Isolation and characterization of a lipopeptide-producing Bacillus sp. strain JK08 with antagonistic activity against Vibrio parahaemolyticus.

AIMS: The present study aimed to isolate a potential antagonist Bacillus sp. and evaluate its capacity for controlling pathogenic Vibrio parahaemolyticus in aquaculture. METHODS AND RESULTS: Strain JK08, which showed inhibitory activity against V. parahaemolyticus VP02r, was isolated from a Penaeus vannamei pond. Based on morphological, physiological, and biochemical characteristics and phylogenetic analysis, strain JK08 was identified as Bacillus sp. Through culture condition optimization, the maximal inhibition zone diameter (18.19 ± 0.16 mm) was observed when strain JK08 was cultivated at a temperature of 30°C, pH of 7, and salinity of 20‰ in Luria-Bertani broth for 24 h. The inhibition zone against V. parahaemolyticus VP02r of strain JK08 (∼7 µg, in mass of crude antimicrobial substance, per tablet) was larger than those (14-18 mm in diameter) of several commercial antibiotics (10 µg per tablet) in the in vitro antagonism assay. Liquid chromatography-tandem mass spectrometry analysis results indicated the presence of three families of lipopeptides in the antimicrobial substance: surfactin (C12-C17), iturin A (C14-C17), and fengycin A (C14-C17) and B (C17), which might be the key components contributing to the antagonistic activity of strain JK08. CONCLUSIONS: Strain JK08, which is capable of producing antibacterial lipopeptides, shows effective antagonistic activity against V. parahaemolyticus VP02r, implying its promising potential for V. parahaemolyticus control in aquaculture.

Dosimetric effects of supine immobilization devices on the skin in intensity-modulated radiation therapy for breast cancer: a retrospective study.

BACKGROUND: The dose perturbation effect of immobilization devices is often overlooked in intensity-modulated radiation therapy (IMRT) for breast cancer (BC). This retrospective study assessed the dosimetric effects of supine immobilization devices on the skin using a commercial treatment planning system. METHODS: Forty women with BC were divided into four groups according to the type of primary surgery: groups A and B included patients with left and right BC, respectively, who received 50 Gy radiotherapy in 25 fractions after radical mastectomy, while groups C and D included patients with left and right BC, respectively, who received breast-conservation surgery (BCS) and 40.05 Gy in 15 fractions as well as a tumor bed simultaneous integrated boost to 45 Gy. A 0.2-cm thick skin contour and two sets of body contours were outlined for each patient. Dose calculations were conducted for the two sets of contours using the same plan. The dose differences were assessed by comparing the dose-volume histogram parameter results and by plan subtraction. RESULTS: The supine immobilization devices for BC resulted in significantly increased skin doses, which may ultimately lead to skin toxicity. The mean dose increased by approximately 0.5 and 0.45 Gy in groups A and B after radical mastectomy and by 2.7 and 3.25 Gy in groups C and D after BCS; in groups A-D, the percentages of total normal skin volume receiving equal to or greater than 5 Gy (V5) increased by 0.54, 1.15, 2.67, and 1.94%, respectively, while the V10 increased by 1.27, 1.83, 1.36, and 2.88%; the V20 by 0.85, 1.87, 2.76, and 4.86%; the V30 by 1.3, 1.24, 10.58, and 11.91%; and the V40 by 1.29, 0.65, 10, and 10.51%. The dose encompassing the planning target volume and other organs at risk, showed little distinction between IMRT plans without and with consideration of immobilization devices. CONCLUSIONS: The supine immobilization devices significantly increased the dose to the skin, especially for patients with BCS. Thus, immobilization devices should be included in the external contour to account for dose attenuation and skin dose increment. TRIAL REGISTRATION: This study does not report on interventions in human health care.

IL-33 attenuates mortality by promoting IFN-γ production in sepsis.

