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1.
Entropy (Basel) ; 21(6)2019 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-33267333

RESUMEN

The performance of a 300 kW organic Rankine cycle (ORC) prototype was experimentally investigated for low-grade waste heat recovery in industry. The prototype employed a specially developed single-stage radial turbine that was integrated with a semi-hermetic three-phase asynchronous generator. R245fa was selected as the working fluid and hot water was adopted to imitate the low-grade waste heat source. Under approximately constant cooling source operating conditions, variations of the ORC performance with diverse operating parameters of the heat source (including temperature and volume flow rate) were evaluated. Results revealed that the gross generating efficiency and electric power output could be improved by using a higher heat source temperature and volume flow rate. In the present experimental research, the maximum electric power output of 301 kW was achieved when the heat source temperature was 121 °C. The corresponding turbine isentropic efficiency and gross generating efficiency were up to 88.6% and 9.4%, respectively. Furthermore, the gross generating efficiency accounted for 40% of the ideal Carnot efficiency. The maximum electric power output yielded the optimum gross generating efficiency.

2.
Photochem Photobiol Sci ; 14(5): 972-81, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25793654

RESUMEN

Photodynamic therapy (PDT) has been successfully implemented as a treatment for wet age-related macular degeneration (AMD), but very few photosensitizers have been developed for clinical use. Herein, we describe a novel formulation of liposomal hypocrellin B (LHB) that was prepared by high-pressure homogenization. The encapsulation efficiency and PDT efficacy in vitro of this new preparation were found to remain nearly constant over 1 year. Moreover, LHB is rapidly cleared from the blood, with a half-life of 2.319 ± 0.462 h and a very low serum concentration at 24 h after injection. Testing in a rat model of choroidal neovascularization (CNV) showed that leakage of blood vessels in CNV lesions was significantly reduced when LHB PDT was given at a dose of 1 mg kg(-1) along with yellow laser irradiation; the damage to the collateral retina and the retinal pigment epithelium was minimal. Skin phototoxicity assays showed that only two of the 200 mice given a 4 mg per kg dose of LHB experienced an inflammatory reaction in the auricle irradiated at 24 h after dosing. These data collectively indicate that LHB may be a safe and effective photosensitizer for vascular-targeted PDT of AMD.


Asunto(s)
Perileno/análogos & derivados , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Quinonas/administración & dosificación , Degeneración Macular Húmeda/terapia , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Células Cultivadas , Neovascularización Coroidal , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Oído/patología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/fisiología , Células Endoteliales/efectos de la radiación , Femenino , Liposomas/síntesis química , Pulmón/irrigación sanguínea , Masculino , Ratones , Microvasos/efectos de los fármacos , Microvasos/fisiología , Microvasos/efectos de la radiación , Tamaño de los Órganos , Perileno/administración & dosificación , Perileno/síntesis química , Perileno/farmacocinética , Perileno/toxicidad , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/farmacocinética , Fármacos Fotosensibilizantes/toxicidad , Quinonas/síntesis química , Quinonas/farmacocinética , Quinonas/toxicidad , Ratas , Retina/efectos de los fármacos , Retina/patología , Retina/efectos de la radiación , Piel/efectos de los fármacos , Piel/patología , Piel/efectos de la radiación , Degeneración Macular Húmeda/patología
3.
Biomed Rep ; 20(4): 68, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38533389

