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Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.
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Objective: This study aimed to analyze clinical factors related to arterial stiffening and establish a risk prediction nomogram of arterial stiffening in the octogenarian(≥80 years). Methods: This study was a retrospective cross-sectional study, which enrolled the octogenarian elderly who underwent physical examination and secondary prevention intervention in the outpatient department of Chinese People's Liberation Army General Hospital from April 2022 to August 2022. Clinical data including demographics, biochemical indicators and medical history were collected. Brachial-ankle pulse wave velocity (baPWV) was detected during the clinical visit. Participants were divided into the control group (baPWV≤1 800 cm/s) and vascular sclerosis group (baPWV>1 800 cm/s). The risk factors of arterial stiffness were analyzed by univariate and logistic regression analysis, and the nomogram model was constructed by R programming language. The predictive effect of the nomogram model was evaluated by the receiver operating characteristic curve (ROC). Results: The median age of the 525 participants was 87.0 (82.0, 92.0) years, 504 (96.0%) were male, 82 in the control group, 443 in the vascular sclerosis group. The baPWV, age, systolic blood pressure, mean arterial pressure and diastolic blood pressure were significantly lower in the control group than those in the vascular sclerosis group (all P<0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol, alanine aminotransferase and amylase were protective factors, and alkaline phosphatase and creatinine were risk factors of arterial stiffening (all P<0.05). The combined nomogram model scores including age, mean arterial pressure and the above five laboratory indicators indicated that mean arterial pressure and serum creatinine levels were strongly correlated with vascular sclerosis. The ROC curve suggested that the nomogram model had good prediction ability. Conclusions: Age, mean arterial pressure, high-density lipoprotein cholesterol, alanine aminotransferase, alkaline phosphatase, amylase and creatinine are independently determinants for increased vascular stiffness. The combined prediction model in this study can provide reference for individualized clinical risk prediction of vascular sclerosis in the octogenarian elderly.
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Idoso de 80 Anos ou mais , Humanos , Masculino , Idoso , Feminino , Índice Tornozelo-Braço , Rigidez Vascular/fisiologia , Octogenários , Estudos Retrospectivos , Estudos Transversais , Alanina Transaminase , Fosfatase Alcalina , Creatinina , Esclerose , Análise de Onda de Pulso , Fatores de Risco , Amilases , Lipoproteínas HDL , ColesterolRESUMO
Objective: This study aimed to analyze clinical factors related to arterial stiffening and establish a risk prediction nomogram of arterial stiffening in the octogenarian(≥80 years). Methods: This study was a retrospective cross-sectional study, which enrolled the octogenarian elderly who underwent physical examination and secondary prevention intervention in the outpatient department of Chinese People's Liberation Army General Hospital from April 2022 to August 2022. Clinical data including demographics, biochemical indicators and medical history were collected. Brachial-ankle pulse wave velocity (baPWV) was detected during the clinical visit. Participants were divided into the control group (baPWV≤1 800 cm/s) and vascular sclerosis group (baPWV>1 800 cm/s). The risk factors of arterial stiffness were analyzed by univariate and logistic regression analysis, and the nomogram model was constructed by R programming language. The predictive effect of the nomogram model was evaluated by the receiver operating characteristic curve (ROC). Results: The median age of the 525 participants was 87.0 (82.0, 92.0) years, 504 (96.0%) were male, 82 in the control group, 443 in the vascular sclerosis group. The baPWV, age, systolic blood pressure, mean arterial pressure and diastolic blood pressure were significantly lower in the control group than those in the vascular sclerosis group (all P<0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol, alanine aminotransferase and amylase were protective factors, and alkaline phosphatase and creatinine were risk factors of arterial stiffening (all P<0.05). The combined nomogram model scores including age, mean arterial pressure and the above five laboratory indicators indicated that mean arterial pressure and serum creatinine levels were strongly correlated with vascular sclerosis. The ROC curve suggested that the nomogram model had good prediction ability. Conclusions: Age, mean arterial pressure, high-density lipoprotein cholesterol, alanine aminotransferase, alkaline phosphatase, amylase and creatinine are independently determinants for increased vascular stiffness. The combined prediction model in this study can provide reference for individualized clinical risk prediction of vascular sclerosis in the octogenarian elderly.
