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Atherosclerosis is a chronic inflammatory disease characterized with innate and adaptive immunity but also involves pyroptosis. Few studies have explored the role of pyroptosis in advanced atherosclerotic plaques from different vascular beds. Here we try to identify the different underlying function of pyroptosis in the progression of atherosclerosis between carotid arteries and femoral. arteries. We extracted gene expression levels from 55 advanced carotid or femoral atherosclerotic plaques. The pyroptosis score of each sample was calculated by single-sample-gene-set enrichment analysis (ssGSEA). We then divided the samples into two clusters: high pyroptosis scores cluster (PyroptosisScoreH cluster) and low pyroptosis scores cluster (PyroptosisScoreL cluster), and assessed functional enrichment and immune cell infiltration in the two clusters. Key pyroptosis related genes were identified by the intersection between results of Cytoscape and LASSO (Least Absolute Shrinkage and Selection Operator) regression analysis. Finally, all key pyroptosis related genes were validated in vitro. We found all but one of the 29 carotid plaque samples belonged to the PyroptosisScoreH cluster and the majority (19 out of 26) of femoral plaques were part of the PyroptosisScoreL cluster. Atheromatous plaque samples in the PyroptosisScoreL cluster had higher proportions of gamma delta T cells, M2 macrophages, myeloid dendritic cells (DCs), and cytotoxic lymphocytes (CTLs), but lower proportions of endothelial cells (ECs). Immune full-activation pathways (e.g., NOD-like receptor signaling pathway and NF-kappa B signaling pathway) were highly enriched in the PyroptosisScoreH cluster. The key pyroptosis related genes GSDMD, CASP1, NLRC4, AIM2, and IL18 were upregulated in advanced carotid atherosclerotic plaques. We concluded that compared to advanced femoral atheromatous plaques, advanced carotid atheromatous plaques were of higher grade of pyroptosis. GSDMD, CASP1, NLRC4, AIM2, and IL18 were the key pyroptosis related genes, which might provide a new sight in the prevention of fatal strokes in advanced carotid atherosclerosis.
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Aterosclerosis , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/genética , Placa Aterosclerótica/metabolismo , Piroptosis/genética , Células Endoteliales/metabolismo , Interleucina-18 , Aterosclerosis/genética , Aterosclerosis/metabolismo , Arterias Carótidas/metabolismoRESUMEN
20(S)-Protopanaxatriol (PPT) is a type of ginsenoside isolated from panax notoginseng or ginseng, which is an essential ingredient in functional food, healthcare products and traditional medicine. However, the research and development of PPT are restricted due to its poor solubility. To circumvent the associated problems, a novel bridged-bis [6-(2,2'-(ethylenedioxy) bis (ethylamine))-6-deoxy-ß-CD] (H4) was successfully synthesized. The four inclusion complexes of the mono-[6-(1,4-butanediamine)-6-deoxy-ß-CD] (H1), mono-[6-(2,2'-(ethylenedioxy) bis (ethylamine)-6-deoxy-ß-CD] (H2) and their corresponding bridged bis(ß-CD)s (H3, H4) with PPT were prepared and studied by UV, 1H NMR, 2D ROESY, FT-IR, XRD and SEM technology. The UV-spectrometric titration showed that H1-4 and PPT formed 1:1 inclusion complexes and the binding constants were 297.61, 322.25, 937.88 and 1742 M-1, respectively. It was further revealed that the size/shape-matching relationship, hydrophobic interactions and hydrogen bond interactions play the crucial role in determining the stability of H1-4/PPT inclusion complexes. The solubility of PPT was evidently enhanced by193, 265, 453 and 593 times after the formation of inclusion complexes with H1-4, respectively. Furthermore, molecular docking was used to verify the inclusion mode of H4/PPT inclusion complex and also to investigate the stability of H4/PPT in water phase. The molecular simulation results agreed well with the experimental results. This research provides an effective way to obtain novel PPT-based functional food and healthcare products.
