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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The inflammatory cytokine storm causes systemic organ damage, especially acute lung injury in sepsis. In this study, we found that the expression of S-phase kinase-associated protein 2 (Skp2) was significantly decreased in sepsis-induced acute lung injury (ALI). Sepsis activated the MEK/ERK pathway and inhibited Skp2 expression in the pulmonary epithelium, resulting in a reduction of K48 ubiquitination of solute carrier family 3 member 2 (SLC3A2), thereby impairing its membrane localization and cystine/glutamate exchange function. Consequently, the dysregulated intracellular redox reactions induced ferroptosis in pulmonary epithelial cells, leading to lung injury. Finally, we demonstrated that intravenous administration of Skp2 mRNA-encapsulating lipid nanoparticles (LNPs) inhibited ferroptosis in the pulmonary epithelium and alleviated lung injury in septic mice. Taken together, these data provide an innovative understanding of the underlying mechanisms of sepsis-induced ALI and a promising therapeutic strategy for sepsis.
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Lesión Pulmonar Aguda , Ferroptosis , Ratones Endogámicos C57BL , Proteínas Quinasas Asociadas a Fase-S , Sepsis , Ubiquitinación , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/etiología , Sepsis/metabolismo , Sepsis/complicaciones , Sepsis/patología , Animales , Ratones , Humanos , Masculino , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Proteínas Quinasas Asociadas a Fase-S/genética , Pulmón/patología , Pulmón/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genéticaRESUMEN
BACKGROUND: HSK3486 (ciprofol), a new candidate drug similar to propofol, exerts sedative and hypnotic effects through gamma-aminobutyric acid type A receptors; however, its potential role in colorectal cancer is currently unknown. AIMS: This study aimed to evaluate the effects of HSK3486 on colorectal cancer cell proliferation. METHODS: Imaging was performed to detect reactive oxygen species and mitochondrial membrane potential. Western blotting was used to determine the expression of target signals. The HSK3486 molecular mechanism was investigated through ATPase inhibitory factor 1 knockdown and xenograft model experiments to assess mitochondrial function in colorectal cancer cells. RESULTS: Cell Counting Kit-8 and Annexin V/propidium iodide double staining assays showed that HSK3486 inhibited colorectal cancer cell proliferation in a concentration-dependent manner. In addition, HSK3486 treatment increased the expression of B-cell lymphoma-2-associated X, cleaved caspase 3, and cleaved poly (ADP-ribose) polymerase, whereas myeloid cell leukemia-1 and B-cell lymphoma 2 expression decreased. HSK3486 promoted mitochondrial dysfunction by inducing ATPase inhibitor factor 1 expression. Furthermore, HSK3486 promoted oxidative stress, as shown by the increase in reactive oxygen species and lactate dehydrogenase levels, along with a decrease in mitochondrial membrane potential and ATP levels. ATPase inhibitor factor 1 small interfering RNA pretreatment dramatically increased the mitochondrial membrane potential and tumor size in a xenograft model following exposure to HSK3486. CONCLUSION: Collectively, our findings revealed that HSK3486 induces oxidative stress, resulting in colorectal cancer cell apoptosis, making it a potential candidate therapeutic strategy for colorectal cancer.
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Apoptosis , Neoplasias Colorrectales , Humanos , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfatasas/farmacología , Adenosina Trifosfatasas/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Potencial de la Membrana Mitocondrial , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proteína Inhibidora ATPasa/efectos de los fármacosRESUMEN
Approximately 20% of colorectal cancer (CRC) patients are first diagnosed with metastatic colorectal cancer (mCRC) because they develop symptoms at an advanced stage. Despite advancements in treatment, patients with metastatic disease still experience inferior survival rates. Our objective is to investigate the association between long noncoding RNAs (lncRNAs) and prognosis and to explore their role in mCRC. In this study, we find that elevated expression of PCAT6 is independently linked to unfavourable survival outcomes in The Cancer Genome Atlas (TCGA) data, and this finding is further confirmed in CRC samples obtained from Fudan University Shanghai Cancer Center. Cell lines and xenograft mouse models are used to examine the impact of PCAT6 on tumor metastasis. Knockdown of PCAT6 is observed to impede the metastatic phenotype of CRC, as evidenced by functional assays, demonstrating the suppression of epithelial-mesenchymal transition (EMT) and stemness. Our findings show the significance of PCAT6 in mCRC and its potential use as a prognostic biomarker.