OBJECTIVE AND DESIGN: Sepsis remains a major clinical problem with high morbidity and mortality. Interleukin (IL)-33 is a recently described member of the IL-1 family that is widely expressed and functions as a new inflammatory mediator. IL-33 has been reported to protect sepsis, but the underlying mechanisms are not well-elucidated. MATERIALS AND METHODS: We measured the interferon gamma (IFN-γ) production in septic mice after IL-33 treatment. RESULTS: IL-33 treatment enhanced the IFN-γ level in blood and promoted mice's survival, so the protective effects of IL-33 depend on IFN-γ. The IL-33 treatment also promoted both γδ T cells and NK cells in septic mice. CONCLUSION: Our data showed that IL-33 attenuates mortality by promoting IFN-γ production in sepsis.

IL-33 Attenuates Sepsis by Inhibiting IL-17 Receptor Signaling through Upregulation of SOCS3.

BACKGROUND/AIMS: Sepsis is a systemic inflammatory response during infection. There are limited therapeutic options for sepsis patients. Interleukin (IL)-33 has been reported recently with a beneficial effect in mouse sepsis. METHODS: In this study, we initiated a clinical study to measure serum levels of pro-inflammatory cytokines including IL-33 in sepsis patients. Next, we employed cecal ligation and puncture (CLP) to study the role of IL-33 during sepsis. To further dissect the molecular mechanism, we used in vivo knockout models and in vitro knockdown murine embryonic fibroblasts (MEFs) to investigate the cross-talk between IL-33 and IL-17 signaling, and to identify the potential downstream mediators. RESULTS: IL-33 and IL-17 were upregulated in both clinical and experimental sepsis. In CLP, IL-33 (-/-) mice showed higher mortality rate, and IL-33 treatment improved the survival rate. Elevated proinflammatory cytokines in sepsis were related to IL-17 from γδT cells. IL-33 treatment suppressed production of these cytokines by targeting IL-17 signaling both in vivo and in vitro. Finally, IL-33 was shown to inhibit the IL-17 pathway via activating suppressor of cytokine signaling (SOCS)-3. CONCLUSION: Collectively, the results suggest that IL-33 plays a negative regulatory role in sepsis progression by inhibiting IL-17 pathway through activating SOCS3. This finding would inspire a new therapeutic strategy for treating sepsis.

Experimental study on the degradation of sandstone-petroglyph carriers in Helankou: Effects of freeze-thaw and wet-dry cycles.

The Helankou petroglyphs offer precious data for understanding the lifeways of ancient pastoralists. However, in Helankou, the combination of unique climate conditions and complex hydrochemical environments has accelerated the weathering of the sandstone-petroglyph carriers, leading to numerous petroglyphs at risk of vanishing. In response, this study employed freeze-thaw and wet-dry cycle experiments to simulate the actual environmental conditions for sandstone. Subsequently, the sandstone that underwent the experiments was subjected to further testing and analysis. The goal was to comprehensively understand the performance change patterns and micro-mechanisms in sandstone under environmental stress, thus providing scientific theoretical support for Helankou petroglyph conservation. The results indicate that under the effects of freeze-thaw and wet-dry, the degradation processes can be attributed to a diverse combination of mechanisms such as swelling-shrinkage, hydrolysis, frost heave, dissolution, and salt crystallization, which alter the physical parameters, particle size distribution, mineral composition, and structural integrity of the sandstone.

HRD effects on first-line adjuvant chemotherapy and PARPi maintenance therapy in Chinese ovarian cancer patients.

Homologous recombination deficiency (HRD) testing has been approved by FDA for selecting epithelial ovarian cancer (EOC) patients who may benefit from the first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy. However, the effects of HRD on the clinical outcomes of first-line chemotherapy and first-line PARPi maintenance therapy have not been rigorously evaluated in Chinese EOC patients. Here, we developed an HRD assay and applied it to two large retrospectively collected Chinese EOC patient cohorts. In the first-line adjuvant chemotherapy cohort (FACT, N = 380), HRD status significantly improved PFS (median, 15.6 months vs. 9.4 months; HR, 0.688; 95% CI, 0.526-0.899; P = 0.003) and OS (median, 89.5 months vs. 60.9 months; HR, 0.636; 95% CI, 0.423-0.955; P = 0.008). In the first-line PARPi maintenance therapy cohort (FPMT, N = 83), HRD status significantly improved PFS (median, NA vs. 12 months; HR, 0.438; 95% CI, 0.201-0.957; P = 0.033) and OS (median, NA vs. NA months; HR, 0.12; 95% CI, 0.029-0.505; P = 0.001). Our results demonstrate that HRD status is a significant predictor for PFS and OS in both first-line chemotherapy and first-line PARPi maintenance therapy, providing strong real-world evidence for conducting genetic testing and improving clinical recommendations for Chinese EOC patients.