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Simulación del Acoplamiento Molecular , Sapogeninas/química , beta-Ciclodextrinas/química , Conformación Molecular , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Although several cases of family clusters with SARS-Cov-2 infection have been reported, there are still limited data preventing conclusions from being drawn regarding the characteristics and laboratory findings in the COVID-19 population within family clusters. In the present study, we retrospectively collected five family clusters with COVID-19 and summarized the dynamic profiles of the clinical characteristics, laboratory findings, immune markers, treatment and prognosis of this population. Furthermore, we also compared clinical and laboratory data between the SARS-Cov-2 infection with family cluster (n = 21) and those without family cluster (n = 16). We demonstrated that the duration of SARS-Cov-2 replication might be varied based on the different family clusters due to their different genetic backgrounds. The onset improved lung radiology might start at the end of the SARS-Cov-2 positive period. Furthermore, the obtained results demonstrated that similar basic characteristics and clinical findings seem to exist between the cases with SARS-Cov-2 and without family clusters. The serum level of ferritin might have a different biological function and be a new biomarker for the family cluster. Further studies with larger numbers of patients are required.
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COVID-19/transmisión , Adolescente , Adulto , Anciano , Antivirales/uso terapéutico , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/virología , Preescolar , China/epidemiología , Familia , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pandemias , Pronóstico , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificaciónRESUMEN
AIM: To investigate the effect of anti-vascular epithelial growth factor (VEGF) agents on the expression of fibrosis-related inflammatory mediators under normoxic and hypoxic conditions, and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS: Human retinal pigment epithelial (RPE) cells were incubated under normoxic and hypoxic conditions. For hypoxia treatment, CoCl2 at 200 µmol/L was added to the media. ARPE-19 cells were treated as following: 1) control group: no treatment; 2) bevacizumab group: bevacizumab at 0.25 mg/mL was added to the media; 3) hypoxia group: CoCl2 at 200 µmol/L was added to the media; 4) hypoxia+bevacizumab group: CoCl2 at 200 µmol/L and bevacizumab at 0.25 mg/mL were added to the media. The expression of interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor (TNF)-α were evaluated using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at 6, 12, 24 and 48h. RESULTS: Both mRNA and protein levels of IL-1ß, IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point, and TNF-α gene and protein expression was only significantly higher only at 24 and 48h (P<0.05). Under hypoxic conditions, bevacizumab significantly increased the expression of IL-1ß, IL-6, IL-8 and TNF-α at 6, 12, 24 and 48h (P<0.05). IL-1ß, IL-8 and TNF-α peaked at 24h and IL-6 peaked at 12h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION: Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under both normoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after anti-VEGF therapy, and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.
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AIM: This study aimed to evaluate the prognostic value of glutathione-S-transferase M3 (GSTM3) gene promoter methylation in patients with acute-on-chronic hepatitis B liver failure (ACHBLF). METHODS: A total of 119 patients with ACHBLF, 60 patients with chronic hepatitis B and 30 healthy controls were enrolled. We used a quantitative methylation detection technique, MethyLight, to examine the methylation levels of GSTM3 in peripheral blood mononuclear cells. RESULTS: The GSTM3 methylation level was significantly higher in patients with ACHBLF than those in patients with chronic hepatitis B and healthy controls (both P < 0.05). In patients with ACHBLF, GSTM3 methylation level percentage of methylated reference (PMR) positively correlated with total bilirubin, international normalized ratio, and Model for End-stage Liver Disease (MELD) score, and negatively correlated with prothrombin activity and albumin (all P < 0.05). The PMR for GSTM3 of non-survivors was significantly increased compared to that of survivors (P < 0.05). Multivariate analysis indicated that GSTM3 methylation level was one of the independent prognostic factors for 3-month mortality of ACHBLF (P = 0.000). The area under the receiver-operator characteristic curve of PMR for GSTM3 in predicting 3-month mortality of ACHBLF was not statistically different from that of MELD score (0.798 vs. 0.716, P = 0.152). However, the area under the curve of PMR for GSTM3 was significantly higher than that of MELD score in predicting 1-month mortality (0.887 vs. 0.737, P = 0.020). CONCLUSION: Promoter methylation levels of GSTM3 in peripheral blood mononuclear cells closely correlated with disease severity and could be used to predict prognosis of patients with ACHBLF.