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Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Células Madre Neoplásicas , ARN Largo no Codificante , Animales , Femenino , Humanos , Masculino , Ratones , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Pronóstico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN no Traducido/genéticaRESUMEN
BACKGROUND:In the current quality control file or technical standards of the hemodialysis catheter,the indicators of the component contents and detection methods of the residual diphenylmethane diisocyanate (MDI) monomer are undefined.To ensure the safety and effectiveness of these products,we should try to establish and improve the quality standards.OBJECTIVE:To establish a method for determination of the residual MDI monomer in a hemodialysis catheter by gas chromatography (GC),and to analyze the bio-security of the MDI.METHODS:Samples collected in the hemodialysis catheter were heated to reflux with ethyl acetate and the residual MDI content was analyzed by the GC.The GC separation was performed on a DB-5 MS column (30 mx0.25 mm),the temperature of which rose by program.The initial temperature was 60 ℃,maintained for 5 minutes,rose to 280 ℃ with a rate of 15 ℃/min,and maintained for 6 minutes.The temperature of the Injector and FID detector was both 280 ℃.Carrier gas was 99.999% nitrogen.RESULTS AND CONCLUSION:The linearity was achieved in the range of 4.970-99.40 mg/L (r=0.999 64) for MDI.The mean recovery rate was 100.9% with the relative standard deviation of 3.2% (n=6).The residue of MDI monomer in the three batches of samples was lower than the tolerable exposure.Therefore,it is a sensitive,rapid,accurate,specific method that can be used for the quality control of the residual MDI monomer in the hemodialysis catheter.
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BACKGROUND: At present, in the quality control file or technical standards of in vitro fertilization medium, indicators for component contents and detection methods have not yet been defined. To ensure the safety and effectiveness of these products, we should try to establish and improve the quality standards. OBJECTIVE: To establish a method for simultaneously testing 18 kinds of amino acids by ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MSMS), and to analyze the difference in the content of different amino acids in the medium for different uses. METHODS: Using the UHPLC-MSMS, we detected the indicator components of 18 different amino acids in the in vitro fertilization medium. These amino acids included glycine, leucine, methionine, tyrosine, histidine, threonine, alanine, isoleucine, tryptophan, cystine, lysine, aspartic acid, valine, phenylalanine, valine, serine, glutamic acid, arginine. The UHPLC separation was performed on a SUPELCO Discovery HS F5-3 column (15 cm×2.1 mm, 3 μm) in a gradient elute mode with acetonitrile and water (both containing 0.1% formic acid) as the mobile phase at a flow rate of 0.35 mL/min. The column temperature was 40 ℃. MS detection was performed with multiple-reaction monitoring mode using negative electro spray ionization. RESULTS AND CONCLUSION: The linearity was achieved in the range of 0.25-12.5 mmol/L for the 18 different amino acids. The average recovery rate of these amino acids ranged 86.3% to 125.3%. The relative standard deviation of the precision experiment and the repeatability experiment was less than 4.7%. These findings indicate that this is a sensitive, rapid, accurate, and specific method that can be used for the quality control of in vitro fertilization medium.