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Idoso de 80 Anos ou mais , Humanos , Masculino , Idoso , Feminino , Índice Tornozelo-Braço , Rigidez Vascular/fisiologia , Octogenários , Estudos Retrospectivos , Estudos Transversais , Alanina Transaminase , Fosfatase Alcalina , Creatinina , Esclerose , Análise de Onda de Pulso , Fatores de Risco , Amilases , Lipoproteínas HDL , ColesterolRESUMO
BACKGROUND@#Treatment of coronary bifurcation lesions remains challenging; a simple strategy has been preferred as of late, but the disadvantage is ostium stenosis or even occlusion of the side branch (SB). Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported. This prospective, multicenter, randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon (PEB) compared with regular balloon angioplasty (BA) in the treatment of non-left main coronary artery bifurcation lesions.@*METHODS@#Between December 2014 and November 2015, a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers. Patients were randomly allocated at a 1:1 ratio to a PEB group (n = 113) and a BA group (n = 109). The primary efficacy endpoint was angiographic target lesion stenosis at 9 months. Secondary efficacy and safety endpoints included target lesion revascularization, target vessel revascularization, target lesion failure, major adverse cardiac and cerebral events (MACCEs), all-cause death, cardiac death, non-fatal myocardial infarction, and thrombosis in target lesions. The main analyses performed in this clinical trial included case shedding analysis, base-value equilibrium analysis, effectiveness analysis, and safety analysis. SAS version 9.4 was used for the statistical analyses.@*RESULTS@#At the 9-month angiographic follow-up, the difference in the primary efficacy endpoint of target lesion stenosis between the PEB (28.7% ± 18.7%) and BA groups (40.0% ± 19.0%) was -11.3% (95% confidence interval: -16.3% to -6.3%, Psuperiority <0.0001) in the intention-to-treat analysis, and similar results were recorded in the per-protocol analysis, demonstrating the superiority of PEB to BA. Late lumen loss was significantly lower in the PEB group than in the BA group (-0.06 ± 0.32 vs. 0.18 ± 0.34 mm, P < 0.0001). For intention-to-treat, there were no significant differences between PEB and BA in the 9-month percentages of MACCEs (0.9% vs. 3.7%, P = 0.16) or non-fatal myocardial infarctions (0 vs. 0.9%, P = 0.49). There were no clinical events of target lesion revascularization, target vessel revascularization, target lesion failure, all-cause death, cardiac death or target lesion thrombosis in either group.@*CONCLUSIONS@#In de novo non-left main coronary artery bifurcations treated with provisional T stenting, SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT02325817; https://clinicaltrials.gov.
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Objective:To understand the nutritional risk in patients with IBD,its related factors and nutritional treatment options.Methods:IBD patients treated in Peking University first hospital from January 2006 to December 2015 were studied.Using the Nutritional risk screening 2002 (NRS2002) nutritional risk assessment of the patients were evaluated.According to the body mass index (BMI),patients were divided into normal BMI group (BMI 18.5 ~ 23.9),low BMI group (BMI < 18.5) and high BMI group (BMI ≥ 24).We analyzed the nutritional risk related factors and compared the difference of nutritional therapy options,regarding the UC and CD patients respectively.Results:A total of 388 patients with IBD were enrolled in the study,with UC 306 and CD 82 patients.The total nutritional risk was 49.5%.Although there was no difference in BMI distribution between UC and CD,CD was more likely to have nutritional risk than UC (CD 64.6%,UC 45.4%,(P =0.002).The nutritional risk of low BMI group was 95.7%.There were no differences in age,sex,and family history in IBD patients for the occurrence of nutritional risk.The more frequently recurrence,severe of disease activity,and the wider rang of disease bring the higher nutritional risk for UC patients.But for CD patients,penetrating type,having a history of surgery and severe of disease activity had higher nutritional risk.Adequate caloric nutrition therapy in patients with CD was 77.4% higher than that of UC 46.8%,(P < 0.001).It was a main principle of our center that UC patients with severe recurrence should not emphasize enteral nutrition and CD patients should first deal with the contraindications before starting enteral nutrition.Conclusions:IBD patients have a high nutritional risk and CD is more obvious than UC,particularly in low BMI patients.The nutritional risk of patients with UC and CD has its own associated factors.It is safe to treat IBD patients with enteral nutrition as long as the indications and contraindications were well controlled.
