Effect of immunological stress to neuroendocrine and gene expression in different swine breeds

Immunological stress is the status of animal in active immune when they are challenged by bacterial, virus and endocrine. It is associated with immunological, neurological, and endocrinological response. An immunological stress model was established in this study using Chinese indigenous breed (Laiwu), crossbred (Lulai), and exotic breed (Yorkshire), to explore the capacity of immunological stress resistance among different breeds. The study was also to reveal the effect of chromium yeast to immunological stress. 48 post-weaning piglets were taken from three breeds, 16 piglets of each breed from Laiwu, Lulai and Yorkshire. The experiment was designed as 2 × 2 factors, immunological stress (Saline, LPS) and Chromium (with Cr, without Cr). There were four treatments: control, LPS, Cr, and Cr+LPS. Blood parameters related to immunological stress, such as IL-1β, TNF-α, GH, and cortisol, were examined after blood sample were taken at 0, 2, 5, and 7 h of post-injection. The results showed that IL-1β, TNF-α, and cortisol increased in group of LPS treatment while GH declined at 2 h of post-injection in comparison to the control (p < 0.01). However, IL-1β, TNF-α, and cortisol in group of Cr+LPS were lower than that in group of LPS while GH were higher (p < 0.05). Total RNA was extractedfrom blood lymphocytes separation samples at 2 h of post-injection. Q-PCR was applied to determine the gene expression of IL-1β, IL-6 and TNF-α. The results showed that LPS injection increased the gene expression of IL-1β, IL-6 and TNF-α. Among three breeds, the expression of IL-1β, IL-6 and TNF-α in Yorkshire were significantly higher than in Laiwu and Lulai (p < 0.05), but there was no difference between Laiwu and Lulai. Among four treatments, the expression of three genes in group of LPS was the highest, compared to the group of Cr+LPS (p < 0.05) and control (p < 0.01). This study concluded that Laiwu had stronger capacity of immunological stress resistance and next was Lulai among three breeds. Chromium yeast helped piglets relieve immunological stress.     

Effect of Lycopene Application in Rats with Experimental Diabetes Using Lipoprotein, Paraoxonase and Cytokines

This study was conducted with the purpose of researching the effect of lycopene application on lipoprotein, paraoxonase (PON) and cytokines that are projected to be used in the diagnosis and treatment of diabetes by making experimental diabetes. At the end of a 1-month trial period, under ether anesthesia with jelly tubes, blood samples were taken from rat hearts. Blood samples were centrifuged and serum was obtained. From the serum samples, HbA_1c, paraoxonase activity, lipoprotein levels and cytokines were determined. HbA_1c levels and PON activity were found to be p < 0.001. At the triglyceride level, with regard to the control group, in all the groups a significant rise occurred (p ≤ 0.001). At the cholesterol level, with regard to the control group, a decline was observed in the other groups (p < 0.05). At the VLDL level, with regard to the control group, a significant rise was observed in the other groups (p < 0.05). At the HDL (p < 0.001) and LDL (p < 0.05) levels, with regard to the control group, a significant decline was observed in the other groups. At the TNF-α, IL-2, IL-6 and IL-10 levels no difference was found (p > 0.05). Experimental diabetes models have an important place in analyzing diabetes complications and determining treatment approaches.     

The Effects of Dietary Chromium(III) Picolinate on Growth Performance, Vital Signs, and Blood Measurements of Pigs During Immune Stress

