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1.
JACC Asia ; 3(4): 678-682, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37614543

RESUMO

Side branch (SB) occlusion remains challenging in bifurcation percutaneous coronary intervention. We have introduced a novel method to protect SB named double kissing inflation outside the stent (DKo), which features twice inflation of protective balloon kissing with stent and postdilation balloon. This study compared protective effects of DKo vs jailed balloon technique (JBT) for bifurcation. This retrospective, single-center study enrolled 875 consecutive bifurcation lesions receiving either DKo (n = 209) or JBT (n = 666). At the 12-month follow-up, major adverse cardiac event occurred less in DKo (6.7% vs 12.0%; P = 0.042), even in 1:2 propensity score matching analysis (6.4% vs 12.3%; P = 0.034). Rewiring and transient SB loss occurred also less in DKo (0.5% vs 13.8% [P < 0.001]; 0.5% vs 4.8% [P = 0.003]). Similar results were observed in matching analysis. This study demonstrated DKo protected SB better than JBT in bifurcation percutaneous coronary intervention.

2.
Spat Spatiotemporal Epidemiol ; 45: 100569, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37301590

RESUMO

Cardiovascular disease (CVD) is the leading cause of death globally, coronary heart disease (CHD) is the main category of it. It has been shown that the urban built environment affects the occurrence of CHD, but most focus on single environmental factors. This study developed two multicomponent Urban Heart Health Environment (UHHE) Indexes (unweighted index and weighted index), which were based on the four main behavioral risk factors for CHD (unhealthy diet, lack of physical activity, smoking, and drinking). And we examined the relationship between the indexes and the prevalence of CHD. The prevalence calculation is based on the database of F Hospital patients, who have had coronary stent implantation (CSI). Furthermore, these single-center data were corrected to reduce underestimation of prevalence. We performed global (Ordinal Least Square) and local (Geographically Weighed Regression) regression analyses to assess the relationship between the two UHHE indexes and CHD prevalence. Both indexes showed a significant negative relationship with CHD prevalence. In its spatial relationship, a non-stationary was discovered. The UHHE indexes may help identify and prioritize geographical areas for CHD prevention and may be beneficial to urban design in China.


Assuntos
Doenças Cardiovasculares , Doença das Coronárias , Humanos , Prevalência , Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Exercício Físico
3.
Eur J Pharmacol ; 945: 175621, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36849103

RESUMO

Autophagy is critically involved in myocardial ischemia-reperfusion (I/R). Autophagy inhibition exacerbates myocardial I/R injury. Few effective agents target autophagy to prevent myocardial I/R injury. Effective drugs that promote autophagy in myocardial I/R warrant further investigation. Galangin (Gal) enhances autophagy and alleviates I/R injury. Here we conducted both in vivo and in vitro experiments to observe the changes in autophagy after galangin treatment and investigated the cardioprotective effects of galangin on myocardial I/R. METHODS: After 45-min occlusion of the left anterior descending coronary artery, myocardial I/R was induced by slipknot release. One day before surgery and immediately after surgery, the mice were injected intraperitoneally with the same volume of saline or Gal. The effects of Gal were evaluated using echocardiography, 2,3,5-triphenyltetrazolium chloride staining (TTC staining), western blotting, and transmission electron microscopy. Primary cardiomyocytes and bone marrow-derived macrophages were extracted in vitro to measure the cardioprotective effects of Gal. RESULTS: Compared with the saline-treated group, Gal significantly improved cardiac function and limited infarct enlargement after myocardial I/R. In vivo and in vitro studies demonstrated that Gal treatment promoted autophagy during myocardial I/R. The anti-inflammatory effects of Gal were validated in bone marrow-derived macrophages. These results strongly suggest that Gal treatment can attenuate myocardial I/R injury. CONCLUSION: Our data demonstrated that Gal could improve left ventricular ejection fraction and reduce infarct size after myocardial I/R by promoting autophagy and inhibiting inflammation.


