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The sluggish kinetics of the oxygen evolution reaction (OER) in alkaline water electrolysis remains a significant challenge for developing high-efficiency electrocatalytic systems. In this study, we present a three-dimensional, micrometer-sized iridium oxide (IrO2)-decorated cobalt carbonate hydroxide (IrO2-P-CoCH) electrocatalyst, which is engineered in situ on a carbon cloth (CC) substrate pretreated with atmospheric-pressure dielectric barrier discharge (DBD) plasma (PCC). The electrocatalyst features petal-like structures composed of nanosized rods, providing abundant reactive areas and sites, including the oxygen vacancy caused by the air-DBD plasma. As a result, the IrO2-P-CoCH/PCC electrocatalyst demonstrates an outstanding OER performance, with overpotentials of only 190 and 300 mV required to achieve current densities of 10 mA cm-2 (j10) and 300 mA cm-2 (j300), respectively, along with a low Tafel slope of 48.1 mV dec-1 in 1.0 M KOH. Remarkably, benefiting from rich active sites exposed on the IrO2-P-CoCH (Ir) heterostructure, the synergistic effect between IrO2 and CoCH enhances the charge delivery rates, and the IrO2-P-CoCH/PCC exhibits a superior electrocatalytic activity at a high current density (300 mV/j300) compared to the commercial benchmarked RuO2/PCC (470 mV/j300). Furthermore, the IrO2-P-CoCH/PCC electrocatalyst shows exceptional OER stability, with a mere 1.3% decrease with a current density of j10 for 100 h testing, surpassing most OER catalysts based on CC substrates. This work introduces a novel approach for designing high-performance OER electrocatalysts on flexible electrode substrates.
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Magnetic fields (MF) have been proven efficient in bioaugmentation, and the internal MFs have become competitive because they require no configuration, despite their application in waste gas treatment remaining largely unexplored. In this study, we firstly developed an intensity-regulable bioaugmentation with internal MF for gaseous chlorobenzene (CB) treatment with modified packing in batch bioreactors, and the elimination capacity increased by up to 26%, surpassing that of the external MF. Additionally, the microbial affinity to CB and the packing surface was enhanced, which was correlated with the ninefold increased secreted ratio of proteins/polysaccharides, 43% promoted cell surface hydrophobicity, and half reduced zeta potential. Furthermore, the dehydrogenase content was promoted over 3 times, and CB removal steadily increased with the rising intensity indicating enhanced biofilm activity and reduced CB bioimpedance; this was further supported by kinetic analysis, which resulted in improved cell adhesive ability and biological utilisation of CB. The results introduced a novel concept of adjustable magnetic bioaugmentation and provided technical support for industrial waste gas treatments. KEY POINTS: ⢠Regulable magnetic bioaugmentation was developed to promote 26% chlorobenzene removal ⢠Chlorobenzene mineralisation was enhanced under the magnetic field ⢠Microbial adhesion was promoted through weakening repulsive forces.
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Biopelículas , Clorobencenos , Adhesión Celular , Cinética , Membrana Celular , GasesRESUMEN
Objective: To explore the key sites in which L-arginine affects the expression of human coagulation factor VIII gene, and to create new drug targets for the treatment of hemophilia. Methods: A total of 5 human FVIII genes (A1, A2, A3, C1 and C2) with B domain deletion were transfected into human umbilical vein endothelial cells (HUVECs) as promoters. Run-on assay and ELISA analysis were performed to observe the driving effect of each domain gene on chloramphenicol acetyl transferase (CAT) gene transcription and expression, and the effect of L-arginine on each promoter. Results: In co-culture with L-arginine, transcriptional expression of the CAT gene was not detected in the PCAT3-Basic group (negative control without promoters), PA3-CAT3-Enhancer group or PC1-CAT3-Enhancer group. The transcriptional expression of CAT gene in the PCAT3-Control group (positive control with promoters) and PA1-CAT3-Enhancer group was unchanged compared with the non-L-arginine intervention, while the transcriptional expression of CAT gene in the PA2-CAT3-Enhancer group was significantly enhanced. Conclusions: A1 and A2 domain genes had promoter function and could initiate the transcription and expression of CAT gene, but A3, C1 and C2 domain genes could not. Moreover, L-arginine can significantly enhance transcription and expression of human coagulation factor VIII via A2 domain.
