Ciprofloxacin and pegylated G-CSF combined therapy mitigates brain hemorrhage and mortality induced by ionizing irradiation.

Introduction: Brain hemorrhage was found between 13 and 16 days after acute whole-body 9.5 Gy 60Co-γ irradiation (IR). This study tested countermeasures mitigating brain hemorrhage and increasing survival from IR. Previously, we found that pegylated G-CSF therapy (PEG) (i.e., Neulasta®, an FDA-approved drug) improved survival post-IR by 20-40%. This study investigated whether Ciprofloxacin (CIP) could enhance PEG-induced survival and whether IR-induced brain hemorrhage could be mitigated by PEG alone or combined with CIP. Methods: B6D2F1 female mice were exposed to 60Co-γ-radiation. CIP was fed to mice for 21 days. PEG was injected on days 1, 8, and 15. 30-day survival and weight loss were studied in mice treated with vehicles, CIP, PEG, or PEG + CIP. For the early time point study, blood and sternums on days 2, 4, 9, and 15 and brains on day 15 post-IR were collected. Platelet numbers, brain hemorrhage, and histopathology were analyzed. The cerebellum/pons/medulla oblongata were detected with glial fibrillary acidic protein (GFAP), p53, p16, interleukin-18 (IL-18), ICAM1, Claudin 2, ZO-1, and complement protein 3 (C3). Results: CIP + PEG enhanced survival after IR by 85% vs. the 30% improvement by PEG alone. IR depleted platelets, which was mitigated by PEG or CIP + PEG. Brain hemorrhage, both surface and intracranial, was observed, whereas the sham mice displayed no hemorrhage. CIP or CIP + PEG significantly mitigated brain hemorrhage. IR reduced GFAP levels that were recovered by CIP or CIP + PEG, but not by PEG alone. IR increased IL-18 levels on day 4 only, which was inhibited by CIP alone, PEG alone, or PEG + CIP. IR increased C3 on day 4 and day 15 and that coincided with the occurrence of brain hemorrhage on day 15. IR increased phosphorylated p53 and p53 levels, which was mitigated by CIP, PEG or PEG + CIP. P16, Claudin 2, and ZO-1 were not altered; ICAM1 was increased. Discussion: CIP + PEG enhanced survival post-IR more than PEG alone. The Concurrence of brain hemorrhage, C3 increases and p53 activation post-IR suggests their involvement in the IR-induced brain impairment. CIP + PEG effectively mitigated the brain lesions, suggesting effectiveness of CIP + PEG therapy for treating the IR-induced brain hemorrhage by recovering GFAP and platelets and reducing C3 and p53.

The effect of Borago officinalis on the signaling pathway of the NLRP3 inflammasome complex, TLR4 and some inflammatory cytokines in type II diabetic patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs become severely inflamed, causing the alveoli to constrict or fill with fluid, which prevents the lungs from functioning properly. This disease becomes more dangerous when it occurs in patients with diabetes. Because of the clinical condition of these patients, it is not possible to treat them with usual medicines. One of the best options for treating these people is to use herbs. Borage (Borago officinalis) is a medicinal herb that, in addition to its anti-inflammatory properties, is also able to control blood sugar. Therefore, in the current study, the effect of borage oil was considered on the signaling pathway of the NLRP3 inflammasome complex, TLR4, and serum levels of inflammatory cytokines (IL-1? and IL-18) in type II diabetic patients with ARDS. For this purpose, 25 diabetic type II patients with ARDS were divided into three groups by ARDS Berlin Definition. Then, after providing the demographic and clinical characteristics of the patients, they were treated with 30 mg/day borage oil for seven days. The expression of NLRP3 and TLR4 genes (by Real-time PCR technique) and serum levels of IL-1? and IL-18 (by ELISA test) were evaluated before and after treatment with borage oil through blood samples taken from patients. The results showed that serum levels of inflammatory cytokines (IL-1? and IL-18), NLRP3 gene, and TLR4 gene were significantly decreased in diabetic type II patients with mild ARDS by treating with borage oil. IL-1? serum level and TLR4 were significantly decreased in diabetic type II patients with moderate ARDS. But there was not any significant decrease or increase in IL-1?, IL-18, NLRP3 gene, and TLR4 gene in diabetic type II patients with severe ARDS after 7 days of treatment with borage oil. According to the obtained results, borage oil can act as a double-edged blade. Thus, in the early and middle stages of ARDS, borage oil can be effective in reducing the inflammasome pathway of inflammation and also reduce blood sugar levels in these diabetic patients. But in the severe stage of ARDS, it not only does not help to treat the ARDS; it also increases systolic and diastolic blood pressure in diabetic patients.