This experiment used 24 pigs (26.0 kg) to investigate the effects of dietary chromium (Cr) on pigs challenged with lipopolysaccharide (LPS). Following 35 days of diet exposure, the immune stress treatments were: (1) phosphate-buffered saline (PBS) injection and no Cr, (2) LPS injection and no Cr, (3) LPS injection and Cr 1,000 ppb, and (4) LPS injection and Cr 2,000 ppb. At 0 h, PBS or LPS was injected intraperitoneally in each pig. During the first 12 h post-injection, pigs challenged with LPS lost 951 g, while the PBS group gained 170 g (p?<?0.001). Compared with the PBS group, LPS-challenged pigs consumed less feed (p?<?0.01) during the first 24 h. The LPS group had higher rectal temperature at 2 and 4 h and higher respiratory rate at 1.3 and 8.5 h than the PBS group (p?<?0.05). Plasma collected at 3 h had higher cortisol (p?<?0.001) and lower glucose (p?<?0.05) concentrations in the LPS group than the PBS group. However, supplemental Cr did not affect the response variables. Overall, the LPS challenge affects growth performance, vital signs, and plasma variables, but dietary Cr is unable to moderate stress-related effects associated with an LPS challenge.     

Serum Trace Elements and Electrolytes Are Associated with Fasting Plasma Glucose and HbA<Subscript>1c</Subscript> in Postmenopausal Women with Type 2 Diabetes Mellitus

The primary aim of the research was to assess the level of trace elements and electrolytes in serum of postmenopausal diabetic women. Sixty-four postmenopausal women with type 2 diabetes mellitus (DM2) and 64 age- and body mass index-matched controls were examined. Serum trace elements were assessed using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). Fasting plasma glucose (FPG) and glycated hemoglobin (HbA_1c) levels were evaluated using Randox kits. The obtained data demonstrate that DM2 patients were characterized by 42 and 34 % higher FPG and HbA_1c levels, respectively (p < 0.001). The level of Cu and Se in diabetic postmenopausal women was increased by 10 and 15 % in comparison to the respective control values (p = 0.002 and <0.001). Serum Mn, Zn, and Ni concentrations were lower than the control ones by 32 % (p = 0.003), 8 % (p = 0.003), and 23 % (p = 0.046), respectively. FPG and HbA_1c levels directly correlated with serum Se (p < 0.001) and Cu (p = 0.014 and p = 0.028) concentrations and inversely related to Zn (p < 0.001) and Tl (p = 0.023 and p = 0.029) levels. Multiple regression analysis demonstrated a significant association between serum Zn and Se and FPG and HbA_1c levels. It is proposed that Zn and Se play an important role in DM2 pathogenesis. Further studies are required to assess the intimate mechanisms of the observed differences.     

Gene Silencing of Selenoprotein K Induces Inflammatory Response and Activates Heat Shock Proteins Expression in Chicken Myoblasts

In the present study, specific small interfering RNA (siRNA) for selenoprotein K (Selk) gene was designed and transfected into chicken myoblasts. Then, the expressions of inflammatory factors (including induced nitric oxide synthase [iNOS], nuclear factor-kappa B [NF-κB], heme-oxygenase-1 [HO-1], cyclooxygenase-2 [COX-2], and prostaglandin E synthase [PTGEs]), inflammation-related cytokines (including interleukin [IL]-1β, IL-6, IL-7, IL-8, IL-17, and interferon [IFN]-γ), and heat shock proteins (HSPs) (including HSP27, HSP40, HSP60, HSP70, and HSP90) were examined at 24 and 72 h after transfection. The results showed that messenger RNA (mRNA) expressions of iNOS, NF-κB, HO-1, COX-2, IL-6, IL-7, IL-8, HSP 27, HSP 40, HSP 60, HSP 70, and HSP 90 were significantly increased (p < 0.05) at 24 and 72 h after siRNA transfection, and the mRNA expressions of PTGEs, IL-1β, IL-17, and IFN-γ were significantly increased and decreased (p < 0.05) at 24 and 72 h after siRNA transfection. The results also showed that the protein expressions of iNOS, NF-κB, HO-1, COX-2, HSP60, HSP70, and HSP90 were significantly increased (p < 0.05) at 24 and 72 h after siRNA transfection. The correlation analysis and principal component analysis (PCA) showed that PTGEs, IL-1β, IL-17, IFN-γ, HSP40, and HSP90 might play special roles in response to Selk silencing in chicken myoblasts. These results indicated that Selk silencing induced inflammation response by affecting the expression levels of inflammatory factors and inflammation-related cytokines, and the heat shock proteins might play protective roles in this response in chicken myoblasts.     

