Sulfonate Derivatives Containing a Kakuol Moiety as Potential Fungicidal Candidates: Design, Synthesis and Antifungal Activity Evaluation.

As a part of our continuing exploration to discover new potential promising fungicide candidates, eighteen sulfonate derivatives (3a-3r) containing a kakuol moiety were designed and synthesized. Synthetic sulfonate derivatives were tested comprehensively for antifungal activities against four plant pathogenic fungi (Botrytis (B.) cinerea, Valsa (V.) mali, Fusarium (F.) graminearum, Sclerotinia (S.) sclerotiorum), and their structure activity relationships were summarized. Especially, derivatives 3i and 3j exhibited remarkable activity against V. mali, with the inhibition rates of 99.8 and 100%, which were slightly superior to that of carbendazim (98.9%), a reference fungicide. Moreover, derivatives 3a, 3k and 3q possess the broader antifungal spectrum against three tested plant pathogenic fungi with inhibition rates over 60%. Structure-activity relationship (SAR) analysis indicated that the introduction of 2-F or 3-F into the benzene ring would give rise to a remarkable increase of the antifungal activity against V. mali.

Co-delivery of docetaxel and p53 gene from cationic nanoparticles based on poly (l-lactide) and low-molecular-weight polyethyleneimine (PEA).

Recent findings revealed that low-concentration paclitaxel(DTX) could enhance cytotoxicity by upregulating p53 expression in lung cancer cell lines. So, co-delivery of DTX and RFP-p53 gene with PEA nanoparticles (NPs) was studied. The prepared DTX loaded PEA NPs (PEA/DTX) were characterized by particle size distribution, morphology, zeta potential, and crystallography and cytotoxicity. Results showed that the PEA/DTX NPs had a mall particle size (≤100 nm), moderate zeta potential (≥40 mV) and drug loading of 9.0%, DTX was released from PEA/DTX NPs in an extended period in vitro. More important, agarose gel electrophoresis showed that PEA/DTX cationic NPs were able to completely bind RFP-p53 gene with mean particles size and zeta potential. Studies on cellular uptake of (PEA/DTX)/RFP-p53 NPs demonstrated that both drug and gene were effectively taken up by A549 tumor cells. It was found that intravenous injection of (PEA/DTX)/RFP-p53 NPs efficiently inhibited growth of subcutaneous A549 carcinoma in vivo (p < 0.05) and was significantly less side effect than that of mice treated with the other groups. Therefore, the (PEA/DTX)/RFP-p53 NPs might be a promising candidate for A549 cancer therapy.

Omnidirectional and compact transmissive chromatic polarizers based on a dielectric-metal-dielectric structure.

High-performance omnidirectional transmissive chromatic polarizers based on a one-dimensional dielectric-metal-dielectric subwavelength grating structure are proposed. The incident angle-insensitive properties, azimuthal angle-insensitive properties and polarization features are investigated thoroughly to realize the proposed omnidirectional transmissive chromatic polarizers. The color difference at different angles for the proposed yellow polarizers is less than 0.9746, and the extinction ratio at different angles for the proposed cyan polarizers exceeds 26. Analysis of the power density profiles for the transverse electric (TE) and transverse magnetic (TM) polarizations show that surface plasmon resonance and high refractive index contrast properties lead to excellent polarization features and high angular tolerance.

[Effect of WS070117M1 on chronic obstructive pulmonary disease in mice and the underling mechanisms of anti-inflammation].

The aim of this study is to investigate the anti-inflammatory effect of the adenosine derivative N6-(3-hydroxylaniline) adenosine (WS070117M1) on cigarette smoke plus LPS (lipopolysaccharide)-induced chronic obstructive pulmonary disease (COPD) in mice and its mechanism. COPD model was established by exposing male BALB/c mice to cigarette smoke and challenged with LPS inhalation. Supernatants of bronchoalveolar lavage fluid (BALF) were harvested and IL-1ß, IL-6, IL-8 and TGF-ß1 levels were measured by ELISA (enzyme-linked immunesorbent assay). The number of total white blood cells and neutrophils in bronchoalveolar lavage fluid was counted separately. Lung tissue was stained with Mayer 's hematoxylin and eosin for histopathologic examination. pAMPKa protein expression and distribution of lung tissue were analyzed by immunohistochemistry method. In vitro, levels of AMPKα phosphorylation in phorbol-12- myristate-13-acetate (PMA) differentiated THP-1 cells was detected by immunohistochemistry, IL-8 level in supernatants of cigarette smoke condensate stimulating PMA differentiated THP-1 cells was measured by ELISA. The results showed that WS070117M1 treatment significantly activated AMPKa in the lung tissue. It also resulted in down regulation of IL-1ß, IL-6, IL-8 and TGF-ß1 levels in bronchoalveolar lavage fluid and IL-8 level in cigarette smoke condensate stimulating PMA differentiated THP-1 cells. In addition, WS070117M1 could inhibit the recruitment of total white blood cells and neutrophils. These results suggest that WS070117M1 may alleviate the airway inflammation by activating AMPK in the lung tissue.