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<p><b>OBJECTIVE</b>To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI).</p><p><b>METHODS</b>Twenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA).</p><p><b>RESULTS</b>Left ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01).</p><p><b>CONCLUSIONS</b>Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.</p>
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Animales , Masculino , Compuestos Alílicos , Farmacología , Usos Terapéuticos , Cardiotónicos , Farmacología , Usos Terapéuticos , Medios de Contraste , Modelos Animales de Enfermedad , Disulfuros , Farmacología , Usos Terapéuticos , Hemodinámica , Infarto del Miocardio , Diagnóstico por Imagen , Quimioterapia , Patología , Reperfusión Miocárdica , Fenómeno de no Reflujo , Diagnóstico por Imagen , Quimioterapia , Patología , Porcinos , Porcinos Enanos , Tiazoles , Metabolismo , UltrasonografíaRESUMEN
<p><b>OBJECTIVE</b>To investigate the relationship between blood pressure variability (BPV) and left ventricular diastolic function in patients with essential hypertension.</p><p><b>METHODS</b>Left ventricular diastolic function of 252 hypertensive patients were assessed by early (E) diastolic transmitral flows to early diastolic mitral annular velocity (Ea) (E/Ea) ratio derived from Doppler echocardiography. Patients were divided into two groups according to normal left ventricular diastolic function group (E/Ea<15, n = 168) and left ventricular diastolic dysfunction group (E/Ea ≥ 15, n = 84). All patients were monitored by ambulatory blood pressure. Standard deviation (SD) and coefficient of variation (CV) of blood pressure were calculated as the BPV. Relationship between BPV and left ventricular diastolic function were analyzed by multivariate logistic regression analysis.</p><p><b>RESULTS</b>All-day average diastolic blood pressure(DBP), the day systolic blood pressure (SBP), night SBP, night DBP, SBPSD, DBPSD and DBPCV in the left ventricular diastolic dysfunction group were significantly higher than in the normal diastolic function group (all P < 0.05). Multivariate logistic regression analysis showed that left ventricular diastolic dysfunction was associated with SBPSD (OR:1.126, 95%CI:1.054-1.203, P < 0.01), SBPCV (OR:1.127, 95%CI:1.036-1.225, P < 0.01) in this patient cohort.</p><p><b>CONCLUSION</b>High variability of SBP is correlated with left ventricular diastolic dysfunction in hypertensive patients.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Presión Sanguínea , Fisiología , Diástole , Fisiología , Hipertensión Esencial , Hipertensión , Modelos Logísticos , Función Ventricular Izquierda , FisiologíaRESUMEN
<p><b>BACKGROUND</b>Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes. How to stabilize vulnerable plaques is still a challenge to medical science. Alprostadil is a biologically active substance with strong activity on vessel. Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation (ALMP) on vulnerable plaques in the brachiocephalic artery of apolipoprotein E (Apo E) knockout mice.</p><p><b>METHODS</b>Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age. At week 17, they were divided randomly into groups for treatment with a high dose (3.6 µg×kg(-1)×d(-1)) or low dose (1.8 µg×kg(-1)×d(-1)) of an ALMP, or 0.2 ml/d normal saline (control group). The drug was administered using a micro-capsule pump. Twenty weeks after drug administration, pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed, and levels of anti-mouse monocyte/macrophage monoclonal antibody (MOMA-2) and superoxide anions in the plaques were detected using immunofluorescence. The soluble intercellular adhesion molecule-1 (ICAM-1) expression was measured by ELISA, and the expression of matrix metalloproteinase-9 (MMP-9) and CD40 mRNA was measured using RT-PCR. Thrombospindin-1 (TSP-1) expression was detected using Western blotting.</p><p><b>RESULTS</b>Compared with the control group, ALMP treatment significantly reduced the plaque area in the brachiocephalic artery (P < 0.01), significantly lowered the contents of the lipid core (P < 0.01), significantly reduced the number of ruptured fibrous caps (P < 0.05), and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage (P < 0.05). ALMP treatment significantly reduced the expression of MOMA-2, superoxide anion, MMP-9, ICAM-1 and CD40 in the plaques (P < 0.01), decreased plasma ICAM-1 expression (P < 0.01), and increased the expression of TSP-1.</p><p><b>CONCLUSIONS</b>Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.</p>
