response especially in the active form of the disease.     

Inactivation of IL-6 and soluble IL-6 receptor by neutrophil derived serine proteases in cystic fibrosis

The ability of IL-6 to signal via both membrane bound and soluble receptors is thought to explain the capacity of this cytokine to act in both the initiation and resolution of acute inflammatory responses. In cystic fibrosis (CF), poorly resolved neutrophillic inflammation of the lungs is a primary cause of morbidity and mortality. Expression of IL-6 has been reported to be low in CF lung secretions, despite ongoing inflammation, but the status of soluble IL-6 receptor (sIL-6R) in these patients is unknown. We hypothesised that sIL-6R may be an important potentiator of IL-6 activity in CF associated lung disease. IL-6, sIL-6R and sgp130 (a natural antagonist of responses mediated by the sIL-6R) were analysed by ELISA and Western blot in bronchoalveolar lavage fluid (BALF) from 28 paediatric CF patients and nine non-CF controls. Total cell counts in CF were four fold higher compared to controls (median: 1.4 × 10⁶ cells/ml v. 0.35 × 10⁶ cells/ml in controls) (p < 0.001) and the infiltrate was dominated by neutrophils which were elevated by 89 fold (0.62 × 10⁶ cells/ml v. 0.007 × 10⁶ cells/ml in controls) (p < 0.001). Other markers of inflammation such as IL-8 and MCP-1 were elevated 17.5 and 3.8 fold respectively (IL-8; median: 1122 pg/ml v. 64 pg/ml in controls, p < 0.01 and MCP-1; median: 692 pg/ml v. 182 pg/ml in controls, p < 0.05). IL-6, although present in 23/32 CF BALF specimens compared to 1/9 controls (p < 0.01), was weakly expressed (median: 50 pg/ml). Expression of sIL-6R and sgp130 in CF was no different to control patients. We tested whether weak expression of all three molecules was due to degradation by CF BALF. Degradative activity was observed in association with BALF elastase activity and could be specifically blocked by serine protease inhibitors. Degradation of sIL-6R by purified serine proteases (elastase, cathepsin G and proteinase 3) was also observed leading to a loss of trans-signalling activity. Interestingly, sIL-6R was protected from proteolysis by interaction with IL-6. Our data identify and define a novel protease mediated deficiency of IL-6 signalling in the CF lung.     

Expression of IL-32 modulates NF-κB and p38 MAP kinase pathways in human esophageal cancer

BackgroundEsophageal cancer is the seventh leading cause of cancer death in males in USA, and there is a strong link has been demonstrated between inflammation and esophageal cancer, interleukin (IL)-32 is a recently described pro-inflammatory cytokine characterized by the induction of nuclear factor NF-κB activation, the p38MAPK also plays an important role in key cellular processes related to inflammation and cancer. We investigated whether the IL-32 expression may be involved in esophageal carcinogenesis through modulates the activity of NF-κB and p-p38 MAPK.MethodMalignant esophageal tissue and blood samples were obtained from 65 operated untreated patients, normal samples was obtained from 35 patients operated for other reasons as control. IL-32 expression visualized by immunohistochemistry, Real time RT–PCR for IL-32 mRNA expression, NF-κB phosphorylation and phosphorylated p38mapk were analyzed by immunoblotting, ELISA for further detection IL-32 and cytokines (TNF-α, IL-1β, IL-6 and IL-8) concentration in the patient’s sera.ResultsIL-32 expression was increased in immunohistochemical staining for malignant esophageal tissue and it’s correlated with the relative expression level of IL-32 mRNA P = 0.007, the P-NF-κB level elevated in tumor tissue compared with control and no difference in the total NF-κB level P = 0.003 while the IL-32 up-regulated the P-pNF-κB in the esophageal tumor P = 0.005. There is increase in p-p38MAPK activation underlying IL-32 expression in tumor P = 0.004, but no change in total p38 MAPK in malignant esophagus. The plasma level of IL-32 expression was increased in malignant esophageal patients P = 0.01, with increased in the levels of the cytokines TNF-α, IL-6, and IL-1β P<0.05.ConclusionsUnderstanding the pathway of IL-32 expression to stimulate the secretion cytokines via the activation of NF-κB and up-regulation of p-p38MAPK may or may not prove to be a therapeutic target, or a biomarker, and future studies will finally answer this hypothesis generated.     