Kynurenine pathway activation and deviation to anthranilic and kynurenic acid in fibrosing chronic graft-versus-host disease.

Fibrosing chronic graft-versus-host disease (cGVHD) is a debilitating complication of allogeneic stem cell transplantation (alloSCT). A driver of fibrosis is the kynurenine (Kyn) pathway, and Kyn metabolism patterns and cytokines may influence cGVHD severity and manifestation (fibrosing versus gastrointestinal [GI] cGVHD). Using a liquid chromatography-tandem mass spectrometry approach on sera obtained from 425 patients with allografts, we identified high CXCL9, high indoleamine-2,3-dioxygenase (IDO) activity, and an activated Kyn pathway as common characteristics in all cGVHD subtypes. Specific Kyn metabolism patterns could be identified for non-severe cGVHD, severe GI cGVHD, and fibrosing cGVHD, respectively. Specifically, fibrosing cGVHD was associated with a distinct pathway shift toward anthranilic and kynurenic acid, correlating with reduced activity of the vitamin-B2-dependent kynurenine monooxygenase, low vitamin B6, and increased interleukin-18. The Kyn metabolite signature is a candidate biomarker for severe fibrosing cGVHD and provides a rationale for translational trials on prophylactic vitamin B2/B6 supplementation for cGVHD prevention.

Novel Relationship Between Plasmalogen Lipid Signatures and Carnosine in Humans.

INTRODUCTION: Carnosine is a naturally occurring dipeptide abundant in the skeletal and cardiac muscle and brain, which has been shown to improve glucose metabolism and cardiovascular risk. This study showed that carnosine supplementation had positive changes on plasma lipidome. Here, this study aimed to establish the relationship of muscle carnosine and serum carnosinase-1 with cardiometabolic risk factors and the lipidome. METHODS AND RESULTS: This study profiles >450 lipid species in 65 overweight/obese nondiabetic individuals. Intensive metabolic testing is conducted using direct gold-standard measures of adiposity, insulin sensitivity and secretion, as well as measurement of serum inflammatory cytokines and adipokines. Muscle carnosine is negatively associated with 2-h glucose concentrations, whereas serum carnosinase-1 levels are negatively associated with insulin sensitivity and positively with IL-18. O-PLS and machine learning analyses reveal a strong association of muscle carnosine with ether lipids, particularly arachidonic acid-containing plasmalogens. Carnosinase-1 levels are positively associated with total phosphatidylethanolamines, but negatively with lysoalkylphosphatidylcholines, trihexosylceramides, and gangliosides. In particular, alkylphosphatidylethanolamine species containing arachidonic acid are positively associated with carnosinase-1. CONCLUSION: These associations reinforce the role of muscle carnosine and serum carnosinase-1 in the interplay among low-grade chronic inflammation, glucose homeostasis, and insulin sensitivity.

Efficacy of low-dose insulin combined with electrolyte in the treatment of pediatric diabetic ketoacidosis and its effect on serum inflammatory factors.

Diabetic ketoacidosis (DKA) is a very serious disease that can occur in both types of diabetes (type 1 and 2). It is caused by a combination of high blood sugar and low insulin levels, which can cause the body to produce too much ketone. Ketones are toxic to human organs. This research aimed to investigate the clinical efficacy of low-dose insulin combined with electrolyte in the treatment of pediatric DKA and its effect on serum inflammatory factors. For this purpose, a total of 122 children with DKA admitted to our hospital from April 2013 to May 2016 were selected as research objects. They were divided into group A with 60 cases and group B with 62 cases. Group B was treated with supplemental electrolytes, and group A was treated with low-dose insulin based on group B. The serum levels of TNF-α, IL-6, and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) before and after treatment, and the blood sugar, sodium, and potassium levels were measured by an automatic biochemical analyzer. The time when blood sugar reached the standard level when acidosis was corrected and hospitalization time was compared between the two groups. The total effective rate of group A was significantly higher than that of group B (p< 0.05). There was no significant difference in blood glucose, sodium, potassium, TNF-α, IL-6, and IL-18 levels between the two groups before treatment. (all p > 0.05). But the blood glucose, sodium and potassium levels in group A were significantly better than those in group B (all p< 0.001). The levels of serum TNF-α, IL-6, and IL-18 in group A were significantly lower than those in group B after treatment (all p< 0.001). After treatment, the time when blood sugar reached the standard level when acidosis was corrected and hospitalization time in group A were significantly shorter than those in group B (all p< 0.001). Low-dose insulin combined with electrolyte supplementation is effective in the treatment of DKA in children, which can effectively control blood sugar, sodium, potassium level, and inflammatory factor concentration.

