Combined Low-Intensity Exercise and Ascorbic Acid Attenuates Kainic Acid-Induced Seizure and Oxidative Stress in Mice

Physical exercise and vitamins such as ascorbic acid (ASC) have been recognized as an effective strategy in neuroprotection and neurorehabilitatioin. However, there is a need to find an efficient treatment regimen that includes ASC and low-intensity exercise to diminish the risk of overtraining and nutritional treatment by attenuating oxidative stress. In the present study, we investigated the combined effect of low-intensity physical exercise (EX) and ASC on kainic acid (KA)-induced seizure activity and oxidative stress in mice. The mice were randomly assigned into groups as follows: “KA only” (n = 11), “ASC + KA” (n = 11), “Ex + KA” (n = 11), “ASC + Ex + KA” (n = 11). In the present study, low intensity of swimming training period lasted 8 weeks and consisted of 30-min sessions daily (three times per week) without tail weighting. Although no preventive effect of low-intensity exercise or ASC on KA seizure occurrence was evident, there was a decrease of seizure activity, seizure development (latency to first seizures), and mortality in “ASC + Ex + KA” compared to “ASC + KA”, “Ex + KA”, and “KA only” group. In addition, a preventive synergistic coordination of low-intensity exercise and ASC was evident in glutathione peroxidase and superoxide dismutase activity compared to separate treatment. These results suggest that low-intensity exercise and ASC treatment have preventive effects on seizure activity and development with alternation of oxidative status.     

Glycyrrhizin Suppresses HMGB1 Inductions in the Hippocampus and Subsequent Accumulation in Serum of a Kainic Acid-Induced Seizure Mouse Model

Glycyrrhizin (GL), a triterpene present in the roots and rhizomes of licorice (Glycyrrhiza glabra), has been shown to have anti-inflammatory and anti-viral effects. In our previous reports, we demonstrated the neuroprotective effects of GL in the postischemic brain and in kainic acid (KA)-induced seizure animal model. In this KA-induced seizure model, the systemic administration of GL 30 min before KA administration significantly suppressed neuronal cell death and markedly suppressed gliosis and proinflammatory marker inductions. In the present study, we showed that high-mobility group box 1 (HMGB1), an endogenous danger signal, was induced in hippocampal CA1 and CA3 regions of the same KA-induced model, and peaked at ~3 h and at 6 days post-KA. HMGB1 was transiently induced in neurons and astrocyte at 3 h post-KA, and it was released from dying neurons and accumulated in serum at 12 h post-KA. Furthermore, after ~4 days of almost undetectable levels in the hippocampus, delayed and marked HMGB1 induction was detected at 6 days post-KA, mainly in astrocytes and endothelial cells, in which HMGB1 was localized in nuclei, and not secreted into serum. Interestingly, GL suppressed HMGB1 inductions in hippocampus and also suppressed its release into serum in KA-treated mice. Since we established previously that GL has anti-inflammatory and anti-excitotoxic effects in this KA-induced seizure model, these results indicate that the neuroprotective effect of GL in the KA-injected mouse brain might be attributable to the inhibitions of HMGB1 induction and release, which in turn, mitigates the inflammatory process.     

Protective effect of calpain inhibitor N-acetyl-l-leucyl-l-leucyl-l-norleucinal on acute alcohol consumption related cardiomyopathy

Excessive alcohol consumption and alcoholism cause medical problems with high mortality and morbidity rates. In this study we aimed to decrease the alcohol related tissue damage by inhibiting calpain activation which plays an important role in apoptosis and necrosis, in rats with cardiomyopathy induced by acute alcohol consumption. Male Sprague–Dawley rats were separated into four groups (control, vehicle, alcohol and alcohol + inhibitor) with 10 rats in each. Control group received isocaloric maltose while vehicle group received isocaloric maltose with DMSO, and alcohol group received 8 g/kg absolute ethanol by gavage. Inhibitor group received 20 mg/kg calpain inhibitor 1 intraperitonally prior to alcohol administration. Calpain activities, cathepsin L levels and cytochrome c release rates were significantly increased in alcohol group compared to control group (p < 0.05). Serum CK MB and BNP levels of alcohol group were excessively increased compared to control group (respectively p < 0.001 and p < 0.01). Serum BNP levels of alcohol + inhibitor group were significantly (p < 0.05) decreased compared to alcohol group. In addition to these, histological evaluation of light microscope images and the results of DNA fragmentation and immunohistochemical caspase-3 activity results showed significant improvement of these parameters in alcohol + inhibitor group compared to alcohol group. Results of our biochemical and histological evaluation results revealed that the calpain inhibitor N-acetyl-leu-leu-norleucinal may have an ameliorating effect on acute alcohol consumption related cardiac tissue damage due to its effects on cell death pathways.     