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Animales , Masculino , Ratones , Alprostadil , Química , Usos Terapéuticos , Ensayo de Inmunoadsorción Enzimática , Inflamación , Quimioterapia , Metabolismo , Patología , Molécula 1 de Adhesión Intercelular , Metabolismo , Liposomas , Química , Ratones Noqueados , Microscopía Fluorescente , Microesferas , Placa Aterosclerótica , Quimioterapia , Metabolismo , Patología , Reacción en Cadena de la PolimerasaRESUMEN
<p><b>OBJECTIVE</b>To compare the physicians' lipid lowering drug prescribing behavior and knowledge on dyslipidemia before and at 8 months after new-issued blood-lipid reports in our hospital.</p><p><b>METHOD</b>Blood-lipid reports in our hospital is newly modified in that the classification of dyslipidemia and lipid-lowering guideline and target lipid level are listed on the back of lipid report besides the normal lipid value listed immediately after the measured lipid levels. Physicians' lipid lowering drug prescribing behavior and knowledge on dyslipidemia before and at 8 months after new-issued blood-lipid reports were examined in 143 doctors from various departments before and at 8 months after new-issued lipid reports.</p><p><b>RESULTS</b>At 8 months after the new issued lipid reports, doctors' cognition rate about the guideline was significantly increased [83.9% (120/143) vs. 67.1% (96/143), P < 0.001] and the guideline was considered more helpful on daily practice [75.3% (58/77) vs. 55.8% (43/77), P = 0.005] compared to baseline. However, the prescription rate of dyslipidemia therapy did not change significantly (69.2% vs. 63.2%, P = 0.117) at 8 months after the new issued lipid reports.</p><p><b>CONCLUSIONS</b>The modification of the blood-lipid reports improved doctors' knowledge on dyslipidemia and on the "Chinese guidelines on prevention and treatment of dyslipidemia in adults". However, the lipid lowering drug prescribing behavior remained unchanged at 8 months after the modification of the lipid reports. Further investigation is warranted to see if the lipid lowering drug prescribing behavior could be changed in the long-term.</p>
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Humanos , Dislipidemias , Sangre , Quimioterapia , Adhesión a Directriz , Conocimientos, Actitudes y Práctica en Salud , Hipolipemiantes , Usos Terapéuticos , Lípidos , Sangre , Médicos , Pautas de la Práctica en Medicina , Prescripciones , Informe de InvestigaciónRESUMEN
<p><b>OBJECTIVE</b>To explore the elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation of the apolipoprotein (Apo E) deficient mice with or without experimental hypertension.</p><p><b>METHODS</b>Eighty male Apo E deficient mice were fed with high-fat diet beginning at six weeks of age. At 8-week old, they were randomly divided into hypertension group and control group (n=40 each), the mice in hypertension group were subjected the suprarenal aortic constriction operation and then randomly divided into two subgroups: 15 weeks age and 30 weeks age groups. At the end of experiment, the vascular elastic lamina degradation and the content of collagen were determined by morphological method, plasma ICAM-1 level was measured by ELISA, and the rennin activity measured by radioimmunoassay, the superoxide anion detected by fluorescence, the MOMA-2 observed by immunofluorescence in all animals. mRNA expression of NF-κB P65 and MMP9 was detected by real-time PCR.</p><p><b>RESULT</b>In 15-week old group, the elastic lamina degradation Grade II and the intima-media thickness in the hypertension group were significantly higher than in the control group [(5.4±3.3)% vs. (8.9±2.5)%, P<0.05; (98.66±18.90) µm vs. (70.08±11.71) µm, P<0.05]. In 30-week old group, the elastic lamina degradation Grade III, the III type of collagen and the intima-media thickness were also significantly higher than in the control group [(15.2±3.7)% vs. (8.1±3.3)%, P<0.01; (23.00±7.73)% vs. (11.00±3.82)%, P<0.05; (147.31±22.60) µm vs. (103.98±17.21) µm, P<0.01]. The level of ICAM-1 in hypertension group was significantly higher than that of control group in both 15-week old and in 30-week old mice [(46.3±3.7) µg/ml vs. (40.6±5.7) µg/ml, P<0.05; (56.0±3.1) µg/ml vs. (45.2±2.8) µg/ml, P<0.05]. The superoxide anion, the MOMA-2, mRNA expression of NF-κB P65 and MMP9 in the hypertension group were significantly higher than in the control group in both 15-week old and in the 30-week old mice. The increase in hypertension group was more pronounced in the 30-week old mice than in the 15-week old mice.</p><p><b>CONCLUSION</b>The elastic lamina degradation and the collagen remodeling of aortic artery as well as oxides stress and inflammation are more significant in the Apo E deficient mice with hypertension than in control Apo E deficient mice.</p>
