Effect of one-lung ventilation on the correlation between left and right cerebral saturation.

BACKGROUND: To investigate if the correlation between left and right cerebral tissue oxygen saturation (SctO2) was affected by one-lung ventilation (OLV) in patients undergoing lung cancer surgery. METHODS: Patients who underwent surgery for lung cancer were enrolled. Left and right SctO2 were collected during anesthesia. The primary outcome was the correlation between left and right SctO2 at 30 min after OLV which was analysed by Pearson correlation and linear regression model. Secondary outcomes included the trend of left-right SctO2 change over the first 30 min after OLV, correlation of left-right SctO2 during OLV for each patient; maximal difference between left-right SctO2 and its relationship with postoperative delirium. RESULTS: Left-right SctO2 was moderately correlated at baseline (r = 0.690, P < 0.001) and poorly correlated at 30 min after OLV (r = 0.383, P < 0.001) in the Pearson correlation analysis. Linear regression analysis showed a poor correlation between left and right SctO2 at 30 min after OLV (r = 0.323, P < 0.001) after adjusting for confounders. The linear mixed model showed a change in left-right SctO2 over the first 30 min after OLV that was statistically significant (coefficient, -0.042; 95% CI, -0.070--0.014; P = 0.004). For the left-right SctO2 correlation during OLV in each patient, 62.9% (78/124) patients showed a strong correlation, 19.4% (24/124) a medium correlation, and the rest a poor correlation. The maximal difference between the left and right SctO2 was 13.5 (9.0, 20.0). Multivariate analysis showed that it was not associated with delirium (odds ratio [OR], 1.023; 95% CI, 0.963-1.087; P = 0.463). CONCLUSIONS: The correlation between left and right SctO2 was affected by one-lung ventilation in patients undergoing lung cancer surgery. This result indicates the requirement of bilateral SctO2 monitoring to reflect brain oxygenation. TRIAL REGISTRATION: This study was a secondary analysis of a cohort study approved by the Clinical Research Review Board of Peking University First Hospital (#2017-1378) and was registered in the Chinese Clinical Trial Registry on 10/09/2017 ( http://www.chictr.org.cn , ChiCTR-ROC-17012627).

Inhibition of Cerebral High-Mobility Group Box 1 Protein Attenuates Multiple Organ Damage and Improves T Cell-Mediated Immunity in Septic Rats.

Sepsis remains one of the leading causes of mortality in intensive care units, but there is a shortage of effective treatments. A dysregulated host immune response and multiple organ injury are major factors for the pathogenesis and progression of sepsis, which require specific mechanism and treatment. In the present study, we performed an intracerebroventricular (ICV) injection of BoxA, a specific antagonist of high-mobility group box 1 protein (HMGB1), in septic rats that were produced by cecal ligation and puncture surgery; we further assessed the functional changes of multiple organs and splenic T lymphocytes. We found that the inhibition of cerebral HMGB1 significantly alleviated multiple organ damage under septic exposure, including damage to the heart, liver, lungs, and kidneys; reversed the immune dysfunction of T cells; and increased the survival of septic rats. These data suggest that central HMGB1 might be a potential therapeutic target for septic challenge and that inhibition of brain HMGB1 can protect against multiple organ dysfunction induced by sepsis.

Disaster Nursing Development in China and Other Countries: A Bibliometric Study.

PURPOSE: China is a country with frequent disasters, and nurses play indispensable roles in the disaster process. The Chinese disaster nursing specialty developed with several deficiencies. This study aimed to identify the limitations in the development of disaster nursing in China and to provide a reference for the future by comparing relevant studies between China and other countries. DESIGN: A systematic literature review was conducted in English and Chinese databases to identify disaster nursing articles published from January 1, 2000, to December 31, 2016. METHODS: This study followed the systematic literature collection tactic and bibliometric method. Basic information such as country, number of publications, and discussed disaster types were described through frequency distributions. Article themes were extracted and divided into the four phases of the International Council of Nurses Framework of Disaster Nursing Competencies. FINDINGS: 1,384 articles were included in the analysis, containing 781 written in Chinese and 603 written in English (with 56 of them written by Chinese researchers). The number of Chinese disaster nursing articles and other publications increased sharply between 2007 and 2009 but dropped significantly afterwards, while the total number of articles in other countries fluctuated, with a general upward trend. Compared to other countries, there were fewer research methods used and less focus on disaster prevention and preparedness in China, an imbalanced focus on disaster types, and a lack of focus on prevention, preparedness, and recovery phases. CONCLUSIONS: In China, there is a lack of stable development of disaster nursing research, a lack of study types, and less focus on disaster prevention, preparedness, and recovery. Varied study methods and an increased focus on disaster prevention and preparedness are required in the future. CLINICAL RELEVANCE: This study analyzed the deficiencies in Chinese disaster nursing, which led to recommendations and proposed directions for future studies and a clinical focus in this field, in compliance with the United Nations guidelines for disaster management.