Assuntos
Traumatismo por Reperfusão Miocárdica , Camundongos , Animais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Volume Sistólico , Função Ventricular Esquerda , Miócitos Cardíacos , Autofagia , Infarto
4.
Scand Cardiovasc J ; 57(1): 2161620, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36573618

RESUMO

Background. Provisional side branch (SB) stenting strategy is the default approach for the majority of bifurcation lesions, but outcomes of SB is suboptimal. Though drug coated balloon (DCB) improving SB outcomes attracts an increasing attention, sequence of DCB hasn't yet been determined. We presented a novel hybrid strategy of DCB and stent for bifurcation lesions. Methods. With lesion preparation, DCB was persistently inflated in SB kissing with main branch (MB) stent deployment and balloon post-dilation of the bifurcation core. Proximal optimization technique was performed strictly not exceeding the bifurcation. Procedural and clinical adverse events were evaluated. Canadian Cardiovascular Society (CCS) angina classification was assessed at baseline and clinical follow-up. Results. Fourteen patients undergoing the hybrid technique from August 2020 to July 2021 were enrolled. The technique was successfully performed in all patients without rewiring or SB compromise. Minimal lumen diameter of SB increased from 0.60 ± 0.40 mm to 2.1 ± 0.2 mm while the percent stenosis decreased from 72.4 ± 17.9% to 19.6 ± 4.7%. In addition, intravascular ultrasound indicated comparable stent symmetry index and incomplete stent apposition between proximal and distal segments of stent. No further intervention was performed, and mean fractional flow reserve of SB (n = 12) was 0.88 ± 0.05. No major adverse cardiac events was noted in hospital and 12-month follow up. The mean CCS angina score was reduced by 84% (2.2 vs 0.4, p < .001). Conclusion. The hybrid strategy facilitates treatment of DCB and stent for bifurcation lesions, which appears to be feasible and acceptable in a short-term follow-up.


Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana , Stents Farmacológicos , Reserva Fracionada de Fluxo Miocárdico , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/métodos , Angiografia Coronária/métodos , Resultado do Tratamento , Fatores de Tempo , Canadá , Stents , Angina Pectoris
5.
J Clin Med ; 11(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36555907

RESUMO

BACKGROUND: Rapid reperfusion of ST-segment elevation myocardial infarction (STEMI) has been challenging during the coronavirus disease 2019 (COVID-19) outbreak. Whether and to what degree there will be a residual impact when the COVID-19 pandemic has passed is unclear. METHODS: This nationwide retrospective study was based on electronic records of STEMI patients registered in the Chinese Cardiovascular Association Database. RESULTS: We analyzed 141,375 STEMI patients (including 4871 patients in Hubei province, where 80% of COVID-19 cases in China occurred in 2019-2020) during the pre-outbreak (23 October 2019-22 January 2020), outbreak (23 January 2020-22 April 2020), and post-outbreak (23 April 2020-22 July 2020) periods. In the post-outbreak period in Hubei province, the increased in-hospital mortality dropped to become insignificant (adjusted odds ratio compared to the pre-outbreak level (aOR) 1.40, [95% confidential interval (CI): 0.97-2.03]) and was lower than that in the outbreak period (1.62 [1.09-2.41]). The decreased odds of primary percutaneous coronary intervention (PCI) (0.73 [0.55-0.96]) and timely reperfusion (0.74 [0.62-0.88]) persisted, although they were substantially improved compared to the outbreak period (aOR of primary PCI: 0.23 [0.18-0.30] and timely reperfusion: 0.43 [0.35-0.53]). The residual impact of COVID-19 on STEMI in the post-outbreak period in non-Hubei provinces was insignificant. CONCLUSIONS: Residual pandemic impacts on STEMI management persisted after the first wave of the COVID-19 outbreak in Hubei province, the earliest and hardest hit area in China.