Epigallocatechin-3-Gallate (EGCG) Attenuates Traumatic Brain Injury by Inhibition of Edema Formation and Oxidative Stress.

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3-gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-1ß and TNF-α mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of p47(phox) translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress.

Effects of crayfish shell powder and bamboo-derived biochar on nitrogen conversion, bacterial community and nitrogen functional genes during pig manure composting.

This study investigated the effects of crayfish shell powder (CSP) and bamboo-derived biochar (BDB) on nitrogen metabolism, bacterial community and nitrogen functional genes during pig manure composting. Four treatments were established: CP (with no additives), TP1 (5 % BDB), TP2 (5 % CSP) and TP3 (2.5 % BDB + 2.5 % CSP). Compared to CP, the germination index (GI) of TP reached > 85 % 10 days earlier. Meanwhile, TP3 reduced NH3 and N2O emissions by 42.90 % and 65.9 %, respectively, while increased TN (total nitrogen) concentration by 5.43 g/kg. Furthermore, additives changed the bacterial structure and formed a beneficial symbiotic relationship with essential N-preserving bacteria, thereby enhancing nitrogen retention throughout the composting process. Metagenomic analysis revealed that additives upregulated nitrification genes and downregulated denitrification and nitrate reduction genes, ultimately improving nitrogen cycling and mitigating NH3 and N2O emissions. In conclusion, the results confirmed that TP3 was the most effective treatment in reducing nitrogen loss.

Glutathione-Sensitive Photosensitizer-Drug Conjugates Target the Mitochondria to Overcome Multi-Drug Resistance in Cancer.

Multi-drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH-sensitive photosensitizer-drug conjugates (CyR-SS-L) are designed and synthesized. CyR-SS-L localized in the mitochondria then is cleaved into CyR-SG and SG-L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR-SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG-L part is used for chemotherapy. CyR-SS-L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR-SS-L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.

[Advance in the research on P2X7 and inflammatory respiratory diseases].

P2X7 is the most important subtype of the ATP receptors known so far. Recent investigations showed that the downstream signaling pathway of P2X7 is coupled with several key inflammatory molecules including IL-1beta and IL-18, this suggests P2X7 might have roles in the inflammatory diseases. Moreover, attenuation of P2X7 by selective antagonists in vitro and knockout mice in vivo reducing the inflammatory response indicated that P2X7 is a potential therapeutic target for inflammatory diseases. However, most previous studies on P2X7 were focused on nerve system diseases most, while its effects in inflammatory respiratory diseases, especially in asthma, chronic obstructive pulmonary disease (COPD) and lung cancer have been poorly investigated. In this paper, we reviewed the research progress on the structure, distribution, biological activities of P2X7 and its relationship with inflammatory respiratory diseases including asthma, COPD and lung cancer, along with the development of P2X7 antagonist as therapeutics.

A novel tetranuclear Cu(ii) complex for DNA-binding and in vitro anticancer activity.

A novel tetranuclear Cu(ii) complex (TNC) was successfully synthesized and characterized by X-ray single crystal diffraction. The interaction of the complex with calf thymus DNA (CT-DNA) has been studied by UV-vis absorption titration, fluorescence technology and molecular docking. The results indicated that TNC could bind to the DNA through an intercalative mode. The agarose gel electrophoresis experiment showed that TNC could cleave supercoiled plasmid DNA into linear DNA. The anticancer activity of TNC was tested on four cancer cell lines: MCF7, A549, 4T1 and HepG2. The results indicated that TNC shown significant activity against all of above cell lines.

[Effects of modified liangge powder contained serum on LPS stimulated TLR4 expression and release of cytokines in mouse platelets].