Protective mechanical ventilation with optimal PEEP during RARP improves oxygenation and pulmonary indexes.

BACKGROUND: This trial aimed to evaluate the effects of a protective ventilation strategy on oxygenation/pulmonary indexes in patients undergoing robot-assisted radical prostatectomy (RARP) in the steep Trendelenburg position. METHODS: In phase 1, the most optimal positive end-expiratory pressure (PEEP) was determined in 25 patients at 11 cmH2O. In phase 2, 64 patients were randomized to the traditional ventilation group with tidal volume (VT) of 9 ml/kg of predicted body weight (PBW) and the protective ventilation group with VT of 7 ml/kg of PBW with optimal PEEP and recruitment maneuvers (RMs). The primary endpoint was the intraoperative and postoperative PaO2/FiO2. The secondary endpoints were the PaCO2, SpO2, modified clinical pulmonary infection score (mCPIS), and the rate of complications in the postoperative period. RESULTS: Compared with controls, PaO2/FiO2 in the protective group increased after the second RM (P=0.018), and the difference remained until postoperative day 3 (P=0.043). PaCO2 showed transient accumulation in the protective group after the first RM (T2), but this phenomenon disappeared with time. SpO2 in the protective group was significantly higher during the first three postoperative days. Lung compliance was significantly improved after the second RM in the protective group (P=0.025). The mCPIS was lower in the protective group on postoperative day 3 (0.59 (1.09) vs. 1.46 (1.27), P=0.010). CONCLUSION: A protective ventilation strategy with lower VT combined with optimal PEEP and RMs could improve oxygenation and reduce mCPIS in patients undergoing RARP. TRIAL REGISTRATION: ChiCTR ChiCTR1800015626 . Registered on 12 April 2018.

Hydroxyethyl starch 130/0.4 inhibits production of plasma proinflammatory cytokines and attenuates nuclear factor-kappaB activation and Toll-like receptors expression in monocytes during sepsis.

BACKGROUND: Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes, and could modulate inflammatory response in sepsis. Our aim of this study was to investigate the mechanism of the effect of HES 130/0.4 by studying plasma levels of inflammatory cytokines, nuclear factor-kappaB (NF-kappaB) activation, and Toll-like receptors (TLRs) expression in peripheral monocytes during polymicrobial sepsis. MATERIALS AND METHODS: Rats with sepsis induced by cecal ligation and puncture (CLP) were treated with HES130/0.4 (7.5, 15, or 30 mL/kg, intravenously); then, rat plasma and monocytes were isolated from blood 5 h later. The plasma level of cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-6), NF-kappaB activity, and mRNA and protein levels of TLRs (TLR2 and TLR4) in peripheral blood monocytes were determined by enzyme-linked immunosorbent assay, electrophoretic mobility shift assay, reverse transcription-polymerase chain reaction, and Western blotting, respectively. RESULTS: HES130/0.4 dose-dependently reduced the plasma level of TNF-alpha and IL-6 in rats with sepsis. HES130/0.4 also significantly inhibited NF-kappaB activation, and TLRs mRNA and protein levels in peripheral monocytes. CONCLUSION: During sepsis, HES130/0.4 can down-regulate the inflammatory response, possibly through inhibition of the TLRs/NF-kappaB signaling pathway, and could be one more appropriate plasma substitute in sepsis.

Correlations of the stability, static dipole polarizabilities, and electronic properties of yttrium clusters.