6.
Front Cardiovasc Med ; 9: 730648, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295252

RESUMO

Background: Current guidewires for transradial coronary angiography had defects of passage difficulty or branch injury. This study sought to investigate the safety and efficiency of a novel method of active knuckle-angle 0.035-inch hydrophilic guidewire in transradial coronary angiography. Methods: Patients undergoing a transradial coronary procedure in our team from August 2015 to June 2020 were retrospectively investigated. We compared the demographic and interventional characteristics of 1,457 patients receiving advancement of unmodified guidewires (Traditional group) and 1,322 patients receiving advancement of the knuckle guidewire (Knuckle group). Afterwards we included 239 patients and randomized them according to a random number table to either the unmodified or the knuckle guidewire to further confirm the efficiency and safety of knuckle guidewire advancement. Results: In the retrospective analysis, unwilling passage of guidewire into branches occurred more in the Traditional group than in the Knuckle group (9.5 vs. 0.08%, p < 0.001). Two patients in the Traditional group experienced guidewire-associated perforation. One patient was treated with covered stent for internal mammarian artery perforation, while the other was managed with compression for brachial branch perforation. In the randomized controlled study, unwilling passage of guidewire also occurred more in the Traditional group (10.8 vs. 1%, p < 0.001). Median duration of guidewire advancement from the sheath to aortic root significantly decreased from 33 seconds in the Traditional group to 21 seconds in the Knuckle group. Conclusion: Active knuckle angle guidewire represented a novel method to prevent unwilling passage and associated perforation with efficiency improvement and a reduction in radiation exposure.

7.
J Thorac Dis ; 13(8): 4723-4730, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34527313

RESUMO

BACKGROUND: Novel coronavirus disease (COVID-19) has spread globally and caused over 3 million deaths, posing great challenge on public health and medical systems. Limited data are available predictive factors for disease progression. We aim to assess clinical and radiological predictors for pulmonary aggravation in severe and critically ill COVID-19 patients. METHODS: Patients with confirmed COVID-19 in Renmin Hospital of Wuhan University, China, between Feb. 6th, 2020 and Feb. 21st, 2020 were retrospectively collected. Enrolled patients were divided into non-progression group and progression group based on initial and follow-up chest CTs. Clinical, laboratory, and radiological variables were analyzed. RESULTS: During the study period, 162 patients were identified and a total of 126 patients, including 97 (77.0%) severe cases and 29 (23.0%) critically ill cases were included in the final analysis. Median age was 66.0 (IQR, 56.0-71.3) years. Median time from onset to initial chest CT was 15.0 (IQR, 12.0-20.0) days and median interval to follow-up was 7.0 (IQR, 5.0-7.0) days. Compared with those who did not progress (n=111, 88.1%), patients in the progression group (n=15, 11.9%) had significantly higher percentage of peak body temperature >38 °C (P=0.002), lower platelet count (P=0.011), lower CD4 T cell count (P=0.002), lower CD8 count (P=0.011), higher creatine kinase level (P=0.002), and lower glomerular filtration rate (P=0.018). On both univariate and multivariable analysis, only CD4 T cell count <200/µL was significant (OR, 6.804; 95% CI, 1.450-31.934; P=0.015) for predicting pulmonary progression. CONCLUSIONS: Low CD4 T cell count predicts progression of pulmonary change in severe and critically ill patients with COVID-19.