Human Milk Oligosaccharide Supplementation Affects Intestinal Barrier Function and Microbial Composition in the Gastrointestinal Tract of Young Sprague Dawley Rats.

Human milk oligosaccharides (HMOs) are chief maternal milk constituents that feed the intestinal microbiota and drive maturation of the infant gut. Our objective was to determine whether supplementing individual HMOs to a weanling diet alters growth and gut health in rats. Healthy three-week-old Sprague Dawley rat pups were randomized to control, 2'-O-fucosyllactose (2'FL)- and 3'sialyllactose (3'SL)-fortified diets alone or in combination at physiological doses for eight weeks. Body composition, intestinal permeability, serum cytokines, fecal microbiota composition, and messenger RNA (mRNA) expression in the gastrointestinal tract were assessed. Males fed a control diet were 10% heavier and displayed elevated interleukin (IL-18) (p = 0.01) in serum compared to all HMO-fortified groups at week 11. No differences in body composition were detected between groups. In females, HMOs did not affect body weight but 2'FL + 3'SL significantly increased cecum weight. All female HMO-fortified groups displayed significant reductions in intestinal permeability compared to controls (p = 0.02). All HMO-fortified diets altered gut microbiota composition and mRNA expression in the gastrointestinal tract, albeit differently according to sex. Supplementation with a fraction of the HMOs found in breast milk has a complex sex-dependent risk/benefit profile. Further long-term investigation of gut microbial profiles and supplementation with other HMOs during early development is warranted.

Reduction of expression of IL-18, IL-1ß genes in the articular joint by sumac fruit extract (Rhus coriaria L.).

BACKGROUND: Osteoarthritis is the most common malignant disease in the world. The disease is caused by changes in the metabolism, the structure and function of multiple joints, and joint tissues. Sumac is one of the indigenous plants of Iran and has traditionally been used as a spice in Iran. The aim of this study was to investigate the reduction of expression of IL-18, IL-1ß genes in the articular joint by sumac fruit extract (Rhus coriaria L.). METHODS: The alcoholic extract of sumac fruit (E.E.R.C.L) was prepared from the Genetic Reserve Center. Bleeding was used to provide synoviocyte cells from the joint and fluid of the anatomical metacarpal limb of the 8-month-old Holstein healthy calf without any signs of inflammation. Using cell-hemocytometer count, their viability was evaluated by trypan blue and after lipopolysaccharide (LPS) proliferation and injection to enhance the level of cytokines. After isolating the RNA and preparing the cDNA, RT-PCR and PCR were performed and then, using the real-time PCR method, the expression of the desired genes was investigated. RESULTS: In this study, after the expression of IL-18 cytokines, IL-1ß increased to 100%, and following the treatment with alcoholic extract, the reduction of expression of these cytokines was 33.61% and 29.01%, respectively. The results of anti-inflammatory effects showed that the alcoholic extract of sumac reduced the IL-1ß, IL-18 expression in LPS-stimulated cells. CONCLUSION: Sumac fruit extract can be an effective medication for reducing pain.

The Effects of OMEGA-3 Fatty Acid Supplementation Upon Interleukin-12 and Interleukin-18 in Chronic Kidney Disease Patients.

