Evaluation of oral nano-curcumin efficacy on respiratory function and quality of life in patients with bronchial non-atopic asthma: A randomized controlled trial.

Objective: Asthma is a common disease and curcumin has modest effect in inflammatory disorders. This study investigated the efficacy of nano-curcumin on asthma. Materials and Methods: In this double-blinded randomized clinical trial, 60 patients with non-atopic bronchial asthma were randomly stratified in two groups of intervention (N=30) and control (N=30) groups. Apart from their standard treatment, the intervention group received 40 mg nano-curcumin (soft gel) three times daily while the control group received placebo. During the 60-day study, patients were assessed using spirometry to measure Forced expiratory volume in first second (FEV1). Asthma control test (ACT) was completed every 30 days and asthma quality of life questionnaire (AQLQ) was completed at the first and end of the study. Results: Totally, 31 patients (51.7%) were male and the mean age was 51.45±12.58 years. FEV1 was improved but there was no significant difference between intervention and control groups. ACT and AQLQ domains scores significantly improved. However, it was not statistically different between control and intervention groups. Conclusion: Nano-curcumin at administered dosage had no additive effect on the standard treatment in asthmatic patients.

Modulation of JAK2, STAT3 and Akt1 proteins by granulocyte colony stimulating factor following carbon monoxide poisoning in male rat.

Carbon monoxide (CO) is an odorless, colorless, tasteless and non-irritating by-product of inefficient combustion of hydrocarbon fuels such as motor vehicle exhausted gases. It is the leading cause of mortality in the USA among all unintentional toxicants. Male rats exposed to CO poisoning in the heart has many cardiovascular effects such as, cardiomyopathy, tachycardia, arrhythmias, and ischemia and in severe cases, myocardial infarction (MI) and cardiac arrest. Cardiomyocyte apoptosis is one of the most frequent consequences in the heart. Granulocyte colony stimulating factor (G-CSF) is a cytokine that mobilizes and differentiates granulocytes from stem cells. It can stimulate many anti-apoptotic pathways such as JAK2-STAT3 and PI3-Akt kinases following cardiac ischemia. G-CSF exerts its anti-apoptotic effects through binding to its specific cell surface receptor. The purpose of this study was to elucidate the mechanism of anti-apoptotic effect of G-CSF following CO poisoning. Rats were exposed to CO 1500 or 3000 ppm for 60 min. Animals received G-CSF 100 µg/kg subcutaneously for five consecutive days after CO intoxication. Western blot analysis was used to evaluate the expression of six proteins namely JAK2, p-JAK2, STAT3, p-STAT3, Akt1 and p-Akt1 following G-CSF 100 µg/kg consecutive dose administration after CO poisoning. There was a significant difference between phosphorylated proteins including p-JAK2, p-STAT3 and p-Akt1 in the G-CSF groups and those in control groups and there were not any significant differences in total protein among the groups.

Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat.

Erythropoietin (EPO) plays a critical role in the development of the nervous system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic protein (GFAP) levels in the serum were determined and water content of brain and the extravasation of a tracer (Evans blue) were measured. Brain lipid peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2 protein relative expressions were determined. Cation exchange chromatography was used to evaluate MBP alterations. Seven days after exposure, pathological assessment was performed after Klüver-Barrera staining. EPO reduced malondialdehyde levels at all doses (2500, 5000 and 10,000 u/kg). Lower doses of EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of GFAP. EPO could not reduce the water content of the edematous poisoned brains. However, at 5000 and 10,000 u/kg it protected the blood brain barrier against integrity loss as a result of CO. EPO could significantly decrease the MPO activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO could partially prevent these biochemical changes. Fewer vacuoles and demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced it 38.86%. These results reveal that EPO could relatively prevent different pathways of neurotoxicity by CO poisoning and thus has the potential to be used as a novel approach to manage this poisoning.

Serum osteopontin concentrations in relation to coronary artery disease.

BACKGROUND AND AIMS: Coronary artery disease (CAD) is a common form of vascular disease and is associated with high mortality and morbidity globally. It has been suggested that serum osteopontin (OPN) may be a useful biomarker of atherosclerosis and vascular calcification. The aim of this study was to assess the association between serum OPN levels and severity of CAD. METHODS: Three hundred and four subjects were studied, 111 with clinically significant angiographically defined CAD (CAD+) (>50% stenosis), 96 with negative angiography (CAD-) (<50% stenosis) and 97 healthy controls. Fasting blood samples were collected from all patients before coronary angiography and serum OPN levels were determined using ELISA. RESULTS: Serum concentrations of OPN were significantly higher in both CAD+ (72.99 [51.05-103.64]) and CAD- (11.11 [8.11-18.23]) (p = 0.001) groups compared with the control group (5.99 [4.26-7.91]) (p = 0.001). CAD+ subjects also had higher serum OPN levels compared with CAD-subjects (p = 0.001). However, OPN levels were comparable between subgroups of CAD+ subjects stratified according to the number of narrowed vessels in angiography. CONCLUSIONS: The present results suggest a positive association between circulating OPN concentrations and the presence but not the extent of CAD.