8.
BMC Cardiovasc Disord ; 21(1): 232, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962571

RESUMO

BACKGROUND: The jailed balloon technique is widely used for coronary bifurcation lesions, but a residual risk of SB occlusion remains, necessitating SB rewiring and further interventions, including balloon inflation or stenting, which may result in failure and SB loss. This study introduced a novel modified technique of small side branch (SB) protection, namely, double kissing inflation outside the stent (DKo) technique, for coronary bifurcations without the need for SB rewiring. METHODS: We performed the DKo technique in consecutive patients in our center from 1/2019 to 12/2019. The procedure was as follows. We inserted a guide wire into both branches followed by proper preparation. The SB balloon was simultaneously inflated with main vessel (MV) stenting. The SB balloon remained in situ until it was kissing inflated with postdilation of the bifurcation core, which is different from traditional strategies. The proximal optimization technique was performed with a short noncompliant balloon strictly not exceeding the bifurcation. Rates of SB loss and in-hospital outcomes were evaluated. RESULTS: The technique was successfully performed in all 117 enrolled patients without any rewiring or SB loss. The mean lesion lengths of the MV and SB were 38.3 ± 19.9 mm and 11.7 ± 7.1 mm, respectively. On average, 1.5 ± 0.6 stents were used per patient, while the mean pressure of the SB balloon was 7.4 ± 3.1 atm. DKo achieved excellent procedural success in the proximal and distal MVs: increased minimal lumen diameter (0.64 ± 0.58 mm to 3.05 ± 0.38 mm, p < 0.001; 0.57 ± 0.63 mm to 2.67 ± 0.35 mm, p < 0.001) and low residual stenosis (11.4 ± 3.4%; 7.2 ± 4.6%). DKo secured the patency of the SB without any rewiring and improved the SB stenosis with minimal lumen diameter (0.59 ± 0.48 mm to 1.20 ± 0.42 mm, p < 0.001) and stenosis (71.9 ± 19.4% to 42.2 ± 14.0%, p < 0.001). No MACE was noted in the hospital. CONCLUSIONS: DKo for bifurcation lesions was shown to be acceptable with high procedural success and excellent SB protection.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Doença da Artéria Coronariana/terapia , Stents , Grau de Desobstrução Vascular , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
12.
Theranostics ; 10(21): 9663-9673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863952

RESUMO

Introduction: To explore the involvement of the cardiovascular system in coronavirus disease 2019 (COVID-19), we investigated whether myocardial injury occurred in COVID-19 patients and assessed the performance of serum high-sensitivity cardiac Troponin I (hs-cTnI) levels in predicting disease severity and 30-day in-hospital fatality. Methods: We included 244 COVID-19 patients, who were admitted to Renmin Hospital of Wuhan University with no preexisting cardiovascular disease or renal dysfunction. We analyzed the data including patients' clinical characteristics, cardiac biomarkers, severity of medical conditions, and 30-day in-hospital fatality. We performed multivariable Cox regressions and the receiver operating characteristic analysis to assess the association of cardiac biomarkers on admission with disease severity and prognosis. Results: In this retrospective observational study, 11% of COVID-19 patients had increased hs-cTnI levels (>40 ng/L) on admission. Of note, serum hs-cTnI levels were positively associated with the severity of medical conditions (median [interquartile range (IQR)]: 6.00 [6.00-6.00] ng/L in 91 patients with moderate conditions, 6.00 [6.00-18.00] ng/L in 107 patients with severe conditions, and 11.00 [6.00-56.75] ng/L in 46 patients with critical conditions, P for trend=0.001). Moreover, compared with those with normal cTnI levels, patients with increased hs-cTnI levels had higher in-hospital fatality (adjusted hazard ratio [95% CI]: 4.79 [1.46-15.69]). The receiver-operating characteristic curve analysis suggested that the inclusion of hs-cTnI levels into a panel of empirical prognostic factors substantially improved the prediction performance for severe or critical conditions (area under the curve (AUC): 0.71 (95% CI: 0.65-0.78) vs. 0.65 (0.58-0.72), P=0.01), as well as for 30-day fatality (AUC: 0.91 (0.85-0.96) vs. 0.77 (0.62-0.91), P=0.04). A cutoff value of 20 ng/L of hs-cTnI level led to the best prediction to 30-day fatality. Conclusions: In COVID-19 patients with no preexisting cardiovascular disease, 11% had increased hs-cTnI levels. Besides empirical prognostic factors, serum hs-cTnI levels upon admission provided independent prediction to both the severity of the medical condition and 30-day in-hospital fatality. These findings may shed important light on the clinical management of COVID-19.