OBJECTIVE(S): Cardiovascular disease (CVD) remains a leading cause of mortality in chronic kidney disease (CKD) patients. Interventions targeting traditional risk factors have largely proven ineffective in CKD patients in part because of the increased role of nontraditional risk factors such as chronic inflammation. Omega-3 fatty acids (ω3FA) are inexpensive and safe natural agents, which target inflammation and have potential cardioprotective benefits. The aim of the study was to determine the effects of ω3FA supplementation upon serum interleukin (IL)-12, IL-18, and highly sensitive C-reactive protein (hsCRP) in patients with Stage 3-4 CKD. METHODS: We performed a post-hoc analysis of a randomized placebo-controlled trial in 73 nondiabetic CKD patients to determine the effects of ω3FA supplementation (4 g daily for 8 weeks) upon serum levels of IL-12, IL-18, and hsCRP. RESULTS: There were no preintervention differences in IL-12, IL-18, or hsCRP between treatment groups. Postintervention levels of IL-12, IL-18, and hsCRP were similar between the treatment groups. However, IL-12 and IL-18 increased in both treatment groups over the intervention period, whereas hsCRP remained unchanged. The magnitude of increase in serum IL-18 (ΔIL-18) was significantly less in participants in the ω3FA treatment group compared to placebo (P = .047). CONCLUSION(S): This study has shown that 4 g daily ω3FA supplementation may lower serum IL-18 levels in patients with moderate CKD. Although there were no apparent effects on several other markers of inflammation, this study provides evidence for a specific effect of ω3FA on inflammatory pathways.

Effect of Morus alba root bark extract on gene-level expression of inflammatory markers in rats subjected to ethanol and cerulein induced pancreatitis- influence of heat shock protein 70.

Background Chronic pancreatitis (CP) is a persistent inflammation of the pancreas clinically presented with severe abdominal pain, progressive fibrosis, and loss of exocrine and endocrine functions. Inflammasomes, cytosolic multiprotein complexes which regulate the formation of proinflammatory cytokines, are influenced by various factors including heat shock proteins (HSPs). Morus alba L., or white mulberry root bark is a valued traditional Asian medicine with a diverse array of phytochemicals. The aim of this investigation was to define the modulatory action of methanolic extract of Morus alba root bark (MEMARB) on NLRP3 inflammasome, and HSPs in pancreas subjected to inflammatory insult. Methods Pancreatitis was induced in male albino Wistar rats by ethanol (0-36%) and cerulein (20 µg/kg b.wt., i.p.) for 5 weeks with or without MEMARB administration. Serum lipase/amylase (L/A) ratio, oxidative stress index (OSI) and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio in the pancreas were evaluated. Levels of serum HSP70 was quantified by ELISA. NF-kappa B, NLRP3-ASC, caspase-1, IL-1ß, IL-18, and HSP70 gene expression was quantified by quantitative real-time polymerase chain reaction (qPCR). Results L/A ratio and oxidative stress determined in terms of OSI and GSH/GSSG ratio were elevated in pancreatitis-induced rats. The levels were restored in MEMARB co-administered animals. Serum level of HSP70 was increased in pancreatitis-induced animals and dropped significantly in MEMARB co-administrated rats. Pancreatitis-induced group showed increased expression of NF-kappa B, IL-1ß, IL-18, caspase-1, NLRP3-ASC and HSP70 mRNA than in MEMARB treated group. Conclusions It can be concluded that the M. alba root extract modulates the expression of HSP70 and NLRP3-ASC which might be attributed to its pancreato-protective effect.

Serum concentrations of interleukin 18 and 25-hydroxyvitamin D3 correlate with depression severity in men with psoriasis.

OBJECTIVE: Psoriasis and depression may have common mechanisms, such as systemic inflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, and vitamin D3 deficiency. Among men with psoriasis, this study examined whether depression severity was associated with serum concentrations of different metabolic and inflammatory markers. METHODS: The study included 85 men with psoriasis (mean age ± standard deviation [SD], 47 ± 14 years) and 65 men without psoriasis (mean age ± SD, 44 ± 13 years). In both groups, we measured the body mass index; blood pressure; and serum concentrations of lipids, uric acid, lipase, interleukins 6 and 18, cortisol, and 25-hydroxyvitamin D3. All participants completed the Beck Depression Inventory. Other variables analyzed included psoriasis duration, the Psoriasis Area Severity Index, and the percentage of body surface area affected by psoriatic lesions. RESULTS: Compared with controls, patients with psoriasis had significantly greater depression severity, higher body mass indices, and higher serum concentrations of total cholesterol and interleukins 6 and 18; moreover, they had significantly lower serum 25-hydroxyvitamin D3 concentrations. In patients with psoriasis, depression severity correlated positively with psoriasis duration, the Psoriasis Area Severity Index, the percentage of body surface area affected by psoriatic lesions, and interleukin-18 concentration. In patients with psoriasis, depression severity correlated negatively with 25-hydroxyvitamin D3 concentration, but it did not correlate significantly with the serum concentrations of interleukin 6 and cortisol. CONCLUSIONS: High concentrations of interleukin 18 and low concentrations of 25-hydroxyvitamin D3 may be associated with depression severity in men with psoriasis. Thus, further studies should examine whether effective anti-inflammatory treatments or vitamin D3 supplementation can improve depression outcomes in these patients.