OBJECTIVE: To observe the effects of Modified Liangge Powder (MLP) on the expressions of platelet toll like receptor 4 (TLR4) and the release of platelet-derived cytokines interleukin 8 (IL-8), beta platelet globulin (beta-TG), soluble CD40 ligand (sCD40L). METHODS: The modulating effects on the release of cytokines from mice platelets by TLR4 ligand through monoclonal antibody blocking TLR4 on platelet were compared. The stimulated platelet by LPS was incubated with low (0.94 g/mL), medium (1.89 g/mL), and high (2.84 g/mL) dose of MLP contained serum. The changes of the platelet TLR4 expression and platelet-derived cytokines were observed. RESULTS: The positive expression rate of platelet TLR4 obviously decreased (P < 0.01) and the release of sCD40L and beta-TG from platelets significantly increased (P < 0.01) after stimulated by LPS. However, the release of sCD40L and beta-TG from platelets obviously decreased by TLR4 monoclonal antibody (P < 0.05, P < 0.01). There was no statistical difference in IL-8 between before and after LPS stimulation (P > 0.05). Platelet TLR4 positive expression rate was significantly higher after incubated by medium and high doses of MLP contained serum (P < 0.01), and the releasing of sCD40L and beta-TG was lower in the serum contained groups. The inhibitory effects were enhanced in a dose-dependent manner. CONCLUSIONS: LPS induced platelet activation by TLR4 and released sCD40L and beta-TG, while the release of platelet IL-8 was not dependent on platelet TLR4-LPS pathway. MLP could inhibit LPS-stimulated sCD40L and beta-TG, inhibit the binding of platelet TLR4 and LPS in a dose-dependent manner, thus reducing the release of platelet cytokines.

Simultaneous self-supply of H2O2 and GSH-depleted intracellular oxidative stress for enhanced photodynamic/photothermal/chemodynamic therapy.

Herein, we designed a new nanoplatform for combined PDT/PTT/CDT through simultaneously self-supplying H2O2 and depleting GSH using one single laser irradiation. The nanoplatform was capable of generating multiple reactive oxygen species (ROS), such as 1O2, O2-˙ and ˙OH, resulting in cell death. Moreover, the nanoplatform demonstrated low dark toxicity, high phototoxicity and better biosafety. In vivo animal experiments showed that the tumor growth was efficiently inhibited.

[The effect of the membrane attack complex C5b-9 on liver cells during traumatic hemorrhagic shock in rat].

OBJECTIVE: To observe whether the membrane attack complex C5b-9 would accumulate in the rats' liver after receiving the assault of traumatic hemorrhagic shock, and whether the membrane attack complex deals an impact on liver apoptosis. METHODS: Fifty male healthy Wistar rats were randomly divided into five groups: normal group, 1, 3, 6, 24 hour model groups. The model of traumatic hemorrhagic shock was reproduced by withdrawal of blood from carotid artery after a bone fracture till the blood pressure lowered to 40 mm Hg (1 mm Hg=0.133 kPa). Plasma membrane attack complex C5b-9 concentration was assayed using enzyme linked immunoadsorbent assay. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood was determined by Rate method. Immunohistochemistry was used to detect C5b-9 deposition in the liver. Apoptosis of liver cells was then detected by the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay. The pathological changes in paraffin sections stained with hematoxylin eosin (HE) were observed under light microscope. RESULTS: A small amount of C5b 9 in plasma was found in normal group, and the values (ng/L) of 1, 3, 6 hour models were significantly higher than those of the normal group (272.91 ± 9.56, 192.01 ± 9.04, 156.78 ± 8.37 vs. 25.98 ± 5.87, all <0.05 ). ALT (U/L) in 3 hour model group and AST (U/L) in 1 hour model group were increased significantly (92.90 ± 8.83, 264.83 ± 31.4), peaked at 24 hours (184.30 ± 12.98, 647.36 ± 60.02), and there was significant difference compared with normal group (38.75 ± 5.40, 66.69 ± 19.95, all P <0.05). In the normal group and the 1 hour and 6 hour model groups, no C5b 9 was found in liver, but in the 3 hour model group a large number of liver parenchymal cells in the portal area were found to contain C5b 9 22.60 ± 1.06), however the number decreased significantly in the 24 hour model (2.20 ± 0.60, P<0.05). In normal group there was no apoptotic cell, and in 1, 6, 24 hour model groups there were scattered apoptotic cells (1.20 ± 0.25, 5.60 ± 0.37, 1.60 ± 0.26). In the 3 hour model group apoptosis of hepatic cells around the central vein was increased to the peak (20.60 ± 0.47), and there was significant difference compared with other groups (all P <0.05) . In the model groups the liver cells became edematous, and the integrity of the membrane was lost, and some cells were even lysed.The pathological damage is most serious in 24 hour model group. CONCLUSION: The membrane attack complex C5b-9 insulted the rats' liver after a traumatic hemorrhagic shock, and apoptosis of hepatic cells and the content of C5b-9 peaked in 3 hour model , though they do not occur in the same site. A low level of C5b-9 in blood 3 hours after shock predict a poor prognosis.