Assuntos
Cardiomiopatias/etiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Troponina I/sangue , Idoso , COVID-19 , Cardiomiopatias/sangue , China , Estudos de Coortes , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
13.
J Intensive Care ; 8: 49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32665858

RESUMO

BACKGROUND: Over 5,488,000 cases of coronavirus disease-19 (COVID-19) have been reported since December 2019. We aim to explore risk factors associated with mortality in COVID-19 patients and assess the use of D-dimer as a biomarker for disease severity and clinical outcome. METHODS: We retrospectively analyzed the clinical, laboratory, and radiological characteristics of 248 consecutive cases of COVID-19 in Renmin Hospital of Wuhan University, Wuhan, China from January 28 to March 08, 2020. Univariable and multivariable logistic regression methods were used to explore risk factors associated with in-hospital mortality. Correlations of D-dimer upon admission with disease severity and in-hospital mortality were analyzed. Receiver operating characteristic curve was used to determine the optimal cutoff level for D-dimer that discriminated those survivors versus non-survivors during hospitalization. RESULTS: Multivariable regression that showed D-dimer > 2.0 mg/L at admission was the only variable associated with increased odds of mortality [OR 10.17 (95% CI 1.10-94.38), P = 0.041]. D-dimer elevation (≥ 0.50 mg/L) was seen in 74.6% (185/248) of the patients. Pulmonary embolism and deep vein thrombosis were ruled out in patients with high probability of thrombosis. D-dimer levels significantly increased with increasing severity of COVID-19 as determined by clinical staging (Kendall's tau-b = 0.374, P = 0.000) and chest CT staging (Kendall's tau-b = 0.378, P = 0.000). In-hospital mortality rate was 6.9%. Median D-dimer level in non-survivors (n = 17) was significantly higher than in survivors (n = 231) [6.21 (3.79-16.01) mg/L versus 1.02 (0.47-2.66) mg/L, P = 0.000]. D-dimer level of > 2.14 mg/L predicted in-hospital mortality with a sensitivity of 88.2% and specificity of 71.3% (AUC 0.85; 95% CI = 0.77-0.92). CONCLUSIONS: D-dimer is commonly elevated in patients with COVID-19. D-dimer levels correlate with disease severity and are a reliable prognostic marker for in-hospital mortality in patients admitted for COVID-19.

14.
Ann Transl Med ; 8(7): 430, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32395474

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (designated as SARS-CoV-2) has become a pandemic worldwide. Based on the current reports, hypertension may be associated with increased risk of sever condition in hospitalized COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) was recently identified to functional receptor of SARS-CoV-2. Previous experimental data revealed ACE2 level was increased following treatment with ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Currently doctors concern whether these commonly used renin-angiotensin system (RAS) blockers-ACEIs/ARBs may increase the severity of COVID-19. METHODS: We extracted data regarding 50 hospitalized hypertension patients with laboratory confirmed COVID-19 in the Renmin Hospital of Wuhan University from Feb 7 to Mar 03, 2020. These patients were grouped into RAS blockers group (Group A, n=20) and non-RAS blockers group (Group B, n=30) according to the basic blood pressure medications. All patients continued to use pre-admission antihypertensive drugs. Clinical severity (symptoms, laboratory and chest CT findings, etc.), clinical course, and short time outcome were analyzed after hospital admission. RESULTS: Ten (50%) and seventeen (56.7%) of the Group A and Group B participants were males (P=0.643), and the average age was 52.65±13.12 and 67.77±12.84 years (P=0.000), respectively. The blood pressure of both groups was under effective control. There was no significant difference in clinical severity, clinical course and in-hospital mortality between Group A and Group B. Serum cardiac troponin I (cTnI) (P=0.03), and N-terminal (NT)-pro hormone BNP (NT-proBNP) (P=0.04) showed significant lower level in Group A than in Group B. But the patients with more than 0.04ng/mL or elevated NT-proBNP level had no statistical significance between the two groups. In patients over 65 years or under 65 years, cTnI or NT-proBNP level showed no difference between the two groups. CONCLUSIONS: We observed there was no obvious difference in clinical characteristics between RAS blockers and non-RAS blockers groups. These data suggest ACEIs/ARBs may have few effects on increasing the clinical severe conditions of COVID-19.