[Sensitive Bands Extraction and Prediction Model of Tomato Chlorophyll in Glass Greenhouse].

In order to predict the content of chlorophyll in tomato rapidly and accurately, this study, with spectrum technology, focused on the extraction of sensitive spectral bands of tomato chlorophyll in glass greenhouse environment and created an effective estimation model. During the period of cultivating tomatoes, leaf spectra were measured with an ASD FieldSpec HH spectrophotometer and chlorophyll content was measured with Type 752 UV-Vis spectrophotometer. Based on the original spectra, absorbance spectra, first derivative spectra and continuum removal spectra, spectral data was preprocessed, in which the effectiveness of spectral features of chlorophyll content of tomato was highlighted and spectral response characteristics of the absorbance spectra in the visible part was enhanced. It was shown that both the continuum removal spectra and the first derivative spectra have strong blue and red absorption valley and green reflection peak. In this paper, the original spectrum, absorbance spectrum, first derivative spectrum and continuum removal spectrum were analyzed and compared, and then optimal spectral feature parameters were extracted with methods of Inter-Correlation analysis and multivariate collinearity diagnosis. Sensitive bands from original spectrum are 639, 672, 696, 750 and 768 nm. Sensitive bands from absorbance spectrum are 638, 663, 750 and 763 nm. Sensitive bands from first derivative spectrum are 516, 559 and 778 nm. Sensitive bands from continuum removal spectrum are 436, 564, 591, 612, 635, 683 and 760 nm. The stepwise multiple regressions were used to develop the prediction models of the chlorophyll content of tomato leaf. The result showed that the prediction model, which used the values from continuum removal spectrum at 436, 564, 591, 612, 635, 683, 760 nm as input variables, had the best predictive ability. The calibration R-Square was 0.88 and the validation R-Square was 0.82.

Atorvastatin-modified dendritic cells in vitro ameliorate experimental autoimmune myasthenia gravis by up-regulated Treg cells and shifted Th1/Th17 to Th2 cytokines.

Conventional therapies for autoimmune diseases produce nonspecific immune suppression, which are usually continued lifelong to maintain disease control, and associated with a variety of adverse effects. In this study, we found that spleen-derived dendritic cells (DCs) from the ongoing experimental autoimmune myasthenia gravis (EAMG) rats can be induced into tolerogenic DCs by atorvastatin in vitro. Administration of these tolerogenic DCs to EAMG rats on days 5 and 13 post immunization (p.i.) resulted in improved clinical symptoms, which were associated with increased numbers of CD4(+)CD25(+) T regulatory (Treg) cells and Foxp3 expression, decreased lymphocyte proliferation among lymph node mononuclear cells (MNC), shifted cytokine profile from Th1/Th17 to Th2 type cytokines, decreased level of anti-R97-116 peptide (region 97-116 of the rat acetylcholine receptor α subunit) IgG antibody in serum. These tolerogenic DCs can migrate to spleen, thymus, popliteal and inguinal lymph nodes after they were injected into the EAMG rats intraperitoneally. Furthermore, these tolerogenic DCs played their immunomodulatory effects in vivo mainly by decreased expression of CD86 and MHC class II on endogenous DCs. All these data provided us a new strategy to treat EAMG and even human myasthenia gravis (MG).

[Visible-NIR spectral feature of citrus greening disease].