RESUMEN

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T cell immunity in tumor-bearing hosts. The present study aimed to examine roles of T and MDSC subsets in lung malignancy. The study analyzed 102 cases with lung malignancy and 34 healthy individuals. Flow cytometry was performed for identification of T cell and MDSC subsets and their phenotypic characteristics in peripheral blood. The lung malignancy cases exhibited lower frequencies of granulocyte-like MDSCs (G-MDSCs) expressing PD-L2 and PD-L1 than healthy controls (P=0.013 and P<0.001, respectively). Additionally, there was a higher frequency of monocyte-like MDSCs (M-MDSCs) expressing PD-L1 in the peripheral blood of patients with lung malignancy than healthy controls (P<0.001). The frequencies of G-MDSCs and M-MDSCs were positively correlated with proportions of PD-1+ and CTLA-4+ regulatory T cells (Tregs). In vitro co-culture assay demonstrated M-MDSCs of lung malignancy enhanced naive T cell apoptosis and promoted Treg subset differentiation compared with M-MDSCs of healthy controls. The findings suggested accumulation of MDSC subsets in lung malignancy and MDSCs expressing PD-L2 and PD-L1 induced Treg expansion by binding to PD-1 on the surface of Tregs.

4.
Front Pediatr ; 12: 1390856, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38803636

RESUMEN

Background: Intestinal malrotation is a rare condition, and its delayed diagnosis can lead to fatal consequences. This study aimed to investigate the identification and treatment of malrotation in children. Methods: Clinical data, imaging, operative findings, and early postoperative outcomes of 75 children with malrotation were retrospectively analyzed. Results: The mean age was 6.18 ± 4.93 days and 51.26 ± 70.13 months in the neonatal group (56 patients) and non-neonatal group (19 patients), respectively. Sixty-seven patients were under the age of 1 year at the time of diagnosis. The occurrence of bilious vomiting and jaundice was significantly higher in the neonatal group (89.29%) than that in the non-neonatal group (37.5%), p < 0.05 and p < 0.01, respectively. The incidence of abnormal ultrasound (US) findings was 97.30% and 100%, respectively, and the sensitivities of the upper gastrointestinal series were 84.21% and 87.5%, respectively. Sixty-six (88%) patients had midgut volvulus, including in utero volvulus (two patients) and irreversible intestinal ischemia (four patients). Most neonates (89.29%) underwent open Ladd's procedure with a shorter operative time (p < 0.01). Reoperation was performed for postoperative complications (four patients) or missed comorbidities (two patients). Conclusions: Non-bilious vomiting was the initial symptom in >10% of neonates and nearly 40% of non-neonates. This highlights the importance for emergency physicians and surgeons to be cautious about ruling out malrotation in patients with non-bilious vomiting. Utilizing US can obviate the need for contrast examinations owing to its higher diagnostic accuracy and rapid diagnosis and can be recommended as a first-line imaging technique. Additionally, open surgery is still an option for neonatal patients.

5.
PLoS One ; 18(9): e0291455, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37756307

RESUMEN

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) have been reported to expand and have a potent ability in the expansion of regulatory T cells in malignant and infectious disease. The current study was performed to investigate the role of MDSCs and possible immune mechanisms in dampening immune responses of community acquired pneumonia (CAP). METHODS: This was a single-center cross-sectional study. The distribution of MDSCs subsets, the PD-1/PD-L1(L2) level of MDSCs subsets and Tregs in the peripheral blood of adult CAP patients and healthy control were measured by flow cytometry analysis. RESULTS: Peripheral blood mononuclear cells (PBMCs) from 63 adult CAP patients contained an elevated frequency of both G-MDSC (4.92±0.30 vs 2.25±0.21,p<0.0001) and M-MDSC (19.40±1.30 vs 9.64±0.57,p<0.001) compared to healthy controls. Treg in the peripheral blood of CAP patients exhibited increased expression of PD-1 and CTLA-4, accompanied by no difference of their frequency. Moreover, up-regulated expression of PD-L1 on MDSC subsets in the peripheral blood of CAP patients was also revealed. Of note, the frequency of circulating MDSCs subset displayed a positive correlation with neutrophil count percentage in blood in CAP patients. CONCLUSIONS: In summary, the significant expansion of circulating MDSCs subsets and the up-regulated expression of PD-1/PD-L1 level in CAP patients may suggest the possible involvement of PD-1/PD-L1axis in MDSCs mediated immune regulation on Treg at least partially in CAP patients.