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Bronchopulmonary dysplasia (BPD) is the most common type of chronic lung disease in infancy, for which no effective therapy is currently available. The aim of the present study was to investigate the effect of treatment with bone marrow mesenchymal stem cells (BMSCs) in combination with recombinant human erythropoietin (rHuEPO) on BPDinduced mouse lung injury, and discuss the underlying mechanism. The BPD model was established by the exposure of neonatal mice to continuous high oxygen exposure for 14 days, following which 1x106 BMSCs and 5,000 U/kg rHuEPO were injected into the mice 1 h prior to and 7 days following exposure to hyperoxia. The animals received four treatments in total (n=10 in each group). After 14 days, the body weights, airway structure, and levels of matrix metalloproteinase9 (MMP9) and vascular endothelial growth factor (VEGF) were detected using histological and immunohistochemical analyses. The effect on cell differentiation was observed by examining the presence of platelet endothelial cell adhesion molecule (PECAM) and VEGF using immunofluorescence. Compared with the administration of BMSCs alone, the body weight, airway structure, and the levels of MMP9 and VEGF were significantly improved in the BMSCs/rHuEPO group. The results of the present study demonstrated that the intravenous injection of BMSCs significantly improved lung damage in the hyperoxiaexposed neonatal mouse model. Furthermore, the injection of BMSCs in combination with intraperitoneal injection of rHuEPO had a more marked effect, compared with BMSCs alone, and the mechanism may be mediated by the promoting effects of BMSCs and EPO. The results of the present study provided information, which may assist in future clinical trials.
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Displasia Broncopulmonar/complicaciones , Eritropoyetina/farmacología , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Animales , Antígenos CD/metabolismo , Técnicas de Cultivo de Célula , Terapia Combinada , Modelos Animales de Enfermedad , Inmunofenotipificación , Lesión Pulmonar/terapia , Metaloproteinasa 9 de la Matriz/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
It is meaningful to research the Triboelectric Nanogenerators (TENG), which can create electricity anywhere and anytime. There are many researches on the structures and materials of TENG to explain the phenomenon that the maximum voltage is stable and the current is increasing. The output voltage of the TENG is high about 180-400 V, and the output current is small about 39 µA, which the electronic devices directly integration of TENG with Li-ion batteries will result in huge energy loss due to the ultrahigh TENG impedance. A novel interface circuit with the high-voltage buck regulator for TENG is introduced firstly in this paper. The interface circuit can transfer the output signal of the TENG into the signal fit to a lithium ion battery. Through the circuit of the buck regulator, the average output voltage is about 4.0 V and the average output current is about 1.12 mA. Further, the reliability and availability for the lithium ion battery and the circuit are discussed. The interface circuit is simulated using the Cadence software and verified through PCB experiment. The buck regulator can achieve 75% efficiency for the High-Voltage TENG. This will lead to a research hot and industrialization applications.
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The interaction between 20(S)-protopanaxatriol (PPT) and bovine serum albumin ( BSA) was studied with fluorescence quenching technique and ultra-violet absorption spectroscopy. The results indicated that PPT led to the intrinsic fluorescence quenching of BSA through a static quenching process .The binding constants of PPT with BSA obtained with fluorescence quenching method were calculated as 0.926 3×10(3) (298 K), 0.618 2×10(3) (308 K), 0.414 4×10(3) L·mol(-1)(318 K), respectively; while the number binding sites n were close to unity. The results showed that the driving force of the interaction between PPT and BSA was hydrogen bond and Van der Waals force. The result of synchronous fluorescence spectra showed that binding of PPT with BSA could induce conformational changes in BSA, that the part of tryptophan became more closely. According to Föster fluorescence resonance energy transfer theory, the binding distance r and energy-transfer efficiency E were respectively 26.2 nm and 0.32.
