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BACKGROUND:Interleukin-8 is an important cytokine that has been found to play an important role in bone regeneration through multiple pathways. OBJECTIVE:To comprehensively review the action mechanism of interleukin-8 effects on bone regeneration to provide ideas for the following studies on interleukin-8. METHODS:By searching the China National Knowledge Infrastructure database for articles published from January 1999 to February 2023 and PubMed database for articles published from January 1985 to February 2023 reporting the role of interleukin-8 in bone-associated cells and vascularisation.Chinese and English search terms were"interleukin-8,bone repair,bone metabolism,mesenchymal stem cells,osteoblasts,osteoclasts,vascularization".The initial review yielded 508 articles in English and Chinese,and a total of 51 articles were included for review and analysis according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:According to the existing research,interleukin-8 can promote bone cell regeneration and assist bone healing through multiple pathways,which is mainly divided into three aspects:(1)Promote the proliferation and differentiation of bone cells such as mesenchymal stem cells and osteoblasts,and promote the development of cells in the direction of promoting bone healing;(2)interleukin-8 can promote angiogenesis and provide sufficient nutrition and oxygen for bone tissue,thus further improving the quality and stability of bone healing.(3)The appearance of interleukin-8 facilitates the expression of hypoxia-inducible factor-1α,vascular endothelial growth factor,and matrix metalloproteinase,which can create a microenvironment conducive to bone regeneration,thus promoting the regeneration and repair of bone tissue.In summary,interleukin-8 plays an important role in bone healing by promoting osteoblast proliferation and differentiation,facilitating angiogenesis and improving the mechanical properties of bone regeneration,as well as influencing bone metabolism through osteoclasts,mesenchymal stem cells,and other action sites.
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SGLT2 inhibitors currently have clear benefits in the treatment of heart failure whether combined with diabetes or not. Ventricular remodeling after myocardial infarction leads to the occurrence and development of heart failure, and eventually leads to death. There are relatively few studies on SGLT2 inhibitors in patients with myocardial infarction. The purpose of this article is to review the research progress of SGLT2 inhibitors application before and after myocardial infarction.
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OBJECTIVE: To analyze the diagnosis of occupational disease and the detection status of suspected occupational disease and occupational contraindication in recent years in a petrochemical enterprise. METHODS: The data of new cases of occupational disease reported by a petrochemical enterprise from 2008 to 2019, the cases of suspected occupational disease and occupational contraindication from 2015 to 2019 were collected. The related data was descriptively analyzed. RESULTS: A total of 30 new cases of occupational disease were reported in this petrochemical enterprise from 2008 to 2019. Among them, there were 16 cases of occupational noise deafness, 10 cases of chronic occupational benzene poisoning, 2 cases of occupational leukemia caused by benzene, 1 case of occupational solvent gasoline poisoning and 1 case of occupational pneumoconiosis. Among the 30 cases of occupational diseases, 28 cases(93.3%) were related to benzene and noise exposure, and 19 cases(63.3%) came from the chemical and oil refining divisions. From 2015 to 2019 in this petrochemical enterprise, 24 cases of suspected occupational disease were reported, of which 17(70.8%) suspected cases were diagnosed as occupational disease, and 63 cases of occupational contraindication were reported, including 47(74.6%) cases of occupational contraindication caused by noise. CONCLUSION: Benzene and noise should be taken as the key factors of occupational hazard for prevention and control in the petrochemical enterprises, and control measures should be adopted for special operation links and job posts to control the hidden dangers of benzene and noise that exceeds the standard limits.
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Objective To study the effect of cardiac contractility modulation (CCM) on TGFβ1/Smad/CTGF signaling pathway.Methods A rabbit heart failure (HF) model was established by ligating the ascending aortic root.Thirty rabbits were divided into sham operation group (n=10),HF group (n=10) and CCM group (n=10).Myocardial tissue collagen Ⅰ and collagen Ⅲ were analyzed with Sirius red staining,myocardial tissue hydroxyproline level was measured by chromometry,and expressions of TGFβ1,Smad3,Smad7,CTGF were detected by Western blot in 3 groups.Results Collagen Ⅰ,collagen Ⅲ and hydroxyproline content were highcr in HF group than in sham operation group,while collagen Ⅰ,collagen Ⅲ and hydroxyproline conten were lower in CCM group than in sham operation group (0.69±0.05 μg/mg vs 0.98±0.04 μg/mg,P<0.05).The expression levels of TGFβ1,Smad3,CTGF were higher while those of Smad7 were lower in HF group than in sham operation group (P<0.05).The expression levels of TGFβ1,Smad3,CTGF were lower while those of Smad7 were higher in CCM group than in HF group (0.49±0.03 vs 0.67±0.04,0.43±0.06 vs 0.59±0.06,0.45±0.08 vs 0.75±0.09,P<0.05;0.43±0.08vs 0.26±0.04,P<0.05).Conclusion CCM can improve the myocardial fibrosis in HF rabbits by downregulating the expression of TGFβ1,Smad3,CTGF and upregulating the expression of Smad7.