Asunto(s)
Infecciones Comunitarias Adquiridas , Células Supresoras de Origen Mieloide , Neumonía , Humanos , Adulto , Regulación hacia Arriba , Antígeno B7-H1 , Estudios Transversales , Leucocitos Mononucleares , Receptor de Muerte Celular Programada 1
6.
Biomed Rep ; 19(2): 55, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37560314

RESUMEN

The roles of myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs) in acute myocardial infarction (AMI) remain elusive. The present study aimed to analyze the proportions of the granulocytic and monocytic populations of MDSCs (G-MDSCs and M-MDSCs, respectively), and Tregs in the peripheral blood mononuclear cells (PBMCs) of patients with AMI. The present study recruited 34 patients with AMI and 37 healthy controls without clinical signs of myocardial ischemia. PBMCs were isolated from the peripheral blood samples of patients with AMI within 24 h following admission to the hospital and from those of the healthy controls during a physical examination. Two subsets of MDSCs, G-MDSCs (CD15+CD33+CD11b+CD14-HLA-DRlow) and M-MDSCs (CD14+CD15-CD11b+HLA-DRlow), and Tregs (CD3+CD4+CD25highCD127low T-cells) in the PBMCs derived from the patients with AMI and healthy controls were analyzed using flow cytometry. The effects of MDSCs derived from patients with AMI on naïve CD4+ T-cells were examined in the co-culture system. The results revealed that the proportions of G-MDSCs and M-MDSCs were higher in the peripheral blood of patients with AMI than in that of the healthy controls. The patients with AMI had significantly higher numbers of programmed death-ligand (PD-L)1- and PD-L2-positive G-MDSCs and M-MDSCs compared with the healthy controls (P<0.05). The MDSCs could acquire a granulocytic phenotype following AMI, and the G-MDSCs and M-MDSCs would be more likely to express PD-L2 and PD-L1, respectively. The ratios of Tregs to CD4+ T-cells and PD-1+ Tregs in the peripheral blood of patients with AMI were significantly higher than those in the healthy controls (P<0.05). The results of flow cytometry demonstrated an increase in the numbers of inducible Tregs in the co-culture system with the G-MDSCs derived from patients with AMI compared with the G-MDSCs derived from the healthy controls (P<0.01). On the whole, the findings presented herein demonstrate the accumulation of MDSCs, and the upregulation of PD-L1 and PD-L2 expression on the surface of MDSCs in patients with AMI. MDSCs can induce the expansion of Tregs by binding PD-1 on the surface of Tregs, thus playing a crucial role in AMI.

7.
Front Genet ; 14: 1289346, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38155713

RESUMEN

The prevalence of Anaplastic Lymphoma Kinase gene (ALK) fusion is about 5% among patients with lung adenocarcinoma, underscoring the importance of pinpointing distinct fusion variants for optimizing treatment approaches. This is the first reported case of a 74-year-old female with stage IV lung adenocarcinoma, featuring a novel Kinesin Family Member 13A (KIF13A)-ALK fusion, identified via next-generation sequencing (NGS) and confirmed with fluorescence in situ hybridization (FISH). Initially undergoing chemotherapy and then crizotinib, she achieved a partial response (PR) before progressing with multiple bone metastases. However, subsequent treatment with alectinib as a third-line option yielded positive results. A stable disease state persisted for an impressive 31 months of progression-free survival (PFS), accompanied by minimal toxicity symptoms. Up until now, a remarkable near 4-year span of overall survival (OS) has been consistently observed and monitored. This report of a KIF13A-ALK fusion case benefit significantly from alectinib with extensive follow-up. The case diversifies the array of ALK fusion partners and holds clinical relevance in refining therapeutic choices for KIF13A-ALK fusion-associated lung cancer.