Identifying candidate genes for discrimination of ulcerative colitis and Crohn’s disease

In this study we aimed to screen effective biomarkers for differential diagnosis of ulcerative colitis (UC) and Crohn’s disease (CD). By using the gene expression profile dataset GSE24287 including 47 ileal CD, 27 UC and 25 non-inflammatory bowel diseases control downloaded from Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) between UC patients and controls as well as between CD patients and controls (|log₂FC(fold change)| > 1 and p < 0.05). Then Gene Ontology (GO) functional enrichment analyses were performed for these DEGs in two groups, followed by the construction of weight PPI (protein–protein interaction) networks. Subnets enriched for the PPIs and differentially expressed genes were constructed based on the weight PPI networks. The overlapping genes between the genes in the top 10 subnets with smallest p value and the DEGs were selected as the candidate genes of disease. A total of 75 DEGs were identified in UC group and 87 ones in CD group. There were 69 and 57 specific DEGs in CD group and UC group, respectively. The DEGs in CD group were mainly enriched in “inflammatory response” and “defense response”, while the most significantly enriched GO terms in UC group were “anion transport” and “chemotaxis”. FOS and SOCS3 were identified as candidate genes for CD and other three genes HELB, ZBTB16 and FAM107A were candidate genes for UC. In conclusion, there were distinct genetic alterations between UC and CD. The candidate genes identified in current study may be used as biomarkers for differential diagnosis of CD and UC.     

Therapeutical Effects and Mechanism of Salubrinal Combined with Ulinastatin on Treating Paraquat Poisoning

To explore therapeutic effects and underlying mechanism of Salubrinal combined with Ulinastatin (UTI) on acute Paraquat (PQ) poisoning. Four hundred rats were randomly allocated into UTI group, SAL group, SAL + UTI and control group according to random number table with 100 rats in each group. Acute PQ poisoning models were established, and all rats received UTI, Salubrinal, SAL + UTI and normal saline injection, respectively. Afterward, we analyzed the change of lung tissue and explored the mechanism. Acute PQ poisoning caused significantly damage in rat lung tissue structure, and UTI could effectively repair lung tissue damage. Salubrinal suppressed hemorrhage and fibrosis, but promoted inflammatory infiltration. In contrast, UTI + Salubrinal suppressed hemorrhage, fibrosis and inflammatory infiltration, but could not improve lung tissue damage. Expression of LC3 and Bcl-2 showed statistically significant difference among different groups (p < 0.05). LC3 and Bcl-2 levels in UTI group were much higher than in the other groups, and LC3 and Bcl-2 levels in UTI + SAL group was second higher. LC expression in SAL group was lower than in UTI group and UTI + SAL group with Bcl-2 in control group significantly lower than in the other groups (p < 0.05). Expression of Caspase-3 and Bcl-2/Bax in lung tissue in different groups had statistically significant difference (p < 0.05). Caspase-3 in UTI group was lower than in the other groups; however, Bcl-2/Bax in UTI group was higher than in the other groups (p < 0.05). Acute PQ poisoning can cause endoplasmic reticulum stress–autophagy in rat, and UTI can increase Bcl-2 expression, decrease Caspase-3, which can inhibit progress of lung injury by suppressing apoptosis and exert good therapeutic effects. Although salubrinal has marked effects on protecting lung tissue, it can increase Bcl-2 expression, which is not beneficial to lung tissue protection. The underlying mechanism still needs further exploration.     