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Objective To investigate the association between interleukin-17 A (IL-17 A) gene promoter polymorphism and blood lipid and inflammatory factors in coronary heart disease.Methods A total of 241 patients with coronary heart disease who were admitted to hospital from April 2010 to December 2016 were enrolled in this study.68 cases of healthy subjects were collected.IL-17 gene promoter rs8193036 genotype,blood lipid and inflammatory factors were detected and compared.Results Compared with the control group,the genotype CC,CT and TT of the rs8193036 genotype in the coronary heart disease group were significantly different (P<0.05),and the frequency of C allele in the coronary heart disease group was significantly higher than that in the control group (P<0.05).The levels of triglyceride,low-density lipoproteinCholesterol,high density lipoprotein cholesterol,interleukin-17a,interleukin-6,interleukin-8 and tumor necrosis factor alpha in CC genotype of tumor necrosis factor alpha group were significantly higher than those in tumor necrosis factor alpha group (P<0.05),high density lipoprotein cholesterol decreased significantly (P<0.05).Total cholesterol and low-density lipoprotein cholesterol had no significant differences (P > 0.05).Conclusion The rs8193036 polymorphism of IL-17A gene promoter is associated with the pathogenesis of coronary heart disease.The C allele is an important genetic marker of coronary heart disease.The polymorphism of IL-17A promoter rs8193036 might affect coronary heart disease by increasing blood lipids and inflammation factors.
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Objective: To observe the impact of cardiac contractility modulation (CCM) on myocardial remodeling in rabbit model of chronic heart failure (CHF) with its possible mechanism. Methods: Rabbit HF model was established by ascending aortic root ligation; the animals were divided into 3 groups: Sham group, the animals received thoracotomy without aortic ligation, HF group and HF+CCM group, the HF animals received CCM treatment for 4 weeks. n=10 in each group. Cardiac function was measured by echocardiography at 12 and 16 weeks in each group respectively; myocardial tissue fibrosis and pathological changes were examined by Masson staining; plasma BNP level was assessed by ELISA; protein expressions of collagen I, collagen II, MMP2,MMP9, TIMP1 and galectin-3 in myocardial tissue were determined by Western blot analysis. Results: ① By echocardiography: with 12 weeks treatment, compared with Sham group, HF group and HF+CCM group had increased LVESD, LVEDD and decreased LVFS, LVEF, all P<0.05; with 16 weeks treatment, compared with HF group, HF+CCM group had improved LVESD, LVEDD, LVEF and LVFS, all P<0.05. ② Pathological changes:compared with Sham group, HF group showed increased collagen content in myocardial tissue, P<0.05; CCM treatment could partially decrease collagen accumulation, P<0.05. ③ After 12 weeks treatment, compared with Sham group, HF group and HF+CCM group presented elevated plasma BNP level, P<0.05; after 16 weeks treatment, compared with HF group, HF+CCM group presented reduced plasma BNP, while it was still higher than that in Sham group, P<0.05. ④ By Western blot analysis: compared with Sham group, HF group demonstrated increased protein expressions of collagen I, collagen II, MMP2, MMP9, TIMP1 and galectin-3 in myocardial tissue; the above indexes were much lower in HF+CCM group while still higher than those in Sham group, all P<0.05. Conclusion: CCM could improve myocardial remodeling in rabbit model of CHF which might be related to down-regulated protein expressions of collagen I, collagen III, MMP2, MMP9, TIMP1 and galectin3 in myocardial tissue.