8.
Biochem Biophys Res Commun ; 422(2): 233-7, 2012 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-22575447

RESUMEN

Light state transition in oxygenic organisms was defined as the ability to equalize the excitation of the two photosystems for maximal photosynthetic efficiency. In cyanobacteria, extensive researches on state transition have continuously provided new knowledge in the past decades but the molecular mechanism and physiological significance are still ambiguous. In this work, kinetics and dynamics of the transition from state 1 to state 2 in cyanobacterium Spirulina platensis cells were studied at different intensity of orange light from 10 to 120 µmol m(-2) s(-1). It was revealed that the state transition worked constantly independent of light intensity while the rates varied. The synchronous fluorescence kinetics for phycobilisome (PBS) and photosystem components indicated that the state transition was entirely regulated by "mobile PBS", and continuously changed fluorescence amplitudes suggested a series of intermediate states were involved between state 1 and state 2. The dynamic property of PBS movement during the state transition was revealed by (1,0) distribution of photo-linkable PBSs, indicating a collective movement of all PBSs. The results suggest that state transition in cyanobacteria possesses not only physiological but also photochemical significance.


Asunto(s)
Luz , Fotosíntesis , Ficobilisomas/fisiología , Spirulina/fisiología , Fluorescencia , Cinética , Ficobilisomas/efectos de la radiación , Spirulina/efectos de la radiación , Spirulina/ultraestructura
9.
Photosynth Res ; 111(1-2): 81-6, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22083175

RESUMEN

Energy transfer (ET) processes between chromophores in R-phycoerythrin (R-PE) from Polysiphonia urceolata were studied by use of ultrafast spectroscopic methods. Several primary ET pathways were elaborated. A fluorescence decay component with a time constant of several hundred picoseconds observed by streak camera is tentatively assigned to the reversible formation of exciton traps between α84 and ß84 pigment pairs. In order to investigate much faster ET processes in R-PE, a noncollinear optical parametric amplifier based femtosecond time-resolved transient fluorescence spectrometer was employed. The results reveal that the ET between α84 and ß84 pigment pair has a time constant of 1-2 ps; the energy migration between α84 and ß84 pairs within the R-PE trimer has a time constant of 30-40 ps. We also demonstrated an ET process from phycourobilin to phycoerythrobilin with a time constant as fast as 2.5-3.0 ps, which was directly observed in fluorescence kinetics by selective excitation of the phycourobilin molecules acting as the energy donor.


Asunto(s)
Transferencia de Energía , Ficoeritrina/química , Rhodophyta/química , Cinética , Modelos Moleculares , Fotoquímica , Ficobilinas/química , Ficoeritrina/aislamiento & purificación , Proteínas de Plantas/química , Proteínas de Plantas/aislamiento & purificación , Conformación Proteica , Espectrometría de Fluorescencia , Factores de Tiempo , Urobilina/análogos & derivados , Urobilina/química
10.
Biochim Biophys Acta ; 1797(3): 339-46, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20004638

RESUMEN

The correlation between the reduction of Q(A) and the oxidation of Tyr(Z) or Car/Chl(Z)/Cyt(b559) in spinach PSII enriched membranes induced by visible light at 10 K is studied by using electron paramagnetic resonance spectroscopy. Similar g=1.95-1.86 Q(A)(-*)EPR signals are observed in both Mn-depleted and intact samples, and both signals are long lived at low temperatures. The presence of PPBQ significantly diminished the light induced EPR signals from Q(A)(-*), Car(+*)/Chl(+*) and oxidized Cyt(b559), while enhancing the amplitude of the S(1)Tyr(Z)* EPR signal in the intact PSII sample. The quantification and stability of the g=1.95-1.86 EPR signal and signals arising from the oxidized Tyr(Z) and the side-path electron donors, respectively, indicate that the EPR-detectable g=1.95-1.86 Q(A)(-*) signal is only correlated to reaction centers undergoing oxidation of the side-path electron donors (Car/Chl(Z)/Cyt(b559)), but not of Tyr(Z). These results imply that two types of Q(A)(-*) probably exist in the intact PSII sample. The structural difference and possible function of the two types of Q(A) are discussed.