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Sapogeninas/química , Albúmina Sérica Bovina/química , Animales , Sitios de Unión , Transferencia Resonante de Energía de Fluorescencia , Enlace de Hidrógeno , Unión Proteica , Espectrometría de Fluorescencia , TermodinámicaRESUMEN
The aim of the present study was to investigate the effect of bone marrowderived mesenchymal stem cells (BMSCs) in the treatment of lung injury in a mouse model of bronchopulmonary dysplasia (BPD) and examine the underlying mechanisms. A mouse model of BPD was created using continuous exposure to high oxygen levels for 14 days. BMSCs were isolated, cultured and then labeled with green fluorescent protein. Cells (1x106) were subsequently injected intravenously 1 h prior to high oxygen treatment. Animals were randomly divided into three groups (n=5 in each): Control group, BPD model group and BMSC injection group. At two weeks posttreatment, the expression of transforming growth factorß1 (TGFß1), vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF) was detected using immunohistochemical staining and immunofluorescence. Compared with the BPD model group, the body weight, airway structure and levels of TGFß1 and VEGF were significantly improved in the BMSCtreated group. Immunofluorescence observations indicated that BMSCs were able to differentiate into cells expressing vWF and VEGF, which are markers of vascular tissues. The present study demonstrated that intravenous injection of BMSCs significantly improved lung damage in a neonatal mouse model of BPD at 14 days following hyperoxiainduced injury. This provides novel information which may be used to guide further investigation into the use of stem cells in BPD.
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Displasia Broncopulmonar/etiología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Animales , Animales Recién Nacidos , Peso Corporal , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patología , Displasia Broncopulmonar/terapia , Técnicas de Cultivo de Célula , Modelos Animales de Enfermedad , Expresión Génica , Genes Reporteros , Ratones , ARN Mensajero/genética , Transfección , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The aim of the present study was to investigate the protective effect of baicalin (BA) against ischemia-reperfusion (I/R) injury in isolated rat hearts. Sprague-Dawley rat hearts were rapidly removed, mounted on a Langendorff apparatus and subjected to 30 min ischemia followed by 30 min reperfusion with Krebs-Henseleit (K-H) solution at 37°C to establish the isolated I/R injury model. All animals (n=50) were randomly divided into five groups (n=10 in each): I, normal control; II, I/R; III, I/R plus 20 mg/kg BA; IV, I/R plus 40 mg/kg BA; and V, I/R plus 80 mg/kg BA. The degree of heart injury caused by the I/R was assessed by evaluating left ventricular function and by detecting the levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the isolated rat hearts. Myocardial infarct size and vascular density were assessed using histology and immunohistochemistry. The apoptotic cardiomyocytes were determined using flow cytometry (FCM). Compared with group II, the BA groups demonstrated improved left ventricular function, reduced CK and LDH release in the coronary effluent and increased SOD and MDA activity (P<0.05). Furthermore, histology and immunohistochemistry results showed that the infarct size was reduced and vessel density was augmented in the BA groups (P<0.01) compared with group II. The FCM results indicated that apoptosis was significantly lower in the BA groups than in group II (P<0.05) and that the protective effect was dose-dependent. In conclusion, these results demonstrated that BA exerts a dose-dependent protective effect on I/R injury in isolated rat hearts, the mechanisms of which may be associated with antioxidant and anti-apoptosis properties. To the best of our knowledge, this study is the first evaluation of the efficacy of BA in isolated rat hearts using histology and immunohistochemistry, providing a foundation for the use of BA in the treatment of acute myocardial infarction.