Protein malnutrition during fetal programming induces fatty liver in adult male offspring rats

We evaluated the effects of protein malnutrition on liver morphology and physiology in rats subjected to different malnutrition schemes. Pregnant rats were fed with a control diet or a low protein diet (LPD). Male offspring rats received a LPD during gestation, lactation, and until they were 60 days old (MM group), a late LPD that began after weaning (CM), or a LPD administrated only during the gestation-lactation period followed by a control diet (MC). On day 60, blood was collected and the liver was dissected out. We found a decrease in MM rats’ total body (p < 0.001) and liver (p < 0.05) weight. These and CM rats showed obvious liver dysfunction reflected by the increase in serum glutamic pyruvic transaminase (SGOT) (MM p < 0.001) and serum glutamic pyruvic transaminase (SGPT) (MM and CM p < 0.001) enzymes, and liver content of cholesterol (MM and CM p < 0.001) and triglycerides (MM p < 0.01; CM p < 0.001), in addition to what we saw by histology. Liver dysfunction was also shown by the increase in gamma glutamyl transferase (GGT) (MM, MC, and CM p < 0.001) and GST-pi1 (MM and CM p < 0.001, MC p < 0.05) expression levels. MC rats showed the lowest increment in GST-pi1 expression (MC vs. MM; p < 0.001, MC vs. CM; p < 0.01). ROS production (MM, CM, and MC: p < 0.001), lipid peroxidation (MM, CM, and MC p < 0.001), content of carbonyl groups in liver proteins (MM and CM p < 0.001, MC p < 0.01), and total antioxidant capacity (MM, CM, and MC p < 0.001) were increased in the liver of all groups of malnourished animals. However, MM rats showed the highest increment. We found higher TNF-α (MM and CM p < 0.001), and IL-6 (MM and CM p < 0.001) serum levels and TGF-β liver content (MM p < 0.01; CM p < 0.05), in MM and CM groups, while MC rats reverted the values to normal levels. Pro-survival signaling pathways mediated by tyrosine or serine/threonine kinases (pAKT) (MM and CM p < 0.001; MC p < 0.01) and extrasellular signal-regulated kinase (pERKs) (MM p < 0.01; CM p < 0.05) appeared to be activated in the liver of all groups of malnourished rats, suggesting the presence of cells resistant to apoptosis which would become cancerous. In conclusion, a LPD induced liver damage whose magnitude was related to the developmental stage at which malnutrition occurs and to its length.     

A mechanism of nucleocytoplasmic trafficking for the homeodomain protein PRH

Although subclinical inflammation and oxidative stress are implicated in the aetiology of diabetes, there are hardly any studies in prediabetes. Therefore, we made an attempt to study the gene expression pattern of certain inflammatory/oxidative genes using lymphocytes from Type 2 diabetic patients, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) subjects. Compared to NGT group, interleukin-6, tumor necrosis factor-α (TNF-α), p²²Phox NADPH oxidase, and thioredoxin interacting protein (TXNIP) mRNA levels were higher and suppressor of cytokine signaling (SOCS-3) mRNA was lower in subjects with IGT and diabetes. The mean (±SE) levels of thiobarbituric acid reactive substances and protein carbonyl content were also elevated in glucose intolerant subjects. In multiple linear regression analysis, TXNIP and TNF-α showed a significant association with HbA1c even after adjusting for TBARS and PCO (TXNIP: β = 1.70, P < 0.01; TNF-α: β = 1.86, P < 0.01). Increased subclinical inflammation/oxidation is seen in Asian Indians with not only Type 2 diabetes but also IGT.     

Anti-inflammatory activity of rhein isolated from the flowers of Cassia fistula L. and possible underlying mechanisms

Objective

Anti-inflammatory activity of rhein in animal models with potential mechanism of actions.