Asunto(s)
Benzoquinonas/química , Frío , Transporte de Electrón , Complejo de Proteína del Fotosistema II/química , Spinacia oleracea/química , Benzoquinonas/metabolismo , Espectroscopía de Resonancia por Spin del Electrón , Cinética , Oxidación-Reducción , Complejo de Proteína del Fotosistema II/metabolismo , Spinacia oleracea/metabolismo , Tirosina/química , Tirosina/metabolismo
11.
Biochim Biophys Acta ; 1797(8): 1421-7, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20206122

RESUMEN

Chloride is an essential cofactor for photosynthetic water oxidation. However, its location and functional roles in active photosystem II are still a matter of debate. We have investigated this issue by studying the effects of Cl- replacement by Br- in active PSII. In Br- substituted samples, Cl- is effectively replaced by Br- in the presence of 1.2 M NaBr under room light with protection of anaerobic atmosphere followed by dialysis. The following results have been obtained. i) The oxygen-evolving activities of the Br--PSII samples are significantly lower than that of the Cl--PSII samples; ii) The same S2 multiline EPR signals are observed in both Br- and Cl--PSII samples; iii) The amplitudes of the visible light induced S1TyrZ* and S2TyrZ* EPR signals are significantly decreased after Br- substitution; the S1TyrZ* EPR signal is up-shifted about 8G, whereas the S2TyrZ* signal is down-shifted about 12 G after Br- substitution. These results imply that the redox properties of TyrZ and spin interactions between TyrZ* and Mn-cluster could be significantly modified due to Br- substitution. It is suggested that Cl-/Br- probably coordinates to the Ca2+ ion of the Mn-cluster in active photosystem II.


Asunto(s)
Complejo de Proteína del Fotosistema II/metabolismo , Tirosina/metabolismo , Bromuros/química , Cloruros/química , Oxidación-Reducción , Complejo de Proteína del Fotosistema II/química , Relación Estructura-Actividad
12.
Biochem Biophys Res Commun ; 408(4): 674-9, 2011 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-21539807

RESUMEN

In Synechocystis sp. PCC 6803, the loop domain (aa 1-70) of the phycobilisome core-membrane linker, L(CM), was found to interact with the glycosyl transferase homolog, Sll1466. Growth of a Sll1466 knock-out mutant was slightly faster in low light, but strongly inhibited in high light; the phenotype is discussed in relation to the regulation of light energy transfer to photosystem II. At the molecular level, the mutant shows the following changes compared to the wild type: (1) a smaller size and higher mobility of phycobilisomes on the thylakoid membrane, and (2) a changed lipid composition of the thylakoid membrane, especially decreased amounts of digalactosyl diacylglycerol. These results indicate a profound regulatory role for Sll1466 in regulating photosynthetic energy transfer.


Asunto(s)
Glicosiltransferasas/metabolismo , Luz , Fotosíntesis , Tolerancia a Radiación , Synechocystis/enzimología , Synechocystis/efectos de la radiación , Glicosiltransferasas/química , Glicosiltransferasas/genética , Mutación , Synechocystis/genética
13.
Technol Health Care ; 28(S1): 207-216, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32364153

RESUMEN

BACKGROUND: The aircraft cockpit is a highly intensive human-computer interaction system, and its design directly affects flight safety. OBJECTIVE: To optimize the display interface design in complex flight tasks, the present study aimed to propose a dynamic conceptual framework and a timeline task analysis method for the quantization of the dynamic time effect of mental workload and the influencing factors of task types in the mental workload prediction model. METHODS: The multi-factor mental workload prediction model based on attention resource allocation was integrated to establish the dynamic prediction model of mental workload. The ergonomics simulation experiment was carried out by recording the data on the performance of embedded subtasks, National Aeronautics and Space Administration-Task Load Index (NASA-TLX) subjective evaluation, and eye tracking. RESULTS: The results indicated that the prediction model had a good prediction accuracy and effectiveness under different simulated interfaces and complex tasks, and the real-time monitoring of pilots' mental workload state was realized. CONCLUSION: In conclusion, the prediction model and the experimental method could be applied to avoid the overload of the pilot throughout the flight phase by optimizing the display interface and adjusting the flight task.