Citrus greening (Huanglongbing, or HLB) is a devastating disease caused by Candidatus liberibacter which uses psyllids as vectors. It has no cure till now, and poses a huge threat to citrus industry around the world. In order to diagnose, assess and further control this disease, it is of great importance to first find a quick and effective way to detect it. Spectroscopy method, which was widely considered as a fast and nondestructive way, was adopted here to conduct a preliminary exploration of disease characteristics. In order to explore the spectral differences between the healthy and HLB infected leaves and canopies, this study measured the visible-NIR spectral reflectance of their leaves and canopies under lab and field conditions, respectively. The original spectral data were firstly preprocessed with smoothing (or moving average) and cluster average procedures, and then the first derivatives were also calculated to determine the red edge position (REP). In order to solve the multi-peak phenomenon problem, two interpolation methods (three-point Lagrangian interpolation and four-point linear extrapolation) were adopted to calculate the REP for each sample. The results showed that there were, obvious differences at the visible & NIR spectral reflectance between the healthy and HLB infected classes. Comparing with the healthy reflectance, the HLB reflectance was higher at the visible bands because of the yellowish symptoms on the infected leaves, and lower at NIR bands because the disease blocked water transportation to leaves. But the feature at NIR bands was easily affected by environmental factors such as light, background, etc. The REP was also a potential indicator to distinguish those two classes. The average REP was slowly moving toward red bands while the infection level was getting higher. The gap of the average REPs between the healthy and HLB classes reached to a maximum of 20 nm. Even in the dataset with relatively lower variation, the classification accuracy of threshold segmentation method by the REP could reach to more than 90%. The four-point linear extrapolation method had slightly better result than the three-point Lagrangian interpolation method. This study provided useful theoretical foundation to detect HLB by spectral reflectance.

The characterization of a concentration-sensitive α-adrenergic-like octopamine receptor found on insect immune cells and its possible role in mediating stress hormone effects on immune function.

Octopamine (OA), the insect equivalent of norepinephrine, links the nervous system and immune system in insects. This study examines the underlying molecular mechanisms (i.e. second messenger systems) mediating OA effects on insect immune cells. At low concentrations (<1µM), OA stimulatedhemocyte spreading and phagocytosis in the larval Lepidopteran (caterpillar) Chilo suppressalis, whereas at high concentrations (>10 µM), OA inhibited hemocyte spreading and phagocytosis. Similarly, OA concentration had differential effects on two intracellular signaling pathways, Ca(2+) and cAMP. Low concentrations of OA increased intracellular Ca(2+), but only high concentrations of OA (>1 µM) led to an increase in both Ca(2+) and cAMP. We identified an α-adrenergic-like octopamine receptor in this species (CsOA1) and confirmed that it is expressed in hemocytes. After heterologous expression in HEK-293 cells, the CsOA1 receptor produced the same OA concentration-dependent responses on intracellular Ca(2+) and cAMP as had been observed in hemocytes. These findings support earlier work showing that OA has both stimulatory and suppressive effects on immune responses, depending on the OA concentration. Our evidence suggests that these biphasic effects are mediated by an octopamine receptor signaling through intracellular Ca(2+) and cAMP second messenger pathways. Stress hormones/neuromodulators have complex effects on immune function in animals across phyla. This complexity may be mediated, in part, by conserved connections between adrenergic-like G-coupled protein receptors and second messenger systems.

The apoptotic effect and associated signalling of HSP90 inhibitor 17-DMAG in hepatocellular carcinoma cells.

Primary liver cancer is one of the highly malignant tumours. The traditional surgery, chemotherapy and radiation therapy only established 6% of 5-year survival rate in HCC (hepatocellular carcinoma). Therefore there is an urgent need to develop new therapeutic strategies. HSP90 (heat shock protein 90) is one of the important molecular chaperones and was identified with high expression in the primary liver cancer. In this study, we evaluated the therapeutic effect of specific HSP90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxy geldanamycin) in HCC cells. The time and concentration effects of 17-DMAG were investigated in HCC cells. Cell proliferation was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and cell counting. Apoptosis was detected by flow cytometry with staining of Annexin V-FITC/PI (propidium iodide). The protein levels of survivin, cyclin D1, p53 and NF-κB (nuclear factor κB) were measured by Western blotting. 17-DMAG inhibited the proliferation of HCC cells in a time- and concentration-dependent manner. Treatment with 400 nmol/l 17-DMAG for 48 h significantly induced early-stage apoptosis (22.4%). Conversely, it induced less late-stage apoptosis (3.03%). The 5 mg/l of cisplatin induced significantly less early-stage apoptosis (6.5%), but similar proportion of late-stage apoptosis (4.89%) compared with 17-DMAG. Inhibition of HSP90 activity by 400 nmol/l 17-DMAG decreased protein levels of survivin, cyclin D1 and NF-κB protein levels, whereas increased p53 protein level. HSP90 plays a key role in HCC cell growth and survival through regulation of survivin, cyclin D1, p53 and nucleus NF-κB protein levels and the specific HSP90 inhibitor 17-DMAG can play a therapeutic role in HCC treatment.