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[ ABSTRACT] AIM:To investigate the different dose of perindopril on cardiac function in the rabbits with ische-mic cardiac dysfunction .METHODS:Male rabbits weighing 2.5~3.0 kg ( n=30) were randomly divided into 3 groups (n=10):high dose perindopril group (HD group), low dose perindopril group (LD group) and cardiac dysfunction group (CD group).The Left anterior descending coronary artery of the rabbits was ligatured for model preparation .In HD group, the rabbits were treated with perindopril split normal saline solution (1 g/L)2 mL· kg-1 · d-1 .In LD group, the rabbits were treated with perindopril split normal saline solution (0.33 g/L)2 mL· kg -1 · d-1.In CD group, the rabbits were treated with normal saline solution 2 mL· kg-1 · d-1 .Four weeks after treatment , the cardiac function was measured via echocardiography , the mRNA expression of angiotensin-converting enzyme 2 ( ACE2 ) and angiotensin type 2 receptor (AT2R) was analyzed by real-time PCR, serum angiotensin (Ang)-(1-9) and Ang-(1-7) levels were detected by ELISA. RESULTS:Compared with CD group , the cardiac function of the 2 groups treated with perindopril was significantly im-proved (P<0.01), and more improvement in HD group was observed than LD group (P<0.05).The serum angiotensin ( Ang)-(1-9) and Ang-(1-7) level and the mRNA expression of ACE 2 and AT2R in the 2 groups treated with perindopril were significantly improved (P<0.01).Compared with LD group, the mRNA expression of ACE2 and AT2R and the ser-um levels of Ang-(1-9) in HD group were significant improved (P<0.05), while no difference of serum Ang-(1-7) level was observed.Correlation analysis revealed that the improvement of the cardiac function was associated with serum Ang -(1-9) level, mRNA expression of ACE2 and AT2R (P<0.01), but has no significant correlation with serum Ang-(1-7) lev-el.CONCLUSION:High dose of perindopril may improve more cardiac function in ischemic cardiac dysfunction model in rabbits.The mechanism may relate to increasing serum Ang-(1-7) level to activate AT2R.
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AAIM:To investigate the effect of atorvastatin ( ATO) on electrical remodeling, atrial ion channel protein expression and cardiac function in atrial tachypacing rabbits, and to explore the potential electrical mechanism of ATO in the prevention of atrial fibrillation.METHODS:The rabbits were subjected to atrial tachypacing at 600 min-1 in the absence or presence of treatment with atorvastatin (ATP and ATO groups) for 48 h, and the other 10 as sham group without pacing ( NP group) .The tachypacing model was performed by attaching pacing and testing electrodes to left atrial and connecting with custom animal cardiac pacemaker in the open-chest situation.The animals in ATO group were pretrea-ted with ATO for 7 d and continued during tachypacing.Serial atrial effective refractory period ( AERP) was measured in each rabbit at baseline, 8 h, 16 h, 24 h, 32 h, 40 h and 48 h with different cycle lengths.The changes of cardiac func-tions and cardiac structure were observed by cardiac ultrasonic cardiogram before and after atrial tachypacing.The expres-sion of atrial ion channel proteins CaLα1 and Kv4.3 was detected by Western blotting.RESULTS:Compared with NP group, AERP at cycle lengths of 150 and 200 ms, the adaption of AERP, and the levels of CaLα1 and Kv4.3 expression were all decreased in ATP and ATO group, especially in ATP group.Left atrial dimension ( LAD) was increased in pacing groups as compared with NP group (P<0.05) after pacing delivery for 48 h, while no difference between the formers was observed.No significant change of the left ventricular dimension ( LVD) and ejection fraction ( LVEF) among groups be-fore and after pacing was found.CONCLUSION:Atrial tachypacing significantly shorten AERP, resulting in poor adap-tion of AERP, while ATO pretreatment significantly attenuates the atrial electrical remodeling in rabbits, but had no effect on cardiac structure.ATO suppresses the down-regulation of atrial ion channel proteins CaLα1 and Kv4.3 expression after 48 h, which may be the potential ionic mechanism of atrial electrical remodeling for ATO.
