Research progress on breast cancer's mechanism of lung pre-metastatic niche formation and Traditional Chinese medicine intervention / 中国药理学通报

Breast cancer is currently one of the caneers with the highest incidence.Clinically, most breast eaneer patients often die due to distant metastasis.In the complex easeade of metasta¬sis, the formation of the pre-metastasis niche ( PMN) has been considered to he cnrcial in the process of distant metastasis of tumors in recent years.Tumors at the primary site secrete tumor- derived secretory factors (TDSF) , extracellular vesicles ( EV) and so on to metastasize target organs.thereby changing the mi- croenvironment of the target organs to adapt to the subsequent distant metastasis of the tumor.Breast cancer is a kind of cancer number of studies have revealed the mechanism of the breast cancer pre-metastatic niche, showing that inhibiting the PMN can reduce breast cancer metastasis.The multi-target and multi- component features of traditional Chinese medicine have been re¬ported to effectively interfere with the formation of PMN.This review summarizes the breast cancer's mechanism of lung pre- metastatic niche formation and traditional Chinese medicine in¬tervention.

PMN-CD11b Levels and Its Correlation with Left Atrial Diameter in Patients with Atrial Fibrillation / 中山大学学报(医学科学版)

@#【Objective】To observe the levels of CD11b expressions in the surface of neutrophils in serum，and its correlation with left atrial diameter ，and to study the inflammatory mechanisms in atrial fibrillation（AF） patients. 【Methods】Clinical characteristics and blood samples of AF group and sinal rhythm group were collected. CD11b levels in the surface of neutrophils were examined by flow cytometry. Left atrial diameter was examined by echocardiography. 【Results】The AF group included 85 patients ：36 with paroxysmal AF；26 with persistent AF；23 with permanent AF. The sinal rhythm group includes 57 patients. PMN- CD11b levels were significantly higher in Af group than in sinal rhythm group（P＜0.01）. The left atrial diameter was larger in AF group than in sinal rhythm group（P＜0.01）. Multivariate analysis revealed that PMN-CD11b，left atrial diameter and Valvular heart disease were independent predictors of atrial fibrillation.【Conclusions】PMN- CD11b levels were elevated in paroxysmal AF when AF was present and in persistent， permanent AF patients，implying atrial fibrillation was closely related to inflammation；PMN-CD11b were correlated with left atrial diameter，inflammation might participate in the atrial structural remodeling in AF patients ；PMN-CD11b levels were elevated in AF patients with high risk thrombosis，inflammation might have some value to embolic risk stratification according to CHA2DS2-VASc score.

Infiltration and activation of neutrophils in lung tissues during Chlamydia muridarum respiratory tract infection / 中华微生物学和免疫学杂志

Objective To investigate the possible mechanism of aggregation and activation of neu-trophils(polymorphonuclear neutrophils,PMN)in mice with chlamydial pneumonitis. Methods C57BL/ 6 mice were inoculated intranasally with 3×103 inclusion-forming units(IFU)of Chlamydia muridarum(Cm) to induce the murine model of chlamydial pneumonitis. Samples of lung tissues collected at different time points after infection were stained by hematoxylin and eosin for histopathological assessment of inflammation. The levels of myelo-peroxidase(MPO)were detected for the evaluation of PMN aggregation. The mononu-clear cells were isolated from lung tissues. The inflammatory cells were counted with Giemsaˊs staining. CD11b+Gr1+ cell population and CD11b expression in lung mononuclear cells were analyzed by flow cytome-try. The expression of chemokines(MIP-2,LIX,KC and MCP-1)in lung tissues at mRNA level was meas-ured by RT-PCR. Results Chlamydial pneumonitis was induced in mice by intranasal inoculation of 3×103 IFU of Cm. Compared with the mice from control group,large amounts of inflammatory cells including PMN, monocytes and lymphocytes were induced in lung tissues of mice with Cm infection. PMN responded earlier than monocytes to the infection. The levels of MPO were significantly increased in mice with Cm infection and reached the highest level on the 7th day after infection. A decline in MPO levels was observed on the 14th day but the levels were still higher than those on day 0. The percentages and total numbers of CD11b+Gr1+ cells were significantly increased after Cm infection. Moreover,an increased expression of PMN CD11b was also detected by flow cytometry. The expression of chemokines(MIP-2,LIX,KC and MCP-1)was in-creased in lung tissues of mice after Cm infection. The results of the study indicated that Cm infection in-duced the expression of PMN chemoattractants,resulting in the recruitment of PMN. Conclusion The infil-tration and activation of PMN in lung tissues of mice were induced by Cm infection through increasing the ex-pression of chemokines. PMN played an important role in immune responses against Cm infection.

