Plasma Concentrations Of TNF-α Research Articles

Inflammatory phenotype, clinicopathologic variables, and effects of long-term methylene blue in dogs with hereditary methemoglobinemia caused by cytochrome b5 reductase deficiency

To determine whether dogs with cytochrome b5 reductase (CYB5R) deficiency have a constitutive proinflammatory phenotype, characterize hematologic and serum chemistry results, and describe changes in methemoglobin (MetHb) levels and serum C-reactive protein (CRP) concentrations after long-term per os (PO) methylene blue (MB) therapy. 21 client-owned dogs (CYB5R deficient, n = 10; healthy controls, 11). In this prospective, case-control study, methemoglobin levels were measured using a blood gas analyzer with co-oximetry. Plasma tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were measured using a canine-specific multiplex bead-based assay. Serum CRP concentrations were measured with a canine-specific commercial ELISA kit. Serum CRP concentration and MetHb levels were measured in 6 dogs with CYB5R deficiency after ≥ 60 days of PO MB therapy. As expected, MetHb levels were higher in dogs with CYB5R deficiency compared to controls (P < .001). Plasma TNF-α, IL-6, IL-10, and serum CRP concentrations were no different between CYB5R-deficient and control dogs. Dogs with CYB5R deficiency had lower absolute lymphocyte (P = .005) and eosinophil counts (P = .04) and higher alanine transaminase (P = .04) and alkaline phosphatase activity (P = .02) than controls, but these changes were not clinically relevant. Methemoglobin levels decreased after PO MB therapy (P = .03). These results suggest that otherwise healthy dogs with CYB5R deficiency do not have a constitutive proinflammatory phenotype and clinically relevant abnormalities in hematologic and serum chemistry panels are not expected. Dogs with decreased quality of life attributed to methemoglobinemia from CYB5R deficiency might benefit from PO MB therapy.

Circulating Monocytes Serve as Novel Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma Patients.

Pancreatic ductal adenocarcinoma (PDAC) ranks among the most fatal cancer diseases, widely accepted to have the most dismal prognoses. Although immunotherapy has broadly revolutionized cancer treatment, its value in PDAC appears to be relatively low. Exhibiting protumoral effects, monocytes have recently been proposed as potential targets of such immunotherapeutic regimens. However, to date, the body of evidence on monocytes’ role in PDAC is scarce. Therefore, we analyzed monocytes in the peripheral blood of 58 PDAC patients prior to surgery and compared them to healthy individuals. PDAC patients showed increased levels of monocytes when compared to healthy controls In addition, patients with perineural infiltration demonstrated a higher percentage of monocytes compared to non-infiltrating tumors and PDAC G3 was associated with higher monocyte levels than PDAC G2. Patients with monocyte levels > 5% were found to have an 8.9-fold increased risk for a G3 and perineural infiltrated PDAC resulting in poorer survival compared to patients with <5% monocyte levels. Furthermore, PDAC patients showed increased expressions of CD86 and CD11c and decreased expressions of PD-L1 on monocytes compared to healthy individuals. Finally, levels of monocytes correlated positively with concentrations of IL-6 and TNF-α in plasma of PDAC patients. Based on our findings, we propose monocytes as a novel prognostic biomarker. Large-scale studies are needed to further decipher the role of monocytes in PDAC and investigate their potential as therapeutic targets.

Цитомегаловирусная инфекция как фактор риска неблагоприятных сердечно-сосудистых событий у больных с хронической сердечной недостаточностью

The purpose — to study the effect of cytomegalovirus (CMV) infection on the production of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and its relationship with functional status in patients with chronic heart failure (CHF) of ischemic genesis. Material and methods. We examined 187 patients with CHF of ischemic etiology, hospitalized in the cardiology department for decompensated heart failure (functional class (FC) CHF II-IV). Subsequently, patients were prospectively monitored for 24 months. The end point was a combined one and was defined as an increase by 1 or more in the FC of CHF (according to NYHA), hospitalization for decompensation of CHF, progressive deterioration of the structural and functional parameters of the left ventricle during the study period, the occurrence of adverse clinical events (cardiovascular death, non-fatal myocardial infarction or acute cerebrovascular accident, pulmonary embolism) during 24 months of prospective observation. After stabilization of patients upon inclusion in the study, plasma concentrations of TNF-α and IL-1β were determined by enzyme-linked immunosorbent assay. Qualitative determination of cytomegalovirus DNA in blood was carried out using the polymerase chain reaction method. Results. Based on the results of quantitative determination of CMV DNA, patients were divided into two groups: group 1 — seropositive (CMV+) (n = 128) and group 2 — seronegative (CMV-) (n = 59). In seropositive patients, functional class IV of CHF was significantly more often recorded (p &lt; 0.035), as well as higher levels of TNF-α (p &lt; 0.001) and IL-1β (p &lt; 0.001) regardless of the FC of CHF. In the group of patients with positive CMV serostatus, adverse cardiovascular events were recorded significantly more often during 24 months of observation compared to seronegative patients: there was a significantly higher number of hospitalizations due to decompensation of CHF (p = 0.023), development of acute coronary syndrome (p = 0.031) and pulmonary embolism (p = 0.042), and lethal cases (p = 0.018). Conclusion. High levels of proinflammatory cytokines in patients with CHF correlate with carriage of CMV infection. Seropositive patients have an increased risk of adverse cardiovascular events compared to seronegative patients with CHF.