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<p><b>BACKGROUND</b>Disrupted Ca2+ homeostasis contributes to the development of colonic dysmotility in ulcerative colitis (UC), but the underlying mechanisms are unknown. This study aimed to examine the alteration of colonic smooth muscle (SM) Ca2+ signaling and Ca2+ handling proteins in a rat model of dextran sulfate sodium (DSS)-induced UC.</p><p><b>METHODS</b>Male Sprague-Dawley rats were randomly divided into control (n = 18) and DSS (n = 17) groups. Acute colitis was induced by 5% DSS in the drinking water for 7 days. Contractility of colonic SM strips (controls, n = 8 and DSS, n = 7) was measured in an organ bath. Cytosolic resting Ca2+ levels (n = 3 in each group) and Ca2+ transients (n = 3 in each group) were measured in single colonic SM cells. Ca2+ handling protein expression was determined by Western blotting (n = 4 in each group). Differences between control and DSS groups were analyzed by a two-sample independent t-test.</p><p><b>RESULTS</b>Average tension and amplitude of spontaneous contractions of colonic muscle strips were significantly enhanced in DSS-treated rats compared with controls (1.25 ± 0.08 g vs. 0.96 ± 0.05 g, P= 0.007; and 2.67 ± 0.62 g vs. 0.52 ± 0.10 g, P= 0.013). Average tensions of carbachol-evoked contractions were much weaker in the DSS group (1.08 ± 0.10 g vs. 1.80 ± 0.19 g, P= 0.006). Spontaneous Ca2+ transients were observed in more SM cells from DSS-treated rats (15/30 cells) than from controls (5/36 cells). Peak caffeine-induced intracellular Ca2+ release was lower in SM cells of DSS-treated rats than controls (0.413 ± 0.046 vs. 0.548 ± 0.041, P= 0.033). Finally, several Ca2+ handling proteins in colonic SM were altered by DSS treatment, including sarcoplasmic reticulum calcium-transporting ATPase 2a downregulation and phospholamban and inositol 1,4,5-trisphosphate receptor 1 upregulation.</p><p><b>CONCLUSIONS</b>Impaired intracellular Ca2+ signaling of colonic SM, caused by alteration of Ca2+ handing proteins, contribute to colonic dysmotility in DSS-induced UC.</p>
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Animais , Masculino , Ratos , Colite , Metabolismo , Colo , Biologia Celular , Metabolismo , Sulfato de Dextrana , Toxicidade , Músculo Liso , Metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , FisiologiaRESUMO
OBJECTIVE: To compare the efficacy of computed tomography enterography and magnetic resonance enterography in diagnosing small intestinal diseases. METHODS: The retrospective study comparing computed tomography enterography and magnetic resonance enterography for diagnosing diseases related to small intestine was conducted at Department of Radiology, Yantai Yuhuangding Hospital, Shandong, China, from July 2012 to February 2014. The efficacy of computed tomography enterography and magnetic resonance enterography results were evaluated for randomly-selected cases to compare the location and characteristics of small intestinal diseases together with small bowel endoscopy and clinical pathology observations. RESULTS: Of the 30 patients in the study, 19(63.3%) were males and 11 (36.7%) were females with an overall mean age of 33.6±19.2 years (range: 24-67 years). the clinical diagnostic accuracy of computed tomography enterography and magnetic resonance enterography was 24(80%) and 21(70%) cases respectively (p>0.05). CONCLUSIONS: Computed tomography enterography and magnetic resonance enterography are two techniques that complement each other for diagnostic purposes.