Emodin alleviates intestinal mucosal injury in rats with severe acute pancreatitis via the caspase-1 inhibition.

BACKGROUND: Emodin, a traditional Chinese medicine, has a therapeutic effect on severe acute pancreatitis (SAP), whereas the underlying mechanism is still unclear. Studies showed that the intestinal mucosa impairment, and subsequent release of endotoxin and proinflammatory cytokines such as IL-1ß, which further leads to the dysfunction of multiple organs, is the potentially lethal mechanism of SAP. Caspase-1, an IL-1ß-converting enzyme, plays an important role in this cytokine cascade process. Investigation of the effect of emodin on regulating the caspase-1 expression and the release proinflammatory cytokines will help to reveal mechanism of emodin in treating SAP. METHODS: Eighty Sprague-Dawley rats were randomly divided into four groups (n=20 each group): SAP, sham-operated (SO), emodin-treated (EM) and caspase-1 inhibitor-treated (ICE-I) groups. SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct. Emodin and caspase-1 inhibitor were given 30 minutes before and 12 hours after SAP induction. Serum levels of IL-1ß, IL-18 and endotoxin, histopathological alteration of pancreas tissues, intestinal mucosa, and the intestinal caspase-1 mRNA and protein expressions were assessed 24 hours after SAP induction. RESULTS: Rats in the SAP group had higher serum levels of IL-1ß and IL-18 (P<0.05), pancreatic and gut pathological scores (P<0.05), and caspase-1 mRNA and protein expressions (P<0.05) compared with the SO group. Compared with the SAP group, rats in the EM and ICE-I groups had lower IL-1ß and IL-18 levels (P<0.05), lower pancreatic and gut pathological scores (P<0.05), and decreased expression of intestine caspase-1 mRNA (P<0.05). Ultrastructural analysis by transmission electron microscopy found that rats in the SAP group had vaguer epithelial junctions, more disappeared intercellular joints, and more damaged intracellular organelles compared with those in the SO group or the EM and ICE-I groups. CONCLUSIONS: Emodin alleviated pancreatic and intestinal mucosa injury in experimental SAP. Its mechanism may partly be mediated by the inhibition of caspase-1 and its downstream inflammatory cytokines, including IL-1ß and IL-18. Our animal data may be applicable in clinical practice.

Apolipoprotein A2 -265 T>C polymorphism interacts with dietary fatty acids intake to modulate inflammation in type 2 diabetes mellitus patients.

OBJECTIVE: Several investigations have been conducted regarding the interaction between Apolipoprotein A2 (APOA2) -265 T>C polymorphism and dietary intake of saturated fatty acids (SFAs) on obesity in healthy individuals or type 2 diabetes mellitus (T2 DM) patients. The aim of the present study is to examine the effect of this interaction on inflammatory markers in T2 DM patients. METHODS: This is a comparative cross-sectional study on 180 T2 DM patients with known APOA2 genotype. Dietary intake was assessed by food-frequency questionnaire and serum levels of inflammatory markers (interleukin [IL]-18, pentraxin 3, and high-sensitivity C-reactive protein [hs-CRP]) were measured. The subjects were dichotomized into "high" and "low" categories, based on the median dietary intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and SFAs. The data were analyzed by analysis of covariance multivariate interaction model. RESULTS: In CC genotype, higher median intake of ω-3 PUFAs and MUFAs was associated with decreased serum levels of IL-18 and hs-CRP (P = 0.014 and 0.008, respectively). In T-allele carriers, higher median intake of SFAs was associated with increased serum hs-CRP level (P < 0.001). There was a significant relationship between APOA2 polymorphism and ω-3 PUFA intake on serum IL-18 level (P interaction = 0.03). Moreover, the relationship between this polymorphism and SFA and MUFA intake on serum hs-CRP level was statistically significant (P interaction = 0.03 and 0.024, respectively). CONCLUSIONS: In T2 DM patients, the dietary intake of antiinflammatory fatty acids, such as ω-3 PUFAs and MUFAs, could reduce the inflammatory effects associated with the CC genotype. In addition, proinflammatory fatty acids, such as SFAs, could overcome the antiinflammatory effect of the T-allele. Further studies are needed to confirm these findings.