Long-term fructose feeding changes the expression of leptin receptors and autophagy genes in the adipose tissue and liver of male rats: a possible link to elevated triglycerides

Long-term fructose consumption has been shown to evoke leptin resistance, to elevate triglyceride levels and to induce insulin resistance and hepatic steatosis. Autophagy has been suggested to function in processes such as lipid storage in adipose tissue and inflammation in liver. Autophagy and the leptin system have also been suggested to regulate each other. This study aimed to identify the changes caused by fetal undernourishment and postnatal fructose diet in the gene expression of leptin, its receptors (LEPR-a, LEPR-b, LEPR-c, LEPR-e and LEPR-f) and autophagy genes in the white adipose tissue (WAT) and liver of adult male rats in order to clarify the mechanism behind the metabolic alterations. The data clearly revealed that the long-term postnatal fructose diet decreased leptin levels (p < 0.001), LEPR (p < 0.001), especially LEPR-b (p = 0.011) and LEPR-f (p = 0.005), as well as SOCS3 (p < 0.001), ACC (p = 0.006), ATG7 (p < 0.001), MAP1LC3β (p < 0.001) and LAMP2 (p = 0.004) mRNA expression in WAT. Furthermore, LEPR (p < 0.001), especially LEPR-b (p = 0.001) and LEPR-f (p < 0.001), ACC (p = 0.010), ATG7 (p = 0.024), MAP1LC3β (p = 0.003) and LAMP2 (p < 0.001) mRNA expression in the liver was increased in fructose-fed rats. In addition, the LEPR expression in liver and MAP1LC3β expression in WAT together explained 55.7 % of the variation in the plasma triglyceride levels of the rats (R _adj. ²  = 0.557, p < 0.001). These results, together with increased p62 levels in WAT (p < 0.001), could indicate decreased adipose tissue lipid storing capacity as well as alterations in liver metabolism which may represent a plausible mechanism through which fructose consumption could disturb lipid metabolism and result in elevated triglyceride levels.     

Neuroprotective Effect of Atorvastatin Involves Suppression of TNF-α and Upregulation of IL-10 in a Rat Model of Intracerebral Hemorrhage

We evaluated the neuroprotective effects of atorvastatin (2, 5, and 10 mg/kg) on experimentally induced intracerebral hemorrhage (ICH) in adult rats; controls were administered PBS. Plasma TNF-α and IL-10 levels before and after ICH were analyzed at various time points by enzyme-linked immunosorbent assay (ELISA) and neurological behavior of rats was assessed by climbing scores. At 3-days postoperatively, brain water contents and TNF-α/IL-10 expression in brain tissue were determined. Histopathological changes and microglial cells in the brain tissue were evaluated by light-microscopy. Post-ICH neurological deficits differed significantly between sham-operated group A and experimental-ICH group B (P < 0.05). Brain water contents were significantly less in group A than in group B (P < 0.05). Significant differences (P < 0.05) between two groups were observed regarding activated microglia, TNF-α and IL-10 levels. Compared with group B, neurological deficits, brain water contents, pathological changes, and activated microglia were reduced (P < 0.05) in groups C (Experimental-ICH + atorvastatin 2 mg/kg), D (Experimental-ICH + atorvastatin 5 mg/kg) and E (Experimental-ICH + atorvastatin 10 mg/kg). Atorvastatin-induced a dose-dependent reduction of TNF-α and increase of IL-10 levels (P < 0.05). Therefore, it was concluded that atorvastatin improved neurofunctional rehabilitation in rats through the suppression of cytokines-mediated inflammatory response and attenuation of brain damage following intracerebral hemorrhage.     