Genome-Wide Identification and Transcriptional Expression Profiles of PP2C in the Barley (Hordeum vulgare L.) Pan-Genome.

The gene family protein phosphatase 2C (PP2C) is related to developmental processes and stress responses in plants. Barley (Hordeum vulgare L.) is a popular cereal crop that is primarily utilized for human consumption and nutrition. However, there is little knowledge regarding the PP2C gene family in barley. In this study, a total of 1635 PP2C genes were identified in 20 barley pan-genome accessions. Then, chromosome localization, physical and chemical feature predictions and subcellular localization were systematically analyzed. One wild barley accession (B1K-04-12) and one cultivated barley (Morex) were chosen as representatives to further analyze and compare the differences in HvPP2Cs between wild and cultivated barley. Phylogenetic analysis showed that these HvPP2Cs were divided into 12 subgroups. Additionally, gene structure, conserved domain and motif, gene duplication event detection, interaction networks and gene expression profiles were analyzed in accessions Morex and B1K-04-12. In addition, qRT-PCR experiments in Morex indicated that seven HvMorexPP2C genes were involved in the response to aluminum and low pH stresses. Finally, a series of positively selected homologous genes were identified between wild accession B1K-04-12 and another 14 cultivated materials, indicating that these genes are important during barley domestication. This work provides a global overview of the putative physiological and biological functions of PP2C genes in barley. We provide a broad framework for understanding the domestication- and evolutionary-induced changes in PP2C genes between wild and cultivated barley.

Nanoparticle-delivered VEGF-silencing cassette and suicide gene expression cassettes inhibit colon carcinoma growth in vitro and in vivo.

The strategies for tumor-specific expression of suicide genes and target tumor angiogenesis have been tested in tumors. However, the anti-tumor efficacy of the combination of these two strategies, particularly, delivering suicide gene and anti-angiogenesis agent by nanoparticles, has not yet been evaluated in colon carcinoma. We constructed a cassette to silence VEGF-A expression and express a fused yCDglyTK gene driven by tumor-specific promoter (shVEGF-CDTK). The DNA carrying shVEGF-CDTK was delivered into colon carcinoma cells by calcium phosphate nanoparticles (CPNPs). Cell proliferation was measured by MTT assay, and apoptosis was detected by flow cytometry. The anti-tumor effect of the combined cassette was tested in xenograft animal model. With 5-fluorocytosine (5-FC), CPNP-delivered shVEGF-CDTK DNA (CPNP-shVEGF-CDTK) showed high expression of fused yCDglyTK gene and effectively silenced VEGF-A expression in vitro and in vivo, which significantly inhibited colon carcinoma cell proliferation and induced apoptosis in vitro. With 5-FC, the systemic delivery of CPNP-shVEGF-CDTK significantly inhibited tumor growth in the colon carcinoma xenograft animal model. The combined cassette is obviously effective in inhibiting tumor cell proliferation and inducing apoptosis in vitro and tumor growth in vivo than the CPNP-shVEGF or CPNP-CDTK alone. The combination of VEGF-A-silencing and tumor-specific expression of suicide gene is an effective strategy for colon carcinoma treatment.

[Prediction of chlorophyll content of greenhouse tomato using wavelet transform combined with NIR spectra].

In quantitative analysis of spectral data, noises and background interference always degrade the accuracy of spectral feature extraction. The wavelet transform is multi-scale decomposition used to reduce the noise and improve the analysis precision. On the other hand, the wavelet transform denoising is often followed by destroying the efficiency information. The present research introduced two indexes to control the scale of decomposition, the smoothness index (SI) and the time shift index (TSI). When the parameters satisfied TSI < 0.01 and SI > 0.100 4, the noise of spectral characteristic was reduced. In the meanwhile, the reflection peaks of biochemical components were reserved. Through analyzing the correlation between denoised spectrum and chlorophyll content, some spectral characteristics parameters reflecting the changing tendency of chlorophyll content were chosen. Finally, the partial least squares regression (PLSR) was used to develop the prediction model of the chlorophyll content of tomato leaf. The result showed that the predictiong model, which used the values of absorbance at 366, 405, 436, 554, 675 and 693 nm as input variables, had higher predictive ability (calibration coefficient was 0. 892 6, and validation coefficient was 0.829 7) and better potential to diagnose tomato growth in greenhouse.