褪黑素对海人酸致痫大鼠海马内TGF-β3水平的影响

目的探讨褪黑素(me1atonin,MT)对海人酸(kainic acid,KA)致痫大鼠海马内TGF-β3的影响,进一步明确其在中枢内的作用。方法将实验大鼠随机分为3组:生理盐水对照组(NS组)、海人酸组(KA组)、褪黑素+海人酸组(MT+KA组)。各组大鼠给予相应试剂处理后观察并记录大鼠行为学改变,用免疫组织化学方法、RT-PCR检测大鼠海马内TGF-β3(transforming growth factor-β3)的表达情况及其mRNA变化。结果动物行为学观察显示,NS组无癫痫发作,KA组发作程度为Ⅲ-V级,MT+KA组为0-Ⅲ级;免疫组织化学结果显示,TGF-β3在3组大鼠海马内均有表达,其中KA组、MT+KA组较NS组表达增强,MT+KA组较KA组增强,差异具有显著性意义(P0.05);RT-PCR结果显示,与NS组相比较,KA组、MT+KA组大鼠海马内TGF-β3 mRNA含量均升高;但MT+KA组升高较KA组多,差异具有显著性意义(P0.05)。结论褪黑素能明显改善海人酸诱发的大鼠癫痫,增强海马内TGF-β3的表达,减轻海马神经元损伤,发挥中枢保护作用。     

Physical activity and alpha-lipoic acid modulate inflammatory response through changes in thiol redox status

α-Lipoic acid (αLA), as an inductor of hydrogen peroxide (H₂O₂) and nitrogen oxide (NO) generation and modulator of thiol redox status, plays an important role in cell signalling pathways. The study was designed to observe the effect of αLA on inflammatory response through changes in H₂O₂ and NO levels as well as thiol redox status. Sixteen physically active males were randomly assigned to one of two groups: placebo or αLA (1,200 mg?d^?1 for 10 days prior to exercise). The exercise trial involved a 90-min run at 65 % VO₂max (0 % gradient) followed by 15-min eccentric phase at 65 % VO₂max (?10 % gradient). Blood samples were collected before the exercise trial and then again 20 min, 24, and 48 h after. αLA significantly elevated H₂O₂ but reduced NO generation before or after exercise. Thiol redox status (GSH_total-2GSSG/GSSG) increased by >50 % after αLA and exercise (ANOVA, P?<?0.05) and correlated with changes in cytokines interleukin-6 (IL-6) (r?=??0.478, P?<?0.05) and IL-10 (r?=??0.455, P?<?0.05). This was caused by strong effect of αLA on GSSG concentration. αLA elevated IL-6 and IL-10 levels at 20 min after exercise and decreased in interleukin-1β and tumor necrosis factor α before and after exercise. This enhanced the regeneration of injured muscles. Creatine kinase activity tended to lower values after αLA intake. The study suggests that the combination of intense exercise with α-lipoic acid intake might be useful to improve the skeletal muscle regeneration through changes in inflammatory response which are associated with H₂O₂ and NO generation as well as thiol redox status.     

The Synergic Effect of Regular Exercise and Resveratrol on Kainate-Induced Oxidative Stress and Seizure Activity in Mice

The synergic effect of regular exercise and resveratrol, a polyphenolic compound with potent antioxidant activity, was investigated against kainate-induced seizures and oxidative stress in mice. After 6 weeks of swimming training, the total body weight decreased and the blood concentration of lactate stabilized statistically in comparison with the sedentary mice, indicate that the training program increased the aerobic resistance of mice. Kainate (30 mg/kg) evoked seizure activity 5 min after injection, and seizure activity was measured seizure rating scores every 5 min up to 2 h. As previously well known experiments, regular exercise and resveratrol (40 mg/kg, daily supplementation for 6 weeks) have an inhibitory effect on kainate-induced seizure activity and oxidative stress. In particularly, a synergistic cooperation of regular exercise and resveratrol was observed in seizure activity, mortality and oxidative stress especially in SOD activity. These results suggest that regular exercise along with an anti-convulsant agent such as resveratrol could be a more efficient method for the prevention of seizure development than exercise alone.     