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Doença de Crohn/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Neoplasias Intestinais/diagnóstico , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Adulto , Idoso , Endoscopia Gastrointestinal , Feminino , Humanos , Enteropatias/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42), tegaserod (1 mg·kg-1·day-1, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.
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Animais , Masculino , Ratos , Hipersensibilidade/metabolismo , Síndrome do Intestino Irritável/metabolismo , /metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Vísceras/metabolismo , Animais Recém-Nascidos , Western Blotting , Doença Crônica , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Fluoxetina/farmacologia , Hipersensibilidade/tratamento farmacológico , Imuno-Histoquímica , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/tratamento farmacológico , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Inibidores Seletivos de Recaptação de Serotonina/farmacologiaRESUMO
Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT(4) receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT(4) receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT(4) receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg · kg(-1) · day(-1), days 36-42), tegaserod (1 mg · kg(-1) · day(-1), day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT(4) receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT(4) receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.
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Hipersensibilidade/metabolismo , Síndrome do Intestino Irritável/metabolismo , Receptores 5-HT4 de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Vísceras/metabolismo , Animais , Animais Recém-Nascidos , Western Blotting , Doença Crônica , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Fluoxetina/farmacologia , Hipersensibilidade/tratamento farmacológico , Imuno-Histoquímica , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Índice de Gravidade de DoençaRESUMO
<p><b>OBJECTIVE</b>To observe the protective effect and mechanism of intermittent hypobaric hypoxia (IHH) on cardiomyocytes induced by hydrogen dioxide.</p><p><b>METHODS</b>Male guinea pigs were divided randomly into two groups (n = 10): intermittent hypoxia group (IHH), and control group (non-IHH). The IHH guinea pigs were exposed to a simulated 5,000 m high altitude and hypoxia in hypobaric chamber for 28 d, 6 h/d. The control guinea pigs were kept in the same environment as IHH except hypoxia exposure. Cardiomyocytes were enzymatically isolated from left ventricle of non-CIHH or CIHH guinea pigs. The contractile was assessed in guinea pigs by a video-based motion edge-detection system. The contents and activities of malondialdehyde(MDA), lactate hydrogenase(LDH) and antioxidant enzymes were evaluated by using biochemical methods.</p><p><b>RESULTS</b>1. Hydrogen peroxide could induce contractile and diastole dysfunction, the latent period was longer in IHH cardiac myocytes. 2. After hydrogen peroxide(300 micromol/L, 10 min) perfusion, LDH and MDA contents in supernatant increased significantly in non-IHH and CIHH cardiomyocytes (P < 0.01), Whereas the contents of MDA and LDH in IHH cardiomyocytes were lower than those in non-IHH cardiomyocytes (P < 0.01). 3. The activities of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in the myocardium of IHH guinea pigs, after hydrogen peroxide (300 micromol/L, 10 min) perfusion, SOD and CAT activities decreased significantly in non-IHH and CIHH cardiomyocytes (P < 0.01), whereas the activities of SOD and CAT in CIHH cardiomyocytes were still higher than those in non-IHH cardiomyocytes.</p><p><b>CONCLUSION</b>IHH had a protective effect on cardiomyocytes injury induced by hydrogen peroxide, which might relate with its antioxidation effects.</p>