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Células Endoteliales , Factor VIII , Humanos , Factor VIII/genética , Factor VIII/metabolismo , Células Endoteliales/metabolismo , Arginina/farmacologíaRESUMEN
BACKGROUND: The potential signaling pathway of TSA suppressing TF expression induced by thrombin was unknown. Thus, the transcription of TF in HUVECs and the expressions of DCF, phospho-p38 MAPK, NADPH oxidase 4, PAR-1, and NF-κB were detected in our study. METHODS: HUVECs were randomly divided into control group, thrombin-treated group (with 5 U/mL of thrombin), and 4 TSA-treated groups (with 5 U/mL of thrombin plus TSA with 4 different concentrations of 1 µg/mL, 10 µg/mL, 100 µg/mL, and 1 mg/mL, respectively). RESULTS: After incubation with thrombin for 6 h at 37°C, the results showed increased TF mRNA, TF procoagulant activity, and antigen of TF in HUVECs of thrombin-treated group (p < 0.01); however, they were restored by TSA in a dose-dependent manner (p < 0.01). In addition, reactive oxygen species (ROS), phospho-p38 MAPK, NADPH oxidase 4, NF-κB, and PAR-1 expressed more intensively, and phosphorylated Akt decreased obviously in HUVECs after thrombin stimulation (p < 0.01); however, they were reversed to different extents by TSA in a dose-dependent manner (p < 0.01). CONCLUSIONS: Study suggests that TSA inhibits TF expression induced by thrombin in cultured HUVECs, and the potential signaling pathway of which is TSA interrupts the activation of PAR-1 and NADPH oxidase as well as derivative ROS generation, thereafter suppresses the activation of NF-κB, the upstream signal molecule of TF, via hampering phosphorylation of p38 MAPK and dephosphorylation of Akt, and finally inhibits thrombin-induced TF overexpression.
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Trombina , Tromboplastina , Humanos , Abietanos , Células Cultivadas , Células Endoteliales de la Vena Umbilical Humana/metabolismo , NADPH Oxidasa 4/metabolismo , NADPH Oxidasas/metabolismo , FN-kappa B/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , ARN Mensajero/metabolismo , Transducción de Señal , Trombina/metabolismo , Trombina/farmacología , Tromboplastina/genética , Tromboplastina/metabolismoRESUMEN
BACKGROUND: Adult chronic idiopathic thrombocytopenic purpura (ITP) is a chronic and usually lifelong hemorrhagic disorder in which enhanced platelet destruction and -weakened platelet production lead to thrombocytopenia. In this study, the p38 mitogen-activated protein kinase (p38-MAPK), early growth response 1 (EGR-1), p53, Bcl-xL, Bak, Bax, and reactive oxygen species (ROS) in platelets from adult patients with chronic ITP were investigated. METHODS: Platelets were isolated from blood samples collected from 20 adult patients with chronic ITP and 20 healthy volunteers. p38-MAPK, EGR-1, p53, Bcl-xL, Bak, Bax, and ROS were determined by flow cytometry, and the results were analyzed by EXPO32 ADC. RESULTS: Flow cytometry showed the expression levels of p38-MAPK (61.66 ± 19.38% vs. 27.52 ± 14.34%), EGR-1 (62.22 ± 20.48% vs. 9.05 ± 5.79%), p53 (56.82 ± 20.07% vs. 4.35 ± 2.04%), Bak (39.86 ± 11.45% vs. 20.82 ± 11.85%), Bax (36.85 ± 15.99% vs. 6.69 ± 5.01%), and ROS (19.98 ± 1.47% vs. 1.29 ± 0.10%) were all elevated (p < 0.05 compared with healthy volunteers). In addition, pro-survival Bcl-xL (5.38 ± 1.52% vs. 21.20 ± 6.04%) was decreased markedly in platelets from adult patients with chronic ITP (p < 0.05 compared with healthy volunteers). CONCLUSIONS: Our findings reveal that platelets in adults with chronic ITP display a proapoptotic gene expression phenotype, based on the enhanced expression of p38-MAPK, EGR-1, p53, Bak, Bax, and ROS, and attenuated expression of Bcl-xL, suggesting increased sensitivity toward apoptosis.