Asunto(s)
Fatiga Mental/fisiopatología , Pilotos , Adulto , Atención , Ergonomía , Movimientos Oculares , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Análisis y Desempeño de Tareas , Factores de Tiempo , Carga de Trabajo/psicología , Adulto Joven
14.
Exp Ther Med ; 20(3): 2099-2105, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32782522

RESUMEN

The aim of the present study was to evaluate the effectiveness of interventional treatment of primary tracheal tumors through flexible bronchoscopy. The clinical data of 38 patients with primary tracheal tumours who underwent flexible bronchoscopy intervention therapy between January 2011 and January 2017 were retrospectively analyzed. The average time interval from onset of symptoms to the appearance of actual clinical manifestations in the 38 patients ranged from 0 to 60 months, with an average of 8.1±11.6 months and a median of 4.2 months. The rate of misdiagnosis at the first visit was 36.8% (14/38). After interventional treatment, the overall efficiency (complete + partial response) of airway stenosis recanalization in the 38 patients was 89.5%. In 3 patients with benign tumors, the anhelation score was reduced following treatment (1.00±0.77 vs. 3.13±1.21 at the pre-treatment stage; P<0.001). The overall survival rates of the 35 patients at 1, 3 and 5 years were 69.3, 48.7 and 20.3%, respectively. Therefore, flexible bronchoscopic intervention may effectively smoothen the airways of patients and relieve the symptoms of anhelation. Combining radiotherapy and chemotherapy may improve patient prognosis and safety.

15.
Biochim Biophys Acta ; 1777(9): 1109-15, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18510941

RESUMEN

In intact PSII, both the secondary electron donor (Tyr(Z)) and side-path electron donors (Car/Chl(Z)/Cyt(b)(559)) can be oxidized by P(680)(+)* at cryogenic temperatures. In this paper, the effects of acceptor side, especially the redox state of the non-heme iron, on the donor side electron transfer induced by visible light at cryogenic temperatures were studied by EPR spectroscopy. We found that the formation and decay of the S(1)Tyr(Z) EPR signal were independent of the treatment of K(3)Fe(CN)(6), whereas formation and decay of the Car(+)/Chl(Z)(+) EPR signal correlated with the reduction and recovery of the Fe(3+) EPR signal of the non-heme iron in K(3)Fe(CN)(6) pre-treated PSII, respectively. Based on the observed correlation between Car/Chl(Z) oxidation and Fe(3+) reduction, the oxidation of non-heme iron by K(3)Fe(CN)(6) at 0 degrees C was quantified, which showed that around 50-60% fractions of the reaction centers gave rise to the Fe(3+) EPR signal. In addition, we found that the presence of phenyl-p-benzoquinone significantly enhanced the yield of Tyr(Z) oxidation. These results indicate that the electron transfer at the donor side can be significantly modified by changes at the acceptor side, and indicate that two types of reaction centers are present in intact PSII, namely, one contains unoxidizable non-heme iron and another one contains oxidizable non-heme iron. Tyr(Z) oxidation and side-path reaction occur separately in these two types of reaction centers, instead of competition with each other in the same reaction centers. In addition, our results show that the non-heme iron has different properties in active and inactive PSII. The oxidation of non-heme iron by K(3)Fe(CN)(6) takes place only in inactive PSII, which implies that the Fe(3+) state is probably not the intermediate species for the turnover of quinone reduction.


