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Even though macrophages have the potential to harm tissues through excessive release of inflammatory mediators, they play protective roles to maintain tissue integrity. In this study, we hypothesized that lysophosphatidylcholine (LPC), via G2A and A2B receptors, puts brakes on macrophages by the induction of adenosine release which could contribute to termination of inflammation. Mechanistically, LPC-induced PGE2 production followed by the activation of cAMP/protein kinase A (PKA) pathway which results in the activation of LKB1/AMPK signaling pathway leading to increasing Mg2+ influx concomitantly with an increase in mitochondrial membrane potential (MMP, Δψm) and ATP production. Then, ATP is converted to adenosine intracellularly followed by efflux via ENT1. In a parallel pathway, LPC-induced elevation of cytosolic calcium was essential for adenosine release, and Ca2+/calmodulin signaling cooperated with PKA to regulate ENT1 permeation to adenosine. Pharmacological blockade of TRPM7 and antisense treatment suppressed LPC-induced adenosine release and magnesium influx in bone marrow-derived macrophages (BMDMs). Moreover, LPC suppressed LPS-induced phosphorylation of connexin-43, which may counteract TLR4-mediated inflammatory response. Intriguingly, we found LPC increased netrin-1 production from BMDMs. Netrin-1 induces anti-inflammatory signaling via A2B receptor. In the presence of adenosine deaminase which removes adenosine in the medium, the chemotaxis of macrophages toward LPC was significantly increased. Hypoxia and metabolic acidosis are usually developed in a variety of inflammatory situations such as sepsis. We found LPC augmented hypoxia- or acidosis-induced adenosine release from BMDMs. These results provide evidence of LPC-induced brake-like action on macrophages by adenosine release via cellular magnesium signaling. [ABSTRACT FROM AUTHOR]

Purpose: Suprascapular nerve block (SSNB) is the most commonly used block for the relief of postoperative pain from arthroscopic rotator cuff repair and can be used in combination with axillary nerve block (ANB). Dexmedetomidine (DEX) is a type of alpha agonist that can elongate the duration of regional block. The aim of this study was to compare the effects of the use of dexmedetomidine combined with SSNB and ANB with those of the use of SSNB and ANB alone on postoperative pain, satisfaction, and pain-related cytokines within the first 48 h after arthroscopic rotator cuff repair. Methods: Forty patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this single-center, double-blinded randomized controlled trial study. Twenty patients were randomly allocated to group 1 and received ultrasound-guided SSNB and ANB using a mixture of 0.5 ml (50 μg) of DEX and 9.5 ml of 0.75% ropivacaine preemptively. The other 20 patients were allocated to group 2 and underwent ultrasound-guided SSNB and ANB alone using a mixture of 0.5 ml of normal saline and 9.5 ml of ropivacaine. The visual analog scale (VAS) for pain and patient satisfaction (SAT) scores were postoperatively checked within 48 h. The plasma interleukin (IL)-6, IL-8, IL-1β, cortisol, and serotonin levels were also postoperatively measured within 48 h. Results: Group 1 showed a significantly lower mean VAS (visual analog scale of pain) score 1, 3, 6, 12, 18 and 24 h after operation, and a significantly higher mean SAT (patient satisfaction) score 1, 3, 6, 12, 18, 24 and 36 h after the operation than group 2. Group 1 showed a significantly lower mean plasma IL-8 level 1 and 48 h after the operation, and a significantly lower mean IL-1β level 48 h after the operation than group 2. Group 1 showed a significantly lower mean plasma serotonin level 12 h after the operation than group 2. The mean timing of rebound pain in group 1 was significantly later than that in group 2 (36 h > 23 h, p = 0.007). Six patients each in groups 1 and 2 showed rebound pain. The others did not show rebound pain. Conclusions: Ultrasound-guided SSNA and ANB with DEX during arthroscopic rotator cuff repair resulted in a significantly lower mean VAS score and a significantly higher mean SAT score within 48 h after the operation than SSNB and ANB alone. Additionally, SSNB and ANB with DEX tended to result in a later mean timing of rebound pain accompanied by significant changes in IL-8, IL-1β, and serotonin levels within 48 h after the operation. The present study could provide the basis for selecting objective parameters of postoperative pain in deciding the optimal use of medication for relieving pain. Level of Evidence: Level I. Trial Registration: 2015–20, ClinicalTrials.gov Identifier: NCT04398589. IRB number: 2015–20, Hallym University Chuncheon Sacred Heart Hospital. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membrane-derived heterogeneous vesicles that mediate intercellular communications. They have recently been considered as ideal vehicles for drug-delivery systems, and immune cells are suggested as a potential source for drug-loaded EVs. In this study, we investigated the possibility of neutrophils as a source for drug-loaded EVs. Neutrophil-like differentiated human promyelocytic leukemia cells (dHL-60) produced massive amounts of EVs within 1 h. The dHL-60 cells are also easily loaded with various cargoes such as antibiotics (penicillin), anticancer drug (paclitaxel), chemoattractant (MCP-1), miRNA, and Cas9. The EVs derived from the dHL-60 cells showed efficient incorporation of these cargoes and significant effector functions, such as bactericidal activity, monocyte chemotaxis, and macrophage polarization. Our results suggest that neutrophils or neutrophil-like promyelocytic cells could be an attractive source for drug-delivery EVs. [ABSTRACT FROM AUTHOR]