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Plaquetas , Púrpura Trombocitopénica Idiopática , Apoptosis/genética , Plaquetas/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor , Proteína X Asociada a bcl-2/genéticaRESUMEN
Autophagy is an evolutionarily ancient process wherein cells are able to break down intracellular contents to support normal physiology and development. Autophagosome formation is regulated by several different proteins, including the key cysteine protease Atg4. The contribution of Atg4 protein in the pathogenic fungus Cryphonectria parasitica, which causes blight in chestnut plants, has not been completely understood. In this context, we aimed to investigate the role of Atg4 during autophagy formation and their contribution to nonautophagic events in C. parasitica. By complementation assay, we determined that the CpAtg4 gene from C. parasitica was able to functionally complement the deletion of yeast Atg4. Using a yeast two-hybrid assay system, we confirmed that CpAtg4 and CpAtg8 directly interact with one another, and amino acids 377 to 409 of CpAtg4 were identified as being responsible for its binding with CpAtg8. The deletion mutant of CpAtg4 did not demonstrate positive monodansylcadaverine staining, which indicated that CpAtg4 is required for autophagy in C. parasitica. Moreover, the ΔCpAtg4 strain exhibited a decrease in aerial hyphae formation and sporulation, and reduction in virulence on apple and chestnut stem. The ΔCpAtg4 strains were also more sensitive to H2O2 and Congo red-induced stress. We further determined that amino acids 377 to 409 of CpAtg4 were essential for the function of CpAtg4 in vivo. Together, our findings indicated that CpAtg4 is required for the autophagy formation, fungal phenotypic traits, stress tolerance, and virulence in C. parasitica.
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Ascomicetos , Peróxido de Hidrógeno , Ascomicetos/genética , Autofagia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Peróxido de Hidrógeno/metabolismo , Enfermedades de las Plantas/microbiología , Virulencia/genéticaRESUMEN
This study was to explore the efficacy and safety of camrelizumab combined with apatinib in patients with advanced liver cancer. Moreover, the relationship between peripheral blood parameters and tumor response rate was also investigated. Patients with unresectable or recurrent primary liver cancer (PLC) who received treatment from July 2019 to July 2020 in the First Affiliated Hospital of Guangxi Medical University were included in this single-center retrospective study. The patients were treated with camrelizumab (200 mg, intravenous q2w) plus apatinib (250 mg, oral qd) until the occurrence of disease progression or unbearable toxicity. All the patients underwent blood routine test and detection of lactate dehydrogenase and serum albumin levels before treatment. The primary endpoints were objective response rate (ORR) and disease control rate (DCR). This study included a total of 45 patients. The overall ORR was 33.3% [95% confidence interval (CI),19.0-47.7] and the overall DCR was 57.8% (95% CI, 42.8-72.8). The ORR and DCR were higher in the first-line treatment than those in the second-line treatment (ORR: 45.5% vs. 21.7%, DCR: 63.6% vs. 52.3%). Median progression-free survival in the second-line treatment was 10.5 months (95% CI, 7.9-13.1, P = 0.022). Adverse events occurred in 39 (86.7%) patients. Grade 3/4 adverse reactions occurred in 7 (15.6%) patients. One patient (4.3%) was terminated from treatment due to adverse events. One patient (4.3%) died, which was potentially associated with adverse events. Subgroup analysis indicated that the remission rate in patients with high lymphocyte to monocyte ratio (H-LMR) was higher than that in patients with low lymphocyte to monocyte ratio (L-LMR) (56.25% vs. 25.93%, P = 0.047), and the remission rate in patients with high Prognostic Nutritional Index (H-PNI) was higher than that in patients with low Prognostic Nutritional Index (L-PNI) (66.7% vs. 26.5%, P = 0.046). Camrelizumab combined with apatinib in the treatment of PLC showed encouraging clinical efficacy, with tolerable toxicities. Levels of PNI and LMR may serve as predictors of the prognosis of advanced PLC patients who receive immunotherapy combined with targeted therapy.