ANGPTL4, IL-6 and TNF-α as regulators of lipid metabolism during a marathon run

The aim of the study was to reveal whether marathon running influences regulators of lipid metabolism i.e. angiopoietin-like protein 4 (ANGPTL4), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α). Plasma concentration of ANGPTL4, IL-6, TNF-α and lipids were determined in samples collected from 11 male runners before the marathon, immediately after the run and at 90 min of recovery. Plasma ANGPTL4 increased during exercise from 55.5 ± 13.4 to 78.1 ± 15.0 ng/ml (P < 0.001). This was accompanied by a significant increase in IL-6, TNF-α, free fatty acids (FFA) and glycerol (Gly) and a decrease in triacylglycerols (TG). After 90 min of recovery ANGPTL4 and TG did not differ from the exercise values, while plasma IL-6, TNF-α, FFA and Gly concentration were significantly lower. The exercise-induced increase in plasma concentration of ANGPTL4 correlated positively with the rise in plasma IL-6, TNF-α, FFA and Gly and negatively with the duration of the run. The increase in plasma IL-6 and TNF-α correlated positively with the rise in Gly. Summarizing, marathon running induced an increase in plasma ANGPTL4 and the value was higher in faster runners. The increase in plasma FFA, IL-6 and TNF-α concentration during a marathon run may be involved in plasma ANGPTL4 release, which could be a compensatory mechanism against FFA-induced lipotoxicity and oxidative stress. All of the analyzed cytokines may stimulate lipolysis during exercise.

Anti-Inflammatory Protein Isolated from Tamarind Promotes Better Histological Aspects in the Intestine Regardless of the Improvement of Intestinal Permeability in a Preclinical Study of Diet-Induced Obesity.

Obesity is associated with metabolic and physiological effects in the gut. In this study, we evaluated the anti-inflammatory effect of trypsin inhibitor isolated from tamarind seeds (TTI) in vitro (interaction with lipopolysaccharide (LPS) and inhibitory activity against human neutrophil elastase (HNE)), and using intestinal co-cultures of Caco-2:HT29-MTX cell lines inflamed with TNF-α (50 ng/mL) and a Wistar rat model of diet-induced obesity (n = 15). TTI was administered to animals by gavage (10 days), and the treated group (25 mg/kg/day) was compared to animals without treatment or treated with a nutritionally adequate diet. In the in vitro study, it showed inhibitory activity against HNE (93%). In co-cultures, there was no protection or recovery of the integrity of inflamed cell monolayers treated with TTI (1.0 mg/mL). In animals, TTI led to lower plasma concentrations of TNF-α and IL-6, total leukocytes, fasting glucose, and LDL-c (p &lt; 0.05). The intestines demonstrated a lower degree of chronic enteritis, greater preservation of the submucosa, and greater intestinal wall thickness than the other groups (p = 0.042). Therefore, the better appearance of the intestine not reflected in the intestinal permeability added to the in vitro activity against HNE point to possibilities for new studies and applications related to this activity.

Effects of oxidized soybean oil on the performance of sows and jejunum health of suckling piglets.