Reduction of Plasma Leptin Concentrations by Arginine but Not Lipid Infusion in Humans

Objective: We examined short-term effects of arginine infusion on plasma leptin in diabetic and healthy subjects. Research Methods and Procedures: Arginine stimulation tests were performed in C-peptide negative type 1 [DM1; hemoglobin A_1c; 7.3 ± 0.3%], hyperinsulinemic type 2 diabetic (DM2; 7.6 ± 0.7%), and nondiabetic subjects (CON; 5.4 ± 0.1%). Results: Fasting plasma leptin correlated linearly with body mass index among all groups (r = 0.61, p = 0.001). During arginine infusion, peak plasma insulin was lower in DM1 than in DM2 (p < 0.05) and CON (p < 0.01). Plasma leptin decreased within 30 minutes by ∼11% in DM1 (p < 0.001), DM2 (p < 0.01), and CON (p < 0.005), slowly returning to baseline thereafter. Plasma free fatty acids (FFAs) were higher in DM1 (0.6 ± 0.1 mM) and DM2 (0.6 ± 0.1 mM) than in CON (0.4 ± 0.1 mM, p < 0.05) and transiently declined by ∼50% (p < 0.05) at 45 minutes in all groups before rebounding toward baseline. To examine the direct effects of FFAs on plasma leptin, we infused healthy subjects with lipid/heparin and glycerol during fasting, and somatostatin-insulin (∼35 pM) -glucagon (∼90 ng/mL) clamps were performed. In both protocols, plasma leptin continuously declined by ∼25% (p < 0.05) during 540 minutes without any difference between the high and low FFA conditions. Discussion: Arginine infusion transiently decreased plasma leptin concentrations both in insulin-deficient and hyperinsulinemic diabetic patients, indicating a direct inhibitory effect of the amino acid but not of insulin or FFAs.     

Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney

The present study was designed to evaluate whether microRNA-146a and its adapter proteins (TRAF6 and IRAK1) are involved in the pathogenesis of diabetes-induced kidney damage. Male Sprague–Dawley rats were divided into control and diabetic groups (n = 6 in each). Diabetes was induced by injection of streptozotocin (55 mg/kg; i.p.) in 12 h fasted rats. Diabetic kidney damage was diagnosed by renal hypertrophy, thickened glomerular basement membrane, widened filtration slits, mesangial expansion, as well as by elevated levels of blood urea and creatinine in diabetic rats 2 months after induction of diabetes. While the expression of NF-κB mRNA and miR-146a were increased in diabetic kidney compared to the sham controls (p < 0.01 for both comparisons), the mRNA levels of IRAK1 and TRAF6 did not statistically reduce. The NF-κB activity and the concentrations of TNF-α, IL-6 and IL-1β in the kidney of diabetic rats were higher than the kidney of controls (p < 0.05 for TNF-α and NF-κB; p < 0.01 for IL-6 and IL-1β). Our results indicate that the upregulation of miR-146a was not accompanied by downregulation of inflammatory mediators in diabetic kidney. It is possible that a defect in the miR-146a-mediated negative loop provides a situation for sustained activation of NF-κB and its targets to promote cells toward abnormalities.     

Oxidized Low Density Lipoprotein and Inflammation in Gout Patients

To analyze the levels of oxidized low density lipoprotein (ox-LDL) and inflammatory cytokines in the plasma of gout patients. The levels of ox-LDL, hypersensitive C-reactive protein (hs-CRP), interleukin-1β, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured in the plasma of 41 gout patients [28 in acute phase episode, 13 in intermittent phase (IP)], and in 40 healthy controls. The relationship between ox-LDL and inflammation was also explored by measuring the levels of several pro-inflammatory cytokines in the plasma. The plasma levels of ox-LDL, hs-CRP, IL-6 and TNF-α were significantly increased in patients with gout in the acute phase compared to those in the IP group and healthy controls (P < 0.05), but the levels of TGF-β were significantly lower in the acute phase group than in the IP group and healthy controls (P < 0.01). The levels of ox-LDL in the gout patients in the IP were significantly higher than those in healthy controls (P < 0.05). Correlation analysis indicated that the levels of ox-LDL were positively correlated with hs-CRP, IL-6 and TNF-α (r = 0.343, r = 0.386, r = 0.659, P < 0.01, respectively), but negatively correlated with TGF-β levels in patients in the acute phase (r = ?0.240, P < 0.05). The levels of ox-LDL in gout patients were significantly higher than those in healthy controls. The changes in ox-LDL levels may be associated with enhanced inflammation in gout patients.     