Static dipole polarizabilities for the ground-state geometries of yttrium clusters (Yn, n < or = 15) are investigated by using the numerically finite field method in the framework of density functional theory. The structural size dependence of electronic properties, such as the highest occupied molecular orbital-lowest occupied molecular orbital (HOMO-LUMO) gap, ionization energy, electron affinity, chemical hardness and softness, etc., has been determined for yttrium clusters. The energetic analysis, minimum polarizability principle, and principle of maximum hardness are used to characterize the stability of yttrium clusters. The correlations of stability, static dipole polarizabilities, and electronic properties are analyzed especially. The results show that static polarizability and electronic structure can reflect obviously the stability of yttrium clusters. The static polarizability per atom decreases slowly with an increase in the cluster size and exhibits a local minimum at the magic number cluster. The ratio of the mean static polarizability to the HOMO-LUMO gap has a much lower value for the most stable clusters. The static dipole polarizabilities of yttrium clusters are highly dependent on their electronic properties and are also partly related to their geometrical characteristics. A large HOMO-LUMO gap of an yttrium cluster usually corresponds to a large dipole moment. Strong correlative relationships of the ionization potential, softness, and static dipole polarizability are observed for yttrium clusters.

(9S,13R,14R)-7,8-Didehydro-3,4,7-trimeth-oxy-17-methyl-morphinan-6-one.

The title compound, C(20)H(25)NO(4), was synthesized by a Mitsunobu reaction of sinomenine [(9S,13R,14R)-7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one] with methanol. The chiral centers were unchanged during the reaction. Intra-molecular C-H⋯O hydrogen bonds result in the formation of six-membered rings.

Effect of intraoperative lung-protective mechanical ventilation on pulmonary oxygenation function and postoperative pulmonary complications after laparoscopic radical gastrectomy.

This study aimed to observe the effects of lung-protective ventilation (LPV) on oxygenation index (OI) and postoperative pulmonary complications (PPCs) after laparoscopic radical gastrectomy in middle-aged and elderly patients. A total of 120 patients who were scheduled to undergo laparoscopic radical gastrectomy with an expected time of >3 h were randomly divided into conventional ventilation (CV group) with tidal volume (TV) of 10 mL/kg without positive end-expiratory pressure (PEEP), and lung-protective ventilation (PV group) with 7 mL/kg TV and personal level of PEEP with regular recruitment maneuver every 30 min. Measurements of OI, modified clinical pulmonary infection score (mCPIS), and PPCs were assessed during the perioperative period. Fifty-seven patients in the CV group and 58 in the PV group participated in the data analysis. Patients in the PV group showed better pulmonary dynamic compliance, OI, and peripheral capillary oxygen saturation during and after surgery. The mCPIS was significantly lower in the PV group than in the CV group after surgery. The incidence rate of PPCs was lower in the PV group than in the CV group and the difference was significant in patients whose ventilation time was longer than 6 h in both groups. LPV during laparoscopic radical gastrectomy significantly improved pulmonary oxygenation function and reduced postoperative mCPIS and the incidence of PPCs during the early period after surgery of middle-aged and elderly patients, especially patients whose mechanical ventilation time was longer than 6 h.

A Novel Nitrite-Base Aerobic Denitrifying Bacterium Acinetobacter sp. YT03 and Its Transcriptome Analysis.

Nitrite in a water environment is very harmful to humans and aquatic animals. A novel aerobic denitrifying bacterium able to utilize NO 2 - -N as the only nitrogen source was isolated for the purpose of removing nitrite from water, which was identified as Acinetobacter sp. and named as YT03. The growth and denitrification activity of strain YT03 was assessed comprehensively. Results showed that the nitrite in water with an initial concentration of 10 mg L-1 could be completely removed within 6 h by strain YT03, and the optimal conditions for strain YT03 to remove nitrite were as follows: sodium succinate as the carbon source, C/N ratio of 16, pH of 6.5, temperature of 30°C, and shaking speed of 250 rpm. An RNA-Seq transcriptome analysis was used to find genes associated with nitrite removal. Compared with the removal of ammonia nitrogen, 47 genes were significantly differentially expressed, including 20 up-regulated and 27 down-regulated genes, mainly involved in the transport process, biosynthetic process, and so on. And among the differentially expressed genes, C4-dicarboxylate transporter (DctA) and nitrate/nitrite transporter (Nrt) might be of importance for the efficient utilization of carbon and nitrogen sources in aerobic nitrite denitrification with sodium succinate by strain YT03.