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<p><b>OBJECTIVE</b>To evaluate the impact of statin therapy on the recurrence rate in patients with persistent atrial fibrillation (AF) after electrical cardioversion.</p><p><b>METHODS</b>PubMed, EMBbase, Cochrane central register of controlled trials were searched up to February 2015 to identify randomized controlled trials, which reported the effect of statin therapy on AF recurrence after electrical cardioversion. The data were analyzed by RevMan 5.3 and Stata 12.0 software.</p><p><b>RESULTS</b>Six trials with 572 patients were included. The result showed that statin therapy had no effect on the recurrence rate in patients with persistent AF after electrical cardioversion (OR=0.60, 95%CI: 0.32-1.11, P>0.05) compared with controls. Four out of the six trials investigated the effect of atorvastatin on the recurrence rate of AF after electrical cardioversion, subgroup analysis of these trials showed that compared with controls, atorvastatin had no effect on the recurrence of AF after electrical cardioversion (OR=0.59, 95%CI: 0.25-1.39, P>0.05). Three out of the six trials had high quality (Jadad score≥3), subgroup analysis of these trials also showed that statins did not affect the recurrence rate of AF after electrical cardioversion (OR=0.76, 95%CI: 0.49-1.16, P>0.05).</p><p><b>CONCLUSION</b>This analysis suggested that statin therapy had no effect on the recurrence rate in patients with persistent AF after electrical cardioversion.</p>
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Humans , Atorvastatin , Atrial Fibrillation , Electric Countershock , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Randomized Controlled Trials as Topic , RecurrenceABSTRACT
[ ABSTRACT] AIM:To investigate the effects of transplantation of bone marrow mesenchymal stem cells ( BMSCs) modified by bcl-2 gene on myocardial cell apoptosis, angiogenesis and cardiac function in the rabbit after acute myocardial in-farction ( MI) .METHODS:The rabbit BMSCs were isolated, cultured and purified in vitro.The BMSCs were transfected with adenovirus or adenovirus-Bcl-2.The rabbit model of MI was established by ligation of left anterior descending branch. The rabbits were injected with Ad-Bcl-2-BMSCs ( MI+Bcl-2-BMSCs group) , Ad-BMSCs ( MI+BMSCs group) and DMEM ( MI group) in infarction marginal zone 2 weeks after ligation.The cardiac function was evaluated by echocardiography.The apoptosis of myocardial cells was measured by TUNEL.The mRNA expression of VEGF was detected by real-time PCR.The expression of CD31 was examined by immunohistochemical staining, and new blood capillaries were counted at 4 weeks after BMSCs transplantation.The correlation of the above values with cardiac function was analyzed.RESULTS: The cardiac function was better, the apoptotic rate was lower, the mRNA expression of VEGF and the capillary density were higher in both MI+Bcl-2-BMSCs group and the MI+BMSCs group than those in MI group, and those in MI+Bcl-2-BMSCs group in-creased more obviously .The left ventricular ejection fraction ( LVEF) had a negative correlation with the myocardial cell ap-optosis rate.A positive correlation with the mRNA expression level of VEGF and the capillary density was also observed. CONCLUSION:The transplantation of BMSCs modified by bcl-2 gene significantly reduces the myocardial cell apoptosis, promotes angiogenesis, improves heart function of the rabbits with MI.
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<p><b>OBJECTIVE</b>To observe the effects of interleukin-8 monoclonal antibody on smooth muscle cell proliferation and balloon inflation-induced abdominal aorta stenosis in rabbits.</p><p><b>METHODS</b>Thirty-six New Zealand white rabbits were randomly assigned to balloon inflation group (group A, n = 12), interleukin-8 monoclonal antibody pre-treated rabbits (2 mg/kg for 3 days before balloon inflation, group B, n = 12) and sham-operated control group (group C, n = 12). Peripheral blood was collected before experiment and at 4 h, 1, 3, 7, 14, and 28 days post balloon inflation or sham operation and the levels of IL-8 were measured by enzyme linked immunosorbent assay (ELISA). The ratio of positive and negative masculine cells in the high power microscopic field was determined in proliferating cell nuclear antigen (PCNA) stained slide. Histopathologic examination was performed in abdominal aorta and luminal area, intima and tunica media area were measured.</p><p><b>RESULTS</b>Plasma interleukin-8 began to rise at 4 h and peaked at 1 day and remained increased up to 28 days after balloon inflation in rabbits of group A, plasma interleukin-8 level in group A was significantly higher than in group B and C at 4 h and thereafter post operation. The ratio of positive and negative masculine cells was significantly increased in group A compared to group C and was significantly lower in group B than in group A. Abdominal aorta stenosis, luminal area, intima and tunica media area were significantly reduced in group B than in group A. Correlation analysis indicated that there were positive relations between plasma IL-8 level and intima thickness, area of intima and tunica media, respectively (r = 0.894, 0.783, 0.801, 0.912, all P < 0.01).</p><p><b>CONCLUSIONS</b>Plasma IL-8 level is increased in this abdominal aorta stenosis model and is positively correlated to the severity of abdominal aorta stenosis. IL-8 monoclonal antibody could significantly reduce abdominal aorta stenosis in this abdominal aorta stenosis model.</p>