Copper in Diabetes Mellitus: a Meta-Analysis and Systematic Review of Plasma and Serum Studies

Copper (Cu) is an important trace element involved in oxidative stress, which is associated with the onset and progression of diabetes mellitus (DM). However, clinical studies comparing plasma or serum Cu levels in patients with DM and in healthy individuals report conflicting findings. Therefore, in this meta-analysis, we analyzed the circulating levels of Cu associated with DM (including type 1 diabetes mellitus [T1DM] and type 2 diabetes mellitus [T2DM]). We searched the articles indexed in PubMed, OVID, and Cochrane databases, published through January 2016 and meeting our predefined criteria. Requisite data were extracted, and a random-effect model or a fixed-effect model was used to conduct the meta-analysis. Fifteen eligible studies involving a total of 1079 DM patients and 561 healthy controls were identified. Overall, the DM patients showed higher Cu levels than the healthy controls (plasma Cu mean difference [MD] = 1.69 μmol/L, p < 0.0001; serum Cu MD = 4.06 μmol/L, p = 0.005; plasma and serum Cu MD = 2.67 μmol/L, p = 0.006). Stratification based on the type of diabetes also indicated higher levels of Cu in the plasma and serum of DM patients than in healthy controls, respectively. Stratification of DM patients associated with and without complications also revealed similar results. This meta-analysis suggests that DM patients carried higher levels of Cu than healthy individuals. However, international cohort studies are needed to corroborate our findings.     

Effects of dietary crude protein and tannic acid on rumen fermentation,rumen microbiota and nutrient digestion in beef cattle

The objectives of the trial were to study the effects of dietary crude protein (CP) and tannic acid (TA) on rumen fermentation, microbiota and nutrient digestion in beef cattle. Eight growing beef cattle (live weight 350 ± 25 kg) were allocated in a 2 × 2 crossover design using two levels of dietary CP [111 g/kg dry matter (DM) and 136 g/kg DM] and two levels of TA (0 and 16.9 g/kg DM) as experimental treatments. Each experimental period lasted 19 d, consisting of 14-d adaptation and 5-d sampling. The impacts of dietary CP and TA on ruminal microbiota were analysed using high-throughput sequencing of 16S rRNA gene. Results indicated that no interactions between dietary CP and TA were found on rumen fermentation and nutrient digestibility. Increasing dietary CP level from 111 to 136 g/kg DM increased the ruminal concentrations of ammonia nitrogen (NH₃-N) (p < 0.01) and improved the CP digestibility (p < 0.001). Adding TA at 16.9 g/kg DM inhibited rumen fermentation and decreased the digestibility of dietary CP (p < 0.001), DM (p < 0.05) and organic matter (p < 0.01). Increasing the dietary CP level or adding TA did not affect the relative abundances of the major bacteria Firmicutes and Proteobacteria at the phylum level and Prevotella_1 and Christensenellaceae_R-7_group at the genus level, even though adding TA increased the Shannon index of the ruminal bacterial community. TA was partly hydrolysed to pyrogallol, gallic acid and resorcinol in rumen fluid and the inhibitory effects of TA on rumen fermentation and nutrient digestibility could have been resulted from the TA metabolites including pyrogallol, gallic acid and resorcinol as well as the protein-binding effect.     

Analysis of Influence of Baicalin Joint Resveratrol Retention Enema on the TNF-α, SIgA,IL-2, IFN-γ of Rats with Respiratory Syncytial Virus Infection