[Platelet parameters and platelet Toll-like receptor 4 (TLR4) expression in patients with sepsis, and the effect of a joint treatment-plan integrating traditional Chinese and western medicine: a clinical study].

OBJECTIVE: To examine the efficacy of a treatment regimen combining modern (Western) medication and a traditional Chinese medicinal recipe Modified Liang-Ge San on sepsis, and its effect on platelet parameters/activation, platelet TLR4 expression and the intensity of inflammatory response in the patients. METHODS: 64 patients with sepsis were randomly assigned to two groups (32 each) to receive Western therapy only (group X) and Western therapy + Modified Liang-Ge San (group L). The values of: platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), the expression of TLR4 and procaspase activating compound-1 (PAC-1) in platelets, plasma concentration of soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) were collected on the day of admission, and 3, 5, 9 days after treatment. Acute physiology and chronic health evaluation II (APACHE II) score, length of stay in intensive care unit (ICU), bleeding events and 28 day mortality in these patients were also analyzed. A group of 15 healthy volunteers (group C) were used as control. RESULTS: Compared to group C, the patients with sepsis have significantly: lower PLT (×10 9/L: 211.37±77.84 vs. 272.33±34.23, P< 0.01 ), increased MPV (fL: 10.24±0.81 vs. 9.64±0.66, P< 0.05) and PDW (fL: 17.79±1.68 vs. 15.61±1.54, P< 0.01), up-regulated platelet TLR4 [(39.93±9.07)% vs. (23.50±4.68)%] and PAC-1 expression [(42.21±8.74)% vs. (21.02±3.49)%], both P < 0.01, and higher level of sCD40L (µg/L: 6.94±1.05 vs. 3.27±0.41)and TNF-α(ng/L: 60.10±9.77 vs. 4.08±3.08), both P< 0.01. Compared to group X, group L had significantly (P< 0.05 or P< 0.01, respectively) lower value in: creatinine (µmol/L: 106.2±34.4 vs. 127.5±43.7); alanine aminotransferase (U/L: 31.7±12.5 vs. 41.9±19.9);aspartate aminotransferase (U/L: 54.1±21.6 vs. 68.5±24.1); TLR4 [(27.14±6.08)% vs. (30.92±5.47)%]; PAC-1 [(27.52±6.51)% vs. (31.24±5.77)%]; sCD40L (3.86±0.69 vs. 4.38±0.73); TNF-α (22.06±7.19 vs. 28.25±8.99), and higher PLT (261.93±55.32 vs. 231.37±63.58, P< 0.05), in the 9 days after treatment. In patients with sepsis, platelet PAC-1 expression correlated significantly to PLT ( r = - 0.409, P< 0.01 ) negatively, and MPV, PDW, platelet TLR4 expression, plasma sCD40L ( r (1) = 0.262, r (2) = 0.318, r (3) = 0.341, r(3) = 0.519, all P< 0.01) positively; sCD40L and TNF-α was positively correlated ( r = 0.542, P < 0.01 ) in these patients. In comparison with group X, the length of stay in ICU (day: 8.06±2.86 vs. 9.31±2.48), the incidence of bleeding (12.5% vs. 21.9%) and APACHE II score (12.75± 4.56 vs. 14.59± 3.97) were significantly lower (all P< 0.05) in group L on the 9 days after treatment. No significant difference was found in 28 day mortality between group L and X (15.63% vs. 18.75%, P> 0.05). CONCLUSION: In patients with sepsis, platelet TLR4 expression is elevated together with platelet activation. The joint application of Western medicine and Modified Liang-Ge San may suppress such up-regulation in TLR4/other inflammatory mediators, and alleviate platelet activation/thrombocytopenia in these patients.

Monolayer-Graphene-Based Tunable Absorber in the Near-Infrared.