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Animais , Masculino , Altitude , Catalase , Metabolismo , Células Cultivadas , Cobaias , Peróxido de Hidrogênio , Farmacologia , Hipóxia , Metabolismo , L-Lactato Desidrogenase , Metabolismo , Malondialdeído , Metabolismo , Miócitos Cardíacos , Metabolismo , Superóxido Dismutase , MetabolismoRESUMO
<p><b>BACKGROUND</b>Pulmonary embolism (PE) is often mistaken as acute coronary syndromes (ACS) because of the considerable overlap in their clinical features. We evaluated the factors causing misdiagnosis of PE as ACS and factors that differentiate PE from ACS to improve the diagnosis efficacy of PE.</p><p><b>METHODS</b>The medical records of 22 consecutive PE patients, between 2001 and 2010, who were initially suspected of ACS were retrieved. ACS was ruled out by coronary artery angiography before a definite diagnosis of PE was given. Twenty-two contemporary cases of ACS matched by age and sex were recruited as controls. Clinical manifestations, electrocardiograms (ECG), and biomarkers of these patients were reviewed retrospectively. The factors causing misdiagnosis of PE as ACS and factors differentiating PE from ACS were evaluated.</p><p><b>RESULTS</b>We found two leading causes of misdiagnosis of PE as ACS. One is that PE can resemble ACS in several clinical aspects (symptoms and signs, ECG findings, plasma cardiac troponin I, and D-dimer). The other is the insufficient recognition of PE by clinicians. Risk factors for venous thromboembolism (VTE), especially deep venous thrombosis (DVT), together with signs of PE, such as unexplained dyspnea or hypoxemia, and right ventricular pressure overload on ECGs are valuable in differentiating the two diseases.</p><p><b>CONCLUSIONS</b>Differentiation between PE and ACS is sometimes challenging. Adequate awareness of the risk factors for VTE and the signs of PE are crucial in the diagnosis of PE.</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Coronariana Aguda , Diagnóstico por Imagem , Angiografia Coronária , Eletrocardiografia , Embolia Pulmonar , Diagnóstico por Imagem , Estudos RetrospectivosRESUMO
This study was aimed to investigate the effect of proteasome inhibitor bortezomib on the migration ability and hepatocyte growth factor (HGF) expression of bone marrow mesenchymal stem cells (MSC) in multiple myeloma patients. Transwell assay was employed to measure the migration ability of bone marrow MSC in vitro before and after treatment with bortezomib. The HGF mRNA expression level was determined by real-time quantitative PCR. The results indicated that after treated with bortezomib of concentrations of 2.5 nmol/L for 48 hours, the migration activity of MSC decreased significantly as compared with control cohorts (p < 0.05). The HGF mRNA level in MSC after bortezomib treatment was significantly lower than that of control group (p < 0.05). It is concluded that bortezomib can inhibit the migration and down-regulate HGF mRNA expression of bone marrow MSC in multiple myeloma patients.