Extracorporeal whole blood immuno-adsorption of passively transferred myasthenia gravis rabbits by cellulose-tryptophan column.

The whole blood immuno-adsorption (WBIA) system, using an adsorbent to remove pathogenic antibodies of Myasthenia Gravis (MG), was studied. Cellulose-tryptophan adsorbent was synthesized and purified in our lab. Experimental autoimmune myasthenia gravis (EAMG) rabbits were passively transferred with immunoglobulin from patients with myasthenia gravis. The rabbits underwent extracorporeal whole blood adsorption for 2 hours. Results showed no significant damage to blood cells and no changes in the concentrations of electrolytes. Total protein decreased by 12.6% (P<0.05) and globulin protein decreased 21.9% (P<0.05). The overall removal of antibodies against nicotinic acetylcholine receptor (nAChR) was 49.85%. The percentage of decrement of compound muscle action potential in 3, 5, 10 Hz of EAMG rabbits all dropped down after the treatment. The quantity of neuromuscular junctions per unit area (25 mm(2)) increased significantly after treatment (P<0.05). In conclusion, the adsorbent was biocompatible, safe for whole blood immuno-adsorption. Whole blood immuno-adsorption improved clinical manifestation and neuromuscular function of the passively transferred EAMG rabbits.

[The spectral characteristics and chlorophyll content at winter wheat growth stages].

The canopy spectral reflectance and chlorophyll content of winter wheat were measured and analyzed in the whole growing season. The characteristics of canopy spectral reflectance indicated that the canopy spectral reflectance changed signifi cantly at different stages. It decreased first and increased later with growth progress in the visible region (400-750 nm) after jointing stage, then the reflectance was lowest at booting stage. In near-infrared region (750-1000 nm) the spectral reflectance climbed sharply. The canopy reflectance was declined at booting stage and rose to the highest point at flowering stage. It dropped to minimum level subsequently at milk-ripe stage. However, the spectral reflectance characteristics at jointing stage and booting stage were used to detect the chlorophyll content. High correlation was observed between the canopy spectral reflectance and chlorophyll content. The positive correlation of canopy spectral reflectance with chlorophyll content was found at jointing stage and booting stage. Because the plant spectral reflectance was effected by chlorophyll greatly in visible region, the correlation coefficient reached 0.89 at 552 nm in booting stage. On the contrary, there was a negative correlation at flowering stage. Meanwhile, the red edge inflection point as one of the most important spectral parameters was analyzed at winter wheat growth stages based on the first derivative of reflectance spectra. The relation between the red edge inflection point and chlorophyll content was observed in each plot and the analysis results illustrated that the red edge inflection points could help detect the chlorophyll content at jointing stage and booting stage. The linear model of chlorophyll content with red edge inflection points was built at jointing stage (R2 = 0.92). High correlation was found between thered edge inflection point and chlorophyll content at booting stage. It was showed that the binomial model (R2 = 0.91) was better than linear model (R2 = 0.73). It was indicated that using spectral analysis to detect the winter wheat chlorophyll content non-destructively was feasible. The obtained conclusions also provided theoretical basis for further researches on measuring methods of chlorophyll content in the field.

[Characteristics of soil spectral reflectance and estimation of soil parameters in Fuxin opencast coal mine].

The surface soil samples of Fuxin opencast coal overburden dumps were collected in the field and the spectral reflectance and characteristic parameters of the soil samples, such as moisture content, pH, electrical conductivity (EC), available potassium (K+) content, and soil organic matter content (SOM), were measured. The Analysis results indicated that the curves of the soil spectral reflectance decreased with increasing the laid years. The possible reasons were the influences of soil texture and color. Although the valleys of the spectral reflectance appeared at 1 420, 1 910 and 2 210 nm, they were not conspicuous on the lime soil and mixture soil reflectance curves at 1 420 and 2 210 nm. With discussing the spectral reflectance of different types of soil texture, it's easy to find that the reflectance of fine grained soil was higher than the rough grained soil. Correlations between soil spectral reflectance and soil parameters were analyzed. The results showed that there was a positive relation between reflectance and pH, and correlation coefficient decreased with the wavelength increasing. There was no relationship between spectral reflectance and EC, and negative relations were observed between spectral reflectance and soil parameters, K+ and SOM, respectively. A high correlation coefficient was found between spectral reflectance and SOM, and the highest correlation coefficient reached -0. 76. The exponential correlation was found between sol spectral reflectance and soil moisture content to analyze all samples. According to different years and textures, more detail was described about the correlation between spectral reflectance of characteristic wavelength (1 910 and 1 943 nm) and soil moisture content. Meanwhile, the linear correlations were found under different conditions and higher correlation coefficients were obtained. In order to estimate SOM, five wavelengths (1 350, 1 602, 1 862, 2 160 and 2 227 nm) were selected based on principal component analysis to build a multiple linear regression model. The multiple correlation coefficient of calibration model (R2(C)) was 0.737 4, and the multiple correlation coefficient of validation (R2(V)) was 0.682 4. It indicated that the model was able to meet the needs of monitoring SOM in Fuxin opencast coal mine.