Purpose: Interscalene brachial plexus block (ISB) is one of the most commonly used regional blocks in relieving postoperative pain after arthroscopic rotator cuff repair. Dexmedetomidine (DEX) is an alpha 2 agonist that can enhance the effect of regional blocks. The aim of this study was to compare the effects of DEX combined with ISB with ISB alone on postoperative pain, satisfaction, and pain-related cytokines within the first 48 h after arthroscopic rotator cuff repair.Methods: Fifty patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this single center, double-blinded randomized controlled trial study. Twenty-five patients were randomly allocated to group 1 and received ultrasound-guided ISB using a mixture of 1 ml (100 μg) of DEX and 8 ml of 0.75% ropivacaine preemptively. The other 25 patients were allocated to group 2 and underwent ultrasound-guided ISB alone using a mixture of 1 ml of normal saline and 8 ml of ropivacaine. The visual analog scale (VAS) for pain and patient satisfaction (SAT) scores were checked within 48 h postoperatively. The plasma interleukin (IL)-6, -8, -1β, cortisol, and substance P levels were also measured within 48 h, postoperatively.Results: Group 1 showed a significantly lower mean VAS score and a significantly higher mean SAT score than group 2 at 1, 3, 6, 12, and 18 h postoperatively. Compared with group 2, group 1 showed a significantly lower mean plasma IL-6 level at 1, 6, 12, and 48 h postoperatively and a significantly lower mean IL-8 level at 1, 6, 12, 24, and 48 h postoperatively. The mean timing of rebound pain in group 1 was significantly later than that in group 2 (12.7 h > 9.4 h, p = 0.006).Conclusions: Ultrasound-guided ISB with DEX in arthroscopic rotator cuff repair led to a significantly lower mean VAS score and a significantly higher mean SAT score within 48 h postoperatively than ISB alone. In addition, ISB with DEX showed lower mean plasma IL-6 and IL-8 levels than ISB alone within 48 h postoperatively, with delayed rebound pain.Level Of Evidence: I.Trial Registration: 2013-112, ClinicalTrials.gov Identifier: NCT02766556. [ABSTRACT FROM AUTHOR]

Waste incineration is a treatment system that reduces waste volume while capturing or destroying potentially harmful substances and recovers energy and chemical contents from wastes. Grate incinerator is one of the thermal treatment methods in waste incinerations. The incineration grates are exposed to high heat flux due to the occurrence of combustion on their surface. Therefore, cooling the incineration grate is one of the main issues in these treatments. In this study, the conjugate heat transfer between the cooling water and incineration grate is investigated numerically. We consider different geometries of the internal guide vane in the cooling channel and analyze the effects of the shapes of the guide vane on the heat transfer performance in the incineration grate. We also calculate the fluid residence time in the cooling channel and investigate the relation between the heat transfer performance and residence time of the cooling fluid. Results confirm that the maximum residence time of the cooling fluid can be reduced, from which the heat transfer performance can be improved. [ABSTRACT FROM AUTHOR]

Plasma concentration of lysophosphatidylcholine (LPC) was reported to decrease in patients with sepsis. However, the mechanisms of sepsis-induced decrease in plasma LPC levels are not currently well known. In mice subjected to cecal ligation and puncture (CLP), a model of polymicrobial peritoneal sepsis, we examined alterations in LPC-related metabolic parameters in plasma, i.e., the plasma concentration of LPC-related substances ( i.e., phosphatidylcholine (PC) and lysophosphatidic acid (LPA)), and activities or levels in the plasma of some enzymes that can be involved in the regulation of plasma LPC concentration ( i.e., secretory phospholipase A2 (sPLA2), lecithin:cholesterol acyltransferase (LCAT), acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT), and autotaxin (ATX)), as well as plasma albumin concentration. We found that levels of LPC and albumin and enzyme activities of LCAT, ATX, and sPLA2 were decreased, whereas levels of PC, LPA, and LPCAT1-3 were increased in the plasma of mice subjected to CLP. Bacterial peritonitis led to alterations in all the measured LPC-related metabolic parameters in the plasma, which could potentially contribute to sepsis-induced decrease in plasma LPC levels. These findings could lead to the novel biomarkers of sepsis. [ABSTRACT FROM AUTHOR]