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos , Farmacologia , Células da Medula Óssea , Biologia Celular , Ácidos Borônicos , Farmacologia , Bortezomib , Movimento Celular , Fator de Crescimento de Hepatócito , Metabolismo , Células-Tronco Mesenquimais , Biologia Celular , Mieloma Múltiplo , Metabolismo , Inibidores de Proteassoma , Farmacologia , Pirazinas , FarmacologiaRESUMO
<p><b>OBJECTIVE</b>To study the differentiation potential of human umbilical cord-derived mesenchymal stem cells (UCMSC) into human sweat gland cells (hSGC) and the role of extracellular signal-regulated kinase (ERK) pathway.</p><p><b>METHODS</b>UCMSC and hSGC were isolated and cultured in vitro. The former was identified with expression of CD14, CD29, CD34, CD44, CD45, CD105, cytokeratin 7 (CK7), CK19, and carcinoembryonic antigen (CEA), while the latter was identified with expression of CK19 and CEA. UCMSC with density of 5 x 10(4) cells per well placed in lower compartment of Transwell chamber were divided into control group (C, cultured with nutrient solution without any stimulation), thermal injury group (TI, treated with heat-shocked hSGC with density of 1 x 10(4) cells per well inoculated into the upper compartment of Transwell chamber for indirect co-culture), thermal injury + EGF group (TIE, treated with indirect co-culture as used in TI group, with addition of 50 ng/mL EGF), thermal injury + PD98059 group (TIP, treated with indirect co-culture as used in TI group, with addition of 10 nmol/mL ERK specific inhibitor PD98059) according to the random number table. One week after culture, the positive expression rates of CK7 and CK19 in UCMSC were detected by flow cytometry, the expression of CK19 and CEA in UCMSC were examined with immunohistochemical staining and the positive expression rate of CEA was calculated, and the expression level of phosphorylated ERK (pERK) was determined by Western blotting. Data were processed with one-way analysis of variance.</p><p><b>RESULTS</b>(1) CD29, CD44, and CD105 were highly expressed in UCMSC, accompanied by low or negative expression of CD14, CD34, CD45, CK7, CK19, and CEA. The expression of CK19 and CEA were positive in hSGC. The two results showed that UCMSC and hSGC were pure. (2) Compared with those of C group [(2.2 +/- 1.5)%, (2.2 +/- 0.7)%, (3.3 +/- 0.7)%, 0.640 +/- 0.026], the expression levels of CK7, CK19, CEA, and pERK in UCSMC of TI group [(6.4 +/- 0.7)%, (5.7 +/- 0.3)%, (7.4 +/- 1.0)%, 0.790 +/- 0.049] and TIE group [(14.3 +/- 1.0)%, (12.6 +/- 1.1)%, (17.6 +/- 2.3)%, 1.200 +/- 0.032] were significantly increased (with F value respectively 78.49, 139.36, 87.13, and 191.74, P values all below 0.01), and those of TIE group were higher than those of TI group (with F value from 50.14 to 145.47, P values all below 0.01). There were no obvious difference in the 4 indexes between TIP group and C group (with F value from 0.00 to 0.13, P values all above 0.05).</p><p><b>CONCLUSIONS</b>UCMSC co-cultured with heat-shocked hSGC can differentiate into hSGC, and ERK signal pathway participates in the process of differentiation of UCMSC into hSGC.</p>
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Humanos , Diferenciação Celular , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular , Citometria de Fluxo , Células-Tronco Mesenquimais , Biologia Celular , Metabolismo , Transdução de Sinais , Glândulas Sudoríparas , Biologia Celular , Metabolismo , Cordão Umbilical , Biologia Celular , MetabolismoRESUMO
This study was aimed to investigate the mRNA expression levels of hepatocyte growth factor (HGF), stromal cell-derived factor-1 (SDF-1), monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) in bone marrow mesenchymal stem cells (MSC) from multiple myeloma (MM) patients. The mRNA expression levels of HGF, SDF-1, MCP-1 and IL-8 in bone marrow MSC from 20 newly diagnosed MM patients were detected by real time quantitative RT-PCR and were compared with that in 9 controls. The results indicated that the mean mRNA expression level of HGF was up-regulated in MM patients, as compared with controls (p < 0.01). However, the mean mRNA expression level of SDF-1 mRNA was down-regulated in MM patients, as compared with controls (p < 0.05). There was no significant difference in the mRNA expression levels of MCP-1 and IL-8 between MM and control cohorts (p > 0.05). It is concluded that BM-MSC from MM patients express HGF, SDF-1, MCP-1, IL-8, but these chemotaxis-related factors expression of bone marrow microenvironment cellular component are dysregulated in MM patients, which may result from the interplay between MM cells and MSC.