Proteomics screening of molecular targets of granulocyte colony stimulating factor in the mouse brain and PC12 cell line.

AIMS: Granulocyte colony stimulating factor (G-CSF), a new neuroprotective agent, binds to its specific receptors in the brain. In this study we hypothesized that at least a part of G-CSF's neuroprotective effect may be mediated through its interaction with other proteins in the brain. MAIN METHODS: Using an immunoprecipitation (IP) kit, at first the antibody of G-CSF was covalently crosslinked to protein A/G agarose. Then the mouse brain or PC12 cell lysate mixed with G-CSF was added to the agarose beads plus antibody. After immunoaffinity isolation of target proteins, gel electrophoresis was performed and protein bands were identified using MALDI-TOF/TOF and MASCOT software. KEY FINDINGS: Our data show that G-CSF physically binds to cellular proteins like sodium/potassium-transporting ATPase, beta actin, aldehyde dehydrogenase, regucalcin and glutathione-s-transferase. These proteins are involved in membrane transportation, cell structure, signal transduction, enzymes involve in calcium related cell signaling and redox homeostasis. SIGNIFICANCE: Interaction of G-CSF with these proteins can explain some of its pharmacological effects in the CNS.

The effect of granulocyte colony-stimulating factor administration on carbon monoxide neurotoxicity in rats.

Granulocyte colony-stimulating factor (G-CSF) is considered to be a novel neuroprotective agent. Beneficial effects have been demonstrated by administrating G-CSF in different experimental stroke models. In this study, we evaluated the efficacy of G-CSF therapy on carbon monoxide (CO) neurotoxicity in rats exposed to acute CO poisoning. Immediately after exposure to 3,000 ppm of CO for 60 minutes, 50, 100, and 150 µg/kg of G-CSF or normal saline were administered to rats. Rats were sacrificed after 24 hours for serum marker analysis or 1 week for histopathological examination. Brain sections were stained with hematoxylin and eosin to assess leukocyte infiltration and hippocampal injury and with Luxol fast blue to assess demyelination. S100ß and glial fibrillary acidic protein (GFAP) serum levels were evaluated by commercial enzyme-linked immunosorbent assay kits. According to histopathological findings, G-CSF administration significantly restricted white-matter demyelination (150 µg/kg) (P = 0.006). Also, serum levels of S100ß in G-CSF-treated groups (100 and 150 µg/kg) decreased significantly (P < 0.01 and P < 0.05, respectively). In all does, G-CSF significantly reduced serum levels of GFAP (P < 0.01 for 50 µg/kg and P < 0.001 for other doses). Administration of G-CSF after CO poisoning attenuates brain cell damage through remyelination. G-CSF also decreases levels of related biomarkers, such as S100ß and GFAP.

Effects of granulocyte colony-stimulating factor on electrocardiogram changes after carbon monoxide poisoning in rats.

Carbon monoxide (CO), which is produced by the incomplete combustion of hydrocarbons, has many toxic effects on different organs, especially the brain and heart. CO-induced cardiotoxicity leads to several deleterious effects, including electrocardiogram (ECG) abnormalities. The present study aimed to evaluate the protective effect of recombinant human granulocyte colony-stimulation factor (G-CSF) on ECG after CO poisoning in rats. Single and multiple doses of G-CSF (10, 50, and 100 µg/kg) were administered to groups, each containing 5 male Wistar rats (16 groups for ECG analysis and 16 groups for pathological analysis). Rats were already exposed to CO at either 1,500 or 3,000 ppm concentrations for 60 minutes. ECG findings (e.g., ST-segment and T-wave changes), cardiac arrhythmias (e.g., heart blocks and ventricular and supraventricular arrhythmias), and histological changes were determined after G-CSF administration. At 3,000 ppm, frequencies of ST elevation, depression, and T inversion in ECG were significantly reduced after G-CSF treatment. Also, some of the cardiac arrhythmias (e.g., atrioventricular block type 1 and 2) after CO poisoning were suppressed after G-CSF treatment. However, G-CSF did not show protective effects on cardiomyocyte pathological consequences in CO-poisoned rats. Therefore, G-CSF could protect against ECG changes after CO-induced cardiac ischemia, but did not affect pathological changes.