A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study.

BACKGROUND: To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions. OBJECTIVES: We compared the effects of EPA supplementation with those of DHA supplementation (re-esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease. DESIGN: In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA. RESULTS: Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% ± 2.8% compared with -0.5% ± 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% ± 1.6% compared with -1.2% ± 1.7%, respectively; P < 0.001). Between DHA and EPA, changes in CRP (-7.9% ± 5.0% compared with -1.8% ± 6.5%, respectively; P = 0.25), IL-6 (-12.0% ± 7.0% compared with -13.4% ± 7.0%, respectively; P = 0.86), and tumor necrosis factor-α (-14.8% ± 5.1% compared with -7.6% ± 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% ± 2.3% compared with -11.9% ± 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% ± 1.3% compared with 0.3% ± 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% ± 1.4% compared with -0.7% ± 1.1%, respectively; P < 0.0001) and LDL cholesterol (6.9% ± 1.8% compared with 2.2% ± 1.6%, respectively; P = 0.04). The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women (P-treatment × sex interaction = 0.046). CONCLUSIONS: DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids. Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT01810003.

Risk factors for and expression of immune and inflammatory factors in atopic dermatitis in Chinese population: A birth cohort study.

OBJECTIVE: To explore the risk factors for atopic dermatitis (AD) and disclose the relationship between immune inflammatory factors (Immunoglobulin E (IgE), interleukin (IL)-4, IL-18) and the prevalence of AD in a Chinese population. METHODS: To evaluate the risk factors for infant AD, a total of 921 mother-newborn pairs were recruited through a questionnaire survey conducted during 2009-2011. Venous blood was collected from the mothers during birth hospitalization and umbilical cord blood was collected during delivery. Thirty-five infants with AD paired with their mothers served as the patient group. Thirty-five non-AD pairs were selected randomly and were used as the control group. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IgE, IL-4, and IL-18. The relationship between the prevalence of AD and the levels of IgE, IL-4, and IL-18 was analyzed. The risk factors for allergy were assessed in IgE positive cases. RESULTS: Family income, parental history of atopy, age of menarche, performing housing renovation before pregnancy, instance of a virus infection during pregnancy, and calcium supplementation during pregnancy were potential factors determining the incidence rate of infant AD. Compared with the control group, the AD patient group showed higher levels of IgE and IL-4 in both the maternal serum and umbilical cord blood (P < 0.01). In the cases with AD, IL-8 was increased only in the maternal serum (P < 0.01). In addition, the allergens dust mite, mugwort pollen, and mycete spores were risk factors for the incidence of IgE-positive AD. CONCLUSION: IgE and IL-4 levels in the maternal serum and umbilical cord blood as well as IL-18 level in the maternal serum are related to the occurrence of childhood AD. Potential factors for infant AD include family income, parental history of atopy, age of menarche, housing renovation before pregnancy, virus infection, and calcium supplementation during pregnancy.

Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments.

LC is an herbal remedy effectively reduced therapeutic dosage of glucocorticoid for systemic lupus erythematosus (SLE) patients in clinical trial (ISRCTN81818883). This translational research examined the impact of LC on biomarkers of endothelial injury in the enrolled subjects. Fifty seven patients with SLE were randomized to receive standard treatment without or with LC supplements. Blood samples were taken serially for quantification of endothelial progenitor cells (EPCs), circulating endothelial cells (CECs) and serological factors. The proportion of EPCs in the placebo group continued to increase during trial and was further elevated after withdrawal of standard treatment. The EPC ratio of LC group remained stationary during the entire observation period. The CEC ratio in placebo group exhibited an increasing trend whereas that in LC group declined. The ratio of apoptotic CECs had an increasing trend in both groups, to a lesser extent in LC group. After treatment, the levels of VEGF and IL-18 have a trend declined to a level lower in the LC group than the placebo group. No significant alteration was noted in serum levels of IFN-α, IL-1ß and IL-6. The reduction of the steroid dosage by adding LC might be correlated with less extensive endothelial injury in SLE patients.