Maternal obesity is associated with gut microbial metabolic potential in offspring during infancy

Children born to obese mothers are at increased risk for obesity, but the mechanisms behind this association are not fully understood. Our study aimed to investigate differences in the functions encoded by the microbiome of infants at 18 months of age when the transition from early infant-feeding to solid family foods is established. To investigate the impact of maternal prepregnancy body mass index on infants’ gut microbiome, faecal samples from infants born to normoweight (n = 21) and obese mothers (n = 18) were analysed by 16S rRNA gene sequencing and a functional-inference-based microbiome analysis. Our results indicated that Firmicutes was significantly enriched in infants born to normoweight mothers whereas Bacteroidetes was significantly enriched in infants born to obese women. In both microbiomes, the greatest number of genes (>50%) that were assigned a function encoded for proteins involved in “metabolism” among tier 1 KEGG Orthology (KO) categories. At lower KO functional categories, the microbiome of infants born to normoweight mothers was characterized by a significant enrichment in the abundances of “pentose phosphate pathway” (p = 0.037), “lysine biosynthesis” (p = 0.043), “glycerolipid metabolism” (p = 0.042), and “C5-branched dibasic acid metabolism” (p = 0.045). Notably, the microbiome of infants born to obese mothers was significantly enriched in “streptomycin biosynthesis” (p = 0.047), “sulphur metabolism” (p = 0.041), “taurine and hypotaurine metabolism” (p = 0.036), and “lipopolysaccharide biosynthesis” (p = 0.043). In summary, our study showed that maternal prepregnancy obesity may imprint a selective gut microbial composition during late infancy with distinct functional performances.     

Effects of Ezetimibe on Endothelial Progenitor Cells and Microparticles in High-Risk Patients

Imbalance on endothelial turnover can predict cardiovascular outcomes. We aimed at evaluating the effects of lipid-modifying therapies on circulating endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and platelet microparticles (PMPs) in high cardiovascular risk subjects with elevated C-reactive protein (CRP). Sixty-three individuals with coronary heart disease (CHD) or CHD risk equivalent on stable statin therapy, with LDL-cholesterol <100 mg/dL and CRP ≥2.0 mg/L were selected. After a 4-week run-in period with atorvastatin 10 mg, those with persistent CRP ≥2.0 mg/L were randomized to another 4-week treatment period with atorvastatin 40 mg, ezetimibe 10 mg or atorvastatin 40 mg/ezetimibe 10 mg. EPC (CD34⁺/CD133⁺/KDR⁺), EMP (CD51⁺), and PMP (CD42⁺/CD31⁺) were quantified by flow cytometry. Atorvastatin 40 mg and atorvastatin 40 mg/ezetimibe 10 mg reduced LDL-cholesterol (P < 0.001, paired T test, vs. baseline). Combined therapy, but not ezetimibe reduced CRP. CD34⁺/KDR⁺ EPC were reduced after ezetimibe alone (P = 0.011 vs. baseline, Wilcoxon test) or combined with atorvastatin (P = 0.016 vs. baseline, Wilcoxon test). In addition, ezetimibe increased CD51⁺ EMP (P = 0.017 vs. baseline, Wilcoxon test). No correlations between these markers and LDL-cholesterol or CRP were observed. These results contribute to understand the link between inflammation and vascular homeostasis and highlight the broader benefit of statins decreasing inflammation and preventing microparticles release, an effect not observed with ezetimibe alone.     

Effects of Nickel Chloride on the Erythrocytes and Erythrocyte Immune Adherence Function in Broilers

This study was conducted to investigate the immune adherence function of erythrocytes and erythrocyte induced by dietary nickel chloride (NiCl₂) in broilers fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg NiCl₂ for 42 days. Blood samples were collected from five broilers in each group at 14, 28, and 42 days of age. Changes of erythrocyte parameters showed that total erythrocyte count (TEC), hemoglobin (Hb) contents, and packed cell volume (PCV) were significantly lower (p?p?p?p?+/K⁺-ATPase) and calcium adenosine triphosphatase (Ca²⁺-ATPase) activities were significantly decreased (p?p?2-treated groups. The results of erythrocyte immune adherence function indicated that erythrocyte C_3b receptor rosette rate (E-C_3bRR) was significantly decreased (p?p?p?p?2 in excess of 300 mg/kg caused anemia and impaired the erythrocytic integrity, erythrocytic ability to transport oxygen, and erythrocyte immune adherence function in broilers. Impairment of the erythrocytes and erythrocyte immune adherence function was one of main effect mechanisms of NiCl₂ on the blood function.     