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Piridinas/uso terapéutico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/patología , Linfocitos/metabolismo , Persona de Mediana Edad , Monocitos/metabolismo , Metástasis de la Neoplasia , Estadificación de Neoplasias , Supervivencia sin Progresión , Piridinas/administración & dosificación , Piridinas/efectos adversos , Estudios RetrospectivosRESUMEN
OBJECTIVE: The objective of this study was to determine the expression of G protein-coupled receptors (GPCRs) in platelets from adult patients with chronic immune thrombocytopenic purpura (ITP). METHODS: Peripheral blood samples were collected from 40 patients with chronic ITP in the Second Affiliated Hospital of Shantou University Medical College, and 40 peripheral blood samples from healthy volunteers were collected; expressions of the adenosine diphosphate receptors (P2Y1 and P2Y12), alpha-2A adrenergic receptor (α2A-AR), and thromboxane A2 receptor (TP) in platelets were detected by flow cytometry. Gα protein, protease-activated receptor 1 (PAR1), and protease-activated receptor 4 (PAR4) were analyzed by Western blot and analyzed statistically. RESULTS: Flow cytometry measurements of mean fluorescence intensities showed platelets from patients with chronic ITP, compared to healthy individuals, had significantly higher levels of P2Y1 (31.4 ± 2.2 vs. 7.8 ± 0.8), P2Y12 (29.6 ± 2.1 vs. 7.2 ± 1.3), α2A-AR (25.8 ± 2.9 vs. 9.8 ± 0.9), and TP (39.8 ± 3.1 vs. 4.7 ± 0.6) (all p < 0.01). Similarly, integrated optical density analysis of Western blots showed that platelets from patients with chronic ITP had significantly higher levels of Gα (1046.3 ± 159.96 vs. 254.49 ± 39.51), PAR1 (832.98 ± 98.81 vs. 203.92 ± 27.47), and PAR4 (1518.80 ± 272.45 vs. 431.27 ± 41.86) (all p < 0.01). CONCLUSION: Expression of GPCRs is increased in platelets from patients with chronic ITP, suggesting that platelets of chronic ITP may participate in the complicated biological process by means of GPCR-mediated signaling pathways.
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Plaquetas/metabolismo , Regulación de la Expresión Génica , Púrpura Trombocitopénica Idiopática/sangre , Receptores Acoplados a Proteínas G/biosíntesis , Transducción de Señal , Adulto , Plaquetas/patología , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/patologíaRESUMEN
In this Letter, multiple foci modulation with controllable positions and intensity ratios is presented with a multi-belt binary phase mask in a tightly focusing system. Different from previous methods, the diffractive optical element (DOE) in our model is first virtually decomposed into two or more simple sub-DOEs. Then, after optimization, the sub-DOEs are combined to form the desired DOE through superposition. By such a decomposed optimization, the optimization complexities are greatly reduced, and the calculation becomes simpler and more effective. Furthermore, since the quantities and structures of sub-DOEs can be adjusted according to the original DOE, the method is very flexible and adaptable. As a demonstration, up to nine foci on the optical axis are studied, and the simulation results show that multiple foci can be well modulated. The proposed method may provide a universal strategy for complex light field modulations in a simple way.
