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Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.
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Objective:To evaluate the effect of paclitaxel on the mast cell-CCL2-macrophage axis in rats with pulmonary hypertension.Methods:Thirty SPF-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 180-220 g, were divided into 3 groups ( n=10 each) using a random number table method: control group (group C), pulmonary hypertension group (group PH), and paclitaxel group (group PTX). The model of pulmonary hypertension was established by subcutaneous injection of monocrotaline 60 mg/kg in rats.At 25 days after establishing the models, paclitaxel 2 mg/kg was injected via the tail vein once every four days, for 4 times in total in group PTX.The equal volume of normal saline was injected in the remaining 2 groups.The mean pulmonary artery pressure (mPAP) was performed at 40 days after establishing the model.The heart was removed and dried, the right ventricle (RV) and left ventricle plus ventricular septum (LV+ S) was weighed, and the Fulton index [RV/(LV+ S)] was calculated.The inferior lobe of left lung was taken, the ratio of media wall thickness of pulmonary vessels was calculated by HE staining, the number of Tryptase + , CD68 + , CD163 + , and Ki67 + cells was recorded by immunohistochemistry, the mean value was calculated, the percentage of Ki67-positive cells in blood vessels was recorded, and the proportion of muscularized blood vessels was calculated.The content of CCL2 was measured by enzyme-linked immunosorbent assay, and the expression of cleaved caspase-3 and Cyclin D1 was detected by Western blot. Results:Compared with group C, the mPAP, Fulton index, ratio of media wall thickness, proportion of muscularized blood vessels, the number of Tryptase + , CD68 + and CD163 + cells and percentage of Ki67 + cells were significantly increased, and the expression of cleaved caspase-3 was down-regulated in PH and PTX groups ( P<0.05), the expression of Cyclin D1 was significantly up-regulated in group PH ( P<0.05), and no significant change was found in group PTX ( P>0.05). Compared with group PH, the mPAP, Fulton index, ratio of media wall thickness, percentage of muscularized blood vessels, the number of Tryptase + , CD68 + and CD163 + cells and percentage of Ki67 + cells were significantly decreased, the expression of CCL2 and Cyclin D1 was down-regulated, and the expression of cleaved caspase-3 was up-regulated in group PTX ( P<0.05). Conclusion:The mechanism by which paclitaxel alleviates pulmonary hypertension is related to inhibiting the mast cell-CCL2-macrophage axis in rats.
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Aim To explore the effects of mangiferin on tissue factor(TF) expression in human umbilical vein endothelial cells(HUVECs) and the underlying mechanisms.Methods HUVECs were isolated and primarily cultured in vitro.After the treatment with mangiferin and oxidized low density lipoprotein(oxLDL), TF expression was determined in HUVECs with real-time PCR and Western blot.Results oxLDLinduced the mRNA and protein expression and pro-thrombotic activity of TF in HUVECs.However, the inductive effects of oxLDL were blocked significantly by mangiferin.Furthermore, mangiferin modified TF expression and activity in a dose-dependent manner.Mangiferin was demonstrated to enhance the activity of peroxisome proliferator-activated receptor gamma(PPARγ).In contrast, GW9662, an antagonist of PPARγ, reversed at least partially the suppressive effects of mangiferin on TF.Conclusion Through activating PPARγ, mangiferin suppresses the expression of TF serving pro-thrombotic functions in endothelial cells.
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Objective To investigate the clinical efficacy of trimebutine combined with Xiangsha Pingwei in the treatment of functional dyspepsia and its effect on gastrointestinal hormone.Methods One hundred and twenty cases of functional dyspepsia were randomly divided into the control group and observation group,60 cases in each group.The control group was treated with trimebutine 0.2 g,3 times/d and the observation group was treated with trimebutine 0.2 g,3 times/d and Xiangsha Pingwei 10 g,2 times/d.Both groups were treated for four weeks,a course of treatment.Clinical efficacy and the influence on gastrointestinal hormone levels were compared between the two groups.Results The symptoms scores in both groups all decreased significantly after treatment.While the postprandial fullness scores,early satiety scores and epigastric pain scores in the observation group were significantly lower than those in the control group (0.62±0.12 vs.1.85±0.25,0.56±0.14 vs.1.46±0.21,0.48±0.15 vs.1.32±0.12,t=34.36,27.62,33.87,P<0.05).The total effective rate in the observation group was significantly higher than that in the control group (90.00% vs.73.33%,χ2=5.57,P<0.05).MOT and GAS levels in both groups increased significantly.While MOT and GAS levels in the observation group were significantly higher than those in the control group (MOT: (355.2±78.1) ng/L vs.(288.7±82.4) ng/L;GAS:(96.5±17.6) ng/L vs.(88.4±16.0) ng/L,t=4.54,2.64,P<0.05).The somatostatin (SS) level in both groups decreased significantly.While the SS level in the observation group was significantly lower than that in the control group ((41.1±11.1) ng/L vs.(48.9±12.9) ng/L,t=3.55,P<0.05).Conclusion Trimebutine combined with Xiangsha Pingwei can significantly improve the clinical symptoms and gastrointestinal hormone in patients with functional dyspepsia.