Antidepressant- and anxiolytic-like activities of an oil extract of propolis in rats

PurposePropolis biological effects are mainly attributed to its polyphenolic constituents such as flavonoids and phenolic acids that were recently described in the chemical composition of an extract of propolis obtained with edible vegetal oil (OEP) by our group. The aim of this study was to evaluate the effect of OEP on the behavior of rats.Materials and methodsAn in vivo open field (OF), elevated Plus-maze (EPM), and forced swimming (FS) tests were performed to evaluate locomotor activity, anxiolytic- and antidepressant effects of the extract. Besides, oxidative stress levels were measured in rat blood samples after the behavioral assays by evaluation of the Trolox equivalent antioxidant capacity (TEAC) and nitric oxide levels.ResultsOEP increased locomotion in the OF test (50 mg/kg) and central locomotion and open arm entries in the OF and EPM tests (10–50 mg/kg) and decreased the immobility time in the FS test (10–50 mg/kg). Moreover, OEP reduced nitric oxide levels in response to swim stress induced in rats.ConclusionOEP exerted stimulant, anxiolytic and antidepressant effects on the Central Nervous System and antioxidant activity in rats, highlighting propolis as a potential therapeutic compound for behavior impairment of anxiety and depression.     

The relationship between interleukin-6 in saliva,venous and capillary plasma,at rest and in response to exercise

IL-6 plays a mechanistic role in conditions such as metabolic syndrome, chronic fatigue syndrome and clinical depression and also plays a major role in inflammatory and immune responses to exercise. The purpose of this study was to investigate the levels of resting and post exercise IL-6 when measured in venous plasma, saliva and capillary plasma. Five male and five females completed 2 separate exercise trials, both of which involved standardized exercise sessions on a cycle ergometer. Venous blood and saliva samples were taken immediately before and after Trial A, venous and capillary blood samples were taken immediately before and after Trial B. IL-6 values were obtained using a high-sensitivity enzyme-linked immunosorbent assay (ELISA). In Trial A venous plasma IL-6 increased significantly from 0.4 ± 0.14 pg/ml to 0.99 ± 0.29 pg/ml (P < 0.01) while there was no increase in salivary IL-6. Venous plasma and salivary IL-6 responses were not correlated at rest, post exercise or when expressed as an exercise induced change. In Trial B venous and capillary plasma IL-6 increased significantly (venous: 0.22 ± 0.18 to 0.74 ± 0.28 pg/ml (P ⩽ 0.01); capillary: 0.37 ± 0.22 to 1.08 ± 0.30 pg/ml (P < 0.01). Venous and capillary plasma responses did not correlate at rest (r = 0.59, P = 0.07) but did correlate post exercise (r = 0.79, P ⩾ 0.001) and when expressed as an exercise induced change (r = 0.71, P = 0.02). Saliva does not appear to reflect systemic IL-6 responses, either at rest or in response to exercise. Conversely, capillary plasma responses are reflective of systemic IL-6 responses to exercise.     

Variations of chemical element composition of bee and beekeeping products in different taxons of the biosphere