16.
Int J Nanomedicine ; 15: 901-912, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103945

RESUMO

BACKGROUND: Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesive mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE-/-) mice based on their multiple sites binding capacity under high shear stress. METHODS: Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo. RESULTS: PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE-/- mice, PNPs exhibited good targeting to sclerotic aortic valves by mimicking platelet multiple adhesive mechanisms. CONCLUSION: PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease.


Assuntos
Plaquetas/citologia , Doenças das Valvas Cardíacas/tratamento farmacológico , Nanopartículas/química , Nanopartículas/metabolismo , Animais , Valva Aórtica/efeitos dos fármacos , Valva Aórtica/patologia , Apolipoproteínas E/genética , Doença da Válvula Aórtica Bicúspide , Plaquetas/química , Membrana Celular/química , Colágeno/metabolismo , Modelos Animais de Doenças , Fibrina/metabolismo , Cardiopatias Congênitas , Doenças das Valvas Cardíacas/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Nanopartículas/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Esclerose , Estresse Mecânico , Fator de von Willebrand/metabolismo
17.
Nanomedicine ; 15(1): 13-24, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30171903

RESUMO

Although certain success has been achieved in atherosclerosis treatment, tremendous challenges remain in developing more efficient strategies to treat atherosclerosis. Platelets have inherent affinity to plaques and naturally home to atherosclerotic sites. Rapamycin features potent anti-atherosclerosis effect, but its clinical utility is limited by its low concentration at the atherosclerotic site and severe systemic toxicity. In the present study, we used platelet membrane-coated nanoparticles (PNP) as a targeted drug delivery platform to treat atherosclerosis through mimicking platelets' inherent targeting to plaques. PNP displayed 4.98-fold greater radiant efficiency than control nanoparticles in atherosclerotic arterial trees, indicating its effective homing to atherosclerotic plaques in vivo. In an atherosclerosis model established in apolipoprotein E-deficient mice, PNP encapsulating rapamycin significantly attenuated the progression of atherosclerosis and stabilized atherosclerotic plaques. These results demonstrated the perfect efficacy and pro-resolving potential of PNP as a targeted drug delivery platform for atherosclerosis treatment.


Assuntos
Aterosclerose/tratamento farmacológico , Plaquetas/fisiologia , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Placa Aterosclerótica/tratamento farmacológico , Sirolimo/farmacologia , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/fisiologia , Aterosclerose/genética , Aterosclerose/patologia , Membrana Celular/química , Membrana Celular/metabolismo , Células Cultivadas , Imunossupressores/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanopartículas/química , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , Adesividade Plaquetária
18.
Oncol Lett ; 15(3): 3178-3184, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29435054

RESUMO

Dihydroartemisinin (DHA) is a derivative of artemisinin. The present study aimed to investigate whether DHA induces apoptosis in the THP-1 human acute monocytic leukemia cell line (AMoL), and to identify the relative molecular mechanisms. The results of the present study demonstrated that the viability of THP-1 cells were inhibited by DHA in a dose- and time-dependent manner, which was accompanied by morphological characteristics associated with apoptosis. After 24 h of 200 µM DHA treatment, the proportion of apoptotic cells was significantly increased compared with the untreated controls (P<0.01). In addition, DHA downregulated the levels of B-cell lymphoma (Bcl)-2, protein kinase B (Akt)1, Akt2 and Akt3 gene expression, and increased the expression of the Bcl-2-associated X protein apoptosis regulator. The protein expression of phospho-Akt and phospho-extracellular signal-regulated kinase (ERK) was also decreased, and the protein expression level of cleaved caspase-3 was increased following treatment with DHA. Therefore, DHA may induce apoptosis in the AMoL THP-1 cell line via currently unknown underlying molecular mechanisms, including the downregulation of ERK and Akt, and the activation of caspase-3.