Purpose: To overcome the therapeutic restrictions offered by hydrophobic quercetin (Qu), this study aims to synthesize MPEG-PLA encapsulated Qu nanoparticle and to evaluate their anticancer efficacy. Materials and Methods: In vitro anticancer potential and apoptotic studies were done by cell cytotoxicity assay and flow cytometry, respectively . MPEG-PLA-Qu nanoparticles were evaluated for anticancer efficacy in vivo using xenograft mice model. TUNEL assay was performed to observe the frequency of apoptotic cells in vivo. Results: The hydrodynamic particle size, polydispersity index, zeta potential and drug loading % of MPEG-PLA-Qu nanoparticle was 155.3 ± 3.2 nm, 0.2 ± 0.05, −3.14 mV and 5.3 ± 1.1%, respectively. Also, MPEG-PLA-Qu showed sustained drug release for 10 days. In vitro results showed that MPEG-PLA-Qu could efficiently induce apoptosis in triple negative breast cancer cell line (MDA-MB-231) with higher amount of quercetin in cell lysate treated with MPEG-PLA-Qu in comparison to free quercetin. In xenograft model for breast cancer, peritumorally injected MPEG-PLA-Qu significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in MPEG-PLA-Qu treated tumors compared to free quercetin at similar dose. Conclusion: Our data suggest that MPEG-PLA-Qu nanoparticle can have a promising clinical potential for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

In the course of isolating preventive agents against sepsis based on the in vivo assay model, eleven known compounds, (−)-catechin ( 1), catechin-7- O-β-apiofuranoside ( 2), catechin-7- O-α-Lrhamnopyranoside ( 3), catechin-3- O-α-L-rhamnopyranoside ( 4), catechin-7- O-β- d-glucopyranoside ( 5), butyl (+)-5′-methoxyisolariciresinol-9′- O-β- d-xylopyranoside ( 6), lyoniside ( 7), nudiposide ( 8), α-nigerose ( 9), butyl α- d-fructofuranoside ( 10), and procyanidin B ( 11) were isolated from the root barks of Ulmus davidiana var. japonica. Compounds 2, 6, and 8 significantly protected against sepsis in a mouse model with survival rates of mice exposed to 10 mg/kg of LPS/ d-GalN ranged from 80%-100%. Among them, 8 exhibited the most potent protective effect and decreased the plasma levels of TNF-α, IL-10 and ALT activity. [ABSTRACT FROM AUTHOR]

The bioassay-guided fractionation of protective agents against sepsis-induced lethality from the root cortex of Paeonia suffruticosa ANDREWS (Ranunculaceae) led to the isolation of eight known compounds: paeonol ( 1), 2,5-dihydroxy-4-methoxyacetophenone ( 2), acetovanillone ( 3), paeonoside ( 4), paeoniflorin ( 5), oxypaeoniflorin ( 6), apiopaeonoside ( 7), and methyl 3-hydroxy-4-methoxybenzoate ( 8). Among them, 3 showed the highest survival rate (100% with a dose of 30 mg/kg versus 17% for the control experiment) and reduced alanine aminotransferase level to be a half of the control value on the sepsis model induced by lipopolysaccharide/D-galactosamine. [ABSTRACT FROM AUTHOR]

Sepsis represents a major cause of death in intensive care units. Here we show that administration of lysophosphatidylcholine (LPC), an endogenous lysophospholipid, protected mice against lethality after cecal ligation and puncture (CLP) or intraperitoneal injection of Escherichia coli. In vivo treatment with LPC markedly enhanced clearance of intraperitoneal bacteria and blocked CLP-induced deactivation of neutrophils. In vitro, LPC increased bactericidal activity of neutrophils, but not macrophages, by enhancing H2O2 production in neutrophils that ingested E. coli. Incubation with an antibody to the LPC receptor, G2A, inhibited LPC-induced protection from CLP lethality and inhibited the effects of LPC in neutrophils. G2A-specific antibody also blocked the inhibitory effects of LPC on certain actions of lipopolysaccharides (LPS), including lethality and the release of tumor necrosis factor-a (TNF-a) from neutrophils. These results suggest that LPC can effectively prevent and treat sepsis and microbial infections. [ABSTRACT FROM AUTHOR]

Administration of dopamine agonist, apomorphine (2 mg/kg, s.c), produces cage climbing behavior in mice that exhibit typical dopaminergic stimulation. The present study investigated the pCREB expression level in several brain regions following apomorphine treatment in order to determine whether the increased the dopaminergic activation produced by apomorphine accompanies the changes in pCREB immunoreactivity. A mouse brain was removed at 0min, 10 min, 30 min, 1 h, 2 h, 7 h, and 24 h after apomorphine treatment. The brain tissue was fixed by an intracardiac perfusion with ice-cold 4% paraformaldehyde in PBS. Immunohistochemical study was conducted using the ABC-DAB method. The data showed that the immunoreactivity of pCREB increased in the striatum, nucleus-accumbens, piriform cortex and the dentate gyrus of the hippocampus of a mouse brain 30 min after the apomorphine treatment. Increased immunoreactivity began to diminish 2 h after the apomorphine treatment in all the brain regions measured. The time course for the pCREB immunoreactivity was similar to the behavioral response induced by the apomorphine treatment. These results suggest that activation of the dopamine receptor is accompanied by an increase in pCREB expression in the mouse brain. [ABSTRACT FROM AUTHOR]

One new phenylpropanoid glucoside ( 3), along with one known phenylpropanoid ( 1), and one known alkyl glucoside ( 2) were isolated from the fruits of lllicium verum and their chemical structures were elucidated on the basis of spectroscopic studies. [ABSTRACT FROM AUTHOR]