Visfatin levels and it's diagnostic value in patients with severe pneumonia / 中华急诊医学杂志

Objective To discuss the value of Visfatin in severity evaluation in patients with severe pneumonia via observation on the variations of the plasma level of Visfatin. Method Seventy subjects including 40 patients with severe pneumonia ( group A) and 30 patients with non-severe pneumonia (group B) admitted to the ICU of emergency department and general wards from June 2009 to June 2010, were enrolled in this prospective study, and another 30 healthy individuals from physical examinees were included as subjects in control group (group C). Patients with severe diseases of heart, brain and kidney, cancers, autoimmune disease, or under special treatment in latest one month were excluded. For the subjects of all three groups, the plasma levels of Visfatin, IL-6, IL-8 and TNF-α were measured by using ELISA, while the level of CRP was assayed by using immunoturbidimetry, and the routine blood test was performed as well. The blood gas analysis and Acute Physiology and Chronic Health Evaluation Ⅱ ( APACHE Ⅱ) were carried out in patients with pneumonia. Comparisons between groups were made by t-tests, ANOVA or nonparametric test. Correlation analysis was carried out by Pearson correlation coefficient or Spearman rank correlation test. Results The plasma level of Visfatin in patients with severe pneumonia (group A) was significantly higher than that in patients with non-severe pneumonia (group B) and in the control subjects (group C) (P < 0. 01) , and the level of Visfatin in pneumonia ( group B) and in control group (group C) , and that in group B was significantly higher than that in the controls (group C) (P <0. 01). In group A, the plasma level of Visfatin was positively correlated with CRP, TNF-α, APACHE Ⅱ and PMN% (rha =0. 653, r = 0.554, r = 0.558, r= 0.484, P <0. 05), while negatively correlated with PaO2 and PaO2/FiO2 ( rha = -0.422, r= -0.543, P <0. 05). Conclusions Visfatin may be involved in the systemic inflammation response in severe pneumonia as a pro-inflammatory cytokine which is valuable in assessing the severity of pneumonia.

Visfatin levels in patients with severe pneumonia / 世界急诊医学杂志（英文）

BACKGROUND: As a cytokine highly expressed in internal organs, visfatin could be used as a biomarker of systemic inflammation response for chronic obstructive pulmonary diseases, but few studies have reported the use of visfatin in severe pneumonia. The present study was undertaken to determine the plasma levels of visfatin in patients with severe pneumonia. METHODS: A total of 70 patients, including 40 patients with severe pneumonia (group A) and 30 patients with non severe pneumonia (group B) who had been admitted to the ICU from June 2009 to June 2010, were enrolled in this prospective study. And another 30 healthy physical examinees served as healthy controls (group C). Patients were excluded if they suffered from severe diseases of the heart, brain and kidney, cancers, autoimmune diseases, or received special treatment in the latest month. The plasma levels of visfatin, IL-6, IL-8 and TNF-α were measured by ELISA, while the level of CRP was determined by immuneturbidimetry, and the routine blood test was performed. Blood gas analysis and Acute Physiology and Chronic Health Evaluation II (APACHE II) were performed in patients with pneumonia. Comparisons between the groups were conducted by Student's t test, ANOVA or nonparametric test. Correlation analysis was carried out by Pearson's correlation test or Spearman's rank-order correlation test. RESULTS: The plasma level of visfatin in group A was significantly higher than that in groups B and C (P<0.001), and the level of visfatin in group B was significantly higher than that in group C (P<0.001). The plasma level of visfatin was positively correlated with CRP, TNF-α, APACHE II and PMN％ in patients with severe pneumonia (rho=0.653, r=0.554, r=0.558, r=0.484, respectively, P<0.05 for all), while it was negatively correlated with PaO2 and PaO2/FiO2 (rho=?0.422, r=?0.543, respectively, P<0.05 for all). CONCLUSION: Visfatin may be involved in the systematic inflammation response in patients with severe pneumonia as a pro-inflammatory cytokine, and it is valuable in assessing the severity of pneumonia..