Compound heterozygous mutations in PARK2 causing early-onset Parkinson disease: A case report.

RATIONALE: Parkinson disease (PD) is a complex neurodegenerative movement disorder characterized by resting tremor, muscular rigidity, bradykinesia, and so on. Genetics has been regarded as an important role in the development of PD. PARK2, an autosomal recessive gene, is the most common one referring to early-onset Parkinson disease (EOPD). Strangely, only a single heterozygous mutation in PARK2 was found in a small minority of patients with PD, which has been reported quite rarely and is difficult to explain. PATIENT CONCERNS: We described a case of 36-year-old male patient, complaining of progressive tremor for 10 years. He 1st presented uncontrolled resting tremor of his left arm. Besides, he also had trouble in completing fine motor tasks such as writing and buttoning. Six years later, tremor of the ipsilateral leg gradually occurred. On neurologic examinations, pronounced parkinsonian symptoms were noted, including resting tremor, body bradykinesia, and hypomimia. The positron emission tomography-computed tomography showed the distribution of dopamine transporter in both putamens decreased obviously. No family history was indentified. He came to hospital because his disease aggravated in the past 4 months. DIAGNOSIS: This patient was diagnosed with PD according to the movement disorder society clinical diagnostic criteria for PD. INTERVENTIONS AND OUTCOMES: With regard to the sequencing of this patient, a heterozygous point mutation of G403C in PARK2 was detected, which was inherited from his unaffected mother, leading to an amino acid alternation of glycine to arginine. Furthermore, deletion mutation of exon 6 in PARK2 was also found in this patient, which was inherited from his normal father. He accepted madopar and benzhexol and showed stable efficacy. To our knowledge, it is the 1st case report to explain the synergistic action of both heterozygous pathogenic point mutation in PARK2 and deletion mutation of exon 6 leading to EOPD. LESSONS: Compound heterozygous mutations in PARK2 with point mutation of G403C and deletion mutation of exon 6 might contribute to the development of EOPD.

Activation of Central Alpha 7 Nicotinic Acetylcholine Receptor Reverses Suppressed Immune Function of T Lymphocytes and Protects Against Sepsis Lethality.

Sepsis remains the leading cause of high mortality and huge financial burden in intensive care units (ICU), but with scarce effective treatments due to refractory multiple organ dysfunction and persistent immunosuppression. Treatments that aim at modulating immune function and attenuating multiple organ injury will certainly benefit septic cases. Alpha 7 nicotinic acetylcholine receptor (α7nAchR) has been reported with potent immunomodulatory properties in various diseases as the essential mediator of the cholinergic anti-inflammatory pathway (CAP). Few studies have demonstrated the potential effect of central α7nAchR on the progression and prognosis of septic response, while its expression was first discovered on neurons and most abundant in the central nervous system. In the present study, it was found severe damage of multiple organs under the operation of cecal ligation and puncture (CLP) in rats, including heart, liver, kidneys, and lungs, as evidenced by abnormal histomorphology and notable elevation of injury markers. Concurrently, the function of spleen CD4+ T cells was disrupted under septic challenge, accompanied by polarization of helper T cell (Th)2, which exhibited outward signs of immunosuppression. Intracerebroventricular injection of PNU282987, a selective agonist of α7nAchR, significantly alleviated multiple organ injury, reversed immunosuppressive state, and improved the outcome of septic rats, while they were exacerbated by treatment with methyllycaconitine, a selective antagonist of α7nAchR. This study provides the first evidence that activation of central α7nAchR is beneficial for attenuating multiple organ dysfunction as well as abnormal immune response, and improving the prognosis of rats when exposed with sepsis.

Gastrodin attenuates microglia activation through renin-angiotensin system and Sirtuin3 pathway.