Geographical variations in element composition of bee products are poorly investigated though a lot of attempts are made to utilize the data in ecological monitoring. So the comparison of chemical element composition of bee and beekeeping products in different taxons of the biosphere may become valuable to test the efficiency of such approach. For this purpose content of 25 elements in bee body, bee bread, propolis and honey from Ribnitsa district of Moldavia (unpolluted area, control), Henty province of Mongolia (selenium deficient area) and Voskresensk district of Moscow region (mineral fertilizers production) were determined by means of the ICP-MS. Among 3 investigated regions Mongolia was characterized by the lowest Se levels and the highest accumulation of Al, Ca, Cd, Cu, Co, K, Mn, Mg, Na, Ni, P, Zn and V in bee bodies. The highest levels of Pb, Cr, Fe, Si, Sr and B, Se, Li, Sn were typical for Voskresensk and Moldavia bees accordingly. The highest correlation coefficients were registered between element concentrations in bee body and bee bread (r = +0.97–0.99, P < 0.0001), less significant – in bee body and propolis (r = +0.5–0.7; P < 0.001) and no correlation was demonstrated between element composition of bee body and honey. Propolis was characterized by significantly higher capacity to accumulate Pb, Cr, Sn and Al than bee body. Compared to bee body honey accumulated the lowest level of Mn and the highest of Si in Se-deficient Mongolia but the opposite phenomenon was demonstrated in Moldavia with moderately increased Se content in the environment. The results suppose that the most promising object for ecological monitoring is bee body. Element composition of propolis seems to reflect prolonged accumulation of elements, especially Pb, Al, Sn and Cr, by plant resin rather than dynamic temporal elements loading. Accumulation levels of elements in bee bread may be used on a par with bee body mineral content only in cases with equal honey content in bee bread. Honey utilization in monitoring of geochemical elements loading should be used with caution due to peculiarities of pollen/nectar elements distribution.     

The −251A>T polymorphism of interleukin-8 is associated with longer mechanical ventilation and hospital staying after coronary surgery

Background: Cardiac surgery is associated with inflammatory responses that are known to affect its outcome. The present study was designed to define whether post-operative release of interleukin (IL)-6, 8 and tumor necrosis factor-alpha (TNF-α) is related to the presence of a certain allele in functional polymorphism and its relationship to clinical outcome after off-pump coronary artery bypass (OPCAB). Methods: One hundred and forty-five patients undergoing first time elective OPCAB were genotyped for IL-6(−174G>C), IL-8(−251A>T) and TNF-α(−308G>A) polymorphisms using polymerase chain reaction (PCR) and gene sequencing. Cytokine levels were measured in plasma samples taken before the operation and 4, 24 and 72 h postoperatively by suspension array system. Results: Levels of IL-6 and IL-8 increased significantly after OPCAB. Patients with IL-6−174GG and IL-8−251AA genotypes had higher post-operative circulating levels of IL-6 and IL-8, respectively. Logistic regression showed that IL-8−251AA genotype was an independent risk factor of ventilation time more than 1 day (OR = 11.80, 95% CI: 1.87–74.48) and hospital staying more than 14 days (OR = 38.00, 95% CI: 4.15–347.87) after surgery. Conclusions: OPCAB results in post-operative inflammatory responses. Genetic backgrounds alter the extent of inflammatory response and might relate to clinical outcome of OPCAB.     

Depot-specific modulation of adipokine levels in rat adipose tissue by diet-induced obesity: The effect of aerobic training and energy restriction

The present study examined the effects of aerobic training and energy restriction on adipokines levels in mesenteric (MEAT) and retroperitoneal (RPAT) white adipose tissue from obese rats. Male Wistar rats were fed with standard laboratory diet (Control group) or high fat diet (HFD). After 15 weeks, HFD rats were randomly assigned to the following groups: rats submitted to HFD, which were sedentary (sedentary HFD, n = 8) or trained (trained HFD, n = 8); or submitted to energy-restriction (ER), which were sedentary (sedentary ER, n = 8) or trained (trained ER, n = 8). Trained rats ran on a treadmill at 55% VO_2max for 60 min/day, 5 days/week, for 10 weeks. ER rats were submitted to a reduction of 20% daily caloric ingestion compared to the Control group. ER and aerobic training decreased body weight, MEAT and RPAT absolute weight, and fat mass. IL-6, IL-10 and TNF-α levels were decreased and adiponectin did not change in RPAT in response to ER protocol. On the other hand, ER and the aerobic training protocol decreased IL-6, TNF-α and adiponectin levels in MEAT. Absolute MEAT weight showed a positive correlation with IL-6 (r = 0.464), TNF-α (r = 0.508); and adiponectin (r = 0.342). These results suggest a tissue-specific heterogeneous response in adipokines level. The combination of the protocols (aerobic training and energy restriction) did not induce an enhanced effect.