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Objective:To investigate the expression of hypoxia-inducible factor-2α (HIF-2α)in non-small cell lung cancer (NSCLC)tissue,and to analyze its relationships with angiogenesis,cell proliferation and chemotherapy resistance. Methods: Total 112 cases of NSCLC and 20 cases of normal lung tissues were selected, immunohistochemical method was used to detect the expressions of HIF-2α,CD31,Ki67 and GST-π in 112 cases of cancer tissue and 20 cases of normal lung tissue,and the correlations of HIF-2α expression with microvessel density (MVD),Ki67, and GST-π were analyzed.Results:The positive expression rate of HIF-2α in NSCLC tissue was significantly higher than that in normal lung tissue (P < 0.05 ), the expression rate of HIF-2α in 112 cases of NSCLC was 47.3% (53/112).The MVD in HIF-2α protein high expression NSCLC group (31.1 ± 14.7)was higher than that in HIF-2αprotein low expression NSCLC group (24.3±15.8)(P <0.05).The cases of high expression of Ki67 in HIF-2αhigh expression group occupied 54.7% (29/53),and it was higher than that in HIF-2αlow expression group (16/59,27.1%);there was significant difference (r = 0.281,P = 0.003).The high expression of HIF-2α had no obvious correlation with the expression of GST-π (r = 0.122,P = 0.202). Conclusion:HIF-2αmay play an important role in the carcinogenesis and development of NSCLC by promoting the angiogenesis and enhancing the cell proliferation of NSCLC,but it may have no correlation with chemotherapy resistance.
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Objective:To investigate the inhibitory effect and mechanism of different doses of Xiao Chai Hu Tang on C6 glioma cells cultured in vitro. Methods:C6 glioma cells were inoculated in 96 holes,24 holes and 6 holes,each culture plate was divided into 4 groups:control group, low dose group, middle dose group and high dose group, when the cells covered the bottom of culture plate 80%-90%,began adding,cultured for 24 hours after the ter mination of training. Cell proliferation activity,cell viability,protein content and protein positive expression intensity of VEGF and ESM-1,cell apoptosis in early and late stage were detected by CCK-8,in vivo staining,ELISA, immunocytochemistry and flow cytometry. Results: CCK-8 assay showed that the growth of C6 glioma cells was inhibited by low,medium and high dose group;ELISA and immunocytochemistry showed that the expression of VEGF and ESM-1 was lower in the lower, middle and high dose groups, and the levels of protein expression and protein levels were decreased. The flow cytometry showed that the low dose of small radix,middle and high dose group could promote the cell apoptosis. Inverted microscope ob-servation showed that with the increase of dose,the number of cells increased gradually,and the number of dead cells increased,and all kinds of detection methods showed that the inhibition effect increased with dose and dose dependence. The difference between the two groups was statistically significant(P<0. 01). Conclusion:The growth of C6 glioma cells was significantly inhibited by Xiao Chai Hu Tang. It may play a role in inhibiting tumor growth by down regulating ESM-1 and VEGF protein level and promoting cell apoptosis.
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Objective To investigate the expressions of inflammatory factors in papillary thyroid carcinoma tissue and their relationships with the clinical pathological characteristics,and to provide an experimental basis for guiding clinical treatment and prognosis.Methods 74 patients with papillary thyroid carcinoma dignosed by puncture were selected as experimental group,and 26 cases of healthy people were used as normal control group.The fasting venous blood samples from the subjects in two groups were collected,and the postoperative specimens from cancer tissue,adjacent normal tissue and the fasting venous blood 7 d after operation of the patients in experimental group were collected again.The interleukin 1α(IL-1α),interleukin 1β(IL-1β)and cyclooxygenase-2 (COX-2)protein expression levels in serum,cancer adjacent normal tissue and cancer tissue were detected by ELISA;the gene and protein expression levels of IL-1α,IL-1βand COX-2 were examined by real-time fluorescent quantitative method and immunohistochemistry;the relationships between their expressions and clinical stages, pathological types,lymph node metastasis of thyroid papillary carcinoma were analyzed.Results The expression levels of serum IL-1α,IL-1βand COX-2 protein of the patients in experimental group were significantly higher than those in normal control group (P<0.01);the gene and protein expression levels of IL-1α,IL-1βand COX-2 in thyroid papillary carcinoma tissue were significantly higher than those in adjacent tissue (P<0.01).There were positive correlations between the expressions of IL-1αand IL-1β,IL-1αand COX-2,IL-1βand COX-2 in thyroid papillary carcinoma tissue (r=0.64,P=0.035;r=0.71,P=0.042;r=0.69,P=0.038).Conclusion The expression levels of IL-1α, IL-1βand COX-2 in thyroid papillary carcinoma tissue are increased, suggesting that inflammation is involved in metastasis and invasion of thyroid papillary carcinoma,its application is expected to become a new means of cancer treatment strategies.