Oils provide a considerable amount of energy to the swine diet, but they are prone to lipid oxidation if not properly preserved. Consumption of oxidized oils can adversely affect the animal organism and even the offspring. This study investigated the impact of oxidized soybean oil in the diets of sows from 107 days gestation to 21 days of lactation on the performance of sows and jejunum health of suckling piglets. Sixteen sows were randomly allocated into two groups: one group (n = 8) was fed with the fresh soybean oil (FSO) diet, and another group (n = 8) was treated with the oxidized soybean oil (OSO) diet. Dietary oxidized soybean oil does not affect sow performance. Antioxidant enzyme activity in the milk was reduced significantly in the OSO group, such as the superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and catalase (CAT) activities (p < 0.05). On Day 21, oxidized soybean oil increased tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 8 (IL-8) levels in sow milk and the concentrations of TNF-α and IL-8 cytokines in plasma (p < 0.05). Suckling piglets from sows fed on OSO showed a trend towards increased IL-6 and TNF-α in plasma (p < 0.1). The mRNA expression of interleukin 1β (IL-1β) was augmented, whereas interleukin 10 (IL-10) was decreased, and zonula occludens-1 (ZO-1) had a tendency to be down-regulated in OSO treatment. This study revealed that the OSO of feed decreased the antioxidant capacity of milk, further contributing to the inflammatory response in the jejunum of suckling piglets.

Selective biomarkers for inflammation and infection are associated with post-operative complications following transperineal template prostate biopsy (TTPB): a single-centre observational clinical pilot-study

BackgroundProstate cancer (PCa) and benign prostatic hyperplasia (BPH) are the most common prostate disorders in the UK, which cause considerable ill health in older men. Transperineal template prostate biopsy (TTPB) has emerged as a reliable procedure for the histopathological diagnosis of PCa and BPH due to its higher cancer detection rates. Although antiseptic preparation and antibiotic prophylaxis are used to ensure safety in patients undergoing surgical intervention, post-operative complications, such as infection and bleeding are still unavoidable, resulting in re-admissions, with resource implications. Currently, there is no biomarker profile to predict outcomes or monitor patients during the post-operative course. The main aim of this single-centre observational clinical pilot-study was to investigate the role of inflammatory and infection biomarkers following TTPB and their association with post-operative complications.MethodsForty-five patients scheduled for elective TTPB were recruited after informed consent at the Wrexham Maelor and Glan Clwyd Hospitals, North Wales, UK (n = 45). Prior to surgery, venous blood samples were collected at baseline and subsequently at 30, 120, and 240 min post-operatively. Urine samples were collected before and 120 min after the procedure. Serum procalcitonin (PCT), serum ferritin, and urine B2MG analysis were done using enzyme-linked fluorescent assay (ELFA) and the magnetic Luminex® multiplex performance assay was used to analyse IL-6, IL-8, IL-10 and TNF-α plasma concentrations. Data on clinical outcomes were collected from patients’ medical records.ResultsFollowing TTPB, significant (p ≤ 0.05) increases were observed in uB2MG, IL-6, IL-8, IL-10 and TNF-α. Significant decreases were observed in ferritin (p ≤ 0.05). No significant change was observed in PCT concentration (p ≥ 0.05). One patient developed an infection and severe haematuria post-operatively following TTPB.ConclusionAlthough not confirmative, changes seen in biomarkers such as uB2MG, IL-10 and TNF-α in our observational clinical pilot-study may warrant further investigation, involving larger cohorts, to fully understand the role of these biomarkers and their potential association with post-operative complications such as infection and bleeding which can develop following TTPB for the diagnosis of PCa and BPH.

Modulatory effect of two regimens of magnesium sulfate on the systemic inflammatory response in pregnant women with imminent eclampsia.

This study compared the modulatory effect of two intravenous magnesium sulfate (MgSO4) regimens on the systemic inflammatory response in pregnant women diagnosed with imminent eclampsia. In a single-blind cross-sectional study, 33 women were allocated according to the Zuspan (n=16) and Sibai (n=17) MgSO4 regimens, and treated for 24h. Blood samples were collected pre-administration of the loading dose, at 24h of the maintenance dose of MgSO4, and at 48h, when patients were without treatment. Plasma was used to determine interleukin (IL)-1 beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), heat shock protein (Hsp70), and heme oxygenase-1 (HO-1) by ELISA. The treatment with the Zuspan's regimen didn't change plasma concentrations of TNF-α, IL-10, and Hsp70 in the three-time points studied. However, it decreased IL-1β at 24h and 48h and IL-6 at 48h, and increased HO-1 concentration at 48h. On the other hand, compared to the pre-treatment period, Sibai's regimen induced a significant decrease in TNF-α, IL-1β, IL-6, and Hsp70, while increased HO-1 levels both at 24h and 48h and, IL-10 concentration at 48h. Sibai's regimen determined an early and efficient immunoregulatory effect on systemic inflammatory response in preeclampsia, suggesting that the maintenance dose of two grams of MgSO4 was better than one gram in the treatment of imminent eclampsia.

A potential link between plasma short-chain fatty acids, TNF-α level and disease progression in non-alcoholic fatty liver disease: A retrospective study.