Ultrastructural changes, nuclear factor-kappaB activation, and tumor necrosis factor-alpha expression in brain after acute normovolemic hemodilution and controlled hypotension in rats.

AIM: To examine brain damage following different degrees of acute normovolemic hemodilution combined with controlled hypotension (ANH-CH) by neuronal morphological analysis and investigate the expression of nuclear factor-kappa B (NF-kappaB) activity and tumor necrosis factor-alpha (TNF-alpha) in the rat. METHODS: Forty rats were randomly assigned to receive a sham operation or ANH-CH (with hematocrit 30%, 25%, 20%, and 15%). ANH was performed after baseline physiological parameters had been monitored for 20 minutes. CH was induced 30 minutes later using sodium nitroprusside and mean arterial pressure was maintained at 50-60 mm Hg for 1 hour. Rats were euthanatized 3 and a half hours after operation. TNF-alpha levels and NF-kappaB activities in cerebral temporal cortex were measured. Ultrastructural alterations in the CA1 region of the rat hippocampi were observed. Changes in mitochondria were evaluated semiquantitatively. RESULTS: Marked ultrastructural alterations, such as mitochondrial denaturalization and nucleus distortion, were observed in the CA1 region of the hippocampus in the ANH-CH hematocrit 20% group and ANH-CH hematocrit 15% group. TNF-alpha expression and NF-kappaB activity in the cerebral temporal cortex significantly increased in all ANH-CH groups and peaked in the ANH-CH hematocrit 25% group. CONCLUSION: Severe ANH-CH with hematocrit < or =20% may induce cerebral damage and should be avoided. NF-kappaB activation and TNF-alpha expression may play a functional role under the ischemic condition. A better understanding of the role of NF-kappaB and TNF-alpha in the brain may lead to a novel approach for preventing and treating various neurological disorders.

1-(1,3-Benzodioxol-5-yl)butan-1-one.

In the mol-ecule of the title compound, C(11)H(12)O(3), the dioxole ring adopts an envelope conformation. In the crystal structure, weak inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into chains.

Regulation of M1­type and M2­type macrophage polarization in RAW264.7 cells by Galectin­9.

Generally considered as a potent pro­inflammatory signal, ß­galactosidelectin suppresses T cell receptor activation, can both promote and inhibit integrin­mediated adhesion and is required in nuclear pre­mRNA splicing. Galectin­9 (Gal­9), a member of ß­galactoside lectin, is involved many processes of T cell­mediated diseases (such as autoimmune diseases and asthma) and immunomodulation of macrophages. Macrophages are involved in the occurrence of inflammation, development and digestion and other stages. At different stages of the inflammatory response, macrophages exhibit different phenotypes, but mainly two subtypes, classically (M1) or alternatively (M2) polarization. The purpose of this work is to investigate the effect of overexpression or knockdown of Gal­9 on the macrophage polarization. Macrophage polarization was detected by flow cytometric profiling of secreted cytokines and specific surface markers expression, including nitric oxide synthase 2 (NOS2) and mannose receptor 1 (CD206). Protein and mRNA expression levels of TNF­α, TGF­ß, IL­6, IL­10, NF­κB, signal transducer and activator of transcription (Stat)1 and Stat3 were determined by ELISA, western blot analysis or qRT­PCR. Our results implied that differentiation of the mouse macrophage line RAW264.7 into M1­type and M2­type macrophages is followed by marked variations of Gal­9 expression. Furthermore, its overexpression and secretion are tightly associated with M2­type macrophages, whereas its downregulation promotes macrophages to polarize into M1­type macrophages, which confirmed by elevated CD206 and NOS2, respectively. In response to the changes of Gal­9 expression, cytokines, transcription factors and regulators, including TNF­α, IL­6, NF­κB, Stat1, TGF­ß, IL­10, and Stat3, were tightly regulated and significantly associated with classically and alternatively activated macrophages. Consistent with characteristics of M1­type macrophages, the transcriptional or translational expression levels or activity of TNF­α, IL­6, Stat1 and NF­κB were markedly increased with knockdown of Gal­9 in macrophages. By contrast, the expression levels or activity of TGF­ß, IL­10 and Stat3 were clearly elevated in macrophages with Gal­9 overexpression, which is closely related with M2­type macrophages. Specific expression and secretion patterns of cytokines, transcription factors and regulators in M1­type and M2­type macrophages contribute to better understanding the role of Gal­9 in regulation in macrophages. This study provides a new insight that Gal­9 may be a new immunomodulatory target for macrophages.