Asunto(s)
Frío , Complejo de Proteína del Fotosistema II/química , Spinacia oleracea/química , Benzoquinonas/farmacología , Coenzimas/metabolismo , Espectroscopía de Resonancia por Spin del Electrón , Transporte de Electrón/efectos de los fármacos , Transporte de Electrón/efectos de la radiación , Hemo/metabolismo , Hierro/metabolismo , Cinética , Luz , Spinacia oleracea/efectos de los fármacos , Spinacia oleracea/efectos de la radiación , Factores de Tiempo
16.
Photochem Photobiol Sci ; 8(12): 1676-82, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20024164

RESUMEN

Elsinochrome A (EA) possesses the highest singlet-oxygen quantum yield (0.98) amongst the perilenoquinoid pigments and may be suitable as a phototherapeutic drug. However, there have been virtually no studies into its medicinal applications. Based on the analysis of chemical derivatives of hypocrellins (the same family as EA), 5-(3-mercapto-1-propanesulfonic acid)-substituted elsinochrome A (MPEA) with an amphiphilicity was designed and synthesized by considering drug delivery and biological activity requirements. MPEA possesses a water solubility of 5.1 mg mL(-1), which is just sufficient to enable dissolution at a clinically acceptable concentration, while its partition coefficient (n-octanol/phosphate buffered saline) of 7 guarantees affinity to biological targets. MPEA could photogenerate semiquinone anion radicals and reactive oxygen species, especially singlet oxygen, at a yield of 0.73, which approaches that for hypocrellin B. Biological tests confirmed that the photodynamic activity of MPEA was as high as 60% of that of its parent EA, which is significantly higher than that of most other photosensitizers.


Asunto(s)
Perileno/análogos & derivados , Fármacos Fotosensibilizantes/química , Quinonas/química , Benzoquinonas/química , Benzoquinonas/metabolismo , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Espectroscopía de Resonancia por Spin del Electrón , Humanos , Radical Hidroxilo/química , Radical Hidroxilo/metabolismo , Perileno/síntesis química , Perileno/química , Perileno/farmacología , Fármacos Fotosensibilizantes/farmacología , Quinonas/síntesis química , Quinonas/farmacología , Oxígeno Singlete/química , Oxígeno Singlete/metabolismo , Espectrofotometría
17.
J Biomed Nanotechnol ; 15(12): 2305-2320, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31748013

RESUMEN

Verteporfin photodynamic therapy (PDT) has been approved for the treatment of exudative age-related macular degeneration (AMD) for over a decade. However, its extensive application has been impeded by inevitably collateral tissue damage and immediate induction of angiogenesis, in addition to the need of multiple treatments. In order to develop prospective photosensitizers for clinical use, a triphenyl phosphonium-modified cationic liposomal hypocrellin B (TPP cationic LHB) for angiogenic targeting and endothelial internalization was constructed. With optimal PDT parameters, TPP cationic LHB can lead to death of choroid-retinal vascular endothelial cells while cause negligible damage to collateral retinal pigment epithelium cells. This is likely due to the mitochondria targeting and effective intracellular singlet oxygen generation of TPP cationic LHB in vascular endothelial cells. Additionally, in vivo chick chorioallantoic membrane assay indicated the elevated neovessel-targeting ability and photo-induced anti-angiogenic activity of TPP cationic LHB. Furthermore, TPP cationic LHB PDT is able to maintain neovessel occlusion for an extended period of time compared with verteporfin PDT, without inducing significant increased expression of some angiogenic factors, such as vascular endothelial growth factor and integrin αvß3. This study describes a facile strategy that may be useful for developing new-generation photosensitizers to circumvent the limitations of PDT treatment of exudative AMD.


Asunto(s)
Degeneración Macular , Perileno/análogos & derivados , Fotoquimioterapia , Quinonas/uso terapéutico , Animales , Neovascularización Coroidal , Células Endoteliales , Liposomas , Degeneración Macular/tratamiento farmacológico , Perileno/uso terapéutico , Fármacos Fotosensibilizantes , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular
18.
RSC Adv ; 9(19): 10927-10936, 2019 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-35515302