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Animals , Rabbits , Antibodies, Monoclonal , Pharmacology , Therapeutic Uses , Aorta, Abdominal , Pathology , Aortic Coarctation , Drug Therapy , Pathology , Cell Proliferation , Interleukin-8 , Allergy and Immunology , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth MuscleABSTRACT
Objective To establish a cell line with overexpression of rat serotonin1A receptor (5-HT1AR).Methods Human neuroblastoma cells-SH-SY5Y were donated by cancer institute attached to the 4 th Affiliated Hospital, Hebei Medical University. Total RNA was extracted from brain tissues of male SD rats and rat 5-HT1A R was obtained by RT-PCR. Plasmid pc-DNA3. 1/hisC containing the rat 5-HT1AR (pc-DNA3.1/hisC-Rat-5-HT1AR)was constructed and transfected into SH-SY5Y cells. The transfected cells were isolated by G418 selection and SH-SY5Y-Rat-5-HT1A R cells were obtained. Expression of 5-HT1A R was detected by Western blot analysis. Cell viability was evaluated by MTT assay. SH-SY5Y-Rat-5-HT1AR cells were further observed for 5-HT1AR by immuno-fluorescence staining. Results Plasmid pc-DNA3. 1/hisC-Rat-5-HT1AR was successfully constructed by linking Rat-5-HT1A R with pc-DNA3.1/hisC and transfected into SH-SY5Y. The SH-SY5Y-Rat-5-HT1A R cells were more slender than SH-SY5Y cells with less and longer processes. MTT showed that the viability of SH-SY5Y-Rat-5-HT1A R cells was much lower than SH-SY5Y. Rat 5-HT1A R was expressed efficiently on the membrane of SH-SY5Y-Rat-5-HT1A R cells. Conclusion A cell line with overexpress of rat 5-HT1A R is successfully established.
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Objective To Compare different methods of quantitative breast density measurement.Methods The study included sixty patients who underwent both mammography and breast MRI. The breast density was computed automatically on digital mammograms with R2 workstation. Two experienced radiologists read the mammograms and assessed the breast density with Wolfe and ACR classification respectively. Fuzzy C-means clustering algorithm (FCM) was used to assess breast density on MRI. Each assessment method was repeated after 2 weeks. Spearman and Pearson correlations of inter- and intrareader and intermodality were computed for density estimates. Results Inter- and intrareader correlation of Wolfe classification were 0. 74 and 0. 65, and they were 0. 74 and 0. 82 for ACR classification respectively.Correlation between Wolfe and ACR classification was 0. 77. High interreader correlation of 0. 98 and intrareader correlation of 0. 96 was observed with MR FCM measurement. And the correlation between digital mammograms and MRI was high in the assessment of breast density (r = 0. 81, P < 0. 01). Conclusion High correlation of breast density estimates on digital mammograms and MRI FCM suggested the former could be used as a simple and accurate method.
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BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can grow in host myocardium, differentiate under myocardial condition, improve cardiac function. However, biological characteristics of BMSC differentiation are still unclear presently.OBJECTIVE: To study the expression and electrophysiological characteristics of BMSC/n vitro connexin-43 following 5-azacitidine (5-aza) treatment.DESIGN, TIME AND SETTING: The cytological in vitro controlled study was perormed at the Heart Center, Hebei Provincial People's Hospital from July 2007 to February 2009.MATERIALS: A total of 24 male pigs aged 2 months were purchased from Exparimental Animal Center, Hebei Medical University.METHODS: Bilateral femoral bone marrow was obtained from pigs under sterile condition. BMSCs were harvested by Percoll density gradient in vitro. At passage 2, BMSCs were treated with 10 μmol/L 5-aza, and incubated in DMeM without inductor 24 hours later. Indices were measured I, 2, 3 weeks following induction. A control group was set up, which was not treated with 5-azacitidine. Following bone marrow extraction, experimental pigs were anesthetized to obtain ventricular muscle. Normal ventricular muscle cells were isolated and cultured by tissue block enzyme digestion method.MAIN OUTCOME MEASURES: Expression of connexin-43 was measured by immunohistochemical staining (ABC method). Ito current density and action potential were determined by patch clamp technique.RESULTS: At 1 and 2 weeks following 5-aza induction, some BMSCs were positive for connexin-43, with the presence of brown particles surrounding nuclei. At 3 weeks, positive rate of connexin-43 was 95%. The area with large cell density was presented with similar structure to normal myocardium. At +80 mV, compared with normal myocardial cells, Ito current density was significantly reduced in BMSCs following 1 and 2 weeks and in the control group (P < 0.05). Ito current density was significantly increased to a normal levels in BMSCs 3 weeks following induction (P > 0.05). No action potential was detected in BMSCs following 1 and 2 weeks of 5-aza, and action potential could be determined 3 weeks following induction, which was identical to normal myocardial cells.CONCLUSION: Through induced by 5-aza for three weeks, BMSCs have the similar expression of connexin-43 and electrophysiological characteristics as normal myocardium.