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We demonstrate a simple, controllable, and stable method for fabricating high fill factor cylindrical microlens array with a novel isolated thermal reflow process. In this method, microstripes with a very small gap were obtained via digital micromirror device-based lithography, then covered with polydimethylsiloxane (PDMS) solution. The prepared microstripes were isolated and were heated and reflowed to a cylindrical microlens array. During the reflow process, the semicross-linked PDMS can serve as a barrier to prevent the diameter change and the bonding of adjacent microlenses. By this special treatment, the fill factor of the cylindrical microlens array can be significantly improved. Moreover, the reflow time and temperature have very little effect on the microlens shape due to the surrounded semicross-linked PDMS. This will make our process stabler than traditional methods. The measured 3D profile is good and satisfactory, and excellent optical performance is demonstrated with the fabricated cylindrical microlens arrays. The proposed method may offer a viable route for fabrication of high fill factor microlens arrays in a very simple and stable way.
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BACKGROUND: Adult chronic immune thrombocytopenia (chronic ITP) is a common autoimmune hemorrhagic disease characterized by decreased platelet production and increased platelet destruction, leading to thrombocytopenia. In this study, Ca2+, calnexin (CNX) and calreticulin (CRT) within platelets from adult patients with chronic ITP were investigated. METHODS: Platelets were isolated from blood specimen collected from 20 adult patients with chronic ITP and 20 healthy volunteers. Ca2+, CNX and CRT were determined by flow cytometry, and the results were analyzed with EXPO32 ADC software. RESULTS: Flow cytometry showed the expressions of Ca2+ (74.19±19.40% vs 22.79±10.47%) was elevated (P<0.05). However, CNX (15.10±7.32% vs 41.79±14.45%) and CRT (25.11±12.66% vs 38.58±12.02%) were decreased markedly in platelets from adult patients with chronic ITP (P<0.05 compared with healthy volunteers). CONCLUSION: Based on enhanced expression of Ca2+ and attenuated expression of CNX and CRT in patients with chronic ITP, Ca2+ concentration and its associated down-regulated proteins may be important regulatory signals in the pathogenesis of chronic ITP.
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BACKGROUND: At present, chemotherapy is still the primary treatment for advanced biliary tract carcinoma, but it is challenging to balance the efficacy and side effects. Network meta-analysis (NMA) is a better way to identify the protocol, and the advantage is that it can be combined with direct and indirect evidence to judge the best treatment regimens. Therefore, we conducted NMA on the searched randomized controlled trials (RCTs). METHODS: NMA was conducted regarding the searched RCTs by comparing progression-free survival (PFS), overall survival (OS), objective remission rates (ORRs), and adverse events (AEs) of different chemotherapy protocols. RESULTS: We screened 24 studies that met the inclusion criteria for further analysis. Compared with other regimens, the best supportive care (BSC) or FUFA protocol has a worse OS. Folfox4, GEMOX+erlotinib, and C+GEMOX can improve patients' PFS compared with BSC. Patients receiving GP+cediranib protocol have higher ORRs. There was reduced neutropenia grade ≥3 when adopting GP+cediranib, GS, C+GEMOX, RAM+GP, and MER+GP than when using FUFA protocol. The probability of vomiting of XELOX is lower than that of GEM+XELOX. There is a lower diarrhea incidence of XELOX than that of GEMOX+erlotinib. The results of cluster grade analysis illustrated that GEMOX+erlotinib owned a higher ORR and a higher surface under the cumulative ranking (SUCRA) of neutropenia and vomiting but also had a lower SUCRA of diarrhea and fatigue. Meanwhile, both GEMOX and C+GEMOX have a better ORR and a higher AE SUCRA. CONCLUSION: The NMA demonstrated that chemotherapy combined with targeted therapy has better efficacy and lower incidence of AEs than chemotherapy alone.