Effects of active ingredients from Coleus forskohlii on human neutrophil / 中华急诊医学杂志

Objective To study the effect of plant Coleus forskohlii active elements Isoforskolin(ISOF)and CT-E(analogs mixture of Isoforskolin)on human neutrophill(PMN)in vitro in order to uncover the mechanism of their properties of mitigating acute lung injury(ALI).Method The effects of ISOF and CF-E on PMN aggregation induced by N-formyl-methiony-leucyl-phenylalanine(fMLP)was performed by using a 4-channel platelet aggregometer.Cytometry Was applied to analyze the effect of tested samples on adhension between PMN and endothelial cells(ECV-304)activated by using lipopolysaccharides(LPS).Expression of LPS-induced PMN adhension molecules was determined with flow cytometry.Radioimmunoassay Was applied to detect the level of TNT-α liberated bv PMN and intracellular cyclic adenosine monophosphate(cAMP)level of PMN.Results It was found that ISOF(25,50,100 μmnol/L)and CF-E(1.25,2.5,5 mg/ml)inhibitted PMN aggregation induced by fMLP,PMN adhemion to ECV-304 indeed by LPS,expression of PMN adhesion molecules,and TNF-α level released by PMN.ISOF and CF-E also increased intracellular cAMP level of PMN.Condusions ISOF and CF-E inhibit PMN aggregation,adhension and adhension molecules,and TNF-α released by PMN,while they increase intracellular cAniP level of PMN.It suggests that their specific alleviating the ALI by the mechanism of the modulation of PMN function.

Effect of sonicated extracts of Enterococcus faecalis on the production of matrix metalloproteinase-8 by human polymorphonuclear neutrophils / 대한치과보존학회지

This in vitro study monitored MMP-8 production on PMN by stimulated with the following three groups; Sonicated extracts of E. faecalis (SEF), SEF treated with Ca(OH)2 (12.5mg/ml) for 7 days, and lipopolysaccharides (LPS) of E. coli. The level of MMP-8 in each group was immediately measured by ELISA. The data were analyzed with Kruskal-Wallis test and Mann-Whitney U test. In the SEF group, the level of production of MMP-8 was higher than the negative control group in low concentration (0.05microg/ml) of SEF (p 0.05). All of the levels in E. coli LPS were increased with increasing concentrations (p 0.05).

Effect of Defibrotide on Rat Reflux Esophagitis

This study was aimed at evaluating the effect of defibrotide on the development of the surgically induced reflux esophagitis, on gastric secretion, lipid peroxidation, polymorphonuclear leukocytes (PMNs) accumulation, polymorphonuclear leukocytes adherence, superoxide anion and hydrogen peroxide production in PMNs, scavenge of hydroxyl radical and hydrogen peroxide, cytokine (interleukin-1beta, tumor necrosis factor-alpha) production in blood, and intracellular calcium mobilization in PMNs. Defibrotide did not inhibit the gastric secretion and not change the gastric pH. Treatment of esophagitis rats with defibrotide inhibited lipid peroxidation, and myeloperoxidase (MPO) in the esophagus in comparison with untreated rats. Defibrotide significantly decreased the PMN adherence to superior mesenteric artery endothelium in a dose-dependent manner. Superoxide anion and hydrogen peroxide production in 1microM formylmethionylleucylphenylalanine (fMLP) - or 0.1microgram/ml N-phorbol 12- myristate 13-acetate (PMA) -activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged the hydrogen peroxide but did not scavenge the hydroxyl radical. Treatment of esophagitis rats with defibrotide inhibited interleukin-1beta production in the blood in comparison with untreated rats, but tumor necrosis factor-alpha production was not affected by defibrotide. The fMLP-induced elevation of intracellular calcium in PMNs was inhibited by defibrotide. The results of this study suggest that defibrotide may have partly beneficial protective effects against reflux esophagitis by the inhibition lipid peroxidation, PMNs accumulation, PMNs adherence to endothelium, reactive oxygen species production in PMNs, inflammatory cytokine production (i.e. interleukin-1beta), and intracellular calcium mobilization in PMNs in rats.