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<p><b>BACKGROUND</b>The necrosis of a large number of myocardial cells after acute myocardial infarction (AMI) results in a decrease of cardiac function and ventricle remodeling. Stem cell transplantation could improve cardiac function after AMI, but the involving mechanisms have not been completely understood. The present study aimed to investigate the effects of transplantation of autologous bone marrow mononuclear cells (BM-MNC) and mesenchymal stem cells (MSCs) via the coronary artery on the ventricle remodeling after AMI as well as the mechanisms of the effects of transplantation of different stem cells on ventricle remodeling.</p><p><b>METHODS</b>A total of 36 male pigs were enrolled in this study, which were divided into 4 groups: control group, simple infarct model group, BM-MNC transplantation group, and MSCs transplantation group. At 90 minutes when a miniature porcine model with AMI was established, transplantation of autologous BM-MNC ((4.7 +/- 1.7) x 10(7)) and MSCs ((6.2 +/- 1.6) x 10(5)) was performed in the coronary artery via a catheter. Ultrasound, electron microscope, immunohistochemical examination and real time reverse transcriptase-polymerase chain reaction were used respectively to observe cardiac functions, counts of blood vessels of cardiac muscle, cardiac muscle nuclear factor (NF)-kappaB, myocardial cell apoptosis, and the expression of the mRNA of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cardiac muscles. Multivariate Logistic regression was used to analyze the correlation factors of left ventricular end-diastolic diameter (EDD).</p><p><b>RESULTS</b>The number of blood vessels in the infarct zone and around its border in the BM-MNC transplantation group was more than those in the infarct model group and MSCs group (P = 0.0001) and there was less myocardial cell apoptosis in the stem cell transplantation group than that in the infarct model group (all P < 0.01). The positive rate of NF-kappaB in the stem cell transplantation group was lower than that in the infarct model group (P = 0.001). The gene expression of VEGF in the infarct border zone of the BM-MNC group was higher than that in the MSCs group (P = 0.0001). The gene expression of bFGF in the infarct border zone in the MSCs transplantation group was higher than that in the infarct model group and the BM-MNC group (P = 0.0001). Left ventricular ejection fraction was inversely proportional to the apoptotic rate of myocardial cells and cardiac muscle NF-kappaB but positively correlated with the number of blood vessels and the expression of VEGF and bFGF in the infarct zone and infarct border zone. The Multivariate Logistic regression analysis on the factors influencing the left ventricular end-diastolic diameter after stem cell transplantation showed that the expression of VEGF mRNA in the cardiac muscles in the infarct zone, the number of apoptotic myocardial cells and the expression of NF-kappaB in the infarct border zone were independent factors for predicting the inhibitory effect on the dilation of left ventricular EDD after stem cell transplantation.</p><p><b>CONCLUSIONS</b>Transplantation of autologous BM-MNC and MSCs in pigs can improve the condition of left ventricular remodeling and recover the cardiac functions after AMI. The improvement of cardiac functions is related to the increase of blood vessels, the increased expression of VEGF and bFGF, the reduction of myocardial cell apoptosis, and the decrease of NF-kappaB level in cardiac muscle tissues after stem cell transplantation.</p>
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Animals , Male , Bone Marrow Transplantation , Methods , Disease Models, Animal , Heart Function Tests , Myocardial Infarction , General Surgery , Stem Cell Transplantation , Methods , Swine , Treatment Outcome , Ventricular RemodelingABSTRACT
BACKGROUND:Bone marrow stem cell transplantation can improve heart function and prevent ventricle remodeling.At present,the adult bone marrow stem cells used for transplantation primarily included bone marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs),and endothelial progenitor cells.The curative effects and precise mechanisms of transplantation of various bone marrow stem cells remain unknown.OBJECTIVE:To compare the effects of transplantation of autologous BM-MNCs and MSCs via the coronary artery on ventricle remodeling subsequent to acute myocardial infarction (AMI). DESIGN,TIME AND SETTING:Randomized controlled animal experiment performed at the Center for Clinical Research,Hebei Provincial People's Hospital,Electron Microscope Room,Hebei Medical University between March 2005 and December 2006.MATERIALS:Thirty-six male Jizhong