Evaluation of annual resolution coral geochemical records as climate proxies in the Great Barrier Reef of Australia

Sampling of annually banded massive coral skeletons at annual (or higher) resolutions is increasingly being used to obtain replicate long-term time series of changing seawater conditions. However, few of these studies have compared and calibrated the lower annual resolution records based on coral geochemical tracers with the corresponding instrumental climate records, although some studies have inferred the climatic significance of annual coral series derived from averages of monthly or sub-annual records. Here, we present annual resolution analysis of coral records of elemental and stable isotopic composition that are approximately 70 years long. These records were preserved in two coexisting colonies of Porites sp. from Arlington Reef, on the Great Barrier Reef in Australia, and are used to evaluate the climatic significance of annually resolved coral geochemical proxies. The geochemical records of coral sample “10AR2,” with its faster and relatively constant annual growth rate, appear to have been independent of skeletal growth rate and other vital effects. The annual resolution of Sr/Ca and Δδ¹⁸O time series was shown to be a good proxy for annual sea surface temperature (SST; r = ?0.67, n = 73, p < 0.0000001) and rainfall records (r = ?0.34, n = 67, p < 0.01). However, a slower growing coral sample, “10AR1” showed significantly lower correlations (r = ?0.20, n = 71, p = 0.05 for Sr/Ca and SST; r = ?0.19, n = 67, p = 0.06 for Δδ¹⁸O and rainfall), indicating its greater susceptibility to biological/metabolic effects. Our results suggest that while annually resolved coral records are potentially a valuable tool for determining, in particular, long timescale climate variability such as Pacific Decadal Oscillation, Interdecadal Pacific Oscillation, and other climatic factors, the selection of the coral sample is important, and replication is essential.     

Effects of Mild and Moderate Hypothemia Therapy on Expression of Cerebral Neuron Apoptosis Related Proteins and Glial Fiber Acidic Protein After Rat Cardio-pulmonary Resuscitation

To explore the effects of different degrees of hypothermia on brain tissue apoptosis after cardio-pulmonary resuscitation (CPR). Cardiac arrest for 5 min induced by asphyxia method was used to create CPR model. 30 SD rats were randomly divided into control group (normothermia), 33 °C hypothermia group and 30 °C hypothermia group with ten rats in each. Rats in control group received routine treatment at 25 °C room temperature after CPR; Rats in mild hypothermia and moderate hypothermia groups were given hypothermia treatment 0.5 h after CPR. Brain tissue in all groups was taken 24 h after CPR, and immunohistochemistry was used to detect the caspase-3 in cerebral cortex and glial fiber acidic protein (GFAP) expression in astrocyte. Western blotting was used to detect Bcl-2 and Bax protein expression, and histopathological change was observed in brain tissue. Compare to the control group, caspase-3 expression in cerebral neurons in hypothermia group was significantly decreased (p<0.01), which was significantly lower in 30 °C group than that in 33 °C group (p > 0.05); GFAP level in hypothermia groups was significantly increased (p < 0.01), which was higher in 30 °C hypothermia group than that in 33 °C hypothermia group (p < 0.05); Bcl-2 expression level in hypothermia group was significantly increased (p < 0.01), which was higher in 30 °C hypothermia group than that in 33 °C hypothermia group (p < 0.05); The level of Bax had no significant difference among the three groups. Hypothermia-regulated GFAP expression by decreasing caspase-3 expression and increasing Bcl-2 expression to promote brain cell signaling transduction, and further inhibited cell apoptosis and reduced brain injury. Moderate hypothermia therapy is more effective than mild hypothermia in preventing brain injure.     

The role of cystatin C in vascular remodeling of balloon-injured abdominal aorta of rabbits