A correlation analysis between tumor imaging changes and p-AKT and HSP70 expression in tumor cells after osteosarcoma chemotherapy.

This study sought to investigate osteosarcoma property changes after neoadjuvant chemotherapy and to analyze any correlation between changes with phospho-AKT (p-AKT) and heat shock protein 70 (HSP70) expression in osteosarcoma cells. Thirty patients with osteosarcoma treated at Liaocheng People's Hospital between January and October, 2016 were given an imaging examination before and after neoadjuvant chemotherapy to examine osteosarcoma tumor properties, with images scored. Immunohistochemistry was used to determine p-AKT and HSP70 expression levels, as well as tumor cell necrosis rate (TCNR), in specimens obtained before and after chemotherapy. The correlation between the imaging changes of osteosarcoma after chemotherapy and the expressions of p-AKT and HSP70 in tumor cells. Compared with pre-chemotherapy, the imaging scores of the 30 patients significantly increased after chemotherapy (P<0.05). The radiographic score of the TCNR ≥90% group was 11.3±0.5, which was significantly higher than that of the TCNR <90% group (8.7±0.3, P<0.05). p-AKT expression in osteosarcoma cells was found in 13.3% of samples (4/30 cases) after chemotherapy, which was significantly lower than prior to chemotherapy (73.3%, 22/30 cases, P<0.05). After chemotherapy, HSP70 expression in osteosarcoma cells was found in 6.7% of samples (2/30 cases), which was significantly lower than prior to chemotherapy (83.3%, 25/30 cases, P<0.05). p-AKT and HSP70 expression levels were found to be correlated with TCNR after chemotherapy (P<0.05). After chemotherapy, p-AKT and HSP70 expression levels demonstrated a positive correlation with TCNR. Tumor property changes, as uncovered by imaging, were significantly inversely correlated with tumor cell p-AKT and HSP70 expression after chemotherapy. Therefore, osteosarcoma properties, as determined through X-ray imaging, were closely related to p-AKT and HSP70 expression in osteosarcoma cells after neoadjuvant chemotherapy. The effect of chemotherapy can be evaluated by observing the above examination results.

The Role of IL-33 on LPS-Induced Acute Lung Injury in Mice.

The objective of the study is to investigate the role and specific molecular mechanism of interleukin-33 (IL-33) acted on acute lung injury (ALI) induced by lipopolysaccharide (LPS). C57BL/6 mice intratracheally instilled LPS to induce ALI model. The mice were randomly divided into three groups: the sham operation group (Sham), ALI group (ALI), and pretreatment with IL-33 of ALI group (IL-33). By observing the survival rate, inflammatory cytokines in bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) levels in lung tissue, lung histopathological examination, pulmonary capillary leakage, lung wet/dry (W/D) weight ratio, fibrosis levels in lung tissue, and associated pathways changes among the different groups, comparing to explore the role of IL-33 pretreatment on ALI mice and the possible molecular mechanisms. IL-33 pretreatment overall decreased the survival rate of ALI mice. IL-33 aggravated inflammation reaction showing as increasing the release of proinflammatory cytokines TNF-α and IL-6, increasing MPO levels in lung tissue, and aggravating lung pathology injury. In addition, IL-33 pretreatment further destroyed adherens junctions (AJs) by increasing the phosphorylation of VE-cadherin, resulting in the concomitantly pulmonary capillary barrier damage and pulmonary edema. During this process, mitogen-activated protein kinase (MAPK) pathways further activated. However, IL-33 pretreatment had no significant impact on collagen content of lung tissue. Our results indicated that IL-33 aggravated inflammatory reaction and increased microvascular permeability, but had little effect on pulmonary fibrosis, associated with the further activation of MAPK family proteins in the process. To sum up, IL-33 decreased survival rate and aggravated LPS-induced ALI.