Neutrophil Apoptosis and H2O2 Release by LPS in Diabetics / 결핵및호흡기질환

BACKGROUND: Bacterial infections in diabetic patients are an important cause of increased morbidity and mortality. It has been reported that bacterial infections in diabetics showed more impaired PMN functions such as reduced PMN respiratory burst and decreased microbicidal activity in inflammed tissues. Also, apoptosis(programmed cell death) is postulated to be a key mechanism for neutrophil elimination. It is very important that PMN apoptosis keeps the balance from an area of inflammation. Actuallly, as little was known about PMN apoptosis and respiratory burst in diabetes, we investigated PMN apoptosis and hydrogen peroxide production after endotoxin exposure. METHODS: Peripheral venous blood samples were collected by routine venipuncture from healthy volunteers and diabetics to harvest neutrophils. We respectively measured the PMN apoptosis, the production of hydrogen peroxide, and the cell viability. RESULTS: Normal neutrophils showed a tendency to decreased apoptosis after endotoxin treatment. In patients with diabetes, PMN apoptosis was significantly decreased compared with healthy controls. In addition, the LPS-induced neutrophils in diabetics demonstrated more decreased apoptosis. However, the production of hydrogen peroxide was not different between groups. CONCLUSION: These observations suggest that the decreased PMN apoptosis in diabetics with endotoxin exposure may also affect the increased susceptibility and severity of infections.

Effects of Thiopental on the Adhesion of Polymorphonuclear Neutrophils and Myocardial Function in an Ischemia/Reperfusion Isolated Guinea Pig Heart Model / 대한마취과학회지

BACKGROUND: The adhesion of polymorphonuclear neutrophils (PMNs) to the coronary endothelium is an crucial step in PMN-mediated reperfusion injury. The purpose of this study was to investigate whether thiopental inhibits the postischemic coronary vascular adhesion of PMNs, and results in reduced postischemic myocardial dysfunction in isolated guinea pig hearts. METHODS: Hearts (n = 6-8/group) were isolated from male-guinea pigs and perfused with modified Krebs-Henseleit solution. After isolation, hearts were stabilized for 10 minutes, perfused for 15 minutes, allowed an ischemic period for 30 minutes, and a reperfusion period of 60 minutes (C group). In the P group, a bolus of 1x10(6) PMNs was infused 2 minutes after reperfusion, and in the T group additional thiopental was infused 5 minutes after the start of reperfusion, and PMNs were infused on 2 minutes after reperfusion. PMN adhesion (%), LVDP, LVEDP, +/-dP/dt, HR, and CF were measured pre- and postischemia. RESULTS: The addition of thiopental (25 microM) to the perfusate reduced the postischemic coronary vascular adhesion of PMNs (72.5+/-4.5% vs 40.0+/-7.4%, P < 0.05) and prevented postischemic myocardial dysfunction compared with group P (73.5+/-6.9% vs 48.4+/-3.0%, P < 0.05). CONCLUSIONS: Postischemic myocardial dysfunction is significantly more pronounced after PMN infusion. Thiopental reduced the postischemic coronary vascular adhesion of PMNs and attenuated the myocardial dysfunction, which was responsible at least in part, for the cardioprotective effect.