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Adult chronic idiopathic thrombocytopenic purpura (cITP) is a chronic and usually life-long haemorrhagic disorder in which enhanced platelet destruction and weakened platelet production lead to thrombocytopenia. Platelets were isolated from blood samples collected from 40 adult patients with cITP and 40 healthy volunteers. Mitochondrial membrane potential (ΔΨm) and plasma membrane phosphatidylserine externalization were determined by flow cytometry, and activation of caspase-3 and expressions of Bax, Bak and Bcl-xL were analysed by western blotting. Flow cytometry showed increased mitochondrial depolarization and lower ΔΨm in platelets from adult patients with cITP. In addition, plasma membrane phosphatidylserine externalization was observed on platelets from adult patients with cITP, but rarely from healthy volunteers. Western blot analysis of platelet proteins revealed that, in adult cITP patients, caspase-3 was activated, which cleaved gelsolin and to release a 47-kDa fragment. Moreover, the expressions of Bax and Bak were elevated, and Bcl-xL was decreased markedly in platelets from adult patients with cITP. Our findings reveal, based on loss of mitochondrial membrane potential (Δψm), phosphatidylserine exposure, caspase-3 activation, enhanced expression of Bax and Bak, and attenuated expression of Bcl-xL, that platelet death in the pathogenesis of thrombocytopenia in chronic ITP in adults is apoptotic.
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Apoptosis , Plaquetas/patología , Púrpura Trombocitopénica Idiopática/patología , Adulto , Plaquetas/metabolismo , Caspasa 3/análisis , Caspasa 3/metabolismo , Enfermedad Crónica , Femenino , Humanos , Masculino , Potencial de la Membrana Mitocondrial , Fosfatidilserinas/análisis , Fosfatidilserinas/metabolismo , Púrpura Trombocitopénica Idiopática/metabolismoRESUMEN
OBJECTIVE: In order to evaluate the effect of dyslipidemia on cellular or humoral immunity in patients, changes in the absolute number of lymphocyte subsets were detected. METHODS: Flow cytometry was applied to determine the absolute value of lymphocyte subsets: B cell, NK cell, CD4+ T cell including the functional subset (CD4+CD28+), native subset (CD4+CD45RA+CD62L+), memory T cell subset (CD4+CD45RA-), CD8+ T cell including the functional subset (CD8+CD28+) and activated subsets (CD8+CD38+ and CD8+DR+). The relationship between lymphocyte subsets and hypercholesterolemia and hypertriglyceridemia was analyzed. RESULTS: The absolute values of CD19+ B cell, CD3+ T cell, CD4+ Th cell, CD4+CD28+ cell, naive CD4+ T cell and memory CD4+ T cell in patients with dyslipidemia were markedly higher than those in healthy controls (P<0.05). There was no significant difference between healthy controls and dyslipidemia patients in other lymphocyte subsets (P>0.05). The absolute values of CD3+ T cell and naive CD4+ T cell were significantly positively correlated with hypercholesterolemia in peripheral blood (r=0.291 and 0.306, respectively, all P<0.05). There was no significant correlation between hypertriglyceridemia and lymphocyte subsets (P>0.05). CONCLUSION: Dyslipidemia has potential effects on immune profiles in lymphocytes subsets, and changes in lymphocyte subsets in dyslipidemia patients may lead to immune dysfunction.
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Acute myelomagakaryocytic leukemia is a diagnostic and therapeutic challenge owing to its heterogeneity and overlapping features with other types of acute leukemia. In order to build a diagnostic profile, we analyzed the biological, clinical and hematologic characteristics of acute myelomagakaryocytic leukemia. We found that, in three patients diagnosed with acute myelomagakaryocytic leukemia, there were two types of leukemia cells. One type was myeloblastic with positive peroxidase (POX) stainig and the expression of antigens CD13 and CD33. The other type was megakaryoblastic with negative POX staining and the expression of antigens CD36, CD41, CD42a and CD61. Three patients displayed the same cytogenetic abnormality, a (9: 22) translocation. Among the three patients with RT-PCR, two patients displayed BCR-ABL fusion gene amplification and one patient showed a previously undescribed OTT-MAL fusion gene amplification.