Hydroxyethyl starch exhibits antiinflammatory effects in the intestines of endotoxemic rats.

We performed the present in vivo study to investigate the effect of hydroxyethyl starch (HES) on intestinal production of inflammatory mediators and activation of transcription factors during endotoxemia. Rats with endotoxemia induced by lipopolysaccharide (LPS) (5 mg/kg, IV) were treated with HES (16 mL/kg, IV) or saline (64 mL/kg, IV). At 2, 3, or 6 h after the LPS challenge, the rat ileal tissues were collected. Various ileal inflammatory mediator levels (tumor necrosis factor-alpha, interleukin [IL]-6, cytokine-induced neutrophil chemoattractant-1, and IL-10), inflammatory mediator messenger RNAs (mRNAs), activities of nuclear factor (NF)-kappaB and activator protein (AP)-1, and ileal myeloperoxidase-positive cells were determined in each group. HES significantly reduced the increased intestinal levels of tumor necrosis factor-alpha, IL-6, cytokine-induced neutrophil chemoattractant-1, and the mRNAs in the endotoxemic rats. Similarly, HES could decrease the myeloperoxidase-positive cells induced by LPS and also inhibit ileal NF-kappaB and AP-1 activations. Our results suggest that during endotoxemia HES may down-regulate intestinal inflammatory mediator production, and this antiinflammatory effect of HES may act through suppression of NF-kappaB and AP-1 activations.

Betamethasone affects cerebral expressions of NF-kappaB and cytokines that correlate with pain behavior in a rat model of neuropathy.

The objective of this study was to investigate whether corticosteroids modulate neuropathic pain by altering cerebral expression of nuclear factor-kappa B (NF-kappaB) and specific cytokines. The effects of topical betamethasone on neuropathic pain and cerebral expression of NF-kappaB and cytokines were studied in a rat model of L5 spinal nerve transaction. Behavioral testing was undertaken on days 1, 3, 7, 14, and 21 post-operation using the von Frey and Hargreaves tests. NF-kappaB activation in the brain was investigated by an electrophoretic mobility shift assay (EMSA), and cerebral expressions of tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-10 (IL-10) were quantified using enzyme-linked immunosorbent assays (ELISA). Spinal nerve transection induced mechanical allodynia and thermal hyperalgesia, which were significantly ameliorated by topical injection of betamethasone around the site of injury. In addition, betamethasone reduced the activation of NF-kappaB and elevation of TNFalpha and IL-1beta, and induced the expression of IL-10 in the brain, all of which correlated with the changes of pain thresholds in rats. The results suggest that topical betamethasone injection inhibits the development and maintenance of neuropathic pain. Betamethasone may act by regulating the expression of NF-kappaB, TNFalpha, IL-1beta and IL-10 in the brain. This study yields new insight into the mechanisms of corticosteroid action in neuropathic pain and may provide a basis for clinical pain control.

Mechanism of the effect of hydroxyethyl starch on reducing pulmonary capillary permeability in a rat model of sepsis.

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. Recent studies have indicated that HES may reduce capillary leakage. The present in vivo study was performed to investigate the effects of HES on pulmonary capillary permeability, inflammatory mediators, and transcription factors in sepsis. Septic rats induced by cecal ligation and puncture (CLP) were treated with different doses of HES (7.5, 15, or 30 ml/kg, iv). At 5 or 12 hr after CLPq the rat lung tissues were collected. Pulmonary microvascular permeability, various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6), mRNA expressions (cytokine-induced neutrophil chemoattractant (CINC), P-selectin, CD 11b/CD18 (Mac-1), and intercellular adhesion molecule-1 (ICAM-1)), and activities of nuclear factor (NF)-kappaB and activator protein (AP)-1 were determined in each group. HES, in a dose-related manner, significantly reduced pulmonary capillary permeability in the CLP model of sepsis. HES also down-regulated pulmonary proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) and mRNA expressions (CINC and P-selectin), and inhibited pulmonary activities of NF-kappaB and AP-1. The results suggest that during sepsis HES reduces pulmonary capillary permeability and this beneficial effect of HES may act through down-regulation of inflammatory mediators and suppression of NF-kappaB and AP-1 activation.