In this paper, a tunable absorber composed of asymmetric grating based on a graphene-dielectric-metal structure is proposed. The absorption of the absorber can be modified from 99.99% to 61.73% in the near-infrared by varying the Fermi energy of graphene, and the absorption wavelength can be tuned by varying the grating period. Furthermore, the influence of other geometrical parameters, the incident angle, and polarization are analyzed in detail by a finite-difference time-domain simulation. The graphene absorbers proposed in this paper have potential applications in the fields of stealth, sense, and photoelectric conversion. When the absorber that we propose is used as a gas sensor, the sensitivity of 200 nm/RIU with FOM can reach up to 159 RIU-1.

A simultaneously GSH-depleted bimetallic Cu(ii) complex for enhanced chemodynamic cancer therapy.

A bimetallic Cu(ii) complex as a novel antitumor chemodynamic therapy agent with glutathione (GSH) depletion properties is successfully synthesized and well characterized. In tumor cells, the Cu2+ ions of the complex are reduced to Cu+ ions by GSH and then catalyzed by the overexpressed H2O2 to generate highly cytotoxic hydroxyl radicals (˙OH) that kill cancer cells. The complex is quickly taken up by cancer cells and distributed in multiple organelles including mitochondria and the nucleus. The complex demonstrates good cytotoxicity toward various cancer cell lines. However, its toxicity toward normal cells is significantly lower than that toward cancer cells due to the limited expression of H2O2. In addition, the complex could arrest the cell cycle of the G0/G1 phase, thereby inducing apoptosis rather than necrosis.

[The influences of propofol on corticosteroid and immunity of rats after hemorrhagic shock and resuscitation].

OBJECTIVE: To observe the influence of propofol on corticosteroid, and cytokines in rats after hemorrhagic shock and resuscitation, as well as its protective effects on vital organs. METHODS: Sixty-six male Wistar rats were randomly divided into three groups: control group, hemorrhagic shock and resuscitation group and propofol treatment group. After the model of hemorrhagic shock and resuscitation was reproduced, propofol was infused in propofol treatment group at the speed of 10 mg.kg(-1).h(-1) via femoral vein, while equal amount of normal saline was infused in hemorrhagic shock and resuscitation group. Abdominal aortic blood, lung and small intestinal tissue samples were collected at 30, 60, 120, 180 and 240 minutes, 6 rats at each time point in hemorrhagic shock and resuscitation group and propofol treatment group. Plasma cortisol, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) concentrations were measured using enzyme linked immunosorbent assay (ELISA). Histopathological changes in lung and small intestine were observed using optical microscope and then histopathological scores were assessed. RESULTS: Comparing with control group, the concentration of cortisol in plasma decreased significantly (all P<0.01), both IFN-gamma and IL-4 increased progressively, and the IFN-gamma/IL-4 ratio decreased gradually with the progress of the course (all P<0.01). Serious injury to lung and small intestinal tissue was observed, and remarkable elevation of histopathological scores was found in hemorrhagic shock and resuscitation group (lung: 3.09+/-0.56 vs. 0.31+/-0.25, small intestine: 7.61+/-1.20 vs. 0.86+/-0.72, both P<0.01). In propofol treatment group, the extent of decrease in corticosteroid level was lessened, the extent of elevation of IFN-gamma and IL-4 was decreased, the downward trend of the IFN-gamma/IL-4 ratio was slowed down (P<0.05 or P<0.01), the extent of injury to lung and small intestinal tissue was alleviated and histopathological scores were reduced remarkably (lung: 1.27+/-0.40, small intestine: 3.69+/-1.28, both P<0.01). CONCLUSION: Propofol can ameliorate the lowering of corticosteroid secretion, moderate inflammatory response, and protect vital organs in rats with hemorrhagic shock.

A novel Mn-Cu bimetallic complex for enhanced chemodynamic therapy with simultaneous glutathione depletion.

A bimetallic complex, containing Mn(ii) and Cu(ii) moieties, was synthesized for chemodynamic therapy (CDT) of cancer. The complex was capable of generating a hydroxyl radical (˙OH) via a Fenton-like reaction involving a Mn complex, and simultaneously depleting glutathione via a Cu complex induced oxidative reaction, thereby enhancing the efficiency of CDT.

[Evaluation of nuclear factor-KappaB and I Kappa B mRNA expression in determining the prognosis of multiple organ dysfunction syndrome].

