The Therapeutic Effect of Melatonin on GC by Inducing Cell Apoptosis and Autophagy Induced by Endoplasmic Reticulum Stress.

Background: Gastric cancer (GC) is the main malignancy affecting a large population worldwide. Lack of effective enough treatment is one of the leading factors contributing to the high mortality rate. Melatonin, a naturally occurring compound, has been proven to exert cytotoxic and antiproliferative effects on human gastric cancers.

Induction of mast cell accumulation by chymase via an enzymatic activity- and intercellular adhesion molecule-1-dependent mechanism.

Background And Purpose: Chymase is a unique, abundant secretory product of mast cells and a potent chemoattractant for eosinophils, monocytes and neutrophils, but little is known of its influence on mast cell accumulation.

Experimental Approach: A mouse peritoneal inflammation model, cell migration assay and flowcytometry analysis, were used to investigate the role of chymase in recruiting mast cells.

Key Results: Chymase increased, by up to 5.

Expression of proteinase-activated receptor (PAR)-2 in monocytes from allergic patients and potential molecular mechanism.

Serine proteases play an important role in inflammation via PARs. However, little is known of expression levels of PARs on monocytes of allergic patients, and influence of serine proteases and PARs on TNF-α secretion from monocytes. Using quantitative real-time PCR (qPCR) and flowcytometry techniques, we observed that the expression level of PAR-2 in monocytes of patients with allergic rhinitis and asthma was increased by 42.

Characterization and bioactivity of novel calcium antagonists - N-methoxy-benzyl haloperidol quaternary ammonium salt.

Background And Purpose: Calcium antagonists play an important role in clinical practice. However, most of them have serious side effects. We have synthesized a series of novel calcium antagonists, quaternary ammonium salt derivatives of haloperidol with N-p-methoxybenzyl (X1), N-m-methoxybenzyl (X2) and N-o-methoxybenzyl (X3) groups.

N-n-butyl haloperidol iodide inhibits H2O2-induced Na+/Ca2+-exchanger activation via the Na+/H+ exchanger in rat ventricular myocytes.

N-n-butyl haloperidol iodide (F2), a novel compound, has shown palliative effects in myocardial ischemia/reperfusion (I/R) injury. In this study, we investigated the effects of F2 on the extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/Na(+)/H(+) exchanger (NHE)/Na(+)/Ca(2+) exchanger (NCX) signal-transduction pathway involved in H2O2-induced Ca(2+) overload, in order to probe the underlying molecular mechanism by which F2 antagonizes myocardial I/R injury. Acute exposure of rat cardiac myocytes to 100 μM H2O2 increased both NHE and NCX activities, as well as levels of phosphorylated MEK and ERK.

N-n-butyl haloperidol iodide ameliorates cardiomyocytes hypoxia/reoxygenation injury by extracellular calcium-dependent and -independent mechanisms.

N-n-butyl haloperidol iodide (F2) has been shown to antagonize myocardial ischemia/reperfusion injury by blocking calcium channels. This study explores the biological functions of ERK pathway in cardiomyocytes hypoxia/reoxygenation injury and clarifies the mechanisms by which F2 ameliorates cardiomyocytes hypoxia/reoxygenation injury through the extracellular-calcium-dependent and -independent ERK1/2-related pathways. In extracellularcalcium-containing hypoxia/reoxygenation cardiomyocytes, PKCα and ERK1/2 were activated, Egr-1 protein level and cTnI leakage increased, and cell viability decreased.

Effects of N-n-butyl haloperidol iodide on the rat myocardial sarcoplasmic reticulum Ca(2+)-ATPase during ischemia/reperfusion.

We have previously shown that N-n-butyl haloperidol iodide (F(2)), a newly synthesized compound, reduces ischemia/reperfusion (I/R) injury by preventing intracellular Ca(2+) overload through inhibiting L-type calcium channels and outward current of Na(+)/Ca(2+) exchanger. This study was to investigate the effects of F(2) on activity and protein expression of the rat myocardial sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) during I/R to discover other molecular mechanisms by which F(2) maintains intracellular Ca(2+) homeostasis. In an in vivo rat model of myocardial I/R achieved by occluding coronary artery for 30-60 min followed by 0-120 min reperfusion, treatment with F(2) (0.

N-n-Butyl haloperidol iodide inhibits the augmented Na+/Ca2+ exchanger currents and L-type Ca2+ current induced by hypoxia/reoxygenation or H2O2 in cardiomyocytes.