Microglia activation and its mediated production of proinflammatory mediators play important roles in different neurodegenerative diseases; hence, modulation of microglia activation has been considered a potential therapeutic strategy to ameliorate neurodegeneration. This study was aimed to determine whether Gastrodin, a common herbal agent known to possess neuroprotective property, can attenuate production of proinflammatory mediators in activated microglia through the renin-angiotensin system (RAS) and Sirtuin3 (SIRT3). Expression of various members of the RAS including ACE, AT1, AT2, and SIRT3 in activated microglia was assessed by immunofluorescence and Western blot in hypoxic-ischemia brain damage (HIBD) in postnatal rats, and in BV-2 microglia in vitro challenged with lipopolysaccharide (LPS) with or without Gastrodin treatment. Expression of NOX-2, a subunit of NADPH oxidase, and proinflammatory mediators including iNOS and TNF-α, was also evaluated. The present results showed that expression of ACE, AT1, NOX-2, iNOS and TNF-α was markedly increased in activated microglia in the corpus callosum of HIBD rats, and in LPS stimulated BV-2 microglia. Remarkably, the expression was markedly attenuated following Gastrodin treatment. Conversely, Gastrodin enhanced AT2 and SIRT3 protein expression. In BV-2 microglia treated with Azilsartan, a specific inhibitor of AT1 (AT1I group), NOX-2 expression was decreased whereas that of SIRT3 in LPS + AT1I and LPS + Gastrodin group was increased when compared with the controls. In LPS + AT1I + Gastrodin group, SIRT3 expression was further augmented. More importantly, Gastrodin effectively reduced caspase 3 protein expression level in the HIBD rats coupled with a significant decrease in caspase 3 positive cells. We conclude that Gastrodin can exert its protective effects against the hypoxic-ischemia brain damage in the present experimental HIBD model. It is suggested that this is mainly through suppression of expression of RAS (except for AT2 and SIRT3) and proinflammatory mediators e.g. TNF-α in activated microglia.

Expression of SIRT3 in various glial cell types in the periventricular white matter in the neonatal rat brain after hypoxia.

Sirtuin 3 (SIRT3) mediates cellular resistance toward various forms of stress. SIRT3 expression in the developing brain, especially its localization in various glial cell types, has not been fully explored. This study aimed to determine SIRT3 expression in the brain of neonatal rats subjected to hypoxia. By immunohistochemistry, immunofluorescence and Western blotting, we show here that SIRT3 expression in the periventricular white matter was up-regulated in hypoxia group compared with the control group at the corresponding time points. Intense SIRT3 expression was detected in microglia at early time points after hypoxia whose cell number was increased with reduced ramifications in hypoxia group compared with the control group. Furthermore, SIRT3 immunoreactivity was obviously enhanced at 24 h, 3 and 7d, but was declined at 14d after hypoxia so that SIRT3 expression between the two groups was comparable. SIRT3 immunofluorescence was also localized in astrocytes labeled with GFAP which was augmented at different time points in hypoxia group. GPAP positive astrocytes exhibited long extending processes being most pronounced at 3d. SIRT3 was moderately expressed at 24 h, 3 and 7d, but was markedly increased at 14d after hypoxia. Moderate SIRT3 expression was also localized in oligodendrocytes labeled with CNPase in the control group. The incidence of CNPase positive oligodendrocytes showing colocalization of SIRT3 increased significantly at 24 h, 3 and 7d after hypoxia. In conclusion, SIRT3 expression was differentially up-regulated in all three major glial cell types following hypoxia. It is suggested that increased SIRT3 expression in the respective glial cell types following hypoxia is involved in different signaling pathways that protect against hypoxic stress in the developing brain.