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Humanos , Células da Medula Óssea , Metabolismo , Células Cultivadas , Quimiocina CCL2 , Metabolismo , Quimiocina CXCL12 , Metabolismo , Fatores Quimiotáticos , Metabolismo , Fator de Crescimento de Hepatócito , Metabolismo , Interleucina-8 , Metabolismo , Células-Tronco Mesenquimais , Metabolismo , Mieloma Múltiplo , Metabolismo , RNA Mensageiro , GenéticaRESUMO
<p><b>BACKGROUND</b>Recent studies have revealed that pretreatment with statin is effective in preventing arrhythmia, but its electrophysiological mechanism is unclear. This study was conducted to investigate the cardioprotective effects of simvastatin on reversing electrical remodeling in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the ionic mechanism responsible for the anti-arrhythmic effect of statin.</p><p><b>METHODS</b>Forty-five rabbits were randomly divided into three groups: ischemic-reperfusion group (I-R), simvastatin intervention group (Statin) and sham-operated control group (CON). Anesthetized rabbits were subjected to 30-minute ischemia by ligation of the left anterior descending coronary artery and a 60-minute reperfusion after a 3-day administration of oral simvastatin of 5 mg x kg(-1) x d(-1) in the Statin group or a placebo in the I-R group. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in the I-R and Statin group and the same anatomical region in the CON animals. The whole cell patch-clamp technique was used to record membrane ionic currents, including sodium current (I(Na)), L-type calcium current (I(Ca-L)) and transient outward potassium current (I(to)). Simultaneously, the level of serum cholesterol was examined.</p><p><b>RESULTS</b>There was no significant difference in the serum cholesterol concentration among the three groups. The peak I(Na) current density (at -30 mV) was significantly decreased in I-R ((-22.46+/-5.32) pA/pF, n=12) compared with CON ((-42.78+/-5.48) pA/pF, n=16, P<0.01) and Statin ((-40.66+/-5.89) pA/pF, n=15, P<0.01), while the peak I(Na) current density in the Statin group was not different from CON (P>0.05). The peak I(Ca-L) current density (at 0 mV) was significantly increased in I-R ((-4.34+/-0.92) pA/pF, n=15) compared with CON ((-3.13+/-1.22) pA/pF, n=13, P<0.05) and Statin ((-3.46+/-0.85) pA/pF, n=16, P<0.05), while the Peak I(Ca-L) current density in Statin was not different from CON (P>0.05). The I(to) current density (at +60 mV) was significantly decreased in I-R ((9.49+/-1.91) pA/pF, n=11) compared with CON ((17.41+/-3.13) pA/pF, n=15, P<0.01) and Statin ((14.54+/-2.41) pA/pF, n=11, P<0.01), although there was a slight reduction in the Statin group compared with CON (P<0.05).</p><p><b>CONCLUSIONS</b>It is implied that ischemia-reperfusion induces significant down-regulation of I(Na) and I(to) and up-regulation of I(Ca-L), which may underlie the altered electrical activity and long abnormal transmembrane action potential duration of the surviving ventricular myocytes, thus contributing to ventricular arrhythmias during acute ischemia-reperfusion period. Pretreatment with simvastatin could attenuate these changes and reverse this electrical remodeling without lowering the serum cholesterol level, contributing to the ionic mechanism of statin in treatment of arrhythmia independent of a decrease in cholesterol.</p>
Assuntos
Animais , Feminino , Masculino , Coelhos , Canais de Cálcio Tipo L , Colesterol , Sangue , Coração , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Canais de Potássio , Sinvastatina , Farmacologia , Canais de SódioRESUMO
Objective To explore the changs of serum brain type creatine kinase isoenzyme(CK-BB),cystatin C of newborns with hypoxic-ischemic encephalopathy(HIE) and assess their applications.Methods The serum concentrations of CK-BB and cystatin C were measured by turbidimertric immunoassay in 56 HIE newborns and 42 normal neonates.Results 1.Compared with controls,the concentration of serum CK-BB in moderate HIE newborns had significant differences(P