The onset and progression of non-alcoholic fatty liver disease (NAFLD) remains unclear, but short-chain fatty acids (SCFAs) in circulation may participate in its pathogenesis by acting as inflammation inhibitors. The aim of this retrospective study was to investigate plasma concentrations of general SCFAs in healthy individuals and in patients with distinct stages of NAFLD. Three main SCFAs (including acetate, propionate and butyrate) were analyzed by gas chromatography. The plasma TNF-α concentration was measured by ELISA. One-way ANOVA, Spearman's correlation and Pearson's correlation analysis were performed to estimate the associations between SCFAs, TNF-α and disease progression. Multiple linear stepwise regression was computed to explore the predictor variables of TNF-α in circulation. A total of 71 patients with NAFLD [including 27 patients with NAFL, 20 patients with non-alcoholic steatohepatitis (NASH) and 24 patients with NAFLD-related cirrhosis (NAFLD-cirrhosis)] and 9 healthy control (HC) subjects were enrolled for analysis. Although not statistically significant, plasma SCFAs were elevated in patients with NAFL compared with HC subjects, whereas the vast majority of SCFAs were statistically reduced in patients with NASH or NAFLD-cirrhosis compared with patients with NAFL. Plasma SCFAs had no significant differences in NASH or NAFLD-cirrhosis patients compared with HC subjects. In addition, significant negative correlations were observed between TNF-α and SCFAs. The progression of NAFLD (β=0.849; P<0.001) and the decline of the total three SCFA concentrations (β=-0.189; P<0.001) were recognized as independent risk variables related to the elevated peripheral TNF-α in the multiple linear stepwise regression model. Plasma SCFA concentrations may alter with the development of NAFLD and may have a potential link to TNF-α and the progression of NAFLD, which may serve a protective role toward disease advancement. Further mechanistic studies, such as analysis of gastrointestinal microecology, signaling pathways and functions involved in TNF-α, need to be performed. Also, therapeutic supplementation of SCFAs for NASH and NAFLD-cirrhosis needs further research and verification.

Peripheral blood inflammatory markers in depression: Response to electroconvulsive therapy and relationship with cognitive performance

The inflammatory response may play a role in depression and the response to antidepressants. Electroconvulsive therapy (ECT), the most acutely powerful antidepressant treatment, can also affect the innate immune system. Here, we determined circulating blood concentrations of the inflammatory mediators C-reactive protein (CRP), IL-1β, IL-6, IL-10, and TNF-α in depressed patients compared to healthy controls and assessed the effect of ECT on their concentrations. Relationships between inflammatory mediator concentrations and mood/cognition scores were also explored. Plasma CRP, IL-1β, IL-6, IL-10, and TNF-α concentrations were examined in 86 depressed patients and 57 controls. Relationships between inflammatory mediators and clinical or cognitive outcomes following ECT were assessed using correlation and linear regression analyzes, respectively. CRP, IL-6, IL-10, and TNF-α were elevated in patients at baseline/pre-ECT compared to controls. However, only IL-6 and TNF-α survived adjustment for potential confounders. IL-1β was undetectable in most samples. ECT did not significantly alter plasma concentrations of any of the inflammatory mediators. No relationship was identified between CRP, IL-6, IL-10, and TNF-α and mood or neurocognitive scores. Overall, our data do not support a major role for these four inflammatory markers in clinical outcomes following ECT or in cognition.

Dietary Crude Protein Levels Alter Diarrhea Incidence, Immunity, and Intestinal Barrier Function of Huanjiang Mini-Pigs During Different Growth Stages.