Increased Hypothalamic Levels of Endozepines, Endogenous Ligands of Benzodiazepine Receptors, in a Rat Model of Sepsis.

BACKGROUND: The mechanisms involved in septic anorexia are mainly related to the secretion of inflammatory cytokines. The term endozepines designates a family of neuropeptides, including the octadecaneuropeptide (ODN), originally isolated as endogenous ligands of benzodiazepine receptors. Previous data showed that ODN, produced and released by astrocytes, is a potent anorexigenic peptide. We have studied the effect of sepsis by means of a model of cecal ligation and puncture (CLP) on the hypothalamic expression of endozepines (DBI mRNA and protein levels), as well as on the level of neuropeptides controlling energy homeostasis mRNAs: pro-opiomelanocortin, neuropeptide Y, and corticotropin-releasing hormone. In addition, we have investigated the effects of two inflammatory cytokines, TNF-α and IL-1ß, on DBI mRNA levels in cultured rat astrocytes. METHODS: Studies were performed on Sprague-Dawley male rats and on cultures of rat cortical astrocytes. Sepsis was induced using the CLP method. Sham-operated control animals underwent the same procedure, but the cecum was neither ligated nor incised. RESULTS: Sepsis caused by CLP evoked an increase of DBI mRNA levels in ependymal cells bordering the third ventricle and in tanycytes of the median eminence. CLP-induced sepsis was also associated with stimulated ODN-like immunoreactivity (ODN-LI) in the hypothalamus. In addition, TNF-α, but not IL-1ß, induced a dose-dependent increase in DBI mRNA in cultured rat astrocytes. An increase in the mRNA encoding the precursor of the anorexigenic peptide α-melanocyte stimulating hormone, the pro-opiomelanocortin, and the corticotropin-releasing hormone was observed in the hypothalamus. CONCLUSION: These results suggest that during sepsis, hypothalamic mRNA encoding endozepines, anorexigenic peptide as well as stress hormone could play a role in the anorexia/cachexia associated with inflammation due to sepsis and we suggest that this hypothalamic mRNA expression could involve TNF-α.

Searsia chirindensis reverses the potentiating effect of prenatal stress on the development of febrile seizures and decreased plasma interleukin-1ß levels.

It is estimated that more than 80% of patients with epilepsy live in developing countries with 50-60% of them being children. This high prevalence is perpetuated by low socio-economic challenges, poor health care facilities and lack of drug affordability. Searsia chirindensis formerly known as rhus chirindensis and commonly known as 'Red Current' is a popular traditional medicinal plant, which has been used to treat a number of illnesses such as heart complaints and neurological disorders. The aim of this study is to investigate the effects of S. chirindensis on the development of febrile seizure in a prenatally stressed rat. Febrile seizures were induced by administering lipopolysaccharide to 14-day-old rat pups followed by kainic acid. A subset of the rats was treated with Searsia after induction of febrile seizures. Interleukin-1ß (IL-1ß) levels were measured in plasma. Lipid peroxidation was determined in liver tissue. Our data shows that treatment with Searsia reduced interleukin-1ß levels in plasma of the febrile seizure rats and prevented lipid oxidation in the liver. Prenatal stress is dampened by the beneficial effects of Searsia on seizure development in rat pups. These results highlight the potentiating effects of Searsia in the reversal of febrile seizures and prenatal stress effects.

Gut microbiota mediated benefits of barley kernel products on metabolism, gut hormones, and inflammatory markers as affected by co-ingestion of commercially available probiotics: a randomized controlled study in healthy subjects.