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PS-341, a proteasome inhibitor, is suggested to prevent the vascular remodeling induced by high-flow pulmonary artery hypertension (PAH), but the mechanism remains unclear. The aim of the current study was to investigate the effects and possible mechanism of PS-341 on hypertension-induced vascular remodeling. Male Sprague-Dawley rats were subjected to surgical methods to produce a shunt model of PAH. Three days after the surgical procedure, the animals randomly assigned to four groups (n = 10 in each group): I: sham group; II: shunt group; III: vehicle; IV: treated group. Eight weeks postoperative, the hemodynamics data were measured through Swan-Ganz catheter; the protein expression level of proliferating cell nuclear antigen, nuclear factor-κB (NF-κB), inhibitor of nuclear factor-κB (I-κBα), transforming growth factor beta-ß (TGF-ß), drosophila mothers against decapentaplegic protein (Smad) and vascular endothelia growth factor (VEGF) were investigated by immunohistochemical and Western blotting; the mRNA expression level of Ubiquitin (Ub), Smad3, TGF-ß1and Smad2 in lung were performed to detect by real-time reverse transcription-polymerase chain reaction analysis. The results showed that hemodynamic data and right ventricular hypertrophy were significantly improved (P < 0.05), the expression level of Ub, NF-κB, TGF-ß1, Smad2 and VEGF were decreased (P < 0.05), but the level of I-κBα was increased in PS-341 treated group as compared with the shunt and vehicle groups (P < 0.05). In conclusion, the present study indicated that PS-341 could significantly improve the lung damage, attenuate pulmonary vascular remodeling induced by high blood PAH model. The mechanism may be mediated by inhibition of NF-κB and TGF-ß/Smad signaling pathway and modulation the effect of VEGF.
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Ácidos Borónicos/administración & dosificación , Hipertensión Pulmonar/patología , Inhibidores de Proteasoma/administración & dosificación , Pirazinas/administración & dosificación , Remodelación Vascular/efectos de los fármacos , Animales , Western Blotting , Bortezomib , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Inmunohistoquímica , Pulmón/patología , Masculino , FN-kappa B/análisis , Antígeno Nuclear de Célula en Proliferación/análisis , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Smad/análisis , Factor de Crecimiento Transformador beta/análisis , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
The aim of the present study was to investigate the effects of PS-341 on vascular remodeling in an experimental rat model of high blood flow-induced pulmonary arterial hypertension (PAH), as well as to elucidate its mechanisms of action. We established the PAH model by a surgical method that implanted a left-to-right shunt. Three days post-surgery, the animals were randomly assigned to 3 groups (n=15 in each group): sham-operated (control), shunt (model) and PS-341 (treated) groups. Eight weeks post-surgery, hemodynamic parameters were significantly improved in the PS-341 group compared with the shunt group (P<0.05). Immunohistochemical analysis indicated that the expression levels of ubiquitin and nuclear factor-κB (NF-κB) p65 were significantly higher in the shunt group compared with the sham-operated group (P<0.05). Semi-quantitative western blot analysis further confirmed that the levels of ubiquitin and NF-κB p65 were decreased, while those of IκB-α (an inhibitor of NF-κB) were significantly increased in the PS-341 group compared with the shunt group (P<0.05). In conclusion, PS-341 attenuates high blood flow-induced pulmonary artery remodeling in rats via inhibition of the NF-κB pathway.