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Animales , Masculino , Ratones , Aorta , Apolipoproteínas E , Genética , Colágeno , Metabolismo , Hipertensión , Metabolismo , Patología , Inflamación , Patología , Ratones Noqueados , Estrés OxidativoRESUMEN
BACKGROUND: Few studies investigated serum uric acid levels in patients with acute ST-elevation myocardial infarction (STEMI). The study was to assess the clinical value of serum uric acid levels in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: Totally 502 consecutive patients with STEMI were retrospectively studied from January 2005 to December 2010. The level of serum lipid, echocardiographic data and in-hospital major adverse cardiovascular events (MACE) in patients with hyperuricemia (n=119) were compared with those in patients without hyperuricemia (n=383). The relationship between the level of serum uric acid and the degree of diseased coronary artery was analyzed. All data were analyzed with SPSS version 17.0 software for Student's t test, the Chi-square test and Pearson's correlation coefficient analysis. RESULTS: Serum uric acid level was positively correlated with serum triglyceride level. Hyperlipidemia was more common in hyperuricemia patients than in non-hyperuricemia patients (43.7% vs. 33.7%, P=0.047), and serum triglyceride level was significantly higher in hyperuricemia patients (2.11±1.24 vs. 1.78±1.38, P=0.014). But no significant association was observed between serum uric acid level and one or more diseased vessels (P>0.05). Left ventricular end-diastolic diameter (LVEDd) was larger in hyperuricemia patients than in non-hyperuricemia patients (53.52±6.19 vs. 52.18±4.89, P=0.041). The higher rate of left systolic dysfunction and diastolic dysfunction was discovered in hyperuricemia patients (36.4% vs. 15.1%, P<0.001; 68.2% vs. 55.8%, P=0.023). Also, hyperuricemia patients were more likely to have in-hospital MACE (P<0.05). CONCLUSIONS: Serum uric acid level is positively correlated with serum triglyceride level, but not with the severity of coronary artery disease. Hyperuricemia patients with STEMI tend to have a higher rate of left systolic dysfunction and diastolic dysfunction and more likely to have more in-hospital MACE.
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Objective To investigate the clinical characteristics,the diagnosis and therapy of synchronous multiple primary esophageal carcinoma.Methods Thirty-two cases of synchronous multiple primary esophageal carcinoma were collected from January 1980 to December 2010 and their clinic data were retrospectively analysised.Results In the whole group,there were totally 66 lesions in 30 cases of double primary lesion and 2 cases of three primary lesion.The length of the lesions were 1 cm to 6.5 cm,and there were 22 lesions in cervical esophagus,10 in upper thoracic esophagus,19 in midthoracic esophagus and 15 in lower thoracic esophagus.Within the 66 lesions,65 lesions were squamous cell carcinoma and 1 was adenocarcinoma.The mucosa between the lesions were normal,with a distance of 4 cm to 9.5 cm,average 7.1 cm.Thirty-two patients with synchronous multiple primary esophageal carcinoma received surgery.Among 32 cases,26 of them were given definite diagnosis before operation.Four of them had exploratory operation,one patient underwent palliative resection,27 patients underwent radical resection.Two cases of the pathologic results of esophageal stump showed carcinoma after operation.The complications occurred in 8 patients.Twenty-eight cases were followed up after operation,the 1,3 and 5-survival rate were 76.9%,43.3 and 14.8%,respectively.Conclusion General pre-operation examination can significant helpful for the definite diagnosis of synchronous multiple primary esophageal carcinoma and surgical treatment is better choice for this disease.