This study aimed to evaluate the role of cystatin C (CysC) in the vascular remodeling of balloon-injured abdominal aorta of rabbits. Forty-eight New Zealand white rabbits were randomly divided into three groups: the balloon-injured injury group (n = 16), the CysC monoclonal antibody group (n = 16), and the sham-operative group (n = 16). Serum CysC levels were detected by enzyme linked immunosorbent assay. Changes in adventitial area, adventitial thickness, lumen area (LA), neointimal area (IA), internal elastic lamina area (IELA), external elastic lamina area (EELA), vascular remodeling index (VRI) and residual stenosis (RS) were measured by the Leica image analysis system. Immunohistochemical analysis of α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) were performed. Serum CysC levels of rabbits in the balloon-injured injury group were significantly higher than those in the CysC monoclonal antibody group and the sham-operative group (both P < 0.05). At 6 weeks after balloon injury, the adventitial area and thickness, LA, IA, IELA and EELA in the balloon-injured injury group were also higher than those in the CysC monoclonal antibody and sham-operative groups (all P < 0.05). In addition, the balloon-injured injury group showed higher VRI and RS than those of the CysC monoclonal antibody group (both P < 0.05). The positive expression of α-SMA in the vascular adventitia and media in the balloon-injured group were higher than that of the CysC monoclonal antibody and sham-operative groups. The balloon-injured group also showed a stronger expression of α-SMA in the neointima than that of the CysC monoclonal antibody group. There was a strong positive expression of PCNA in the vascular adventitia and neointima in the balloon-injured and CysC monoclonal antibody groups. However, the number of PCNA-positive cells in the balloon-injured group was higher than that of the CysC monoclonal antibody group (25.45 ± 4.21 vs. 6.75 ± 1.11, P = 0.003). Our findings provide empirical evidence that serum CysC levels may play an important role in the vascular remodeling of balloon-injured abdominal aorta of rabbits.     

Role of CC-chemokine receptor 5 on myocardial ischemia–reperfusion injury in rats

The expression level of CC-chemokine receptor 5 (CCR5) is enhanced post inflammatory stimulations and might play a crucial role on inflammatory cells infiltration post myocardial ischemia. The purpose of this study was to evaluate the role of CCR5 on myocardial ischemia–reperfusion (I/R) injury in rats. Adult male rats were randomized to sham group, I/R group (I/R, 30 min coronary artery occlusion followed by 2-h reperfusion), ischemic preconditioning (I/R + Pre), CCR5 antibody group [I/R + CCR5Ab (0.2 mg/kg)], and CCR5 agonist group [I/R + CCR5Ago, RNATES (0.1 mg/kg)], n = 12 each group. The serum level of creatine kinase (CK) and tumor necrosis factor α (TNF-α) were measured by ELISA. Myocardial infarction size and myeloperoxidase (MPO) activity were determined. Myocardial protein expression of CCR5 and intercellular adhesion molecule-1 (ICAM-1) were evaluated by Western blotting and immunohistochemistry staining, respectively. Myocardial nuclear factor-kappa B (NF-κB) activity was assayed by electrophoretic mobility shift assay. Myocardial CCR5 protein expression was significantly reduced in I/R + Pre group (P < 0.05 vs. I/R) and further reduced in I/R + CCR5Ab group (P < 0.05 vs. I/R + Pre). LVSP and ±dP/dt _max were significantly lower while serum CK and TNF-α as well as myocardial MPO activity, ICAM-1 expression, and NF-κB activity were significantly higher in I/R group than in sham group (all P < 0.05), which were significantly reversed by I/R + Pre (all P < 0.05 vs. I/R) and I/R + CCR5Ab (all P < 0.05 vs. I/R + Pre) while aggravated by I/R + CCR5Ago (all P < 0.05 vs. I/R). Our results suggest that blocking CCR5 attenuates while enhancing CCR5 aggravates myocardial I/R injury through modulating inflammatory responses in rat heart.     

De novo expression of fetal ED-A+ fibronectin and B+ tenascin-C splicing variants in human cardiac allografts: potential impact for targeted therapy of rejection