BACKGROUND AND AIMS: Barley kernel based products have been shown to induce benefits on blood glucose regulation, cardio-metabolic risk markers and appetite regulating hormones in a time perspective of 11-16 h after intake. The mechanisms have been assigned to gut fermentation of indigestible carbohydrates. The purpose of the present study was to evaluate if the modulatory effects of barley on markers of metabolic- and appetite regulation are affected by a dietary background including a mixture of commercially available probiotics. METHODS: Barley kernel bread was included in the normal diet of 21 healthy subjects in two 4-day intervention periods; with (BB-pro) or without (BB) dietary supplement with a combination of probiotics (Bifidobacterium animalis DN-173 010, Lactobacillus reuteri DSM 17938, and Lactobacillus plantarum 299v). A white wheat flour based bread was included as a reference product (WWB-ref) in a separate 4-day bread intervention period. A cross-over design was applied concerning BB- and WWB-ref; the BB-pro intervention was last in the test sequence. The BB-pro intervention was preceded by 10 days priming with probiotics. The 4 day BB- and WWB-ref intervention periods included dietary supplementation with placebo, and the interventions were preceded with 10 days priming with the placebo. The day after each intervention period, blood samples were collected at fasting and postprandially after a standardized breakfast (0-210 min) for determination of markers of glucose metabolism (blood glucose, serum (s-) insulin), inflammation (s-IL-6, s-IL-18, s-CRP, PAI-1), and concentrations of gut derived hormones involved in satiety and glucose homeostasis (plasma (p-) PYY, p-GLP-1) and intestinal barrier integrity (p-GLP-2). Breath hydrogen was determined as a marker of colonic fermentation. RESULTS: Four days intervention with BB, in comparison to WWB-ref, lowered blood glucose response after a subsequent standardized breakfast (0-210 min, P < 0.05). BB and BB-pro interventions increased p-GLP-1 (0-120 min, P < 0.05) and breath H2 (0-210 min, P < 0.05). BB-pro intervention, in comparison to BB and WWB-ref, increased levels of s-PAI-1 (P < 0.05), and p-GLP-2 (0-210 min, P < 0.05) after the standardized breakfast. CONCLUSIONS: With the exception of increased p-GLP-2 and an unexpected increase in s-PAI-1 concentrations, co-ingestion of a mixture of probiotics did not affect the metabolic outcome of BB; neither positively nor importantly negatively. The study was registered at: ClinicalTrials.gov, register number NCT01718418 (www.clinicaltrials.gov/ct2/show/NCT01718418).

[Effect of Acupuncture and Moxibustion Intervention on Contents of Serum Interleukin-7 and In- terleukin-18 in Cyclophosphamide-induced Immune Suppression in Tumor-bearing Mice].

OBJECTIVE: To observe the effect of acupuncture and moxibustion intervention on the contents of serum IL-7 and IL-18 and white blood cell counts in cyclophosphamide (CTX)-induced hypofunction of immunity in tumor-bearing mice, so as to explore its mechanism underlying improvement of immune suppression caused by chemotherapy. METHODS: Sixty-four male Kunming mice were implanted with S 180 sarcoma at the left armpit (for making tumor-bearing model) , and then, randomized into control group, model group, acupuncture group and moxibustion group( 16 mice in each group). The mice of the latter 3 groups were injected with CTX (i. p. , 150 mg · kg(-1) · d(-1)), and those of the control group were injected (i. p.) with normal saline. Filiform acupuncture needle or moxibustion was applied to "Dazhui" (GV 14) , unilateral "Geshu" (BL 17) , "Shenshu"(BL 23) and "Zusanli"(ST 36) once daily for 3 or 5 days. Contents of serum IL-7 and IL-18 were detected by ELISA. RESULTS: In comparison with the control group, the plasma leukocyte counts from day 2 to day 5, the spleen index and serum IL-18 contents on day 3 and 5 after administration of CTX were significantly decreased, and serum IL-7 contents on day 3 and 5 after CTX remarkably increased in the model group (P < 0.05). Following the treatment, the spleen index on day 3 and serum IL-18 content on day 5 in the moxibustion group, serum IL-7 and IL-18 contents on day 3 and 5 in the acupuncture group were significantly up-regulated (P < 0.05). The effect of acupuncture was markedly superior to that of moxibustion in up-regulating serum IL-18 contents on day 3 and 5 after the treatment (P < 0.05). No significant differences were found between the acupuncture and moxibustion groups in the leukocyte counts and spleen index after the treatment, and in serum IL-7 contents on day 3 (P > 0.05). CONCLUSION: Acupuncture and moxibustion can up-regulate the serum IL-7 and IL-18 and white blood cell levels in immuno-suppression mice, wnicn may contribute to their effects in relieving immune hypofunction caused by alkylating agent CTX.