Huanjiang mini-pig is an indigenous pig breed in China; however, the optimal dietary crude protein (CP) levels for this pig breed during different growth stages has not been standardized yet. This study investigated the effects of different CP levels on diarrhea incidence, immunity, and intestinal barrier function in pigs. A total of 360 Huanjiang mini-pigs were assigned to three independent trials and fed the following CP diets: 5−10 kg stage, 14, 16, 18, 20, and 22%; 10−20 kg stage, 12, 14, 16, 18, and 20% and 20−30 kg stage, 10, 12, 14, 16, and 18%. In the 5−10 kg stage, the 22%; diet increased the plasma IL-1β, IL-6, IL-8, and TNF-α concentrations compared to the 14−20% diets and decreased IL-10 and TGF-β; however, these results were fluctuated in the later stages, including the decrease of IL-1β and IL-8 in the 20% group, TNF-α in the 18−20% groups, and the increase of IFN-γ in the 20% group at the 10−20 kg stage and the decrease of TNF-α in the 16% group at the 20−30 kg stage. The 20% diet increased the jejunal and ileal IL-10 concentration compared to the 14% diet at the 5−10 kg stage, as well as in the 16% diet compared to the 12% diet at the 10−20 kg stage. In addition, ileal IL-10 concentration was increased in the 16% diet compared to the 10, 12, and 18% diets at the 20−30 kg stage. Furthermore, the 18% diet at the 5−10 kg stage and the 16% diet at the 10−20 kg stage decreased jejunal IL-6 expression, whereas the 20% diet increased the TNF-α and IFN-γ at the 5−10 kg stage. The 20% diet increased the Claudin, Occludin, ZO-1, ZO-2, Mucin-1, and Mucin-20 expressions at the 5−10 kg stage, as well as TLR-2, TLR-4, and NF-κB in the 22 and 20% diets at the 5−10 and 10−20 kg stages, respectively. Collectively, these findings suggest optimal dietary CP levels of 16, 14, and 12% for Huanjiang mini-pigs during the 5−10, 10−20, and 20−30 kg growth stages, respectively; and provide the guiding significance of dietary CP levels for Huanjiang mini-pigs during different growth stages.

The Preventive Effect of Transcutaneous Electrical Acupoint Stimulation on Postoperative Delirium in Elderly Patients with Time Factors: A Randomized Trial

Objectives: There is currently no exact and effective treatment for postoperative delirium (POD). The purpose of this study was to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) before surgery and during surgery in elderly patients with POD. Materials and Methods: A total of 90 patients were randomly divided into three groups: a preoperative TEAS group (group E1), an intraoperative TEAS group (group E2), and a control group (group C). In group E1, TEAS was applied at the Shenting, Baihui, bilateral Neiguan, and Hegu points for 30 min 1 day before surgery and before the induction of anesthesia. In group E2, TEAS was applied during surgery. In group C, electrodes were applied to the points just cited, but no electric stimulation was administered. The incidence of delirium was assessed within 5 days after surgery, and the plasma concentration of propofol at bispectral index (BIS) = 50 was recorded. Blood samples were collected to measure neuron-specific enolation (NSE), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1β 1 day before surgery and 1 and 5 days after surgery. Results: The incidence of delirium in group E1 was decreased in comparison with group C and group E1 (both p < 0.05). The propofol plasma concentration at BIS = 50 in group E1 was also decreased in comparison with group C and group E2 (both p < 0.05). Compared with group C, the concentrations of NSE, TNF-α, and IL-1β in plasma were decreased in group E1 and group E2 1 and 5 days after surgery (both p < 0.05), and the concentrations of NSE and IL-1β in plasma in group E1 were decreased 1 and 5 days after surgery in comparison with group E2. Conclusion: The TEAS can reduce the dosage of propofol required during surgery and the occurrence of delirium after surgery. Its mechanism may be related to inhibiting inflammation response and alleviating brain injury. Compared with intraoperative application, the effect of preconditioning with TEAS before surgery is better. Clinical Trial Registration: ChiCTR-INR-17012501. Date of registration: August 29, 2017.

LPS-induced TNF-α production is attenuated by intake with PHGG via gut microbial fermentation in mice

Objectives: Intake of dietary fibers promotes the production of short-chain fatty acids (SCFAs), which can affect host inflammation via gut microbial fermentation. Although partially hydrolyzed guar-gum (PHGG) is a water-soluble dietary fiber with lower viscosity, its benefits in acute inflammation are yet to be determined. The aim of this study was to investigate the effect of PHGG intake on the lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production.Methods: Nine-wk-old male C3 H/HeN mice were used in this study, and they were randomly divided into control diet (CD) and CD + 5% PHGG (GGCD) groups. After a dietary intervention of 6 wk, LPS (1 mg/kg) was injected into the orbital vein. Plasma TNF-α concentration and SCFAs in cecum contents were then measured. Also, the effect of gut microbiota on LPS-induced TNF-α production was evaluated in PHGG-fed mice before and after antibiotic treatment.Results: PHGG intake accelerated a dramatic suppression of LPS-induced TNF-α production (P < 0.01). PHGG-induced low pH in feces (P < 0.05) indicates that the gut microbiota induced high fermentation. Indeed, SCFAs in cecum contents of GGCD mice were significantly higher than in the CD group (P < 0.05). Furthermore, PHGG intake after antibiotic treatment did not induce the suppression of TNF-α.Conclusion: These results demonstrated that inflammation was inhibited by habitual PHGG ingestion, suggesting that this phenomenon might be associated with changes in gut microbiota-induced SCFAs production.