Explore the influence of baicalin joint resveratrol retention enema on TNF-α, SIgA, IL-2, and IFN-γ of rats with respiratory syncytial virus (RSV) infection. The 60 SD rats were randomly divided into normal group, model group, baicalin group, resveratrol group, joint group, and ribavirin group. For model group, baicalin group, resveratrol group, joint group, and ribavirin group, rats were given RSV virus suspension intranasally for 3 days, and model group was not given administration. Baicalin group, resveratrol group, joint group, and ribavirin group were, respectively, given baicalin 100 mg/kg/day, resveratrol 30 mg/kg/day, baicalin joint resveratrol, and ribavirin 1 g/kg/day retention enema. After continuously given administration 7 days, rats were measured in serum TNF-α, IL-2, IFN-γ levels and SIgA levels in bronchoalveolar lavage fluid. Model group, TNF-α, IL-2, IFN-γ, and SIgA were significantly higher than the normal group (P < 0.05); Baicalin group, resveratrol group, ribavirin group, TNF-α, IL-2, IFN-γ, and SIgA were significantly higher than the model group (P < 0.05); TNF-α, IL-2 between baicalin group, resveratrol group, ribavirin group, have no significant difference (P > 0.05); Baicalin group, resveratrol group, joint group, IFN-γ, and SIgA were significantly higher than the ribavirin group (P < 0.05); Joint group TNF-α, IL-2, IFN-γ, and SIgA were significantly higher than baicalin group, resveratrol group, and ribavirin group (P < 0.05). Baicalin joint resveratrol retention enema can increase RSV infection model in rats serum TNF-α, IL-2, IFN-γ levels and SIgA levels in bronchoalveolar lavage fluid, which may anti-virus through this mechanism.     

Circulating proinflammatory cytokines and N-terminal pro-brain natriuretic peptide significantly decrease with recovery of left ventricular function in patients with dilated cardiomyopathy

Background Increased levels of TNF-α, IL-6, their soluble receptors, and NT-proBNP have been observed in patients with dilated cardiomyopathy (DCM). In the present study, we assessed the possible involvement of proinflammatory cytokines and their soluble receptors with and without recovery of LV function in DCM patients. Methods and results Forty patients with DCM were enrolled and divided into two groups: Group I consisted of DCM patients (n = 30) whose left ventricular ejection fraction (LVEF) had not recovered on follow up and Group II comprised DCM patients (n = 10) whose LVEF had recovered. Ten healthy subjects were included as controls (Group III). TNF-α, IL-6,TNFR1, TNFRII, gp130, and NT-proBNP levels were significantly increased in Group I and were significantly lower in patients with LVEF recovery as compared to those without recovery of LVEF (P < 0.05). Conclusion Circulating TNF-α, IL-6, and NT-proBNP appear to correlate with the LV function recovery of patients with DCM and could be used as prognostic biomarkers.     

Epigenetic patterns of two gene promoters (TNF-α and PON) in stroke considering obesity condition and dietary intake

Some causal bases of stroke remain unclear, but the nutritional effects on the epigenetic regulation of different genes may be involved. The aim was to assess the impact of epigenetic processes of human tumor necrosis factor (TNF-α) and paraoxonase (PON) promoters in the susceptibility to stroke when considering body composition and dietary intake. Twenty-four patients (12 non-stroke/12 stroke) were matched by sex (12 male/12 female), age (mean 70?±?12 years old), and BMI (12 normal-weight/12 obese; mean 28.1?±?6.7 kg/m²). Blood cell DNA was isolated and DNA methylation levels of TNF-α (?186 to +349 bp) and PON (?231 to +250 bp) promoters were analyzed by the Sequenom EpiTYPER approach. Histone modifications (H3K9ac and H3K4me3) were analyzed also by chromatin immunoprecipitation in a region of TNF-α (?297 to ?185). Total TNF-α promoter methylation was lower in stroke patients (p?<?0.001) and showed no interaction with body composition (p?=?0.807). TNF-α and PON total methylation levels correlated each other (r?=?0.44; p?=?0.031), especially in stroke patients (r?=?0.72; p?=?0.008). The +309 CpG methylation site from TNF-α promoter was related to body weight (p?=?0.027) and the region containing three CpGs (from ?170 to ?162 bp) to the percentage of lipid intake and dietary indexes (p?<?0.05) in non-stroke patients. The methylation of PON +15 and +241 CpGs was related to body weight (p?=?0.021), waist circumference (p?=?0.020), and energy intake (p?=?0.018), whereas +214 was associated to the quality of the diet (p?<?0.05) in non-stroke patients. When comparing stroke vs non-stroke patients regarding the histone modifications analyzed at TNF-α promoter, no changes were found, although a significant association was identified between circulating TNF-α level and H3K9ac with H3K4me3. TNF-α and PON promoter methylation levels could be involved in the susceptibility to stroke and obesity outcome, respectively. The dietary intake and body composition may influence this epigenetic regulation in non-stroke patients.     