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Objective:To observe the expression of the tumor suppressor gene (P53),apoptosis signal receptor (Fas),tumor necrosis factor alpha ( TNF-α) and Cyclin E ( Cyclin E) in serum and cancer tissues with papillary thyroid cancer patients ,and explore their relationship with the clinical pathology characteristics of thyroid papillary carcinoma .Methods:The puncture diagnosis in patients with papillary thyroid carcinoma as the experimental group (n=74),physical examination of healthy people as the normal control group (n=26).The two groups were fasting venous blood samples ,the experimental group in postoperative specimens from cancer tissue , adjacent normal tissue and 7 days after the fasting venous blood was sampled again.Protein content of P53,Fas,TNF-αand Cyclin E was detected by ELISA in serum , cancer adjacent normal tissue and cancer tissue;using real-time fluorescent quantitative assay to observe the gene expression of P53,Fas,TNF-αand Cyclin E in thyroid papillary carcinoma and adjacent normal tissues ; protein expression by immunohistochemical methods in papillary thyroid carcinoma and adjacent normal tissues P 53,Fas,TNF-αand Cyclin E analysis;the clinical expression with papillary thyroid cancer staging , pathological Type and has no relationship to lymph node metastasis.Results:The protein concentration in serum of patients with papillary thyroid carcinoma P 53 , Fas and TNF-αwere significantly lower than that of the normal control group ,Cyclin E protein content was significantly higher than that of normal control group ,the differences were statistically significant (P<0.01);thyroid papillary carcinoma P53,Fas and TNF-αprotein content,protein expression strength and gene expression levels were significantly lower than the normal tissues adjacent to cancer ,protein content ,Cyclin E protein expression and gene expression intensity was significantly higher than that in normal tissues ,the difference was statistically significant (P<0.05).Conclusion:The expression of p53,Fas and TNF-αin papillary thyroid carcinoma lower and expression level of Cyclin E increase ,may play an important role in papillary thyroid cancer invasion and metastasis.Combined detection of the four can be used as markers for early diagnosis of papillary thyroid cancer ,enhance the rate of early diagnosis of thyroid papillary carcinoma.
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Objective To investigate the elationship between the expression of Cathepsin D and Laminin receptors with the invasion and metastasis of gastric cancers.Methods Cathepsin D and Laminin receptors immunoreactivities were evaluated in 96 patients with gastric cancer using streptavaclin pemxidase method.Results Over expression of Cathepsin D in gastric cancer tissue was significantly related with the depth of invasion,lymphnode metastasis and grade of differentiation (P<0.01,P<0.01 and P<0.05, respectively).Moreover,the high expression of Lamninin receptors in gastric cancer had significant correlations with the invasion depth and grade of differentiation(P<0.05 and P<0.01);The positive expression of Laminin receptors were not significantly related with lymph node metastasis(P>0.05).By statistics analysis Cathepsin D had a significant positive correlation with Laminin receptors (P<0.05). Conclusion Cathepsin D and Laminin Receptors play all important role in the invasion and metastasis of gastric Cancers.
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Objective To investigate the characteristics of Wallerian degeneration (WD) of secondary pyramidal tract after supratentorial cerebrovascular diseases, and to study the relationship between secondary WD and clinical performance. Methods We retrospectively reviewed and investigated the results of brain CT films of 272 cases suffered from supratentorial cerebral vascular diseases during 2001 till 2004. The number of supratentorial disorders was counted respectively in WD group and non-WD group, the distribution feature of these disorders was analyzed, and the changes in the cerebral peduncles of the midbrain and Activities of Daily Living Scale (ADLs) were determined. The information obtained was analyzed statistically respectively. Results Seventy-four cases of secondary WD were found, the rate of WD outbreak was 27.2%. In WD group, the ipsilateral cerebral peduncle of supratentorial disorder was significantly narrower than contralateral cerebral peduncle (P
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Objective To evaluate the relationship between carotid arteriosclerosis and ischemic cerebral vascular disorders (ICVD). Method We examined 126 ICVD patients and 126 non-ICVD patients in the alterations of carotid dimension and intramembrane morphology with magnetic resonance angiography (MRA). Results Carotid plaques to various extent were detected in 82 cases of ICVD patients and 38 cases of non-ICVD patients. The incidence of carotid plaques was 68.3% and 35.7%, respectively in these two groups of patients. Furthermore, patients either with age over 60 years, hypertension, or hyperlipemia were found to be more susceptible to carotid arteriosclerosis. Conclusion MRA is very useful to detect early-stage carotid arteriosclerosis, and the occurrence in the carotid arteriosclerosis is closely related to ICVD.