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<p><b>BACKGROUND</b>It has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning.</p><p><b>METHODS</b>Sixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated.</p><p><b>RESULTS</b>ADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats.</p><p><b>CONCLUSIONS</b>Cardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.</p>
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Animales , Masculino , Ratas , Proteínas ADAM , Metabolismo , Proteína ADAMTS1 , Envejecimiento , Metabolismo , Fisiología , Inmunohistoquímica , Precondicionamiento Isquémico Miocárdico , Infarto del Miocardio , Metabolismo , Patología , Miocardio , Metabolismo , Patología , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of Qingre Quyu Granule (清热祛瘀颗粒, QRQYG) on stabilizing vulnerable plaques in apolipoprotein E (ApoE) deficient mice.</p><p><b>METHODS</b>Seventy-two male ApoE deficient mice were given a high-fat diet from 6 weeks of age. At the 16th week, all the mice were randomized into 3 groups: the QRQYG group, the simvastatin group, and the control group. Sixteen weeks after administration of 0.9 g/kg QRQYG, 3 mg/kg simvastatin or 10 mg/kg sodium chloride per day to the respective groups, the animals were euthanized. The pathological morphologic changes in the vulnerable plaques were evaluated, the matrix metalloprotease-9 (MMP-9) expression was measured by immunohistofluorescence, the soluble intercellular adhesion molecule 1 (ICAM-1) was determined by ELISA, the nuclear factor kappaB (NF-κB) subunit p65 was measured by quantitative RT-PCR, and, finally, thrombospondin-1 (TSP-1) was determined by the immunohistochemical method.</p><p><b>RESULTS</b>The plaque cross-sectional area in the brachiocephalic artery (23.7%, P<0.01), the lipid core of the plaque (43.1%±3.1%), and the number of buried fibrotic caps of the plaque were significantly decreased in the QRQYG group compared to the control group (both P<0.01); furthermore, the thickness of the fibrotic cap of the plaque increased and the intra-plaque hemorrhage of the plaque decreased. The serum soluble ICAM-1 (27.1±5.1 μg/mL), the protein expression of MMP-9 and TSP-1 and the p65 mRNA expression increased in the QRQYG group in comparison with the control group (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>QRQYG could stabilize the vulnerable plaque through inhibition of the inflammatory response.</p>
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Animales , Masculino , Ratones , Apolipoproteínas E , Genética , Aterosclerosis , Patología , Tronco Braquiocefálico , Metabolismo , Patología , Medicamentos Herbarios Chinos , Farmacología , Ensayo de Inmunoadsorción Enzimática , Molécula 1 de Adhesión Intercelular , Metabolismo , Metaloproteinasa 9 de la Matriz , Metabolismo , Ratones Noqueados , FN-kappa B , Metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Simvastatina , Farmacología , Cloruro de Sodio , Farmacología , Trombospondina 1 , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate whether adiponectin plays a role in the protection of myocardium in the rat myocardial ischemia preconditioning (IPC) model.</p><p><b>METHOD</b>Infarct size was measured by Masson's Trichrome staining, the expression of protein and mRNA of adiponectin at 0, 6, 12 and 24 h after IPC was examined by immunohistochemistry and quantitative real time RT-PCR, plasma levels of adiponectin at above mentioned four time points after IPC were detected by ELISA in IPC and MI rats.</p><p><b>RESULT</b>Infarct size was smaller in IPC than in MI rats (20% ± 2% vs. 31% ± 3%, P < 0.05). The expression of adiponectin mRNA at 6 h and 12 h after IPC was 2.2 and 2.1 times higher than in Sham rats at respective time points (P < 0.05). Immunohistochemistry staining evidenced increased adiponectin expression in the ischemic area and weak expression of adiponectin in non-ischemic area (P < 0.05). Compared to the sham group, the plasma level of adiponectin increased significantly at 0, 6 and 12 h after IPC (0 h: 7.40 ± 0.47 vs. 10.90 ± 1.74; 6 h: 8.18 ± 1.41 vs. 10.98 ± 1.74; 12 h: 6.97 ± 1.02 vs. 9.31 ± 0.96, P < 0.05).</p><p><b>CONCLUSION</b>IPC reduced infarction size, upregulated the myocardial expression of adiponectin at mRNA and protein levels, and increased plasma adiponectin concentration, suggesting that the adiponectin may play a critical role in the protective effect of IPC.</p>