pigs,were randomly divided into 4 groups:control group (n = 6),infarct model group (n = 10),BM-MNC group (n = 10),and MSC group (n = 10).METHODS:Porcine autologous BM-MNCs were isolated by gradient density centrifugation,and MSCs were obtained by adherence method.Prior to transplantation,both BM-MNCs and MSCs were colloidal gold labeled.Except the infract model group,pigs in the other 3 groups were developed into AMI models by oppressing the left anterior descending branch with balloon catheter.Ninety minutes after modeling,(6.0±1.3)×107 autologous BM-MNCs and (4.5±2.1)x 107 MSCs were respectively transplanted into pigs in the BM-MNC group and the MSC group via the coronary artery and cultured for 28 days.MAIN OUTCOME MEASURES:Observation of pathological changes of cardiac muscle tissue by light and electron microscope;Examination of cardiac function by ultrasonograph;Detection of the number of blood vessels and apoptotic myocardial cells,and expression of nuclear factor-κB (NF-κB) and troponin Ⅰ and its correlation to cardiac function by immunohistochemistry;Detection of mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cardiac tissue as well as its correlation to cardiac function by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS:In the MSC group,there was proliferation of a great deal of blood vessels as well as growth of abnormal cell masses around the coronary vessels,while the BM-MNC group exhibited the "budding" of many capillary vessels.Prior to transplantation,cardiac function indices were basically similar among each group (F = 1.550,P>0.05).Twenty-eight days after transplantation,left ventricular ejection fraction was significantly lower in the control,BM-MNC,and MSC groups than in the infarct model group (F = 5.30,P<0.05),while endocardial fractional shortening was significantly higher (F = 10.67,P<0.01).Compared with the infarct model group,the number of blood vessels in the infarct zone and infarct border zone was increased in the BM-MNC group (F=29.56-34.87,P<0.01) and had no apparent change in the MSC group.In the BM-MNC and MSC groups,apoptotic myocardial cells in the infarct zone and infarct border zone were significantly reduced (F=14.31-35.34,P<0.01 ) and troponin I expression rate was significantly increased (F=19.05,P<0.01 ),as compared with the infarct model group.In addition,NF-κB positive rate in the infarct border zone was significantly lower in the BM-MNC and MSC groups than in the infarct model group (F=19.05,P<0.01).VEGF gene expression level in the infarct border zone was significandy higher in the BM-MNC group than in the infarct model group and MSC group (F = 49.41,P<0.01).bFGF gene expression level in the infarct border zone was significantly higher in the MSC group than in the infarct model and BM-MNC groups (F=4.71,P<0.01).LVEF was negatively correlated to myocardial cell apoptosis rate and NF-κB level (r=-0.441 1,P<0.05;r=-0.579 6,P<0.01 ).LVEF was positively correlated to number of blood vessels,VEGF and bFGF expression (r=0.775,P<0.01;r=0.565 1,P<0.05;r=0.573 5,P<0.05).CONCLUSION:Transplantation of both autologous BM-MNC and MSC via coronary artery can improve the condition of left ventricular remodeling subsequent to myocardial infarction.The improvement of cardiac functions is related to the increase of blood vessels,VEGF and bFGF expression,the decrease of myocardial cell apoptosis and NF-κ B level in cardiac muscle tissues after stem cell transplantation.BM-MNC transplantation better promotes blood vessel proliferation and VEGF expression in the cardiac tissue but produces worse effects on bFGF gene expression than MSC transplantation.
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<p><b>OBJECTIVE</b>To investigate the effects of autologous bone mesenchymal stem cells (MSC) transplantation on malignant arrhythmia induced by electrophysiological (EP) stimulation and cardiomyocyte ion channels remodeling in a mini-swine model of acute myocardial infarction (AMI).</p><p><b>METHODS</b>Immediately after AMI (LAD occluded for 120 min), MSC (10 x 10(7), labeled by colloidal gold and co-cultivated with 5-azacytidine, 5-aza, n = 12) or equal volume saline (n = 10) were injected through over-the-wire (OTW) balloon in LAD at distal over D(1). EP stimulation is performed after 2 hours and 4 weeks in both groups to induce arrhythmia. The variance of heterogeneity of sodium currents (I(Na)) and I(Na) steady-state inactivation curves in different zones of infracted wall were investigated by patch clamp technology and the relationship between ionic channel and ventricular arrhythmia is analyzed.