Physical exercise attenuates obesity development in Western-diet fed obese rats independently of vitamin D supplementation.

Physical inactivity, associated with the ingestion of hypercaloric foods, contributes to obesity development. In contrast, physical exercise training (ET) can slow obesity progression. Vitamin (Vit) D, a hormone that regulates adipocyte metabolism, may represent a strategy to reduce obesity; however, it is currently not known whether Vit D enhances the anti-obesity benefits of physical exercise. We hypothesized that swimming ET may prevent Western diet (WD)-induced obesity, and that Vit D supplementation could enhance the anti-obesity actions of ET. Male Wistar rats were fed, from 21 to 90 days of age, on a standard diet, or a WD, in association or not (sedentary control [CTL-SED] and WD [WD-SED] groups) with swimming ET for 15 min/day, 3 days a week (exercised CTL [CTL-EXE] and WD [WD-EXE] groups). Additionally, at 60 days of age, half of the CTL-EXE and WD-EXE groups were submitted, or not, to oral Vit D supplementation (CTL-EXE-VD and WD-EXE-VD groups, respectively). At 91 days old, WD-SED rats displayed increased body weight, abdominal adiposity, hypercholesterolemia, hyperleptinaemia and high circulating levels of tumour necrosis factor (TNF)-α. Swimming ET attenuated the increase in abdominal adiposity induced by WD. Furthermore, the WD-EXE group exhibited reductions in glycaemia, triglyceridaemia, cholesterolaemia, leptinaemia and in plasma TNF-α concentrations. Vitamin D supplementation, combined with ET, did not provide any additive benefit against adiposity, only potentiating the effects of ET action on the reduction in triglyceridaemia. Exercise training, independently of Vit D, provides a strategy to attenuate the adiposity expansion that is induced by WD, mediated in part by reductions in leptinaemia and TNF-α levels.

Effects of a multicomponent microbial feed additive containing prebiotics and probiotics on health, immune status, metabolism, and performance of newly weaned beef steers during a 35-d receiving period.

We examined the effects of dietary supplementation of a multicomponent blend of prebiotics and probiotics on health, immune status, metabolism, and performance of newly weaned beef steers during a 35-d receiving period. Eighty newly weaned crossbred steers (12-hour postweaning; 206 ± 12 kg of body weight [BW]) from a single source were stratified by BW into four pens (20 steers per pen) such that each pen had similar BW at the beginning of the experiment. The pens were randomly assigned to receive a corn silage-based diet with no additive (CON; two pens; n = 40 steers) or a basal diet supplemented with SYNB feed additive at an average of 28 g/steer/d (SYNB; two pens; n = 40 steers). The SYNB additive is a blend of live Saccharomyces cerevisiae and the fermentation products of S. cerevisiae, Enterococcus lactis, Bacillus licheniformis, and Bacillus subtilis and was supplemented for the first 21 d only. Percentage of steers treated for bovine respiratory disease (BRD) was calculated for each dietary treatment. Daily dry matter intake (DMI) and meal events (meal frequency and duration) were measured. Weekly BWs were measured to calculate average daily gain (ADG). Blood samples collected on days 0, 14, 21, 28, and 35 were used for ex-vivo tumor necrosis factor alpha (TNF-α) release assay following lipopolysaccharides (LPS) stimulation, plasma metabolome analysis, and mRNA expression analysis of 84 innate and adaptive immune-related genes. Compared with CON, supplemental SYNB increased (P ≤ 0.05) ADG, DMI, and meal events during the first 7 d. At d 21, there was no treatment effect (P > 0.05) on final BW, DMI, ADG, and meal events; however, beef steers fed supplemental SYNB had greater (P = 0.02) meal duration. Over the entire 35-d receiving period, beef steers fed supplemental SYNB had greater (P = 0.01) ADG and feed efficiency, tended to have greater (P = 0.08) meal duration, and had lower percentage (35 vs. 50%) of animals treated for BRD and lower percentage of sick animals treated for BRD more than once (7.15 vs. 45%). Whole blood expression of pro-inflammatory genes was downregulated while that of anti-inflammatory genes was upregulated in beef steers fed supplemental SYNB. Beef steers fed supplemental SYNB had lower (P = 0.03) plasma concentration of TNF-α after LPS stimulation. Six nutrient metabolic pathways associated with health benefits were enriched (false discovery rate ≤ 0.05) in beef steers fed supplemental SYNB. This study demonstrated that dietary supplementation of SYNB during the first 21 d of arrival reduced BRD morbidity, improved the performance, immune, and metabolic status of beef steers over a 35-d receiving period thereby extending the SYNB effect by a further 14 days post supplementation.