RESUMEN

Lung cancer is the most frequent cause of cancer deaths in the world, and smoking is considered as one of the major causes. Small cell lung carcinoma (SCLC) represents a highly malignant and particularly aggressive form, with properties of widespread metastases and poor prognosis. Herein, twenty-five Scolopendra subspinipes mutilans L. Koch Oligopeptides (SSMOs) were isolated and their structures were identified, and the anti-proliferative activity against lung cancer cell lines was evaluated. Results showed that SSMO-5 induced the production of reactive oxygen species (ROS) markedly in NCI-H446 cells. Furthermore, SSMO-5 decreased the mitochondrial membrane potential (MMP) and enhanced the mitochondria-related apoptosis. These results demonstrate that in NCI-H446 cells, the apoptotic and cytotoxic effects of SSMO-5 are mediated by the intrinsic mitochondria-mediated apoptotic pathway, which in turn causes the activation of caspases and increases Bax expression, while decreases Bcl-2 and Bcl-xL expressions and regulates the interaction of p53/MDM2. In conclusion, a ROS-mediated mitochondrial pathway plays an important role in the process of SSMO-5-induced apoptosis against SCLC.

19.
Biochim Biophys Acta ; 1767(1): 15-21, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17188231

RESUMEN

The cell-wide mobility of PBSs was confirmed by synchronously monitoring the fluorescence recovery after photobleaching (FRAP) and the fluorescence loss in photobleaching (FLIP). On the other hand, a fluorescence recovery was still observed even if PBSs were immobile (PBSs fixed on the membranes by betaine and isolated PBSs fixed on the agar plate) or PBS mobility was unobservable (cell wholly bleached). Furthermore, it was proved that some artificial factors were involved not only in FRAP but also in FLIP, including renaturation of the reversibly denatured proteins, laser scanning-induced fluorescence loss and photo-damage to the cell. With consideration of the fast renaturation component in fluorescence recovery, the diffusion coefficient was estimated to be tenfold smaller than that without the component. Moreover, it was observed that the fluorescence intensity on the bleached area was always lower than that on the non-bleached area, even after 20 min, while it should be equal if PBSs were mobile freely. Based on the increasing proportion of the PBSs anti-washed to Triton X-100 (1%) with prolonged laser irradiation to the cells locked in light state 1 by PBQ, it was concluded that some PBSs became immobile due to photo-linking to PSII.


Asunto(s)
Cianobacterias/química , Complejo de Proteína del Fotosistema II/metabolismo , Ficobilisomas/metabolismo , Recuperación de Fluorescencia tras Fotoblanqueo/métodos , Rayos Láser , Octoxinol , Complejo de Proteína del Fotosistema II/química , Ficobilisomas/química , Renaturación de Proteína , Transporte de Proteínas/fisiología , Factores de Tiempo
20.
Biochim Biophys Acta ; 1760(3): 333-9, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16481115

RESUMEN

In the current work, the molecular recognition and interaction were studied by taking advantages of the environmentally sensitive fluorescence of hypocrellin B (HB) and the structural knowledge of hyaluronan (HYA), a polysaccharide over-expressed in tumor cells or tissues. Interestingly, it was found that, binding to HYA, the absorbance of HB would be greatly strengthened, suggesting HB fitting to a hydrophobic environment in HYA, while the fluorescence seriously quenched at pH 7.0, which was very distinct from the binding of HB to proteins, liposome, other polysaccharide molecules or HYA at pH 2.0. Synchronously, the particle size of HYA would become bigger after interaction with HB, suggesting an aggregation of HYA. Considering the spectral responses of HB and the particle size change of HYA, a specific interaction of HB with HYA was proposed, that is, an HB molecule would link two HYA molecules not only by hydrophobic interaction but also by formations of intermolecular hydrogen bonds at physiological pH values. Furthermore, the estimated binding constant suggests a quite high affinity of HB to HYA. Besides, an oxygen-dependent degradation of HYA and photobleaching of HB were observed via photosensitization of HB.


Asunto(s)
Ácido Hialurónico/química , Perileno/análogos & derivados , Fármacos Fotosensibilizantes/química , Quinonas/química , Ácido Hialurónico/efectos de la radiación , Luz , Peso Molecular , Perileno/química , Perileno/efectos de la radiación , Quinonas/efectos de la radiación , Espectrometría de Fluorescencia
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