N-n-butyl haloperidol iodide (F(2)), a novel quaternary ammonium salt derivative of haloperidol, was reported to antagonize myocardial ischemia/reperfusion injuries. To investigate its mechanisms, we characterized the effects of F(2) on Na(+)/Ca(2+) exchanger currents (I(NCX)) and the L-type Ca(2+) channel current (I(Ca,L)) of cardiomyocytes during either hypoxia/reoxygenation or exposure to H(2)O(2). Using whole-cell patch-clamp techniques, the I(NCX) and I(Ca,L) were recorded from isolated rat ventricular myocytes.

Baicalein suppresses the SOS response system of Staphylococcus aureus induced by ciprofloxacin.

Numerous antibiotics can induce an SOS repair system in bacteria that leads to antibiotic-resistant mutation of the bacterium. Therefore, searching for drugs that can prevent the SOS response and thus improve the long-term viability of some antibiotics is important. In this study, we aimed to detect the suppressive effects of baicalein on the SOS system and rifampin-resistant mutation in Staphylococcus aureus.

N-n-butyl haloperidol iodide preserves cardiomyocyte calcium homeostasis during hypoxia/ischemia.

Aims: N-n-Butyl haloperidol iodide (F(2)) is a novel compound derived from haloperidol. In our previous work, F(2) was found to be an L-type calcium channel blocker which played a protective role in rat heart ischemic-reperfusion injury in a dose-dependent manner. In the current study, we aimed to investigate the effects and some possible mechanisms of F(2) on calcium transients in hypoxic/ischemic rat cardiac myocytes.

The protective effects of Egr-1 antisense oligodeoxyribonucleotide on cardiac microvascular endothelial injury induced by hypoxia-reoxygenation.

Early growth response 1 (Egr-1) over-expression has been demonstrated in myocardial ischemia-reperfusion injury, which is closely associated with endothelial dysfunction. In the present study we investigated the expression of Egr-1 on cultured cardiac microvascular endothelial cells (CMECs) to help define the mechanism of myocardial ischemia-reperfusion injury. A model of cultured CMECs exposed to hypoxia-reoxygenation was developed in which synthesized Egr-1 sense and antisense oligodeoxyribonucleotide were transfected into the cells.

Modulation of mast cell proteinase-activated receptor expression and IL-4 release by IL-12.

It has been recognized that protease-activated receptors (PARs), interleukin (IL)-4 and IL-6 are involved in the pathogenesis of allergic diseases, and that IL-12 plays a role in adaptive immune response. However, little is known of the effect of IL-12 on protease-induced cytokine release from mast cells. In the present study, we examined potential influence of IL-12 on mast cell PAR expression and IL-4 and IL-6 release.

Induction of monocyte chemoattractant protein-1 release from A549 cells by agonists of protease-activated receptor-1 and -2.

Hypersecretion of cytokines and serine proteases has been observed in asthma. However, the influence of proteases and protease-activated receptors (PARs) on monocyte chemoattractant protein-1 (MCP-1) release from airway epithelial cells remains largely unknown. In the present study, A549 cells were challenged with agonists of PARs, and levels of MCP-1 released in the supernatant and mRNA expression were examined by ELISA and real time polymerase chain reaction (PCR), respectively.

Induction of release and up-regulated gene expression of interleukin (IL)-8 in A549 cells by serine proteinases.

Background: Hypersecretion of cytokines and serine proteinases has been observed in asthma. Since protease-activated receptors (PARs) are receptors of several serine proteinases and airway epithelial cells are a major source of cytokines, the influence of serine proteinases and PARs on interleukin (IL)-8 secretion and gene expression in cultured A549 cells was examined.

Results: A549 cells express all four PARs at both protein and mRNA levels as assessed by flow cytometry, immunofluorescence microscopy and reverse transcription polymerase chain reaction (PCR).

[Human lung epithelial cells produce interleukin-8 through protease-activated receptor 1].

Objective: To investigate the actions of protease-activated receptor 1 (PAR1) agonists and thrombin on the secretion of interleukin-8 (IL-8) from human lung epithelial cells.

Methods: A549 cells were cultured in a 12-well culture plate. The challenge was performed by addition of various concentrations of PAR1 agonist peptides SFLLR and its reverse peptides RLLFS, thrombin or hirudin, a thrombin inhibitor, into each well, respectively.