Role of expression of X-linked inhibitor of apoptosis protein in polymorphonuclear neutrophils during acute pancreatitis / 中国普通外科杂志

Objective To explore the role of apoptosis and the expression of X-linked inhibitor of apoptosis protein(XIAP) in polymorphonuclear neutrophils(PMNs) during acute pancreatitis(AP).Methods Blood from normal control(NC,n=15),mild acute pancreatitis(MAP,n=15) and severe acute pancreatitis(SAP,n=15) were collected.PMNs apoptosis was detected by flow cytometry.PMNs were isolated from each group and XIAPmRNA and protein levels were assessed by RT-PCR and Western Blotting.Results PMNs apoptosis in SAP group was(2.15?0.40)%,MAP group was(4.16?0.14)%,NC group was(4.31?0.12)%.PMNs apoptosis rate in SAP and MAP groups was decreased compared to NC group(P

Effect of topically applied Na-hyaluronan on experimental corneal alkali wound healing

The effect of topically applied 1% sodium hyaluronate (Na-HA) on the healing of a standardized corneal alkali wound was studied. The healing of the epithelium, stroma, and endothelium was evaluated separately, using quantitative methods. Central corneal alkali wound was produced in one eye of the rabbits by applying a 5.5-mm round filter paper, soaked in 1 N NaOH, for 60 seconds. 1% Na-HA in the treatment group and phosphate buffered saline (PBS) in the control group were given topically 4 times per day for 2 days, 1- and 3-weeks. Epithelial and endothelial healing was assessed morphometrically from standardized photographs and micrographs, respectively. Stromal healing was determined by counting polymorphonuclear leukocytes (PMN) and keratocytes in the central and marginal wound areas. A positive healing influence was observed in the epithelium. In stromal healing, 1% Na-HA treated corneas showed less PMNs and more keratocytes than the control group, suggesting that topically applied 1% Na-HA may suppress the stromal PMN infiltration and enhance the keratocyte repopulation during corneal alkali wound healing. However, no significant difference was found in morphometric evaluation of endothelial healing between the two groups.

Effect of nifedipine on polymorphonuclear leukocytes oxygen metabolism in coronary heart disease / 中国药理学通报

Luminol dependent chemilumi-nescence (CL) method was used to observe effect of nifedipine on polymorphonuclear leukocytes (PMN) oxygen metabolism in coronary heart disease (CHD). Studied subjects including 24 cases of coronary heart disease non using nifedipine, 26 cases of coronary heart disease using nifedipine group (10.mg tid on 3~7 days), 30 cases of normal drug-free subjects.The results showed that: 1. PMN-CL in using nifedipine CHD group was sigrlifficantly lower, its PMN- CL backgroud, peak value andphargocyte index was signifficantly lower than that in non using nifedipine CHD group. 2. PMN-CL peak value and phargocyte index in using nifedipine CHD group had no signifficantly differences compared with normal group. 3. Parameters of PMN- CL in non using nifedipine CHD group were signifficantly higher than that in normal group.

THE INFLUENCE OF QUERCETIN ON PMN METABOLISM AND FUNCTION / 中国药理学通报

Quercetin (0.05~0.20 mmol/L, final concentration) obviously inhibited the aggregation and production of PGE2 and TXB2 of human PMN which were induced by AA ( 0.66 mmol/L), LTB4 ( 0.002 mmol/L) and the fourth composition of cobra venom of Guangxi Province ( 4.8mg/L) in vitro. These effects were dose dependent, the IDg50 of PMN aggregation induced by AA, LTB4 and the fourth composition of cobra venom of Guangxi Province was 68?mol/L, 59?mol/L and 61?mol/L respectively. At the concentration of 0.50?mol/L, it can also inhibit lysozyme release of PMN induced by AA, LTB4 and the fourth composition of cobra venom of Guangxi Province.

Inhibitory effects of muscone on PMNs adherence to HUVEC and the expression of ICAM-1,VCAM-1 and CD44 of HUVEC / 中国免疫学杂志

Objective:Based on the model of human umbilical vein endothelial cell(HUVEC) treated by tumor necrosis factor-alfa(TNF),We investigate the effects of muscone on polymophonulear leukocytes(PMN)-HUVEC adhesion and its adhesion molecules(CAMs) expression.Methods:Confocal system was used for identifying cultured HUVEC,MTT assay for its activity,Rose Bengal Staining for PMN-HUVEC adhesion,and fluorescent-immunocytochemistry techniques for CAMs expression.Results:After HUVEC treated by TNF,the adhesion between PMN and HUVEC increased dramatically(P