OBJECTIVE: To observe the value of nuclear factor-KappaB(NF-KappaB) and I Kappa B mRNA expression estimation on determining the prognosis of patients with multiple organ dysfunction syndrome (MODS). METHODS: Forty-three MODS patients were divided into two groups based on their prognosis: the survivor group (n =28) and the non-survivor group (n=15). Another group of 10 healthy persons served as normal control group. The expression of NF-Kappa B and I Kappa B-alpha mRNA levels in monocytes/neutrophils of patients and controls were detected by reverse transcription-polymerase reaction (RT-PCR), and the results were compared among groups. RESULTS: The expression of NF-KappaB mRNA levels of MODS patients was higher than that of normal control group(1. 35+/-0.53 vs. 0.74+/-0.25, P<0.01),and the expression of I Kappa B-alpha mRNA levels were lower than those of the control group (1. 24+/-0.60 vs. 1. 97+/-0.71,P<0.01). There was no significant difference in NF-KappaB mRNA levels between the survivor group and the non-survivor group (1. 27+/-0.37 vs. 1.39+/-0.60,P>0.05), but the expression of I Kappa B-alpha mRNA levels in the non-survivor group was significantly lower than that of survivors(0.94+/-0.46 vs. 1. 40+/-0.61, P<0.05). The results suggested that there was a negative correlation between the expression of I Kappa B-alpha mRNA level and acute physiology and chronic health evaluation II (APACHE II)(r=-0.340, P<0.05). Moreover, when the cutoff value of the expression of I Kappa B-alpha mRNA level was 1. 34, the Youden index was 0.51, and it was the highest in all the cutoff values, and the specificity was 90.72%,the sensitivity was 60.75%. CONCLUSION: The expression of I Kappa B-alpha mRNA level can be a useful guide for determining the prognosis of patients with MODS.

Complement depletion with cobra venom factor alleviates acute hepatic injury induced by ischemia­reperfusion.

Increasing evidence has demonstrated that complement activation is required for ischemia­reperfusion injury (IRI)­induced hepatic damage, and cobra venom factor (CVF) can deplete the complement components. The aim of the current study was to investigate the effect and intrinsic mechanism of CVF pretreatment on IRI­induced acute hepatic injury in rats. Acute hepatic injury in rats was induced by bone fracture to simulate trauma, followed by hemorrhage for 90 min, and then the rats were resuscitated for a period of 20 min of reperfusion. The survival times under different CVF treatment doses and schedules for rats with IRI were evaluated. Hepatic tissues and serum samples were analyzed for acute hepatic injury, complement activation, inflammatory mediator release and apoptosis at predetermined times and compared between the IRI group and the CVF pretreatment + IRI groups. Compared to the rats with IRI alone, the survival times were significantly improved among rats with IRI receiving a high­dose or low­dose CVF pretreatment (all P<0.01). Upon histological examination, severe hepatic damage was observed in the rats with IRI, accompanied by liver function deterioration, complement and membrane attack complex activation, inflammatory mediator release and hepatic cell apoptosis. CVF pretreatment significantly attenuated the hepatic injury through depletion of anaphylatoxic C5a and membrane attack complex C5b­9 activation, and subsequent inhibition of inflammatory mediator release and hepatic cell apoptosis (all P<0.05). The results indicated that CVF pretreatment ameliorates IRI­induced acute hepatic injury. However, further studies are required to determine whether this therapy could be a potential agent for the treatment of IRI injuries in clinical settings.

Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation.

Silybin is one of the main flavonoids produced by milk thistle, which has been used in the treatment of liver diseases. In this study, we examined the protective effects and possible mechanisms of action of silybin in lipopolysaccharide (LPS)­induced lung injury and inflammation. Pre-treatment of mice with silybin significantly inhibited LPS-induced airway inflammatory cell recruitment, including macrophages, T cells and neutrophils. The production of cytokines, such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in bronchoalveolar fluid and serum was also decreased following treatment with silybin. Elevated cytokine mRNA levels induced by LPS in lung tissue were all suppressed by silybin and lung histological alterations were also improved. In addition, experiments using cells indicated that silybin significantly decreased the mRNA levels and secretion of IL-1ß and TNF-α in THP-1 cells. Moreover, the mechanisms responsible for these effects were attributed to the inhibitory effect of silybin on nuclear factor-κB (NF-κB) signaling and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. The data form our study thus support the utility of silybin as a potential medicine for the treatment of acute lung injury­associated inflammation and pathological changes. Silybin exerts protective effects against lung injury by regulating NF-κB signaling and the NLRP3 inflammasome activation.