Management of acute and especially chronic rejection after human cardiac transplantation is still challenging. Chronic rejection, represented by allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) is known to cause severe long-term complications. Rejection associated tissue-remodelling entails the reoccurrence of fetal variants of Fibronectin (Fn) and Tenascin-C (Tn-C), which are virtually absent in adult human organs. In a rat model, an extensive re-expression could be demonstrated for ED-A⁺ Fn with spatial association to CAV and CIF. Thus, it is of great interest to investigate the cardiac tissue expression and distribution in human samples. From 48 heart transplanted patients, 64 tissue specimens derived from right ventricular biopsies were available. Histopathological analysis was performed according to the International Society for Heart and Lung Transplantation (ISHLT) guidelines for the detection of acute rejection. By immunohistochemistry, protein expression of ED-A⁺ Fn, B⁺ Tn-C, alpha-smooth muscle actin, CD31 and CD45 was assessed and analysed semiquantitatively. Co-localisation studies were performed by means of immunofluorescence double labelling. Histopathological analysis of the 64 samples revealed different ISHLT grades (0R in 36 cases, 1R in 20 cases and 2R in 8 cases). There was a distinct and quantitatively relevant re-occurrence of ED-A⁺ Fn and B⁺ Tn-C in most samples. Semi-quantitative evaluation did not show any correlation to the acute rejection grade for all markers. Interestingly, significant correlations to the extent of inflammation could be shown for ED-A⁺ Fn (r = 0.442, p = 0.000) and B⁺ Tn-C (r = 0.408, p = 0.001) as well as between both proteins (r = 0.663, p = 0.000). A spatial association of ED-A⁺ Fn and B⁺ Tn-C to CAV and CIF could be demonstrated. A relevant re-occurrence of ED-A⁺ Fn and B⁺ Tn-C following human heart transplantation could be demonstrated with spatial association to signs of rejection and a significant correlation to tissue inflammation. These data might contribute to the identification of novel biomarkers reflecting the rejection process and to the development of promising strategies to image, prevent or treat cardiac rejection.     

The association between C-159T polymorphism in CD14 gene and susceptibility to tuberculosis: a meta-analysis

The association between CD14 gene C-159T polymorphism and tuberculosis (TB) susceptibility remains inconclusive. To derive a more precise estimation of the correlation, we performed a meta-analysis summarize the possible at a systematic manner. PubMed, HighWire and ScienceDirect databases covering all papers (up to November 2012) were searched. Statistical analyses were conducted by Rev-Man and STATA. Random- and fixed-effect models were used to estimate pooled odds ratios (ORs) and 95 % confidence intervals (CIs), based on between-study heterogeneity. Eight published case–control studies investigating the relationship between C-159T polymorphism in CD14 gene and TB susceptibility were included. Results showed that individuals with T allele have an increased risk of TB compared with those with C allele (OR (95 % CI) was 1.52 (1.11, 2.08) for TT vs. TC + CC, P < 0.001; 1.27 (1.01, 1.61) for T vs. C, P = 0.04). When stratified by ethnicity, variant TT homozygote carriers had an 86 % increased risk of TB in Asians (OR (95 % CI) was 1.86 (1.57, 2.20) for TT vs. TC + CC, P < 0.001), but not in Caucasians (OR (95 % CI) was TT vs. TC + CC: OR = 0.78, 95 % CI = 0.51–1.21, P = 0.61). This meta-analysis suggests that C-159T polymorphism in CD14 gene is associated with increased risk of TB, especially in Asians, but not in Caucasians.     

Mechanisms of Na+ uptake,ammonia excretion,and their potential linkage in native Rio Negro tetras (Paracheirodon axelrodi,Hemigrammus rhodostomus,and Moenkhausia diktyota)

Mechanisms of Na⁺ uptake, ammonia excretion, and their potential linkage were investigated in three characids (cardinal, hemigrammus, moenkhausia tetras), using radiotracer flux techniques to study the unidirectional influx (J _in), efflux (J _out), and net flux rates (J _net) of Na⁺ and Cl^?, and the net excretion rate of ammonia (J _Amm). The fish were collected directly from the Rio Negro, and studied in their native “blackwater” which is acidic (pH 4.5), ion-poor (Na⁺, Cl^? ~20 µM), and rich in dissolved organic matter (DOM 11.5 mg C l^?1). J _in ^Na , J _in ^Cl , and J _Amm were higher than in previous reports on tetras obtained from the North America aquarium trade and/or studied in low DOM water. In all three species, J _in ^Na was unaffected by amiloride (10^?4 M, NHE and Na⁺ channel blocker), but both J _in ^Na and J _in ^Cl were virtually eliminated (85–99 % blockade) by AgNO₃ (10^?7 M). A time course study on cardinal tetras demonstrated that J _in ^Na blockade by AgNO₃ was very rapid (<5 min), suggesting inhibition of branchial carbonic anhydrase (CA), and exposure to the CA-blocker acetazolamide (10^?4 M) caused a 50 % reduction in J _in ^Na _.. Additionally, J _in ^Na was unaffected by phenamil (10^?5 M, Na⁺ channel blocker), bumetanide (10^?4 M, NKCC blocker), hydrochlorothiazide (5 × 10^?3 M, NCC blocker), and exposure to an acute 3 unit increase in water pH. None of these treatments, including partial or complete elimination of J _in ^Na (by acetazolamide and AgNO₃ respectively), had any inhibitory effect on J _Amm. Therefore, Na⁺ uptake in Rio Negro tetras depends on an internal supply of H⁺ from CA, but does not fit any of the currently accepted H⁺-dependent models (NHE, Na⁺ channel/V-type H⁺-ATPase), or co-transport schemes (NCC, NKCC), and ammonia excretion does not fit the current “Na⁺/NH₄ ⁺ exchange metabolon” paradigm. Na⁺, K⁺-ATPase and V-type H⁺-ATPase activities were present at similar levels in gill homogenates, Acute exposure to high environmental ammonia (NH₄Cl, 10^?3 M) significantly increased J _in ^Na , and NH₄ ⁺ was equally or more effective than K⁺ in activating branchial Na⁺,(K⁺) ATPase activity in vitro. We propose that ammonia excretion does not depend on Na⁺ uptake, but that Na⁺ uptake (by an as yet unknown H⁺-dependent apical mechanism) depends on ammonia excretion, driven by active NH₄ ⁺ entry via basolateral Na⁺,(K⁺)-ATPase.     