Effect of Platelet-derived P-selectin on Neutrophil Recruitment in a Mouse Model of Sepsis-induced Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a severe disease in critically ill patients. Neutrophil infiltration into kidney was associated with the development of AKI, and P-selectin may be involved in the process of neutrophil recruitment in kidney. This study aimed to explore the potential effect of platelet-derived P-selectin on neutrophil recruitment in a mouse model of sepsis-induced AKI. METHODS: A total of 30 C57BL/6 male mice were divided into five groups (n = 6 in each): sham group, sepsis group, anti-Ly6G group, anti-P-selectin group, and platelet depletion group. Sepsis was induced by cecal ligation and puncture. Serum creatinine concentration and platelet activity were measured by biochemical detector and flow cytometry, respectively. Histological and pathological features were analyzed using hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining, respectively. Myeloperoxidase (MPO) activity was detected with MPO assay. Unpaired t-test was used for data analysis. RESULTS: Serum creatinine increased significantly in septic group compared to sham group (2.68 ± 0.27 mg/dl vs. 0.82 ± 0.19 mg/dl, t = 12.06, P = 0.0000) but attenuated in antibodies-treated animals compared to septic group (anti-Ly6G: 1.62 ± 0.30 mg/dl vs. 2.68 ± 0.27 mg/dl, t = 5.76, P = 0.0004; anti-P-selectin: 1.76 ± 0.31 mg/dl vs. 2.68 ± 0.27 mg/dl, t = 4.92, P = 0.0012; and platelet depletion: 1.93 ± 0.29 mg/dl vs. 2.68 ± 0.27 mg/dl, t = 4.14, P = 0.0032). Platelet amount significantly decreased compared to sham group (658.20 ± 60.64 × 109/L vs. 822.00 ± 48.60 × 109/L, t = 4.71, P = 0.0015) in septic mice, especially in platelet depletion group (240.80 ± 44.98 × 109/L vs. 822.00 ± 48.60 × 109/L, t = 19.63, P = 0.0000). P-selectin activity was significantly increased in septic group compared to sham group (16.54 ± 1.60% vs. 1.90 ± 0.29%, t = 15.64, P = 0.0000) but decreased significantly in platelet depletion group compared to septic group (3.62 ± 0.68% vs. 16.54 ± 1.60%, t = 12.89, P = 0.0002). IHC analysis shown that neutrophil infiltration increased in septic mice compared to sham group (36.67 ± 3.79% vs. 9.17 ± 1.61%, t = 11.58, P = 0.0003) and function-blocked groups (anti-Ly6G: 36.67 ± 3.79% vs. 15.33 ± 1.53%, t = 9.05, P = 0.0008; anti-P-selectin: 36.67 ± 3.79% vs. 21.33 ± 1.53%, t = 6.51, P = 0.0029; and platelet depletion: 36.67 ± 3.79% vs. 23.33 ± 3.06%, t = 4.75, P = 0.0090). MPO increased significantly in septic group compared to control (49.73 ± 1.83 ng/mg prot vs. 13.04 ± 2.16 ng/mg prot, t = 19.03, P = 0.0000) but decreased in function-blocked groups compared to septic group (anti-Ly6G: 26.52 ± 3.86 ng/mg prot vs. 49.73 ± 1.83 ng/mg prot, t = 9.59, P = 0.0000; anti-P-selectin: 33.06 ± 6.75 ng/mg prot vs. 49.73 ± 1.83 ng/mg prot, t = 4.85, P = 0.0013; and platelet depletion: 33.37 ± 2.25 ng/mg prot vs. 49.73 ± 1.83 ng/mg prot, t = 5.33, P = 0.0007). CONCLUSION: Platelets-derived P-selectin may be involved in the development of septic AKI through inducing neutrophil infiltration into kidney.

[Effects of folic acid cooperated with soybean isoflavone on the neural tube defects pregnant rats].

OBJECTIVE: To study the effect of folic acid cooperating with soybean isoflavone on the oxidative status of neural tube defects (NTDs) pregnant rats induced by cyclophosphamide, to observe the relationship of the two factors, folic acid and the isoflavone and to look for the best co-intervention group. METHODS: The 100 pregnant rats of 2.5-3 months old were randomly divided into the control group, model group, co-intervention groups and solo-intervention groups. The animals were executed on the 20th day of gestation as to examining the levels of antioxidative indices (GSH, GSH-Px, Se, Mn, Fe) in blood. The incidence rates of NTDs were calculated. RESULTS: The interaction of folic acid and isoflavone had significant effect on the indices related with antioxidation (P < 0.05). Folic acid 0.7 mg/kg cooperated with isoflavone 160 mg/kg had the best intervention effects in our study. Compared with the solo-intervention by folic acid 1.4 mg/kg and isoflavone 320 mg/kg, the effect of co-intervention (folic acid 0.7 mg/kg cooperated with isoflavone 160 mg/kg) was significantly better (P < 0.05). CONCLUSION: Folic acid should be the main protective factor of NTDs, and isoflavone might reinforce the protective effects of folic the acid on NTDs by increasing the antioxidative ability, however, the effect is related with the ratio of the two factors.