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Velocidad del Flujo Sanguíneo/efectos de los fármacos , Ácidos Borónicos/farmacología , Hipertensión Pulmonar/tratamiento farmacológico , Arteria Pulmonar/efectos de los fármacos , Pirazinas/farmacología , Factor de Transcripción ReIA/metabolismo , Animales , Bortezomib , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Hipertensión Pulmonar Primaria Familiar , Hipertensión Pulmonar/prevención & control , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Masculino , Inhibidor NF-kappaB alfa , Arteria Pulmonar/fisiopatología , Ratas , Ratas Wistar , Transducción de Señal , Factor de Transcripción ReIA/antagonistas & inhibidores , Factor de Transcripción ReIA/genéticaRESUMEN
The aim of the present study was to investigate the effect of bone marrow mesenchymal stem cell (BMSC) transp1antation on lung and heart damage in a rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). The animals were randomly divided into 3 groups: control, PAH and BMSC implantation groups. Structural changes in the pulmonary vascular wall, such as the pulmonary artery lumen area (VA) and vascular area (TAA) were measured by hematoxylin and eosin (H&E) staining, and the hemodynamics were detected by echocardiography. Two weeks post-operation, our results demonstrated that sublingual vein injection of BMSCs significantly attenuated the pulmonary vascular structural and hemodynamic changes caused by pulmonary arterial hypertension. The mechanism may be executed via paracrine effects.
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UNLABELLED: Pulmonary arterial hypertension (PAH) is characterized by functional and structural changes in the pulmonary vasculature, and despite the drug treatment that made significant progress, the prognosis of patients with advanced PH remains extremely poor. In the present study, we investigated the early effect of bone marrow mesenchymal stem cells (BMSCs) on experimental high blood flow-induced PAH model rats and discussed the mechanism. BMSCs were isolated, cultured from bone marrow of Sprague-Dawley (SD) rat. The animal model of PAH was created by surgical methods to produce a left-to-right shunt. Following the successful establishment of the PAH model, rats were randomly assigned to three groups (n=20 in each group): sham group (control), PAH group, and BMSC group (received a sublingual vein injection of 1-5 × 10(6) BMSCs). Two weeks after the administration, BMSCs significantly reduced the vascular remodeling, improved the hemodynamic data, and deceased the right ventricle weight ratio to left ventricular plus septal weight (RV/LV+S) (P<0.05). Real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry analysis results indicated that the inflammation factors such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) were reduced (P<0.05); the expression of matrix metallo proteinase-9 (MMP-9) was lower (P<0.05); vascular endothelial growth factor (VEGF) was higher in BMSC group than those in PAH group (P<0.05). CONCLUSION: Sublingual vein injection of BMSCs for 2 weeks, significantly improved the lung and heart injury caused by left-to-right shunt-induced PAH; decreased pulmonary vascular remodeling and inflammation; and enhanced angiogenesis.
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Hipertensión Pulmonar/patología , Trasplante de Células Madre Mesenquimatosas , Neovascularización Patológica/prevención & control , Comunicación Paracrina/fisiología , Animales , Citocinas/genética , Citocinas/metabolismo , Regulación de la Expresión Génica , Células Madre Mesenquimatosas/fisiología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: We investigated the safety and feasibility of intratracheal administration of autologous bone marrow-derived mononuclear cells (ABM-MNCs) and observed the effects in a canine model of pulmonary hypertension (PH). METHODS AND RESULTS: The PH model was induced by intravenous injection of 3mg/kg dehydromonocrotaline (DMCT) via the right atrium. Two weeks after DMCT administration, the animals received 4 different treatments (n=10 in each group): (I) negative control group; (II): ABM-MNCs group; (III) PH group; (IV) PH+ABM-MNCs group. Six weeks after injection of cells (107), the hemodynamic data were significantly improved in group IV compared with group III (P<0.05). The ratio of right ventricular weight to left ventricular plus septal weight was significantly decreased in group IV compared with group III (P<0.05). The mRNA levels of vascular endothelial growth factor, preproendothelin-1, interleukin-6 and tumor necrosis factor-α were significantly improved in group IV compared with group III (P<0.05). The immunofluorescence result showed that 6 weeks after administration ABM-MNCs could differentiate into pulmonary vascular endothelial cells. CONCLUSIONS: Six weeks after intratracheal administration, ABM-MNCs significantly improved the impairment caused by DMCT in a canine model of PH (ie, decreased pulmonary arteriolar narrowing, alveolar septum thickening and right ventricular hypertrophy, enhanced angiogenesis) and this provides a firm foundation for a clinical trial.