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Leucemia Mieloide Aguda , Enfermedad Aguda , Aberraciones Cromosómicas , Proteínas de Fusión bcr-abl/genética , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Translocación GenéticaRESUMEN
BACKGROUND: Solitary fibrous tumour (SFT) is a mesenchymal tumour of fibroblastic type, and it develops in almost any part of the human body. However, according to previous studies, the occurrence of intravascular SFTs is extremely rare. CASE PRESENTATION: We reported a case of intravascular SFT in a 67-year-old woman who has been experiencing swelling and pain in the right leg for 2 months. Computed tomography venography scan revealed a well-defined mass obstructing the inferior vena cava (IVC). Surgical resection was performed, and histopathologic and immunohistochemical results were consistent with SFT. Further, next-generation sequencing (NGS) analysis was performed, and results revealed two tumour-related gene mutations (deletion of PMS2 and variation of ESR1 [L536P]). The patient did not receive any adjuvant therapy, and no signs of tumour progression were observed during the 6-month follow-up. CONCLUSION: To the best of our knowledge, this study first presented about SFT arising from the IVC and carried out an NGS analysis to validate the molecular mechanism of such condition.
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Edema/patología , Tumores Fibrosos Solitarios/patología , Vena Cava Inferior/patología , Anciano , Angiografía por Tomografía Computarizada/métodos , Edema/diagnóstico , Femenino , Humanos , Flebografía/métodos , Tumores Fibrosos Solitarios/diagnóstico , Vena Cava Inferior/diagnóstico por imagenRESUMEN
Luteolin (Lu) is one of the flavonoids with anticancer activity, but its poor water solubility limits its use clinically. In this work, we used monomethoxy poly(ethylene glycol)-poly(e-caprolactone) (MPEG-PCL) micelles to encapsulate Lu by a self-assembly method, creating a water-soluble Lu/MPEG-PCL micelle. These micelles had a mean particle size of 38.6 ± 0.6 nm (polydispersity index = 0.16 ± 0.02), encapsulation efficiency of 98.32% ± 1.12%, and drug loading of 3.93% ± 0.25%. Lu/MPEG-PCL micelles could slowly release Lu in vitro. Encapsulation of Lu in MPEG-PCL micelles improved the half-life (t½ ; 152.25 ± 49.92 versus [vs] 7.16 ± 1.23 minutes, P = 0.007), area under the curve (0-t) (2914.05 ± 445.17 vs 502.65 ± 140.12 mg/L/minute, P = 0.001), area under the curve (0-∞) (2989.03 ± 433.22 vs 503.81 ± 141.41 mg/L/minute, P = 0.001), and peak concentration (92.70 ± 11.61 vs 38.98 ± 7.73 mg/L, P = 0.003) of Lu when the drug was intravenously administered at a dose of 30 mg/kg in rats. Also, Lu/MPEG-PCL micelles maintained the cytotoxicity of Lu on 4T1 breast cancer cells (IC50 = 6.4 ± 2.30 µg/mL) and C-26 colon carcinoma cells (IC50 = 12.62 ± 2.17 µg/mL) in vitro. These data suggested that encapsulation of Lu into MPEG-PCL micelles created an aqueous formulation of Lu with potential anticancer effect.
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Antineoplásicos/química , Luteolina/química , Micelas , Poliésteres/química , Polietilenglicoles/química , Animales , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Luteolina/sangre , Luteolina/farmacocinética , Luteolina/farmacología , Ratones , Nanopartículas/química , Ratas , Ratas Sprague-Dawley , SolubilidadRESUMEN
Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol)-poly(É-caprolactone) (MPEG-PCL) micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These QU/MPEG-PCL micelles with DL of 7% had a mean particle size of <34 nm, and could release QU for an extended period in vitro. The in vivo study indicated that intravesical application of MPEG-PCL micelles did not induce any toxicity to the bladder, and could efficiently deliver cargo to the bladder. Moreover, the therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle treatment efficiently reduced the edema and inflammatory cell infiltration of the bladder in an Escherichia coli-induced acute cystitis model. These data suggested that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL micelles may have potential application in acute cystitis therapy.