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Animales , Masculino , Ratas , Adiponectina , Metabolismo , Precondicionamiento Isquémico Miocárdico , Infarto del Miocardio , Metabolismo , Isquemia Miocárdica , Metabolismo , Miocardio , Metabolismo , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>to observe the effect of ischemia preconditioning (IPC) on the expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and arteriogenesis.</p><p><b>METHODS</b>rat heart IPC model was made by 4 circles of occluding the LAD for 6 min followed by 6 min of reperfusion. The expression of VEGF, PDGF-B and ADAMTS-1 in the ischemic area was examined with immunohistochemistry at 6, 12 and 24 h after IPC. IPC plus myocardial infarction model was induced by LAD ligation 24 h after IPC, 14 days later, the anti-SM-α-actin antibody was used to detect the mature neovascularization in the border of the infracted area.</p><p><b>RESULTS</b>VEGF, PDGF-B and ADAMTS-1 were significantly upregulated in the ischemic area in IPC group compared with the control group (P < 0.05). Density of mature arteries was also significantly increased in IPC plus MI group than that in MI group (P < 0.05).</p><p><b>CONCLUSION</b>IPC promoted the formation of mature new arteries which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.</p>
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Animales , Masculino , Ratas , Proteínas ADAM , Metabolismo , Proteína ADAMTS1 , Arterias , Metabolismo , Patología , Precondicionamiento Isquémico , Neovascularización Fisiológica , Proteínas Proto-Oncogénicas c-sis , Metabolismo , Ratas Sprague-Dawley , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular , MetabolismoRESUMEN
Objective To determine whether the combination of traditional risk factors and quantitative coronary angiography (QCA) assessment could provide accurate prognostic information on a population-based study including 1137 adults with subclinical artherosclerosis and with coronary risk factors. Methods Participants underwent coronary angiography examination before the minimal stenotic diameters, segment diameters, percent stenosis, plaque areas. Other parameters were analyzed by the computer-assisted Coronary Angiography Analysis System. The Framingham Risk Score for each participant was assessed. During the 1 year follow-up period, all kinds of endpoint cardiovascular events were screened. Endpoint events were defined as death from coronary heart disease, nonfatal myocardial infarction (MI) or unstable angina pectoris. Results During the 1 year of follow-up period, a total of 124 participants developed an endpoint event, which was significantly associated with the Framingham Risk Score, calcium of plaques and the plaque areas (all Ps<0.05).The QCA score incorporated with the QCA parameters was related to the endpoint events. The Framingham Risk Score was combined with QCA score through logistic regression for prediction of end-point events. Data from the ROC analysis showed the accuracy of this prediction algorithm was superior to the accuracy when variables themselves were used. The event-free survival rate was inferior to the control group in participates under high risk, when being screened with this prediction algorithm (P<0.05). Conclusion The risk of cardiovascular attack in subclinical artherosclerosis individual seemed to be associated with the Framingham Risk Score, calcium of plaques and the plaque areas. When the traditional risk factors (the Framingham Risk Score) were combined with QCA, the new method could provide more prognostic information on those adults with subclinical artherosclerosis.
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<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of a once daily valsartan/amlodipine 80/5 mg combination tablet in Chinese mild to moderate hypertensive patients without adequate blood pressure control by monotherapy.</p><p><b>METHODS</b>Two multicenter, randomized, double-blind, double dummy, active-controlled, parallel group trials were conducted. After a washout period (no medication) of 1-4 weeks, patients with Mean Sitting Diastolic Blood Pressure (MSDBP) > or = 95 mm Hg (1 mm Hg = 0.133 kPa) and < 110 mm Hg received a monotherapy of either Amlodipine 5 mg (in study 1) or valsartan 80 mg (in study 2) for 4 weeks. Patients with MSDBP > or = 90 mm Hg and < 110 mm Hg at the end of the monotherapy period were randomized to receive valsartan/amlodipine 80/5 mg treatment, or continue with the monotherapy.</p><p><b>RESULTS</b>In study 1, compared with amlodipine 5 mg, valsartan/amlodipine 80/5 mg once daily further reduced mean sitting systolic blood pressure (MSSBP)/MSDBP 4.4/3 mm Hg (P < 0.0001). In study 2, compared with valsartan 80 mg, valsartan/amlodipine 80/5 mg once daily further reduced MSSBP/MSDBP 6.4/4.2 mm Hg (P < 0.0001). The blood pressure (BP) control rates (BP < 140/90 mm Hg) of combination treatment group were 71.0% and 71.2% respectively, and significantly higher than the monotherapy groups in both trials. Incidence of adverse events was comparable in monotherapy and combination therapy groups.</p><p><b>CONCLUSION</b>Our results showed that valsartan/amlodipine 80/5 mg was superior to amlodipine 5 mg or valsartan 80 mg alone in lowering blood pressure and BP control in patients with mild to moderate hypertension not adequately controlled with amlodipine 5 mg or valsartan 80 mg monotherapy. No new or unexpected safety issues were identified with valsartan/amlodipine combination therapy compared with monotherapy.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Amlodipino , Antihipertensivos , Presión Sanguínea , Método Doble Ciego , Quimioterapia Combinada , Hipertensión , Quimioterapia , Tetrazoles , Valina , ValsartánRESUMEN