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Trasplante de Médula Ósea , Células Endoteliales/trasplante , Hipertensión Pulmonar/cirugía , Arteria Pulmonar/fisiopatología , Trasplante de Células Madre , Animales , Trasplante de Médula Ósea/efectos adversos , Diferenciación Celular , Separación Celular/métodos , Rastreo Celular/métodos , Modelos Animales de Enfermedad , Perros , Células Endoteliales/metabolismo , Endotelina-1/genética , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Hemodinámica , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Hipertrofia Ventricular Derecha/fisiopatología , Hipertrofia Ventricular Derecha/cirugía , Interleucina-6/genética , Monocrotalina/análogos & derivados , Neovascularización Fisiológica , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , ARN Mensajero/metabolismo , Trasplante de Células Madre/efectos adversos , Factores de Tiempo , Trasplante Autólogo , Factor de Necrosis Tumoral alfa/genética , Factor A de Crecimiento Endotelial Vascular/genética , Función Ventricular DerechaRESUMEN
INTRODUCTION: Pulmonary hypertension (PH) is a rapidly progressive and fatal disease. In recent years, despite drug treatment made significant progress, the prognosis of patients with advanced PH remains extremely poor. The authors implanted bone marrow-derived mesenchymal stem cells (BMSCs) intravenously into the PH model rats and observed the effect of MSCs on right ventricular (RV) impairments. METHODS: BMSCs were isolated, cultured from bone marrow of rats and stained with the cross-linkable membrane dye in vitro. One week after, a PH model was induced by subcutaneous injection of monocrotaline, the animals were randomly divided into 4 groups (n = 20 in each group): I, control; II, MSCs implantation; III, PH and IV, PH + MSCs implantation. Two weeks after MSCs implantation, the authors observed the MSC survival and transformation by immunofluorescence microscopy. On the other hand, RV hypertrophy and the elevation of systolic pressure were detected by echocardiography. RESULT: Three weeks after monocrotaline injection, RV systolic pressure, mean right ventricular pressure and mean pulmonary arterial pressure were significantly elevated in group III than in group I and II (P < 0.05) but significantly lower in group IV than in group III (P < 0.05). These results showed that implantation of MSCs could improve RV impairments caused by experimental PH. Histochemical results confirmed that transplanted MSCs were still alive after 2 weeks and part of the cells could differentiate into pulmonary vascular endothelial cells. CONCLUSION: Intravenous implantation of MSCs could significantly reduce or even reverse the progression of MCT-induced PH, improve cardiac function and hemodynamics.
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Hipertensión Pulmonar/terapia , Trasplante de Células Madre Mesenquimatosas , Disfunción Ventricular Derecha/terapia , Animales , Células de la Médula Ósea/citología , Hemodinámica , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/complicaciones , Inyecciones Subcutáneas , Masculino , Células Madre Mesenquimatosas/citología , Monocrotalina , Ratas , Ratas Sprague-Dawley , Disfunción Ventricular Derecha/etiologíaRESUMEN
BACKGROUND AND AIMS: Lamivudine, a nucleoside analog, is commonly used for treatment of chronic hepatitis B (CHB) but its durability of effectiveness after withdrawal is still uncertain. This study was designed to assess the durability of lamivudine treatment with stringent cessation criteria in hepatitis B e antigen (HBeAg)-negative patients and to explore potential predictive factors. METHODS: Sixty one HBeAg-negative CHB patients who had received lamivudine for at least 24 months and had maintained undetectable serum hepatitis B virus (HBV) DNA plus normal alanine aminotransferase for ≥ 18 months before withdrawal were included. They were followed up monthly during the first 4 months and at 3-month or 6-month intervals thereafter. Relapse was defined as serum HBV DNA ≥ 10(4) copies/mL. RESULTS: Thirty one of 61 patients relapsed during follow-up, over 90% occurred within 18 months after lamivudine withdrawal. Cumulative relapse rates at months 6, 12, 24, 36, 48 and 60 were 26.2%, 43.6%, 49.7%, 52.1%, 56.1% and 56.1%, respectively. Cox regression revealed that age was the only predictive factor for relapse, with lower relapse rates found in younger patients. Hepatitis B surface antigen (HBsAg) turned negative in eight patients, and none of them relapsed during follow-up. CONCLUSION: Effectiveness of lamivudine treatment is not durable in HBeAg-negative CHB patients even when stringent cessation criteria are adopted, with the exception of patients aged ≤ 20 years. The ideal end point of lamivudine treatment is clearance of serum HBsAg.