Quantitative Assessment of the Association Between HDMX Polymorphism and Sarcoma

To investigate the effects of the HDMX polymorphism on sarcoma risk. Relevant studies were identified by searching the PubMed, Embase, and Web of Science databases. Data were extracted by two independent investigators. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using a fixed-effects model to assess the association between the HDMX polymorphism and sarcoma risk. We also conducted heterogeneity test, sensitivity analysis, and publication bias test. A meta-analysis of four published case–control studies involving 1,115 subjects (379 cases and 736 controls) showed no statistical association between the HDMX polymorphism and sarcoma risk (OR_{TT vs. GG}  0.88, 95 % CI  0.68–1.14, P _{heterogeneity}  0.819; OR_{TT + TG vs. GG} 0.95, 95 % CI  0.79–1.15, P _{heterogeneity}  0.937; OR_{TT vs. TG + GG}  0.82, 95 % CI  0.65–1.04, P _{heterogeneity}  0.589; OR_{T allele vs. G allele}  0.91, 95 % CI  0.79–1.05, P _{heterogeneity}  0.727; OR_{TG vs. GG}  0.95, 95 % CI  0.74–1.22, P _{heterogeneity} = 0.869). This null result did not alter when data were stratified according to ethnicity. Our meta-analysis indicates that the HDMX polymorphism is unlikely to contribute to individual susceptibility to sarcoma.     

Effects of Qufeng Xuanfei Decoction in Animal Model of Post-Infectious Cough

This study evaluated the effects and potential mechanisms of Qufeng Xuanfei decoction in animal model of post-infectious cough. Sixty SD rats were randomly divided into six groups (10 animals per group): control, disease model, low- (4.62 g kg^?1), medium- (9.24 g kg^?1), and high-dose (13.86 g kg^?1) decoction, and positive treatment groups (dextromethorphan hydrobromide, 8 mL kg^?1). To model post-infectious cough, all but control group animals were challenged with exposure to 50 g sawdust and 10 cigarette smokes for 30 min day^?1 for a total of 10 days, followed by subsequent exposures to lipopolysaccharide (20 µg) and capsaicin (10^?4 M) aerosols. The drugs were given by oral gavage for 15 days after which lung pathology, cell counts and cell differentials in bronchoalveolar lavage (BAL), and concentrations of neuropeptides [substance P (SP), neurokinins A (NKA) and B (NKB), and calcitonin gene-related peptide (CGRP)] in BAL (ELISA) were assessed. Compared with control group animals, significant inflammation and damage to bronchial epithelium were observed in the disease model group. A marked decrease in BAL percentages of all types of inflammatory cells was observed in the decoction-treated groups, with most changes in the medium-dose decoction group (p < 0.001 vs. disease model group). Further, airway inflammation and damage, as well as the levels of SP, NKA, NKB, and CGRP in BAL decreased the most in the medium-dose group (p < 0.001 vs. disease model group). In conclusion, medium-dose Qufeng Xuanfei decoction efficiently decreases the levels of neuropeptides, attenuates airway inflammation, and promotes recovery from disease.