Lipopolysaccharide challenge following intravenous amino acid infusion in postpartum dairy cows: II. Clinical and inflammatory responses

Amino acids (AA) are integral nutrients for a functioning immune system. Postpartum cows experience AA deficits early postpartum that may influence the response to immune activation. This study investigated the clinical and inflammatory responses to a systemic inflammatory stimulus after a 4-d intravenous (IV) AA infusion with a mix of essential and nonessential AA designed to ameliorate the estimated metabolizable protein deficit in early postpartum cows. Our objectives were (1) to describe the clinical and inflammatory response to an acute IV lipopolysaccharide (LPS) challenge in early postpartum cows, and (2) to compare these clinical and inflammatory responses between IV AA-treated and control cows. Cows (n = 14, 4 ± 1 d in milk) were continuously infused IV for 4 d in a matched-pair randomized controlled design and received 0.9% NaCl (CTRL) or IV AA (IVAA) to supply 1 g/kg of BW per day of combined essential and nonessential AA. After infusion ended, cows were challenged with IV LPS (0.0625 µg/kg of BW over 1 h), and serial blood samples were collected for complete blood cell counts and to quantify plasma cytokines and acute-phase proteins. Body temperature, heart rate, and respiratory rate were monitored for 24 h during challenge. During challenge, maximum body temperature was greater in IVAA (41.3 ± 0.20°C) than in CTRL (40.6 ± 0.19°C). In both groups, respiratory rate increased during the first 2 h following challenge, whereas heart rate first decreased over the first 2 h and then increased to reach a maximum at 4 h. Acute leucopenia occurred within 1 h of challenge in both groups before leukocytosis was observed at 24 h, with white blood cell counts returning to baseline values within 72 h. Plasma haptoglobin and serum amyloid A concentrations increased 3-fold and 4-fold in both groups and peaked at 48 and 24 h following challenge, respectively. Plasma concentrations of TNF-α and IL-10 increased within 1 h and peaked at 2 h following the start of challenge. Plasma IL-10 concentrations increased to a greater extent in CTRL compared with IVAA during challenge. Despite differences in IL-10 concentration, previous AA infusion did not alter the acute-phase protein response to LPS challenge. We conclude that AA infusion before systemic inflammatory challenge decreased the anti-inflammatory response but did not alter concentrations of other systemic markers of inflammation.

Pre-treatment plasma cytokine levels as potential predictors of short-term remission of depression

Objectives The response to antidepressants varies significantly among individuals and is difficult to predict before treatment. In this randomised control trial, we explored cytokines that correlate with the therapeutic effect of mirtazapine (MIR) and selective serotonin reuptake inhibitors (SSRIs) and whether they could be predictors of remission for each antidepressant. Methods Plasma cytokines, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were assayed in 95 participants before medication and assayed by the enzyme-linked immunosorbent assay. The Hamilton Rating Scale for Depression assessed depressive symptoms over 4 weeks. Results In the SSRI group, the baseline GM-CSF level was significantly higher in the remission group than in the non-remission group (p = .022). In the MIR group, the baseline level of TNF-α was significantly higher (p = .039) and IL-2 was lower (p = .032) in the remission group than in the non-remission group. In patients prescribed with MIR, the cut-off values of TNF-α (10.035 pg/mL) and IL-2 (1.170 pg/mL) calculated from the receiver operating characteristic curve suggested that the remission rate, which corresponds to a positive predictive value, could be increased from 31.3% to 60.0% and 50.0%, respectively. For those prescribed with SSRIs, the remission rate was 37.0% and using the cut-off value of GM-CSF (0.205 pg/mL), the remission rate could be almost doubled to 70%. Conclusions Our study shows that pre-treatment plasma concentrations of TNF-α, IL-2, and GM-CSF may suggest the predictability of remission by SSRIs or MIR.