19.
Pak J Pharm Sci ; 30(5): 1697-1707, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29084692

RESUMO

The purpose of this paper was to explore a new method for screening lipid-lowering drugs in zebrafish models. The suitable drug concentrations of atorvastatin (ATV), fenofibrate (FEF) and ezetimibe (EZE) were first determined. Then, the serum cholesterol and triglyceride levels were detected in high-fat diet (HFD)-fed zebrafish. The HFD zebrafish models were constructed and the effects of drugs on them were observed by Oil red O staining and fluorescence labeling. Statistical analyses among groups were conducted using SPSS software. The lowest drug concentration (LDC) and the highest (HDC) of ATV, FEF and EZE were 0.3 µM/37.0µM, 1.2µM/3.5µM, and 6.3 µM/26.4µM, respectively, while, the intermediate (IDC) was, in order, 18.5µM, 1.8µM, 13.2µM. The cholesterol and triglyceride levels in HFD-fed zebrafish were increased after 7 weeks fat feeding (p<0.05). Moreover, the levels of triglyceride were significantly decreased after LDC of ATV and FEF treated (p<0.05), but not that of EZE. While, the cholesterol levels were reduced in three groups (p<0.05). Moreover, the 5 dpf high-fat zebrafish model was established successfully and maintained stably for 24h. ATV produced effects in a concentration-dependent manner, while only IDC and HDC of FEF and EZE made effects on this model. Intravascular cholesterol levels were significantly increased after HCD treatment and decreased after drug treated. The high-fat zebrafish model induced by HFD-fed was available and successful, besides, the Oil red O staining may be an available and rapid method for screening lipid-lowering drugs.


Assuntos
Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Peixe-Zebra/sangue , Animais , Atorvastatina/farmacologia , Biomarcadores/sangue , Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Ezetimiba/farmacologia , Fenofibrato/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Masculino , Triglicerídeos/sangue
20.
Mol Med Rep ; 15(6): 3840-3846, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28393190

RESUMO

Galectin­3, a galactoside­binding protein, is highly expressed in carotid plaques and plays an important role in the atherosclerotic lesions. The phenotype transformation of vascular smooth muscle cells is the basic pathological change of atherosclerosis. This study investigated the effects of exogenous galectin­3 on the function and phenotype transformation of human umbilical vascular smooth muscle cells (HUSMC). In this study, we treated vascular smooth muscle cells with recombinant galectin­3 and tested its effect on cell proliferation, migration, and phenotype transformation. Our results showed that exogenous galectin­3 promoted human umbilical vascular smooth muscle cells (HUSMC) proliferation and migration. Exogenous galectin­3 enhanced the expression of the smooth muscle synthetic protein osteopontin, smooth muscle contractile proteins calponin and smooth muscle α­actin. The galectin­3­induced change in cell phenotype was associated with the activation of canonical Wnt signaling, as measured by ß­catenin axin2 and cyclin D1 expression. ß­catenin inhibition by small interfering RNA reduced cell proliferation, decreased cell motility, and blocked galectin­3­induced phenotype transformation of human umbilical vascular smooth muscle cells (HUSMC). Our data suggest galectin­3 promotes the phenotype transformation of human umbilical vascular smooth muscle cells (HUSMC) by activating Wnt/ß­catenin signaling pathway.


Assuntos
Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Galectina 3/farmacologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fenótipo , Via de Sinalização Wnt/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia
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