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Antivirales/administración & dosificación , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/administración & dosificación , Adulto , Factores de Edad , Alanina Transaminasa/sangre , Biomarcadores/sangre , China , ADN Viral/sangre , Esquema de Medicación , Monitoreo de Drogas , Femenino , Estudios de Seguimiento , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
OBJECTIVE: To explore role of perforin/granzyme expression of peripheral blood lymphocyte in injury of hepatocyte in severe hepatitis B, and evaluate relationship between perforin/granzyme expression levels and hepatitis B virus (HBV)-DNA load. METHODS: Thirty eight patients of severe hepatitis B were enrolled in the study. Fasting venous blood was collected on following morning of admission. Twenty adult healthy subjects served as healthy control group. Perforin/granzyme expression of peripheral blood lymphocyte was detected by flow cytometry, and serum HBV-DNA load was detected by fluorescence quantitative polymerase chain reaction (PCR). RESULTS: Positive rate of perforin/granzyme in peripheral blood lymphocyte in severe hepatitis B was higher than that of the healthy control group [perforin: (43.42+/-19.28)% vs. (19.65+/-9.27)%, granzyme: (40.35+/-12.26)% vs. (22.28+/-9.35)%, both P<0.01]. There was a significant negative correlation between the perforin/granzyme expression of peripheral blood lymphocyte and serum HBV-DNA load (r(perforin) =-0.92, r(granzyme) =-0.96, both P<0.01), the higher serum HBV-DNA load, the lower perforin/granzyme expression in severe hepatitis B. CONCLUSION: Perforin/granzyme overexpression in peripheral blood lymphocyte is an important factor in injury of hepatocyte in patients with severe hepatitis B, and the expression may be involved in HBV-DNA cleanup.
Asunto(s)
Granzimas/sangre , Hepatitis B/sangre , Perforina/sangre , Adulto , Estudios de Casos y Controles , ADN Viral/sangre , Femenino , Virus de la Hepatitis B , Humanos , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Carga ViralRESUMEN
OBJECTIVE: The present study was designed to investigate the influence of Congenital Heart Disease (CHD) on the mentality and behavior in children, and to compare post operative mentality and behavior in children receiving interventional therapy and congenital heart surgery. METHOD: Mentality and behavior of 232 children suffering from CHD were examined with Achenbach Child Behavior Checklist (CBCL) edited by XU Tao-yuan in 1992 and 100 sex, age, education and achievement-matched children with pneumonia were enrolled as controls. RESULTS: The mentality and behavior abnormal rates of the boys and girls suffering from CHD were significantly higher than those of controls (P < 0.01, P < 0.05). The behavior abnormities of the boys presented as depression, social flinch, physical complains, assault and violate rules. Whereas the girls presented as depression, social flinch, physical complains and violate rules. The total cursory mark of postoperative check result of the interventional and surgical children, both in girls and in boys, were significantly lower than those of the preoperative children (P < 0.05). The total and assault cursory mark of postoperative check result of children treated with interventional therapy were significantly lower than those of children treated with the surgical operations (P < 0.05). The abnormal rates of mentality and behavior positively correlated with the disease course. CONCLUSIONS: CHD is associated with increased abnormal mentality and behavior of the children. Early treatment, especially the interventional therapy can significantly improve the mentality and behavior of the children with CHD.