</p><p><b>RESULTS</b>EP induced malignant ventricular arrhythmia (VT) rate was similar (MSC 75% vs. saline 90%, P = 0.455) at 2 hours post AMI and was significantly lower in MSC group (25% vs. 80%, P = 0.012) at 4 weeks post AMI. The Peak I(Na) current densities of the Endo, Media and Epi were significantly lower in MSC group [(-14.04 +/- 3.82) pA/pF, (-29.26 +/- 5.70) pA/pF, (-12.43 +/- 3.04) pA/pF] compared those in saline group [(-9.71 +/- 3.38) pA/pF, (-18.98 +/- 4.05) pA/pF, (-8.47 +/- 3.34) pA/pF, all P < 0.05]. The I(Na) steady-state inactivation curves of the Epi, Endo and Media in mini-swine with VT in MSC group [(-126.2 +/- 10.9) mV, (-106.7 +/- 11.9) mV, (-105.4 +/- 11.0) mV] were similar as those in saline group with VT [(-129.1 +/- 10.9) mV, (-112.2 +/- 9.9) mV, (-109.7 +/- 9.2) mV, all P > 0.05] while significantly lower compared to MSC group without VT [(-93.1 +/- 13.8) mV, (-95.2 +/- 15.5) mV, (-103.4 +/- 8.7) mV, all P < 0.05]. The multiple logistic regression analysis showed that I(Na) current density (RR = 1.449, 95% CI 1.276 - 2.079, P = 0.029) and I(Na) steady-state inactivation curves (RR = 1.092, 95% CI 1.008 - 1.917, P = 0.012) were the independent factors for reduced VT.</p><p><b>CONCLUSIONS</b>Autologous MSC attenuated malignant ventricular arrhythmia induced by EP at 4 weeks in mini-swine with AMI which might due to altered cardiomyocyte ion channels remodeling induced by MSC.</p>
Subject(s)
Animals , Female , Male , Arrhythmias, Cardiac , Bone Marrow Transplantation , Disease Models, Animal , Mesenchymal Stem Cell Transplantation , Myocardial Infarction , General Surgery , Patch-Clamp Techniques , Swine , Swine, Miniature , Transplantation, AutologousABSTRACT
Objective To investigate the influence of two different dose of atorvastatin on the prognosis and endothelial function in post-PCI acute coronary syndrom patients.Methods 92 post-PCI ACS patients were randomly divided into two groups,atorvastatin 20mg and atorvastatin 10 mg group.In each group the patients were treated with atorvasta- tin 20mg or 10mg respectively.After one month we add or decrease the dose of atorvastatin according to the blood lipid level.After 12 month the blood lipid level、FMD、NO、ET、NOS、UAP、AMI were compared between two groups. Results The clinical setting have no significant association between two groups before treating,After treated 1 and 12 month the TC,LDL-C level were significantly decreased as compared with the base level before treating in each group. After treated 1 month,in atorvastatin 20 mg group the TC,LDL-C level were significantly decreased and NO、NO/ET level were significantly higher than those in atorvastatin 10 mg group.During 12 month follow up the incidence of angina pectoris onset and rehospitalization were significantly higher in atorvastatin 10 mg group(P
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Objective To evaluate the safety of a surgical appwach for transabdominal cardial carci- noma.Methods We retrospectively analyzed 326 patients undergoing transabdominal esophagastrostomy or esophagojejunostomy from 1998 to 2006 via the EEA(end-to-end anastomosis)stapler.Results By the surgi- cal approach for transabdominal cardial carcinoma,the average length of reseete esophagus above the carci- noma was about 6~8 cm realized the low average of remnant carcinoma at the margin and operation mortality and anastomotic leakage,which was lower than those in the thoraeotomy appmaeh significantly.Conclusion The transabdominal approach makes a clear operative field in posterio-inferior mediastinum,it is beneficial for radical resection of eardial carcinoma and intramediastinal esophagogastric or esophagojejunal mechanical anastomosis,and it fits to the old,the weakening and with the disease of heart and lung.
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Objective To study the clinical characteristics and curative effects of pancreatic cystade- nocarcinoma in order to improve its diagnostic and therapeutic accuracy.Methods A retrospective analysis was done on the clinical materials of 13 cases of pancreatic cystadenocarcinoma hospitalized in Shanxi Cancer Hospital from 1990 to 2006.Results The preoperative diagnosis were as follows:pancreatic cystadenocarci- noma 6 cases,pancreatic cystadenoma 2 cases,pancreatic cancer 1 case,pancreatic pseudocyst 4 cases.The misdiagnosis rate was 53.8 %.Surgical operation was done on the 13 cases,and 10 of them were treated by radical operation.A 5-year follow-up was done on 6 still alive cases,and 1 of them lived over 11 years.3 cases were treated by palliative operation,and all of them died within 3 years.Conclusion Since there is no specific clinical manifestations of pancreatic cystadenocarcinoma,it is very difficult to get an accurate preop- erative diagnosis.Radical operation is the most effective therapeutic methods.