In Vivo Effects of Coffee Containing Javamide-I/-II on Body Weight, LDL, HDL, Total Cholesterol, Triglycerides, Leptin, Adiponectin, C-Reactive Protein, sE-Selectin, TNF-α, and MCP-1

BackgroundDiet plays an unequivocal role in the development of obesity. Interestingly, recent studies have demonstrated that coffee products containing javamide-I/-II may be commonly found in the market. However, there is no information about in vivo effects of coffee containing javamide-I/-II (CCJ12) on obesity-related metabolic factors (body weight, LDL, HDL, total cholesterols, triglycerides, adiponectin, and leptin) in nonobese people. ObjectivesThe objective of this study was to investigate in vivo effects of CCJ12 on these metabolic factors as well as inflammatory/cardiovascular disease risk factors [C-reactive protein (CRP), soluble E-selectin (sE-selectin), TNF-α, monocyte chemoattractant protein-1 (MCP-1)] in a nonobese model. MethodsSprague-Dawley male rats were fed a complete diet for 20 wk with either drinking water containing CCJ12 [coffee containing javamide-I/-II group (CG), n = 10] or unsupplemented drinking water [water control group (NCG), n = 10]. The amounts of javamide-I/-II in CCJ12 were quantified by HPLC. Water/food consumption and body weight were monitored weekly, and the concentrations of metabolic/inflammatory/cardiovascular disease risk factors were measured by ELISA. ResultsThere was no significant difference in water/food consumption between the NCG and CG during the study. Also, no significant difference was found in average body weights between the groups either. In addition, after 20 wk, both groups did not show any significant difference in plasma LDL, HDL, and total cholesterol concentrations. Likewise, adiponectin and leptin concentrations were not significantly different between the groups. As expected, the 2 groups did not show any significant difference in plasma concentrations of CRP and sE-selectin. Furthermore, there was no significant difference in plasma concentrations of TNF-α and MCP-1 between the groups. ConclusionsThe data suggest that CCJ12 may not have significant effects on the metabolic/inflammatory/cardiovascular disease risk factors in the CG, compared with the NCG.

Microbiome-Related Indole and Serotonin Metabolites are Linked to Inflammation and Psychiatric Symptoms in People Living with HIV.

Background:People living with HIV (PLHIV) exhibit dysregulation of tryptophan metabolism. Altered gut microbiome composition in PLHIV might be involved. Mechanistic consequences within the 3 major tryptophan metabolism pathways (serotonin, kynurenine, and indoles), and functional consequences for platelet, immune and behavioral functions are unknown. We investigated plasma tryptophan metabolites, gut microbiome composition, and their association with platelet function, inflammation, and psychiatric symptoms.Methods:This study included 211 PLHIV on long-term antiretroviral treatment (ART). Plasma tryptophan pathway metabolites were measured using time-of-flight mass spectrometry. Bacterial composition was profiled using metagenomic sequencing. Platelet reactivity and serotonin levels were quantified by flowcytometry and ELISA, respectively. Circulating inflammatory markers were determined using ELISA. Symptoms of depression and impulsivity were measured by DASS-42 and BIS-11 self-report questionnaires, respectively.Results:Plasma serotonin and indole metabolites were associated with gut bacterial composition. Notably, species enriched in PLHIV were associated with 3-methyldioxyindole. Platelet serotonin concentrations were elevated in PLHIV, without effects on platelet reactivity. Plasma serotonin and indole metabolites were positively associated with plasma IL-10 and TNF-α concentrations. Finally, higher tryptophan, serotonin, and indole metabolites were associated with lower depression and anxiety, whereas higher kynurenine metabolites were associated with increased impulsivity.Conclusion:Our results suggest that gut bacterial composition and dysbiosis in PLHIV on ART contribute to tryptophan metabolism, which may have clinical consequences for immune function and behavior.

Peripheral Inflammatory Biomarkers of Methamphetamine Withdrawal Patients Based on the Neuro-Inflammation Hypothesis: The Possible Improvement Effect of Exercise.

Methamphetamine (MA) induced addiction and neuroinflammation has been implicated. Based on the neuroinflammation hypothesis, this study aims to investigate how exercise influences the craving of patients in MA withdrawal, and explore the mechanism of peripheral inflammation. A total of 90 patients in MA withdrawal were recruited. No difference was noted in the number of years of drug use and the frequency of drug use among patients, and the withdrawal time was within 2 months. The subjects were grouped based on the degree of craving induced by the cues: non-craving control group (NCC group), craving control group (CC group), and craving exercise group (CE group). The CE group was subjected to aerobic combined resistance training. Then, the ELISA method was used to detect plasma IL-6, TNF-α, and IL-1β concentrations; Visual Analog Scale (VAS) measurement of cue-induced cravings under Virtual Reality (VR) exposure (VR-VAS) and the Desires for Drug Questionnaire (DDQ) were used to assess cravings. Consequently, plasma IL-6, TNF-α, IL-1β, levels, and the VR-VAS and DDQ scores of MA withdrawal patients were significantly reduced after exercise. This study confirmed that 8 weeks of incremental load aerobic combined with resistance training reduces peripheral inflammation and significantly reduces the level of craving for MA.