<p><b>OBJECTIVE</b>To assess left ventricular (LV) geometry, LV diastolic and systolic function in maintenance hemodialysis uremic patients.</p><p><b>METHODS</b>Forty uremic patients and forty-five normal subjects were included in this study. LV volume, LV mass index (LVMI), relative wall thickness (RWT), LV mass and diastolic volume ratio (LVM/EDV) were measured. Mitral flow E velocity and A velocity ratio, deceleration time, mitral flow E velocity and mitral annulus Ea velocity ratio (E/Ea), pulmonary vein flow S velocity and D velocity ratio, atrial flow reversal velocity of pulmonary vein flow, mitral inflow propagation velocity, left atrium volume (LAV) and pulmonary artery systolic pressure (PASP) were determined for diastolic function evaluation. LV ejection fraction (LVEF) and single volume (SV) were derived from 3D echocardiography, systolic velocity of mitral valve annulus (Sa) by pulse tissue Doppler imaging (TDI) were used to evaluate systolic function. The time to peak systolic velocity (Ts) and early diastole velocity (Td) of LV 12 segments were measured using TDI. The maximal difference of Ts and Td (Ts-Dif and Td-Dif) were calculated to assess LV systolic and diastolic asynchrony.</p><p><b>RESULTS</b>RWT, LVMI and LVM/EDV were significantly increased in uremic patients. There were 50% concentric, 17.5% eccentric hypertrophy and 17.5%concentric remodeling, respectively in uremic patients. The indices for LV diastolic function (E/Ea, LAV and PASP) were significantly higher in uremic patients than those in control subjects (P < 0.01). About 85% of the diastolic dysfunction in uremic patients presented as impaired relaxation pattern and 32.5% as increased filling pressure. LVEF and SV were similar between uremic patients and control subjects. Sa was significantly lower in uremic group than that in controls (P < 0.05). Ts-Dif was similar between the 2 groups while Td-Dif was significantly higher in uremic patients than control subjects (P < 0.05).</p><p><b>CONCLUSION</b>LV hypertrophy, LV mass increase and LV diastolic dysfunction were the major characteristic of myocardial injury in uremia patients.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Ecocardiografía , Diálisis Renal , Uremia , Diagnóstico por Imagen , Terapéutica , Remodelación VentricularRESUMEN
<p><b>OBJECTIVE</b>To compare the effects of perindopril and enalapril on the development of atherosclerotic lesions in ApoE knockout mice.</p><p><b>METHODS</b>ApoE knockout mice were treated with perindoprilor (1.5 mg.kg(-1).d(-1), n = 20), enalapril (7.5 mg.kg(-1).d(-1), n = 20) or saline (0.2 ml saline/d, n = 20) per gavage for 20 weeks. Blood pressure and lipids were measured at the study end. Aortic root atherosclerotic plaque was then quantified and the content of collagen and the size of lipid core in the plaque assessed. Cryostat sections were used to quantify the expressions of monocyte/macrophage-2 (MOMA-2), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and matrix metalloproteinases-9 (MMP-9) in the plaque by immunofluorescence method.</p><p><b>RESULTS</b>Blood pressure and lipid profiles were similar among different groups. Compared with control group, the plaque areas of perindopril group and enalapril group displayed significantly decrease (25.33% and 22.86%, respectively, both P < 0.01). However, no significant different were observed in the plaque size between the different ACE inhibitors groups. Perindopril group and enalapril group also significantly decreased the size of lipid core (52.98% and 38.98%, respectively, both P < 0.01) and the expression of MOMA-2 (88.38% and 52.16%, respectively, both P < 0.01), ICAM-1 (80.87% and 49.59%, respectively, both P < 0.01), VCAM-1 (77.56% and 56.44%, respectively, both P < 0.01) and MMP-9 (86.93% and 55.56%, respectively, both P < 0.01), and increased the plaque collagen content (298.36% and 168.14%, respectively, both P < 0.01) and the effects of perindopril was superior to those of enalapril (all P < 0.05).</p><p><b>CONCLUSIONS</b>ACE inhibitors significantly suppressed tissue inflammation and attenuated the development of atherosclerosis in ApoE knockout mice independent of their effects on the lipid and blood pressure. Perindopril is superior to enalapril in stabilizing the plaques and has similar effect on reducing the plaque size as that of enalapril.</p>