A polymorphism in the visfatin gene promoter is related to decreased plasma levels of inflammatory markers in patients with coronary artery disease

Visfatin, a newly identified proinflammatory adipokine, has been linked to coronary artery disease (CAD). The ?1535C>T polymorphism (rs61330082) located in the visfatin gene promoter is reportedly associated with proinflammatory status. However, it is unclear whether this polymorphism correlates with plasma levels of inflammatory markers including visfatin, hs-CRP, IL-6 and TNF-?? in CAD patients. The present study was to investigate the potential association of the ?1535C>T polymorphism with plasma levels of visfatin, IL-6, C reactive protein (hs-CRP) and TNF-?? in patients with CAD. We conducted a hospital based study with 171 CAD patients to examine the association between the ?1535C>T polymorphism and plasma levels of visfatin, hs-CRP, IL-6 and TNF-??. Plasma visfatin levels were markedly different between patients with stable angina pectoris (SAP, 11.91 ± 0.70 ng/l) and those with unstable angina pectoris (UAP, 17.49 ± 0.20 ng/l) or acute myocardial infarction (AMI, 16.63 ± 0.22 ng/l; SAP versus UAP or AMI, P < 0.05). Compared with the CC genotype, variant genotypes CT and TT correlated with significantly lower levels of visfatin, hs-CRP, IL-6 and TNF-?? in the SAP group (P < 0.05), with lower levels of hs-CRP and IL-6 in the UAP group (P < 0.05), and with lower levels of visfatin in the AMI group (P < 0.05) after adjustment for age, gender, smoking, hypertension, diabetes, dyslipidemia and medication. Our results suggest that the ?1535C>T polymorphism is associated with decreased plasma levels of inflammatory markers in CAD patients, reflecting that this polymorphism might provide a useful marker for predicting the development of CAD events.     

Frailty has a stronger association with inflammation than age in older veterans

Background

Upregulation of pro-inflammatory cytokines has not only been associated with increased morbidity and mortality in older adults but also has been linked to frailty. In the current study we aimed to compare the relative relationship of age and frailty on inflammation and thrombosis in older veterans.

Results

We analyzed 117 subjects (age range 62–95 years; median 81) divided into 3 cohorts: non-frail, pre-frail and frail based on the Fried phenotype of frailty. Serum inflammatory markers were determined using commercially available ELISA kits. Frail and pre-frail (PF) subjects had higher levels than non-frail (NF) subjects of IL-6 (NF vs. PF: p?=?0.002; NF vs. F: p?<?0.001), TNFR1 (NF vs. F: p?=?0.012), TNFRII (NF vs. F: 0.002; NF vs. PF: p?=?0.005) and inflammatory index: = 0.333*log(IL-6)?+?0.666*log(sTNFR1) (NF vs. F: p?=?0.009; NF vs. PF: p?<?0.001). Frailty status explained a greater percent of variability in markers of inflammation than age: IL-6 (12 % vs. 0.3 %), TNFR1 (5 % vs. 4 %), TNFR2 (11 % vs. 6 %), inflammatory index (16 % vs. 8 %). Aging was significantly associated with higher fibrinogen (p?=?0.04) and D-dimer levels (p?=?0.01) but only among NF subjects.

Conclusion

In conclusion, these data suggest that among older veterans, frailty status has a stronger association with inflammation and the inflammatory index than age does. Larger studies, in more diverse populations are needed to confirm these findings.