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Cistitis/tratamiento farmacológico , Micelas , Nanocápsulas/administración & dosificación , Quercetina/farmacología , Enfermedad Aguda , Análisis de Varianza , Animales , Cistitis/metabolismo , Modelos Animales de Enfermedad , Femenino , Histocitoquímica , Ratones , Ratones Endogámicos BALB C , Nanocápsulas/química , Nanocápsulas/toxicidad , Tamaño de los Órganos/efectos de los fármacos , Tamaño de la Partícula , Poliésteres/química , Polietilenglicoles/química , Quercetina/química , Quercetina/farmacocinética , Distribución Tisular , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/metabolismoRESUMEN
BACKGROUND: Gene therapy provides a novel method for the prevention and treatment of cancer, but the clinical application of gene therapy is restricted, mainly because of the absence of an efficient and safe gene delivery system. Recently, we developed a novel nonviral gene carrier, ie, heparin-polyethyleneimine (HPEI) nanoparticles for this purpose. METHODS AND RESULTS: HPEI nanoparticles were used to deliver plasmid-expressing mouse survivin-T34A (ms-T34A) to treat C-26 carcinoma in vitro and in vivo. According to the in vitro studies, HPEI nanoparticles could efficiently transfect the pGFP report gene into C-26 cells, with a transfection efficiency of 30.5% ± 2%. Moreover, HPEI nanoparticle-mediated ms-T34A could efficiently inhibit the proliferation of C-26 cells by induction of apoptosis in vitro. Based on the in vivo studies, HPEI nanoparticles could transfect the Lac-Z report gene into C-26 cells in vivo. Intratumoral injection of HPEI nanoparticle-mediated ms-T34A significantly inhibited growth of subcutaneous C-26 carcinoma in vivo by induction of apoptosis and inhibition of angiogenesis. CONCLUSION: This research suggests that HPEI nanoparticle-mediated ms-T34A may have a promising role in C-26 colon carcinoma therapy.
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Antineoplásicos/administración & dosificación , Antineoplásicos/química , Neoplasias del Colon/terapia , Terapia Genética/métodos , Proteínas Inhibidoras de la Apoptosis/genética , Nanopartículas/química , Polietileneimina/química , Proteínas Represoras/genética , Animales , Antineoplásicos/farmacología , Apoptosis/genética , Línea Celular Tumoral , Supervivencia Celular/genética , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Sistemas de Liberación de Medicamentos/métodos , Femenino , Heparina/química , Histocitoquímica , Proteínas Inhibidoras de la Apoptosis/biosíntesis , Ratones , Ratones Endogámicos BALB C , Nanopartículas/administración & dosificación , Neovascularización Patológica/patología , Neovascularización Patológica/terapia , Proteínas Represoras/biosíntesis , Survivin , Transfección/métodos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
N-doped TiO(2) (N-TiO(2)) nanocrystals with anatase and rutile mixed phases were prepared by partial oxidation of TiN. The samples were further modified by Fe-ions through incipient wetness impregnation method. The as-prepared samples were characterized by XRD, TEM, XPS, Raman, EPR, UV-vis DRS, and PL in detail. The results indicated that Fe mainly existed as Fe(3+)/Fe(2+) ions on the catalyst surface. The addition of small amounts of Fe-ions to N-TiO(2) nanocrystals caused several times enhancement of the photocatalytic activity under visible, UV and UV-vis light irradiation in degradation of gaseous toluene. The optimized Fe-ions content in this investigation was 0.02 wt.%. EPR and PL clearly showed that Fe(3+)/Fe(2+) redox cycle facilitated electron/hole charge separation, and contributed to the enhanced photocatalytic performance. Moreover, the photochemical stability of N-TiO(2) nanocrystals under visible light was improved due to the stabilization of nitrogen atoms in TiO(2) lattice by surface Fe-ions modification. The N-doped TiO(2) nanocrystals without Fe-ions modification suffered from a gradual deactivation due mainly to the loss of lattice-nitrogen during the photocatalytic reaction. The way to modification of nonmetal-doped TiO(2) nanomaterials brought new concept in enhancing the photocatalytic performance from the viewpoint of practical application.